NEXT GENERATION BIOWEAPONS: 

THE TECHNOLOGY OF GENETIC ENGINEERING 

APPLIED TO BIOWARFARE AND BIOTERRORISM

by 

Michael J. Ainscough, Colonel, USAF 

The Counterproliferation Papers 

Future Warfare Series No. 14 

USAF Counterproliferation Center

Air War College

Air University 

Maxwell Air Force Base, Alabama
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Next Generation Bioweapons: 

The Technology Of Genetic Engineering 

Applied To Biowarfare And Bioterrorism 

Michael J. Ainscough, Colonel, USAF 

April 2002 

The Counterproliferation Papers Series was established by the USAF 

Counterproliferation Center to provide information and analysis to assist 

the understanding of the U.S. national security policy-makers and USAF 

officers to help them better prepare to counter the threat from weapons of 

mass destruction. Copies of No. 14 and previous papers in this series are 

available from the USAF Counterproliferation Center, 325 Chennault 

Circle, Maxwell AFB AL 36112-6427. The fax number is (334) 953-

7530; phone (334) 953-7538. 

Counterproliferation Paper No. 14 

USAF Counterproliferation Center

Air War College 

Air University 

Maxwell Air Force Base, Alabama 36112-6427

The internet address for the USAF Counterproliferation Center is: 

http://www.au.af.mil/au/awc/awcgate/awc-cps.htm

Contents 

Page 

Disclaimer.....................................................................................................i

The Author.................................................................................................. ii

Acknowledgments ..................................................................................... iii

I. Introduction .............................................................................................1 

II. The Former Soviet Union’s Biological Warfare Program.....................3 

III. Genetic Engineering, Bioterrorism and Biowarfare ...........................11 

IV. Six Paths to Enhance Biothreats.........................................................17 

V. Six Ways Science Can Improve Biodefense........................................23 

VI. Conclusions ........................................................................................27 

Notes..........................................................................................................29 

i

Disclaimer 

The views expressed in this publication are those of the author and do 

not reflect the official policy or position of the U.S. Government, 

Department of Defense, or the USAF Counterproliferation Center. 
ii

The Author 

Colonel Michael J. Ainscough, M.D., M.P.H., is an Air Force 

flight surgeon and a diplomat of the American Board of Preventive 

Medicine in Aerospace Medicine. Prior to attending Air War College in 

residence, he was the 92d Aeromedical-Dental Squadron Commander at 

Fairchild AFB, Washington. Other assignments included tours as Chief of 

Aerospace Medicine at the 343d Medical Group, Eielson AFB, Alaska; 

Chief of Operations Branch, Hyperbaric Medicine Division, Armstrong 

Laboratory, Brooks AFB, TX; Chief, Aeromedical Evacuation Branch, 

Professional Services Directorate, Office of the Air Mobility Command 

Surgeon; and then Chief, Clinical Aeromedical Evacuation for the 

Global Patient Movement Requirements Center of USTRANSCOM at 

Scott AFB, IL. Colonel Ainscough completed USAF Squadron Officers 

School in residence and was an outstanding graduate of the Air Command 

and Staff and Air War College seminar programs. He earned his 

Bachelor’s degree from the St. Louis College of Pharmacy and his 

Doctorate of Medicine from the Southern Illinois University School of 

Medicine. He completed a USAF Residency in Aerospace Medicine and a 

Fellowship in Hyperbaric Medicine at Brooks AFB, TX. He also 

completed a Masters in Public Health degree at the University of Texas. 

Colonel Ainscough’s military decorations include the Defense Meritorious 

Service Medal, the Meritorious Service Medal with three Oak Leaf 

Clusters, the Air Force Commendation Medal, the Air Force Achievement 

Medal, and the Humanitarian Service Medal. In 1989, he was named the 

Alaskan Air Command Flight Surgeon of the Year, and in 2001 he was 

nominated by Air Mobility Command for the Paul Myers Award. He is a 

Senior Flight Surgeon with 1,100 total flying hours in over 20 types of 

military aircraft. 
iii

Acknowledgments 

I would like to express my sincere appreciation to my Air War 

College faculty advisors, Dr. Barry Schneider and Col (Dr.) Jim Davis, 

who serve as the Director and Deputy Director of the USAF 

Counterproliferation Center, respectively. Their encouragement, 

mentoring, and guidance significantly contributed to the value of this 

work. I also must thank my wonderful wife Cathy and our sons, Ty and 

Drew, for their understanding and support throughout my entire Air Force 

career. 
iv
Next Generation Bioweapons . . . 1 

Next Generation Bioweapons: 

The Technology of Genetic Engineering 

Applied to Biowarfare and Bioterrorism 

Michael J. Ainscough 

I. Introduction 

The history of warfare and the history of disease are unquestionably 

interwoven. Throughout the history of warfare, disease and non-battle 

injury have accounted for more deaths and loss of combat capability than 

from actual battle in war itself. The most striking example is the great 

influenza pandemic during World War I that killed 20 million people or 

more worldwide in 1918.1

 Although this was a naturally occurring event, 

what if a country could create a biological agent that could yield the same 

catastrophic loss of life on the enemy? That, in essence, is the potential 

effect of applying genetic engineering2

 for biological warfare (BW) or 

bioterrorism (BT). 

Today, we face not only natural diseases (including emerging 

infectious diseases), but also threats of BW or BT, possibly with 

genetically engineered agents, that may resist known therapies. In simple 

terms, genetic engineering is the process of human intervention to transfer 

functional genes (DNA) between two biological organisms. In the 

BW/BT context, it is the manipulation of genes to create new pathogenic 

characteristics (increased survivability, infectivity, virulence, drug 

resistance, etc). Organisms with altered characteristics are the “next 

generation” biological weapons. 

In this century, it is widely predicted that advances in biology and 

biotechnology will revolutionize society and life as we know it. At the 

same time, the “black biology” of biotechnology which can be used to 

create biological weapons, will be one of the gravest threats we will face. 

In this era when cloning and “designer genes” are topics of the evening 

news, much has been written about biowarfare and bioterrorism resulting 

from genetically altered microbes, and it is often difficult to discern fact 

from fiction. This paper has two purposes. The first part consolidates 
2 . . . Next Generation Bioweapons

accounts of genetic engineering from sources close to the former Soviet 

Union’s BW program. The remainder of the paper discusses near-term 

future capabilities of genetic engineering and biological warfare from an 

American perspective. The “next generation” of biological weapons made 

possible through genetic engineering will be asymmetric weapons par 

excellence. 
Next Generation Bioweapons . . . 3 

II. The Former Soviet Union’s Biological Warfare Program 

Biopreparat 

Despite signing the 1972 Biological and Toxin Weapons Convention 

(BWC), it is now certain that the former Soviet Union (FSU) continued a 

clandestine and illegal offensive biological weapons program until at least 

the early 1990s. Biopreparat (a huge military program with civilian cover) 

was organized to develop and weaponize biological agents for BW.3

 It 

employed approximately half of the Soviet Union’s 60,000 workers in 

more than 18 BW facilities, and in the 1980s had an annual budget 

equivalent to tens of millions of U.S. dollars.4

 Unlike the American 

offensive BW program (1942-69) that worked primarily with organisms 

that were not contagious in humans (e.g., anthrax and tularemia), the 

Soviet BW research and development program also sought out the most 

contagious and lethal bacteria (e.g., plague) and viruses (e.g., smallpox) 

known to man.5

Because Biopreparat and other Soviet BW research facilities operated 

under the highest security classification of “Special Importance” (higher 

than Top Secret), the U.S. intelligence community did not even know it 

existed until 1989 when a top ranking scientist from the BW program 

defected to the United Kingdom.6 From his extensive debrief, and 

subsequent collaboration by two other defectors from the program, we 

now know detailed information on the genetic engineering successes and 

other advances in Russian microbiology. Obviously much of the data 

remains classified, but the three defectors’ accounts have been 

documented to some extent in various unclassified books and articles. 

This paper discusses their open-source accounts. 

Pasechnik 

In October 1989, Dr. Vladimir Pasechnik, the first primary source 

from inside the Soviet program, defected to England.7 A top Soviet 

microbiologist and Director of the Institute for Ultra Pure Biological 

Preparations in Biopreparat, he described the extensive organization of 

biological research and production facilities in the program. 
4 . . . Next Generation Bioweapons

In addition to confirming that the Soviet Union had an offensive BW 

program in violation of the 1972 BWC, he disclosed that the Soviets had 

an “extensive genetic engineering program aimed at developing new kinds 

of biological weapons against which the West would be defenseless.”8 His 

institute’s top priority was to increase the lethality of plague and 

tularemia, and at the same time make them more resistant to antibiotics 

and temperature extremes. By introducing specially engineered plasmids9

into successive generations of tularemia cultures, the strain became 

resistant to all known Western antibiotics. The dried, powdery superplague became the Soviet weapon of choice (20 tons in stock at all times) 

and was loaded on various munitions. The use of BW had been integrated 

into Soviet special war plans for a range of tactical operations where they 

would have been delivered using spray tanks and cluster bombs and 

strategic operations where intercontinental ballistic missiles (ICBMs) and 

strategic bombers would have carried plague, anthrax, or smallpox.10 

Pasechnik also detailed work on perfecting other new strains of 

bacteria and viruses that would aerosolize well for use in weapons.11 

After 30 years of experimentation, Soviet scientists had solved the 

problems of fragile microbe survival in major atmospheric pressure 

changes and temperature extremes during missile flight by fitting BW 

rockets with astronaut cabin-like protective systems. They solved the 

“destruction on explosion” problem by selecting the hardiest strains and 

calculating the required redundant quantity needed based on explosive 

testing done in Biopreparat and other BW research labs. 

