Impacts of Neuroscience

March 1984

NTIS order #PB84-196716

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Recommended Citation:Impact of Neuroscience—A Background Paper (Washington, D.C.: U.S. Congress, Officeof Technology Assessment, OTA-BP-BA-24, March 1984).

Library of Congress Catalog Card Number 84-601020

For sale by the Superintendent of DocumentsU.S. Government Printing Office, Washington, D.C. 20402

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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 Con-gressional Research Service, surveys the scientific basis of research on the nervous sys-tem, identifies several medical applications, examines some of the social effects, anddiscusses some of the difficult ethical and political issues that may arise from discoveriesin neuroscience.

This paper is part of an assessment of Technology and Aging in America that wasrequested by the Senate Special Committee on Aging, the House Select Committee onAging, and endorsed by the House Committee on Education and Labor. The paper arosenaturally from inquiry into diseases and conditions that affect the health of older Amer-icans. Neuroscience research has led to new treatments for major causes of death inboth the developed world (cardiovascular disease and stroke), and developing nations(parasitic diseases), in addition to advancing knowledge about neurological and psychiatricdisorders. In the United States, the aging of the population provides one of the strongestincentives for research on the nervous system, because of the burden of illness im-posed by several mental and organic brain disorders that become increasingly com-mon with age, such as depression, insomnia, and Alzheimer disease.

Alzheimer disease alone affects more than 1 million Americans, and causes severefinancial and emotional stress on each family that it affects. Alzheimer disease is oneof the most significant causes of need for long-term care in the United States. One ofthe most important motives driving neuroscience research is the desire for solutionsto the ravages of brain diseases like Alzheimer disease. * This background paper focuseson the status of basic neuroscience research, and was extended, in accordance withthe OTA mandate, to investigate not only the current status and potential medical ap-plications, but also to include broad social and ethical issues that might arise from suchresearch.

● More detailed discussion of Alzheimer disease and related disorders will be found in the OTA assessment Technologyand Aging in America to be published subsequently.

. . .///

OTA Impacts of Neuroscience Staff and Contractors

H. David Banta* and Roger Herdman, * * Assistant Director, OTAHealth 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 1983Congressional Research Service, Library of Congress

Project Staff

Eleanor Pitts

Pr inc ipa l Contrac tors

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

Spec ia l Contr ibutor

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

ContentsPage

INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1Why is Neuroscience Important Now?..... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1Basis for Congressional Interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2Relationship of This Background Paper to the OTA Aging Study . . . . . . . . . . . . . . . . . . . . . . . . . 3Organization of This Paper . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

WHAT IS NEUROSCIENCE? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4Interdisciplinary Nature of Neuroscience . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4Basic Concepts of Neuroscience . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5Wide Variety of Technologies Used in Neuroscience. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5MEDICAL IMPACTS OF NEUROSCIENCE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6Neurological and Psychiatric Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6Other Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7Issues Affecting Development of Drugs for the Nervous System . . . . . . . . . . . . . . . . . . . . . . . . . . 8Support for Biomedical Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

SOCIAL IMPACTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10Neurotoxic exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10Alcohol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12Drug Abuse and Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12Biological Rhythms and Work Schedules. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13Industrial Productivity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14Long-Term Effects on Industry. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14Crime and Violence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15Sex Differences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15Education. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16Ethical and Legal Aspects of Neuroscience . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

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

APPENDIX A–FEDERAL SUPPORT FOR NEUROSCIENCE RESEARCH. .,... . . . . . . . . . . . . . . . . 23Funding Levels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23Coordination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23Funding Cycles and Funding Stability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25Policy Questions Regarding Federal Support For Neuroscience . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

APPENDIX B–FEDERAL REGULATION OF AND RESEARCH ON NEUROTOXIC EXPOSURE . . . 26Federal Regulation of Toxic Substances, Including Neurotoxins. . . . . . . . . . . . . . . . . . . . . . . . . . . 26Pesticide Regulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26Federal Research on Toxicology, Including Neurotoxicology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

APPENDIX C–STATEMENT BY DAVID L. BAZELON. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28APPENDIX D–WORKSHOP PARTICIPANTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32

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

Tables f

Table No. PageA-1. Estimated Funding Levels for Federal Neuroscience R&D Fiscal Year 1983 . . . . . . . . . . . . . 24B-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 sys-tem, how it affects behavior, and how it is affectedby disease. The goal of neuroscience is to defineand understand the continuum from molecule tocell to behavior. New tools available to scientistspromise to clarify some of the mysteries of howbehavior is related to molecular, cellular, and elec-trical events in the brain.

The 50 million Americans with disabilitiescaused by neurological and psychiatric diseasesprovide compelling justification for studying dis-eases that affect the nervous system. Damage tothe nervous system from exposure to toxic agents,both at work and in the environment, is receiv-ing renewed attention from policy makers asknowledge increases. Neuroscience research maycontribute to the solution of some problemsrelated to crime and substance abuse. * The healthand productivity of the American work force maybe altered by application of principles derivedfrom neuroscience. The multiplicity of ways inwhich understanding human behavior can impacton society underscores the need to understandthe concepts of neuroscience and how that sci-ence relates to public policy. How social andpolitical institutions will face the challengesbrought by new knowledge based on neurosci-ence cannot be predicted, but future options willbe determined, in part, by actions taken now.

Why is neuroscience important now?

The wide diversity of applications of knowledgeabout behavior and other brain functions wouldmake neuroscience interesting at any point in time.Neuroscience is especially important now becausein addition to intrinsic interest in the nervous sys-tem, the field has been developing at an increas-ingly rapid pace. Progress over the past decadehas 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 poten-tially damaging substances,

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

Identified neurons from /+e/koma growing in cellculture and stained with a fluorescent antibody to

reveal the presence of the transmitter serotonin

cause of newly available scientific techniques,innovative institutional arrangements for studyingthe nervous system at universities, and coopera-tion among different scientific disciplines. Con-tinued rapid progress is likely if present levels ofsupport for research are maintained.

Many applications of neuroscience researchmay come to fruition in the next decade. Suchapplications may include new pharmaceuticalagents, improved human factors engineering, im-proved pesticides, and prevention of mental dis-abilities due to prenatal events or toxic exposures.Improved treatment of psychiatric disorders maybenefit many potential patients, Better under-standing of cognitive abilities, mood, and memorymay permit personal control of such functionsor at least elaboration of why control is notpossible.

As these applications are realized, the risks andethical issues raised by advances in neurosciencemay well become more evident and pose newquestions for public policy. This backgroundpaper is an attempt to outline the scientific basisof neuroscience, to describe some of its poten-

1

2 ● Impacts of Neuroscience—Background Paper

tial applications, and to identify some of the ethi-cal questions that may arise so that policymakerscan better anticipate issues that may emerge.

Basis for congressional interest

Congress, and other branches of the FederalGovernment, are involved with neuroscience inseveral ways. Most funding for basic neurosci-ence research in the United States is channeledthrough agencies of the Federal Government. Pay-ment for medical costs due to disorders affectingthe brain is accomplished through the Federalagencies that manage the Medicare, Medicaid, andmental health programs. Congressional legislationhas provided the backbone for regulatory actionsthat have reduced illness and accidents (and thushealth care costs) by preventing exposure tochemicals that injure the nervous system. Con-gress 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 inthe cerebellum. This photograph was taken by anelectron microscope of a special preparation of tissue

called “freeze fracture”

hearings on the nuclear and airline industries,citing the potential for accidents due to irregu-lar work hours and disregard of scientific knowl-edge about daily biological rhythms. Use of drugsthat affect mental function is a policy concern forseveral levels of government; regulation of druglaws, enforcement of drug abuse statutes, andpayment for treatment of drug addiction areshared among Federal, State, and local govern-ments.

The diversity of ways to apply neuroscience isreflected by the various congressional activitiesrelated to neuroscience. Over the past year, hear-ings on funding of neuroscience research havebeen held before authorizing and appropriationscommittees of both the U.S. House of Representa-tives and the U.S. Senate, Three committees haveheld hearings on various aspects of Alzheimerdisease, Applying neuroscience research to sched-uling of shift workers was the subject of one re-cent hearing; testimony reviewing the possiblerelationship between acid rain and injury to nervecells was heard in another. Numerous hearingson environmental exposure and pesticide regu-lation have been convened.

The optimal mechanism for funding biomedicalresearch has been a topic of extensive politicaldebate. This has resulted in competing bills thatmandate different levels of congressional involve-ment in funding decisions for the National Insti-tutes of Health (NIH), the largest Federal agenc,ythat supports biomedical research. Several differ-ent congressional bills creating a Federal agencyfor scientific and public discussion of topicsrelated to biology and bioethics have been intro-duced.

All these congressional activities potentially af-fect, and are affected by, developments in neuro-science. Each of the topics summarized in thisbackground paper is within the purview of somecongressional function. One purpose of this sum-mary is to point out the role of neuroscience re-search and its applications in these many congres-sional activities.

Several Federal agencies have identified neuro-science as an important and rapidly evolving field.In 1982, the Office of Science and TechnologyPolicy (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 bya scanning electron microscope

seven areas for review by the National Academyof Sciences* (l). The OSTP report and othersissued by branches of the Public Health Serviceand the National Science Foundation (NSF) docu-ment rapid advances in neuroscience research.

Relationship of this backgroundpaper to the OTA aging study

This background paper is part of an assessmentof Technology and Aging in America by the Officeof Technology Assessment (OTA). The prevalenceof diseases affecting the brain, primarily psychiat-ric and neurological diseases, is projected to rise incoming decades, as the population ages, becauseage increases the risk of developing depression,dementia, * * and other brain disorders. BecauseAmericans are living longer, they run greaterrisks of developing the diseases of old age. Greaternumbers of people reaching old age and rising

—● A report was prepared by the Committee on Science, Engineer-

ing, and Public Polic~’ (COSEPUP) of the National Academy of Sci-ences, highlighting some of the most promising areas of researchin neuroscience. It was used to brief George Keyworth, directorof OSTP, and was intended, in part, to provide guidance for theOffice of hlanagement and Budget and the J$rhite House.

● ● Dementia is the diminution of higher menta[ functions suchas memory, or the ability to calculate and think.

average longevity both contribute to the increas-ing prevalence of mental and neurological dis-eases. Developments in neuroscience thereforemay affect the health and well-being of the elderlypopulation far more than the general population.Assessment of biomedical research on neurolog-ical and psychiatric diseases is thus an integralpart of understanding these future changes.

A workshop was conducted on policy implica-tions of neuroscience research as an element ofthe assessment of Technology and Aging inAmerica. Because OTA evaluates indirect, as wellas direct, impacts of science and technolo~v, par-ticipants discussed not only the medical risks andbenefits of neuroscience for the elderly, but alsoseveral relevant social, medical, industrial, andpublic policy issues. *

Organization of this paper

Several papers on various aspects of neurosci-ence were written by contractors in preparationfor the workshop. Some of these papers, togetherwith chapters prepared by OTA, are printed underseparate cover as hqmcts of~euroscience: Work-ing Papers, available from the National TechnicalInformation 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, andincludes points raised in discussion at the work-shop.

An introductory description of neuroscience isfollowed by a review of selected applications andother topics related to neuroscience, emphasiz-ing the role of the Federal Government.

*Discussion of chemical and biological warfare was not includedon the workshop agenda because it would be impractical for theHealth and Life Sciences Division of OTA to arrange for retriew ofclassified information in an open workshop. The topic of chemicaland biological warfare, while extremely important, therefore wasomitted.

25-359 0 - 84 - 2 : QL 3

4 Impacts of Neuroscience—Background paper

what is neuroscience?

Neuroscience is the term applied to researchon how the nervous system works and how it isaffected by disease. The complexity of behavioris reflected in the complexity of the body’s mostsophisticated control system: the nervous system.The central nervous system (the brain and spinalcord) is composed of more than 10 billion nervecells and 100 billion supporting cells. Nerve cellsare arranged in specific circuits in precise ana-tomical arrangements. How nerve cells work in-dividually to conduct electrical signals, or in con-

Photo credit: Dennis Landis, Depafiment of Neurology,Massachusetts Genera/ Hospital

Photograph from an electron microscope of a cell thatsecretes the hormone prolactin from the

pituitary gland of a rat

cert to result in behavior, thought, and con-sciousness, are questions addressed by researchin neuroscience. Neuroscience also contributesto several medical disciplines. Diseases primari-ly affecting the nervous system afflict 50 millionAmericans; these diseases are the focus of re-search in neurology, psychiatry, neurosurgery,and other medical fields.

