Impacts of Neuroscience

March 1984

NTIS order #PB84-196716
Recommended Citation:

Impact of Neuroscience—A Background Paper (Washington, D.C.: U.S. Congress, Office

of Technology Assessment, OTA-BP-BA-24, March 1984).

Library of Congress Catalog Card Number 84-601020

For sale by the Superintendent of Documents

U.S. Government Printing Office, Washington, D.C. 20402
.

Preface

Neuroscience is one of the fastest growing areas of scientific inquiry in biology.

This background paper, prepared by OTA with significant contribution by the Congressional Research Service, surveys the scientific basis of research on the nervous system, identifies several medical applications, examines some of the social effects, and

discusses some of the difficult ethical and political issues that may arise from discoveries

in neuroscience.

This paper is part of an assessment of Technology and Aging in America that was

requested by the Senate Special Committee on Aging, the House Select Committee on

Aging, and endorsed by the House Committee on Education and Labor. The paper arose

naturally from inquiry into diseases and conditions that affect the health of older Americans. Neuroscience research has led to new treatments for major causes of death in

both the developed world (cardiovascular disease and stroke), and developing nations

(parasitic diseases), in addition to advancing knowledge about neurological and psychiatric

disorders. In the United States, the aging of the population provides one of the strongest

incentives for research on the nervous system, because of the burden of illness imposed by several mental and organic brain disorders that become increasingly common with age, such as depression, insomnia, and Alzheimer disease.

Alzheimer disease alone affects more than 1 million Americans, and causes severe

financial and emotional stress on each family that it affects. Alzheimer disease is one

of the most significant causes of need for long-term care in the United States. One of

the most important motives driving neuroscience research is the desire for solutions

to the ravages of brain diseases like Alzheimer disease. * This background paper focuses

on the status of basic neuroscience research, and was extended, in accordance with

the OTA mandate, to investigate not only the current status and potential medical applications, but also to include broad social and ethical issues that might arise from such

research.

● More detailed discussion of Alzheimer disease and related disorders will be found in the OTA assessment Technology

and Aging in America to be published subsequently.

. . . ///
OTA Impacts of Neuroscience Staff and Contractors

H. David Banta* and Roger Herdman, * * Assistant Director, OTA

Health and Life Sciences Division

Gretchen S. Kolsrud, Biological Applications Program Manager

David McCallum, Project Director, Technology and Aging in America, June 1982-September 1983

Robert Harootyan, Project Director, Technology and Aging in America, since September 1983

Robert Mullan Cook-Deegan, Study Director, Congressional Science Fellow

Miriam Davis, Environmental Sciences Fellow, September 1982-September 1983

Congressional Research Service, Library of Congress

Project Staff

Eleanor Pitts

Principal Contractor s

George Adelman Stephanie Bird Stanley Molner Eleanor Pitts

Principal Edito~ Impacts of Neuroscience

Rebecca A. Bean

Editon Technology and Aging in America

Phyllis Avedon

Staff Reviewers

James Thomas Susan Clymer Louise Williams

Nanette Newell Debora Burch Robert Harootyan

Special Contributor

Michael Simpson, Congressional Research Service

Support Staff

Elma Rubright Fatimah Scott

OTA Publishing Staff

John C. Holmes, Publishing Officer

John Bergling Kathie S. Boss Reed Bundy Debra M. Datcher

Joe Henson Glenda Lawing Linda A. Leahy Cheryl J. Manning

“Until August 1983.

● ● From Dec. 26, 1983,

iv
Contents

Page

INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Why is Neuroscience Important Now?..... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Basis for Congressional Interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

Relationship of This Background Paper to the OTA Aging Study . . . . . . . . . . . . . . . . . . . . . . . . . 3

Organization of This Paper . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

WHAT IS NEUROSCIENCE? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

Interdisciplinary Nature of Neuroscience . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

Basic Concepts of Neuroscience . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Wide Variety of Technologies Used in Neuroscience. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

MEDICAL IMPACTS OF NEUROSCIENCE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Neurological and Psychiatric Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Other Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Issues Affecting Development of Drugs for the Nervous System . . . . . . . . . . . . . . . . . . . . . . . . . . 8

Support for Biomedical Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

SOCIAL IMPACTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

Neurotoxic exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

Alcohol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

Drug Abuse and Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

Biological Rhythms and Work Schedules. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

Industrial Productivity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

Long-Term Effects on Industry. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

Crime and Violence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

Sex Differences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

Education. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

Ethical and Legal Aspects of Neuroscience . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

CONCLUSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

APPENDIX A–FEDERAL SUPPORT FOR NEUROSCIENCE RESEARCH. .,... . . . . . . . . . . . . . . . . 23

Funding Levels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

Coordination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

Funding Cycles and Funding Stability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

Policy Questions Regarding Federal Support For Neuroscience . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

APPENDIX B–FEDERAL REGULATION OF AND RESEARCH ON NEUROTOXIC EXPOSURE . . . 26

Federal Regulation of Toxic Substances, Including Neurotoxins. . . . . . . . . . . . . . . . . . . . . . . . . . . 26

Pesticide Regulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

Federal Research on Toxicology, Including Neurotoxicology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

APPENDIX C–STATEMENT BY DAVID L. BAZELON. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28

APPENDIX D–WORKSHOP PARTICIPANTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32

APPENDIX E–REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34

Tables f

Table No. Page

A-1. Estimated Funding Levels for Federal Neuroscience R&D Fiscal Year 1983 . . . . . . . . . . . . . 24

B-I. Selected Federal Agencies and Laws Regulating Neurotoxic Exposure. . . . . . . . . . . . . . . . . . 26

Figure

Figure No. Page

B-1. Selected Agencies Doing Federal Research on Neurotoxicity. . . . . . . . . . . . . . . . . . . . . . . . . . 27

v
Impacts of Neuroscience

Introduction

Neuroscience is the study of the nervous system, how it affects behavior, and how it is affected

by disease. The goal of neuroscience is to define

and understand the continuum from molecule to

cell to behavior. New tools available to scientists

promise to clarify some of the mysteries of how

behavior is related to molecular, cellular, and electrical events in the brain.

The 50 million Americans with disabilities

caused by neurological and psychiatric diseases

provide compelling justification for studying diseases that affect the nervous system. Damage to

the nervous system from exposure to toxic agents,

both at work and in the environment, is receiving renewed attention from policy makers as

knowledge increases. Neuroscience research may

contribute to the solution of some problems

related to crime and substance abuse. * The health

and productivity of the American work force may

be altered by application of principles derived

from neuroscience. The multiplicity of ways in

which understanding human behavior can impact

on society underscores the need to understand

the concepts of neuroscience and how that science relates to public policy. How social and

political institutions will face the challenges

brought by new knowledge based on neuroscience cannot be predicted, but future options will

be determined, in part, by actions taken now.

Why is neuroscience important now?

The wide diversity of applications of knowledge

about behavior and other brain functions would

make neuroscience interesting at any point in time.

Neuroscience is especially important now because

in addition to intrinsic interest in the nervous system, the field has been developing at an increasingly rapid pace. Progress over the past decade

has exceeded expectations by a wide margin be-

“Substance abuse refers to deliberate use of drugs or alcohol,

smoking, inhalation of sol~’ents (“glue sniffing”), and other potentially damaging substances,

Photo credit: Sfadey 8. Kater, Department of Zoology, Unlverslty of Iowa

Identified neurons from /+e/koma growing in cell

culture and stained with a fluorescent antibody to

reveal the presence of the transmitter serotonin

cause of newly available scientific techniques,

innovative institutional arrangements for studying

the nervous system at universities, and cooperation among different scientific disciplines. Continued rapid progress is likely if present levels of

support for research are maintained.

Many applications of neuroscience research

may come to fruition in the next decade. Such

applications may include new pharmaceutical

agents, improved human factors engineering, improved pesticides, and prevention of mental disabilities due to prenatal events or toxic exposures.

Improved treatment of psychiatric disorders may

benefit many potential patients, Better understanding of cognitive abilities, mood, and memory

may permit personal control of such functions

or at least elaboration of why control is not

possible.

As these applications are realized, the risks and

ethical issues raised by advances in neuroscience

may well become more evident and pose new

questions for public policy. This background

paper is an attempt to outline the scientific basis

of neuroscience, to describe some of its poten1
2 ● Impacts of Neuroscience—Background Paper

tial applications, and to identify some of the ethical questions that may arise so that policymakers

can better anticipate issues that may emerge.

Basis for congressional interest

Congress, and other branches of the Federal

Government, are involved with neuroscience in

several ways. Most funding for basic neuroscience research in the United States is channeled

through agencies of the Federal Government. Payment for medical costs due to disorders affecting

the brain is accomplished through the Federal

agencies that manage the Medicare, Medicaid, and

mental health programs. Congressional legislation

has provided the backbone for regulatory actions

that have reduced illness and accidents (and thus

health care costs) by preventing exposure to

chemicals that injure the nervous system. Congress has expressed concern for public safety in

Photo credit: Dennis Landis, Depaflment of Neurology,

Massachusetts General Hospital

A view of the interior and membrane of nerve cells in

the cerebellum. This photograph was taken by an

electron microscope of a special preparation of tissue

called “freeze fracture”

hearings on the nuclear and airline industries,

citing the potential for accidents due to irregular work hours and disregard of scientific knowledge about daily biological rhythms. Use of drugs

that affect mental function is a policy concern for

several levels of government; regulation of drug

laws, enforcement of drug abuse statutes, and

payment for treatment of drug addiction are

shared among Federal, State, and local governments.

The diversity of ways to apply neuroscience is

reflected by the various congressional activities

related to neuroscience. Over the past year, hearings on funding of neuroscience research have

been held before authorizing and appropriations

committees of both the U.S. House of Representatives and the U.S. Senate, Three committees have

held hearings on various aspects of Alzheimer

disease, Applying neuroscience research to scheduling of shift workers was the subject of one recent hearing; testimony reviewing the possible

relationship between acid rain and injury to nerve

cells was heard in another. Numerous hearings

on environmental exposure and pesticide regulation have been convened.

The optimal mechanism for funding biomedical

research has been a topic of extensive political

debate. This has resulted in competing bills that

mandate different levels of congressional involvement in funding decisions for the National Institutes of Health (NIH), the largest Federal agenc,y

that supports biomedical research. Several different congressional bills creating a Federal agency

for scientific and public discussion of topics

related to biology and bioethics have been introduced.

All these congressional activities potentially affect, and are affected by, developments in neuroscience. Each of the topics summarized in this

background paper is within the purview of some

congressional function. One purpose of this summary is to point out the role of neuroscience research and its applications in these many congressional activities.

Several Federal agencies have identified neuroscience as an important and rapidly evolving field.

In 1982, the Office of Science and Technology

Policy (OSTP) selected neuroscience as one of
/introduction . 3

Photo credit: Dennk Landis, Depatiment of Neurology,

Massachusetts General Hospital

View of glial cells growing in tissue culture taken by

a scanning electron microscope

seven areas for review by the National Academy

of Sciences* (l). The OSTP report and others

issued by branches of the Public Health Service

and the National Science Foundation (NSF) document rapid advances in neuroscience research.

Relationship of this background

paper to the OTA aging study

This background paper is part of an assessment

of Technology and Aging in America by the Office

of Technology Assessment (OTA). The prevalence

of diseases affecting the brain, primarily psychiatric and neurological diseases, is projected to rise in

coming decades, as the population ages, because

age increases the risk of developing depression,

dementia, * * and other brain disorders. Because

Americans are living longer, they run greater

risks of developing the diseases of old age. Greater

numbers of people reaching old age and rising

—

● A report was prepared by the Committee on Science, Engineering, and Public Polic~’ (COSEPUP) of the National Academy of Sciences, highlighting some of the most promising areas of research

in neuroscience. It was used to brief George Keyworth, director

of OSTP, and was intended, in part, to provide guidance for the

Office of hlanagement and Budget and the J$rhite House.

● ● Dementia is the diminution of higher menta[ functions such

as memory, or the ability to calculate and think.

average longevity both contribute to the increasing prevalence of mental and neurological diseases. Developments in neuroscience therefore

may affect the health and well-being of the elderly

population far more than the general population.

Assessment of biomedical research on neurological and psychiatric diseases is thus an integral

part of understanding these future changes.

A workshop was conducted on policy implications of neuroscience research as an element of

the assessment of Technology and Aging in

America. Because OTA evaluates indirect, as well

as direct, impacts of science and technolo~v, participants discussed not only the medical risks and

benefits of neuroscience for the elderly, but also

several relevant social, medical, industrial, and

public policy issues. *

Organization of this paper

Several papers on various aspects of neuroscience were written by contractors in preparation

for the workshop. Some of these papers, together

with chapters prepared by OTA, are printed under

separate cover as hqmcts of~euroscience: Working Papers, available from the National Technical

Information Service. The papers are titled:

● A Primer of Neural Function;

● Medical Impacts of Neuroscience;

● New Technologies in Neuroscience;

● Social Impacts of Neuroscience; and

● The Federal Role in Neuroscience.

This publication summarizes the above papers,

gives further background on selected topics, and

includes points raised in discussion at the workshop.

An introductory description of neuroscience is

followed by a review of selected applications and

other topics related to neuroscience, emphasizing the role of the Federal Government.

*Discussion of chemical and biological warfare was not included

on the workshop agenda because it would be impractical for the

Health and Life Sciences Division of OTA to arrange for retriew of

classified information in an open workshop. The topic of chemical

and biological warfare, while extremely important, therefore was

omitted.

25-359 0 - 84 - 2 : QL 3
4 Impacts of Neuroscience—Background paper

what is neuroscience?