In summary, Pasechnik had disclosed that the Soviets (1) had 

genetically engineered bacteria and viruses, (2) weaponized the microbes in 

a powder form, (3) loaded them onto various munitions, and (4) integrated 

BW into their doctrine and had specific plans for use of BW.12 

“Temple Fortune” 

In the spring of 1992, a lower-level bench scientist who had worked 

on plague research in Pasechnik’s lab also defected to the United 

Kingdom.13 He has remained undercover and is referred to by code-name 

“Temple Fortune.” He fully corroborated Pasechnik’s previous account, 

and then updated the British on Soviet BW work in the 30-month interval 

from Pasechnik’s departure to that of “Temple Fortune.” President 
Next Generation Bioweapons . . . 5 

Mikhail Gorbachev had ordered the termination of biological offensive 

programs in 1990, and despite the fact that President Boris Yeltsen had 

also announced (by televised address to the Russian people and in a 

personal commitment to President Bush) termination of the program, 

research on new forms of plague had secretly continued.14 

“Temple Fortune” stated that, in addition to being even more resistant 

to multiple antibiotics, the improved super-plague would be non-virulent 

in its stored form, but could be easily converted into a deadly antibioticresistant form when needed for weaponization.15 The genes that cause 

plague virulence are located on a plasmid. What he was describing was a 

binary biological weapon, where benign bacterial plague cells would be 

mixed with virulence-enhancing plasmids immediately before loading on a 

weapon, and the transformation would take place in a small bioreactor on 

the weapon itself.16 

Alibekov 

In late 1992, shortly after “Temple Fortune’s” defection, Dr. Kanatjan 

Alibekov became the third defector from the Russian BW program.17 As 

the Deputy Director (number-two man) of Biopreparat and an infectious 

disease physician/epidemiologist, he was the highest ranking defector ever 

from the program. (Dr. Alibekov anglicized his name and now goes by 

Ken Alibek.) In 1999, Alibek published Biohazard, a first-hand detailed 

account of his experiences. Alibek disclosed a virtual encyclopedia of 

intimate details on Biopreparat from the top down: personnel and 

facilities, history of the offensive research, medical and microbiological 

discoveries, special production methods, weaponization techniques, 

aerosol testing, Russian BW defensive innovations, prior deceptions and 

secret plans, and the future direction of the program.18 

Alibek confided that Soviet biologists in the 1960s and 1970s were 

already interested in using genetics and gene manipulation to produce BW 

agents. In 1973, President Leonid Brezhnev established the “Enzyme” 

program to modernize the BW program and develop genetically altered 

pathogens.19 Early in his career, Alibek had been in charge of developing 

Biopreparat’s first vaccine-resistant tularemia bomblet.20 Later, by 1986, 

his team had also tripled the potency of the “battle strain” of anthrax 
6 . . . Next Generation Bioweapons

(Strain 836).21 He was the first to weaponize glanders, and supervised the 

first Soviet tests with the Marburg virus (an Ebola-like virus).22 

Alibek disclosed that by 1992 the Russians possessed a grand total of 

fifty-two different biological agents or combination of agents, including 

deadly Marburg, Ebola, and smallpox viruses, that could be weaponized. 

The most infectious and easiest to manufacture and transport microbes 

were labeled “battle strains.”23 The favorite “battle strains” were anthrax 

(Strain 836), Pasechnik’s super-plague, and a special Russian strain of 

tularemia (Schu-4). By 1991, Alibek stated that Russian scientists had 

“improved” all three of these so that they could overcome all immune 

systems and current medical treatments.24 In May 1998, Alibek testified 

before the U.S. Congress: 

It is important to note that, in the Soviet’s view, the best 

biological agents were those for which there was no 

prevention and no cure. For those agents for which 

vaccines or treatment existed – such as plague, which can 

be treated with antibiotics – antibiotic-resistant or 

immunosuppressive variants were to be developed.25 

Although Biopreparat had worked with a highly virulent, rapidly 

infectious “battle strain” of smallpox (India-1) since 1959, they began 

research in 1987 to develop an even more virulent smallpox weapon, and 

tested it in 1990.26

In his book Biohazard, Alibek wrote about using plasmids to increase 

virulence or antibiotic resistance in bacteria.27 This corroborated 

Pasechnik’s and “Temple Fortune’s” prior statements. He also discussed 

transfer of a gene for myelin toxin to Yersinia pestis (plague bacteria), 

however this agent was reportedly not yet weaponized. He said that a new 

Moscow-based company named Bioeffekt Ltd. had offered, by mail order, 

three strains of tularemia produced by “technology unknown outside 

Russia” (i.e., genetically engineered strains). 

Most astounding of all, Alibek revealed that genetic engineering 

research was underway to create entirely new life forms.28 The goal of 

hybrid “chimera” viruses was to insert genes from one virus into another 

to create an even more lethal virus. Alibek stated that the Russians had 

created the first chimera virus from inserting DNA from Venezuelan 
Next Generation Bioweapons . . . 7

equine encephalitis (VEE) virus into vaccinia virus (genetic structure 

almost identical to the smallpox virus).29 Chimeras, of VEE, Ebola, and 

Marburg genes inserted into the actual smallpox virus, were in the 

research phase when he left in 1991. 

Near the end of his book, Alibek talks about how biotechnical 

knowledge was shared with other countries.30 For many years the 

Russians taught courses in “genetic engineering and molecular biology for 

scientists from Eastern Europe, Cuba, Libya, India, Iran, Iraq, and other 

countries.” In fact, Cuba had set up a pharmaceutical company near 

Havana and was producing interferon from a genetically altered bacteria 

that contained an inserted plasmid. 

Yeltsen and Sverdlovsk 

In 1979, an accidental release of anthrax spores from the BW facility 

at Sverdlovsk (now Yekaterinberg, Russia) killed at least 66 people. In 

1998, a DNA sequencing study done on preserved samples from eleven 

victims revealed the simultaneous presence of up to four distinct genetic 

variants of Bacillus anthracis. These findings indicate that at least some 

level of engineering of military anthrax had taken place, because only one 

strain would likely be found after a natural outbreak.31 The Soviet Union 

at the time denied the existence of a military program and the official in 

charge of the province where the incident occurred was none other than 

Boris Yeltsen. 

More than a decade later, after becoming President of Russia, Boris 

Yeltsen visited Britain in 1992. In a public speech, discussing biological 

warfare research, he stated that the Russians “had undertaken research on 

the influence of various substances on human genes.” Yeltsen’s 

statements substantiated the existence of a previous Soviet genetic 

engineering research program.32 Yeltsen, as Russia’s President, later 

issued a public decree outlawing the entire Russian BW research and 

production program. 

Scientific Reports 

In 1995, Russian scientists presented a study at a conference in 

Britain that they later published in the British medical journal Vaccine in 
8 . . . Next Generation Bioweapons

December 1997.33 They reported that they had successfully transferred 

genes from Bacillus cereus into Bacillus anthracis cultures, making the 

anthrax resistant to Russian anthrax vaccine (at least in hamsters). This 

raised the obvious question about effectiveness of the American anthrax 

vaccine. American agencies sought to obtain a sample of the more potent 

Russian anthrax strain.34 Unable to do so, in early 2001 the Pentagon 

made plans to duplicate the Russian work and genetically engineer its own 

modified strain for biodefense purposes.35

Implications 

Biological-type weapons have been used many times in history. 

Humanity’s ancient enemies are, after all, microbes.36 What is new today 

is the tailored development of more contagious and lethal pathogens and 

the increasing number of states and terrorist groups that may have access 

to the knowledge or cultures of them.33 The above accounts from 

Russians knowledgeable about their BW programs indicate active research 

and success in genetic engineering, chimera agents, and binary biologicals. 