Interdisciplinary nature ofneuroscience

The character of research in neuroscience hasbeen defined by its interdisciplinary nature. Theobjects of study—behavior, biology, electrical phe-nomena, membrane biophysics, and diverse medi-cal applications —do not fit easily into traditionalacademic disciplines. As a consequence, neurosci-ence has drawn on talent from such diverse fieldsas anatomy, physiology, physics, electronics, ge-netics, biochemistry, optics, pharmacology, ethol-ogy, psychology, neurology, psychiatry, neurosur-gery, internal medicine, and information science.

Although early studies of the electrical proper-ties of individual cells depended on advances inelectronics, extensive knowledge of natural his-tory, especially marine biology, was equally im-portant for neuroscience research. Study of suchmarine organisms as squids, lobsters, and horse-shoe crabs has proved invaluable in neuroscienceresearch. This curious aspect of neuroscience isdue to many “experiments of nature” in marineorganisms that render them especially appropri-ate for the study of neural phenomena. One goodexample of this is the ‘(electric eel,” Torpedocalifornicum, which uses a special organ in itsbody to store electrical charge for stunning ene-mies and prey. The electrical organ uses the samechemical for cell-to-cell communication that hu-mans use for normal muscular contraction. Thisspecial organ has provided a plentiful, muchneeded source of receptor protein for studyinghow muscles contract and investigating thehuman disease myasthenia gravis. A number ofimportant scientific and medical discoveries thusderive from the study of this bizarre creature ofthe hydrosphere.

What Is Neuroscience? ● 5

Neuroscience investigators have borrowed ex-tensively from the fields of mathematics andphysics to explain the interactions of molecules,cells, and networks of cells. Most recently, neuro-science has been blended with the fields of mo-lecular biology, genetics, and biochemistry. Manyof the most dramatic recent advances in neuro-science were based on fundamental new tech-niques developed in the fields of molecular genet-ics and biochemistry.

Neuroscience encompasses the study of hownerve cells are born and die in roundworms, howleech nerve cells act in concert to produce eatingand reproductive behaviors, how pesticides workon the insect nervous system, and how Alzheimerdisease causes dementia.

Basic concepts of neuroscience

The study of neuroscience is unified by certainbasic concepts (2):

●

●

●

on explication of how such anatomic connec-tions are made.Understanding of nerve cell networks alsodepends on knowledge about cell-to-cell com-munication between individual nerve cells.Electrical properties of individual cells are im-portant in the transmission of impulses andin intercellular communication.The electrical properties of nerve and mus-cle cells are controlled by molecules on thesurface of the cell (ion channels and specificreceptors).

Scientists believe that behavior arises frommany cells working in concert. The basic preceptsof neuroscience have been derived from study-ing the electrical properties of individual nervecells. The classic work of scientists in the 1940’sand 1950’s was concerned largely with describ-ing the way nerve and muscle cell membranescould propagate electrical impulses. Over the nexttwo decades, scientists discovered many of themechanisms involved in the journey of an impulsealong a single nerve cell, The next major task wasto describe the way nerve cells communicate. Theideas underlying neurotransmission * were estab-lished in the following decades and continue toevolve rapidly today. The list of chemicals in-volved in neurotransmission, once limited to ahandful of simple compounds, has rapidly length-ened to include complex proteins and proteinfragments, hormones, and other types of mole-

● Behavior, perception, and cognition areresults of integrated actions of networks ofnerve cells.

● The activities of nerve cell networks are char-acterized by extremely precise anatomicalspecificity and enormous complexity. Under-standing of neural phenomena will depend

cules.

Wide variety of technologies usedin neuroscience

The advance of knowledge in neurosciencedepended, in large part, on new technolog

Photo credit: Dennis Landis, Depatiment of Neurology,Massachusetts General Hospital

The specialized membrane of an astrocyte—a supportcell of the central nervous system—in the mouse. Thisis taken from an area near the blood supply to the brainthat prevents toxic materials from crossing into the

brain from the bloodstream

hases.

Scientists can now watch the functioning brain,investigate the behavior of whole organisms buystudying molecular interactions, obtain electricalmeasurements of events in single nerve cells, andperform computer analysis of events in nerve cell

*In a process called neurotransmission, a nerve cell excites anothernerve cell through precise anatomical connections called synapses.A specific chemical called a neurotransmitter is released by the send-ing cell into the synapse and attaches itself to receptor moleculeson a receiving cell. Attachment of the neurotransmitter to the recep-tor causes electrical changes in the receiving cell, in a neural chainreaction.

6 ● lmpacts of Neuroscience—Background Paper

networks. New drugs allow analysis of molecularevents affecting the electrical properties of nervecells.

New methods of visualizing the human brainwithout invasive procedures rely on develop-ments in electronics, organic chemistry, numer-ical modeling, and computers. Investigation ofnerve cells’ electrical properties has required newtypes of electronic amplifiers and tools for manip-ulating fine instruments. Enlarged capacity forelectronic memory has assisted greatly in the anal-

ysis of electronic data from multiple nerve cellsand in reconstructing images from series of elec-tron-microscope photographs of individual nervecells. Recombinant DNA (rDNA) techniques havepermitted the study of genes important in nervecell function, and monoclinal antibodies (MAb) *promise to revolutionize understanding of hownerve cells work at the molecular level.

“Monoc]onal antibodies are molecules produced by new labora-tory techniques. They are useful for purification and identificationof specific proteins and for other purposes.

Medical impacts of neuroscience

Neurological and psychiatric diseases

The study of psychiatric and neurological illnesshas a long and colorful history. Ancient Greekphysicians knew that brain damage could lead toaberrant behavior. Precise definition of the anat-omy of the nervous system and correlation ofanatomy to specific neural functions were impor-tant parts of European medicine early in the 20thcentury. Freud presented theories about subcon-scious mental processes, while others were de-scribing the first correlations between diseasesand anatomic changes in the brain. These correla-tions led to new diagnostic categories and facili-tated differentiation of groups of patients thatonce had been categorized together. Refined diag-nosis made it possible to introduce new therapiesfor specific groups.

The introduction of drugs to treat neurologi-cal and psychiatric diseases began relativelyrecently. New drug treatments have been devel-oped for some important disorders, althoughthese treatments are not complete. Effective treat-ments for Parkinson disease, depression, manic-depressive illness, insomnia, pain, epilepsy, andacute anxiety have led to optimism that other dis-eases also may prove treatable and that presenttreatments might be improved.

The potential for improvement of current ther-apies is great. There is no effective treatment ormeans of prevention for many of the most preva-lent and costly diseases; for example, there is a

great need for effective prevention or treatmentof Alzheimer disease, which affects over a millionolder Americans and is a major source of needfor long-term care. Treatments for depression,anxiety, insomnia, and other disorders also canbe further improved by reducing adverse effectsof present treatments, or by reaching those whodo not respond to current therapies.

Advances also can be anticipated in neurosurgi-cal techniques, rehabilitation therapies for injuryto the brain and spinal cord, and replacement oflimbs and sensory organs. Research in nerve re-generation, leg and arm replacement, and sophis-ticated hearing and seeing devices someday maylead to effective compensation for lost abilities.New technologies for visualizing the brain haveled to less risky and more effective ways to detectbrain tumors, areas of tissue death due to stroke,and patterns of activity associated with epilepsyand organic brain diseases. There has been a dra-matic growth in knowledge about molecular andcellular aspects of pain. Some of the most impor-tant relationships between the brain and thebody’s other control systems (e.g., the variousglands that make up the endocrine system) havebeen elucidated only in the last decade.

The recent history of treatment for schizophre-nia illustrates the complex interactions betweenscientific advance, medical treatment, and publicpolicy. Many schizophrenic patients who former-ly were institutionalized can now undergo drug

Medical Impacts of Neuroscience ● 7

treatment outside mental hospitals. New drugtherapies have encouraged public policies in-tended to reduce the number of patients in mentalhospitals. Such policies have been highly suc-cessful: there has been substantial depopulationof mental institutions (3). However, reinstitution-alization of psychiatric patients has brought withit some social costs of incomplete treatment. Cur-rent drugs tend to improve the symptoms of hal-lucination and delusion but do not correct othersymptoms of apathy, withdrawal, and lack of mo-tivation (4). Patients are “better but not well” (5).Many patients now released to participate in soci-ety are not capable mentally of doing so but arenot offered the option of institutional care (3).Although drug treatment of schizophrenia has re-duced some Federal and State health care ex-penditures through depopulation of mental insti-tutions, the policy goal of deinstitutionalizationhas not yet led to equitable or optimal care ofpsychiatric patients.

The medical, social, and public policy interac-tions regarding schizophrenia treatment under-score the point that while neuroscience can im-prove the medical treatment of many diseases,medical care is only one factor in the effectivemanagement of disease. Some of the concepts re-garding public policy and schizophrenia might beapplied as well to other disorders that affect men-tal function, such as Alzheimer disease and severedepression.

Other diseases

The usefulness of neuroscience research is notrestricted to neurological and psychiatric diseases.There is great potential for advances in manag-ing fertility and infertility, cardiovascular disease,infectious and parasitic diseases, developmentaldisabilities, and immunologic disorders.

In the developed world, cardiovascular diseasesare a major source of illness and death, especial-ly in older individuals. The development of newdrugs for cardiovascular diseases has depended,in large part, on advances in understanding thephysiology and electrical properties of nerve andmuscle cells. Two classes of drugs recently intro-duced for the treatment of hypertension and car-diovascular disease—the so called “beta blockers”

and “calcium antagonists’ ’—were tools for thestudy of nerve and muscle cells for years beforethey were shown to have clinical applications (6).

In the developing world, parasitic diseases areserious health problems. Ancylostomiasis (hook-worm infection) affects 20 to 25 percent of man-kind. A group of drugs working at specific nervereceptors constitute the primary treatment of thisdisease. The drugs work by interfering withneurotransmission, paralyzing the worm. Becausethe drugs do not enter the brain or spinal cordof the host, only the worm is affected (7,8).

Schistosomiasis, a parasitic disease, affects over200 million people, mainly in Asia, Latin America,and Africa, where it is a major cause of death anddisability. Treatment involves paralyzing the para-site with drugs similar to hypnotic/sedative agentscurrently in use (8).

The treatment of both of these major parasiticdiseases thus has depended on increased under-standing of the interactions between nerve cellsand their neurotransmitter chemicals. Develop-ment of these new treatments also has dependedon understanding the neurobiology of inverte-brate organisms, an area of research that is notas well funded as study in mammals and otherhigher animals. The use of chemicals to combatparasitic diseases is an important example of howneuroscience research on seemingly unimportantinvertebrate organisms has led to widespreadhuman benefits.

Fertility and infertility are concerns in both thedeveloped and developing worlds. Advances inneuroscience, focusing on the neural mechanismsin the hypothalamus that regulate hormone re-lease and reproductive function, promise to yieldeffective and safe methods of managing fertilityand infertility for both men and women (9).

Behavioral medicine, the study of how behaviorrelates to disease, is another widely applicablefield. Research on how to control smoking, alco-holism, and stress may improve prevention ofcancer, liver disease, and cardiovascular illness;further study might help explain the brain’s in-fluences over the body’s defense mechanisms. Ad-diction has a behavioral component whose studymight lead to better control of drug and substanceabuse. Research in behavioral medicine may allow

— — . —

8 ● Impactgs of Neuroscience—Background Paper

better control of eating disorders by controllingappetite or by identifying environmental variablesthat trigger inappropriate eating.

Nutritional factors affect brain developmentand function. Most nutritional disorders involveseveral different organ systems, but the nervoussystem often is affected first or most severely. Forexample, malnutrition during embryonic, fetal,and early infant development leads to permanent-ly diminished mental capacity. Severe deficiencyof most water-soluble vitamins leads to well-defined neurological syndromes manifested bybehavioral, sensory, and motor disabilities. Goodnutrition depends on an adequate number ofmeals, well-balanced meals, and economic andsocial mechanisms for providing food to thepopulation. Neuroscience research can help iden-tify some of the factors that influence eatingbehavior, set minimum dietary standards fornutrients, and clarify the consequences of nutri-tional deficiency.

