D

espite the vital importance of the emerging area of biotechnology 

and its role in defense planning and policymaking, no definitive 

book has been written on the topic for the defense policymaker, 

the military student, and the private-sector bioscientist interested in the 

“emerging opportunities market” of national security. This edited volume 

is intended to help close this gap and provide the necessary backdrop for 

thinking strategically about biology in defense planning and policymaking. 

This volume is about applications of the biological sciences, here called 

“biologically inspired innovations,” to the military. Rather than treating 

biology as a series of threats to be dealt with, such innovations generally 

approach the biological sciences as a set of opportunities for the military 

to gain strategic advantage over adversaries. These opportunities range 

from looking at everything from genes to brains, from enhancing human 

performance to creating renewable energy, from sensing the environment 

around us to harnessing its power.

Edited by Robert E. Armstrong, Mark D. Drapeau, Cheryl A. Loeb, and James J. 

Valdes, with contributions from:

John B. Alexander

Paul Bartone

Yaakov Benenson

William E. Bentley

William D. Casebeer

James P. Chambers

Timothy Coffey

Francis Doyle III

Eleanore Edson

Andrew Ellington

Richard Genik III

Christopher Green

Justin Grubich

Thomas X. Hammes

João Hespanha

Edmund G. (Randy) 

 Howe

Adrienne Huston

Eric W. Justh

Jeffrey Krichmar

Michael Ladisch

Judith Lytle

Thomas McKenna

Michael Moodie

David C. Peters II

Joseph Rutigliano, Jr.

Joel Schnur

John Socha

Elizabeth Stanley

Dimitra Stratis-Cullum

James Sumner

Roy G. Thompson

Erica R. Valdes
Bio-inspired Innovation 

and National Security

Bio-inspired 

Innovation and

National Security

Robert E. Armstrong

Mark D. Drapeau 

Cheryl A. Loeb 

James J. Valdes

edited by

Published for the 

Center for Technology and National Security Policy

by National Defense University Press

Washington, D.C.

2010
Library of Congress Cataloging-in-Publication Data

Bio-inspired innovation and national security / edited by Robert E.

Armstrong ... [et al.].

 p. ; cm.

 Includes bibliographical references.

 1. Bionics. 2. Biomimetics. 3. Biological warfare. 4.

Bioterrorism--Prevention. 5. National security--United States. I.

Armstrong, Robert E., 1948-2008. II. National Defense University. Center

for Technology and National Security Policy.

 [DNLM: 1. Biological Warfare--trends--United States. 2. Biological

Warfare--prevention & control--United States. 3. Civil

Defense--methods--United States. 4. Public Policy--United States. 5.

Security Measures--trends--United States. UG 447.8 B6137 2010]

 Q317.5.B56 2010

 358’.38--dc22

 2010002967

NDU Press publications are sold by the U.S. Government Printing Office. For ordering information, call (202) 

512–1800 or write to the Superintendent of Documents, U.S. Government Printing Office, Washington, D.C. 

20402. For GPO publications on-line access their Web site at: http://www.access.gpo.gov/su_docs/sale.html.

For current publications of the Institute for National Strategic Studies, consult the National Defense University 

Web site at: http://www.ndu.edu.

Opinions, conclusions, and recommendations expressed or implied within are solely 

those of the contributors and do not necessarily represent the views of the Defense 

Department or any other agency of the Federal Government. Cleared for public 

release; distribution unlimited.

Portions of this book may be quoted or reprinted without permission, provided that 

a standard source credit line is included. NDU Press would appreciate a courtesy 

copy of reprints or reviews.
This book is dedicated to the memory of Dr. Robert Armstrong, 

visionary colleague, scholarly mentor, and good friend to all who 

knew him. Bob served the Nation as a Soldier and scientist and was 

passionate about the contributions that the biological sciences could 

make to national security. His provocative, often contrarian ideas 

challenged the status quo and were the genesis of this book.

vii

List of Illustrations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi

Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiii

Andrew W. Marshall

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xvii

part one 

Perspectives on Biological Warfare

chapter 1

Biotech Impact on the Warfighter . . . . . . . . . . . . . . . . . . . . . . 1

Thomas X. Hammes 

chapter 2

New Biological Advances and Military Medical Ethics . . . . . . . . . . . . 9

Edmund G. Howe

chapter 3

The Life Sciences, Security, and the Challenge 

of Biological Weapons: An Overview . . . . . . . . . . . . . . . . . . . . . 21

Michael Moodie 

Contents
viii ix Bio-IInspired IInnovation and ovation and NNational SSecurity

Chapter 4

Biological Warfare: A Warfighting Perspective . . . . . . . . . . . . . . . . 39

John B. Alexander 

part two

Biomolecular Engineering

chapter 5

Abiotic Sensing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55

James J. Valdes, Andrew Ellington, William E. Bentley, 

Roy G. Thompson, and James P. Chambers

chapter 6

Biosensors and Bioelectronics . . . . . . . . . . . . . . . . . . . . . . . . 77

Dimitra Stratis-Cullum and James Sumner 

chapter 7

Bioenzymes and Defense . . . . . . . . . . . . . . . . . . . . . . . . . . . 105

Adrienne Huston 

chapter 8

Bioenergy: Renewable Liquid Fuels . . . . . . . . . . . . . . . . . . . . . . 119

Michael Ladisch 

chapter 9

Bio-inspired Materials and Operations . . . . . . . . . . . . . . . . . . . . 139

Erica R. Valdes 

part three

Bio-inspired Machines

chapter 10

Learning Unmanned Vehicle Control from Echolocating Bats . . . . . . . . 157

Eric W. Justh 

chapter 11

Neurorobotics: Neurobiologically Inspired Robots . . . . . . . . . . . . . . 169

Jeffrey Krichmar 
contents ix

chapter 12

Biomimetic, Sociable Robots for Human-Robot Interaction . . . . . . . . . 177

Eleanore Edson, Judith Lytle, and Thomas McKenna

chapter 13

Biomechanically Inspired Robotics . . . . . . . . . . . . . . . . . . . . . . 195

John Socha and Justin Grubich 

chapter 14

Biological Automata and National Security . . . . . . . . . . . . . . . . . . 207

Yaakov Benenson 

part four

Human Applications

chapter 15

Enhanced Human Performance and Metabolic Engineering . . . . . . . . . 219

James J. Valdes and James P. Chambers

chapter 16

Functional Neuroimaging in Defense Policy . . . . . . . . . . . . . . . . . 227

Richard Genik III, Christopher Green, and David C. Peters II

chapter 17

Forging Stress Resilience: Building Psychological Hardiness . . . . . . . . 243

Paul Bartone 

chapter 18

Neuroplasticity, Mind Fitness, and Military Effectiveness . . . . . . . . . . 257

Elizabeth Stanley

chapter 19

Bio-inspired Network Science . . . . . . . . . . . . . . . . . . . . . . . . 281

João Hespanha and Francis Doyle III
x Bio-Inspired Innovation and National Security 

part five

Implications for the Department of Defense

chapter 20

Ethics and the Biologized Battlefield: Moral Issues in 21st-century Conflict . . 293

William D. Casebeer

chapter 21

Legal Issues Affecting Biotechnology . . . . . . . . . . . . . . . . . . . . 305

Joseph Rutigliano, Jr.

chapter 22

Building the Nonmedical Bio Workforce for 2040 . . . . . . . . . . . . . . 323

Timothy Coffey and Joel Schnur 

Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 339

About the Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . 343
xi

Figures

figure 3–1. The Biological Risk Spectrum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28

figure 8–1. Production of Biodiesel and Bioethanol in the European Union 15 . . . . . . . . . . . . 122

figure 8–2. Comparison of Fossil Energy Ratio from Four Different Energy Sources . . . . . . . . . 123

figure 8–3. Scheme of Lignocellulosic Material . . . . . . . . . . . . . . . . . . . . . . . . . . . 125

figure 8–4. Stage Products of Cellulose-to-Ethanol Process . . . . . . . . . . . . . . . . . . . . 125

figure 8–5. Unit Operations of Biorefinery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126

figure 8–6. Pretreatment Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128

figure 8–7. Modular Nature of Cellulolytic Proteins . . . . . . . . . . . . . . . . . . . . . . . . . 133

figure 8–8. Stages and Contents of Department of Energy Biofuels Roadmap . . . . . . . . . . . 135

figure 17–1. Factors that Influence Resiliency . . . . . . . . . . . . . . . . . . . . . . . . . . . . 248

figure 17–2. Mental Hardiness and the Effects of Combat Stress . . . . . . . . . . . . . . . . . . 249

figure 22–1. Defense Spending, 1929–2005 (in fiscal year 2000 dollars) . . . . . . . . . . . . . . 325

figure 22–2. Defense Outlays as Percent of Gross Domestic Product, 1929–2003 . . . . . . . . . . 326

figure 22–3. Defense Science and Engineering Workforce, 1958–2005 . . . . . . . . . . . . . . . 327

illustrations
xii Bio-Inspired Innovation and National Security 

figure 22–4. Scientists and Engineers by Occupational Group (as percent of total) 

Nationwide, 1950–2000, and in Department of Defense, 1960 and 2005 . . . . . . . 328

figure 22–5. Department of Defense Scientists and Engineers as Percent of 

National Scientists and Engineers . . . . . . . . . . . . . . . . . . . . . . . . . . . 330

Tables

table 8–1. Biofuel Consumption in the United States, Brazil, and Europe . . . . . . . . . . . . . 120

table 8–2. Effect of Various Pretreatment Methods on Chemical Composition 

and Chemical/Physical Structure of Lignocellulosic Biomass . . . . . . . . . . . . . . 127

table 8–3. Representative Pretreatment Conditions of Considered Technologies . . . . . . . . . . 130

table 9–1. Areas in Which Natural Biological Materials Excel . . . . . . . . . . . . . . . . . . . 141

table 9–2. Areas for Potential Military Application of Bio-inspired Materials . . . . . . . . . . . . 154

table 17–1. Primary Stressor Dimensions in Modern Military Operations . . . . . . . . . . . . . . 245

table 22–1. Projected Scientists and Engineers Employed in Scientific and 

Engineering Work, 2040 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331

table 22–2. Projected Scientists and Engineers Employed in 2040 Biotech Workforce, 

Scenario 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 332

table 22–3. Projected Scientists and Engineers Employed in 2040 Biotech Workforce, 

Scenario 2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 333

table 22–4. Projected Scientists and Engineers in 2040 Department of Defense 

Civilian Base Workforce under Status Quo and 2 Percent Scenarios . . . . . . . . . . 333

table 22–5. Projected Biotech Scientists and Engineers in 2040 Department of Defense 

Civilian Base Workforce under Status Quo and 2 Percent Scenarios . . . . . . . . . . 334

table 22–6. Science and Engineering Fields Relevant to 

Nonmedical/Health Biotechnology . . . . . . . . . . . . . . . . . . . . . . . . . . . 335
xiii

Ever since man took to the battlefield, biology has played a significant 

role—both unintentionally and intentionally—in conflict. Prior to the 

discovery of the germ theory of disease, most combat deaths were the 

result of infections. And even before that understanding, biology was used in 

an offensive role. An early example was the Tatars’ hurling of plague victims’ 

bodies over the wall of the Crimean city of Kaffa in 1346, which probably 

helped spread the Black Death.  

Despite various treaties and protocols, offensive biological weapons use 

has continued to this day, with the anthrax attacks of 2001 being the most 

recent incident. Such activity has led to a strong defensive program, with 

medical science developing numerous countermeasures that have benefited 

both civilian and military populations. 

But that is the “old” biological warfare.  Covert programs for the 

development of novel weapons will advance; likewise, the development of 

countermeasures will also continue. The present volume, however, does not 

address these issues. Rather, it reviews and analyzes current research and 

likely future developments in the life sciences and how they will significantly 

influence the biological material available to warfighters—not as weapons 

systems, but as augmentation to currently available equipment.  This is the 

“new” face of biological warfare.

The editors of this volume have assembled experts in research, 

warfighting, and defense policy to describe biological applications from the 

smallest to the largest scale. In addition, they show how thinking in biological 

terms can improve our procurement cycle and enhance our development 

time and costs.  Finally, no description of biotechnology would be complete 

foreword
xiv Bio-Inspired Innovation and National Security

without a consideration of ethical and legal issues related to such research and 

development. 

This edited book is an important contribution to the literature and 

nicely captures a number of ongoing military basic science research projects 

with long-term implications for the Department of Defense.  It does not 

purport to be an exhaustive accounting, but it is an excellent introduction for 

policymakers to garner an understanding of where biology is going to fit into 

21st-century readiness and preparedness for our fighting force. 

Andrew W. Marshall

Director of Net Assessment

U.S. Department of Defense
Bio-inspired Innovation 

and National Security

xvii

For the average person, the mainstream media, and perhaps even the 

typical warfighter, the application of biology to military operations probably 

conjures up negative thoughts of Cold War–era biological weapons programs, 

the use of plague or other diseases as weapons during war, the effects of the 

Spanish flu on forces in Europe during World War I, medical treatments 

for severed limbs caused by battlefield injuries, and mental anguish caused 

by post-traumatic stress disorder or traumatic brain injury. It is unfair to 

blame people for thinking of biological weapons or applications of biology to 

medicine when “biology in the military” is mentioned.1 To some degree, the 

two are difficult to separate from each other. 

Particularly outside national security circles, much biotechnology 

research focuses on medical or health issues, agriculture, and industrial 

processes. Yet while these are very important topics, they are a narrow and 

limited way of viewing biology and its potential applications to national 

security. This volume is about applications of the biological sciences, which we 

call “biologically inspired innovations,” to the military. Rather than treating 

biology as a series of threats to be dealt with, such innovations generally 

approach the biological sciences as a set of opportunities for the military to 

gain strategic advantage over adversaries. These opportunities range from 

looking at tiny genes to large brains, from enhancing human performance 

to creating renewable energy, from sensing the environment around us to 

harnessing its power. 

Many developments in the biological sciences have increasingly made 

an opportunities-based approach to biology and the military possible. 

During the past 20 years, advances ranging from DNA sequencing to various 

introduction
xviii xix Bio-IInspired IInnovation and ovation and NNational SSecurity

biotechnology manipulations to the intersection of biology with engineering, 

mathematics, and even aeronautical engineering have empowered the field 

to grow far more influential than it once was. Bioengineering, bio-inspired 

research, and biological metaphors have all become quite useful to the military 

and, indeed, society at large. 

This trend shows no signs of abating and in fact is spreading globally and 

becoming less expensive. There are commercial DNA synthesis facilities in 

numerous countries, including Australia, Canada, China, Denmark, France, 

Germany, Iran, Japan, India, Russia, South Africa, Sweden, Switzerland, the 

United Kingdom, and the United States. One can buy high-quality DNA 

synthesizing machines on the auction site eBay and other places online for a 

few thousand dollars, not to mention less sophisticated yet incredibly useful 

biotech equipment such as PCR machines and centrifuges. Technology is 

increasingly powerful, reagents often can be readily acquired by trading, and 

data are freely available in repositories such as GenBank. It is an open market 

for innovative people who want to get in on biotechnology and all it has to 

offer. In response, a field known as synthetic biology—the goal of which is to 

engineer biology like so many building blocks of nature—is burgeoning. 

In 1864, William Sellers introduced a standardized system of screw 

threads and nuts—connectors that were crucial for building things in the 

physical world. What will be the equivalent standard set of connectors in 

the biological engineering world? Perhaps the “BioBricks” project from the 

Massachusetts Institute of Technology (MIT), which seeks to create “Lego” 

block–like biological parts with standard ends that plug into each other 

simply and easily. These “bricks” are freely available from the MIT Web site, 

which keeps track of a Registry of Standard Biological Parts.2

 In association 

with this, the annual International Genetically Engineered Machine (iGEM) 

competition challenges high school students from around the world to 

develop new parts and products. U.S. students have competed against teams 

from Africa, Canada, India, Japan, Scotland, Slovenia, South Korea, Spain, 

Switzerland, and the United Kingdom. 

It is difficult to bridge the gap between what is happening in the world 

of iGEM and the research and operations inside the Department of Defense 

(DOD). There are very few “bio types” in the military, the DOD, or in national 

security jobs more generally. Getting an advanced degree in biology is not a 

typical route to becoming a senior military officer, a Foreign Service Officer, 

or even a DOD scientist. Biology is not emphasized at military academies, 

where students are much more likely to be trained in traditional engineering, 

computer science, or military history. Conversely, there are very few “military 

types” in biology jobs in academia, biotech companies, and the like. Despite 

many genuine advances in medicine inspired by war3 that have helped 
introduction xix

humanity, the stigma attached to the intersection of biology and the military 

for the aforementioned reasons widens the gap still further. 

Yet there are many revolutionary opportunities for the military 

stemming from biologically inspired innovations (BII) beyond traditional 

“threat-based” medicine and weapons applications of the technology. 

Biotechnologies can:

• impact logistics by reducing the size and weight of objects carried by 

warfighters 

• provide novel portable power sources 

• potentially influence manufacturing via rapid prototyping or other 

engineering advances 

• provide opportunities for new kinds of battlefield sensors, soldier 

monitoring and therapeutics, human performance enhancement, 

health monitoring, foods that can provide vaccines and nutrients and 

other chemicals in novel ways, data analysis, combat identification 

involving biology, and various forms of camouflage and concealment 

inspired by the natural world. 

Biological systems—from flocks of geese to complete ecosystems—are 

complex adaptive systems that affect human existence in fundamental ways. 

From the food supply to global climate change, humans are part of a global 

ecosystem, and biology impacts us at the core. Biological science, combined 

with engineering principles, can bridge the gap between today’s standards and 

systems and desired long-term capabilities important for national security. 

In the flat, global economy that is the backdrop of the military-industrial 

complex, this is not just about America. Many other countries have invested 

heavily in biology, realizing that it is the future. As one example, Singapore 

has set up a plan called Intelligent National 2015 to help the country meet 

the demands of its national security and economic growth structures and the 

population. The plan will use sensors, biocomputing, and nanotechnology.4 

Does the United States have such a roadmap—a national strategy for biology? 

This volume is designed as an overview of the many applications of 

biology to the military and national security writ large (with the exception of 

bioweapons and biomedicine). Policy issues are covered, and original research 

is presented. The diversity of the authors’ backgrounds reflects the breadth of 

applications and opportunities of biology to modern problems. The reader 

should walk away enlightened as to the many possible ways in which biology 

is influencing and will continue to influence national security. Authors were 

asked to provide foresight on trends and indicators in their areas of interest 

(but not forecasts, which would describe a single future state) in order to 

better understand their implications for the next 20 years or so. 
xxi xx Bio-IInspired IInnovation and ovation and NNational SSecurity

The chapters are organized into five sections. Part one, “Perspectives 

on Biological Warfare,” contains four chapters that review some traditional 

threat-based perspectives on biology and the military and place them in the 

opportunity-based framework of this volume. We asked warfighters, ethicists, 

and bioweapons experts to put emerging biologically inspired innovations 

into context. How do they change bioethics considerations? How will 

biotechnology impact the average warfighter? Is a spider silk net bazooka 

a bioweapon in an international legal context? Could it ever be? Should it? 

There are many issues to be considered against the backdrop of the more 

advanced research in later chapters. 

The contributors to part two, “Biomolecular Engineering,” are all active 

laboratory scientists who have worked on engineering in the small world of 

living molecules. Despite the scale of biomolecular work being tiny, generally 

at the level of genetic material, proteins, or cells, the implications range from 

large to small—from custom-designing molecules for specific tasks such 

as new materials that soldiers can wear, to creating large-scale renewable 

energy resources. 

The authors in part three, “Bio-inspired Machines,” paint a broader 

picture. Here, the natural world’s behavior and design become an inspiration 

for building nonliving machines that perform desired tasks. In one case, 

researchers have built autonomous machines that can learn using an artificial 

brain modeled after neurobiological principles. In another, animals such 

as dogs and octopi become the design of robots that can walk and pick up 

objects in unconventional ways. Still other authors write about the humanrobot interface, an important issue for warfighters as autonomous machines 

become more prevalent on the battlefield. 

In part four, “Human Applications,” authors examine how to better 

understand human beings for the purpose of enhancing their performance 

in some way. A good deal of the work being done in this field is in the general 

area of neuroscience, including neural plasticity, learning, resilience, and brain 

imaging. In one chapter, the authors look at bio-inspired network science, an 

attempt to comprehend how human networks are related at a fundamental 

level to genomic, hive, traffic, and other networks so we can better understand 

how humans interact in groups and how those groups interact with other 

kinds of nonhuman groups. 

Finally, in part five, “Implications for the Department of Defense,” 

authors discuss thorny issues surrounding BII policy that DOD and other 

parts of the Government currently (and will continue to) face. A military 

ethicist looks at potential ethical pitfalls related to the kind of research 

outlined in earlier chapters. A military lawyer considers the legality of 

biological inventions and their use in warfare. Finally, two lifelong defense 
introduction xxi

scientists take a quantitative point of view on where the future BII workforce 

will come from, and the results are not encouraging; change will have to occur 

in order to ensure that DOD is prepared to take strategic advantage of BII 

opportunities during the next 20 years.

All of these biological advances are part of the larger picture of a “global 

technology revolution” in which we are engulfed.5

 The United States is no 

longer the sole proprietor of world-class research and development (R&D) 

programs, and emerging technologies in numerous areas combined with 

niche specialty companies will ensure that this trend continues. Moreover, 

as the world changes, technologies in other parts of the world will evolve 

in response to their own novel environments, and not necessarily to ones 

familiar to those looking only at how technologies are used within the 

United States. Intersecting developments on numerous scientific and 

technological fronts (in addition to biology), including nanotechnology, 

materials science, information technology, and human factors research, are 

creating new subfields and inventions of possible strategic importance. World 

events that involve emerging technologies could evolve in predictable—or 

unpredictable—ways that create disruptive game-changers affecting U.S. 

grand strategy and international security and stability. 

Advances in other areas of science and technology will also bear on BII 

as they converge. The fields of nanotechnology, biotechnology, information 

technology, and cognitive science (collectively termed NBIC) increasingly 

interact in the laboratory and the industrial space. It is difficult to predict 

accurately the long-range effects this interaction will have, but clearly the 

trends in each of these areas separately, and more so together, are important 

to monitor. To some degree, advances in BII outlined in this volume, and the 

ethical, legal, education and training, and budgetary issues associated with 

them, must be seen in this greater NBIC context.

Analysts in the Office of Net Assessment in the Pentagon as well as 

thinkers in other institutions have been talking for about a decade about the 

emerging area of biotechnology and how it affects the military. They have 

previously recommended that DOD exploit the power of BII to address 

military challenges, that leaders inside DOD should formally advocate for 

rapid BII integration into DOD processes and programs (for example, by 

establishing a Department of Biotechnology and Military Life Sciences), and 

that DOD should establish a cooperative framework with the commercial 

biotechnology industry to support BII R&D. Yet there is no definitive book 

on the topic written for the defense policymaker, the military student, and the 

private-sector bioscientist interested in the “emerging opportunities market” 

of national security. We hope that this edited volume helps to close this gap 

and provides the necessary backdrop for thinking strategically about biology 
xxii Bio-Inspired Innovation and National Security

in defense planning and policymaking. DOD biology writ large needs to be 

better understood, should be a higher budget priority, needs a comprehensive 

human resource plan, and should collaborate with and be wary of other 

countries’ biological efforts, as appropriate. 

As DOD and other Government agencies move from study and research 

on BII toward product development and deployment on a large scale,6

 we 

hope that this book helps educate current and future leaders in the national 

security realm to take advantage of opportunities that biotechnology has 

created and to develop sustained U.S. technological dominance. 

Notes

1 Guo Ji-wei and Xue-sen Yang, “Ultramicro, Nonlethal, and Reversible: Looking Ahead to 

Military Biotechnology,” Military Review (July-August 2005), 75–78.

2 For more information on the Registry of Standard Biological Parts, see http://parts.mit.edu.

3 The history of biology and warfare is reviewed by Robert E. Armstrong and Jerry B. Warner, 

Biology and the Battlefield, Defense Horizons 25 (Washington, DC: National Defense 

University Press, 2003), and “History of Biological Warfare,” available at www.gulfwarvets.

com/biowar.htm. 

4 Comtex News Network, “Singapore Announces Latest 10-year IT Roadmap,” Xinhua, March 

9, 2005. 

5 Richard Silberglitt et al., The Global Technology Revolution 2020 (Santa Monica, CA: RAND, 

2006). See also www.dni.gov/nic/NIC_2025_project.html. 

6 The Office of Net Assessment has published a number of reports that were some inspiration 

for this volume, including “Exploring Biotechnology: Opportunities for the Department 

of Defense” (January 2002), “Biotechnology II: Capitalizing on Technical Opportunities” 

(October 2002), and “An Investment Strategy for Non-Traditional Applications of 

Biotechnology for the Department of Defense” (October 2005).
part one

perspectives on

biological warfare

1

The past few decades have been shaped by the remarkable evolution of 

information technology (IT), which has allowed humans to connect 

in ways we never considered possible in the past. Yet in its fascination 

with these new technologies, the United States has made major mistakes in 

how it integrated them into its strategic concepts. We assumed that technology, 

as represented by network-centric warfare, would allow us to dominate war. 

As a result, we focused investments, force structure, and training on ways 

to establish dominance by replacing people with technology. Unfortunately, 

despite claims by its proponents that IT fundamentally changed the nature 

of war, it proved incapable of overcoming 4,000 years of recorded history. 

The enemy continued to have a vote. Today, America’s enemies have voted 

to use irregular/fourth-generation warfare to counter U.S. dominance in 

high-technology conventional weaponry. Only the painful lessons of Iraq, 

Afghanistan, and the global war on terror forced the Pentagon to accept the 

fact that humans remain the dominant factor in war.

The next few decades will see a similar explosion in both biotechnology 

and nanotechnology. Today, these sciences are about where computers were in 

the late 1970s. Considering that it took us less than three decades to go from 

floppy disks with eight kilobytes of random access memory to terabyte hard 

drives, we have to expect the next few decades will bring progress as unforeseen 

as the Internet was in 1975. The United States must not make the same mistake 

in trying to apply the new technologies to replace humans. Rather, it should 

explore how to use the technologies to enhance and support humans. Given 

the nature of biological advances, this should be a commonsense approach to 

integrating biotechnology advances into our strategic concepts. 

chapter 1

biotech impact on the warfighter

Thomas X. Hammes
23 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Short-term Developments

Although we are on the verge of the biotechnology explosion, the uncomfortable 

reality is that the early products of this biological revolution have much more 

potential to empower terrorists than to provide state-based warfighters with 

effective new tools.

This is not to say that modern biotechnology is not delivering some 

enhancements for today’s warfighter—just that the current enhancements 

are less impressive than the perceived threat. Looking first at the advantages 

that biotechnology is bringing to the warfighter, we can see some progress in 

pharmaceuticals, significant advances in combat medical care, solid progress 

in sensors and new materials, and even some “green” manufacturing for 

propellants and other energetics. 

For instance, pharmaceuticals that manipulate circadian rhythms are 

being used to enhance pilot alertness on long missions. More advanced tests 

indicate it might be possible to chemically sustain a person’s alertness as long 

as several days without adverse effect, then allow the person to fully recover 

in one 10- to 12-hour stretch of sleep. 

In a similar vein, sports medicine is constantly seeking ways, both legal 

and illegal, to enhance athlete performance. While legality is not a critical issue 

for combat soldiers, safety is. Current strength enhancers that cause long-term 

health problems obviously cannot be employed by the military. However, one 

area with promise is blood doping—that is, simply providing the soldier with 

more of his own red blood cells to increase his oxygen carrying capacity. In 

an extension of this concept, experiments with artificial blood cells that carry 

oxygen present another possibility of enhancing human performance. These 

are fairly minor improvements in performance with limited applications. 

While there is no doubt that biotechnology will bring dramatic changes 

in the capabilities of humans, it will take time, and improvements will be 

incremental in nature. 

In contrast to human enhancement, major progress has been made in 

trauma care for wounded personnel. Not only have survival rates increased 

dramatically, in part due to new biological products, but also postinjury care 

is greatly improving the quality of life of those treated. In particular, prosthetic 

devices have made enormous strides. We have developed devices that can be 

directly controlled by a patient’s nervous system. As progress continues, artificial 

limbs will improve in strength and agility until they exceed natural capabilities. 

Despite the obvious ethical questions, we can assume some individuals, groups, 

and perhaps even nations will experiment with fighters using artificial limbs. 

In a more benign development, the Defense Advanced Research Projects 

Agency has produced a cooling glove that vastly enhances human performance 
biotech impact on the warfighter 3

in hot or cold environments. Slipped over the hand, the glove cools or heats 

the subject’s blood as it passes under the glove and has resulted in considerable 

improvements in physical capability in the lab. In some hot environment tests, 

strength is increased 50 percent for short duration tasks, while endurance 

increases dramatically. Although the glove is a mechanical device, it clearly 

capitalizes on biological research into how the body functions under stress. 

Other forms of technology have already enhanced individual human 

performance. We take night vision and thermal imagery for granted as normal 

capabilities for an individual soldier. We are working hard on exoskeletons 

that will allow individuals to carry heavy loads without fatigue or physical 

injury, although providing sufficient power will probably restrict operations 

to base camps with adequate power generation capability. As an interim step, 

we are exploring “super” Segways that allow an individual soldier to control 

the vehicle while remaining able to fire a machinegun and transport over 

1,000 pounds. With its narrow wheelbase, this “super” Segway functions as 

a first-generation exoskeleton that allows soldiers to move quickly, with light 

armor protection, into small spaces.

The current state of biotechnology indicates that short-term 

enhancements will most likely come primarily from the use of technology 

to mechanically enhance human performance rather than directly from 

biological improvements. 

Short-term Dangers

While there is great potential for long-term benefits to the warfighter and 

society as a whole from biotechnology, the primary short-term impact of 

biotechnology is to put biological weapons within reach of even small, poorly 

funded groups.

A primary short-term risk lies in synthetic biology, which differs from 

genetic engineering primarily in that the latter is the manipulation of existing 

living systems by modifying the genome (by either adding or subtracting 

genetic material), whereas synthetic biology is the creation of new genomes 

and organisms. The objective of the genetic engineering is simply to modify 

the genome of an organism or to bring the beneficial traits of one organism 

to another; synthetic biology seeks to reengineer entire organisms, create 

existing organisms using only their genetic base pairs, and even create new 

ones that have never been seen in nature. 

Synthetic biology obviously has enormous potential for changing 

any element of our world—from creating plants that will produce energetic 

compounds or inexpensive medicines in theater, to producing organisms 

that neutralize industrial waste. Synthetic biology’s potential is limited only 
45 Bio-IInspired IInnovation and ovation and NNational SSecurity 

by imagination and funding. Unfortunately, the same may (and I emphasize 

may, since this is easier said than done for a number of technical reasons) also 

be true of its potential as a weapon.

The following disconnected but very important developments 

foreshadow the potential for even small terrorist groups to successfully create 

biological weapons in the future:

• The nucleotides to make smallpox can be purchased from a variety of 

suppliers without identity verification. 

• Smallpox has about 200,000 base pairs. DNA with up to 300,000 base 

pairs has already been successfully synthesized.

• An Australian research team enhanced the pathogenicity of mousepox 

virus by activating a single gene. The modification increased its lethality, 

killing all 10 mice in the experiment. It was even lethal to 60 percent of 

an immunized population. The team posted its results on the Internet.1 

• Biohackers are following in the footsteps of their computer software 

hacker predecessors. They are setting up labs in their garages and 

creating products. A young researcher recently invested $20,000 in 

equipment and produced two new biological products before selling 

the company for $22 million. We can assume that others will try to 

replicate her actions. 

Smallpox offers an example of the potential devastation a terrorist release 

of a biological weapon could cause. The disease is well known for its high 

mortality rate and propensity to leave survivors with disfiguring facial and body 

scars. Smallpox is communicable from person to person and has an incubation 

period of 7 to 17 days. While a vaccine for smallpox does exist, there is no 

completely effective medical treatment once a person displays overt symptoms 

of the disease. Smallpox is considered a potential terrorist threat because the 

virus was declared eradicated in 1980 and countries halted their mandatory 

smallpox vaccination campaigns, thus leaving the current population highly 

susceptible to the virus if it were to be released by a terrorist group. 

DARK WINTER, an exercise conducted in 2001, simulated a smallpox 

attack on three U.S. cities. In a period of 13 days, smallpox spread to 25 states 

and 15 countries in several epidemiological waves, after which one-third of the 

hundreds of thousands of Americans who contracted the disease died. It was 

estimated that a fourth generation of the disease would leave 3 million infected 

and 1 million dead, although there are questions about the assumptions 

underpinning the epidemiological model. The good news is that this exercise 

was one of the key drivers behind the U.S. Government purchase of enough 

smallpox vaccine to inoculate every American in an emergency. Unfortunately, 

most of the world does not have access to adequate supplies of the vaccine. 
biotech impact on the warfighter 5

It is essential to remember that not only could a terrorist release of 

smallpox cause an exceptional number of deaths, but it could also shut down a 

large portion of global trade until the outbreak is controlled or burns itself out. 

Given that the 2002 West Coast longshoremen’s strike cost the U.S. economy 

$1 billion per day, the cost of a complete shutdown of all transportation would 

be catastrophic. 

Biological weapons have the potential to kill many more people than 

a nuclear attack. Further, unlike nuclear weapons, which are both difficult 

and relatively expensive to build, biological weapons are quickly becoming 

inexpensive to produce as life sciences and related technologies advance. 

While smallpox was selected as an example for this chapter, other agents 

could also be selected. An attack using a contagious human disease represents 

the worst case scenario. However, there are numerous less devastating and 

correspondingly less difficult biological attacks that possibly could occur. 

For example, a terrorist could use a series of anthrax attacks similar to those 

perpetrated in 2001 to cause massive disruption but few deaths among the 

population (anthrax is not contagious). By routing anthrax letters through 

every major mail and package distribution center in the Nation, he could 

force the various carriers to shut down while they decontaminate their 

facilities and devise safeguards to prevent further contamination. A terrorist 

could also simply introduce foot and mouth disease into feedlots in America, 

then announce the presence of the disease on the Internet or with video to 

the news media. Repeated attacks could cause massive financial losses and 

security costs for the beef industry. Similar attacks using mad cow disease 

could also be high impact. 

Longer Term Developments

It has already become a cliché that the 20th century was the century of physics 

and the 21st will be the century of biology. The fact that it is a cliché does not 

make it any less true. In the longer term, we can see a number of intriguing 

possibilities coming from biotechnology. We are already extracting spider 

silk from transgenic goats. Five times stronger than steel, spider silk offers 

some novel potential for new materials ranging from clothing with body 

armor capabilities to lightweight but incredibly strong ropes. While we are 

still learning to weave the material, we have proven that industrial quantities 

can be produced. This should be one of the first of a series of developments 

that make use of the natural evolution of materials and structures that have 

evolved over millions of years. 

In the same way that we are learning to make materials as effectively as a 

spider does, we are studying many aspects of other natural designs to improve 
67 Bio-IInspired IInnovation and ovation and NNational SSecurity 

how we build and process material and even deal with complexity. Thus, the 

study of biological systems is improving our manmade ones, as is pointed out 

in chapter 19 of this book, where network science—understanding one kind of 

network, such as bird flocking or fish schooling behavior—has larger implications 

for other networks, such as unmanned micro-aerial vehicles that can swarm.

Beyond the exploitation of biology to improve technology lies the 

frontier of actual genetic manipulation of humans. While there are huge 

ethical questions about even experimenting in this field, we have to accept 

that in a society where parents give their children human growth hormones 

to make them more athletically competitive, some individuals, organizations, 

or nations will seek genetic enhancement. Ethical issues such as these are 

discussed in more detail by other authors in this volume.

Because we are on the knee of the change curve, we cannot begin to 

predict the impacts biology will have on the warfighter in the next 30 years—

only that biotechnology, like IT before it, will revolutionize not just security 

but all aspects of our lives as well. 

Implications for the Warfighter

While the longer term exceeds our ability to predict, the short-term impacts 

of biology are already becoming clear. We know that the use of biological 

weapons will present unprecedented political and strategic issues to our 

senior leadership. While those considerations exceed the purview of the 

warfighter, the impact will be no less intensive. In any major biological attack 

on the United States, the military, in particular the National Guard and the 

Reserve Components, will be called upon to execute an extensive and perhaps 

unanticipated range of tasks. These tasks could easily range from providing 

emergency medical treatment to establishing refugee centers to enforcing 

quarantines. While the first two are fairly routine, the third has enormous 

implications. Beyond the legal ramifications, we have to consider the practical 

aspects. Will U.S. troops fire on apparently healthy civilians if ordered? What 

tactics, training, procedures, and equipment would allow us to enforce a 

quarantine without using deadly force? What other tasks might we be called 

upon to execute? Distribution of food into contaminated zones? Protection 

of vaccines or medical facilities? Closing U.S. borders? Operating critical 

infrastructure? How do we operate when the families of our Servicepeople 

are exposed to the same threat? Clearly, we are unprepared to assist our nation 

in the event of a major domestic biological attack. 

We also have to consider the use of biological weapons by various 

players on U.S. forces overseas. Such attacks could be designed to either 

create large numbers of casualties or render the force ineffective. What force 
biotech impact on the warfighter 7

protection measures, equipment, tactics, and training are necessary to protect 

a force against a potential terrorist attack with biological agents? How will 

we even determine whether we are under attack? Might the disease be a 

new outbreak of a naturally occurring disease? What are the procedures for 

identifying, verifying, and acting against such an attack? What is the impact 

of biological protective equipment? For many diseases, simple high efficiency 

particulate air filter masks to protect respiration will suffice. Others will travel 

by other vectors. How will an enemy introduce such weapons into our forces? 

Are there implications for how we provide contractor support in a combat 

zone? Would a terrorist go after the contracted logistics to cripple our forces? 

The questions above barely scratch the surface of the variables in a 

biological environment. Obviously, we must work on systems to protect our 

personnel from a wide variety of agents and to rapidly identify a particular 

agent and on processes for rapid development of treatments and vaccines 

for newly identified agents. It is not a matter of too few resources but rather 

of priorities. Currently, we spend billions in the hope of shooting down an 

inbound missile that might carry a small nuclear warhead—a weapon very 

few nations in the world will ever develop. Even those that do develop the 

system know such an attack would bring a devastating if not annihilating 

response. Yet we spend comparatively minuscule amounts on countering 

weapons that we know could be available to a range of nonstate actors in 

the near future. Some will simply not be deterrable. It is time to rethink our 

priorities. Our current commitments to Iraq and Afghanistan provide us with 

a unique opportunity to do so.

Reset for What?

The extensive wear and tear on our forces in Iraq and Afghanistan has altered 

the debate about the future military force. Many have come to the conclusion 

we will have to focus our efforts on resetting rather than transforming the force. 

Of course, the key question is, “Reset for what?” Do we rebuild our forces to 

fight a near-peer competitor? Or to fight a smaller state? Or to fight a prolonged 

insurgency? Whatever scenarios we prepare for, there is a high probability 

they will include some form of biological weapons. We have to use the reset 

requirement to incorporate biological defense in our future force structure. 

Note

1 Federation of American Scientists, “Mousepox Case Study,” available at 

www.fas.org/biosecurity/education/dualuse/FAS_Jackson/2-8.html.

9

Rapid advances in biotechnology and the changing nature of modern 

warfare have raised ethical questions for the military and for military 

physicians. Issues such as the treatment of prisoners of war, the use 

of psychotropic drugs on soldiers on the battlefield, and the requirement of 

certain protective measures against chemical and biological weapons are all 

difficult ethical issues to be considered by the military physician.1

In this chapter, I present some examples of ethical concerns for the 

physician on the battlefield. New developments in biotechnology, nanoscience, 

and neurobiology further complicate these ethical concerns by opening the 

possibility of manipulating the fundamental nature of human physiology, but 

these developments can contribute greatly to combat success. Whether and 

how such technologies should be employed remain uncertain and must be 

weighed with respect to both ethics and national security. Overall, I suggest 

that now, as before, the overriding priority must be the military’s missions.2 

If it is not, countless lives could be lost. However, at the same time that the 

military’s missions are given highest priority, limits still must be established 

regarding acceptable means with which to achieve victory. Where these lines 

should be drawn is the crux of many of the ethical questions that will be posed. 

Military Medical Triage

An ethical dilemma that has been posed for some time in military medicine is 

how triage should be carried out during combat.3 In civilian settings, physicians 

are generally required to treat dying patients first. In some combat situations, 

however, this may not always be the case, and military physicians may be faced 

chapter 2

New Biological Advances 

and Military Medical Ethics

Edmund G. Howe
101 Bio-IInspired IInnovation and ovation and NNational SSecurity 

with difficult decisions when the military priority is to meet the needs of the 

military mission before meeting the needs of the individual patient. 

In optimal conditions, when the resources are available (such as time, 

personnel, equipment, and supplies), and the combat situation allows for it, 

the most seriously ill patients would be treated first. In nonoptimal conditions, 

the military medical triage principle holds that military physicians can give 

priority to less severely ill or injured soldiers in two instances: if it would save 

a substantially greater number of soldiers’ lives, and if it is necessary to treat 

soldiers so they can return to combat. In these circumstances, it is likely that 

the injured soldiers are needed on the front lines in order to prevail against 

enemy forces or in order for the mission to be completed.4

 When military 

medical physicians make these difficult decisions, they recognize that by 

doing so, some patients may die who would have survived under different 

circumstances and with adequate resources. 

One example of this difficult decision process occurred during World 

War II in North Africa. Despite a shortage of penicillin, the decision was made 

to use it to treat soldiers infected with venereal disease in order to ensure that 

the soldiers would recover quickly and return to the front lines. Because of 

this policy, however, soldiers infected with other illnesses such as pneumonia 

did not receive the penicillin they needed, and, in some cases, they died as a 

result of their injuries/illnesses.5

Military physicians share their commitment to saving patients’ lives 

with their civilian counterparts.6 Civilian physicians performing medical 

triage after a natural disaster such as an earthquake or flood, in fact, adopt a 

practice comparable to that of military physicians. The ethical justification of 

sacrificing individuals’ lives to save greater numbers of soldiers or to further 

the mission has not changed in recent years.7 What may have changed is the 

way in which these principles should be applied. 

Rescuing Soldiers on the Battlefield

Recent advances in the life sciences, such as in biotechnology, nanoscience, 

and neurobiology, have introduced new questions about when soldiers, such 

as medics, should risk their lives to try to save the lives of other soldiers 

wounded on the battlefield.8

 An ethical question posed now, as in the past, is 

how many soldiers should risk their lives to try to rescue one fallen colleague. 

New technology has altered how this question might be answered. 

Thanks to new biosensors that can, for example, monitor vital signs such as 

the heartbeat of a wounded soldier, military physicians and their commanders 

can better monitor how the soldier is faring on the battlefield.9

 If the physician 

observes that the soldier’s pulse is falling due to blood loss, for example, he or 
New Biological Advances and Military Medical Ethics 11

she may feel a heightened sense of urgency to carry out a rescue attempt. These 

new observations raise the question of what medical criteria should be used 

to determine if a rescue attempt should be made and how much weight each 

criterion should have on the decision. During the heat of battle, commanders 

can best decide what risks to both fallen soldiers and rescuers are warranted. 

However, military physicians can best judge the clinical implications of a 

soldier’s vital signs. Thus, new biotechnology developments may require 

commanders and physicians to find ways to work together more closely.10

In addition to preserving the maximum number of soldiers’ lives, an 

important ethical value is to respect soldiers’ dignity by trying to save them.11

This value may justify a second or third soldier attempting a rescue, even when 

the life of a previous rescuer has been lost. If rescue attempts are not made, 

soldiers’ morale may be undermined. Higher morale will, of course, result in 

soldiers feeling more motivated to fight. The overriding ethical considerations 

here must be the same ones underlying military medical triage. The battle 

must be won. If this can be accomplished and a substantially greater number 

of soldiers’ lives will not be lost, the next most important value to be furthered 

is respecting soldiers’ dignity. 

Paradoxically, the choices that most promote soldiers’ dignity may be the 

same ones that would result in the most sacrifice of their individual interests. 

Soldiers know that their lives will be sacrificed if and when it is necessary for 

the mission. When soldiers enter the military, they promise implicitly to give 

their lives if they must. Military physicians, analogously, implicitly promise 

both the soldiers who will be their patients and the military that they will abide 

by military triage principles when their commanders indicate that they must.

Both soldiers and military physicians want to fulfill these prior 

promises, which are their reasons for serving in the first place. Thus, to fully 

respect soldiers’ dignity, military physicians must allow them to sacrifice their 

individual interests when necessary for the mission.

Treating Soldiers for Combat Fatigue

Another dilemma involving conflicting values arises when military doctors 

must treat soldiers temporarily immobilized by combat fatigue.12 Combat 

fatigue, also known as battle fatigue and shell shock, is a neurotic disorder 

cause by the stress involved in war. Combat fatigue has a number of 

characteristics including hypersensitivity to noises, movement, and lights, 

easy irritability leading in extreme cases to violence, and sleep disturbances 

including nightmares, restlessness, and insomnia.13

Under optimal conditions, one potential option for treating soldiers 

experiencing combat fatigue could be to remove them permanently from the 
123 Bio-IInspired IInnovation and ovation and NNational SSecurity 

front lines. This might increase the severity and permanence of their psychiatric 

symptoms but eliminate the possibility that they would die during battle. If 

asked, many might choose to be permanently removed from combat rather 

than risk death by reentering it. In civilian contexts, doctors generally respect 

what patients want, even when they are significantly emotionally impaired.

In combat, however, removing the soldier from the battlefield might 

result in extremely negative consequences. First, other soldiers might also 

want to be relieved from the front lines and the attendant risk of death. If 

they had learned that soldiers experiencing combat fatigue could be removed 

permanently from further duty, they might develop symptoms of combat 

fatigue themselves, consciously or unconsciously, in order to be removed 

from combat. These actions could decimate the war effort.14

Military physicians, therefore, are taught to treat such soldiers near 

the front lines if possible and give them food, sleep, and emotional support, 

with the clear expectation that they will rejoin their unit in battle within 

days, rather than treating them far from the front lines.15 Treating soldiers 

for combat fatigue may require giving priority to the needs of the military 

mission to avoid unintentionally opening the floodgates to soldiers wanting 

to escape front line duty.

This practice has been successful in the past. In general, soldiers 

temporarily removed from duty and treated in this manner have done well 

emotionally after rejoining their units. Depending on their closeness and 

loyalty to their unit, they will likely receive emotional support from others in 

their unit. The powerful emotional influence of unit cohesion is believed to be 

a reason that returning soldiers to their unit helps them to overcome combat 

fatigue.16 On the other hand, permanent removal from the front lines could 

further enhance their combat fatigue symptoms, partly as a result of survivor 

guilt—feeling guilty that other soldiers in their unit stayed at the front and died. 

Further, if soldiers are returned to serve in a more isolated environment, 

the benefits of unit cohesion could be reduced, and they could experience 

relapses of combat fatigue. This situation could occur in the future due to 

the ongoing counterinsurgency that U.S. forces are fighting in Iraq and 

Afghanistan. Soldiers in unprotected environments may fear that their lives 

are always in danger and may be traumatized more than once, either by being 

wounded themselves or by seeing a fellow soldier wounded or killed. Repeated 

trauma may result in their combat fatigue becoming worse, particularly if 

they remain in this situation. It may be, then, that in this kind of environment, 

the criteria for removing soldiers from the front lines versus returning them 

to duty should change. 

The ethical priority is again to do whatever is necessary to maximize 

the success of the mission. Military physicians treating soldiers with combat 
New Biological Advances and Military Medical Ethics 13

fatigue as they traditionally have done—with the expectation that the soldiers 

will return to the front lines—may therefore be more necessary than it has 

been in the past. As a result of this practice, soldiers may pay a dearer price.17

This suggests in turn the possibility of a greater need to try to prevent 

combat fatigue before it occurs. One example of the ethical problems this 

uncertainty brings about is whether to place mental health personnel at or 

near the front lines. If such personnel are stationed with soldiers, they may 

better gain their trust and thus be able to treat them more quickly. Yet this 

would also place these personnel, who are limited in number, at higher risk. 

Such a deployment of mental health personnel to the front lines raises the same 

kinds of questions discussed previously in regard to rescue attempts. How 

much risk to other soldiers, who in this instance are mental health personnel, 

is justifiable to possibly benefit soldiers at increased risk for combat fatigue?

Preventive Measures

In the future, new approaches may be developed to prevent soldiers from 

experiencing combat fatigue.18 One possibility is the use of medications.19 

Another is genetic screening, which would eliminate soldiers who are more 

genetically vulnerable to stress from serving in combat conditions in which 

they would be more likely to experience combat fatigue.

Medication might decrease soldiers’ risk of developing combat fatigue 

by reducing physiological responses to stress, such as heart palpitations, 

trembling, and sweating. This, could, in turn, reduce their subsequent 

emotional morbidity and could potentially be accomplished with so-called 

beta-blocking medications such as propranolol. This medication was first 

developed to treat hypertension and is often used to treat chest pain, high 

blood pressure, irregular heartbeats, migraine headaches, and tremors.20 Other 

uses of propranolol have included the treatment of anxiety and stress, and it 

has been used by performers and others to prevent stage fright. However, 

because neither this nor any other approach has been shown to be successful 

in reducing occurrences of combat fatigue, further research needs to be 

conducted. It may be that the fear and stress some soldiers experience during 

combat could be so profound that it would overcome preventive efforts.21

The use of a medication such as propranolol could potentially have 

serious negative effects. Such medication could potentially cause soldiers to 

be more callous during combat and/or to remember less of the horrors of war. 

Empirically, it is questionable whether these negative effects would actually 

occur, and more research is necessary before a true analysis can be made. 

Persons under the influence of hypnosis, for example, will not carry out acts 

that violate their personal conscience, whereas the influence of some drugs 
145 Bio-IInspired IInnovation and ovation and NNational SSecurity 

or alcohol may cause people to behave in ways out of character for them that 

could even be harmful to others. Ethically, it may not be the case that good 

and bad effects (if both occurred) should be balanced in some way to produce 

the “best overall result.” To do this would subject soldiers to unnecessary 

risk—a disrespectful and possibly ethically impermissible course of action.

Further, research into the use of psychotropic medications, including 

some beta-blocking medications, and psychostimulants such as amphetamines, 

which could be used to help soldiers stay awake and fight fatigue, must be 

measured against the adverse risk of addiction and potentially serious side 

effects such as psychosis.22

Genetic Screening

Alternatively, the risk of soldiers experiencing combat fatigue might be reduced 

by excluding from combat those who are genetically susceptible to being 

psychologically harmed due to stress—for example, if they had exceptional 

vulnerability based on genetic testing, if they had prior responses of exceptional 

anxiety, or even if they had close relatives with anxiety disorders.23

A study published in the November 2009 edition of the Archives 

of General Psychiatry, for example, has shown that a gene variant makes 

people who experienced trauma as children or adults more susceptible to 

psychiatric disease, including post-traumatic stress disorder (PTSD). The Yale 

researchers who undertook the study “looked at a particular variant, or allele, 

of the serotonin transporter protein gene, which was previously linked to an 

increased risk for depression in individuals who had experienced adverse 

events. People with this allele were more likely to develop PTSD if they had 

experienced childhood adversity or adult trauma.”24

Performing genetic screening on soldiers and excluding some from 

combat on the basis of their results could, however, violate soldiers’ privacy 

and equality by requiring other soldiers to take disproportionate risks.25 

Both concerns would also be more ethically problematic because the extent 

to which more genetically vulnerable soldiers would be likely to experience 

combat fatigue is uncertain.

This challenging nature of discriminating on a genetic-related basis 

was manifested previously when soldiers with the sickle cell trait were barred 

from being military pilots, even if they had flown previously without having 

negative symptoms.26 These soldiers felt that their dignity had been violated, 

particularly because there was only a slightly increased likelihood, if any, that 

those with this trait would develop more symptoms. 

There are numerous other examples in which genetic screening could 

also be used to try to reduce risks,27 such as screening out soldiers with 
New Biological Advances and Military Medical Ethics 15

certain genes who may be more vulnerable to heat effects if serving in desert 

environments.28 Key considerations in determining whether this kind of 

screening is justifiable are the magnitude and probability of harm to soldiers 

genetically at risk. Unless this harm is substantial and/or likely, the inherent 

violation of soldiers’ privacy and dignity would tend to preclude this screening 

from being ethically justifiable. 

A still more problematic potential use of screening is to exclude soldiers 

from specific roles on the basis of conditions that will affect them later in their 

lives. An example of such a condition is Huntington’s disease. Screening can 

determine that a person carries this gene and thus will, with some degree of 

certainty, be affected in the future. Such individuals could be excluded from 

certain military specialties. 

In summary, excluding soldiers on the basis of their genes violates their 

privacy and the principle of equality. Research into genetic screening must 

take these factors into account. However, the importance of the military 

mission should prevail if this discrimination was necessary to heighten the 

chance of victory. 

Preventive Measures against Biological and Chemical Weapons

Policy

During the first Gulf War (1990–1991), soldiers were required to take certain 

protective measures against possible biological and chemical weapons attack, 

even though these protective agents had not been fully tested for these 

purposes.29 The courts determined that such measures were permissible because 

there was a need to give absolute priority to saving the maximum number of 

soldiers’ lives and to support the military’s mission. It held specifically that 

under the circumstances then existing, soldiers could be vaccinated to protect 

them from chemical and biological agents even against their will because of 

the belief that Iraq would use weapons of mass destruction against American 

forces. After the war, it was discovered that Iraq did indeed have chemical and 

biological weapons and the delivery apparatuses, such as missiles, for them. 

The ethical argument in these instances is straightforward. While these 

protective agents may not have provided total protection from these types 

of weapons, and the enemy may not have even deployed them, requiring 

soldiers to get vaccinated against suspected threats was not only the best but 

also the only means of protecting U.S. troops in the Persian Gulf if Iraq chose 

to use this weaponry. 

In the future, there may be new threats and the need to balance the 

risks of potentially protective measures against these threats. These agents 
167 Bio-IInspired IInnovation and ovation and NNational SSecurity 

cannot be tested on humans to determine their actual efficacy because testing 

could seriously harm or even kill them.30 Furthermore, in the future it is 

possible that novel biological and chemical weapons will be developed at a 

pace that far outstrips a nation’s capacity to develop prophylactic vaccines or 

other protective measures in response to these new threats. In this case, the 

obligatory use of preventive measures might no longer be ethically justifiable.31

Because events and circumstances change often, vaccination policies 

should be continually reevaluated. The scientific conclusions regarding these 

agents should be made by those who are most knowledgeable, and the policy 

decisions should be made by persons who most understand the threats at 

stake. If the risks seem small, but the likelihood that an enemy would use 

this weaponry is great, the ethical choice is to require protection, just as the 

military requires soldiers to wear helmets. 

Honesty in Communication

In the first Gulf War, soldiers were initially told that they would have booster 

shots (in this case, three injections of the vaccine over a specific time frame) 

of the vaccine against botulism. When supplies later ran out, they were told 

that one dose of the botulinum toxoid vaccine would actually be sufficient in 

order for them to obtain protection against the toxin. Some soldiers felt angry 

and others afraid when they heard of this shift in immunization policy. This 

experience exemplifies the importance of the degree to which soldiers should 

be accurately informed and the importance of honest communication.

The military acknowledges and accepts the notion that information 

may be withheld from soldiers when necessary for the mission. Should 

soldiers be given information when such knowledge could result in their 

feeling unnecessarily angry or afraid? How this question should be answered 

is difficult to determine. What should be done, for example, if there is an 

attack using radiological weapons? What if the dosage soldiers receive will 

ultimately be fatal? If military physicians told soldiers that they had received 

a lethal dose of radiation, the possible effects could be quite different. Soldiers 

who knew they were going to die might feel that they had nothing to lose and 

fight harder. On the other hand, they might lose their will to continue to fight.

What should be done, then, if new biological or chemical weapons of 

known or suspect lethality are used?32 What if the presence of these weapons 

is detected on the battlefield but the prophylactics required to protect against 

these agents are unknown? What should military physicians say? Should they 

tell soldiers under these circumstances that they have been or may have been 

lethally affected? Or should they withhold this information, at least for a time, 

so that they would still fight? Soldiers implicitly agree, when volunteering to 

serve, to forego information and to undergo any other sacrifice, including loss 
New Biological Advances and Military Medical Ethics 17

of life, when necessary for the success of the mission. The military’s need for 

soldiers’ sacrifice underlies the justification of military physicians giving them 

protective agents such as vaccines against botulism without their consent. 

Protecting Others

Should military physicians offer the protective agents they would give to 

soldiers to prisoners of war (POWs) and detainees? These prisoners may also 

be at risk of being subjected to biological or chemical warfare. The Geneva 

Convention holds that since a POW is no longer a threat, he or she should 

be given equal treatment.33 Ethically, the same equity could be extended to 

apply to detainees. This would suggest that all protective measures offered to 

soldiers, and especially those that they are required to take, should be offered 

to POWs and detainees as well.34

The same question can be raised regarding civilians. For example, 

if Saddam Hussein had used biological weapons during the first Gulf War, 

civilians in Kuwait would have needed the same protection as our own soldiers, 

Allied soldiers, and POWs. Providing such protective measures, however, 

raises greater problems regarding adequate supplies. Unlike many countries, 

the United States has not agreed to the section in the Geneva Convention 

that would require it to provide civilians with the same medical supplies it 

must give its own soldiers and POWs.35 The U.S. refusal occurred because the 

United States believed that in some situations, it would be unable to provide 

the potentially vast amount of medical resources to soldiers, POWs, and 

civilians that equal treatment might require. 

Undoubtedly, as the war on terror and the wars in Afghanistan and 

Iraq continue, military physicians will face ethical dilemmas regarding the 

treatment of detainees and civilians if chemical or biological weapons are used. 

Conclusion

The increased risks and heightened concerns posed by technological advances 

and the changing nature of modern warfare have raised a number of ethical 

questions for the military physician. Indeed, the pace of biotechnological 

advances and their availability for use by lay persons have outstripped 

society’s ability to understand their full ethical implications. Prior to this new 

“age of biology,” moral priorities had been carefully worked out in regard to 

conflicts in military medicine.36 However, new advances in technology and 

the battlefield require that we reexamine traditional ethical assumptions, 

including principles of military medical triage, procedures for treating soldiers 

with combat fatigue, and grounds for providing soldiers with protection from 

biological and chemical warfare without their consent.
189 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Notes

1 E.G. Howe, “Dilemmas in Military Medical Ethics Since 9/11,” Kennedy Institute of Ethics 

Journal 13, no. 2 (2003), 175–188.

2 R.J. Ursano and D.R. Jones, “The Individual’s Versus the Organization’s Doctor? Value 

Conflict in Psychiatric Aeromedical Evacuation,” Aviation, Space, and Environmental 

Medicine 52, no. 11 (1981), 704–706.

3 U.S. Department of Defense, Emergency War Surgery, 1st rev. ed. (Washington, DC: 

Department of Defense, 1975).

4 T.E. Beam, “Medical Ethics on the Battlefield: The Crucible of Military Medical Ethics,” in 

Military Medical Ethics, vol. 2 (Washington, DC: Office of the Surgeon General, Department 

of the Army, 2003). 

5 E.G. Howe, “Mixed Agency in Military Medicine: Ethical Roles in Conflict,” in Military 

Medical Ethics, vol. 2. 

6 J.T. Janousek et al., “Mass Casualty Triage Knowledge of Military Medical Personnel,” 

Military Medicine 164, no. 5 (May 1999), 332–335; E.G. Howe, “Ethical Issues in Military 

Medicine: Mixed Agency,” in Principles and Practice of Military Forensic Psychiatry, ed. R.G. 

Lande and D.T. Armitage (Springfield, IL: Charles C. Thomas, 1997), 469–514.

7 M.C. Brickness, “The Evolution of Casualty Evacuation in the 20th Century (Part 5)—Into the 

Future,” Journal of the Royal Army Medical Corps 149, no. 4 (December 2003), 357–363.

8 R.F. Bellamy, “Conserving the Fighting Strength,” Military Medicine 153, no. 4 (1988), 

185–187; R.G. Malish, “The Medical Preparation of a Special Forces Company for Pilot 

Recovery,” Military Medicine 164, no. 12 (December 1999), 881–884.

9 R.W. Hoyt et al., “Combat Medical Informatics: Present and Future,” Proceedings of the 

American Medical Informatics Association Symposium (2002), 335–339.

10 M. Pueschel, “Pilot FBI Unit Links Medicine and Intelligence in Combating Bioterrorism,” 

U.S. Medicine, May 14, 2004.

11 E.G. Howe, “Ethical Issues Regarding Mixed Agency of Military Physicians,” Social Science 

and Medicine 23, no. 8 (1986), 803–815.

12 H.T. Engelhardt, “Fear of Flying: The Psychiatrist’s Role in War,” Hastings Century Reprint 6, 

no. 1 (1976), 21.

13 Encyclopedia Britannica Online, “Combat Fatigue,” 2009, available at 

www.britannica.com/EBchecked/topic/127295/combat-fatigue.

14 S. Hazen and C. Llewellyn, “Battle Fatigue Identification and Management for Military 

Medical Students,” Military Medicine 156, no. 6 (June 1991), 263–267.

15 J. Pearn, “Traumatic Stress Disorders: A Classification with Implications for Prevention 

and Management,” Military Medicine 165, no. 6 (June 2000), 434–440; S.M. Gerardi, “The 

Management of Battle-Fatigued Soldiers: An Occupational Therapy Model,” Military 

Medicine 16, no. 8 (August 1996), 483–438.

16 A. Fontana, R. Rosenheck, and T. Horvath, “Social Support and Psychopathy in the War 

Zone,” Journal of Nervous and Mental Disease 185, no. 11 (November 1997), 675–681; F. 

Armfield, “Preventing Post-Traumatic Stress Disorder Resulting From Military Operations,” 

Military Medicine 159, no. 12 (December 1994), 739–746.

17 C.W. Hogue et al., “Combat Duty in Iraq and Afghanistan, Mental Health Problems, and 

Barriers to Care,” New England Journal of Medicine 251, no. 1 (July 1, 2004), 13–22. 

18 D.W. Foy et al., “Trauma Focus Group Therapy for Combat-Related PTSD: An Update,” 

Journal of Clinical Psychology 58, no. 8 (August 2002), 907–918; Z. Kaplan, I. Iancu, and F. 
New Biological Advances and Military Medical Ethics 19

Bodner, “A Review of Psychological Debriefing After Extreme Stress,” Psychiatric Services 52, 

no. 6 (June 2001), 824–827.

19 G. Miller, “Learning to Forget,” Science 304, no. 5667 (April 2004), 4–36.

20 MedicineNet.com, “Medications and Drugs: Propranolol,” available at 

www.medicinenet.com/propranolol-oral/article.htm.

21 D. Grossman, “On Killing II: The Psychological Cost of Learning,” International Journal of 

Emergency Mental Health 3, no. 3 (Summer 2001), 137–144.

22 T.E. Beam and E.G. Howe, “A Look Toward the Future,” in Military Medical Ethics, vol. 2. 

23 K.C. Koenen et al., “A Twin Registry Study of Familial and Individual Risk Factors for 

Trauma Exposure and Posttraumatic Stress Disorder,” Journal of Nervous Mental Disorders

190, no. 4 (April 2002), 209–218; D.S. McLeod et al., “Genetic and Environmental Influences 

on the Relationship Among Combat Exposure, Posttraumatic Stress Disorder Symptoms, 

and Alcohol Use,” Journal of Traumatic Stress 14, no. 2 (April 2001), 259–275.

24 PhysOrg.com, “Gene Increases Susceptibility to Post-Traumatic Stress, Researchers Find,” 

available at www.physorg.com/news176408321.html.

25 N.A. Lewis, “Two Marines Who Refused to Comply with Genetic-Testing Order Face 

Court-Martial,” The New York Times, April 13, 1996, A7.

26 E.G. Howe, J.A. Kark, and D.G. Wright, “Studying Sickle Cell Trait in Healthy Army 

Recruits: Should the Research Be Done?” Clinical Research 31, no. 2 (1983), 119–125.

27 E.H. Hanson et al., “An Aviator with Cardiomyopathy and Genetic Susceptibility to 

Hereditary Hemochromatosis: A Case Report,” Aviation, Space, and Environmental Medicine

72, no. 10 (October 2001), 924–927; W.C. Fox and W. Lockette, “Unexpected Syncope and 

Death During Intense Physical Training: Evolving Role of Molecular Genetics,” Aviation, 

Space, and Environmental Medicine 74, no. 12 (December 2003), 1223–1230.

28 D. Woods et al., “Elite Swimmers and the D allele of the ACE I/D Polymorphism,” Human 

Genetics 108, no. 3 (March 2001), 230–232.

29 E.G. Howe and E.D. Martin, “Treating the Troops/The Use of Investigational Drugs Without 

Obtaining Servicepersons’ Consent,” Hastings Century Reprint 21, no. 20 (1991), 21–24.

30 Howe, “Mixed Agency in Military Medicine,” 337.

31 Ibid., 338.

32 A.L. Brooks, “Biomarkers of Exposure and Dose: State of the Art,” Radiation Protection 

Dosimetry 97, no. 1 (2001), 39–46. 

33 “Geneva Conventions of 1949,” in Human Rights Documents: Compilations of Documents 

Pertaining to Human Rights (Washington, DC: U.S. Government Printing Office, 1983).

34 J.A. Singh, “American Physicians and Dual Loyalty Obligations in the ‘War on Terror,’” BMC 

Medical Ethics 4, no. 4 (2003). 

35 W.H. Parks, Memorandum for the Surgeon General, Article 10, 1977; Protocols Additional 

to the Geneva Convention, August 12, 1949.

36 E.M. Spiers, “The Use of the Dum-Dum Bullet in Colonial Warfare,” Journal of Imperial 

Commonwealth History 4 (1975), 3–14.

21

S

ince the tragedies of September 11, 2001, and the mailings later that 

year of letters containing anthrax that resulted in the deaths of five 

people, the prospect of a biological weapons (BW) attack against the 

United States or its interests overseas has come to be considered, along with 

the possibility of a nuclear attack, as a paramount challenge to U.S. national 

security. Since that time, the United States has pursued a wide-ranging agenda 

both at home and abroad to address the BW risk. To that end, it has spent tens 

of billions of dollars to prevent and protect itself against such a contingency. 

Despite all the attention the issue of biological weapons has received, not 

everyone agrees that it deserves to be made such a high priority. Indeed, since 

perceptions of heightened biological-related security risks came to the fore in 

the mid- to late 1990s, a debate has raged over the extent to which biological 

weapons—whether used by states or terrorists—represent a significant national 

security challenge. The public debate has often swung like a pendulum between 

hype and complacency, and at times it has been hard to hear the voices calling 

for an approach that provides calibrated responses to this multifaceted problem 

based on a sophisticated understanding of all its dimensions. The challenge of 

getting the approach to biological weapons “right” is exacerbated by the rapidly 

changing context within which the BW risk is shaped and manifested. Major 

developments such as rapid advances in relevant sciences and related technology, 

sweeping trends such as globalization, and shifts in the style, location, and form of 

conflict in today’s world are all fostering a strategic environment far different from 

the one in which modern concerns about BW emerged almost a century ago.

An appropriate, cost-effective, and, most importantly, successful response 

to meeting the BW challenge demands an appreciation of its complexity and 

chapter 3

The life sciences, security, and the

challenge of biological weapons: 

an overview

Michael Moodie
223 Bio-IInspired IInnovation and ovation and NNational SSecurity 

an awareness of those changes that will shape its form and expression in the 

future. It will call for a policy and strategy that are as multifaceted as the issue 

is multidimensional. It will also require the active involvement of a wider 

range of players—both government and nongovernment—than has been the 

case traditionally in addressing national security issues. Clearly, a significant 

challenge lies ahead.

Biological Weapons: Background

Biological weapons can be defined as living organisms or their inanimate 

byproducts that are used as weapons against humans, animals, and plants. They 

can take several forms including bacteria, or small, single-celled organisms; 

viruses, or organisms requiring living cells in which to replicate; rickettsia, or 

microorganisms with characteristics similar to both bacteria and viruses; and 

toxins, or poisonous chemical substances produced by living things. Examples 

of traditional biological weapons that fall into these categories include the 

bacteria anthrax, brucellosis, and plague; the smallpox virus as well as viruses 

that produce dengue fever or hemorrhagic fevers such as Ebola and Marburg; 

and rickettsia such as Q fever or Rocky Mountain spotted fever. Examples of 

toxins include snake venom, ricin (a byproduct of processing castor beans), 

and saxitoxin, a poison produced by shellfish.

Biological weapons have their roots in antiquity.1 Most discussions 

of biological weapons, however, begin with the 1346 siege of Kaffa (now 

Feodosiya) on the Crimean coast during which Tatars catapulted plagueinfested bodies into the city. Other early uses included the distribution of 

plague-infested blankets by the British among Native Americans during 

the French and Indian War, and the possible spreading by British troops of 

smallpox in Boston following their evacuation of the city during the American 

Revolution.2 In more modern times, the Germans initiated sabotage programs 

using BW in World War I, such as the use of glanders in an attempt to sicken 

U.S. Cavalry horses that were to be shipped to Europe.3 Virtually all of the 

major participants in World War II had active BW programs, although Japan 

is the only major power to have attempted to use them. The infamous Unit 731 

conducted a number of experiments and attacks, for example, in Manchuria 

during Japan’s occupation of that territory in the late 1930s.4

The 50 years following the end of World War II witnessed virtually no 

BW use, although a number of states pursued BW programs in the decades 

following the war. The search for effective offensive biological weapons was 

supposed to end, however, after President Richard Nixon announced the 

unilateral termination of the U.S. offensive BW program in 1969. President 

Nixon’s decision also prompted negotiations with the Soviet Union and 
life sciences, security, and biological weapons 23

other countries that eventually produced the Biological and Toxin Weapons 

Convention (BWC), which was concluded in 1972 and entered into force in 

1975. The BWC was a historic milestone because it was the first arms control 

agreement in history to ban totally an entire class of weapons, making it illegal 

to develop, produce, otherwise acquire, store, deploy, or transfer them.5

The BWC’s entry into force did not fully eliminate concerns about the 

weapons, however, particularly as the treaty had no provisions to verify a state 

party’s compliance with its treaty obligations or to investigate allegations that 

states were in noncompliance. For the next two decades, the United States 

continued to allege that at various times, between a dozen and two dozen 

countries were violating their treaty commitments and pursuing offensive 

BW programs.6

Washington was especially concerned about illicit BW activities in the 

Soviet Union. Although it had been concerned about the Soviet program from 

the time of the BWC’s 1975 entry into force, U.S. allegations became much 

more public following an anthrax outbreak in the Siberian city of Sverdlovsk 

in 1979, which Washington claimed originated in an illegal BW research 

facility but which Soviet authorities dismissed as the product of people eating 

tainted meat. U.S. concerns intensified substantially following the defection to 

Britain in the late 1980s of a Soviet scientist who had been deeply involved in 

the illegal program. Vladimir Pasechnik provided significant details about the 

so-called Biopreparat program, which had been created in the Soviet Union’s 

civil sector shortly after Moscow signed the BWC as a parallel effort to an 

existing military program. Biopreparat, which was funded by the defense 

ministry but which operated under the auspices of the Main Administration 

of Microbiology Industry and had close ties to the health and agriculture 

ministries, involved hundreds of research facilities and production plants, 

employed tens of thousands of people, and operated on a budget of 100 to 

200 billion rubles per year.7 Western intelligence services knew nothing about 

it. It was not until Pasechnik’s defection that they began to appreciate the 

enormity of the Soviet effort. As one British report noted, “The information 

was stunning: a whole ministry exposed; billions of rubles spent; a complete 

organization shown to be a front; and there was the clear involvement of 

Gorbachev, this friend of the West. It just went on and on.”8 It was the defection 

of Pasechnik that set in motion major U.S. and U.K. efforts to bring the illegal 

Soviet effort to a halt, including meetings “at the highest levels.” Following a 

public accusation by the United States and Britain of Soviet noncompliance 

at the 1991 Third BWC Review Conference, Boris Yeltsin, who had become 

President of Russia following the collapse of the Soviet Union, acknowledged 

in April 1992 that the claims about the illegal Soviet program were correct and 

ordered the program to be shut down.9
245 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Apprehensions about BW were reinforced during this same general 

time period by developments in Iraq. After Operation Desert Storm reversed 

the Iraqi invasion of Kuwait in 1991, discoveries by the United Nations 

Special Commission on Iraq were especially distressing. In particular, Iraq 

was discovered to have had an extensive offensive BW program on the eve 

of Desert Storm. The program included research and development (R&D) 

on a wide spectrum of agents, large-scale weaponization of botulinum 

toxin, anthrax, and the carcinogen aflatoxin, and potential use of a variety 

of delivery systems including aerial bombs and al-Hussein missiles. Several 

facilities, some of which were also engaged in civilian efforts, were involved 

in the program. Many Iraqi BW scientists were found to have received their 

scientific training at universities and other facilities in Europe and the United 

States. What was never made clear, however, was Iraq’s concept of operations 

for use of its BW or the conditions under which such weapons would be used. 

A third major development in this period that moved biological 

weapons up on the national security agenda even before 9/11 and the 

“Amerithrax” letters was the emergence of terrorist interest in BW capabilities. 

Most notable in this regard were the activities of the Aum Shinrikyo, the 

Japanese cult responsible for the March 1995 sarin chemical weapons attacks 

in the Tokyo subway. Following that attack, investigations revealed that 

the group’s activities were not limited to production and use of chemical 

weapons; indeed, biological weapons may have been their weapon of choice. 

The Aum performed research, for example, on both anthrax and botulinum 

toxin, and reportedly it attempted to conduct at least nine separate attacks 

against both Japanese targets and U.S. military bases in Japan, all of which 

failed. Fortunately, the cult had acquired an attenuated strain of anthrax that 

rendered it useless. Reports also indicated that the Aum tried unsuccessfully 

to secure a sample of Ebola under the guise of sending a “mercy mission” to 

what was then Zaire.10

The revelations regarding Aum Shinrikyo prompted attention to other 

instances in which groups rather than states had tried to use biological materials, 

including in the United States. One such case was the use in 1986 of salmonella 

on restaurant salad bars in The Dalles, Oregon, by the Rajneeshi cult in order 

to influence the outcome of a local election and referendum. Another was the 

attempted use of ricin by the Minnesota Patriots Council, an American militia 

group, to kill jurists who were engaged in legal proceedings against them.11

This coming to light of nonstate actor interest in BW heightened 

perceptions that such capabilities were insufficiently appreciated as a risk to 

national security. The fact that the Japanese subway attack and the bombing 

of the Murrah Federal Building in Oklahoma City were juxtaposed closely 

in time fostered the sense among both policymakers and the public that 
life sciences, security, and biological weapons 25

the United States was now vulnerable to terrorist attacks, that those attacks 

could include unconventional weapons, and that the United States was not 

prepared to handle such attacks or their consequences. Efforts to address these 

unconventional threats, then, including BW, began in the mid-1990s, before 

the events of 9/11 and the autumn of 2001. The challenges posed by biological 

weapons have been at or near the top of the national security agenda ever since.

The Current Challenge

Today’s BW challenge has two dimensions, and debate continues over which 

one is the more important. To some, the major risk continues to emanate 

from states. For the last two decades, concern has existed that up to perhaps 

two dozen countries have been pursuing offensive BW programs. Countries 

that have admitted to programs include the United States, United Kingdom, 

France, the Soviet Union, South Africa, and Iraq. Other countries with past 

or current programs include Iran, Syria, Israel, China, North Korea, and 

Taiwan. Little information is available in the public record about any of their 

programs, with the exception of those that have admitted to past offensive 

BW efforts (the United States, United Kingdom, and France).

For much of the Cold War, the United States indicated that it believed 

that as many as a dozen or more states were engaged in illegal BW efforts. 

In recent years, however, it has moved to a somewhat different formulation. 

At the Sixth BWC Review Conference in late 2006, for example, John Rood, 

Assistant Secretary of State for International Security and Nonproliferation, 

alleged only that three states—North Korea, Iran, and Syria—were engaged 

in activities in violation of the BWC.12 Although the most recent State 

Department assessment of nations’ compliance with their arms control 

obligations (published in 2005) noted that the U.S. Government had “concerns 

regarding the activities of other countries,” the report itself focused only on 

alleged noncompliance with the BWC by Russia, China, and Cuba, in addition 

to the three countries mentioned by Secretary Rood.13

Those who argue that state-based BW programs should be the primary 

concern do so because they see states as the entities with the technical and 

financial resources to develop such capabilities. There are other reasons, 

however, why states might be interested in these weapons: they are relatively 

simple and cheap to produce, especially compared to either nuclear weapons 

or large quantities of chemical weapons; the necessary agents and equipment 

are widely available because they are also used in legitimate scientific and 

commercial enterprises; the entry costs for beginning a program are relatively 

low; covert programs are reasonably easy to conceal because neither a large 

space nor specialized equipment is needed to produce a significant amount 
267 Bio-IInspired IInnovation and ovation and NNational SSecurity 

of agent; and gains in such scientific and technological fields as genetic 

engineering and biotechnology are diminishing the barriers that traditionally 

have made BW development, production, and weaponization difficult.

A further reason that states might be interested in biological weapons 

is that, used in the right conditions, they could be strategic in their impact. A 

well-regarded study by the Office of Technology Assessment in 1993 estimated, 

for example, that, used under ideal meteorological conditions (that is, a clear, 

calm night), an aerosol version of anthrax could kill between 1 million and 3 

million people, a total equivalent to the impact of a small nuclear weapon.14

Some of these attractions are also of concern to those who argue that 

the more severe risks related to BW stem from their potential use by terrorists 

rather than states. As noted, the autumn 2001 “Amerithrax” letters represent 

the latest in a series of events in which nonstate actors have sought to exploit 

biological weapons. Moreover, they highlighted a few important points that 

perhaps had not been well understood until those attacks. First, biological 

weapons do not have to produce catastrophic levels of casualties in order to 

have a mass effect. Although only five people died, the impact on the public’s 

psyche was enormous, exemplified by the fear people had of retrieving and 

opening their daily mail. Underscoring the disruption that BW can cause 

was the fact that because of necessary decontamination procedures, it took 

months for Congressional offices to return to their normal operations, and the 

Brentwood postal facility did not reopen for more than a year. Second, because 

of the nature of biological weapons, it will be difficult to attribute an attack. 

The question of technical skill is important because some analysts 

downplay, if not dismiss, the risks of terrorist BW use in the belief that 

terrorist groups have neither the inclination nor the capability to conduct 

such attacks.15 This may, however, be changing. It is clear, for example, that 

al Qaeda has developed an elaborate rationale justifying the use of chemical, 

biological, nuclear, or radiological weapons, and materials found in caves in 

Afghanistan document the group’s interest in and pursuit of such capabilities. 

Heavy emphasis on the technical capabilities of a terrorist group 

skews to some extent the analysis of potential terrorist BW use. Such singlefactor analyses oversimplify the issues and imply a precision in the ability to 

identify bioterrorism risks that does not exist. The risk of biological terrorism 

is in fact the product of a complex interaction among several categories of 

factors—actors, agents, targets, and operational considerations—each of 

which includes many variables. Taken together, these variables produce 

a matrix that offers a large set of possible combinations and permutations, 

each of which constitutes a pathway to a particular outcome. Some of these 

pathways produce catastrophic consequences; others result in significant 

casualties; still others yield no consequences at all. As a terrorist seeks to 
life sciences, security, and biological weapons 27

achieve the more demanding goals of higher casualties or more widespread 

disruption, fewer pathways are available to reach them, and those that remain 

are more difficult. The degree of risk declines, therefore, as the level of desired 

casualties/disruption increases, insofar as it becomes less likely. This is not to 

say, however, that the degree of risk is zero, or even negligible.

Looking to the Future

The key question regarding the prospects of both state and terrorist BW use 

is whether the future will resemble the past. Will the factors that have shaped 

the BW challenge for the last 50 years remain the dominant influences, or are 

changes under way that could reshape it?

Three factors are converging that probably will promote considerable 

change in both the security landscape and the form that the biological challenge 

is likely to take in the future. Adapting to those changes represents perhaps 

the most significant demand confronting policymakers with responsibility for 

meeting the biological challenge.

Rapidly Advancing Science and Technology

The speed at which the science and technology related to the biological 

challenge are moving is hard to exaggerate; indeed, it is happening at a rate 

faster than the well-known Moore’s Law in information technology.16 The 

rate at which the life sciences and its associated technologies are progressing 

and knowledge of the processes of life at the molecular level is advancing has 

led some commentators to suggest that the life sciences are undergoing a 

profound “revolution.” They contend that the 21st century could well be “the 

century of biology.” The expansion of knowledge in the life sciences, however, 

is not only rapid, but it is also deep, broad in that it encompasses a wide range 

of disciplines, and widely available.

Moreover, the knowledge that is being gained is being put to use; that 

is, it is not just remaining in the realm of basic science. More and more of that 

knowledge is applied in forms that are increasingly making it a commodity. 

This “commoditization” has several significant implications. Most importantly, 

it demonstrates that the civilian sector—both science and business—is the key 

driver in pushing this scientific and technological advance. The corollary is 

that governments are less and less in control of scientific and technological 

progress and “spinning on” those commercially driven developments into 

their products, including in the security realm. 

An Expanding Risk Spectrum

The second major factor shaping the future perspective of the biological 
289 Bio-IInspired IInnovation and ovation and NNational SSecurity 

challenge is the growing practice of placing the biological weapons problem 

along a wider biological risk spectrum (see figure 3–1).

At one end of this risk spectrum stand naturally occurring developments 

such as chronic disease and emerging or reemerging infectious diseases. 

The spectrum then runs through human-induced developments, including 

accident or misadventure (the unintended consequences of otherwise benign 

activities), to the other end at which stands deliberate misuse, whether for 

political power, ideology, or greed. 

The two elements of this risk spectrum that have received the greatest 

attention in recent years are naturally occurring infectious diseases and 

deliberate misuse. Over the last few years, the relationship between these two 

issues has undergone a distinct change. Following 9/11, bioterrorism was the 

overwhelming focus. The argument was made that if effective bioterrorism 

preparations could be developed, they would also have utility in dealing with 

a naturally occurring disease outbreak. Recently, however, perhaps prompted 

by the SARS experience, the threat of an influenza pandemic such as the recent 

H1N1 pandemic, and the continuing scourge of HIV/AIDS, the priority given 

to these two elements has been completely reversed. Today, more attention 

seems to be given to infectious disease; deliberate misuse in such forms as 

bioterrorism has become the “lesser included case.” Some analysts might 

suggest that this assertion is an exaggeration and that health and bioterrorism 

threats are addressed at the same level. There is no question that these issues 

are often considered together because many of the requirements for dealing 

with either contingency are the same. 

This shifting priority is not just an interesting intellectual point. It has 

repercussions for policy priorities and the allocation of limited resources, 

particularly the balance of investment in efforts to address infectious disease 

and those that are directed toward more narrow bioterrorism and biodefense 

concerns. Moreover, the relative priority given to each of these components 

along this spectrum could be an issue of some disagreement between the United 

States and those it wants and needs to work with in combating proliferation. FIGURE 3–1. THE BIOLOGICAL RISK SPECTRUM

Chronic Disease Accident Deliberate Misuse

Infectious Disease/

Emerging Infectious Disease

Misadventure

figure 3–1. the biological risk spectrum
life sciences, security, and biological weapons 29

At the same time, it is important to appreciate this spectrum because, 

in fact, segments are not readily divided but blend into one another. This has 

important implications for policy because measures designed to deal with 

one aspect of the problem will have important implications—and sometimes 

important tradeoffs—for others. Development of medical treatments for 

infectious disease or biological attacks is only the most obvious of many 

potential examples.

Globalization

The third key factor promoting the complexity of the future biological 

challenge is globalization. It is a trend marked by multiplying, deepening, 

intensifying, accelerating, and more complex interactions, transactions, and 

interrelationships among a growing number of players on a worldwide scale. 

It is further characterized by the exploitation of the information revolution, 

innovation, and an increasingly prominent role of nonstate actors. 

The importance of globalization for the biological challenge is difficult 

to underestimate. First, globalization has fostered a rapid diffusion of the 

life sciences and related technologies across the world, driven largely by the 

creation of small- to medium-sized biotechnology firms. 

Biotechnology growth, however, is not occurring only in the developed 

world. China and India in particular have been identified as developing 

countries that are likely to be biotechnology leaders in years to come. Many 

other countries outside the “developed world,” including Singapore, Malaysia, 

South Korea, Cuba, Brazil, and South Africa, are also investing heavily in 

biotechnology as a driver of their future economic growth. As a result of these 

developments, today a critical scientific or commercial breakthrough could 

come from almost anywhere in the world.

Second, globalization has transformed patterns of industrial production 

at both national and international levels, including in life sciences industries. 

Together with new production processes, agile manufacturing, miniaturization, 

lower technology costs, and increased productivity of a global talent pool, 

these trends are restructuring business enterprises in fundamental ways. 

Third, globalization has spurred the emergence of nongovernmental 

entities operating on an international basis and in greater numbers. More and 

more, these new and increasingly empowered nonstate actors are able to express 

their singular interests through the tools and channels globalization provides, 

allowing them to operate beyond the control of any single government.The 

result is that even relatively weak actors can have disproportionate impact 

both positively and negatively. 

This changing scientific and technological landscape has critical 

implications for security. The accelerating pace of discovery in the life sciences 
301 Bio-IInspired IInnovation and ovation and NNational SSecurity 

and its widespread diffusion around the globe have fundamentally altered the 

threat spectrum, which is now exceptionally broad and continually evolving: 

• The number of regions of the world where people can be found with the 

requisite ability to exploit knowledge that can do harm has obviously 

grown significantly. That people might know how to apply this knowledge 

for malign purposes does not, of course, mean automatically that they will. 

But an increase in the number of people with the requisite knowledge does 

imply an increase in the burden of potential risk that must be managed.

• These trends have created lower entry costs for joining the proliferation 

process as well as the potential to enter that process at a higher point on 

the learning curve. 

• The new structures of commercial and scientific enterprises will provide 

a wider range and more diverse array of legitimate dual-use covers for 

malign activities. They could also create multiple, parallel, possibly 

nontraditional pathways to the development of critical biological or 

chemical weapons–related capabilities. 

• These trends will make it even harder to determine noncompliance 

with global norms, leading to uncertain enforcement and response at 

both the international and national levels. 

In such an environment, serious problems exist with respect to governments’ 

abilities to meet the challenges that lie ahead. Government bureaucracies are 

notoriously slow to adapt, as are international institutions. How, then, can 

governments and international institutions keep pace with the speed at which 

science and technology are moving, especially in terms of understanding both 

the negative and positive implications of those changes for security? 

Treaty regimes could be especially affected. The BWC, for example, is now 

almost 35 years old, and the need to adapt it to this new set of circumstances 

is perhaps the single greatest challenge confronting BWC states parties. The 

inability to do so will have an extremely corrosive effect. But adaptation will be 

unsuccessful if those responsible fall back on business as usual.

What Constitutes “Proliferation”?

The traditional view of proliferation is that a government, for a variety of 

reasons, makes a commitment to achieve a nuclear, chemical, or biological 

weapons capability, and then moves through a series of programmatic steps 

to the eventual deployment of full military systems. In light of the trends 

discussed above, however, the process of proliferation is moving away from 

this classic paradigm for several reasons.

First, the decision to seek a BW capability is not likely to be primarily 

driven by the perceived efforts of an adversary, but propelled by ongoing global 
life sciences, security, and biological weapons 31

advances in microbiology, biomedical research, and biotechnology. Rather, as 

a report by the Institute of Medicine of the U.S. National Academies of Science 

put it, “Tomorrow’s world of proliferating threats . . . may be quite different 

from the twentieth-century agents and indeed may not even exist at this time.”17

Second, if scientific and technological advances are becoming the 

drivers of actors’ interest in BW capabilities, the process of proliferation may 

become increasingly characterized by a move down a path toward those 

capabilities without necessarily a commitment to the deployment of a specific 

weapons system or the implementation of a well-developed concept of use. 

Advancing science and technology make “dabbling” much more possible, and 

they increase the potential for the creation of a “warm capabilities base” or a 

latent capability on which an actor could rapidly build if perceived changes in 

the security environment or other factors propel it to do so.

Third, the shift in technological innovation from the military to the civilian 

sector suggests that much of the R&D phase of a BW program need not be 

conducted in a dedicated military facility or even in the context of an offensive 

military program. Since many questions relating to development and performance 

of agents and delivery devices are the same for civilian and military applications, 

understanding of fundamentals can be achieved without engaging in activities 

that would be considered violations of international treaty obligations. Drug 

companies, for example, for perfectly legitimate reasons are strenuously exploring 

improvements in aerosol technology, which bear directly on what the single most 

difficult technical challenge is in developing an effective weapons capability. 

Fourth, proliferation is not just the province of governments. The problem 

now encompasses a wider range of potential actors. It is not only the number of 

possible participants in the process of proliferation, however, that has changed, 

but also the nature of their interaction. Traditionally, proliferation was seen as 

the product of a hierarchical, top-down process that began with a government’s 

commitment to seek a given capability. Today, the process is much more free 

form. The operation of formal or informal networks is especially important. 

The emergence of networks is one of the key factors that have empowered the 

wide array of players now active in the security landscape, and it has facilitated 

the flow and exchange of not only critical materials and equipment, but also 

the increasingly important element of scientific and technological knowledge 

that now resides at the core of the proliferation process.

Proliferation today, then, is not so much about classic military programs. 

Rather, it is about the security implications of key trends, including:

• expansion of knowledge and the capability provided by technology

• growth in the number of legitimate applications of advancing life sciences 

and technology
323 Bio-IInspired IInnovation and ovation and NNational SSecurity 

• the increase in the number and variety of players able to exploit that 

knowledge base

• the geographic expansion of regions of the world where such expertise 

can be found.18

The argument is not that latent capabilities become realized with no 

effort, but that the process of that realization will take a very different form 

than the traditional notion of proliferation and that the time needed for such 

a transformation will be shorter and shorter. Moreover, the issue is about an 

interaction between intent and capability that is much less straightforward 

than the standard proliferation model suggests. 

New Responses for an Evolving Challenge

The changing nature of the biological challenge demands as much new 

thinking about the response as it does about the nature of the problem. The 

first requirement is a change in thinking. Those who have responsibility for 

meeting the biological challenge must jettison the comfortable reliance on old 

concepts and past practice to address the future. 

The United States has already demonstrated such a conceptual shift and 

has provided considerable leadership in promoting new measures that seek to 

respond to the changes mentioned above. For some people, U.S. efforts in this 

regard reflect its discarding of traditional approaches, and multilateralism in 

particular, in favor of either a “go-it-alone” model or efforts of “coalitions of the 

willing.” In particular, they lament the U.S. rejection of the draft protocol to the 

BWC designed to enhance confidence in compliance with the treaty. British 

analyst Jez Littlewood points out, however, that “[a]ny approach to dealing 

with BW that is based only on the BWC or, alternatively, based on anything 

but the BWC is politically simplistic and fails to grasp the scale of the BW 

problem.”19 Rather, what is needed is a strategy that combines old and new into 

a policy framework that is as multidimensional as the problem is multifaceted 

and that can accommodate contributions from the full range of players—

government and nongovernment—that will be needed to be effective.

Nor is the issue one of choice between multilateral and unilateral 

approaches. Posing the issue in such terms is overly simplistic; it is not an 

“either/or” choice. But the answer of “both” multilateralism and unilateralism 

is also inadequate, although both national and multinational efforts are, 

indeed, required. So, too, are local efforts within countries as well as regional 

measures involving several neighboring states or ad hoc arrangements among 

geographically disparate states.20 Again, some of these measures, such as regional 

cooperative arrangements to counter proliferation (in the former Soviet Union, 
life sciences, security, and biological weapons 33

for example) are already in place, at least in a basic form. But more is needed. 

Finally, governments cannot do the job of managing biological risks 

alone. As has already been suggested, governments will find it hard to keep 

up. To do so, they must benefit from the inputs of those “working at the 

coal face” of scientific and technological change every day. This means in 

the first instance that governments must reach out to the academic research 

community and life sciences industries. Moreover, many of the assets on which 

governments must rely for managing biological risks lie outside government 

control, in the private sector. 

Managing the risks associated with developments in the life sciences, 

therefore, will require a range of new partners, especially in the private sector. 

However, creating enduring partnerships also demands new thinking and 

new approaches on the part of all of those who must be engaged.