From public record accounts, we know that the former Soviet Union 

(FSU) used genetic engineering techniques in their massive offensive BW 

program.38 

Because the FSU classified its offensive BW program as “Special 

Importance” (higher than Top Secret), it is clear that they considered BW 

missiles to be as valuable as their nuclear missiles.39 Because of the 

protective military secrecy, it is plausible that even many top ranking 

Soviet/Russian officials did not know the full extent and details of the 

offensive program nor have control over it.40 This Mafia-like secrecy may 

explain Gorbachev’s and Yeltsen’s confusions, hesitancies, and 

contradictions when talking to the West about treaty violations.41 

Incredibly, Pasechnik claimed that he had never been told about the 

existence of the Biological and Toxin Weapons Convention and learned of 

it first from his British debriefers.42 Indeed, despite Yeltsen’s decree to 

dismantle the FSU’s offensive BW program, many intelligence analysts 

suspect that it is still viable, hidden deep in the military structure which is 

reluctant to surrender their BW secrets.43 

Major General John Parker, Commanding General, U. S. Army 

Medical Research and Materiel Command, acknowledged that 
Next Generation Bioweapons . . . 9 

“bioterrorists could just re-engineer diseases such as anthrax to negate the 

effect of existing vaccines.”44 Some western intelligence experts believe a 

Russian genetic engineering program such as Alibek described is still in 

its infancy.45 The pace of recent discoveries in molecular biology makes it 

imperative to contemplate new BW threats.46 Advances in “the dark side” 

of biotechnology predict a future of antibiotic-resistant bacteria, vaccineresistant viruses, and the creation of completely new pathogens 

(chimeras).47 The expertise and technology to create lethal new strains of 

viruses and bacteria are available at most major universities around the 

world. Some American scientists predict that we have some 20 years 

before genetic engineering will effectively make current biological 

defenses completely ineffective and obsolete against BW attacks. Science 

fiction may become science fact within two decades.48 

The threat of a war with ICBM exchange with Russia has been 

greatly reduced in recent years. However, as nuclear and BW missiles 

were decommissioned and Biopreparat and portions of the rest of the BW 

scientific infrastructure were dismantled, many Russian scientists were 

suddenly unemployed. There is concern that knowledge of genetic 

engineering, or even cultures of highly infectious agents (sold, stolen, or 

smuggled), may have been transmitted to “nations of concern” or terrorist 

organizations. If true, such leaks, combined with the ease of flow of 

technology and information around the world, would result in a proliferation 

of capability that makes biological weapons use increasingly likely in major 

theater wars, smaller scale contingencies, and terrorist events.49

A biological weapon consists of both the biological agent and its 

means of delivery. Growing microbes is easier than their weaponization 

or dissemination. As Larry Johnson, former deputy director of the State 

Department’s Office of Counter-Terrorism, said, “producing these 

weapons requires infrastructure and expertise more sophisticated than a 

lab coat and a garage.”50 However, terrorists may attempt to recruit 

former biological weapons researchers to obtain information on 

weaponization techniques. Well-funded terrorist organizations might be 

able to buy the Russian scientists they need. A small subset of terrorist 

groups is likely to possess the technical know-how needed to carry out an 

effective biological attack.51 Unless they are able to buy knowledge or 

microbe cultures from large programs such as the former Soviet BW 
10 . . . Next Generation Bioweapons

program, it is unlikely, though not impossible, that small terrorist units 

would have access to or produce genetically engineered biologicals. 
Next Generation Bioweapons . . . 11

III. Genetic Engineering, Bioterrorism and Biowarfare 

Revolutions in Medicine and Military Affairs

The techniques of genetic engineering began to be developed in the 

1970s.52 In the 1980s, genetic engineering was already a global 

multibillion-dollar industry.53 In the last decade of the 20th century, the 

knowledge of molecular biology increased exponentially. The recent 

revolution in molecular biology may have incidentally unleashed a new 

threat to mankind, in the form of genetically engineered pathogens, which 

could be used to develop many new offensive biological weapons. The 

same biotechnology that has promised to save lives by treatment of many 

human diseases, also has a dark side that could be misused for the 

development of deadly bioweapons. The future of this “black biology” is 

the subject of the remainder of this paper. 

The revolution in molecular biology and biotechnology can be 

considered as a potential Revolution in Military Affairs (RMA). Andrew 

F. Krepinevich noted 10 RMAs in the history of warfare.54 Four elements 

are required for a RMA: technological advancement, incorporation of this 

new technology into military systems, military operational innovation, and 

organizational adaptation in a way that fundamentally alters the character 

and conduct of conflict. The Gulf War has been seen as introducing the 

space/information warfare RMA. From the technological advances in 

biotechnology, biowarfare with genetically engineered pathogens may 

constitute a future such RMA. The Russians have integrated BW into 

their doctrine, but fortunately there is no present evidence that they have 

had any occasion to practice it in the past few decades. 

Lieutenant General Paul Van Riper, USMC (Ret.), former 

commanding general, Marine Corps Combat Development Command, 

asserts that we are at the front end of strategic change and that there are 

currently multiple RMAs in progress.55 It is difficult to assess their impact 

and meaning while they are still works in progress. Indeed, only time can 

prove that a technological innovation will contribute to a RMA. It may 

take 20 or 30 years until we fully understand their significance. It is 

currently believed by some that the next true major threats to our national 

security are in information and biological warfare.56 We are arguably 

farther along in the information warfare RMA than a biowarfare RMA. 
12 . . . Next Generation Bioweapons

Ironically, genetic engineering is becoming routine and commonplace 

while weaponization of biologicals is currently a less developed art. 

However, the recent spate of anthrax-laced letters sent through the mail 

communicates the message that terrorists can be very creative in their 

delivery methods.57 

Whether or not biotechnology contributes to a future RMA, it 

certainly is revolutionizing medicine. The human genome has been 

sequenced. Gene therapy, which will allow the replacement or repair of 

faulty genes, promises to be the Holy Grail of modern medicine.58 The 

techniques of molecular genetics, genome sequencing, and gene splicing 

therapy have dual-use potential. Paradoxically, the same biotechnology 

for developing a new drug or new vaccine may be used to develop more 

virulent bioweapons. The same science that can be used to save lives may 

also used to take lives. The rise of biotechnology knowledge presently 

parallels an increase in the willingness of terrorists to inflict mass 

casualties and increased devastation.59 Following the historical pattern of 

interaction between warfare and disease, these two relatively new 

phenomena of unprecedented biotechnology and terrorists willing to inflict 

mass casualties will very likely intersect in history. The anthrax attacks in 

the United States following the September 11, 2001, terrorist attacks on 

the twin towers of the World Trade Center and the Pentagon likely are 

previews of coming events. 

Emerging Infectious Diseases 

Richard Preston’s 1997 novel The Cobra Event was a fictional 

scenario of bioterrorism with a genetically engineered supervirus.60 

President Clinton’s reading of this novel sensitized him to the bioterrorist 

threat. He looked more deeply into the BW/BT threat and subsequently 

issued two Presidential Decision Directives to address national security 

deficiencies related to biological and chemical terrorism and warfare.61 In 

the wake of the September 11 terrorist attacks on the World Trade Center 

and the Pentagon, and the multiple anthrax-tainted letters subsequently 

sent to national legislators, the Governor of New York, and news media 

offices, President Bush established the Homeland Security Council to 

coordinate a national effort of some 40 diverse agencies and organizations 

that were already involved in homeland security. 
Next Generation Bioweapons . . . 13

Because we do not know what new diseases will arise, we must 

always be prepared for the unexpected.62 The Centers for Disease Control 

and Prevention (CDC) in Atlanta is the nation’s lead agency for disease 

epidemics and tracks naturally occurring emerging infectious diseases 

worldwide. The CDC has traveled all over the world and investigated 

outbreaks of Ebola hemorrhagic fever, Marburg virus, hantavirus, and 

other emerging diseases.63 These were challenging natural outbreaks of 

pathogens that had not been previously known to man. An outbreak of a 

biologically engineered pathogen might create a similar situation and may 

have an even greater disease potential (contagion and mortality) than 

recently discovered naturally emerging diseases. The epidemiological 

investigations of these emerging infectious diseases and other outbreaks 

serve as templates for responses to future biowarfare and bioterrorist 

events.

Natural versus Biologically Engineered Pathogens 

In late 2001, anthrax spores in letters mailed through the U.S. Postal 

Service resulted in more terror than actual morbidity. In the three months 

following the anthrax letter attacks, five people died of inhalational 

anthrax and a total of 18 others had contracted some form of the disease.64 

Over 50,000 people took broad-spectrum antibiotics, and many more 

people purchased antibiotics for future prophylaxis. “Anthrax anxiety” 

was reported on the nightly news. Hundreds of thousands of the “worried 

well” deluged the medical care system. 

Yet, as bad as anthrax-by-mail was, an outbreak of a biologically 

engineered pathogen could be potentially even more devastating. 

Although highly lethal, the anthrax of September 2001 was determined to 

be a well-known strain and it was not contagious (spread from person to 

person). Although anthrax spores are highly stable and can remain viable 

for years, compared to other pathogens a relatively large number of 

organisms is required to cause illness.65 These facts may explain why 

investigators found traces of anthrax spores in many office buildings and 

post offices, but only a few people actually contracted the disease. 

Furthermore, if evidence of an anthrax attack is determined (as was the 

case just after September 11), people can be screened for exposure and/or 
14 . . . Next Generation Bioweapons

treated with antibiotics that are highly effective if taken before symptoms 

begin. There is also an FDA-approved vaccine for anthrax. 

Genetically engineered pathogens would likely prove to be a more 

difficult challenge than the 2001 anthrax attacks. Most likely they would 

be novel in characteristics with either higher transmissivity, 

communicability, or antibiotic resistance. Such “tailoring” of classical 

pathogens could make them harder to detect, diagnose, and treat. In 

effect, they would be more militarily useful.66 Obviously, a vaccine would 

not be available for a novel pathogen. Biological warfare expert Steven 

Block outlines other qualitative differences and attributes possibly 

expected from genetically engineered pathogens. They could be made 

safer to handle, easier to distribute, capable of ethnic specificity, or be 

made to cause higher morbidity or mortality rates.67 

The entire DNA sequence of the smallpox genome is known, and 

some scientists fear that it has already been genetically manipulated.68 

Although the only authorized laboratories in the world for smallpox are 

the CDC in Atlanta and the Russian State Research Center for Virology 

and Biotechnology in Koltsovo, it is believed that cultures may exist 

elsewhere in the FSU and possibly have been transferred to other nations 

of concern or to non-state organizations.69 Ken Alibek described in his 

book Biohazard that the FSU was working on genetic modifications of 

smallpox in 1992.70 Because it was eradicated from the world’s 

population in 1980, any release of even the original form of the disease 

would affect millions of people and constitute an epidemic of worldwide 

concern. Certainly, a biologically “improved” strain of smallpox would be 

ominous. 