Issues affecting development of drugsfor the nervous system

The length of patent protection from competingmanufacturers, the development of drugs for rarediseases, and the effects of international competi-tion in the pharmaceutical industry are issuesrelated to the development of all drugs. Whilethese issues are important, they are not discussedhere because they are not directly related toneuroscience. There are, however, several uniqueissues related to drugs that specifically affect thenervous system,

Central nervous system drugs constitute a largefraction of the total pharmaceutical market com-pared with other drug types, but developmentcosts also are higher (10). The costs of develop-ment are believed by some to be due to the ab-sence of adequate animal models for study of be-havioral effects. The period used for U.S. Foodand Drug Administration (FDA) approval for druguse is longer for drugs affecting mental functionthan for other classes of drugs, such as cardio-vascular drugs and antibiotics (11). It is claimedthat psychoactive drugs are regulated more strin-gently for demonstrated efficacy than other drugsbecause the illnesses and disorders that are

treated often are not life-threatening, and fewerundesirable side effects are permissible (12).

Indications for use of psychoactive drugs havebeen confused in the past because of the difficultyin establishing definitive psychiatric diagnosis. Dif-ficulties in defining diagnoses and symptoms havecomplicated the testing and use of psychoactivedrugs (u), although recently published standardsfor diagnosis of mental illness may promote con-sistency (13).

The ethical problem of research using mental-ly incompetent patients is another impediment todevelopment of psychoactive drugs. Such patientsinclude those suffering from dementia and severepsychiatric disease—precisely those patients forwhom many nervous system drugs are mostneeded.

Many psychoactive drugs have been introducedin the last two decades. There is promise of de-veloping new drugs to affect “higher” functionssuch as memory and learning, but dramatic newdevelopments probably are not imminent (14,15).Some drugs intended to affect mental abilities,particularly among demented patients, are beingtested now in the United States and Europe. Psy-choactive agents now under development do notappear much more powerful than existing drugs,Thus, fears of new social problems from recrea-tional and occupational use may be premature(14). It is impossible to predict whether drugs thatsubstantially improve mental function can be de-veloped in the future; there is insufficient evi-dence now to make such a judgment (15).

There is a higher potential for abuse with psy-choactive drugs than with other types of drugs.This leads to several regulatory effects that areunique to psychoactive drugs. For example, thosedrugs deemed prone to abuse are registered withthe Drug Enforcement Administration of the U.S.Department of Justice, which may restrict dissem-ination and monitor use.

Support for biomedical research

The Federal Government, through Congressand numerous executive agencies, is the primarysource of support for biomedical research ingeneral and neuroscience in particular. Appro-

Medical Impacts of Neuroscience ● 9

priations for biomedical research were over $4billion in fiscal year 1983 and included approx-imately $500 million for neuroscience research(see app. A). The funding of biomedical researchis a public investment intended to increase under-standing of diseases and biological mechanismsfor the future benefit of citizens. Some of thejustifications for such research are the oppor-tunities to:

● reduce future morbidity and mortality, andassociated medical costs;

● increase industrial productivity by reducingloss of time from work due to illness;

● augment public health through preventionbased on new knowledge; and

● improve medical treatment based on scien-tific advances.

In addition to these features that are shared byneuroscience and other fields of biomedical re-search, there are some aspects of neuroscienceresearch that distinguish it from other areas.

The prevalence of neurological and psychiatricdisease is increasing, largely due to aging of theU.S. population. Disorders such as Alzheimer dis-ease and depression, for example, are becomingmore common because they are more frequentin the expanding elderly population. The increas-ing prevalence of neurological and psychiatric dis-eases contrasts with decreasing mortality fromsome other types of diseases such as hyperten-sion, atherosclerosis, and cancers other than lungcancer. This rising prevalence of brain diseasesmay increase future health care costs.

Neuroscience is distinctive in its rapid growthand its potential for continued growth. Technicalinnovations and institutional arrangements forresearch in neuroscience have led to accelerationof the scientific pace in the last decade. New tech-nologies promise to enhance further the powerof scientific investigation of the nervous system.Creation of new neuroscience programs and de-partments focuses academic attention on thisyoung scientific field. Growth requires supportfrom the Federal Government and private in-dustry.

Neuroscience has reached its adolescence at atime of budget austerity, in contrast to the fieldof cancer research, which grew when Federalfunding for science was rapidly expanding. Thissuggests that neuroscience now may be re-strained because the resources available to sup-port it are constrained by budgetary pressures.

Research in neuroscience is highly interdisci-plinary. This makes institutional arrangements atuniversities and other research centers more dif-ficult for neuroscience than for research alongdisciplinary lines. It is more difficult to sustainsupport for an activity that has no departmentalor other institutional home. In recent years, thetrend in funding agencies has been to focus, evenmore than in the past, on investigator-initiatedgrants rather than institutional grants for inter-disciplinary research. This has made sustenanceand creation of centers of excellence for neuro-science more difficult.

Training of personnel to do research in neuro-science is of particular concern. Funding for train-ing programs has been cut more severely thanfor research grants. A recent study by NSF, incooperation with the Society for Neuroscience,found that despite rapid expansion of scientificopportunities, jobs for young investigators arelimited, and training programs do not appear tobe growing a rapidly as in the recent past. * Itis significant that only five universities hadseparate neuroscience departments-most de-grees in neuroscience were granted by other de-partments in traditional disciplines.

Recent advances in technology and basic knowl-edge have rapidly expanded the frontiers ofneuroscience. The field thus may have great scien-tific potential at present, so that investment nowcould be especially productive.

*Most research positions are at universities, and most universitiesare not hiring. This is a major reason for limitation of new job op-portunities,

10 ● Impacts of Neuroscience—Background paper

Social impacts

Neurotoxic exposure

An important topic in any discussion of Federalpolicy involving neuroscience is damage to thenervous system from toxic substances, or neuro-toxicity. Injury to the nervous system is mani-fested by irritability, personality changes, fatigue,lack of control of body movement, loss of sensa-tion, and other symptoms. Often, symptoms ofneurotoxic injury are wrongly ascribed to agingof the individual or to social factors. Damage tonerves can occur from food, beverages, drugs,environmental agents, or occupational exposureto toxic agents. Many drugs have neurological sideeffects, particularly those intended to affect someaspect of neural or cardiovascular function (manyof these drugs are prescribed deliberately to af-fect one part of the nervous system, but also mayaffect another part in an undesirable manner).Metals and chemicals in the environment can af-fect individuals who inhale contaminated air oringest contaminated water and food. Occupationalexposure to neurotoxic substances also is quitecommon.

Clinical research and toxicity testing alreadyhave established that “roughly one-fourth of thechemicals most frequently encountered in indus-try and of known toxicologic significance havedocumented neurotoxic effects [and] this repre-sents only a small part of the total problem” (16).Discoveries of the severe effects of heavy metals,some pesticides, and many organic solvents haveled to improved industrial and environmental con-trols and have prevented recurrence of many ofthe disasters of the early industrial period. Manyinstances of neurotoxic injury probably have notbeen discovered yet, hidden because of the dif-ficulty of establishing a link between changes incognition or behavior and the presence of an oc-cupational or environmental toxic substance.

Neurotox ic i ty dur ing bra in deve lop-ment.–Early human development, particularlyduring the embryonic and fetal stages, is a periodof special vulnerability to neurotoxic exposure.Such exposure can be tragic because of the limitedability of the nervous system to recover from ser-

ious insults. In general, nerve cells cannot beregenerated; remaining cells can only readjusttheir connections to compensate for lost cells.Such compensation is often incomplete. There-fore, damage done to embryonic, fetal, and infantbrains often is associated with permanent disabil-ity. Examples of this are the lifelong mental retar-dation associated with maternal malnutrition dur-ing pregnancy (17), and long-lasting mental inca-pacity due to toxic lead exposure during infancy.

Interactions between chemicals encountered atwork or in the environment and other factors alsomay damage the developing nervous system. Ani-mal experiments have shown that effects due toalcohol can be exacerbated by exposure to organicsolvents (18). Such interactions would be difficultto detect in normal human settings because of thelarge number of potentially confounding vari-ables.

D i f f i c u l t i e s i n d e t e c t i n g n e u r o t o x i cdamage.-one reason that the problem ofneurotoxic exposure has not been identifiedearlier is the difficulty in detecting neural damage.The symptoms of toxic injury to the nervous sys-tem often are changes in behavior, mood, and per-sonality that may be wrongly ascribed to factorsother than chemical exposure. For example, the“fetal alcohol syndrome” was not discoveredbecause of its deleterious effect on brain develop-ment that leads to permanent retardation butbecause of distinctive facial and skeletal abnor-malities in affected infants (19). The mental ef-fects of prenatal alcohol exposure, which causethe most serious long-term disability and lead tomost of the costs of care, only later were iden-tified. In adults, many neurotoxic symptoms areascribed to stress, personal problems, or aging,rather than to chemical or other environmentalexposures. Symptoms of irritability, forgetfulness,and hostility often may be due to factors otherthan chemical exposure, but the relative impor-tance of the various factors cannot be ascertain-ed because so little is known about the frequen-cy of neurotoxic injury,

Social Impacts ● 1 1

Another factor that makes detection of neuro-toxic injury difficult is the long period betweentime of first exposure and identification of thefirst definite symptoms. Most industrial neurotox -ic hazards have been found because of relative-ly quick development of symptoms associatedwith use of a particular chemical, or massive ex-posure levels. Examples of rapidly developing tox-icity include episodes of chlordecone (Kepone) ex-posure in a Virginia plant in 1975 and methyl-N-butyl ketone (MBK) toxicity in an Ohio coated-fab-rics factory in 1973 (20). Massive exposure is ex-emplified by the “lead palsy” identified decadesago, when lead levels were so high that workersshowed overt signs of disease within months,

In the tragedy of Minamata Bay in Japan, 121people were afflicted by a mysterious illness, and46 died (20). Many infants were born with irre-versible mental retardation, and many fishermenwere affected, The pattern of exposure suggestedcontamination of the water or food supply. In-vestigative work revealed mercury compoundsemanating from effluent discharged into the bayby a local factory that was using mercury com-pounds in chemical production. The industrialwaste was entering the marine ecosystem, even-tually contaminating fish and shellfish. Localresidents had ingested the contaminated fish. TheMinamata Bay episode was only one of severalinstances of mercury poisoning identified in Japanand Iran in the 1970’s.

The Minamata Bay episode is a classic exampleof the complexity of neurotoxic exposure. Socialfactors, dietary habits, industrial practices, ecolog-ical processes, occupational exposures, and de-velopmental vulnerabilities of infants and fetuseswere all part of this web of interactions. Yet theMinamata Bay exposure had a better chance ofdetection than other types of exposure becausethe effects of toxic injury appeared quickly in thelocal population. Rapid identification was possi-ble because the symptoms were severe and couldbe related easily to a change in an industrialprocess.

The more insidious effects of long-term, low-level exposure are not known for most chemicals.The syndrome of “mad hatters)” who were ex-posed chronically to toxic levels of mercury com -

pounds in the manufacture of hats, is an exam-ple of long-term exposure leading to behavioralabnormality that has been known for almost acentury, Workers in factories in the United States,however, still suffer from tremors due to mer-cury poisoning (21). Neurotoxic effects of otherchemicals may not be identified if neural damageoccurs only after long periods of exposure. Re-search on this aspect of neurotoxicity is still inits infancy.

One possible, but as yet unproven, hypothesisrelates acid rain to nerve cell injury. Congres-sional hearings were held recently by the HumanServices Subcommittee of the House Select Com-mittee on Aging to look into a possible, but as yethighly speculative, association between acid rainand certain neurological illnesses, The link is pos-tulated to be due to increased leaching of metals,such as aluminum, from soils under acidic condi-tions. The hearings demonstrated the need forincreased research into possible links betweenchronic brain disease and environmental factors.

Scientific activity has led to improved methodsof detecting neurotoxic injury, A recent surveyof behavioral toxicology studies found more than90 publications, almost all of which had been pub-lished since 1973 (22). New methods of detectionbased on changes in animal behavior have pro-gressed, and the use of drugs to increase sensitivi-ty of animal tests and tissue preparations also ismaking headway (23), Such tests, however, havenot been incorporated into standard protocolsanalogous to those used in testing potentialmutagenic and carcinogenic agents.

Progress in detecting and testing for neurotoxicinjury is important because effective regulationof chemicals, drugs, and other potential toxicagents must rely on findings based on reliable sci-entific methods.

Federal regulation and research. * —Even ifmethods of detection can be found, there is con-cern that Federal agencies may not be caable ofpromulgating and enforcing regulations forneurotoxicity. The two largest Federal agenciesinvolved in regulating toxic exposure are the

*See app. B for details on Federal agencies imrohred in regulationand research of neurotoxic exposure.