The foundation for effectively promoting new partnerships is a shared 

conceptual approach to the problem among all the stakeholders, on both the 

national and international level. This is not to argue for a unanimously agreed 

threat or risk assessment. It is unlikely that a consensus could or ever will be 

achieved. But neither is it necessary. What is important is finding enough 

common ground to create sufficient shared space for working together. 

Developing that common ground might begin with agreement on the 

following assumptions: 

• First, “biological threats to security” do not represent problems to 

be solved but rather risks to be managed. Work in the life sciences 

should and will continue for important legitimate reasons. This means, 

however, that the potential for misuse of those sciences remains a 

permanent reality. The challenge inherent in managing the risks of 

that misuse—whether by states or nonstate actors—is not to prevent 

international actors from acquiring the capabilities to exploit biology 

for malign purposes. That is not possible. Rather, the challenge is, as 

British Ministry of Defence official Paul Schulte put it, “to keep it out of 

their behavioral repertoires.” 

• Second, even if it cannot be totally eliminated, the risk of deliberate 

misuse can be reduced. But risk reduction is a multifaceted, complex 

challenge that includes deterrence, norm building, prevention, 

defense, preparedness, and consequence management, mitigation, and 

amelioration. No single instrument will be sufficient. 

• Third, resources to meet the biological challenge are not endless, even 

if many countries are involved. In order to maximize the impact of 

limited resources (in terms of time, money, and people), smart choices 

must be made.
345 Bio-IInspired IInnovation and ovation and NNational SSecurity 

• Finally, the task of dealing effectively with the biological challenge 

cannot be met by trying to predict precisely what form an attack using 

biological agents will take. Rather, the objective must be preparedness 

for as wide a range of plausible contingencies as possible. That can 

only be accomplished if a country has a robust set of critical response 

capabilities that are integrated into a genuinely strategic approach that 

stresses flexibility and adaptability. 

Developing those capabilities is not easy. It entails identifying 

requirements, establishing criteria to determine the appropriate level of 

capabilities to meet those requirements, balancing a wide set of competing 

interests, and involving the right set of players. One set of required capabilities 

that emphasizes prevention includes measures in such critical areas as law 

enforcement, intelligence, pathogen security, export controls, and cooperative 

threat reduction. A second set of requirements relates to preparedness and 

includes such elements as effective disease surveillance and reporting, health 

monitoring, good epidemiology, robust laboratory-based analysis, appropriate 

diagnostics and medical countermeasures, and sufficient medical stockpiles, 

among others. Both sets of capabilities must be supported by a dynamic R&D 

agenda and facilitated by effective communications strategies for policymakers 

and responders as well as for the general public. Finally, a capabilities-based 

strategy should be implemented in a context of international cooperation. 

Creating New Partnerships

These demands will be met successfully only if all of the critical stakeholders 

are involved and their cooperation is fully integrated. In particular, strong 

partnerships are vital between government and the private sector. Past 

approaches to dealing with the biological challenge failed to generate badly 

needed inputs from these important players. The life sciences communities, 

in particular, were not well integrated, despite the fact that they stand at the 

cutting edge of both the remarkable scientific advances and their applications 

that are shaping the environment within which the biological challenge must 

be addressed. 

Those involved in life sciences research and commerce emphasize their 

enormous contributions to improving the quality of life for people around the 

world. They are right to do so. But what has been missing from their thinking 

is recognition of their role and responsibility in helping to manage the risks of 

misuse of the science and technology with which they are involved. 

The attitudes of those working in the life sciences contrast sharply 

with the nuclear community. From the beginning of the nuclear age, with 

the active participation of Albert Einstein himself, physicists understood that 
life sciences, security, and biological weapons 35

they had to not only think about the negative implications of atomic power, 

but also to participate actively in managing the risks they had helped to create. 

That recognition has been lacking in life sciences communities. Their singleminded focus on the good they are trying to do for humanity or on scientific 

discovery for its own sake has too often blinded life scientists to the risks that 

stand alongside the benefits they seek. At best, security issues have been kept 

at arm’s length. 

Such an attitude is an unaffordable luxury. As the drivers of critical 

science and technology, industry and the academic scientific community 

must understand their stakes in the challenge and be fully integrated into the 

response. The direct contribution that this community can make to dealing 

with the problem is obvious. It should be the source of the technical tools 

that must be deployed to help manage biological risks, including sensors for 

detection and identification, new medical treatments, and improvements in 

passive and active protective gear. 

The indirect contribution of the life sciences community, however, is 

also crucial. Even scientists and companies that have no direct relationship 

to the security sector engage in activities with risks attached. Insufficient 

safety and security measures at laboratories and other facilities pose clear and 

obvious risks. But what about risks that are not so obvious? A device for the 

application of medical treatments without the use of needles—for example, 

involving absorption of a drug through the skin, or a flu vaccine in an aerosol 

form—could be of great medical value. But in some contexts, such devices 

might also be useful for terrorists. This does not mean that these beneficial 

products should not be made. But they should go forward with the relevant 

communities being fully aware of the risks that might be involved. 

While attitudes within life sciences communities appear to be changing, 

they still have a long way to go before they can provide the requisite strong 

leadership and sustained engagement. Life scientists should now work with 

governments to help strengthen the norms against biological weapons 

research, acquisition, and use. Codes of conduct, peer reviews and panels, and 

self-regulation that define appropriate restrictions in scientific research are all 

ways in which the scientific community can contribute to the development of 

a culture of responsibility with respect to risk management. 

For its part, governments must encourage this development further and 

engage the life sciences community in a way that takes into account legitimate 

security concerns without harming the innovation and creativity that are such 

a key feature of work in the life sciences. Governments must exercise caution, 

therefore, to ensure that they do not, in fact, drive scientists away from 

such engagement. Onerous requirements that force scientists or companies 

to conclude that potential benefits from particular research or commercial 
367 Bio-IInspired IInnovation and ovation and NNational SSecurity 

ventures are not worth the hassle will lead them to forego efforts that could 

prove to be valuable from both a scientific and a security standpoint. 

Anecdotal evidence suggests that just such things are happening. 

Therefore, governments must focus on developing means for managing 

security-related risks that achieve an acceptable balance with the requirements 

of the scientific process and good business practices.

International cooperation is especially important in reconciling 

such tensions. The world’s life science and technology base is thoroughly 

globalized, with capabilities available worldwide that can contribute to 

domestic security for many nations. Success in exploiting these capabilities 

will be possible, however, only if nations’ efforts are informed by awareness 

of developments elsewhere. Information must be exchanged on an ongoing 

basis. No country has the resources to fund all of its demands for security 

investments, and maximizing the return on whatever investment is made 

requires a coordinated international approach.

Notes

1 See, for example, Adrienne Mayor, Greek Fire, Poison Arrows, and Scorpion Bombs: Biological 

and Chemical Warfare in the Ancient World (New York: Overlook Duckworth, 2003).

2 For more detail, see Mark Wheelis, “Biological Warfare Before 1914,” in Biological and 

Toxin Weapons: Research, Development, and Use from the Middle Ages to 1945, ed. Erhard 

Geissler and John Ellis van Courtland Moon (London: Oxford University Press for the 

Stockholm International Peace Research Institute, Chemical and Biological Warfare 

Studies no. 18, 1999), 8–34.

3 See Mark Wheelis, “Biological Sabotage in World War I,” in ibid., 35–62.

4 See Sheldon H. Harris, Factories of Death: Japanese Biological Warfare, 1932–1945, and the 

American Cover-Up (London and New York: Routledge, 1994). For details on other countries’ 

biological weapons (BW) programs prior to 1945, see the respective chapters on Poland, France, 

Germany, the Soviet Union, Britain, Canada, and the United States in Geissler and Moon. 

5 Thus, the Biological Weapons Convention (BWC) complemented the 1925 Geneva Protocol, 

which outlawed the use of both chemical and biological weapons. The protocol, however, 

had not been ratified by a number of countries, including the United States, at the time that 

the BWC entered into force. Moreover, several countries that had ratified the protocol had 

done so with reservations, making it little more than a no-first-use agreement.

6 The BWC is especially difficult to verify because it does not ban any specific activity, but 

rather any action that is in service of an offensive BW program. Therefore, many of the same 

activities (for example, certain forms of research) can be either legal or illegal depending on 

the intent of the country taking that action.

7 For a detailed discussion of the operations of Biopreparat, see Ken Alibek with Stephen 

Handelman, Biohazard (New York: Random House, 1999). Alibek defected following 

Pasechnik. Alibek had an M.D. and Ph.D. in microbiology and served, at the rank of 

colonel, as first deputy chief of the Biopreparat program.
life sciences, security, and biological weapons 37

8 Cited in James Adams, The New Spies: Exploring the Frontiers of Espionage (London: 

Hutchinson, 1999), 270–283. 

9 For more detail regarding these efforts and the U.S. approach in general to Soviet 

noncompliance with the BWC, see Michael Moodie, “The Soviet Union, Russia, and the 

Biological and Toxin Weapons Convention,” Nonproliferation Review 8, no. 1 (Spring 2001).

10 For more details on the Aum Shinrikyo, see David A. Kaplan and Andrew Marshall, The 

Cult at the End of the World (New York: Crown, 1996).

11 For the most authoritative public source on such events, see W. Seth Carus, Bioterror and 

Biocrimes: Illicit Use of Biological Agents Since 1900 (Washington, DC: Center for the Study 

of Weapons of Mass Destruction, National Defense University, February 2001).

12 John C. Rood, “Remarks to the Sixth BWC Review Conference,” U.S. Department of State, 

November 20, 2006.

13 The report also took note of the past illicit programs of Libya and Iraq. “Adherence to and 

Compliance with Arms Control, Nonproliferation, and Disarmament Agreements and 

Commitments,” U.S. Department of State, August 2005.

14 U.S. Congress, Office of Technology Assessment, Proliferation of Weapons of Mass Destruction: 

Assessing the Risks (Washington, DC: U.S. Government Printing Office, August 1993), 54.

15 See, for example, Milton Leitenberg, Assessing the Biological Weapons and Bioterrorism 

Threat (Carlisle, PA: U.S. Army War College, Strategic Studies Institute, December 2005).

16 See Rob Carlson, “The Pace and Proliferation of Biological Technology,” Biosecurity and 

Bioterrorism: Biodefense Strategy, Practice, and Science 1, no. 3 (August 2003).

17 Institute of Medicine, Globalization, Biosecurity, and the Future of the Life Sciences

(Washington, DC: National Academies of Science, 2006), 59.

18 Gerald L. Epstein, Global Evolution of Dual-Use Biotechnology: A Report of the Project on 

Technology Futures and Global Power, Wealth, and Conflict (Washington, DC: Center for 

Strategic and International Studies, April 2005), 3–4.

19 Jez Littlewood, Managing the Biological Weapons Proliferation Problem: From the Individual 

to the International, Weapons of Mass Destruction Commission Paper no. 14 (Stockholm: 

Weapons of Mass Destruction Commission, August 2004).

20 Ibid., 9. Littlewood points out, for example, that the ad hoc groupings that have emerged in 

recent years did not do so because of a desire on the part of some states to restrict certain 

activities “to a ‘club’ of states or some desire to push forward the boundaries of international 

law or control mechanisms per se. They were created because of the perception that they 

were required to perform necessary tasks.” 

39

Biological warfare is insidious, repulsive, frightening, effective, and 

marginal. Social, legal, military, and practical constraints have limited, 

but not eliminated, the employment of biological weapons (BW) in 

past conflicts. Currently at issue is whether weaponization of the agents 

resulting from the rapid advances in biology and related fields can possibly 

be restrained. Given the likely asymmetric nature of future conflicts and 

the difficulty of holding nonstate adversaries at risk, it seems probable that 

BW will be employed at some point in the future. While adding an order of 

complexity to the traditional battlefield, the most likely applications will be 

attacks against supporting elements and independent civilian targets. Despite 

low probability of a major attack, the extremely high-risk nature of the BW 

threat demands that greater attention be paid to this problem. 

Role of the Fear Factor

Reduced to the lowest common denominator, the psychological effects 

that are generated by the potential for BW far outweigh the physical effects 

in most cases. Paradoxically, the threat is both overstated and understated. 

While the threat from disease is real and must be addressed, it has taken on 

near-mythical properties in the minds of many observers and certainly in 

the news media. To function in an environment in which biological weapons 

are available, realism in assessing the situation is essential. As expert Milton 

Leitenberg concludes, “Bioterrorism may or may not develop into a serious 

concern in the future, but it is not ‘one of the most pressing problems we 

have on the planet today.’”1

 Still, there are viruses such as smallpox that, if 

chapter 4

Biological Warfare: 

A Warfighting Perspective

John B. Alexander
401 Bio-IInspired IInnovation and ovation and NNational SSecurity 

reintroduced into an urban population, could ignite massive outbreaks of 

disease. Because smallpox was declared eradicated in 1980, vaccinating the 

general population was stopped, leaving billions of people vulnerable to the 

virus. In addition, and as will be described later, there are categories of BW 

agents that can attack other than living targets that should be of concern to 

military planners. 

While biological weapons are categorized as weapons of mass 

destruction (WMDs), this categorization could be considered a misnomer. 

Unlike nuclear weapons that inflict massive infrastructural damage, even 

small amounts of BW can have large-scale impact without doing much 

physical damage. Therefore, it can be stated that they are weapons of mass 

effect, although that term is not in the accepted canon.

Recent history has persuasively demonstrated the mass effectiveness of 

BW in disrupting civil operations, if not in causing massive casualties. The 

most glaring example of disproportional effects was seen in the 2001 anthrax 

attacks that took place along the East Coast of the United States. In September 

and October of that year, a perpetrator launched two waves of attacks against 

high-profile people and institutions from postal facilities in New Jersey. The 

targets initially included news media, but later two U.S. Senators, Tom Daschle 

of South Dakota and Patrick Leahy of Vermont, also received letters. As a 

result of those mailings, 22 people developed anthrax infections, resulting in 

5 deaths. While some of the victims included U.S. Postal Service personnel or 

people receiving the letters, others had no known established relationship to 

the chain of events.

In response to these small-scale but highly publicized attacks, near-panic 

set in across the country. The fact that these attacks occurred right after 9/11 

intensified the psychological effect, and many people who came in contact 

with a powder they could not immediately identify notified law enforcement 

authorities of possible terrorist incidents. The investigation was massive, and 

numerous Congressional hearings were held. By September 2006, the Federal 

Bureau of Investigation reported having participated in over 9,100 interviews, 

issued over 6,000 grand jury subpoenas, and conducted many extensive 

searches.2

 The case was recently closed following the apparent suicide of the 

primary suspect, a government scientist who worked with biological agents.

There were other disproportionate direct and indirect costs incurred by 

taxpayers. More than $200 million was spent to decontaminate buildings, and 

some estimates place the total damage at over $1 billion. Due to public pressure, 

Congressional funding of BW defense, including the Project Bioshield Act of 

2004, which provides $5.6 billion over 10 years, rose dramatically.3

While the five deaths were terrible, the casualty level was small when 

compared with other far worse statistics that evoked little response. As 
Biological Warfare: A Warfighting Perspective 41

examples, each day in 2001 in the United States, approximately 104 people 

died in traffic accidents, and another 44 were murdered. Even the deaths of 

over 1,500 people per day from cancer did not get the same level of publicity 

as the BW events. Clearly, the response was disproportionate to the scale of 

the attack, highlighting the severe fear and psychological responses biological 

weapons invoke in individuals.

Fielded Military Implications

The psychological impact of BW is as apparent in military forces as it is in 

civilian circles. During Operation Iraqi Freedom, there was constant concern 

that Iraqi forces would deploy BW and chemical weapons (CW) against U.S. and 

Coalition forces. As part of the predeployment activities, anthrax vaccinations 

became mandatory for all U.S. troops going into the Gulf region. During ground 

operations, when initially approaching Baghdad, troops were ordered into 

protective gear as some commanders thought such an attack was imminent. 

Even though no BW attack was ever launched, the mere threat was 

sufficient to take the precautionary measures even while understanding 

their potential negative consequences for operational performance. While 

the protective gear works relatively well, it can dramatically degrade the 

physical capability of the fighter, the degree of degradation increasing with 

the level of protection required. Some of the generic impacts are problems 

in communication, impaired hearing, loss of visual acuity, dehydration, heat 

injuries, combat stress, and impaired thinking and judgment.4

Selected examples from specific studies on the effects of wearing 

protective gear reported the following observations:

• task degradation of between 20 and 50 percent occurred

• leader performance declined as they become exhausted and disoriented

• sensory awareness was reduced, making it harder to stay awake

• soldiers required 11⁄2 to 3 times longer to perform manual dexterity tasks

• individual rate of weapons fire dropped 20 to 40 percent

• calls for indirect fire increased 3 times

• communication was about half as effective, and total time on radio doubled

• cognitive tasks declined up to 23 percent

• land navigation was seriously impaired, especially at night

• units bunched up to maintain control.

After-action reports from Operation Iraqi Freedom outlined a number 

of problems inherent in deploying to an environment in which a CW/BW 

attack is anticipated. Highlighted was the need for involvement of leaders at 
423 Bio-IInspired IInnovation and ovation and NNational SSecurity 

all levels as well as enhancing individual and collective skills required to respond 

to these threats. The report also noted that the new protective suits were lighter 

and better suited for operations in warm temperatures. However, while allowing 

better performance, they tended to rip and caused problems with many activities. 

Of specific concern was damage to gear worn by infantry Soldiers.5

The recommendation for increased emphasis on training should not 

come as a surprise. That call has been sounded for decades, but in general 

CW/BW has been put in the too tough to handle bin. Like nuclear weapons 

before it, while the BW threat is acknowledged, it is often ignored in training 

and wargames as it can overwhelm the players and the outcome. Therefore, 

the rationale is to limit or eliminate the BW possibility so that other aspects of 

the game can produce useful results. 

This is not to say there has not been training conducted; there has. 

The problem is that the amount of training required to adequately prepare 

to fight in a contaminated environment is too extensive for the total training 

time allotted for either individual skills or unit training. The conundrum that 

emerges is that adequate training is essential for survival on the CW/BW 

battlefield, yet it must compete with realistic time constraints that will always 

fall short of optimal, or even acceptable, standards.

This leads to a strategic observation that indicates that with CW/BW, the 

advantage always goes to an enemy force willing to employ them. In addition, 

armed forces tend to consider the threat from a military perspective—that 

is, how will they fight on a potentially contaminated battlefield. Thus, in 

preparing for the potential battle, they become a somewhat hardened target 

and reduce the threat to themselves in the direct fight. 

Three Legs of Biological Warfare

The problem is very complex, and it is the author’s opinion that even the 

approved Department of Defense (DOD) definition of BW is incomplete. The 

official definitions reads, “Biological operations: employment of biological 

agents to produce casualties in personnel or animals, or damage to plants.”6 

There is no mention made of the potential of BW agents that attack nonliving 

targets. There are three legs to the BW threat, and only two—antipersonnel 

agents and those that attack agricultural targets such as animals or crops—

are covered by this definition. The third leg, and the one that is unaccounted 

for, is antimateriel attacks by biological organisms that degrade inanimate 

material objects. 

The majority of DOD efforts in countering BW have rightfully focused 

on prevention of infectious diseases. Many Americans do not realize that 

naturally occurring diseases have caused more casualties than enemy 
Biological Warfare: A Warfighting Perspective 43

combatants in most wars prior to World War II. Even so, disease has been 

a major concern for military medical personnel. Therefore, it is a logical 

extrapolation that controlling specific diseases and employing them on the 

battlefield is a method to be considered in destroying the enemy force.

The use of disease as a weapon dates back many centuries. Because of the 

catastrophic consequences, the siege at the Crimean peninsula city of Kaffa, now 

known as Feodosiya, Ukraine, is often cited as an example. In 1346, invading 

Tatar forces experienced a deadly outbreak of bubonic plague and began to 

catapult infected bodies over the city walls to infect the defending forces within. 

This ultimately resulted in an outbreak of plague in the defending city. Shortly 

thereafter, the surviving defending forces sailed for Constantinople, carrying 

with them what became known as the Black Death, which would ultimately 

cause approximately 25 million deaths throughout Europe.7

In the last century, BW received considerable attention. Based on the 

dreadful experience with chemical weapons in World War I, the Geneva Protocol 

was adopted in 1925 (officially known as the Protocol for the Prohibition of the 

Use in War of Asphyxiating, Poisonous or Other Gases, and of Bacteriological 

Methods of Warfare), which banned the use of both biological and chemical 

weapons in war. While many countries continued to conduct research on BW 

agents, the only known military use of biological weapons during this time was 

by Japan against the Chinese during World War II. 

In 1972, the Biological and Toxin Weapons Convention was signed by 

all major parties involved in the Cold War. While the United States honored 

the treaty and halted all offensive BW research and development, the Soviet 

Union initiated the largest and most comprehensive program of its kind. 

Ken Alibek, a former senior official in the Soviet BW program, alleged that 

this program moved production of selected agents, such as anthrax, to an 

industrial scale, explored a wide range of antipersonnel agents, and developed 

the essential distribution means by which they could be delivered.8 The 

program continued undetected until a defector provided partial information 

about it in 1989.

Anthrax offers a good case study for the potential damage that could 

be caused by a successful large-scale BW attack, especially against a civilian 

population. If early diagnosis and immediate treatment do not occur, the 

mortality rate could be greater than 85 percent for inhalational anthrax (other 

forms of anthrax, such as cutaneous or gastrointestinal, have lower mortality 

rates).9 In 1993, the U.S. Congressional Office of Technology Assessment 

estimated that 100 kilograms of agent dispersed from a low flying aircraft in 

a densely populated area, while a low probability event, could kill between 

1 million and 3 million people within 5 to 7 days.10 It should be noted, 

however, that these numbers are not universally agreed upon in the scientific 
445 Bio-IInspired IInnovation and ovation and NNational SSecurity 

community, and the successful delivery of anthrax requires a terrorist group 

to overcome numerous technical challenges.

When a specific BW agent is known, prophylaxes (for example, vaccines) 

or therapeutics (for example, antibiotics) can be employed to prevent or treat 

the disease. However, when confronted by multiple possibilities, it is nearly 

impossible to defend against all of the agents. After defecting from the Soviet 

Union, Alibek indicated that the Soviet program did include a mix-andmatch capability, thus increasing the difficulty in countering such an attack. 

Even if vaccines were available for each agent, the combinations would likely 

have devastating health effects.

Since the breakup of the Soviet Union in 1992, numerous programs, 

such as the Nunn-Lugar Cooperative Threat Reduction Program, have 

strived to keep former weapons scientists gainfully employed in their fields of 

expertise. The Soviet BW program, however, employed thousands of people, 

and only a small subset of the researchers have been hired via the Cooperative 

Threat Reduction Program to prevent the spread of this technical knowledge. 

There have been cases where former Soviet BW scientists, with sufficient 

information to be quite dangerous, have either emigrated to suspected 

proliferant countries or attempted to sell their expertise on the black market. 

It is also known that terrorists groups such as al Qaeda have actively sought 

access to both BW information and weapons.

The second leg of the BW triad involves attacks against agriculture, both 

plants and animals. Despite decades of known research by many countries into 

biological weapons targeting agriculture, it has only recently been recognized 

as a national security threat. The potential impact of agroterrorism is huge. 

In the United States, farming employs only 2 percent of the population, but 

a total of 16 percent work in food- and fiber-related industries. This sector 

accounts for 11 percent of America’s gross domestic product and 23 percent 

of wheat, 54 percent of corn, and 43 percent of soybean exports.11

There is an extensive range of possible agents that could be used against 

crops and livestock. Some of them are zoonotic, meaning that the disease 

could be transmitted to humans via animal vectors. Among the most studied 

agents are anthrax, Rinderpest, African swine fever, foot and mouth disease, 

wheat blast fungus, fowl plague, and many others. In addition, there are many 

nonindigenous insects and rodents that could be used to spread disease, and 

these would be difficult to detect until a major outbreak has begun.

Agricultural production is vital to our economic interests. Unlike many 

industrial facilities, by its nature, agricultural production is geographically 

dispersed and thus nearly impossible to secure. Experience has shown that 

even a single case of a debilitating illness can shut down international trade 

for extended periods of time.
Biological Warfare: A Warfighting Perspective 45

The potential impact that a limited BW attack could have on American 

products is seen in response to a case of bovine spongiform encephalopathy 

(BSE), popularly known as mad cow disease. In December 2003, a single case 

of BSE was detected in the American food chain. This led to full or partial 

bans on beef imports by 65 countries at an estimated loss of over $2 billion 

each of the following years. Once import bans are established, it often takes 

years to lift them. While the introduction of BSE was not intentional, this 

example does point to the large economic vulnerabilities that exist in the 

agriculture sector.12

There are other examples, including intentional terrorist acts that 

have adversely affected international trade. Some suggest that in 1989, an 

ecoterrorist group called the Breeders released Mediterranean fruit flies into 

California groves. The estimated cost in lost revenue and other damage was 

nearly $900 million.13 Estimates for such an insect infestation happening now 

would be the demise of 132,000 jobs and $13.4 billion in lost revenue.14 In an 

article in the Boston Globe, Jeffery Lockwood described insects as “the box 

cutters of biological weapons—cheap, simple, and wickedly effective.”

In addition to direct fiscal costs, there are other indirect vulnerabilities. 

Some analysts are concerned that a successful agroterrorism attack could 

degrade public confidence in the existing government. In the United States, 

we have established a carefully balanced food production and distribution 

system that relies on the smooth operation of many parts.15 The public is quick 

to respond to small outbreaks such as the incident of contaminated spinach 

in September 2006, which caused 205 confirmed illnesses and 3 deaths.16 If 

confronted with severe disruption in availability of food, public confidence 

in developed countries would be tested. However, such interruption in 

developing countries could be sufficient to destabilize governments.17

Militarily, agroterrorism is a strategic versus a tactical issue. Fielded 

forces have sufficient reserves of prepackaged food to be able to conduct 

immediate missions even in the event of substantial interruption of supplies. 

More at risk are popular support for the conflict and confidence that the 

government can protect the society. 

The definition of biological warfare must be revised to include 

antimateriel agents as the third leg of the BW triad. The potential threat has 

enormous implications and is growing at a rate that should not be ignored. In 

addition, advances in genetically engineered designer microorganisms will 

increase the potential threat dramatically.

The issues of antimateriel BW can be understood easily in nontechnical 

terms. Trash and environmental contamination are global problems. The 

volume of waste material produced by developed countries greatly exceeds 

their proportionate population and their ability to dispose of it. Trash is an 
467 Bio-IInspired IInnovation and ovation and NNational SSecurity 

arbitrary designation assigned when an item is no longer deemed useful to the 

owner. The trash items contain the same physical properties they had when 

they were still useful. To deal with this mounting problem, bioremediation 

and microbial biodegradation are often used. That means that biological 

organisms are applied that intentionally degrade the physical material. There 

is almost nothing that some biological organism will not attack. Therefore, 

research is rapidly advancing to identify organisms that can be used to reduce 

the volume of waste material and to eliminate contaminating materials from 

the environment. This is considered positive and encouraged as a peaceful 

application of biological development. 

However, from a military perspective, the same research and 

development can be employed as an offensive biological weapon. The only 

change is the intent for which the biological agent is introduced to the target. 

Therefore, offensive and defensive antimateriel BW research is virtually 

indistinguishable. The development of these agents will continue to accelerate 

and has strategic implications.

In my book Future War, I posited the application of nonlethal systems, 

including biological agents, to create strategic paralysis of a complex target set. 

In that case, it was a nation-state that was vulnerable to attack, albeit over time. 

The reality is that microorganisms could be developed that could accomplish 

that mission.18 Most military analysts are aware that bioremediation is the 

treatment of choice when oil spills occur on the seas. It only takes a small 

step in logic to understand the implications of introduction of those same 

microorganisms into fuel or lubricant supplies at any stage from national 

petroleum reserves to vehicle fuel tanks. Once vehicle engines are befouled, they 

are extremely difficult to cleanse and repair short of depot level maintenance. 

There are many other substances that are vulnerable to attacks of 

microorganisms. With the possible exception of titanium, all common 

metals and alloys are susceptible to biocorrosion.19 Possibly most surprising 

to military planners will be that even concrete can be degraded, thus 

rendering many bridges, dams, and buildings as potential targets. Widely 

used polyurethane plastics, while resistant to oxidation, are also susceptible 

to biodegradation, especially when employed as thin films. That means it 

is not necessary to destroy bulk quantities of plastic to successfully damage 

key components of sensitive equipment. Relatively small amounts applied at 

critical locations would be sufficient to degrade operational capabilities of 

the item. Even fiberglass and polymeric composites can be targeted so as to 

degrade the integrity of the item. 

Except by using the most advanced techniques, it would be difficult to 

detect and monitor an antimateriel BW program. The equipment necessary 

to initiate the project is easy to both obtain and conceal. A simple approach 
Biological Warfare: A Warfighting Perspective 47

to acquiring microorganisms of interest is to go to a dump where the desired 

target material has been buried for some time. Due to their inherent ability 

to mutate and adapt to environmental changes, it is highly likely that the 

microorganisms of interest have already begun to degrade that material. It 

is then a matter of harvesting those agents and initiating a breeding program 

to develop the desired characteristics of the BW agent. As an example, 

introduction of a biocide will kill most, but not all, of the organisms. The 

surviving organisms are then bred until a biocide-resistant strain is produced. 

A major constraint to application of antimateriel BW agents is that they 

are very slow to produce the degradation of the target. For that reason, many 

experts have discounted the probability of them being employed. There is no 

doubt that American military leaders want to know that when they pull the 

trigger, an immediate and predictable effect will occur. This is a shortsighted 

view and some potential adversaries are willing to move on timelines that are 

quite different from ours, and we must guard against discounting this threat 

because it does not mirror how we would prefer to accomplish the task.

Full-spectrum Analysis

Threat analysis must include the full spectrum of vulnerabilities, and it 

is insufficient to divide complex systems into small elements and establish 

protection for each part independently. Synergistically, the threat is greater 

than the sum of the parts, and seamless defensive system architectures are 

required. Combat systems must be evaluated in their entirety, and it is then 

essential that the analysis be broadened to a national or even an international 

level. Most threats to the military will not be constrained within the DOD 

organizational structures.

As previously indicated, troops in the field, while vulnerable, 

represent a somewhat hardened target set. However, the recent propensity 

for contracting services in a variety of areas dramatically complicates BW 

defensive measures. For operations in the Gulf theater, the ratio of military to 

contractors reached about 1:1. Contractors were deeply involved in all aspects 

of the logistics and maintenance systems as well as many other areas such as 

security. From the beginning, this was problematic from a BW perspective. 

In fact, one of the findings in the Third Infantry Division after-action report 

was that their supporting civilian contractors arrived without any protective 

equipment. This placed a burden on the deploying forces to supply them with 

the necessary equipment.20 Not even addressed was whether or not those 

contractors had any training on how to respond in the event of a BW attack.

When evaluating military support systems, consideration must be given 

to the nationality of those performing services and what access they have 
489 Bio-IInspired IInnovation and ovation and NNational SSecurity 

at every stage. In Operation Iraqi Freedom, it was common to have thirdparty, and even host-nation, workers employed at fairly sensitive locations. 

The threat is twofold. Distribution of BW agents is one of the most difficult 

issues for offensive operations. If cooperation can be obtained from a worker 

already inside the chain of operations, a BW agent could be introduced 

directly to the targeted personnel. As an example, consider who works in 

consolidated mess facilities, where food is procured, how it is transported, 

where is it stored, and what level of protection is afforded throughout the 

process. It would only take one operative at a critical location to inject the 

BW agent, with deadly consequences. 

The second issue is the impact a BW attack, or threat of an attack, might 

have on the workforce. As contractors, these workers cannot be forced to 

remain in a hostile environment. Rumors are likely to spread rapidly in the 

event of unexplained illnesses. Fear of further contamination would likely lead 

to large defections of foreign contractors. Strategically, threats of BW attacks 

could be used to drive a wedge between coalition partners, similar to what 

was accomplished by selective targeting of suicide bombings. While tolerance 

for violent casualties is already relatively low, threats of BW casualties would 

have serious repercussions in all countries and at all levels of the population. 

Recommendations

Most of the BW threats have not gone unnoticed. In some areas, there have 

been Congressional hearings and funding increases to boost protection. These 

are extremely difficult threats against which to defend but there are tasks to 

be undertaken. Specifically, we must improve intelligence collection, develop 

and deploy near-ubiquitous sensors, establish perception management, and 

conduct training programs that extend to all sectors.

Intelligence

Probably the most important countermeasure is to expand intelligence 

collection aimed at the entire spectrum of the BW threat. It is vitally important 

that as much information as possible is collected about what specific biological 

agents are being researched, developed, and manufactured. Given the rapid 

advances that are occurring in biology, it can be assumed that new technologies 

and agents will be adapted as potential weapons. The Intelligence Community 

needs to stay current and be able to predict future innovations. 

While human intelligence activities targeted against tribal adversaries 

are difficult, every effort must be made to ascertain the capabilities and 

intentions of potential adversaries. Every means available should be dedicated 

to this effort. Also useful is development of advanced computer models 
Biological Warfare: A Warfighting Perspective 49

that can provide threat warnings and be predictive about the direction BW 

research, development, and applications will take. 

Sensors

Sensor technologies are advancing at rates that parallel those of the BW field. 

Given the extremely broad vulnerabilities of both military units and society 

in general, there is a need for ubiquitous sensors that can quickly detect the 

presence of chemical or biological agents and report them immediately. 

State-of-the-art nanoscale sensors should be placed at every anticipated site 

of vulnerability. Lab-on-a-chip technology already provides the capability to 

constantly observe, and simultaneously test for, a wide range of agents. This 

effort should be perpetually technically upgraded and distribution expanded 

to the maximum extent conceivable. 

Perception Management

As indicated, psychological factors play an extremely important role in the 

effectiveness of BW attacks. Unfortunately, news media often proclaim worstcase scenarios even without supporting facts. The best countermeasure is to 

provide honest and accurate information directly to the public as quickly 

as possible, as success depends on the public having a high degree of trust 

in the reporting agencies. There is little doubt that the American people 

currently have diminished confidence in the accuracy and honesty of the 

information provided by government sources. It is therefore essential that 

all information that is provided during noncrisis situations be completely 

open and honest. While difficult to accomplish, there should be a long-term 

comprehensive program to educate news media personnel about the realities 

of BW and provide them with an understanding about how their doomsday 

prognostications directly support the goals of the adversaries.

Training

Training for BW events must continue at all levels of the military. Realistic 

scenarios should be included in high-level wargames. They should be played 

out even if they disrupt the anticipated flow of the exercise. Individual and unit 

BW training should be conducted continuously. There can never be too much.

In addition, military commanders must ensure that nonmilitary support 

elements can function in a BW environment by providing adequate equipment and 

training. Support contracts should include specific requirements that contractors 

have minimum established levels of training for operations in contaminated 

environments. There will certainly be additional costs associated with including 

BW/CW capabilities requirements, but if the units must rely on contractor support, 

the latter must be capable of functioning in the same threat situations. 
501 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Hold at Risk

Worth considering is development of policy that might be called Biological 

Assured Destruction. The policy would be aimed at nation-states that might 

be tempted to make a large-scale BW attack or support other groups that 

might carry out such an act. The message would be clear: Any nation that 

attempts or supports a major BW act against the United States or its interests 

will risk conventional but lethal countermeasures.

Notes

1 Milton Leitenberg, Assessing the Biological Weapons and Bioterrorism Threat (Carlisle, PA: 

U.S. Army War College, Strategic Studies Institute, December 2005). 

2 Federal Bureau of Investigation, “Amerithrax Fact Sheet,” September 2006, available at 

www.fbi.gov/anthrax/amerithrax_factsheet.htm.

3 Susan Wright, “Taking Biodefense too Far,” Bulletin of the Atomic Scientists 60, no. 6 

(November-December 2004). 

4 Office of the Special Assistant for Gulf War Illnesses, “MOPP Information Paper,” available 

at www.gulflink.osd.mil/mopp/mopp_s03.htm.

5 Third Infantry Division (Mech) After Action Report—Operation Iraqi Freedom, available at 

www.globalsecurity.org/military/library/report/2003/3id-aar-jul03.pdf.

6 Joint Publication 1–02, Department of Defense Dictionary of Defense and Associated Terms

(Washington, DC: Department of Defense, amended October 17, 2007).

7 John B. Alexander, Future War: Non-Lethal Weapons in Twenty-First Century Warfare

(New York: St. Martin’s Press, 1999).

8 Ken Alibek, Biohazard: The Chilling True Story of the Largest Covert Biological Weapons 

Program in the World—Told from the Inside by the Man Who Ran It (New York: Random 

House, 1999).

9 According to the U.S. Army Medical Research Institute of Infectious Diseases, the mortality 

rate for cases of inhalational anthrax in the 2001 anthrax attacks was only 45 percent. It is 

suggested that this decrease in mortality rates could be due to advancements in intensive 

care medicine. 

10 U.S. Congress, Office of Technology Assessment, Proliferation of Weapons of Mass Destruction: 

Assessing the Risks (Washington, DC: U.S. Government Printing Office, August 1993).

11 Jim Monke, Agroterrorism: Threats and Preparedness, RL32521 (Washington, DC: 

Congressional Research Service, August 13, 2004).

12 Colm A. Kelleher, Brain Trust: The Hidden Connection Between Mad Cow and Misdiagnosed 

Alzheimer’s Disease (New York: Paraview Pocket Books, 2004).

13 Robert P. Kadlec, “Biological Weapons for Waging Economic Warfare,” in Battlefield of the 

Future: 21st-Century Warfare Issues (Maxwell Air Force Base, AL: U.S. Air Force Air University, 

1995), available at www.airpower.maxwell.af.mil/airchronicles/battle/chp10.html.

14 Jeffery A. Lockwood, “Bug Bomb: Why Our Next Terrorist Attack Could Come on Six 

Legs,” The Boston Globe, October 21, 2007.

15 Monke.
Biological Warfare: A Warfighting Perspective 51

16 U.S. Food and Drug Administration press release, “FDA Finalizes Report on 2006 Spinach 

Outbreak,” March 23, 2007.

17 Mark Wheelis, “Agriculture and Bioterrorism: An Analytical Framework and 

Recommendations for the Fifth BTWC Review Conference,” presented at annual meeting 

of the Association of Politics and the Life Sciences in Atlanta, Georgia, September 1999, 

available at www.fas.org/bwc/agr/agwhole.htm.

18 Alexander.

19 Margaret E. Kosal, “Anti-Materials Agents,” Encyclopedia of Bioterrorism Defense (New York: 

John Wiley and Sons, 2005).

20 Third Infantry Division (Mech) After Action Report. 

part two

biomolecular 

engineering

55

We all feel humble in the face of the ingenuity and complexity of 

nature. Yet it need not prevent us from learning, exploring, and 

even attempting to construct useful artificial systems having a few 

of the simpler properties of their natural component.

—T.M.S. Chang 

The most obvious quality of living cells is that they are complicated and 

highly organized. However, these complex structures and functions are 

made from simple lifeless molecules that, in appropriate combinations 

and number, can now be hypothetically put together in such a manner as 

to render “lifelike” functional circuits and networks exhibiting distinct and 

extraordinary properties. 

The most sensitive biodetector known today is the olfactory system of 

animal species such as dogs and pigs,1 capable of detecting a few molecules of 

C4 escaping from explosives hidden underwater, from cocaine frozen inside ice 

blocks, or from truffles buried underground. It was clear more than two decades 

ago that biological detection systems that capitalize on an understanding of the 

molecular physiology of ligand-receptor interaction, as well as the integrative 

properties of neuronal systems, would offer the best prospects for developing 

true biosensors. An early 1980s concept for threat agent detection involved 

coupling neuroreceptors with microsensors to create biosensors capable of 

detecting classes of threat agents. For example, using the acetylcholine receptor 

as the biological recognition element (BRE) would enable the detection of more 

than 60 cholinergic neurotoxins, while using the enzyme acetylcholinesterase 

would permit detection of all organophosphorus nerve agents and pesticides. 

chapter 5

Abiotic Sensing

James J. Valdes, Andrew Ellington, William E. Bentley, 

Roy G. Thompson, and James P. Chambers
567 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Such broad-spectrum, almost generic, biosensors are desirable for a 

number of reasons. From a military point of view, threat agents can be broadly 

considered to be xenobiotic entities that interact with human physiology and 

in some way interrupt normal function. This interaction is mediated by BREs 

known generically as “receptors.” Receptors are the key to communication among 

the body’s many networks as well as with the external environment, and recently 

a vast body of literature has identified nodes at the organ, cellular, subcellular, 

and genomic levels that are critical to proper function of these networks.

The nature of the military—and, by extension, public health—threat is 

now such that it cannot be predicted a priori. Broadly defined, nontraditional 

agents include genetically engineered pathogens, midspectrum agents such 

as toxins and biological regulators, lentiviral and other vectors capable of 

introducing genetic material into host genomes, and new classes of chemical 

agents, to name but a few. The Cold War–era approach of threat-oriented 

detection must necessarily give way to a target-oriented approach, the targets 

being BREs. While this shift was postulated two decades ago, the technology 

to bring it to fruition simply did not exist. 

The technological bottlenecks in the 1980s were many. A number of 

receptors had been purified and studied but most were membrane bound and 

could not function outside of their native membranes, which were necessary 

to maintain proper conformation. Some receptors were cloned and produced 

in small quantities but manufacturing technology was essentially nonexistent. 

Many studies therefore relied on isolating acetylcholine receptors from 

rich sources such as the torpedo electric organ, or isolating synaptosomes 

from animal brains. Many receptors have since been cloned and efficiently 

expressed. G-protein–coupled receptors (GPCRs) are now known to be 

important targets for drug discovery, and assay kits for high throughput 

screening have been developed.2

A second technological barrier was lack of knowledge about the 

interactions between BREs and nonbiological supports. Specifically, 

techniques required to keep BREs and whole cells stable and functional on 

sensor platforms were very crude. Driven by the development of prosthetics 

and artificial organ systems, the interface between synthetic and biological 

materials has been an object of intense study in recent years.3

Third, there was a very limited ability to design novel BREs tailored 

for specific affinities or selectivity; nor was there much success with artificial 

receptors such as molecular imprints or engineered antibodies such as 

Fabs. Defining the minimum requirements for biomolecular interaction is 

critical for the design of stable artificial BREs. Two such approaches are the 

minimization of known protein binding motifs or, conversely, a biomimetic 

approach in which binding pockets are designed de novo.4

 Engineering novel 
Abiotic Sensing 57

antibodies is another successful approach, and these include recombinant 

antibody fragments (for example, Fab, scFv) and variants such as diabodies 

and triabodies.5 Finally, molecular imprints made from synthetic materials 

have been successfully applied to both analyte detection and drug release.6 

More importantly, the genomic tools required to identify all proteins required 

for both normal and abnormal functioning, the precise role of the proteins 

in key metabolic pathways, or even determining a receptor’s natural ligand 

did not exist. Using modern genomics mapping techniques, one can now 

identify all relevant proteins, but it is still problematic to definitively elucidate 

function. Nevertheless, enormous strides have been made in understanding 

GPCR cascades, signal amplification, and translocation of cellular proteins to 

specific intracellular compartments, knowledge that will result in design of 

high-content and high-throughput screens for drug discovery.7

Finally, the materials and micromachining techniques required to 

assemble an integrated biosensor were inadequate. Nanotechnology and its 

offshoots provide unprecedented control over material properties via structural 

control using directed and self-assembly. Advances in microcontact printing, 

soft photolithography, microfluidics, and laser desorption techniques have 

proceeded rapidly in recent years. Micropatterning techniques, which include 

laminar flow patterning and microchannels, have resulted in the design of 

numerous functional biosensors.8

Synthetic Biology

The term synthetic biology was coined in the literature over 20 years ago. The 

first use of the term referred to the genetic engineering of bacteria using 

recombinant DNA technology,9 in which natural biological systems are 

altered by scientists to produce a biological system that performs unnatural 

function(s)—an approach that initiated the emerging field of bioengineering. 

The term was somewhat usurped in 200010 to describe the field of 

chemistry striving to design the synthesis of unnatural molecules that could 

function in living systems. In this use, synthetic biology became an extension 

of biomimetic chemistry, in which artificial molecules are synthesized that can 

functionally replace natural biological molecules, such as artificial enzymes, 

aptamers, and peptide mimics.11, 12, 13, 14 The extension of biomimetic chemistry 

to fulfill the larger scope of synthetic biology requires the assembly of 

individual chemical constructs into a larger chemical system that displays the 

natural, functional properties of a living system such as sustained metabolic 

activity, cell synthesis, and genetic evolution. Most recently, the term synthetic 

biology has been adopted by an engineering cohort to define the process by 

which natural biological molecules (enzymes, DNA, proteins, and so forth) 
589 Bio-IInspired IInnovation and ovation and NNational SSecurity 

are extracted from living systems and defined as basic building blocks to be 

reassembled in unnatural order and environments to create novel “devices 

or machines” that perform specific, predictable functions that may or may 

not be found in natural biological systems. This engineering approach differs 

significantly from systems biology in that the individual biological constructs 

most suited to constructing a device are those units that act independently 

in contributing to the whole: the whole can be predicted from the sum of its 

individual parts. 

Artificial Cells 

The unit of life is the cell, the smallest entity capable of displaying attributes 

associated with the living state: growth, metabolism, stimulus response, and 

replication. Even the simplest of cells (for example, prokaryotes) possess 

and utilize highly integrated networks of chemical reactions. Despite great 

diversity in form and function, all cells share extensive biochemistry. How 

many genes does it take to make a cell or, beyond that, a network of different 

cells? Important insight can be gleaned from the smallest known genome 

for an independently replicating organism, that of Mycoplasma genitalium. 

M. genitalium DNA consist of 517 genes, in contrast to 30,000 genes in the 

human genome. Thus, there exists a broad hierarchy of cell complexity as well 

as component processes to borrow and engineer into artificial systems. 

A number of advances in fields such as evolutionary biology, synthetic 

biology, and nanotechnology have made it possible to contemplate the 

development of acellular networks of synthetic genetic circuits (Xcells). 

In conception, Xcells would be nonreplicating compartments genetically 

programmed to process information, make decisions, and carry out reactions, 

and would network with one another to form artificial ecologies (Xcologies) 

that would in turn perform higher order parallel and even emergent tasks. 

Some of the advances that make possible Xcell and Xcology development 

include the explosion of knowledge about systems and synthetic biology, and 

the robust development of acellular biotechnologies. Furthermore, there 

is much precedent for formation of acellular supramolecular complexes of 

nucleic acid, either DNA or RNA, encapsulated in a protein coat and, in 

some instances, surrounded by a membrane envelope (that is, the viruses). 

Although viruses are not alive, they represent supramolecular assemblies that 

act as parasites of cells, underscoring the functional “culling out” of specific 

cellular processes, albeit within the confines of living cells.

Systems biology is the integration of the many different levels of 

knowledge (genomics, proteomics, metabolomics) about cells and organisms 

to gain a global understanding of function. The informatics tools for systems 

biology, including databases such as Genbank and the Kyoto Encyclopedia 
Abiotic Sensing 59

of Genes and Genomes and analytical tools such as Cytoscape, now make 

possible the ready visualization and analysis of virtually any set of pathways, 

natural or contrived. 

As a counterpart, genes, proteins, and functionalities are becoming 

increasingly fungible real-world entities that are being engineered as 

synthetic biology “parts,” such as BioBricks, that can be readily put together 

in novel synthetic genetic circuits. The modularity of synthetic biology 

parts is useful not only for creating circuits in vivo but also for generating 

tools and pathways in acellular systems. The modularity of many BREs has 

become increasingly apparent from basic research into signal transduction 

and biotechnology explorations of directed evolution. Many cellular receptors 

and signal transduction enzymes can already be readily “rewired” to take 

on new functions. For example, Wendell Lim and coworkers have retasked 

the yeast mating pathway to generate osmoresistance, as opposed to mating 

type changes,15 and new receptors can be created almost at will by directed 

evolution techniques such as phage display, cell surface display, and Systematic 

Evolution of Ligands by Exponential Enrichment. 

Other processes necessary to support BREs and signal transduction 

pathways can now be brought together in an acellular milieu. As a result of years 

of product development in molecular biology, complex biological reactions such 

as transcription and translation can now routinely be carried out efficiently in 

vitro. Moreover, in vitro transcription, translation, and other cellular machines 

can be ensconced within in vitro compartments that resemble cells.16, 17 

While it may be possible to standardize synthetic circuits in the context 

of a minimal biological cell, another more visionary approach is to generate 

a cell-like compartment that could reproducibly and programmably support 

Xcells. Several elements might be considered in Xcell approaches:

• Beyond the in vitro compartmentalization methods so far cited, it 

may be possible to design and evolve self-amplifying or self-selecting 

genetic circuits completely within an Xcell18 and to harness these to 

robust extracellular energy generating and harvesting systems for 

biology that have become available as a result of years of bioprocess 

development in industry.

• The boundaries of the Xcell can potentially be much more robust 

and more functional than conventional membrane-based vesicles or 

liposomes, due to intense efforts in nanotechnology and drug delivery 

that have led to the generation of “smart” materials and particles that 

are interactive with their environments. For example, it has now proven 

possible to create “double emulsions” in which dispersed water droplets 

are further compartmentalized and moved to aqueous environments, 
601 Bio-IInspired IInnovation and ovation and NNational SSecurity 

much as the bilayer allows cells to have an aqueous interior and 

exterior.19 Moreover, by using surfactants with “tails” that can be 

photopolymerized, it should be possible to encapsulate individual 

droplets into hard shells and actually make “sheets” or films of droplets, 

much like colonies on a Petri plate. Alternatively, organotypic matrices 

such as hydrogel lattices or nanoporous materials might be used for the 

encapsulation or immobilization of genetic circuits. 

• Finally, efforts have led to methods for chemical, photoluminescent, 

and electronic signaling between small, independent biological or 

physical units. Transduction between biological recognition elements, 

signal transduction pathways, and signaling modalities sets the stage for 

the abiological networking of Xcells into Xcologies. Networked Xcells 

could evolve adaptive and emergent behaviors, similar in character to 

either molecular “predator-prey” systems 20 or to cellular automata.

The development of an Xcell will involve integration of all of these 

disparate advances: an Xcell must be an encapsulated compartment in which 

chemical or light energy is captured and used for biopolymer synthesis. 

The biopolymers must be capable of processing signals, sending signals, 

and performing programmed tasks based on communication with their 

environment. Communication between Xcells should lead to the competitive 

development of Xcologies that can perform a particular task or task set.

Beyond the technical achievements that will emerge from this program, 

there are fundamental scientific advantages to positing the development of 

Xcells and Xcologies, not the least of which is that it will better illuminate 

fundamental biological principles of living systems. Currently, the only 

example of living systems is cell-based, and there is no agreed upon or even 

self-consistent definition of “life” or its properties. By providing an example of 

a programmable, acellular ecology, this largely philosophical problem is deftly 

avoided and engineers can begin to understand what principles and practices 

are most suited to adapting living systems and their mimics to military tasks. 

Beyond this advantage, having one example of a programmable Xcell will 

allow engineering standards to finally be set in place for further development. 

While explorations of synthetic biology have not so far yielded anything 

equivalent to very large scale integration, it seems likely that the production 

of Xcell circuitry will engender a revolution similar to the one that occurred 

in electronics in the early 1980s.

Natural Proteins as Engineering Units

Proteins exhibit a wide diversity of physical and catalytic properties. The 

question of whether enzymes involved in known metabolic pathways can be 
Abiotic Sensing 61

isolated and reassembled as basic building blocks to generate new pathways 

has been pursued for several decades. Recombinant DNA technology has 

significantly aided the ability to pick and choose enzymes from various 

organisms and then direct their reassembly into a single organism, hence 

conferring the ability to synthesize an unnatural product in the host 

organism.21 Here, bacterial strains are genetically engineered by inserting 

genes for various synthetic steps in the metabolic pathways from several 

different microorganisms into the host. A strain of E. coli, for example, 

has been developed that can synthesize an isoprenoid precursor for the 

antimalarial drug artemisinin using enzymes assembled from three different 

microorganisms.22 Genes from two other organisms were introduced into the 

R. eutropha bacterium to produce a copolymer from fructose.23

Genetic Regulation and Signaling Pathways 

A prime example of modularity in biological systems is evident in genetic 

regulatory and signaling pathways, where combinations of proteins can 

function as molecular switches affecting gene expression and ultimately the 

phenotype. Thus, the “wiring” of the many signal transduction pathways is 

based upon particular protein domains, present in transduction proteins that 

bring components of signal transduction pathways together. Here, ligand 

binding, chemical reactions, or the physical translocation of a component 

generates an event that can serve as an input for another switch.24, 25 Using this 

approach, synthetic circuits have been synthesized that show AND and OR 

logic gating based on ligand input.26, 27, 28 An artificial oscillatory network has 

also been constructed from three transcriptional repressor systems that are not 

naturally paired in any biological system,29 and a molecular automaton that 

plays tic-tac-toe against a human has been designed based on 23 molecular 

scale logic gates using deoxyribozymes as the building module.30

Signal-transduction pathways have many common functional/

architectural elements and hierarchical structure enabling the creation of 

“plug and play” signal transduction cassettes that can be incorporated into 

acellular systems (for example, ANTS). Due to their simplicity, microbes 

represent a source from which much can be borrowed for purposes of 

engineering acellular networks. Microbial quorum sensing is responsible 

for a variety of phenotypes and is rich in diversity and modes of action. As 

such, quorum sensing represents a “guide” for learning how signals can be 

translated to altered phenotype(s) as well as for designing of useful acellular 

prototype signal transduction networks. Quorum sensing may be the 

foundation upon which the more sophisticated intracellular communication 

found in higher order organisms has evolved. If this is the case, methods that 

incorporate native signaling architecture may be engineered for acellular 
623 Bio-IInspired IInnovation and ovation and NNational SSecurity 

network purposes, exerting greater control with less collateral damage to 

other resident, nontargeted processes. 

Although there have been few technological or commercial applications 

derived directly from adapting or rewiring the quorum sensing signaling 

process, metabolically engineered signaling modules have been constructed 

to alter phenotype giving rise to recombinant gene products.31, 32 For example, 

Bulter et al.33 created an artificial genetic switch using acetate for modulating 

cell to cell signaling in Escherichia coli. Neddermann et al.34 developed a hybrid 

expression system by incorporating the quorum circuitry of Agrobaterium 

tumefaciens into a eukaryotic transcriptional controller for HeLa cells. Weber 

et al.35 implanted the Streptomyces bacterial QS system for tuning heterologous 

protein expression in mammalian cell culture and mice (human primary and 

mouse embryonic stem cells). 

The molecular basis by which quorum sensing works varies among 

different species, both in the synthesis of the signaling compounds and in 

the modes of their perception. However, this diversity affords a vast array of 

potential acellular applications—the types of rewired systems for achieving 

specific outcomes can vary greatly and are limited by imagination and 

ability to abstract regulatory features and reconstruct them into modular, 

transplantable controllers. There are also many modes by which the regulatory 

function is translated into altered gene expression. Most of the wellstudied systems modulate protein transcriptional regulators. Additionally, 

there is also evidence that small RNAs are involved as riboregulators, and 

posttranscriptional regulation has been linked to quorum sensing systems 

and quorum sensing signal transduction.

Devices

A device is construed from decomposition of a system into basic functional 

parts that perform physical processes. Devices process inputs to produce 

outputs by performing metabolic or biosynthetic functions and interface 

with other devices and the environment. Devices can represent one or more 

biochemical reactions involving transcription, translation, ligand/receptor 

binding, protein phosphorylation, or enzymatic reactions. Devices can be 

composed of few reactants (for example, a protein phosphorylation device 

consists of a kinase and substrate), or multiple reactants and products (for 

example, a regulated gene, transcription factors, promoter site, and RNA 

polymerase compose a transcriptional device). Devices can be extracted 

unaltered from nature, such as transcription factors and promoter of a 

regulated gene, or by modifying biochemical reactions. Transcription or 

translation control devices are controlled by the specificity and efficiency of 

nucleotide interactions and are relatively easy to build based on the specified 
Abiotic Sensing 63

order of the reaction. Transcriptional control systems have been employed 

for signal amplification, control of downstream devices, and multifactorial 

control by multiple transcription factors.36, 37, 38 While transcription and 

translational devices are fairly easy to connect and can offer great logical 

complexity, changes in output are relatively slow (minutes) and consume a 

large amount of cellular resources to support the protein synthesis events that 

mediate the output.

Devices employing protein-ligand or protein-protein interactions have 

different input-output characteristics and usually require more complex 

modification of their natural substrates. Protein switches have been been 

created by inserting allosteric domains into existing enzymes, replacing protein 

domains randomly followed by directed evolution, or using computational 

chemistry to model receptor binding sites and selectively mutate key residues 

to confer altered activity. Multiple examples exist of modifying proteins/

enzymes to significantly alter their ligand/substrate response and serve as the 

initial input device for extended metabolic cascades.39, 40, 41, 42, 43 Designing and 

building protein interaction devices carry several caveats. The proteins must 

be well characterized to allow the designer to determine where deletions, 

additions, or replacements of key domains should or can occur so as not to 

negate the protein’s 3–D structure that plays a critical role in protein interactions. 

Connecting protein devices also poses more difficulty than connecting 

translation/transcriptional devices. Protein devices must be well matched and 

one must validate that information transfer between devices is predictable and 

reliable. The benefits of protein interaction devices are that output is very fast 

(output in sub-second timescale), signals can be readily amplified by other cell 

reactions (that is, kinases and enzymes), and proteins can mediate repeated 

interactions while consuming nominal cellular resources. 

Modules 

A module is defined as a distinct set of individual devices with well-defined 

interconnections and functions that can perform a more complex task than 

a device. In the natural cell, modules are defined in the form of pathways, 

such as a metabolic or signal transduction pathway. Synthetic biology seeks to 

understand and establish the rules of composition whereby the function of a 

whole pathway can be derived from the additive function of each component 

part, which can be engineered as a device. Constructing modules from wildtype devices found in naturally occurring systems is rarely successful, since 

evolution has already selected wild-type devices to perform optimally in 

their natural context. Modeling and rational mutation of devices have proven 

effective in altering wild-type devices to properly interact with each other when 

combined into a module function, as long as the properties of the individual 
645 Bio-IInspired IInnovation and ovation and NNational SSecurity 

devices are well known. In the absence of well-known characteristics of a 

device, where rational mutation of selected sites would be expected to yield 

improved properties, directed evolution has proven useful in optimizing 

device and module functionality. The onus of directed evolution is having 

some a priori idea of which features of the system need to evolve and being 

able to apply selective pressure toward those criteria.

Synthetic transcriptional regulatory networks are the best characterized 

modules created to date and include cascade, feed-forward, and feedback 

motifs. Cascade modules generally generate a steady-state output that is 

monotonic to its input, though physical variations have shown their ability to 

control temporal sequencing of gene expression and the ability to attenuate 

gene expression noise. Two feed-forward transcription modules have been 

constructed and allow for a transient non-monotonic response to a step-like 

stimulus. Incoherent feed-forward modules accelerate response to the stepup in stimulus, but not the step-down. Coherent feed-forward modules delay 

response to the step-up in stimulus, but not the step-down. These constructs 

have yielded modules that can function as persistence detectors, delay 

elements, and pulse generators, which conceivably could be used to construct 

parallel circuits to carry information at different rates.44, 45, 46 Applying regulatory 

feedback to a module can provide state and memory functions. Positive 

feedback produces bistability, while negative feedback can yield oscillation. 

Genetic “toggle” switches and various oscillators have been produced using 

regulatory feedback designs.47, 48, 49

Synthetic protein signaling modules have focused on modifying and 

assembling signal transduction devices. Synthetic metabolic networks use 

transcriptional and translational control elements to regulate the expression 

of enzymes that synthesize or break down metabolites. Here, metabolite 

concentration serves as an input for other devices. In the most publicized 

demonstration of this approach, Martin et al. transplanted the entire 

mevalonate isoprenoid pathway for synthesizing isopentyl pyrophosphate 

from S. cerevisiae into E. coli, which, when coupled with an inserted synthetic 

amorpha-4, 11-diene synthase produced the precursor to the antimalarial drug 

artemisinin. Artificial circuits have also been demonstrated where metabolic 

pathways have been connected to regulatory proteins and transcriptional 

control elements.50

Two major metrics of success in constructing functional devices and 

modules in synthetic biology are predictability and reliability, where the system 

performs the function it was designed to and it performs that function at the 

expected level of fidelity each time. It is prudent to consider that functional 

modules will typically reside in a cell environment that is subject to a range of 

biological uncertainties and cell “noise” stemming from other cell functions/
Abiotic Sensing 65

processes. Synthetic biology does not demand that cells behave perfectly, only 

that a significant number of the cell population performs the desired task. 

Design and fabrication methods that account for this uncertainty will greatly 

facilitate the on-demand engineering, versatility, and robustness of biological 

devices and modules. 

Synthetic Organelles 

Nature provides exquisitely refined and accurate capabilities that are thus 

far impossible to recreate in abiotic structures, two of which are ultra-highresolution recognition and the assembly of multicomponent enzymatic 

complexes. Such processes can be mimicked using abiotic structures, creating 

a generic, bioinspired enzymatic technique that enables the template-directed 

synthesis of a biochemical pathway within a compartmentalized abiotic 

multicomponent macromolecule. 

The targeted assembly of proteins is an essential aspect of life. Within a 

cell, protein assembly is often directed through the compartmentalization of 

individual proteins into specific organelles or membranes. Compartmentalization 

provides a method for concentrating and therefore enhancing the assembly 

of functional macromolecular structures, such as the multicomponent light 

harvesting structures found in chloroplasts or the transcriptional complexes 

located in the nucleus. In almost all cases, specific signal peptides direct this 

targeted compartmentalization within a cell. 

Signal peptides are generally short, 3 to 60 amino acids in length. Each 

class of signal peptide interacts with an organelle-specific protein to facilitate 

its import and/or retention. Using this process as a model, engineered signal 

peptides could be used for the bioinspired compartmentalization of proteins 

within molecularly imprinted polymers. Molecular imprinting is a technique 

that creates synthetic materials containing highly specific receptor sites having 

an affinity for a target molecule. Three-dimensional cavities are created within 

a polymeric matrix complementary to the size, shape, and functional group 

orientation of the target molecule. The size and shape of the cavity allow the 

target molecule or similar molecules to occupy the cavity space, while the 

functional group orientation within the cavity will preferentially bind in 

specific locations to only the target molecule and not to similar molecules. 

Molecular imprinted polymers (MIPs) can mimic the recognition and binding 

capabilities of natural biomolecules such as antibodies and enzymes. MIPs 

have several advantages over natural biomolecules, such as modular synthesis 

that can provide functional hydrogels in high yields and selectivities. 

The MIP hydrogel can be treated like a cellular organelle that could 

be engineered to bind specific signal peptide sequences. Thus, in order to 

compartmentalize any set of proteins into the MIPs, one would need to attach 
667 Bio-IInspired IInnovation and ovation and NNational SSecurity 

a specific signal sequence to them in order to mimic enzymatic chemistry 

inside the imprinted hydrogel. This method, if successful, would have the 

benefit of being universal—that is, any set of proteins could be assembled 

as long as they contain the right signal peptide. Thus, the potential to do 

multicomponent enzymatic chemistry directly in the hydrogel would be 

considerably higher. Additionally, MIPs could be imprinted with multiple 

tags, perhaps even patterned in some way to create a desired network. By 

arranging the spatial configuration of enzymes in an MIP cavity, one may 

be able to alter product specificity, much like reengineering the active site in 

directed evolution studies. To accomplish this, it is necessary to make signal 

peptides of specific geometries that, when imprinted into a polymer hydrogel, 

can later be recognized for assembly of a multiprotein complex.

Materials for Membranes and Support 

One of the challenges will be to select and develop appropriate technologies 

for the environmental interface, support structure, and/or membranes within 

and through which the functional components work. Because the functional 

components are the heart of the system, the specifics of these supports need to 

be tailored to the structure and function of the components, yet the successful 

interactions of the components are likely to be at least partially dependent on 

the membranes and support materials. Thus, it is essential to take a holistic 

approach and address promising membranes and support technologies that 

could support any of a number of likely scenarios. This will provide the 

agility to construct an encapsulation and support system appropriate to the 

functional technologies as they develop and mature. 

During the development of the functional components, there will 

be the need for testing and integrating well before technologies are fully 

downselected. In fact, these tests and integration experiments will be an 

integral part of the downselect process. Using an agile approach to materials 

technology will facilitate these evaluation steps and maximize the potential 

for each technology. 

Biotic Sensors 

Historically, one of the failing points of biotic sensors was the environmental 

needs associated with maintaining cell viability. In general, biochemical 

activity is carried out in aqueous solutions that make it incompatible with 

long-term unattended operation in real-life scenarios. Abiotic functional 

components of ANTS may share some of these issues, depending on the 

fidelity with which the abiotic synthesis mimics natural biology. The matrix 

materials will need to address the range of environmental dependence and 
Abiotic Sensing 67

consider the possibility of hybrid matrices to address different levels of 

dependence within one sensor. This poses several scenarios:

• The functional components are subject to the same or equivalent 

environmental requirements as their biological homologues and require 

the same or equivalent through-membrane and intracellular mobility. 

• The functional components are not dependent on environment but do 

require through-membrane and intracellular mobility.

• The functional components neither depend on the environment nor require 

through-membrane mobility, but they do require intracellular mobility.

• The functional components depend on neither the environment nor 

intracellular mobility, but they do require through-membrane mobility. 

Historically, biotic sensors were based on living cells or tissues, and 

the morphology of these cells and tissues was fixed by nature. In contrast, 

the ANTS morphologies will be driven by functional aspects of how the 

evolved system is to be deployed, operate (functional components), and 

communicate. The morphology issue will have some bearing on appropriate 

matrix material, while again the matrix material requirements of the 

functional components may partially dictate the available morphologies and 

deployment/communication options. This situation will also benefit from the 

holistic approach.

Recognition, transduction, and associated devices will be evolving 

concurrent with the evolution of an appropriate support matrix. The purpose 

of the support matrix research is two-fold; first, to provide appropriate 

materials in which to study evolving synthetic biology products and, second, 

to work toward hardened materials that include both functionalized and 

support aspects, tailored to the abiotic cell product.

Research will begin by supporting BRE research at the current state of 

the art. Initial goals will be to rapidly provide matrices in which early BREs 

and transduction devices can be studied. For these purposes, we will build 

on existing technologies associated with channel-based sensing, starting with 

lipid bilayers and suspended liposomes. Stabilization of these “conventional” 

membranes using nanoparticle technology will be investigated for three 

purposes: to extend the viability of these membranes to allow temporally 

extended experiments on device function; to elucidate fundamental facts 

concerning the distinction between lipid-suspended particles and lipidwetted agglomerates (that is, at what particle loading does a liposome lose 

its properties vis-à-vis BRE functionalization and how do these limits affect 

device function); and to determine whether nanoparticles can function as 

rafts in a lipid bilayer system. The results of this stage of research are unlikely 

to result in a hardened matrix for a final product; they will facilitate synthetic 
689 Bio-IInspired IInnovation and ovation and NNational SSecurity 

biology work toward the required devices and may provide essential parts of 

an inhomogeneous or layered “cell.”

Beyond the fragile lipid-based matrices are supported membranes, 

hydrogels, and chitosan products. All of these approaches have been used in 

conjunction with synthetic biology or related research and all provide some 

stability advantage over simple lipid membranes or liposomes. Hydrogels 

and supported membranes are likely to provide the “breadboards” for device 

development and integration, while the unique properties of chitosan make 

it a likely candidate both for use in evolving breadboard systems and as a 

component in hardened cells. 

Moving toward Xcells hardened against the environment and 

suitable for incorporation into myriad military systems, membrane and 

matrix support directions will need to be tailored to evolving functional 

components. At this stage, the rapid advances in directed and self-assembly 

will be investigated as manufacturing tools, while materials including porous 

inorganics, polymerosomes shells, chitosan, cellulosic materials, and aerogels 

will be considered for their advantageous properties. Structure analysis is 

expected to be a central part of this research, along with functionalization and 

device interface. Hybridization of materials to provide an appropriate mix of 

properties is likely to be required where assembly technology alone cannot 

provide the necessary functions in homogeneous materials.

Chitosan 

Individually, biotechnology and microelectronics revolutionized our ability 

to detect and communicate threats. Biotechnology provides the tailored 

biological components to recognize threats to specific physiological targets. 

Microelectronics provides autonomous devices that are cheap, robust, 

and small and that offer data and signal processing capabilities for nearinstantaneous communication over vast distances. Coupling biotechnology 

and microelectronics will allow unprecedented capabilities for recognizing 

and responding to a plethora of threats, but this coupling will require the 

seamless integration of biological components into microelectronic devices.

Biology and microelectronics communicate through markedly different 

signaling modes. Electronic devices signal through the flow of electrons or the 

transmission of light, while biology signals with ions (for example, Na+, K+, 

and Ca2+) and molecules (such as hormones and neurotransmitters). Bridging 

this communication gap is essential to fusing the individual strengths of 

biology and electronics. 

Chitosan possesses unique properties that enable it to interconnect 

biology and devices.51 Chitosan can be “connected” to device addresses because 

the pH-responsive film-forming properties of this aminopolysaccharide 
Abiotic Sensing 69

allow electrodeposition in response to localized electrical signals.52, 53 

Chitosan’s electrodeposition is spatially54 and temporally55 selective, while 

the electrodeposited films are stable in the absence of an applied voltage. 

Chitosan can be “connected” to bio-components (for example, nucleic 

acids,56 proteins,57, 58, 59 and virus particles60) in two different ways—chitosan’s 

nucleophilicity facilitates covalent conjugation,61 while the electrodeposited 

film can entrap nanoscale components (such as proteins).62 Thus, chitosan 

allows device-imposed electrical signals to guide the interconnection of 

biological components to devices.63

In addition to enabling biodevice interconnection, chitosan possesses 

properties that allow biological signals to be transduced into signals readily 

processed by common devices. Specifically, chitosan films are permeable to 

ions and small molecules allowing signaling through electrical modes.64, 65 

Further, chitosan films are transparent, which facilitates signaling through 

optical modes (for example, through integrated waveguides).66 Finally, 

chitosan films are stimuli-responsive, enabling mechanotransduction.67 Thus, 

chitosan can icrosyste environmental stimuli into multiple signaling modes.

Power 

Biological systems operate on energy transductions in the mitochondria. 

That is, the energy powering the cells is derived biochemically. In the case 

of an abiotic system performing selected cell-like functions and modeled 

almost exclusively on biotic cell architecture, the biochemical approach 

will provide the most directly usable form of energy. It will be necessary to 

first develop complete understanding of the energy transfer to, and energy 

use by, the cell functions being duplicated in the abiotic system. In order to 

duplicate the energy-producing biochemical functions in the abiotic cell, one 

must determine energy requirements of the abiotic system, develop chemical 

reactions that are triggered by recognition events, and couple that energy to 

the signaling event. These small-scale energy requirements differ markedly 

from traditional power and energy issues faced by macroscopic and even 

mesoscopic equipment. 

On the small scales associated with cell function, whether artificial 

or biotic, it is possible to consider energy on the basis of thermodynamics 

of individual molecular interactions. In the simplest of terms, some will 

require energy and some will release energy. In a living eukaryotic cell, ATP is 

synthesized from ADP and Pi

 and oxidative phosphorylation involving input 

energy derived from dissipation of a proton gradient or electrical potential. 

However, this is not the only source of ATP generation. Phosphorylation of 

ADP to ATP is also observed coupled to oxidation via thioester intermediate 
701 Bio-IInspired IInnovation and ovation and NNational SSecurity 

formation and dehydration reactions resulting in generation of enol phosphates 

that have high phosphoryl transfer potential as typified by the two ATP generating 

steps in Glycolysis. It is noteworthy that the above two reactions represent the sole 

source of de novo synthesis of ATP in the red blood cell. Thus, engineering of 

circuits involving the respective glycolytic enzymes which are cytosolic (soluble) 

within a compartment could serve as source of ATP generation for other ATP 

requiring circuits as long as a few key metabolites (3-Phosphoglyceraldehyde, 

NAD+

, Pi, and pyruvate) were provided the system. A lactate dehydrogenase 

“recycling” circuit can even be included to recycle reduced NAD+ (that is, NADH) 

as well as pH control. Therefore, acellular “substrate level phosphorylation” 

circuits are well within reach due to the soluble nature of this system and its not 

requiring elaborate membrane bound oxidative phosphorylation functions (that 

is, electron transport). Thus, in an abiotic system adopting cell-like functions, 

the energy required to drive these functions can be engineered to include such 

functions and capabilities. Substrate phosphorylation alluded to above constitutes 

a recognition event resulting in a thermodynamically spontaneous reaction that 

can supply enough power for subsequent signal transduction events. 

Additionally, an external energy source can be coupled to a catalytic 

wheel and provide the activation energy for ion pumping.68 Understanding 

biological energy balances and duplicating them in abiotic systems is a 

promising approach to powering the cellular functions mimicked in an abiotic 

cell. The goal in the case of an abiotic cell is to use elegant thermodynamic 

design as well as partitioning of the reactions involved in recognition, 

signaling and transduction, taking advantage of catalytic enzyme activity, 

substrate binding, and conformational events.

Although ideally the cells would “find,” convert, and use energy on 

an as-needed basis, in the practical use of power, storage requirements need 

to be considered. Nanocapacitors69 have been demonstrated to be practical 

approaches to this problem and have in fact been used on the meso scale to power 

telemetry functions. In separate investigations, carbon nanotubes have been 

used to enhance the efficiency of ultracapacitors. The possibility exists through 

combined technologies to develop a nano-enhanced nano-ultracapacitor to 

store and supply energy converted from environmental solar or thermal energy.

In a living system, interactions between the organism and the environment 

typically involve cooperative functioning of many cells. In the special case of 

single-cell organisms, these interactions are either limited by or dependent on 

the multiplicity of organisms—that is, bacteria respond to their environment by 

multiplying and affect their surroundings by the cooperative effects of many cells.

In the case of abiotic unicellular systems, it is likely that the energy 

requirements for signal amplification and communication to macroscopic 

indicators or telemetry will not be served by simulated biochemical energy. It 
Abiotic Sensing 71

is also an undeniable fact that biological systems, efficient though they are, do 

require a certain amount of “input” fuel, and it may not be possible to load an 

abiotic cell with sufficient fuel to support functioning throughout its lifetime. 

For these situations, alternate energy sources must be considered.

With the expanding volume of research in nanotechnology and 

microelectromechanical systems, there have been significant strides in the 

areas of nanocapacitors, nanowires, nontraditional solar photovoltaics, 

thermal photovoltaics, and biomimetic solar energy conversion. These, 

combined with conductive polymer technology and recent successes in 

the area of molecular switching, provide ample technology for powering 

and controlling signaling and telemetry operations in an abiotic cell. For 

these requirements of tailored application of nontraditional but universally 

applicable power sources, we will rely on the research and technology 

advances of existing energy and power programs. 

The level of amplification of the desired signal and the process of 

telemetry are not native functions of typical biotic cells, and it will be necessary 

to link the cell signal to a non-native cell function. This may be achieved by 

the use of nanowires and nanoswitches. A use of nanowires to detect events 

in single cells has been demonstrated for the case of live neuron activity and 

photon activity.70, 71 Biological molecules have been identified that operate as 

molecular switches, and the switching mechanisms have been demonstrated 

up to and including the complexity of a 4-way switch.72 

Harnessing of ubiquitous environmental energy to power amplification 

and telemetry will be essential to a self-maintaining system. The two most 

amenable sources of power for these applications are solar and thermal, 

and the energy conversion processes of photosynthesis can be mimicked 

abiotically.73 Like the mitochondrial-based oxidative phosphorylation 

systems, photosynthetic systems also utilize a proton gradient in oxygenic 

photosynthesis. There are numerous photosynthetic bacterial systems from 

which abiotic circuit components can be modeled. Solar photovoltaics based on 

nanoparticles have been demonstrated at the macro scale and in fact are mature 

to the level of commercialization. Engineering these materials to a smaller scale 

has not been reported, although this is likely an artifact of the phenomenon that 

the challenge in solar energy is to scale up rather than down. Likewise, novel 

thermal photovoltaic systems are under investigation on the nano scale.

Signal Transduction 

A transducer is a device that converts information from one domain to the other. 

Any analytical measurement is a series of conversions from nonelectrical and 

electrical domains. Understanding the data domains involved in a particular 
723 Bio-IInspired IInnovation and ovation and NNational SSecurity 

sensing operation can help in understanding its operation, applications, 

limitations, and adaptability. Information through a transduction event 

could be encoded as the magnitude of an electrical signal, continuous in 

both amplitude and time (analog); signal fluctuations around a threshold; or 

as a simple two-level system (ON or OFF). Biological recognition elements 

can translate information about target analyte concentration directly into a 

mechanical signal (for example, shape change74, 75 or change in pore size),76 

optical signal, another molecule or ion more easily sensed, or directly into an 

electrical signal. Research is needed in these areas to determine the tradeoffs 

of each approach and to determine where technologies can be combined for 

greater effect.

Conclusion 

It is clear that a biomimicry approach in which one designs an artificial 

organism that possesses all of the key receptors and metabolic machinery 

required to detect and respond to toxicants in the external environment 

would address the needs of biological and chemical detection for military, 

medical, environmental, and industrial process control applications. It is also 

clear that advances in receptor biochemistry, synthetic and systems biology, 

metabolic engineering, bioinformatics, protein-protein and protein-surface 

interactions, and micro-manufacturing technologies have reached a point 

where it would be possible to design a completely synthetic and intelligent 

sense and respond system. 

Notes

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3 The National Science Foundation has established a Center for Biosurfaces at the State 

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Abiotic Sensing 73

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77

The focus of this chapter will be on biosensors and bioelectronics and 

the relevance to Department of Defense (DOD) applications. The 

overwhelming majority of the current biosensors market is made up 

of glucose monitors that are used by diabetics for monitoring blood sugar, 

but medical applications will not be covered here. Since understanding 

the biorecognition and transduction processes is critical to understanding 

biosensors, extensive discussion of these topics is included. Bioelectronics 

is an exciting new field that brings together multiple disciplines of science 

including biology, chemistry, physics, engineering, and material science. New 

and emerging bioelectronic research areas that have the potential to impact 

future DOD operations and applications are also introduced in this chapter. 

Biosensors 

A biosensor is a self-contained integrated device that is capable of providing 

specific quantitative or semi-quantitative analytical information using a 

biological recognition element (biochemical receptor) that is retained in direct 

spatial contact with a transduction element. However, a common working 

definition is that a biosensor is an analytical device that uses biological 

macromolecules to recognize an analyte and subsequently activate a signal 

that is detected with a transducer. Some authorities subdivide biosensors into 

affinity biosensors and catalytic biosensors based upon the activity of the 

biorecognition element. Thus, affinity biosensors have as their fundamental 

property the recognition (binding) of the analyte by the biorecognition 

element (for example, antibody-antigen), whereas catalytic biosensors have 

chapter 6

Biosensors and Bioelectronics

Dimitra Stratis-Cullum and James Sumner
789 Bio-IInspired IInnovation and ovation and NNational SSecurity 

as their biorecognition element proteins (or microorganisms) that not only 

bind the analyte but also catalyze a reaction involving the analyte to produce 

a product (for example, glucose biosensors). 

Ideal Biosensor Characteristics 

In many cases, biosensors are single use, although for many applications 

regeneration is desirable. The ideal biosensor is frequently described as being 

robust, selective, reproducible, and sensitive with a large dynamic range, an 

ideal that is seldom attained. Bioanalytical systems such as immunoassay may 

well use the same elements (that is, bioreceptors, transduction devices) but 

require additional processing steps such as reagent addition and washings, 

and usually involve reading the completed assay on some separate piece of 

instrumentation. These are to be distinguished from biosensors. Thus, a very 

large volume of related literature exists on the use of immunoassays, nucleic 

acid–based assays, and so forth for detection of various analytes where 

the techniques described in such assays may well have applications to the 

development of actual biosensor devices. 

Assay Formats 

In general, a variety of assays can be employed with the many different 

biorecognition and transduction elements described below. Assay formats 

can be either direct or indirect. In the direct methods, analyte binding to the 

biorecognition element is detected directly by such techniques as mass changes, 

changes in refractive index or impedance, pH, and so forth. For indirect 

techniques, an additional reaction (other than the biorecognition binding 

event) has to occur in order to detect the binding of analyte and bioreceptor. 

Another type of assay format is a competitive but indirect strategy where the 

analyte and a competitor molecule (labeled in some fashion) compete for 

limited numbers of biorecognition binding sites. There is also a noncompetitive 

indirect assay format in which a second biorecognition element with a label is 

added to the analyte sample, so that signal is only generated when the analyte 

binds to the immobilized biorecognition element and the second biorecognition 

element also binds to the analyte. For the indirect type of assay, the label can 

be optical-, electrochemical-, or mass-related. In the case of direct assays 

and noncompetitive indirect assays, the signal is directly proportional to the 

analyte concentration, while in the case of competitive indirect assays, the 

signal is inversely proportional to analyte concentration. Frequently, biosensor 

assay formats involve some form of amplification, the rationale for this being 

increased sensitivity of the assay. Either the analyte molecules themselves may be 

amplified (for example, polymerase chain reaction [PCR] of DNA sequences) or 

the biorecognition event may be amplified (for example, ELISA immunoassays). 
Biosensors and Bioelectronics 79

Applications 

Bacterial Biosensors for Environmental Monitoring 

Several types of biosensors can be used for environmental monitoring 

applications, but whole cell bioreporters that respond to certain pollutants/

toxicological conditions are beginning to find favor in environmental 

sensing. Applications range from detection of contaminants, measurement 

of pollutant toxicity, monitoring of genetically engineered bacteria released 

into the environment, and even uses for detection of stresses such as ionizing 

radiation and oxidative damage. In general, such whole cell sensors should 

not be called biosensors unless the cells are integrated somehow into a 

standalone sensing/transduction/readout system. Some whole cell sensors 

use genetically engineered bacteria into which a lux gene construct (coding 

for an active luciferase) are under the control of an inducible promoter. The 

general sensing strategy is to put the luciferase construct under control of a 

promoter that recognizes the analyte of interest, although in some cases, the 

bioreporter organism can be engineered to respond to many analytes (broad 

specificity) by using a heat-shock promoter. 

For example, the seminal work in this arena described a naphthalene 

biosensor organism (genetically engineered Pseudomonas fluorescens) 

that detected the bioavailability of naphthalene (serving as a surrogate for 

polyaromatic hydrocarbons) and salicylate in contaminated soil by induction 

of the lux reporter, and subsequent bioluminescence as a result of expression 

of the reporter gene. The naphthalene biosensor described above is an example 

of a catabolic bioreporter. Catabolic bioreporters produce luminescence only 

in the presence of a specific contaminant, since the lux genes are linked to a 

degradation pathway promoter. 

Metabolic bioreporters, on the other hand, have reporter genes 

downstream of a strong constitutive promoter, and thus luminescence 

is directly affected by toxic agents that interfere with metabolism. These 

concepts have been subsequently used to develop a variety of bioreporter 

organisms. Other investigators have used genetically engineered bacteria in 

which the green fluorescent protein, gfp (or derivatives thereof) from the 

jellyfish Aequorea Victoria, functions as a bioreporter in the same manner 

as the lux gene. Some arguments have been advanced that the expression of 

bioluminescence is a more direct bioreporter than gfp expression, since the 

expression of gfp is only detected upon excitation with the correct wavelength 

of light. However, in practical terms, bioluminescence must be quantified 

by some sort of photodetector/luminometer, so the difference between that 

and a fluorescence excitation/emission detection system seems minimal. 
801 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Beta-galactosidase enzymes have also been used as biomarkers. Others have 

used naturally luminescent bacteria (that is, Vibrio fischeri) as bioreporter 

organisms, since toxic compounds can disturb metabolic processes, thus 

causing a reduction in their bioluminescence. 

Microbial biosensors have been developed to assay biological oxygen 

demand (BOD), a value related to total content of organic materials in 

wastewater. These sensors often measure BOD by evaluating the rate at which 

microbial cells deplete oxygen. It is not possible to provide a comprehensive 

list of whole cell sensor applications in this chapter. Very seldom are these 

bioreporter organisms integrated into a complete sensing package where a 

microculture environment, integrated luminometer or fluorometer, and light 

tight-enclosure can produce a true biosensor device. 

Food Biosensing 

Food biosensing applications range from monitoring the quality of the food 

to food safety and security applications. The assessment of food quality can 

be subjective, as factors such as appearance, taste, smell, and texture may 

enter into the overall evaluation. Sensor technologies that measure specific 

parameters such as sugar content and composition, total titratable acidity 

(for example, for fruit), and specific chemicals such as glucose, sucrose, 

lactate, alcohol, glutamate, and ascorbic acid provide more objective means of 

evaluating food quality and freshness or spoilage. 

Also, quantitative detection of food contaminants, such as growth 

hormones fed to animals, antibiotics, and pesticides, is important. Testing 

for genetically modified organisms (GMOs) will probably become more 

frequent with regard to food, and some authorities expect this area to see the 

fastest growth of any testing market in the food industry. Biosensor research 

for GMO detection presently seems to be focused on DNA-based detection 

technologies. Finally, there is the issue of pathogen and/or pathogen toxin 

contamination of food. This last is of great concern because of the potential 

for outbreaks of foodborne illnesses, such as are seen periodically. Fatalities 

can result from such exposures, and recent such outbreaks have generated 

much media interest. 

There is a clear role for biosensors in many areas related to food 

quality and safety including pathogen detection in food products. Recent 

reviews of statistics regarding pathogen testing (all types of tests, including 

biosensors) in the food industry prove interesting in regard to future 

biosensor development. For example, for 1999, approximately 16 percent of 

all microbial tests in the industry were for specific pathogens, ~16 percent 

were for yeast and mold, roughly 31 percent were for coliform and E. coli, and 

~37 percent were for total viable organisms. The same statistical survey found 
Biosensors and Bioelectronics 81

that microbial testing in each of the food sectors was as follows: 36 percent 

for the processed food sector, 10 percent for fruits and vegetables, 22 percent 

for meat, and 32 percent for dairy. The U.S. food industry performed ~ 144.3 

million microbiological tests in 1999. 

Unfortunately, heavy reliance is still placed upon conventional culturing 

techniques, so there are significant time gaps between sampling for microbial 

contamination and detection of microbial contamination, and these techniques 

are often labor-intensive and require expertise in interpreting results. Other 

investigators also point out the importance of pathogen detection in the food 

industry—that is, that the food industry accounts for ~38 percent of total 

research in the field of pathogen detection.1

 The other major areas of research 

interest for biosensors are water and environment quality control (16 percent) 

and clinical applications (18 percent). In terms of research articles describing 

biosensors applied to pathogen detection, a review article summarizes a 

number of interesting points.2

Thus, of research articles concerning pathogen detection, techniques for 

detection of Salmonellae species are the most abundant (33 percent), followed 

by E. coli (27 percent), with Listeria (14 percent) and Campylobacter (11 

percent) species the other major pathogens. Legionella account for 7 percent 

of research articles discussing detection techniques, with all other bacterial 

species accounting for 8 percent. This relative abundance of research articles 

published with regard to detection schemes clearly indicates the emphasis 

upon pathogen detection for food safety. This same review also discusses some 

relevant statistics regarding detection technologies for pathogens, gleaned 

from a review of the relevant literature over the past 20 years. The most 

popular methods by far relate to culture/colony counting with PCR following 

closely behind. ELISA assays are in third place in terms of abundance, with 

biosensors following in fourth place. In the biosensor category, the most used 

techniques are optical (35 percent), followed by electrochemical (32 percent), 

piezoelectric (16 percent), and all other categories (16 percent). 

The tried and true methods of microbiology involving concentration of 

microbes from food samples; plating, culture, and growth in selective media; 

and colony counting are still the gold standard with regard to identification 

and quantification. Nevertheless, these techniques are time- and laborintensive, and there is clearly a need for rapid, low-cost techniques that 

provide automated or semi-automated pathogen analysis. Even better would 

be systems that integrate all aspects of the analysis from sampling to final 

quantitative result. Biosensors seem well suited to fill at least some of this 

niche in the food safety testing market. 

A major problem facing all such attempts to move pathogen testing 

from classical microbiological procedures to biosensor-based analysis is 
823 Bio-IInspired IInnovation and ovation and NNational SSecurity 

the issue of sensitivity. Recent literature indicates that the infectious dose of 

Salmonella or E. coli 0157:H7 is 10 organisms, while the existing coliform 

standard for E. coli in water is 4 cells per 100 milliliters. Culture methods can 

and do attain this sensitivity. From a review of recent biosensor literature that 

the authors carried out, this level of sensitivity is not achievable by most of the 

biosensor research devices currently proposed. It seems clear that biosensors 

will only see their full potential realized with regard to pathogen detection 

for food safety, when specificity and sensitivity can compare to established 

methods and such biosensors can also be cost-competitive (or cost-saving) 

with current techniques. 

Biodefense Biosensing Applications

Events of recent years have indicated the need for sensors of pathogens/

toxins that could be used by military enemies or for terrorist purposes. Much 

research effort is currently focused on analytical strategies to detect these 

agents. A major difficulty with biological attacks is actually determining in 

a timely manner whether the attack has occurred, to enable early response 

and minimize casualties. The ideal sensor for biological warfare agents 

(BWA) that could be used for attack would provide highly sensitive and 

selective identification of threat organisms in virtually real time. Also, since 

the potential release of BWA could be on the battlefield or in urban settings, 

the surrounding environment/atmospheric milieu may be highly complex 

(smoke, dust, particulate matter), and the analytical technique must be able to 

detect organisms of interest without interference from background material. 

To date, these requirements have provided a daunting analytical challenge. 

Attempts to meet this challenge have employed molecular techniques 

that can identify chemical markers of BWA. In general, detection of BWAs 

can follow one of two paths. In one, positive identification of a BWA must 

be obtained in a few hours, the so-called detect-to-treat option. Such 

detection would give medical personnel the means to successfully treat 

individuals that have been exposed to BWA. The time frame of several 

hours makes the analytical task easier than in the case with the other 

detection scenario. In this latter case, a detect-to-warn sensor must be able 

to provide a warning within a few minutes that a BWA release has occurred. 

If such sensors could be developed, then perhaps therapeutic treatment of 

all members of an exposed population might be an option. The variety of 

BWA that potentially could be used, such as bacteria (vegetative or spores, 

gram-negative or gram-positive), viruses, and toxins, adds difficulty to the 

sensing task. Specificity and sensitivity are both critical for useful BWA 

sensors. False positives are unacceptable due to the consequences attendant 

upon an assumed BWA incident. 
Biosensors and Bioelectronics 83

False negatives are also unacceptable for obvious reasons. It is true 

that nucleic acid–based biosensing technologies have been demonstrated to 

have the sensitivity to detect one organism or one spore. Also, in general, 

nucleic acid–based sensing systems are more sensitive than antibody-based 

detection systems. Such analyses, however, depend upon amplification of the 

target nucleic acid, a process that takes time (although intensive efforts have 

been and are being made to shorten this step). Further, nucleic acids from 

nonrelevant sources may interfere in PCR amplifications, and nucleic acid–

based detection will not work for toxins. Detection of BWA with extreme 

sensitivity is important since some of the organisms manifest infectivity at 

extremely low levels. Nucleic acid–based detection also offers the best chance 

for detection of novel, engineered organisms or so-called stealth organisms, 

where virulence genes are inserted into an otherwise innocuous microbe. In 

these cases, the nucleic acid sequence of the virulence elements still provides 

a diagnostic signature. 

Integration of all steps (lysing cells/spores to prepare nucleic acids, 

amplification of target sequences, and detection of the same) required for 

nucleic acid sensing is crucial for a true biosensor, and so far, reducing 

the entire assay time to a few minutes has been unreachable. Thus, there 

has been interest in nucleic acid–based techniques that provide genebased specificity, but do not require amplification steps to attain detection 

sensitivity to the required levels. Such exquisitely sensitive detection almost 

precludes techniques like surface plasmon resonance (SPR) and recommends 

procedures like fluorescence detection. 

This difficulty has led others to suggest that detectors based on 

surface features (for example, immunogenic molecular species) of the 

threat organisms may be a more tractable route for development of detectto-protect devices. Such devices must have a rapid response, must not give 

false positives, and must have high sensitivity and the ability to detect the 

target in aerosol samples, when the natural environment for most detecting 

biomolecules is aqueous. The major factors for successful immunosensing 

of BWA are the efficiency of the antigen-antibody complex formation and 

the ability to sensitively detect these complexes. Nonspecific binding can be 

a problem for such techniques, particularly as sensitivity is pushed. There is 

also an urgent need for multiplexed detection in BWA sensors, since the list 

of potential agents, while not extensive, still numbers more than a handful. 