Offensive Biological Weapons Capabilities 

The Office of the Secretary of Defense has identified countries that 

maintain various levels of offensive biological warfare capabilities or 

research facilities. This list includes Russia, China, Iraq, Iran, North 

Korea, Syria, Libya, India, and Pakistan. The Henry L. Stimson Center 

also lists Egypt, Israel, and Taiwan as countries of “proliferation 

concern.”71 Also, the Al Qaeda network reportedly sought to buy 

biological agents. 
Next Generation Bioweapons . . . 15

Most developed nations maintain some level of defensive capability 

against biological warfare and bioterrorism. This typically includes 

deployment military mission-oriented protective posture (MOPP) gear and 

civilian hazardous material (HAZMAT) responder “space suits.” Also 

important are vaccines and antibiotics stockpiled against the BW/BT 

threats. The United States Department of Defense maintains a defensive 

capability. In 1969, President Nixon issued an executive order to 

unilaterally and unconditionally renounce biological weapons. Our 

program was terminated and stockpiles were destroyed.72 The closure of 

our offensive program has had a serious and limiting effect on our ability to 

develop medical defensive measures, such as our capability to develop 

appropriate vaccines, antibiotics, and other treatments.73 

Biowar and Bioterrorism 

As our adversaries look for “asymmetric”74 advantages, biological 

weapons are always a consideration. Bellicose national leaders and terrorists, 

allured by the potentially deadly power of biological weapons, persevere in 

seeking to acquire them. Yet, curiously, when biological weapons have been 

employed in battle, they have proven relatively ineffectual. They have been 

undependable and uncontrollable.75 Because they have been difficult to 

deploy reliably, their military value has been marginal.76 Stabilizing 

biological agents and deploying them, either overtly with sophisticated 

weaponry or covertly without endangering the perpetrator or friendly forces,77

requires expertise not widely held. Possibly, with the capabilities of 

biological engineering and a new generation of weapons, this may change. 

Nation-state and nonstate actors obviously have differing capabilities, 

requirements, and expectations for biological weapons. Whereas military 

troops often train to operate in chemical and biological environments, 

vulnerable civilian populations do not have either the protective equipment or 

defensive training for a biological attack, and would therefore be the most 

likely target in a bioterrorist attack. It is increasingly likely that nonstate 

terrorists will use biological attacks as appears to be the case of the anthrax 

mail attacks following the September 11th attacks on the Pentagon and the 

World Trade Center towers.78 

In the event of an attack with a genetically engineered pathogen, it would 

likely require some time to sort out whether we were confronting simply a 
16 . . . Next Generation Bioweapons

naturally occurring event or one triggered by those with a sinister motive.79 

Identification of the cause may be delayed. Initially, there may not be a high 

index of suspicion. The disease may not be recognizable if it takes the initial 

form of a familiar complex of symptoms. Most physicians have never seen 

patients with anthrax or smallpox, and few have had training to diagnose the 

most likely bioterrorism pathogens. For example, one of the U.S. postal 

workers who died of anthrax in late 2001 was diagnosed as having a harmless 

viral syndrome and released from a physician’s care. In the initial stages of 

an investigation, it might be difficult to determine if the outbreak is a 

naturally occurring event, an act of terrorism, or an act of war. For example, 

the first inhalational anthrax victim in Florida in late 2001 was initially 

thought to have been infected from natural exposure because he was an 

outdoorsman. It may be difficult for investigators to determine the source of 

the pathogen or the mechanism of exposure. It took some time before 

anthrax spores from letters were connected to the first anthrax cases. At the 

time of this writing, the perpetrator of the events in the United States and the 

source of the anthrax remain unknown. 

A terrorist attack with a biologically engineered agent may unfold unlike 

any previous event. The pathogen may be released clandestinely so there will 

be a delay between exposure and onset of symptoms. Days to weeks later, 

when people do develop symptoms, they could immediately start spreading 

contagious diseases. By that time, many people will likely be hundreds of 

miles away from where they were originally exposed, possibly at multiple 

international sites. Acutely ill victims may present themselves in large 

numbers to emergency rooms and other medical treatment facilities. In this 

scenario, medical professionals would be “on the front lines” of the attack. If 

the pathogen was highly contagious, medics would then become secondarily 

infected. Unsuspecting hospitals would become contaminated and soon 

overwhelmed. This would necessitate the quarantine of a large number of 

people, with the situation exacerbated by the declining numbers of medical 

care givers. The media would contribute to public anxiety. Civil disorder 

and chaos may ensue. We have very little experience in coping with such an 

epidemic. Advanced warning of an impending specific bioterrorist incident, 

especially with a genetically engineered BW agent, will be extremely rare—

similar to an emerging disease outbreak. Unless we happen to have excellent 

intelligence, we can only be prepared to respond after the fact.80 
Next Generation Bioweapons . . . 17

IV. Six Paths to Enhance Biothreats 

At about the same time The Cobra Event became popular in 1997, the 

United States Department of Defense released Proliferation: Threat and 

Response, which identified trends in biological warfare capabilities. 

These included the increasing use of genetically engineered vectors and 

the growing understanding of both infectious disease mechanisms and the 

immune defense system.81 An annex to Proliferation: Threat and 

Response stated “the current level of sophistication of BW is 

comparatively low, but there is enormous potential—based on advances in 

modern molecular biology, fermentation, and drug delivery technology—

for making sophisticated weapons.82 The most recent Report of the 

Quadrennial Defense Review (September 2001) also recognizes that “the 

biotechnology revolution holds the potential for increasing threats of 

biological warfare.”83 

Also in 1997, a group of academic scientists met to discuss “the threat 

posed by the development and use of biological agents.” This JASON84

Group provides technical advice to the U.S. government and “facilitates 

the contributions of scientists to problems of national security and public 

benefit.” Their meeting concentrated on the near-term future threat of 

biological warfare, specifically on genetically engineered pathogens and 

weapons. 

The JASON Group that met in 1997 grouped potential genetically 

engineered pathogens into six broad groups of potential futuristic threats.85 

• Binary biological weapons 

• Designer genes 

• Gene therapy as a weapon 

• Stealth viruses 

• Host-swapping diseases 

• Designer diseases

The biotechnology exists today for some of these possibilities. 

Indeed, some genetically engineered agents may have already been 

produced and stockpiled. 
18 . . . Next Generation Bioweapons

1) Binary Biological Weapons:

86 Analogous to a binary chemical 

weapon, this is a two-component system consisting of innocuous parts that 

are mixed immediately prior to use to form the pathogen. This process 

occurs frequently in nature. Many pathogenic bacteria contain multiple 

plasmids (small circular extrachromosomal DNA fragments) that code for 

virulence or other special functions. The virulence of anthrax, plague, 

dysentery, and other diseases is enhanced by these plasmids. What occurs 

naturally in nature can be artificially conducted with basic biotechnology 

techniques in the laboratory. Virulent plasmids can be transferred among 

different kinds of bacteria and often across species barriers. 

To produce a binary biological weapon, a host bacteria and a virulent 

plasmid could be independently isolated and produced in the required 

quantities. Just before the bioweapon was deployed, the two components 

would be mixed together. The transformation of the host organism back 

into a pathogen could conceivably take place after a weapon is triggered 

and during transport/flight. “Temple Fortune” indicated that scientists in 

the FSU had mastered this technique. 

2) Designer Genes:

87 The Human Genome Project has decoded the 

alphabet of life and provided a human molecular blueprint.88 Likewise, 

the complete genome sequences are now known for 599 viruses, 205 

naturally occurring plasmids, 31 bacteria, one fungus, two animals, and 

one plant.89 Many of these genomes have been published in unclassified 

journals and on the internet. To the bioweaponeer these are essentially 

blueprints that would enable him to make microorganisms more harmful.90 

Now that the codes are known, it seems only a matter of time until 

microbiologists develop synthetic genes, synthetic viruses, or even 

complete new organisms. Some of these could be specifically produced 

for biological warfare or terrorism purposes. 

Perhaps the most obvious way to increase the effectiveness of any 

biological warfare pathogen is to render it resistant to antibiotics or 

antiviral agents. Some bacteria naturally develop resistance to antibiotics 

fairly quickly. Many antibiotic resistance genes have been identified. The 

best known of these is the gene that codes for beta-lactamase, the enzyme 

that defeats the action of penicillin. Such genes could be activated or 

introduced into other pathogens. 
Next Generation Bioweapons . . . 19

Entire viruses may similarly be created, analogous to the natural 

mutation of the influenza virus. A new strain of influenza could be 

created by induced hybridization of viral strains, simply swapping out 

variant or synthetic genes. Slightly altering a common virus like influenza 

to make it deadlier might be easier than manipulating more rare or 

biologically complicated pathogens. 