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12 ● Impacts of Neuroscience—Background Paper

Environmental Protection Agency (EPA) and theOccupational Safety and Health Administration(OSHA) of the Department of Labor. Some con-gressional oversight has touched on issues relatedto neurotoxicity. For example, the Subcommitteeon Department Operations, Research, and ForeignAgriculture of the House Committee on Agricul-ture recently heard testimony that the resourcesof EPA may be insufficient to review adequatelythe needed studies or to process the registrationand testing of pesticides. Pesticides may be im-portant sources of environmental neurotoxicityto those in the general population who eat treatedfood, and of occupational exposure to those en-gaged in pesticide production or agriculture. *

Urban dwellers are also subject to chemicalsthat adhere to or are incorporated into foodstuffs.Some countries allow use of agents that arebanned in the United States, and importation offoods from these countries may be a source ofneurotoxicity. Vegetables and other foods grownin urban gardens maybe contaminated by delib-erate garden spraying or from treatment of trees,shrubs, and grasses located nearby. Spraying oftrees, golf courses, and garden plants, and ex-posure to heavy metals from industry and auto-mobile emissions all contribute to neurotoxicresidues that might accumulate on food grownin urban environments.

Deliberate neurotoxic exposure.—Thereis one category of neurotoxic exposure that indi-viduals impose upon themselves. The use ofneurotoxic inhalants to alter consciousness is oneexample of deliberate exposure. “Glue sniffing”and inhalation of other organic solvents is com-mon, especially among some innerwity popula-tions. Inhalation of many organic solvents yieldsa temporary feeling of euphoria but may damagethe nervous system and other organs (24). suchsubstance abuse is just one form of selfdestruc-tive behavior, analogous to other examples ofdrug abuse listed below.

● Pesticides are of particular concern because many act by affect-ing the transmission of impulses in the insect nervous system. Thereis concern that pesticides may not be completely specific to the pestbut may also affect people and animals.

Alcohol

Alcohol is one of the most common neurotox-ins in this country; it is estimated that 9 percentof adults in the United States drink heavily on aregular basis (25). Half of all automobile accidentsprobably involve alcohol abuse, and the annualeconomic cost of alcohol use in the United Statesmay be as high as $120 billion (25). Most of thecosts are incurred as health costs for treating al-coholism or loss of productivity due to illness andalcohol-related disability.

In addition to the usual symptoms of alcoholuse, there are also numerous long-term healthconsequences of heavy use. There are at least 15neurological syndromes associated with alcohol,as well as numerous blood, liver, and cardiovas-cular disorders. Certain cancers and infectiousdiseases are also more common or more lethalin alcoholic patients. Adults are not alone in theirexposure to damage from alcohol use: womenwho drink during pregnancy can cause mentaland physical disability in the fetus. “Fetal alcoholsyndrome” is a severe example of such toxicity(26).

Military preparedness also may be jeopardizedby alcohol use. A recent Department of Defensesurvey concluded that 34 percent of all militarypersonnel suffer alcohol-related productivity loss(27).

Alcohol causes economic, social, military, medi-cal, and family problems. Many of the effects ofalcohol that lead to lost productivity and increasedsusceptibility to accidents are due to its neurotox -icity. This is characteristic of many drugs ofabuse: they are used because they affect mentalfunction, yet may be dangerous for the samereason.

Drug abuse and addiction

Use of drugs that affect the brain, such ashallucinogens, depressants, stimulants, and tran-quilizers, is common in the United States, A re-cent article in the New England Journal of Medicine- referred to the use of psychoactive drugs inAmerica as a “modern epidemic,” noting that a

Social Impacts ● 1 3

half million Americans are addicted to heroin, asmany as 13 million may have used amphetamineswithout medical supervision, and more than 50miIlion have used marijuana at least once (28). Thesame article reported that 11 percent of highschool seniors use marijuana daily, and more than8 million Americans have used it over 100 times.Evidence suggests that use of illicit psychoactivedrugs has increased about twentyfold in the lasttwo decades (28).

Addiction to opiate drugs is an extreme exam-ple of drug abuse. Addiction appears to be dueto a combination of behavioral and biological com-ponents. Behavioral medicine may lead to furtherunderstanding of addiction; basic neurosciencemay contribute to understanding the biologyunderlying addiction. Research findings over thelast half decade have led to startling insights intothe molecules involved in cells affected by drugssuch as morphine and heroin. Dramatic accelera-tion of progress has followed the discovery ofnatural molecules, endorphins and encephalins,that are manufactured by the brain to affect thesame receptors influenced by opiate drugs (29).

It is possible that treatment of physical depend-ency on drugs might improve as a result of a bet-ter understanding of addiction. Increased knowl-edge may permit identification of individual varia-tions in biological susceptibility to certain agents.Neuroscience by itself cannot resolve the prob-lem of psychoactive drug abuse, whose roots maybe social as well as biological, but advances inunderstanding and treatment are needed tounderpin social interventions and public policy.

Neuroscience may also help clarify the impor-tant distinction between drug addiction that hasserious public health and social consequences(e.g., encouraging crime to support the biologicalneed for drug use) and “recreational” use that hasfew deleterious effects. Drug abuse ranges fromcaffeine to heroin, and public policy is based, inpart, on differences in biological effects of theagents. Caffeine use is not regulated, but heroinproduction, sale, and use are illegal. Betweenthese two extremes, there is widespread disagree-ment as to what should be regulated. For exam-ple, there is wide variation among the States inenforcement of alcohol and marijuana statutes.

This diversity reflects disagreement over theseriousness assigned to use of particular drugs.Further research in neuroscience may narrow therange of disagreement by providing data on bio-logical effects. However, physiological and medi-cal effects are only two of many criteria used fordetermining “serious” drug abuse in different con-texts and cultures.

Biological rhythms and workschedules

New work patterns demanded by modern man-ufacturing and service industries have led to ris-ing rates of shift work. A significant fraction ofthe American work force, 27 percent of maleworkers and a slightly lower fraction of femaleworkers, is subject to disruption of sleep, in-creased incidence of gastrointestinal distress, anddifficulties in socializing with families and friendsas a consequence of night and shift work (30). Fur-ther, it has been shown that worker errors aremore common during late-night shifts and areconcentrated in the early morning hours. For ex-ample, the accident in Reactor II at the Three MileIsland nuclear powerplant occurred during the3 a.m. to 5 a.m. period, a time during which ahighly disproportionate number of accidents oc-cur, as demonstrated in numerous industrialstudies (31).

Shift-and night-work schedules are of Federalconcern because they involve worker health andsafety, public safety, and industrial productivity.Many functions performed or supervised by theFederal Government, such as air traffic controlat commercial airports, staffing of missile silos,and operation of nuclear powerplants, must beperformed around the clock. Congressional inter-est in shift work was expressed recently in hear-ings before the Subcommittee on Investigationsand Oversight of the House Committee on Scienceand Technology. Innovations in shift work weredescribed, and several Federal agencies involvedin protecting public safety testified on presentshift-work practices. Evidence was presentedshowing that current shift-work practices oftenfail to take account of data regarding optimumwork schedules and ignore recent neuroscienceresearch on biological rhythms.

74 ● Impacts of Neuroscience—Background Paper

Experiments on natural circadian rhythms haveled to discovery of at least two “biological clocks”that correlate with hormone levels, body tempera-ture, sleep cycles, and attentiveness. Work sched-ules more closely in accord with natural biologicalrhythms have yielded improvements in produc-tivity, decreased error rates, and increased work-er satisfaction (32). Simple social and industrialinterventions based on neuroscientific knowledgecan ameliorate some problems—in this case, bymerely altering the periods of rotation betweenshifts and changing the direction of rotation fromshift to shift.

Industrial productivity

Neuroscience may help eliminate or alleviatesome causes of lost worker productivity by reduc-ing substance abuse and by identifying and pre-venting neurotoxic exposure among workers.Work schedules can be improved by use of prin-ciples derived from neuroscientific experiments.Education and retraining may be improved asmore is discovered about learning, memory, andcommunication. The advance of neuroscience,therefore, probably will lead to changes not onlyin those industries directly linked to biology anddrug development but in other industries as well.

Long-term effects on industry

International Competition. -Congressionalconcern for the international competitiveness ofU.S. industry has increased in recent years. Therelative position of the United States comparedto other countries may prove important in thoseindustries affected by neuroscience. It appearsthat the United States supports more activity inbasic neuroscience research than any other coun-try, much as it has had the largest national effortin molecular genetics and immunology. The highdegree of development of basic science, the pres-ence of mechanisms for training persomel, theflexibility of university-industry relations, andFederal support for basic science in the UnitedStates have proved important in the early phasesof development of those industries related to bio-technology (33). The relatively good position ofthe United States also could prove important inany future ‘(high tech” industrial applications

based on neuroscience. An industrial sector basedon neuroscience could develop in pharmaceuti-cals, chemicals, or information technology andmanagement, albeit with very different timescales. Contributions to the drug industry are like-ly to predate applications in information scienceand managment.

The development of new psychoactive drugs islikely to be important for future growth of drugcompanies because psychopharmaceuticals pro-vide a highly profitable and growing market. Itis not clear, however, how American-based com-panies will fare in the competition for new psy -chopharmaceutical markets. A recent study bythe National Academy of Engineering expressedconcern that the pharmaceutical industry in theUnited States may be losing some of its competi-tive advantage over foreign industries (34). Theamount of neuroscientific research in the UnitedStates might be construed to confer competitiveadvantage in the psychopharmaceutical sector toAmerican companies. Yet, scientific excellencemay not translate to more jobs or income forAmerican workers. The American lead in sciencemay be undercut by the extensive worldwide in-tegration of pharmaceutical markets (leading torapid international technology diffusion and lesscompetitive advantage to the country of origin)and the relative stringency of the drug approvalprocess in the United States (providing incentivesfor introduction of drugs abroad, rather than inthe American market).

Creation of New Industrial Sectors.—Neuroscience also is expected to contribute to de-velopments in other industries such as food pro-duction, pesticide manufacture, and informationprocessing. Industrial applications of neuro-science may be analogous to other nascent high-technology applications, such as those derivingfrom biotechnology and semiconductors. Knowl-edge about human cognition may include howbetter to use tools such as electronic and mechan-ical equipment. This might lead to improved“human factors engineering” of such tools.

Future developments in agriculture may yielda second “green revolution” based on biotech-nology and neuroscience. Neuroscience can con-tribute to development of new, more specific pes-ticides affecting insect nervous systems and

—

Social Impacts 15

prepare the way for discovery of other ways tocontrol pests, such as growth factors and airborneinsect hormones. Such innovations will dependin part on studying pest behavior and biochem-istry under controlled conditions with methodsdeveloped in neuroscience.

The development of an entirely new industrybased on biological substrata, such as artificiallygrown nerve cell networks or “biochips” made bymicro-organisms, may be possible in the future.Artificial intelligence programing of computersmay contribute to understanding how complexinformation-processing networks work, possiblyyielding fertile analogies for the study of nervecell interactions. Understanding of brain functionand cognitive processes, conversely, may furtherunderstanding in information science, leading tonew applications. Although only general predic-tions can be made about the industrial develop-ment of neuroscience, it seems likely that neuro-science will prove more important in the future.

Crime and violence

Neuroscience may provide some insights intoways to prevent or better understand violenceand suicide and may even allow treatment ofsome selected problems (when they are due toidentifiable and correctable aberrations). For ex-ample, researchers recently have found that levelsof 5-hydroxyindolacetic acid (5-HIAA)) a byprod-uct of a specific neurotransmitter family, areelevated in the spinal fluid of those who have com-mitted suicide by violent methods [35). This find-ing strengthens the link between depression,which is also associated with elevation of 5-HIAA,and suicide. This knowledge, combined with high-ly effective drug treatments for several forms ofdepression, eventually may provide a method forprevention of some violent suicides. However, theuse of 5-HIAA measurement as a means of iden-tifying those who might commit suicide is highlyunlikely because only a small fraction of thosewith the biochemical change are suicidal.

Researchers also have found 5-HIAA in somewho have histories of multiple violent criminaloffenses. The previously mentioned link of bothaggression and suicide with depression is intrigu-ing but also illustrates the problems associatedwith trying to use biochemical measurement as

a predictive tool for criminal enforcement: thoseprone to violence are probably only a smallminority of those with elevated 5-HIAA levels.