Biorecognition Elements 

The biorecognition element of biosensors has classically been some natural 

biomolecule, antibodies being the most common example. However, 

biorecognition elements also include bioreceptors such as nucleic acids, enzymes, 
845 Bio-IInspired IInnovation and ovation and NNational SSecurity 

cell membrane receptors, and even larger biological units, such as whole 

cells. The biorecognition element plays a crucial role to the overall biosensor 

performance, imparting selectivity for a particular analyte. If the definition of 

biorecognition elements only includes natural biomolecules (up to the collection 

of biomolecules comprising a whole cell), such artificial recognition elements as 

imprinted polymers or peptide nucleic acids would be excluded. This rigorous 

definition seems too restrictive, however, and in this chapter the authors include 

biosensors using such biorecognition elements as aptamers, peptide nucleic 

acids, liposomes, and molecularly imprinted polymers. A brief description of the 

various types of biorecognition elements follows. 

Antibodies 

Antibodies are proteins produced by the immune system that have as their 

unique feature antigen recognition sites that bind antigens by noncovalent 

interactions in an exquisitely specific fashion and often with relatively high 

affinity. The antigen-binding portions of the molecule are the VH (heavy chain 

variable region) and the VL (light chain variable region) regions, which both 

fold to provide a sort of “lock and key” fit for the specific antigen. Included 

in antibody categories would be polyclonal and monoclonal antibodies. 

Antibodies are probably the most commonly used of all biorecognition 

elements for sensor applications. Frequently, sensor design makes use of 

antibody “sandwiches,” where, for example, captured antibodies immobilize 

the analyte, while other labeled detector antibodies bind to the analyte and thus 

provide a sensing signal. It is also common to use some sort of amplification 

technique (for example, enzymes-ELISA assays) to provide a more robust 

signal of the recognition process. Ingenious combinations of nucleic acid and 

immunological techniques (such as immuno-PCR, immuno-rolling circle 

amplification) can also be used for amplification. 

Antibody Fragments/Engineered Antibody Fragments 

For biosensing applications, the molecular recognition site(s) of the antibody 

(the antigen combining sites) are of overwhelming importance, while the 

function of the fixed chain region, of importance physiologically, may not 

be required for sensing applications. Also, antibodies are often immobilized 

on solid substrates for sensing applications, and here the orientation of 

the antibodies is critical, as the antigen combining site should ideally be 

oriented in a spatially accessible manner. Thus, smaller antibody fragments 

may have certain advantages, such as more defined points of immobilization 

through thiol groups liberated after cleavage of the whole molecule, and also 

these fragments could be more densely packed upon a sensor surface, thus 

increasing the epitope density over that found with intact immunoglobulin 
Biosensors and Bioelectronics 85

and so perhaps enhancing sensitivity. Enzymatic cleavage of immunoglobulin 

molecules to produce fragments such as an antigen-binding fragment is one 

way to produce these smaller recognition elements. 

Using the techniques of phage display or ribosome display for antibody 

gene cloning and expression, antigen-binding fragments of antibody 

molecules called single chain variable fragments (scFv) can be obtained. These 

fragments feature the VH and VL

 domains joined by a flexible polypeptide 

linker that can be engineered to have desirable properties for immobilization 

(for example, a thiol group of cysteine). Some studies have found the scFv 

antibody fragments to be superior to either the antigen-binding fragment or 

the whole immunoglobulin molecule for sensor applications. 

Enzymes 

Enzymes are catalytic proteins that have an active site that shares some of the 

features of the antigen-binding site of antibodies—that is, exquisite specificity 

for certain molecular structures, referred to as their substrates. Again, 

genetically engineered enzymes with altered properties can be used. Enzymes 

are not frequently used as biorecognition elements per se, but are usually 

a component of a multiple molecular biorecognition package, where the 

enzyme is included to provide amplification (such as in ELISA immunoassays 

or coupling to an electrochemical detection transduction system [for example, 

horseradish peroxidase, urease for electrochemical detection schemes]). An 

example where an enzyme functions as a direct biorecognition element would 

be the use of cholinesterase enzymes to detect certain organic phosphate 

pesticides/chemical warfare agents that are cholinesterase inhibitors. 

Proteins/Peptides with Specific Binding Properties (Phage Display) 

Using techniques developed in recent years, it is now possible to produce and 

evolve peptides/proteins with strong binding affinity for specific proteins. 

These techniques include phage, bacterial, and ribosome display. It is outside 

the scope of this article to provide an in-depth review of these procedures. In 

each technique, iterative rounds of affinity purification enrich proteins/peptides 

with desired binding properties for a specific ligand. The unique feature of 

phage display is that the production of 107

 to 108 short peptides on the surface 

of filamentous bacteriophages can be achieved through the fusion of an epitope 

library of DNA sequences with one of several coat proteins (the minor coat 

protein, phage gene III, was used initially). An epitope library of such cloning 

can display 107

 or greater peptides that can be panned for peptides that bind 

specifically to an analyte of interest. Proteins made from the phage display 

technique have been used to detect bacteria, bacterial spores, toxins, and viruses. 
867 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Nucleic Acids 

Included here are oligo- or polynucleotides such as DNA and RNA. DNA is 

used more frequently due to its inherent greater stability under a variety of 

conditions. The biorecognition process consists of noncovalent interactions 

between bases of complementary nucleic acid strands by Watson-Crick base 

pairing rules, and is manifested by hybridization of two single strands having 

such complementary base sequences. Exquisite specificity can be obtained due 

to the cumulative specific interaction of many bases to their complementary 

units on the opposite polynucleotide chain. Nucleic acid sensors are 

frequently coupled to schemes that utilize amplification of diagnostic nucleic 

acid sequences (for example, PCR, nucleic acid sequence-based amplification, 

rolling circle amplification, and so forth) with the potential for extreme 

sensitivity, since a large number of copies of an initially low copy number 

sequence can be obtained by amplification techniques. 

Aptamers 

Aptamers can also be included as nucleic acid biorecognition elements, since 

they are made up of single strands of nucleic acid (DNA or RNA), but here 

the biorecognition is not via base pairing but by folding to form a unique 

structure. In contrast to base pairing as the biorecognition feature, the 

aptamer folds in such a manner that it forms a highly specific 3-dimensional 

structure that recognizes a specific analyte molecule, somewhat similar to the 

nature of the antibody-antigen interaction. 

Aptamer selectivity and binding affinity can be similar to the specificity 

and affinities of antibodies. An advantage of aptamers over antibodies is that 

the aptamer structure is inherently more robust than the antibody quaternary 

structure, so that aptamers can be subjected to numerous rounds of denaturation 

and renaturation, thus providing for easy regeneration of the sensor as well as 

an overall more robust biosensor. Antibodies are fundamentally products of 

animal immune systems, with all the limitations that implies. 

Aptamers are produced by chemical synthesis after selection rather 

than via immune system cells, and so can be readily modified to enhance 

stability and affinity. Also, aptamers can be selected against certain targets that 

can cause the immune system to fail to respond, such as bacterial toxins or 

prions. Because of all these advantages, aptamers are being used increasingly 

as biosensor elements. 

A recent development has been designing RNA sensors that combine 

aptamers with ribozymes (catalytic RNAs) to produce RNA molecules (these 

structures have been called aptazymes) whose catalytic activity depends in 

some manner upon binding of a specific ligand, the analyte. The binding 

of the analyte can either stabilize or destabilize the catalytic domain and so 
Biosensors and Bioelectronics 87

adjust the catalytic activity. Thus, detection of the analyte species is signaled 

by changes in the enzyme’s activity.

Peptide Nucleic Acids 

Peptide nucleic acid (PNA) structures are not strictly natural biorecognition 

molecules, since they are a hybrid of a series of N-(2-aminoethyl)-glycine units 

making up the backbone structure (instead of the sugar-phosphate backbone of 

natural nucleic acids) with the standard bases bound to the peptide backbone. 

All intramolecular distances and configurations of the bases are similar to those 

of natural DNA. Thus, hybridization to DNA or RNA molecules is readily 

achieved. Since the PNA backbone is uncharged, PNA–DNA duplexes are more 

thermally stable than DNA–DNA duplexes, and so single-base mismatches have 

a more destabilizing effect in PNA–DNA hybrids. The PNA structure is stable 

over a wide temperature and pH range and resistant to nuclease and protease 

activity and so has obvious applications in the biosensor area. Also, PNAs can 

be used for the detection of double-stranded DNA directly, eliminating the 

requirement for thermal denaturation, due to the ability of PNAs to form higher 

order complexes (3- and 4-stranded) with DNA. 

Also to be mentioned are another type of nucleotide analog called 

locked nucleic acids (LNA). These nucleic acid analogs have modified RNA 

nucleosides where a ribonucleoside has a methylene linkage between the 

number 2-oxygen and the number 4-carbon. These LNA have the usual 

hybridization properties expected of nucleic acids with other desirable 

properties such as highly stable base pairing, high thermal stability, 

compatibility with most enzymes, and predictable melting behavior. 

Molecular Beacons 

This is a subset of nucleic acid biorecognition molecules, generally synthetic 

oligonucleotides that are designed to have a hairpin (stem-loop) structure. 

The loop contains a nucleotide sequence complementary to the analyte 

sequence to be detected, while the stem structure has only a small number of 

complementary bases, forming a short double-stranded portion. Fluorophore 

and quencher molecules are held in close proximity on the two ends of the 

double-stranded stem, when the molecular beacon is in the closed position. 

Upon binding of the analyte sequence to the loop portion, the stem opens, the 

quenching effect on the fluorophore is relieved, and the resulting fluorescence 

signals the presence of the analyte sequence. Aptamers can also serve as 

molecular beacon biosensors in that they can be used to detect nonnucleic acid 

analytes, such as proteins or small organic molecules. PNAs can also be used to 

form molecular beacon-type structures and these can be stemless, in contrast 

to the usual stem-loop structure found in natural DNA molecular beacons. This 
889 Bio-IInspired IInnovation and ovation and NNational SSecurity 

stemless structure has advantages (less sensitive to ionic strength, quenching 

not affected by DNA-binding proteins) as compared to DNA beacons. 

Cell Surface Receptors/Glycoproteins, Glycolipids/Glycans 

Many of the molecular recognition events having to do with cell-cell 

interaction, pathogen attack upon cells, and so forth take place in the 

glycocalyx layer of the cell membrane. The glycocalyx layer consists primarily 

of oligosaccharide headgroups of glycoproteins and glycolipids. The lipid or 

protein portion of these molecules is embedded in the membrane, while the 

hydrophilic oligosaccharide chain is extended into the outer environment. As 

the molecular biology of pathogen and toxin interaction with the cell surface 

is elucidated at the molecular level, these receptor molecules are receiving 

increasing attention as biorecognition elements. 

One of the major difficulties heretofore with exploitation of these 

receptors is the complexity of the cell membrane, making mimicry of this 

structure a daunting task. Simpler models of cell membranes with defined 

chemical compositions include liposomes (vesicles) and Langmuir-Blodgett 

monolayers. Recent advances have formulated biorecognition molecules into 

these synthetic lipid structures. 

In some cases, pathogens or toxins produced by pathogens target 

specific cell surface receptor sites. These same cell-based receptors can then 

become biosensor recognition elements. Thus, biorecognition elements seeing 

use in sensors include gangliosides, glycosphingolipids, which are localized 

upon certain cell types, as well as carbohydrate/oligosaccharide structures 

found on the cell surface. For example, ganglioside GT1b has been used as 

a recognition element for botulinum toxin, while N-acetylneuraminic acid 

and N-acetylgalactosamine bound cholera and tetanus toxin, respectively, in 

a semi-specific manner. Uropathogenic E. coli strains attach to uroepithelial 

cells by adhesion to the glycolipid globotetraosylceramide (globoside), and so 

sensors for these E. coli strains can be formulated using this globoside. Human 

gastric mucin has been used in a biosensor format to study the interaction 

of Helicobacter pylori with the extracellular matrix components. Lectins, a 

broad class of proteins/glycoproteins that bind with high affinity to specific 

carbohydrate moieties, have also been incorporated into biosensing devices. 

Often, oligosaccharides form primary molecular components and 

markers on pathogen surfaces, and thus may form the basis for diagnostic 

sensors for specific bacteria or groups of bacteria. For example, the 

lipopolysaccharide molecules (commonly known as bacterial endotoxin) that 

are found on the cell surface of Gram-negative bacteria can serve as targets for 

biorecognition by lectins or other proteins. 
Biosensors and Bioelectronics 89

Whole Cells 

In this chapter, the term whole cells refers exclusively to bacterial cells. In some 

ways, whole cells do not fit the strict definition of a biosensor biorecognition 

element, since they are most often used to function as bioreporters. That is, 

the cells are genetically altered to synthesize a certain marker that produces 

a detectable signal of some sort (luminescence, fluorescence) when they 

encounter specific compounds/environmental conditions. Such whole cell 

sensors have been applied to environmental analysis and monitoring. A brief 

description of such applications is included later in this chapter. There are, 

however, some examples of whole cells being used as biosensors, particularly 

microbial cells. Often in these instances, the whole cellular machinery 

functions in a sense as a biorecognition/processing system for the analyte, as, 

for example, using bacterial cells induced to constitutively produce an aminoacid metabolizing enzyme to detect that particular amino acid. Another 

innovative approach using whole cells is to genetically engineer cells of the 

immune system to respond to specific pathogen binding events by producing 

a detectable signal from some genetically inserted reporter construct. 

Bacteriophage 

Bacteriophage, by virtue of the fact that they recognize in a specific manner 

their host bacteria, can become biorecognition elements. The bacteriophage 

themselves may be used, with appropriate labels (for example, fluorescent 

dyes) to detect the binding event, or the phage may be selected for binding 

to a specific analyte via fusion proteins on the phage coat (that is, phage 

display). This latter paradigm has even been extended to expression of the 

biorecognition peptide as an N-terminal add-on to the major coat protein 

of the phage. In this case, there is a display of thousands of copies of the 

recognition protein on the phage surface, thus potentially greatly increasing 

the sensitivity of the assay by increasing the density of the epitopes displayed. 

Thus, the phage themselves become both biorecognition (by virtue of peptides 

displayed on their surface) and amplification (multiple copies of fluorescent 

dye per phage) elements. This type of biosensor could be considered a whole 

cell biosensor (bacteriophage) that has a bioreceptor on its surface. 

Biomimetic Materials 

Liposomes. Liposomes are synthetic lipid vesicles, mimicking in some 

respects cell membranes, although they are not nearly as complex. Liposomes 

are frequently used as components of biorecognition systems, but usually the 

liposomal membrane structure is modified with a standard biorecognition 

element such as an antibody or oligonucleotide, and these molecules provide 
901 Bio-IInspired IInnovation and ovation and NNational SSecurity 

the specific recognition. In such cases, the liposome may have encapsulated 

fluorescent dyes, enzymes, electrochemically active species, and so forth, 

which, upon biorecognition, may be released, and thus the liposome itself 

functions as an amplification system. More direct involvement of liposomes 

as sensing elements per se are occasionally also encountered. For example, 

insertion of the ganglioside GM1 into the liposomal membrane has been used 

to develop a sensor for cholera toxin, since the GM1 has specific affinity for 

it. In a similar vein, liposomes containing cholesterol in the membrane could 

function as sensors for the toxin listeriolysin. 

Molecularly imprinted polymers (MIPs). A recent development that may in 

the future provide artificial macromolecular bioreceptors is the technique of 

molecular imprinting. In this procedure, a target molecule (that is, the analyte), 

acting as a molecular template, is used as a pattern to direct the assembly of 

specific binding elements (that is, monomeric units), which are subsequently 

polymerized with a cross linker. The interaction of the monomeric units with 

the template molecule may be either through noncovalent (the more usual 

method) or covalent bonding. Following polymerization, the target molecule 

is removed from the polymeric matrix (by suitable solvent or chemical 

cleavage), leaving a cavity within the polymeric matrix, which is a molecular 

“negative” image of the target molecule. The monomeric subunits that interact 

with the target molecule in a noncovalent molecular imprinting scheme do so 

by interactions such as hydrogen bonding, van der Waal’s forces, hydrophobic 

interactions, and so forth, just as antibody-antigen interactions take place. 

The subsequent interaction with the cross-linker freezes the binding groups 

in a specific orientation. 

Ideally, once the target molecule is removed from the polymer, a binding 

site exists that is complementary in size and chemical functionality to the 

original target molecule. In a number of studies, MIPs have been shown to have 

binding characteristics similar to those of antibodies and other bioreceptors. 

A potentially important advantage of MIPs is enhanced stability compared 

to natural biomolecules. The use of MIPs for the analysis of small molecules 

is becoming established, but detection of larger biomolecules (for example, 

proteins and protein toxins) is more problematic. Here, the formation of 

the template cavity to conform to the 3–D image of the total protein may 

be difficult (for example, individual antibodies to proteins respond to one 

antigenic determinant or epitope). Similarly, use of MIPs for sensing whole 

microorganisms can be challenging. 

Biomimetic chromic membranes. A specific biomimetic system that has 

been used for convenient colorimetric sensing of bacterial toxins, bacteria, or 

viruses is the employment of cell membrane–mimicking materials (“smart” 
Biosensors and Bioelectronics 91

materials) into which cell surface receptor residues are inserted. These systems 

use polydiacetylenic membranes (Langmuir-Blodgett or vesicle bilayers) 

containing either cell surface gangliosides, sialic acid, or carbohydrate 

residues to detect the presence of toxins such as cholera toxin or influenza 

virus, the binding event being signaled by a color change (bichromic shift). 

The specificity of the sensor resides in the ganglioside or sialic acid residues 

in the polymeric assembly. Gm1 ganglioside is the primary target of cholera 

toxin on the intestinal cell surface, while GT1b gangliosides are located at the 

neuromuscular junction and form the target for botulinum toxin. In the case 

of influenza virus, the sialic acid residues on glycolipids form targets for the 

viral surface hemagglutinin of the influenza virus, by which pathway the virus 

is endocytosed into the cell. When these receptor molecules are incorporated 

into the polydiacetylenic structure, binding of the virus or bacterial toxins 

apparently induces a distortion of the conjugation plane of the polymer, 

leading to the color change. 

Transduction Mechanisms 

As described above, the transducer is the portion of the biosensor responsible 

for converting the biorecognition event into a measurable signal. It is possible 

to exploit a change in a number of physical and chemical properties (mass, 

temperature, electrical properties, and optical properties) to allow for different 

transduction formats. The four basic transduction types—electrochemical, 

piezoelectric, calorimetric, and optical—are reviewed here, with emphasis 

on the advantages and disadvantages to each, and recent advances toward 

idealizing biosensor performance. 

Electrochemical

Electrochemical transduction is one of the most popular transduction 

formats employed in biosensing applications. One of the main advantages of 

biosensors that employ electrochemical transduction is the ability to operate 

in turbid media and often in complex matrices. Another distinct advantage 

of electrochemical transduction is that the detection components are 

inexpensive and can be readily miniaturized into portable, low-cost devices. 

In general, electrochemical-based sensing can be divided into three main 

categories: potentiometric, amperometric, and impedance. Potentiometric 

sensors typically rely on a change in potential caused by the production of 

an electroactive species that is measured by an ion selective electrode. For 

a biosensor system, this change in electroactive species concentration is 

usually brought about by an enzyme. In an amperometric sensor system, a 

change in current is directly measured. Electrochemical sensors based on 
923 Bio-IInspired IInnovation and ovation and NNational SSecurity 

impedance most commonly utilize impedance spectroscopy since controlled 

AC electrical stimulus over a range of frequencies is used to detect variations 

in the sensor surface properties (that is, charge transfer and capacitance 

at the interface layer). In this way, the resistance to flow of an alternating 

current is measured as voltage/current. For example, metabolic changes (for 

example, growth) have been shown to correspond to an increase or decrease 

in impedance. Some of the many variations of potentiometric, amperometric, 

and impedance biosensors that provide for improved biosensor performance 

include field effect transistors (FET) and electrochemiluminescence (ECL). 

Field effect transistors. Many researchers have recently looked to field 

effect transistors as a means to miniaturize potentiometric sensors, while 

providing increased sensitivity due to minimal circuitry. A particularly 

promising FET advance includes the light addressable potentiometric 

sensor (LAPS), which consists of an n-type silicon semiconductor-based 

sensor and an insulating layer that maintains contact with the biological 

solution. Potential changes occurring at this silicon interface are monitored 

as differences in charge distribution between the insulator surface and the 

FET. To accomplish this, alternating photocurrents generated by a light 

emitting diode are utilized, so that changes in potential can be transduced 

into voltage per time differentials. Successful application of the LAPS has 

been demonstrated with commercially available systems for the detection 

of biological threats of interest to defense applications, as well as foodborne 

pathogen threats of concern to food safety applications. 

Eletrochemiluminescence. ECL combines the advantages of 

chemiluminescence (high sensitivity and low background) with electrochemical 

transduction. ECL utilizes a controlled voltage potential at the surface of an 

electrode to power a luminescent redox reaction. The redox reaction most 

commonly employs a ruthenium (II) trisbipyridal chelate coupled with a 

tripropyl amine, although recent studies have demonstrated success with other 

fluorophore species. 

Mass 

Biosensors that detect the change in mass due to target and biorecognition 

element interactions predominantly rely on piezoelectric transduction. 

Piezoelectric transduction relies on an electrical charge produced by 

mechanical stress, which is correlated to a biorecognition binding event 

causing a change in the mass on the piezoelectric device. The main advantage 

to the piezoelectric transduction (that is, mass sensor) approach includes the 

ability to perform label-free measurements of the binding events, including 

real-time analysis of binding kinetics. Advantages and disadvantages of the 

various types of mass transduction are discussed below. 
Biosensors and Bioelectronics 93

Bulk wave. The most commonly employed transducer is the 

quartz crystal microbalance (QCM), which relies on a bulk wave effect. A 

QCM device consists of a quartz disk that is plated with electrodes. Upon 

introduction of an oscillating electric field, an acoustic wave propagates across 

the device. The change in mass associated with bioreceptor-target interactions 

causes a decrease in the oscillation frequency that is directly proportional 

to the amount of target. This transduction format can be coupled to a wide 

variety of bioreceptors (for example, antibody, aptamer, imprinted polymer, 

and so forth), provided that the mass change is large enough to produce a 

measurable change in signal. Not surprisingly, QCM transduction is not 

capable of small molecule detection directly and usually requires some sort of 

signal amplification to be employed. 

Surface acoustic wave. Changes in the overall mass of the biomolecular 

system due to association of the bioreceptor with the target analyte can be 

measured using alternative piezoelectric transducer devices, which offer 

some advantages over bulk wave sensing. For example, surface acoustic wave 

(SAW) devices exhibit increased sensitivity compared to bulk wave devices 

and transmit along a single crystal face, where the electrodes are located on 

the same side of the crystal and the transducer acts as both a transmitter and 

receiver. SAW devices can directly sense changes in mass due to binding 

interactions between the immobilized bioreceptor and target analytes and 

exhibit increased sensitivity compared to bulk wave devices. However, the 

acoustic wave is significantly dampened in biological solutions, limiting its 

utility for biosensing applications. Some improvements using dual channel 

devices, and special coated electrode systems allowing for non-contact SAW 

devices that can function in biological solution interfaces have been produced. 

However, reliable biosensor application incorporating these devices is still 

under pursuit, as improvements in sensitivity are still required for specific 

microbial analyses. 

Micro- and nano-mechanical devices. Micro- and nano-mechanical 

cantilevers can be manufactured through silicon fabrication techniques 

developed in the electronics industry. Under ambient temperature 

conditions, the cantilever devices naturally oscillate, and this resonant 

frequency can be monitored. Through modifications with bioreceptors, 

target interactions can be monitored as changes in mass, and hence the 

resonant frequencies, upon binding. Obvious advantages of this form of 

transduction include low cost and mass production. However, practical 

applications to biosensing are limited due to oscillation dampening in 

liquid solutions, compared to air- and vacuum-packed cantilever systems. 

To address this limitation, there have been recent advances toward 

incorporating hollow channels inside the microcantilever to immobilize 
945 Bio-IInspired IInnovation and ovation and NNational SSecurity 

the bioreceptors internal to the device. In other words, high resonant 

efficiencies obtained through vacuum packaging can be maintained, while 

specific mass changes can be monitored by flowing the sample through the 

inside of the device. Further signal enhancements can be obtained through 

use of nanoparticle and magnetic bead amplification to cause larger 

frequency shifts and produce a more sensitive analysis. 

Flexural-plate wave. A flexural-plate wave (FPW) transducer contains 

a thin membrane that can propagate a surface acoustic wave. The FPW is in 

contact with a thin film of liquid that vibrates with the membrane, and 

hence the change in mass of a vibrating element can be detected to indicate 

biological interactions. This technique is not very sensitive but, like SAW 

devices, can provide for real-time analyses. 

Thermal/Calorimetric 

Calorimetric sensors utilize thermistor probes to monitor changes in 

temperature due to exothermic chemical reactions. Many biological 

reactions are exothermic (for example, enzyme reactions), and hence 

calorimetric detection allows for a near-universal transduction format. 

One key disadvantage of this approach is that environmental temperature 

fluctuations must be shielded from the sensor system. Calorimetric 

biosensors traditionally have been large and bulky, although advances in 

silicon microfabrication technologies and microfluidics have allowed for 

miniaturization and improved performance. 

Optical 

Due to a number of advantages, optical transduction is one of the most widely 

used biosensor transduction formats. For example, optical transduction can 

be very rapid where the limiting factor for the speed of detection is often 

a diffusion-limited process of the biomolecular recognition event, rather 

than the optical transducer. Another advantage of optical transduction 

is that the interferences that can hinder electrochemical transduction 

measurements (such as voltage surges, harmonic induction, corrosion of 

electrode elements, and radio frequency interferences) are not present. 

Some of the disadvantages of using optical transduction formats include 

detection challenges when analyzing turbid samples and the cost associated 

with detection system components. A wide variety of optical transduction 

formats have been employed, where changes of the interaction of light with 

the biomolecular system are used to produce a measurable signal. These 

changes can be based on differences in refractive index, production of 

chemiluminescent reaction products, fluorescence emission, fluorescence 

quenching, radiative and nonradiative energy transfer, temporal changes 
Biosensors and Bioelectronics 95

in optical emission properties, and scattering techniques, well as other 

optical effects. 

These effects can be monitored using a variety of optical platforms 

including total internal reflectance and evanescent wave technologies, 

interferometric, resonant cavities, and biochip devices. The following 

paragraphs review the most common as well as most popular emerging optical 

transduction formats: fluorescence, interferometry, chemiluminescence, 

surface plasmon resonance, and surfaced enhanced raman. 

Fluorescence. Fluorescence is the most popular form of optical 

transduction due to the high sensitivity that is fundamental to this type of 

optical process. Another advantage of fluorescence-based methods is that they 

generally do not have the interference issues that SPR and other refractiveindex based methods possess. However, in most cases, the intrinsic sample 

fluorescence is not sufficient for analysis, and a fluorogenic reporter is used 

to label an affinity reagent to create a bioreporter. By monitoring the intensity 

of the fluorogenic reporter, it is possible to determine the presence and 

concentration of the target analytes, as illustrated in the bioassay techniques 

already described. 

It is also possible to monitor shifts in the wavelength of the fluorophore 

reporter, as well as energy transfer phenomena, and time dependence of the 

fluorescence emission, all of which can be related to binding interactions 

depending on the assay employed. The distinguishing features between 

biosensors, besides the above mentioned properties that can be monitored, 

include the optical detection format used. For example, it is possible to 

utilize fiber-optic probes to immobilize bioreceptors at the tip of the fiber 

and use total internal reflectance properties of the fiber to transmit excited 

and emitted light. Total internal reflectance can also be employed in an 

evanescent wave format, where a residual amount of (evanescent) light at 

the reflectance point that escapes is used to excite immobilized bioreceptors 

only in close proximity to the surface, rather than in bulk solution. 

This format allows for controlled excitation and can allow for minimal 

fluorescence background. 

However, a key disadvantage is the lack of evanescent excitation power, 

and sometimes poor coupling of the emission when using similar collection 

geometries. Fluorescence detection can be used with a wide variety of 

detection formats. For example, it is routinely coupled with flow cytometry 

and microfluidic platforms or imaging array systems such as biochips 

that utilize spatial patterning of biological recognition elements to match 

fluorescence location to target species. 

Interferometry. Interferometers can measure biomolecular interactions 

that take place at a surface within an evanescent field that causes a refractive 
967 Bio-IInspired IInnovation and ovation and NNational SSecurity 

index change and a corresponding change in the phase of the propagating 

light. To accomplish this, two channels are used, one of which serves as a 

continuous reference that does not experience refractive index changes due to 

the target analyte’s presence. By combining light from the reference and sample 

beams, an interference pattern is created, which can be used to determine the 

presence of the associated target species. Although this approach has been in 

existence for quite some time, it is primarily a laboratory technique, since it 

is not a very robust biosensor technology and suffers from significant false 

positive results. 

Chemiluminescence. Chemiluminescence is a type of optical sensor 

technology that relies on a series of chemical reactions, usually employing 

oxidation of a luminol reactant, to produce a reaction product that gives off 

characteristic light. The intensity of this light is correlated to a sample target of 

interest, by coupling some of the reaction products to biorecognition elements, 

to serve as chemiluminescent reporters. The advantage of chemiluminescent 

transduction is the very low optical background. The only background from 

the biosensor may be due to any cross-reactivity from the biorecognition 

element with nonanalyte species, leading to a very sensitive (high signal-tobackground) measurement. The reaction usually employs signal amplification 

and bioassays with multiple washing and labeling steps, which leads to a 

somewhat time-consuming analysis. 

Surface plasmon resonance. Surface icrosy resonance is a phenomenon 

that can exist at the interface between a metal and a dielectric material such 

as air or water. A surface plasmon (commonly excited by optical radiation) of 

the electrons at the surface of the metal results in an associated surface bond 

and evanescent electromagnetic wave of optical frequency. This evanescent 

wave has a maximal intensity at the interface and decays exponentially with 

distance from the interface. In SPR-based biosensing, changes at the interface 

(that is, biological recognition element and analyte binding) cause changes 

in the local refractive index, which in turn causes changes in the resonance 

excitation of the surface icrosy. 

SPR is a form of reflectance spectroscopy, where change in a surface 

icrosy resonance that occurs during optical illumination of a metal surface 

is harnessed to detect biomolecular interactions. The SPR chip consists of a 

prism with a thin gold film upon which the bioreceptors are immobilized. 

Light is totally internally reflected from the metal-coated prism face, and 

the changes in reflectivity are measured. Surface plasmons are excited at a 

specific incident angle and result in a massive reduction in reflectivity at that 

angle. Changes in the refractive index at the interface result in a change of the 

optimal angle required for excitation. 
Biosensors and Bioelectronics 97

Any change in the optical properties of the medium in contact with 

the immobilized layer will cause changes in the characteristics of the surface 

plasmon wave. Specifically, these changes can be measured as changes in 

wavelength, intensity, phase, or angle of incidence. SPR techniques are 

widely popular in contemporary biosensor development because it is a 

surface-sensitive technique that can measure real-time interactions between 

unlabeled species. 

Although SPR is a simple technique with a number of advantages, it 

is not the most sensitive. However, one variation of SPR includes a resonant 

mirror format that utilizes a series of polarizing filters to block light that is 

internally reflected. At a particular incident resonant angle, the light is diverted 

through a spacer layer that has a low refractive index into a higher refractive 

index guide so that the signal peak appears on a dark background. Despite 

these advances, one of the primary limitations of SPR-based biosensors is that 

anything that alters the refractive index at the sensing surface will interfere 

with the analysis, including nonhomogenous (complex) sample matrices and 

nonspecific binding interactions. 

Surface enhanced raman. Another type of plasmonic spectroscopy that 

is gaining popularity in biosensing applications is surfaced enhanced raman 

spectroscopy (SERS). SERS is an enhanced form of raman spectroscopy, 

where a nano-roughened metal surface is used to enhance the scattered raman 

signal. The SERS enhancement is thought to be the result of a combination 

of intense localized fields arising from surface icrosy resonance in metallic 

nanostructures and chemical effects. 

Advantages of this approach include the ability to obtain a spectroscopic 

fingerprint, similar to infrared absorption spectroscopy, while being relatively 

interference-free from water. Also, since SERS is an enhanced technique, it can 

be used to see very low concentrations of even biological materials, as evidenced 

by recent interest in a variety of immuno-SERS methods under development. 

The difficulties often encountered with SERS biosensors stem primarily from 

signal reproducibility challenges, which are directly tied to the reproducibility 

of nanostructured SERS substrate fabrication. Of the transduction methods 

covered in this chapter, SERS is one of the least established for biosensor 

development but shows much promise for continued development. 

Biosensors: Summary 

This discussion of biosensors has shown that the field is an emerging one 

that has not by any means reached its full potential. Unfortunately, the gap 

between biosensor prototypes that work in the laboratory and commercial 
989 Bio-IInspired IInnovation and ovation and NNational SSecurity 

biosensors that can see routine use in real-world environments is often still 

large. The many varied biorecognition elements, transducers, and detection 

strategies lead to a wealth of potential applications. 

The field of biosensor research/applications is still probably in the stage 

where it is not clear which biorecognition elements/transducers/detection 

schemes will be most productive, and indeed, the field may well continue 

to evolve in different directions as techniques such as MIPs become more 

established. Also, the large number of potential applications may demand 

a varied armamentarium of biosensor techniques. In general, robustness of 

the biorecognition element continues to be a concern for many applications. 

The use of transducers/detection mechanisms that involve sophisticated/

expensive instrumentation also will preclude such devices from many routine 

applications. Simpler is not necessarily always better, but dipstick sensors for 

certain applications are attractive. 

This section will end with a few comments regarding two other areas 

that the authors believe will have increasing importance in the field of 

biosensor applications. Array biosensors, biochips, labs-on-a-chip—that is, 

devices that permit multi-analyte detection (multiplex analysis) and ideally 

that can integrate all processing steps into a micro-analytical system—will 

certainly see increased interest in the future. Such integrated devices have a 

number of advantages, such as the ability to assay large numbers of samples in 

minutes, savings on expensive reagents, and reduction in time for individual 

assay steps due to decreased assay volumes. 

Unfortunately, a number of obstacles still need to be overcome with 

regard to these systems. Among these are such things as further development 

of microfluidics systems, sample preparation modules, sensitive detection 

modules, and robust assay methodologies. Another area receiving much 

recent interest is in the area of nanotechnology—more specifically, the 

use of nanomaterials, such as nanoparticles, in biosensor development. 

Nanoparticles do not serve as biorecognition elements per se, but can be 

modified by attachment of appropriate molecular species (for example, 

antibodies or DNA fragments) to become nanosized carriers of biorecognition 

elements that can also serve valuable transduction functions (that is, magnetic 

properties, fluorescence). The unique properties of nanoparticles (colloidal 

gold and quantum dots) also recommend them for novel sensing applications. 

A number of investigators have mentioned the potential use of nanoparticles, 

particularly quantum dots, as molecular bar codes. Metallic nanoshells and 

semiconductor quantum dots are highly promising markers for use in highthroughput screening and bar coding by virtue of spectral multiplexing. 

However, much work remains to be done before the full promise of these 

materials is applied to practical and useful biosensors.
Biosensors and Bioelectronics 99

Bioelectronics 

Overview 

The journal Biosensors and Bioelectronics published an excellent description of 

bioelectronics: “The emerging field of Bioelectronics seeks to exploit biology 

in conjunction with electronics in a wider context encompassing, for example, 

biological fuel cells and biomaterials for information processing, information 

storage, electronic components and actuators. A key aspect is the interface 

between biological materials and electronics.” 

Bioelectronics is not as developed as the field of biosensors; however, 

DOD is making research investments to find out what possibilities lay ahead 

for future military applications. Bioelectronics is a multidisciplinary field 

involving researchers from biology, chemistry, physics, materials science, and 

engineering. This diversity is necessary in order to understand the nuances 

of biology as electrical systems. In this section, we will seek to describe 

several research areas including the phenomena being exploited, level of 

development, and future applications. 

Biological Fuel Cells 

Biological fuel cells come in two main varieties: enzymatic and microbial. The 

goal of using these technologies is to develop environmentally friendly power 

sources capable of operation on fuels that would be readily available in the 

environment, generated in the field, or already included in the logistics train. 

These fuels would also be nontoxic and yield harmless emissions. 

Two electrodes are required for a fuel cell reaction: the anode and the 

cathode. An example of a reaction in either type of biological fuel cell would 

be reacting glucose, a sugar, with water at the anode, producing electrons 

and protons that can be used to do work. At the cathode, the protons react 

with oxygen and the electrons are passed through a load to produce water. 

The main difference between enzymatic and microbial fuel cells is which 

biological system is catalyzing the reaction. 

Enzymes are proteins generated by all life in order to catalyze chemical 

reactions. These reactions can be either catabolic—breaking larger molecules 

into smaller ones—or anabolic—linking smaller molecules to form larger 

ones. By selecting the appropriate catabolic enzyme, a desired fuel, such as 

a sugar, alcohol, or organic acid, can be broken down to liberate electrons 

to be harvested by the anode. These selected enzymes are produced in 

microorganisms, extracted, and purified for use. Enzymatic fuel cells are 

much more developed than microbial fuel cells and have an energy density 

that is higher by orders of magnitude, and some U.S. companies are already 
1001 Bio-IInspired IInnovation and ovation and NNational SSecurity 

starting to market the technology after having learned how to protect the 

enzymes during storage and operation. 

Microbial fuel cells utilize whole microorganisms instead of purified 

enzymes as the biological catalyst. This means that they are capable of using a 

variety of fuels instead of just one specific fuel such as in enzymatic systems. 

Some of the fuels that have been demonstrated include but are not limited to 

sugars, organic acids, cellulose, waste water, ground water contaminated by 

fuel oil, and decomposing organic material in aquifers. 

The Naval Research Laboratory has invested several years of work on 

sediment-based microbial fuel cells that utilize naturally occurring organisms 

and fuels by burying the anode in the anaerobic region of aquifer sediments 

and leaving the cathode above the sediment. These types of fuel cells have 

been used to operate meteorological sensors and transmit the results to the 

laboratory for years at a time. 

Microbial fuel cells can also be designed in a similar fashion to 

conventional chemical fuel cells where the organisms are contained in an anode 

compartment that is kept anaerobic while the cathode is exposed to oxygen. 

This type of platform is commonly used in laboratory experimentation and 

for applications such as complex fuel utilization and waste remediation. These 

have been used, for example, to obtain power and reduce organic content in 

agricultural waste water and starch runoff from paper plants. 

Microbial systems have a large disadvantage in terms of power 

production, but they hold some promise for other reasons. First, as enzymes, 

fail they cannot be replaced, but whole organisms are self-replicating. 

Microbial systems are also capable of utilizing a variety of complex fuels 

rather than just a single fuel. This opens the door to performing operations 

such as power reclamation from wastes, cleaning of waste water flows, and 

possible production of other simpler fuel molecules such as organic acids, 

sugars, and alcohols, which could then be used in enzymatic or conventional 

chemical fuel cell technologies. 

Electronic Biomaterials/Components 

There is great interest in biology’s capability of assembling complex 

and well-ordered structures through “bottom-up” fabrication. As our 

knowledge of fundamental biotechnology expands, we are poised to 

harness this knowledge and these processes for future military capabilities. 

Three broad application areas through the inclusion of biotechnology are 

catalysis, sensing, and photonic structures. Specific research areas such as 

self-assembly of periodic 3–D structures using DNA templates, enzymeassisted nanolithography, virus templating, directed protein assembly, and 

biomineralization could be harnessed to push the limits of nanofunctionality, 
Biosensors and Bioelectronics 101

develop sense and respond surfaces, and develop bottom-up assembly of 

electronic and photonic structures. 

Electronic biomaterials and components can be described in two main 

classifications: using biologicals as templates and relying on the biological/

biologically derived material itself. Templates that have been demonstrated 

include DNA, viruses, proteins, and short synthetic polypeptides. 

Researchers at the University of Utah utilized DNA as a template to link 

microscopic electrodes with gold nanoparticles, while others at the 

Massachusetts Institute of Technology have used mutated viruses to attach 

multiple types of metals and semiconductors to the short proteins expressed 

on its surface. 

Researchers at the University of Washington have taken this to the 

next step through an Army Multidisciplinary University Research Initiative 

where they have developed a polypeptide tool box for linking metallic 

and semiconductor materials. The short poly peptides operate free from 

the organism, are short enough to synthesize, and are capable of being 

combined so that dissimilar materials can be linked to each other. It has even 

been found that doping organic light-emitting diodes with DNA has also 

proven to increase brightness, possibly due to bringing order to the organic 

semiconductors. 

The use of biomaterials as electronic materials has also been studied. 

While many of these experiments are far from a technological reality, much 

knowledge has been gained from these studies. Recently, it has been reported 

that some bacteria are capable of producing nanofilaments that appear to 

be conductive. These are reported to be biological nanowires ranging from 

10 to 100 nanometers in diameter depending on the microorganism. Many 

researchers have also attempted to modify field effect transistors with a 

variety of proteins. Some have shown semiconductor characteristics that 

change depending on environmental conditions, but only one has been 

constructed into a demonstration device, and this will be discussed in more 

detail later in the chapter. 

Another area where biologically directed assembly will capitalize on 

is the use of biomineralization, the accumulation and assembly of inorganic/

organic or purely inorganic materials by biological organisms or purified 

enzymes. Bacteria, archaea, and algae have been studied extensively in this 

area and a host of pure metals, pure metalloids, oxides, sulfides, and selenides 

have been produced from the whole organisms. Over 30 elements including 

transition metals, actinides, lanthanides, and main group elements have 

been studied and reported in the literature, many with interesting electronic, 

optical, or catalytic characteristics. These organisms or purified enzymes could 

be immobilized and provided nutrients containing the desired elemental 
1023 Bio-IInspired IInnovation and ovation and NNational SSecurity 

reactants to produce nanoparticles of specific compositions and morphologies 

on solid supports and could be extended to flexible substrates in the future. 

This work could be performed in conjunction with nanostamping or dip-pen 

lithography to form polycrystalline infrared microlenses or nanostructured 

catalysts for rapid and efficient decontamination. 

Information Processing/Storage 

The ultimate goal in biotechnology for information processing and storage 

is to develop technologies that would eventually approach the abilities of the 

brain. It would be desirable to approach the brain’s low power consumption 

and high level of processing. All of this is performed with simple on/off 

functionality but with a yet unmapped complex connectivity, logic, and 

redundancy. To achieve this goal, much research is needed in the realm of not 

only neurobiology but also biological materials to understand how this high 

level of processing is truly obtained. 

In the meantime, biological materials have been selected in an attempt 

to start understanding the manipulation, utilization, and connections of 

biologicals to the inorganic world of electronics. The most studied class of these 

materials are proteins from the rhodopsin family. Rhodopsins are surfacebound proteins expressed in microorganisms that typically live in high salt or 

acidic environments and are utilized as proton pumps. These pumps are light 

activated and remove excess protons from the inside of the cell. Early application 

attempts were to design biological photovoltaics. While concentrating charge 

across a gradient was achieved, building practical photovoltaics failed, due 

partially due to the fact that the system was based on protons instead of electrons 

and no practical/efficient conversion was developed. 

In the studies of how rhodopsin proteins operated, the discovery was 

made that light caused the protein to change to a conformation with different 

spectroscopic characteristics. Some of these conformations could be locked 

in placed for years if maintained in a controlled environment, meaning that it 

was possible to build a light-activated memory device that could be written to 

and read like a CD or DVD—except in this case, the memory material would 

be biological and could be reset to its original state instead of etched. 

Actuators 

A few examples of bioelectronic actuators have been described in the 

literature. Most have come from studies of animals such as pit vipers, beetles, 

and butterflies, which are extremely heat sensitive. Pit vipers have pores in the 

snout that seem to collect temperature information to allow discrimination 

of just fractions of a degree, while butterflies can collect sunlight on their 

wings to find warm locations in the environment, and certain beetles have 
Biosensors and Bioelectronics 103

demonstrated the ability to detect heat from a forest fire over 2 kilometers 

away. These creatures have been studied extensively for clues on how to design 

and construct infrared sensor technology that would be inexpensive, flexible, 

and very sensitive. 

One of the few devices that have actually been constructed utilizing 

biological material is based on the semiconductor gel from a shark’s 

Ampullae of Lorenzini, or sensing organs. This gel has been identified as a key 

component that allows a shark to track its prey based on the electromagnetic 

radiation released from swimming and injured fish. Upon exposure to 

electric, magnetic, and thermal gradients, this gel has been demonstrated 

to expand and contract. The device developed from this substance under an 

Air Force contract was an infrared sensor where the gel was layered between 

two very thin layers of gold. Upon irradiation, the gel would swell and the 

gold layers would be spread further apart, thus increasing the capacitance 

of the device. While it was not a particularly sensitive device or capable of 

constructing small enough pixels for a high-resolution camera, it was the first 

demonstration of using a biological material in an application previously only 

performed by inorganic materials. 

Conclusion 

While bioelectronics is a very young field, there are many lessons to be learned 

that will yield a variety of useful technologies for defense applications. The 

earliest applications will likely be bio-inspired. This is where we learn how 

a certain task is performed successfully in biology and design the physical 

solution from those lessons. Next, using the capability of life to self-organize, 

we will be able to direct the assembly of electronic structures. Later, we may 

actually see limited use of biological materials with that ultimate goal of 

capitalizing on biology’s abilities of efficient operation, replication, and repair. 

Notes 

1 See O. Lazcka, F.J. Del Campo, and F.X. Munoz, “Pathogen Detection: A Perspective of 

Traditional Methods and Biosensors,” Biosensors and Bioelectronics 22 (2007), 1205–1217.

2 Ibid.

105

The Age of Biology 

Over the past several decades, scientific and technological advances 

have challenged long-held views about genetic diversity and 

biological processes. Advances in culturing techniques have allowed 

a greater proportion of the Earth’s microscopic inhabitants to be grown and 

studied in laboratory environments, while advances in DNA sequencing 

capabilities have enabled the analysis of an organism’s entire genome and 

large fragments of genomic material collected directly from the environment. 

Our knowledge of biological processes now extends to the molecular scale 

as we seek to understand the physiological limits of life on this planet and 

continue to search for novel tools and materials to address societal needs. 

Numerous uses of biomolecules in the agricultural, defense, energy, 

food, medical, structural material, and textile manufacturing sectors that 

would have been written off as science fiction merely a decade ago have been 

realized. As humans investigate ways to move away from a hydrocarbontoward a bio-based economy, and novel applications for the gene products 

found in the Earth’s diverse ecosystems continue to be realized, access to 

genetic diversity as a resource will likely be of great societal and national 

security interest in the future.1

Humans are most familiar with organisms that thrive in moderate climes. 

Due to our physiological limitations, our visions of a hospitable environment 

tend to be limited to moderate conditions of temperature, salt, and pH. 

Microorganisms are much more adaptable, however, and the majority of the 

Earth’s biosphere is located in environments exhibiting extreme conditions. 

chapter 7

Bioenzymes and Defense

Adrienne Huston
1067 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Such environments include the hydrothermal vents at the bottom of the ocean 

whose temperatures exceed 100°C, polar sea ice floes whose temperatures 

can dip below -20°C, sulfurous environments (pH values close to 0), soda 

lakes (pH values reaching 14), hypersaline environments such as the Dead 

Sea (with salinities reaching 6 M NaCl), and deep sea environments (where 

hydrostatic pressures approach 0.1 megapascals). In particular, 75 percent of 

the Earth’s biosphere is estimated to be harbored in stably cold environments 

whose temperatures never exceed that of our kitchen refrigerators, including 

the little-explored deep sea, polar, and alpine regions, caves, and the upper 

atmosphere. The microorganisms that successfully inhabit such environments, 

aptly named extremophiles, possess numerous physiological adaptations that 

enable growth and activity under these conditions. Already, extremophiles and 

their biomolecules (that is, enzymes) occupy a significant niche in the global 

industrial enzyme market, whose current value is estimated at $2.1 billion, and 

conservative estimates forecast a growth curve of 10 to 15 percent annually.2

Enzymes are catalytic, globular proteins that are the product of specific 

genes contained within an organism’s genome. Their activities are highly 

specific, accelerating the particular biochemical reaction to which they were 

designed. Most of us are familiar with degradative/digestive enzymes—such as 

the ones present in our saliva and digestive tracts that aid us in the breakdown 

of food products. However, enzymes are also necessary for virtually every 

biochemical reaction that takes place in all living organisms, including 

DNA replication, metabolic regulation, and transformations resulting in the 

synthesis of new chemicals. 

Because enzymes are crucial for the maintenance of life, among the 

known adaptations to extreme environments are molecular changes within 

an enzyme’s structure enabling the maintenance of vital catalytic powers 

across a broad range of conditions. An organism found in hydrothermal vent 

areas, for example, possesses thermostable enzymes capable of withstanding 

temperatures that would render most human-derived enzymes inactive. On 

the other end of the temperature scale, enzymes produced by bacteria found 

in polar environments such as sea ice are able to catalyze chemical reactions 

at near-freezing temperatures, but they denature (lose their appropriate 

structural configuration allowing activity) at temperatures nearing our body 

temperature. Other types of structural adaptations are found in relation to 

environmental variables such as pressure, salinity, water availability, and pH. 

Nature thus has provided us with a wealth of enzymes capable of catalyzing 

virtually every biochemical reaction necessary for life under every habitable 

environment present on Earth.

Perhaps the most famous and lucrative application of an extremophilederived product to date is Taq DNA polymerase isolated from Thermus 
Bioenzymes and Defense 107

aquaticus, a thermophilic bacterium first isolated from a geothermal spring 

in Yellowstone National Park.3 DNA polymerases catalyze the polymerization 

of nucleic acids into a DNA strand using an existing, complementary 

DNA template during the replication process. The thermostability of Taq 

DNA polymerase is the crucial feature that enabled the automation and 

commercial success of the polymerase chain reaction, the method currently 

used to exponentially amplify a specific gene or DNA fragment in laboratory 

environments without using living organisms. 

This technique has revolutionized the field of molecular biology and 

is used in numerous processes such as detection of infectious and hereditary 

diseases, detection of disease-causing organisms in a given environment, 

screening and identification of specific genes within gene libraries, forensic 

identification (genetic “fingerprinting”), and generation of mutations in 

genes and transgenic organisms. The world market for this enzyme reaches 

approximately $500 million per year, and it plays a central role in the 

agricultural, biomedical, defense, food, and forensic industries. 

Mining the Earth’s Biosphere for Diverse Enzymes 

Traditionally, the method of identifying novel enzymes, such as Taq 

polymerase, from the Earth’s microbial biosphere relied upon the ability to 

cultivate and study live microorganisms in laboratory settings. However, 

most microbial communities are very complex, requiring currently unknown 

growth factors and consisting of different species within consortia whose 

growth is interdependent. These complexities have made it very difficult to 

isolate and cultivate microorganisms in laboratory conditions. Traditional 

cultivation techniques are estimated to recover less than 1 percent of 

microorganisms in a given environment,4 which has resulted in culture 

collections that significantly underrepresent the genetic diversity and 

biotechnological potential of the microbial biosphere. 

Fortunately, novel culturing methods are enabling the cultivation and 

isolation of a greater proportion of the microbial community. Additionally, the 

emerging field of metagenomics (also known as community or environmental 

genomics) has recently enabled scientists to clone, sequence, assemble, 

and express gene products and to screen large amounts of genomic DNA 

extracted directly from the environment,5 thus bypassing the need to cultivate 

microorganisms. By unlocking the world’s vast hidden microbial biodiversity, 

the field of metagenomics is revolutionizing the study and understanding of 

microorganisms and already has revealed novel genes whose products have 

found economical applications. 
1089 Bio-IInspired IInnovation and ovation and NNational SSecurity 

For example, in a recent study of microbial genomic DNA collected 

from the Sargasso Sea, a low-nutrient, open-ocean ecosystem, over 1 million 

previously unknown genes were discovered, many of which are believed to 

encode novel enzymes.6 Sea ice environments in particular are hypothesized 

to be a rich source of novel gene products due to the convergence of numerous 

stressors such as fluctuations in temperature, water availability, ultraviolet 

irradiation, salinity, and pH.7, 8 Studies are currently under way to investigate 

the microbial biodiversity contained within this fragile environment.

A further benefit of metagenomics approaches is the ability to 

perform high-throughput screening of gene libraries to identify enzymes 

with a specific desired activity. Using these methods, hundreds of variants 

of a similar enzyme can be identified that have evolved to catalyze reactions 

under environmental conditions ranging from the soil in your backyard to 

hydrothermal vents and polar regions. Having such diversity on hand enables 

enzyme-based technologies (for example, environmental biosensors that can 

quickly detect the presence of disease-causing organisms such as anthrax) 

to be easily adapted to different environmental or combat conditions by 

substituting appropriate enzyme variants. 

When natural genetic diversity is not sufficient, protein engineering 

techniques enable the mutation and fine-tuning of natural enzymes to address 

specific industrial or defense needs. Using the natural enzyme as a backbone, 

a variety of protein engineering approaches can produce a designer enzyme 

with enhanced properties by introducing mutations in a controlled, measurable 

manner. These approaches include rational protein design, whereby mutations 

are intentionally made at targeted sites, or “directed evolution” techniques, 

whereby mutations are made randomly in a gene whose product is then 

subjected to a selection or screening step to identify enzyme variants exhibiting 

desired properties. Using these approaches, scientists have successfully 

engineered variants of natural enzymes to possess altered rates of activity, 

substrate selectivity, and environmental tolerance. 

Industrial and Defense Enzyme Applications 

Industries are facing increasing global competition in addition to political 

and consumer pressure to strive toward streamlined, sustainable, and 

innovative technologies. Traditional reliance on processes that require high 

temperatures, pressures, or harsh chemical additives to drive reactions has 

resulted in high energy consumption and harmful byproducts that require 

significant financial investments to address. As environmental concerns arise, 

industrialization in emerging regions continues, and energy costs continue to 

soar, biological tools are increasingly replacing harsh chemical and physical 
Bioenzymes and Defense 109

means of synthesizing chemicals and processing materials, and are harboring 

promise for creating cost-effective, renewable energy and chemical product 

alternatives to those derived from petrochemical sources. 

Enzymes in particular offer numerous advantages over chemical processes 

in that they are highly specific in their catalytic activity (thus producing fewer 

unwanted byproducts), exhibit fast reaction rates, operate under specified 

conditions of temperature and pH, are derived from renewable resources, and 

are biodegradable. Due to their diverse properties and high specific activities, 

minute quantities can be used for applications ranging from large-scale organic 

synthesis of pharmaceutical building blocks, production of fuels, plastics, and 

fine chemicals from biological feedstocks, degradation of natural polymers as 

well as toxic compounds, and biosensor technology, to name a few. 

In the same way that industries are looking to streamline their processes 

and gain a competitive edge, the U.S. military can also optimize its warfighting 

practices and shorten the logistics tail by taking advantage of the vast powers 

of enzymes. What follows are examples of potential applications of diverse 

enzymes to benefit industrial practices, while highlighting some of their uses 

on the battlefield.

Enzymes to Fight Infectious Agents 

Very few new antibiotics have been developed over the last several decades. 

While medicine’s arsenal of antibiotics has remained relatively stagnant, 

new infectious diseases are constantly emerging and antibiotic resistance 

is becoming increasingly widespread. As antibiotics lose their ability 

to control diseases, scientists are looking to nature for new and effective 

drugs. One approach includes taking advantage of the millions of years of 

experience the microbial world has had while engaging in its own version 

of biological warfare. 

Bacteriophages—viruses that specifically infect bacteria—represent an 

enormous resource from which to obtain agents to control pathogenic bacteria. 

Following infection and replication inside a bacterial host, bacteriophages 

must exit the bacterial cell in order to disseminate their progeny phage and 

continue subsequent infection cycles. To enable this step, they have evolved 

enzymes called lysins that degrade the host bacterial cell wall from within, 

thus resulting in cell lysis and death.

Because bacteriophages are highly specific in the bacterial hosts they are 

able to infect, their lysins are also highly specific in their ability to kill certain 

bacterial strains. Using such specific mechanisms to control the growth of 

pathogenic bacteria would be a great advantage over the current use of broadrange antibiotics in that the unwanted side effects of killing “friendly” bacteria 
1101 Bio-IInspired IInnovation and ovation and NNational SSecurity 

in the human body and enabling further development of antibiotic resistance 

in the bacterial community would be reduced. 

Due to the fear of increasing antibiotic resistance, there are no direct 

preventative measures to control the carrier state of pathogens, and the current 

practice instead is to provide treatment after infection has occurred. This 

practice leads to increased health risks for immune-compromised patients, 

insufficient control of epidemics throughout populations, and reduced battlefield 

performance as warfighters recover from infection. The use of antimicrobial 

agents such as lysins that are specific for certain strains of pathogens promises a 

new, preventative approach to containing and fighting disease. 

Indeed, several examples of the potential benefits of lysins have already 

been demonstrated. An icros has been isolated from a bacteriophage specific 

for Bacillus anthracis that could be used to specifically detect vegetative or 

spore forms of the bacterium in certain environments as well as prevent and 

treat anthrax infections.9

 Animal tests have also shown that lysins specific 

for the pathogens Streptococcus pneumonia, Streptococcus pyogenes, and 

group B streptococci can be used nasally or orally to prevent and reduce 

serious infections via a “lysis from without” mechanism.10 The use of such 

preventative measures could significantly reduce the occurrence of disease 

by targeting the reservoir of pathogens in a specific environment (such as 

hospitals, nursing homes, or disease-infested communities) and could also 

protect civilian populations and warfighters against the ravages of epidemics 

and biological weapons. 

Enzymes to Neutralize Toxic Chemicals 

The biocatalytic destruction of organophosphates has become an important 

research area as technologies are sought for decommissioning chemical 

weapons, remediating contaminated sites, counteracting nerve agent attacks, 

and protecting against organophosphate pesticide poisoning. The chemical 

warfare (CW) agents that have received the most attention since World War II 

are the organophosphorus (OP) nerve agents such as the type “G” agents sarin, 

soman, and tabun, and the type “V” agents. The toxicity of these compounds is 

attributed to their inhibition of the enzyme acetylcholinesterase, which plays a 

crucial role in regulating concentrations of the neurotransmitter acetylcholine 

within the human nervous system. OP nerve agents are believed to be the 

most likely CW agent to be used during asymmetric warfare or terrorist 

attacks because they are relatively easy to produce and their possession can 

be difficult to detect.

Organophosphate-based CW agents have traditionally been 

decontaminated using harsh chemicals such as oxidizing compounds or 
Bioenzymes and Defense 111

bleaches. These treatment chemicals are often toxic themselves or can generate 

toxic breakdown products, thus posing a threat to response teams as well as 

the surrounding environment. Enzymes that catalyze the hydrolysis of OP 

compounds, on the other hand, can provide a safe, effective, and sustainable 

approach to CW agent decontamination. Two enzymes in particular, 

organophosphorus hydrolase and organophosphorous acid anhydrolase, have 

received considerable attention for their ability to hydrolyze nerve agents to 

stable, benign products. 

Scientists at the U.S. Army Edgewood Chemical Biological Center have 

joined forces with Genencor to facilitate large-scale production and testing 

of advanced catalytic enzyme systems, resulting in a commercially available 

product line of decon enzymes. They are nontoxic, noncorrosive, easy to use, 

and environmentally friendly and have been shown to be stable and active 

in a variety of forms including mixed with both fresh and salt water, and in 

firefighting sprays, foams, and degreasers. They are also highly active, and 

small doses can achieve desired decontamination levels, thereby reducing the 

logistics tail in military and emergency response situations. For example, it 

has been shown that just 1 gram of enzyme can decompose 1.7 kilograms of 

sarin agent within 15 minutes of contact at room temperature.11

OP compounds are the most widely used insecticides, accounting for 

an estimated 34 percent of worldwide sales. Soil contaminated by pesticides 

as a result of bulk handling, application in the field, or accidental release may 

occasionally lead to contamination of surface and ground water. In addition 

to accidental release of OP compounds through agricultural or industrial 

use, drinking water distribution systems supplying soldiers at the front lines 

or large population centers must be seriously considered as potential CW 

targets for terrorists. 

Because of their nontoxic, noncorrosive, and environmentally 

benign properties, enzymes may also provide an ideal method for cleanup 

or bioremediation of toxic agents, pesticides, or other chemicals in water 

systems. Due to the large volumes of water contained in water distribution and 

treatment systems, a decon enzyme would need to be active for a much longer 

time than would be required during direct military operations. Scientists are 

exploring ways to stabilize enzymes to extend their lifetime once released into 

a body of water, and are also investigating ways to immobilize and entrap 

enzymes within filters to treat flowing water systems. Using advances in 

biotechnology such as protein engineering and metagenomics, companies 

such as Genencor not only are altering the stability and lifetime of existing 

enzymes, but also are searching for a wider variety of enzymes capable of 

neutralizing chemical and biological weapons for different applications. For 

example, the destruction of biological agents in pipes could be performed by a 
1123 Bio-IInspired IInnovation and ovation and NNational SSecurity 

combination of enzymes that bind to, attack, and degrade the polysaccharide 

matrix of biofilms. 

Enzymes may also harbor promise for safely counteracting the activity of 

OP nerve agents in humans with minimal side effects. A number of multistep 

pretreatment and postexposure antidotes exist for preventing the lethal effects 

of OP nerve agents, but they do not prevent pharmacological side effects that 

can lead to performance decrements and in some cases permanent brain 

damage. The development of a single inhalable or injectable antidote that 

would remain active in the bloodstream could work to protect the warfighter 

against OP nerve agents and optimize performance by decreasing reliance 

on burdensome protective suits and preventing postexposure incapacitation. 

Currently under investigation are several detoxifying enzymes derived 

from outdated human plasma that bind to or catalyze the breakdown of OP 

nerve agents, such as human butyrylcolinesterase and paraoxoniase-1. Because 

these bioscavenger enzymes are of human origin, they are unlikely to initiate 

an immune response and are stable for long periods in the bloodstream. 

However, there is not enough human plasma available to meet the demands 

of affordably producing bioscavenger enzymes for military or emergency 

response situations. Recombinant technology, such as producing human 

enzymes in the milk of other animals, will likely be needed to produce sufficient 

quantities.12 Enzymes with catalytic anti-OP activity have also been identified 

from numerous bacterial sources. Ongoing protein engineering studies may 

yield variants of these enzymes, with structural alterations enabling improved 

binding and catalytic properties, greater stability during storage and in the 

bloodstream, and greater immunological compatibility for human use.

Enzymes to Process Pharmaceuticals and Food 

Enzyme catalysis has proven to be an important tool in the industrial 

synthesis of bulk chemicals, chemical building blocks for pharmaceuticals, 

active pharmaceuticals, and processing of food ingredients. Current 

examples of large-scale industrial applications of enzyme catalysis include the 

thermolysin-catalyzed synthesis of aspartame (the low-calorie sweetener)13

and antibiotic synthesis.14 For any industrial process, numerous performance 

parameters must be met, and enzymes offer advantages over traditional 

chemical catalysis due to their specificity and ability to catalyze reactions 

that are challenging for classical organic chemistry practices. For example, 

the synthesis of compounds obtained from substrates that are not soluble 

in aqueous media can be achieved using enzymes that operate under low 

water conditions, such as enzymes adapted to low-temperature or high-salt 

environments.15
Bioenzymes and Defense 113

The increasing demand for enantiomerically pure drugs and asymmetric 

pharmaceutical intermediates has also led to a rapid expansion of the use of 

biocatalysis in organic synthesis. As chemical and pharmaceutical industries 

continually look for new biocatalysts to apply to biotransformation and 

biosynthetic processes, it is predicted that enzymes will provide a superior 

solution over classical chemistry in many existing processes.16 Enzymes hold 

particular promise for the production of biobased platform chemicals for a 

variety of purposes,17 including bioplastics, solvents, antifreeze compounds, 

and many more products that may find industrial and defense applications. 

Enzymes are particularly useful for the processing and preservation 

of foods. Proteases can be used for tenderization and taste improvement 

of meat products, and pectin-depolymerizing enzymes can be used for the 

degradation of pectin compounds in fruits and vegetables. Cold-adapted 

galactosidases can improve the digestibility of dairy products for lactoseintolerant consumers and enhance sweetness at temperatures that minimize 

contamination. In baking, the combined activities of enzymes such as 

xylanases, proteases, amylases, lipases, and glucose oxidases can result in 

improved elasticity and machinability of dough, resulting in a larger volume 

and improved crumb structure. 

Applications specific to the defense industry include food ration 

development, where nutrition, personnel acceptance, cost, shelf life, and 

performance enhancement are primary developmental parameters. For 

example, during the processing of ready-to-eat rations, meat items must 

first be enzyme-inactivated to become shelf-stable. Inactivation is in part 

accomplished by heating the product, which results in a partially cooked 

product that has a “warmed over” flavor upon reheating prior to serving. 

Addition of thermostable proteases or peptide hydrolases that are inactive at 

storage temperatures but reactivate solely upon reheating can produce protein 

hydrolysates that enhance the flavor of the meat product. 

Enzymes can furthermore act as antistaling compounds for 

carbohydrate-based food items in ready-to-eat rations. Different types of 

amylases with different functionalities can be used in combination to convert 

starch into forms that resist firming.18 Use of thermostable amylases that 

survive the baking step and remain active during storage can prolong the 

product’s shelf life. Enzymes can thus effectively work to increase product 

quality and menu variety of ready-to-eat rations, boosting morale of the 

troops in the front lines and enhancing the acceptance of carbohydrates and 

meat products. 

Food items can also be amended with enzymes of intermediate stability 

that remain active in the human digestive tract to enhance the digestibility 

and uptake of important vitamins and minerals. This practice could lead 
1145 Bio-IInspired IInnovation and ovation and NNational SSecurity 

to enhanced warfighter performance through nutritional initiatives while 

decreasing the amount of food that needs to be ingested to provide sufficient 

energy. Enzymes can furthermore be used to convert native biomass such as 

plants and trees to hydrolyzed, digestible food products capable of supporting 

soldiers in survival situations. 

Growing Toward a Bio-based Economy: Biofuels and Bioenergy 

Over the next half century, the human population is predicted to grow to 

nearly 9 billion people. Given the current projections of fossil fuel shortfalls, 

there is increasing worldwide interest in developing alternative sources 

of energy. Biofuels, including ethanol made from the fermentation of 

carbohydrates produced in plant matter, represent a renewable energy source 

that can also provide increased energy security, a reduction in greenhouse gas 

emissions, economic benefits for rural communities, and decreased burden of 

agro-industrial residue waste disposal.19

However, to be economically competitive with traditional energy 

sources, the current cost of biomass processing for ethanol must be reduced. 

In the conventional ethanol production process, a starchy feedstock such as 

corn is first milled and slurried with water containing the heat-stable amylase. 

This slurry is then cooked at high temperatures (105° to 150°C) to gelatinize 

and liquefy the starch, and the resulting product is then cooled to ~60°C, and 

a glucoamylase is added to convert the liquefied starch to fermentable sugars. 

In the final step of the process, yeast is added to the mixture and incubated at 

temperatures below 35°C for 48 to 55 hours to ferment the sugars to ethanol.

The conventional ethanol production process is not energetically or 

economically efficient as it requires high heat levels and specialized equipment, 

and limits the production capacity of biorefineries. 

Industrial enzyme companies are working to develop a low-energy 

ethanol production process involving raw starch hydrolysis, also known 

as cold hydrolysis. This process essentially eliminates the energy- and 

equipment-intensive liquefaction cooking step, resulting in energy savings, 

higher ethanol yields, fewer unwanted side products, and savings on capital 

expenses by reducing and miniaturizing the necessary equipment. Due to 

their high activities and specificities at the low temperatures compatible with 

fermentation (28° to 35°C),20 cold-active enzymes derived from bacteria 

adapted to colder climates may afford a reduction in biocatalyst loading 

and prove to be an economically attractive alternative. Industrial enzyme 

companies are also pursuing methods for inexpensive ethanol production 

from low-cost lignocellulosic biomass, including agricultural waste, forestry 

waste, energy crops, and municipal solid waste. For military purposes, 
Bioenzymes and Defense 115

one might imagine the development and use of mobile biorefineries that 

use local biomass and waste products, possibly generated by the troops 

themselves, to produce ethanol, thus reducing the cost and logistical burden 

of transporting fossil fuels.21

Enzymes also play a key role in the biological production of hydrogen, 

recognized as another promising energy source for the future. Using 

available sunlight, water, and biomass, unicellular green algae, cyanobacteria, 

photosynthetic, and dark fermentative bacteria can generate hydrogen via 

several processes including biophotolysis and dark fermentation. Involved 

in each of these processes are the hydrogen-producing enzymes hydrogenase 

and nitrogenase. The primary technical challenge at present is to lower costs of 

production in order to make biologically produced hydrogen a commercially 

viable primary energy carrier. Several Federal agencies are involved in funding 

basic research to bio-prospect for hydrogen-generating microorganisms, 

characterize the hydrogen-generating apparatus, perform directed evolution 

experiments aimed at optimizing hydrogen-generating enzymes, and 

furthermore engineer metabolic pathways to eliminate unnecessary draining 

of energy equivalents away from the hydrogen-generating apparatus. 

Scientists are also investigating the feasibility of integrating different 

photobiological processes and fermentative production of hydrogen to 

maximize solar spectral use, efficiently recycle biomass and waste products, 

and improve process economics. Sometimes the enzymes relevant to 

optimizing these processes are isolated from bacteria living in the unlikeliest 

of places, such as methane producers growing in sewage sludge, or cellulosedegrading bacteria living in a termite’s hindgut.22 The most important 

application of hydrogen to date has been in space programs, where the 

light fuel presents a significant payload advantage. As their power densities 

increase with technological advances, one can imagine hydrogen-powered 

fuel cells replacing batteries as a lighter electrochemical power source for a 

number of defense applications.

In addition to large-scale energy generation to power vehicles, living 

quarters, and factories, enzymes can also be used for small-scale energy 

generation to power tiny devices such as biosensors and other implantable 

electronic systems. As outlined earlier in this book, biosensors can be used 

for a variety of applications, including detection of dangerous agents in the 

environment, and as implantable devices for detection of key metabolites to 

determine the physiological state of soldiers. 

To fuel such electronic systems, scientists are exploring the feasibility 

of producing miniature, membraneless implantable glucose-O2

 biofuel cells 

whereby “wired” enzymes capture energy from living tissues by simultaneous 

glucose oxidation and oxygen reduction.23 The continuous power output 
1167 Bio-IInspired IInnovation and ovation and NNational SSecurity 

observed from such cells is thought to be sufficient for operating implanted 

sensors and transmission of data to an external source for periods up to several 

weeks. When linked to a sensor-transmitter system, automated assessments 

of soldier readiness can be sent to a command network (such as proposed by 

Future Combat Systems) to enable highly informed decisionmaking processes. 

One can even imagine the eventual development of self-activating, implantable 

devices capable of delivering therapeutic agents upon sensing the presence of 

biological or chemical weapons or a change in physiological status. 

Enzymes to Build Functional Materials 

The discussion in this review has primarily been focused on enzymes 

produced by microorganisms, as their genomes are the most easily targeted 

by the functional screening tools available in metagenomics, and they are 

thought to represent the largest reservoir of biodiversity on this planet. 

However, eukaryotes may also hold the key to elucidating several important 

processes, particularly when investigating ways in which nature builds 

efficient structures. 

In the field of materials science, chemical synthesis of mineral/organic 

composites, and silica-based materials such as nanostructured resins, 

molecular sieves and electronic materials have traditionally required harsh 

chemicals and extremes of temperature, pressure, and pH. In nature, however, 

large quantities of structural materials are synthesized biologically from 

molecular precursors at low temperatures, pressures, and neutral pH into 

complex nanostructures such as the skeletons of diatoms, radiolarians, and 

sponges, often with a precision that exceeds current engineering capabilities.24

A study of the mechanisms enabling the biological synthesis of silica 

spicules in a marine sponge revealed that structure-directing enzymes were 

responsible for the polymerization of silica.25 Since this discovery, numerous 

enzymatic and enzyme-inspired (biomimetic) methods for the synthesis of 

nanostructured materials at low temperatures and mild chemical conditions 

have been illustrated.26

Due to the mild synthetic conditions as well as the high selectivity 

and precision when compared with traditional chemical techniques, these 

methods can be used to synthesize a new generation of polymeric biomaterials 

containing functional organic molecules such as enzymes or antibodies. 

Such capabilities will enable the design of novel sensors with environmental 

and biomedical applications, the synthesis of functional materials such as 

“active” protective wear, and perhaps even the synthesis of self-replicating 

materials capable of wound healing or self-repair. Further investigations will 

surely reveal additional biological and bio-inspired methods of synthesizing 
Bioenzymes and Defense 117

nanostructured materials under mild conditions, resulting in inexpensive, 

environmentally friendly generation of novel functional materials. 

Conclusion 

Microorganisms are the most abundant and adaptable life form on Earth. 

Over the past several billion years, they have had the opportunity to evolve 

to survive in almost any environment. Now, metagenomic and genetic 

engineering tools exist to exploit this natural biodiversity and to adapt gene 

products and metabolic pathways for numerous applications. Because extreme 

environments contain such a large portion of the Earth’s diverse biosphere, 

further investigations of these regions yield great promise for revealing 

biological molecules and processes that can find numerous applications.

Ever-changing economics of sequencing will enable rapid sequencing 

of warfighters’ genomes to identity susceptibilities or physiological strengths 

in certain conditions, in addition to sequencing the transcriptome of soldiers 

in the field to quickly determine their current physiological state before 

deployment.

As technology advances, our economy will move toward a bio-based 

economy and away from our dependence on petroleum hydrocarbons for fuel 

and chemical feedstocks.

Research topics should be focused on innovation of biotechnologies to 

not only enhance the protection of personnel, but also expand warfighting 

capabilities by enhancing the physiological performance of soldiers and 

decreasing logistical burdens.

Notes 

1 R.E. Armstrong, From Petro to Agro: Seeds of a New Economy, Defense Horizons 20 

(Washington, DC: National Defense University Press, 2002).

2 Presentation from the Ninth Chemical Industry Finance and Investments Conference, 

2005, available at www.novozymes.com/NR/rdonlyres/64054ABC-F525-4B62-A1EB5BBE6A55468E/0/Chemicals_Conference_ML_2005.pdf.

3 T.D. Brock and H. Freeze, “Thermus aquaticus gen. n. and sp. N., a Nonsporulating Extreme 

Thermophile,” Journal of Bacteriology 98, no. 1 (1969), 289–297.

4 S.J. Giovannoni et al., “Genetic Diversity in Sargasso Sea Bacterioplankton,” Nature 345, no. 

6270 (1990), 60–63. 

5 C.S. Riesenfeld, P.D. Schloss, and J. Handelsman, “Metagenomics: Genomic Analysis of 

Microbial Communities,” Annual Review of Genetics 38 (2004), 525–552.

6 J.C. Venter et al., “Environmental Genome Shotgun Sequencing of the Sargasso Sea,” Science

304, no. 5667 (2004), 66–74.
118 Bio-Inspired Innovation and National Security

7 R. Cavicchioli et al., “Low-temperature Extremophiles and their Applications,” Current 

Opinion in Biotechnology 13, no. 3 (2002), 253–261.

8 J.W. Deming, “Psychrophiles and Polar Regions,” Current Opinion in Microbiology 5, no. 3 

(2002), 301–309.

9 R. Schuch, D. Nelson, and V.A. Fischetti, “A Bacteriolytic Agent that Detects and Kills 

Bacillus Anthracis,” Nature 418, no. 6900 (2002), 884–889.

10 V.A. Fischetti, “Bacteriophage Lytic Enzymes: Novel Anti-Infectives,” Trends in Microbiology

13, no. 10 (2005), 491–496.

11 J.K. Rastogi et al., “Biological Detoxification of Organophosphorus Neurotoxins,” in 

Biodegradation Technology Developments, vol. 2, ed. S.K. Sikdar and R.L. Irvine (Lancaster, 

PA: Technomic Publishing Company, 1998).

12 See D.E. Lenz et al., “Stoichiometric and Catalytic Scavengers as Protection against Nerve 

Agent Toxicity: A Mini Review,” Toxicology 233, no. 1–3 (2007), 31–39. 

13 K. Oyama, “The Industrial Production of Aspartame,” in Chirality in Industry, ed. A.N. 

Collins, G.N. Sheldrake, and J. Crosby (Chichester: Wiley, 1997). 

14 A. Bruggink, E.C. Roos, and E. De Vroom, Organic Process Research and Development 2 

(1998), 128. 

15 A.L. Huston, “Biotechnological Aspects of Cold-adapted Enzymes,” in Psychrophiles: From 

Biodiversity to Biotechnology, ed. R. Margesin et al. (Berlin: Springer-Verlag, 2008).

16 P. Lorenz and J. Eck, “Metagenomics and Industrial Applications,” Nature Reviews 

Microbiology 3, no. 6 (2005), 510–516.

17 P. Turner, G. Mamo, and E. Nordberg Karlsson, “Potential and Utilization of Thermophiles 

and Thermostable Enzymes in Biorefining,” Microbial Cell Factories 6 (2007), 9.

18 T. Olesen, “Antistaling Process and Agent,” patent no. US6197352.

19 C.E. Wyman, “Potential Synergies and Challenges in Refining Cellulosic Biomass to Fuels, 

Chemicals, and Power,” Biotechnology Progress 19, no. 2 (2003), 254–262.

20 Y. Lin and S. Tanaka, “Ethanol Fermentation from Biomass Resources; Current State and 

Prospects,” Applied Microbiology and Biotechnology 69, no. 6 (2006), 627–642.

21 R.E. Armstrong and J.B. Warner, Biology and the Battlefield, Defense Horizons 25 

(Washington, DC: National Defense University Press, 2003). 

22 F. Warnecke et al., “Metagenomic and Functional Analysis of Hindgut Microbiota of a 

Wood-feeding Higher Termite,” Nature 450, no. 7169 (2007), 560–565.

23 A. Heller, “Miniature Biofuel Cells,” Physical Chemistry Chemical Physics 6 (2004), 209–216.

24 D. Kisailus et al., “Enzymatic Synthesis and Nanostructural Control of Gallium Oxide at 

Low Temperature,” Advanced Materials 17, no. 3 (2005), 314–318.

25 K. Shimizu et al., “Silicatein a: Cathepsin L-like protein in sponge biosilica,” Proceedings of the 

National Academy of Sciences of the United States of America 95, no. 11 (1998), 6234–6238.

26 For review, see Huston.
119

Becoming independent of crude oil imports, mainly from the Middle 

East, is an urgent concern for many countries all over the world. 

In order to secure a sustainable energy supply, especially in the 

transportation sector, governments need to apply policies that promote the 

use of renewable energy technologies.

The dependence on crude oil imports decreases as the production of 

total energy from renewable sources (renewable liquid fuels) increases. There 

are two major factors that will influence the amount of final energy production 

from renewable sources.

First, sufficient quantities of biomass need to be acquired for conversion 

into liquid fuels. If a country cannot provide enough biomass, it has to 

compensate by importing it, which does not lead to energy independence. 

Biomass is a limited resource. Even though countries like the United States 

and Canada encompass large areas of rural land, agriculture and forestry have 

distinct impacts for the economy as well as for the environment. The use of 

biomass for conversion to energy competes with other purposes such as food 

supply and forestry products. Land availability and crop yields are key criteria 

in determining the quantities of biomass that can be obtained for energy 

use within a country. What is more, the production of biomass for energy 

use must be sustainable, which requires a thorough understanding of the 

environmental impacts and the likely demand scenarios for renewable fuels.

The amount of final energy obtained from domestic renewable energy 

also depends on the applied conversion technologies. The efficiency of 

processing biomass into liquid fuels affects the energy input-output ratio. The 

less energy needed to run the processes, the more that is available to enter 

chapter 8

Bioenergy: 

Renewable Liquid Fuels

Michael Ladisch
1201 Bio-IInspired IInnovation and ovation and NNational SSecurity 

the market. Moreover, a change from the current conservative conversion 

methods to a new generation of technologies will highly influence the total 

amount of liquid fuels derived from biomass in the long term. A significant 

characteristic of the new generation technologies is the fact that a larger 

portion of the available biomass is convertible into biofuels.

Current Role of Biomass for Liquid Transportation Fuels 

National governments, particularly in North America and Europe, are 

promoting the use of liquid fuels from renewable resources. Since the 

consumption of biofuel is mainly driven by its market price, various means 

of promoting biofuels intend to make them economically feasible for the 

customer. These means include tax reductions on gasoline and diesel blended 

with bioethanol and biodiesel, respectively, as well as on vehicles that utilize 

biofuels. Some countries, such as Brazil and the United Kingdom, enforce 

legislation that mandate a minimum biofuel blending level. In the long term, 

financial support for research and development in renewable derived fuels is 

important to establish a sustainable biofuel industry. The U.S. Department 

of Energy (DOE), for example, has been funding research centers and the 

development of commercial cellulosic ethanol plants since 2007.1

Bioethanol and Biodiesel in the United States, Brazil, and Europe 

An overview of the impact of renewable fuels for the transportation sector in 

the United States in comparison to Brazil and Europe (see table 8–1) shows 

U.S. bioethanol production to be comparable to Brazil, with Europe producing 

much less than either country. In comparison, biodiesel consumption in 

Europe exceeds that of the United States. Sources of feedstocks that are 

converted to biofuels vary by region.

table 8–1. Biofuel Consumption in the United States, Brazil, and Europe

United States Brazil Europe

Bioethanol

Output, 2006 (billion gallons) 4.9 4.7 0.42

Main sources Corn Sugar cane Wheat, sugar beet

Market share 2.9 percent 40 percent < 0.1 percent

Biodiesel

Consumption, 2006 (million gallons) 263 n/a 1,200

Main sources Soybean n/a Rapeseed
Bioenergy: Renewable Liquid Fuels 121

While the United States consists of a total of 2 billion acres of land, 33 

percent are used as forestlands and 46 percent as agricultural lands, of which 

26 percent is grassland or pasture and 20 percent is croplands. In 2006, 190 

million dry tons of biomass per year were used for bioenergy and bioproducts. 

Most of the biomass is burned for energy; only 18 million dry tons are used to 

produce biofuels (mainly corn grain ethanol).2

In 2004, 1.26 billion bushels of corn (11 percent of all harvested corn) 

were converted to 3.41 billion gallons of starch ethanol (one-third of world 

ethanol production).3 The ethanol was produced in 81 plants in 20 states. In 

2006, 4.9 billion gallons of ethanol were produced,4 and a 5.5-billion-gallon 

capacity was planned until 2007.5 Although demand for fuel ethanol more 

than doubled between 2000 and 2004, ethanol satisfied only 2.9 percent of 

U.S. transportation energy demand in 2005.6, 7 Over 95 percent of ethanol 

production in the United States comes from corn, with the rest made from 

wheat, barley, milo, cheese whey, and beverage residues.8

U.S. biodiesel consumption was 75 million gallons in 20059 and 263 

million gallons in 2006.10 Total diesel fuel consumption in 2006 was 63 billion 

gallons. While blended in conventional diesel fuel, the most important 

biodiesel source is soybean.11

Brazil reached a bioethanol output of 4.7 billion gallons in 2006, 

contributing to one-third of world ethanol production.12, 13, 14 Ethanol 

currently comprises about 40 percent of the total vehicle fuel used in the 

country.15 Brazil accounted for almost 90 percent of the ethanol imported into 

the United States in 2005.16

European countries produced 13 percent of the world’s ethanol. In 2006, 

approximately 416 million gallons were consumed (= 557,000 tons/year).17

Germany, Spain, and France were the main producers, using wheat and sugar 

beet as the predominant crops.18, 19 Biodiesel consumption was approximately 

1.2 billion gallons in 2006 (= 3,852,000 tons/year).20 Rapeseed (84 percent) 

and sunflower (13 percent) were the main feedstock.21 In 2005, the overall 

transportation energy use of liquid fuels was 290,000,000 tons/year.22

Figure 8–1 displays the high growth rate for biofuels in Europe and 

the dominant role of biodiesel. Policies in Europe vary among countries, but 

leading biofuel consuming countries have set targets to reach a total market 

share of about 6 percent within the next 3 years. Current market share is about 

2 percent. There are significant differences in composition of market share 

within Europe. However, biodiesel has the biggest share in most European 

countries. Only a few countries, including Poland, Sweden, and Spain, 

consume more bioethanol than biodiesel. Sweden and Germany consume 

notable amounts of biogas (methane generated by anaerobic digestion) and 

pure vegetable oil for transportation use, respectively.23
1223 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Prospects of Biomass Use for Liquid Fuels within the United States 

In 2006, 142 million dry tons of biomass were already used by the forest 

products industry for bioenergy and bioproducts. Residues from the industry 

include tree bark, woodchips, shavings, sawdust, miscellaneous scrap wood, 

and black liquor, a byproduct of pulp and paper processing. Other potential 

forestry biomass resources include logging and site-clearing residues (such 

as unmerchantable tree tops), forest thinning, fuel wood (roundwood or logs 

for space heating or other energy uses), and urban wood residues such as 

municipal solid waste (discarded furniture and packing material).24

Agricultural biomass resources include annual crop residues, perennial 

crops, miscellaneous process residues, and grain (primarily corn). Annual crop 

residues are mainly stems and leaves (such as corn stover and wheat straw) from 

corn, wheat, soybeans, and other crops grown for food and fiber. Perennial 

crops comprise grasses or fast-growing trees grown specifically for bioenergy.25 FIGURE 8–1. PRODUCTION OF BIODIESEL AND BIOETHANOL IN THE EUROPEAN UNION 15*

**Data for 2004 relates to EU25.

 Source: Biofuels Barometer 2007, Le Journal des Energies Renouvables, no. 179, available at 

 http://ec.europa.eu/energy/res/sectors/bioenergy_publications_en.htm.

2,500

2,000

1,500

1,000

500

0

199319941995199619971998199920002001200220032004**

Thousand tons

Biodiesel Production Bioethanol Production

**Austria, Belgium, Denmark, Finland, France, Germany, Greece, Ireland, Italy, Luxembourg,

 The Netherlands, Portugal, Spain, Sweden, United Kingdom.

figure 8–1. Production of Biodiesel and Bioethanol in the European Union 15*
Bioenergy: Renewable Liquid Fuels 123

Potential of Cellulose 

A DOE and U.S. Department of Agriculture joint study examined whether 

land resources in the United States are sufficient to harvest over 1 billion dry 

tons of biomass annually, which would be enough to displace 30 percent or 

more of the Nation’s liquid transportation fuels. This study projected that 

1.366 billion dry tons of biomass could be available for large-scale bioenergy 

and biorefinery industries by the mid-21st century while still meeting demand 

for forestry products, food, and fiber. Of the 1.366 billion dry tons of biomass, 

368 million dry tons are obtained from forests, and 998 million dry tons are 

sourced from agriculture.

The potential of the “billion-ton” study is based upon conservative 

assumptions. The scenario displayed in this study assumes “business as usual” 

and therefore does not mark an upper limit. The study assumes continuing 

improvements, such as in yields per acre and harvesting technologies. It does 

not take future technologies, particularly cellulose-to-ethanol, into account. 

Cellulosic ethanol has the potential to meet most, if not all, transportation fuel 

need since it is potentially possible to harvest the 1.366 billion tons of biomass 

required on an annual basis. Cellulosic material, available in large quantities, 

will provide the feedstocks needed for biomass processing (see figure 8–2).26 

However, the second-generation conversion technologies that are 

implemented in demonstration facilities are not yet economically feasible. FIGURE 8–2. COMPARISON OF FOSSIL ENERGY RATIO FROM FOUR DIFFERENT ENERGY SOURCES 

Fossil Energy Ratio = Energy Delivered to Customer

Fossil Energy Used

Projected

Current

Cellulosic

Ethanol

Biorefinery

Corn

Ethanol

Gasoline Electricity

Fossil Energy Ratio

1.36

11

10

9

2

1

0

10.3

0.81

0.45

figure 8–2. Comparison of Fossil Energy Ratio from Four Different Energy Sources
1245 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Today’s cellulosic biorefineries convert the biomass in numerous complex, 

costly, and energy-intensive steps.

Production of Cellulosic Ethanol 

Research on processing cellulosic material to ethanol has been conducted for 

many years. The following section gives an overview of its state of the art and 

will serve as an introduction to display some barriers in commercialization.

Characteristics of Lignocellulose 

The strength and the complexity of lignocellulosic material, which makes 

hydrolysis difficult, are a result of its structure and composition. The strength 

of the cell wall is created by the network formed of hemicellulose and cellulose 

and the presence of lignin. The variability of these characteristics accounts for 

the varying digestibility between different sources of lignocellulosic biomass, 

which mainly consists of the polymers cellulose and hemicellulose, as well as 

lignin, which is nonfermentable. 

Since cellulose is a heterogeneous substrate, it makes cellulolytic enzyme 

hydrolysis difficult to model. Cellulose is composed of chains of glucose 

(arranged in layered sheets) connected by beta 1–4 glycosidic bonds. The two 

most dominating characteristics of cellulose are as follows. The specific surface 

area (SSA) is defined as the amount of surface area per mass of cellulose. SSA 

is significant because it determines the number of enzymes that are adsorbed 

by the substrate. An increase in SSA leads to an increasing rate of hydrolysis. 

The crystallinity index states the relative amount of crystalline cellulose as 

opposed to the amount of amorphous cellulose. When endoglucanases (Egs) 

attack the amorphous regions, the crystallinity index increases.27

By using enzymes to break down the polymers, nearly theoretical 

yields of sugars can be obtained.28 However, a pretreatment step is essential 

to achieve these high yields. In this step, cellulose is liberated from the lignin 

seal and from its crystalline structure, rendering it accessible for the enzymes 

during the hydrolysis (see figure 8–3). 

Cellulose-to-Ethanol Process Overview 

The first step of the process is biomass handling, where the size of the 

lignocellulose is reduced to make handling easier and ethanol production more 

efficient. During pretreatment, the lignin seal is broken, the hemicellulose is 

partially removed, and SSA is increased. After pretreatment, the cellulose 

and hemicellulose fractions are more accessible to enzymes in the forms of 

polymers and oligomers. Hydrolysis then breaks the chains into monomers. 
Bioenergy: Renewable Liquid Fuels 125

The monomers can be fermented by natural yeast (glucose fermentation) 

or by genetically engineered bacteria (pentose fermentation). The result of 

fermentation is a mixture of water, ethanol, and residues, with carbon dioxide 

being formed and removed as a gas from the fermentation (see figure 8–4). 

Finally, ethanol is purified in a distillation column while the residues 

can be either burned to power the process or converted to co-products. 

FIGURE 8–3. SCHEME OF LIGNOCELLULOSIC MATERIAL

Source: T.A. Hsu, M.R. Ladisch, and G.T. Tsao, “Alcohol From Cellulose,” Chemical Technology 10, no. 5 (1980).

Lignin

Cellulose

Amorphous

Region

Crystalline

Region

Pretreatment

Hemicellulose

{

{

figure 8–3. Scheme of Lignocellulosic Material

FIGURE 8–4. STAGE PRODUCTS OF CELLULOSE-TO-ETHANOL PROCESS

Lignocellulose

Monomers of

Glucose and Pentose Ethanol

+ CO2

 + H2O + Residues

Polymers and Oligomers

of Glucose and Pentose

Pretreatment Hydrolysis Fermentation

HH

HH

H CC OH

figure 8–4. Stage Products of Cellulose-to-Ethanol Process
1267 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Hydrolysis and fermentation can be done separately or in the same tank, 

which reduces costs. In a biorefinery, nonfermentable material, such as lignin, 

is used to power the process. Furthermore, expensive catalysts are recovered 

for reuse. Carbon dioxide is recycled into plant matter through production 

agriculture. Figure 8–5 shows the process sequence of a biorefinery.

High concentrations of sugar and ethanol should be aimed at, so that 

the amount of energy needed for distillation can be minimized.

Feedstock Preparation and Pretreatment 

Handling of the feedstock is an important step because it facilitates the 

biochemical conversion of lignocellulosic biomass. Size reduction makes the 

feedstock more accessible to process media and therefore reduces enzyme 

loadings as well as the amounts of water and chemicals needed. After the 

mechanical process of milling, the biomass particles are pretreated. The 

two main goals of the pretreatment step are improving the rate (amount of 

converted monomers per time unit) of enzyme hydrolysis, and increasing the 

yield of fermentable sugars from cellulose or hemicellulose.