Neuroscience is the term applied to research

on how the nervous system works and how it is

affected by disease. The complexity of behavior

is reflected in the complexity of the body’s most

sophisticated control system: the nervous system.

The central nervous system (the brain and spinal

cord) is composed of more than 10 billion nerve

cells and 100 billion supporting cells. Nerve cells

are arranged in specific circuits in precise anatomical arrangements. How nerve cells work individually to conduct electrical signals, or in conPhoto credit: Dennis Landis, Depafiment of Neurology,

Massachusetts Genera/ Hospital

Photograph from an electron microscope of a cell that

secretes the hormone prolactin from the

pituitary gland of a rat

cert to result in behavior, thought, and consciousness, are questions addressed by research

in neuroscience. Neuroscience also contributes

to several medical disciplines. Diseases primarily affecting the nervous system afflict 50 million

Americans; these diseases are the focus of research in neurology, psychiatry, neurosurgery,

and other medical fields.

Interdisciplinary nature of

neuroscience

The character of research in neuroscience has

been defined by its interdisciplinary nature. The

objects of study—behavior, biology, electrical phenomena, membrane biophysics, and diverse medical applications—do not fit easily into traditional

academic disciplines. As a consequence, neuroscience has drawn on talent from such diverse fields

as anatomy, physiology, physics, electronics, genetics, biochemistry, optics, pharmacology, ethology, psychology, neurology, psychiatry, neurosurgery, internal medicine, and information science.

Although early studies of the electrical properties of individual cells depended on advances in

electronics, extensive knowledge of natural history, especially marine biology, was equally important for neuroscience research. Study of such

marine organisms as squids, lobsters, and horseshoe crabs has proved invaluable in neuroscience

research. This curious aspect of neuroscience is

due to many “experiments of nature” in marine

organisms that render them especially appropriate for the study of neural phenomena. One good

example of this is the ‘(electric eel,” Torpedo

californicum, which uses a special organ in its

body to store electrical charge for stunning enemies and prey. The electrical organ uses the same

chemical for cell-to-cell communication that humans use for normal muscular contraction. This

special organ has provided a plentiful, much

needed source of receptor protein for studying

how muscles contract and investigating the

human disease myasthenia gravis. A number of

important scientific and medical discoveries thus

derive from the study of this bizarre creature of

the hydrosphere.
What Is Neuroscience? ● 5

Neuroscience investigators have borrowed extensively from the fields of mathematics and

physics to explain the interactions of molecules,

cells, and networks of cells. Most recently, neuroscience has been blended with the fields of molecular biology, genetics, and biochemistry. Many

of the most dramatic recent advances in neuroscience were based on fundamental new techniques developed in the fields of molecular genetics and biochemistry.

Neuroscience encompasses the study of how

nerve cells are born and die in roundworms, how

leech nerve cells act in concert to produce eating

and reproductive behaviors, how pesticides work

on the insect nervous system, and how Alzheimer

disease causes dementia.

Basic concepts of neuroscience

The study of neuroscience is unified by certain

basic concepts (2):

●

●

●

on explication of how such anatomic connections are made.

Understanding of nerve cell networks also

depends on knowledge about cell-to-cell communication between individual nerve cells.

Electrical properties of individual cells are important in the transmission of impulses and

in intercellular communication.

The electrical properties of nerve and muscle cells are controlled by molecules on the

surface of the cell (ion channels and specific

receptors).

Scientists believe that behavior arises from

many cells working in concert. The basic precepts

of neuroscience have been derived from studying the electrical properties of individual nerve

cells. The classic work of scientists in the 1940’s

and 1950’s was concerned largely with describing the way nerve and muscle cell membranes

could propagate electrical impulses. Over the next

two decades, scientists discovered many of the

mechanisms involved in the journey of an impulse

along a single nerve cell, The next major task was

to describe the way nerve cells communicate. The

ideas underlying neurotransmission * were established in the following decades and continue to

evolve rapidly today. The list of chemicals involved in neurotransmission, once limited to a

handful of simple compounds, has rapidly lengthened to include complex proteins and protein

fragments, hormones, and other types of mole-

● Behavior, perception, and cognition are

results of integrated actions of networks of

nerve cells.

● The activities of nerve cell networks are characterized by extremely precise anatomical

specificity and enormous complexity. Understanding of neural phenomena will depend

cules.

Wide variety of technologies used

in neuroscience

The advance of knowledge in neuroscience

depended, in large part, on new technolog

Photo credit: Dennis Landis, Depatiment of Neurology,

Massachusetts General Hospital

The specialized membrane of an astrocyte—a support

cell of the central nervous system—in the mouse. This

is taken from an area near the blood supply to the brain

that prevents toxic materials from crossing into the

brain from the bloodstream

has

es.

Scientists can now watch the functioning brain,

investigate the behavior of whole organisms buy

studying molecular interactions, obtain electrical

measurements of events in single nerve cells, and

perform computer analysis of events in nerve cell

*In a process called neurotransmission, a nerve cell excites another

nerve cell through precise anatomical connections called synapses.

A specific chemical called a neurotransmitter is released by the sending cell into the synapse and attaches itself to receptor molecules

on a receiving cell. Attachment of the neurotransmitter to the receptor causes electrical changes in the receiving cell, in a neural chain

reaction.
6 ● lmpacts of Neuroscience—Background Paper

networks. New drugs allow analysis of molecular

events affecting the electrical properties of nerve

cells.

New methods of visualizing the human brain

without invasive procedures rely on developments in electronics, organic chemistry, numerical modeling, and computers. Investigation of

nerve cells’ electrical properties has required new

types of electronic amplifiers and tools for manipulating fine instruments. Enlarged capacity for

electronic memory has assisted greatly in the analysis of electronic data from multiple nerve cells

and in reconstructing images from series of electron-microscope photographs of individual nerve

cells. Recombinant DNA (rDNA) techniques have

permitted the study of genes important in nerve

cell function, and monoclinal antibodies (MAb) *

promise to revolutionize understanding of how

nerve cells work at the molecular level.

“Monoc]onal antibodies are molecules produced by new laboratory techniques. They are useful for purification and identification

of specific proteins and for other purposes.

Medical impacts of neuroscience

Neurological and psychiatric diseases

The study of psychiatric and neurological illness

has a long and colorful history. Ancient Greek

physicians knew that brain damage could lead to

aberrant behavior. Precise definition of the anatomy of the nervous system and correlation of

anatomy to specific neural functions were important parts of European medicine early in the 20th

century. Freud presented theories about subconscious mental processes, while others were describing the first correlations between diseases

and anatomic changes in the brain. These correlations led to new diagnostic categories and facilitated differentiation of groups of patients that

once had been categorized together. Refined diagnosis made it possible to introduce new therapies

for specific groups.

The introduction of drugs to treat neurological and psychiatric diseases began relatively

recently. New drug treatments have been developed for some important disorders, although

these treatments are not complete. Effective treatments for Parkinson disease, depression, manicdepressive illness, insomnia, pain, epilepsy, and

acute anxiety have led to optimism that other diseases also may prove treatable and that present

treatments might be improved.

The potential for improvement of current therapies is great. There is no effective treatment or

means of prevention for many of the most prevalent and costly diseases; for example, there is a

great need for effective prevention or treatment

of Alzheimer disease, which affects over a million

older Americans and is a major source of need

for long-term care. Treatments for depression,

anxiety, insomnia, and other disorders also can

be further improved by reducing adverse effects

of present treatments, or by reaching those who

do not respond to current therapies.

Advances also can be anticipated in neurosurgical techniques, rehabilitation therapies for injury

to the brain and spinal cord, and replacement of

limbs and sensory organs. Research in nerve regeneration, leg and arm replacement, and sophisticated hearing and seeing devices someday may

lead to effective compensation for lost abilities.

New technologies for visualizing the brain have

led to less risky and more effective ways to detect

brain tumors, areas of tissue death due to stroke,

and patterns of activity associated with epilepsy

and organic brain diseases. There has been a dramatic growth in knowledge about molecular and

cellular aspects of pain. Some of the most important relationships between the brain and the

body’s other control systems (e.g., the various

glands that make up the endocrine system) have

been elucidated only in the last decade.

The recent history of treatment for schizophrenia illustrates the complex interactions between

scientific advance, medical treatment, and public

policy. Many schizophrenic patients who formerly were institutionalized can now undergo drug
Medical Impacts of Neuroscience ● 7

treatment outside mental hospitals. New drug

therapies have encouraged public policies intended to reduce the number of patients in mental

hospitals. Such policies have been highly successful: there has been substantial depopulation

of mental institutions (3). However, reinstitutionalization of psychiatric patients has brought with

it some social costs of incomplete treatment. Current drugs tend to improve the symptoms of hallucination and delusion but do not correct other

symptoms of apathy, withdrawal, and lack of motivation (4). Patients are “better but not well” (5).

Many patients now released to participate in society are not capable mentally of doing so but are

not offered the option of institutional care (3).

Although drug treatment of schizophrenia has reduced some Federal and State health care expenditures through depopulation of mental institutions, the policy goal of deinstitutionalization

has not yet led to equitable or optimal care of

psychiatric patients.

The medical, social, and public policy interactions regarding schizophrenia treatment underscore the point that while neuroscience can improve the medical treatment of many diseases,

medical care is only one factor in the effective

management of disease. Some of the concepts regarding public policy and schizophrenia might be

applied as well to other disorders that affect mental function, such as Alzheimer disease and severe

depression.

Other diseases

The usefulness of neuroscience research is not

restricted to neurological and psychiatric diseases.

There is great potential for advances in managing fertility and infertility, cardiovascular disease,

infectious and parasitic diseases, developmental

disabilities, and immunologic disorders.

In the developed world, cardiovascular diseases

are a major source of illness and death, especially in older individuals. The development of new

drugs for cardiovascular diseases has depended,

in large part, on advances in understanding the

physiology and electrical properties of nerve and

muscle cells. Two classes of drugs recently introduced for the treatment of hypertension and cardiovascular disease—the so called “beta blockers”

and “calcium antagonists’ ’—were tools for the

study of nerve and muscle cells for years before

they were shown to have clinical applications (6).

In the developing world, parasitic diseases are

serious health problems. Ancylostomiasis (hookworm infection) affects 20 to 25 percent of mankind. A group of drugs working at specific nerve

receptors constitute the primary treatment of this

disease. The drugs work by interfering with

neurotransmission, paralyzing the worm. Because

the drugs do not enter the brain or spinal cord

of the host, only the worm is affected (7,8).

Schistosomiasis, a parasitic disease, affects over

200 million people, mainly in Asia, Latin America,

and Africa, where it is a major cause of death and

disability. Treatment involves paralyzing the parasite with drugs similar to hypnotic/sedative agents

currently in use (8).

The treatment of both of these major parasitic

diseases thus has depended on increased understanding of the interactions between nerve cells

and their neurotransmitter chemicals. Development of these new treatments also has depended

on understanding the neurobiology of invertebrate organisms, an area of research that is not

as well funded as study in mammals and other

higher animals. The use of chemicals to combat

parasitic diseases is an important example of how

neuroscience research on seemingly unimportant

invertebrate organisms has led to widespread

human benefits.

Fertility and infertility are concerns in both the

developed and developing worlds. Advances in

neuroscience, focusing on the neural mechanisms

in the hypothalamus that regulate hormone release and reproductive function, promise to yield

effective and safe methods of managing fertility

and infertility for both men and women (9).

Behavioral medicine, the study of how behavior

relates to disease, is another widely applicable

field. Research on how to control smoking, alcoholism, and stress may improve prevention of

cancer, liver disease, and cardiovascular illness;

further study might help explain the brain’s influences over the body’s defense mechanisms. Addiction has a behavioral component whose study

might lead to better control of drug and substance

abuse. Research in behavioral medicine may allow
——. —

8 ● Impactgs of Neuroscience—Background Paper

better control of eating disorders by controlling

appetite or by identifying environmental variables

that trigger inappropriate eating.

Nutritional factors affect brain development

and function. Most nutritional disorders involve

several different organ systems, but the nervous

system often is affected first or most severely. For

example, malnutrition during embryonic, fetal,

and early infant development leads to permanently diminished mental capacity. Severe deficiency

of most water-soluble vitamins leads to welldefined neurological syndromes manifested by

behavioral, sensory, and motor disabilities. Good

nutrition depends on an adequate number of

meals, well-balanced meals, and economic and

social mechanisms for providing food to the

population. Neuroscience research can help identify some of the factors that influence eating

behavior, set minimum dietary standards for

nutrients, and clarify the consequences of nutritional deficiency.

Issues affecting development of drugs

for the nervous system

The length of patent protection from competing

manufacturers, the development of drugs for rare

diseases, and the effects of international competition in the pharmaceutical industry are issues

related to the development of all drugs. While

these issues are important, they are not discussed

here because they are not directly related to

neuroscience. There are, however, several unique

issues related to drugs that specifically affect the

nervous system,

Central nervous system drugs constitute a large

fraction of the total pharmaceutical market compared with other drug types, but development

costs also are higher (10). The costs of development are believed by some to be due to the absence of adequate animal models for study of behavioral effects. The period used for U.S. Food

and Drug Administration (FDA) approval for drug

use is longer for drugs affecting mental function

than for other classes of drugs, such as cardiovascular drugs and antibiotics (11). It is claimed

that psychoactive drugs are regulated more stringently for demonstrated efficacy than other drugs

because the illnesses and disorders that are

treated often are not life-threatening, and fewer

undesirable side effects are permissible (12).