For a bioweaponeer, the databases of increasing numbers of microbial 

genomes provide a virtual “parts list” of potentially useful genes for a 

genetic “erector set” to design and produce a new organism. It is possible 

to pick and choose the most lethal characteristics.91 Some think it may be 

possible to create an entirely new organism from scratch. Some animal 

viruses are so small that their entire genome could be stitched together, at 

least in principle, from machine-synthesized fragments using current 

technology. Mycoplasma, an organism that causes pneumonia in humans, 

has the smallest known bacterial genome.92 Genetic analyses of strains of 

mycoplasma indicate that only 265 to 350 genes are essential under 

laboratory growth conditions. Thus, it may be possible to create an 

entirely synthetic “minimal genome”93 organism in the near future. If a 

streamlined cell of this type were available, it would be an attractive 

template to build a bioweapon.94 

As stated previously about viruses, although it may be possible to 

create life artificially from a set of component parts, this would probably 

be beyond the sophistication of most bioterrorists. It would be extremely 

difficult to engineer all of the desired “attributes” into a single pathogen 

and still have an organism that transmitted effectively and predictably. It 

would be much more likely that an existing pathogen would be subtly 

genetically modified to be more difficult to detect, more virulent, or more 

resistant to drugs, all within the capabilities of today’s biotechnology.95 

3) Gene Therapy as a Weapon:

96 Gene therapy will revolutionize 

the treatment of human genetic diseases. The goal is to effect a permanent 

change in the genetic composition of a person by repairing or replacing a 

faulty gene. Genes have already been spliced into bacteria to produce 

“human” insulin in large quantities.97 The eventual goal is to splice a 

gene that codes for the production of insulin into human pancreatic tissue 

to cure diabetes. Similar research is progressing on adding in the missing 
20 . . . Next Generation Bioweapons

gene to prevent the symptoms of cystic fibrosis. However, the same 

technology could be subverted to insert pathogenic genes. 

There are two general classes of gene therapy: germ-cell line 

(reproductive) and somatic cell line (therapeutic). Changes in DNA in 

germ cells would be inherited by future generations. Changes in DNA of 

somatic cells would affect only the individual and could not be passed on 

to descendants. Manipulation of somatic cells is subject to less ethical 

scrutiny than manipulation of germ cells. 

This concept has already been used to alter the immunity of animals. 

The vaccinia virus (a poxvirus used to make immunization against 

smallpox) has been used as a vector to insert genes in mammalian cells. 

This genetically engineered virus has been used successfully to produce an 

oral vaccine to prevent rabies in wildlife. 

Research for similar gene splicing in humans continues for possible 

vectors to carry the replacement genes to their targets.98 As has been done 

for animals, there is potential for human “vaccination” against certain 

diseases, or as a targeted delivery capability for therapeutic drugs or 

cytotoxic effects.99 

One class of experimental vectors is the retroviruses which 

permanently integrate themselves into human chromosomes.100 HIV, 

which causes AIDS, is a retrovirus. So it should not be hard to understand 

that gene therapy might have sinister capability. 

A viral vector has already produced a lethal strain of mousepox 

virus.101 The genetically manipulated virus completely suppressed the 

cell-mediated response (the arm of the immune system that combats viral 

infections) of the lab mice.102 Even mice previously vaccinated against the 

natural mousepox virus died within days of exposure to the super virus. 

Mousepox (which does not infect humans) and smallpox are related 

viruses. If smallpox were to be similarly genetically manipulated, our 

current vaccine may not protect against it. These vectors are not yet very 

efficient in introducing genes into tissue cells. But if a medical technique 

is perfected, similar vectors might eventually be used to insert harmful 

genes into an unsuspecting population.103 

Techniques for cloning tissues and embryos continue to advance. 

Reproductive (germ-cell) cloning aims to implant a cloned embryo into a 

woman’s uterus leading to the birth of a cloned baby. Therapeutic 

(somatic cell) cloning aims to use genes from a person’s own cells to 
Next Generation Bioweapons . . . 21

generate healthy tissue to treat a disease. For example, such cloning could 

be used to grow pancreatic cells to produce insulin to treat diabetes, or to 

grow nerve cells to repair damaged spinal cords.104 

Already sheep, mice, swine, and cattle have been cloned. However, 

success (defined as births of live animals) rates are low.105 Initial cloning 

work with human embryos to produce omnipotent stem cells has been 

reported.106 Theoretically, the stem cells could in turn grow into virtually 

any cell type and serve as replacement tissue in diseases like diabetes.107 

Researchers have also used a virus to insert a jellyfish gene into a rhesus 

monkey egg and produced the first genetically altered primate.108 The use 

of embryos and germ cells has raised many ethical questions. 

4) Stealth Viruses:

109 The concept of a stealth virus is a cryptic viral 

infection that covertly enters human cells (genomes) and then remains 

dormant for an extended time. However, a signal by an external stimulus 

could later trigger the virus to activate and cause disease. This 

mechanism, in fact, occurs fairly commonly in nature. For example, many 

humans carry herpes virus which can activate to cause oral or genital 

lesions. Similarly, varicella virus will sometimes reactivate in the form of 

herpes zoster (shingles) in some people who had chicken pox earlier in 

life. However, the vast majority of viruses do not cause disease. 

As a biological weapon, a stealth virus could clandestinely infect the 

genome of a population. Later, the virus could be activated in the targeted 

population, or a threat of activation could be used as blackmail. 

Oncogenes are segments of DNA that, when switched on, can initiate 

wild cellular growth and misbehavior—the hallmarks of cancer. Some 

viruses have segments of DNA that can mimic oncogenes and directly, or 

perhaps through bioregulators or host genes, cause cancer. These changes 

may take years for clinical effect, but the concept may still be considered 

by bioterrorists.110 

5) Host-Swapping Diseases:

111 As previously stated, the vast 

majority of viruses do not cause disease. In nature, animal viruses tend to 

have narrow, well-defined host ranges. Unlike bacteria, viruses often 

infect only one or just a few species. When a virus has a primary reservoir 

in an animal species, but is transmissible to humans, it is called a zoonotic 

disease. Animal viruses tend to have a natural animal reservoir where 
22 . . . Next Generation Bioweapons

they reside and cause little or no damage. Examples of reservoirs include 

birds for the West Nile Virus, water fowl for Eastern equine encephalitis 

and rodents for hantavirus. The bat is thought to be the reservoir for Ebola 

virus, and the chimpanzee is thought to have been the original reservoir 

for the HIV virus that causes AIDS. When viruses “jump species” they 

may occasionally cause significant disease. These examples illustrate that 

manageable infectious agents can be transformed naturally into organisms 

with markedly increased virulence.112 

When this happens naturally, the process results in an emerging 

disease. If it were to be induced by man, it would be bioterrorism. In the 

laboratory of inspired, determined and well-funded bioterrorists, an animal 

virus may be genetically modified and developed specifically to infect 

human populations. Emerging diseases could have serious implications 

for biological warfare or terrorism applications. 

6) Designer Diseases:

113 Our understanding of cellular and 

molecular biology has advanced nearly to the point where it might be 

possible to propose the symptoms of a hypothetical disease and then 

design or create the pathogen to produce the desired disease complex. 

Designer diseases may work by turning off the immune system, by 

inducing specific cells to multiply and divide rapidly (like cancer), or 

possibly by causing the opposite effect, such as initiating programmed cell 

death (apotosis). This futuristic biotechnology would clearly indicate an 

order-of-magnitude advancement in offensive biological warfare or 

terrorism capability.114 

The concepts and mechanisms of the six classes of biological 

innovations that could be weaponized, as outlined by the JASON Group 

and discussed above, have some overlap. These classes were meant to 

identify a spectrum of conceivable bioterrorist threats based on current or 

near-future biotechnological capabilities. They were not meant to be allinclusive or mutually exclusive of possibilities.115 

Another authority on biological warfare, Malcolm Dando asserts that 

benign microorganisms might be genetically engineered to produce BW 

toxins, bioregulator compounds, or venoms.116 Pathogens may also be 

genetically manipulated to enhance their aerosol or environmental 

stability, or defeat current identification, detection, and diagnostic 

capabilities. 
Next Generation Bioweapons . . . 23

V. Six Ways Science Can Improve Biodefense 

Biological warfare and bioterrorism are multifactorial problems that 

will require multifactorial solutions. We need our best critical thinkers 

and biological researchers to solve this constantly evolving problem. 

Fortunately, the same advances in genomic biotechnologies that can be 

used to create bioweapons can also be used to set up countermeasures 

against them. There are six areas where biotechnology will likely make 

significant contributions: 

• Understanding the human genome 

• Boosting the immune system 

• Understanding viral and bacterial genomes 

• Bio-agent detection and identification equipment 

• New vaccines 

• New antibiotics and antiviral drugs

1) Understanding the human genome.

117 The Human Genome 

Project will have a profound influence on the pace of molecular biology 

research and help solve the most mysterious and complex of life’s 

processes. New biotechnology should allow the analysis of the full 

cascade of events that occur in a human cell following the infection with a 

pathogen or the uptake of a toxin molecule. Circumstances that cause 

individual susceptibility to infectious diseases will become clear. 

Currently, the functions of nearly half of all human genes are unknown. 

Functional genomics studies should elucidate these unknowns and enable 

design of possible new strategies for prevention and treatment in the form 

of vaccines and anti-microbial drugs. 