Pretreatment is one of many steps in the cellulose-to-ethanol process, 

but it currently represents a critical and expensive step that must take place 

for hydrolysis to occur. Therefore, it cannot be engineered without regard to 

the other steps. An effective pretreatment has several attributes, including 

reducing particle size and conditions that avoid degradation of pentose 

from hemicellulose or glucose from cellulose, and limiting formation of 

degradation products that inhibit growth of fermentative microorganisms 

(which are needed for the fermentation process). Pretreatments should also 

limit energy, chemical, and/or enzyme usage in order to limit the cost of the 

pretreatment process itself.29 FIGURE 8–5. UNIT OPERATIONS OF BIOREFINERY

Feedstock Enzymes

Microbes

(Yeast, Bacteria) Fuel

Energy Residue

Co-products

CO2

1 Feedstock

Preparation 2 Pretreatment 3 Hydrolysis 4 Fermentation 5 Separations

6 Combustion or

Gasification

Catalysts

figure 8–5. Unit Operations of Biorefinery
Bioenergy: Renewable Liquid Fuels 127

The question arises of how much economic effort should be devoted 

to pretreatment. To answer this question, the process parameters must be 

balanced against their impact on the cost of all other process steps before 

and after pretreatment. In addition, a tradeoff between operating costs, capital 

costs, and biomass costs have to be taken into account.

There are two different pathways for pretreatment: physical and 

chemical. Comminution, or mechanically reducing the particle size, and 

steam explosion (see below) are physical means. Chemical pathways are 

adding solvents to dissolve the cellulose (an effective but expensive method) 

or using other chemicals.30

Each pretreatment pathway has distinct effects on the chemical 

composition and chemical/physical structure of lignocellulosic biomass. Table 

8–2 gives an overview of the effects caused by different pretreatment methods. 

One effect is the increase of SSA by creating pores in the cellulose structure, 

thus improving the micro-accessibility of the cellulases. Decrystalization of 

cellulose refers to disrupting the hydrogen bonds that tie up the cellulose 

chains. Decrystalization increases the macro-accessibility of the cellulases. 

The removal of both hemicellulose and lignin weakens the structure of 

lignocellulose, because it eliminates part of the network that accounts for the 

strength of the cell wall. The enzymes’ accessibility to the cellulose fibrils is 

table 8–2. Eff ect of Various Pretreatment Methods on Chemical Composition 

and Chemical/Physical Structure of Lignocellulosic Biomass

Increases 

specific 

surface area

Decrystalizes 

cellulose

Removes 

hemicellulose

Removes 

lignin

Alters 

lignin 

structure

Uncatalyzed steam explosion X X *

Liquid hot water X ND X *

pH controlled hot water X ND X ND

Flowthrough liquid hot water X ND X * *

Dilute acid X X X

Flowthrough acid X X * X

Ammonia fiber explosion X X * X X

Ammonia recycled percolation X X * X X

Lime X ND * X X

X = Major effect * = Minor effect ND = Not determined

Source: M.S. Mosier et al., “Features of Promising Technologies for Pretreatment of Lignocellulosic Biomass,” 

Bioresource Technology 96 (2005), 677.
1289 Bio-IInspired IInnovation and ovation and NNational SSecurity 

improved when hemicellulose is solubilized and lignin is partially solubilized. 

Altering the lignin structure means partially cracking it and breaking the 

bonds between cellulose and its lignin sheathing. Different pretreatment 

methods emphasize certain effects, and the combinations of these effects 

increase the overall efficiency of the pretreatment.31

Pretreatment increases the yields of sugars and ethanol during 

hydrolysis and fermentation, respectively, when operated at optimal 

conditions. However, biomass pretreated at overly harsh conditions can lead 

to formation of degradation products, which decreases sugar and ethanol 

yields. The pretreatment model in figure 8–6 illustrates the process of cellulose 

saccharification and degradation.

Pretreatment renders the recalcitrant cellulose fraction of the biomass 

more accessible to enzymes by altering its structure. During this step, 

crystalline (C) and amorphous (C*) cellulose is converted into glucose 

oligomers (Gn). If the process conditions are too severe, the bonds in the 

cellulose chain will break further into sugar monomers (G), which will 

eventually degrade to toxic substances. The constant k represents the rate of 

reaction at each stage. The rates and the exposure time of the cellulose to the 

pretreatment environment determine the level of degradation.32

Pretreatment Technologies 

Uncatalyzed steam explosion. High-pressure steam is applied to the biomass 

without addition of chemicals.33 The rapid thermal expansion following the 

compression opens up the particle structure. Then, the water itself or SO2 acts 

as an acid at high temperatures. During steam explosion, acids are released. 

This leads to removal of hemicellulose (from the complex lignocellulosic 

structure), improving their accessibility to the enzymes. 

C

C*

k1

k2

Gn G Degradation

k2

, k3 >>k1

k3 k4

Source: N.S. Mosier et al., “Features of Promising Technologies for Pretreatment of Lignocellulosic Biomass,” 

Bioresource Technology 96 (2005), 675.

FIGURE 8–6. PRETREATMENT MODEL

figure 8–6. Pretreatment Model
Bioenergy: Renewable Liquid Fuels 129

Liquid hot water pretreatments. Cooking the biomass in hot water breaks 

lignocellulosic particles without adding acid. Pressure is needed for this 

process in order to maintain the water in a liquid state. However, water 

pretreatment requires no neutralization or conditioning of chemicals because 

of the absence of acid. A highly digestible cellulose results when enzyme is 

added, high yields of sugars from hemicellulose occur, and more than half of 

the lignin is dissolved during pretreatment. By maintaining the pH constant 

between 5 and 7, the hemicellulose fraction is converted into oligosaccharides 

while minimizing the formation of monomeric sugars. Thus, degradation 

reactions, which would lower the yield of fermentable sugars, are hindered.

There are three methods of transporting the hot water through the 

biomass: co-current, countercurrent, and flowthrough. This leads to diverse 

appliance constructions with distinct yields and concentrations of sugar.

Experiments with corn stover have shown that about 40 percent of the 

lignocellulose can be dissolved during pretreatment releasing sugar oligomers. 

In the following hydrolysis of the pretreated biomass, nearly 80 percent of the 

cellulose and 70 percent of the hemicellulose have been converted into glucose 

and pentose, respectively. This is due to the change of the chemical composition 

of corn stover. In addition, the physical appearance of corn stover is affected in 

such a way that the surface becomes perforated. The pores increase the enzymeaccessible surface area, which increases the enzyme digestibility. The result of 

pretreatment, in terms of yield and avoiding degradation, is mainly a function 

of temperature, pressure, pH, and time. While high temperature tends to reduce 

the required time for pretreatment, lower temperature may be preferred since 

the operational pressure, and therefore the energy demand, is lower.34 The 

relevance of pH and the effect of degradation will be discussed in detail.

Acid pretreatment. Lignin is disrupted and hemicellulose is removed when 

dilute sulfuric acid is added to the heated biomass, enhancing digestibility of 

cellulose in the residual solids. The yields are very high, but so are the costs. 

The latter is due to:

• expensive construction materials (because of corrosion)

• the acid neutralization step (acid degrades the sugars) 

• the release of natural biomass fermentation inhibitors

• the disposal of neutralization salts

• long reaction time

• high enzyme demand

• high energy demand for the cellulose grinding.35, 36

Flow-through acid pretreatment. Most of the disadvantages of acid 

pretreatment can be avoided when configuring the acid level at lower than 0.1 
1301 Bio-IInspired IInnovation and ovation and NNational SSecurity 

percent. The sugar yields are very high, and only few acids are released during 

the reaction. However, the system requires significant energy for pretreatment 

and product recovery as a result of the great amount of water processed.37

Lime pretreatment. Lime, calcium oxide, is an alkali and can be dissolved 

in water, where it becomes a medium strength base. Lignocellulose can be 

treated with lime water at ambient conditions. Low temperature and pressure 

will result in long reaction times, while high temperature and pressure will 

accelerate the reaction. The major effect of this technology is the removal of 

lignin from the biomass. A limitation occurs because some of the alkali is 

converted to irrecoverable salts or incorporated as salts into the biomass.38

Ammonia pretreatment. Liquid ammonia causes swelling of the 

lignocellulose, which increases SSA. In ammonia recycled percolation, 

ammonia reacts primarily with lignin. The ammonia depolymerizes the lignin 

and breaks the lignin-cellulose linkages. Ammonia fiber/freeze explosion 

simultaneously reduces lignin content and removes some hemicellulose 

while decrystallizing cellulose.

While the cost of ammonia and especially ammonia recovery drives 

the cost of this pretreatment, the sugar yields are very high and the enzyme 

loadings as well as the degradation are low.39 Table 8–3 shows the main 

characteristics of the technologies described above.

table 8–3. Representative Pretreatment Conditions of Considered Technologies

Pretreatment 

technology Chemicals used Temperature, °C

Standard 

atmospheric 

pressure, absolute

Reaction 

times (minutes)

Uncatalyzed 

steam explosion Water 240 40 <15

Liquid hot water Water 180–220 24–27 15–20

Dilute sulfuric acid

0.5%–3% 

sulfuric acid 130–200 3–15 2–30

Flowthrough acid

0.0%–0.1% 

sulfuric acid 190–200 20–24 12–24

Lime

0.05 gram–0.15 gram 

Ca(OH)2/gram biomass 70–130 1–6 60–360

Ammonia recycled 

percolation

10–15 weight 

percent ammonia 150–170 9–17 10–20

Ammonia fiber 

explosion

100% (1:1) 

anhydrous ammonia 70–90 15–20 <5
Bioenergy: Renewable Liquid Fuels 131

pH Monitoring during Pretreatment 

Harsh pretreatment environments, like liquid water temperatures above 200°C 

and pH below 5, decrease the yield of fermentable sugars and thus the yield of 

ethanol. The pH decreases when the temperature decreases during pretreatment. 

At low pH, organic acids can form, thus leading to dissociation of hydrogen ions. 

The existence of hydrogen ions during pretreatment promotes autohydrolysis, 

or hydrolysis of cellulose to oligosaccharides and glucose in absence of enzymes. 

Autohydrolysis has a negative impact on the entire process for two reasons:

• Glucose tends to degrade to organic acids in the harsh pretreatment 

conditions. The organic acids such as furfur then form more hydrogen 

ions, which further accelerates utohydrolysis.

• Degradation decreases the extent of enzymatic conversion of 

polysaccharides and oligosaccharides to monosaccharides, which are 

needed for fermentation.

The reduction of pH can be avoided by means of adding KOH, which 

is a strong base. Controlling the pH at about 7 (neutral) results in a higher 

percentage of solid cellulose and a lower concentration of hydrogen ions after 

the pretreatment. A higher pH leads to bacterial contamination and must be 

avoided as well.

The formation of organic acids is relevant only to the cellulose fraction 

of biomass. The solubilization of hemicellulose during pretreatment, which 

occurs to almost 100 percent, does not result in the formation of significant 

amounts of acids.

The choice of chemicals used, pH, temperature, and pressure applied:

• affects the construction design of the pretreatment unit (cost of 

pretreatment itself)

• influences the yields from cellulose and hemicellulose

• releases cellulose and hemicellulose in distinct states of polymerization.

Due to the varying structure and composition of different lignocellulosic 

resources, the pretreatment methods applied should depend on the raw 

material used.40

Hydrolysis 

The rigid crystalline structure of cellulose needs to be decrystallized in order 

to produce ethanol. There are two pathways of hydrolyzing: the use of acids 

and of enzymes (the latter being focused on here). Enzymatic hydrolysis has 

the potential to make ethanol, derived from cellulose biomass, competitive 

when compared to other liquid fuels on a large scale.41 Cellulolytic enzymes, 

evolved from fungi and bacteria, are used in these processes as well as in other 
1323 Bio-IInspired IInnovation and ovation and NNational SSecurity 

industries (such as the textile industry) to liberate the individual glucose 

monomers that will then be fermented to ethanol. Hydrolysis refers to a 

mechanism of breaking the bonds of the glucose chain by adding water.42

For improving the efficiency of the hydrolysis, it is important to gain 

knowledge in the substrate parameters (different crystal forms, varying 

degrees of crystallinity) and the enzymatic system applied (number of 

enzymes, synergistic effects, and product inhibition). Due to the high cost of 

cellulolytic enzymes, the enzymatic system needs to be optimized. The enzyme 

loading also depends on the results of pretreatment. The more accessible the 

cellulose is for the enzymes, the lower is the required enzyme loading.43

Cellulases are enzymes that catalyze cellulolysis (hydrolysis of cellulose). 

Cellulases are classified into three main groups: cellobiohydrolases (CBHs), 

endoglucanases, and beta-glucosidases. These groups play distinct roles in 

the hydrolysis. While CBHs attack the chain ends of the cellulose polymers, 

Egs attack the amorphous regions of the cellulose chains. After breaking the 

cellulose, beta-glucosidase hydrolyzes the generated cellobiose to glucose.44 

The three types of enzymes operate synergistically. The effect of the most 

obvious synergism, called endo-exo, is that Egs generate more chain ends by 

random scission for the CBHs to attack.45

The majority of the cellulases (CBHs and Egs) are modular proteins with 

two distinct, independent domains. The catalytic core is responsible for the 

hydrolysis of cellobiose from the cellulose chain. The cellulose binding domain 

(CBD) has a dual activity. The CBD is in charge of binding the enzyme to the 

cellulose layer, and it also affects the cellulose structure. After the enzyme has 

bound to the cellulose, it reduces the cellulose’s particle size, therefore increasing 

SSA. Since the enzyme is connected to the cellulose layer via the CBD, the catalytic 

core can work independently from the CBD. This molecular architecture allows 

the enzyme to release the product while remaining bound to the cellulose chain. 

A linker region joins the independent catalytic core to the CBD (see figure 8–7).46

Fermentation and Separation 

The glucose monomers that are released during hydrolysis can be fermented 

to ethanol using yeast. Saccharomoyces are natural yeasts that feed on the 

glucose to produce ethanol and are currently applied in the large-scale 

corn-to-ethanol and sugar cane-to-ethanol industries. However, ethanol 

production from lignocellulose requires fermentation of not only glucose, 

but also pentose sugars. Saccharomoyces are not able to ferment pentose. 

One way to manage fermentation of pentose is the utilization of genetically 

modified yeasts, specifically engineered for this purpose.47

Hydrolysis performed separately from fermentation is known as separate 

hydrolysis and fermentation. Cellulose hydrolysis carried out in the presence 
Bioenergy: Renewable Liquid Fuels 133

of the fermentative organism is referred to as simultaneous saccharification 

and fermentation. Simultaneous saccharification of both cellulose (to glucose) 

and hemicellulose (to pentose) and co-fermentation of both glucose and 

pentose are realized by genetically engineered microbes.48

Ethanol is recovered from the fermentation broth by distillation.49

The residual lignin, unreacted cellulose and hemicellulose, ash, enzyme, 

organisms, and other components end up in the bottom of the distillation 

column. These materials may be concentrated and burned as fuel to power the 

process, or converted to various coproducts.50

Challenges 

Fundamental research in biochemistry has been conducted in order to achieve 

the state-of-the-art technologies. However, feedstocks, pretreatment, and 

hydrolysis as well as the use of enzymes and yeast are not yet fully understood 

individually and as a system. This knowledge is critical in order to make 

current technologies more efficient so that cellulosic ethanol can be produced 

on a commercial scale.

Guideline and Time Frame for Establishing a Biofuel Industry 

The usage of cellulose biomass has the potential to become the key source for 

meeting America’s future transportation fuel needs. As mentioned above, a 

sustainable biofuel industry is based on supply of sufficient biomass and on costand energy-efficient conversion technologies. In 2006, DOE set up a technical 

strategy to develop a viable cellulosic biomass to biofuel industry over the next 

figure 8–7. Modular Nature of Cellulolytic Proteins

FIGURE 8–7. MODULAR NATURE OF CELLULOLYTIC PROTEINS

Source: N.S. Mosier et al., “Reaction Kinetics, Molecular Action, and Mechanisms of Cellulytic Proteins,” 

in Advances in Biochemical Engineering/Biotechnology, vol. 65, ed. T. Scheper (Berlin: Springer, 1999), 33.

Linker Region

Cellulose Binding Domain

Cellulose Fiber

Catalytic Core
1345 Bio-IInspired IInnovation and ovation and NNational SSecurity 

5 to 15 years.51 This strategy includes concurrent development of innovative 

energy crops with new biorefinery treatment and conversion processes.

The development is built on three successive phases. The research 

phase will provide the basis of knowledge in the fields of agriculture and 

biochemistry. This knowledge will be transferred into technology modules 

in the technology deployment phase. In the systems integration phase, 

all modules will be consolidated as a system to ensure productivity and 

sustainability. The roadmap is summarized in figure 8–8.

Research Phase 

Fundamental knowledge in three critical areas—plant design, deconstruction 

of lignocellulose, and fermentation and recovery—has to be acquired.

The traits of current energy crops have to be optimized, since the 

crops play an important role in the bioenergy system. The biofuel industry 

strives for crops with high yields and improved robustness that are also 

uncomplicated to process. However, growing such crops in large quantities 

will require a sustainable soil ecosystem. Research in plant design will enhance 

understanding of cell-wall polymer organization and interactions.

Further research in pretreatment of cellulosic biomass will focus 

on improving hydrothermal and mechanical pathways. Also, a deeper 

understanding of enzyme function is required. This will lead to higher 

hydrolysis rates and increased icrosyst robustness. A goal is to be able to 

redesign cellulosome (containing the full repertoire of degrading various 

polysaccharides) for a diversity of feedstock.

An organism needs to be found that allows simultaneous saccharification 

and co-fermentation—that is, not only co-fermentation of pentose and 

hexose, but also incorporating hydrolysis and co-fermentation in one single 

step, thus reducing the number of processing steps. Due to the nature of the 

process, such an organism must have high tolerance to stress, inhibitors, and 

high alcohol concentrations.

Technology Deployment Phase 

In this phase, plant domestication technologies will reach a mature state. 

This includes availability of multiple crops for distinct regional and global 

agroecosystems. Furthermore, improved pretreatment procedures, enzymes, 

and fermentation organisms will be deployed in existing biorefineries. 

First results of the concurrent development of feedstock and processing 

technologies will be recognizable. Deconstruction of lignocellulose should 

become easier to handle due to the domestication of the energy crops.
Bioenergy: Renewable Liquid Fuels 135

Systems Integration Phase 

Feedstocks and processes will be fully consolidated as a bioenergy system and 

will accelerate and simplify the end-to-end production of ethanol. Bioenergy 

systems do not only function in a single area. They also are tailored for specific 

regional climate and soil characteristics. Toolkits will be made available that 

enable rapid diagnosis and manipulation of all critical aspects of the biosystem 

(field and facilities).

FIGURE 8–8. STAGES AND CONTENTS OF DEPARTMENT OF ENERGY BIOFUELS ROADMAP

Source: U.S. Department of Energy, Breaking the Biological Barriers to Cellulosic Ethanol: A Joint Research Agenda, 

DOE/SC–0095 (Washington, DC: U.S. Department of Energy Office of Science and Office of Energy Efficiency and 

Renewable Energy, 2006), available at www.doegenomestolife.org/biofuels.

Roadmap to 

Biofuels

Bioenergy Systems Integration

• Consolidation of feedstocks and

 processes as a system

• Tailoring of bioenergy system

 for specific area

• Toolkits for rapid system

 diagnosis and manipulation

Increasing Performance

Increasing Integration

Technology Deployment

Feedstocks

• Matured plant

 domestication

• Crops for regional

 and global

 agroecosystems

Deconstruction and Fermentation

• Deployment of improved

-pretreatment procedures

-enzymes

-fermentation organisms

Plant Design

5 years 10 years 15 years

Integrated Bioenergy Crop and Process Research

High

yield

Improved 

processability

Sustainable

soil 

ecosystem

Improved

robustness

Deconstruction 

of Lignocellulose

Fermentation 

and Recovery

-Hydrothermal and mechanical pretreatment

-Develop deeper understanding in enzyme function

-Enable simultaneous saccharification and 

 co-fermentation

figure 8–8. Stages and Contents of Department of Energy Biofuels Roadmap
1367 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Conclusion 

Successfully establishing a cellulose-to-biofuel industry requires 

understanding of a complex system of parameters. Biomass availability, 

technological progress, international fuel markets, and fuel utilization are 

parameters that will play major roles in the biofuel area.

In order to make biofuels economically feasible, several requirements 

have to be met. First, large quantities of biomass must be made available for 

biofuel use in order to reduce competition with other agricultural industries 

(food and feed), while high crop yields will reduce agricultural land use. 

Sufficient production of biomass and efficient land usage are important 

factors for avoiding the effect of price increase for feedstock. Technological 

progress in both plant domestication and conversion processes will drive this 

development and ensure sustainability.

Biofuel production and trade have to be considered on an international 

stage since production externalities affect the market price. Production 

costs vary among countries due to different fuel sources (such as sugar cane, 

bagasse, corn stover, sugar beet), land availability, labor cost, and so forth. 

Producing biofuels in an environmentally friendly and sustainable manner 

is important but also cost effective. However, there are not yet international 

legislations or incentive measures to ensure equal market opportunities for 

all producing countries. Low-cost biofuel imports to the United States will 

therefore have an impact on the feasibility of domestic production.

Action within the automotive industry can accelerate the biofuel market 

share. This includes providing the vehicle market with engines that are able 

to drive with a variety of fuels. Due to the nature of the conversion processes, 

biorefineries are economically feasible when they can generate a great diversity 

of products, including a variety of transportation fuels. However, this variety 

of liquid fuels is only marketable if there is a demand for a range of biofuels. 

Continuing the development of flexible fuel vehicles and promoting their 

acceptance in society will therefore be a key in establishing a biofuel industry.

Notes

1 U.S. Department of Energy, Breaking the Biological Barriers to Cellulosic Ethanol: A Joint 

Research Agenda, DOE/SC-0095 (Washington, DC: U.S. Department of Energy Office of 

Science and Office of Energy Efficiency and Renewable Energy, 2006), available at 

www.doegenomestolife.org/biofuels.

2 Ibid., 9. 

3 European Biomass Industry Association, “Bioethanol and the World,” available at 

www.eubia.org/212.0.html.
Bioenergy: Renewable Liquid Fuels 137

4 U.S. Department of Energy, Energy Information Administration, “Petroleum Navigator,” August 

28, 2009, available at http://tonto.eia.doe.gov/dnav/pet/hist/m_epooxe_yop_nus_1M.htm.

5 Breaking the Biological Barriers to Cellulosic Ethanol, 12.

6 Ibid. 

7 “Petroleum Navigator.”

8 Barry D. Solomon, Justin R. Barnes, and Kathleen E. Halvorsen, “Grain and Cellulosic 

Ethanol: History, Economics, and Energy Policy,” Biomass and Bioenergy 31, no. 6 (June 

2007), available at www.sciencedirect.com/science/article/B6V22-4N7YFWT-3/2/26b377

d735b2a30e206fa35ed64903cf, 417.

9 Doris de Guzman, “Biodiesel: Boom or Bust,” ICIS Chemical Business Americas, 

February 5, 2007.

10 F.O. Lichts, World Ethanol and Biofuels Report 6, no. 1 (September 6, 2007). 

11 de Guzman. 

12 Solomon, Barnes, and Halvorsen. 

13 “Bioethanol and the World.”

14 U.S. Department of Energy, Energy Information Administration, “Country Analysis Briefs: 

Brazil,” October 2008, available at www.eia.doe.gov/emeu/cabs/Brazil/pdf.pdf.

15 Solomon, Barnes, and Halvorsen.

16 Ibid. 

17 877,000 tons/year = 36,831,000 gigajoules (GJ)/year (1 ton = 42 GJ); energy content of 

ethanol (LHV) = 0.0234 GJ/liter; 3.785 liters = 1 gallon. 

18 “Biofuels Barometer 2007,” Le Journal des Energies Renouvables, no. 179, available at http://

ec.europa.eu/energy/res/sectors/ bioenergy_publications_en.htm.

19 “Bioethanol and the World.”

20 3,852,000 tons/year = 161,787,000 gigajoules (GJ)/year (1 ton = 42 GJ); energy content of 

biodiesel (LHV) = 0.034 GJ/liter; 3.785 liters = 1 gallon.

21 “Biofuels Barometer 2007.”

22 Available at http://epp.eurostat.ec.europa.eu/portal/page?_pageid=1996,39140985&_

dad=portal&_schema=PORTAL&screen=detailref&language=en&product=sdi_

tr&root=sdi_tr/sdi_tr/sdi_tr_gro/sdi_tr1230.

23 Ibid. 

24 Breaking the Biological Barriers to Cellulosic Ethanol.

25 Ibid. 

26 Ibid. 

27 N.S. Mosier et al., “Reaction Kinetics, Molecular Action, and Mechanisms of Cellulytic 

Proteins,” in Advances in Biochemical Engineering/Biotechnology vol. 65, ed. T. Scheper 

(Berlin: Springer, 1999), 26. 

28 C.E. Wyman et al., “Coordinated Development of Leading Biomass Pretreatment 

Technologies,” Bioresource Technology 96 (2005), 1961.

29 N.S. Mosier et al., “Features of Promising Technologies for Pretreatment of Lignocellulosic 

Biomass,” Bioresource Technology 96 (2005), 675.

30 Ibid., 676. 

31 Ibid. 

32 J.R. Weil, “Unified Model for Hydrolytic Effect during Cellulose Pretreatment,” master’s 

thesis, Purdue University, 1993, 10. 
138 Bio-Inspired Innovation and National Security

33 Cristobal Cara et al., “Influence of Solid Loading on Enzymatic Hydrolysis of Steam 

Exploded or Liquid Hot Water Pretreated Olive Tree Biomass,” Process Biochemistry 42, 

no. 6 (June 2007), available at www.sciencedirect.com/science/article/B6THB-4NCSGST 

2/2/66e5b58a04cca8acf97941b13dd5c21f.

34 N.S. Mosier et al., “Optimization of pH Controlled Liquid Hot Water Pretreatment of Corn 

Stover,” Bioresource Technology 96 (2005).

35 Wyman et al.

36 Mosier et al., “Features of Promising Technologies.”

37 Ibid. 

38 Ibid. 

39 Ibid. 

40 J. Weil et al., “Continuous pH Monitoring During Pretreatment of Yellow Poplar Wood 

Sawdust by Pressure Cooking in Water,” Applied Biochemistry and Biotechnology 70–72 (1998).

41 C.E. Wyman, “Biomass Ethanol: Technical Progress, Opportunities, and Commercial 

Challenges,” Annual Review of Energy and the Environment 24 (1990), 190.

42 Mosier et al., “Reaction Kinetics, Molecular Action, and Mechanisms of Cellulytic Proteins,” 36.

43 Breaking the Biological Barriers to Cellulosic Ethanol, 31–32. 

44 Mosier et al., “Reaction Kinetics, Molecular Action, and Mechanisms of Cellulytic Proteins,” 

24–25.

45 Ibid., 31. 

46 Ibid., 33–36. 

47 N.W.Y. Ho et al., “Genetically Engineered Saccharomyces Yeasts for Conversion of 

Cellulosic Biomass to Environmentally Friendly Transportation Fuel Ethanol,” American 

Chemical Society Symposium Series, 2000, 144. 

48 Mosier et al., “Features of Promising Technologies,” 674.

49 M.R. Ladisch et al., (1984) “Cornmeal Absorber for Dehydrating Ethanol Vapors,” I&EC 

Process Design and Development (1984), 23.

50 C.E. Wyman, “Ethanol from Lignocellulosic Biomass: Technology, Economics, and 

Opportunities,” Bioresource Technology (1995), 50.

51 Breaking the Biological Barriers to Cellulosic Ethanol.
139

We all feel humble in the face of the ingenuity and complexity of 

nature. Yet it need not prevent us from learning, exploring, and even 

attempting to construct clinically useful artificial systems having a 

few of the simpler properties of their natural counterparts.

—Thomas Ming Swi Chang1

I

n 1956, Dr. Chang, then an undergraduate, had the audacity to believe 

he could build artificial blood cells. Working in his own residence room, 

he proved himself correct.2 Today, Dr. Chang has been joined by a legion 

of scientists and engineers working to duplicate materials and functions 

formerly restricted to the realm of nature.

It is impossible to address the full breadth of this field in a single 

chapter. The goals here are rather to present some of the main factors driving 

the recent explosion of bio-inspiration, to provide some specific examples of 

successes in the field, to address some of the more relevant topics in current 

research, and to provide some future possibilities and military applications. 

Why Bio-inspired Materials? 

The living world can now be viewed as a vast organic Lego kit 

inviting combination, hybridization, and continual rebuilding.

—Edward Yoxen3

This quotation can be considered the catch phrase of modern 

biotechnology; it applies to all bio-inspired materials and functions as well. 

chapter 9

Bio-inspired 

Materials and Operations

Erica R. Valdes
1401 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Nature has perfected countless astounding capabilities, and our role is to 

recognize them, learn from them, and use them in all the myriad combinations 

they present. 

Strictly speaking, biotechnology is the use of biological science to 

create chemicals, materials, and organisms through the control of biological 

processes. There is no presupposition that the target products be naturally 

occurring biological or biochemical entities; in reality, it is more typical 

that the targets result from some degree of engineering to provide products 

not identical to those of nature. Bio-inspired is the current terminology 

used to describe the class of materials based either directly or indirectly 

on material structures and functions observed in the biosphere. Clearly, 

there is overlap where a biotechnological manufacture approach is adopted 

in the production of chemicals, materials, and organisms to be used for 

nonbiological applications and where a product is a hybrid of products of 

strict biotechnology and abiotic analogs of biological forms or functions. 

Products of early biotechnology were often classified as biomaterials. 

This term is ambiguous. To a material scientist working in the area of 

materials intended for implant into the body, biomaterials are ones designed 

to be compatible with living tissue. The term was well established in that 

community before the current explosion in bio-inspired materials began. 

In response to this confusion, two other terms were adopted: biotics and 

biomimetics. Biotics refers to direct use of materials of biological origin, while 

biomimetics refers to the use of abiotic methods to mimic the structure and/

or properties of biological materials. Currently, the term bio-inspired is used 

to encompass both biotic and biomimetic materials.

Biological systems excel over traditionally manmade systems in a 

number of arenas. In some cases, the advantages are primarily structural; 

nature has developed methods of achieving complex structures that are ideally 

suited to their applications. These structures provide inspiration both in 

direct emulation for similar applications and in paradigmatic studies allowing 

extension to distantly related applications. Other cases provide primarily 

functional advantages. These provide inspiration in specific solutions to 

functionality requirements in manmade systems. 

Lastly, some cases provide processing and fate advantages. Natural 

synthesis processes are generally environmentally benign, and natural 

products are typically biodegradable. A range of areas in which biological 

systems excel and bio-inspired materials can provide advantages is identified 

according to the advantage category in table 9–1. Clearly, there is significant 

advantage to be gained by studying and emulating materials found in natural 

biological systems.
Bio-inspired Materials and Operations 141

Simple Examples 

At the dawn of civilization, the only materials available to man were either 

biological or mineral, and prior to the development of tools there were limits 

on what could be done with rocks. Biomaterials were clearly the answer. 

Historically, people have been using and mimicking biological materials for 

ages. From the first fig leaf, people have been using biological material for 

clothing and shelter: plant and animal fibers for threads, yarns, and rope; 

animal hides and fur for warmth and shelter; reeds and grasses for woven 

containers; and wood for supports and structures. As civilization advanced 

and the written word evolved, stone tablets were replaced as a writing surface 

by papyrus, bark, animal skins, and eventually paper, bioderived materials 

that provided significant advantages over stone.

Nor is the use of materials to build artificial parts to replace biological 

parts new. Dentures, peg legs, glass eyes, and hand hooks illustrate the point that 

biocompatibility and “medical implants” have in fact been around for centuries.

From the standpoint of biomimetic bio-inspiration—that is, emulating 

a biological function in either an organism not naturally provided with that 

function or a nonbiological item—there are also historical examples. Man’s 

obsession with the power of flight has been in evidence throughout folklore, 

Structural Benefits Functional Benefits Processing/Fate Advantages

Broad range of polymer 

properties accessible

Adaptation to environment Environmentally benign 

processing Signal amplification

Atomic level control 

of structure

Biocompatibility Biodegradation

Range and control of color change Self-assembly

Conformational changes Catalysis

Ambient conditions

Hierarchical structure Computation

Lightweight materials Energy conversion/conservation

Micro- and nano-devices Functional adaptation/evolution

Self-repair Lubricants

Structure/function 

relationships Adhesives

Membranes/transport control

Multifunctional materials

Smart materials/sensor and response

table 9–1. Areas in Which Natural Biological Materials Excel
1423 Bio-IInspired IInnovation and ovation and NNational SSecurity 

mythology, and history. Likewise, our fascination with the aquasphere has led 

us to submarines and scuba gear. 

The Beginning of Modern Bio-inspiration 

In the 1980s, a revolution in bio-inspired materials began. Several aspects of 

natural biological materials came to the forefront for various reasons. 

Bone 

Biocompatible material and implant researchers were interested in developing 

a more natural artificial bone. Bone is unique in its structure and properties. 

In structure, it is a composite of organics (collagen fibers) and minerals 

(crystalline hydroxyapatite). The structural properties vary according to the 

location in the body. Overall, the material is a strong but generally brittle 

composite of varying ductility. In a living system, bone is also self-healing 

and sensing. Stress-generated electrical signals allow living bone to respond 

to demands placed on it by preferential growth, in essence customizing 

itself to its needs. Since the beginning of the interest in bone, scientists have 

succeeded in developing structural mimics using hydroxyatpatite crystals in 

composite with polyethylene. The more complex goals of making a sensing 

and self-healing bone replacement have yet to be achieved.

Soft Tissue 

Soft tissue was recognized in the 1980s to have properties unheard of in the 

abiotic world. Collagen systems have the unusual characteristic of having 

mechanical properties that change with the hydration state of the material. 

Collagen shows the additional advantage of the ability for the individual fibrils 

to self-assemble. Thus, collagen works on several levels: first, the individual 

fibers are themselves connected to form larger fibers; second, the larger fibers 

have unique elastic properties; third, these fibers are variously incorporated 

into composite materials throughout the body. As the main structural fiber of 

the animal kingdom, it is found in applications ranging from tendons to skin 

and bone. Variations between the myriad applications come from the ways in 

which the fibers are incorporated into the composites. 

A specific example of collagen in the body is the intervertebral disc. 

From a mechanical standpoint, they are particularly interesting in that they 

are designed to convert structural compressive stresses into tensional stresses 

in the disc material. This conversion is achieved by using what is termed 

hierarchical structure, in which the interaction between multiple levels of 

structure results in unique or favorable properties. Again, this is the reason 

behind broadly divergent applications of the same material in organisms. 
Bio-inspired Materials and Operations 143

In concluding the discussion of soft tissue concepts, consider the aortic 

valve. As an example of the astounding capabilities of biological tissue, this 

valve opens and closes at a rate of 60 times per minute nonstop. Over the course 

of a typical lifetime, this amounts to something on the order of three billion 

flex cycles, an enviable number to anyone concerned with material fatigue. 

Exoskeletons/Invertebrates 

During the same time frame, looking to invertebrates provided even more 

insight and inspiration. The insect exoskeleton is of particular interest to the field 

of structural composites. A major difficulty in the manufacture of composites is 

control of final product shape and the alignment of reinforcing fibers. Ideally, a 

composite part is produced in “net shape” rather than in a bulk form that is later 

cut. A typical process might include initial “lay-up” of the reinforcing fibers 

(in the case of fiber-reinforced materials), followed by impregnation processes 

driving matrix materials around and between the fibers, and a curing process to 

polymerize (carbon-carbon composites), flame (carbon-ceramic composites), 

or sinter and anneal (metal matrix composites) the matrix. The resulting 

material is likely to undergo shape changes that are difficult to control, and the 

desirable properties of the product make it difficult to machine to final state. 

Insect exoskeletons are in fact fiber-reinforced composites with precise 

reproducibility. Characterization of the shell of the bessbug showed that it is a 

model composite with single-fiber thickness per layer with helical orientation. 

Copying the fiber orientation array of the bessbug shell resulted in polymer 

matrix composites that exit the curing process in a shape nearly identical to 

that of the shell, moving us a step closer to the goal of net shape control. 

Another interesting material from the invertebrate world is nacre, 

also known as mother of pearl, which is also known for its impact strength. 

Microscopically, nacre is composed of layers of brittle platelets of the mineral 

aragonite (a calcium carbonate) separated and held together by sheets of elastic 

biopolymers including acidic macromolecules, silk-like proteins, and b-chitin. 

This classical composite approach combines the strength of the mineral with 

the ductility of the polymers to produce a tough and resilient material. 

However, the story does not end there. In addition to layer strength 

with ductility, the mineral platelets in nacre are typically hexagonal platelets 

arranged in single layers that are staggered like brickwork with biolpolymer 

acting as the mortar. This arrangement is particularly useful in the inhibition 

of crack formation. Biologically, this structure is secreted by the epithelial 

cells of certain mollusks, either as a protective layer inside a shell (mother 

of pearl) or to encapsulate a foreign object (eventually forming a pearl). 

Abiotically, scientists attempt to mimic the composite structure in order to 

achieve similar control over mechanical properties.
1445 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Invertebrates also excel in the area of adhesives. The most familiar 

example of this is the barnacle, which spends all of its adult life cemented 

to one spot—so indelibly cemented, in fact, that it can damage naval vessels. 

Significant research has gone into understanding the barnacle adhesive 

in attempts to protect against it. A related effort has arisen to understand 

it with the intent of recreating it as a superior adhesive for marine 

applications. These studies have migrated to other biological adhesives in 

aquatic environments including that of the mussel, which has yielded the 

first example of a proteinaceous adhesive that is “cured” by cross-linkages 

that form when the organism extracts iron from the surrounding seawater. 

Again, from the biological side these studies are directed at understanding 

and preventing adhesion to naval vessels while the materials applications 

may yield unprecedented adhesives, particularly for use under water. 

A final invertebrate worth mentioning for adhesive applications is the 

banana slug. Its slime is a versatile material that it uses for everything from 

lubrication to personal protection. This substance has also been claimed as the 

strongest adhesive found in nature. Attempts at understanding and recreating 

this slime have been unsuccessful to date.

Biomineralization/Ceramics 

As with composites, minerals and ceramics can be very dependent on 

the microstructure of the material. In the case of ceramics and composites, 

the final material comprises small particles of component materials. Typical 

fabrication processes for ceramics use sol-gel processing, which begins with 

the generation of a liquid suspension of very fine particles called a colloidal 

suspension. This suspension then forms a gel in which the particles link 

together. The gel is then treated by a combination of compression, drying, 

and baking to produce the final ceramic. The properties of the product 

depend on the success in controlling or eliminating the void space between 

the particles. Thus, control of colloidal particles in the production of ceramics 

is an important challenge to ceramists. 

Looking to biology, the biominerals found in, for example, bone and 

shells are grown rather than processed. They are built biochemically in a 

controlled and methodical way, leaving little to chance. This approach directly 

addresses several issues that regularly haunt ceramic processing ventures: room 

temperature sintering, limitations on packing density, undesirable interactions 

of particles in solution, and effects of additives on products. When incorporating 

ceramics into composites, another significant concern is the alignment of the 

particles. Depending on the application, it may be desirable for the particles 

to be either randomly oriented or, as in the case of near–net shape processing 

mentioned earlier, aligned very precisely in specific conformations.
Bio-inspired Materials and Operations 145

This is another area in which biological systems excel. In many cases, 

the biochemical control not only produces near-perfect ceramic particles, but 

also produces them in the desired conformation and simultaneously produces 

the surrounding matrix material. A typical case is the abalone shell, in which 

a soft organic component is generated as a foundation that guides the growth 

of calcium carbonate plates. The level of control is on the size scale of 10 

nanometers (nm) for the scaffolding and 200 nm for the mineral plates, or 

approximately 0.001 and 0.02 times the width of a human hair, respectively. 

In another case, that of diatoms, a single-cell algae produces a self-assembled 

organic scaffold that allows directed synthesis of a silica shell. The familiar 

microscopic shells remain long after the organism has died and decomposed. 

Studying and reproducing both the mechanical and biochemical aspects of 

these biological production processes can provide unprecedented control 

over ceramic and ceramic composite structure and function.

Current Research and Future Materials 

Silk/Advanced Fibers and Spider Silk 

For thousands of years, people have used the cocoon fiber of Bombyx 

mori as a textile fiber. The silkworm cocoon is in fact one continuous fiber 

approximately 10 microns in diameter, an order of magnitude smaller than a 

human hair, and close to 1,000 meters long, providing the staggering aspect 

ratio of 100 million. It is also an impressively strong fiber, silk fabrics having 

been observed to provide ballistic protection as early as the 1800s. The 

silkworm remained the main source of silk primarily because of the relative 

ease of farming the worms and harvesting the fibers. 

In recent years, the incredible strength of spider silk has led researchers 

to investigate the possibility of reproducing it without the spider. Considering 

the strength of fibers, there are three properties typically considered. These are 

the stiffness, which is a measure of how much an object resists deflection when 

a force is applied; the strength, which is a measure of the force required to break 

it; and the toughness, which is its ability to withstand impact without breaking. 

There are in fact several types of silk produced by spiders for specific 

purposes. Two of the more familiar are the dragline, which is recognizable as 

the support frame of the web, and the capture silk, which is the fine sticky silk 

that ensnares the prey. Although based on the same components, each type of 

silk has different properties, though all are at or above the strength of Kevlar, 

tough, processed in ambient conditions, and made of renewable resources. 

The military application most often mentioned with regard to spider silk is 

bulletproof clothing. Both dragline and capture fibers can absorb more energy 
1467 Bio-IInspired IInnovation and ovation and NNational SSecurity 

than Kevlar. Dragline specifically can absorb as much as 10 times the energy, 

most of which is converted to heat. 

Unfortunately, spiders are difficult to farm and harvesting of natural 

spider silk is impractical. Taking a genetic approach to this problem, scientists 

have identified the spider genes responsible for the fibroin proteins that 

comprise spider silk. Cloning those genes and placing them in goats has 

resulted in goats that produce spider silk fibroins in their milk. Media reports 

might lead one to think that this development has put spider silk armor right 

around the corner. In reality, this solves just a small part of the puzzle. As 

with so many biological materials, the morphology—the size and shape of 

the fiber—and the microstructure—the specific arrangement of the protein 

molecules within the fibers—of spider silk are complex and relevant to 

function. Spiders deal with these issues through a combination of mechanics 

and biochemistry in their spinnerets. Current challenges to the scientists in 

this field involve manipulating the goat-produced proteins to reproduce or 

exceed the physical properties of natural spider silk. 

Resilin 

Another important protein in arthropods is resilin, an elastomeric protein 

that confers on fleas the ability to jump more than 100 times their height. The 

protein is capable of many millions of cycles of extension and contraction, and 

as such is one of the most elastic proteins known. As much as 97 percent of 

the energy stored in compression of resilin can be recouped in the following 

expansion. This process allows cicadas to chirp, flies to flap their wings almost 

a million times an hour, and otherwise brittle insect shells to bend and then 

revert to their original shape. 

In addition to this compression and expansion, resilin can stretch up 

to three times its length without breaking. These combined properties arise 

from the structure of resilin on the molecular level and make it more resilient 

than any current manmade material. Recent research has resulted in the 

production of pro-resilin by E. coli. The current challenge is to address the fact 

that in nature, resilin requires water to function properly. In nonbiological 

applications this is seldom practical, so the task remains to recreate the 

properties of resilin in a dry system.

Multifunctional Coatings 

A common requirement in science and engineering is the modification of 

surfaces to allow, encourage, or enhance surface properties and interactions. 

Although numerous approaches are used to modify surfaces, most are limited 

by expense, complexity, or chemical specificity. Taking a bio-inspired approach, 

researchers have focused on the mussel Mytilums edulis. This organism forms 
Bio-inspired Materials and Operations 147

adhesive bonds with almost any surface, including Teflon. Scientists are 

currently deciphering the mechanism that allows this adhesion. Using lessons 

learned, they have successfully demonstrated that a structural mimic of the 

relevant biochemicals allows deposition of thin polymer films on practically 

any surface.4 Moreover, these films are amenable to fictionalization. This and 

similar approaches will significantly reduce the complexity, expense, and 

reliance on highly specific chemistries in the building of functional coatings. 

Artificial Cell 

The value of the artificial cell has been recognized for decades. Scientists, 

engineers, and industry continue to investigate this area for the biomedical 

community. In general, the goal is not to duplicate all cellular activity but 

rather to duplicate the desired activity in a cell or synthetic cell designed 

for use in the body. Extending this thought beyond the biomedical arena, 

scientists are beginning to investigate the possibility of reproducing specific 

cell functions in the environment that exists outside the body. 

One of the challenges in this area will be to devise a support material 

that allows full operation of the cell-inspired functions in an environment 

radically different from a living body. In the cell, the support is the cell 

membrane, and in research directed at aqueous applications, this is typically 

mimicked by lipid bilayers and hydrogels. For the case of dry applications 

these systems need to be either stabilized in air,5, 6 enclosed by environmentally 

hardened materials that allow the encased material to interact freely with its 

surroundings, or replaced entirely by materials that allow or enhance the 

desired function. Some of the areas that can be expected to contribute to 

this process include chitosan, alginate hydrogels, molecular imprints, porous 

inorganic membranes, phosphorylcholine-polymer surface technology, and 

polymerosomes.

Octopus 

The octopus, just one example of a familiar organism, has an impressive array of 

talents that are enviable from a military perspective. It is a structurally complex 

invertebrate, with its beak being its only one small hard feature. The structure 

and movements of the animal arise entirely from the muscles. As a result, its 

structure is quite changeable. Octopuses have been known to squeeze their 

bodies through small cracks—for example, between an aquarium container 

and its lid—or curl themselves up into a slightly ajar clamshell. Some species 

have been found to use two arms to “walk” while using the remaining arms for 

camouflage.7

 While walking is generally believed to require both muscles and 

skeleton, the octopus uses orthogonal bands of muscle to provide flexibility 

and motion while the constant internal volume lends support. 
1489 Bio-IInspired IInnovation and ovation and NNational SSecurity 

This atypical locomotion provides an unusual type of camouflage, 

allowing the kinematics of the animal to mimic other organisms. Unlike just 

shape and color change camouflage, this is effective even when the animal 

moves relatively rapidly. 

The more conventional method of camouflage, hiding by matching 

the surroundings with shape and color changes, is another area in which 

the octopus excels. Using a complex chromatophore system that includes 

reflective iodophores as well as hue-changing cells, the octopus can change 

not only the color but also the pattern and even the texture of its skin, and it 

can make these changes in as little as 3 seconds. 

In addition to impressive mechanical capabilities and camouflage 

strategies, the octopus has a sense of taste 1,000 times that of humans, vision 

that allows detection of polarization, and a far better sense of touch than 

humans. The suckers on the arms of the octopus have chemical receptors 

as well as conventional touch receptors, allowing them to “taste” what they 

touch. Even the well-known ink cloud used by the octopus to visually elude 

its enemies has lesser known qualities of interfering with the senses of the 

enemy, enhancing the effect of the obscuring ink. 

Dry Adhesion and the Gecko 

Often, biology relies on probability as a means to an end. This is evident in 

two examples of dry adhesion. The first of these is the hook and loop fastener, 

most recognized by the trade name Velcro. In basic terms, these fasteners 

involve two pieces: a soft array of loops and a wiry array of hooks. Contact 

between the two pieces causes some of the hooks to attach to some of the 

loops. The large numbers of hooks and loops on each piece ensure that enough 

will engage to provide the required adhesion. This technology precedes 

today’s interest in biological inspiration by several decades. Nevertheless, it 

was inspired by a familiar biological system: the burr. Burrs and similar plant 

structures are covered in stiff hooks that attach to almost any passing fiber, 

from dog fur to clothing, an observation that ultimately led to the invention 

of hook and loop–type fasteners. 

There has been much recent interest in the feet of geckos. Many species 

of this common lizard can readily climb walls and even walk across ceilings. 

The interesting facet of this is that unlike most adhesive organisms, geckos 

do not require any fluid adhesive to successfully defy gravity. Microscopic 

studies of gecko feet reveal that each footpad is covered with hundreds of 

thousands of setae, each of which is comprised of up to 1,000 spatulae that 

are held to surfaces by van der Waals attractions, generally considered to be 

fairly weak intermolecular forces. Scientists have been attempting to recreate 

this phenomenon using nanofibers. By ensuring that all the tips of nanofibers 
Bio-inspired Materials and Operations 149

in an array can contact a surface simultaneously, they have succeeded in 

matching and even exceeding the adhesive powers of the gecko foot. 

Although the gecko is the current hot topic in biomimetic access to 

extra-human locomotion, it is by no means the only organism from which 

we can learn. Mosquitoes and water gliders are well known for their ability 

to walk on water. This ability arises from hierarchical structures on their legs, 

fine hairs that are grooved on the nanoscale to trap air, effectively producing 

air cushions between the insect’s feet and the surface of the water. 

This mechanism is akin to that of gecko climbing in that the ability to 

accomplish astounding feats at the macroscopic scale arises from massive 

arrays of structures found at the microscopic or nanoscopic level. This 

effectively transfers the unusual properties associated with nanotechnology 

into significant abilities on more familiar size scales. This is a recurring 

theme in bio-inspiration and one that has only recently been investigated for 

practical applications.

Plants 

Although much of the interest in bio-inspiration arises from the animal 

kingdom, there are striking examples of bio-inspired success from the plant 

kingdom, and much remains to be explored. A number of plants, among them 

the lotus and jewelweed, are recognized for their ability to repel water. The 

leaves have microscopic level roughness that reduces both the contact area of 

foreign particles on the leaf and the contact angle of water with the surface. 

The result is that particles do not adhere well to the leaves and water droplets 

roll around on the leaves, effectively picking up the particles and cleaning 

the leaves. This effect has been used commercially in the development of an 

exterior paint and textiles that are dubbed “self-cleaning.” 

Bio-inspired Computing and Decentralization 

If you cut off a spider’s head, it dies; but if you cut off a starfish’s leg, it 

grows a new one, and that leg can grow into an entirely new starfish.

—Ori Brafman and Rod A. Beckstrom8

The comparison between a spider and a starfish illustrates decentralization 

at work. While the spider is controlled by a discrete, identifiable head as the 

ultimate authority, the starfish is not dependent on a single control center; 

rather, it is a decentralized organism. Within the biosphere, this phenomenon 

of decentralization is not limited to simple organisms lacking centralized 

nervous systems. It is equally evident on a community level in the functioning 

of ant colonies, bee hives, and bird flocks. 
1501 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Until recently, the tendency even among scientists was to assume some 

centralized control node among these creatures: the flock of birds must be 

following a leader; the ants and bees must be getting orders from the queen. 

The observed behaviors in these and similar groups are now recognized to be 

the result of autonomous collectives. Each animal is operating independently 

according to a set of simple sense and respond rules, and the result is behavior 

that appears to be driven by an elegant master plan. 

A simple example is a group of ants looking for food. The relevant sensing 

functions are the ability to sense food and the ability to sense pheromones. 

The relevant responses are to pick up the food and to release pheromones. 

The rules are simple: if you find food, pick it up and release pheromones, and 

if you sense pheromones, follow the trail emitting the highest level of them. 

With these simple rules, you have a situation where the first ant encountering 

food picks some up, releases some pheromones, and goes on its way. Other 

ants sense the pheromones and head toward the food, where they pick some 

up and release more pheromones, strengthening the signal to even more ants. 

A path to the food is quickly established as more and more ants are attracted. 

Soon the familiar army of ants marching back and forth between the food 

source and home is established, all with no centralized authority. After the food 

source has been depleted, there is no further enforcing of the pheromone trail, 

it erodes with time, and the trail of ants to that particular location dwindles. 

There is no “leader ant” that can be eliminated to put an end to the invasion. 

If the goal is to end the invasion, the only recourse short of reprogramming 

the sense and response functions is to eliminate enough individual ants that 

the pheromone trail erodes more quickly than it is generated. 

Another element that often accompanies discussions and systems of 

decentralization and as such deserves brief mention is stochastics. In simplest 

terms, this refers to randomness or noise. In the case of the ants, this would 

involve a certain amount of aimless wandering and the collective discovery of 

richer food sources or new food sources when old ones are depleted. 

Bio-inspiration in the world of computation predates bio-inspired 

materials or systems as a discipline by several decades. The two most recognized 

examples of this are artificial intelligence and neural networks. The first of these 

is best described as the field addressing synthetically intelligent machines. It 

generally uses conditional programming of the “if X, then Y” variety, in which Y

can be either a classification/identification decision or an action to be carried out 

on the condition of X. In terms of biological inspiration, this is the programming 

approach used in task-oriented robotics designed to carry out specific human 

functions. Simple sensing elements are used to address “if X” and are linked 

to mechanical or electronic output elements to execute Y. This has become so 

ubiquitous that young children can build and program simple robots.
Bio-inspired Materials and Operations 151

The second familiar example of bio-inspiration in the computational 

realm is neural networks. Unlike the linear single-task model of typical artificial 

intelligence applications, neural networks address massive interconnections 

between large numbers of information nodes. Neural nets started as a truly 

bio-inspired attempt to model and in part duplicate the activity of the human 

brain, with the goal of providing the ability for an artificial system to not only 

execute linear if-then processes but also to adapt in response to information 

flowing through the network. More recently, the field has moved away from 

the biological model to focus on statistical and signal processing aspects of 

specific practical applications. Arguably the major advance afforded by neural 

network efforts is the ability to design computing systems capable of making 

observations and inferring functions based on these observations—that is, 

computing systems with the ability to learn and evolve.

In both artificial intelligence and neural network science, the general 

paradigm is still one of centralized and, in most cases, linear processing. In this 

context, the term centralized refers to systems that feed into or out of a single 

node, such as a spider’s head. That is, a centralized system is an organization, 

network, or organism in which a single “leader” receives all available input 

and is the source of all actionable output. For most of us, centralized systems 

are intuitively comfortable; they tend to agree with our instinctive feel for “the 

way things work” as it is developed by childhood familial and institutional 

environments and reinforced by our routine interaction with myriad examples 

of one-to-one cause-and-effect correspondence (often with manmade devices 

specifically built with this direct linear approach). 

Presently, there is a pervasive movement away from centralization and 

linear function in almost all walks of our culture. The most familiar example 

of cultural decentralization is the Internet, the expanding influence of which 

throughout the world has encouraged decentralization in many other areas. 

Although beyond the scope of this chapter, the decentralization theme is often 

used to address organizations, cultures, business models, and even military 

strategies. For further investigation in these areas, a number of currently 

available books address decentralization for the layperson.9, 10, 11, 12

So what does this have to do specifically with bio-inspired materials? 

From the standpoint of computing, it is the concept of massively parallel 

processing, while from the standpoint of biological systems, it ranges from 

the concept of “swarm intelligence” to the difference between a spider 

and a starfish. The starfish, on an organism level, or the ant colony, on an 

organizational level, both reap great benefit from the decentralized paradigm. 

In all cases the recurrent themes are the absence of a functionally necessary 

control node and the presence of massive redundancy and massively parallel 

activity, each of which provide significant advantages over centralized systems.
1523 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Extending this inspiration from general philosophical analogies 

applied to computation and networking systems, bio-inspired structural 

and functional materials can be combined to build networks based on 

decentralized processing approaches. The result would be a purely abiotic 

system comprised of multiple interconnected subsystems and operating in a 

very organic, responsive, and adaptive way.

Applying the principles of decentralization to a traditional hierarchy 

such as the military would be folly. However, applications to specific military 

systems can have huge advantages. One very current example is outlined in 

chapter 5 of this book, “Abiotic Sensing.” The heart of this system is a collection 

of bio-inspired materials conjoined to execute specific sense and respond 

rules in a platform of massively redundant and operationally parallel entities. 

Although the specific sense and response system described is best envisioned 

as a chemical or biological (CB) “detector,” the model can be applied equally 

to other aspects of the CB defense arena. For example, a network of massively 

parallel entities can be deployed with the abilities of detecting agents, sending 

signals in response to positive detection, and detecting. Because these entities 

are identical, there is no individual entity that is crucial to the function of 

the network as a whole. A similar decentralized network can be, for example, 

built into personal protective equipment. 

Multidisciplinary Process 

Historically, much science and engineering has been conducted through 

specialization. For example, many years ago it was possible to be a chemist 

and as such to be relatively well versed in most areas of chemistry and to 

make significant advances using only chemistry. As science and technology 

expanded, specialization became increasingly important and the simple 

chemist became a biochemist, an organic chemist, a physical chemist, and 

so forth. Further specialization turned the organic chemist into a polymer 

chemist, a petroleum chemist, or any of an endless list of subspecialties, 

which can in turn be further subdivided. This was very useful for detailed 

understanding of narrow but significant topics. However, it resulted in an 

ever-widening gap between the major disciplines as the gaps widened between 

the subdisciplines. 

As research and development workers increasingly recognize the 

distinct advantages of bio-inspiration in materials, it has become clear that 

this field straddles several scientific disciplines that are not traditionally 

linked. Extensive collaboration and interdisciplinary programs are required 

to “make it work.” Typically, a capability is recognized in the biological realm 

and identified as desirable. Even at this very early stage, there must be cross-
Bio-inspired Materials and Operations 153

disciplinary activity. A naturalist might recognize the value of a biological 

structure and mention it to a structural engineer, or an adhesives chemist 

fishing at the dock may take note of the barnacles on the pilings and take it 

upon himself to locate a marine biologist. 

In these and most cases, it takes more than one discipline simply to 

connect the biological phenomenon with the bio-inspired application. A 

research and characterization phase looks to fully characterize the materials 

and functions that lead to the capability. Again, the effort probably will require 

a number of different disciplines. A biologist is likely to provide the materials; 

a chemist, materials scientist, or biochemist to analyze the materials; a 

materials scientist, physicist, mechanical engineer, or other specialist to 

identify the relevant structures and mechanisms. Investigations are likely 

to lead to either a harvesting or a synthetic approach and again the success 

is likely to hinge on effective multidisciplinary activities. In harvesting, 

the biological materials are simply used as found in nature or farmed and 

extracted for use, while in synthesis, a production process is developed. In the 

case of synthesis, a decision is then required between a biosynthesis approach, 

using biotechnology to yield biological materials for abiotic applications, or 

a synthetic approach, applying the lessons learned from nature to traditional 

chemical or materials processing methods. 

The challenge for scientists in the area of bio-inspired materials is to 

bridge the gaps not only between the subdisciplines in, for example, chemistry 

but also to build bridges between seemingly disparate subdisciplines in 

chemistry with subdisciplines buried deep in biology, physics, mechanical 

engineering, materials science, and computer and network science. 

Conclusion 

With advances in biotechnology, nanotechnology, and material 

characterization technologies, bio-inspired materials are rapidly growing in 

availability and application. Careful scientific pursuit of desired biological 

properties has been shown to yield successful results. However, the original 

inspiration is often unplanned. Forethought and planning can predict 

neither the unusual sources from which bio-inspiration might spring nor 

the elegant applications to which it is applied. The key to success in this 

area is multidisciplinary research and engineering, along with a willingness 

to consider some fantastic possibilities. A 2001 Board of Army Science and 

Technology report13 identified a broad range of military applications for 

biotechnology, many of which address bio-inspired materials. Table 9–2 

summarizes a number of these and other potentials for military applications. 
154 Bio-Inspired Innovation and National Security

Notes

1 T.M.S. Chang, Artificial Cells (Springfield, IL: Charles C. Thomas, 1972), available at 

www.medicine.mcgill.ca/artcell/1972bookCovercr.pdf.

2 A. Picard, “The Red Blood Cell Man,” McGill News 76, no. 4 (1996), 22–25.

3 E. Yoxen, The Gene Business: Who Should Control Biotechnology? (London: Pan Books, 1983).

4 H. Lee et al., “Mussel-Inspired Surface Chemistry for Multifunctional Coatings,” Science 318 

(2007), 426.

5 Helen K. Baca et al., “Cell Directed Assembly of Lipid-Silica Nanostructures Providing 

Extended Cell Viability,” Science 313 (2006), 337. 

6 Liangfang Zhang and S. Granick, “How to Stabilize Phospholipid Liposomes (Using 

Nanoparticles),” Nanoletters 6, no. 4 (2006), 694–698.

7 Christine L. Huffard, F. Boneka, and R.J. Full, “Underwater Bipedal Locomotion by 

Octopuses in Disguise,” Science 25, no. 307 (2005), 1927.

8 Ori Brafman and Rod A. Beckstrom, The Starfish and the Spider (London: Penguin Books 

Ltd., 2006).

9 Ibid.

10 Mitchel Resnick, Turtles, Termites, and Traffic Jams; Explorations in Massively Parallel 

Microworlds (Cambridge: MIT Press, 1994).

11 David Freedman, A Perfect Mess (New York: Little, Brown, and Co., 2007).

12 R. Frenay, Pulse (New York: Farrar, Straus and Giroux, 2006).

13 Board on Army Science and Technology, Opportunities in Biotechnology for Future Army 

Applications (Washington, DC: National Academy of Sciences, 2001), available at 

www.nap.edu/books/0309075556/html/index.html.

APPLICATION DESCRIPTION

Camouflage and concealment

Bio-inspired materials with stealth characteristics, 

nonilluminating coatings

Combat identification Biomarkers

Computing

DNA computers, biological models, amorphous computing, 

decentralization

Lightweight armor

Bio-derived and -inspired materials for weight reduction and 

self-healing armor

Mobility enhancement

Bio-derived and -inspired materials for unprecedented mobility 

(people, vehicles, robotics)

Novel materials Biodegradable consumables, bio-derived and -inspired materials

Performance enhancement Prosthetics, biointegration

Power Biological photovoltaics, synthetic photosynthesis

Radiation resistant electronics Based on nanobiotechnology, biomolecular devices

Sensors Biological processes, biomimetic processes in abiotic cell

Size/weight reduction Molecular electronics, self-assembly, bio-inspired armor

table 9–2. Areas for Potential Military Application of Bio-inspired Materials
part three

bio-inspired 

machines

157

With nightfall, the aerial hunters camouflaged in black emerge 

by the thousands from their base carved into a hillside. The first 

challenge they face is evading opposing forces attacking from the 

air as they emerge. Using advanced ultra–wide band transceivers 

for both communication and navigation, they traverse the 

darkness, dodging obstacles and flying through foliage with ease. 

They are on a search-and-destroy mission, and their quarry are 

flying distributors of a biological agent responsible for the deaths 

of half of the human population of the planet. After a night of 

carnage, they return to their base and regroup, preparing for more 

combat the following night.

Does this passage describe a futuristic battle between armies of 

unmanned aerial vehicles (UAVs)? Perhaps one day. But in fact, 

this scenario has been replayed nightly for several months out of 

the year for tens of thousands of years. The aerial hunters are Mexican freetailed bats, their bases are caves spread from the southern United States (such 

as Bracken Cave near San Antonio) through Central America and northern 

South America. The opposing forces waiting to attack the bats as they emerge 

from the caves are hawks. The bats’ advanced ultra–wide band transceivers are 

based on ultrasound, and their quarry are mosquitoes and other flying insects 

(of which they consume 200 tons per night near Bracken Cave alone). Malaria 

is the biological agent, which some believe is responsible for killing half of all 

the humans who have ever lived.1

 Bats have the ability to navigate in cluttered 

environments and can distinguish the wingbeats of prey insects within foliage.2

chapter 10

Learning Unmanned Vehicle 

Control from Echolocating Bats

Eric W. Justh
1589 Bio-IInspired IInnovation and ovation and NNational SSecurity 

The above vignette is but one instance of how the natural world is 

replete with inspiration applicable to the engineering challenges of tomorrow’s 

warfare. A confluence of trends in technology and university research 

makes the connection between biology and defense research a particularly 

timely topic. Of course, biology is a wide-ranging discipline and defense 

research encompasses many diverse activities, so the nexus is quite broad. 

Here, however, we focus specifically on one aspect of the interface between 

biology and the field of systems and control: sensing and feedback used by 

echolocating bats. The overall message is the power of biological analogy in 

framing certain problems in modeling and feedback control.

There are a variety of levels at which to study biology, and it is useful 

to distinguish among them because they take quite different points of view. A 

brief comparison among genomics, systems biology, and behavioral biology 

(the focus of this chapter) conveys an inkling of the richness of the synergy 

between biology and technology.

Genomics is a major field of research in which DNA sequences for a 

variety of judiciously selected plant and animal species (in addition to humans) 

are recorded (with varying degrees of statistical confidence, depending on the 

research objective), catalogued, and processed. Genomics has connections to 

micro- and nanofabrication (gene chips), as well as information technology for 

managing the vast amounts of information and associated degree of statistical 

uncertainty. An example of the depth and richness of bioinformatics based on 

this technology is the identification, cataloging, and tracking of the different 

species of Vibrio bacteria, which are responsible for the waterborne disease 

cholera.3

 These bacteria, which are endemic to bodies of water worldwide, 

are able to incorporate various genetic elements associated with toxicity and 

antibiotic resistance. Tracking different strains both geographically and in real 

time is key to managing outbreaks and pandemics but is quite a challenging 

task, since it is necessary to incorporate geography (for example, river flows), 

infrastructure (such as sanitation systems), medical data (for example, 

patients with digestive symptoms, their response to different antibiotics, and 

mortality rates), historical records (such as pandemic strains dating back to 

the early 20th century), as well as genetic microarray measurements of Vibrio

samples from selected patients.4

Although quite complex and enormously useful, in the context of our 

discussion, genomics is essentially a descriptive exercise: the goal is primarily 

to identify particular genes, associate them with observable traits, and develop 

techniques for manipulating them in order to alter observable traits. Since the 

biomechanical systems by which genes lead to observable traits are only partially 

(if at all) understood, a trial and error process is required. While this approach 

has led to some stellar successes for the pharmaceutical industry (for example, 
Learning Unmanned Vehicle Control from Echolocating Bats 159

human insulin of recombinant DNA origin in the 1970s) and therefore has 

undisputable economic and social importance, it is a field whose success does 

not depend on understanding detailed models of system dynamics. 

Systems biology is a newly emerging discipline that seeks to explain the 

system dynamics of the cellular and biomolecular building blocks of life.5

Loosely speaking, systems biology can be considered an attempt to understand 

the engineering principles underlying the “design” of living systems. A broad 

range of topics within systems biology has emerged. For example, biological 

systems are complex systems that inherently represent a juxtaposition of 

great robustness to threats for which they were designed (or evolved) but 

extreme vulnerability to threats that were not anticipated (or seen during the 

evolutionary process).6

 To the extent chemical reaction chains within cells can 

be teased out, there is often a seeming paradox that the standard equations 

for the chemical kinetics yield a narrow range of parameters over which an 

observed behavior (for example, a chemical timer) is stable, and yet the observed 

behavior may appear experimentally to be highly robust.7 This suggests a flaw 

in using the standard chemical kinetics equations in this setting and has led 

to alternative modeling approaches that capture the robustness, but are not 

as clearly connected to the underlying chemical kinetics.8 How quantization 

effects should be included in models at the cellular and subcellular level is 

also an open question. An example of a “success” of systems biology could be 

coopting structures within a cell in an artificial feedback system to perform a 

new task that “nature” has not envisioned.

Behavioral biology is a longstanding discipline, but one that is poised for 

transformation based on recent advances in off-the-shelf technologies. (Here, 

the term behavioral biology is used in the neuroscience and biophysiology 

sense, not in the deliberative or social behavior sense.) While systems biology 

is cutting-edge in terms of the advanced (and expensive) technology required 

for experimentation, behavioral biology can capitalize on the dramatic cost 

reductions of maturing technologies. Behavioral biology (for purposes of this 

chapter) deals with how sensorimotor tasks are performed at the organism level. 

Sensing modalities, neural processing, biomechanics of motion, communication 

with others, and environmental interactions are all encompassed. Behavioral 

biology has a descriptive side, analogous to genomics: animals can be categorized 

by their behavioral characteristics. But there is also a systems-modeling side, 

where the objective (in analogy to systems biology) is to understand the role 

of feedback in observed behaviors. For specialists in the field of systems and 

control, it is self-evident that modeling feedback is the essence of behavioral 

biology. For a broader audience, it is a point worth clarifying.

The echolocating bat’s interaction with its environment, communication 

with other bats, evasion of hawks, and use of echolocation to find, track, and 
1601 Bio-IInspired IInnovation and ovation and NNational SSecurity 

intercept insects all fall under the purview of behavioral biology. Genomics 

could provide insight into how particular echolocation strategies evolved over 

time,9 and systems biology could eventually yield insight into how particular 

signaling processes within the bat’s neural system operate. It is currently 

much simpler, and still fruitful, to observe, record, and measure from the 

bat itself, and then build models that capture the phenomenology. These 

measurements range from passive collection of position and echolocation 

data from free-flying bats to experiments in which constrained bats are 

subjected to stimuli while various structures in their brains are probed using 

electrode arrays. 

Analogous studies have been conducted in other types of animals as 

well. The Mauthner cells in fish, a pair of large neurons that take vestibular 

and sensory inputs and coordinate the “tail flip” escape reflex, have been 

studied extensively.10 Experiments in which insect visual systems are subjected 

to artificial scenes in order to tweeze out the design of their sensorimotor 

systems date back 20 years.11 Historically, studies of the squid giant axon12 and 

of the lamprey spinal cord13 date back even further.

Current technology now allows “payloads” attached to the head of a 

flying bat to connect to probes in its brain, record vocalizations as they are 

made, and transmit the data wirelessly to a ground station in real time. 

Furthermore, high-frame-rate, high-resolution infrared cameras can be used 

to record the detailed motion of the bat’s wings and body while in flight. In 

addition to dramatically expanding the ability to collect data, technology 

also affords the possibility of generating data in novel ways. Through the 

use of speakers, it already is possible to alter a tethered bat’s perception of 

its surroundings based on echolocation. Taking the concept a step further, 

interacting with free-flying bats through automation (either an array of 

networked sensors or a flying vehicle) would allow an even richer class of 

experiments to be performed.

Modeling and Feedback 

Feedback is intrinsic to all biological processes and systems, although different 

terms (like regulation or compensation) are often used. The motion of the 

echolocating bat, for example, is clearly “sensor driven” in the sense that the bat 

is continuously sampling its environment and responding accordingly—that 

is, using feedback. Thus, understanding behavior really means understanding 

a dynamical system model involving feedback. 

While the history of feedback in engineered systems goes back at least 

to James Watt’s flyball governor (for steam engines) in 1788, or even the 

Polynesian outrigger canoe more than 3,000 years ago,14 the negative feedback 
Learning Unmanned Vehicle Control from Echolocating Bats 161

amplifier for communications, credited to Harold Black at Bell Labs in 1927, 

is closer to the birth of systems and control as a distinct discipline. During 

the post–World War II period and the advent of the Cold War, both the 

United States and the Soviet Union supported basic research in the systems 

and control field for military purposes. From the early gun-director systems 

of World War II15 through the Cold War Aegis shipboard air defense system 

(still in use today), experts in the systems and control field have provided 

the necessary mathematical techniques to close the feedback loop between 

sensors (radar) and actuators (munitions and launchers). During this period, 

feedback systems started to permeate the commercial sector as well. Motor 

vehicles are a prime example: computer-controlled fuel injection, antilock 

brakes, roll-stability control, cruise control, and, most recently, adaptive cruise 

control are all examples of rigorously engineered feedback systems that have 

entered society in a largely transparent way. In addition to transportation, 

models incorporating feedback have penetrated manufacturing, operations 

research (that is, supply-chain management and logistics), finance, medical 

equipment, and other areas. 

In some sense, the success of the systems and control field is reflected 

by the extent to which its contribution to technology is ubiquitous but 

completely transparent to the vast majority of the population. However, there 

is still a pressing need for the Department of Defense (DOD) to maintain a 

knowledge base and research infrastructure in the systems and control area 

in order to be able to tackle its next-generation feedback control challenges. 

These include cooperative control of multiple unmanned vehicles, as well as 

systems to recognize, track, and counter hostile teams of weaponized manned 

and unmanned vehicles.

The landscape of scientific research evolves over time, changes in 

response to political imperatives, and is interconnected to some extent with 

society at large. Although change (such as declining DOD research funding) 

can result in immediate pain for individual researchers and programs, the 

effects on a discipline as a whole tend to only reveal themselves with the 

passage of time and are not easily predicted. Because of their mathematical 

grounding, researchers in the systems and control field generally are able to 

move into new application areas and carve out niches. Recent years have seen 

a number of researchers who have long been associated with engineering 

applications in the systems and control field start to publish on problems 

in systems biology. University bioengineering departments are also being 

established and are growing rapidly, partially offsetting declining enrollment in 

traditional engineering disciplines. On a lesser scale, collaborations involving 

behavioral biologists and researchers in systems and control have emerged, 

and this is where it is important for DOD not to overlook opportunities.
1623 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Bio-inspired Research as a DOD Resource 

In the 21st century, biology is replacing electronics as the main frontier 

for research and innovation. However, replacing is not quite the right 

word, because it is the commoditization of 70 years of intense activity and 

technological advancement in electronics that is enabling the ongoing 

revolution in biology. Medical imaging systems, gene chips, automated DNA 

sequencing, and databases for storing and cataloging intracellular chemical 

reaction networks are examples of technologies that have had enormous 

impact on biological research. 

However, these new technologies actually create new research 

challenges. Voluminous amounts of new data can be collected, but simply 

having a lot of data does not imply greater understanding. The real challenge 

ahead, for both systems biology and behavioral biology, is using the newly 

emerging technologies for acquiring information to actually improve our 

understanding of how various biological systems operate. What understanding

really means in this context is having a model, generally involving feedback, 

that is consistent with experimental measurements of a phenomenon as well 

as with descriptive explanations of the phenomenon. This is no different 

from “understanding” in the context of engineered systems, and of course 

there are different levels of modeling at which different types of models apply. 

For example, a lawnmower can be considered a well-understood system: 

faithful, well-explained, and universally agreed-upon models for internal 

combustion engines (ICE) exist, and the coupling of the engine to the blade 

and the interaction of the blade with the outside world (grass, rocks) can 

be modeled as well. Temperatures and pressures from the ICE model yield 

mechanical requirements on the materials used, helping to further explain 

the morphology of the lawnmower. Different ICE models can be used, 

ranging from a torque-speed curve up to a three-dimensional finite-element, 

computational fluid dynamics model. There is often tension between highlevel and detailed models, with aspects of one informing aspects of the other, 

resulting in an iterative process of refinement.

The challenge in biology is that we tend to observe complex interactions 

and behaviors, from which we must deduce appropriate models that lead to 

understanding. There is no computer algorithm that will perform this task 

for us—it requires two manifestly human capabilities: pattern recognition 

and creativity. Here, pattern recognition means being able to relate observed 

biological phenomena to a “library of models” from experience in studying and 

designing feedback control systems. Creativity is needed to interpret, as well as 

to expand, this library of models in the face of new biological data. To illustrate, a 

couple of examples involving bat pursuit and echolocation are described below.
Learning Unmanned Vehicle Control from Echolocating Bats 163

Bat Pursuit Example 

Various pursuit problems have been explored both in nature and in 

engineering, and biologically motivated pursuit strategies include classical 

pursuit, constant-bearing pursuit,16 and motion-camouflaged pursuit. In an 

engineering context, pursuit is exemplified by the field of missile guidance.17 

When the evader can sense and respond to the motion of the pursuer, the 

theory of differential games may be appropriate to properly understand the 

engagement.18 Indeed, certain insects that bats prey upon have developed 

countermeasures that are remarkable in their own right, and the sensorimotor 

systems and biomechanics of, for example, moths have been explored in 

detail.19 Moths flying at night, where visual processing is of limited utility, have 

developed sensitive gyroscopic force sensors (for roll, pitch, and yaw rates) to 

enable high-performance maneuvers in three dimensions to evade predators.

Recent work on pursuit laws in nature demonstrates how behavioral 

phenomena can be explained or modeled in terms of sensor-driven feedback 

laws.20, 21 The phenomenon of motion camouflage was initially observed in 

the territorial maneuverings of insects—the hoverflies Syritta pipiens—by 

Srinivasan and Davey22 (using data that had been obtained earlier by Collett 

and Land23). In motion-camouflaged pursuit, a pursuer approaches a target 

(the “evader”) such that the pursuer always appears to the evader to either lie 

along a line of sight with the same fixed object, or to be at constant bearing. 

In the former case, the pursuit is stealthy because the evader cannot use 

motion parallax cues to distinguish the pursuer from the background. In the 

latter case, the pursuit is stealthy because the motion parallax of the pursuer 

is indistinguishable from that of a very distant object. (Compound eyes 

are much more sensitive to optic flow rather than looming, making this an 

effective strategy for insects.) Both types of motion-camouflaged pursuit are 

observed in insect maneuvers,24, 25 but being at constant bearing, which can be 

considered motion camouflage “with respect to a point at infinity,” is easier to 

analyze mathematically.26, 27

Although the phenomenon of motion camouflage had been documented 

in experiments with insects, a feedback law to achieve motion camouflage was 

not formulated until later.28 It was also observed that trajectories of free-flying 

echolocating bats (Eptesicus fuscus) pursuing prey insects in an instrumented 

room were geometrically indistinguishable from motion-camouflaged pursuit 

(during a particular stage of the engagement).29 For bat-insect engagements, 

the term motion camouflage is a bit awkward, because the engagements take 

place in the dark, and acoustic sensing predominates over visual sensing 

for both the pursuer and evader. (In fact, in these experiments, the insect’s 

hearing organ is disabled to prevent the insect from executing stereotyped 

evasive maneuvers in response to the bat vocalizations.) Therefore, the term 
1645 Bio-IInspired IInnovation and ovation and NNational SSecurity 

constant absolute target direction (CATD) is used to denote the bat’s strategy 

(equivalent to motion camouflage with respect to a point at infinity). The 

missile guidance strategy known as pure proportional navigation guidance

(PPNG) is very similar to the CATD strategy.

Roughly speaking, the feedback law associated with CATD takes the 

sensory information available to the bat and causes it to maneuver so as to 

approach the insect along a line of constant bearing. The sensor measurement 

required by the bat to achieve this is the transverse component of the relative 

velocity of the bat and insect—that is, the component of the relative velocity 

that is perpendicular to an imaginary line joining the bat and insect. The bat 

is able to measure this quantity using echolocation. An analogous sensing 

task occurs with PPNG for missile guidance: the rotation of the line-of-sight 

vector is the corresponding sensor measurement. The bat (or missile) then 

“steers” so as to null its sensor measurement. There is a versatile formulation 

of this pursuit model (and related models of interacting animals or vehicles) 

that allows precise mathematical conclusions to be reached.30, 31 Modeling 

(in the sense used here) really means developing a mathematical model 

within a particular formulation that balances intuitive insight and physically 

meaningful representation of a phenomenon of interest. Therefore, both the 

mathematical (systems and control) expertise and natural science knowledge 

are prerequisites.

The power of the pursuit model and other behavioral models is that they 

occupy a status separate from the specific implementation platform (that is, 

the insects, bats, or missiles). The platform-dependent details, such as sensor 

capabilities and constraints, can be interpreted in the context of these models 

to yield insight as to why nature has made certain (evolutionary) choices. 

Thus, models help us to organize and prioritize biological data.

Bat Echolocation Example 

Bat echolocation is of military interest both because of the analogies between 

radar and sonar processing and because ultrasound may prove useful in its own 

right as a complementary sensing modality for unmanned vehicles. Bats use 

ultrasound for both sensing and communication, although here we are focused 

on sensing. Many decades of research have led to an appreciation of how truly 

remarkable bats’ acoustic sensing capabilities are, and we are still learning.32

With advances in solid-state electronics, we are better positioned than ever 

before to take advantage of this body of knowledge in actual sensor systems.33

To give some idea of what bats have managed to accomplish, and to 

offer a comparison to radar, note that the speed of sound in air is on the order 

of 1,000 feet (ft)/second. Although there are many different types of bats with 

various ranges of echolocation frequencies, 40 kilohertz (kHz) to 100kHz is 
Learning Unmanned Vehicle Control from Echolocating Bats 165

a typical frequency range. The corresponding wavelength range is then 0.01 

ft to 0.025 ft, or 3 millimeters (mm) to 8mm. By analogy, the speed of light 

is roughly 1,000 ft/microsecond, so that for radar frequencies of 40 gigahertz 

(GHz) to 100GHz, the corresponding wavelength is also 3mm to 8mm. Bats are 

limited at the high-frequency end of their range by atmospheric attenuation 

and at the low-frequency end by the size of prey insects they need to be able to 

detect. They are able to achieve sub-wavelength resolution, detecting insects 

with diameters down to a millimeter, and avoiding wires with diameters less 

than 0.1mm.34 Bats can detect insect wingbeats, distinguish surface textures, 

and compensate for Doppler shift resulting from their own flight.35 They can 

also determine azimuth and elevation using binaural processing.

Detection of wires is a serious problem for UAVs flying in urban 

environments. Currently, the only reliable, commercially available on-board 

sensor for this purpose is lidar, and even the smallest lidar systems are on the 

order of 10 pounds, limiting their use to relatively large (greater than 10-foot 

wingspan), liquid-fuel–powered UAVs (for example, Tier II UAVs). Smaller 

UAVs, such as Dragon Eye, would seem to be more logical candidates for lowflying missions in urban environments, but wires (such as power lines) pose a 

significant challenge. This puts into perspective how a sensing task that a bat 

would consider trivial is nevertheless quite challenging for humans.

Although different types of bats use a variety of waveforms, an analogy 

can be drawn between a typical bat and a so-called frequency-modulated 

continuous wave (FMCW) radar. FMCW waveforms include pulses (at 

constant or varying center frequencies), chirped waveforms, and tones 

(continuous wave signals). “Automotive radars,” which are starting to appear 

and could become ubiquitous if a low enough price point is achieved, use 

frequencies around 80GHz and FMCW waveforms. Automotive radars are 

assigned to this band and use FMCW waveforms so as to limit the propagation 

distance to a few hundred meters and to avoid interference among multiple 

radars operating in close proximity. Although the percent bandwidths and 

percent Doppler shifts are quite different for bat ultrasound and automotive 

radar, the analogy between them is still quite strong. In radar processing, the 

term micro-Doppler is used to describe the extraction of motion information 

(for slowly moving objects, such as humans walking) from radar returns.36

What we can learn from bats is how they use feedback control in their 

echolocation processing to extract information from their surroundings. 

As bats move through their environment and probe it acoustically, they are 

somehow able to build up, in ways we have yet to understand, a mental image 

of what is important to them. Further complicating the situation is the fact 

that even in low light, bats are generally able to incorporate visual sensing 

along with acoustic sensing. By studying the acoustic waveforms bats use, 
1667 Bio-IInspired IInnovation and ovation and NNational SSecurity 

and observing the bats in carefully controlled experiments, the capabilities of 

their acoustic sensing systems can be determined. The next step is deducing 

what feedback mechanisms are present in their acoustic processing, and 

how they are used. For example, certain bats use intensity compensation: as 

a prey insect is approached, the vocalization intensity is reduced, so that a 

constant intensity reaches the bat’s ears.37 Another example is increasing pulse 

repetition rate as a target is approached. These adjustments made on the fly 

(that is, based on feedback) presumably serve to keep the return signals in the 

right “range” to interact with banks of neural filters that are “wired” for high 

sensitivity to particular features. What type of neural filtering is used and why 

certain feedback mechanisms are present are questions best tackled jointly 

by biologists and experts in the field of systems and control. The answers are 

likely to have a significant impact on design of sensor systems in general and 

sensor systems for unmanned vehicles in particular.

Conclusion 

In the opening vignette, reference was made to futuristic battles between 

armies of UAVs. We believe that if these futuristic battles were to take place, 

they would extensively incorporate biologically motivated technology and 

processing. In the Tactical Electronic Warfare Division at the Naval Research 

Laboratory, a multivehicle simulation testbed for coordinated control of 

unmanned vehicles, including UAVs and unmanned surface vessels, is being 

built.38, 39 Making contact with biology has already proved indispensable in 

communicating with the academic research community and in designing 

various components of this testbed effectively. On its face, this may seem 

surprising in the context of an engineered system with an engineeringoriented set of applications. In an earlier era, connecting such an effort to 

biology would indeed have been improbable. But today, our effort would be 

stifled if not for contact made with biology.

Notes

1 J. Whitfield, “Portrait of a Serial Killer: A Roundup of the History and Biology of the 

Malaria Parasite,” Nature News (2002).

2 M. Vespe, G. Jones, and C.J. Baker, “Biologically Inspired Waveform Diversity for Synthetic 

Autonomous Navigation Sensing,” unpublished, 2007. 

3 G.J. Vora et al., “Microarray-based Detection of Genetic Heterogeneity, Antimicrobial 

Resistance, and the Viable but Nonculturable State in Human Pathogenic Vibrio spp,” 

Proceedings of the National Academies of Science 102, no. 52 (2005), 19109–19114.

4 Ibid. 
Learning Unmanned Vehicle Control from Echolocating Bats 167

5 E.D. Sontag, “Molecular Systems Biology and Control,” European Journal of Control 11, no. 

4–5 (2005), 396–435.

6 M.E. Csete and J.C. Doyle, “Reverse Engineering of Biological Complexity,” Science 295, no. 

5560 (2002), 1664–1669.

7 R. Ghaemi and D. Del Vecchio, “Evaluating the Robustness of a Biochemical Network 

Model,” Proceedings of the 46th IEEE Conference on Decision and Control (2007), 615–620.

8 D. Angeli and E.D. Sontag, “Oscillations in I/O Monotone Systems under Negative 

Feedback,” IEEE Transactions on Circuits and Systems, Special Issue on Systems Biology, 2008.

9 G. Jones and E.C. Teeling, “The Evolution of Echolocation in Bats,” Trends in Ecology and 

Evolution 21, no. 3 (2006), 149–156.

10 H. Korn and D.S. Faber, “The Mauthner Cell Half a Century Later: A Neurobiological 

Model for Decision-making?” Neuron 47 (2005), 13–28.

11 M.V. Srinivasan and S. Zhang, “Visual Motor Computations in Insects,” Annual Review of 

Neuroscience 27 (2004), 679–696.

12 J.R. Clay, “Excitability of the Squid Giant Axon Revisited,” Journal of Neurophysiology 80 

(1998), 903–913.

13 A.H. Cohen and P. Wallén, “The Neuronal Correlate of Locomotion in Fish,” Experimental 

Brain Research 41, no. 1 (1980), 11–18.

14 D. Abramovitch, “The Outrigger: A Prehistoric Feedback Mechanism,” Control Systems 

Magazine (2005), 57–72.

15 D.A. Mindell, Between Human and Machine: Feedback, Control, and Computing before 

Cybernetics (Baltimore: The Johns Hopkins University Press, 2004).

16 B.R. Fajen and W.H. Warren, “Visual Guidance of Intercepting a Moving Target on Foot,” 

Perception 33 (2004), 689–715.

17 N.A. Shneydor, Missile Guidance and Pursuit (Chichester, UK: Horwood, 1998).

18 R. Isaacs, Differential Games (New York: John Wiley and Sons, 1965).

19 S.P. Sane et al., “Antennal Mechanosensors Mediate Flight Control in Moths,” Science 315 

(2007), 863–866.

20 E.W. Justh and P.S. Krishnaprasad, “Steering Laws for Motion Camouflage,” Proceedings of 

the Royal Society of London 46 (2006), 3629–3643.

21 P.V. Reddy, E.W. Justh, and P.S. Krishnaprasad, “Motion Camouflage in Three Dimensions,” 

Proceedings of the 45th IEEE Conference on Decision and Control (2006), 3327–3332.

22 M.V. Srinivasan and M. Davey, “Strategies for Active Camouflage of Motion,” Proceedings of 

the Royal Society of London 259 (1995), 19–25. 

23 T.S. Collett and M.F. Land, “Visual Control of Flight Behaviour in the Hoverfly, Syritta 

pipiens,” Journal of Comparative Physiology 99 (1975), 1–66.

24 Srinivasan and Davey. 

25 A.K. Mizutani, J.S. Chahl, and M.V. Srinivasan, “Motion Camouflage in Dragonflies,” Nature 

423, no. 604 (2003).

26 Justh and Krishnaprasad.

27 Reddy, Justh, and Krishnaprasad.

28 Justh and Krishnaprasad.
168 Bio-Inspired Innovation and National Security

29 K. Ghose et al., “Echolocating Bats Use a Nearly Time-optimal Strategy to Intercept Prey,” 

Public Library of Science Biology 4, no. 5 (2006), 865–873, e:108. These experiments were 

conducted in the Auditory Neuroethology Lab led by Professor Cynthia Moss at the 

University of Maryland; available at www.bsos.umd.edu/psyc/batlab/. 

30 Justh and Krishnaprasad.

31 Reddy, Justh, and Krishnaprasad.

32 Vespe, Jones, and Baker.

33 C.J. Baker, M. Vespe, and G.J. Jones, “Target Classification by Echo Locating Animals,” 

Proceeding of the IEEE Conference on Waveform Diversity and Design (2007), 348–352.

34 Vespe, Jones, and Baker. 

35 Ibid. 

36 V.C. Chen et al., “Micro-Doppler Effect in Radar: Phenomenon, Model, and Simulation 

Study,” IEEE Transactions on Aerospace and Electronic Systems, 42, no. 1 (2006), 2–21.

37 Vespe, Jones, and Baker.

38 E.W. Justh and V. Kowtha, “Biologically Inspired Models for Swarming,” in Evolutionary 

and Bio-inspired Computation: Theory and Applications, Proceedings of the SPIE 6563 (2007), 

656302.

39 R.S. Cortesi, K.S. Galloway, and E.W. Justh, “A Biologically Inspired Approach to Modeling 

Unmanned Vehicle Teams,” Proceedings of the SPIE 6964 (2008), 696405. 
169

Neurorobots1

 are robotic devices that have control systems based 

on principles of the nervous system. These models operate on the 

premise that the “brain is embodied and the body is embedded in 

the environment.” Therefore, neurorobots are grounded and situated in a 

real environment. The real environment is required for two reasons. First, 

simulating an environment can introduce unwanted and unintentional biases 

to the model. For example, a computer-generated object presented to a vision 

model has its shape and segmentation defined by the modeler and directly 

presented to the model, whereas a device that views an object hanging on 

a wall has to discern the shape and figure from ground segmentation based 

on its on active vision. Second, real environments are rich, multimodal, and 

noisy; an artificial design of such an environment would be computationally 

intensive and difficult to simulate. However, all these interesting features of the 

environment come for “free” when a neurorobot is placed in the real world.

A neurorobot has the following properties:

• It engages in a behavioral task. 

• It is situated in a real-world environment.

• It has a means to sense environmental cues and act upon its environment.

• Its behavior is controlled by a simulated nervous system having a design 

that reflects, at some level, the brain’s architecture and dynamics.

As a result of these properties, neurorobotic models provide heuristics for 

developing and testing theories of brain function in the context of phenotypic 

and environmental interactions. 

chapter 11

Neurorobotics: 

Neurobiologically 

Inspired Robots

Jeffrey Krichmar
1701 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Although there have been great advances in autonomous systems,2, 3, 4, 5

the controllers of these machines are still very much tailored to specific missions 

and do not have the behavioral repertoire we normally associate with that of 

biological organisms. Behavior-based robotics6 do not learn from experience 

and cannot adapt to environmental change. Probabilistic robot controllers7

need an accurate model of their sensors and actuators. Robots controlled by 

reinforcement learning or machine learning8

 are driven by reward expectation 

and do not address attention, novelty, and threat assessment.

Neurorobotic models may provide a foundation for the development of 

more effective robots, based on an improved understanding of the biological 

bases of adaptive behavior. A robotic controller modeled after the vertebrate 

nervous system, in which the robot’s behavior approaches the complexity and 

flexibility associated with higher order animals, would be a major step forward 

in the design of autonomous systems. Advances in computational models of 

the brain as well as computation power are making this a distinct possibility in 

the not too distant future. Neurally inspired robotic control would be flexible, 

experience-dependent, and autonomous—just like a biological organism.

Classes of Neurorobotic Models 

There are too many examples of neurobiologically inspired robotic devices to 

exhaustively list in this brief review. However, the approach has been applied 

to several distinct areas of neuroscience research:

• motor control and locomotion

• learning and memory systems

• value systems and action selection.