Difficulty in using screening tests for criminalbehavior has precedent. The use of chromosomaltyping once was regarded as promising for detect-ing criminal predisposition, when some reportswere published showing a relatively high in-cidence of a particular chromosomal finding (thepresence of an extra “Y” chromosome) amongprison inmates. Later studies led to abandonmentof the test as a predictor of criminal behaviorbecause they proved the method had little predic-tive value and its use led to unfounded stigmatiza-tion of those who had the chromosomal changewithout the purported proclivity for criminalviolence (36).

It seems unlikely that science will provide a bet-ter predictor of criminal behavior than previouscriminal behavior. However, neuroscience, incombination with the social sciences, may in-crease our understanding of some forms of vio-lence. If mechanisms to preserve individual auton-omy are provided, treatments tailored to theneeds and wants of particular individuals some-day may help to manage some forms of violentbehavior. Such efforts, however, will be additionsto, rather than replacements for,nisms of dealing with crime and

other mecha -violence.

Sex differences

One area receiving renewed attention is thefield of sex-difference research. There are demon-strable differences between men and women intheir mathematical and geometric abilities (37),and in development of moral reasoning (38). Theextent to which these differences are due tosocialization rather than physiology is a topic ofongoing controversy. Progress in behavioralneuroscience may help establish the factual basisfor academic and political dispute, but the moralquestions regarding social equality of both sexeswill not be answered by scientific inquiry.

One particularly interesting topic arising fromresearch into sex differences is premenstrual syn-drome (PMS). PMS affects some women in thedays preceding menstrual periods and is charac -

16 ● Impacts of Neuroscience—Background paper

terized by fluid retention, depression, irritabili-ty, and moodiness. PMS varies widely in intensi-ty and type of symptoms expressed. It was firstreported more than half a century ago (39), andhas received recent attention because courts inthe United Kingdom and France have acknowl-edged PMS as a mitigating factor in violent crimes(40). American courts may follow their Europeancounterparts. Interest in PMS may increase asmore is learned about how hormones, includingsex hormones, affect behavior and other brainfunctions. PMS presents a particularly thornyproblem: how to balance the conflict between adesire to help those who suffer with PMS and con-cern that it may be used as an excuse to excludewomen from certain occupations and endeavors.

There is danger of premature or misdirectedapplication of new knowledge about sex differ-ences. In studies that have identified differencesbetween males and females, the findings applyto population differences, not individual differ-ences. On some tests of mathematical ability, forexample, girls’ scores are lower on average thanboys’ scores. Within the group of boys or girls,however, there is a diversity of scores, and manyindividual girls do better than an average boy. Thedifferences may not be gender-specific but onlyloosely associated with being biologically male orfemale. Public policy based on sex differencesmust take such heterogeneity into account.However, it is not clear how to do this fairly. Thestudies showing sex differences in mathematicalability have led to some suggestions about deal-ing differently with boys and girls for purposesof mathematics research (41) and training (42).Such recommendations must be scrutinized care-fully so that individual choice is not jeopardizedand public policy is not imbued with social pre-judice.

It is also important that public policy not beerected on theories that are not widely shared.There is agreement that there are differences inmathematical ability, but there is no consensusthat this is biologically determined, despite at-tempts to control for educational background inanalyzing test scores. Thus, it might be prematureto change educational institutions on other thanan experimental basis because of knowledgeabout sex-related differences.

Education

Neuroscience may improve understanding ofthe causes of some forms of learning disability,such as autism or dyslexia. * Research on thesedisorders has refined understanding of the per-ceptual deficiencies involved. Psychological in-novations have led to improved methods of teach-ing children with these learning disabilities (43).Further understanding in some instances mayallow effective treatment or compensation by pro-viding a basis for introduction of new teachingmethods.

Behavioral science also can improve educationby better characterizing the mechanisms of learn-ing, memory, and perception in normal childrenand adults. Indeed, the most important long-termimprovements in education may derive from dis-coveries about cognitive function and neural proc-essing; knowing how the brain works may welllead to better methods of teaching.

Ethical and legal aspects ofneuroscience

There are positive and negative aspects of ad-vances in neuroscience. Public ambivalence isreflected in the different attitudes toward psy-choactive drugs in two novels by Aldous Huxley.In Brave New World, the drug “soma” is used asa means of avoiding reality—as a method of mindcontrol by the state. In Mind, psychoactive drugsare used to expand human experience benignly,

There are legal and ethical issues that derivefrom loss or change of mental function, in addi-tion to concerns over the proper use of technol-ogies that affect the brain. For example, it hastaken several decades to attain general acceptanceof the concept of brain death in medical circles.Several examples of ethical and legal issues relat-ing to neuroscience are summarized here.

Public Concern Regarding Science.—Pub-lic 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 sep-arated from the external environment. Recent treatments have in-volved drugs and behavioral intervention. Dyslexia is a diminishedability to read. It can have many different causes, including traumaand stroke. One common form, found in children, appears to havean important genetic component.

Social Impacts ● 1 7

for example, substantial public concern over theapplication and misapplication of biotechnology.The furor over laboratory and community safe-ty of rDNA has been supplanted by fear of theuse of “genetic engineering” in humans. Public ap-prehension about science and technology is oftena mix of both rational concern about possible mis-use and uncertainty about the science or tech-nology itself. Uncertainty about the subject mat-ter is associated with ambivalence regarding theextent to which decisions should be left to experts.In an open and democratic society, public percep-tions often have Federal policy implications. *

When there is dispute over executive actions,the courts often must decide whether scientificevidence has been used properly (44). For exam-ple, Federal courts have been involved in con-troversies about environmental protection, work-er safety standards, and public safeguards in theuse of nuclear power. However, the courts areill-equipped to make scientific judgments, andthey are inefficient in regulating social activities.The courts are best suited to judging whether thedecisionmaking process is fair and appropriate;court decisions are poor substitutes for coherentlegislation (45).

At present, there is no permanent Federal insti-tution for dealing with areas of science that areassociated with public apprehension, Up to now,public concern over technologies has been dealtwith on a case-by-case basis. One illustrative ex-ample concerns public perceptions of the dangersof rDNA research. Much of the controversy overrDNA might have been avoided had a mechanismalready been in place for voicing public concernsand airing scientific evidence. The potential ef-ficacy of such mechanisms has been demon-strated by the same controversy. Public fearseems to have decreased since the establishmentof the Recombinant DNA Advisory Committee(RAC) at NIH.

Two important components in assuaging publicapprehension seem to have been the inclusion ofnonscientists on the RAC and the openness of the

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

process by which regulatory decisions were made(45).

Other controversies invoIving neurosciencehave arisen over the experimental use of hallu-cinogens on unsuspecting patients by the Depart-ment of Defense and the Central IntelligenceAgency, and the Soviet Government practice ofcommitting dissidents to psychiatric institutionsand forcibly treating them with psychoactivedrugs. It thus seems highly probable that therewill be future controversies based on public ap-prehension about some aspects of neuroscience.

Mental Competence and Informed Con-sent.— Ethical issues related to neuroscience arenot restricted to public concerns; there are alsomany issues of individual rights, One recurringissue, as noted in the context of drug develop-ment, is the inability of psychiatrically disabledor demented patients to consent to medical treat-ment or experimental research. Demented pa-tients cannot judge the adequacy of treatment orevaluate the risks of experimentation for them-selves. Who should decide for such patientswhether they should participate in a clinical trialof a drug for dementia, and what should be thestandards for ensuring protection of their rights?This question is especially difficult when experi-mentation is unlikely to benefit the patient dir-ectly. * Determining who should decide is impor-tant, because new drugs for dementia cannot bedeveloped without using appropriate patients. Itmay prove necessary to establish clear guidelinesby legislation or executive action.

Current guidelines focus on the role of the familyor courts in substituting judgment for the patientin question (46). In most cases, present policiesare not controversial. However, for those patientswithout families and those who come from famil-ies whose best interests may not coincide withthose of the patient, there are no formal mecha-nisms for making decisions. Many controversieshave arisen from disagreement among familymembers, courts, hospitals, and health care pro-

*Direct benefit may be unlikely either because a treatment hasnm’er been tried, and so there is no basis for expecting benefit, orbecause the research is intended to pro~ide information that \*illallo~~’ future benefits but that mill not affect care of the patient be-ing studied.

18 ● /mpacts of Neuroscience—Background Paper

fessionals on a proper course of action. Dramaticexamples of conflict about when to terminate life-sustaining treatment of mentally incompetent pa-tients have received national media coverage.Such publicity highlights the inadequacy of pre-sent methods for dealing with the difficult eth-ical, moral, financial, legal, and social issues sur-rounding mentally incompetent individuals.

Several Federal bodies, including the President’sCommission for the Study of Ethical Problems inMedicine and Biomedical and Behavioral Research,and the National Commission for the Protectionof Human Subjects of Biomedical and BehavioralResearch, have considered the difficult issues in-volved in research and treatment of those whoare demented or psychiatrically disturbed (47).In 1978, recommendations based on commissionactivities were submitted to the Department ofHealth and Human Services regarding the use ofpsychosurgery and the care of those institution-alized as mentally infirm; no regulations havebeen issued yet by the Department.

Forcible administration of psychiatricdrugs. -whether psychopharmaceuticals can, insome instances, be administered to psychiatric pa-tients without their consent is under review bythe courts (48). Advocates of rights for psychiatricpatients object to institutional judgments abouttreatment that override the autonomous decision-making power of individuals, while others assertthat such psychiatrically disturbed individuals areincapable of rational autonomous choice. Resolu-tion of this problem will require substantial ef-fort by those in bioethics and the law and mayrequire new legislation.

Insanity defense against criminal pros-ecution.—The insanity defense against criminalprosecution has long been a subject of medicaland legal disagreement (49). The validity of thelegal concept of insanity is receiving renewedscrutiny, and the mechanism for verifying men-tal deviation is also being debated. Those in thepsychiatric and legal professions are attemptingto resolve the issue by developing guidelines forboth psychiatric diagnosis and legal use of psychi-atric opinion.

The power of the concept of abnormal-ity.—Special mention should be made of the per-

vasive effects of the concepts of normal andabnormal as applied to mental, cognitive, andemotional states. The power of the label “abnor-mal” is substantial in public policy concerningmental retardation, psychiatric illness, and neuro-logical handicaps. It is important to acknowledgethe power of labeling patients so that adequatecare is taken to ascertain both the validity of thelabel for a particular patient and the integrity ofthe label itself (50). The diagnosis of major psy-chiatric illness is associated with a multitude ofmedical, institutional, and social stigmata. Neuro-science can assure that differences between nor-mal and abnormal have scientific merit; neuro-scientist and others may ensure that knowledgeis applied responsibly and equitably.

Animal welfare.—The use of animals forpsychological and medical research and in testingof drugs and cosmetics is currently a focus of con-troversy. The neuroscience are involved becauseanimals are used in many experiments on pain,recovery of neural function, and new surgicaltechniques. Many topics in neuroscience must bestudied in higher animals, including primates,because of the need to extrapolate findings to thehighly complex nervous system of humans. Howto balance the need for medical and scientificprogress against the moral imperative to avoidanimal suffering is a problem subject to acrimo-nious public debate. Legislation on this topicalready exists, and the need for additional regu-lation is being considered by several States andthe Federal Government.

Other areas of potential moral disagreement.–Findings regarding the biochemistry ofcrime and violence may lead to ethical debateregarding appropriate public policy. Revelationsabout the genetics of mental disease may alsoengender moral controversy. Knowledge ap-plicable to education, sex differences, substanceabuse, nutrition programs, worker monitoring fortoxic exposure or personal drug use, and manyother social problems also may lead to difficultethical and legal dilemmas.

Recent congressional initiatives have respondedto the disbanding of the President’s bioethics com-mission and to delays by executive agencies in im-plementing its recommendations. Congressional

Conclusion ● 1 9

activity has ranged from proposed authorization sion (which disbanded in early 1983). There alsoof a new commission specifically focused on hu- has been discussion about creating a new Federalman applications of molecular genetics (which body charged with investigation of ethicalmight largely exclude concerns related to neuro- concerns.science) to extension of the President’s commis-

Conclusion

Progress in neuroscience research during thelast few decades has led to new understandingof behavior, the functioning of the nervous sys-tem, how chemicals affect the mind, and mech-anisms involved in neurological and psychiatricdisorders. Many of the most important promisesof neuroscience research have yet to be fulfilled;there is not yet sufficient knowledge to preventor treat effectively many highly prevalent anddisabling neurological and psychiatric diseases.Most of the risks and benefits related to social ap-plications of neuroscience remain possibilitiesrather than facts. The diverse social ramificationsof neuroscience applications can only be anti-cipated, not confidently projected. Neuroscienceis an area that bears watching by scientists, healthcare professionals, industrialists, and policy mak-ers. Now may be a propitious time to search forways to translate neuroscience into application,and to anticipate the need for public discussion.