There have been reports of biological agents to target specific ethnic 

groups.118 Although “biological ethnic cleansing” is a theoretical 

possibility, most experts are skeptical of this potential.119 Analysis of the 

human genome sequence to date has failed to reveal any polymorphisms120

that can be used to absolutely define racial groups. Several studies have 

shown that genetic variation in human populations is low relative to other 

species and most diversity exists within, rather than between, ethnic groups. 
24 . . . Next Generation Bioweapons

2) Boosting the immune system.

121 The complete sequencing of the 

human genome also provides a new starting point for better understanding 

of, and potential manipulation of, the human immune system. This has a 

tremendous potential against biological warfare. 

After years of effort in the FSU to genetically engineer pathogens for 

biological warfare, Dr. Ken Alibek is now working to protect against the 

use of biological agents. He is researching mechanisms to boost the 

immune system to defend the body against infectious diseases. One of his 

initial projects is conducting cellular research that could lead to protection 

against anthrax. Similar immunological research in other labs has great 

promise to heighten the general human immune response to microbial 

attack in an effort to move beyond the “one bug-one drug” historical 

approach. 

3) Understanding viral and bacterial genomes.

122 The genome 

projects for various microorganisms will explain why pathogens have the 

characteristics of virulence or drug resistance. A “minimal genome” was 

discussed previously in this paper. Creating a minimal genome would be 

an important milestone in genetic engineering as it would prove the 

capability to create organisms simply from the blueprint of their genomes. 

This research may provide insight into the very origins of life, bacterial 

evolution, and understanding the cellular processes of more complex life 

forms. 

Bacteria may also be modified to produce bioregulators against 

pathogens. For example, E. coli has been genetically engineered to 

produce commercial quantities of interferon,123 a natural protein that has 

antiviral activity against a variety of viruses. Xoma Corporation has 

patented a bactericidal/permeability-increasing (BPI) protein made from 

recombinant DNA (genes inserted into DNA sequences) technology that 

reverses the resistance of some bacteria to some widely used antibiotics. 

The search is on for other bioactive proteins that can affect the human 

response to infections. 

4) Rapid/accurate bio-agent detection and identification 

techniques and equipment.

124 Biotechnologists need to continually 

develop more definitive, rapid, and automated detection equipment, 

regardless of whether or not bacteria have been genetically engineered. 
Next Generation Bioweapons . . . 25

The capability to compare genomes using DNA assays is already possible. 

It is reasonable to contemplate a DNA microchip that could identify the 

most important human pathogens by deciphering bacterial and viral 

genomes. This detector could provide information on the full genetic 

complement of any BW agent even if it contained genes or plasmids from 

other species, had unusual virulence or antibiotic-resistance properties, or 

was a synthetic organism built from component genes. The ability to 

quickly identify and characterize a potential BW agent with a single test 

will greatly reduce the delays in current detection methods. 

Geneticists deciphered the genome of the anthrax bacteria contained 

in the terrorist letters after September 11, 2001. DNA tests confirmed that 

the anthrax in every letter was the Ames strain.125 Forensic scientists also 

looked for human DNA that might be inside the letters. The information 

was used for both the criminal investigation (gene clues that might help 

track back to the perpetrator or origin of the culture) and for further 

medical research for diagnosis and treatment.126 Gene sequencing 

techniques (molecular fingerprinting) for anthrax and other microbes will 

undoubtedly contribute to future forensics and diagnostics. 

5) New vaccines.

127 Vaccines stimulate humoral128 immunity, the 

production of specific antibodies for specific pathogens. The availability 

of many pathogen genome sequences has already led to development 

advances in new vaccines for some meningitis and pneumonia bacteria. 

Researchers have genetically engineered viruses in an attempt to create 

novel vaccines that would stimulate immunity against multiple diseases 

with a single treatment.129 A California laboratory, Maxygen, is 

combining proteins from related pathogens in hope of developing vaccines 

that could provide broad protection.130 Several other laboratories also 

have initiated genome-enabled efforts investigating ways to boost cellmediated immunity against those pathogens for which it might be most 

effective. As yet, this approach has not been as successful as the 

development of vaccines but, as a result of genome sequencing, having 

knowledge of all available antigens has been enormously valuable. 

6) New antibiotics and antiviral drugs.

131 Advances in microbial 

genomics hold great promise in the design of new anti-microbial drugs. 

Current antibiotics target three processes in bacterial cells: DNA 
26 . . . Next Generation Bioweapons

synthesis, protein synthesis, and cell-wall synthesis. From deciphered 

genome information, any other protein essential for cell viability is a 

possible target for a new class of antibiotics. Although the first such 

antibiotics may be “silver bullets” for a specific infectious agent, the 

information gained may lead to broad-spectrum anti-microbial agents. 

If the 1950s were the golden age of antibiotics, we are now in the 

early years of the age of antivirals.132 With viral genomes decoded, 

scientists will soon decipher how viruses cause disease, and which stage of 

the disease-producing process might be vulnerable to interruption. 

Insights gleaned from the human genome and viral genomes have opened 

the way to development of whole new classes of antiviral drugs. 
Next Generation Bioweapons . . . 27

VI. Conclusions 

Genetically engineered pathogens constitute the “next generation” of 

biological warfare agents. Evidence indicates that the Russians have 

genetically engineered biological warfare agents. Ken Alibek’s original 

debriefings were so shocking that some military and intelligence personnel 

preferred to believe that he was exaggerating.133 As his statements about 

genetic engineering and FSU capabilities began to be substantiated, 

however, the reality began to sink in. Such genetic innovations obviously 

enhance adversarial offensive biological warfare effectiveness and complicate 

our defensive capability. Because we cannot know with certainty the 

specifics of these agents (lethality, communicability, and antibiotic 

resistance), it is imperative that we prepare for the unexpected. Two quotes 

come to mind. George Orwell said, “Life is a race between education and 

catastrophe.” Further, Gene Kranz said, “Failure is not an option.” 

Although biologically engineered weapons may currently be less of a 

concern than their naturally occurring counterparts, the threat they pose can 

only increase as technology develops.134 We are only in the initial stages of a 

revolution in biotechnology.135 Historically, the available state-of-the-art 

biotechnology has been used in offensive BW programs (i.e., FSU applied the 

technology of the 1970s and ‘80s). Biotechnology is the ultimate doubleedged sword. Once knowledge is attained, there is no going back.136 As is 

the case with most powerful technologies, they can be employed for good or 

evil.137 We must proceed with caution when developing new life-forms.138 

As new organisms are introduced into our delicate bio-equilibrium, we cannot 

fully predict all potential consequences to the biosphere. The same 

technology that is used to benefit mankind may paradoxically pose a threat to 

our military forces and civilian populations either by accident or by sinister 

forces. It is possible today to genetically engineer microorganisms for 

specific positive medical and industrial purposes. It is likewise possible to 

genetically engineer pathogens for biological warfare purposes. It seems 

likely that such weapons will be used in our lifetimes. Inevitably, sometime, 

somewhere, someone seems bound to try something with genetically 

engineered pathogens.139 If they are ever released, they will pose an ominous 

challenge for medical care and governmental response. 

The use of biological warfare agents on the battlefield against the 

United States has been restrained in recent history. There have been many 
28 . . . Next Generation Bioweapons

declarations and conventions to attempt to define international norms and to 

regulate the use of biological weapons. In the end, the law of war is 

somewhat of an oxymoron.140 Several signatories of the 1972 BWC, 

including Iraq and the former Soviet Union, have participated in activities 

outlawed by the convention.141 These events demonstrate the 

ineffectiveness of the convention as the sole means for eradicating 

biological weapons and preventing further proliferation. Ultimately, the 

most effective deterrent to their use has turned out to be fear of 

retaliation.142 During the Gulf War, it is believed that Iraq was deterred 

from using biologicals and chemicals because Saddam Hussein feared 

nuclear or otherwise overwhelming retaliation.143 We cannot be sure that 

future enemies will be so intimidated. Certainly, non-state terrorists actors 

will not be deterred as easily. Biotechnology has made it possible to inflict 

mass casualties using only small scale special operations that can evade 

detection in attempt to avoid retribution. In asymmetric warfare, biological 

weapons are seen as a “great equalizer.” 

The probability of a terrorist use of a genetically engineered biological 

agent on a given city is very low, but the consequence of such an event 

would obviously be very high.144 With maximum casualties the likely goal, 

metropolitan areas are at the highest risk.145 This dilemma is the challenge 

of local communities, which are sensitive to the need for preparedness, but 

have finite resources. Local communities must have a plan and sufficient 

medical and public health resources accessible to sustain a response for up 

to 24 hours. A robust federal assistance would be made available promptly, 

but it would not be immediate. Currently, dozens of federal entities fiercely 

compete for the missions and money associated with the unconventional 

terrorism response.146 The Homeland Security Council is charged to 

coordinate a more efficient network of disaster response capability.147 At 

present, all military and civilian populations throughout the world are 

vulnerable to a BW attack.148 We remain grossly ill-prepared to respond to 

an epidemic caused by a novel genetically engineered biological agent. 