The remainder of this article will briefly touch on a few representative 

examples.

Motor Control and Locomotion 

Neurorobots have proved useful for investigating animal locomotion and 

motor control and for designing robot controllers. Neural models of central 

pattern generators, pools of motorneurons that drive a repetitive behavior, 

have been used to control locomotion in robots.9, 10, 11 Kimura and colleagues 

have shown how neurorobotics can provide a bridge between neuroscience 

and biomechanics by demonstrating emergent four-legged locomotion 

based on central pattern generator mechanisms modulated by reflexes. Their 

group developed a model of a learnable pattern generator and demonstrated 

its viability using a series of synthetic and humanoid robotic examples. 

Ijspeert and colleagues constructed an amphibious salamander-like robot 
Neurorobotics: Neurobiologically Inspired Robots 171

that is capable of both swimming and walking, and therefore represents a 

key stage in the evolution of vertebrate-legged locomotion. A neurorobotic 

implementation was found necessary for testing whether the models could 

produce locomotion both in water and on ground and investigating how 

sensory feedback affects dynamic pattern generation.

An intriguing neural inspiration for the design of robot controllers is 

the mirror neuron system found in primates. Mirror neurons in the premotor 

cortex are active both when a monkey grasps or manipulates objects and when 

it watches another animal performing similar actions.12 Neuroroboticists, 

using this notion of mirror neurons, have suggested that complex movements 

such as reaching and locomotion may be achieved through imitation.13, 14, 15, 16, 17

Another strategy for motor control in neurally inspired robots is to use a 

predictive controller to convert awkward, error-prone movements into smooth, 

accurate ones. Recent theories of motor control suggest that the cerebellum 

learns to replace primitive reflexes with predictive motor signals. The idea is 

that the outcomes of reflexive motor commands provide error signals for a 

predictive controller, which then learns to produce a correct motor control 

signal prior to the less adaptive reflex response. Neurally inspired models 

have used these ideas in the design of robots that learn to avoid obstacles,18, 19

produce accurate eye,20 and generate adaptive arm movements.21, 22, 23

Learning and Memory Systems 

A major theme in neurorobotics is neurally inspired models of learning and 

memory. One area of particular interest is navigation systems based on the 

rodent hippocampus. Rats have exquisite navigation capabilities in both the light 

and the dark. Moreover, the finding of place cells in the rodent hippocampus, 

which fire specifically at a spatial location, have been of theoretical interest 

for models of memory and route planning.24 Robots with models of the 

hippocampal place cells have been shown to be viable for navigation in mazes 

and environments similar to those used in rat spatial memory studies.25, 26, 

27, 28 Recently, large-scale systems-level models of the hippocampus and its 

surrounding regions have been embedded on robots to investigate the role of 

these regions in the acquisition and recall of episodic memory.29, 30, 31

Another learning and memory property of importance to the 

development of neurorobotics is the ability to organize the unlabeled signals 

that robots receive from the environment into categories. This organization 

of signals, which in general depends on a combination of sensory modalities 

(for example, vision, sound, taste, or touch), is called perceptual categorization. 

Several neurorobots have been constructed that build up such categories, 

without instruction, by combining auditory, tactile, taste, and visual cues 

from the environment.32, 33, 34
1723 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Value Systems and Action Selection 

Biological organisms adapt their behavior through value systems that provide 

nonspecific, modulatory signals to the rest of the brain that bias the outcome 

of local changes in synaptic efficacy in the direction needed to satisfy global 

needs. Examples of value systems in the brain include the dopaminergic, 

cholinergic, and noradrenergic systems.35, 36, 37 Behavior that evokes positive 

responses in value systems biases synaptic change to make production of 

the same behavior more likely when the situation in the environment (and 

thus the local synaptic inputs) is similar; behavior that evokes negative value 

biases synaptic change in the opposite direction. The dopamine system and 

its role in shaping icrosys making has been explored in neurorobots and 

brain-based devices.38, 39, 40 Doya’s group has been investigating the effect of 

multiple neuromodulators in the “cyber-rodent,” a two-wheeled robot that 

moves autonomously in an environment.41 These robots have drives for 

self-preservation and self-reproduction exemplified by searching for and 

recharging from battery packs on the floor and then communicating this 

information to other robots nearby through their infrared communication 

ports. In addition to examining how neuromodulators such as dopamine 

can influence decisionmaking, neuroroboticists have been investigating 

the basal ganglia as a model that mediates action selection.42 Based on the 

architecture of the basal ganglia, Prescott and colleagues embedded a model 

of it in a robot that had to select from several actions depending on the 

environmental context. 

Conclusion 

Higher brain functions depend on the cooperative activity of an entire nervous 

system, reflecting its morphology, its dynamics, and its interaction with the 

environment. Neurorobots are designed to incorporate these attributes such 

that they can test theories of brain function. The behavior of neurorobots 

and the activity of their simulated nervous systems allow for comparisons 

with experimental data acquired from animals. The comparison can be 

made at the behavioral level, the systems level, and the neuronal level. These 

comparisons serve two purposes: first, neurorobots can generate hypotheses 

and test theories of brain function. The construction of a complete behaving 

model forces the designer to specify theoretical and implementation details 

that can be easy to overlook in an ungrounded or disembodied theoretical 

model. Moreover, it forces these details to be consistent. Second, by using 

the animal nervous system as a metric, neurorobot designers can continually 

make their simulated nervous systems and resulting behavior closer to those 
Neurorobotics: Neurobiologically Inspired Robots 173

of the model animal. This, in turn, allows the eventual creation of practical 

devices that may approach the sophistication of living organisms.

Notes

1 A.K. Seth, O. Sporns, and J.L. Krichmar, “Neurorobotic Models in Neuroscience and 

Neuroinformatics,” Neuroinformatics 3 (2005), 167–170.

2 A. Cho, “Robotics. Robotic Cars Tackle Crosstown Traffic—and Not One Another,” Science

318 (2007), 1060–1061.

3 W.W. Gibbs, “From Finish to Start. Was the Grand Challenge Robot Race in March the 

Fiasco it Appeared To Be? Hardly, Argues William ‘Red’ Whittaker. The Annual Event is 

Pushing Mobile Robotics to Get Real,” Scientific American 291 (2004), 33–34.

4 S. Squyres, Roving Mars: Spirit, Opportunity, and the Exploration of the Red Planet (New 

York: Hyperion, 2005).

5 B. Yenne, Attack of the Drones (St. Paul, MN: Zenith Press, 2004); J. Jones and D. Roth, Robot 

Programming: A Practical Guide to Behavior-Based Robotics (New York: McGraw-Hill, 2003).

6 Jones and Roth.

7 S. Thrun, W. Burgarde, and D. Fox, Probabilistic Robotics (Cambridge: MIT Press, 2005).

8 R.S. Sutton and A.G. Barto, Reinforcement Learning: An Introduction (Cambridge: MIT 

Press, 1998).

9 A.J. Ijspeert et al., “From Swimming to Walking with a Salamander Robot Driven by a 

Spinal Cord Model,” Science 315 (2007), 1416–1420.

10 H. Kimura, Y. Fukuoka, and A.H. Cohen, “Biologically Inspired Adaptive Walking of 

a Quadruped Robot,” Philosophical Transactions Series A: Mathematical, Physical, and 

Engineering Sciences 365 (2007), 153–170.

11 M. Lewis, F. Tenore, and R. Etienne-Cummings, “CPG Design using Inhibitory Networks,” 

paper presented at IEEE Conference on Robotics and Automation, Barcelona, 2005.

12 G. Rizzolatti and M.A. Arbib, “Language within Our Grasp,” Trends in Neuroscience 21 

(1998), 188–194.

13 A. Billard and M.J. Mataric, “Learning Human Arm Movements by Imitation: Evaluation of 

a Biologically Inspired Connectionist Architecture,” Robotics and Autonomous Systems 37 

(2001), 145–160.

14 S. Schaal, “Is Imitation Learning the Route to Humanoid Robots?” Trends in Cognitive 

Sciences 3 (1999), 233–242.

15 S. Schaal, A. Ijspeert, and A. Billard, “Computational Approaches to Motor Learning by 

Imitation,” Philosophical Transactions Series B: Biological Sciences 358 (2003), 537–547.

16 S. Schaal and N. Schweighofer, “Computational Motor Control in Humans and Robots,” 

Current Opinion in Neurobiology 15 (2005), 675–682.

17 J. Tani, M. Ito, and Y. Sugita, “Self-organization of Distributedly Represented Multiple 

Behavior Schemata in a Mirror System: Reviews of Robot Experiments using RNNPB,” 

Neural Networks 17 (2004), 1273–1289.

18 J.L. McKinstry, G.M. Edelman, and J.L. Krichmar, “A Cerebellar Model for Predictive Motor 

Control Tested in a Brain-based Device,” Proceedings of the National Academy of Sciences of 

the United States of America 103 (2006), 3387–3392.
1745 Bio-IInspired IInnovation and ovation and NNational SSecurity 

19 B. Porr and F. Worgotter, “Isotropic Sequence Order Learning,” Neural Computation 15 

(2003), 831–864.

20 P. Dean et al., “Saccade Control in a Simulated Robot Camera-head System: Neural Net 

Architectures for Efficient Learning of Inverse Kinematics,” Biological Cybernetics 66 

(1991), 27–36.

21 Ibid. 

22 S. Eskiizmirliler et al., “A Model of the Cerebellar Pathways Applied to the Control of a 

Single-joint Robot Arm Actuated by McKibben Artificial Muscles,” Biological Cybernetics 86 

(2002), 379–394.

23 C. Hofstotter, M. Mintz, and P.F. Verschure, “The Cerebellum in Action: A Simulation and 

Robotics Study,” European Journal of Neuroscience 16 (2002), 1361–1376.

24 J. O’Keefe and L. Nadel, The Hippocampus as a Cognitive Map (Oxford: Clarendon Press, 1978).

25 A. Arleo and W. Gerstner, “Modeling Rodent Head-direction Cells and Place Cells for Spatial 

Learning in Bio-mimetic Robotics,” in From Animals to Animats 6: Proceedings of the Sixth 

International Conference on Simulation of Adaptive Behavior (Cambridge: MIT Press, 2001).

26 N. Burgess et al., “Robotic and Neural Simulation of the Hippocampus and Rat Navigation,” 

Biological Science 352 (1997), 1535–1543.

27 M.J. Mataric, “Navigating with a Rat Brain: A Neurobiologically-inspired Model for Robot 

Spatial Representation,” in From Animals to Animats, ed. J. Arcady Meyer, and S.W. Wilson 

(Cambridge: MIT Press, 1991), 169–175.

28 M.J. Milford, G.F. Wyeth, and D. Prasser, “RatSLAM: A Hippocampal Model for 

Simultaneous Localization and Mapping,” paper presented at 2004 IEEE International 

Conference on Robotics and Automation, New Orleans, LA, 2004.

29 J.P. Banquet et al., “A Hierarchy of Associations in Hippocampo-cortical Systems: Cognitive 

Maps and Navigation Strategies,” Neural Computation 17 (2005), 1339–1384.

30 J.G. Fleischer et al., “Retrospective and Prospective Responses Arising in a Modeled 

Hippocampus during Maze Navigation by a Brain-based Device,” Proceedings of the National 

Academy of Sciences of the United States of America 104 (2007), 3556–3561.

31 J.L. Krichmar et al., “Spatial Navigation and Causal Analysis in a Brain-based Device 

Modeling Cortical-hippocampal Interactions,” Neuroinformatics 3 (2005), 197–221.

32 J.L. Krichmar and G.M. Edelman, “Machine Psychology: Autonomous Behavior, Perceptual 

Categorization, and Conditioning in a Brain-Based Device,” Cerebral Cortex 12 (2002), 

818–830.

33 A.K. Seth et al., “Spatiotemporal Processing of Whisker Input Supports Texture 

Discrimination by a Brain-based Device,” in Animals to Animats 8: Proceedings of the 

Eighth International Conference on the Simulation of Adaptive Behavior, ed. S. Schaal et al. 

(Cambridge: MIT Press, 2004), 130–139.

34 A.K. Seth et al., “Visual Binding Through Reentrant Connectivity and Dynamic 

Synchronization in a Brain-based Device,” Cerebral Cortex 14 (2004), 1185–1199.

35 G. Aston-Jones and F.E. Bloom, “Nonrepinephrine-containing Locus Coeruleus Neurons 

in Behaving Rats Exhibit Pronounced Responses to Non-noxious Environmental Stimuli,” 

Journal of Neuroscience 1 (1981), 887–900.

36 M.E. Hasselmo et al., “Neuromodulation, Theta Rhythm and Rat Spatial Navigation,” Neural 

Networks 15 (2002), 689–707.

37 W. Schultz, P. Dayan, and P.R. Montague, “A Neural Substrate of Prediction and Reward,” 

Science 275 (1997), 1593–1599.
Neurorobotics: Neurobiologically Inspired Robots 175

38 A. Arleo, F. Smeraldi, and W. Gerstner, “Cognitive Navigation Based on Nonuniform Gabor 

Space Sampling, Unsupervised Growing Networks, and Reinforcement Learning,” IEEE 

Trans Neural Networks 15 (2004), 639–652.

39 J.L. Krichmar and G.M. Edelman, “Machine Psychology: Autonomous Behavior, Perceptual 

Categorization, and Conditioning in a Brain-Based Device,” Cerebral Cortex 12 (2002), 

818–830.

40 O. Sporns and W.H. Alexander, “Neuromodulation and Plasticity in an Autonomous Robot,” 

Neural Networks 15 (2002), 761–774.

41 K. Doya and E. Uchibe, “The Cyber Rodent Project: Exploration of Adaptive Mechanisms 

for Self-Preservation and Self-Reproduction,” Adaptive Behavior 13 (2005), 149–160.

42 T.J. Prescott et al., “A Robot Model of the Basal Ganglia: Behavior and Intrinsic Processing,” 

Neural Networks 19 (2006), 31–61.

177

Ever since Isaac Asimov coined the term robotics in a short story 

published over 60 years ago,1 science fiction has inundated the collective 

imagination with countless scenarios of people interacting with robots 

that strongly resemble humans in both form and behavior. Since the mid20th century, science and engineering communities have labored to make 

the robots of reality attain the sophistication of their fictional counterparts. 

But the current state of the art is a far cry from the friendly and intelligent 

humanoid robots envisioned in popular culture.

Military science and technology (S&T) programs endeavor to bridge 

this gap between fiction and reality. An Office of Naval Research (ONR) S&T 

program in human-robot interaction (HRI) is working to develop biologically 

inspired, or biomimetic, robots that can naturally communicate and cooperate 

in human-robot teams during military operations. Fruition of these HRI 

projects will have numerous impacts on U.S. defense policy.

Why Biomimetic, Sociable Robots? 

Currently, humans rely upon robots to perform a diverse array of functions.2 

Widespread use of robots in manufacturing and other physically laborious 

tasks precipitated economic and societal changes in developed countries 

during the 20th century. As robots became more advanced and specialized, 

humans began employing them in dangerous tasks related to scientific 

exploration,3 search and rescue missions in urban environments,4, 5 hazardous 

material handling,6

 and military operations, such as disarming improvised 

explosive devices (IEDs) in Iraq and Afghanistan.7 For the past several decades, 

chapter 12

Biomimetic, Sociable Robots for

Human-Robot Interaction

Eleanore Edson, Judith Lytle, and Thomas McKenna
1789 Bio-IInspired IInnovation and ovation and NNational SSecurity 

physically challenged populations, such as the elderly and the handicapped, 

have used robots for transportation and other types of assistance in navigating 

day-to-day activities. More recently, an interesting new application of robots 

has arisen: companionship for humans. The Japanese-designed AIBO, built to 

resemble a small dog, is the most famous autonomous entertainment robot. 

The makers of AIBO followed up with the creation of SDR–3X and SDR–4X II, 

humanoid robots that not only navigate, walk, and dance, but also feature facial 

recognition as well as speech comprehension and production capabilities.8

Designing sociable robots for companionship purposes is one thing. 

Less intuitive is the application of humanoid robots for military use. Which 

operational needs of the military, and specifically the U.S. Navy and Marine 

Corps, require biologically inspired, sociable robots?

Military Operational Needs 

The military’s predominant need is to find ways to reduce the risk of injury 

or mortality related to dangerous missions. A relatively mundane task such 

as driving a supply truck can be deadly if the driver must navigate through a 

hostile environment or treacherous terrain. Moreover, the current conflict in 

Iraq has posed an unprecedented level of threat of being harmed by IEDs or 

other explosives. 

In addition to reducing casualties, the military wants to reduce the 

financial cost of operations. Productivity of military personnel can be 

extended by reducing the types of tasks humans are required to perform. For 

example, the personnel productivity of the Navy is limited by ship occupancy 

and expeditionary manpower. 

To assess remote or dangerous environments and increase productivity, 

the military employs robots and—increasingly—autonomous ones. Current 

use of autonomous systems is limited by available manpower and skill types; 

at present, military personnel who interact with robots do so in a supervisory 

role that requires more attention and specialization than interacting with a 

peer. In order for robots to continue to meet the evolving needs of the military, 

these machines will need to require less human supervision and be more 

adaptable to the unpredictable nature of the real world: in essence, robots will 

need to achieve even greater degrees of autonomy. 

Enhanced autonomy is necessary but not sufficient, however, for 

robots to help humans conduct complex tasks in increasingly uncertain 

environments. One potential solution to the military’s sophisticated 

operational problems and needs is to expand the ability for military personnel 

to collaborate in peer-to-peer teams with unmanned systems. In order for 

robots to be teammates, they must be not only more autonomous but also 

capable of natural, “mixed-initiative” interactions with humans.9
Biomimetic, Sociable Robots for Human-Robot Interaction 179

Science and Technology Solutions 

Natural interactions between humans and robots require autonomous systems 

to be as biologically realistic as possible. Biological systems, from basic 

organisms to complex organs such as the human brain, are characterized by 

several qualities, including adaptability, robustness, versatility, and agility.10 

Endowing autonomous systems with these desirable properties would markedly 

improve robots’ task versatility as well as their ability to operate in dynamic, 

unpredictable real-world environments. Most importantly, biological qualities 

will enable robots to engage in efficient and natural teamwork.11

However, today’s state of the art in autonomous systems is characterized 

by several major shortcomings. First, current autonomous systems are 

prone to communications loss. Second, present-day systems require highlevel communication and reasoning to coordinate planning and execution 

in dynamic battle spaces. Finally, acute problems exist with sending 

autonomous vehicles into urban areas with mixed populations (friend, foe, 

unknown, casualties). 

Modern-day warfighters’ tasks require not only a range of skills but 

also a growing demand on their working memories. The lower a warfighter’s 

cognitive load is, the easier it is to concentrate on the tasks at hand. However, 

proper control of an autonomous robot requires the supervision of one or 

more human operators. As a result, autonomous systems become another task 

consuming humans’ time and attention. 

In recent years, the Department of Defense (DOD) has come to recognize 

the significant importance of developing methods and technologies to enable 

autonomous systems to not only learn from humans but also collaborate 

naturally and effectively as peers. Such a dynamic between warfighters and 

robots could result in higher productivity, survivability, reliability, and efficacy 

of military missions. In response to this need, DOD has provided the Navy, 

Air Force, and Army with increased funding for accelerating the research and 

development (R&D) in the field of HRI. 

For the past 3 years, ONR’s program has invested in HRI projects at 

both military facilities (such as the Naval Research Laboratory) as well as 

private and public academic institutions. At present, a recent influx of DOD 

funding has allowed ONR to oversee an ambitious multidisciplinary effort 

to create cognitive models and dexterous mobile robots to enable direct 

HRI and team collaboration. These ONR-funded HRI research efforts are 

at the forefront of science, working to address fundamental scientific and 

engineering questions about intelligent systems, perception, communication, 

cognition, and psychology in order to create robots that will help humans 

meet the challenges of modern warfare. 
1801 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Background on Biologically Inspired Robots 

For the purposes of the military, robots need to collaborate effectively and 

naturally in human-robot teams. For these interactions to become a reality, 

robots must be as similar to humans as possible. Creation of a biomimetic 

robot—that is, an autonomous, intelligent, and sociable one—presents 

many scientific and technological challenges that will require a bridging of 

neuroscience, cognitive psychology, engineering, and robotics to overcome. 

In order for robots to be capable “team players,” they must possess an 

intelligent system that is based upon the types of representations and cognitive 

function found in the human brain.12 Thus, autonomous robots must have 

various cognitive abilities, such as perception and situation assessment, 

learning and working memory, problem-solving, goal maintenance, language 

understanding, and communication skills. Further, these cognitive capabilities 

must be linked to sensory and motor systems that can collect information 

about the external environment and then allow the robot to respond to that 

environment.13

Human Brain Basics 

The human brain is the most complex and powerful computational device 

on Earth. The cerebral cortex is the general region responsible for complex 

brain function and its higher level processing occurring in the neocortex, an 

area of the brain unique to mammals that composes the top-most layer of the 

cerebral cortex. 

The basic working unit of the brain is the neuron, of which there are 

approximately 130 billion in the average adult human brain. The human 

neocortex alone contains an estimated 22 billion neurons.14, 15 The basic 

components of a neuron are its cell body; extensions from the cell body 

that receive information called dendrites; and the long “output” process that 

sends information called an axon. The predominant site of transmission of 

information between neurons is called the synapse, typically formed between 

one neuron’s axonal end and another neuron’s dendrite; there are an estimated 

150 trillion synapses in the human neocortex.16

Far from being a homogenous organ, the adult brain’s billions of 

neurons and trillions of synapses are organized into different regional areas 

that perform one or more functions. Complex brain functions such as 

language, sensory processing, and abstract thinking are carried out in the four 

major sections of the cerebral cortex: the occipital, temporal, parietal, and 

frontal lobes. The association of information from different sensory areas into 

an organized understanding of the outside environment is carried out by the 

occipital, temporal, and parietal lobes. This complex is also responsible for the 
Biomimetic, Sociable Robots for Human-Robot Interaction 181

comprehension and creation of language, abilities that are separately governed 

by the Wernicke’s and Broca’s areas, respectively. The frontal lobe, also known 

as the prefrontal cortex, can be thought of as the center of intellect, allowing 

humans to plan behavior, reason, problem-solve, and think abstractly. 

The foundation of computational modeling is biological realism,17 with 

different types of cognitive architectures/neural networks being influenced 

by the brain’s structure and function to varying degrees. Biologically, neurons 

are real, living processing elements and have powerful computational 

capabilities.18 Their computational equivalents are simple, neuron-like 

processing elements that constitute the building blocks of neural networks.19

The axonal and dendritic processes in a brain are simulated as network 

connections of neural networks, while synaptic strength is simulated 

as adjustable strengths of network connections between the processing 

elements. The human brain relies upon parallel processing in order to handle 

countless, simultaneous calculations, thoughts, observations, reasoning, and 

so forth. Accordingly, neural networks also function via parallel processes.20

However, there are some caveats to biologically realistic cognitive 

architectures; artificial neural networks cannot replicate the human brain 

with absolute fidelity for a few reasons. First, in order to function properly, 

neural networks need to have some built-in constraints that do not necessarily 

exist in the real brain.21 Second, it is not currently possible to reduce certain 

biological phenomenon such as consciousness to a sum of its constituent 

parts. Even if it were, artificial neural networks are not yet sophisticated 

enough to accurately and thoroughly simulate all of the subtle inputs that 

produce complex functions of the brain.22 Finally, there is a great deal to learn 

about the biological mechanisms that underlie human cognitive capabilities 

and behavior. 

Crucial Component of Human Behavior: Mirror Neurons 

When it comes to physical movement, whether it is a toddler being taught 

how to wave or eat with a utensil or a pitcher getting coached on throwing 

a curve ball, humans often learn new movements by watching and imitating 

others. Imitation is thought to be central not only for humans’ ability to learn 

motor skills, but also for the development of communication skills.23, 24, 25, 26, 27 

Imitation is also thought to underlie understanding of the intention behind 

other’s actions.28 The paramount importance of imitation is revealed when 

one considers how social organization and, more fundamentally, survival are 

dependent on understanding the actions of others.29

What neurological mechanisms allow the human brain to perceive 

and interpret actions, and how does this ability relate to communication 

and empathy? Nearly two decades ago, researchers investigating the visual 
1823 Bio-IInspired IInnovation and ovation and NNational SSecurity 

and motor areas of monkey brains discovered a special set of neurons that 

responded to both a monkey’s movement as well as its observation of the same 

movement performed by another.30, 31, 32 Accordingly, these types of neurons 

became known as mirror neurons.

33

In monkeys, mirror neurons are part of a cortical circuit that involves 

the parietal lobe along with a section of the frontal lobe that governs sensory 

guided movement: the premotor cortex.34, 35 This parietal-premotor cortical 

circuit links observation of a movement to the preparation to execute that 

same movement.36 Motor neurons also selectively respond to performing and 

perceiving “goal-directed” actions, such as grabbing an object, and do not 

activate in response to more elementary movements.37, 38 These findings from 

monkey experiments made researchers curious about whether human brains 

also feature mirror neurons. 

To search for mirror neurons in human brains, researchers cannot 

record from single neurons. Instead, scientists use imaging techniques to 

view activity levels in specific regions of the human brain in response to 

performance and observation of motor acts. In the past dozen years, various 

neuroimaging techniques have revealed that the human premotor and 

parietal regions, just as in the monkey brain, also show activity in response 

to performing a certain action and perceiving that same action performed 

by others.39, 40 A crucial difference between human and monkey brains that 

reflects human’s sophistication compared to primates is that the core region 

for the human mirror system is Broca’s area, the brain region credited with 

producing language.41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53 The emergent theory from this 

work was that humans’ use of visual and auditory systems to recognize others’ 

actions eventually gave rise to language.54, 55

Moreover, mirror neurons in both monkeys and humans respond only 

to “biological actions”—that is, actions performed by a living being as opposed 

to a machine.56, 57 Mirror neurons also respond to sounds associated with goaldirected actions.58 These various discoveries led researchers to theorize that 

mirror neurons code for the “overall goal” and not just individual elements 

of an action.59

Researchers elucidated more crucial information about the functional 

role of mirror neurons by testing how much visual information about a goaldirected action is required to active mirror neurons. In this set of experiments, 

various goal-directed movements (combinations of grasping, holding, and 

placing an object) were performed but the final stages of the actions (handobject contact) were obscured from the monkeys’ view. Recordings from 

premotor cortical mirror neurons demonstrated that the monkeys’ mirror 

neurons still fired in response to the goal-directed movements. This implied 

that the monkeys’ premotor cortex had internally generated an understanding 
Biomimetic, Sociable Robots for Human-Robot Interaction 183

of the full action and that mirror neurons were involved in inference of the 

action’s goals.60

As for human mirror neurons’ role in prediction, neuroimaging of 

human subjects found that their observation of others’ movements coupled 

with the subjects’ intention to imitate those actions resulted in greater activity 

in premotor and parietal areas compared to observation coupled with plans 

to recognize those same actions in the future.61, 62 Based on these findings, 

scientists proposed that mirror neurons constitute the basic units of “a more 

sophisticated predictive system that allows humans to infer goals from the 

observation of actions.”63, 64, 65

This hypothesis was tested in human brain imaging studies, which 

found that parietal neurons had different responses to identical actions that 

had different goals. These findings provided evidence that mirror neurons are 

involved in prediction of an action’s intention.66 Thus, researchers postulated 

that mirror neurons constitute a basic key element in social communication 

and understanding of others, also known as empathy.67, 68, 69, 70, 71

Neural Networks Model the Brain 

For the past several years, the HRI field has sought to create artificial models 

of cognition that are “human compatible.”72 Such models, also referred to as 

cognitive architectures or neural networks, are products of a multidisciplinary 

effort of neurobiology, computational neuroscience, cognitive science, 

engineering, computer science, robotics, and psychology. These models, 

or neural networks, endow robots with abilities that range from object 

recognition to decisionmaking to “mind-reading.” At the most rudimentary 

level, basic mechanisms and fundamental principles of synaptic transmission 

can be the basis for modeling spatial and temporal pattern recognition 

processes. Because of their abilities to solve a wide range of complex tasks 

such as cognitive skills while also being biologically relevant, neural networks 

constitute extremely important feats of engineering.73

The neural network field is diverse and can be classified into several 

major categories based on how and to what degree the brain is modeled. As 

discussed in the book Artificial Intelligence and Neural Networks,

74 the major 

subfields are the following:

• Computational neuroscience. This field consists of modeling the brain 

at various levels of sophistication—from single neurons to entire 

functional regions—in great detail. Simulations of brain activity in 

these model systems are performed, resulting in predictions that can be 

empirically tested. The purpose of this subfield is to simulate the brain 

as realistically as possible, so the biological realism of new algorithms is 

of paramount importance. 
1845 Bio-IInspired IInnovation and ovation and NNational SSecurity 

• Artificial neural networks. Neural networks are leveraged in this 

engineering and industrial field to solve engineering problems and 

build electronic devices for certain applications. Successful and 

simple performance of the devices’ function(s) is the priority, whereas 

biological realism is irrelevant. 

• Connectionism. This is the field of modeling cognitive architectures that 

are inspired by biological neurons and neural connections. The emphasis 

is on developing networks that have simple, elegant representations. 

• Biological neural networks. This represents a small but important 

emerging subfield that reverse-engineers the nervous system in order 

to generate new neural architectures. These novel neural networks are 

then incorporated into general technological applications. 

Designing Mirror Neuron Function in Robots 

Given mirror neurons’ crucial role in human learning, “emotional” 

intelligence, and behavior, the neural network field has aspired to replicate 

mirror neurons in robots in order to allow them to emulate human emotion 

and understand human intent.75

In order to reach this goal, an interdisciplinary research community 

consisting of neuroscientists, computational neuroscientists, computer 

engineers, and robotic engineers is working on two long-term goals that have 

yet to be realized. First, robots must be able to both understand the goals 

of the human they are observing and mimic those goal-directed actions. 

Second, once the robot has successfully observed, understood, and mimicked 

the human’s goals, it must be capable of adapting those goals under different 

circumstances and in different environments.76

What is the current state of the art? A distilled and simplified explanation 

of the fundamental elements of computational mirror systems is described 

here. The first stage must involve the robot perceiving and mapping an observed 

action and then converting that information to its own internal frame of 

reference. “Perception algorithms” may be written to allow the robot to observe 

and measure human movement. The next phase will involve the robot learning 

to generate motions based on what is observed. This may involve scaling and 

converting the observed information into the robot movement that most 

closely resembles the human movement. Part of the challenge of translating 

movement is determining how to abstract the observed motion so that only 

the crucial information about goals is retained while the irrelevant information 

is discarded. In some cases, a neural network mirror system will contain a 

“closed-loop mode,” where the outputs of movement prediction are fed back 
Biomimetic, Sociable Robots for Human-Robot Interaction 185

as inputs, as opposed to outside observations of the human’s movement, to 

the robot’s learning system. This internal, closed-loop, feedback system is the 

computational equivalent of the robot visualizing the observed movements. 

Another method for removing the need for a human to repeatedly 

demonstrate a motion is to program reinforcement learning, whereby a reward 

function motivates the robot to learn how to execute the motion by practicing 

the action. Although this reward function is effective for teaching the robot 

how to perform various movements, it is ineffective in inferring the human’s 

goals. Finally, some systems will enable the robot to recognize a motion. In the 

recognition phase, the mirror neuron system relies on what has been learned 

and generated in order to predict human actions. This prediction ability allows 

the robot to recognize the same motion again. Some neural network models 

of a mirror system, such as a connectionist neural network program, have a 

dynamic quality to them that allows real-time interaction and synchronization 

between “top-down behavior generation” and “bottom-up recognition” 

processes: a parallel behavior recognizer and generator system.77, 78

Advances in Human-Robot Interaction R&D

A major S&T goal at ONR is to develop human-centric robots that can 

work in partnership with humans in a peer-to-peer dynamic, as well as in 

remote teams. For this to be possible, robots must be compatible with human 

cognitive, attentive, and communications capabilities and limitations. This 

compatibility requires robots to have several basic capabilities, including the 

ability to recognize faces and individuals, communicate in natural language 

styles of humans, as well as understand and perform communicative 

gestures.79 A more sophisticated requirement for successful HRIs in realworld scenarios is the integration of cognitive models, action schemes, and 

statistical estimations. Furthermore, integration of behavior models and 

distributed control capabilities is essential for effective tasking across humanrobot teams. These capabilities will allow robots to cope with and react to 

their changing environments in real time, as well as interact with their human 

counterparts accordingly. 

However, as discussed earlier, the current state of the art in HRI 

is several stages behind such peer-to-peer interactions, due to several 

inherent challenges in human-robot collaborations: noisy signals due to 

visual or auditory recognition problems, lack of spatial awareness due to 

communication restraints, lack of shared knowledge or misunderstanding 

of capabilities and limitation, linguistic ambiguities, and interpretations of 

perceived intent (including situational awareness, local tasking, and so forth). 
1867 Bio-IInspired IInnovation and ovation and NNational SSecurity 

To overcome these challenges and realize the goal of biomimetic, 

human-compatible robots, ONR has invested in an ambitious multi-university 

research initiative (MURI). What follows is a brief overview of the MURIbased advances in engineering artificial sensory, language, and cognitive 

abilities. Further, this summary will describe interface designs that will allow 

trust to increase between humans and robots as well as enable them to share 

the same goal structure. 

Visual and Auditory Recognition 

Humans are highly visual and communicate through a wide variety 

of visual cues including eye gaze direction, body language, and facial 

expressions. Accordingly, there has been considerable work on modeling 

the human visual system for robotics applications. Since there is a large 

amount of visual data in a given field of view, attention systems are also 

incorporated. Habituation filters, which encourage robots to continually 

search for interesting things, are also included. Bottom-up, or stimulusdriven, processing draws attention toward specific objects in the visual field, 

whereas top-down processing is task-based.

Photoelectric devices and charge-coupled device cameras have given 

way to biologically inspired vision sensors, which include artificial foveas and 

circuitry that mimic the neuronal connectivity of the human retina. These 

artificial retinas have some of the same visual processing capabilities as the 

human retina, including lateral inhibition (a method by which nerve cells can 

determine the origin of a stimulus) and temporal sensitivity.80 Currently, a 

novel retinal circuit is being developed that focuses on the ganglion cell, one 

of several cell types involved in retinal processing. This novel circuit enhances 

the response of cells to approaching objects, which may signal danger, in the 

context of a demanding visual environment.81 Visual recognition of human 

activity, or kinematic tracking, is also being undertaken.82

Biomimetic robots also generally include a microphone sound sensor. 

Processing of incoming sound waves is permitted with software models, or 

with hardware models mimicking the human hearing organ, the cochlea.83

This model mimics hippocampal function, with cochlea-like preprocessing. 

Current work focuses on biologically based pattern recognition systems in 

space and time for acoustic signal identification. The goal is to transition this 

application to security-breaching noise detection systems using progressively 

elaborate models with complex connectivity patterns and network 

architectures.84

Other research being done on multimodal sensor fusion with 

neuromorphic sensors for both visual and auditory processing is based on 

sensory systems of the barn owl. A silicon retina can respond to relative 
Biomimetic, Sociable Robots for Human-Robot Interaction 187

changes in intensity, and helps shape the auditory spatial map. For auditory 

processing, a silicon cochlea models responses as a set of bandpass filters. 

In each modeling paradigm, signal processing occurs similarly to biological 

processes of vision or hearing.

Somatosensory Function 

The human somatosensory system includes the sensations of light touch, 

pain, pressure, temperature, and joint and muscle position sense, or 

proprioception. In robotics, artificial touch sensors are generally composed 

of grids of pressure sensors that contain resistive or capacitive components. 

Proprioceptive feedback is provided by position sensors, which include 

potentiometers, magnetic sensors, linear displacement sensors, and digital 

encoders, among other sensors. Velocity is measured with tachometers, force 

is measured with stretch sensors coupled to position sensors, and position 

gauges register small movements in space.85

Language 

If peer-to-peer interaction between humans and robots is to occur naturally, 

it makes sense to program robots with an understanding of human 

communication styles.86 Humans largely communicate through verbal 

language. Human-machine language interaction consists of automated speech 

recognition and synthesis, language processing, dialogue and discourse, and 

affect recognition and expression. Currently, learning-by-doing algorithms 

create composite methods that result in interleaved perception and action 

responses.87 One thrust is perception-motor learning by imitation, where 

a robot learns a sound and attempts to repeat it. This will evolve from a 

sensorimotor grammar capability to linguistic grammar capabilities, resulting 

in elementary language interaction, elementary reasoning, and learning. 

More intense study into robust natural language and dialogue systems, affect 

recognition, and effective conveyance of critical information is also being 

undertaken to improve HRI.88

Learning 

Robots must continually learn about themselves, about the humans with 

whom they interact, and about their environments. Algorithms have 

historically been based on single-robot, single-human interactions, and 

have used simple models of human intentional states, not learned models. 

More recently, planning algorithms and models have been generalized to 

multiperson teams and multiple objectives. Ongoing research suggests that 

the human brain uses Bayesian principles for inferring actions and subsequent 

behavior.89 Bayesian inference provides a mathematically rigorous platform 
1889 Bio-IInspired IInnovation and ovation and NNational SSecurity 

for information processing given uncertain situations. Bayesian modeling 

is being applied to design anthropomorphic robots that can learn from 

observation and experience. Additionally, a noninvasive brain-robot interface 

is being developed that will allow for control of virtual or physical objects 

directly through brain activity.

In order to learn and communicate effectively, robot partners require 

flexible memory models similar to those of their human counterparts. A 

vast amount of literature already exists on the neuropsychology of memory 

reconsolidation. Ongoing research into the neural circuitry that supports 

episodic memory (that is, the memory of events, times, places, and so forth, 

and its associated emotions) and spatial navigation seeks to demonstrate a 

causal relationship between specific neural activity patterns and memory 

performance.90 Current work on information flow focuses on reconsolidation 

at the computational or behavioral level, as well as at the functional or 

algorithmic level.91 The goal is a human-like working memory system that 

involves adaptive recognition and new memory formation. 

Mind Reading 

Optimal peer-to-peer HRI requires interactive training in human-robot teams. 

This type of learning includes acquainting human partners with both the 

capabilities and limitations of robot partners, establishing common knowledge 

about strategies and procedures, negotiating roles for joint activities, and 

mastering joint activities through practice. Such robust and adaptable 

collaboration in dynamic environments requires “mind-reading” skills. 

Research into mirror neuron function is being applied to mind-reading 

skills in robotics. Biologically speaking, mirror neurons are key elements in a 

predictive system that allows for inference of intent, goals, and the like from 

observation. In robotics and neural network modeling, emulation of mirror 

neuron activity in prediction tasks and action recognition is currently being 

applied to learning.92 The immediate goal is to improve robot learning by 

implementing algorithms based on imitation—learn by doing. The long-term 

goal is the establishment of highly functioning human-robot teams that can 

participate effectively in collaborative decisionmaking processes.

Collaborative decisionmaking is useful for understanding and 

predicting human behavior by the robot. In turn, humans can apply their own 

mental models to understand and predict the behavior of the robot. Prior 

work in this area has included ambiguity resolution and visual and mental 

perspective-taking for collaborative efforts with multiple human partners. 

This research is currently being extended with studies to incorporate language 

and nonverbal behavior in estimating mental models. Perspective-taking is 

also being integrated with models of spatial cognition to model human beliefs 
Biomimetic, Sociable Robots for Human-Robot Interaction 189

and goals.93, 94, 95 This architecture is organized around the ability to understand 

the environment from the perspective of another individual. 

Increase Trust 

Trust between peers is a major foundation of effective teamwork, especially 

in the dangerous environments encountered during military operations. In 

order to increase the level of trust between humans and robots, a human 

must understand a robot’s limitations and abilities. The consequent need 

is optimal human-robot visualizations and interfaces. Such interfaces will 

provide scalable visualizations, support situational awareness, and allow 

transitions with an understanding of historical context. Technical advances 

in this area have included the development of an integrated HRI system for 

multiple human users and mixed-type robot systems. For example, research 

is currently being performed to develop a robotic platform for security and 

service applications.96 The goal of this project is to develop intelligent systems 

that can work in self-organizing teams able to respond robustly to changing 

inputs. This work will result in a fully configurable multirobot network that 

can self-organize in task allocation and can execute practical task requests by 

human collaborators.

In order for robots to operate safely alongside humans, the status of 

shared goals and plans must be continually monitored. Sensing capabilities, 

multiagent cooperation, plan learning and execution, and sensory channels 

(speech, gestures, actions) all present real challenges to safety. Advances in 

gesture recognition, personal identification, visual tracking and activity 

recognition, and dialogue capabilities technologies are being developed to 

improve trust and increase effectiveness of human-robot collaboration.97, 98, 99

Conclusion

Reducing casualties and the financial cost of operations as well as increasing 

the productivity of military personnel are the primary driving forces behind 

defense S&T investments. To help meet these objectives, autonomous robots 

will need to be more adaptable to the unpredictable nature of the real-world 

environment as well as be capable of collaborating in peer-to-peer teams 

with military personnel. Natural interactions between robots and human 

teammates require robots to be compatible with human cognitive, attentive, 

and communications capabilities and limitations. Further, these human-robot 

collaborations are dependent on trust, which requires robots to understand 

the goals of their human teammates and necessitates that humans understand 

the limitations and abilities of the robot. Thanks to advances in the fields of 

neurobiology, computational neuroscience, cognitive science, engineering, 
1901 Bio-IInspired IInnovation and ovation and NNational SSecurity 

computer science, robotics, and psychology, it is possible to engineer robots 

with artificial sensory, language, and cognitive abilities in order to make 

autonomous systems more biologically realistic. The ONR is at the forefront 

of this ambitious, multidisciplinary effort to create biomimetic robots that are 

capable of more natural and efficient human-robot interaction. Fruition of 

these HRI projects will have numerous impacts on U.S. defense policy.

Notes

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6 Ibid. 

7 A. Klein, “The Army’s $200 Billion Makeover: March to Modernize Proves Ambitious and 

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8 M. Fujita, “How to Make an Autonomous Robot as a Partner with Humans: Design 

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9 C. Breazeal et al., “Tutelage and Collaboration for Humanoid Robots,” International Journal 

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11 Breazeal et al., 315–348.

12 D. Perzanowski et al., “Building a Multimodal Human-robot Interface,” IEEE Intelligent 

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18 T.M. McKenna, “The Role of Interdisciplinary Research Involving Neuroscience in the 

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22 Ibid. 

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28 Iacoboni et al., 2526–2528.

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32 V. Gallese et al., “Action Recognition in the Premotor Cortex,” Brain 119 (1996), 593–609.

33 Ibid. 

34 Rizzolatti et al., 491–507.

35 Taira et al., 29–36.

36 L. Fadiga et al., “Motor Facilitation during Action Observation: A Magnetic Stimulation 

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37 Rizzolatti et al., 491–507.

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39 Fadiga et al., 2608–2611.

40 Iacoboni et al., 2526–2528.

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49 M. Petrides, “Broca’s Area in the Human and the Nonhuman Primate Brain,” in Broca’s 

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51 L. Fadiga et al., “Speech Listening Specifically Modulates the Excitability of Tongue Muscles: 

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54 G. Rizzolatti and M.A. Arbib, “Language within our Grasp,” Trends in Neurosciences 21 

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55 L. Craighero et al., “The Mirror-neurons System: Data and Models,” Progress in Brain 

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56 J. Grèzes, N. Costes, and J. Decety, “The Effects of Learning and Intention on the Neural 

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57 Rizzolatti, Fogassi, and Gallese, 661–670.

58 E. Kohler et al., “Hearing Sounds, Understanding Actions: Action Representation in Mirror 

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59 S.J. Blakemore and C. Frith, “The Role of Motor Contagion in the Prediction of Action,” 

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60 M.A. Umiltà et al., “I Know What You Are Doing. A Neurophysiological Study,” Neuron 31 

(2001), 155–165.

61 Grèzes, Costes, and Decety, 1875–1887.

62 Blakemore and Frith, 260–267. 

63 V. Gallese and A. Goldman, “Mirror Neurons and the Simulation Theory of Mind-reading,” 

Trends in Cognitive Sciences 2, no. 12 (1998), 493–501.

64 Jeannerod, S103–109. 

65 Blakemore and Frith, 260–267.

66 L. Fogassi et al., “Parietal Lobe: From Action Organization to Intention Understanding,” 

Science 308 (2005), 662–667. 

67 Gallese and Goldman, 493–501.

68 Jeannerod, S103–109. 

69 P.L. Jackson and J. Decety, “Motor Cognition: A New Paradigm to Study Self-Other 

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70 Fogassi, 662–667.

71 K. Nakahara and Y. Miyashita, “Understanding Intentions: Through the Looking Glass,” 

Science 308 (2005), 644–645.

72 Breazeal et al., 315–348.

73 Hanson and Olson, eds. 

74 McKenna, 75–92.

75 M. Arbib, “Robot Brains and Emotions. Interview on the Talking Robots Postcast,” available 

at http://lis.epfl.ch/index.html?content=resources/podcast/. 

76 Ibid. 

77 C.G. Atkeson et al., “Using Humanoid Robots to Study Human Behaviour,” IEEE Intelligent 

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78 J. Tani, M. Ito, and Y. Sugita, “Self-organization of Distributedly Represented Multiple 

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79 A. Schultz and G. Trafton, “Toward Cognitively Plausible Human Robot Interaction,” 

presentation, Office of Naval Research (ONR) Program Review: Human Robot Interaction 

and Human Activity Recognition, May 3–4, 2007, Arlington, VA.

80 B. Roska, “A Mammalian Looming Detector and Its Neural Circuit,” presentation, ONR 

Program Review: Computational Neuroscience, Sensory Augmentation, and Brain Machine 

Interface, April 25–26, 2007, Arlington, VA.

81 Ibid. 

82 G. Mori and J. Malik, “Recovering 3D Human Body Configurations Using Shape Contexts,” 

IEEE Transactions on Pattern Analysis and Machine Intelligence 28, no. 7 (2006), 1052–1062.

83 T. Berger, “Biologically-based Temporal Pattern Recognition Systems for Acoustic Signal 

Identification,” presentation, ONR Program Review: Computational Neuroscience, Sensory 

Augmentation, and Brain Machine Interface, April 25–26, 2007, Arlington, VA.

84 Ibid. 

85 G.A. Bekey, Autonomous Robots: From Biological Inspiration to Implementation and Control

(Cambridge: MIT Press, 2005).

86 Perzanowski et al., 16–21.

87 R. Granger, “End to End Brain-Circuit Framework for Interactive Cognitive Robotics,” 

presentation, ONR Program Review: Human Robot Interaction and Human Activity 

Recognition, May 3–4, 2007, Arlington, VA.

88 M. Scheutz, “Effective Human-Robot Interaction Under Time Pressure Through Robust 

Natural Language Dialogue and Dynamic Autonomy,” presentation, ONR Program Review: 

Human Robot Interaction and Human Activity Recognition, May 3–4, 2007, Arlington, VA.

89 R. Rao, “Probablistic Neuromorphic Systems,” presentation, ONR Program Review: 

Computational Neuroscience, Sensory Augmentation, and Brain Machine Interface, April 

25–26, 2007, Arlington, VA.

90 P. Lipton, “Real Time Recording and Stimulation of Brain Cell Assemblies,” presentation, 

ONR Program Review: Computational Neuroscience, Sensory Augmentation, and Brain 

Machine Interface, April 25–26, 2007, Arlington, VA.

91 H. Siegelmann, “Memory Reconsolidation and Computational Learning,” presentation, 

ONR Program Review: Computational Neuroscience, Sensory Augmentation, and Brain 

Machine Interface, April 25–26, 2007, Arlington, VA.
194 Bio-Inspired Innovation and National Security

92 O. Jenkins, “Dynamical Motion Vocabularies for Human-Robot Interactions,” presentation, 

ONR Program Review: Human Robot Interaction and Human Activity Recognition, May 

3–4, 2007, Arlington, VA.

93 C. Breazeal, “Three Projects on Human Robot Teaming,” Presentation, ONR Program 

Review: Human Robot Interaction and Human Activity Recognition, May 3–4, 2007, 

Arlington, VA.

94 Jenkins. 

95 Schultz and Trafton.

96 M. Nicolescu, “Understanding Intent Using a Novel Hidden Markov Model Representation 

Robotic Platform for Security and Service Application,” presentation, ONR Program 

Review: Human Robot Interaction and Human Activity Recognition, May 3–4, 2007, 

Arlington, VA.

97 C. Jones, “Peer-to-Peer Embedded Human Robot Interaction,” presentation, ONR Program 

Review: Human Robot Interaction and Human Activity Recognition, May 3–4, 2007, 

Arlington, VA.

98 P. Rybski, “Peer-to-Peer Embedded Human Robot Interaction,” presentation, ONR Program 

Review: Human Robot Interaction and Human Activity Recognition, May 3–4, 2007, 

Arlington, VA.

99 Schultz and Trafton. 
195

The tens of millions of species in existence on Earth today are the 

products of 3.8 billion years of evolution. Some of these organisms 

survive and flourish at astounding physiological extremes of 

temperature, pressure, and pH, and exist in the most inhospitable habitats, 

from the depths of the oceans to arid deserts and remote frozen glaciers of 

Antarctica. Beyond their innate abilities to grow, heal, and reproduce, the 

great diversity of organisms that have evolved can, from an engineering 

perspective, perform some remarkable feats. Nature has produced creatures 

that are capable of a vast range of functional abilities. On dry land, they 

can walk, run, or jump over complex terrain and climb, slide, or crawl over 

slippery surfaces. Some take to the air with active flight or glide through the 

trees to bypass the terrestrial clutter below. Still others have conquered the 

aquatic realm with unrivaled swimming and maneuvering abilities, while 

some remain hidden using serpentine bodies to burrow and slither between 

cracks and small spaces in the earth. How do our current robotics stack up 

to the wide-ranging and impressive mechanical capabilities of nature? These 

questions are currently being answered by integrative research initiatives that 

combine multiple disciplines in engineering, physics, chemistry, and more 

recently biology. 

While the reproduction of behaviors such as running and climbing in 

robots may seem simple on the surface, it is in actuality an immensely complex 

feat that requires an understanding of multiple layers of mechanics and control: 

force productions, counterbalances, kinematic motions, and even material 

properties of soft, hard, and compliant tissues. Hundreds of parameters and 

many thousands of measurements might be required to accurately describe 

chapter 13

Biomechanically 

Inspired Robotics

John Socha and Justin Grubich
1967 Bio-IInspired IInnovation and ovation and NNational SSecurity 

the dynamics of such behaviors through three-dimensional space. Building 

a robotic device to mimic these types of highly complex behaviors requires 

interdisciplinary teams of researchers that integrate expertise from fields of 

science such as computer and mechanical engineering, materials science, 

biomechanics, and neurobiology. The goal of this chapter is to introduce 

concepts of biomimetics (that is, the use of biological organisms as models for 

new robotic designs) and describe some of the cutting edge robots with uses 

for military as well as civilian applications that have resulted from these types 

of research programs. Finally, we will advocate that the promise of future 

unforeseen breakthroughs in biologically inspired robotics will continue to 

rely upon support for basic research in biodiversity and zoology that can 

lead to the discovery of new organismal capabilities and subsequently, novel 

biomechanical principles for engineers to mimic. 

Why Look to Nature? 

Biomimetics is a field that looks to nature for mimicry or inspiration 

in engineering design. “Why reinvent the wheel when nature has done 

it already?” is the rationale that motivates its research goals (although, 

interestingly, nature has never invented a wheeled organism).1 However, 

before diving into a discussion of bio-inspired robotics, we start with a 

caveat. Although the biological world is extremely diverse and ripe with 

fodder for inspiration, literally copying biology is not recommended or 

even practical for many applications. If one endeavors to design robotics 

that can perform as well as or better than their biological counterparts, one 

must be aware of two major realities of biology: first, organisms are products 

of their evolutionary history, where multiple, often antagonistic selection 

pressures can result in suboptimal designs; and second, evolution has shaped 

organisms using materials and designs that are not necessarily superior 

to human technologies. To put it another way, organisms are historical 

beings, products of a continuous line of ancestry and the shaping forces of 

evolution. Any changes in a new generation must build upon or alter the 

previous genetic stock, severely constraining the realm of what is currently 

possible. In human engineering, inventors are free to change whatever aspect 

of design they choose; they can use new materials, add or take away parts, or 

even scrap everything wholesale and start afresh. Organisms cannot do that, 

being inexorably limited by their past. 

Furthermore, the primary driving forces of evolution—natural and 

sexual selection—do not act on individual traits (for example, the ability to 

jump high) but instead favor success in one simple endeavor: the production 

of viable offspring. Because of these forces, biological systems are rarely 
Biomechanically Inspired Robotics 197

optimized for one particular function. Furthermore, not every component 

of a system is vital to its function, as evolution does not always weed out 

redundant or unnecessary parts as commonly believed. For example, consider 

the magnificent Emperor penguins made famous in the documentary, “March 

of the Penguins.” Emperor penguins spend months each year at sea, swiftly 

swimming through the frigid ice-capped waters, hunting and being hunted, 

until that time comes in the fall when they make landfall on Antarctica to 

begin their breeding migration. They march hundreds of miles inland over icy 

crevices and crumbling glaciers to mate, lay eggs, and incubate their offspring 

through the long dark winter where temperatures can reach more than -50°C. 

Now consider the many functions of the “marching” feet of these icrosystem 

birds. They use them to steer like rudders while swimming, to walk and 

climb for hundreds of miles over slippery craggy terrain, and finally, to hold, 

incubate, and protect the eggs that will produce the next generation. Hence, 

the feet of Emperor penguins have over time evolved to perform multiple 

tasks that are at odds with each other. In addition, their feet must do each of 

these functions adequately enough to ensure their survival and that of their 

offspring. Thus, is it equally unfair to critique the penguin foot solely for being 

an imperfect rowing device, as it is unwise to blindly copy it as a propulsor. 

Organisms are multifaceted, and biology is not always the best answer for a 

particular human design goal.

Second, this difference in the processes of design (evolution versus 

human engineering), combined with differential availability of usable 

material and resources, has resulted in profoundly different technologies. 

Although fundamental physics and chemistry are the same for nature and 

human engineering, the results of their gestalt designs are often profoundly 

different. As pointed out by Vogel,2

 nature is wet, soft, and squishy; engineered 

structures are dry, hard, and stiff. Nature has more far more curved surfaces 

than flat, and rarely do you see a sharp corner or right angles. Our designs 

tend to focus on stiffness, whereas strength matters more in nature. Engineers 

make joints that slide, whereas natural structures bend, twist, or stretch, 

and can often reconfigure to accommodate forces. Metals are widely used 

in engineered structures but are entirely absent as a material in biology. 

Organisms experience more tensile forces; compression is more common in 

engineered structures. Rolling and rotation are common and important in 

society’s technology, but almost completely absent in biology. The rotation 

at the heart of many engines, in particular, is entirely different from the 

engine that drives animal movement, muscle, which can only shorten. Lastly, 

engineered devices are designed for minimal, modular repair, but most 

organisms have continuous cell replacement—you literally are not the same 

person you were a year ago. 
1989 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Recent Advances in Biologically Inspired Animal Robotics 

The primary collaboration that drives modern robotics projects is between 

engineers and biologists. For engineers, the goal is to use biology to improve 

or create new robotics. Informed by the contrasts and caveats discussed 

above, “bio-inspiration” is more common than mimicry per se. This means 

that many designers take biological principles and run with them and do not 

adhere strictly to the rules of biology. For biologists, robots provide a way to 

test hypotheses of function and control.3

 Although computational modeling 

and simulations are possible, only physical modeling will work for many realworld situations.4

In the spirit of both goals—to answer biological questions and to push 

the boundaries of engineering—research teams have developed a multitude of 

bio-inspired robots based on a broad array of organisms, including humans, 

dogs, salamanders, snakes, fish, insects, spiders, lobsters, and octopi. Below 

we highlight some novel findings in current and past projects as an entrée 

into the bio-robotics world. For each, we discuss the sources of biological 

inspiration, examples of current robotics, challenges and goals for future 

improvements, and application for military usage.

Conquering Complex Terrain: Challenges for Land-based Locomotors 

Existing robotic platforms that use wheels and tracks are limited in their 

mobility in the rugged environments and complex urban terrain where 

military personnel and first responders operate. The unique load-carrying 

and climbing capabilities and agility that terrestrial four-legged animals 

such as horses, rocky mountain goats, and antelopes have evolved are being 

mimicked in the robotic platforms known as Big Dog, a four-legged platform 

designed to carry heavy loads over rough or uneven terrain.

Biomechanical research of legged animals was key to establishing the 

behavioral dynamics of motion, force, balance, and control principles that 

have led to dramatic increases in the capabilities of robotic technologies in 

the Big Dog program. In particular, high speed video and force platforms 

were used to describe the climbing and running ability of billy goats and 

guinea fowl over rough rocky terrain and steep grades.5

 By integrating live 

animal biomechanics data as blueprints of performance, the Big Dog robots 

can replace traditional tracked or wheeled systems with legged mobility that 

can move through rocky terrain, travel efficiently, and even recover from 

stumbles. Indeed, the latter ability was a major breakthrough for legged 

robotic designs. The findings from biomechanical research of how legged 

animals kinematically and neuromuscularly control their balance and velocity 

in rough terrain gave engineers insights into how simple mechanical models 
Biomechanically Inspired Robotics 199

of walking or climbing extend to unsteady conditions, and thereby provided 

inspiration for the design of the dynamically stable Big Dog legged robot. 

The ultimate goal of the Big Dog effort that has emerged from the former 

Biodynotics program is to develop, on a commercial scale, a biologically 

inspired robotic mule that can navigate difficult rugged environments 

while carrying additional payloads of supplies, weapons, tools, or sensors to 

facilitate military and disaster relief missions.

A challenge in designing many-legged robots is control and actuation 

of the multiple legs and joints while maintaining balance. With simplicity 

in walking in mind, Dennis Hong and colleagues at Virginia Tech have 

created an unusual three-legged robot called STriDER (Self-excited Tripedal 

Dynamic Experimental Robot).6

 This bizarre-looking creation is all legs and 

hips with no body—imagine a tripod of bending legs connected by rotating 

joints. The inspiration came from a principle of human walking: during the 

swing phase, in which the lifted leg swings forward like a pendulum, there is 

minimal neural control. Unlike many other legged robots that actively control 

leg movement throughout all phases, STriDER uses a similar passive swing 

phase, simplifying the required control. 

The key design features of STriDER include a single DC motor and 

gear set that can move each leg independently, and three joints that allow 

this centrally located motor to rotate with each step. The robot takes a step 

by moving one leg at a time. First, the robot shifts its center of mass forward 

on two legs; as it falls forward, the remaining third leg swings between the 

stationary two and lands in front. The central section containing the motor 

is flipped 180 degrees during the step, which is enabled by the multiple joints 

at the leg ends. Depending on the sequence of which leg swings through, the 

robot either moves straight forward, albeit in a zig-zag fashion, or turns. 

STriDER, like Big Dog, is a tall robot. Because of its height and inherent 

stability when all three legs are static, it may be best used as a platform for 

cameras or other remote sensing in hard-to-reach areas. Of all the robots 

discussed in this chapter, this is probably the most bio-inspired rather than 

biomimetic per se, but it clearly shows the benefits of borrowing choice 

features of natural design.

Beneath the Surface: Swimming with Four Limbs 

Underwater swimmers come in many forms, ranging from animals that 

use the whole body for propulsion, such as eels and jellyfish, to those with 

rigid bodies and flexible fins, such as boxfish. Multiple types of bio-inspired 

swimmers have been developed, the most prominent of which is Robotuna, 

a flexible-bodied robot based on the blue-fin tuna, one of the fastest cruising 

swimmers in the ocean. One purpose of such robots is to create new 
2001 Bio-IInspired IInnovation and ovation and NNational SSecurity 

autonomous underwater vehicles (AUVs), which have traditionally involved 

use of rotary propellers. However, current propeller-based and fish-based 

designs alike suffer in their ability to hold position or to accelerate quickly, 

making them unsuited for some applications. 

Turtles provide an alternative inspiration for underwater locomotion. 

With four flippers and central rigid body, they are able to easily hover in 

place and can create quick movements for acceleration and adjustment to 

perturbances. Two robotic turtles take advantage of these features: Madeleine, 

a collaborative project led by John Long at Vassar College, and Roboturtle, led 

by Michael Triantafyllou at MIT. Both robots consist of a sealed, rigid body 

packed with sensors and controllers and with room for other potential payload 

and four bilaterally symmetrical flippers that can be actuated in any pattern. 

Madeleine’s flippers have an airfoil shape and are flexible, matching the 

material properties of real turtle appendages, and they pitch up and down 

to produce propulsive vortices. Roboturtle’s flippers add an extra degree of 

freedom, able both to pitch along the fore-aft axis and flap to the side. The 

mobility and coordination of these flippers gives the robots unprecedented 

control, allowing them to easily hold position in the water and to generate 

large forces quickly for acceleration and maneuverability. Roboturtle’s extra 

degree of freedom of movement in the flippers makes it especially good at 

reacting to transient forces in unsteady environments, such as choppy seas or 

changing currents. 

In addition to aims for AUV development, robots such as Madeleine 

nicely illustrate how biologists can learn from engineered devices. One 

longstanding question in functional morphology concerns why it is that 

modern aquatic tetrapods—animals with four appendages like sea turtles, 

penguins, seals, sea lions, dolphins, and whales—employ only the front 

or rear limbs for steady, straight swimming.7

 Why not take advantage of 

the propulsion ability of all four limbs? Puzzlingly, extinct species such as 

plesiosaurs used all four, as inferred by their anatomy. By using the robot 

Madeleine, it was possible to isolate specific patterns of flipper movement to 

directly test this question. Long and colleagues found that during cruising, 

two flippers produced the same top speed but at half the power cost as with 

four flippers. However, when starting from a complete stop, the four-flippered 

configuration produced the highest acceleration, lending evidence to previous 

hypotheses that plesiosaurs were acceleration specialists. 

Up the Wall: Robotic Climbers 

Scansorial movement—travel up vertical surfaces—faces its main challenge 

from gravity. Insects, spiders, lizards, and frogs are expert animal climbers that 

can, for example, nimbly attach to surfaces, run up and down, and jump off 
Biomechanically Inspired Robotics 201

if needed. They can even do this upside-down, suspended from a horizontal 

surface such as a ceiling. They can move over smooth or rough surfaces, and 

have no problems returning to normal locomotion on the ground. How do 

animals stick to the side of a building, tree, or rock face with the force of 

body weight pulling downward, and how do they move up or down without 

becoming unbalanced and tipping over?

The key physical factor in the building of robots that climb is adhesion. 

The issue is not producing enough adhesive force—this is easy to do with 

magnets, suction, or pressure sensitive adhesives (such as sticky tape)—but 

controlling the adhesion. Consider a limbed animal climbing a wall. To move 

upward, the animal must lift at least one appendage off the surface, and in 

doing so, must produce enough force to overcome adhesion, advance the 

appendage, and “restart” the adhesive force. In the meantime, the lifted 

appendage changes the force balance on the animal, such that the other 

appendages have to support the weight and counter any torques created when 

the limb is lifted off. Despite these issues, animals use a range of mechanisms to 

adhere and climb. Generally, larger animals such as cats use claws to penetrate 

into a compliant surface such as bark; these animals cannot scale smooth, 

hard surfaces. Tree frogs and some insects use sticky pads, and other insects 

use small spines that can catch on tiny surface irregularities. Geckos and some 

spiders use fine hair-like structures that adhere to almost any surface using 

intermolecular forces.

Multiple climbing robots have been produced following the inspiration 

of these mechanisms. The RiSE (Robots in Scansorial Environments) project, 

a large multi-institution collaboration, is a particularly nice example of how a 

detailed knowledge of biological systems can be integrated with engineering to 

produce impressive climbing robots.8

 The most advanced climbers produced 

by this Defense Advanced Research Projects Agency (DARPA)–funded 

team include Spinybot, inspired by insects that use small, claw-like hooks, 

and Stickybot, modeled after geckos, which have highly specialized feet and 

toes. Here we highlight Stickybot for its unusual and highly biologically based 

components—peeling toes, directional adhesion, and differential control of 

toe placement. 

A robot such as Stickybot never would have been made without an 

understanding of the gecko’s specialized adaptations for climbing. Geckos are 

amazing climbers, able to stick to almost any surface on Earth, even under 

water or in a vacuum.9

 Although extremely sticky, a gecko can attach and 

detach its toes in milliseconds; furthermore, the toes do not stick to each 

other. Even more remarkably, gecko toes are self-cleaning—dirt is whisked 

away after a few steps of walking. Unlike sticky tape, the bottom of the toes 

does not degrade into a gooey and less effective mess over time. 
2023 Bio-IInspired IInnovation and ovation and NNational SSecurity 

The way that gecko toes stick is a combination of the complex toe pad 

anatomy and the particular direction and timing of forces during locomotion. 

Gecko toes are hierarchical structures, with key features from the macro to 

nano scales. Toe pads have ridges called lamellae that run perpendicularly 

along the long axis of the toe, and these lamellae are composed of hair-like 

stalks called setae. Each seta branches into multiple split ends, with each end 

being tipped by an extremely small plate called a spatula. Spatulae, which are 

less than a micron in width, are the sites of contact and adhesion between 

the gecko and the substrate. Kellar Autumn and colleagues have shown in a 

series of experiments how this system functions as a programmable adhesive, 

dependent on both the anatomical features and the gecko’s movement patterns. 

When the lizard pulls its foot across the surface, it preloads the setae and angles 

them properly to set up the attachment force. This force is extremely high—a 

tokay gecko can hang from a single toe with no problem. However, the force is 

dependent on the angle of the setal stalk with the substrate. If angled more than 

30 degrees from upright, the adhesion force disappears, allowing detachment. 

The way that the gecko unsticks while moving is by curling its toes backward, 

a feat termed digital hyperextension, which increases the setal angle enough 

to detach. Unlike pulling sticky tape from a surface, the gecko uses very little 

force for this detachment, contributing to a very energy-efficient system. The 

toes then uncurl when placed back on the surface, and reattach. 

Stickybot is a climbing machine that mimics the gecko’s mechanisms of 

climbing from the macro to micro scale. The general gecko-inspired features 

include a flexible body, toes that curl, and hierarchical toe pads with hairlike adhesives. Starting at the smallest scale, the toe pads are composed of 

directional polymer stalks that mimic the setae and spatulae together. The 

stalks are made of polyurethane from a mold, which imbues the stalks with 

slanted tips, an important feature that gives the robot a form of controllable 

adhesion. When the stalks are loaded (that is, when the foot presses down and 

pulls across the surface), the tip face has maximum surface area in contact 

and adheres to the surface. Detachment in the robot’s foot is also inspired 

by the gecko. To release the toes, steel cables connected to their tips cause 

them to curl upward when pulled back, changing the angle of the stalks 

and thus decreasing the attachment force. At the macro level, Spinybot has 

a differential rocker system that actuates the toes, which allows them to 

move independently and conform to uneven surfaces. Lastly, Stickybot has 

a flexible spine and sensors in the shoulders to help distribute forces more 

evenly among the legs.

The net effect of these features is a robot that can vertically climb a 

variety of surfaces including glass, glossy tile, and granite. Though extremely 

impressive, Stickybot (and other biomimetic climbers) are still far less capable 
Biomechanically Inspired Robotics 203

than their natural counterparts. For example, although Stickybot can deal 

with small surface irregularities, it cannot maneuver over larger bumps or 

accommodate larger obstacles such as a window ledge. Most climbing robots 

have difficulties negotiating the vertical to horizontal transition (such as 

reaching the top of a cliff), but the use of large, flexible tails to create favorable 

force balance is ameliorating that problem as well. A further challenge includes 

issues of scale: as the robots become bigger, their self-weight or added payload 

increases disproportionately compared to the adhesive forces created by the 

surface area of contact. This means that larger climbing robots may need to 

use different design principles, or look elsewhere for inspiration. 

Manipulation: Grasping with Agility in Three Dimensions 

Mammal tongues, elephant trunks, and cephalopod tentacles can perform 

an amazing variety of functions that allow these animals to deftly interact 

with and manipulate their environment. For instance, giraffes can wrap their 

tongues around high tree branches to strip off leaves using gross motions, or 

they can more deftly and delicately pick off leaves while avoiding the many 

spiny thorns found in acacia trees. Elephant trunks are amazing appendages 

that are strong enough to pull down trees and yet agile enough to pick a peanut 

out of your hand. Squid have eight arms and two specialized tentacles, while 

octopi have only eight multitalented arms. Squid tentacles are specialized for 

quick-strike prey capture. The arms of squid and octopi perform a myriad 

of more general manipulation and locomotion behaviors. These biological 

manipulators have inspired the design and application of soft robotic 

manipulators.10 There are many potential applications that can be imagined 

for an octopus-like robotic manipulator. For example, search-and-rescue 

robots equipped with “octopus arms” could efficiently navigate a rubble pile, 

searching for victims in crevices, analyzing structural integrity in a collapsed 

building, and grasping and handling payloads of varying dimensions, threats, 

and fragility (for example, rocks, unexploded ordnance, and injured humans).

Inspiration from these fantastically flexible limbs led a multidisciplinary 

team in the DARPA Biodynotics program to conduct research on the design 

and use of an innovative style of robotic limb known as OctArm. The OctArm 

is a soft robotic manipulator based on the biological model of an octopus arm. 

Octopus arms, like mammal tongues and elephant trunks, work as muscular 

hydrostats. The anatomical design of these types of appendages is devoid of 

bones and instead uses a pressurized chamber that is controlled by a range 

of unique muscle architectures. The function is similar to a balloon that, 

when squeezed at one end, elongates as the other end extends away from the 

increase in pressure. Because of this design, muscular hydrostats have extreme 

flexibility translating into a vast range of motor capabilities. Octopus arms can 
2045 Bio-IInspired IInnovation and ovation and NNational SSecurity 

shorten, elongate, twist, and bend in any plane at any point along their length, 

making them excellent animal models to mimic for dexterous grasping and 

manipulating robotic devices. In contrast to rigid links, levers, and rotating 

joints, which most conventional robot limbs are based upon, OctArm has 

three pneumatic tube sections that can create continuous bending motions. 

Thus, the OctArm is a highly flexible robotic limb that is able to achieve 

similar performance capabilities to a living octopus arm in that it can pivot, 

extend, shorten, and bend at almost any point along its length. 

This enhanced functional ability over conventional robotics allows for 

compliant whole-arm manipulation of objects. Instead of using a hand or 

claw to grasp via a pinch grip, the OctArm is able to encircle an object and 

grasp with distributed pressure. This allows the arm to lift objects that are 

many times larger than those graspable by traditional manipulators. The soft, 

compliant nature of OctArm allows it to firmly grasp uniquely shaped objects 

and successfully handle fragile materials. In addition, the arm’s ability to wrap 

around an object eliminates the potential of piercing it. The arm has been 

designed to attach to a small, unmanned ground vehicle, which allows the 

vehicle’s operator to enter a hazardous environment and manipulate objects 

while remaining at a safe distance. 

The OctArm has been tested in several battlefield tasks including mock 

scenarios where it successfully grasped and removed heavy mannequin soldiers 

from a battlefield without further “injuring” them and while providing safety 

to the remote operator. In addition, OctArm has been successful in search 

and recovery of mock destroyed buildings. With its tip-mounted camera and 

octopus-inspired suction cup devices, it is able to navigate its flexible limb 

into irregularly rocky rubble, sense objects, and retrieve them. 

Squeezing through Cracks: Inspiration from Single-celled Locomotion 

Many kinds of cells can move on their own. Unicellular organisms such as 

bacteria or protists use rotating or undulating flagella, or wave with rows of 

smaller cilia. Individual amoebae, as well as many types of animal cells such 

as leucocytes, keratocytes, and fibroblasts, move not with an engine such as a 

flapping flagellum, but by extending a protrusion, attaching it to the substrate, 

and then pulling themselves forward, a sort of “bootstraps” way of movement. 

The particulars of how one unicellular species moves have served as 

inspiration for an unusual type of cylindrical robot conceived by Dennis Hong 

and his colleagues. Their “whole-skin locomotion” (WSL) device is loosely 

based on movement of the “giant” amoeba Amoeba proteus.

11 The body form 

of the amoeba can be thought of as a membraneous bag surrounding a rigid 

gel and a liquid inner core. To move, the giant amoeba extends a protrusion 

(a pseudopod, or “false foot”) forward, with the inner liquid moving to the 
Biomechanically Inspired Robotics 205

tip. The bottom surface contacts the substrate and remains stationary, and 

the back end contracts. Amoebae can even advance forward in fine capillary 

tubes, with all surfaces in contact circumferentially.

Hong’s amoeba-inspired WSL device is an elongated torus, a sausageshaped robot with a hollow middle. It works in icrosy by turning itself inside 

out in the following manner. The outer skin is used for traction, and as it rolls 

forward the device as a whole moves too. As the outer skin moves forward 

and reaches the forward end, it rolls over the edge and back down the middle 

and becomes the inner skin, marching backward as the device moves forward 

as a whole. Another way of thinking of this is as a three-dimensional tank 

tread that rolls in on itself—the tread itself is the vehicle. 

Because of its ability to squeeze between cracks and obstacles, this 

device has tremendous potential for uses such as search and rescue, where it 

could follow along through spaces such as rubble piles. Additionally, it can be 

used to travel through piping and could be especially valuable in systems with 

variable diameter or surface roughness, and flexible tubing; it could even be 

used to search the human digestive system. One challenge with development 

and deployment of a WSL robot for military usage is how to take advantage 

of the design; because the device as a whole constantly rotates around itself, 

there is no stationary platform for objects such as cameras. However, this is 

likely to be a minor technical issue, as it is possible to embed sensors or other 

material into the skin itself. WSL may ultimately prove to be a valuable tool 

for crawling and searching through uneven terrain. 

Continuing Sources of Biological Inspiration 

The root of these realized robotics projects is biological inspiration. Engineers 

are perfectly capable of identifying principles in plain view—the Wright 

brothers’ bird watching led to their use of wings in design for flight—but 

for basic biological research to flourish, it is critical to provide continuing 

sources of inspiration. A large proportion of research and funding today 

centers around model systems such as fruit flies, mice, and zebrafish, and 

for good reason—with many basic questions worked out, they are expedient 

for addressing higher level questions. But the biological world is extremely 

diverse and complex, and these model systems are not always so model. 

Different organisms have solved life’s problems in their own particular ways, 

something that we are still only beginning to appreciate. How can we mimic 

or be inspired by phenomena that have not been discovered or explained? 

In the past few years alone, we have learned of ants that explosively propel 

themselves with their jaws, a new species of shark that instead of swimming 

actually crawls on modified fins, an octopus that walks uniquely across the 
206 Bio-Inspired Innovation and National Security

seafloor by sequentially rolling only two tentacles, and snakes and ants that 

glide through the air. The research that uncovered these stories was motivated 

not by promises of future practical applications such as robotics, but by 

desires to understand the rich spectrum of functional mechanisms among 

all organisms. Can we extract useful robotics principles from these diverse 

phenomena? Whether or not it is possible, we cannot know until we have 

first identified and understand what is out there to begin with. To do this 

we must continue to support basic biological research. What we have left to 

understand in areas such as biomechanics, physiology, and neural control, 

in species known and yet to be discovered, is immense. It is imperative 

that we preserve and discover the Earth’s richness in diversity and continue 

supporting the research that brings this to light. 

Notes

1 M. LaBarbera, “Why Wheels Won’t Go,” The American Naturalist 121, no. 3 (March 1983). 

2 Steven Vogel, Cat’s Paws and Catapults: Mechanical Worlds of Nature and People (New York: 

W.W. Norton and Company, May 1998). 

3 R.E. Ritzman et al., “Insect Walking and Biorobotics: A Relationship with Mutual Benefits,” 

BioScience (January 2000).

4 R. Pfiefer, M. Lungarella, and L. Fumiya, “Self-organization, Embodiment, and Biologicallyinspired Robotics,” Science 318, no. 5853 (November 16, 2007). 

5 M.A. Daley and A.A. Biewener, “Running over Rough Terrain Reveals Limb Control for 

Intrinsic Stability,” Proceedings of the National Academy of Sciences 103, no. 42 (2006), 

15681–15686.

6 I. Morazzani et al., “Novel Tripedal Mobile Robot and Considerations for Gait Planning 

Strategies Based on Kinematics,” in Recent Progress in Robotics: Viable Robotic Service to 

Human, ed. Sukhan Lee, Il Hong Suh, and Mun Sang Kim (Berlin: Springer, 2009). 

7 J.H. Long et al., “Four Flippers or Two? Tetrapodal Swimming with an Aquatic Robot,” 

Bioinspiration and Biomimetics 1 (March 2006), 20–29. 

8 K. Autumn et al., “Robotics in Scansorial Environments,” Proceedings of SPIE 5804 (2005).

9 K. Autumn, “How Gecko Toes Stick,” American Scientist 94 (2006), 124–132. 

10 W. McMahan et al., “Robotic Manipulators Inspired by Cephalopod Limbs,” 2004, funded 

by DARPA BioDynotics Program, Contract N66001–03–C–8043.

11 M. Ingram, “Whole Skin Locomotion Inspired by Amoeboid Motility Mechanisms: 

Mechanics of the Concentric Solid Tube Model,” thesis, Virginia Polytechnic Institute and 

State University, August 10, 2006, available at http://scholar.lib.vt.edu/theses/available/

etd-09182006-152023/unrestricted/Ingram_WSL_Thesis_ETD.pdf.
207

Automata are associated with two rather distinct notions: a commonly 

used one of any “machine that is relatively self-operating,” and a 

specialized, computer science concept of finite state machines, in 

particular finite automata. Biological automata referred to in this chapter 

follow the former notion; specifically, they resemble the autonomous, selfoperating systems best described in Norbert Wiener’s book Cybernetics:

automata effectively coupled to the external world . . . by flow of 

incoming messages and of the actions of outgoing messages. . . . 

Between the receptor or sense organ and the effector stands an 

intermediate set of elements, whose function is to recombine the 

incoming impression into such form as to produce a desired type 

of response in the effectors. . . . The information fed into the central 

control system will very often contain information concerning 

the functioning of the effectors themselves. . . . Moreover, the 

information received by the automaton need not be used at once 

but may be delayed or stored so as to become available at some 

future time. This is the analogue of memory. Finally, its very rules 

of operation are susceptible to some change on the basis of the 

data which have passed through its receptors in the past, and this 

is not unlike the process of learning.1

Wiener discussed at length the similarities between mechanical and “natural” 

automata—a discussion whose origins date back to Rene Descartes, who 

described animals as “biological automata.” 

chapter 14

Biological Automata 

and National Security

Yaakov Benenson
2089 Bio-IInspired IInnovation and ovation and NNational SSecurity 

In the natural world, single cells were for a long time considered the 

smallest “automata” with a nontrivial behavior. An aggregation of billions of 

cells in higher organisms endows these organisms with irreducibly complex 

high-level behavior that determines how they respond as a whole to changing 

environments and in particular how they make decisions under uncertain 

conditions and with incomplete information. This complexity reaches its peak 

in humans who excel in nondeterministic behavioral patterns that are light years 

away from the simple reflexes of lower organisms. However, all the way down 

to organs and individual cells we find molecular-scale processes, otherwise 

called pathways or networks, that themselves act as autonomous information 

processors and that respond to environmental information in a programmed, 

mostly deterministic fashion. For example, hormones are secreted in our body 

and are sensed by individual cells via special receptor molecules on their surface. 

These receptors then report about the presence of a hormone to the intracellular 

components; ultimately, multiple data from a variety of external stimuli are 

integrated by a cell to take an appropriate action (for example, to activate a 

stress response). These natural molecular systems sense, process, and respond 

to environmental molecular signals; therefore, they fit Wiener’s definition of an 

automaton. Intuitively, we may not regard them as automata because they have 

no physical boundary and are not separated from the environment in which 

they operate. Instead, the whole molecular ensemble, when placed in a certain 

volume, represents one “distributed” automaton that has a certain emergent 

behavior. A useful analogy may be found in the world of chemical engineering: 

there, a control system of a plant has sensors and actuators distributed over 

large distances. The separation between the system and its environment (the 

plant itself) is done by listing all the elements that directly belong to the system. 

Similarly, a specification of a molecular automaton is a list of all molecules that 

comprise the automaton, their concentrations, and the parameters of their 

interactions with the environment and among themselves.

Interpretation of biological processes in these and similar terms (for 

example, as signal-processing and information-processing systems, control 

systems, circuits, and so forth) has a rich history. It has recently inspired an 

effort in a synthetic direction—namely, design and construction of artificial 

molecular systems with novel sensory, computation, and actuator properties. 

Success in this endeavor will supplant natural automata with engineered 

ones and afford a wide range of applications from sophisticated intracellular 

sensing to single-cell diagnostic tools and “designer” organisms with novel 

functionalities.
Biological Automata and National Security 209

Design Paradigm and Potential Applications 

Development of biological automata is still in its infancy. Eventual success in 

this endeavor will require massive integration of cutting-edge results from a 

few tangential technologies still under active development. Apart from that, 

real ingenuity will be required on the developers’ part to solve both conceptual 

problems pertaining to the systems’ architecture and technical issues that may 

impede delivery of working applications. However, the anticipated benefits 

of the technology could be substantial. It is therefore instructive to consider 

these benefits even at this early stage.

We can predict the impact of biological automata by examining the 

impact made by the advent of digital computing machines. Conceptually, 

both technologies deal with the processing of information, but in practice 

a lot depends on what generates this information and how it is relayed to a 

“computer.” One kind of data is generated by humans. These data by definition 

must be stored and transmitted by ways accessible to other humans and 

therefore should be formulated as a sequence of symbols, sounds, and images. 

It can be relatively easily digitized and fed into a digital computer for further 

processing. Another kind of information does not result from an intelligent 

human activity but has its origins in the natural world. Its availability to digital 

computer processing depends on our ability to collect these data via sensing. 

In essence, anything that can be measured by a physical device and converted 

into an electric current can be digitized and fed as an input to a computer. 

The combination of sensors and computers is very powerful. Meteorology 

stations use measurements from a large number of environmental sensors to 

feed predicting models that run on a supercomputer, making highly reliable 

weather forecasts that have become indispensable for seamless functioning 

of a modern society. Yet certain events in nature can never be observed, due 

either to the lack of sensors or our inability to gather the data because of the 

temporal or spatial features of an event.

As shown by the weather forecast example, a capability to rapidly 

process large amounts of data has significantly advanced many aspects of 

human existence. It is important to note that it is a combination of powerful 

sensing and computation technologies that is most useful. In the absence of 

practical methods with which to gather and relay data, computer programs 

would largely remain worthless. All human-generated data can be fed into a 

digital computer due to either its inherently digital character (symbols) or its 

easy digitations (sound and images). In parallel, increasing amounts of data 

from natural sources are becoming accessible as more and more sensors are 

being developed. However, not all information from natural sources can be 

extracted and processed using existing tools. One such kind of information is 
2101 Bio-IInspired IInnovation and ovation and NNational SSecurity 

generated by a living organism to coordinate the activity of its parts, organs, 

and cells. These are normally chemicals or specialized cells that circulate in an 

organism. We may expect that these organism-wide indicators will eventually 

be rendered accessible by miniature conventional sensors introduced in a 

human body. Even today, tiny cameras can transmit images from the depths 

of the digestive tract, while nuclear imaging can uncover abnormalities with 

high spatial precision. 

On an even smaller scale, an individual cell generates vast amounts of 

molecular information to regulate the activity of its various pathways. These 

and other molecular indicators can tell a lot about the physiology of a cell 

and, more importantly, report on problems. A problem with a single cell 

in an organism can eventually become a problem for the entire organism if 

not checked in time. For example, a cancer usually develops from a single 

abnormal cell. Moreover, many early molecular signals precede an emergence 

of a problem, and they potentially could be used to trigger a preventive 

action. Sensing multiple molecular features in a single cell could both tell us 

about the current state in this cell and help us predict its future. However, 

as of today, we have neither the required sensors that would operate inside 

individual live cells nor the computers capable of processing this information. 

Considering the sensory component, we contend that there are basic physical 

limitations to developing sensors that would convert molecular signals in 

single cells to an electrical current or other comparable outputs. Even if these 

sensors could be developed, there is hardly a conceivable way to transmit 

the sensory output to a computer for processing. What is required here is 

a change in paradigm, which may come from carefully studying biology. In 

fact, biology solves similar tasks using very different engineering principles. 

Biological sensors convert molecules to other molecules instead of converting 

molecules to an electrical current. Biological processors are built from 

molecules that interact with the molecular outputs of the sensors to generate 

a response. These processors operate inside single cells. We can use these 

principles to design artificial systems with novel and powerful capabilities. 

Molecular automata technology will combine the power of sensing of 

multiple molecular indicators in individual live cells with their programmable 

processing inside these cells. They will be biology-friendly so that they can 

function in individual cells and will be built much like the natural molecular 

pathways, with sensors, computers, and actuators all composed of biological 

molecules. In fact, in certain cases the operation of these automata could go 

completely unnoticed by an outside observer, much like the action of myriad 

biological transformations inside our bodies go unobserved, at least as long 

as they function properly.
Biological Automata and National Security 211

To recapitulate, molecular automata comprising a set of versatile 

molecular sensors and a general-purpose, programmable molecular 

computing module will be used in a broad sense to collect and distill molecular 

information from individual cells and to use the result of a molecular 

computation to trigger a desired response. Specifically, the applications will 

include detection of normal complex cell phenotypes in an organism in real 

time; detection of diseased cells and their labeling or destruction; making 

predictions about a future development of a disease; creating “designer” 

cells with novel properties; and many more. Unlike digital computers that 

are only useful for complex problems that cannot be solved by an unaided 

human brain, molecular automata will be useful even if their computational 

power is modest, as their utility stems from the capacity to gather and process 

information at a place where existing approaches fail. Even a trivial automaton 

with a single sensor could be extremely useful. 

Successes and Challenges 

The work on biological automata has just begun. However, some encouraging 

results have emerged in recent years (theoretical work on these issues dates 

back to the 1960s). A large effort has focused on biochemical systems—

that is, systems composed of biological components that operate outside of 

the native biological environment. These systems sometimes approximate 

real biological processes, although care must be taken when making any 

conclusions due to many complicating factors peculiar to the real-life 

biological milieu. These biochemical systems focused on two complementary 

models of computation, those of logic circuits and a state machine. The latter 

system in its most advanced form represented a fully functional molecular 

automaton that worked outside of a live cell. Nevertheless, it demonstrated 

the complete sequence of steps, beginning with sensing molecular signals, a 

decisionmaking computation and, ultimately, actuation. In parallel, the work 

on purely biological systems has been focused on the development of simple 

logic circuits as precursors for biological computers and, separately, on the 

development of biosensors. Recently, new work has looked at a framework for 

a scalable, general-purpose automaton that may function inside human cells. 

This automaton utilizes a computation core based on logic evaluation. 

To summarize, development of biological automata has progressed 

significantly along both theoretical and practical axes. From a theoretical 

standpoint, we have moved from a few vague ideas toward concrete feasible 

designs whose implementation is only a matter of time. We have also identified 

a few key challenges we must tackle in order to deliver real-life applications. 

From a practical perspective, we have tested a variety of approaches and have 
2123 Bio-IInspired IInnovation and ovation and NNational SSecurity 

a good understanding of their relative merits and drawbacks. If in the past we 

faced conceptual challenges, they have largely been overcome, and we are in a 

position to advance to real-life applications. 

This transition raises a number of issues, one of which is the delivery 

of bio-automata into the cells of an organism. According to the common 

wisdom in the field, the automata will be built as a set of genes, with each 

gene coding for one structural component of the system. Ideally, the genes 

are to be delivered transiently into all cells of an organism and function 

there for a period of time just long enough to gather and process the relevant 

information. Delivering a collection of genes to all cells of an organism is 

a technical challenge that is being addressed by active research in the field 

of gene therapy, which also requires similarly efficient delivery. Besides, the 

timing of an automaton action has to be precisely controlled. Moreover, as the 

genes are successfully delivered to a cell, we must rely on cellular processes 

to generate the gene products. Unfortunately, a cell is not a completely 

predictable machine, as illuminated by the current research in systems 

biology. Instead, a cell is characterized by a great deal of randomness; for 

example, the exact amount of a gene product generated in a unit time cannot 

be predicted precisely. Therefore, an automaton design should anticipate 

and counter this randomness by a variety of compensatory and stabilizing 

elements, and engineering these elements is a challenge in its own right. 

Nevertheless, we expect that these and other challenges will be overcome as 

a few tangential technologies mature. For example, automata delivery to cells 

will be solved by methods developed in gene therapy. Similarly, development 

of robust architectures will be informed by the studies in systems biology and 

insights from natural systems that have similar performance requirements. 

Implications for National Security 

Being both an emerging and an enabling technology, the exact impact of 

biological automata on the issues of national security is hard to predict. In a 

very broad sense, these systems will open ways to entirely new approaches to 

a medical treatment, preventive or therapeutic. In particular, these automata 

will be capable of detecting the very early onset of disease symptoms with 

highest possible spatial precision, that of a single cell. As such, they could 

potentially be used to fight biological and chemical warfare agents, especially 

in their preventive capacity. Specifically, we may expect this new technology 

to supplant immunization as a way of fighting bio-agents and supplant 

antidotes in fighting chemical agents. As a matter of fact, our body is under 

constant attack by foreign agents; these attacks are normally dwarfed by the 

immune system or other response mechanisms in our body. Biological agents, 
Biological Automata and National Security 213

by definition, are the ones that have no appropriate built-in response in an 

organism. In other words, our biology has not evolved to resist these agents, 

probably because their occurrence has been rare or nonexistent and thus has 

not warranted an “invention” of such response. Currently, the best known 

protection against biological agents is immunization using a vaccine. However, 

immunization often fails because it responds directly to the attacking agent; 

mutating the agent or slightly modifying it in other ways may render an 

immune response useless. Bio-automata technology will enable us to develop 

new types of responses, based on those characteristics of the biological or 

chemical agents that are not easily modified. For example, if a certain toxin 

blocks ion channels, the sensors of a bio-automaton will detect changes in 

ion-transport properties and other metabolic parameters inside the cell 

rather than the toxin itself. This sensing will generate a similar response to all 

toxins that have this particular mechanism. Moreover, the automata residing 

in individual cells may respond by synthesizing a novel type of channel not 

blocked by a toxin, or simply by boosting the synthesis of the native ion 

channel in order to overcome the impact of the toxin. When the toxin will 

have been removed from an organism, the automaton will self-inactivate in 

order to maintain a normal number of ion channels per cell. Given that the 

number of mechanisms by which different agents may cause damage is much 

more limited than the number of agents, we could in principle envision a 

general-purpose automaton that would fight all major agents in the same 

time. To reiterate, this new approach will focus on mechanistic consequences 

of an agent action, rather than on the agent itself, and thus will significantly 

decrease the degrees of freedom of agents’ developers, as it is much harder 

to devise a new action mechanism than to design a new compound whose 

mechanism is established already.

Launching automata to probe the physiological state of a live cell 

is only one possible level of operation for these systems. A higher level of 

application complexity will result from the development of “designer cells” 

harboring these automata that receive their input information from the larger 

environment. The sensors therefore will reside on the cell membrane, but 

the computational module and the actuation could still function inside the 

cell. As a result, designer cells will act as individual agents interacting with 

each other and their environment and perform organism- and environmentlevel tasks. Within the medical realm, designer cells harboring biological 

automata could revolutionize emergency medical treatment in the battlefield. 

In particular, they could substantially enhance current efforts to deliver 

new cell-based regenerative treatments. For example, stem cells and their 

derivatives are currently viewed as a potential source of biological material 

to replace or replenish damaged or absent tissue, respectively. However, using 
2145 Bio-IInspired IInnovation and ovation and NNational SSecurity 

nonmodified stem cells might result in poor control over the regeneration 

process and, potentially, tumor formation as demonstrated in a few cases. 

Moreover, the regeneration process, even if successful, could take weeks or 

months to complete. 

It is becoming increasingly clear that these cell therapies will operate 

best once the therapeutic cells are enhanced with a variety of automata-like 

mechanisms. These mechanisms should include an ability to discern the 

location within the organism and the organ/tissue to be regenerated; safety 

mechanisms to sense and prevent potential tumorigenesis; and mechanisms 

that accelerate growth when needed but slow it down once the regeneration 

process is completed. A number of specialized treatments could be developed, 

for example, to fight the loss of eyesight due to an eye injury. This case could 

be one of the first areas where regenerative treatments will be implemented 

in an emergency mode, because the actual damaged area is small, while the 

consequences are devastating and a fast response is crucial. The complexity 

of an eye, combined with its relatively small size, warrants inclusion of highly 

sophisticated automata-like mechanisms into the therapeutic cell agents. 