Indications for use of psychoactive drugs have

been confused in the past because of the difficulty

in establishing definitive psychiatric diagnosis. Difficulties in defining diagnoses and symptoms have

complicated the testing and use of psychoactive

drugs (u), although recently published standards

for diagnosis of mental illness may promote consistency (13).

The ethical problem of research using mentally incompetent patients is another impediment to

development of psychoactive drugs. Such patients

include those suffering from dementia and severe

psychiatric disease—precisely those patients for

whom many nervous system drugs are most

needed.

Many psychoactive drugs have been introduced

in the last two decades. There is promise of developing new drugs to affect “higher” functions

such as memory and learning, but dramatic new

developments probably are not imminent (14,15).

Some drugs intended to affect mental abilities,

particularly among demented patients, are being

tested now in the United States and Europe. Psychoactive agents now under development do not

appear much more powerful than existing drugs,

Thus, fears of new social problems from recreational and occupational use may be premature

(14). It is impossible to predict whether drugs that

substantially improve mental function can be developed in the future; there is insufficient evidence now to make such a judgment (15).

There is a higher potential for abuse with psychoactive drugs than with other types of drugs.

This leads to several regulatory effects that are

unique to psychoactive drugs. For example, those

drugs deemed prone to abuse are registered with

the Drug Enforcement Administration of the U.S.

Department of Justice, which may restrict dissemination and monitor use.

Support for biomedical research

The Federal Government, through Congress

and numerous executive agencies, is the primary

source of support for biomedical research in

general and neuroscience in particular. Appro-
Medical Impacts of Neuroscience ● 9

priations for biomedical research were over $4

billion in fiscal year 1983 and included approximately $500 million for neuroscience research

(see app. A). The funding of biomedical research

is a public investment intended to increase understanding of diseases and biological mechanisms

for the future benefit of citizens. Some of the

justifications for such research are the opportunities to:

● reduce future morbidity and mortality, and

associated medical costs;

● increase industrial productivity by reducing

loss of time from work due to illness;

● augment public health through prevention

based on new knowledge; and

● improve medical treatment based on scientific advances.

In addition to these features that are shared by

neuroscience and other fields of biomedical research, there are some aspects of neuroscience

research that distinguish it from other areas.

The prevalence of neurological and psychiatric

disease is increasing, largely due to aging of the

U.S. population. Disorders such as Alzheimer disease and depression, for example, are becoming

more common because they are more frequent

in the expanding elderly population. The increasing prevalence of neurological and psychiatric diseases contrasts with decreasing mortality from

some other types of diseases such as hypertension, atherosclerosis, and cancers other than lung

cancer. This rising prevalence of brain diseases

may increase future health care costs.

Neuroscience is distinctive in its rapid growth

and its potential for continued growth. Technical

innovations and institutional arrangements for

research in neuroscience have led to acceleration

of the scientific pace in the last decade. New technologies promise to enhance further the power

of scientific investigation of the nervous system.

Creation of new neuroscience programs and departments focuses academic attention on this

young scientific field. Growth requires support

from the Federal Government and private industry.

Neuroscience has reached its adolescence at a

time of budget austerity, in contrast to the field

of cancer research, which grew when Federal

funding for science was rapidly expanding. This

suggests that neuroscience now may be restrained because the resources available to support it are constrained by budgetary pressures.

Research in neuroscience is highly interdisciplinary. This makes institutional arrangements at

universities and other research centers more difficult for neuroscience than for research along

disciplinary lines. It is more difficult to sustain

support for an activity that has no departmental

or other institutional home. In recent years, the

trend in funding agencies has been to focus, even

more than in the past, on investigator-initiated

grants rather than institutional grants for interdisciplinary research. This has made sustenance

and creation of centers of excellence for neuroscience more difficult.

Training of personnel to do research in neuroscience is of particular concern. Funding for training programs has been cut more severely than

for research grants. A recent study by NSF, in

cooperation with the Society for Neuroscience,

found that despite rapid expansion of scientific

opportunities, jobs for young investigators are

limited, and training programs do not appear to

be growing a rapidly as in the recent past. * It

is significant that only five universities had

separate neuroscience departments-most degrees in neuroscience were granted by other departments in traditional disciplines.

Recent advances in technology and basic knowledge have rapidly expanded the frontiers of

neuroscience. The field thus may have great scientific potential at present, so that investment now

could be especially productive.

*Most research positions are at universities, and most universities

are not hiring. This is a major reason for limitation of new job opportunities,
10 ● Impacts of Neuroscience—Background paper

Social impacts

Neurotoxic exposure

An important topic in any discussion of Federal

policy involving neuroscience is damage to the

nervous system from toxic substances, or neurotoxicity. Injury to the nervous system is manifested by irritability, personality changes, fatigue,

lack of control of body movement, loss of sensation, and other symptoms. Often, symptoms of

neurotoxic injury are wrongly ascribed to aging

of the individual or to social factors. Damage to

nerves can occur from food, beverages, drugs,

environmental agents, or occupational exposure

to toxic agents. Many drugs have neurological side

effects, particularly those intended to affect some

aspect of neural or cardiovascular function (many

of these drugs are prescribed deliberately to affect one part of the nervous system, but also may

affect another part in an undesirable manner).

Metals and chemicals in the environment can affect individuals who inhale contaminated air or

ingest contaminated water and food. Occupational

exposure to neurotoxic substances also is quite

common.

Clinical research and toxicity testing already

have established that “roughly one-fourth of the

chemicals most frequently encountered in industry and of known toxicologic significance have

documented neurotoxic effects [and] this represents only a small part of the total problem” (16).

Discoveries of the severe effects of heavy metals,

some pesticides, and many organic solvents have

led to improved industrial and environmental controls and have prevented recurrence of many of

the disasters of the early industrial period. Many

instances of neurotoxic injury probably have not

been discovered yet, hidden because of the difficulty of establishing a link between changes in

cognition or behavior and the presence of an occupational or environmental toxic substance.

Neurotoxicity during brain development.–Early human development, particularly

during the embryonic and fetal stages, is a period

of special vulnerability to neurotoxic exposure.

Such exposure can be tragic because of the limited

ability of the nervous system to recover from serious insults. In general, nerve cells cannot be

regenerated; remaining cells can only readjust

their connections to compensate for lost cells.

Such compensation is often incomplete. Therefore, damage done to embryonic, fetal, and infant

brains often is associated with permanent disability. Examples of this are the lifelong mental retardation associated with maternal malnutrition during pregnancy (17), and long-lasting mental incapacity due to toxic lead exposure during infancy.

Interactions between chemicals encountered at

work or in the environment and other factors also

may damage the developing nervous system. Animal experiments have shown that effects due to

alcohol can be exacerbated by exposure to organic

solvents (18). Such interactions would be difficult

to detect in normal human settings because of the

large number of potentially confounding variables.

Difficulties in detecting neurotoxi c

damage.-one reason that the problem of

neurotoxic exposure has not been identified

earlier is the difficulty in detecting neural damage.

The symptoms of toxic injury to the nervous system often are changes in behavior, mood, and personality that may be wrongly ascribed to factors

other than chemical exposure. For example, the

“fetal alcohol syndrome” was not discovered

because of its deleterious effect on brain development that leads to permanent retardation but

because of distinctive facial and skeletal abnormalities in affected infants (19). The mental effects of prenatal alcohol exposure, which cause

the most serious long-term disability and lead to

most of the costs of care, only later were identified. In adults, many neurotoxic symptoms are

ascribed to stress, personal problems, or aging,

rather than to chemical or other environmental

exposures. Symptoms of irritability, forgetfulness,

and hostility often may be due to factors other

than chemical exposure, but the relative importance of the various factors cannot be ascertained because so little is known about the frequency of neurotoxic injury,
Social Impacts ● 1 1

Another factor that makes detection of neurotoxic injury difficult is the long period between

time of first exposure and identification of the

first definite symptoms. Most industrial neurotox -

ic hazards have been found because of relatively quick development of symptoms associated

with use of a particular chemical, or massive exposure levels. Examples of rapidly developing toxicity include episodes of chlordecone (Kepone) exposure in a Virginia plant in 1975 and methyl-Nbutyl ketone (MBK) toxicity in an Ohio coated-fabrics factory in 1973 (20). Massive exposure is exemplified by the “lead palsy” identified decades

ago, when lead levels were so high that workers

showed overt signs of disease within months,

In the tragedy of Minamata Bay in Japan, 121

people were afflicted by a mysterious illness, and

46 died (20). Many infants were born with irreversible mental retardation, and many fishermen

were affected, The pattern of exposure suggested

contamination of the water or food supply. Investigative work revealed mercury compounds

emanating from effluent discharged into the bay

by a local factory that was using mercury compounds in chemical production. The industrial

waste was entering the marine ecosystem, eventually contaminating fish and shellfish. Local

residents had ingested the contaminated fish. The

Minamata Bay episode was only one of several

instances of mercury poisoning identified in Japan

and Iran in the 1970’s.

The Minamata Bay episode is a classic example

of the complexity of neurotoxic exposure. Social

factors, dietary habits, industrial practices, ecological processes, occupational exposures, and developmental vulnerabilities of infants and fetuses

were all part of this web of interactions. Yet the

Minamata Bay exposure had a better chance of

detection than other types of exposure because

the effects of toxic injury appeared quickly in the

local population. Rapid identification was possible because the symptoms were severe and could

be related easily to a change in an industrial

process.

The more insidious effects of long-term, lowlevel exposure are not known for most chemicals.

The syndrome of “mad hatters)” who were exposed chronically to toxic levels of mercury com -

pounds in the manufacture of hats, is an example of long-term exposure leading to behavioral

abnormality that has been known for almost a

century, Workers in factories in the United States,

however, still suffer from tremors due to mercury poisoning (21). Neurotoxic effects of other

chemicals may not be identified if neural damage

occurs only after long periods of exposure. Research on this aspect of neurotoxicity is still in

its infancy.

One possible, but as yet unproven, hypothesis

relates acid rain to nerve cell injury. Congressional hearings were held recently by the Human

Services Subcommittee of the House Select Committee on Aging to look into a possible, but as yet

highly speculative, association between acid rain

and certain neurological illnesses, The link is postulated to be due to increased leaching of metals,

such as aluminum, from soils under acidic conditions. The hearings demonstrated the need for

increased research into possible links between

chronic brain disease and environmental factors.

Scientific activity has led to improved methods

of detecting neurotoxic injury, A recent survey

of behavioral toxicology studies found more than

90 publications, almost all of which had been published since 1973 (22). New methods of detection

based on changes in animal behavior have progressed, and the use of drugs to increase sensitivity of animal tests and tissue preparations also is

making headway (23), Such tests, however, have

not been incorporated into standard protocols

analogous to those used in testing potential

mutagenic and carcinogenic agents.

Progress in detecting and testing for neurotoxic

injury is important because effective regulation

of chemicals, drugs, and other potential toxic

agents must rely on findings based on reliable scientific methods.

Federal regulation and research. * —Even if

methods of detection can be found, there is concern that Federal agencies may not be caable of

promulgating and enforcing regulations for

neurotoxicity. The two largest Federal agencies

involved in regulating toxic exposure are the

*See app. B for details on Federal agencies imrohred in regulation

and research of neurotoxic exposure.

25-359 0 - 84 - 3 : QL 3
12 ● Impacts of Neuroscience—Background Paper

Environmental Protection Agency (EPA) and the

Occupational Safety and Health Administration

(OSHA) of the Department of Labor. Some congressional oversight has touched on issues related

to neurotoxicity. For example, the Subcommittee

on Department Operations, Research, and Foreign

Agriculture of the House Committee on Agriculture recently heard testimony that the resources

of EPA may be insufficient to review adequately

the needed studies or to process the registration

and testing of pesticides. Pesticides may be important sources of environmental neurotoxicity

to those in the general population who eat treated

food, and of occupational exposure to those engaged in pesticide production or agriculture. *

Urban dwellers are also subject to chemicals

that adhere to or are incorporated into foodstuffs.

Some countries allow use of agents that are

banned in the United States, and importation of

foods from these countries may be a source of

neurotoxicity. Vegetables and other foods grown

in urban gardens maybe contaminated by deliberate garden spraying or from treatment of trees,

shrubs, and grasses located nearby. Spraying of

trees, golf courses, and garden plants, and exposure to heavy metals from industry and automobile emissions all contribute to neurotoxic

residues that might accumulate on food grown

in urban environments.

Deliberate neurotoxic exposure.—There

is one category of neurotoxic exposure that individuals impose upon themselves. The use of

neurotoxic inhalants to alter consciousness is one

example of deliberate exposure. “Glue sniffing”

and inhalation of other organic solvents is common, especially among some innerwity populations. Inhalation of many organic solvents yields

a temporary feeling of euphoria but may damage

the nervous system and other organs (24). such

substance abuse is just one form of selfdestructive behavior, analogous to other examples of

drug abuse listed below.

● Pesticides are of particular concern because many act by affecting the transmission of impulses in the insect nervous system. There

is concern that pesticides may not be completely specific to the pest

but may also affect people and animals.

Alcohol

Alcohol is one of the most common neurotoxins in this country; it is estimated that 9 percent

of adults in the United States drink heavily on a

regular basis (25). Half of all automobile accidents

probably involve alcohol abuse, and the annual

economic cost of alcohol use in the United States

may be as high as $120 billion (25). Most of the

costs are incurred as health costs for treating alcoholism or loss of productivity due to illness and

alcohol-related disability.