The 20th century was dominated by physics, but recent breakthroughs 

indicate that the next 100 years likely will be “the Biological Century.”149 

There are those who say: “the First World War was chemical; the Second 

World War was nuclear; and that the Third World War – God forbid – will 

be biological.”150 
Next Generation Bioweapons . . . 29

NOTES 

1. Stephen M. Block, “Living Nightmares: Biological Threats Enabled by 

Molecular Biology,” in The New Terror: Facing the Threat of Biological and Chemical 

Weapons, eds. Sidney Drell, Abraham D. Sofaer, and George D. Wilson (Stanford, CA: 

Hoover Institution Press, 1999), 58; see also, Robert G. Webster, William J. Bean, 

Owen T. Gorman, Thomas M. Chambers, and Yoshihiro Kawaoka, “Evolution and 

Ecology of Influenza A Viruses,” Microbiological Reviews, March 1992, 152-179. 

2. Genetic engineering is a type of molecular biotechnology that uses laboratory 

techniques to isolate, manipulate, transfer, recombine, and allow expression of genes 

(DNA segments) between different organisms. In biological warfare or bioterrorism, 

adversaries might use genetically engineered agents that included both modified existing 

microbes and possibly novel synthetic life forms created to render them more effective as 

biological weapons than found in naturally occurring organisms. 

3. Tom Mangold and Jeff Goldberg, Plague Wars (New York: St. Martin’s Press, 

1999), 92. 

4. Ken Alibek with Stephen Handelman, Biohazard (New York: Random House, 

1999), 43; see also, Lester C. Caudle III, “The Biological Warfare Threat,” in Textbook of 

Military Medicine: Medical Aspects of Chemical and Biological Warfare, eds. Frederick 

R. Sidell, Ernest T. Takafuji, and David R. Franz (Washington D.C.: Office of the 

Surgeon General, US Army, 1997), 454. Biopreparat constituted only half of the Soviet 

BW program. See Alibek’s Biohazard. 

5. Jonathan B. Tucker, Toxic Terror: Assessing Terrorist Use of Chemical and 

Biological Weapons (Cambridge, MA: MIT Press, 2000), 4-5; and Jim A. Davis, “The 

Anthrax Terror,” Aerospace Power Journal, Vol XIV, no. 4 (Winter 2000): 17. 

6. Mangold and Goldberg, 182. 

7. Ibid., 91-105; and Caudle, 453-4. 

8. Mangold and Goldberg, 93-5. 

9. Caudle, 454. Bacterial cells frequently contain extrachromosomal (located 

outside the cell nucleus), autonomously replicating DNA molecules known as plasmids. 

Some plasmids carry DNA sequences that can produce antibiotic resistance, virulence, or 

infectivity. Plasmids can move between bacteria. 

10. Mangold and Goldberg, 94-5, 164; Col John Alexander, Future War:

Non-Lethal Weapons in the Twenty-First Century (New York: St Martin’s Press, 1999), 

191. 
30 . . . Next Generation Bioweapons

11. Mangold and Goldberg, 93-7. 

12. Ibid., 91-9. 

13. Ibid., 163-5. 

14. Alexander, 192; Mangold and Goldberg, 158-63. 

15. Ibid., 164. 

16. Block, 55-6. 

17. Mangold and Goldberg, 177-95; Alibek, ix-xi. 

18. Mangold and Goldberg, 178-9,182; Alibek, 3-304. 

19. Alibek, 40-2, 155-6; Alexander, 191. Immediately after the 1972 Biological 

Weapons Convention treaty, President Brezhnev initiated the largest biological weapons 

program in history. 

20. Mangold and Goldberg, 186. 

21. Ibid., 180. 187-8. 

22. Ibid. 

23. Ibid., 179. 

24. Ibid., 180. 

25. Block, 49-50. 

26. Mangold and Goldberg, 181. 

27. Alibek, 160-1, 163-7, 272. 

28. Ibid., 259; and Mangold and Goldberg, 181. 

29. Alibek, 258-61; Mangold and Goldberg, 181. 

30. Alibek, 273-5. 

31. Block, 50-1, Alibek, 69-86. 
Next Generation Bioweapons . . . 31

32. Plague War, Frontline, PBS Home Video, Public Broadcasting Service, FROL1706, 1998, 60 minutes. 

33. A.P. Pomerantsev, N.A. Staritsin, Yu V. Mockov, and L.I. Marinin, “Expression 

of Cereolysine AB Genes in Bacillus anthracis Vaccine Strain Ensures Protection Against 

Experimental Hemolytic Anthrax Infection,” Vaccine, Vol. 15, No. 17/18, 1997, 1846-

1850. 

34. Judith Miller, Stephen Engelberg, and William Broad, Germs: Biological 

Weapons and America’s Secret War (New York, Simon and Schuster, 2001), 218-220. 

35. Judith Miller, Stephen Engelberg, and William J. Broad, “U.S. Germ Warfare 

Research Pushes Treaty Limits,” New York Times, 4 September 2001, A1, A6. 

36. Laurie Garrett, The Coming Plague (New York: Penguin Books, 1994), 10. 

37. Peter R. Lavoy, Scott D. Sagan, and James J. Wirtz, Planning the Unthinkable: 

How New Powers Will Use Nuclear, Biological, and Chemical Weapons (Ithica, NY: 

Cornell University Press, 2000), 5. 

38. Malcolm R. Dando, The New Biological Weapons: Threat Proliferation, and 

Control (Boulder, CO: Lynne Rienner Publishers, Inc, 2001), 11. 

39. Mangold and Goldberg, 182. 

40. Ibid., 110,159-61, 176. 

41. Ibid., 183. 

42. Ibid., 98. 

43. Tucker, 5. 

44. Association of Military Surgeons of the United States Newsletter, vol. 9, issue 2, 

(Summer 2001), 4. 

45. Mangold and Goldberg, 181; Alibek, xi. 

46. Block, 41-5. 

47. Lavoy et al, 4-5. 

48. Mangold and Goldberg, 373. 
32 . . . Next Generation Bioweapons

49. Peter L. Hays, Vincent J. Jodoin, Alan R. Van Tassel, Countering the 

Proliferation and Use of Weapons of Mass Destruction (New York: The McGraw-Hill 

Companies, Inc., 1998), 9; Zilinskas estimates that it may only take five years for 

scientists working for “proliferant governments or subnational groups” to develop 

biological weapons from the new biotechnologies. R.A. Zilinskas (Ed.) Biological 

Warfare: Modern Offense and Defense (Boulder, CO: Lynne Rienner, 2000). 

50. Tucker, 9. 

51. Ibid., 8-9. Lavoy et al, 232, 257. 

52. Raymond A. Zilinskas, Biological Warfare: Modern Offense and Defense 

(Boulder, CO: Lynne Rienner Publishers, 2000), 2-3. 

53. Laurie Garrett, The Coming Plague: Newly Emerging Diseases in a World of 

Balance (New York: Penguin Books, 1994), 53. 

54. Andrew F. Krepinevich, “Cavalry to Computer: The Pattern of Military 

Revolutions,” The National Interest, No. 37, (Fall 1994), 30-42. 

55. Moisés Naím, “Reinventing War,” Foreign Policy, November/December 2001, 

37. 

56. Claire M. Fraser and Malcolm R. Dando, “Genomics and Future Biological 

Weapons: The Need for Preventive Action by the Biomedical Community,” Published 

online: 22 October 20001 by Nature Publishing Group @ http//genetics.nature.com, p. 1. 

57. Even crop duster aircraft and mosquito sprayer equipment are potential delivery 

mechanisms for bioterrorism. 

58. Block, 60. 

59. Ian O. Lesser, et. al, Countering the New Terrorism (Santa Monica, CA: 

RAND, 1999), 7-38. Although the total number of terrorist events worldwide has 

declined in the 1990s, the percentage of terrorist events resulting in fatalities (and total 

numbers of fatalities) increased; Ehud Sprinzak, “The Lone Gunman,” Foreign Policy, 

November/December 2001, 72-3. According to Sprinzak, today’s “megalomaniacal 

hyperterrorists” are innovators and developers. They incessantly look for original ways 

to surprise and devastate the enemy. They think big, seeking to go beyond 

“conventional” terrorism and, unlike most terrorists, could be willing to use weapons of 

mass destruction. If the intent of terrorists is to inflict mass casualties, then biological 

agents are likely to be used. 
Next Generation Bioweapons . . . 33

60. Richard Preston, The Hot Zone (New York: Anchor Books/Doubleday, 1994). 

Tom Clancy’s Executive Orders and Michael Critchton’s The Andromeda Strain were 

other popular books on pathogens. 

61. Alexander, 215. PDD-62 contained major initiatives to combat 

internationalterrorism. PDD-63 addressed protection of the nation’s critical infrastructure 

from both physical and cyber attacks. 

62. Preventing Emerging Infectious Diseases: A Strategy for the 21st Century, 

(Atlanta: U.S. Department of Health and Human Services, Centers for Disease Control 

and Prevention, reprinted August 2000), vii. 

63. Garrett, 6; Block, 59. New infectious diseases are thought to emerge due to 

situations where humans now live in close proximity to animals. 

64. William J. Broad, “Genome Offers ‘Fingerprint’ for Anthrax: Analysis of 

Bacterium Could Help Investigators,” New York Times, 28 November 2001, B-1-8. 

65. Block, 45. The minimum lethal dose for inhalational anthrax (reported to 

be5,000 to 10,000 spores) is high compared to some other biological agents. 

66. Fraser and Dando, 2. 

67. Block, 46-7. 

68. Drell, 355. 

69. Ibid., 355; Sheryl Gay Stolberg with Melody Peterson, “U.S. Orders Vast 

Supply of Vaccine for Smallpox,” New York Times, 29 November 2001, B-8. 