Similar considerations apply for certain brain and/or nervous system injuries 

that could be limited in size but extremely dangerous in their consequences. 

It is fair to say that our level of basic understanding of both the eye and the 

nervous systems has to improve significantly to make possible emergency 

regenerative therapies, but the development of basic enabling technologies 

has to continue hand in hand with the basic biomedical research so that both 

can converge at some point in the future.

Apart from battlefield-specific medical applications, molecular automata 

embedded in designer cells may address a variety of needs for situations that 

require interacting with and affecting chemical and biological agents on the 

battlefield. The very nature of these agents makes them amenable to detection 

and treatment using antidotes in the form of engineered biological entities. 

Ideally, an area contaminated with the nonconventional agents will be treated 

with biological antidotes such as microorganisms or even primitive multicellular 

organisms such as worms or flies. These antidotes will be programmed to detect 

and be attracted to high concentrations of the harmful agents, decontaminate 

them by digestion or chemical neutralization, and self-destruct once their 

mission is accomplished. Once again, the built-in automata will be used not 

only to enable the basic antidote function of the organism, but also to ensure its 

safety for the environment by preventing its escape into the wild.

More mundane tasks, such as decontamination of the environment from 

common toxic wastes that remain on a battlefield and its surroundings, could 

also be accomplished by similar means. Given an anticipated complexity of 

the automata, we could envision a single generic “bug” that would manage 
Biological Automata and National Security 215

the majority of common contaminations, as opposed to specialized bugs that 

fight individual agents separately. 

Apart from the above applications, we believe that many new uses of 

the technology for national security will emerge. Digital computers, initially 

intended to serve as fast calculating machines, have transformed all aspects of 

our daily life as well as the practices of modern warfare in all its aspects. The 

capacity to process biological information in situ, either in individual cells, 

organisms, or the natural environment, will lead to multiple ideas that as of 

now are completely unanticipated.

Conclusion 

Biological automata comprising molecular sensors, computers, and actuators 

have the potential to access biological signals in individual cells of an organism 

in real time, process these signals in a programmable fashion, and generate an 

appropriate response. Although these ideas have been around for some time, 

only recently have we reached a point when actual technical solutions are 

becoming feasible and may be tested in live cells in culture. There is a long way 

from a cell culture to an organism, but once feasibility has been demonstrated, 

we may expect that increased investment will drive the technology forward at 

a much faster pace, resulting in real-life applications in a relatively short period 

of time. The anticipated impact of biological automata may be compared 

to that of digital computing machines. Digital computers fed with real-life 

sensory data have proven indispensable in monitoring and controlling largescale manmade systems as well as in the analysis and forecast of natural 

phenomena. Similarly, biological automata may become indispensable in 

monitoring, diagnosing, and ultimately controlling molecular processes at 

the level of a single cell and, consequently, an entire organism. Like other 

transformative technologies of this kind, it will undoubtedly have an impact 

on various aspects of national security, in particular in bio-defense. However, 

past experience has shown that most applications arise after an enabling 

technology is developed. We expect that this will be the case with biological 

automata.

Note

1 Norbert Wiener, Cybernetics: or Control and Communication in the Animal and the Machine

(Cambridge: MIT Press, 1948).

part four

human applications

219

The transformation of the current legacy U.S. Army to the Future Force 

will require a degree of doctrinal and technical innovation surpassing 

that of any past revolutions in military affairs. The Future Force can 

best be described as smaller, lighter, faster, and more agile, flexible, and lethal 

than any army today. The Future Force will also possess an unprecedented 

degree of autonomy, with small units operating with limited support for 

lengthy periods. These conditions will necessarily place enormous physical 

and mental demands on the Soldier.

The biological sciences have been largely treated with benign neglect 

by military planners, at best relegated to medical and biodefense applications. 

The physical sciences and information technology have played a dominant 

role in the transformation to date, making spectacular and devastating 

enhancements to the effectiveness of the current force. With rapid advances 

in biotechnology within the past decade culminating in the sequencing of 

the human genome, the biological sciences have crossed a technological 

threshold and are poised to play a pivotal role in shaping the Future Force. 

From biosensors to new energy sources, biofuels to lightweight materials, 

molecular computing to new therapeutics, the biological revolution will have 

an enormous impact on materiel, training, and the Soldier.1, 2

Athletes and Performance 

The key to any army is the individual soldier. Training and materiel are 

critical, but monitoring soldiers’ physiological status and readiness and 

possibly enhancing their metabolic efficiency and performance are within 

chapter 15

Enhanced Human Performance 

and Metabolic Engineering

James J. Valdes and James P. Chambers
2201 Bio-IInspired IInnovation and ovation and NNational SSecurity 

our technological grasp. Certainly, there are precedents, crude as they are, 

in the sports world. Current approaches can be reduced to nutritional 

supplements (often called nutriceuticals),3 drugs (such as anabolic steroids), 

and gene doping.4

Juhn’s5 excellent article on supplements and ergogenic (or performance 

enhancing) aids reviews the supplements of choice for athletes and points 

out the many methodological flaws in much of the research on them. Also 

noteworthy are the wide variety of individual responses to supplements as 

well as observable deficiencies in responses of trained versus untrained 

subjects. For example, the popular supplement creatine, a primary supplier of 

the energy source adenosine triphosphate (ATP), appears to be ergogenic in 

repetitive cycling and possibly weight lifting, but not in running, swimming, 

or other activities requiring endurance. Protein, amino acid, and antioxidant 

supplements appear to have no ergogenic effects at all, although they cause no 

harm as dietary supplements. Interestingly, caffeine is one of the most reliably 

ergogenic supplements, while having negligible side effects. 

The most well-known performance enhancing drugs used by athletes 

comprise the class known as anabolic steroids. That these drugs are highly 

effective as ergogenics while having deleterious effects on general health is 

beyond dispute. Kicman and Gower’s6 fine review article on the use of anabolic 

steroids in sports examines both positive and negative aspects of these drugs. 

The body of evidence supports the conclusion that anabolic steroids increase 

muscle mass in women and children, with smaller effects in adult healthy 

males, and may also increase performance by stimulating the production 

of icrosystems (erythropoietin, or EPO) and erthyrocytes7 (red blood cells); 

the negative effects include liver disease,8 psychological effects including 

aggression,9 and possible cardiovascular disease.10

Gene therapy has the potential to correct metabolic deficiencies caused 

by genetic mutations but can also be used to artificially enhance metabolic 

capacity. The Finnish cross-country skier and Olympic gold medalist Eero 

Mantyranta had a genetic mutation that increased his red blood cell mass and 

hence his oxygen carrying capacity.11 This effect can now be accomplished 

artificially by taking the drug EPO or by delivering the appropriate EPO 

gene using gene therapy techniques. This constitutes only the first step in 

performance enhancement using genomic approaches, as a map of health- and 

performance-related genes published by Rankinen et al. is continually being 

expanded.12 Notwithstanding the corrective and self-regulating mechanisms 

of metabolic pathways and unresolved problems with gene therapy, it is 

not fantasy to suggest the possibility of “tailoring” the human genome and 

metabolic pathways for optimal performance purposes. 
Enhanced Human Performance and Metabolic Engineering 221

The Physiology of Energy 

ATP is the immediate source of energy for all cellular processes and must be 

present in living systems at all times to drive energy-dependent processes. 

The two major sources of ATP are the tricarboxylic acid cycle and the electron 

transport chain, and glycolysis. The respective metabolic pathways are all 

interconnected via glycogen, fat, and protein reserves for storage and ATP 

retrieval, and these pathways are exquisitely fine-tuned and regulated. Indeed, 

they are so important to life and so conserved evolutionarily that many known 

mutations are lethal.

Mitochondria are dynamic intracellular organelles with an interesting 

history. They are thought to have been ancient aerobic bacteria that were 

assimilated into (taken up by) our ancestral cells, known as pro-eukaryotes, 

to form a symbiotic relationship that allowed the evolution of multicellular 

aerobic organisms.13 Mitochondria produce roughly 80 percent of the cell’s 

energy, although this amount differs from tissue to tissue and in response 

to metabolic challenge. Theoretical modeling of the metabolic pathways 

involved in energy production supports the commonsense notion that 

millions of years of evolution have resulted in highly efficient pathways with 

similar structured features.14 That said, individual variations and data from 

clinical studies suggest that there is room for improvement. Put another way, 

there is no generic mitochondrion, and cell, tissue-specific, and individual 

differences remain to be studied and exploited.15 

A few words on the structure of mitochondria are important to 

demonstrate the experimental accessibility of these organelles. They have 

both an inner and outer membrane. The inner membrane is impervious to 

essentially all ions and most uncharged particles, possessing specific protein 

carriers—transporters—for a number of important constituents in the energy 

production process. Some key features of mitochondria include a respiratory 

assembly (also known as a respirasome), which is an integral component of 

the inner membrane, and enzymes critical to the citric acid cycle and fatty 

acid oxidation. These coupled enzymatic reactions occur on the matrix side 

of the inner mitochondrial membrane, are all critical in finality to production 

of ATP, and can be manipulated experimentally. Additionally, respirasomes 

are now known to be highly organized multi-subunit protein electron 

transporting complexes.16

Mitochondria are not simply passive energy factories that produce ATP 

at a maximal rate. Their efficiency, expressed as a ratio of ATP produced to 

oxygen consumed, varies across tissues. This variation is determined by the 

physiological “mission” of the mitochondria, which, from a global metabolic 

point of view, could be maximizing ATP production and cellular phosphate 
2223 Bio-IInspired IInnovation and ovation and NNational SSecurity 

potential while minimizing the cost of ATP production, or performing any 

of these processes either individually or in combination,17 depending on the 

tissue and metabolic demands. 

Oxidative phosphorylation (OP) is a key element in this metabolic 

balance. OP, the enzymatic phosphorylation of ATP precursor adenosine 

diphosphate (ADP) to ATP coupled to election transport from substrate 

to molecular oxygen, is a key controlling element in this balance. It is an 

aerobic (hence, an oxidative) process, as distinguished from glycolytic 

phosphorylation, which can occur anaerobically. Approximately three 

molecules of ATP are formed from ADP and phosphate for each atom of 

oxygen, as shown below: 

NADH + H+ 1/2 + 3ADP + 3P2 + NAD+ + 4H2O + 3ATP

The key feature of OP is that protons (H+) are moved via the Fi/Fo 

ATPase complex from the mitochondrial matrix to the intermitochondrial 

space, establishing a proton, that is, pH, a gradient. The respirasomes and 

Fi/Fo ATPase complex that synthesizes ATP within the inner mitochondrial 

membrane are independent systems linked by this proton gradient. Thus, 

OP can be “uncoupled” by dissipating the gradient. The degree or tightness 

of coupling of OP is critical to the efficiency of the process, and aberrant 

metabolic states arising from the effects of various toxins that uncouple 

OP result in the generation of heat at the expense of energy. A convenient 

measurement, which can be performed experimentally, is determination of 

the ratio of inorganic phosphate per atom of oxygen consumed.

To summarize, oxidation of NADH is coupled to phosphorylation of 

ADP, arising from proton movement from the intermitochondrial space back 

through the inner mitochondrial membrane to the matrix side. Three protonmoving complexes have been experimentally reconstituted, and electron 

transport at these sites induces conformational changes in respirasomes. 

Finally, ADP and ATP transport into and out of the mitochondria is coupled 

(that is, ADP enters only when ATP exits), and this is mediated by an ATPADP translocase. Any interference of translocase function will uncouple 

OP. Uncoupling OP results in thermogenesis (heat generation). Excluding 

naturally occurring hibernation in many animals, such uncoupling can be 

seen in metabolic diseases, hormonal control via norepinephine, or toxicosis 

with plant glycosides such as atractyloside. The key point is that despite 

numerous feedback controls and a highly evolutionarily conserved system, 

individual and tissue differences exist and the entire system is accessible to 

nutritional, pharmaceutical, and genomic interventions. 
Enhanced Human Performance and Metabolic Engineering 223

Metabolic Interventions 

The term genomics, which refers to the study of genes and their expression, 

has become widely used in mass media. Less well known is the emerging field 

of metabolomics, the study of the many metabolites in the body that represent 

the sum of human physiological activity. It is now possible to quickly measure 

a broad array of metabolites from a small blood sample and obtain a metabolic 

“snapshot” of an individual. Physicians currently assess a few such biomarkers, 

triglycerides and cholesterol being the primary ones, but the ultimate aim 

of metabolomics would be to build integrated databases across populations 

and to use this information to design nutritional, pharmaceutical, and/or 

training interventions to enhance performance.18 More to the point, these 

interventions could be tailored to the individual.

The focus of metabolic assessment in today’s health care system is 

disease oriented. That is, the physician uses particular markers such as 

cholesterol ratios or blood glucose levels to diagnose conditions such as 

cardiovascular disease and diabetes. A future science of metabolomics will 

focus on health and will look at a broad array of lipid and protein metabolites 

with respect to health status, drug effects, stress, and other environmental 

challenges such as heat, cold, and altitude. Since lipid metabolic pathways are 

well characterized, any changes induced by artificial interventions would yield 

immediate clues about approaches to either ameliorate deleterious effects or 

enhance performance. 

The ultimate goal is to tailor diet and training to an individual Soldier’s 

personal metabolism and to do so with reference to mission requirements and 

environmental conditions. An individual’s metabolism could be fine tuned 

to the desired task for optimal performance under any mission conditions: 

cold, heat, high altitude, sleep deprivation, and so forth. It is now known, for 

example, that after conditions of prolonged strenuous activity, it is necessary 

to provide both carbohydrates and fats, rather than carbohydrates alone, to 

replenish the cell’s energy stores. Individual metabolic profiling would take 

this to the next level of sophistication.

Other nutritional approaches are also possible. The carnitine transport 

system moves long-chain fatty acids (LCFA) into the mitochondria. Fat is 

a rich source of energy, and LCFAs are required for ATP production. The 

carnitine transporter can be up- or down-regulated in a number of ways. 

The stress experienced and strenuous activity undertaken during military 

missions would likely deplete levels of ATP, resulting in relatively higher levels 

of ADP and NAD+. The result would be to up-regulate the electron transport 

chain, and this could be exploited by increasing the availability of nutritional 

substrates such as LCFAs.
2245 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Adipocytes (fat cells), like glial cells in the brain, were once thought 

to be inert. They are now known to be intimately involved in metabolism 

and may be manipulated to good effect. Adipocytes are known to secrete 

many cytokines, which are involved in energy storage, mobilization, and 

metabolism, and to participate in a network of adipose tissue signaling 

pathways allowing adaptation to metabolic challenges.19

White adipocytes secrete leptin, a protein that is involved in the 

regulation of food intake, energy expenditure, insulin regulation, and energy 

balance.20 The gene for leptin has now been cloned, and administration of 

leptin reduces food intake. Leptin is regulated by neuropeptide Y and its 

secretion can be regulated by, among others, cortisol, insulin, and betaadrenergic agonists. Thus, this system, key to energy regulation, is subject to 

manipulation. 

Finally, we come to direct genetic engineering approaches. While it is no 

trivial task to alter one, let alone multiple, key protein in metabolic pathways, 

the potential payoff could be substantial. Gene therapy, the introduction 

of healthy genes into cells to compensate for defective genes, relies on safe 

and efficient gene delivery systems and the regulation and control of gene 

expression, techniques that are being developed and refined today. Metabolic 

engineering, the directed improvement of cellular properties through the 

modification of specific biochemical reactions or the introduction of new 

ones, will afford the systematic elucidation of metabolic control via a topdown control analysis. 

There are more physiologically invasive ways by which one might 

increase ATP synthesis. Under normal physiological conditions, if ATP is 

not turned over as a result of biological work, ADP is a rate-limiting factor. 

Similarly, if the turnover rate of ATP is high, the ADP transporter may not 

be able to keep pace with the demands for ADP. Genetic manipulation of the 

ADP transporter has the potential to increase its efficiency, hence making 

more ADP available for phosphorylation to ATP.

Perhaps the area with the greatest potential to enhance metabolic 

efficiency is with the respiratory chain supercomplexes known as 

respirasomes.21 There are five such supercomplexes, each composed of 

multiple subunits. The functional roles of respirasomes are now largely 

known. One strategy that could result in increased ATP production is to alter 

the subunits via genetic engineering. Respirasomes are involved in electron 

transport, and altering the affinity of the subunits for transported electrons 

could result in the generation of four, rather than three, ATP molecules 

for each electron pair transported. Metabolic engineering of mammalian 
Enhanced Human Performance and Metabolic Engineering 225

respirasomes to either increase their affinity for electron transport or 

to produce megacomplexes is clearly testable with current gene therapy 

technology and experimental models. 

Conclusion 

The mitochondrial pathways involved in energy production are highly 

conserved genetically and possessed of complex regulatory feedback 

mechanisms. Mutations are often lethal. That said, the fact that considerable 

individual phenotypic differences exist at all levels of the systems, coupled with 

our evolving understanding of mitochondrial diseases, suggests that genetic 

manipulation of key components is possible. Further, the ability of drugs 

and toxins such as atractyloside and bongkrekic acid and of neurohormonal 

systems to alter energy metabolism indicates the possibility of nutritional and 

pharmaceutical interventions. Finally, while the ability to selectively enhance 

human metabolic performance is speculative, it is clearly a testable concept 

using cell culture, animal models, and genomic techniques available today. 

Notes

1 Board on Army Science and Technology, Opportunities in Biotechnology for Future Army 

Applications (Washington, DC: National Academy Press, 2001).

2 Office of Net Assessment, Exploring Biotechnology: Opportunities for the Department of 

Defense (Washington, DC: Information Assurance Technology Assessment Center, 2002).

3 M.S. Juhn, “Popular Sports Supplements and Ergogenic Aids,” Sports Medicine 30, no. 12 

(2003), 921–939. 

4 P. McCrory, “Super Athletes or Gene Cheats?” British Journal of Sports Medicine 37 (2003), 

192–193.

5 Juhn, 921–939. 

6 A.T. Kicman and D.B. Gower, “Anabolic Steroids in Sport: Biochemical, Clinical, and 

Analytical Perspectives,” Annals of Clinical Biochemistry 40 (2003), 321–356.

7 A.D. Mooradian, J.E. Morley, and S.G. Korenman, “Biological Actions of Androgens,” 

Endocrine Reviews 8 (1987), 1–28.

8 M.G. DiPasquale, Anabolic Steroid Side Effects: Facts, Fiction and Treatment (Ontario, 

Canada: MGD Press, 1990), 63.

9 H.G. Pope, Jr., and D.L. Katz, “Homocide and Near Icrosys by Anabolic Steroid Users,”

Journal of Clinical Psychiatry 51 (1950), 28–31.

10 B.F. Hurley et al., “Effects of High Intensity Strength Training on Cardiovascular Function,” 

Medicine and Science in Sports and Exercise 16 (1984), 483–488.

11 C. Aschwanden, “Gene Cheats,” New Scientist (2000), 24–29.

12 T. Rankinen et al., “The Human Gene Map for Performance and Health Related Fitness 

Phenotypes,” Medicine and Science in Sports and Exercise 34 (2002), 1219–1233.
226 Bio-Inspired Innovation and National Security

13 L. Margulis, Symbiosis in Cell Evolution (San Francisco: W.H. Freeman, 1981).

14 O. Ebenhoh and R. Heinrich, “Evolutionary Optimization of Metabolic Pathways. 

Theoretical Reconstruction of the Stoichiometry of ATP and NADH Producing Systems,” 

Bulletin of Mathematical Biology 63, no. 1 (2001), 25–55.

15 I.E. Scheffler, “A Century of Mitochondrial Research: Achievements and Perspectives,” 

Mitochondrion 1 (2000), 3–31.

16 H. Schagger and K. Pfeiffer, “The Ratio of Oxidative Phosphorylation Complexes I-V in 

Bovine Heart Mitochondria and the Composition of Respiratory Chain Super Complexes,” 

Journal of Biological Chemistry 276, no. 41 (2001), 37861–37867.

17 C.B. Cairns et al., “Mitochondrial Oxidative Phosphorylation Thermodynamic Efficiencies 

Reflect Physiological Organ Roles,” American Journal of Physiology 274, no. 5 (1998), 

R1376–R1383.

18 S.M. Watkins and J.B. German, “Towards the Implementation of Metabolic Assessment of 

Human Health and Nutrition,” Current Opinions in Biotechnology 13 (2002), 512–516.

19 G. Fruhbeck et al., “The Adipocyte: A Model for Integration of Endocrine and Metabolic 

Signaling in Energy Metabolism Regulation,” American Journal of Physiology Endocrinology 

and Metabolism 280, no. 6 (2001), E827–847.

20 K.L. Houseknecht, “The Biology of Leptin: A Review,” Journal of Animal Science 76, no. 5 

(1998), 1405–1420.

21 H. Schagger and K. Pfeiffer, “Supercomplexes in the Respiratory Chains of Yeast and 

Mammalian Mitochondria,” The EMBO Journal 19, no. 8 (2000), 1777–1783.
227

Functional neuroimaging is the use of technology to measure and monitor 

aspects of the working brain in real time. This is an important part of 

the biotechnology revolution that is affecting many parts of our daily 

lives and will play an important role in defense policy decisions in the near 

future. Several devices perform functions that are capable of providing pieces 

of this immensely complicated puzzle, including electroencephalography, 

computerized tomography, functional magnetic resonance imaging, positron 

emission tomography, magnetoencephalography, functional transcranial 

doppler sonography, and functional near-infrared spectroscopy. 

It is critical to understand that future applications will depend on 

multimodal methodologies and miniaturization technologies that are 

still under development. Scanning devices will become smaller and more 

portable. The techniques will increasingly become cheaper and easier to use. 

Ultimately, disparate devices will merge into comprehensive brain scanning 

tools that provide extensive, integrated, interactive information about the 

brain in real time.

The capability of measuring the working brain in real time has potentially 

important implications for a number of practical applications relevant to defense 

and national policy issues. Predictions about future applications of technology 

are always speculative, but we are definitely far enough down the road of this 

emergent technology to reliably predict likely advances. These will include, but 

will not be limited to, quick and secure data transmission, reliable intelligence 

acquisition from captured unlawful combatants, enhanced training techniques, 

augmented cognition and memory enhancement of soldiers and intelligence 

operatives, screening terrorism suspects at checkpoints or ports of entry not 

chapter 16

Functional Neuroimaging 

in Defense Policy

Richard Genik III, Christopher Green, and David C. Peters II
2289 Bio-IInspired IInnovation and ovation and NNational SSecurity 

covered by constitutional protections (such as airports), and furthering the 

goal of soldier-machine interface devices such as remotely piloted vehicles 

and prosthetics. Many important and fast-advancing contributions in this field 

have already been made to clinical and battlefield medicine.

Functional Specialization 

The human brain evolved in layers, with evolutionarily newer structures covering 

older ones. The developing brain in a human embryo grows outward in a pattern 

that largely mirrors human evolution. The brain is divided into discrete regions 

controlling vital functions such as sensory transduction and cognition for the 

cortex. This functional specialization is a critical element in brain research, and 

it arises mainly from layered development. These functionally specific regions 

activate when a person is presented with a stimulus, such as a scent exciting an 

area of the temporal lobe, or a vision exciting the occipital lobe.

Mapping these areas of activation and the circuits that control specific 

behaviors and cognitive processes is the goal of functional neuroimaging. It is 

an enormous goal, and creating even a crude map of the functionality of the 

brain is daunting. The brain involves many, many more connections than even 

the most advanced computer. This is because, unlike a computer that utilizes 

binary connections, brain circuits involve thousands of neurons and millions 

of permutative connections to perform even the simplest task of cognition or 

behavior. Indeed, one can think of gray matter neurons as transistors (or the 

“cell” of a computer processing unit), and white matter fibers as the wires that 

connect the transistors—although in the brain, each neuron can have up to 

10,000 or more connections. 

To provide some perspective on the enormity of the task of mapping 

connected areas, consider that a typical human infant’s brain has approximately 

200 billion gray matter neurons at birth. With the exception of some interesting 

findings suggesting ongoing neurogenesis in the dentate gyrus (a portion of the 

“reptilian” or mid-brain), the newborn will never grow any more neurons. Yet by 

age 1, the child’s brain has filled the skull and tripled in size from approximately 

350 grams to a near-adult size of 1,000 grams. If almost no new neurons are 

developing, where does all this extra mass come from? Although the number 

of neurons is largely fixed from birth, the brain continually forms complex 

white matter connections between neurons at an almost inconceivable rate. The 

human infant may form 20,000 distinct neural connections every second for the 

first year of life. These are merely individual connections. If we factor in circuits 

that involve thousands or tens of thousands or even millions of permutated 

reciprocal connections,1

 it becomes clear that there are far more combinations 

of neural circuits in the cerebral cortex than atoms in the known universe.2
Functional Neuroimaging in Defense Policy 229

Undaunted, scientists are cautiously but busily mapping the connectivity 

of the human brain, publishing thousands of new papers on the topic each 

year. Many studies are being published investigating correlative classifications 

between traditional psychological testing, clinical observations, and brain 

scans to establish biomarkers for pathological states, cognitive and behavioral 

tasks, task-specific aptitude measures, detecting deception, and even 

predicting neuropathological propensity.

Electroencephalography 

The oldest device used to assess brain function in real time is the 

electroencephalograph (EEG), which works by placing electrodes on the scalp 

and recording the summated electrical signal from nominally 50,000 local 

neurons. Early clinical electroencephalography was used primarily to detect 

and diagnose epilepsy, but with advances in computer technology, informative 

new experimental paradigms and techniques are being developed. EEG 

recordings can be separated into two major types: continuous and discrete. 

Continuous recordings are the traditional multitrace waveforms recorded 

since EEGs began in the late 19th century, and activity is classified by the 

frequency of the dominant waveform (0–30 hertz) on any given channel—for 

example, alpha waves constitute frequencies between 8 and 13 hertz. Discrete 

recordings are triggered by an event, such as an external flash of a light, after 

which the next 1 to 2 seconds of activity are recorded. In discrete recordings, 

the “normal” EEG waves are considered background.

Discrete recordings, the current main area of basic research, are 

called evoked potentials when the brain response peak above background 

is unconscious, nominally classified as any signal before 100 microseconds 

from an external stimulation. Event-related potentials are generally any other 

peak in the recording, the evoked nomenclature being dropped due to the 

possibility that conscious thought intervened in a decision process. 

Quantitative EEG (QEEG) uses postrecording computer analysis 

common to other functional imaging techniques to analyze the relationship 

between each of the electrodes placed at the scalp. By comparing the relative 

signal strength of each electrode, and precisely measuring the latency (time 

between stimulus onset and onset of the electrical response) and amplitude 

(strength of the electrical signal) at each location on the scalp, the likely 

location of the neuronal source can be inferred.3

 However, localization 

methodology continues to be a matter of intense scientific investigation.4

Neurotherapy is an experimental technique that uses a QEEG brain 

map to analyze psychiatric problems from attention deficit disorder to 

depression to schizophrenia. Patients are then subjected to a conditioning 

protocol to train the abnormal brain activity toward a statistically more 
2301 Bio-IInspired IInnovation and ovation and NNational SSecurity 

normal pattern. Neurotherapy has been shown to reduce aberrant symptoms 

of many conditions in a number of studies.5

EEG has several advantages over other functional neuroimaging techniques:

• equipment is relatively cheap (around $15,000) 

• reliable recordings only require a single technician 

• unmatched temporal resolution is measured in milliseconds.

The main drawback of EEG is that the source localization has only 1 centimeter 

resolution at present.

Positron Emission Tomography 

Harvard University psychologist Stephen Kosslyn spent many years of his life 

attempting to solve the source localization problem in EEG. In 1986, after 

several years of equivocal research findings and no publications, he gave a 

dejected talk about his “dismal failure.” As he was leaving the stage, two young 

medical physicists approached to tell him about something new they were 

working on that they called positron emission tomography (PET).6

The physicists had been experimenting by injecting radioactive bioassays 

(biologically active substances that are absorbed by cellular metabolism) 

directly into their carotid arteries. When the short-lived radioactive bioassay 

decays, it emits a positron. Positrons quickly annihilate with a local electron 

to produce two or three high-energy photons. These photons are detected by 

the PET imager, and their origin is determined by projecting their path back 

to intersection. Since the substances were metabolized and incorporated into 

the working brains of the subjects, areas of greater positron emission were 

assumed to be regions that were recently more “active.”

However, PET techniques for observing the functional brain in real 

time are more limited for several reasons:

• temporal resolution (function of time) is extremely low, 30–90 minutes

• results depend on scanning speed and how quickly data can be collected

• spatial resolution (function of distance) is substandard, within a few 

centimeters

• results depend on the precision of the recording method and whether 

data has a specifically identifiable location

• equipment cost is enormous

• huge number of team members is required 

• technique is invasive 

• technique is already outdated in many circumstances. 
Functional Neuroimaging in Defense Policy 231

There are several important clinical uses of PET, particularly for imaging 

blood flow and metabolic activity.7 The “ground truth” of PET will remain 

extremely important in better understanding and assessing other neuroscience 

tools. Dr. Kosslyn continues his work attempting to identify the circuits and 

functional brain regions involved in image generation and formation using the 

full array of neuroscience tools, including PET.8

Computerized Tomography 

Computerized tomography (CT) relies on x-rays and computer technology. 

The original systems were dedicated to head imaging only, but whole body 

systems with larger patient openings became available in 1976. CT works by 

directing a tightly focused x-ray beam at the target from many different angles 

around a single axis of rotation. A computer combines the multiple “slices”9

into an integrated, three-dimensional picture of the brain and surrounding 

hard tissue structures. 

Since CT is an x-ray–based technique, it best images hard tissues and 

has limited application for functional analysis of soft tissue. However, CT is 

unmatched in structural imaging. CT neuroscans are used clinically primarily 

to diagnose aneurisms and other cerebrovascular events because blood 

outside a vessel is imaged quite well by x-ray. The use of contrast agents in the 

blood allows better, albeit indirect, imaging of functional brain activity at the 

price of increased invasiveness.

Current multislice CT systems can image the entire brain and skull in 

5 seconds, reconstruct the images, and send them to a radiologist at a remote 

site before the patient has time to stand up. As CT scan times have grown 

faster, more anatomy can be scanned in less time. Faster scanning helps to 

eliminate artifacts from patient motion caused by physiology such as normal 

respiration, heartbeat, or peristalsis. 

The main drawback of CT is its use of ionizing radiation. One CT scan 

can deliver the same radiation dose as dozens of chest x-rays.10 Beginning in 

the early 1990s, research efforts began to focus more on imaging techniques 

that did not rely on carcinogenic radiation.

Functional Magnetic Resonance Imaging 

Along with CT, magnetic resonance imaging (MRI) is widely accepted as 

a gold standard in medical imaging. Functional MRI (fMRI), however, has 

technical challenges that have slowed its introduction into common clinical 

use.11 The first clinical fMRI diagnostic codes were approved in 2006.12 The 

technique is used in pre-neurosurgical mapping of functional brain regions 

before excision procedures. For example, one option for intractable epilepsy 

is neurosurgery to remove the excitable brain regions causing the seizures. 
2323 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Using functional imaging, doctors can avoid removing regions of the brain 

that are functionally important and should not be removed.

Functional MRI relies on the blood oxygen level–dependent (BOLD) 

effect. Scientists have known for over 100 years that changes in blood flow and 

blood oxygenation in the brain are linked to neural activity. A complicated 

computer bank using technology developed with CT scanners creates a series 

of pictures that can identify the regions of the brain as they activate. A magnetic 

movie of blood oxygenation patterns in the working brain lets the researcher 

infer brain activity in real time as it thinks and responds. Even with such 

amazing technologies, we are at the very beginning of understanding the brain.

fMRI has many advantages over other functional imaging techniques: 

• spatial resolution of the activation patterns is incredible, measured in 

millimeters

• temporal resolution is good, measured in a few seconds

• there are no known risk factors in healthy subjects.13

Despite the advantages of fMRI, these downsides remain: 

• technique is still enormously expensive, with equipment costing 

millions of dollars

• scan typically takes a full hour per subject

• team of computer programmers is needed to adjust and interpret the 

data over several days.

Magnetoencephalography 

Magnetoencephalography (MEG) is a completely noninvasive, nonhazardous 

technology for functional brain mapping that localizes and characterizes the 

electrical activity of the central nervous system by measuring the associated 

magnetic fields emanating from the brain. Every electrical current generates 

a magnetic field. However, unlike an electrical signal, magnetic fields are not 

distorted by traveling through the skull. Thus, with MEG, the source of the 

summated magnetic fields can be triangulated within a couple of millimeters. 

Modern MEG scanners use as many as 300 superconducting quantum 

interference device14 detectors, allowing very fast acquisition and extremely 

high localization of the source of the electromagnetic signal. The information 

MEG provides is entirely different from that provided by structural imaging 

techniques like CT or MRI. MEG is a dedicated functional scanner that 

provides functional mapping information of the working brain and 

measures actual neurological function. This provides complementary 

information to the excellent anatomical imaging capabilities of MRI and 
Functional Neuroimaging in Defense Policy 233

CT. Using MEG, we are finally able to measure brain activity in real time 

with excellent spatial resolution.

MEG is also superior in many respects to other functional imaging 

modalities. It:

• offers vastly superior temporal and spatial resolution 

• can be used to localize brain tumors or identify seizure activity

• provides presurgical mapping target for excision.

However, MEG has its disadvantages. It:

• costs more than MRI

• requires a team of technicians and engineers to keep it running

• needs huge levels of refrigeration and several layers of insulation

• requires a specially constructed scan room to limit measurement 

interference. 

Transcranial Sonography 

The common ultrasound provides stunning pictures of a fetus through the 

abdominal wall of a pregnant female. Unfortunately, transcranial sonography 

is considerably more limited because it is much more difficult to image 

structures hidden beneath the cranium. However, the skull is thin enough in 

a few “sonographic windows”15 to provide a path for the ultrasonic signal. The 

transorbital window located above the zygomatic arch (the temple) is used to 

image the posterior, anterior, and medial cerebral arteries along with a few of 

the branches. Since portions of these arteries provide blood flow to various 

parts of the brain, doppler sonography can provide highly accurate real-time 

measurements of blood flow velocity changes. For example, the posterior cerebral 

artery innervates regions of the brain associated with visual interpretation. 

Although both rely on blood flow, sonography is very different from 

fMRI, which measures blood oxygenation level changes with a spatial 

resolution of a couple millimeters. In functional transcranial doppler 

sonography (fTDS), the spatial resolution is determined by the size of the 

brain innervated by the blood vessel under study. These areas can be quite 

large, making the spatial resolution of fTDS extremely limited. Changes in 

blood velocity, which are presumed to directly measure changes in resistance 

of the artery, occur nearly instantaneously in an event-related experimental 

paradigm giving exceptional temporal resolution.

There remain several technical problems with fTDS. Only a limited 

number of large arteries can be imaged. Even in the arteries that are large 

enough and located within sight of the few available ultrasonic windows, the 
2345 Bio-IInspired IInnovation and ovation and NNational SSecurity 

angle of the ultrasonic beam can make it very difficult to accurately measure 

blood flow changes.

However, fTDS has several advantages over other functional neuroimaging 

techniques. It: 

• is very cost effective

• is portable

• offers continuous monitoring of blood flow activity

• provides excellent temporal resolution.

A significant amount of useful information about the working brain can 

be learned from sonography, particularly if one were willing to increase the 

number or size of the available ultrasonic windows in the skull.

Near-infrared Spectroscopy 

Infrared spectroscopy depends on measurements of energy outside the visible 

spectrum. Near-infrared spectroscopy (NIRS) was first used during World War 

I to monitor blood oxygenation of bomber crews, a critical measurement prior 

to the B–29 innovation of pressurized cabins. Similar devices are employed 

today to measure pulse rates and blood oxygen saturation using a fingertip 

sensor. Water (the primary component by weight of most biological tissue) is 

almost transparent to the NIRS spectrum (700- to 900-nanometer wavelength). 

This makes BOLD signals in the first few millimeters of cerebral cortex through 

an intact skull accessible to monitoring using a light source and sensors.16

Although NIRS functional research has been ongoing since the late 1930s, the 

recent breakthroughs in fMRI have renewed interest in this technology.

There are no approved clinical neuroimaging uses for this technique, but 

the potential experimental uses are very exciting, and it has the advantages of:

• costing between $25,000 and $300,00017

• being portable (even wireless) and completely noninvasive

• offering temporal resolution similar to fMRI.18

NIRS can theoretically be combined with EEG, transcranial sonography, 

and other functional neuroimaging sensors. Unlike fMRI, where the subject is 

confined to the bore of the magnet, NIRS movement artifacts can be limited 

by proper affixation of sensors to the scalp. An experimental subject can 

sit upright, walk around, and perform tasks while his or her brain is being 

monitored. The only drawback is that NIRS measures best the first few 2 to 3 

centimeters of cortex, so deep brain imaging, at least through an intact skull, 

is very challenging. According to the biogenetic theory, the outermost layer of 

the cortex should be the most functionally advanced, and there is little doubt 

that a significant amount of measureable brain function occurs there. 
Functional Neuroimaging in Defense Policy 235

Screening and Detecting Deception 

There is already a considerable amount of research on the objective of detecting 

deception using neuroimaging instruments. The traditional polygraph has 

been in use for many decades, but this instrument relies on galvanic skin 

response, pulse, and respiration measures. The assumption underlying the 

polygraph is that the nearly universal cultural prohibitions against telling an 

untruth for personal gain will result in increased sympathetic activity when a 

subject tells a lie. In plain terms, telling a lie should make a person nervous, and 

this can be picked up by measuring autonomic responses. The problem is that 

trained intelligence or military persons, psychopathic or antisocial subjects, 

and others can effectively beat the polygraph by suppressing the expected 

autonomic response to the telling of an untruth. Functional neuroimaging 

instruments rely on intrinsic responses of the brain and therefore do not 

depend on this cultural assumption.

Much of the recent deception research has used fMRI to image patterns 

of activation in the brain during tasks that require the two states of deception 

and truthfulness. When a subject answers a question, he or she must either 

recall an actual memory or recall a false memory and thus confabulate. 

Theoretically, the brain activation patterns should be quite different when a 

subject is activating the circuits of an actual memory than when activating 

the circuits of false memories because actual memories are stored in the 

hippocampus, while the recollection of false memories (and the ability to 

create new false memories) is largely stored in the cortex. 

Lie or truth events are both mediated in the frontoparietal network, 

but a lie event is characterized by increased working memory and intensive 

activity in the inferolateral cortex involved in task and response selection 

inhibition.19 Several fMRI studies using a number of different paradigms have 

found that activations in the dorsal, medial, and ventral lateral prefrontal 

cortex are specific neural correlates of committing deception.20 However, the 

use of fMRI is limited by the tremendous cost and size of the equipment, the 

difficulty in processing the data, and the fact that subjects must hold their 

head absolutely still inside the bore of a magnet during the scanning session.

In contrast, since NIRS scanners can be wireless and completely 

portable, they can be used practically in field experiments. In the first 

published NIRS study on detecting deception, 21 right-handed persons wore 

a functional NIRS device while playing a poker-like card game. Twenty of the 

21 subjects showed greater activation in the ventral lateral prefrontal cortex 

and mid-frontal gyrus (a portion of the medial prefrontal cortex) when they 

were bluffing than when they were telling the truth.21
2367 Bio-IInspired IInnovation and ovation and NNational SSecurity 

There are many applications of this technology in screening suspected 

security threats. For example, NIRS could be used covertly without any 

knowledge on the part of the subject at airports or security checkpoints. When 

homeland security personnel, soldiers, or other officials detect a possible 

security threat or believe that a person moving through a checkpoint is acting 

suspiciously, the subject could be taken to a private room where a covert NIRS 

scanner is located. The subject could be questioned and scanned without 

even knowing that his or her brain is being assessed. A reliable, although 

preliminary, determination of the truthfulness of his or her statements to 

security officials could be made.

The pace of neuroscience research in the area of detecting deception is 

increasing exponentially. In the near future, the primary barrier to implementing 

this technology is likely to come not from technical or scientific challenges, but 

rather from the constitutional and legal arenas that are well outside the scope 

of this chapter.

Multimodal Imaging 

The pinnacle of neuroscience research would be combining the exquisite 

temporal resolution of EEG/MEG data with the incredible spatial resolution 

of fMRI/NIRS data. One of many problems with doing so is that these devices 

measure different aspects of functional neuroimaging. EEG measures the 

electrical forces of the brain at the scalp, while MEG measures the magnetic 

force generated by those electrical field potentials. Both fMRI and NIRS 

measure the hemodynamic response, which cannot yield a better temporal 

resolution than the few seconds it takes for the contiguous blood vessels to 

dilate and deliver the increased levels of oxygenated blood to the parts of the 

brain that have been recently active. Transcranial doppler sonography permits 

near-instantaneous temporal resolution by measuring the blood flow velocity 

rather than oxygenation, but there are several practical limitations. Combining 

these different data streams into one image of the brain is the challenge. 

There are essentially three ways that merging multimodal data has been 

attempted.22 Converging evidence is the most common method and relies on 

either taking joint or time-locked consecutive measurements using multiple 

scanning devices. The two modalities can then be fused to create a composite 

image of function and anatomy. Currently, several multimodal scanners are 

available. CT/fMRI and CT/PET scanners can locate structural anomalies 

such as brain tumors much more readily than either technique used alone. 

MEG/MRI scanners also have considerable clinical potential. The estimated 

source location from MEG is combined with MRI images to create magnetic 

source images. The two sets of data are combined by measuring the location 
Functional Neuroimaging in Defense Policy 237

of a common set of fiducial points marked during MRI with lipid markers and 

during MEG with electrified coils of wire that give off the magnetic fields. The 

locations of the fiducial points in each data set are then used to define a common 

coordinate system so that superimposing (or coregistering) the functional 

MEG data onto the structural MRI data is possible. Several other multimodal 

scanners in development include nonferrous EEG devices for use in functional 

MRI scanners, NIRS/EEG, and fMRI/PET scanners. The problem is that many 

of these dual-use scanners create significant confounds in the data stream, and 

the resolution of these artifacts remains an active area of research.23

The other two methods for coregistering data from multimodal 

measurements are direct data fusion and computational modeling.24 Direct 

data fusion attempts to combine the multimodal data streams using a 

mathematical/statistical algorithm.25 Currently, the most commonly used 

program is the low-resolution electric tomography algorithm, which attempts 

to collapse the electrophysiological data from EEG into known spatial/

temporal points. However, important nodes in the data network can be 

missed because of where two conditions are measured during two different 

activation conditions; a correspondence between them could represent one 

node as active as another node even though there are significant changes in 

interregional connectivity.

Finally, the multimodal problem could be addressed by developing 

a neural model that incorporates hypotheses about how the brain 

activates in response to a particular cognitive or behavioral operation. 

Unfortunately, although work continues in this area, nobody has developed 

a reliable computational model that predicts activation patterns for both 

electrophysiological (EEG/MEG) and hemodynamic (fMRI/NIRS) data.

In order to fully accomplish the goal of integrating multiple scanners, the 

electronic sensors need to become cheaper, smaller, and more efficient. This 

is extremely likely to happen, as a commonsense review of the development 

of virtually any electronic equipment demonstrates. For example, scientists 

predict that the multi-million-dollar fMRI scanners that weigh thousands of 

pounds could be reduced to a couple hundred pounds within just a few years.26

This capability could even be mostly obsolete by then because we will have 

already coregistered NIRS (which is already small and portable) with the deep 

brain scans of fMRI and the instantaneous measurements of EEG and MEG.

Communication and Data Transfer 

When a reliable computational model can predict activation patterns in the 

hippocampus (an important region of the brain responsible for learning and 

memory formation), it could be possible to effectively “beam” memories 
2389 Bio-IInspired IInnovation and ovation and NNational SSecurity 

into the brain.27 Several research groups are attempting to understand how 

images and sound signals are transducted in the hippocampus into memories. 

Neurons encode information by forming complicated circuits with other 

neurons. This web of connectivity occurs in multiple neurons reciprocally 

linked together, encoding and linking information. Most, and probably 

almost all, of these memory circuits link through the hippocampus. 

In parallel, other groups are developing a neurochip, a silicon chip 

containing actual living neurons designed to mimic the human brain. The 

neurochip could, theoretically, be implanted into a brain, grow functional 

connections, and then interface directly with a computer.28 At least one group 

has already developed a chip based on a portion of the hippocampus called the 

CA3, a very thin layer that receives input from the cerebral cortex and sends it 

back again. For various reasons, the CA3 layer of the hippocampus is thought 

to be where memory formation actually occurs and where this information is 

stored and linked.29 Studies are already well under way that involve implanting 

the neurochip into the hippocampus of animals and transmitting simple 

memories directly into their brains. When this is accomplished, it might be 

possible to begin the process of laying down more complex memories.

This development has staggering implications for future defense policy. 

Instant and secure data transmission directly to the brains of soldiers on the 

battlefield would be possible. Augmented cognition of intelligence operatives 

would be a goal. Perhaps learning how to operate an aircraft could be 

accelerated from years of technical training to a few days. Perhaps reasonably 

proficient language skills could be implanted within just a few hours; the 

ability to reproduce technical schematics within a few minutes; the entire 

family and tribal history of a high-value target or a mission update report 

within a few seconds. We can only begin to imagine the potential applications 

of this new emergent technology.

Brain-Computer Interface 

Functional neuroimaging devices detect various forms of energy emissions 

from the working brain, but these emissions are not static. The electrical energy 

of working neurons is detected by EEG and MEG, and the hemodynamic 

response of functional regions of the brain is measured using light (NIRS) and 

the distortions of a powerful magnetic field (fMRI). The metabolism of these 

neurons in the functional regions of the brain can be measured by a gamma 

ray detector using bioactive radioactive assays injected into the blood (PET). 

A critical feature of these various energy emissions that is not very well 

understood is the concept of neuroplasticity. The working brain adapts function 

very quickly and very readily. Under an operant conditioning paradigm (that 
Functional Neuroimaging in Defense Policy 239

is, with training), the brain can quickly learn and adapt functioning. This 

remarkable organ is so flexible that a subject can learn to activate and deactivate 

functional regions as well as the electrical distribution, metabolic activity, and 

brain wave patterns throughout the brain after just few hours of training.

A brain-computer interface (BCI) takes advantage of the important 

feature of neuroplasticity by activating and controlling electronic or mechanical 

devices based only on brain activity.30 There is a surprising amount of recent 

work in the area of connecting the brain directly to prosthetics. EEG and 

MEG scanners can record oscillation signals from the whole brain or from 

functional regions of it and activate a device when the subject specifically 

controls this activity. Slow cortical potentials and sensorimotor rhythm have 

both been used to activate electronic devices. Evoked potentials recorded by 

EEG, especially the P300 wave, have been used to activate and even operate 

communications equipment.31 The BOLD signal and NIRS instruments 

measuring cortical blood flow have also been used as a BCI.32 The main goal 

of research so far has usually been to exert some degree of control over a 

prosthetic or communication device.

However, we would pose a question: Is the operation of a human (or 

at least a human-like) hand or arm more complicated than the operation of 

an aircraft? The level of detail in the human organ can lead to the conclusion 

that operating an aircraft by thought alone might actually be easier than 

operating a hand or arm by thought alone. While it is far beyond the scope of 

this chapter to attempt a quantitative calculation of the number of functions 

in the operation of an aircraft versus the number of functions in the operation 

of a hand or arm, we could reasonably speculate that the number of functions 

in each, and the degree to which they could be automated, probably is not 

staggeringly different.

Brain-Computer Interface for Weapons Systems 

If an aircraft can be controlled solely by the energy emissions of a working 

brain, then almost any conceivable weapons system could be similarly 

controlled. Unmanned tanks, artillery pieces controlled from thousands 

of miles away, and even search-and-destroy killer robots that discriminate 

between combatants and noncombatants are much closer than most of us can 

imagine. Combining the very fast operations of largely automated weapons 

systems with the unique judgment of a human brain would be especially 

helpful in an urban environment where a mission-critical goal is selectivity. 

Multimodal scanning technology with integrated EEG, NIRS, and possibly 

fMRI, PET, fTDS, and MEG components could operate many types of 

weapons systems with a very high degree of precision. 
2401 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Functional neuroimaging technology can already reliably discriminate 

between men and women. It would not require exceptional advances in 

technology to have the capability to reliably discriminate between combatants 

with hostile intent and noncombatants without hostile intent. One early 

military application of this idea may be the use of NIRS technology on gun 

scopes, once sensors advance beyond the requirement of scalp contact. A 

sniper could take aim from a considerable distance and reliably determine 

if the target is male or female, a hostile combatant, or a civilian, simply from 

the infrared activation patterns in the first few millimeters of cerebral cortex. 

A weapons system, perhaps completely controlled via BCI, could reliably roll 

through a heavily defended urban center, selectively shooting and killing only 

the men with aggressive thoughts while sparing the women and children 

and men who are behaving and thinking peacefully. Full-scale production of 

killing machines based on these controversial ideas is just a few years away. 

The question is no longer what, but when. Given the speed at which these 

automated determinations could be made, and the possible uncertainty 

in targets of hostile thoughts, this intent identification technology is best 

implemented in combination with nonlethal weapons systems. 

Conclusion 

Any attempt to use known information to extrapolate a potential trajectory 

into the future is highly speculative. Some of the theoretical applications 

proposed here will be shown to be technically impossible, impractical, or 

even infeasible. Some applications that cannot even be imagined today will 

become common in 20 to 40 years. Currently, the technology—the numerous 

scanning devices that have been developed—is far in front of the science—the 

interpretation of the functional imaging data collected from these devices. 

The technology is now focused on making the scanning devices smaller, 

easier to use, and cheaper each year. Whatever the ultimate applications 

of this technology, we can be certain that the experimental paradigms will 

become easier to implement, and the pace of scientific discovery will continue 

to increase for the foreseeable future. However, within the next 20 to 40 years, 

there is no suggestion that the science will catch up to the technology. The only 

certainty is that functional neuroimaging research will provide unimagined 

benefits and applications in every area of our lives, including defense policy, 

but the human brain will remain largely a mystery.
Functional Neuroimaging in Defense Policy 241

Notes

1 For example, if there are 1,000 possible combinations in the first link of a neural circuit, 

then the number of permutations or combinations with a second reciprocal link would be 

1,000 x 999 x 998 all the way down to 1, or 1,000! ~ 102568.

2 See www.holisticeducator.com. There are only around 1080 atoms in the visible universe 

and perhaps 1082 including nonluminous matter.

3 K.L. Coburn et al., “The Value of Quantitative Electroencephalography in Clinical 

Psychiatry: A Report by the Committee on Research of the American Neuropsychiatric 

Association,” Journal of Neuropsychiatry and Clinical Neurosciences 18, no. 4 (Fall 2006), 

460–500.

4 J. Polich and J.R. Criado, “Neuropsychology and Neuropharmacology of P3a and P3b,” 

International Journal of Psychophysiology 60, no. 2 (2006), 172–185.

5 D.J. Fox, D.F. Tharp, and L.C. Fox, “Neurofeedback: An Alternative and Efficacious 

Treatment for Attention Deficit Hyperactivity Disorder,” Applied Psychophysiology and 

Biofeedback 30, no. 4 (December 2005), 365–373.

6 John McCrone, Going Inside: A Tour Round a Single Moment of Consciousness (New York: 

Fromm International, 2001), 28.

7 For example, brain tumors often provide a distinctive vasculature (angiogenesis) that is 

easily imaged by bloodborne radioactive assay techniques.

8 S.M. Kosslyn et al., “Two Types of Image Generation: Evidence from PET,” Cognitive, 

Affective, and Behavioral Neuroscience 5, no. 1 (March 2005), 41–53. 

9 The word tomography derives from the Greek word tomos, which means slice. These slices 

are axial to the body. Computerized tomography was originally known as computed axial 

tomography, terminology that survives among laypersons and seasoned professionals.

10 This is about same radiation exposure an airplane crew experiences in an entire year of 

flight operations. 

11 “Official Position of the Division of Clinical Neuropsychology (APA Division 40) on the 

Role of Neuropsychologists in Clinical Use of fMRI,” The Clinical Neuropsychologist 18 

(2004), 349–351.

12 American Medical Association, CPT Changes 2007: An Insider’s View, November 2006.

13 The primary reports of injury during magnetic resonance imaging resulted from the 

magnetic field attraction of ferrous substances within the body. Proper screening of subjects 

by attending personnel eliminates this risk. 

14 Superconducting quantum interference device is a super-cooled electronic component 

designed to detect extremely small changes in magnetic fields.

15 S. Duscheck and R. Schandry, “Functional Transcranial Doppler Sonography as a Tool in 

Psychophysiological Research,” Psychophysiology 40 (2003), 436–454.

16 S.C. Bunce et al., “Functional Near-Infrared Spectroscopy: An Emerging Neuroimaging 

Modality,” IEEE Engineering in Medicine and Biology Magazine (July-August 2006), 54–62.

17 Ibid.

18 Currently, NIRS can localize hemodynamic changes within about 1 centimeter, while the 

best fMRI scanner can localize changes within a few millimeters.

19 D. Langleben and J. Loughead, “Telling Truth from Lie in Individual Subjects with Fast 

Event Related fMRI,” Human Brain Mapping 26 (2005), 262–272.

20 L. Phan et al., “Neural Correlates of Telling Lies: A Functional Magnetic Resonance Imaging 

Study at 4 Tesla,” Academic Radiology 12 (2005), 164–172.
242 Bio-Inspired Innovation and National Security

21 S.C. Bunce et al., “Detecting Deception in the Brain: A Functional Near-infrared 

Spectroscopy Study of Neural Correlates of Intentional Deception,” Proceedings of the SPIE

5769 (2005), 24–32.

22 B. Horwitz and D. Poeppel, “How Can EEG/MEG and fMRI/PET Data Be Combined?” 

Human Brain Mapping 17 (2002), 1–3.

23 K. Krakow et al., “EEG Recording during MRI Recording,” Human Brain Mapping 10, no. 1 

(April 2000), 10–15.

24 Horwitz and Poeppel.

25 Ibid.

26 R. Genik and C. Green, “Cognitive Avionics and Watching Space Crews Think: Generation 

After Next Applications in Functional Neuroimaging,” Aviation, Space, and Environmental 

Medicine 76 (June 2005), B208–212.

27 H. Hoag, “Neuroengineering: Remote Control,” Nature 423 (2003), 796–798.

28 E. Singer, “Silicon Brains,” Technology Review (May-June 2007), 94–96.

29 Ibid.

30 N. Birbaumer, “Breaking the Silence: Brain-Computer Interfaces (BCI) for Communication 

and Motor Control,” Psychophysiology 43 (2006), 517–532.

31 N. Birbaumer and L. Cohen, “Brain-Computer Interfaces: Communication and Restoration 

of Movement in Paralysis,” Journal of Physiology 579, no. 3 (2007), 621–636.

32 Ibid.
243

Today’s military forces must operate in environments of increasing 

complexity, uncertainty, and change, a fact that has increased stress 

levels along with the challenge to adapt. For some people, such 

stressful conditions can lead to a range of health problems and performance 

decrements. But this is not true for everyone. Many, indeed most, people 

remain healthy and continue to perform effectively despite high stress levels. 

While much attention is devoted to understanding and treating stress-related 

breakdowns, relatively little has gone toward understanding healthy, resilient 

response patterns and identifying the factors that protect people from the ill 

effects of stress. With better knowledge about resilience, future selection and 

training programs can focus more on maximizing stress-resilient response 

patterns and enhancing human health and performance. Extensive research 

over the last 25 years has determined that psychological hardiness is a key 

stress-resilience factor for many people. 

Modern life is inherently stressful and is getting more so as the pace of 

technological change continues to increase. This is even truer for U.S. military 

forces, who are deploying more and for longer periods of time, on missions that 

are multifaceted, changeable, and ambiguous. While much attention has been 

devoted to studying those who break down under stress, the majority of people 

appear to respond with remarkable resilience even to severe or traumatic stress.1

If the factors or pathways that lead to human resilience under stress were better 

understood, perhaps some of these factors could be developed or amplified in 

those individuals who are low in resilience and more vulnerable to stress. 

This chapter focuses attention on psychological hardiness, one of several 

potential “pathways to resilience” posited by Bonanno.2

 It will first delineate 

chapter 17

Forging Stress Resilience: 

Building Psychological 

Hardiness

Paul Bartone
2445 Bio-IInspired IInnovation and ovation and NNational SSecurity 

the major psychological stress factors salient in modern military operations. 

Next, the concept of psychological hardiness is described, including theoretical 

background and representative research findings. Finally will be a discussion 

of how the hardy cognitive style can be built up in organizations through leader 

actions and policies. By focusing more attention on increasing psychological 

hardiness, military organizations can enhance human health and performance, 

while also preventing many stress-related problems before they occur. Based 

on both theoretical and empirical grounds, I argue that leaders in organizations 

can foster increases in the kinds of cognitions and behaviors that typify the 

high hardy person’s response to stressful circumstances.

Psychological Stress Factors in Modern Military Operations 

Military operations entail stressors of various kinds for the troops involved. 

Combat-related stressors are the most obvious ones and have garnered the most 

attention, but military operations in the post–Cold War era entail additional 

challenges and stress factors. The number of peacekeeping, peacemaking, 

humanitarian, and other kinds of operations has increased, even as military 

organizations shrink in size with the shift to all-volunteer forces, causing units 

to deploy more frequently. Increased deployments bring other stressful changes 

in military units as well, such as higher frequency and intensity of training 

exercises, planning sessions, and equipment inspections, all of which add to 

the workload and pace of operations.3 Also, more frequent deployments require 

more family separations, a well-recognized stressor for Servicemembers.4

One possible avenue for reducing the stress associated with military 

operations is to lessen the frequency and duration of deployments. 

Unfortunately, political and strategic imperatives and troop shortages may 

prevent such an approach. The military is not alone in this regard; the same 

is true (at least at times) in other occupations and contexts. For example, 

following the September 11, 2001, terrorist attack on the World Trade Center, 

fire, police, and other emergency personnel necessarily maintained operations 

around the clock with the goal of locating possible survivors, as well as 

restoring essential services to the affected areas. Thousands of disaster response 

workers were involved in rescuing victims and restoring basic services in New 

Orleans following Hurricane Katrina in August 2005. In such crisis situations, 

continuous operations and extreme efforts are necessary to save lives; easing 

the pace of work may be considered unacceptable or even unethical. 

When reducing stressful operations or activities is not a policy option, 

what can be done to minimize or counter the stressors associated with such 

operations? Answering this question with respect to the military case must 

begin with a clear understanding of the nature of the stressors personnel 
Forging Stress Resilience: Building Psychological Hardiness 245

encounter on modern military deployments. Extensive field research with U.S. 

military units deployed to Croatia, Bosnia, Kuwait, and Saudi Arabia from 1993 

through 1996, including interviews, observations, and survey data, identified 

five primary psychological stress dimensions in modern military operations: 

isolation, ambiguity, powerlessness, boredom, and danger.5, 6 Today, with the 

greatly increased frequency and pace of deployments for U.S. forces and the 

long work periods involved,7

 an additional significant stress factor should 

be added to the list: workload or operations tempo. These dimensions are 

summarized in table 17–1. Although these stress dimensions are discussed as 

six distinct factors, in practice they overlap and interact in multiple ways.8, 9

table 17–1. Primary Stressor Dimensions in Modern Military Operations

Stressor Characteristics

Isolation

Remote location 

Foreign culture and language 

Far from family/friends 

Unreliable communication tools 

Newly configured units with unfamiliar coworkers

Ambiguity

Unclear/changing mission 

Unclear rules of engagement (ROE) 

Unclear command/leadership structure 

Role confusion 

Unclear norms, standards of behavior 

Powerlessness

Movement restrictions

ROE constraints on response options

Policies prevent intervening, providing help

Forced separation from local culture, people, events, places

Unresponsive supply chain—trouble getting needed supplies/repair parts

Differing standards of pay, movement, behavior for different units in area

Indeterminate deployment length

Do not know/cannot influence what is happening with family at home 

Boredom

(alienation)

Long periods of repetitive work activities without variety

Lack of work that can be construed as meaningful, important

Overall mission/purpose not understood as worthwhile or important

Few options for play, entertainment

Danger

(threat)

Real risk of serious injury or death from:

• enemy fire, bullets, mortars, mines, explosive devices

• accidents, including “friendly fire”

• disease, infection, toxins in the environment

• chemical, biological, or nuclear materials used as weapons

Workload

High frequency, duration, and pace of deployments

Long work hours/days during the deployments

Long work hours/days before and after deployments
2467 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Isolation 

Military personnel typically deploy to remote areas, far from home and their 

families, and frequently lacking reliable methods for communicating. Troops 

are in a strange land and culture, away from familiar surroundings. Furthering 

the sense of psychological isolation is the fact that personnel may not know 

each other, since deployed units are typically task forces specially constituted 

for a particular mission. 

Ambiguity 

In modern military operations, a unit’s mission and rules of engagement are 

often unclear, multiple missions might be in conflict, or the missions may 

change over time. The role and purpose of the military person may be similarly 

unclear. Confusion and mystery in the command structure often add to the 

uncertainty (Who is in charge of what?). Lack of understanding of host nation 

language and cultural practices, and how these may affect deployed forces, 

also increases the uncertainty (Which norms and practices are acceptable in 

the host culture, and which are not?). These ambiguities can also affect other 

military contingents as well as contractors in a multinational coalition force. 

All of these factors generate a highly ambiguous social environment.

Powerlessness 

Security and operational concerns often lead to movement restrictions 

as, for example, when troops are restricted from leaving their base camp. 

Troops may also be banned from any interaction with the local populace and 

prevented from participating in familiar activities such as jogging for exercise 

or displaying the flag. There are frequently multiple constraints on dress and 

activities, and troops have few choices in their daily existence. Movement 

and communication restrictions also impede them from learning about local 

culture and language and resources that might be available in the area. All of 

this adds to a sense of powerlessness and lack of control over the surrounding 

environment. Troops may also see military personnel from other Services 

or countries operating under different rules and privileges in the same 

environment, but have no explanation for these alternate standards. Soldiers 

may observe local people who are wounded, ill, hungry, and in need of help 

but be unable to proffer assistance due to movement and contact restrictions 

and rules of engagement.10

Boredom 

Modern military missions frequently involve long periods of “staying in 

place,” often without much real work to do. As the weeks and months crawl 

by, troops start to get bored. To some degree, this boredom can be countered 
Forging Stress Resilience: Building Psychological Hardiness 247

by providing more entertainment and sports activities. But the real problem of 

boredom is traceable to the lack of meaningful work or constructive activities 

to engage in. Daily tasks often take on a repetitive dullness, with a sense that 

nothing important is being accomplished. 

Danger 

This dimension encompasses the real physical hazards and threats that can 

result in injury or death that are often present in the deployed environment. 

Things such as bullets, mines, bombs, or other hazards in the deployed setting 

are included, as well as the risk of accidents, disease, and exposure to toxic 

substances. Current U.S. and coalition operations in Iraq and Afghanistan 

include many hidden dangers such as suicide bombers, snipers, and 

improvised explosive devices. This source of stress can be direct, posing a 

threat to the individual soldier, or indirect, representing threats to his or her 

comrades. Exposure to severely injured or dead people, and the psychological 

stress this can entail, also adds to the sense of danger for troops.

Workload 

This factor represents the increasing frequency and duration of deployments 

that many military units are experiencing. Also, most deployments are 

characterized by a 24/7 work schedule in which soldiers are always on duty, 

with no time off. Work-related sleep deprivation is often a related feature. 

Training and preparation activities in the period leading up to a deployment 

also usually entail a heavy workload and extremely long days. The same is 

generally true for military units returning home from a deployment, who 

must work overtime to assure that all vehicles and equipment are properly 

cleaned, maintained, and accounted for. 

What tools, strategies, or coping mechanisms can be applied in order to 

increase resilience or resistance to these stressors, at both the individual and 

unit levels? I focus next on the cognitive style of hardiness and suggest how 

leaders might utilize this construct to increase individual and group resilience 

under stress. It is also important to remember, however, that many other 

factors at various levels also influence how individuals behave and respond to 

work-related stress. Figure 17–1 lists some of these factors at the individual, 

organizational policy, and organizational structure levels.

Psychological Hardiness 

The “hardiness” theoretical model first presented by Kobasa11 provides insight 

for understanding highly resilient stress response patterns in individuals and 

groups. Conceptually, hardiness was originally seen as a personality trait or 
2489 Bio-IInspired IInnovation and ovation and NNational SSecurity 

style that distinguishes people who remain healthy under stress from those 

who develop symptoms and health problems.12, 13 Hardy persons have a high 

sense of life and work commitment and a greater feeling of control, and are 

more open to change and challenges in life. They tend to interpret stressful 

and painful experiences as a normal aspect of existence, part of life that is 

overall interesting and worthwhile. 

Rather than a personality trait, psychological hardiness may be more 

accurately described as a generalized style of functioning that includes 

cognitive, emotional, and behavioral features, and characterizes people who 

stay healthy under stress in contrast to those who develop stress-related 

problems. The hardy-style person is also courageous in the face of new 

experiences as well as disappointments, and tends to be highly competent. 

The high hardy person, while not impervious to the ill effects of stress, is 

strongly resilient in responding to stressful conditions.

figure 17–1. factors that influence resiliency

RESOURCES

Macro level:

National priorities

Laws

Presidential directives

DOD and agency regulations

Uniform Code of Military Justice

Mission definition

Rules of engagement

Deployment policies

Pay and benefits

Micro level:

Unit policies

Leader communications

Definition of work-mission

Handling of losses

Discipline

Uniform and training standards

Deployment policies, stop-loss

Unit cohesion, social support

Factors include:

Unit size/configuration

Unit basing

Force manning–

Ratio: leaders to troops

Types of units

Size of units

Separate or joint forces

Place of Reserve/Guard

C2 relations

Factors include:

Education level

Social background

Personality

Work/life experience

Previous training

Maturity

Intelligence

Fitness

Family circumstances

Selection

Training and

education

Organizational

structure

Individual

Organizational

policies,

procedures,

culture

Figure 17–1: Factors that Influence Resiliency
Forging Stress Resilience: Building Psychological Hardiness 249

The concept of hardiness is theoretically grounded in the work of 

existential philosophers and psychologists such as Heidegger,14 Frankl,15 and 

Binswanger16 and involves the creation of meaning in life, even life that is 

sometimes painful or absurd, and having the courage to live life fully despite its 

inherent pain and futility. It is a global perspective that affects how one views the 

self, others, work, and even the physical world (in existential terms, Umwelt, the 

“around” or physical world; Mitwelt, the “with” or social world, and Eigenwelt, 

the “world of the self” or me). As early as 1967, using somewhat different terms, 

Maddi outlined the hardy personality type and contrasted it with the non-hardy 

“existential neurotic.”17 He used the term ideal identity to describe the person 

who lives a vigorous and proactive life, with an abiding sense of meaning and 

purpose and a belief in his own ability to influence things. 

Since Kobasa’s original 1979 report on hardiness and health in executives,18

an extensive body of research has accumulated showing that hardiness protects 

against the ill effects of stress on health and performance. Studies with a variety 

of occupational groups have found that hardiness operates as a significant 

moderator or buffer of stress.19 Hardiness has also been identified as a moderator 

of combat exposure stress in Gulf War soldiers.20 Psychological hardiness has 

emerged as a stress buffer in other military groups as well, including U.S. Army 

casualty assistance workers,21 peacekeeping soldiers,22 Israeli soldiers in combat 

training,23 Israeli officer candidates,24 and Norwegian navy cadets.25 Studies 

have found that troops who develop post-traumatic stress disorder (PTSD) 

symptoms following exposure to combat stressors are significantly lower in 

hardiness than those who do not exhibit PTSD.26 Using data from this study of 

U.S. soldiers in the Gulf War, figure 17–2 shows the typical, and rather robust, 

figure 17–2. Mental Hardiness and the Eff ects of Combat Stress*

* Displays Hardy x CSE interaction (p. <.001) in regression model, N=824 Active duty, 

 unstandardized betas used to map regression lines

LOW STRESS HIGH STRESS

Combat Stress Exposure (CSE)

High Hardy

Low Hardy

Impact of Events Scale

0

10

20

30

40
2501 Bio-IInspired IInnovation and ovation and NNational SSecurity 

interaction effect of hardiness and stress. Under low-stress conditions, those 

high in hardiness are fairly similar to those low in hardiness in terms of health—

in this case, PTSD symptoms. However, under high-stress conditions, the 

resiliency effects of hardiness are most apparent. Here, those high in hardiness 

report significantly fewer PTSD symptoms than those low in hardiness (PTSD 

symptoms measured by the Impact of Events Scale).27

Psychological Hardiness as a Framework for 

Understanding Positive Leader Influence 

How does hardiness increase resilience to stress? While the underlying 

mechanisms are still not fully understood, a critical aspect of the hardiness 

resilience mechanism likely involves the meaning that people attach to events 

around them and their own place in the experiential world. High hardy 

people typically interpret experience as overall interesting and worthwhile, 

something they can exert control over, and challenging, presenting 

opportunities to learn and grow. In organized work groups such as military 

units, this “meaning-making” process is something that can be influenced by 

leader actions and policies. Military units by their nature are group-oriented 

and highly interdependent. Common tasks and missions are group actions, 

and the hierarchical authority structure frequently puts leaders in a position 

to exercise substantial control and influence over subordinates. By the policies 

and priorities they establish, the directives they give, the advice and counsel 

they offer, the stories they tell, and perhaps most importantly the examples 

they set, leaders may alter the manner in which their subordinates interpret 

and make sense of experiences. Some empirical support for this notion comes 

from a study by Britt, Adler, and Bartone,28 who found (using structural 

equation modeling) that hardiness increases the perception of meaningful 

work, which in turn increases the perception of positive benefits associated 

with a stressful military deployment to Bosnia.

Many authors have commented on how social processes can influence 

the creation of meaning by individuals. For example, Janis29 used the term 

groupthink to describe how people in groups can come to premature closure 

on issues, with multiple individuals conforming to whatever is the dominant 

viewpoint in the group. Berger and Luckmann30 argue that “reality” or 

perceptions of individuals reflect “social constructions,” an incorporation into 

the individual mind of social definitions of the world. Karl Weik31 discusses 

the process by which organizational policies and programs can influence 

how individuals within the organization “make sense” of or interpret their 

experiences, particularly at work. Even Gordon Allport,32 a distinguished 

American personality psychologist, viewed individual meaning as often largely 
Forging Stress Resilience: Building Psychological Hardiness 251

the result of social influence processes. Peers, leaders, and entire work units 

or organizational cultures can influence how experiences get interpreted. In 

particular, leaders who are high in hardiness themselves can exert substantial 

influence on those around them to process stressful experiences in ways 

characteristic of high hardy persons. 

Thus, the operative power of psychological hardiness to defuse stressful 

experiences is related to the particular interpretations of such experiences that 

are typically made by the hardy person. If a stressful or painful experience can 

be cognitively framed and made sense of within a broader perspective that 

holds that all of existence is essentially interesting, worthwhile, fun, a matter 

of personal choice, and a learning experience, then the stressful event can 

have beneficial psychological effects instead of harmful ones. In a small group 

context, leaders are in a unique position to shape how stressful experiences 

are understood by members of the group. The leader who, through example 

and discussion, communicates a positive construction or reconstruction of 

shared stressful experiences may exert an influence on the entire group in 

the direction of his/her interpretation of experience. Leaders who are high 

in hardiness likely have a greater impact in their groups under high-stress 

conditions when, by their example as well as by the explanations they give to 

the group, they encourage others to interpret stressful events as interesting 

challenges to be met. This process itself, as well as the positive result (a 

shared understanding of the stressful event as something worthwhile and 

beneficial), could be expected to also generate an increased sense of shared 

values, mutual respect, and cohesion. Further support for this interpretation 

comes from a study showing that hardiness and leadership interact to affect 

small group cohesion levels following a rigorous military training exercise.33

This interaction effect signifies that the positive influence of leaders on the 

growth of unit cohesion is greater when hardiness levels in the unit are high. 

This suggests that effective leaders encourage positive interpretations of 

stressful events and increase group solidarity, especially in a context of higher 

psychological hardiness levels. 

As an example of the kind of leadership that can foster hardy-resilient 

response patterns throughout a unit, consider the case of a U.S. Army 

company commander who led a Patriot missile air defense artillery unit 

approaching the end of a 6-month deployment to Southeast Asia. The unit 

mission, which was to be prepared to shoot down any Scud missiles that 

might be launched from Iraq, had become rather dull and boring. Morale 

and cohesion were found to be quite low throughout the battalion. But 

surprisingly, one company/battery stood out as different from the rest, 

reporting very high morale and cohesion levels: the Headquarters and 

Maintenance Company. Further investigation revealed that shortly after 
2523 Bio-IInspired IInnovation and ovation and NNational SSecurity 

arriving in theater, the company commander had set a major task for the 

unit, one that provided a common goal and a tangible mission to work on 

during their 6 months in the desert. He had heard about a large area nearby 

that had been used as an equipment dump after the Gulf War. There, several 

tons of discarded equipment and parts were buried in the sand, rusted and 

dirty. The commander set for his unit the task of excavating the dump and 

recovering, cleaning, and repairing as much equipment as possible over 

the course of the deployment. Five months later, they had salvaged over $1 

million worth of equipment, which was returned to the Army supply system 

in good working order. Proudly displayed on the walls of the company 

work area and meeting room were large before-and-after photographs of 

the equipment dump, which the Soldiers had also rebuilt into a multisport 

athletic field. In interviews, all unit members spoke with great pride about 

this feat and of having saved considerable taxpayer dollars. 

This case illustrates how a proactive, committed, high hardy leader 

can mobilize an entire work group in the direction of greater hardiness 

and stress resilience. The company commander asserted creative control 

under ambiguous conditions and sought out and found a meaningful, 

albeit secondary, mission for his unit. Without compromising the primary 

mission (maintaining the equipment and resources of the battalion), he 

created a major, challenging task that they could “get their arms around” 

and exercise control over. He was enthusiastic and worked alongside his 

Soldiers in the dump, helping them develop a shared sense of commitment 

to the task. Soldiers were also involved in planning the job, building a sense 

of commitment and control. The task was challenging but had a clear goal 

that could be accomplished within the 6-month deployment period. The 

commander also understood the importance of recognition and made 

sure that Soldiers received awards as well as military media attention for 

their accomplishments. Recognition in media such as the Stars and Stripes

newspaper, as well as from senior leaders such as the Sergeant Major of the 

Army, further reinforced the sense of commitment and positive meaning 

within the unit, a shared belief that what they had done was important 

and valuable. While other units in the same battalion grew more alienated, 

bored, and powerless over the course of the deployment, one insightful and 

resilient leader showed how psychological hardiness—commitment, control, 

and challenge—could be increased within his part of the organization. This 

example shows how a high hardy leader may be able to influence an entire 

unit toward more hardy interpretations of experience, and the positive, 

resilient reactions that can follow.

Although more research is needed on this issue, sufficient evidence 

exists to support the view that leaders can increase high hardiness response 
Forging Stress Resilience: Building Psychological Hardiness 253

patterns within their organizations and to provide a preliminary sketch of 

how the high hardy leader behaves in order to influence hardiness and stress 

resilience in the organization. The prototypical hardy leader:

• leads by example, providing subordinates with a role model of the 

hardy approach to life, work, and reactions to stressful experiences. 

Through actions and words, he or she demonstrates the strong sense of 

commitment, control, and challenge, and a way of responding to stressful 

circumstances that demonstrates stress can be valuable, and that stressful 

events always at least provide the opportunity to learn and grow.

• facilitates positive group sensemaking of experiences, in how tasks and 

missions are planned, discussed, and executed, and also how mistakes, 

failures, and casualties are spoken about and interpreted. While most 

of this “sensemaking” influence occurs through normal day-to-day 

interactions and communications, occasionally it can happen in the 

context of more formal after-action reviews or debriefings that can 

focus attention on events as learning opportunities and create shared 

positive constructions of events and responses around events.34

• seek out (and create if necessary) meaningful/challenging group tasks, 

and then capitalizes on group accomplishments by providing recognition, 

awards, and opportunities to reflect on and magnify positive results 

(such as photographs, news accounts, and other tangible mementos).

The leader who by example, discussion, and established policies communicates 

a positive construction or reconstruction of shared stressful experiences exerts 

a positive influence on the entire group in the direction of interpretation 

of experience toward more resilient and hardy sensemaking. And while 

leadership is important, other factors also may influence how individuals make 

sense of experiences. Policies and regulations throughout the organization not 

only can have the effect of increasing or decreasing stress levels, but may also 

directly and indirectly influence commitment, control, and challenge aspects 

of the hardy resilient response pattern. A better knowledge of all these factors 

will permit more effective approaches to build stress resilience not just in 

military organizations, but anywhere people are exposed to highly stressful 

circumstances.

This chapter is based in part on “Harnessing Hardiness: Psychological Resilience in Persons and 

Organizations,” a paper presented by the author at the Human Sciences Research Conference on 

Harnessing Talent for Complex Operations, held at National Defense University on March 21, 2007, 

and sponsored by Assistant Secretary of the Navy for Manpower and Reserve Affairs, the Honorable 

William A. Navas, Jr.
2545 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Notes

1 G.A. Bonanno, “Loss, Trauma and Human Resilience: Have We Underestimated the Human 

Capacity to Thrive after Extremely Aversive Events?” American Psychologist 59 (2004), 20–28.

2 Ibid. 

3 C. Castro and A. Adler, “OPTEMPO: Effects on Soldier and Unit Readiness,” Parameters 29 

(1999), 86–95.

4 D.B. Bell et al., USAREUR Family Support during Operation Joint Endeavor: Summary

Report, ARI Special Report 34 (Alexandria, VA: U.S. Army Research Institute for the 

Behavioral and Social Sciences, 1997).  

5 P.T. Bartone, A.B. Adler, and M.A. Vaitkus, “Dimensions of Psychological Stress in 

Peacekeeping Operations,” Military Medicine 163 (1998), 587–593.

6 P.T. Bartone, “Psychosocial Stressors in Future Military Operations,” paper presented at the 

Cantigny Conference Series on Future of Armed Conflict, Wheaton, IL, June 2001.

7 Castro and Adler.

8 Bartone, Adler, and Vaitkus, 587–593.

9 Bartone, “Psychosocial Stressors in Future Military Operations.” 

10 Other studies have also identified powerlessness as a damaging influence for soldiers 

on peacekeeping operations. For example, Lars Weisaeth and Arne Sund found that in 

Norwegian soldiers serving in Lebanon in the United Nations peacekeeping mission, the 

feeling of being powerless to act or intervene when witnessing some atrocity was a main 

contributor to post-traumatic stress symptoms. See Weisaeth and Sund, “Psychiatric 

Problems in UNIFIL and the UN Soldier’s Stress Syndrome,” International Review of the 

Army, Navy, and Air Force Medical Service 55 (1982), 109–116.

11 S.C. Kobasa, “Stressful Life Events, Personality, and Health: An Inquiry into Hardiness,” 

Journal of Personality and Social Psychology 37 (1979), 1–11.

12 Ibid. 

13 S.R. Maddi and S.C. Kobasa, The Hardy Executive (Homewood, IL: Dow Jones-Irwin, 1984).

14 M. Heidegger, Being and Time (New York: Harper Collins Publishers, 1986).

15 V. Frankl, The Doctor and the Soul (New York: Knopf, 1960).

16 L. Binswanger, Being in the World: Selected Papers of Ludwig Binswanger, tr. J. Needleman 

(New York: Basic Books, 1963).

17 S.R. Maddi, “The Existential Neurosis,” Journal of Abnormal Psychology 72 (1967), 311–325.

18 Kobasa, 1–11.

19 See, for example, R.J. Contrada, “Type A Behavior, Personality Hardiness, and Cardiovascular 

Responses to Stress, Journal of Personality and Social Psychology 57 (1989), 895–903; S.C. 

Kobasa, S.R. Maddi, and S. Kahn, “Hardiness and Health: A Prospective Study,” Journal of 

Personality and Social Psychology 42 (1982), 168–177; D.L. Roth et al., “Life Events, Fitness, 

Hardiness, and Health: A Simultaneous Analysis of Proposed Stress-resistance Effects,” 

Journal of Personality and Social Psychology 57 (1989), 136–142; and D.J. Wiebe, “Hardiness 

and Stress Moderation: A Test of Proposed Mechanisms,” Journal of Personality and Social 

Psychology 60 (1991), 89–99.

20 P.T. Bartone, “Psychosocial Predictors of Soldier Adjustment to Combat Stress,” paper 

presented at the Third European Conference on Traumatic Stress, Bergen, Norway, June 

1993; P.T. Bartone, “Hardiness Protects against War-related Stress in Army Reserve Forces,” 

Consulting Psychology Journal 51 (1999), 72–82; P.T. Bartone, “Personality Hardiness as a 

Predictor of Officer Cadet Leadership Performance,” paper presented at the International 
Forging Stress Resilience: Building Psychological Hardiness 255

Military Testing Association Meeting, Monterey, CA, November 1999; and P.T. Bartone, 

“Hardiness as a Resiliency Factor for United States Forces in the Gulf War,” in Posttraumatic 

Stress Intervention: Challenges, Issues, and Perspectives, ed. J.M. Violanti, D. Paton, and C. 

Dunning (Springfield, IL: C. Thomas, 2000), 115–133.

21 P.T. Bartone et al., “The Impact of a Military Air Disaster on the Health of Assistance 

Workers: A Prospective Study,” Journal of Nervous and Mental Disease 177 (1989), 317–328.

22 T.W. Britt, A.B. Adler, and P.T. Bartone, “Deriving Benefits from Stressful Events: The 

Role of Engagement in Meaningful Work and Hardiness,” Journal of Occupational Health 

Psychology 6 (2001), 53–63.

23 V. Florian, M. Mikulincer, and O. Taubman, “Does Hardiness Contribute to Mental Health 

during a Stressful Real Life Situation? The Role of Appraisal and Coping,” Journal of 

Personality and Social Psychology 68 (1995), 687–695.

24 M. Westman, “The Relationship between Stress and Performance: The Moderating Effect of 

Hardiness,” Human Performance 3 (1990), 141–155.

25 P.T. Bartone et al., “Factors Influencing Small Unit Cohesion in Norwegian Navy Officer 

Cadets,” Military Psychology 14 (2002), 1–22.

26 Bartone, “Hardiness Protects against War-related Stress in Army Reserve Forces”; Bartone, 

“Personality Hardiness as a Predictor of Officer Cadet Leadership Performance.” 

27 M. Horowitz, N. Wilner, and W. Alvarez, “Impact of Events Scale: A Measure of Subjective 

Stress,” Psychosomatic Medicine 41 (1979), 209–218.

28 Britt, Adler, and Bartone, 53–63.

29 I. Janis, Groupthink, 2d

 ed. (Boston: Houghton Mifflin, 1982).

30 P.L. Berger and T. Luckmann, The Social Construction of Reality (Garden City, NY: 

Doubleday, 1966); Binswanger.

31 K.E. Weik, Sensemaking in Organizations (Thousand Oaks, CA: Sage, 1995).

32 G.W. Allport, “The Historical Background of Social Psychology,” in Handbook of Social 

Psychology, 3d ed., vol. 1, ed. G. Lindzey and E. Aronson (New York: Random House, 1985), 

1–46.

33 Bartone et al., “Factors Influencing Small Unit Cohesion in Norwegian Navy Officer 

Cadets.” 

34 A 2002 National Institute of Mental Health report on best practices for early psychological 

interventions following mass violence events noted great confusion regarding the term 

debriefing. The authors recommend that the term be reserved for operational after-action 

reviews and not be applied to psychological treatment interventions such as critical incident 

stress debriefing. See J.T. Mitchell and G.S. Everly, Critical Incident Stress Debriefing: An 

Operations Manual for CISD, Defusing and Other Group Crisis Interventions, 3d

 ed. (Ellicott 

City, MD: Chevron Publishing, 1997. For groups such as the military, after-action group 

debriefings, properly timed and conducted and focused on events rather than emotions and 

reactions, can have great therapeutic value for many participants by helping them to place 

potentially traumatizing events in a broader context of positive meaning. See P.T. Bartone, 

“Predictors and Moderators of PTSD in American Bosnia Forces,” 5th European Conference 

on Traumatic Stress, Maastricht, The Netherlands, June 1997. 

257

In COIN [counterinsurgency], the side that learns faster 

and adapts more rapidly—the better learning organization—

usually wins. Counterinsurgencies have been called learning 

competitions.1

—U.S. Army Field Manual 3–24/U.S. Marine Corps 

Warfighting Publication 3–33.5, Counterinsurgency

The missions that the U.S. military is being called upon to execute in today’s 

security environment require a tremendous amount of awareness—of 

self, others, and the wider environment. Situational awareness, mental 

agility, and adaptability have become buzzwords for the characteristics we want 

to cultivate in the military to succeed in complex, fluid, and unpredictable 

environments. In part, this complexity comes from the number and nature 

of the different missions the military must concurrently conduct. As Leonard 

Wong argues, “OIF [Operation Iraqi Freedom] requires junior leaders to be 

warriors, peacekeepers, and nation-builders—simultaneously.”2 Many soldiers 

call this state of complexity and unpredictability “the faucet,” requiring 

adjustment to situations that could change from hot to cold instantaneously. 

Servicemembers are being asked to navigate morally ambiguous situations 

with balance and nonreactivity, while drawing on stores of cultural awareness 

to “win hearts and minds.” Finally, these missions require that decisionmaking 

be pushed down to the lowest levels. As General Charles Krulak, USMC (Ret.), 

points out with his concept of the “strategic corporal,”3

 a corporal manning a 

checkpoint could make a split-second lethal decision that could be broadcast 

on al Jazeera and end up having strategic significance. In short, the key to these 

chapter 18

Neuroplasticity, Mind Fitness, 

and Military Effectiveness

Elizabeth Stanley
2589 Bio-IInspired IInnovation and ovation and NNational SSecurity 

kinds of operations is awareness, which is the foundational metaskill for being 

able to “learn and adapt.” 

This chapter proposes a new way to achieve such awareness. It draws 

on the well-documented theory of neuroplasticity, which states that the brain 

changes in response to changes in environment. The first section examines 

some of the ways that “negative” experiences such as stress and trauma can 

change the brain in deleterious ways. Given that decisionmaking in the 

military operational environment is stressful, this research is very relevant for 

a military audience. In contrast, the second section examines some of the ways 

that “positive” experiences such as mind fitness training can change the brain 

in beneficial ways. The third section builds on these ideas to propose ways 

that mind fitness training could enhance military effectiveness. Given that 

the brain is constantly building new neural connections from all of our daily 

experiences, it makes sense to concentrate on skills that build those neural 

connections most beneficial for operational effectiveness and soldier wellbeing. The conclusion extends this research by examining potential limitations 

and highlighting possible applications in the national security environment.

Negative Experiences: Stress and Trauma 

In the last 20 years, our understanding of how the brain regenerates itself 

has changed dramatically. We used to believe that when a baby was born, 

it had the most neurons it would have for its entire life, and that over time, 

these would die off and not be regenerated. We now know that the brain is 

plastic, fluid, and ever-changing—it generates new synapses and neurons 

and discards old ones in response to sensory input from the environment. 

It is not overly dramatic to say that every experience we have changes our 

brains. Every moment, waking or sleeping, our brains experience continuous 

fluctuation in the flow of arterial blood and the utilization of oxygen and 

glucose within different regions. For example, areas of the brain that control 

vision will get extra blood flow when we gaze at a painting or the horizon 

or when we imagine a visual image. Areas of the brain that control motor 

skills get extra blood flow when we ride a bicycle or take a walk. Areas of the 

brain that control our response to threat or danger receive more blood flow 

if a person tells a story describing an assault, rape, or battle. The prominence 

of these changes to brain blood flow and energy use varies from person to 

person, based on his or her specific pattern of life experience. As neurologist 

and trauma researcher Robert Scaer argues, “Life experience, based on specific 

sensory experiences, therefore changes the brain permanently in the way that 

it specifically reacts to subsequent similar experiences.”4
Neuroplasticity, Mind Fitness, and Military Eff ectiveness 259

There is also evidence that the physical structure of the brain also 

changes with life experience. New connections are formed between neurons. 

New neurons may also be formed and existing ones discarded, at least in the 

hippocampus, the region of the brain that controls conscious memory. Thus, 

not only might patterns of blood flow and energy use be altered in different 

brain regions, but areas of the brain might also shrink or expand—become 

more or less functional—based on experience. In other words, the brain, 

like the rest of the body, builds the “muscles” it most uses, sometimes at the 

expense of other abilities. Any time we perform any type of task (physical or 

mental), the region of the brain that serves that particular function shows 

increased neuronal activity. Experience and training can produce a functional 

and structural reorganization of the brain.

Given that all experience changes the brain, we might categorize 

experiences as negative and positive. From the negative perspective, a variety 

of research indicates that harmful conditions such as chronic stress, neglect, 

and abuse produce deleterious changes in the brain. Stress is produced by real 

or imagined events that are perceived to threaten an individual’s physical and 

mental well-being. Today, stress is commonly understood to mean external 

events or circumstances, and as a result, we tend to think of stress as something 

external to us. However, as originally conceived, stress is a perceived, internal 

response. The right amount of stress will allow a decisionmaker to function at 

peak performance. However, excessive stress has biological and psychological 

consequences that reduce working memory and the capacity to process new 

information and learn. Stressors may bias decisionmaking more toward a 

reactive, unconscious emotional process. Stress can also trigger habits, which 

are recurrent, often unconscious patterns of behavior and thought acquired 

through frequent repetition. 

For example, the brains of animals that received prolonged exposure 

to high levels of cortisol, the hormone researchers use to measure the stress 

response in the body, showed damage in their hippocampi, the brain region 

that controls conscious memory. Similarly, Vietnam veterans who suffered 

from post-traumatic stress disorder (PTSD) were found to have smaller 

hippocampi.5

 Imaging studies in the brains of victims of various types of 

trauma, especially trauma experienced in childhood, have also consistently 

shown decreased hippocampal volume. Douglas Bremner deduced that loss 

of hippocampal volume in these individuals caused deficits in memory. When 

he tested memory function in combat veterans with PTSD and victims of 

childhood trauma or sexual abuse, both groups showed deficits in a variety 

of types of memory function, including declarative memory, short-term 

memory, immediate and delayed recall, and percent retention of memory.6
2601 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Recent empirical research about decisionmaking in stressful military 

environments demonstrates that trauma and stress lead to deficits in both 

cognitive functioning and cognitive adaptation to the stressful circumstances. 

One large study of U.S. Army troops found that Soldiers who served in 

Iraq were highly likely to show subtle lapses in memory and an inability to 

focus, a deficit that often persisted more than 2 months after they arrived 

home.7

 In the study, 654 Soldiers who deployed to Iraq between April 2003 

and May 2005 performed significantly worse in tasks that measured spatial 

memory, verbal ability, and their ability to focus than 307 Soldiers who had 

not deployed. In contrast, the Soldiers who had deployed outperformed those 

who had not in terms of quick reaction time (for example, how long it takes 

to spot a computer icon and react). This finding suggests that the Soldiers’ 

minds had adapted to the dangerous, snap-judgment conditions of war, but 

in the process saw other cognitive capabilities degrade. In effect, the deployed 

Soldiers’ brains built the capacity for quick reaction time, a function more 

necessary for survival in Iraq, at the expense of other mental capacities. 

While this adaptation could be construed as positive, recent research 

shows that mind fitness training techniques can lead to more efficient mental 

processing, which may decrease the need for such a dramatic degradation of 

some mental capacities in order to build others. In other words, although the 

“untrained” minds of the Iraqi veterans showed a positive adaptation, with 

mind fitness training, more efficient mental processing may allow the brain to 

cultivate new capacities such as quick reaction time without degrading others. 