In addition to the usual symptoms of alcohol

use, there are also numerous long-term health

consequences of heavy use. There are at least 15

neurological syndromes associated with alcohol,

as well as numerous blood, liver, and cardiovascular disorders. Certain cancers and infectious

diseases are also more common or more lethal

in alcoholic patients. Adults are not alone in their

exposure to damage from alcohol use: women

who drink during pregnancy can cause mental

and physical disability in the fetus. “Fetal alcohol

syndrome” is a severe example of such toxicity

(26).

Military preparedness also may be jeopardized

by alcohol use. A recent Department of Defense

survey concluded that 34 percent of all military

personnel suffer alcohol-related productivity loss

(27).

Alcohol causes economic, social, military, medical, and family problems. Many of the effects of

alcohol that lead to lost productivity and increased

susceptibility to accidents are due to its neurotox -

icity. This is characteristic of many drugs of

abuse: they are used because they affect mental

function, yet may be dangerous for the same

reason.

Drug abuse and addiction

Use of drugs that affect the brain, such as

hallucinogens, depressants, stimulants, and tranquilizers, is common in the United States, A recent article in the New England Journal of Medicine-

 referred to the use of psychoactive drugs in

America as a “modern epidemic,” noting that a
Social Impacts ● 1 3

half million Americans are addicted to heroin, as

many as 13 million may have used amphetamines

without medical supervision, and more than 50

miIlion have used marijuana at least once (28). The

same article reported that 11 percent of high

school seniors use marijuana daily, and more than

8 million Americans have used it over 100 times.

Evidence suggests that use of illicit psychoactive

drugs has increased about twentyfold in the last

two decades (28).

Addiction to opiate drugs is an extreme example of drug abuse. Addiction appears to be due

to a combination of behavioral and biological components. Behavioral medicine may lead to further

understanding of addiction; basic neuroscience

may contribute to understanding the biology

underlying addiction. Research findings over the

last half decade have led to startling insights into

the molecules involved in cells affected by drugs

such as morphine and heroin. Dramatic acceleration of progress has followed the discovery of

natural molecules, endorphins and encephalins,

that are manufactured by the brain to affect the

same receptors influenced by opiate drugs (29).

It is possible that treatment of physical dependency on drugs might improve as a result of a better understanding of addiction. Increased knowledge may permit identification of individual variations in biological susceptibility to certain agents.

Neuroscience by itself cannot resolve the problem of psychoactive drug abuse, whose roots may

be social as well as biological, but advances in

understanding and treatment are needed to

underpin social interventions and public policy.

Neuroscience may also help clarify the important distinction between drug addiction that has

serious public health and social consequences

(e.g., encouraging crime to support the biological

need for drug use) and “recreational” use that has

few deleterious effects. Drug abuse ranges from

caffeine to heroin, and public policy is based, in

part, on differences in biological effects of the

agents. Caffeine use is not regulated, but heroin

production, sale, and use are illegal. Between

these two extremes, there is widespread disagreement as to what should be regulated. For example, there is wide variation among the States in

enforcement of alcohol and marijuana statutes.

This diversity reflects disagreement over the

seriousness assigned to use of particular drugs.

Further research in neuroscience may narrow the

range of disagreement by providing data on biological effects. However, physiological and medical effects are only two of many criteria used for

determining “serious” drug abuse in different contexts and cultures.

Biological rhythms and work

schedules

New work patterns demanded by modern manufacturing and service industries have led to rising rates of shift work. A significant fraction of

the American work force, 27 percent of male

workers and a slightly lower fraction of female

workers, is subject to disruption of sleep, increased incidence of gastrointestinal distress, and

difficulties in socializing with families and friends

as a consequence of night and shift work (30). Further, it has been shown that worker errors are

more common during late-night shifts and are

concentrated in the early morning hours. For example, the accident in Reactor II at the Three Mile

Island nuclear powerplant occurred during the

3 a.m. to 5 a.m. period, a time during which a

highly disproportionate number of accidents occur, as demonstrated in numerous industrial

studies (31).

Shift-and night-work schedules are of Federal

concern because they involve worker health and

safety, public safety, and industrial productivity.

Many functions performed or supervised by the

Federal Government, such as air traffic control

at commercial airports, staffing of missile silos,

and operation of nuclear powerplants, must be

performed around the clock. Congressional interest in shift work was expressed recently in hearings before the Subcommittee on Investigations

and Oversight of the House Committee on Science

and Technology. Innovations in shift work were

described, and several Federal agencies involved

in protecting public safety testified on present

shift-work practices. Evidence was presented

showing that current shift-work practices often

fail to take account of data regarding optimum

work schedules and ignore recent neuroscience

research on biological rhythms.
74 ● Impacts of Neuroscience—Background Paper

Experiments on natural circadian rhythms have

led to discovery of at least two “biological clocks”

that correlate with hormone levels, body temperature, sleep cycles, and attentiveness. Work schedules more closely in accord with natural biological

rhythms have yielded improvements in productivity, decreased error rates, and increased worker satisfaction (32). Simple social and industrial

interventions based on neuroscientific knowledge

can ameliorate some problems—in this case, by

merely altering the periods of rotation between

shifts and changing the direction of rotation from

shift to shift.

Industrial productivity

Neuroscience may help eliminate or alleviate

some causes of lost worker productivity by reducing substance abuse and by identifying and preventing neurotoxic exposure among workers.

Work schedules can be improved by use of principles derived from neuroscientific experiments.

Education and retraining may be improved as

more is discovered about learning, memory, and

communication. The advance of neuroscience,

therefore, probably will lead to changes not only

in those industries directly linked to biology and

drug development but in other industries as well.

Long-term effects on industry

International Competition. -Congressional

concern for the international competitiveness of

U.S. industry has increased in recent years. The

relative position of the United States compared

to other countries may prove important in those

industries affected by neuroscience. It appears

that the United States supports more activity in

basic neuroscience research than any other country, much as it has had the largest national effort

in molecular genetics and immunology. The high

degree of development of basic science, the presence of mechanisms for training persomel, the

flexibility of university-industry relations, and

Federal support for basic science in the United

States have proved important in the early phases

of development of those industries related to biotechnology (33). The relatively good position of

the United States also could prove important in

any future ‘(high tech” industrial applications

based on neuroscience. An industrial sector based

on neuroscience could develop in pharmaceuticals, chemicals, or information technology and

management, albeit with very different time

scales. Contributions to the drug industry are likely to predate applications in information science

and managment.

The development of new psychoactive drugs is

likely to be important for future growth of drug

companies because psychopharmaceuticals provide a highly profitable and growing market. It

is not clear, however, how American-based companies will fare in the competition for new psy -

chopharmaceutical markets. A recent study by

the National Academy of Engineering expressed

concern that the pharmaceutical industry in the

United States may be losing some of its competitive advantage over foreign industries (34). The

amount of neuroscientific research in the United

States might be construed to confer competitive

advantage in the psychopharmaceutical sector to

American companies. Yet, scientific excellence

may not translate to more jobs or income for

American workers. The American lead in science

may be undercut by the extensive worldwide integration of pharmaceutical markets (leading to

rapid international technology diffusion and less

competitive advantage to the country of origin)

and the relative stringency of the drug approval

process in the United States (providing incentives

for introduction of drugs abroad, rather than in

the American market).

Creation of New Industrial Sectors.—

Neuroscience also is expected to contribute to developments in other industries such as food production, pesticide manufacture, and information

processing. Industrial applications of neuroscience may be analogous to other nascent hightechnology applications, such as those deriving

from biotechnology and semiconductors. Knowledge about human cognition may include how

better to use tools such as electronic and mechanical equipment. This might lead to improved

“human factors engineering” of such tools.

Future developments in agriculture may yield

a second “green revolution” based on biotechnology and neuroscience. Neuroscience can contribute to development of new, more specific pesticides affecting insect nervous systems and
—

Social Impacts 15

prepare the way for discovery of other ways to

control pests, such as growth factors and airborne

insect hormones. Such innovations will depend

in part on studying pest behavior and biochemistry under controlled conditions with methods

developed in neuroscience.

The development of an entirely new industry

based on biological substrata, such as artificially

grown nerve cell networks or “biochips” made by

micro-organisms, may be possible in the future.

Artificial intelligence programing of computers

may contribute to understanding how complex

information-processing networks work, possibly

yielding fertile analogies for the study of nerve

cell interactions. Understanding of brain function

and cognitive processes, conversely, may further

understanding in information science, leading to

new applications. Although only general predictions can be made about the industrial development of neuroscience, it seems likely that neuroscience will prove more important in the future.

Crime and violence

Neuroscience may provide some insights into

ways to prevent or better understand violence

and suicide and may even allow treatment of

some selected problems (when they are due to

identifiable and correctable aberrations). For example, researchers recently have found that levels

of 5-hydroxyindolacetic acid (5-HIAA)) a byproduct of a specific neurotransmitter family, are

elevated in the spinal fluid of those who have committed suicide by violent methods [35). This finding strengthens the link between depression,

which is also associated with elevation of 5-HIAA,

and suicide. This knowledge, combined with highly effective drug treatments for several forms of

depression, eventually may provide a method for

prevention of some violent suicides. However, the

use of 5-HIAA measurement as a means of identifying those who might commit suicide is highly

unlikely because only a small fraction of those

with the biochemical change are suicidal.

Researchers also have found 5-HIAA in some

who have histories of multiple violent criminal

offenses. The previously mentioned link of both

aggression and suicide with depression is intriguing but also illustrates the problems associated

with trying to use biochemical measurement as

a predictive tool for criminal enforcement: those

prone to violence are probably only a small

minority of those with elevated 5-HIAA levels.

Difficulty in using screening tests for criminal

behavior has precedent. The use of chromosomal

typing once was regarded as promising for detecting criminal predisposition, when some reports

were published showing a relatively high incidence of a particular chromosomal finding (the

presence of an extra “Y” chromosome) among

prison inmates. Later studies led to abandonment

of the test as a predictor of criminal behavior

because they proved the method had little predictive value and its use led to unfounded stigmatization of those who had the chromosomal change

without the purported proclivity for criminal

violence (36).

It seems unlikely that science will provide a better predictor of criminal behavior than previous

criminal behavior. However, neuroscience, in

combination with the social sciences, may increase our understanding of some forms of violence. If mechanisms to preserve individual autonomy are provided, treatments tailored to the

needs and wants of particular individuals someday may help to manage some forms of violent

behavior. Such efforts, however, will be additions

to, rather than replacements for,

nisms of dealing with crime and

other mecha -

violence.

Sex differences

One area receiving renewed attention is the

field of sex-difference research. There are demonstrable differences between men and women in

their mathematical and geometric abilities (37),

and in development of moral reasoning (38). The

extent to which these differences are due to

socialization rather than physiology is a topic of

ongoing controversy. Progress in behavioral

neuroscience may help establish the factual basis

for academic and political dispute, but the moral

questions regarding social equality of both sexes

will not be answered by scientific inquiry.

One particularly interesting topic arising from

research into sex differences is premenstrual syndrome (PMS). PMS affects some women in the

days preceding menstrual periods and is charac -
16 ● Impacts of Neuroscience—Background paper

terized by fluid retention, depression, irritability, and moodiness. PMS varies widely in intensity and type of symptoms expressed. It was first

reported more than half a century ago (39), and

has received recent attention because courts in

the United Kingdom and France have acknowledged PMS as a mitigating factor in violent crimes

(40). American courts may follow their European

counterparts. Interest in PMS may increase as

more is learned about how hormones, including

sex hormones, affect behavior and other brain

functions. PMS presents a particularly thorny

problem: how to balance the conflict between a

desire to help those who suffer with PMS and concern that it may be used as an excuse to exclude

women from certain occupations and endeavors.

There is danger of premature or misdirected

application of new knowledge about sex differences. In studies that have identified differences

between males and females, the findings apply

to population differences, not individual differences. On some tests of mathematical ability, for

example, girls’ scores are lower on average than

boys’ scores. Within the group of boys or girls,

however, there is a diversity of scores, and many

individual girls do better than an average boy. The

differences may not be gender-specific but only

loosely associated with being biologically male or

female. Public policy based on sex differences

must take such heterogeneity into account.

However, it is not clear how to do this fairly. The

studies showing sex differences in mathematical

ability have led to some suggestions about dealing differently with boys and girls for purposes

of mathematics research (41) and training (42).

Such recommendations must be scrutinized carefully so that individual choice is not jeopardized

and public policy is not imbued with social prejudice.

It is also important that public policy not be

erected on theories that are not widely shared.

There is agreement that there are differences in

mathematical ability, but there is no consensus

that this is biologically determined, despite attempts to control for educational background in

analyzing test scores. Thus, it might be premature

to change educational institutions on other than

an experimental basis because of knowledge

about sex-related differences.

Education

Neuroscience may improve understanding of

the causes of some forms of learning disability,

such as autism or dyslexia. * Research on these

disorders has refined understanding of the perceptual deficiencies involved. Psychological innovations have led to improved methods of teaching children with these learning disabilities (43).

Further understanding in some instances may

allow effective treatment or compensation by providing a basis for introduction of new teaching

methods.

Behavioral science also can improve education

by better characterizing the mechanisms of learning, memory, and perception in normal children

and adults. Indeed, the most important long-term

improvements in education may derive from discoveries about cognitive function and neural processing; knowing how the brain works may well

lead to better methods of teaching.

Ethical and legal aspects of

neuroscience

There are positive and negative aspects of advances in neuroscience. Public ambivalence is

reflected in the different attitudes toward psychoactive drugs in two novels by Aldous Huxley.

In Brave New World, the drug “soma” is used as

a means of avoiding reality—as a method of mind

control by the state. In Mind, psychoactive drugs

are used to expand human experience benignly,

There are legal and ethical issues that derive

from loss or change of mental function, in addition to concerns over the proper use of technologies that affect the brain. For example, it has

taken several decades to attain general acceptance

of the concept of brain death in medical circles.