A number of neuroscience-related issues arelikely to emerge. In some areas, there already ap-pears to be sufficient scientific basis for congres-sional investigation. Some of these, such as theapplication of knowledge about biological clocksto work situations involving public safety, alreadyhave received some congressional attention.other issues, such as sex-differences research,have been identified but lack consensus regardingtheir importance. Still other areas of application,such as drug abuse, enhancement of productivi-

ty, development of new industries, crime preven-tion, and improvement of education show greatpromise in the long term, but the base of knowl-edge deriving from neuroscience research is nowtoo scant to support Federal policy initiatives.

Some areas related to neuroscience appear todeserve congressional attention. These are char-acterized by their magnitude, extensive Federalinvolvement, and an adequate science base to sup-port meaningful investigation. Such topics in-clude:

●

●

●

problems arising from environmental, thera-peutic, and occupational exposure to neuro-toxic agents, identifying numbers of peopleaffected, scientific progress in detection,methods of prevention, and regulatory issues;support for basic research and personneltraining in neuroscience, highlighting rapidityof progress, numbers of people who mightbenefit, and social and industrial applications;andpublic and governmental mechanisms fordealing with difficult ethical and legal ques-tions related to neuroscience, including howto determine mental competence, how tomake decisions for the mentally incompetent,how to control legitimate uses of drugs af-fecting the mind, and how to establish legalcriteria for determining criminal responsibility.

Appendixes

Appendix A

Federal Support forNeuroscience Research*

Funding levels

There has been rapid growth in the field of neuro-science in the United States in the past 10 years.Membership in the Society for Neuroscience hasgrown from 250 members at its inception in 1971 to8,000 in 1983.** Graduate and postgraduate programsin neuroscience have expanded by an estimated 200-300 percent during the same period (l). The most re-cent data suggest a leveling of the growth rate (51).

Neuroscience research is funded by a variety of ex-ecutive agencies. * * * In each agency, neurosciencefunding priorities are related to the mission of theagency, and funds are distributed accordingly for re-search projects. The National Institutes of Health (NIH)receive the majority of the funds for neuroscienceresearch. The National Institute of Neurological andCommunicative Disorders and Stroke (NINCDS), oneof the NIH research institutes, receives over half ofall Federal neuroscience research dollars. Althoughthere are no authoritative assessments of Federalresearch support for neuroscience, preliminary esti-mates of fiscal year 1983 funding levels at each of thegranting agencies, as requested from the budget of-fice of each agency, appear in table A-1.

The fiscal year 1983 funding level for neuroscience,including behavioral research, is estimated at $503.56million. The NINCDS appropriations history providessome indication of Federal funding trends. t

NINCDS Appropriations Levels

Actual appropriationFiscal ~fear (in millions)1975 . . . . . . . . . . . . . $142.01 9 7 6 144.71 9 7 7 155,31978 . . . 178.41979 ., . . . 212.51 9 8 0 242.51981 . . . . . . . . . . . . . . . . . 252.61982 . . . . . . . . . 277.71983 . . . . . . . . . . . . . . . . . . 295.7

SOIIRCE, Natmnal Institutes of Health F’wal }’ear 1984 Draft Justlftcal]on of ,4pproprlatwn F.stlmates for Commltlf’e on Appropriations

● This appendix was written primarily by Miriam Davis, EnvironmentalSciences Fellow at the Congressional Research Service

● ● The rate of growth is somewhat overestimated by these figures, becauseIt took several years for awareness about the societ.v to spread, and becausemore 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 per-cent between fiscal years 1975 and 1983, but this rep-resents a real increase of only 14 percent in constant1975 dollars (52). Further, appropriations have fallenshort of earlier expectations: in 1979, when the budgetneeds of NINCDS were projected into the 1980’s, theywere targeted at $450 million in fiscal year 1983 (53),a value considerably greater than the actual appropria-tion of $295 million.

The Alcohol, Drug Abuse, and Mental Health Admin-istration (ADAMHA) is the other major agency respon-sible for support of neuroscience. Three institutes sup-port research and other activities related to mentalhealth, drug abuse, and alcoholism and alcohol abuse.More than 75 percent of ADAMHA neuroscience fund-ing is channeled through the National Institute of Men-tal Health (NIMH). NIMH appropriations between 1975and 1983 increased by 64 percent overall, and fund-ing for basic and clinical neuroscience increased by83 percent. In constant dollars, however, there wasa 7-percent decrease in overall NIMH funding. Fund-ing for neuroscience research increased slightly, tak-ing up an increased fraction of the total NIMH budget.

Competition for funds is keen among research scien-tists. In fiscal year 1982, 524 of the 1,483 approvedgrant applications to NINCDS were actually funded.An additional 298 grant applications were disap-proved, so that 29.4 percent of all grants, or 35.3 per-cent of approved grants, were funded (54). Current-ly, the Neuroscience Program at NSF funds 20 percentof grant applications, whereas 10 years ago, 40 per-cent of similar applications were funded; further, theaverage dollar amount for grants awarded by NSF inneuroscience has dropped steadily over the past 5years. In 1982, NIMH funded 25 percent of 1,443 totalresearch applications in basic and clinical neuro-science. A comparable decline has been observed atmost of the other NIH institutes.

Coordination

To ensure that research investigators applying forextramural funds do not receive grants from differentagencies for the same research project, investigatorsare required to list existing and pending sources offunds on all grant applications. Computer links be-tween NSF and NIH assure that program officers ateach 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 . . . . . . . . . . . . . . . . . . . . . . . . . . . . $189.4NEI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47.2NIB . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.6NIGHS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .NiEHS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.3

$36.36.12.62.80.78

Neuroiogicai disorders and strokeVision and eye disorders: basic and clinical researchDementia and basic neuroscienceBasic neuroscienceBehavioral and neurological toxicology

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

ADAMHA:NIMH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . $ 16.5

47.6NIDA. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.0NIAAA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.0

$48.58

$22.021.4

.—

Basic neuroscienceCiinical neuroscienceNeuroscienceBiological basis of alcoholism

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

DOD:Army Medical R&D Command . . . . . . . . . $ 6.5Walter Reed Institute . . . . . . . . . . . . . . . . —institute of Chemical Defense . . . . . . . . . 7.2Aviation Research Lab(Ft. Racker). . . . . —AFOSR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.7ONR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.4

U.S. Army Research Office . . . . . . . . . . . . 1.1Totai . . . . . . . . . . . . . . . . . . . . . . . . . . . $20.7

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

FDA:NCTR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.06

CDC:NIOSH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.315

NASA: 1.OV A : . . . : : ; ; ; : ; ; ; ; ; ; ; ; ; : ; ; ; ; ; ; ; ; ; ; : : : 21.4

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

$43.4

$ 2 <—

0.42.5—

1.0$ 13.1

—

0.71

0.5021.0—

1.79

Chemical defenseBasic neuroscienceChemical defenseVision researchNeurophysioiogy; vision research; chemical defenseChemical defense; Iearning and memory; neuro-

physioiogy; behavior

Basic neuroscience and

Behavioral toxicology

NeurotoxicologyVestibuiar physiology

behavior

Aging; neurology and neurobiology;drug dependence;behavioral science; spinal cord disorders

Neurotoxicolocw-.Total . . . . . . . . . . . . . . . . . . . . . . . . . . . . . $394.48 $109.06

$503.56KEY: 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 ResearchNINCDS—National Institute of Neurological and Communicative ONR—Office of Naval Research

Disorders and Stroke NSF—National Science FoundationNEI —National Eye Institute NASA—National Aeronautics and Space AdministrationNIA—National institute on Aging VA—Veterans AdministrationNIGMS—National institute of General Medical Science EPA—Environmental Protection AgencyNIEHS—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 HealthNIMH—National institute of Mental Health FDA—Food and Drug AdministrationNIDA—National Institute on Drug Abuse NCTR—National Center for Toxicological ResearchNIAAA—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 Environmentalin 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 Institutegroup consists of representatives from many of the for Occupational Safety and Health (NIOSH), is coor-granting agencies that sponsor neuroscience research. dinated under the National Toxicology Program, whichThe meetings are voluntary and the group is not sep- was created in 1978 to coordinate and provide infor-arately 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 re-search are funded by annual appropriations by Con-gress. Selected institutes and programs at NIH andADAMHA are subject to periodic reauthorization aswell.

In recent years, some members of Congress haveexpressed concern over problems with the annualfunding cycle and about establishing the budget stabili-ty needed for long-term research and development(R&D). Discussions also have focused on the difficul-ty of assessing complex R&D programs annually. TheGeneral Accounting Office (GAO) has suggested that“instituting a multiyear R&D authorization processwould be an important first step in improving R&Dplanning, budgeting, and oversight” (55). Others haveexpressed concern that a loss of oversight and ac-countability could result.

Policy questions regarding Federalsupport for neuroscience

Questions policymakers may face with respect toFederal support for neuroscience research include thefollowing:

1. Is the level of funding adequate to support growthin the neuroscience field? Are current levels ofsupport for research matched by support fortraining those to do the research?

2. What is the impact of a decrease in the percent-age of grants that are funded? How many labora-tories are closed due to lack of funds? What is theoptimum number of neuroscience laboratories?What is the optimum approval and funding ratefor research grants in neuroscience?

3. IS the degree of coordination among Federal agen-cies supporting neuroscience adequate to assurea productive and efficient use of funds? Are pres-ent mechanisms for coordination working? Whatare the advantages and disadvantages of fundingthrough multiple Federal agencies?

4. Does the authorization/appropriation cycle forR&D funds hamper research productivity? Is ittoo cumbersome for Congress?

5. What is the level of support for basic neuroscienceresearch by private industry? Is this growing ordeclining as a fraction of Federal support? Isprivate industry supporting certain sectors morethan others (e.g., training programs, or researchrelated to pharmacological applications)?

Appendix B

Federal Regulation of and Researchon Neurotoxic Exposure

Legislation on toxic agents of many kinds providesthe framework for Federal regulation of many in-dustrial and environmental agents. Those activitiesrelevant to regulation and research on substances tox-ic to the nervous system are reviewed in this appen-dix, Agents toxic to other organs and organ systemsare regulated in a similar manner in many cases, butregulation of agents toxic to other organs is not sum-marized here.

Federal regulation of toxic substances,including neurotoxins

The Environmental Protection Agency [EPA) isresponsible for enforcement of several laws that reg-ulate toxic substances. The Toxic Substances ControlAct (TSCA), the Clean Water Act, the Clean Air Act,the Resource Recovery and Conservation Act (RRCA)amendment to the Solid Waste Act, and the FederalInsecticide, Fungicide, and Rodenticide Act (FIFRA),with its sister legislation, the Federal EnvironmentalPesticide Control Act (FEPCA), all provide authorityto regulate exposure to toxic substances. The Food andDrug Administration (FDA) regulates drugs, food, andcosmetics under the Food, Drug, and Cosmetic Act;and the Occupational Safety and Health Administra-tion (OSHA) of the Department of Labor administersthe Occupational Safety and Health Act. The majorlaws, agencies, and regulated entities are summarizedin table B-1.

The FDA, OSHA, and EPA have enabling legislationto include setting standards for neurotoxicity in reg-ulation of drugs and cosmetics, occupational expo-sures, and environmental exposures, respectively.Some of OSHA’S regulatory standards have been basedpartially on neurotoxic effects, and neurological sideeffects of drugs are monitored by FDA. However, noneof these agencies has published standards for testingof neurotoxic effects. One reason for the absence ofguidelines is the unsettled state of the science ofmeasuring neurotoxicity. No consensus on standardmethods for determining guidelines regarding neuro-toxic exposure has been established, although therehas been much recent progress. To explore the possi-bilities of standardizing neurotoxicity tests, the FDAhas undertaken a long-term project that is examiningbatteries of neurotoxic tests with the goal of estab-lishing a reliable, cheap, and effective means of testingfor neurotoxic effects.