Other studies of military environments have found substantial degradation 

in cognitive performance when subjects experience sleep deprivation and other 

environmental stressors. A recent study of sleep deprivation among Navy 

SEALs and Army Rangers during a field training exercise demonstrated that the 

lack of sleep affected soldiers so badly that after a week they performed worse 

on cognitive tests than if they were sedated or legally drunk. In this study, the 

SEALs and Rangers showed severe degradation in reaction time, vigilance, visual 

pattern recognition, short-term memory, learning, and grammatical reasoning 

skills.8

 Another group of studies examined more than 530 soldiers, sailors, 

and pilots during military survival training, including time in mock prisoner 

of war camps, to prepare them to withstand the mental and physical stresses 

of capture. In these studies, exposure to acute stress resulted in symptoms of 

disassociation (alterations of one’s perception of body, environment, and the 

passage of time), problem-solving deficits (as measured by objectively assessed 

military performance), and significant inaccuracies in working memory and 

spatial memory (as measured by eyewitness identification tests). For example, 

only one-third of the volunteers could correctly identify their interrogator in 

photo spreads or lineups 24 hours after being released from the camp.9

 These 
Neuroplasticity, Mind Fitness, and Military Eff ectiveness 261

findings corroborated those of other studies that found that multistressor 

environments lead to substantial degradation of cognitive skills that correspond 

to “higher brain” (as opposed to “limbic brain”) functions.10 Such declines in 

cognitive function have been linked to battlefield errors, such as friendly fire 

incidents and collateral damage.11

These findings about how stress and trauma change the brain are 

very salient for the military, because the national security environment is 

stressful. Decisionmaking in this environment is characterized by uncertainty, 

unpredictability stemming from interaction with adversaries and third parties, 

intense time pressure, and incomplete and ambiguous information. Moreover, 

soldiers face emotional and mental stress, including the loss of comrades, as 

well as physical distress and deprivation (sleep loss, hunger, physical danger, 

lack of privacy, harsh environmental conditions, and physical exertion). These 

stressors can impede operational effectiveness and soldier well-being.

Positive Experiences: Mind Fitness Training 

Not all experiences are harmful to the brain. The brain of an expert such as 

a surgeon, taxi driver, or musician is functionally and structurally different 

from that of a nonexpert. For example, researchers studying London cab 

drivers found that they have larger hippocampi than matched controls, and 

the amount of time an individual worked as a cab driver predicted the size 

of the posterior hippocampus. These differences in hippocampus size are 

thought to be the result of experience and training as a cab driver, not of 

preexisting differences in the hippocampal structure.12 In another study, 

monkeys were trained to maintain hand contact with a rotating disk in order 

to get bananas. The training caused a clear reorganization of the cortical 

region, a reorganization that lasted for a significantly long time after the 

training was discontinued.13 This research demonstrates how experience and 

training can produce a functional and structural reorganization of the brain.

The role of training has been recognized in the military context for a 

long time, although there has been less focus on training the brain. A more 

nuanced look at the data from studies about stressful military environments 

leading to degradation of cognitive functioning shows that soldiers showed 

variation in physiological and psychological stress, and much of this variation 

was correlated with training. Soldiers with more training released less cortisol, 

which is the hormone used to measure the stress response and associated with 

hippocampal damage. These soldiers also produced more neuropeptide-Y, 

which has been associated with reducing anxiety responses. In other words, 

these soldiers were not only better equipped for handling stress, but they also 

recuperated more quickly so that they were better prepared to handle any 
2623 Bio-IInspired IInnovation and ovation and NNational SSecurity 

subsequent stressors. Because of findings such as these, military training has 

long been designed as “stress immunization” to habituate soldiers to a variety 

of stressors and thus reduce the stress response. As we will see below, mind 

fitness training could complement and strengthen such training by helping 

soldiers to perceive and relate to those stressors differently.

Because of neuroplasticity, humans can create new neural pathways, 

often with beneficial results. This scientific fact is starting to be recognized and 

applied with mind fitness training, as a variety of bestselling books suggest.14 

Mind fitness training techniques have existed for thousands of years, having 

originated in Eastern spiritual traditions, but in recent decades they have been 

adapted for secular use, including in corporations, prisons, and elementary 

schools. Mind fitness training has also been incorporated into several 

interventions that are now widely available in medical and mental health 

settings. For example, UCLA researcher Gary Small and a team of experts 

in memory training, stress reduction, and other healthy longevity strategies 

offer a one-day “Brain Boot Camp” to teach brain-healthy lifestyles and 

enhance memory ability.15 However, the most common health intervention 

is mindfulness-based stress reduction; more than 250 U.S. hospitals offer 

programs in the technique.16 Recently, these techniques have been extended 

to Iraq War veterans returning with PTSD. There are at least five mindfulnessbased interventions with war veterans under way at this time.17

Mind fitness includes the capacities of mental agility, emotional 

intelligence, improved attention and working memory, and awareness of self, 

others, and the wider environment. Like physical fitness, mind fitness can 

be strengthened through attention and concentration practices that literally 

change the brain structurally and functionally. And like physical fitness, mind 

fitness is protective, building resiliency and leading to faster recovery from 

mental and psychological stress. Mind fitness may also slow the cognitive 

degradation associated with aging by building cognitive reserve, the capacity 

to optimize performance by recruiting alternative brain networks or cognitive 

strategies in response to the demands of a task.

How does mind fitness training work? Each time we choose to ignore 

an old, maladaptive habit, we weaken the neural circuitry associated with that 

pattern (what we could call a “brain groove”). Each time we choose to build 

a new habit, we strengthen a new brain groove. This concept is something 

that athletes, musicians, and martial artists have known for a long time: with 

repetition, the body begins to develop muscle memory. Physical trainers talk 

about developing muscle memory with 300 repetitions and muscle mastery 

with 3,000 repetitions. But the same process can occur with habits of mind. 

For example, it is possible to change our conditioning toward anxious or 

angry trains of thought. To do this, when the anxious or angry thought 
Neuroplasticity, Mind Fitness, and Military Eff ectiveness 263

arises, rather than follow the impulse, a person can turn his mind elsewhere, 

“starving” the old thought pattern, and consciously choose to see the situation 

in a different way, “feeding” a new thought pattern. Mind fitness allows an 

individual to experience even very strong emotions with greater objectivity 

and less reactivity, which serves to counter our habitual tendency to avoid 

or deny difficult emotional states. Instead, individuals can learn to use such 

states as information (“What is this anger trying to tell me?”), which can lead 

them to access a wider, more adaptive range of coping skills. 

Mind fitness is cultivated through a variety of training techniques, but 

most of them are based on a foundational skill called mindfulness. Mindfulness 

has been described as a process of “bringing one’s attention to the present 

experience on a moment-by-moment basis”18 and as “paying attention in a 

particular way, on purpose, in the present moment and non-judgmentally.”19

Mindfulness differs from a more conceptual mode of processing information, 

which is often the mind’s default way of perceiving and cognizing. In other 

words, paying attention is not the same thing as thinking, although we often 

confuse the two.

Numerous training techniques have been designed to develop 

mindfulness skills. One central practice is to teach individuals to train their 

attention by focusing attention on their breath and returning to the breath when 

they notice that their attention has wandered. Other practices focus on paying 

attention to other internal experiences such as emotions, thoughts, or bodily 

sensations. Still others focus on paying attention to aspects of the external 

environment, such as sounds and sights. Some techniques are practiced while 

the individual is sitting still, others while the individual is moving about 

or interacting with others.20 Perhaps the most common way to cultivate 

mindfulness skills is meditation, but the martial arts, physical exercise, eating, 

talking, and even washing dishes can all serve as mindfulness training. For 

this reason, incorporating mind fitness training into existing military training 

would not require much additional time on the training schedule. 

For example, the military already incorporates mindfulness training—

although it does not call it this—into perhaps the most foundational soldier 

skill, firing a weapon. Soldiers learning how to fire the M–16 rifle are taught 

to pay attention to their breath and synchronize the breathing process to 

the trigger finger’s movement, “squeezing” off the round while exhaling. 

This synchronization has two effects. The gross motor effect is to steady the 

soldier’s aim, so that the round is more likely to hit its target. But this training 

also has the more subtle psychological effect of helping to steady the soldier’s 

concentration and heart, to offer something concrete to focus on as bullets 

are whizzing past. It provides an anchor in the midst of very trying physical 

and psychological conditions.
2645 Bio-IInspired IInnovation and ovation and NNational SSecurity 

There is growing empirical scientific evidence that increasingly supports 

the efficacy of mindfulness-based interventions. Clinical studies of civilian 

mindfulness-based interventions demonstrate that patients who participate 

in such programs see improvement in many conditions, including anxiety 

disorders, depression, fibromyalgia, chronic pain, substance abuse, insomnia, 

binge eating, cancer, smoking cessation, menopause, irritable bowel syndrome, 

hypertension, HIV/AIDS, and skin-related diseases. Moreover, patients report 

a decrease in mood disturbance from and stress related to these conditions.21

Mindfulness training has also been shown to produce brain changes consistent 

with more effective handling of emotion under stress, with significant increases 

in left-sided activation of the anterior cortical area of the brain as well as an 

increase in immune functioning.22

Given this evidence that mind fitness training can have such positive 

effects in other environments, there appears to be an intriguing and timely 

opportunity to adapt such training techniques to the national security 

context. And given how stressful the contemporary security environment is, 

these techniques could be particularly helpful for deploying soldiers. Mind 

fitness, together with mission essential skills and physical fitness, is one of 

three components necessary for optimal soldier readiness and operational 

effectiveness. While all three components are crucial for equipping soldiers 

to handle the challenges and stressors of deployment, there is a dearth of 

training in the mind fitness arena. 

Mind Fitness Training and Military Effectiveness 

Mind fitness training could help soldiers cultivate a variety of critical 

competencies that are often in short supply on the modern battlefield. For 

example, soldiers are frequently asked to perform tasks outside their usual 

specialties and take on roles they never envisioned. This requires an immense 

capacity to adapt to new routines and learn new tasks quickly, from negotiating 

with the local sheik to rebuilding an electrical power grid. Moreover, they are 

asked to exhibit self-awareness and situational awareness and tailor decisions 

to these constraints. This state is similar to how the U.S. Army defines 

adaptability: “an individual’s ability to recognize changes in the environment, 

identify the critical elements of the new situation, and trigger changes 

accordingly to meet new requirements.”23 Finally, they are asked to make 

decisions, allocate resources, and take actions that are internally consistent 

with and supportive of broader strategic and political goals. Means-ends 

consistency is particularly important for counterinsurgency operations: as 

U.S. Army Field Manual 3–24/Marine Corps Warfighting Publication 3–33.5, 

Counterinsurgency, argues, “Unity of effort must be present at every echelon 
Neuroplasticity, Mind Fitness, and Military Eff ectiveness 265

of a COIN operation. Otherwise, well-intentioned but uncoordinated actions 

can cancel each other or provide vulnerabilities for insurgents to exploit.”24

Given the importance of such competencies, and the fact that soldiers 

are simultaneously being exposed to a variety of stressors while being called 

upon to exhibit these competencies, mind fitness training could help in six 

ways: by improving self-regulation, enhancing attention skills, increasing 

flexibility in awareness and attention, decreasing reactivity, cultivating 

emotional and social intelligence, and enhancing values clarification and 

integrity. The rest of this section draws on recent neuroscience and clinical 

psychological research from civilian contexts to suggest exactly how mind 

fitness training could enhance these six competencies.

Improved Self-regulation 

Self-regulation involves making conscious, intentional choices about 

how to relate to the current situation in a way that supports personal or 

organizational needs, values, and interests. Mindfulness can improve selfregulation by cultivating ongoing attention and sensitivity to psychological, 

somatic, and environmental clues.25 Such information allows for more 

deliberate decisionmaking so that decisionmakers can employ a wider, more 

flexible, and more adaptive range of coping skills, even in highly stressful 

environments. In addition, self-regulation can help an individual cultivate a 

higher tolerance for unpleasant internal and external conditions, as well as the 

ability to remain clear-headed in these situations. This, in turn, can increase 

an individual’s cognitive, emotional, and behavioral flexibility. Finally, 

mindfulness helps individuals to not act on impulse, but rather to access the 

gap between intention and action, so that all decisions and resulting behavior 

can be deliberate and intentional.

While performing brain surgery that required the patients to remain 

conscious, neurosurgeon Benjamin Libet asked them to move their finger and 

report the precise moment when they became aware of the urge to do so. 

During this process, Libet monitored the electrical activity in the patients’ 

brains that regulated the movement, allowing him to separate the moment 

of intention to move from the moment of awareness of that intention and 

from the moment of actual action. He discovered that freely voluntary acts 

are preceded by a specific electrical change in the brain (what he called the 

readiness potential) that begins 550 milliseconds (ms) before the act. The 

patients become aware of the intention to act 350–400 ms after the readiness 

potential starts, but 200 ms before the actual action. He concluded that the 

volitional process is thus initiated unconsciously, but the conscious mind 

could still control the outcome—it could veto the actual act, and thus “free 

will” is not excluded.26 In other words, once a person is aware of the intent 
2667 Bio-IInspired IInnovation and ovation and NNational SSecurity 

to move, there is another quarter-second before the movement begins. This 

is the crucial window during which mindfulness is so important. With 

mindfulness, this window allows a conscious choice-point to break the chain 

of reactivity or habit and choose responses that are most aligned with our 

interests and needs.

For example, mindfulness training has been shown to increase tolerance 

of unpleasant physical states, such as pain. Recent studies about mindfulness 

and pain suggest that experienced mindfulness meditation practitioners 

required an average of 2 degrees more thermal heat applied to their legs 

before perceiving pain, and they showed a lower breathing rate during the 

heat stimulus than control subjects. Moreover, when all participants were 

asked to concentrate directly on the heat stimulation on their legs, control 

subjects reported much higher levels of subjective unpleasantness than the 

mindfulness practitioners did.27

Self-regulation also helps individuals to feel more autonomous and 

in charge of their decisions and actions.28 With improved self-regulation, 

individuals can learn that although they cannot control what they are 

experiencing internally or externally, they can always choose consciously 

and control how they relate to that experience. Autonomy and self-esteem 

are important qualities for cultivating initiative, which is important when 

decisionmaking authority gets devolved down to the lowest levels. Selfregulation depends on an individual taking responsibility for his own 

thoughts, emotions, and actions. In other words, self-regulation leads to 

professional accountability.

In his study of distress and war termination, Stephen Rosen argues 

that uncontrollable, unpredictable stressors in the environment, such as 

those experienced by the losing side in war, can produce distress among 

those fighting on the losing side. Without training, these soldiers can become 

pessimistic about the outcomes of their actions, lack energy to perform their 

tasks, and perceive and understand less information from their environment 

that could be relevant to finding solutions for their problems. This lack of 

attention and energy can lead to a vicious, self-reinforcing cycle, as the distress 

of one soldier can quickly spread to his comrades.29 Self-regulation can break 

this cycle. In other words, by increasing distress tolerance and undercutting 

fear-based reactivity, self-regulation can lead to social control.

Better Attention Skills 

Mind fitness training can also improve different facets of attention. Cognitive 

psychology delineates many different aspects of attentional abilities, including 

the capacity to attend for long periods of time to one object (vigilance or 

sustained attention),30 the ability to shift the focus of attention between 
Neuroplasticity, Mind Fitness, and Military Eff ectiveness 267

objects or mental sets at will (switching),31 and the ability to inhibit secondary 

processing of thoughts, feelings, and sensations (cognitive inhibition).32

Similarly, one neuroscience model proposes that attention consists of three 

distinct cognitive networks that carry out the operations of alerting, orienting, 

and conflict monitoring. Alerting consists of achieving and maintaining 

a vigilant or alert state of preparedness, orienting directs and limits the 

attention to a subset of possible inputs, and conflict monitoring prioritizes 

among competing tasks and responses.33

How could better attention skills improve decisionmaking in military 

operations? First, soldiers could maintain a vigilant and alert state while on 

patrol or while manning checkpoints during deployments. Given that “every 

soldier is a collector” of intelligence, improved alerting skills could lead to 

more accurate and timely intelligence information for decisionmakers at 

higher levels. Second, decisionmakers with better orienting and conflictmonitoring skills could strengthen concentration and filter out distractions 

and extraneous information. Moreover, concentration enables decisionmakers 

at all levels to learn new tasks and assimilate new technologies. Finally, 

stronger attention skills can improve what Jeremy Gray and his colleagues call 

“fluid intelligence,” the intelligence associated with using facts (rather than 

simply knowing them).34

Mind fitness training has been shown to be effective in increasing 

alerting and orienting skills and working memory, which decreases the need 

to rely on cognitive “shortcuts.”35 Mindfulness practitioners have also been 

shown to have greater cortical thickening in areas of the right prefrontal 

cortex and right anterior insula, brain areas that are associated with sustained 

attention and awareness.36

In addition to these grosser aspects of attention, recent research shows 

that mind fitness training can also affect more subtle attentional processes. 

One of these is called the attentional blink (AB), which occurs when the 

brain has difficulty processing two temporally close stimuli roughly a halfsecond apart. With AB, the brain devotes too many resources to processing 

the first stimulus and, as result, misses the second one. However, mindfulness 

training has been associated with decreasing the size of the AB window, so 

that individuals can see the fast-following second target more often. In one 

recent study, relative to controls, study participants who had just completed 

a 3-month meditation retreat showed a significantly smaller AB window 

and were able to see targets inside the typical AB window more often. The 

scientists argue that because detecting the second target is dependent on 

efficient mental processing of the first one, mindfulness training can decrease 

the mental resources devoted to the first target and allow the brain to process 

the second one more easily.37
2689 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Increased Flexibility in Awareness and Attention 

Related to better attention skills is cognitive flexibility,38 which allows 

decisionmakers to access information from a wider variety of channels and 

decrease filters on that information coming in. Cognitive flexibility also 

allows decisionmakers to gain a larger perspective, which promotes insight 

into self, others, and the wider environment. From this larger perspective, 

decisionmakers are better able to discern which new tasks they need to learn 

to operate most effectively in their environment. As a result, mindfulness 

may enhance behavioral flexibility, particularly through adaptive responding 

based on actual, rather than imagined, contingencies.39 Learning to see 

clearly—indeed, learning in general—depends upon the ability to disengage 

from prior patterns and beliefs. 

Most importantly, increased flexibility in awareness and attention leads 

decisionmakers to display greater accuracy and more objectivity in assessing 

situations, making decisions and allocating scarce resources.40 U.S. Army Field 

Manual 6–22, Army Leadership, calls this trait “mental agility,” defined as “a 

flexibility of mind, a tendency to anticipate or adapt to uncertain or changing 

situations.”41 Mental agility is important today because leaders need to adapt 

to the external environment and other actors, including potential adversaries, 

allies, and local populations. They also need to be able to transition quickly 

from fighting in one moment to relating peacefully with the local community 

in the next. This requires accessing information from a wider variety of 

channels and displaying greater accuracy and more objectivity in gathering 

information. These improved inputs to decisionmaking can lead to more 

creative brainstorming, as well as a more realistic assessment of various 

alternatives. In other words, increased flexibility in awareness and attention 

could help protect against the whiplash of the “the faucet”—the rapid cycle 

between hostile and friendly encounters that soldiers in COIN environments 

face—and offer new methods for coping with its effects.

Less Reactivity 

Mind fitness training can also enhance a soldier’s capacity for nonreactivity. 

Recent studies have demonstrated that mindfulness is strongly associated 

with less reactivity.42 Nonreactive decisionmakers are better able to maintain 

contact with threatening emotional stimuli and make decisions from a 

place of receptive and realistic observation rather than emotional judgment. 

Nonreactive decisionmakers can also diminish impulsive or defensive 

reactions to unpleasant experiences and thus inhibit escalatory spirals with 

others. As a result, they can use improved self-awareness to respond instead of 

habitually or impulsively reacting. 
Neuroplasticity, Mind Fitness, and Military Eff ectiveness 269

Nonreactivity can be a powerful weapon in today’s environment. As 

the Counterinsurgency field manual argues, sometimes doing nothing is the 

best reaction. Often insurgents carry out a terrorist act or guerrilla raid with 

the primary purpose of enticing the counterinsurgents to overreact, or at 

least react in a way that insurgents can exploit—for example, opening fire 

on a crowd or executing a clearing operation that creates more enemies than 

it takes off the streets. If an assessment of the effects of a course of action 

determines that more negative than positive results may result, an alternative 

should be considered, potentially including not acting.43

Obviously, nonreactivity is linked to self-regulation, because it requires 

self-control and emotional regulation. Nonreactivity and self-regulation 

work hand in hand so that individuals can better override or change inner, 

often habitual, responses and refrain from acting on undesired behavioral 

tendencies. Both capacities in tandem allow decisionmakers to diminish 

impulsive or defensive reactions to unpleasant experiences and inhibit 

escalatory spirals with others. 

Mindfulness and the nonreactivity it cultivates allow decisionmakers to 

act from a place of realistic observation rather than emotional judgment. Thus, 

decisionmakers could become more accurate and less biased at gathering 

information and assessing situations. Mindfulness allows a clear perception 

of incoming sensory data, from the external environment as well as internally 

from the body, emotions, and thoughts. Mind fitness training allows soldiers 

and leaders to “get out of their heads” and access somatic information (“trust 

your gut”). Such an impartial, balanced view of incoming data helps the 

decisionmaker to see all of the information available with clarity and cut 

through cognitive and emotional biases. This improved input and a wider 

perspective could lead to more appropriate and thus more effective decisions.

Improved Emotional and Social Intelligence 

Emotional intelligence refers to an individual’s ability to fully comprehend 

his own emotions and thoughts, as well as notice and interpret the moods, 

temperaments, motivations, and intentions of others.44 Emotional intelligence 

comprises four skills: knowing one’s emotions, managing emotions, recognizing 

emotions in others, and handling relationships. Decisionmakers with high 

emotional intelligence are more in tune with their own strengths and weaknesses 

and open to feedback. They are also more likely to understand the moods of 

those around them and stay in touch with the mood of their organization. 

They show greater awareness of others’ affective tone and nonverbal behavior, 

and exhibit more open and less defensive responses to challenging people and 

events. This can lead them to a better assessment of themselves, other people, 

and their environment, as others candidly share information they need to know.
2701 Bio-IInspired IInnovation and ovation and NNational SSecurity 

In addition, emotional intelligence allows decisionmakers to more 

easily see situations from and respect others’ perspectives. This capacity 

is obviously important in cross-cultural situations, such as during COIN 

operations, where building social rapport and trust are paramount to the goal 

of “winning hearts and minds.” The capacity to see situations from and respect 

others’ perspectives can also be important across organizational cultural lines, 

such as between the military, the State Department, and humanitarian relief 

nongovernmental organizations (NGOs), which must work together on these 

kinds of missions. Emotional intelligence allows decisionmakers to recognize 

how their own conditioning creates biases and filters to incoming information 

and see through that conditioning to assess themselves, others, and the 

environment more realistically. With more awareness of others’ perspectives, 

as well as of their own conditioning, decisionmakers are more able to seat 

themselves appropriately within wider social, cultural, and political contexts. 

Finally, emotional intelligence allows decisionmakers to establish better 

rapport with others, improve team cohesion, and lead more effectively.

Given its ongoing operations in Afghanistan, Iraq, and other locations, 

the U.S. Government is placing a greater focus on awareness of the cultures 

of potential adversaries, the nations where U.S. forces are deployed, and their 

allies and partners in multinational operations. Most soldiers deploying to 

Iraq, for example, have the opportunity to be trained at mock Iraqi villages 

at the National Training Center at Fort Irwin, California. Moreover, those 

soldiers who will be assigned as advisors to train indigenous Iraqi military 

and police units participate in a rigorous 60-day training program.45 The 

U.S. military is also recruiting psychologists, cultural anthropologists, and 

others with local cultural expertise to deploy and participate in “Human 

Terrain Teams” that advise Provincial Reconstruction Teams in Afghanistan 

and Iraq. This kind of training is crucial for having what the military calls 

“domain knowledge” of cultural, geographic, and political differences and 

sensitivities. The domain knowledge is particular context-specific facts about 

other cultures, their customs, traditions, doctrinal principles, and operational 

methods. However, it is important to note that emotional intelligence is a 

necessary complement to domain knowledge, because it provides the more 

general, foundational social skills that allow decisionmakers to access those 

context-specific facts and use them in their interactions with others. 

Thus, emotional intelligence would be useful for at least four kinds of 

interactions in the national security context: with the indigenous population 

where the soldier is deployed, with allies or coalition partners from other 

countries that are participating in the mission, with members of humanitarian 

relief and other NGOs that often have very different organizational cultures, 

values and, goals, and with members of other U.S. Government agencies 
Neuroplasticity, Mind Fitness, and Military Eff ectiveness 271

or organizations that likewise may have different organizational cultures, 

doctrines, and operational methods. 

Given the importance of emotional intelligence for responsiveness, 

how can mindfulness enhance this quality? Scholars have theorized that 

mindfulness may promote a greater ability or willingness to take interest in 

others’ thoughts, emotions, or welfare.46 It may also enhance communication 

with others through improved listening skills and greater awareness of others’ 

affective tone and nonverbal behavior.47 At the same time, a person with 

mindfulness may be more aware of his or her own cognitive, emotional, and 

verbal responses in communication, which can reduce impulsive, destructive 

behavior in social settings.48 Similarly, scholars have suggested that greater 

insight into the self, others, and human nature, along with the easing of egobased concerns, encourages more empathy with others.49 Self-report empirical 

research provides some support for these hypotheses.50 Finally, mindfulness is 

associated with a more open and less defensive response to challenging social 

events. For example, in a study of being excluded from a group, participants 

with a high degree of mindfulness were less likely to perceive rejection and 

“take it personally.”51

Enhanced Values Clarification and Integrity 

Given the importance of means-ends consistency in the national security 

realm—linking tactical actions to strategic policy choices—enhanced values 

clarification is an important quality. It is virtually impossible for individuals 

to make decisions that are supportive of strategic goals until they identify 

what those goals are. Similarly, it is difficult for individuals to identify strategic 

goals until they know what they value. Norms and values, whether implicit 

or explicit, are crucial for helping us constitute our identities, worldviews, 

interests, and goals.52 Mindfulness may help individuals to recognize what is 

meaningful for them and what they truly value. 

As the discussion above about self-regulation suggested, automatic 

processing often limits individuals from considering options that would 

be most congruent with their interests, needs, and values. In contrast, as a 

study of participants using pagers over 3 weeks to record their daily activities 

showed, empirical evidence suggests that when subjects are “acting mindfully,” 

they act in ways that are more congruent with their actual interests, needs, 

and values.53 In other words, decisions and actions become more intentional, 

more internally consistent, and more likely to support broader personal and 

organizational goals and interests.

Correspondingly, mindfulness, and the improved attention it cultivates, 

makes it less likely that decisionmakers will “pretend not to know” and avoid 

or deny unpleasant truths; default to cognitive or emotional dissonance while 
2723 Bio-IInspired IInnovation and ovation and NNational SSecurity 

gathering and processing information, assessing situations, and making 

decisions; and act in ways not aligned to their values or interests. Instead, 

mindfulness helps decisionmakers to recognize what is meaningful for them 

and their organizations and then act congruently with their actual values, 

interests, and needs. This allows them to assess the situation, respond to it, 

and act authentically and consistently. 

These traits can lead to consistency in thought, word, and action, 

which is how the military profession defines integrity. At the personal 

level, integrity allows for personal integration, having the various aspects of 

ourselves come together and be expressed outwardly with consistency and 

authenticity. Integrity and integration at the organizational or state level 

are holographically similar: an organization is integrated if its actions are 

consistent with its strategic goals and values. At the organizational or strategic 

level, integrity allows decisionmakers to choose policies that are aligned with 

personal and organizational values, link those policies to the strategic goals of 

the organization or state, and choose policy tools that align with those values 

and goals. Thus, it is no wonder that when policies are not aligned with values 

and goals, we say the policies “lack integrity.”

Mind Fitness Training in the National Security Environment 

Winning “hearts and minds,” coping with complex, fluid, and unpredictable 

environments, navigating moral ambiguity, and empowering leaders at lower 

levels require a tremendous amount of awareness of self, others, and the 

wider environment. This chapter has proposed a new way to achieve such 

awareness. New research into neuroplasticity and clinical studies of the 

effects of mindfulness show that humans can rewire their neural pathways 

and strengthen skills that allow them to make better decisions. Mind fitness 

training inoculates against stress by permitting more adaptive responses to 

and interpretation of stressors, providing a type of “mental armor.” In addition, 

mind fitness training can help to optimize soldier performance by cultivating 

six competencies critical for today’s security environment: improved selfregulation, better attention skills, increased flexibility in awareness and 

attention, less reactivity, improved emotional and social intelligence, and 

enhanced values clarification and integrity. 

In other words, mind fitness training could not only help deploying 

soldiers relate more effectively to the stressors of the deployment, but it 

could also enhance the skills of immense flexibility and agility in thinking 

and behavior that these kinds of missions require. Mind fitness can ease 

these transitions by helping individuals to increase their tolerance of and 

exhibit more open, less defensive responses to challenging people and events. 
Neuroplasticity, Mind Fitness, and Military Eff ectiveness 273

Building social rapport and trust is paramount. Mind fitness training could 

help deploying individuals to better recognize their own conditioning and how 

that conditioning affects interactions with others, as well as to see situations 

more easily from and respect others’ perspectives. These skills would be useful 

for both cross-cultural and cross-organizational cultural interactions. 

To be sure, there are some potential limitations that need to be explicitly 

acknowledged. Regarding the existing clinical research, many early studies had 

methodological weaknesses that make it difficult to draw strong conclusions 

about the effects of mindfulness-based interventions, including small sample 

size, lack of control groups, static research protocols that did not control for 

preexisting conditions or brain structure, and poor self-report measures of 

mindfulness. Nevertheless, these preliminary data are promising, especially 

when considered with more recent research that has begun to correct for 

such weaknesses. This underscores the need for additional rigorous empirical 

research to further delineate the causal mechanisms at work.

More importantly, there are at least four possible issues with 

incorporating mind fitness training in the national security context. First, 

unlike instantaneous and simple solutions, mind fitness training is not a 

quick-fix “silver bullet.” While mind fitness skills are easily taught, they require 

ongoing effort and commitment to develop and strengthen over time—just 

like physical exercise for the body. Second, although the end result is less 

reactivity, more self-control, and more inner strength, individuals may need 

to go through a destabilizing period during the training. Third, it is critical 

that students have access to a well-trained instructor who has a longstanding 

personal practice. Thus, there is some tension between providing effective 

instruction, on the one hand, and creating a training program that would be 

replicable and scalable, on the other. Finally, mind fitness training and the 

kinds of attributes it inculcates could be threatening to hierarchical institutions 

like the military. At the very least, it presents a paradox: to develop the physical 

and mental qualities that the military says it wants—flexible, agile leaders with 

initiative, creative problemsolving skills, and emotional intelligence—it is also 

necessary to develop skills that the bureaucratic elements may find threatening. 

Despite these potential limitations and given that these training 

techniques have worked in other contexts, applying them to the military could 

provide an intriguing and timely opportunity to enhance military effectiveness. 

A natural first step to investigating this chapter’s ideas in a concrete way is 

to implement a prospective study of the effects of mind fitness training on 

operational effectiveness and individual soldier well-being, as Amishi Jha, a 

neuroscientist at the University of Pennsylvania, and I are currently doing. 

This training will be provided prior to deployment. We argue that such mind 

fitness training is likely to lead to improvements in operational effectiveness 
2745 Bio-IInspired IInnovation and ovation and NNational SSecurity 

during the deployment and reduce the rate of psychological dysfunction such 

as PTSD, depression, and anxiety upon return.

There are at least four other ways that mind fitness training could be 

effectively incorporated into civilian and military professional development. 

These ideas are included to suggest a longer term vision of what might be 

possible, ranging from conventional to radical, both in terms of the targeted 

population and the potential effects on national security decisionmaking. 

First, mind fitness training could be offered to chaplains, ombudsmen, 

inspectors general, Judge Advocate General attorneys, and medical and 

mental health professionals who provide care for soldiers, tactical leaders, 

and strategic decisionmakers. It could also be offered to rear detachment 

commanders and other community service providers who support families at 

home while units are deployed. In both cases, mind fitness training could help 

these individuals improve their own capacity to be present with their clients’ 

needs without suffering burnout. 

Second, mind fitness training could be incorporated into the training of 

anyone deploying in counterinsurgency, stability operations, or postconflict 

reconstruction missions. Similarly, mind fitness training could be offered 

to teams that advise and train indigenous militaries as part of the U.S. 

counterterrorism strategy abroad. While the COIN training the military 

already conducts, such as scenarios at mock “Iraqi villages” that soldiers 

encounter during their Joint Readiness Training Center and National Training 

Center rotations—can help to reduce soldiers’ stress response by habituating 

them to a variety of COIN-related stressors, mind fitness training could 

complement and strengthen that training by helping soldiers to perceive and 

relate to those stressors differently.

Third, mind fitness training could be incorporated into the professional 

development of intelligence collectors and analysts. For intelligence collectors, 

mind fitness training could help them to access information from a wider 

variety of channels and display greater accuracy and more objectivity in 

gathering information. For intelligence analysts, the training could help them 

recognize how their own conditioning creates filters to incoming information 

and see through that conditioning, in order to process all available information 

with clarity and cut through cognitive and emotional biases.

Finally, mind fitness training could be incorporated in the regular 

professional development of enlisted soldiers, noncommissioned officers, 

officers, and civilian government officials in the national security realm. The 

military officer corps is perhaps the most promising target audience. Being 

selected for these courses is a sign of future promotion potential, which 

suggests that the officers who attend are likely to incur even larger leadership 

roles with greater decisionmaking responsibilities in the future. Mind fitness 
Neuroplasticity, Mind Fitness, and Military Eff ectiveness 275

training could be beneficial not only for these leaders and the quality of the 

decisions they make, but also for the command climate they create. 

Given the frequency of these courses, initial mind fitness training 

could occur early in a leader’s career, and refresher training could be offered 

in subsequent courses. While leaders attend one of these courses, they 

would be relieved of regular command or staff responsibilities so that they 

can concentrate on their professional development. Moreover, because the 

operational tempo at these courses is much slower, many of the stressors 

discussed in this paper are muted. Finally, leaders attend these courses with 

a group of peers who could provide a support network during new skill 

acquisition. Having these skills and habits cemented before they return to line 

duty increases the potential that they will be able to maintain the new skills, 

given how easy it is to fall back into habitual or automatic conditioning under 

stress. Thus, professional development courses are perhaps the most ideal 

time for leaders to learn mind fitness skills and new behavioral, cognitive, and 

emotional habits, which take some time to develop and stabilize.

The security environment today is complex and rapidly changing, 

and those who work in this environment need new competencies that rely 

on the foundational skill of awareness. Mind fitness—together with mission 

essential skills and physical fitness—is one of the three components necessary 

for optimal soldier readiness, yet there is a dearth of training in this area. This 

chapter has proposed ways that mind fitness training could be incorporated 

into the military setting. Given that the brain is constantly building new neural 

connections from all of our daily experiences, the question becomes: how 

can we build neural connections that will be most beneficial for operational 

effectiveness and soldier well-being, rather than neural connections that will 

lead to reactivity and cognitive degradation in stressful environments?

Notes

1 U.S. Army Field Manual 3–24/U.S. Marine Corps Warfighting Publication 3–33.5, 

Counterinsurgency (Washington, DC: Headquarters Department of the Army, December 

2006), ix–x.

2 Leonard Wong, Developing Adaptive Leaders: The Crucible Experience of Operation Iraqi 

Freedom (Carlisle, PA: US Army War College Strategic Studies Institute, July 2004), 4.

3 Charles C. Krulak, “The Strategic Corporal: Leadership in the Three Block War,” Marines 

Magazine (1999).

4 Robert Scaer, The Trauma Spectrum: Hidden Wounds and Human Resiliency (New York: 

W.W. Norton, 2005), 17.

5 Paul J. Rosch, “Stress and Memory Loss: Some Speculations and Solutions,” Stress Medicine

13 (1997), 1–6.
2767 Bio-IInspired IInnovation and ovation and NNational SSecurity 

6 Douglas Bremner, Does Stress Damage the Brain? Understanding Trauma-related Disorders 

from a Mind-Body Perspective (New York: W.W. Norton, 2002).

7 Jennifer J. Vasterling et al., “Neuropsychological Outcomes of Army Personnel Following 

Deployment to the Iraq War,” Journal of the American Medical Association 296, no. 5 (2006), 

519–529.

8 Harris R. Lieberman et al., “Severe Decrements in Cognition Function and Mood Induced 

by Sleep Loss, Heat, Dehydration and Under-nutrition During Simulated Combat,” 

Biological Psychiatry 57 (2005), 422–429.

9 Charles A. Morgan III et al., “Accuracy of Eyewitness Memory for Persons Encountered 

during Exposure to Highly Intense Stress,” International Journal of Law and Psychiatry 27 

(2004), 265–279; Charles A. Morgan III et al., “Stress-induced Deficits in Working Memory 

and Visuo-constructive Abilities in Special Operations Soldiers,” Biological Psychiatry 60 

(2006), 722–729; Charles A. Morgan III et al., “Accuracy of Eyewitness Identification is 

Significantly Associated with Performance on a Standardized Test of Face Recognition,” 

International Journal of Law and Psychiatry 30 (2007), 213–223.

10 D.R. Haslam, “The Military Performance of Soldiers in Sustained Operations,” Aviation, 

Space, and Environmental Medicine 55 (1984), 216–221; Harris R. Lieberman et al., “Effects 

of Caffeine, Sleep Loss and Stress on Cognitive Performance and Mood during U.S. Navy 

Seal Training,” Psychopharmacology 164 (2002), 250–261; K. Opstad, “Circadian Rhythm of 

Hormones is Extinguished during Prolonged Physical Stress, Sleep, and Energy Deficiency 

in Young Men,” European Journal of Endocrinology 131(1994), 56–66.

11 G. Belenky et al., “Sustaining Performance during Continuous Operations: The U.S. 

Army’s Sleep Management System,” in Pennington Center Nutritional Series, Vol. 10, 

Countermeasures for Battlefield Stressors, ed. K. Friedl, H. Lieberman, D.H. Ryan, and G.A. 

Bray (Baton Rouge: Louisiana State University Press, 2000).

12 E.A. Maguire et al., “Navigation Expertise and the Human Hippocampus: A Structural Brain 

Imaging Analysis,” Hippocampus 13, no. 2 (2003), 250–259.

13 William M. Jenkins et al. “Functional Reorganization of Primary Somatosensory Cortex 

in Adult Owl Monkeys after Behaviorally Controlled Tactile Stimulation,” Journal of 

Neurophysiology 63 (1990), 82–104; John J. Ratey, A User’s Guide to the Brain (New York: 

Vintage Books, 2002), 167–171.

14 Sharon Begley, Train Your Mind, Change Your Brain (New York: Random House, 2007); 

Ryuta Kawashima, Train Your Brain: 60 Days to a Better Brain (New York: Kumon 

Publishing, 2005); Joel Levy, Train Your Brain: The Complete Mental Workout for a Fit and 

Agile Mind (New York: Barnes and Noble Publishing, 2007).

15 Offered by the UCLA Semel Institute Memory and Aging Center. See www.npi.ucla.edu/

memory/brain.php. 

16 Amishi P. Jha et al., “Mindfulness Training Modifies Subsystems of Attention,” Cognitive, 

Affective, and Behavioral Neuroscience 7, no. 2 (2007), 109–119.

17 First, a recent pilot study with mindfulness-based group therapy at the Ann Arbor Veterans 

Administration (VA) PTSD clinic found that war veterans, relative to their pre-study 

baselines, showed decreased PTSD symptoms after the 8-week intervention. Available 

laboratory data in this chronic PTSD group—including neuroimaging, saliva cortisol, 

skin conductance, and heart rate—suggested decreased psychological and physiological 

reactivity to trauma recall. The Ann Arbor VA is now conducting a second pilot study with 

an active control group. Researchers on the study believe that an 8-week intervention is not 

long enough for effective PTSD treatment, and they are considering an additional 8-week 

course on emotional regulation to complement the mindfulness skills. Similarly, the Emory 

University School of Medicine and the Atlanta VA Medical Center are jointly starting 

a study with returning Iraq War veterans that will compare a Mindfulness-Based Stress 
Neuroplasticity, Mind Fitness, and Military Eff ectiveness 277

Reduction intervention with an active control group receiving supportive therapy, including 

hatha yoga and other techniques. Similar mindfulness-based training programs with war 

veterans suffering from PTSD are ongoing at VA hospitals in Albuquerque, Puget Sound, 

and Palo Alto. Interview with Anthony King, investigator on the study at the Ann Arbor 

VA PTSD clinic and University of Michigan, June 7, 2007; interview with Sandra DiVitale, 

investigator on the study at Emory University, June 8, 2007; email correspondence with 

Sarah Bower, University of Washington and Puget Sound VA medical center, July 22, 2007.

18 G.A. Marlatt and J.L. Kristeller, “Mindfulness and Meditation,” in Integrating Spirituality into 

Treatment: Resources for Practitioners, ed. William R. Miller (Washington, DC: American 

Psychological Association, 1999), 67–84, at 68.

19 Jon Kabat-Zinn, Wherever You Go, There You Are: Mindfulness Meditation in Daily Life (New 

York: Hyperion, 1994), 4.

20 Thich Nhat Hanh, The Miracle of Mindfulness (Boston: Beacon Press, 1976); Bhante H. 

Gunaratana, Mindfulness in Plain English (Boston: Wisdom Publications, 2002); Jon KabatZinn, Wherever You Go and Full Catastrophe Living: Using the Wisdom of Your Body and 

Mind to Face Stress, Pain and Illness (New York: Delacorte, 1990); Joan Borysenko, Minding 

the Body, Mending the Mind (New York: Bantam Books, 1987).

21 For a good overview of mindfulness-based clinical interventions and the empirical results 

of clinical studies of these interventions, see Ruth A. Baer, “Mindfulness Training as a 

Clinical Intervention: A Conceptual and Empirical Review,” Clinical Psychology: Science 

and Practice 10, no. 2 (Summer 2003), 125–143; and K.W. Brown et al., “Mindfulness: 

Theoretical Foundations and Evidence for its Salutary Effects,” Journal of Clinical Psychology

18, no. 4 (2007), 211–237. For studies that focused especially on stress symptoms and 

mood disturbance, see M. Speca et al., “A Randomized, Wait-list Controlled Clinical Trial: 

The Effect of a Mindfulness Meditation-Based Stress Reduction Program on Mood and 

Symptoms of Stress in Cancer Outpatients,” Psychosomatic Medicine 62 (2000), 613–622; 

and Kirk Warren Brown and Richard M. Ryan, “The Benefits of Being Present: Mindfulness 

and Its Role in Psychological Well-Being,” Journal of Personality and Social Psychology 84, 

no. 4 (2003), 822–848, especially the fifth study.

22 Richard J. Davidson et al., “Alterations in Brain and Immune Function Produced by 

Mindfulness Meditation,” Psychosomatic Medicine 65, no. 4 (2003), 564–570. 

23 Field Manual 6–22, Army Leadership (Washington, DC: Headquarters Department of the 

Army, October 2006), section 10–48.

24 Field Manual 3–24, Counterinsurgency (Washington, DC: Headquarters Department of the 

Army, December 2006), 1–22.

25 R.M. Ryan and E.L. Deci, “Self-determination Theory and the Facilitation of Intrinsic 

Motivation, Social Development and Well-being,” American Psychologist 55 (2000), 68–78; 

Brown and Ryan, 822–848.

26 Benjamin Libet, “Do We Have Free Will?” Journal of Consciousness Studies 6, no. 8–9 (1999), 47–57.

27 Joshua Grant, “Pain Perception, Pain Tolerance, Pain Control, and Zen Meditation,” 

presentation at the Mind and Life Summer Research Institute, June 5, 2007.

28 Brown and Ryan, 822–848.

29 Stephen Peter Rosen, War and Human Nature (Princeton: Princeton University Press, 2005), 127.

30 Raja Parasuraman, The Attentive Brain (Cambridge: MIT Press, 1998).

31 M.I. Posner, “Orienting of Attention,” Quarterly Journal of Experimental Psychology 32, no. 1 

(1980), 3–25.

32 J.M.G. Williams, A. Mathews, and C. MacLeod, “The Emotional Stroop Task and 

Psychopathology,” Psychological Bulletin 120, no. 1 (1996), 3–24.
2789 Bio-IInspired IInnovation and ovation and NNational SSecurity 

33 M.I. Posner and S.E. Peterson, “The Attention System of the Human Brain,” Annual Review 

of Neuroscience 13 (1990), 25–42.

34 Jeremy R. Gray et al., “Neural Mechanisms of General Fluid Intelligence,” Nature 

Neuroscience 6 (2003), 316–322.

35 E.R. Valentine and P.L.G. Sweet, “Meditation and Attention: A Comparison of the Effects 

of Concentrative and Mindfulness Meditation on Sustained Attention,” Mental Health, 

Religion, and Culture 2 (1999), 59–70; Jha et al. 

36 Sara Lazar et al., “Meditation Experience Is Associated with Increased Cortical Thickness,” 

NeuroReport 16 (2005), 1893–1897. Because this study was not longitudinal in design, it 

could not control for preexisting differences in brain structure; nonetheless, its suggestive 

findings argue for the need for further research. 

37 Heleen Slater et al., “Mental Training Affects Distribution of Limited Brain Resources,” PLoS 

Biology 5, no. 6 (2007), e138. 

38 Brown et al., “Mindfulness: Theoretical Foundations,” 9, in unpublished manuscript; 

J.M.G Williams et al, “Mindfulness-based Cognitive Therapy Reduces Over-general 

Autobiographical Memory in Formerly Depressed Patients,” Journal of Abnormal Psychology

109 (2000), 150–155; C.N. Alexander et al., “Transcendental Meditation, Mindfulness, 

and Longevity: An Experimental Study with the Elderly,” Journal of Personality and Social 

Psychology 57 (1989), 950–964.

39 T.D. Borkovec, “Life in the Future Versus Life in the Present,” Clinical Psychology: Science 

and Practice 9 (2002), 76–80.

40 C.E. Lakey et al., “The Role of Mindfulness in Psychological Gambling,” unpublished 

manuscript (2006), cited in Brown et al., “Mindfulness: Theoretical Foundations.”

41 Army Leadership, section 6–3.

42 Brown et al., “Mindfulness: Theoretical Foundations,” 29; Lisbeth Nielsen and Alfred 

W. Kasniak, “Awareness of Subtle Emotional Feelings: A Comparison of Long-Term 

Meditators and Non-meditators,” Emotion 6, no. 3 (2006), 392–405; J.J. Arch and M.G. 

Craske, “Mechanisms of Mindfulness: Emotion Regulation Following a Focused Breathing 

Induction,” Behavior Research and Therapy 44 (2006), 1849–1858; J. David Cresswell et al., 

“Neural Correlates of Mindfulness during Affect Labeling,” draft manuscript, 2006.

43 Counterinsurgency, 1–27.

44 Daniel Goleman, Emotional Intelligence (New York: Bantam Books, 1996); David Abrams, 

“Emotional Intelligence and Army Leadership: Give It to Me Straight!” Military Review

(March-April 2007), 86–93.

45 Michael R. Gordon, “Army Expands Training for Advisors Who Will Try to Improve Iraq’s 

Security Forces,” The New York Times, November 25, 2006; email communication with 

advisory team leader MAJ J.R. Deimel, USA, January 3, 2007.

46 John Welwood, Love and Awakening (New York: HarperCollins, 1996).

47 It is important to note that even when a high degree of mindfulness has been developed, 

actual training in communication, listening, and perspective taking skills is often helpful 

(or depending upon the person, even necessary) for improved social interaction abilities. 

However, mindfulness can dramatically increase the retention and utilization of such skills. 

48 Sylvia Boorstein, Transpersonal Psychotherapy (Albany: State University of New York Press, 1996).

49 Richard J. Davidson and Anne Harrington, eds., Visions of Compassion: Western Scientists 

and Tibetan Buddhists Examine Human Nature (New York: Oxford University Press, 2002).

50 L. Tickle-Degnan and R. Rosenthal, “The Nature of Rapport and its Nonverbal Correlates,” 

Psychological Inquiry 1 (1990), 285–293; Baer et al.; Brown and Ryan, 822–848. Because this 

body of research is largely built on self-report questionnaires, taking these studies at face 
Neuroplasticity, Mind Fitness, and Military Eff ectiveness 279

value may be problematic. To some degree, asking individuals without mindfulness training 

to assess their level of mindfulness is asking them to do something they cannot do. 

51 J. D. Cresswell, N.I. Eisenberger, and M.D. Lieberman, “Neurobehavioral Correlates of 

Mindfulness during Social Exclusion,” unpublished manuscript (2006), cited in Brown et al., 

“Mindfulness: Theoretical Foundations.”

52 There is a large constructivist literature that elaborates on this point. See, for example, James 

A. Aho, The Things of the World: A Social Phenomenology (Westport, CT: Praeger, 1998), 

and Peter L. Berger and Thomas Luckmann, The Social Construction of Reality (New York: 

Anchor Books, 1966).

53 Brown and Ryan, 822–848.

281

At the beginning of the 21st century, we find ourselves in a technological 

revolution that is changing our lives as much as the Industrial 

Revolution did in the late 18th century. Our revolution started in the 

late 1980s as personal computers started to become household items and is 

now in full force as broadband Internet is also widely available. However, a 

next qualitative step is about to occur and it is being triggered by advances 

in very-large-scale integration fabrication and design, which resulted in the 

availability of low-cost, low-power, small computational elements that are able 

to communicate wirelessly. In addition, advances in micro-electromechanical 

systems are producing solid-state sensors and actuators. The net result is 

inexpensive computation and ubiquitous embedded sensing, actuation, 

and communication, which provide tremendous opportunities for societal 

impact, but also present great challenges in the design of networked systems. 

Although both the scientific community and industry have recognized the 

possibilities enabled by these advances and are starting to plan and build truly 

large-scale systems, appropriate design methods are lacking.

In broader terms, for the large-scale networked systems that are 

appearing to fully realize their potential, a logical and systematic approach to 

the analysis and design of such systems needs to be developed. Moreover, 

this approach should strive for laws that are generalizable to broad classes of 

systems and thus permit transfer of knowledge across domains. What we just 

described constitutes a science, specifically a network science.

In this chapter, we discuss how large-scale networks that arise in 

biological systems can make significant contributions to the development of a 

network science, not only by serving as a subject matter to exercise and validate 

chapter 19

Bio-inspired Network Science

João Hespanha and Francis Doyle III
2823 Bio-IInspired IInnovation and ovation and NNational SSecurity 

new analytical tools, but also by providing inspiration for the development of 

new methodologies and architectures to design artificial networks. 

We start by focusing our attention on biochemical networks that 

express complex interactions between the chemical species that regulate 

cell behavior. While such networks are characterized by great uncertainty at 

the level of individual components, they typically exhibit levels of aggregate 

robustness that are unmatched by comparable engineered systems. In addition 

to enabling fundamental contributions for the development of a network 

science, the study of biochemical networks has the potential for a tremendous 

impact in medicine. 

We also discuss the biological networks formed by groups of 

individuals engaged in activities that benefit from a group effort. We focus 

our discussion on activities that involve motion coordination, falling under 

the generic term of “swarming.” Biological swarms typically achieve tight 

motion coordination by relying only on “noisy” local interactions between 

individuals. Understanding the design principles behind this feat will enable 

the design of large-scale artificial networked systems. 

Biochemical Networks 

As with engineering networks, biophysical networks are remarkably diverse, 

cover a wide spectrum of scales, and inevitably are characterized by a range 

of complex behaviors. These networks have attracted a great deal of attention 

at the level of gene regulation, where dozens of input connections may 

characterize the regulatory domain of a single gene in a eukaryote, as well as 

the protein level where literally thousands of interactions have been mapped 

in so-called protein interactome diagrams that illustrate the potential coupling 

of pairs of proteins.1, 2 However, these networks also exist at higher levels, 

including the coupling of individual cells via signaling molecules, the coupling 

of organs via endocrine signaling, and ultimately the coupling of organisms 

in ecosystems. To elucidate the mechanisms employed by these networks, 

biological experimentation and intuition are by themselves insufficient. The 

field of systems biology has laid claim to this class of problems, and engineers, 

biologists, physicists, chemists, mathematicians, and many others have united 

to embrace these problems with interdisciplinary approaches.3

 In this field, 

investigators characterize dynamics via mathematical models and apply 

systems theory with the goal of guiding further experimentation to better 

understand the biological network that gives rise to robust performance.4

An ideal example of such networked biological complexity is the 

circadian clock, which coordinates daily physiological behaviors of 

most organisms. The mammalian circadian master clock resides in the 
Bio-inspired Network Science 283

suprachiasmatic nucleus (SCN), located in the hypothalamus.5 It is a 

network of multiple autonomous noisy oscillators, which communicate via 

neuropeptides to synchronize and form a coherent oscillator.6, 7 At the core of 

the clock is a gene regulatory network in which approximately six key genes 

are regulated through an elegant array of time-delayed negative feedback 

circuits. The activity states of the proteins in this network are modulated 

(activated/inactivated) through a series of chemical reactions including 

phosphorylation and dimerization. These networks exist at the subcellular 

level. Above this layer is the signaling that leads to a synchronized response 

from the population of thousands of clock neurons in the SCN. Ultimately, 

this coherent oscillator then coordinates the timing of daily behaviors, such as 

the sleep/wake cycle. Left in constant conditions, the clock will free-run with 

a period of only approximately 24 hours such that its internal time, or phase, 

drifts away from that of its environment. Thus, vital to a circadian clock is its 

ability to entrain to external time through environmental factors.8, 9, 10

A second example is the apoptosis network in which an extracellular 

input “controls” the response of the cell as a result of this information 

processing network. (Apoptosis is the process of “programmed cell death,” 

machinery that nature uses to strategically kill off unneeded cells. However, 

this mechanism becomes impaired in cancer, leading to unchecked 

proliferation.) The specific example employed here details the response of 

kidney cells to exposure to staphylococcal enterotoxin B (SEB), a problem 

of particular interest to the military. Understanding apoptosis in a broader 

sense will lead to a better knowledge of the common platform for emergence 

of cancer cells, and perhaps point to possible cures for certain types of cancer. 

The complexity of apoptosis, however, makes the understanding very difficult 

without a systems level approach using a mathematical representation of the 

pathway. Further, analysis of an apoptosis model can reveal the fragility points 

in the mechanism of programmed cell death that can have physiological 

implications not only for explaining the emergence of cancer cells but also for 

designing drugs or treatment for reinstating apoptosis in these cells.

Biological Inspiration for Engineered Networks 

Biological networks offer a number of opportunities for inspired design of 

engineering networks. Aside from the overlapping computational toolkit 

(for example, simulation methods for high-dimensional, stochastic, stiff, 

multiscale systems), there are numerous behaviors in biological networks that 

offer promise for improved communications and sensors networks. Given the 

space constraints, we highlight only a few of them here.11
2845 Bio-IInspired IInnovation and ovation and NNational SSecurity 

The coexistence of extreme robustness and fragility constitutes one 

of the most salient features of highly evolved or designed complexity. 

Optimally, robust systems are those that balance their robustness to frequent 

environmental variations with their coexisting sensitivity to rare events. As a 

result, robustness and sensitivity analysis are key measures in understanding 

and controlling system performance. Robust performance reflects a relative 

insensitivity to perturbations; it is the persistence of a system’s characteristic 

behavior under perturbations or conditions of uncertainty. Measuring the 

robustness of a system determines the behavior (the output or performance) as 

a function of the input (the disturbance). Formal sensitivity analysis allows the 

investigation of robustness and fragility properties of mathematical models, 

yielding local properties with respect to a particular choice of parameter 

values. Natural systems have honed the robust performance characteristics 

over millennia of evolutionary pressure, and consequently have achieved 

levels of performance unrivaled in engineering networks. 

Synchronization is manifested in natural circuits in, among other 

ways, the coherent response of an ensemble of otherwise noisy components. 

There are a number of examples of this behavior in neuronal systems, most 

notably the coherence in circadian timekeeping achieved by cells in the 

suprachiasmatic nucleus.12 The remarkable feature of these cells is that their 

individual characteristics are remarkably diverse, with individual periods 

ranging from 21 to 26 hours; moreover, a given cell may exhibit fluctuations 

in the period of its firing rate from 2 to 10 hours between consecutive cycles. 

Despite this huge range of “component tolerances,” the intact signaling 

network is able to reduce this dispersion by over an order of magnitude in 

timekeeping precision. By contrast, engineering networks are built from 

high precision components, yet often struggle with network performance 

characteristics such as time synchrony.13

The Role of Networks for Medical Applications 

Systems biology is driving the interdisciplinary approach to unraveling 

design principles in complex biological networks. From a basic research 

perspective, the field has revolutionized thinking about networks as opposed 

to components, and how the coordinated actions in a network must be 

understood in order to unravel the principles involved in a particular 

phenotype, such as a disease state.

The medical driving forces include the identification of “targets” in the 

network for therapeutic intervention. A “systems” analysis reveals that a single 

point perturbation is often less effective than a vectoral perturbation, and at 

the same time, a point perturbation will often propagate beyond the intended 
Bio-inspired Network Science 285

action, leading to undesirable side effects. Systems methods are also applied 

to these networks to determine “signatures,” or markers, of the propagation 

of a disease state. For example, the temporal progression of the SEB-induced 

response in the network could be tracked by gene expression profiling, and 

one can determine the time course of the response and apply appropriate 

therapy at the optimal point in the disease progression. 

The size and complexity of cellular networks make intuition inadequate 

for deducing cellular behavior from the underlying gene and protein 

interactions. Systems analysis can help to unravel this complexity. One such 

method is sensitivity analysis,14 in which linear sensitivities quantify how 

much the system behavior changes as the parameters are varied. In cellular 

networks, high sensitivities point to the weakest links in the system that cellular 

behavior strongly depends on. Perturbations on these links can potentially 

lead to a large disruption in the network behavior—that is, the network is not 

robust to the uncertainty in these pathways. By mapping critical pathways 

back to the genome, one can point to the set of genes and interactions that 

controls the cellular behavior. Such information can be used for guiding datafitting and model refinement in the reverse-engineering of cellular networks.

These hot spots (or fragile nodes) have several implications. First, 

further model refinements on the hot spots in the network may be necessary. 

Second, when the model is sufficiently accurate, the differences between the 

analysis with and without SEB treatment can have physiological relevance and 

provide the candidate pathways in the network for targeted detection and/or 

therapy of the SEB toxin response. 

Swarms 

Coordinated motion is commonly observed in flocks of geese, schools of 

sardines, herds of wildebeests, and packs of wolfs. The emergence of these 

complex behaviors indicates that coordinated motion can provide a significant 

evolutionary advantage that outweighs the costs incurred by the individuals 

in developing a swarming behavior.

Migratory birds such as ducks, geese, and pelicans provide the best 

example of motion coordination. Especially in long-range migrations, these 

birds fly in a V-shaped formation with a bird in the lead and the remaining 

birds trailing behind in two straight lines. Several hypotheses have been 

proposed to explain what benefits can be drawn from this flying formation. 

There is widespread consensus that it can improve aerodynamic efficiency, 

but it has also been noted that this formation can optimize the visual contact 

between the individual members. Energy savings arise as a trailing bird uses 

the wingtip vortices of the bird ahead to gain lift. These types of vortices 
2867 Bio-IInspired IInnovation and ovation and NNational SSecurity 

generally increase drag for the wing that produces them, resulting in less 

efficient flight. However, they also create upwash regions that essentially 

provide free lift to a second wing flying behind. This extra lift allows a trailing 

bird to flap its wings less often and less hard, meaning that its muscles do not 

work as hard and its heart rate drops. It has been theoretically shown that the 

increased aerodynamic efficiency of formation flight can allow 25 birds to 

increase their range by about 70 percent as compared to a bird flying alone.15

These predictions have been experimentally validated on several bird species. 

For example, great white pelicans show an energy savings of as much as 11 

to 14 percent when flying in the vortex wake generated by another bird.16 In 

addition to energy savings, V-shaped formations also improve visual contact 

between individuals, and evidence exists of some agreement between the 

formation structure and the visual anatomy of several bird species.17 Although 

manned aircraft can also exploit the drag-reduction benefits of formation 

flight, this is generally not done because it is difficult to maintain the required 

close formation with current technology. Nevertheless, military aircraft 

squadrons still operate in V formations to maintain visibility in the same way 

that birds do. However, these aircraft formations are generally spaced too far 

apart to enjoy energy savings. 

Fish schooling refers to the synchronized motion of individuals of 

similar size, generally moving in the same direction. It is believed that this 

complex behavior can be observed in over 10,000 species,18 which raises the 

question of what evolutionary mechanisms could be responsible for schooling. 

The most widely accepted hypotheses are related to antipredatory adaption. 

Schooling may have evolved as a “cover-seeking” response, as each individual 

tries to reduce its chance of being caught by a predator.19, 20 According to this 

explanation, schooling may not necessarily benefit the overall population by 

reducing a predator’s success rate, but it may simply arise because natural 

selection may favor individuals that are prone to schooling.21, 22 It has also been 

proposed that schooling evolved as a mechanism to simultaneously improve 

the probability of detecting predators and confuse an attacking predator.23, 24

The hypothesis that schooling evolved as an antipredatory response is 

supported by experimental evidence. For example, guppy populations 

subject to intense predation exhibit a more pronounced schooling behavior, 

and even within the same species, schooling can be more pronounced in 

environments that lack predators.25 Schooling has also been proposed as a 

mechanism by which social individuals gain hydrodynamic advantage over 

solitary ones. This hypothesis has been tested experimentally and supporting 

evidence was found mostly for large predatory species,26 whereas for prey fish, 

antipredatory mechanisms seemed to dominate the formation of schools.27, 28

This dichotomy can be explained by the fact that predatory schools are free 
Bio-inspired Network Science 287

from predation and therefore free to adopt a hydrodynamically efficient 

structure, whereas prey schools may not be.

Challenges Posed by the Network Structure 

One of the key challenges in swarming behavior is the need to coordinate the 

motion of a large number of individuals. In natural swarms this coordination 

typically relies on visual queues and on sensory organs through which an 

individual can perceive vortices created by its neighbors.29 Regardless of the 

sensing mechanism used, individuals are generally only able to monitor the 

motion of a few close neighbors and the overall motion of the swarm must 

emerge from local interactions between neighboring individuals. 

The requirement that the motion of a swarm must emerge from 

distributed control laws that only use local measurements imposes limitations 

on the agility of the swarm and also on how large the swarm can grow. This 

can be understood by analyzing simple distributed control laws by which an 

individual adjusts its heading based on the positions of its neighbors so as to 

achieve synchronized motion. While many such laws can be shown to lead to 

stable flocking behavior,30 a small amount of noise in the local measurement 

can be amplified by the network structure and result in large stochastic 

fluctuations of the individuals.31, 32 This effect is especially noticeable in swarms 

for which the graph that characterizes the interactions between individuals 

resembles a one-dimensional lattice, such as the V-shaped formations 

observed in many species of migratory birds, which never grow very large 

when compared, for example, to three-dimensional fish schools. 

Biological Inspiration from Natural Swarms 

Synchronized motion has numerous applications in engineered systems. 

Formations of spacecraft can provide distributed sensing for gravitational 

field mapping or contemporaneous spatial sampling of atmospheric data, 

whereas formations of aircraft can provide near-simultaneous observations 

of the same science target by instruments on multiple platforms or synthetic 

aperture imagery. Formation control of aircraft also has the potential to 

reduce energy consumption. In addition, many of the algorithms discovered/

constructed to achieve synchronized motion can also be used to accomplish a 

multitude of other tasks ranging from time synchronization to sensor fusion.33

One of the most well known biologically inspired models for swarming 

was introduced for the creation of computer animations of flocking 

behavior.34 This work was eventually granted the Scientific and Engineering 

Award presented by The Academy of Motion Picture Arts and Sciences for 
2889 Bio-IInspired IInnovation and ovation and NNational SSecurity 

pioneering contributions to the development of three-dimensional computer 

animation for motion picture production. The heuristic model was based on 

three rules to govern flocking behavior: cohesion, which causes an individual 

to stay close to nearby flockmates; separation, which prevents collision with 

nearby flockmates; and alignment, which is responsible for matching velocity 

with nearby flockmates. Although a complete analysis of this type of algorithm 

is still unavailable, some of its simplest forms are sufficiently well understood 

to be applied to distributed estimation and control problems.35, 36, 37

The observation that several animal species were able to achieve tight 

motion coordination for very large swarms prompted the search for network 

structures that could be used to overcome stochastic fluctuations caused by 

noise in local measurements. This led to the discovery that in formations 

with interaction graphs that resemble one-dimensional lattices, noise has an 

additive effect and, as the number of individuals grows, distributed control 

laws result in stochastic fluctuations whose variance grows linearly with the 

size of the formation. On the other hand, swarms such as fish schools for which 

the interaction graphs form three-dimensional structures exhibit much more 

favorable noise attenuation properties and simple distributed control laws 

can achieve tight formation control even in the presence of significant noise 

in the local measurements.38, 39 These theoretical results are consistent with 

observations of natural swarms as, although birds in V-shaped formations 

could benefit from ever increasing formation sizes, they never grow as much 

as three-dimensional fish schools.

Notes

1 A.L. Barabasi, “Network Biology: Understanding the Cell’s Functional Organization,” Nature 

Reviews Genetics 5 (2004), 101–113.

2 A.M. Malcolm and L.J. Heyer, Discovering Genomics, Proteomics, and Bioinformatics (San 

Francisco: Benjamin Cummings, 2003).

3 H. Kitano, “Systems Biology: A Brief Overview,” Science 295 (2002), 1662–1664.

4 Ibid. 

5 S.M. Reppert and D.R. Weaver, “Coordination of Circadian Timing in Mammals,” Nature

418 (2002), 935–941.

6 E.D. Herzog et al., “Temporal Precision in the Mammalian Circadian System: A Reliable 

Clock from Less Reliable Neurons,” Journal of Biological Rhythms 19 (2004), 35–46.

7 A.C. Liu et al., “Intercellular Coupling Confers Robustness against Mutations in the SCN 

Circadian Clock Network,” Cell 129 (2007), 605–616.

8 Z. Boulos et al., “Light Visor Treatment for Jet Lag after Westward Travel across Six Time 

Zones,” Aviation, Space, and Environmental Medicine 73 (2002), 953–963.

9 J.C. Dunlap, J.J. Loros, and P.J. DeCoursey, eds., Chronobiology: Biological Timekeeping 

(Sunderland, MA: Sinauer Associates, Inc., 2004).
Bio-inspired Network Science 289

10 S. Daan and C.S. Pittendrigh, “A Functional Analysis of Circadian Pacemakers in Nocturnal 

Rodents. II. The Variability of Phase Response Curves,” Journal of Comparative Physiology

106 (1976), 253–266.

11 For additional details, see the National Research Council, Network Science (Washington, 

DC: National Academies Press, 2005).

12 Herzog et al., 35–46.

13 J. Elson and D. Estrin, “Time Synchronization for Wireless Sensor Networks,” Parallel and 

Distributed Processing Symposium, Proceedings 15th International (2001), 1965–1970.

14 Dunlap, Loros, and DeCoursey, eds.

15 P.B.S. Lissaman and Carl A. Shollenberger, “Formation Flight of Birds,” Science 168, no. 3934 

(1970), 1003–1005.

16 H. Weimerskirch et al., “Energy Saving in Flight Formation,” Nature 413, no. 6857 (2001), 

697–698.

17 John P. Badgerow, “An Analysis of Function in the Formation Flight of Canada Geese,” The 

Auk 105, no. 4 (1988), 749–755.

18 E. Shaw, “Schooling Fish,” American Scientist 66 (1978), 166–175.

19 G.C. Williams, Adaptation and Natural Selection (Princeton: Princeton University Press, 

1966).

20 W.D. Hamilton, “Geometry for the Selfish Herd,” Journal of Theoretical Biology 31, no. 2 

(1971), 295–311.

21 Ibid. 

22 D. Bumann, J. Krause, and D.I. Rubenstein, “Mortality Risk of Spatial Positions in Animal 

Groups: The Danger of Being in the Front,” Behaviour 134, no. 13–14 (1997), 1063–1076.

23 H.R. Pulliam, “On the Advantages of Flocking,” Journal of Theoretical Biology 38 (1973), 

419–422.

24 Douglass H. Morse, “Feeding Behavior and Predator Avoidance in Heterospecific Groups,” 

BioScience 27, no. 5 (1977), 332–339.

25 Benoni H. Seghers, “Schooling Behavior in the Guppy (Poecilia icrosyste): An Evolutionary 

Response to Predation,” Evolution 28, no. 3 (1974), 486–489.

26 Brian L. Partridge, Jonas Johansson, and John Kalish, “The Structure of Schools of Giant 

Bluefin Tuna in Cape Cod Bay,” Environmental Biology of Fishes 9, no. 3–4 (1983), 253–262.

27 B.L. Partridge and T.J. Pitcher, “Evidence against a Hydrodynamic Function for Fish 

Schools,” Nature 279 (1979), 418–419.

28 Mark V. Abrahams and Patrick W. Colgan, “Risk of Predation, Hydrodynamic Efficiency 

and their Influence on School Structure,” Environmental Biology of Fishes 13, no. 3 (1985), 

195–202.

29 T.J. Pitcher, B.L. Partridge, and C.S. Wardle, “A Blind Fish Can School,” Science 194, no. 4268 

(1976), 963–965.

30 R. Olfati-Saber, “Flocking for Multi-Agent Dynamic Systems: Algorithms and Theory,” IEEE 

Transactions on Automatic Control 51, no. 3 (2006), 401–420.

31 P. Barooah and J. Hespanha, “Estimation on Graphs from Relative Measurements: Distributed 

Algorithms and Fundamental Limits,” IEEE Control Systems Magazine 27, no. 4 (2007).

32 P. Barooah and J. Hespanha, “Graph Effective Resistances and Distributed Control: Spectral 

Properties and Applications,” in Proceedings of the 45th Conference on Decision and Control, 

December 2006.

33 Barooah and Hespanha, “Estimation on Graphs from Relative Measurements.”
290 Bio-Inspired Innovation and National Security

34 C. Reynolds, “Flocks, Herds, and Schools: A Distributed Behavioral Model,” ACM 

SIGGRAPH Computer Graphics, published in Computer Graphics 21, no. 4 (1987), 25–34.

35 Olfati-Saber, “Flocking for Multi-Agent Dynamic Systems,” 401–420.

36 Barooah and Hespanha, “Estimation on Graphs from Relative Measurements.”

37 Barooah and Hespanha, “Graph Effective Resistances and Distributed Control.”

38 Barooah and Hespanha, “Estimation on Graphs from Relative Measurements.”

39 Barooah and Hespanha, “Graph Effective Resistances and Distributed Control.”
part five

Implications for the

Department of Defense

293

I

magine that the nation-state of which you are a citizen is at war with 

another. The conflict has gone badly for your country; at times, it seems as 

though your nation’s very survival as a political entity is at stake. Happily, 

your scientists engineer a virus that can be released into the opposing country 

that will temporarily disable anyone it infects. It is short lived, and should not 

spread beyond the borders of that nation, perhaps barely even beyond the 

capital region where it will be released. You fully expect the virus to completely 

decimate the command and control infrastructure of your adversary for 

several days and destroy almost all the biological neural nets responsible for 

decisionmaking in the enemy’s autonomous tank brigades. One downside: 

it causes permanent blindness in 40 percent of the people it infects. Do you 

release the virus into the capital city?

Picture a second scenario. Your nation is combating a deadly insurgency. 

The guerrillas are as indiscriminate as terrorists come, killing innocents at a 

whim. While you expect this behavior will eventually cause their movement 

to collapse, their charismatic leader is holding things together in the short 

term, and the guerrillas have holed up for the winter in a series of valleys. You 

know that, in anticipation of the bad weather, the insurgents have stockpiled 

the wheat they will need to survive the season. That grain is the favorite food 

of a kind of weevil, and your ecologists recommend you seed the weevil—a 

species not native to this biome—into the valley in order to decimate the 

wheat stockpiles and force the insurgents into the cities, where you will better 

be able to confront them. You will take some risks, among them the possibility 

of not being able to control the spread of the weevil. On the other hand, if 

you do not act, you are fairly certain that the insurgency will kill thousands 

chapter 20

Ethics and the Biologized 

Battlefield: Moral Issues 

in 21st-century Conflict

William D. Casebeer
2945 Bio-IInspired IInnovation and ovation and NNational SSecurity 

more innocent people, as you have intelligence indicating that, owing to their 

apocalyptic beliefs, they may have a dirty bomb under development that they 

would be willing to use in case of imminent defeat. Do you introduce the 

weevils into the valley’s ecosystem?

A third case. Biological augmentation has become more common. 

Soldiers of other countries routinely use designer drugs and genetic 

enhancements to increase their combat efficiency. Your nation has decided 

to heavily regulate the use of everything from “super pep pills” that obviate 

the need for sleep for weeks, to genetically tailored enhancements that boost 

memory and recall and can produce mental giants capable of thinking clearly 

in times of combat stress. You hope that by regulating these developments 

you can set an example for other countries that will prevent a biological 

augmentation arms race. However, your soldiers—involved in stabilization 

and reconstruction operations in another country far away, and stretched to 

the limit with a theater-wide humanitarian intervention in another region—

ask (actually, demand) that the government release some of these drugs and 

therapies for use in contingency circumstances. To do so will short-circuit 

standard safety testing and present multiple risks such as addiction and the 

need for post-military treatment, but you know that giving in will help out 

dramatically in the short term, even if it would mean violating a combat 

pharmacology protocol ratified by Congress 3 years ago that prohibits the use 

of many of the enhancements. Do you give in to the demands of your soldiers?

These are difficult cases posing challenging questions. At first glance, they 

may seem unanswerable. But even as the biological sciences—widely thought 

to be the king of 21st-century science in the wake of physics’ domination of the 

20th—simultaneously enhance and undermine our ability to answer normative 

questions, we have on hand at least some of the ethical tools required to reason 

well about what we ought to do in these circumstances. While the biologized 

battlefields of this century will present moral and ethical complications, they are 

not ones for which we are “at sea” when it comes to general guidelines. Exactness 

in ethics may be too much to ask, but by reasoning well together we will be able 

to rate some answers to these pressing moral questions as “beyond the pale” or 

“poor,” others as at least “acceptable,” and some as “very good.” The introduction 

of these technologies and techniques complicates our decisionmaking, but 

will drive home one general trend in the morality of the professionalized use 

of violence: it is becoming more important that we equip individual soldiers 

at the lowest ranks with the cognitive kit they will need to be able to think 

comprehensively about what they can and cannot do, about what kinds of people 

they ought to be, and what kinds of outcomes they ought strive to produce.

In this chapter, I will discuss some traditional moral reasoning tools—

ethical theories—that produce general guidance for questions about what we 
Moral Issues in 21st-century Conflict 295

ought to do. After reviewing how some of the big-picture moral distinctions 

such as that between combatant and noncombatant will be blurred by the 

biologized battlefield, I will briefly discuss how the questions posed and 

tentatively answered by these theories interact with the circumstances of 

the brave new world of biowarfare to make it even more important that we 

produce individual soldiers with sound moral reasoning. New circumstances 

may also require that we modify or reject previous answers to questions on 

the regulation of violence, such as those supplied by the traditional just war 

theory. The rapid pace of evolution in the biologized battlefield heightens the 

importance of pushing down responsibility for sensible moral judgment to 

the line soldier. This is where it has always ultimately resided, and biowarfare 

is merely clarifying.

Basics of Ethical Theory 

Ethical questions are normative questions. They deal with what we ought 

to do, what is permitted in good and right thought and conduct, and what 

kind of people we ought to be. Humans have struggled with these questions 

for millennia. A useful beginning to any question of morality might then be 

to look at the three grand traditions of ethical theory for assistance: virtue 

theory, deontology, and utilitarianism. These theories deal with three different 

aspects of moral questions. The first tackles the person taking an action; the 

second focuses on the nature of the action being taken; the third highlights 

the consequences of the action. All but the most adamant partisans of a 

particular approach to moral theory can agree that, at least for heuristic value, 

these three traditions have thrived because they focus attention on ethical 

aspects of a situation that we might otherwise be prone to ignore. Here, then, 

are thumbnail sketches of each approach. It is important to note that these 

are secular ethical theories that assume no particular position about religious 

metaphysical questions. Given the plurality of religious views in the world, and 

the prevalence of natural law reasoning in the Western tradition (which points 

out that the use of reason can lead you to the same moral truths revealed by the 

normative aspects of the great faith traditions), contemporary applied ethicists 

generally set aside what are called “divine-command theories” of morality. 

Virtue theorists, such as the Greek philosophers Plato (427–347 BCE)1

and Aristotle (384–322 BCE),2 make paramount the concept of “human 

flourishing”: to be maximally moral is simply to function as well as one can 

given one’s nature. This is a practical affair that involves the cultivation of 

virtues such as wisdom, and the avoidance of vices such as intemperance. 

Deontologists, exemplified by the Prussian philosopher Immanuel Kant 

(1724–1804),3

 do not place emphasis upon the consequences of actions, as 
2967 Bio-IInspired IInnovation and ovation and NNational SSecurity 

utilitarians would, or on the character of people, as a virtue theorist would. 

Instead, they focus on the maxim of the action, the intent-based principle that 

plays itself out in an agent’s mind. We must do our duty as derived from the 

dictates of pure reason and the “categorical imperative” for duty’s sake alone. 

Deontologists are particularly concerned to highlight the duties that free and 

reasonable creatures (paradigmatically, human beings, but potentially any 

creature that can be shown to possess a free will that can be “conditioned” by 

the dictates of reason) owe to one another. Maximizing happiness or cultivating 

character is not the primary goal of this scheme; instead, ensuring that we 

do not violate another’s rights is paramount. The typical utilitarian, such as 

British philosopher John Stuart Mill (1806–1873),4

 thinks one ought to take 

that action or follow that “rule” that, if taken (or followed) would produce 

the greatest amount of happiness for the largest number of sentient beings 

(where, by happiness, Mill means the presence of pleasure or the absence of 

pain). The second flavor of utility we just described, “rule utilitarianism,” is 

probably the most popular.

For any given biowarfare development, we can ask: Would developing 

and implementing this technology corrupt our character or somehow make 

us dysfunctional as human beings? Would it constitute a rights violation 

or somehow lead to disrespect for human dignity and autonomy? Would 

it produce bad results in terms of increasing net unhappiness among the 

world’s sentient creatures in the long run? These questions of virtue, duty, and 

consequence lay at the heart of moral reasoning.

One brief aside: there is insufficient space in this chapter to discuss and 

dismiss two alternatives to the moral worldview. One says that attempting 

to answer questions like these is silly, as every answer is equally good. This 

“moral relativism” is not a useful approach to decisionmaking, as it offers 

no advice regarding what one ought to do since any decision is as good as 

any other. That you are bothering to read this chapter indicates that you 

are concerned about making good decisions in the biowarfare realm and is 

good enough reason to dismiss moral relativism as a serious approach to 

normative questions. The other alternative is a radical realism, which says 

that, especially in warfare, moral questions have no place and nations are free 

to do what is in their unenlightened interest. If this means killing innocents in 

wartime, not worrying about the long-term ecological impact of a bioweapon, 

or freely using your own citizen-soldiers as mere tools by engineering their 

genome even against their wishes, then so be it. All is permitted in this view 

of nature. This other nihilist alternative is equally implausible. To consider 

moral prohibitions and obligations on the conduct of both war and peace, 

then, is a reasonable approach that allows us to steer between these extremes 

of relativism and nihilism.
Moral Issues in 21st-century Conflict 297

These moral theories themselves underpin several distinctions that 

have proven useful in the history of warfare, such as that between combatant 

and noncombatant. For utilitarian reasons, it is useful to distinguish between 

those contributing to the war effort and those who are not. At the very least, 

harming those not involved in actually inflicting violence upon others would 

be a waste of resources that could otherwise be channeled toward actually 

winning the war. More robustly, ensuring that the war is ended in a manner 

appropriate to reestablishing a long-term peace requires discrimination—

that is, telling the difference between combatants and noncombatants. 

Otherwise, you set yourself up for a continuation of the violence later. From 

a deontic view, it is easy to see why the combatant/noncombatant distinction 

is justified. People have a right, and we have a corresponding duty to respect 

that right, not to be treated merely as a means to an end. Killing an innocent 

person is a canonical example of that violation of the “categorical imperative,” 

the demands that duty makes upon us as a result of our natures as free and 

rational creatures. In this view, innocent people such as noncombatants have 

a right to not be killed even if doing so would end the war sooner. Finally, 

from a virtue-theoretic perspective, the just and virtuous person would harm 

only those who deserve to be harmed—the guilty or, in the context of war, 

combatants. So, one important wartime distinction has its roots in all three 

moral theories. They each justify a combatant/noncombatant distinction in 

their own way.

The three major Western approaches to morality support and undergird 

other aspects of the justice of war as well. While it is beyond the scope of this 

chapter to explore just war theory and its connections to morality in any 

detail, a brief primer on the theory will help set the stage for the next section 

of the paper.

Jus ad bellum (“the justice of the war”) considerations govern when one 

can begin to wage a war in a morally permissible manner. Traditionally, there 

are seven tenets of jus ad bellum:

5

• Just cause: The purpose must be the preservation and protection of 

value, such as defending the innocent, punishing evil, or reclaiming 

wrongly taken property.

• Right authority: The agent authorizing the use of force must be the 

representative of a sovereign body.

• Right intention: The intent must accord with the just cause; the war must 

not be fought for territorial aggrandizement or out of bloodlust.

• Proportionality of ends: The net good achieved by the war must outweigh 

the net harm caused by waging it.

• Last resort: No other means are available to achieve the ends sought.
2989 Bio-IInspired IInnovation and ovation and NNational SSecurity 

• Reasonable hope of success: There must be a good chance that the means 

used will actually achieve the ends sought.

• Aim of peace: We should strive to end the war in a fashion that will 

restore security and the chance for peaceful interaction.

Of course, we should not think of these considerations as an absolute 

checklist, as there may very well be wars that fail to meet a few of the tenets 

but that are nonetheless just. These guidelines are distillations of the practical 

experience of those concerned about beginning wars in a morally permissible 

and hopefully morally praiseworthy fashion and are not intended to be an 

unquestionable list of necessary and sufficient conditions for the morality of war. 

There are two traditional tenets of jus in bello (“justice in the war”) that 

govern the conduct of operations that take place while the war is being waged:

• Proportionality of means: Acts causing gratuitous or unnecessary harm 

are to be avoided; the good achieved by a particular means should 

outweigh the harm done by employing it.

• Noncombatant protection (“discrimination”): Direct harm to 

noncombatants should be avoided; efforts should be taken to protect 

noncombatants.

Generally, considerations of jus ad bellum and jus in bello do not interact. 

That is, if you are waging an unjust war from the ad bellum perspective, this 

does not mean that you are “cleared hot” to violate the in bello tenets (indeed, 

what excuse could you have for not following them given that the war you are 

waging is itself unjust?). Conversely, the fact that you are waging a just war 

does not give you permission to wage it in an unjust manner (although see 

Michael Walzer’s interesting identification of a possible exception to this rule 

that he captured in 1977 with his doctrine of “supreme emergency,”6

 the name 

of which was originally articulated by Winston Churchill in World War II).

These just war considerations do more than summarize the thoughts 

and practices of those involved in waging war in an ethical manner. In many 

respects, they have close connections to the general moral theories we all use 

at one point or another to help us reason about what we ought to do or how 

we ought to behave. 

There are other moral distinctions in warfare that are driven by recognition 

of the seeds of moral truth contained in all three of these traditional approaches 

to ethics. The next section of this chapter discusses how the evolving biological 

battlefield might influence just war theory and these critical distinctions.
Moral Issues in 21st-century Conflict 299

The Evolving Biological Battlefield 

As the scope of the volume you hold in your hands reveals, the use of 

biotechnology in the controlled application of violence will further complicate 

what is an already complicated battlefield environment. Biotechnology offers 

the promise of spurring technological advances in everything ranging from 

efficient use of energy, self-repairing armor, genetically enhanced soldiers, 

bio-engineered weapons, adaptive camouflage, autonomous and semiautonomous battlefield agents, combat medical advances, and the like. 

Reviewing the moral upshot of each of these technologies in turn would take 

far too long. Instead, in this section, I highlight some general features of these 

developments that have moral and ethical upshots.

Many of these technologies will be perfectly orthogonal to moral 

considerations: that is, their use and development will have no particularly 

unique ethical implications. For example, the development of a new kind of 

pistol that has a slightly longer range probably offers no unique moral issues. 

However, the development of a weapon that could kill instantly from halfway 

around the world would spur unique moral questions (for example, on the 

battlefield, soldiers are thought of as being moral equals in the sense that they 

expose themselves to the same risks and dangers while waging war. If soldiers 

do not have to expose themselves to these same risks, do they then lose some 

of the unique moral protections offered to soldiers in wartime?). In general, 

the technologies discussed in this book break down or make more problematic 

the distinction between combatant and noncombatant, accelerate the observeorient-decide-act (OODA) loop for moral decisionmaking, boost the chances 

of unintended consequences, offer a new suite of tools for warfighters that 

lowers the moral obligation to not use force in some circumstances but raises 

it in others, and pose fundamental questions about changing the nature of 

what it means to be human. I will discuss each of these in turn.

The combatant/noncombatant distinction is justified by the three major 

moral theories discussed earlier. Observing it on the battlefield is conducive 

to the greater good (utilitarianism), respects the obligations we have to 

bearers of rights (deontology), and makes us better human beings (virtue 

theory). It is probably the most important of the in bello aspects of just war 

theory. Biologized battlefields complicate this distinction both by breaking 

it down and by making it more difficult to distinguish between combatants 

and noncombatants when there is a distinction to be made. The combatant/

noncombatant distinction is supported at least in part by considerations 

regarding what it means for someone to be an agent: the kind of creature that 

is autonomous and able to structure its decisions according to the dictates of 

reason. Being free and rational creatures is what gives us “moral standing” 
3001 Bio-IInspired IInnovation and ovation and NNational SSecurity 

in a Kantian deontic worldview, gives us a human dignity that makes us 

bearers of rights, and makes us worthy of a respect. As we invent and deploy 

autonomous agents—for example, a highly autonomous combat tank that is 

driven by a biological neural network—questions of agency will arise. Is a 

tank that can make decisions of its own accord and in conformance with its 

simple logic an agent worthy of some moral consideration, or is it just another 

tool like a pistol? For now, this question may seem merely academic, but in 

the future it will be of critical moral importance. Let us stipulate that at some 

point in the relatively near future, autonomous agents will be given some sort 

of deontic respect—we will think of them in the same way we think, perhaps, 

of children, as being bearers of rights but not possessing full agency (in which 

case we hold the parents fiducially responsible for the actions of the child). 

The presence of children on the battlefield in places such as Africa already 

complicates moral decisionmaking for the line soldier. Imagine what will 

happen if we introduce a third class of agents on the battlefield, one for which 

we have little day-to-day experience making moral judgments about how we 

ought to treat them and who ought to be held responsible for their behavior. 

If we eventually settle on some sort of mechanism for dealing with this new 

class of autonomous creatures, we have the problem of identifying them on 

the battlefield. For human beings, we use uniforms and other markers of 

combatancy status. What will be the equivalent for agents who come in all 

shapes and sizes on the late 21st-century battlefield?

A second complication is related to this first development. Biotechnology 

threatens to accelerate the rate at which we must make important moral 

choices. The literature on how technology, especially the biological sciences, 

accelerates decisionmaking in general is rich and varied. When advances in 

biowarfare are factored in, the problem space enlarges yet again. Is this swarm 

of autonomous agents approaching me merely a flock of birds or a deadly 

assortment of networked micro–unmanned aircraft systems? Does the use of 

a genetically engineered virus with a fast burn-time justify quickly unleashing 

a counter-virus? Battlefield decisions have always been complex and timesensitive—biologized battlefields even more so. Our OODA loops will be 

more compressed, amplifying the challenge of getting inside our adversaries’ 

OODA loop while still making morally defensible decisions.

This highlights a third moral danger for the biologized battlefield: the 

chances of unintended harmful moral consequences resulting from actions 

is far higher in the ecologically complex battlespaces of the 21st century. 

The danger presented by bioweapons in this regard is obvious, and is one 

reason why precursors and analogues to robust biological weapons such 

as pathogenic bacteria have been highly regulated. When dealing with 

ecosystems, especially ecosystems that contain agents (human beings, 
Moral Issues in 21st-century Conflict 301

animals, artificial life forms, sapient autonomous technologies), the chance 

that the introduction of a new technology will have a radically different 

effect than intended increases. For example, it is very difficult to predict the 

consequence that an introduced species will have on the environment. While 

the kudzu vine might have provided nice shade initially, its introduction has 

had a dramatic and unforeseen negative economic impact on southern areas 

of the United States.

A fourth challenge presented by these developments deals with what 

justifies using military force, as opposed to another kind of force, to redress 

wrongdoing. This is not a trivial distinction, as members of the military are 

allowed to use force in a very different manner than are members of a police 

force. In general, military professionals are obligated to use as much force as 

is permitted to achieve their objectives within the general limits set by just 

war theory. Members of a police force, on the other hand, use as little force 

as is required to keep the peace. This is because the contexts in which the two 

different kinds of force are applied is very different, in one case against other 

human beings who are not necessarily citizens of your own nation-state, and 

in another case in a situation where the chances of great harm coming from 

not acting are very different. These facets of what amount of force is required 

will generate conflicting obligations on the biologized battlefield. On the one 

hand, the stakes could be very high—a failure to act quickly might produce 

devastating consequences for humanity, in which case you might be morally 

permitted to use more force than would otherwise be the case to forestall the 

great harm (think of Walzer’s case of supreme emergency). On the other hand, 

biologized battlefields will be extended battlefields in that the arena in which 

the struggle takes place will be fluid and will often overlap with traditionally 

“civilian” areas of concern, in which case you might be obligated to act more 

like a policeman using only minimal nondeadly force than like a soldier looking 

down the barrel of a gun. Of course, these complications are already with us 

even in more traditional forms of warfare; the biologized battlefield merely has 

the potential to greatly complicate the interaction between the harm that is to 

be prevented and the harm allowed to be done in order to prevent it.

On the whole, biological developments will force us to face a final 

existential moral challenge. As our tools and weapons become more like us 

and we more like them, at what point do we refuse to use biotechnology out 

of fear that embracing it will cause us to become something other than we are? 

Questions about the use of genetic enhancement and biological (especially 

neurobiological) augmentation confront these issues explicitly. At what 

point do soldiers become mere tools and, if they are mere tools, what moral 

obligations do we have to them over and above the obligations we owe to, say, 

a screwdriver? When one has finished using a screwdriver, one can put it back 
3023 Bio-IInspired IInnovation and ovation and NNational SSecurity 

into the toolbox. Will engineering, augmentation, and specialization prevent 

me from demobilizing my soldiers at the end of conflict so they can return to 

an otherwise normal human life or an approximation thereof? Worries about 

post-traumatic stress disorder may seem trivial compared to these big-picture 

existential questions that radical biotechnologies will force us to confront. 

This is a question that traditional just war theory has not grappled with in any 

meaningful way.

Whither Ethics and Warfare? 

One response to these developments might be to suggest that we start anew. 

Traditional just war theory and the three major moral theories that underpin 

it are not useful for thinking about these issues (the critic might say). 

However, this reaction would be too quick. While the questions that just war 

theory has us ask traditionally might be too limiting in many circumstances 

(for example, what does the requirement to declare a war mean in a world 

where the primary opponent is a nonstate actor?), the moral theories that 

give shape to jus ad bellum and jus in bello considerations are still very useful 

and applicable. They have been around for hundreds or, in the case of virtue 

theory, thousands of years, and have proven their usefulness in the fields 

of practical action: what ought I to do here, now? Consider the three cases 

introduced at the start of this chapter. We can usefully interrogate all three 

using the major moral theories, drawing upon the resources of just war theory 

where appropriate. What are the utilitarian, deontic, and virtue-theoretic 

aspects of targeted killing? What complications present themselves when we 

start to target the entire system of an adversary and not just fielded military 

forces? What does it mean to be a good human being, let alone a good soldier, 

in the genetically enhanced and cognitively augmented extended battlefield? I 

will not discuss these cases in any detail, as this chapter is intended to serve as 

an invitation to start a moral conversation about the use of these technologies. 

I merely want to point out that it is entirely sensible to dissect these cases 

using traditional tools of moral inquiry, keeping in mind the complications 

and provisos discussed in the last section. 

The Moral Big Picture and the Importance of Individual Judgment 

The development of robust biotechnologies will have a disruptive effect on 

some traditional moral issues in warfare. The lines between war and peace and 

the distinction between combatant and noncombatant will become blurred. 