Several examples of ethical and legal issues relating to neuroscience are summarized here.

Public Concern Regarding Science.—Public concern regarding neuroscience is not unique;

it is shared with many other sciences. There is,

● Autism is a disorder in which the individual appears to be separated from the external environment. Recent treatments have involved drugs and behavioral intervention. Dyslexia is a diminished

ability to read. It can have many different causes, including trauma

and stroke. One common form, found in children, appears to have

an important genetic component.
Social Impacts ● 1 7

for example, substantial public concern over the

application and misapplication of biotechnology.

The furor over laboratory and community safety of rDNA has been supplanted by fear of the

use of “genetic engineering” in humans. Public apprehension about science and technology is often

a mix of both rational concern about possible misuse and uncertainty about the science or technology itself. Uncertainty about the subject matter is associated with ambivalence regarding the

extent to which decisions should be left to experts.

In an open and democratic society, public perceptions often have Federal policy implications. *

When there is dispute over executive actions,

the courts often must decide whether scientific

evidence has been used properly (44). For example, Federal courts have been involved in controversies about environmental protection, worker safety standards, and public safeguards in the

use of nuclear power. However, the courts are

ill-equipped to make scientific judgments, and

they are inefficient in regulating social activities.

The courts are best suited to judging whether the

decisionmaking process is fair and appropriate;

court decisions are poor substitutes for coherent

legislation (45).

At present, there is no permanent Federal institution for dealing with areas of science that are

associated with public apprehension, Up to now,

public concern over technologies has been dealt

with on a case-by-case basis. One illustrative example concerns public perceptions of the dangers

of rDNA research. Much of the controversy over

rDNA might have been avoided had a mechanism

already been in place for voicing public concerns

and airing scientific evidence. The potential efficacy of such mechanisms has been demonstrated by the same controversy. Public fear

seems to have decreased since the establishment

of the Recombinant DNA Advisory Committee

(RAC) at NIH.

Two important components in assuaging public

apprehension seem to have been the inclusion of

nonscientists on the RAC and the openness of the

“A statement relet’ant to this section was deliyered by Senior Circuit Court Judge Da\rid L. Bazelon at the OTA workshop and is included as app. C to this background paper.

process by which regulatory decisions were made

(45).

Other controversies invoIving neuroscience

have arisen over the experimental use of hallucinogens on unsuspecting patients by the Department of Defense and the Central Intelligence

Agency, and the Soviet Government practice of

committing dissidents to psychiatric institutions

and forcibly treating them with psychoactive

drugs. It thus seems highly probable that there

will be future controversies based on public apprehension about some aspects of neuroscience.

Mental Competence and Informed Consent.— Ethical issues related to neuroscience are

not restricted to public concerns; there are also

many issues of individual rights, One recurring

issue, as noted in the context of drug development, is the inability of psychiatrically disabled

or demented patients to consent to medical treatment or experimental research. Demented patients cannot judge the adequacy of treatment or

evaluate the risks of experimentation for themselves. Who should decide for such patients

whether they should participate in a clinical trial

of a drug for dementia, and what should be the

standards for ensuring protection of their rights?

This question is especially difficult when experimentation is unlikely to benefit the patient directly. * Determining who should decide is important, because new drugs for dementia cannot be

developed without using appropriate patients. It

may prove necessary to establish clear guidelines

by legislation or executive action.

Current guidelines focus on the role of the family

or courts in substituting judgment for the patient

in question (46). In most cases, present policies

are not controversial. However, for those patients

without families and those who come from families whose best interests may not coincide with

those of the patient, there are no formal mechanisms for making decisions. Many controversies

have arisen from disagreement among family

members, courts, hospitals, and health care pro-

*Direct benefit may be unlikely either because a treatment has

nm’er been tried, and so there is no basis for expecting benefit, or

because the research is intended to pro~ide information that \*ill

allo~~’ future benefits but that mill not affect care of the patient being studied.
18 ● /mpacts of Neuroscience—Background Paper

fessionals on a proper course of action. Dramatic

examples of conflict about when to terminate lifesustaining treatment of mentally incompetent patients have received national media coverage.

Such publicity highlights the inadequacy of present methods for dealing with the difficult ethical, moral, financial, legal, and social issues surrounding mentally incompetent individuals.

Several Federal bodies, including the President’s

Commission for the Study of Ethical Problems in

Medicine and Biomedical and Behavioral Research,

and the National Commission for the Protection

of Human Subjects of Biomedical and Behavioral

Research, have considered the difficult issues involved in research and treatment of those who

are demented or psychiatrically disturbed (47).

In 1978, recommendations based on commission

activities were submitted to the Department of

Health and Human Services regarding the use of

psychosurgery and the care of those institutionalized as mentally infirm; no regulations have

been issued yet by the Department.

Forcible administration of psychiatric

drugs. -whether psychopharmaceuticals can, in

some instances, be administered to psychiatric patients without their consent is under review by

the courts (48). Advocates of rights for psychiatric

patients object to institutional judgments about

treatment that override the autonomous decisionmaking power of individuals, while others assert

that such psychiatrically disturbed individuals are

incapable of rational autonomous choice. Resolution of this problem will require substantial effort by those in bioethics and the law and may

require new legislation.

Insanity defense against criminal prosecution.—The insanity defense against criminal

prosecution has long been a subject of medical

and legal disagreement (49). The validity of the

legal concept of insanity is receiving renewed

scrutiny, and the mechanism for verifying mental deviation is also being debated. Those in the

psychiatric and legal professions are attempting

to resolve the issue by developing guidelines for

both psychiatric diagnosis and legal use of psychiatric opinion.

The power of the concept of abnormality.—Special mention should be made of the pervasive effects of the concepts of normal and

abnormal as applied to mental, cognitive, and

emotional states. The power of the label “abnormal” is substantial in public policy concerning

mental retardation, psychiatric illness, and neurological handicaps. It is important to acknowledge

the power of labeling patients so that adequate

care is taken to ascertain both the validity of the

label for a particular patient and the integrity of

the label itself (50). The diagnosis of major psychiatric illness is associated with a multitude of

medical, institutional, and social stigmata. Neuroscience can assure that differences between normal and abnormal have scientific merit; neuroscientist and others may ensure that knowledge

is applied responsibly and equitably.

Animal welfare.—The use of animals for

psychological and medical research and in testing

of drugs and cosmetics is currently a focus of controversy. The neuroscience are involved because

animals are used in many experiments on pain,

recovery of neural function, and new surgical

techniques. Many topics in neuroscience must be

studied in higher animals, including primates,

because of the need to extrapolate findings to the

highly complex nervous system of humans. How

to balance the need for medical and scientific

progress against the moral imperative to avoid

animal suffering is a problem subject to acrimonious public debate. Legislation on this topic

already exists, and the need for additional regulation is being considered by several States and

the Federal Government.

Other areas of potential moral disagree

ment.–Findings regarding the biochemistry of

crime and violence may lead to ethical debate

regarding appropriate public policy. Revelations

about the genetics of mental disease may also

engender moral controversy. Knowledge applicable to education, sex differences, substance

abuse, nutrition programs, worker monitoring for

toxic exposure or personal drug use, and many

other social problems also may lead to difficult

ethical and legal dilemmas.

Recent congressional initiatives have responded

to the disbanding of the President’s bioethics commission and to delays by executive agencies in implementing its recommendations. Congressional
Conclusion ● 1 9

activity has ranged from proposed authorization sion (which disbanded in early 1983). There also

of a new commission specifically focused on hu- has been discussion about creating a new Federal

man applications of molecular genetics (which body charged with investigation of ethical

might largely exclude concerns related to neuro- concerns.

science) to extension of the President’s commisConclusion

Progress in neuroscience research during the

last few decades has led to new understanding

of behavior, the functioning of the nervous system, how chemicals affect the mind, and mechanisms involved in neurological and psychiatric

disorders. Many of the most important promises

of neuroscience research have yet to be fulfilled;

there is not yet sufficient knowledge to prevent

or treat effectively many highly prevalent and

disabling neurological and psychiatric diseases.

Most of the risks and benefits related to social applications of neuroscience remain possibilities

rather than facts. The diverse social ramifications

of neuroscience applications can only be anticipated, not confidently projected. Neuroscience

is an area that bears watching by scientists, health

care professionals, industrialists, and policy makers. Now may be a propitious time to search for

ways to translate neuroscience into application,

and to anticipate the need for public discussion.

A number of neuroscience-related issues are

likely to emerge. In some areas, there already appears to be sufficient scientific basis for congressional investigation. Some of these, such as the

application of knowledge about biological clocks

to work situations involving public safety, already

have received some congressional attention.

other issues, such as sex-differences research,

have been identified but lack consensus regarding

their importance. Still other areas of application,

such as drug abuse, enhancement of productivity, development of new industries, crime prevention, and improvement of education show great

promise in the long term, but the base of knowledge deriving from neuroscience research is now

too scant to support Federal policy initiatives.

Some areas related to neuroscience appear to

deserve congressional attention. These are characterized by their magnitude, extensive Federal

involvement, and an adequate science base to support meaningful investigation. Such topics include:

●

●

●

problems arising from environmental, therapeutic, and occupational exposure to neurotoxic agents, identifying numbers of people

affected, scientific progress in detection,

methods of prevention, and regulatory issues;

support for basic research and personnel

training in neuroscience, highlighting rapidity

of progress, numbers of people who might

benefit, and social and industrial applications;

and

public and governmental mechanisms for

dealing with difficult ethical and legal questions related to neuroscience, including how

to determine mental competence, how to

make decisions for the mentally incompetent,

how to control legitimate uses of drugs affecting the mind, and how to establish legal

criteria for determining criminal responsibility.
Appendixes
Appendix A

Federal Support for

Neuroscience Research*

Funding levels

There has been rapid growth in the field of neuroscience in the United States in the past 10 years.

Membership in the Society for Neuroscience has

grown from 250 members at its inception in 1971 to

8,000 in 1983.** Graduate and postgraduate programs

in neuroscience have expanded by an estimated 200-

300 percent during the same period (l). The most recent data suggest a leveling of the growth rate (51).

Neuroscience research is funded by a variety of executive agencies. * * * In each agency, neuroscience

funding priorities are related to the mission of the

agency, and funds are distributed accordingly for research projects. The National Institutes of Health (NIH)

receive the majority of the funds for neuroscience

research. The National Institute of Neurological and

Communicative Disorders and Stroke (NINCDS), one

of the NIH research institutes, receives over half of

all Federal neuroscience research dollars. Although

there are no authoritative assessments of Federal

research support for neuroscience, preliminary estimates of fiscal year 1983 funding levels at each of the

granting agencies, as requested from the budget office of each agency, appear in table A-1.

The fiscal year 1983 funding level for neuroscience,

including behavioral research, is estimated at $503.56

million. The NINCDS appropriations history provides

some indication of Federal funding trends. t

NINCDS Appropriations Levels

Actual appropriation

Fiscal ~fear (in millions)

1975 . . . . . . . . . . . . . $142.0

197 6 144.7

197 7 155,3

1978 . . . 178.4

1979 ., . . . 212.5

198 0 242.5

1981 . . . . . . . . . . . . . . . . . 252.6

1982 . . . . . . . . . 277.7

1983 . . . . . . . . . . . . . . . . . . 295.7

SOIIRCE, Natmnal Institutes of Health F’wal }’ear 1984 Draft Justlftcal]on of ,4p

proprlatwn F.stlmates for Commltlf’e on Appropriations

● This appendix was written primarily by Miriam Davis, Environmental

Sciences Fellow at the Congressional Research Service

● ● The rate of growth is somewhat overestimated by these figures, because

It took several years for awareness about the societ.v to spread, and because

more scientists ha}e recentlj’ come to define their actil’itj’ as neuroscience

● ” ● See table A- I for a list of agencies that fund neuroscience research.

IThese figures differ from those in table A-1 because they include admin.

istrati}re costs and other costs not covered in the table.

Actual NINCDS appropriations increased by 108 percent between fiscal years 1975 and 1983, but this represents a real increase of only 14 percent in constant

1975 dollars (52). Further, appropriations have fallen

short of earlier expectations: in 1979, when the budget

needs of NINCDS were projected into the 1980’s, they

were targeted at $450 million in fiscal year 1983 (53),

a value considerably greater than the actual appropriation of $295 million.

The Alcohol, Drug Abuse, and Mental Health Administration (ADAMHA) is the other major agency responsible for support of neuroscience. Three institutes support research and other activities related to mental

health, drug abuse, and alcoholism and alcohol abuse.

More than 75 percent of ADAMHA neuroscience funding is channeled through the National Institute of Mental Health (NIMH). NIMH appropriations between 1975

and 1983 increased by 64 percent overall, and funding for basic and clinical neuroscience increased by

83 percent. In constant dollars, however, there was

a 7-percent decrease in overall NIMH funding. Funding for neuroscience research increased slightly, taking up an increased fraction of the total NIMH budget.

Competition for funds is keen among research scientists. In fiscal year 1982, 524 of the 1,483 approved

grant applications to NINCDS were actually funded.

An additional 298 grant applications were disapproved, so that 29.4 percent of all grants, or 35.3 percent of approved grants, were funded (54). Currently, the Neuroscience Program at NSF funds 20 percent

of grant applications, whereas 10 years ago, 40 percent of similar applications were funded; further, the

average dollar amount for grants awarded by NSF in

neuroscience has dropped steadily over the past 5

years. In 1982, NIMH funded 25 percent of 1,443 total

research applications in basic and clinical neuroscience. A comparable decline has been observed at

most of the other NIH institutes.