Pesticide regulation

One aspect of Federal involvement in regulation ofneurotoxic chemicals that deserves special mention isthe registration of pesticides. Pesticides are regulatedby the EPA Office of Pesticide Programs. Proposedpesticides and pesticide ingredients are subject to EPAapproval. Such approval requires testing for toxicity.However, approval for some uses can be obtained byapplication for emergency exemptions or provisionsfor “special local needs.”

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

Agency Law ApplicationEnvironmental Protection Agency Toxic Substance Control Act Chemical substances

Federal Insecticide, Fungicide and Pesticides and other antibioticRodenticide Act agents

Solid Waste Act Solid wastes (including groundwater contamination)

Clean Air Act Airborne pollutants (including leadand gases)

Clean Water Act Water pollutantsOccupational Safety and Health Occupational Safety and Health Act Occupational exposures

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

cosmeticsSOURCE: Office of Technology Assessment.

26

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

Congressional hearings on pesticide regulation andrelated topics were held by the Subcommittee on De-partment Operations Research and Foreign Agricul-ture of the House Committee on Agriculture on Feb-ruary 22-23, 1983. Documents submitted as testimonyidentified concerns regarding operation of the Officeof Pesticide Programs at EPA. Concern was expressedabout the adequacy of EPA resources to meet pro-jected needs, methods of approval that avoid formalregistration, and the scientific basis for approval ofpesticides at EPA. EPA has since issued a more than400 page set of guidelines for pesticide testing.

Federal research on toxicology,including neurotoxicology

Several Federal agencies are involved in research onneurotoxicity. All those mentioned in this paragraphand in figure B-1 are parts of the Public Health Serv-ice of the Department of Health and Human Services.The National Institute of Environmental Health Sci-ences (NIEHS) and the National Institute of Neurologi-

cal and Communicative Disorders and Stroke (NINCDS),both institutes of the National Institutes of Health, con-duct studies on neurotoxicity. The National Instituteof Mental Health has a laboratory devoted to researchon Developmental and Behavioral Neurotoxicity. TheFDA has a Nationa] Center for Toxicological Research(NCTR), which is charged with developing and validat-ing test procedures. The Centers for Disease Controlinclude the National Institute for Occupational Safetyand Health (NIOSH), which does research and providesexposure guideline recommendations to OSHA. TheNational Toxicology Program, headed by NIEHS, coor-dinates the activities of NIEHS, NCTR, and NIOSH intoxicology. The institutional arrangement of some ofthe major agencies doing research on neurotoxicologyis shown in figure B-1.

Research on pesticides is carried out in industriallaboratories, by university scientists, and at severalland-grant universities supported in part by the U.S.Department of Agriculture. Information based on re-search into efficacy, specificity, and health effects, in-cluding neurotoxicity, is submitted to EPA as part ofthe pesticide registration process.

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

I 1 1I

iIL — - --- —— --- -- ~ . . ~

Appendix C

Statement by David L. BazelonSenior Circuit Judge

U.S. Court of Appeals for the District of Columbia Circuitat 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. Icould not begin to describe the difference betweena neuron and a beta-blocker. I called Dr. Cook-Deegan,intending to decline, When he later came to my cham-bers, I told him that, given my lack of technical ex-pertise, I could never presume to advise a group ofdistinguished physicians and scientists as to the valueof a particular line of scientific research. My sole in-volvement 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 greatmany regulatory agencies grappling with the problemsposed by scientific and technological development.These decisions involve, just to name a few, the criticalsocioscientific issues of acid rain, cotton dust and ben-zene levels in the workplace, exposure to asbestos andradiation, and the disposal of nuclear and toxic waste.I tried to impress upon Dr. Cook-Deegan that I wasqualified to address nothing more than the role of thecourts in monitoring public policymaking in the scien-tific arena. Much to my surprise, he assured me thatthis was exactly the focus he hoped I would bring tothe panel.

I hardly need to tell a group such as this that witheach new advance in neuroscience come previouslyunforeseen dangers. Neuroscience is not unlike anyother field of scientific endeavor in this regard.Ironically, scientific progress not only creates newrisks but also uncovers previously unknown risks. Asour understanding of the world grows exponentially,we are constantly learning that old activities, oncethought safe, in fact pose substantial hazards.

For example, new psychopharmaceutical drugs, ca-pable of controlling antisocial behavior among largenumbers of psychiatric patients, have been developed.Many of the drugs have known side effects and stillothers may be discovered in the future.

Similarly, advances in genetics offer the hope ofeliminating many genetically transmitted diseases.However, with this hope comes the threat of introduc-ing previously unknown and presently untreatableviruses and bacteria.

Nuclear power can provide a virtually inexhausti-ble supply of cheap energy. It may also reduce nation-wide cancer caused by burning fossil fuels. But, it mayincrease cancer risks for those living near reactors,and our inability to dispose of radioactive waste safe-ly may place future generations in jeopardy.

The question then is not whether we will have riskat all, but rather how much risk, and from whatsource. Perhaps even more important, the questionis who shall decide.

In a democracy, such choices are reserved for thepublic. Thus it falls to the Congress, as our repre-sentative body, to guide the direction that scientificdevelopment will take in our society. But most mem-bers of Congress are no more scientists than am I. Con-gress often lacks the expertise to penetrate the deepscientific mysteries at the core of important issues ofpublic concern. Consequently, it has chosen to addressthe problems and opportunities of this new agethrough regulatory agencies. It gives those agenciesthe resources and authority to employ and developexpertise and to make difficult policy choices in thescientific arena.

The legislature has not, however, granted theseagencies wholly unbridled discretion. First, an agen-cy must often act within the narrow parameters ofa specific statutory mandate. For example, the DelaneyClause, an amendment to the Food and Drug Act, es-tablishes an irrebuttable presumption against the safe-ty of any food additive found to induce cancer inanimals. Second, agencies must comply with statutori-ly created procedural requirements. For instance, eachagency must provide ample notice of all proposedrules and regulations. It must also solicit and fully con-sider the input of both outside experts and the publicat large. Finally, Congress has attempted to ensureagency accountability by establishing a mechanism forjudicial review.

The exact nature of judicial review of agency actionis all too often misunderstood. This was brought hometo me in a conversation with Alvin Weinberg, a pio-neer of the nuclear age. “Most people,” he said, “havethe idea that the court weighs the arguments and thetechnical evidence and decides which side has comenearest 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 shoutingit: that idea is wrong. It is wrong, first, because courtslack the technical competence to resolve scientific con-troversies. It is wrong, second, because courts lack thepopular mandate to make the critical value choicesthat this kind of decisionmaking requires.

In reviewing regulatory actions, the court does notweigh again the agency’s evidence and reasoning. In-stead the court monitors only the process of decision-making, leaving factual conclusions and policy choicesto the agency. The role of the judiciary is to stand out-side the scientific and political debate and to ensurethat all of the issues are thoroughly aired.

First, courts must ensure that an agency’s interpreta-tion and application of its statutory mandate are rea-sonable and that the agency is behaving in a mannerthat is neither arbitrary nor capricious. Second, in therealm of science, courts can insist that the data bedescribed, hypotheses articulated, and above all, inthose areas where we lack knowledge, that ignorancebe confessed. In the sphere of values, courts can askthat decisionmakers explain why a particular tradeoffis acceptable. Perhaps most important, in the netherrealm, at the interface of fact and value, courts canhelp assure that the value component of decisions isexplicitly acknowledged, not hidden in quasi-scientificjargon.

I have long argued that even society’s most technicaldecisions must be ventilated in a public forum withpublic input and participation. In fact, I have beenpushing this theme for so long that I worry that I maybe a little like my friend the amateur cellist. One even-ing his long-suffering wife dared ask why cellists inthe orchestra “move their fingers up and down thenecks of their instruments, while you always keepyour fingers fixed in one place.” ‘(Ah yes,” my friendreplied. “I’m glad you noticed that. They are lookingfor the right note. I have found it!”

Full disclosure of agency decisionmaking is in every-one’s best interest, including that of the decision-makers themselves. If the decisionmaking process isopen and candid, it will inspire more confidence inthose who are affected, further reducing the risk thatimportant information will be overlooked or ignored.Finally, openness will promote peer review of both fac-tual determinations and value judgments.

Agency resistance to the requirements of full dis-closure may come from either of two sources. First,in reaction to the public’s often emotional responseto risk, agency experts are often tempted to disguisecontroversial value decisions in the cloak of scientificobjectivity, obscuring those decisions from political ac-countability. I have heard scientists held in the highestregard say that they would consider withholding infor-

mation concerning risks which, in the scientist’s view,are insignificant, but which might alarm the public iftaken out of context. This problem is not mere specula-tion. I am reminded of my involvement several yearsago in a hearing on the development of guidelines toregulate recombinant DNA technology in the UnitedStates. Added to the heated controversy over the sub-stance of the guidelines themselves was an equallyheated debate within the National Institutes of Healthconcerning the degree to which the risks and reason-ing underlying the guidelines should be disclosed tothe general public. Speaking to the Royal Society Con-ference on Recombinant DNA in England, my goodfriend Donald Fredrickson, the distinguished Direc-tor of the National Institutes of Health, said:

The hearing demonstrated the difficulties of holdinga town meeting on molecular biology and exposed thefull range of opinions on the risks of the new tech-nology. It was apparent that our decisions would haveto run the gamut of adversarial reactions and, in theend, might well be tested in the courts. After the hear-ing, the voice of Judge Bazelon lingered longest in mymind: “the healthiest thing that can happen is to letit all hang out, warts and all, because if the publicdoesn’t accept it, it just isn’t worth a good damn.”

It is certainly true that the public’s reaction to riskis not always proportionate to the seriousness andprobability of the threatened harm. Nevertheless, ex-perts must resist the temptation to belittle these con-cerns, however irrational they may seem. Regulatoryagencies must not turn their backs on the politicalprocess to which we commit societal decisions. Scien-tists, like all citizens, must play an active role in thediscussion of competing values. Their special exper-tise will inevitably and rightly give them a persuasivevoice when issues are discussed in our assemblies andon our streets, But ultimately the choices must bemade in a politically responsible fashion. To those whofeel the public is incapable of comprehending theissues and, so, unable to make informed value choices,I respond with the words of Thomas Jefferson:

I know no safe depository of the ultimate powersof the society but the people themselves; and if wethink them not enlightened enough to exercise theircontrol with a wholesome discretion, the remedy isnot to take it from them, but to inform their discretion.

At times, however, agency resistance to publicdisclosure may derive not so much from a desire tokeep the public “in the dark” as from the uncertaintythat characterizes much of the process of risk assess-ment itself. To say the least, science is often incapableof stating risks with certainty. For some activities, themagnitude of potential harm and the probability ofits occurrence may be essentially unknown. For ex-ample, another of my good friends, Dr. Theodore

30 ● lmpacts of Neuroscience—Background Paper

Puck, a noted medical researcher, tells me that tox-icologists have no way of establishing with certaintythe permissible, as opposed to the lethal dose of a newdrug. Engineering predictions may rest on untestableassumptions, such as the behavior of materials afterthousands of years. Risk estimates may depend on fu-ture contingencies of human behavior or other highlycomplex and unpredictable variables. Historical experi-ence may even be totally lacking, as when the NationalAeronautics and Space Administration had to fix aquarantine period for returning lunar explorers. Thebest risk estimates are subject to an unknown degreeof residual uncertainty and may thus overstate orunderstate the dangers involved. Indeed, many timesan agency must act in circumstances that make a crapgame look as certain as death and taxes.

Those who must make practical decisions may betempted to disregard or even suppress any lack of con-fidence they may have. Ignorance is messy in decision-making. It cannot always be stated as an objectivequantity or factored into a decision as if it were a riskof known probability. Decisionmakers must assimilatedata from many disciplines, And yet uncertainty de-tracts from simplicity of presentation, ease of under-standing, and uniformity of application. To focus onuncertainties is to invite paralysis; to disclose them isto risk public misunderstanding, loss of confidence,and opposition. Even though some uncertainty is inev-itable, pointing it out will always create pressures for“just one more study.” But the decisionmaker knowstoo well that delay is also a choice, with risks of itsown.