70. Alibek, 258-61; Block, 49. The FSU’s biological warfare program was 

massive, totaling over 18 complexes and 60,000 workers. Considering that this dwarfed 

the worldwide commitment to the Human Genome Project, there is significant concern 

about what the FSU bioscientists were able to accomplish. Despite President Yeltsen’s 

order to close the Russian BW program, biological warfare research is thought to 

continue in the FSU. 

71. Block, 51. 

72. Caudle, 63-4. 

73. Personal conversation with Bill Patrick, 6 September 2001. 

74. Asymmetric warfare is the use of less technological, less expensive, and/or 

more unconventional weapons, tactics and strategies. Historically, this has taken the 
34 . . . Next Generation Bioweapons

form of guerilla warfare, but today includes cyber war and the use of weapons of mass 

destruction. 

75. Zilinskas, 1-2. 

76. Katherine McIntire Peters, “Behind in the Biowar,” Government 

Executive,December 2001, 28. 

77. Ibid., 28. The potential to inflict damage on the enemy is obvious. Less clear is 

how to protect friendly troops from disease while spreading it among the enemy. 

78. The Worldwide Biological Warfare Weapons Threat, 2001, 1. 

79. Zilinskas, 6. 

80. David Franz quoted by Peters in “Behind in the Biowar,” 30. 

81. Fraser and Dando, 2. 

82. Dando, 58. 

83. Donald Rumsfeld, Report of the Quadrennial Defense Review, (Washington, 

D.C.: Department of Defense, September 2001), 7. 

84. Block, 39-40. 

85. Ibid., 51-70. 

86. Ibid., 52-56. 

87. Ibid., 56-60. 

88. International Human Genome Sequencing Consortium, “Initial Sequencing and 

Analysis of the Human Genome,” Nature, Vol 409, 15 February 2001, 860-921 

(http://www.tigr.org/tdb/mdb/mdbcomplete.html); see also, David Baltimore, “Our 

Genome Unveiled,” Nature, Vol 409, 15 February 2001, 814-816. 

89. International Human Genome Sequencing Consortium, 860-921. 

90. Rachel Nowak, “Disaster in the Making,” New Scientist, 13 January 2001, 4-5. 

91. Fraser and Dando, 3. 

92. Clyde A. Hutchison, et al, “Global Transposon Mutagenesis and a Minimal 

Mycoplasma Genome,” Science, Vol 286, 10 December 1999, 2165-2169. 
Next Generation Bioweapons . . . 35

93. A minimal genome can be defined as the smallest set of genes that allows 

forreplication of the organism in a particular environment. 

94. Philip Cohen, “A Terrifying Power,” New Scientist, 30 January 1999, 10. 

95. Carina Dennis, “The Bugs of War,” Nature, 17 May 01, p. 232-235. 

96. Block, 60-63. 

97. Zilinskas, 13. The bacteria E. coli have been genetically engineered to produce 

commercial quantities of valuable complex proteins, including insulin, human growth 

hormone, interferon, hepatitis B surface antigens, and angiotensin. 

98. Bernard Moss, “Genetically Engineered Poxviruses for Recombinant Gene 

Expression, Vaccination, and Safety,” Proceedings of the National Academy of Sciences 

of the United States of America, 1996, Vol. 93, 11341-11348, as abstracted in the Journal 

of the American Medical Association, 6 August 1997, Vol. 278, No.5., 350. 

99. Block, 60. 

100. Ibid., 62. 

101. Ronald J. Jackson, et. al., “Expression of Mouse Interleukin-4 by a 

Recombinant Ectromelia Virus Suppresses Cytolytic Lymphocyte Responses and 

Overcomes Genetic Resistance to Mousepox,” Journal of Virology, February 2001, 

1205-1210. 

102. Nowak, 4-5; see also, Stanley L. Robbins, Ramzi S. Cotran, and Vinay 

Kumar, Pathologic Basis of Disease, Third Ed. (Philadelphia: W.B. Saunders Company, 

1984), 158. The immune response compromises all the phenomena that result from the 

specific interaction of cells of the immune system with antigens (foreign material). 

Entrance of an antigen into the body can have two possible outcomes: (1) a humoral 

immune response, involving the synthesis and release of antibody molecules within the 

blood and extracellular fluids; or (2) cell-mediated immunity, manifested by production 

of “sensitized” lymphocytes capable of interacting with antigens such as bacterial toxins 

and cause neutralization of the toxin, or they can coat the antigenic surfaces of 

microorganisms and render them susceptible to lysis by complement or to phagocytosis 

by macrophages. In the second type of reaction, the sensitized cells are responsible for 

such actions as rejection of foreign tissue grafts and resistance against many intracellular 

microbes, i.e., viruses, fungi, and some bacteria. 

103. Dennis, 232-235. 
36 . . . Next Generation Bioweapons

104. Jose B. Cibelli, Robert P. Lanza and Michael D. West, with Carol Ezzell, 

“The First Human Cloned Embryo,” Scientific American, January 2002. 

105. Gina Kolata with Andrew Pollack, “A Breakthrough on Cloning? Perhaps, or 

Perhaps Not Yet,” New York Times, 27 November 2001, A1-12. 

106. Cibelli, x. 

107. Gina Kolata, “Company Says It Produced Embryo Clones,” New York Times, 

26 November 2001, A-14. 

108. Sharon Begley, “Brave New Monkey,” Newsweek, 22 January 2001, 50-52. 

109. Block, 63-65. 

110. Garrett, 226-233. 

111. Block, 65-68. 

112. Zilinskas, 18. 

113. Block, 68-71. 

114. Fraser and Dando, 2. 

115. Block, 51. 

116. Dando, 41. 

117. Fraser and Dando, 3. 

118. Block, 47-48; Dando, 125-129. 

119. Dennis, 232-235. 

120. Fraser and Dando, 4; see also Dando, 127. Polymorphisms are differences in a 

specific gene. Single nucleotide polymorphisms (SNP) arise from the change of just one 

base pair in the DNA sequence. SNPs are markers that may lead to the genetic basis of 

many diseases. Theoretically, a SNP or sets of SNPs may provide new targets for new 

drugs, toxins, or bioregulators. 

121. Peters, 30. 
Next Generation Bioweapons . . . 37 

122. Mildred K. Cho, David Magnus, Arthur L. Caplan, Daniel McGee and the 

Ethics of Genomics Group, “Ethical Considerations in Synthesizing a Minimal Genome,” 

Science, Vol 286, 10 December 1999, 2087-2090. 

123. Zilinskas, 13-15. 

124. Fraser and Dando, 3. 

125. Rick Weiss, “A Terrorist’s Fragile Footprint,” The Washington Post, 29 

November 2001, 1. 

126. Broad, B1-8. 

127. Fraser and Dando, 3. 

128. Robins, 158. See footnote 102 for definitions of humoral and cell-mediated 

immunity. 

129. Zilinskas, 21. 

130. Dennis, 232-235. 

131. Fraser and Dando, 3. 

132. William A. Haseltine, “Beyond Chicken Soup,” Scientific American, 

November 2001, 56-63. 

133. Peters, 30. 

134. Dennis, 232-235. 

135. Dando, 11. 

136. Block, 71. 

137. Zilinskas, 5-6. 

138. Alexander, 119-121, 196. 

139. Block, 42. 

140. Alexander, 190. 
38 . . . Next Generation Bioweapons

141. Lt Col George W. Christopher, LTC Theodore J. Cieslak, MAJ Julie Pavlin, 

and COL Edward M. Eitzen, “Biological Warfare: A Historical Perspective,” Journal of 

the American Medical Association, Vol 278, No.5, 6 August 1997, 412-417. 

142. Alexander, 192. 

143. Jeffery K. Smart, “History of Chemical and Biological Warfare: An American 

Perspective,” in Textbook of Military Medicine: Medical Aspects of Chemical and 

Biological Warfare, eds. Frederick R. Sidell, Ernest T. Takafuji, and David R. Franz 

(Washington D.C.: Office of the Surgeon General, US Army, 1997), 73. 

144. Drell, 358. 

145. Jeffery D. Simon, “Biological Terrorism: Preparing to Meet the Threat,” 

Journal of the American Medical Association, Vol 278, No.5, 6 August 1997, 428-430. 

146. Amy Smithson, et. al, Ataxia: The Chemical and Biological Terrorism Threat 

and the U.S. Response, October 2000, as quoted by Peters in “Behind in the Biowar,” 33. 

147. Elizabeth Becker and Tim Weiner, “New Office to Become a White House 

Agency,” New York Times, 28 September 2001. 

148. Zilinskas, 128. 

149. Alexander, 116. 

150. Sir William Stewart as quoted by Patricia Reaney, “Animal Disease is 

Reminder of Bioterrorism Danger,” in Reuters news report, 3 September 2001. 
USAF Counterproliferation Center 

 The USAF Counterproliferation Center was established in 1999 to provide 

education and research to the present and future leaders of the USAF, to assist them in 

their activities to counter the threats posed by adversaries equipped with weapons of mass 

destruction 

Barry R. Schneider, Director 

USAF Counterproliferation Center 

325 Chennault Circle 

Maxwell AFB AL 36112-6427 

Email: Barry.Schneider@maxwell.af.mil

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The Counterproliferation Papers 

Email: JoAnn.Eddy@maxwell.af.mil

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