We will have to make decisions more quickly and with more of a chance that 

the stakes will be very high than in the past. Unintended consequences will 
Moral Issues in 21st-century Conflict 303

be at the forefront of our minds. The moral bar that must be cleared before 

we can apply lethal force will change more often, and more rapidly, than in 

the past, complicating our moral decisionmaking. But the flip side of the 

biologized battlefield also offers moral promise and ethical hope: we may be 

able to prevent grave harms more easily. We might be able to attack problems 

using a police model rather than a military model, preventing the harm that 

accompanies outright war. And at the end of the day, we might be able to 

confront challenges such as cognitive augmentation and genetic enhancement 

in a manner that reaffirms, rather than attacks, our fundamental humanity.

The key to dealing sensibly with the moral challenges of the biologized 

battlefield will be cultivation of good moral judgment at the individual level. 

Perhaps more so than in the past, the strategic corporal, the ethical airman, 

and the sensible seaman will be critically important. Confronting these 

developments in an intelligent and humane way means developing individuals 

of good judgment, with thoughts and sensibilities tutored by our best ethical 

theories, as applied to the new circumstances of war.

Notes

1 Plato, The Republic, trans. Robin Waterfield (New York: Oxford University Press, 1998).

2 Aristotle, Nichomachean Ethics, trans. Terence Irwin (Indianapolis: Hackett Publishing 

Company, Inc., 1985).

3 Immanuel Kant Groundwork of the Metaphysics of Morals, trans. H.J. Paton (San Francisco: 

Harper Torchbooks, 1964).

4 John Stuart Mill, On Liberty and Other Essays (New York: Oxford University Press, 1998).

5 See James Turner Johnson, Morality and Contemporary Warfare (New Haven, CT: Yale 

University Press, 1999), for an enlightening discussion of the nature and origin of these tenets.

6 Michael Walzer, Just and Unjust Wars (Basic Books: New York, 1977).

305

The Biological Weapons Convention (BWC) of 19721

 prohibits the 

development, production, stockpiling, acquisition, or retention of 

“microbial or other biological agents, or toxins whatever their origin 

or method of production, of types and in quantities that have no justification 

for prophylactic, protective or other peaceful purposes.”2 This, in combination 

with the Geneva Protocol of 1925,3 which bans the use of “bacteriological 

methods of warfare,” effectively eliminates an entire class of weapons. The 

United States officially renounced its offensive biological weapons program 

in 1969, but the existence of restrictions and prohibitions in the law can be 

traced back thousands of years. 

In this chapter, I will briefly explore early uses of biological agents in 

warfare, and what, if any, the “legal” response was to those uses. I will then 

examine the present legal regime to help clarify the parameters. Finally, I will 

look at some of the advances in biotechnology and comment on how we may 

be able to move forward without violating our domestic law and international 

treaty obligations.

Historical Overview 

There are indications dating as far back as 1885 BCE that biological agents 

may have been used for nefarious purposes. The Bible indicates that during 

the time of Joseph, the Egyptian Pharaoh employed a cupbearer whose sole 

purpose was to ensure the Pharaoh would not be poisoned.4 Solomon, who 

began his rule in 971 BCE, also employed cupbearers.5

 And Nehemiah, who 

chapter 21

Legal Issues Affecting 

Biotechnology

Joseph Rutigliano, Jr.
3067 Bio-IInspired IInnovation and ovation and NNational SSecurity 

returned to Jerusalem in 444 BCE6 to rebuild the city, was cupbearer to the 

Persian king, Artaxerxes.7 While it is not clear whether a chemical or biological 

substance was the poison of choice, it is not unreasonable to assume a natural 

or biological substance was being used as a poison.

In approximately 1500 BCE, on the Indian subcontinent, the Laws of 

Manu specifically prohibited the use of poison in warfare: “When he fights 

with his foes in battle, let him not strike with weapons concealed (in wood), 

nor with (such as are) barbed, poisoned, or the points of which are blazing 

with fire.”8

 This is the earliest known proscription against the use of biological 

agents that this author could find. The existence of the proscription suggests 

biological warfare, at least in the form of poisons, had been resorted to or, at 

the very least, threatened.

Around 600 BCE, the Athenians are reported to have used biological 

agents by contaminating a stream with a poisonous type of lily root. The 

stream supplied the water for the adversary’s city, and when the inhabitants 

drank the contaminated water, many became ill.9 The Carthaginians 

were also known to use poisons against their enemies. In fact, Hannibal is 

alleged to have catapulted pots of poisonous snakes into enemy ships, and 

other Carthaginian generals poisoned wine before retreating so when their 

adversaries took control of the abandoned property, they would become ill or 

die from drinking the wine.10

In the Middle Ages, use of biological agents continued, sometimes with 

catastrophic effect. For instance, in the 1346 siege of Kaffa on the Crimea, 

Mongol hordes catapulted corpses infected with plague into the city. The 

infected residents fled to Italy as the city fell to the Mongols, and the plague 

subsequently spread throughout Europe, killing an estimated one-quarter of 

the European population.11

In 1763, British troops traded smallpox-infected blankets with 

American Indians. The following year, the Mingoe, Delaware, and Shawanoe 

tribes suffered smallpox epidemics. It has been reported that the British 

troops were under orders to “do well to try to inoculate the Indians by means 

of the blankets, as well as to try every other method that can serve to extirpate 

this execrable race.”12

During the Civil War, Confederate forces forced farm animals into 

ponds where they were shot and left to contaminate the water.13 On the 

Union side, the 20th Maine, commanded by Lieutenant Colonel Joshua L. 

Chamberlain, was quarantined during the battle of Chancellorsville because 

of an epidemic of smallpox. Apparently, poorly prepared serum used to 

inoculate the 20th Maine resulted in the outbreak. Frustrated when General 

Daniel Butterfield refused his request for the 20th Maine to get into the fight, 

Chamberlain said, “If we couldn’t do anything else we would give the rebels 
Legal Issues Aff ecting Biotechnology 307

the smallpox!” General Butterfield, “not too impressed with such a modern 

and devastating conception of warfare,” detailed the 20th Maine to guard a 

telegraph line.14

During World War I, the Germans infected livestock of Allied nations, 

as well as that of neutral nations in an attempt to prevent its sale to the Allies. 

They used anthrax and glanders, an infectious horse bacterium. In addition 

to attacking livestock, the Germans also targeted French cavalry horses and 

mules in Mesopotamia.15

Between World War I and II, Belgium, Canada, France, Great Britain, 

Italy, the Netherlands, Poland, and the Soviet Union reportedly conducted 

experiments with biological weapons.16 During World War II, the infamous 

Japanese Unit 731 developed plague, cholera, and typhoid agents and 

experimented on prisoners of war and Chinese civilians. Although it was 

reported that Japanese use of biological weapons caused approximately 

10,000 casualties among its own troops, including 1,700 dead from cholera,17

Chinese survivors claim that as many as 94,000 people were killed by bubonic 

plague between 1937 and 1945.18 The Japanese also made preparations to use 

biological weapons against U.S. forces and the U.S. mainland. They built a 

bacterial bomb, a defoliation bacilli bomb, weather balloons to reach across 

the Pacific (even sending test balloons as far as South Dakota), and submarinelaunched weapons. Moreover, they made plans to use germ-infected suicide 

troops who would charge advancing U.S. forces in an attempt to infect them.19

While the United States and the Allies never used biological weapons 

during World War II, they did experiment with them. In fact, the United States 

planned to produce 500,000 anthrax bombs per month, and experimented 

with biotoxins for potential use against Japanese crops.20 The United Kingdom 

conducted tests on sheep with anthrax on the Scottish island of Gruinard. 

Because of the stability of the anthrax bacillus, and the fact it can remain 

dormant for up to 100 years, the island remained uninhabitable after the 

experiments.21 In 1986, the British attempted to decontaminate it.22

After World War II, the United States experimented with, and 

developed, biological weapons until 1969, when it formally rejected them.23

In fact, the Pentagon admitted to conducting experiments over San Francisco, 

Minneapolis, St. Louis, Key West, and Panama City, Florida, and more specific 

tests in the New York City subway, at National Airport in Washington, DC, and 

on the Pennsylvania Turnpike. Chemicals designed to simulate the spread of 

the agents rather than actual biological weapons were used. These chemicals 

themselves caused an outbreak of urinary tract infections in San Francisco, 

resulting in one death.24 Although the Soviet Union and other communist 

countries alleged that the United States engaged in biological warfare, none of 

the charges could be substantiated.25
3089 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Ironically, the Soviets did not have the same view toward biological 

agents that the United States developed in 1969, and may have begun a 

biological warfare program as early as the mid-1920s.26 A German assessment 

done during World War II stated that Joseph Stalin officially began a biological 

and chemical weapons program in 1939.27 In the late 1970s, the vice president 

of the Soviet Academy of Sciences began a program to develop biological 

agents using modern biotechnology, including genetic engineering, in order to 

persuade the Ministry of Defense to fund research into genetics and molecular 

biology.28 This program grew to employ over 25,000 scientists and technical 

workers at more than 30 scientific institutes and 5 production plants during its 

peak in the late 1980s. The existence of this particular program was kept secret 

through civilian cover until Boris Yeltsin admitted its existence in 1992.29 This 

program existed even after the Russians became a party to the BWC. 

The Russians continued to pursue development of biological weapons 

until 1992,30 when they agreed to terminate offensive weapons research, 

dismantle experimental technological lines for the production of biological 

agents, and close biological weapons testing facilities. They also agreed to 

cut the number of personnel involved in military biological programs by 

50 percent, reduce military biological research funding by 30 percent, and 

dissolve the department in the Ministry of Defense responsible for the 

offensive biological program, creating in its stead a new department for 

radiological, biological, and chemical defense.31

During the first Gulf War, Iraq deployed but did not use anthrax.32

Iraq did possess Scud missiles armed with biological agents but did not use 

any against Israel.33 After the war, the United Nations Special Commission 

(UNSCOM) documented Iraq’s efforts to acquire weapons of mass destruction 

(WMD), including biological weapons and long-range ballistic missiles 

developed to serve as delivery systems. In fact, UNSCOM reported that 

Iraq had produced large quantities of microbial agents and toxins for use as 

biological weapons.34 The reports made it clear that the Iraqis had developed 

and produced biological weapons systems, including artillery shells, bombs, 

ballistic missiles, rockets, and aerosol spray devices.35 Because of the secrecy 

of Iraq’s WMD program, UNSCOM’s understanding of it is incomplete. Most 

of Iraq’s biological weapons facilities were undamaged during the conflict.36

States are not the only players in the biowarfare realm. Terrorist 

organizations and various cults have been known to be in pursuit of biological 

weapons, or to have actually used them. In 1984, the Rajneeshee cult, in 

an attempt to disrupt local elections, poisoned salad bars in The Dalles, 

Oregon, with salmonella, resulting in over 700 illnesses.37 The Japanese cult 

Aum Shinrikyo, in addition to building its own sarin gas factory capable of 

producing 70 tons,38 developed a biological weapons program that progressed 
Legal Issues Aff ecting Biotechnology 309

to the testing stage for anthrax and botulism.39 Even though they attempted 

to release anthrax on more than one occasion, the cult was unsuccessful for 

a number of reasons. In 1995, U.S. law enforcement authorities caught and 

convicted two members of a Minnesota militia group of planning an attack 

on government officials with ricin.40 Perhaps most worrisome of all is Osama 

bin Laden’s statement that obtaining WMD is a “religious duty.”41 Subsequent 

to the attacks on 9/11, anthrax was used in a number of attacks through the 

U.S. mail, killing 5 people and infecting 17 others. 

Proscriptions of Biowarfare 

The previous discussion demonstrates a consistent pattern throughout the 

ages of a resort to some level of biological warfare. These uses did not go 

unanswered by the international community. For example, the prohibition 

against using poison in the Laws of Manu was part of the code regarding the 

duties and responsibilities of kings.42

The general rule against the use of biological agents existed only in the 

form of customary international law until very recently, when it was codified 

in treaties of the 19th and 20th centuries. Customary international law is 

based on two prongs: the practice of states, and the sense of legal obligation 

on which state practice is based. A continuous line of development can be 

traced from Italian jurist Alberico Gentili (1552–1608) and Dutch jurist 

Hugo Grotius (1583–1645), whom many consider to be the father of modern 

international law, through The Hague Conventions of 1899 and 1907, the 

Geneva Protocol of 1925, and the 1972 BWC.43 This is not to say prohibitions 

were not codified before the Hague Conventions. For instance, during the 

Civil War, President Abraham Lincoln commissioned Dr. Francis Lieber to 

promulgate instructions governing the Union armies.44 The Lieber Code, as it 

has came to be known, stated, “Military necessity does not admit of cruelty—

that is, the infliction of suffering for the sake of suffering or for revenge, nor of 

maiming or wounding except in fight, nor of torture to extort confessions. It 

does not admit of the use of poison in any way, nor of the wanton devastation 

of a district.”45 In Article 70, the Lieber Code makes a strong statement against 

the use of poisons, and for the universal condemnation of such use. It states, 

“The use of poison in any manner, be it to poison wells, or food, or arms, is 

wholly excluded from modern warfare. He that uses it puts himself out of the 

pale of the law and the usages of war.”46

Shortly after the Civil War, there were several treaties and draft treaties 

that specifically addressed the issue of biological warfare. The Declaration of 

St. Petersburg of 1868 stated that the “contracting Parties engage mutually to 

renounce, in case of war among themselves, the employment by their military 
3101 Bio-IInspired IInnovation and ovation and NNational SSecurity 

or naval troops of any projectile of a weight below 400 grammes, which is either 

explosive or charged with fulminating or inflammable substances.”47 The treaty 

stated that “the employment of such arms would therefore be contrary to the 

laws of humanity.”48 This is evidence that there existed as of 1868 a longstanding 

custom of abhorrence toward chemical and, presumably, biological weapons.

In 1874, a conference in Brussels resulted in a declaration concerning the 

law of war, in which it was stated that it was “especially forbidden” to employ 

“poison or poisoned weapons.”49 The Brussels Declaration also reiterated the 

prohibition of using projectiles banned under the St. Petersburg Declaration 

and prohibited the “employment of arms, projectiles or material calculated to 

cause superfluous injury.”50 While the Brussels Declaration was never ratified 

by the countries involved in the negotiation, it laid the groundwork for the 

First International Peace Conference, held at The Hague, in 1899.51 The Hague 

Convention of 1899 provided for the same prohibition against the employment 

of poison or poisoned weapons, as well as forbidding the employment of “arms, 

projectiles, or material calculated to cause unnecessary suffering.”52

Following the Russo-Japanese War of 1905, and at the behest of President 

Theodore Roosevelt, among others, the international community once again 

met at The Hague to address the laws and customs of war. In 1907, one of 

the resulting conventions again set forth the prohibition to employ poison or 

poisoned weapons, as well as limiting the rights of belligerents to adopt means of 

injuring the enemy by prohibiting weaponry “calculated to cause unnecessary 

suffering.”53 These obligations, however, only applied to nations that became a 

party to the convention. In fact, it specifically stated that the convention and 

its annexed regulations “do not apply except between Contracting Powers, and 

then only if all the belligerents are parties to the Convention.”54

Although there had been a string of treaties addressing the use of poisons, 

and containing prohibitions against causing superfluous injury or unnecessary 

suffering, during World War I, Germany used both chemical and biological 

weapons. This resulted in the issue being directly addressed in the Treaty of 

Versailles, which ended World War I. Article 171 of the treaty states: “The use 

of asphyxiating, poisonous or other gases and all analogous liquids, materials 

or devices being prohibited, their manufacture and importation are strictly 

forbidden in Germany.” The same applies to materials specially intended for 

the manufacture, storage, and use of the said products or devices.55

Subsequent to World War I, and before the Geneva Protocol of 1925 

was signed, there were two more documents that addressed the issue of 

biological warfare. In 1922, the United States signed the Treaty of Washington 

regarding the use of submarines and noxious gases. Article V of this treaty 

states the following: 
Legal Issues Aff ecting Biotechnology 311

The use in war of asphyxiating, poisonous or other gases, and 

all analogous liquids, materials or devices, having been justly 

condemned by the general opinion of the civilized world and a 

prohibition of such use having been declared in Treaties to which 

a majority of the civilized Powers are parties, 

The Signatory Powers, to the end that this prohibition shall be 

universally accepted as a part of international law binding alike 

the conscience and practice of nations, declare their assent to such 

a prohibition, agree to be bound thereby as between themselves 

and invite all other civilized nations to adhere thereto.56

This treaty was concluded among the United States, the United Kingdom, 

Italy, France, and Japan, but never entered into effect because France failed to 

ratify it. France’s reasons for not ratifying the treaty had nothing to do with 

Article V quoted above.57 The existence of this treaty, however, among these 

major powers, is a clear indication that the use of chemical and biological 

agents was considered beyond the pale. While asphyxiating, poisonous or other 

gases could be interpreted to mean strictly chemical weapons, all analogous 

liquids, materials or devices could equally well be interpreted to include 

bacteriological agents. 

One year later, five Central American states asserted their agreement 

with this principle by signing a convention wherein the contracting parties 

agreed that “the use in warfare of asphyxiating gases, poisons, or similar 

substances as well as analogous liquids, materials or devices, is contrary to 

humanitarian principles and to international law, and obligate themselves . . . 

not to use said substances in time of war.”58

It must be stated that in the Treaties of Versailles and Washington, as well 

as in the Geneva Protocol of 1925, there is an argument that the prohibitions 

only applied to chemical warfare unless the term all analogous liquids, 

materials or devices could be interpreted to include biological agents. Some of 

the delegates who helped draft the Geneva Protocol thought that was indeed 

the interpretation, although the protocol itself includes the clause, “agree to 

extend this prohibition to the use of bacteriological methods of warfare.”59

The additional language could be interpreted to be a simple restatement of 

the longstanding customary prohibition against biological warfare. It appears 

to this author that use of the word poison would include the use of biological 

agents as well as chemical agents. The bottom line is that whether a biological 

or chemical method was used to poison, say, a water source, it would have been 

considered an insidious and treacherous means of warfare, and a violation of 

all of the treaties and conventions mentioned above.60
3123 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Geneva Protocol of 1925 

The pertinent part of the protocol states:

Whereas the use in war of asphyxiating, poisonous or other gases, 

and of all analogous liquids, materials or devices, has been justly 

condemned by the general opinion of the civilized world; and

Whereas the prohibition of such use has been declared in Treaties 

to which the majority of Powers of the world are Parties; and

To the end that this prohibition shall be universally accepted as 

a part of International Law, binding alike the conscience and the 

practice of nations;

Declare:

That the High Contracting Parties, so far as they are not already 

Parties to Treaties prohibiting such use, accept this prohibition, 

agree to extend this prohibition to the use of bacteriological 

methods of warfare and agree to be bound as between themselves 

according to the terms of this declaration.61

Some interpretations of this language are in order. First, the prohibition 

against the use of chemical and biological agents applies only during war. 

This raises the issue of what war actually means. It would appear that a 

commonsense reading of the language of the protocol indicates that the term 

would mean armed conflict between two or more of the High Contracting 

parties. The language indicates this when it states, “the High Contracting 

Parties . . . agree to be bound as between themselves.” Subsequent treaties also 

indicate that the term war refers to actually declared wars between nations, or 

any other armed conflict that may exist between two or more nations.62 This 

would mean that the Geneva Protocol would not apply to those conflicts not 

of an international character.63

The term “between themselves” also makes clear the prohibition does 

not extend to nations that did not ratify the protocol. While this may be true, 

there is a very strong argument to be made that the prohibition existed in 

the form of customary international law before it was codified in the Geneva 

Protocol. For instance, the protocol itself clearly states that this method of 

warfare “has been justly condemned by the general opinion of the civilized 

world.” This is important, because unlike treaty law, which is generally binding 

only on those nations that are party to the treaty, customary international law 

is binding on all nations.

This language also is different from that contained in Hague IV, which 

stated it applied only with respect to other High Contracting Parties, and as 
Legal Issues Aff ecting Biotechnology 313

long as all the belligerents to a conflict were parties to the convention. Here, the 

parties were restricted from use against other parties to the conflict regardless 

of whether all belligerents to a conflict were parties to the Geneva Protocol. 

This, coupled with the fact that the Geneva Protocol only prohibits the use 

of chemical and biological agents, led to many nations filing reservations 

when they became a party. Most notable were France, Great Britain, and the 

Soviet Union, which became parties in 1926, 1930, and 1928, respectively. The 

reservations were virtually identical. The reservation of France read: “The said 

Protocol shall ipso facto cease to be binding on the Government of the French 

Republic in regard to any enemy State whose armed forces or whose allies fail 

to respect the prohibitions laid down in the Protocol.”

In essence, the Geneva Protocol forced the parties to it to adopt a nofirst-use policy. This essentially was the U.S. position. When the United States 

ratified the Geneva Protocol in 1975, it filed the following reservation: “With 

reservations to Protocol as follows: to cease to be binding as regards use of 

chemical agents with respect to any enemy State whose armed forces or allies 

do not observe provisions.” Note the United States limited its reservation 

to “chemical agents,” reserving a right to retaliate with chemical weapons 

should it be attacked with chemical weapons. The United States limited its 

reservation to chemical agents only because, simultaneously with ratifying 

the Geneva Protocol, it ratified the BWC, which banned biological agents for 

offensive purposes.

This overview has demonstrated that the prohibition against the use of 

biological agents in warfare has been with us for some time. In the form of 

treaty law, it has existed for the past 150 years. It clearly existed beforehand in 

the form of customary international law as nearly all the treaties noted above 

refer to condemnation by the “civilized world” of use of biological weapons. 

Now, we will explore the current legal regime.

The Biological Weapons Convention of 1972 

Understanding what the BWC was intended to cover will allow for 

determinations of what biotechnologies may be permissible. While this 

may appear axiomatic, there are cases that at first blush are not clear cut. 

For instance, several years ago, the Judge Advocate General (JAG) of the Air 

Force was preparing a legal review of a nonlethal weapon system referred to as 

pepper foam. It was so-called because it contained oleoresin capsicum (OC), 

or pepper spray. The United States has declared OC to be a riot control agent 

pursuant to the Chemical Weapons Convention (CWC) of 1993.64 Overlooked 

in previous legal reviews of OC was the fact that it is derived from a living 

organism and had never been analyzed under the lens of the BWC. This 
3145 Bio-IInspired IInnovation and ovation and NNational SSecurity 

author conducted research into the applicability of the BWC to OC, which 

was incorporated into the Air Force JAG legal review of pepper foam.65 The 

following discussion is taken from that research. Keep in mind that while the 

discussion specifically relates to OC, it is clear that many biotech capabilities 

could easily be inserted into the analysis.

The BWC prohibits the development, production, stockpiling, or 

acquisition by other means, or retention of microbial or other biological 

agents or toxins, as well as weapons, equipment, or means of delivery designed 

to use such agents or toxins for hostile purposes or in armed conflict.66 While 

the BWC does not define what biological agents or toxins are, the World 

Health Organization (WHO) has formulated a definition of biological agents 

considered to be authoritative.67 In a 1970 report, the WHO defined biological 

agents “as those that depend for their effects on multiplication within the 

target organism and are intended for use in war to cause disease or death in 

man, animals or plants; they may be transmissible or non-transmissible.”68

Clearly, OC is excluded from this definition of a biological agent 

because it does not depend for its effect on multiplication within the target 

organism. Neither is it intended for use in war to cause disease or death in 

man, animals, or plants. This was the prevailing definition at the time the 

BWC was negotiated; therefore, it is clear the parties to the BWC were not 

contemplating prohibiting substances such as OC, but rather were more 

concerned with weapons of mass destruction. The same can be said for toxins, 

which are “poisonous products of organisms; unlike biological agents, they 

are inanimate and not capable of reproducing themselves.”69 OC would be 

excluded from the definition of toxin because it is not intended for use in 

war to cause disease or death in man, animals, or plants. “Since toxins are 

chemicals by nature, their inclusion in the [BWC] was a step towards the 

projected ban on chemical weapons.”70 Therefore, the U.S. position that OC is 

a riot control agent and is governed by the CWC and Executive Order 1185071

and not by the BWC is correct.

This conclusion is supported further by the phrase in the BWC, “hostile 

purposes or in armed conflict” which, based on the U.S. position at the time, is 

consistent with the CWC term “method of warfare.” The Department of State, 

in its letter to President Nixon recommending the BWC be transmitted to the 

Senate for its advice and consent to ratification, pointed out that on November 

25, 1969, after receiving the results of a comprehensive study of U.S. policies 

and programs relating to chemical and biological warfare, Nixon “announced 

that the United States was unilaterally renouncing biological methods of 

warfare, and would destroy its existing stocks of these weapons.” It further 

pointed out that on February 14, 1970, “The United States also renounced the 

use of toxins as a method of warfare.” Included in the November 25 statement 
Legal Issues Aff ecting Biotechnology 315

was express support by the United States for the principles and objectives of 

the draft Convention on Biological Weapons, which had been proffered by 

the United Kingdom in July 1969. Therefore, the final language of the BWC, 

“hostile purposes or in armed conflict,” must be read to be consistent with 

the U.S. position of banning biological agents and toxins as a method of 

warfare. As a riot control agent, OC may not be used as a method of warfare. 

Therefore, the BWC does not prohibit the acquisition and use of OC, either 

as a spray or foam.

Furthermore, in 1969, when the United States renounced the use 

of biological weapons, it was clear that the President was talking about the 

horrors of biological agents that have “massive, unpredictable, and potentially 

uncontrollable consequences,” with the potential to produce “global epidemics 

and profoundly affect the health of future generations.”  OC does not fit that 

description.  Also, consider what President Nixon actually said in banning 

biological weapons: “I have decided that the USA will renounce the use of any 

form of deadly biological weapons that either kill or incapacitate.”

Therefore, it is only those deadly agents that can either kill or incapacitate 

that are banned. For example, smallpox is a deadly disease that does not 

always kill. It can, however, certainly incapacitate for lengthy periods those it 

fails to kill. No reasonable person can consider OC to be a deadly agent.  

In a statement made to the Senate during the BWC ratification process 

in 1974, General George Brown, then Chairman of the Joint Chiefs of Staff, 

reinforced this view when he explained that: 

Biological warfare could produce massive, unpredictable, and 

potentially uncontrollable consequences.  The specter of global 

epidemics, with their profound impact on the health of present 

or future generations, is not a happy one.  This Convention was 

designed to reduce this specter and to enhance the security of the 

world community.

Thus, it is clear that the BWC was designed to prohibit biological 

weapons of mass destruction, not personal protection substances such as OC. 

The Biological Weapons Anti-Terrorism Act 

The act, which implements the BWC, defines the term biological 

agent as:

any microorganism (including, but not limited to, bacteria, viruses, 

fungi, rickettsiae, or protozoa) or infectious substance, or any 

naturally occurring, bioengineered, or synthesized component 

of any such microorganism or infectious substance, capable 
3167 Bio-IInspired IInnovation and ovation and NNational SSecurity 

of causing . . . death, disease, or other biological malfunction 

in a human, an animal, a plant, or another living organism; . . . 

deterioration of food, water, equipment, supplies, or material of 

any kind; or . . . deleterious alteration of the environment.72

The act defines toxin as: 

The toxic material or product of plants, animals, microorganisms 

(including, but not limited to, bacteria, viruses, fungi, rickettsiae 

or protozoa), or infectious substances, or a recombinant or 

synthesized molecule, whatever their origin and method of 

production, and includes . . . any poisonous substance or biological 

product that may be engineered as a result of biotechnology 

produced by a living organism; or . . . any poisonous isomer or 

biological product, homolog, or derivative of such a substance.73

The United States has not taken a position on whether OC and 

capsaicin constitute biological agents or toxins. While it appears OC 

would fall outside the statutory definition of biological agent, the statutory 

definition of toxin is broad enough to seemingly cover substances such as 

OC and capsaicin. In my opinion, OC, capsaicin, and pepper sprays were 

not intended to, and do not, fall within the purview of the BWC or the 

statutory prohibitions on biological and toxin weapons. The legislative 

history to the act bears this out.

In Senate Report 101–210,74 it is made clear that the act was meant to 

address the threat posed by weapons of mass destruction, not self-defense 

devices such as OC. For instance, the report noted:

Although they are often associated in the public mind, biological 

weapons are different than chemical weapons. Most biological 

weapons embody living organisms that multiply once inside the 

victim, whereas chemical weapons—nerve gas, for example—are 

inanimate. Biological weapons usually consist of some form of 

bacteria, virus, or fungus. Examples would be typhus, cholera, 

anthrax, and yellow fever. But there are also biological weapons 

that contain dead substances made from living organisms. These 

are known as toxins, and examples would include the botulism 

toxin and shellfish poison. Toxins are substances that fall between 

biological agents and chemicals, because while inanimate, they 

are produced by biological or microbic processes.

In 1925, the Geneva Protocol prohibited the first use in war of chemical 

and biological weapons, but it did not prohibit their development, production, 

possession, or transfer. Consequently, the United States and other nations 
Legal Issues Aff ecting Biotechnology 317

sought to outlaw the manufacture and stockpiling of these heinous weapons 

of mass destruction.75

It is clear from this statement that the Congress viewed the BWC as a 

step toward banning weapons of mass destruction. OC is not a weapon of 

mass destruction. Hence, Congress did not view either the BWC or the act as 

preventing the acquisition and use of OC. The statement of President George 

Bush upon signing the act further supports this position. The President noted 

on May 22, 1990, that:

This Act will impose new criminal penalties against those who 

would employ or contribute to the dangerous proliferation of 

biological weapons, and it will add teeth to our efforts to eradicate 

such horrible weapons. . . . The United States has renounced these 

weapons, as have all civilized countries, by joining the Biological 

Weapons Convention of 1972. . . . I call upon the leaders of all 

nations to join us in our drive to rid the world of biological and 

chemical weapons and to do everything in their power to stop the 

proliferation of these weapons of mass destruction.76

There can be no doubt that the purpose of the BWC and the act is to 

address the problem of weapons of mass destruction, not to eliminate OC for 

use in self-defense devices. 

Biological Weapons 

Even if OC itself could be considered a toxin under the definition of the act 

or the WHO definition, this device would not be banned by either the act or 

the BWC because it is not a prohibited weapon. Article I of the BWC clearly 

states that it applies to “weapons . . . designed to use such agents or toxins for 

hostile purposes or in armed conflict.” As has been demonstrated above, the 

term “hostile purposes or in armed conflict” is synonymous with the CWC 

term “method of warfare.” Since pepper spray and foam devices will not 

be used as a method of warfare—that is, with hostile purposes or in armed 

conflict—they are not the type of weapon governed by the BWC or the act. 

These systems are properly governed under the riot control agents regime of 

the CWC and Executive Order 11850.

The custom and practice of nations since the signing of the BWC further 

support this conclusion. Article VI of the BWC affords any party “which finds 

that any other State Party is acting in breach of obligations deriving from the 

provisions of the [BWC] may lodge a complaint with the Security Council of the 

United Nations.” While there have been several allegations of noncompliance 

with the BWC, we are unaware of any involving the use of OC.77
3189 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Moreover, additional evidence that the international community does 

not consider OC as prohibited under the BWC is that OC, capsaicin, and 

pepper sprays are not controlled items on the Australia Group’s78 List of DualUse Biological Agents for Export Control. This document does not include 

OC or capsaicin on the list of toxins or other biological agents that are subject 

to export or transfer controls such as those imposed by the BWC. We also 

note that OC and capsaicin are not listed in the Australia Group’s Control List 

of Dual-Use Chemicals.

Conclusion 

It is apparent from the discussion of the BWC and the Biological Weapons 

Anti-Terrorism Act using OC as an example that most biotechnologies will not 

run afoul of our international and domestic legal obligations. Biotechnologies 

that result in stronger material or more protective clothing or are designed 

for other peaceful purposes do not violate the BWC or the act, because both 

provide exceptions for “prophylactic, protective or other peaceful purposes.”79

Biotechnologies that are being considered for hostile purposes or use in 

armed conflict will have to undergo stringent review. Any weaponization of a 

biotechnology will be required to undergo a legal review80 as well as an arms 

control treaty review.81 Many of the factors considered in the analysis of OC 

will need to be considered. 

Biotechnology is a promising area that offers capabilities that can better 

protect our Servicemembers. It also can provide alternatives to deadly force, 

which under certain circumstances may not be the best manner of responding. 

The BWC and the act are primarily geared to address those biological agents 

that can cause mass casualties and result in the spread of deadly disease. 

Clearly, there is a lot of room to maneuver under the current legal regime to 

take advantage of these promising biotechnologies. 

Notes

1 Convention on the Prohibition of the Development, Production, and Stockpiling of 

Bacteriological (Biological) and Toxin Weapons and on their Destruction, April 10, 1972 

(26 UST 583; TIAS 8062; 1015 UNTS 163) (hereinafter, the “BWC”), available at www.

opbw.org/. The BWC entered into force on March 26, 1975.

2 BWC, Article I (1), available at www.opbw.org/.

3 Protocol for the Prohibition of the Use in War of Asphyxiating, Poisonous or Other Gases, 

and of Bacteriological Methods of Warfare, Geneva, June 17, 1925 (26 UST 571; TIAS 8061; 

94 LNTS 65) (hereinafter, the “Geneva Protocol”). This treaty entered into force on February 

8, 1928, but not for the United States, which became a party to this treaty on April 10, 1975.
Legal Issues Aff ecting Biotechnology 319

4 See Genesis 40; also for dates, see Nelson’s Complete Book of Bible Maps and Charts

(Nashville: Thomas Nelson, 1996), at first chart. The King James Version refers to Pharaoh’s 

butler; but the Hebrew word used for “butler” is the same word used for “cupbearer” in 

1 Kings, 2 Chronicles, and Nehemiah. See James Strong et al., The Strongest Strong’s—

Exhaustive Concordance of the Bible (Grand Rapids, MI: Zondervan, 2001). 

5 See 1 Kings 10:15, and 2 Chronicles 9:4; for dates, see Nelson’s, 112–113.

6 See Nelson’s, 160.

7 See Nehemiah 1:11.

8 The Laws of Manu, Chapter VII (translated by George Bühler, Sacred Books of the East, 

volume 25), available at www.sacred-texts.com/hin/manu.htm.

9 Paul Christopher, The Ethics of War and Peace: An Introduction to Legal and Moral Issues (New 

York: Prentice Hall, 1994), 202, cited in Scott Keefer, “International Control of Biological 

Weapons,” ILSA Journal of International and Comparative Law 107 (Fall 1999), 112–113.

10 Paul Christopher, note 6, 202–203; cited in Keefer, note 6, 113.

11 Keefer, note 6, 113, citing Paul Christopher, note 6, 204; also citing John D. Steinbruner, 

“Biological Weapons: A Plague Upon All Houses,” Foreign Policy 109 (1997–1998) 85, 

86; George W. Christopher, “Biological Warfare: A Historical Perspective,” Journal of the 

American Medical Association 412 (1997) (which states this account of infected corpses may 

oversimplify the spread of the plague in Europe, as other carriers may have contributed).

12 Francis Parkman, The Conspiracy of Pontiac, cited in Paul Christopher, note 6, 204.

13 Paul Christopher, note 6, 205.

14 Willard M. Wallace, Soul of the Lion—A Biography of General Joshua L. Chamberlain (New 

York: T. Nelson, 1960), 66–67.

15 Keefer, note 6, 113–114, citing George W. Christopher, note 8, 413.

16 Ibid.

17 Keefer, note 6, 114, citing Paul Christopher, note 6, 205, and George W. Christopher, note 8, 413.

18 Jonathan Watts, “Japan Taken to Court over Germ Warfare Allegations,” Lancet 657 (1998), 

351, cited in Keefer, note 6, 39.

19 Keefer, note 6, 114, citing Thomas B. Allen and Norman Polmar, Code-Name Downfall: The 

Secret Plan to Invade Japan and Why Truman Dropped the Bomb (New York: Simon and 

Schuster, 1993), 187–189, 256–257.

20 Keefer, note 6, 114, citing Allen and Polmar, note 16, 178–183.

21 Keefer, note 6, 114, citing Robin Clarke and J. Perry Robinson, “Research Policy: United 

Kingdom,” in CBW: Chemical and Biological Warfare, ed. Steven Rose (Boston: Beacon 

Press, 1969), 105, 108–109.

22 Keefer, note 6, note 43, citing George W. Christopher, note 8, 413.

23 Keefer, note 6, 115, citing George W. Christopher, note 8, 414.

24 Leonard A. Cole, The Eleventh Plague: The Politics of Biological and Chemical Warfare (New 

York: Henry Holt, 1997), 18; and George W. Christopher, note 8, 414.

25 George W. Christopher, note 8, 415.

26 Rita R. Colwell and Raymond A. Zilinskas, “Bioethics and the Prevention of Biological 

Warfare,” in Biological Warfare: Modern Offense and Defense, ed. Raymond A. Zilinskas 

(Boulder, CO: Lynne Rienner, 2000), 225, 227.

27 Ibid.

28 Ibid.
3201 Bio-IInspired IInnovation and ovation and NNational SSecurity 

29 Ibid.

30 Richard Boucher, Office of Public Affairs, U.S. Department of State, Press Release, 

September 14, 1992, “Joint US/UK/Russian Statement on Biological Weapons.”

31 Ibid.

32 Keefer, note 6, 117, citing Steinbruner, note 8, 87.

33 Keefer, note 6, 117, citing Raymond A. Zilinskas, “Iraq’s Biological Weapons: The Past as 

Future?” Journal of the American Medical Association 278 (1997), 418, 422.

34 Colwell and Zilinskas, note 23, 225.

35 Ibid.

36 Ibid.

37 Keefer, note 6, 118, citing George W. Christopher, note 8, 416. There were 751 cases of 

enteritis reported, with 45 hospitalizations. 

38 Presentation of Jonathan B. Tucker, Ph.D., Senior Fellow, Center for Nonproliferation 

Studies, Monterey Institute of International Studies, March 14, 2006.

39 Keefer, note 6, 118, citing Robert P. Kadlec et al., “Biological Weapons Control: Prospects 

and Implications for the Future,” Journal of the American Medical Association 278 (1997), 

351, 354.

40 Keefer, note 6, 118, citing Richard Danzig and Pamela B. Berkowsky, “Why Should We Be 

Concerned About Biological Warfare?” Journal of the American Medical Association 278 

(1997), 431, 432, and George W. Christopher, note 8, 416.

41 Tucker, note 35.

42 Ibid., see chapter VII, line 1. 

43 Stockholm International Peace Research Institute (SIPRI), The Problem of Chemical and 

Biological Warfare, Volume III, CBW and the Law of War, 1973, 23.

44 “Instructions for the Government of Armies of the United States in the Field,” promulgated 

as General Order No. 100, by President Abraham Lincoln, on April 24, 1864, available at 

http://fletcher.tufts.edu/multi/texts/historical/LIEBER-CODE.txt.

45 Ibid., article 16.

46 Ibid., article 70. 

47 Declaration of St. Petersburg of 1868 to the Effect of Prohibiting the Use of Certain 

Projectiles in Wartime, November 29–December 11, 1868. The United States is not a party.

48 Ibid.

49 Article XIII, Brussels Conference of 1874, International Declaration Concerning the 

Laws and Customs of War, signed at Brussels, August 27, 1874 (hereinafter, the “Brussels 

Declaration”).

50 Ibid.

51 See SIPRI, note 41, 96.

52 Article XXIII, Annex of Regulations Respecting the Laws and Customs of War on Land, to 

the Convention with Respect to the Laws and Customs of War on Land, First International 

Peace Conference, The Hague, 1899, Acts signed at The Hague, July 29, 1899 (32 Stat. 1803; 

TS 403; 1 Bevans 247) (hereinafter, the “Hague Convention of 1899”), and entered into 

force September 4, 1900; for the United States, on April 9, 1902. Note the use of the term 

“superfluous injury” in the Brussels Declaration, and the use of the term “unnecessary 

suffering,” found in the Hague Convention of 1899. This is the codification of the Law of 

War principle of Humanity, which is also known as “Unnecessary Suffering.” Both terms 
Legal Issues Aff ecting Biotechnology 321

are found in more modern treaties. See Article 35(2), Protocol Additional to the Geneva 

Conventions of August 12, 1949, and Relating to the Protection of Victims of International 

Armed Conflicts (Protocol I), of June 8, 1977.

53 See Hague Convention No. IV Respecting the Laws and Customs of War on Land (“Hague 

IV”), and Annex Thereto Embodying Regulations Respecting the Laws and Customs of War 

on Land (“Hague Regulations IV”), October 18, 1907 (36 Stat. 2277; TS 539; 1 Bevans 631), 

in particular, Articles XXII and XXIII, to the Annexed Regulations. This convention entered 

into force January 26, 1910. The United States is a party.

54 Article 2, Hague IV.

55 Treaty of Peace with Germany, concluded at Versailles, June 28, 1919. The United States is 

not a party because the U.S. Senate refused to provide its advice and consent to ratification.

56 Treaty of Washington of 1922 Relating to the Use of Submarines and Noxious Gases in 

Warfare, signed at Washington, February 6, 1922.

57 See SIPRI, note 41, 22.

58 See Article V, Convention for the Limitation of Armaments of Central American States, 

signed at Washington, February 7, 1923. The convention entered into force on November 

24, 1924. The five Central American countries were Guatemala, El Salvador, Costa Rica, 

Honduras, and Nicaragua.

59 See SIPRI, note 41, 23.

60 Ibid., 93–96. “As regards biological weapons . . . it is indisputable, first, that toxins, evidently, 

come under the definition of poison. . . . Second, it is certain that no rule of customary 

law has emerged which could have the effect of excluding biological agents from the 

prohibition of poison.” In fact, the Hague Regulations appear to have implicitly included the 

spreading of contagious diseases under the heading of ‘poison and poisoned weapons,’ for 

as the minutes of the two Hague Conferences show, the expression was taken over without 

discussion from the Declaration of the Brussels Conference of 1874, which had never been 

ratified by the governments but formed the basis for the Hague Conference of 1899. The 

records of the Brussels Conference show that in 1874 the reference to poison and poisoned 

weapons was meant to include the spreading of disease on enemy territory. In line with 

this, the U.S. Army manual from 1914 (as well as the manual from 1940) stated that the 

prohibition of poison expressed in Article 23(a) of the Hague Regulations applied ‘to the use 

of means calculated to spread contagious diseases’.”

61 Geneva Protocol, note 3.

62 See Common Article 2, Geneva Conventions of August 12, 1949, which states, “The present 

Convention shall apply to all cases of declared war or of any other armed conflict which may 

arise between two or more of the High Contracting Parties, even if the state of war is not 

recognized by one of them.”

63 There are those who argue that the mere fact an insurgent party is not bound to the terms of an 

international treaty because it is not an official party to that treaty raises only a formal problem. 

“The obligation of an insurgent party within a state to observe humanitarian rules accepted by 

that state is no more paradoxical than is the obligation of a new state, born into a community of 

states, to observe the customary rules of that community.” See SIPRI, note 41, 29.

64 The Convention on the Prohibition of Development, Production, Stockpiling and Use of 

Chemical Weapons and on Their Destruction, dated January 13, 1993, entered into force 

April 29, 1997 (hereinafter, the “CWC”). The United States became a party on April 29, 1997.

65 See “AF/JA Memorandum for HQ AMC/JA dated 17 April 2003, Subject: Legal Review of 

MK3 First Defense/Pepper Foam” (on file with author).

66 BWC, article I.
322 Bio-Inspired Innovation and National Security

67 Jozef Goldblat, “The Biological Weapons Convention: An Overview,” International Review of 

the Red Cross 318 (June 30, 1997), 251–265.

68 Ibid., 253–254 (citing World Health Organization, Health Aspects of the Use of Chemical and 

Biological Weapons, Geneva, 1970).

69 Goldblat, 254.

70 Ibid.

71 Executive Order 11850, “Renunciation of Certain Uses in War of Chemical Herbicides and 

Riot Control Agents,” April 8, 1975. This Executive Order establishes Presidential approval 

for use of riot control agents (RCA) in time of war, and then only for defensive military 

modes to save lives. The Executive Order gives four examples of defensive modes where the 

use of RCA may be permitted. They are the use of RCA in riot control situations in areas 

under direct and distinct U.S. military control, to include rioting prisoners of war; use of 

RCA in which civilians are used to mask or screen attacks and civilian casualties can be 

reduced or avoided; use of RCA in rescue missions in remotely isolated areas, of downed 

aircrews and passengers, and escaping prisoners; and use of RCA in rear echelon areas 

outside the zone of immediate combat to protect convoys from civil disturbances, terrorists, 

and paramilitary organizations. 

72 18 U.S.C. §178(1).

73 18 U.S.C. §178(2).

74 See 1990 U.S. Code Congressional and Administrative News, 186.

75 Ibid., 188.

76 Ibid., 195.

77 The most notorious incidents, the “Sverdlovsk” and “Yellow Rain” incidents, led to U.S. 

accusations of noncompliance by the Soviet Union. Sverdlovsk involved the airborne release 

of anthrax, which caused an outbreak in the city of Sverdlovsk, in April and May 1979. The 

Yellow Rain incident involved an allegation made by the United States that the Soviet Union 

had been involved in the production, transfer, and use of trichothecene mycotoxins in Laos, 

Kampuchea, and Afghanistan in the late 1970s. See Goldblat, 262–263. 

78 The Australia Group was instituted in 1984 by states dedicated to impeding the proliferation 

of chemical and biological weapons and agents by encouraging countries to adopt and 

enforce export controls on these weapons and agents, and encouraging compliance with 

the 1925 Geneva Protocol, the Chemical Weapons Convention, and the Biological Weapons 

Convention. The Australia Group currently has 30 members, including the United States. It 

maintains a list of controlled biological and chemical substances. 

79 See BWC, Article I, section (1); 18 U.S.C. §175.

80 See paragraph E1.1.15, Department of Defense (DOD) Directive 5000.1, “The DOD 

Acquisition System,” May 12, 2003; for nonlethal weapons, see paragraph E.6.b, DOD 

Directive 3000.3, “Policy for Non-Lethal Weapons,” July 9, 1996.

81 See generally paragraph 4.6, DOD Directive 2060.1, “Implementation of, and Compliance with, 

Arms Control Agreements,” of January 9, 2001, certified current as of November 24, 2003.
323

I

n the 21st century, biology is becoming a major factor in the development of 

emerging technologies. A number of critical breakthroughs in areas such as 

molecular biology, genetics, and bio-informatics have led to the emergence 

of the rapidly growing biotechnology sector of the economy. At present, this 

sector accounts for about 0.003 percent of the Nation’s gross domestic product 

(GDP). However, the sector has been showing about a 14 percent1 annual 

growth rate since 1992. If this growth rate were to persist through 2040 and 

if the GDP maintained its average growth rate of 3.3 percent, then the biotech 

sector would account for about 16 percent of the Nation’s GDP in 2040. While 

this seems to be a very high percentage, it should be noted that the information 

technology (IT)–producing sector was in a similar situation 40 years ago. This 

sector now accounts for about 8 percent of U.S. GDP.2

If biotechnology were to follow a path similar to that followed by IT 

over the past 40 years, then a 2040 estimate of 16 percent of GDP may be 

high but could be in the ballpark. If this were to happen, then the matter 

of providing for the scientific and engineering workforce to support 

that sector becomes an undertaking of significant consequence. Today, 

the biotechnology sector employs about 66,000 scientific and technical 

personnel, about half of whom are scientists.3

 The biotechnology industry 

today is principally focused on medical and health issues and markets. 

However, it is expected that nonmedical biotechnology will become 

increasingly important. Areas of particular interest for future development 

in nonmedical biotechnology include energy, sensors, materials, and 

agriculture. As these new areas develop, we expect that the makeup of the 

biotech science and engineering (S&E) workforce will change considerably. 

chapter 22

Building the Nonmedical 

Bio Workforce for 2040

Timothy Coffey and Joel Schnur
3245 Bio-IInspired IInnovation and ovation and NNational SSecurity 

The number of scientists and engineers that will need to be educated to 

provide this workforce will be in the millions. 

As the field of biotechnology develops and matures, it is vital for the 

Department of Defense (DOD) to have a knowledgeable S&E workforce in 

order to recognize and provide the internal advocacy needed to take rapid 

advantage of relevant breakthroughs from this new area as they emerge. 

Historically, most of the internal scientific and technical competence of 

DOD has resided in the military laboratories and the military research 

and development centers. This is likely to remain the case, and the vitality 

and competence of the S&E workforces of these organizations will play an 

important role in determining whether DOD will effectively exploit the 

science and technology (S&T) emerging from new fields, such as nonmedical 

biotechnology. There are many issues now confronting these organizations 

that will impact the outcome regarding DOD’s ability to exploit new S&T 

developments in the coming years.4

 This chapter will focus primarily on one 

issue: namely, the requirements confronting the Nation and DOD regarding 

the development of the 2040 biotechnology workforce. The chapter will 

attempt to identify special problems that will likely confront DOD over the 

intervening time. 

It is, of course, impossible to accurately project 30 years into the future 

for a fledgling field like biotechnology. There is no “first principles” basis from 

which to make such predictions. There are, however, considerable data regarding 

the evolution of S&T, the S&E workforce, and the DOD program since World 

War II. The trends in this data can be very helpful in making rough order of 

magnitude (ROM) estimates of future states. This is the approach that will be 

used in this chapter. The underlying analytical technique utilized will be that of 

separation of time scales. This allows the data to be expressed as a sum of a base 

function that changes slowly with time upon which is superimposed a more 

rapidly varying function that oscillates about the base function. The rapidly 

varying function is usually associated with a specific transient event (such 

as World War II, the Korean War, or the Vietnam conflict). Future transients 

are not predictable. However, the base functions appear to have some robust 

characteristics and are the basis upon which our ROM estimates will be made. 

Trends in the DOD Program 

While the purpose of this chapter is to address future DOD manpower 

requirements in the area of nonmedical biotechnology, such predictions are 

always best cast in the reality of the past. In that regard, it is helpful to examine 

the post–World War II history of the DOD program and DOD civilian 

employment therein. Figure 22–1 provides a summary of DOD expenditures 
Building the Nonmedical Bio Workforce for 2040 325

from 1929 through 2005. The funds are expressed in fiscal year (FY) 2000 

dollars. The huge impact of World War II is evident. It can be viewed as a 

discontinuity followed by a train of oscillations with an average periodicity 

of about 17 years. The major peaks in these oscillations represent the Korean 

War, the Vietnam conflict, the Ronald Reagan–era buildup, and the Iraq War. 

The line represents the base about which the oscillations occur during the 

period from 1940 through 2005. The trend line (base function) is linear in this 

case and shows that the program has, on average, experienced slow but real 

growth of about FY 2000 $0.87 billion per year. The backward extrapolation 

from 1940 shows the large permanent change of state in the Defense program 

caused by World War II. 

figure 22–1. Defense Spending, 1929–2005 (in fiscal year 2000 dollars)

Figure 22–1. Defense Spending, 1929–2005 (in fiscal year 2000 dollars) 

Source: Office of Management and Budget, Historical Tables, Budget of the U.S. Government, Fiscal Year 2005, 

available at www.whitehouse.gov/omb/budget/Fy2005/pdf/hist.pdf.

1920193019401950196019701980199020002010

Year

0

100

200

300

400

500

600

700

800

900

Defense Spending

Trend 1940–2005

Spending (billions)

It is helpful to put the DOD program into perspective regarding the 

economy that it supports (see figure 22–2). 

Prior to World War II, defense spending appears to have been in 

equilibrium with GDP at about 1.5 percent of GDP. It is clear that the war 
3267 Bio-IInspired IInnovation and ovation and NNational SSecurity 

created a large transient that drove the Defense program far out of equilibrium 

and that, since the war, defense spending has been searching for a new 

equilibrium. While this search has been interrupted by transients such as the 

Korean War, the Cold War, the Vietnam conflict, the Reagan buildup, and 

now the Iraq and Afghanistan wars, the search has led, on average, to steadily 

reducing defense programs when measured relative to GDP. Fortunately, 

the growth in GDP has allowed some small but real growth in the defense 

program even as it fell relative to GDP. If the trend continues, by 2050 the 

defense program will be about 1 percent of GDP. 

As was seen in figure 22–1, a decline relative to GDP does not imply 

a decline in absolute terms. Indeed, since World War II, the absolute size of 

the defense program has, on average, been maintained even though defense 

expenditures have fallen relative to GDP. It is conceivable that this could go on 

indefinitely if the economy continues to grow. While this is comforting, it is 

also troubling that the defense program should approach zero when measured 

relative to the nation’s economy that it exists to protect. At some point, this 

trend may become a threat to national security in that adequate preparedness 

may not be maintained relative to the scale of the nation’s economic interests. 

figure 22–2. Defense Outlays as Percent of Gross Domestic Product, 1929–2003

Figure 22–2. Defense Outlays as Percent of Gross Domestic Product, 1929–2003

Source: Office of Management and Budget, Historical Tables, Budget of the U.S. Government, Fiscal Year 2005, 

available at www.whitehouse.gov/omb/budget/fy2005/pdf/hist.pdf. Percent

50

45

40

35

30

25

20

15

10

5

0

1920193019401950196019701980199020002010

Year

Data 1929–2003

Exponential Trend 1940–2003
Building the Nonmedical Bio Workforce for 2040 327

Defense Workforce Trends 

The previous section provided a brief summary of historical trends in the 

defense program and trends relative to the economy at large. This section 

will attempt a similar review of the defense S&E workforce. Figure 22–3 

summarizes the total DOD civilian S&E workforce that supported the DOD 

program from 1958 to 2005. 

figure 22–3. Defense Science and Engineering Workforce, 1958–2005

Figure 22–3. Defense Science and Engineering Workforce, 1958–2005 Number (thousands)

120

100

80

60

40

20

0

1950196019701980199020002010

Year

DOD S&E

Linear (DOD S&E)

The defense S&E workforce has, on average, tracked the defense 

program. This presents the defense S&E workforce with long-term problems 

similar to those confronting the defense program. These S&E workforce issues 

relate largely to DOD’s ability to maintain expertise in the developments 

occurring in the national and international S&E workforces. This becomes 

evident when one compares the evolution of the national S&E workforce with 

the defense S&E workforce. Figure 22–4 summarizes the evolution of the 
3289 Bio-IInspired IInnovation and ovation and NNational SSecurity 

U.S. S&E workforce from 1950 to 2000 and compares that evolution with the 

defense S&E workforce between 1960 and 2005. 

In 1960, the DOD S&E workforce was representative of the national 

S&E workforce. However, it can be seen from figure 22–4 that the DOD 2005 

S&E workforce is more representative of the 1960 national workforce than it 

is of today’s national workforce. The difference is especially noteworthy when 

one compares the engineering components and the math/IT components 

of DOD and the Nation. It should be recalled that IT was fledgling in 1960. 

From 1960 to 2000, the Nation roughly tripled its engineering workforce and 

increased its IT workforce by a factor of 100, resulting in about as many IT 

professionals as engineers by 2000. The Nation was able to exploit a growing 

economy to continue to expand its engineering workforce while radically 

increasing its IT workforce. The total S&E workforce over this period grew by a 

factor of 5.5. DOD was not able to do this since its S&E workforce, on average, 

increased by a factor of 1.4 during this period. Since DOD is a hardware-/

figure 22–4. Scientists and Engineers by Occupational Group (as percent of total) 

Nationwide, 1950–2000, and in Department of Defense, 1960 and 2005

Figure 22–4. Scientists and Engineers by Occupational Group (as percent of total)

Nationwide, 1950–2000, and in Department of Defense, 1960 and 2005

Year

0

10

20

30

40

50

60

70

80

90

1950 (Nation)1960 (Nation)

1960 (DOD)

1970 (Nation)

1980 (Nation)1990 (Nation)

2005 (DOD)2000 (Nation)

Percentage of Total Engineers

Life

Physical

Engineer

Math/IT

Social
Building the Nonmedical Bio Workforce for 2040 329

engineering-focused organization, decisions were made to accommodate 

the workforce constraints by predominantly outsourcing its growing IT 

workforce needs. This resulted in an imbalance between engineers and IT 

professionals in DOD compared to the Nation. DOD now finds itself poorly 

positioned to understand the “art of the possible” in IT, an area that is having 

a rapidly growing impact on DOD programs. A growing number of major 

DOD acquisition program problems are now IT-related. For example, it is 

estimated that 55 percent of military large software projects are terminated 

prior to completion.5

 Some of this may be related to the imbalance regarding 

IT professionals in the DOD civilian workforce. In support of a possible 

connection to the lack of adequate IT expertise in the DOD S&E workforce, 

we note that the General Accounting Office (GAO) reported in 2004 that IT 

programs with unrealistic objectives are established, requirements are poorly 

specified, and management and oversight of the programs are deficient.6 

While the GAO attributes the problem to management deficiencies, it seems 

more likely that it is due to lack of adequate DOD expertise in the appropriate 

scientific and technical disciplines that form the foundation of IT. 

One of the important roles that the DOD civilian S&E workforce plays is 

that of maintaining awareness of and currency regarding developments in the 

national and international S&E workforces. The national S&E workforce grew 

at an annual rate of about 3.8 percent from 1970 to 2000. This is slightly faster 

than the GDP growth during this period. However, the DOD S&E workforce 

followed the trend shown in figure 22–3, meaning it has been declining 

exponentially, with a negative annual growth rate of about 3.8 percent relative 

to the national S&E workforce. It is informative to extrapolate this trend to 

the 2040 time frame considered in this chapter. To do this, we assume that the 

national S&E workforce will continue its past trend (growing slightly faster 

than the expected GDP) and the DOD S&E workforce continue its historical 

trend. The result of this extrapolation is shown in figure 22–5, which projects 

the DOD S&E workforce as a percentage of the national S&E workforce. 

Figure 22–5 shows that if past DOD practices continue, its S&E 

workforce will exponentially approach zero relative to the national S&E 

workforce. By 2040, the ratio will be about 0.5 percent. This has profound and 

disturbing implications regarding the DOD ability to remain current in S&T 

developments (such as nonmedical biotechnology) and thereby to be able to 

predict and prepare for the impact of those developments on national security. 

It also has significant implications regarding the DOD ability to judge the 

merit of proposed scientific and technical work and to properly oversee work 

once it is funded. Furthermore, it has serious implications regarding DOD’s 

ability to build the nonmedical biotechnology government workforce it will 

need as this new field develops. It is likely that the development of nonmedical 
3301 Bio-IInspired IInnovation and ovation and NNational SSecurity 

biotechnology will be rapid over the next 30 years, as was IT development 

over the past 30 years. It is also likely that nonmedical biotechnology will 

significantly impact defense systems in the coming years as did IT. If DOD 

manages its future S&E workforce as it did over the past 30 years, it quite likely 

will find itself in 2040 once again poorly positioned to exercise stewardship 

over an area of increasing importance to DOD missions. 

The 2040 Biotech S&E Workforce 

The previous sections of this chapter have provided some background on 

the evolution of the national and defense S&E workforces. This section will 

attempt to provide estimates of the 2040 biotechnology S&E workforce and 

issues associated with developing it. In this regard it is helpful to examine 

the past evolution of this workforce. From 1970 to 2000, the total number 

of scientists and engineers supporting the U.S. GDP underwent an annual 

growth rate of about 3.85 percent—slightly faster than the typical GDP growth 

rate. In a mature economy, it seems reasonable that the S&E workforce would 

roughly track the GDP since that workforce exists to support it. If one assumes 

figure 22–5. Department of Defense Scientists and Engineers as Percent 

of National Scientists and Engineers

Figure 22–5. Department of Defense Scientists and Engineers as Percent of 

National Scientists and Engineers

195019601970198019902000201020202030204020502060

Year

8

7

6

5

4

3

2

1

0

Percent 1960–2000

Projected percent

Percent
Building the Nonmedical Bio Workforce for 2040 331

that the S&E workforce will roughly follow the GDP, then the S&E workforce 

of 2040 will employ about 18 million scientists and engineers. Figure 22–4 

indicates that, during the 1970 to 2000 period, the total number of life plus 

physical scientists remained relatively stable at about 13 percent of the S&E 

workforce. Based on this data, we will assume that this trend will continue. 

The major change that occurred during this period was the rapid 

growth in the Math/IT category. This growth occurred mainly at the expense 

of the engineering category. It seems unlikely that this trend can continue 

much longer. Indeed, if the Math/IT category continues to grow as it has over 

the past 30 years, then it will employ about 52 million people by 2040. This 

exceeds by nearly a factor of three the projected number for all S&Es in 2040. 

This suggests that the current growth rate for the Math/IT category is not 

sustainable. The mix of engineers and math/IT professionals must come into 

equilibrium soon. Therefore, for the purpose of this projection at the S&E 

category level of description, it is assumed that there will be no radical changes 

beyond the 2000 relative percentages of scientists and engineers employed in 

the workforce at large over the next 30 years. Using this assumption, table 

22–1 estimates the makeup of the 2040 S&E workforce for the Nation. 

We expect that the 18 million total is reasonable based on historical GDP 

growth. The split among the S&E categories is likely to be much less accurate but, 

nevertheless, does give some indication of the number of individuals that must 

be educated over the next 30 years. The next step is to construct a similar table for 

the 2040 biotechnology workforce. One approach to this is to extrapolate from 

today’s biotechnology S&E workforce that consists of 73.5 percent scientists, 

11 percent engineers, 8.4 percent math/IT professionals, and 6.9 percent social 

scientists. If biotechnology continues to grow at 14 percent per year, by 2040 it 

will account for about 16 percent of the GDP (assuming that GDP grows at 3.3 

percent per year). This biotech growth rate seems very aggressive but is assumed 

table 22–1. Projected Scientists and Engineers Employed 

in Scientific and Engineering Work, 2040*

S&E Category 2000 Number (millions) % of Total 2040 Projection (millions)

Scientists (Life & Physical).61 13 2.34

Engineers 1.92 40 7.2

Math/Information 1.88 40 7.2

Social Scientists.347 7 1.26

Total 4.757 100 18

*Using the 2000 percentages shown in figure 22–4
3323 Bio-IInspired IInnovation and ovation and NNational SSecurity 

to be the case for the purpose of these projections. If we assign a pro rata share 

of the 2040 S&E workforce to biotechnology, the ROM estimate for the 2040 

biotechnology S&E workforce is 2.9 million. Table 22–2 shows the results if 

today’s biotechnology category breakout persists through 2040. 

A comparison of table 22–1 and table 22–2 indicates that, under this 

projection, nearly all scientists in the 2040 total S&E workforce would be in 

the biotechnology workforce. This seems highly, unlikely since biotechnology 

accounts for only 16 percent of the 2040 GDP. This suggests that the current 

biotechnology workforce percentages by S&E category are unlikely to persist 

through 2040. It seems more likely that, as biotechnology becomes a major 

part of the economy, its workforce will develop a different mix of S&Es and 

become more like the economy at large. Table 22–3 indicates the limit where a 

mature biotechnology S&E workforce supporting 16 percent of GDP in 2040 

reflects the S&E workforce at large. 

Table 22–3 is likely to be a better representation of the 2040 biotechnology 

workforce than is table 22–2. However, in order to achieve the table 22–3 

projections, the S&T biotechnology workforce will need to grow at an annual 

rate of 10 percent for the next 30 years. This is three times the expected GDP 

growth rate. The engineering and math/IT components of the biotechnology 

workforce will need to grow at about 14 percent per year over this period. 

Meeting these requirements will place significant demands on the Nation’s 

engineering and IT education systems and curricula. A large number of 

engineers and math/IT professionals will require training in the biotechnology 

fields they will be employed to support. This will be a daunting task and could 

become a limiting factor regarding the growth of biotechnology. 

The DOD civilian 2040 biotechnology S&E workforce will depend 

upon how DOD manages its S&T workforce over the next 30 years. We will 

table 22–2. Projected Scientists and Engineers Employed in 2040 Biotech Workforce, 

Scenario 1

Category

2002 Number 

(millions)

Percent 

of Total

2040 Projections 

(millions)*

Scientists (life and physical).0365 73.5 2.114

Engineers.0055 11.321

Math/information technology.0041 8.4.241

Social scientists.0037 6.9.20

Total .0498 100 2.9

*Based on assumption that 2000 biotech workforce scientist and engineer category breakdown persists and if 

 biotech is 16 percent of U.S. gross domestic product.
Building the Nonmedical Bio Workforce for 2040 333

consider two of the several scenarios could develop. In the first scenario, 

DOD and Congress allow the S&E trend shown in figure 22–3 to continue 

over this period. The total defense base S&E workforce in 2040 will be about 

107,000—about 0.5 percent of the expected national S&E workforce at that 

time. We will call this the “Status Quo” projection. The actual number would 

be greater or less depending on what the transient contribution was at that 

time. In the second scenario, the “2 Percent” projection, DOD and Congress 

maintain the ratio of the DOD civilian base S&E workforce to the national 

S&E workforce at its present value of 2 percent. In this scenario, the 2040 

DOD civilian base S&E workforce would be about 321,000. Again, the actual 

value would depend on the transients in effect at the time. In both scenarios, 

we will assume that DOD will strive to achieve an S&E category breakdown 

that is representative of the national breakdown shown in table 22–1. Under 

table 22–4. Projected Scientists and Engineers in 2040 Department of Defense Civilian 

Base Workforce under Status Quo and 2 Percent Scenarios*

table 22–3. Projected Scientists and Engineers Employed in 2040 Biotech Workforce, 

Scenario 2

Category 2002 Number (millions) 2040 Projections (millions)*

Scientists.0365.374

Engineers.0055 1.152

Math/information technology.0041 1.152

Social scientists.0037.20

Total .0498 2.9

Category

2005 Number 

(thousands)

2040 “Status Quo 

Projection”

(thousands)

2040 2 Percent 

Projection 

(thousands)

Scientists 10.6 14 41.7

Engineers 77 42.8 128

Math/information technology 10 42.8 128

Social scientists 3.7 7.4 22.5

Total 101 107 321

*Based on assumption that current national workforce scientist and engineer category breakdown percentages 

 apply and if biotech is 16 percent of U.S. gross domestic product.

*Assuming that Department of Defense scientist and engineer workforce is representative of 2040 national 

 scientist and engineer workforce breakdown projected in figure 22–3.
3345 Bio-IInspired IInnovation and ovation and NNational SSecurity 

these assumptions, the 2040 DOD civilian base S&E workforce category 

breakdown for both scenarios is shown in table 22–4. 

The next matter is to project the 2040 biotechnology component of the 

DOD civilian base S&E workforce. The nature of biotechnology developments 

over the next 30 years will determine this. Since these are not predictable, there 

is no rigorous way to make the projection. We will simply assume that the 

2040 biotechnology fraction of the Defense civilian base S&E workforce will 

be the same as biotechnology’s projected fraction of the national workforce, 

namely 16 percent. This results in table 22–5. 

Of course, all of the above projections may not be correct to the 

smallest details, but they provide a reasonable sense of possible outcomes. 

The 2040 breakdown between medical and nonmedical biotechnology is 

also difficult to estimate. The majority of biotechnology efforts today are 

related to medical and health technologies. This probably explains the high 

percentage of scientists in the current biotechnology workforce. It is likely 

that substantial growth will need to occur in nonmedical/health areas if 

biotechnology is to become a significant factor in GDP generation. The 

marketplace will ultimately determine the 2040 split between medical/

health biotechnology and nonmedical/health biotechnology. For the 

purposes of this analysis, it will simply be assumed that a 50/50 split 

will develop by 2040. Furthermore, we will assume that table 22–3 will 

be representative of the biotechnology workforce in 2040. While these 

assumptions are somewhat arbitrary, they do provide a means to quantify, 

for the purpose of discussion, the requirements that will be placed on 

the education of S&Es in various disciplines. These assumptions imply 

that, at the national level, the 2040 nonmedical national biotechnology 

workforce will employ 187,000 scientists, 576,000 engineers, and 576,000 

math/IT professionals. The number employed by DOD will depend upon 

the workforce strategy that DOD and Congress decide to follow. Past 

table 22–5. Projected Biotech Scientists and Engineers in 2040 Department of Defense 

Civilian Base Workforce under Status Quo and 2 Percent Scenarios

Category

2040 “Status Quo” 

Projection (thousands)

2040 2 Percent 

Projection (Thousands)

Scientists 2.24 6.7

Engineers 6.8 20.5

Math/information technology 6.8 20.5

Social scientists 1.18 3.6

Total 17 51.3
Building the Nonmedical Bio Workforce for 2040 335

experience suggests that it will be very difficult for DOD to grow the 

required nonmedical biotechnology S&E workforce if the “Status Quo” or 

a lesser strategy is chosen. 

The fields of science and engineering that are believed to be of special 

consequence to nonmedical/health biotechnology are shown in table 22–6. 

table 22–6. Science and Engineering Fields Relevant to Nonmedical/Health Biotechnology

Bureau of Labor Statistics

Designation Field

Science

19–1011 Animal Scientists

19–1012 Food Scientists and Technologists

19–1013 Soil and Plant Scientists

19–1014 Biochemists and Biophysicists

19–1015 Microbiologists

19–1023 Zoologists and Wildlife Biologists

19–1029 Biological Scientists, all other

19–1099 Life Scientists, all other

19–2012 Physicists

19–2031 Chemists

19–2032 Materials Scientists

19–2041 Environmental Scientists and Specialists, including Health

Engineering

17–2021 Agricultural Engineers

17–2022 Biomedical Engineers

17–2023 Chemical Engineers

17–2024 Computer Hardware Engineers

17–2025 Electrical Engineers

17–2026 Electronics Engineers, except Computer

17–2081 Environmental Engineers

Math/Information Sciences

15–1011 Computer and Information Scientists, Research

15–1031 Computer Software Engineers, Applications

15–1032 Computer Software Engineers, Systems Software

15–1061 Database Administrators

15–2041 Statisticians

15–2042 Mathematical Science Occupations, all other
3367 Bio-IInspired IInnovation and ovation and NNational SSecurity 

The fields that will make up the DOD nonmedical biotechnology 

S&E workforce will likely be the same as those that make up the national 

nonmedical biotechnology S&E workforce. The majority of the DOD 

nonmedical biotechnology S&E workforce would be employed in the DOD 

laboratories and R&D centers. If the system were orchestrated properly, 

the labs and R&D centers would serve as training grounds for technically 

competent and experienced program managers for system and material 

acquisitions that have a large biotechnology component. 

Conclusion 

Since World War II, the U.S. defense program, on average, has shown slow 

but real growth. During the same period, the DOD civilian S&E workforce, 

on average, has shown real growth similar to the real growth in the average 

defense program. However, an examination of the DOD S&E workforce 

indicates that its makeup in terms of scientific and technical disciplines is not 

representative of today’s national S&T workforce. This raises concerns about 

DOD’s ability to judge the “art of the possible” regarding the new technologies 

that have emerged over the past few decades. 

There are also several additional and disturbing trends evident at this 

time. For example, on average, the defense program is approaching zero 

exponentially when measured relative to the GDP. Furthermore, the DOD 

civilian S&E workforce is approaching zero exponentially relative to the national 

S&E workforce. As a result of this, there has emerged a significant shadow S&E 

workforce that is providing the DOD “brain cells” regarding new developments 

in science and technology and thereby new directions for defense. There are 

serious long-term public policy issues associated with this development. 

Most of these trends are simply the result of the various tradeoffs 

needed in order to get the government’s business done. However, there 

are a number of significant potential negative consequences of allowing 

these trends to continue indefinitely. If the defense civilian S&E workforce 

continues to decline relative to the national workforce, a point will be reached 

where it becomes irrelevant. It will not be able to renew itself and it will not 

be able to maintain competence in the newly developing fields of science and 

technology while at the same time maintaining competence in the traditional 

fields that will continue to be important to DOD. This could result in the 

government not being able to distinguish a good S&T proposal from a bad 

one or to competently oversee S&T work that has been funded. In addition, 

the defense S&E workforce will not be able to provide compelling advocacy 

within the government for important new S&T initiatives. Of special concern 

to the subject of this chapter is that DOD will find it difficult to grow internal 
Building the Nonmedical Bio Workforce for 2040 337

competence in the important new area of nonmedical biotechnology. As a 

result, there will be no community internal to DOD that is advocating the 

importance of and the potential impact of this emerging field. 

Notes 

1 Biotechnology Industry Organization, “Biotechnology Industry Facts,” available at 

http://bio.org/speeches/pubs/er/statistics.asp.

2 D. Henry and D. Dalton, “Information Technology Producing Industries—Hopeful Signs in 

2003,” available at https://www.esa.doc.gov/reports/DE-Chap1.pdf.

3 U.S. Department of Commerce, “A Survey of the Use of Biotechnology in U.S. Industry,” 

available at www.technology.gov/reports/Biotechnology/CD120a_0310.pdf

4 See, for example, Don De Young, “Silence of the Labs,” Defense Horizons 21 (Washington, 

DC: National Defense University Press, January 2003); Timothy Coffey, Kenneth W. Lackie, 

and Michael L. Marshall, “Alternative Governance: A Tool for Military Laboratory Reform,” 

Defense Horizons 34 (Washington, DC: National Defense University Press, November 2003); 

R. Kavetsky, M. Marshall, and D. Anand, From Science to Seapower: A Roadmap for S&T 

Revitalization (EPSC Press, 2006).

5 C. Jones, “Project Management Tools and Software Failures and Successes,” available at 

www.stsc.hill.af.mil/crosstalk/1998/07/tools.asp.

6 General Accounting Office, “Defense Acquisitions: Stronger Management Practices Are 

Needed to Improve DOD’s Software-Intensive Management Acquisitions,” report to the 

Committee on Armed Services, 2004.

339

Advances in the biological sciences, as has been true in other fields, will 

most likely be a case of the haves and the have-nots when it comes to 

a nation’s capacity to research, develop, and produce new products. 

However, dual-use and possibly seemingly innocuous biological products 

within an increasingly digital world and global economy can be acquired 

more easily by countries that are lagging behind scientifically. 

This situation poses relatively new challenges for strategic defense planning. 

More generally, as noted in a recent RAND report, “If countries are to stay ahead 

in their capacity to implement applications, they will need to make continuing 

efforts to ensure that laws, public opinion, investment in R&D, and education and 

literacy are drivers for, and not barriers to, technology implementation.”1

Of course, having biological technology does not necessarily mean 

adopting it or deploying it. Lack of knowledge about its importance or the 

existence of other economic or defense priorities could cause the technology 

to languish, leading different countries to have different levels of biological 

adoption that could have downstream consequences. 

On the one hand, the United States is struggling to maintain its 

predominance in science and technology. Many other countries have become 

scientifically advanced in general or in specific areas. Mike Moodie has pointed 

out that even Cuba has a relatively sophisticated biotechnology (and medical) 

operation occurring within a relatively poor and isolated island country—the 

Cubans see this ability as a strategic advantage. On the other hand, biological 

products are increasingly easy to buy, transport, and hide. In both cases, 

increased education in the biological sciences and how they impact the national 

security of the United States is prudent. 

conclusion
3401 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Some advancements are perhaps more likely than others. The 

aforementioned RAND report maps the “implementation feasibility” (whether 

something fills a niche versus broad market and the level of policy difficulty 

it might face) and the “technical feasibility” (whether it is feasible, uncertain, 

or relatively unlikely to develop in the first place) of certain developments. 

Biological developments such as rapid biosensors/bioassays, biological 

sources related to hybrid vehicles and solar energy, targeted drug delivery, and 

tissue engineering are squarely in the middle of being both highly feasible in 

both categories. On the other end of the spectrum (doubly low feasibility) are 

biological technologies such as quantum computers, “super soldiers,” drugs 

tailored to individual genetic makeups, and memory enhancement. This is 

not to say that these technologies are impossible (people are working on them 

right now); they are just relatively unlikely to be implemented by 2020. Of 

course, more scientifically advanced countries will have a greater chance of 

implementing less feasible technologies. 

This biotechnological development also should be viewed within 

the framework of an increasing trend toward “sustainable development”—

meeting the needs of the present without compromising the ability to meet 

these same needs in the future. The “triple bottom line” for sustainable 

industry has been described2

 as economically viable (creating value and 

profits), environmentally compatible (using eco-efficient products/processes to 

prevent pollution and depletion of natural resources), and socially responsible

(behaving in an ethical manner). It has been posited that in order to achieve 

such a grand improvement, a paradigm shift to using biomimicry in industrial 

biotechnology is necessary. It is clear that many of the topics discussed in 

this volume will most likely have implications to the intertwined worlds of 

military research and industrial production. 

Where will the interface between the natural world, biological scientists, 

industrial engineers, and military strategists lie? Storehouses of information 

like that maintained by the Biomimicry Institute are one idea.3

 In the future, 

engineers will be able to query a biomimicry digital library to map engineering 

concepts to biomimetic concepts that have evolved over 3.85 billion years in 

nature, to find inspirations and solutions. 

According to Janine Benyus of the Biomimicry Institute,4 four types 

of knowledge about the natural world need to be a part of such a database. 

Using an owl as an example, the four types are semantic (for example, the 

names of an owl’s wing parts), procedural (how an owl flies), structural (where 

feathers connect to muscle), and functional (ecological relationship with 

a prey species). With the recorded number of worldwide species about 1.6 

million, with estimates of the total number between 5 million and 30 million, 

and a huge amount of information to be catalogued for any given species, 
conclusion 341

there is a lot of work to do in this area that will consume biologists for years 

to come. It is worth pointing out for educational purposes that this kind of 

descriptive work will be done by evolutionists, ecologists, animal behaviorists, 

physiologists, functional morphologists, and the like—people who tend to 

study the outsides of organisms rather than life at the molecular level. 

Utilizing naturally occurring enzymes, evolving new ones through 

artificial evolution, using cells as mini-reactors in a process of metabolic 

engineering, and engaging the concept of industrial ecology in which companies 

work with materials in a faux ecosystem to avoid anything going to waste may 

all come into play. This also harkens the notion of a “bio-based economy”5

in which genes replace petroleum as the basic unit of global commerce. 

Whereas the past 150 years or so might be termed the “Age of Geology,” we 

may be moving toward an “Age of Biology” in which bio-based sustainable 

practices are the norm. Things such as genetically modified foods are a start 

but are only the beginning of this trend, and there are vast implications of 

this for the military: If the raw material of diverse genes is more important to 

America than the raw material of petroleum, this may influence where and 

whom the military fights for resources, and will also pose new challenges to 

foreign policy, international stability, and law. Already there are controversies 

over who rightfully owns intellectual property rights to discoveries of drugs 

that stem from rare, indigenous organisms. The host country? The biotech 

company? The explorer/discoverer? Maybe all, maybe none. 

Notes 

1 R. Silbergritt et al., The Global Technology Revolution 2020, RAND report prepared for the 

National Intelligence Council, 2006. 

2 Organisation for Economic Co-operation and Development, The Application of 

Biotechnology to Industrial Sustainability—A Primer, Working Party on Biotechnology, 

Directorate for Science, Technology, and Industry, Committee for Scientific and 

Technological Policy, 2002.

3 The mission of The Biomimicry Institute is to nurture and grow a global community of 

people who are learning from, emulating, and conserving life’s genius to create a healthier, 

more sustainable planet. See www.biomimicryinstitute.org/.

4 See also Janine Benyus, Biomimicry: Innovation Inspired by Nature (New York: Harper 

Collins, 1998).

5 Robert E. Armstrong, “From Petro to Agro: Seeds of a New Economy,” Defense Horizons 20 

(Washington, DC: National Defense University Press, 2002). There is also the interesting 

question posed in this paper of whether agriculture (genes) is a “critical infrastructure” of 

the United States. 

343

Volume Editors

Robert E. Armstrong was a Senior Research Fellow in the Center for 

Technology and National Security Policy (CTNSP) at the National Defense 

University. He received a B.A. in psychology from Wabash College, an 

M.A. in experimental psychology from Oxford University, and an M.S. in 

biology and a Ph.D. in plant breeding and genetics from Purdue University. 

A Vietnam veteran and lifelong Army Reservist, COL Armstrong was also a 

graduate of the U.S. Army War College.

Mark D. Drapeau was the 2006–2008 American Association for the 

Advancement of Science (AAAS) Science and Technology Policy Fellow in 

CTNSP. Dr. Drapeau earned a B.S. in biology from the University of Rochester 

and a Ph.D. in ecology and evolutionary biology from the University of 

California–Irvine. 

Cheryl A. Loeb is a Research Associate in CTNSP, where she works on health 

security and biological weapons proliferation threats. Previously, she worked 

at the Monterey Institute of International Studies as a chemical and biological 

weapons nonproliferation analyst. Ms. Loeb is a Ph.D. candidate in the Public 

and International Affairs program at George Mason University. 

James J. Valdes is a Senior Research Fellow in CTNSP and the U.S. Army’s 

Scientific Advisor for Biotechnology. He received his doctorate in neuroscience 

from Texas Christian University and was a postdoctoral fellow in neurotoxicology 

at The Johns Hopkins University. Dr. Valdes is the author of more than 120 

scientific papers and a winner of a 2009 Presidential Rank Award.

about the contributors
3445 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Contributing Authors

COL John B. Alexander, USA (Ret.), served in key positions in Special Forces, 

intelligence, and research and development. Upon retirement, he joined Los 

Alamos National Laboratory, where he developed the concept of nonlethal 

defense. More recently, he served with the Army Science Board. He is author 

of several books and many articles on international security issues.

Paul Bartone is a Senior Research Fellow in the CTNSP Life Sciences 

Directorate. He has conducted numerous field studies of stress, health, and 

adaptation among military personnel and their families. Dr. Bartone is a 

charter member of the Association for Psychological Science and a Fellow 

of the American Psychological Association. He earned a B.A. in psychology 

from the University of Massachusetts and an M.S. and a Ph.D. in psychology 

and human development from the University of Chicago.

Yaakov Benenson is a Principal Investigator at Harvard University’s Laboratory 

for Molecular Automata. He has a Ph.D. in computer science and biological 

chemistry from the Weizmann Institute of Science in Israel. 

William E. Bentley is the Robert E. Fischell Distinguished Professor and Chair 

of the Fischell Department of Bioengineering at the University of Maryland. 

He holds joint appointments with the Maryland Technology Enterprise 

Institute and the University of Maryland Biotechnology Institute. He received 

B.S. and M.S. degrees from Cornell University and a Ph.D. from the University 

of Colorado, all in chemical engineering.

Lt. Col. William D. Casebeer, USAF, is the Chief of Eurasia Analysis at the 

North Atlantic Treaty Organization Military Headquarters. His previous 

positions include associate professor of philosophy at the U.S. Air Force 

Academy, Middle East analyst with the Ninth Air Force, and project fellow at 

the Carr Center for Human Rights Policy at Harvard University. Lieutenant 

Colonel Casebeer has a Ph.D. in cognitive science and philosophy from the 

University of California at San Diego. 

James P. Chambers is Professor of Biochemistry in the Department of Biology and 

an Adjunct Professor of Biochemistry in the Department of Biochemistry at the 

University of Texas at San Antonio. Dr. Chambers has worked on Department 

of Defense–sponsored research projects over the past 25 years, is a recipient of 

numerous research awards, and has published extensively in peer-reviewed 

scientific journals. He holds a Ph.D. in biochemistry from the University of Texas.

Timothy Coffey has been a Distinguished Research Fellow at the National 

Defense University since 2001. He held a joint appointment as Senior Research 
about the contributors 345

Scientist at the University of Maryland and as Edison Chair for Technology at 

the National Defense University from 2001 to 2007. Previously, he served as the 

Director of Research of the U.S. Naval Research Laboratory from 1982 to 2001. 

Francis Doyle III holds the Duncan and Suzanne Mellichamp Chair in Process 

Control in the Department of Chemical Engineering at the University of 

California, Santa Barbara, as well as appointments in the electrical engineering 

department and the biomolecular science and engineering program. He 

received a B.S. from Princeton University, a Certificate of Postgraduate Study 

from Cambridge, and a Ph.D. from California Polytechnic State University, all 

in chemical engineering. 

Eleanore Edson is a Life Sciences and Public Health Analyst at Booz Allen 

Hamilton. Previously, she was an AAAS Science and Technology Policy Fellow 

at the Office of Naval Research. Dr. Edson received her Ph.D. in neurobiology 

from Harvard University. 

Andrew Ellington is the Fraser Professor of Biochemistry in the Department 

of Chemistry and Biochemistry at the University of Texas at Austin. 

Previously, Dr. Ellington was an Associate Professor in the Department of 

Chemistry at Indiana University and a Research Fellow in the Department 

of Genetics at Harvard University and the Department of Molecular Biology 

at Massachusetts General Hospital. He received a B.S. in biochemistry from 

Michigan State University and a Ph.D. in biochemistry and molecular biology 

from Harvard University. 

Richard Genik III is Director of the Emergent Technology Research Division 

and Interim Director of the Transportation Imaging Laboratory at the Wayne 

State University School of Medicine. His expertise is in magnetic resonance 

imaging sequence design, functional magnetic resonance imaging data 

analysis, and integration of emerging technologies. 

Christopher Green leads the Emergent Technology Research Division in the 

Department of Psychiatry at the Wayne State University Medical School. He 

holds a faculty position in both psychiatry and diagnostic radiology. Dr. Green 

was previously the Executive Director for Global Science and Technology Policy 

for General Motors and Chief Technology Officer for its Asia-Pacific operations.

Justin Grubich is an Assistant Professor of Biology at the American University 

in Cairo. Previously, he was a foreign affairs advisor on environmental and 

scientific issues in the Office of the Science and Technology Advisor to 

Secretary of State Hillary Clinton. Dr. Grubich received his doctorate in 

evolution and ecology from Florida State University.
3467 Bio-IInspired IInnovation and ovation and NNational SSecurity 

Thomas X. Hammes is a Senior Research Fellow in the Institute for National 

Strategic Studies (INSS) at the National Defense University. Colonel Hammes’ 

final tour prior to retiring from the U.S. Marine Corps was as Senior Military 

Fellow in INSS. He has an M.A. in historical research and a Ph.D. in modern 

history from Oxford University. He is the author of The Sling and the Stone: 

On War in the Twenty-First Century (Zenith Press, 2006).

João Hespanha is a Professor and Department Vice Chair in the Electrical and 

Computer Engineering Department at the University of California, Santa Barbara. 

Edmund G. (Randy) Howe is a Professor in the Department of Psychiatry, 

Director of Programs in Medical Ethics, and Senior Scientist at The Center 

for the Study of Traumatic Stress at the Uniformed Services University of the 

Health Sciences, where he has been on the faculty since 1977. His research has 

focused on medical ethics with an emphasis on ethics in military medicine 

and clinical care at the end of life. Dr. Howe holds an undergraduate degree 

from Yale University, an M.D. from Columbia University, and a law degree 

from Catholic University. 

Adrienne Huston is a Staff Scientist at the Verenium Corporation. She is a 

biochemist and microbiologist with over 10 years of laboratory research 

experience, in addition to science policy and program management experience 

at the National Science Foundation. 

Eric W. Justh is with the Tactical Electronic Warfare Division of the Naval 

Research Laboratory.  He received a Ph.D. in electrical engineering from the 

University of Maryland and held a half-time appointment as an Assistant 

Research Scientist in the Institute for Systems Research at the University of 

Maryland from 2001 to 2006.

Jeffrey Krichmar is an Associate Professor in the Department of Cognitive 

Sciences and the Department of Computer Science at the University 

of California, Irvine. Previously, he was a Senior Fellow in Theoretical 

Neurobiology at The Neurosciences Institute. He received a B.S. and an M.S. 

in computer science from the University of Massachusetts at Amherst and The 

George Washington University, respectively, and a Ph.D. in computational 

sciences and informatics from George Mason University. 

Michael Ladisch is a Distinguished Professor of Agricultural and Biological 

Engineering in the College of Engineering and the Director, Laboratory of 

Renewable Resources Engineering, at Purdue University. 

Judith Lytle is the Director of Science and Technology Division at Avian 

Engineering, LLC. Previously, she was a Science and Technology Policy 

Fellow at AAAS. 
about the contributors 347

Thomas McKenna works on neuroscience and biorobotics in the Life Sciences 

Research Division at the Office of Naval Research. 

Michael Moodie is a consultant with CTNSP who has worked for more than 

15 years in chemical and biological weapons issues in government and the 

policy research community. He headed the Chemical and Biological Arms 

Control Institute and served as assistant director for multilateral affairs at the 

U.S. Arms Control and Disarmament Agency.

David C. Peters II is on the faculty of the Wayne State University School of 

Medicine Department of Psychiatry and Behavioral Neuroscience. He is a 

Ph.D. candidate in the Department of Sociology at Wayne State University 

and is also an attorney. 

Joseph Rutigliano, Jr., a former Marine Corps officer, has been an international 

law specialist at Headquarters, U.S. Marine Corps, since 1998.

Joel Schnur is at the College of Science at George Mason University. In 1983, 

he founded the Center for Bio/Molecular Science and Engineering at the 

Naval Research Laboratory, where he was director until 2008. Dr. Schnur has 

a B.A. from Rutgers College and an M.S. in physics and chemistry and a Ph.D. 

in physical chemistry from Georgetown University. 

John Socha is an Assistant Professor in Biomechanics in the College of 

Engineering at Virginia Technical University. He is an organismal biomechanist 

studying the relationship between form and function in animals, with a broad 

range of projects involving locomotion, breathing, and feeding.

Elizabeth Stanley is an Assistant Professor of Security Studies in the Edmund 

A. Walsh School of Foreign Service and the Department of Government 

at Georgetown University. Previously, she served as Associate Director 

of Georgetown’s Security Studies Program and the Center for Peace and 

Security Studies. She served in Bosnia, Germany, Macedonia, Italy, and 

Korea as a U.S. Army military intelligence officer, leaving service with the 

rank of captain.

Dimitra Stratis-Cullum is a Research Chemist at the U.S. Army Research 

Laboratory in Adelphi, Maryland. Previously, she was a postdoctoral research 

fellow at Oak Ridge National Laboratory. Dr. Stratis-Cullum earned a B.S. in 

chemistry from Marist College and a Ph.D. in chemistry from the University 

of South Carolina. 

James Sumner is a Research Chemist at the U.S. Army Research Laboratory, 

where he serves as the Team Leader for the Bio-Inspired Devices and Sensors 

Team in the Sensors and Electron Devices Directorate. Dr. Sumner earned a 
348 Bio-Inspired Innovation and National Security

B.S. in chemistry from High Point University and a Ph.D. in chemistry from 

Clemson University.

Roy G. Thompson is Chief of Molecular Engineering at the U.S. Army 

Edgewood Chemical Biological Research Center, and has formerly held 

positions as Assistant Professor at Texas Christian University, Research 

Associate at The Johns Hopkins University, Associate Member of the 

Vanderbilt Institute for Integrative Biological Research and Education, and 

Assistant Program Manager to the Deputy Assistant Undersecretary of 

Defense for Environmental Security. He received a B.A. in chemistry and 

psychology from Youngstown State University and has doctoral training in 

neuroscience at Texas Christian University.

Erica R. Valdes is a Research Chemist in the Chemical/Biological Forensic 

Analysis Center at the U.S. Army Edgewood Chemical Biological Research 

Center, where she has 27 years of research experience ranging from ultrafine 

particle studies and biologically inspired materials to forensic investigation 

of hazardous materials. Dr. Valdes holds an M.S. in chemistry and a Ph.D. in 

materials science from The Johns Hopkins University. 
D

espite the vital importance of the emerging area of biotechnology 

and its role in defense planning and policymaking, no definitive 

book has been written on the topic for the defense policymaker, 

the military student, and the private-sector bioscientist interested in the 

“emerging opportunities market” of national security. This edited volume 

is intended to help close this gap and provide the necessary backdrop for 

thinking strategically about biology in defense planning and policymaking. 

This volume is about applications of the biological sciences, here called 

“biologically inspired innovations,” to the military. Rather than treating 

biology as a series of threats to be dealt with, such innovations generally 

approach the biological sciences as a set of opportunities for the military 

to gain strategic advantage over adversaries. These opportunities range 

from looking at everything from genes to brains, from enhancing human 

performance to creating renewable energy, from sensing the environment 

around us to harnessing its power.

Edited by Robert E. Armstrong, Mark D. Drapeau, Cheryl A. Loeb, and James J. 

Valdes, with contributions from:

John B. Alexander

Paul Bartone

Yaakov Benenson

William E. Bentley

William D. Casebeer

James P. Chambers

Timothy Coffey

Francis Doyle III

Eleanore Edson

Andrew Ellington

Richard Genik III

Christopher Green

Justin Grubich

Thomas X. Hammes

João Hespanha

Edmund G. (Randy) 

 Howe

Adrienne Huston

Eric W. Justh

Jeffrey Krichmar

Michael Ladisch

Judith Lytle

Thomas McKenna

Michael Moodie

David C. Peters II

Joseph Rutigliano, Jr.

Joel Schnur

John Socha

Elizabeth Stanley

Dimitra Stratis-Cullum

James Sumner

Roy G. Thompson

Erica R. Valdes