Coordination

To ensure that research investigators applying for

extramural funds do not receive grants from different

agencies for the same research project, investigators

are required to list existing and pending sources of

funds on all grant applications. Computer links between NSF and NIH assure that program officers at

each agency are aware of this information before

23
24 ● Impacts of Neuroscience—Background Paper

Table A-l .—Estimated Funding Levels for Federal Neuroscience R&D Fiscal Year 1983 (miiiions of doiiars)

Agency Extramural Intramural Subject areas

NIH:

NiNCDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . $189.4

NEI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47.2

NIB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.6

NIGHS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

NiEHS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.3

$36.3

6.1

2.6

2.8

0.78

Neuroiogicai disorders and stroke

Vision and eye disorders: basic and clinical research

Dementia and basic neuroscience

Basic neuroscience

Behavioral and neurological toxicology

Total . . . . . . . . . . . . . . . . . . . . . . . . . . . $247.5

ADAMHA:

NIMH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . $ 16.5

47.6

NIDA. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.0

NIAAA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.0

$48.58

$22.0

21.4

.

—

Basic neuroscience

Ciinical neuroscience

Neuroscience

Biological basis of alcoholism

Total . . . . . . . . . . . . . . . . . . . . . . . . . . . $ 81.1

DOD:

Army Medical R&D Command . . . . . . . . . $ 6.5

Walter Reed Institute . . . . . . . . . . . . . . . . —

institute of Chemical Defense . . . . . . . . . 7.2

Aviation Research Lab(Ft. Racker). . . . . —

AFOSR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.7

ONR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.4

U.S. Army Research Office . . . . . . . . . . . . 1.1

Totai . . . . . . . . . . . . . . . . . . . . . . . . . . . $20.7

NSF: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21.4

FDA:

NCTR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.06

CDC:

NIOSH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.315

NASA: 1.O

VA: . ..::;;;:;;;;;;;;;:;;;;;;;; ;;:: : 21.4

EPA: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.0

$43.4

$ 2 <

—

0.4

2.5

—

1.0

$ 13.1

—

0.71

0.502

1.0

—

1.79

Chemical defense

Basic neuroscience

Chemical defense

Vision research

Neurophysioiogy; vision research; chemical defense

Chemical defense; Iearning and memory; neurophysioiogy; behavior

Basic neuroscience and

Behavioral toxicology

Neurotoxicology

Vestibuiar physiology

behavior

Aging; neurology and neurobiology;drug dependence;

behavioral science; spinal cord disorders

Neurotoxicolocw-.

Total . . . . . . . . . . . . . . . . . . . . . . . . . . . . . $394.48 $109.06

$503.56

KEY: NIH—National institutes of Health(part of the Public Health Sewice of the DOD—Department of Defense

Department of Health and Human Services) AFOSR—Air Force Office of Scientific Research

NINCDS—National Institute of Neurological and Communicative ONR—Office of Naval Research

Disorders and Stroke NSF—National Science Foundation

NEI —National Eye Institute NASA—National Aeronautics and Space Administration

NIA—National institute on Aging VA—Veterans Administration

NIGMS—National institute of General Medical Science EPA—Environmental Protection Agency

NIEHS—Nationai institute of Environmental Heatth Sciences CDC—Centers for Disease Control

ADAMHA—Alcohol, Drug Abuse and Mental Health Administration NIOSH—National institute for Occupational Safety and Health

NIMH—National institute of Mental Health FDA—Food and Drug Administration

NIDA—National Institute on Drug Abuse NCTR—National Center for Toxicological Research

NIAAA—National Institute on Alcohol Abuse and Alcoholism

SOURCE: Individual agency budget offices.

grants are awarded. The Interagency Working Group icology at the National Institute of Environmental

in Neuroscience was formed to facilitate information Health Sciences (! WEHS), the National Center for Tox -

exchange among extramural grantees. The working ecological Research (NCTR), and the National Institute

group consists of representatives from many of the for Occupational Safety and Health (NIOSH), is coorgranting agencies that sponsor neuroscience research. dinated under the National Toxicology Program, which

The meetings are voluntary and the group is not sep- was created in 1978 to coordinate and provide inforarately funded. Research in neurobehavioral tox- mation about potentially toxic chemicals.
App. A—Federal Support for Neuroscience Research ● 25

Funding cycles and funding stability

Most Federal agencies supporting neuroscience research are funded by annual appropriations by Congress. Selected institutes and programs at NIH and

ADAMHA are subject to periodic reauthorization as

well.

In recent years, some members of Congress have

expressed concern over problems with the annual

funding cycle and about establishing the budget stability needed for long-term research and development

(R&D). Discussions also have focused on the difficulty of assessing complex R&D programs annually. The

General Accounting Office (GAO) has suggested that

“instituting a multiyear R&D authorization process

would be an important first step in improving R&D

planning, budgeting, and oversight” (55). Others have

expressed concern that a loss of oversight and accountability could result.

Policy questions regarding Federal

support for neuroscience

Questions policymakers may face with respect to

Federal support for neuroscience research include the

following:

1. Is the level of funding adequate to support growth

in the neuroscience field? Are current levels of

support for research matched by support for

training those to do the research?

2. What is the impact of a decrease in the percentage of grants that are funded? How many laboratories are closed due to lack of funds? What is the

optimum number of neuroscience laboratories?

What is the optimum approval and funding rate

for research grants in neuroscience?

3. IS the degree of coordination among Federal agencies supporting neuroscience adequate to assure

a productive and efficient use of funds? Are present mechanisms for coordination working? What

are the advantages and disadvantages of funding

through multiple Federal agencies?

4. Does the authorization/appropriation cycle for

R&D funds hamper research productivity? Is it

too cumbersome for Congress?

5. What is the level of support for basic neuroscience

research by private industry? Is this growing or

declining as a fraction of Federal support? Is

private industry supporting certain sectors more

than others (e.g., training programs, or research

related to pharmacological applications)?
Appendix B

Federal Regulation of and Research

on Neurotoxic Exposure

Legislation on toxic agents of many kinds provides

the framework for Federal regulation of many industrial and environmental agents. Those activities

relevant to regulation and research on substances toxic to the nervous system are reviewed in this appendix, Agents toxic to other organs and organ systems

are regulated in a similar manner in many cases, but

regulation of agents toxic to other organs is not summarized here.

Federal regulation of toxic substances,

including neurotoxins

The Environmental Protection Agency [EPA) is

responsible for enforcement of several laws that regulate toxic substances. The Toxic Substances Control

Act (TSCA), the Clean Water Act, the Clean Air Act,

the Resource Recovery and Conservation Act (RRCA)

amendment to the Solid Waste Act, and the Federal

Insecticide, Fungicide, and Rodenticide Act (FIFRA),

with its sister legislation, the Federal Environmental

Pesticide Control Act (FEPCA), all provide authority

to regulate exposure to toxic substances. The Food and

Drug Administration (FDA) regulates drugs, food, and

cosmetics under the Food, Drug, and Cosmetic Act;

and the Occupational Safety and Health Administration (OSHA) of the Department of Labor administers

the Occupational Safety and Health Act. The major

laws, agencies, and regulated entities are summarized

in table B-1.

The FDA, OSHA, and EPA have enabling legislation

to include setting standards for neurotoxicity in regulation of drugs and cosmetics, occupational exposures, and environmental exposures, respectively.

Some of OSHA’S regulatory standards have been based

partially on neurotoxic effects, and neurological side

effects of drugs are monitored by FDA. However, none

of these agencies has published standards for testing

of neurotoxic effects. One reason for the absence of

guidelines is the unsettled state of the science of

measuring neurotoxicity. No consensus on standard

methods for determining guidelines regarding neurotoxic exposure has been established, although there

has been much recent progress. To explore the possibilities of standardizing neurotoxicity tests, the FDA

has undertaken a long-term project that is examining

batteries of neurotoxic tests with the goal of establishing a reliable, cheap, and effective means of testing

for neurotoxic effects.

Pesticide regulation

One aspect of Federal involvement in regulation of

neurotoxic chemicals that deserves special mention is

the registration of pesticides. Pesticides are regulated

by the EPA Office of Pesticide Programs. Proposed

pesticides and pesticide ingredients are subject to EPA

approval. Such approval requires testing for toxicity.

However, approval for some uses can be obtained by

application for emergency exemptions or provisions

for “special local needs.”

Table B-l. -Selected Federal Agencies and Laws Regulating Neurotoxic Exposure

Agency Law Application

Environmental Protection Agency Toxic Substance Control Act Chemical substances

Federal Insecticide, Fungicide and Pesticides and other antibiotic

Rodenticide Act agents

Solid Waste Act Solid wastes (including ground

water contamination)

Clean Air Act Airborne pollutants (including lead

and gases)

Clean Water Act Water pollutants

Occupational Safety and Health Occupational Safety and Health Act Occupational exposures

Administration

Food and Drug Administration Food, Drug, and Cosmetics Act Food, food additives, drugs, and

cosmetics

SOURCE: Office of Technology Assessment.

26
App. B—Federal Regulation of and Research on Neurotoxic Exposure ● 2 7

Congressional hearings on pesticide regulation and

related topics were held by the Subcommittee on Department Operations Research and Foreign Agriculture of the House Committee on Agriculture on February 22-23, 1983. Documents submitted as testimony

identified concerns regarding operation of the Office

of Pesticide Programs at EPA. Concern was expressed

about the adequacy of EPA resources to meet projected needs, methods of approval that avoid formal

registration, and the scientific basis for approval of

pesticides at EPA. EPA has since issued a more than

400 page set of guidelines for pesticide testing.

Federal research on toxicology,

including neurotoxicology

Several Federal agencies are involved in research on

neurotoxicity. All those mentioned in this paragraph

and in figure B-1 are parts of the Public Health Service of the Department of Health and Human Services.

The National Institute of Environmental Health Sciences (NIEHS) and the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS),

both institutes of the National Institutes of Health, conduct studies on neurotoxicity. The National Institute

of Mental Health has a laboratory devoted to research

on Developmental and Behavioral Neurotoxicity. The

FDA has a Nationa] Center for Toxicological Research

(NCTR), which is charged with developing and validating test procedures. The Centers for Disease Control

include the National Institute for Occupational Safety

and Health (NIOSH), which does research and provides

exposure guideline recommendations to OSHA. The

National Toxicology Program, headed by NIEHS, coordinates the activities of NIEHS, NCTR, and NIOSH in

toxicology. The institutional arrangement of some of

the major agencies doing research on neurotoxicology

is shown in figure B-1.

Research on pesticides is carried out in industrial

laboratories, by university scientists, and at several

land-grant universities supported in part by the U.S.

Department of Agriculture. Information based on research into efficacy, specificity, and health effects, including neurotoxicity, is submitted to EPA as part of

the pesticide registration process.

Figure B-l.—Selected Agencies Doing Federal Research on Neurotoxicity

I 1 1

I

i

IL — - --- —— --- -- ~ . . ~
Appendix C

Statement by David L. Bazelon

Senior Circuit Judge

U.S. Court of Appeals for the District of Columbia Circuit

at the OTA Workshop on Impacts of Neuroscience, July 27, 1983

When I was first invited to participate on this panel,

I must confess, I was bewildered. I am not a scientist,

and I know virtually nothing about neuroscience. I

could not begin to describe the difference between

a neuron and a beta-blocker. I called Dr. Cook-Deegan,

intending to decline, When he later came to my chambers, I told him that, given my lack of technical expertise, I could never presume to advise a group of

distinguished physicians and scientists as to the value

of a particular line of scientific research. My sole involvement with science is in my capacity as a judge.

Throughout my 34-year tenure as a judge on the U.S.

Court of Appeals for the District of Columbia Circuit,

it has been my task to review the decisions of a great

many regulatory agencies grappling with the problems

posed by scientific and technological development.

These decisions involve, just to name a few, the critical

socioscientific issues of acid rain, cotton dust and benzene levels in the workplace, exposure to asbestos and

radiation, and the disposal of nuclear and toxic waste.

I tried to impress upon Dr. Cook-Deegan that I was

qualified to address nothing more than the role of the

courts in monitoring public policymaking in the scientific arena. Much to my surprise, he assured me that

this was exactly the focus he hoped I would bring to

the panel.

I hardly need to tell a group such as this that with

each new advance in neuroscience come previously

unforeseen dangers. Neuroscience is not unlike any

other field of scientific endeavor in this regard.

Ironically, scientific progress not only creates new

risks but also uncovers previously unknown risks. As

our understanding of the world grows exponentially,

we are constantly learning that old activities, once

thought safe, in fact pose substantial hazards.

For example, new psychopharmaceutical drugs, capable of controlling antisocial behavior among large

numbers of psychiatric patients, have been developed.

Many of the drugs have known side effects and still

others may be discovered in the future.

Similarly, advances in genetics offer the hope of

eliminating many genetically transmitted diseases.

However, with this hope comes the threat of introducing previously unknown and presently untreatable

viruses and bacteria.

Nuclear power can provide a virtually inexhaustible supply of cheap energy. It may also reduce nationwide cancer caused by burning fossil fuels. But, it may

increase cancer risks for those living near reactors,

and our inability to dispose of radioactive waste safely may place future generations in jeopardy.

The question then is not whether we will have risk

at all, but rather how much risk, and from what

source. Perhaps even more important, the question

is who shall decide.

In a democracy, such choices are reserved for the

public. Thus it falls to the Congress, as our representative body, to guide the direction that scientific

development will take in our society. But most members of Congress are no more scientists than am I. Congress often lacks the expertise to penetrate the deep

scientific mysteries at the core of important issues of

public concern. Consequently, it has chosen to address

the problems and opportunities of this new age

through regulatory agencies. It gives those agencies

the resources and authority to employ and develop

expertise and to make difficult policy choices in the

scientific arena.

The legislature has not, however, granted these

agencies wholly unbridled discretion. First, an agency must often act within the narrow parameters of

a specific statutory mandate. For example, the Delaney

Clause, an amendment to the Food and Drug Act, establishes an irrebuttable presumption against the safety of any food additive found to induce cancer in

animals. Second, agencies must comply with statutorily created procedural requirements. For instance, each

agency must provide ample notice of all proposed

rules and regulations. It must also solicit and fully consider the input of both outside experts and the public

at large. Finally, Congress has attempted to ensure

agency accountability by establishing a mechanism for

judicial review.

The exact nature of judicial review of agency action

is all too often misunderstood. This was brought home

to me in a conversation with Alvin Weinberg, a pioneer of the nuclear age. “Most people,” he said, “have

the idea that the court weighs the arguments and the

technical evidence and decides which side has come

nearest to the truth. If that’s not what you do, you’d

28
App. C—Statement by David L. Bazelon ● 29

better shout it from the roof tops!” So, I’m shouting

it: that idea is wrong. It is wrong, first, because courts

lack the technical competence to resolve scientific controversies. It is wrong, second, because courts lack the

popular mandate to make the critical value choices

that this kind of decisionmaking requires.

In reviewing regulatory actions, the court does not

weigh again the agency’s evidence and reasoning. Instead the court monitors only the process of decisionmaking, leaving factual conclusions and policy choices

to the agency. The role of the judiciary is to stand outside the scientific and political debate and to ensure

that all of the issues are thoroughly aired.

First, courts must ensure that an agency’s interpretation and application of its statutory mandate are reasonable and that the agency is behaving in a manner

that is neither arbitrary nor capricious. Second, in the

realm of science, courts can insist that the data be

described, hypotheses articulated, and above all, in

those areas where we lack knowledge, that ignorance

be confessed. In the sphere of values, courts can ask

that decisionmakers explain why a particular tradeoff

is acceptable. Perhaps most important, in the nether

realm, at the interface of fact and value, courts can

help assure that the value component of decisions is

explicitly acknowledged, not hidden in quasi-scientific

jargon.

I have long argued that even society’s most technical

decisions must be ventilated in a public forum with

public input and participation. In fact, I have been

pushing this theme for so long that I worry that I may

be a little like my friend the amateur cellist. One evening his long-suffering wife dared ask why cellists in

the orchestra “move their fingers up and down the

necks of their instruments, while you always keep

your fingers fixed in one place.” ‘(Ah yes,” my friend

replied. “I’m glad you noticed that. They are looking

for the right note. I have found it!”

Full disclosure of agency decisionmaking is in everyone’s best interest, including that of the decisionmakers themselves. If the decisionmaking process is

open and candid, it will inspire more confidence in

those who are affected, further reducing the risk that

important information will be overlooked or ignored.

Finally, openness will promote peer review of both factual determinations and value judgments.

Agency resistance to the requirements of full disclosure may come from either of two sources. First,

in reaction to the public’s often emotional response

to risk, agency experts are often tempted to disguise

controversial value decisions in the cloak of scientific

objectivity, obscuring those decisions from political accountability. I have heard scientists held in the highest

regard say that they would consider withholding information concerning risks which, in the scientist’s view,

are insignificant, but which might alarm the public if

taken out of context. This problem is not mere speculation. I am reminded of my involvement several years

ago in a hearing on the development of guidelines to

regulate recombinant DNA technology in the United

States. Added to the heated controversy over the substance of the guidelines themselves was an equally

heated debate within the National Institutes of Health

concerning the degree to which the risks and reasoning underlying the guidelines should be disclosed to

the general public. Speaking to the Royal Society Conference on Recombinant DNA in England, my good

friend Donald Fredrickson, the distinguished Director of the National Institutes of Health, said:

The hearing demonstrated the difficulties of holding

a town meeting on molecular biology and exposed the

full range of opinions on the risks of the new technology. It was apparent that our decisions would have

to run the gamut of adversarial reactions and, in the

end, might well be tested in the courts. After the hearing, the voice of Judge Bazelon lingered longest in my

mind: “the healthiest thing that can happen is to let

it all hang out, warts and all, because if the public

doesn’t accept it, it just isn’t worth a good damn.”

It is certainly true that the public’s reaction to risk

is not always proportionate to the seriousness and

probability of the threatened harm. Nevertheless, experts must resist the temptation to belittle these concerns, however irrational they may seem. Regulatory

agencies must not turn their backs on the political

process to which we commit societal decisions. Scientists, like all citizens, must play an active role in the

discussion of competing values. Their special expertise will inevitably and rightly give them a persuasive

voice when issues are discussed in our assemblies and

on our streets, But ultimately the choices must be

made in a politically responsible fashion. To those who

feel the public is incapable of comprehending the

issues and, so, unable to make informed value choices,

I respond with the words of Thomas Jefferson:

I know no safe depository of the ultimate powers

of the society but the people themselves; and if we

think them not enlightened enough to exercise their

control with a wholesome discretion, the remedy is

not to take it from them, but to inform their discretion.

At times, however, agency resistance to public

disclosure may derive not so much from a desire to

keep the public “in the dark” as from the uncertainty

that characterizes much of the process of risk assessment itself. To say the least, science is often incapable

of stating risks with certainty. For some activities, the

magnitude of potential harm and the probability of

its occurrence may be essentially unknown. For example, another of my good friends, Dr. Theodore
30 ● lmpacts of Neuroscience—Background Paper

Puck, a noted medical researcher, tells me that toxicologists have no way of establishing with certainty

the permissible, as opposed to the lethal dose of a new

drug. Engineering predictions may rest on untestable

assumptions, such as the behavior of materials after

thousands of years. Risk estimates may depend on future contingencies of human behavior or other highly

complex and unpredictable variables. Historical experience may even be totally lacking, as when the National

Aeronautics and Space Administration had to fix a

quarantine period for returning lunar explorers. The

best risk estimates are subject to an unknown degree

of residual uncertainty and may thus overstate or

understate the dangers involved. Indeed, many times

an agency must act in circumstances that make a crap

game look as certain as death and taxes.

Those who must make practical decisions may be

tempted to disregard or even suppress any lack of confidence they may have. Ignorance is messy in decisionmaking. It cannot always be stated as an objective

quantity or factored into a decision as if it were a risk

of known probability. Decisionmakers must assimilate

data from many disciplines, And yet uncertainty detracts from simplicity of presentation, ease of understanding, and uniformity of application. To focus on

uncertainties is to invite paralysis; to disclose them is

to risk public misunderstanding, loss of confidence,

and opposition. Even though some uncertainty is inevitable, pointing it out will always create pressures for

“just one more study.” But the decisionmaker knows

too well that delay is also a choice, with risks of its

own.

Combined with the uncertainty inherent in scientific risk assessment itself is the lack of specific

guidance provided to administrative decsisionmakers.

Often Congress, faced with its own inability to foresee

the course that technological research and development may take, is forced to speak in broad generalities

when providing statutory direction to regulatory decisionmakers. At times, legislators embroiled in conflicts

of political ideology may intentionally employ vague

and ambiguous language so that each faction may

claim its own “victory. ” I point, for example, to the

“cost-benefit” analysis required of agencies by numerous statutory schemes. Such analysis often calls for

controversial quantitative valuations of human life and

health. It frequently presumes to compare incomparable) such as the harm of radiation exposure versus

the benefits of nuclear power. And, perhaps most

troubling of all, cost-benefit analysis breaks down completely at one of the most crucial points in the decisionmaking process: How can one quantify the impact

of utterly unknown risks?

This quandary was vividly illustrated in the recent

Vermont Yankee cases. Confronted with the unenviable task of quantifying the hazards posed by the

construction and operation of a nuclear reactor, the

agency assigned a value of zero to the risk of exposure

to radioactive waste products. Apparently, this assessment was based on the assumption that some safe

method of permanent waste disposal, not presently

available, would be developed at some time in the future. This supposition may well prove to be correct.

However, all efforts to date to develop such technology

have failed miserably, and if the hypothesis that future

efforts will succeed proves false, the damage could be

inestimable. Yet nowhere in the agency’s environmental impact statement was this assumption, or the foundations upon which it was based, explicitly revealed.

If courts reject this sort of administrative sleight-ofhand, they are not attempting to obstruct the path of

scientific progress. Rather, they are merely attempting to carry out Congress’s mandate that decisionmaking be honest, open, thorough, rational, and fair. As

we confront the perils and promises of this scientific

age, both democracy and human dignity demand that

we be told of the risks, uncertainties, and value choices

that are made in our names.

In primitive societies, when the need to choose between cherished but conflicting values threatened to

disrupt the community, the simplest path was decision by a shaman or wizard, who claimed miraculous

insight. In our time, some would invoke the special

wizardry of those who wear a scientist’s lab coat, a

judge’s black robes, or a risk assessor’s business suit

rather than religious garb. But the genius of our system is its checks on centers of accumulated power.

Whatever its price, nothing but full disclosure can

guarantee that the regulators or the new guild of risk

assessors will not become the new elite.

If the Supreme Court’s most recent opinion in the

Vermont Yankee case portends a new trend of judicial

indulgence toward agency nondisclosure, Congress

may need to reaffirm its intention that the administrative decisionmaking process be subject to a searching and meaningful judicial review. In any event, when

undertaking an assessment of technological development in neuroscience-or in any other area of scientific endeavor—the Office of Technology Assessment

must take care to see that the risks are treated openly and evenhandedly, In this regard, I might note that,

in the draft document we are considering today, * con-

● The draft document referred to was reviewed at the OTA workshop. Some

parts of the draft are reprinted in the working papers for Impacts of

Neuroscience.
App. C—Statement by David L. Bazelon ● 31

siderable attention has been devoted to the benefits

promised by neuroscientific advances, while treatment

of the attendant risks has been confined primarily to

a scant five pages in the introduction and scattered

references elsewhere in the manuscript. Finally, I

would like to add my own endorsement to the proposal that OTA undertake an independent assessment of

the adequacy and openness of decisionmaking processes in the scientific arena.

Some may argue that society might balk if it knew

just how blindly we march into the future—and at

what cost. But false reassurances, unjustified confidence, and hidden agendas will only create cynicism

and destroy credibility. Our people have always been

prepared to accept risks and to pursue the larger good

of society. Progress can hardly be achieved in any

other way. Choices will be made despite uncertainty

and despite the social disruptions and dislocations. To

choose rationally, however, society must be informed

about what is known, what is feared, what is hoped,

and what is yet to be learned.
Appendix D

workshop Participants*

Panel

Barbara Mishkin, M. A., J. D., Panel Chairman

Hogan &. Hartson

W. Kent Anger, Ph. D.

Chief, Neurobehavioral Research Section

Applied Psychology and Ergonomics Branch

National Institute for Occupational Safety

and Health

Raymond Bartus, Ph. D.

American Cyanamid Co.

Medical Research Division

Lederle Laboratories

The Honorable David L. Bazelon

Senior Circuit Judge

U.S. Court of Appeals

District of Columbia Circuit

Floyd E. Bloom, M. D.

Director, Davis Center of Behavioral Neurobiology

Salk Institute

Greg R. Christoph, Ph. D.

Central Research and Development Department

E. I. du Pent de Nemours & Co., Inc.

David Cohen, Ph. D.

Department of Neurobiology and Behavior

State University of New York, Stony Brook

Joe Dan Coulter, Ph. D.

University of Texas Medical Branch

Marine Biomedical Institute

Miriam Davis, Ph. D.

Science Policy Research Division

Congressional Research Service

Library of Congress

John Dowling, Ph. D.

Department of Biology

Harvard University

John Hildebrand, Ph. D.

Department of Biological Sciences

Columbia University

Jack Houck, Ph. D.

President, Endorphin, Inc.

Zaven Khachaturian, Ph. D.

National Institute on Aging

National Institutes of Health

● Affiliations at the time of July 27, 1983, workshop

32

Dennis Landis, M. D.

Department of Neurology

Massachusetts General Hospital

Candace Pert, Ph. D.

Adult Psychiatry Branch

National Institute of Mental Health

Dominick P. Purpura, M. D.

Dean, Stanford University

School of Medicine

Mick Riddiough, Ph. D.

Syntex Corp.

Joshua Sanes, Ph. D.

Department of Physiology and Biophysics

Washington University Medical Center

Other participants

Constance Atwell, Ph. D.

Chief, Amblyopia, Strabismus, and Visual

Processing Branch

National Eye Institute

Nancy Beang

Society for Neuroscience

Katherine Bick, Ph. D.

Deputy Director

National Institute of Neurological and

Communicative Disorders and Stroke

Harold E. Booker, M. D.

Director, Neurological Services

Veterans Administration Central Office

H. Westley Clark, M. D., J. D., M. P. H.

Minority Counsel

Senate Committee on Labor and Human Resources

Sheila P. Duffy

House Select Committee on Aging

June Ewing

National Academy of Sciences

Carol Grundfest, M. A.

Senior Research Associate

Science and Technology Division

Pharmaceutical Manufacturers Association

Genevieve Haddad, Ph. D.

Program Manager

Air Force Office of Scientific Research/NL
App. D—Workshop Participants ● 3 3

Cynthia Kapphahn

Environmental Defense Fund

Jorge Lambrinos

Staff Director

House Select Committee on Aging

Jack Lubowsky, Ph. D.

Congressional Science and Engineering Fellow

Sen. John Glenn

James McCullough, Ph. D.

Chief, Science Policy Research Division

Congressional Research Service

Library of Congress

Robert Newburgh, Ph. D.

Leader, Biological and Biomedical Sciences

Office of Naval Research

Norine E. Noonan, Ph. D.

Office of Management and Budget

Harold Pincus, M. D.

Special Assistant to the Director

National Institute of Mental Health

Zeda Rosenberg, Ph. D.

Congressional Science and Engineering Fellow

Rep. David R. Obey

Michael Simpson

Science Policy Research Division

Congressional Research Service

Library of Congress

Philip G. Sokolove, Ph. D.

Congressional Science and Engineering Fellow

Rep. Albert Gore, Jr.

Fred Solomon, M. D.

Institute of Medicine

Division of Mental Health and Behavioral Medicine

Emmanuel M. Stadlan, M. D.

Acting Director, Demyelinating, Atrophic, and

Dementing Disorders Program

National Institute of Neurological and

Communicative Disorders and Stroke

Harlee S. Strauss, Ph. D.

American Chemical Society

Eugene Streicher, Ph. D.

Director, Fundamental Neuroscience Program

National Institute of Neurological and

Communicative Disorders and Stroke

Lawrence Tremonti, M. D.

Legislative Assistant

Robert Wood Johnson Fellow

Sen. William Bradley

Janett Trubach, Ph. D.

National Institute of Neurological and

Communicative Disorders and Stroke

Randall Wedin, Ph. D.

Congressional Science and Engineering Fellow

Rep. George E. Brown, Jr.

Nancy Wexler, Ph. D.

Neurology Disorders Program

National Institute of Neurological and

Communicative Disorders and Stroke

William A. Yost, Ph. D.

Program Director, Sensory Physiology

and Perception

National Science Foundation

Bambi Batts Young, Ph. D.

Director, Environment and Behavior Project

Center for Science in the Public Interest
Appendix E

References

1. Committee on Science, Engineering, and Public

Policy, “Report of the Research Briefing Panel

on Neuroscience” (Washington, D.C.: National

Academy Press, 1983).

2. This section was prepared by OTA based on material obtained in large part through the summer

course in Neurobiology of the Marine Biology

Laboratory at Woods Hole, Mass. The course was

sponsored by the National Institutes of Health and

the Grass Foundation. Other sources include

course notes prepared for Harvard Medical School

by David D. Potter and Edwin J. Furshpan, and

several textbooks. The books used most extensively

were: E. R. Kandel and J. H. Schwartz, Principles

of Neural Science (New York: Elsevier, 1981); and

S, W. Kuffler and J. G. Nicholls, From Neuron to

Brain: A Cellular Approach to the Function of the

Nervous System (Sunderland, Mass.: Sinauer Associates, 1976).

3, Braun, P., et al., “Overview: Deinstitutionalization

of Psychiatric Patients, a Critical Review of Outcome Studies,” American Journal of Psychiatry

138:736-749, 1981; Feldman, S., “Out of the Hospital, Onto the Streets: The Overselling of Benevolence)” The Hastings Center Report, June 1983, pp.

5-7.

4, Sharfstein, S. S., Deputy Medical Director, American Psychiatric Association, personal communication, September 1983.

5. The phrase is taken from Dr. Gerald Klerman,

cited in reference 4.

6. Fleckenstein, A., “Specific Pharmacology of Calcium in Myocardium, Cardiac Pacemakers, and

Vascular Smooth Muscle,” Annual Review Pharmacology and Toxicolo# 17:149-166, 1977; Reuter,

H., “Calcium Channel Modulation by Neurotransmitters, Enzymes, and Drugs,” Nature 301:569-574,

1983.

7. Campbell, W. C., et al., “Ivermectin: A Potent New

Antiparasitic Agent,” Science 221:823-828, 1983.

8. Wang, C. C., “Current Problems in Antiparasite

Chemotherapy,” Trends in Biochemical Sciences

7:354-356, October 1982.

9. de Kretser, D. M., “Agents for Male Fertility Control, ” Trends in Pharmacological Sciences

4:221-223, May 1983; Harper, M. J. K., “Prospects

for New or Improved Birth Control Technologies

by the Year 2000 A. D.,” working paper, vol. II,

pt. A, for World Population and Fertility Planning

Technologies, the Next 20 Years (Washington, D.C.:

U.S. Congress, Office of Technology Assessment,

OTA-HR-157, February 1982).

10. Grabowski, H. G., and Vernon, J. M., “The Pharmaceutical Industry, ” Government and Technical

Progress, a Cross-Industry Analysis, R. R. Nelson

(cd.) (New York: Pergamon Press, 1982), pp.

283-360.

11. Idanphan-Heikkila, J., “New Drug Permits,” Na- —

12,

13,

14.

15.

16.

tional Center for Drugs and Biological, Food and

Drug Administration, Department of Health and

Human Services, June 1983.

Molner, S., contract on drug development prepared for OTA, May 1983.

American Psychiatric Association, Diagnostic and

Statistical Manual, 3d ed. (Washington, D.C.: American Psychiatric Association, 1980).

Bartus, R., “Workshop on Impacts of Neuroscience)” Office of Technology Assessment, July 27,

1983.

Personal communication from officials at the National Institute of Mental Health and National Institute on Neurological and Communicative Disorders and Stroke, August 1983.

Anger, W. K., “Neurobehavioral Testing of Chemicais: Impact on Recommended S~andards,”

Neurobehavioral Toxicology and Teratology, in

press, 1983.

17. Cravioto, J., “Nutrition, Stimulation, Mental Devel -

18.

19.

20.

opment and Learning,” Nutrition Today, September/October 1981, pp. 4-15; Correa, H., Population,

Health, Nutrition, and Development, D. C. Heath

& CO.) 1975, Pp. 15-16.

Nelson, B, K., Brightwell, W. S., Setzer, J. V., and

O’Donohue, T. L., “Prenatal Interactions Between

Ethanol and the Industrial Solvent 2+thoxyethanol

in Rats: Neurochemical Effects in Their Offspring, ”

Neurobehaw”oral Toxicology and Teratology 4:395-

401, 1982.

Voorhees, C. V., “Environmental Assaults on the

Nervous System and Human Behavior: A New

Health Challenge,” symposium at the Annual Meeting of the American Association for the Advancement of Science, Jan. 8, 1982; citing Smith, D. W.,

“The Fetal Alcohol Syndrome,” Hospital Practice,

October 1979, pp. 121-128.

Schaumburg, H. H., and Spencer, P. S., “Selected

Outbreaks of Neurotoxic Disease,” Experimental

and Clinical Neurotoxicologv, P. S. Spencer and

H. H. Schaumburg (eds.), 1980, pp. 883-889.

21. Wood, R. W., Weiss, A. B., and Weiss, B., “Hand

34
App. E—References ● 3 5

22

23

Tremor Induced by Exposure to Inorganic Mercury,” Archives of Environmental Health 27:249-

252, 1973.

Johnson, B. L., and Anger, W. K., “Behavioral Toxicolo~y, ” Environmental and Occupational Medicine, W. N. Rom (cd.), 1983, pp. 329-350.

Silbergeld, E. K., “Experimental and Environmental Neurotoxins: Correlation of Behavioral and

Biochemical Effects,” Behavioral Models and the

Analysis of Drug Action, M. Y. Spiegelstein and A.

Levy (eds.), 1982, pp. 297-315; Silbergeld, E. K.,

“Current Status of Neurotoxicology, Basic and Applied)” Trends in Neuroscience 5:291-294, 1982.

24. Santos, Y., personal communication from the

House Select Committee on Aging. Ms. Santos cited:

National Institute on Drug Abuse, Series 30, #2: inhalants, National Institute on Drug Abuse Clearinghouse, Washington, D. C., July 1978; Sharp,

C. W., and Brehm, M. L. (eds.), Rew”ew of Inhalants:

Euphoria to Dysfunction, Department of Health,

25.

26.

27.

28.

29.

30.

Education, and Welfare, Publication No. 80-553,

Washington, D.C., 1977; Wyse, D. G., “Deliberate

Inhalation of Hydrocarbons—A Review,” Canadian

Medical Association Journal 108:71-74, 1973;

another relevant reference is: Commission of Inquiry into the Non-Medical Use of Drugs, Final

Report, Ottawa: Information Canada, 1973, see

especially app. A-9: “Volatile Substances: Solvents

and Gases. ”

The Effectiveness and Costs of Alcoholism Treatment, Health Technology Case Study 22, part of

the OTA Assessment of Medical Technology and

Costs of the Medicare Program (Washington, D.C.:

U.S. Congress, Office of Technology Assessment,

OTA-HCS-22, March 1983).

Enloe, C. F., “Thalidomide II,” Nutrition TodaeV,

January/February 1982, pp. 16-17.

Hiatt, F., “One-third in Military Affected by Alcohol,” Washington Post, Aug. 26, 1983, p. A13.

Nicholi, A. M., ‘(The Nontherapeutic Use of Psychoactive Drugs, A Modern Epidemic)” New England

Journal of Medicine 308:925-933, 1983.

Terenius, L., “Characteristics of the Receptor for

Narcotic Analgesics in Synaptic Plasma Membrane

Fraction From the Rat Brain)” Acta Pharmacolo#”a

Toxicologic 33:377-384, 1973; DeWied, D., and

Jones, J., “Neuropeptides Derived From Pro-opiocortin, Behavioral, Physiological and Neurochemical Effects,” Physio)ogica) Review 62:976-1059,

1982; Marx, J. L., “Synthesizing the Opioid Peptides, ” Science 220:395-397, 1983; Rossier, J., and

Chapouthier, G., “Brain Opiates,” Endeavor, New

Series 6:168-176, 1982.

Taste, D. L., et al., “Stanford Research Institute:

31

32.

33.

Shift Work Practices in the United States,” Department of Health, Education, and Welfare Document

No. 77/148 available through the National Technical Information Service as PB-274-707, March 1977;

Moore-Ede, M. C., Czeisler, C. A., and Richardson,

G. S., “Circadian Timekeeping in Health and

Disease: Part 2, Clinical Implications of Circadian

Rhythmicity, ” New England Journal of Medicine

309:530-536, 1983.

Hearings before the Subcommittee on Oversight

and Investigations, House Committee on Science

and Technology, Mar. 23, 1983; Hamburg, D. A.,

et al., Institute of Medicine: Health and Behavior

(Washington, D.C.: National Academy press, 1982).

Czeisler, C. A., Moore-Ede, M. C., and Coleman R.

M., “Rotating Shift Work Schedules That Disrupt

Sleep Are Improved by Applying Circadian Principles, “ Science 217:460-463, 1982.

Commercial Biotechnology: An International Analysis (Washington, D. C.: U.S. Congress, Office of

Technology Assessment, OTA-BA-218, January

1984).

34. Pharmaceutical Panel, Committee on Technology

and International Economic and Trade Issues, Office of the Foreign Secretary, National Academy

of Engineering, and Commission on Engineering

and Technical Systems, National Research Council, The Competitive Status of the U.S. Pharmaceutical Industry (Washington, D .C.: National

Academy Press, 1983).

35. Brown, G. L., et al., ‘

(Aggression, Suicide, and

Serotonin: Relationships to Cerebrospinal Fluid

Amine Metabolizes, ” American Journal of PSuVchiatqy 139:741-746, 1982.

36. Bird, S., “Social Impacts of Neuroscience, ” see accompanying working papers for this report.

37. Benbow, C. P., and Stanley, J. D., “Sex Differences

in Mathematical Ability: Fact or Artifact?” Science

210:1262-1264, 1980.

38. Gilligan, C., In a Different Voice: Psychological

Theory and Women’s Development (Cambridge,

Mass.: Harvard University Press, 1982).

39. Frank, R. T., “The Hormonal Causes of Premenstrual Tension, ” Archives Neuro)ogV and Psychiatry 26:1053-1057, 1931.

40. Gonzalez, E. R., “Premenstrual Syndrome: An Ancient Woe Deserving of Modern Scrutiny, ” Journal of the American Medical Association 245:

1393-1396, 1981.

41. Schafer, A. T., and Gray, M. W., “Sex and Mathematics, ” Science 211:31, 1981.

42. “Mathematical Ability: Is Sex A Factor?” letters to

Science 212:114-121, 1981.

43. Ross, A. O., “Behavioral Therapy With Children,”
36 . /rnpacts of Neuroscience—Background paper

Handbook of Psychotherapy and Behavioral

Change: An Empirical Analysis (2d cd.), S.L. Garfield and A. E. Bergin (eds.) (New York: Wiley,

1978), pp. 599-602.

44. Bazelon, D. L., “Statement Delivered at Workshop

on Impacts of Neuroscience,” Office of Technology

Assessment, July 27, 1983.

45. Bazelon, D. L,, “Governing Technology: Values,

Choices, and Scientific Progress, ” Technology in

Society 5:15-25, 1983.

46. Gutheil, T. G., and Appelbaum, P. S., “Substituted

Judgment: Best Interests in Disguise,” The Hastings

Center Report, June 1983, pp. 8-11.

47. The President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research has issued several reports related to topics influenced by neuroscience. These

are listed, and are available through the Government Printing Office: Summing Up, Defining

Death, Making Health Care Decisions (covering informed consent), Screening and Counseling for

Genetic Conditions, Implementing Human Research Regulations, and Protecting Human Subjects.

48. Arkin, H. R., “Forcible Administration of Antipsy -

49,

50,

51.

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