Combined with the uncertainty inherent in scien-tific risk assessment itself is the lack of specificguidance provided to administrative decsisionmakers.Often Congress, faced with its own inability to foreseethe course that technological research and develop-ment may take, is forced to speak in broad generalitieswhen providing statutory direction to regulatory deci-sionmakers. At times, legislators embroiled in conflictsof political ideology may intentionally employ vagueand ambiguous language so that each faction mayclaim its own “victory. ” I point, for example, to the“cost-benefit” analysis required of agencies by numer-ous statutory schemes. Such analysis often calls forcontroversial quantitative valuations of human life andhealth. It frequently presumes to compare incompar-able) such as the harm of radiation exposure versusthe benefits of nuclear power. And, perhaps mosttroubling of all, cost-benefit analysis breaks down com-pletely at one of the most crucial points in the deci-sionmaking process: How can one quantify the impactof utterly unknown risks?

This quandary was vividly illustrated in the recentVermont Yankee cases. Confronted with the unen-viable task of quantifying the hazards posed by theconstruction and operation of a nuclear reactor, theagency assigned a value of zero to the risk of exposureto radioactive waste products. Apparently, this assess-ment was based on the assumption that some safemethod of permanent waste disposal, not presentlyavailable, would be developed at some time in the fu-ture. This supposition may well prove to be correct.However, all efforts to date to develop such technologyhave failed miserably, and if the hypothesis that futureefforts will succeed proves false, the damage could beinestimable. Yet nowhere in the agency’s environmen-tal impact statement was this assumption, or the foun-dations upon which it was based, explicitly revealed.

If courts reject this sort of administrative sleight-of-hand, they are not attempting to obstruct the path ofscientific progress. Rather, they are merely attempt-ing to carry out Congress’s mandate that decisionmak-ing be honest, open, thorough, rational, and fair. Aswe confront the perils and promises of this scientificage, both democracy and human dignity demand thatwe be told of the risks, uncertainties, and value choicesthat are made in our names.

In primitive societies, when the need to choose be-tween cherished but conflicting values threatened todisrupt the community, the simplest path was deci-sion by a shaman or wizard, who claimed miraculousinsight. In our time, some would invoke the specialwizardry of those who wear a scientist’s lab coat, ajudge’s black robes, or a risk assessor’s business suitrather than religious garb. But the genius of our sys-tem is its checks on centers of accumulated power.Whatever its price, nothing but full disclosure canguarantee that the regulators or the new guild of riskassessors will not become the new elite.

If the Supreme Court’s most recent opinion in theVermont Yankee case portends a new trend of judicialindulgence toward agency nondisclosure, Congressmay need to reaffirm its intention that the adminis-trative decisionmaking process be subject to a search-ing and meaningful judicial review. In any event, whenundertaking an assessment of technological develop-ment in neuroscience-or in any other area of scien-tific endeavor—the Office of Technology Assessmentmust take care to see that the risks are treated open-ly 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. Someparts of the draft are reprinted in the working papers for Impacts ofNeuroscience.

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

siderable attention has been devoted to the benefitspromised by neuroscientific advances, while treatmentof the attendant risks has been confined primarily toa scant five pages in the introduction and scatteredreferences elsewhere in the manuscript. Finally, Iwould like to add my own endorsement to the propos-al that OTA undertake an independent assessment ofthe adequacy and openness of decisionmaking proc-esses in the scientific arena.

Some may argue that society might balk if it knewjust how blindly we march into the future—and at

what cost. But false reassurances, unjustified confi-dence, and hidden agendas will only create cynicismand destroy credibility. Our people have always beenprepared to accept risks and to pursue the larger goodof society. Progress can hardly be achieved in anyother way. Choices will be made despite uncertaintyand despite the social disruptions and dislocations. Tochoose rationally, however, society must be informedabout 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 ChairmanHogan &. Hartson

W. Kent Anger, Ph. D.Chief, Neurobehavioral Research SectionApplied Psychology and Ergonomics BranchNational Institute for Occupational Safety

and Health

Raymond Bartus, Ph. D.American Cyanamid Co.Medical Research DivisionLederle Laboratories

The Honorable David L. BazelonSenior Circuit JudgeU.S. Court of AppealsDistrict of Columbia Circuit

Floyd E. Bloom, M. D.Director, Davis Center of Behavioral NeurobiologySalk Institute

Greg R. Christoph, Ph. D.Central Research and Development DepartmentE. I. du Pent de Nemours & Co., Inc.

David Cohen, Ph. D.Department of Neurobiology and BehaviorState University of New York, Stony Brook

Joe Dan Coulter, Ph. D.University of Texas Medical BranchMarine Biomedical Institute

Miriam Davis, Ph. D.Science Policy Research DivisionCongressional Research ServiceLibrary of Congress

John Dowling, Ph. D.Department of BiologyHarvard University

John Hildebrand, Ph. D.Department of Biological SciencesColumbia University

Jack Houck, Ph. D.President, Endorphin, Inc.

Zaven Khachaturian, Ph. D.National Institute on AgingNational Institutes of Health

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

32

Dennis Landis, M. D.Department of NeurologyMassachusetts General Hospital

Candace Pert, Ph. D.Adult Psychiatry BranchNational Institute of Mental Health

Dominick P. Purpura, M. D.Dean, Stanford UniversitySchool of Medicine

Mick Riddiough, Ph. D.Syntex Corp.

Joshua Sanes, Ph. D.Department of Physiology and BiophysicsWashington University Medical Center

Other participants

Constance Atwell, Ph. D.Chief, Amblyopia, Strabismus, and Visual

Processing BranchNational Eye Institute

Nancy BeangSociety for Neuroscience

Katherine Bick, Ph. D.Deputy DirectorNational Institute of Neurological and

Communicative Disorders and Stroke

Harold E. Booker, M. D.Director, Neurological ServicesVeterans Administration Central Office

H. Westley Clark, M. D., J. D., M. P. H.Minority CounselSenate Committee on Labor and Human Resources

Sheila P. DuffyHouse Select Committee on Aging

June EwingNational Academy of Sciences

Carol Grundfest, M. A.Senior Research AssociateScience and Technology DivisionPharmaceutical Manufacturers Association

Genevieve Haddad, Ph. D.Program ManagerAir Force Office of Scientific Research/NL

App. D—Workshop Participants ● 3 3

Cynthia KapphahnEnvironmental Defense Fund

Jorge LambrinosStaff DirectorHouse Select Committee on Aging

Jack Lubowsky, Ph. D.Congressional Science and Engineering FellowSen. John Glenn

James McCullough, Ph. D.Chief, Science Policy Research DivisionCongressional Research ServiceLibrary of Congress

Robert Newburgh, Ph. D.Leader, Biological and Biomedical SciencesOffice of Naval Research

Norine E. Noonan, Ph. D.Office of Management and Budget

Harold Pincus, M. D.Special Assistant to the DirectorNational Institute of Mental Health

Zeda Rosenberg, Ph. D.Congressional Science and Engineering FellowRep. David R. Obey

Michael SimpsonScience Policy Research DivisionCongressional Research ServiceLibrary of Congress

Philip G. Sokolove, Ph. D.Congressional Science and Engineering FellowRep. Albert Gore, Jr.

Fred Solomon, M. D.Institute of MedicineDivision of Mental Health and Behavioral Medicine

Emmanuel M. Stadlan, M. D.Acting Director, Demyelinating, Atrophic, and

Dementing Disorders ProgramNational Institute of Neurological and

Communicative Disorders and Stroke

Harlee S. Strauss, Ph. D.American Chemical Society

Eugene Streicher, Ph. D.Director, Fundamental Neuroscience ProgramNational Institute of Neurological and

Communicative Disorders and Stroke

Lawrence Tremonti, M. D.Legislative AssistantRobert Wood Johnson FellowSen. William Bradley

Janett Trubach, Ph. D.National Institute of Neurological and

Communicative Disorders and Stroke

Randall Wedin, Ph. D.Congressional Science and Engineering FellowRep. George E. Brown, Jr.

Nancy Wexler, Ph. D.Neurology Disorders ProgramNational Institute of Neurological and

Communicative Disorders and Stroke

William A. Yost, Ph. D.Program Director, Sensory Physiology

and PerceptionNational Science Foundation

Bambi Batts Young, Ph. D.Director, Environment and Behavior ProjectCenter for Science in the Public Interest

Appendix E

References

1. Committee on Science, Engineering, and PublicPolicy, “Report of the Research Briefing Panelon Neuroscience” (Washington, D.C.: NationalAcademy Press, 1983).

2. This section was prepared by OTA based on mate-rial obtained in large part through the summercourse in Neurobiology of the Marine BiologyLaboratory at Woods Hole, Mass. The course wassponsored by the National Institutes of Health andthe Grass Foundation. Other sources includecourse notes prepared for Harvard Medical Schoolby David D. Potter and Edwin J. Furshpan, andseveral textbooks. The books used most extensivelywere: E. R. Kandel and J. H. Schwartz, Principlesof Neural Science (New York: Elsevier, 1981); andS, W. Kuffler and J. G. Nicholls, From Neuron toBrain: A Cellular Approach to the Function of theNervous System (Sunderland, Mass.: Sinauer Asso-ciates, 1976).

3, Braun, P., et al., “Overview: Deinstitutionalizationof Psychiatric Patients, a Critical Review of Out-come Studies,” American Journal of Psychiatry138:736-749, 1981; Feldman, S., “Out of the Hospi-tal, Onto the Streets: The Overselling of Benevo-lence)” The Hastings Center Report, June 1983, pp.5-7.

4, Sharfstein, S. S., Deputy Medical Director, Ameri-can Psychiatric Association, personal communica-tion, September 1983.

5. The phrase is taken from Dr. Gerald Klerman,cited in reference 4.

6. Fleckenstein, A., “Specific Pharmacology of Cal-cium in Myocardium, Cardiac Pacemakers, andVascular Smooth Muscle,” Annual Review Phar-macology and Toxicolo# 17:149-166, 1977; Reuter,H., “Calcium Channel Modulation by Neurotrans-mitters, Enzymes, and Drugs,” Nature 301:569-574,1983.

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U.S. Congress, Office of Technology Assessment,OTA-HR-157, February 1982).

10. Grabowski, H. G., and Vernon, J. M., “The Phar-maceutical Industry, ” Government and TechnicalProgress, a Cross-Industry Analysis, R. R. Nelson(cd.) (New York: Pergamon Press, 1982), pp.283-360.

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tional Center for Drugs and Biological, Food andDrug Administration, Department of Health andHuman Services, June 1983.Molner, S., contract on drug development pre-pared for OTA, May 1983.American Psychiatric Association, Diagnostic andStatistical Manual, 3d ed. (Washington, D.C.: Amer-ican Psychiatric Association, 1980).Bartus, R., “Workshop on Impacts of Neurosci-ence)” Office of Technology Assessment, July 27,1983.Personal communication from officials at the Na-tional Institute of Mental Health and National In-stitute on Neurological and Communicative Dis-orders and Stroke, August 1983.Anger, W. K., “Neurobehavioral Testing of Chem-icais: Impact on Recommended S~andards,”Neurobehavioral Toxicology and Teratology, inpress, 1983.

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

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opment and Learning,” Nutrition Today, Septem-ber/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., andO’Donohue, T. L., “Prenatal Interactions BetweenEthanol and the Industrial Solvent 2+thoxyethanolin Rats: Neurochemical Effects in Their Offspring, ”Neurobehaw”oral Toxicology and Teratology 4:395-401, 1982.Voorhees, C. V., “Environmental Assaults on theNervous System and Human Behavior: A NewHealth Challenge,” symposium at the Annual Meet-ing of the American Association for the Advance-ment 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., “SelectedOutbreaks of Neurotoxic Disease,” Experimentaland Clinical Neurotoxicologv, P. S. Spencer andH. 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 Mer-cury,” Archives of Environmental Health 27:249-252, 1973.Johnson, B. L., and Anger, W. K., “Behavioral Tox-icolo~y, ” Environmental and Occupational Medi-cine, W. N. Rom (cd.), 1983, pp. 329-350.Silbergeld, E. K., “Experimental and Environmen-tal Neurotoxins: Correlation of Behavioral andBiochemical Effects,” Behavioral Models and theAnalysis of Drug Action, M. Y. Spiegelstein and A.Levy (eds.), 1982, pp. 297-315; Silbergeld, E. K.,“Current Status of Neurotoxicology, Basic and Ap-plied)” Trends in Neuroscience 5:291-294, 1982.

24. Santos, Y., personal communication from theHouse Select Committee on Aging. Ms. Santos cited:National Institute on Drug Abuse, Series 30, #2: in-halants, National Institute on Drug Abuse Clear-inghouse, Washington, D. C., July 1978; Sharp,C. W., and Brehm, M. L. (eds.), Rew”ew of Inhalants:Euphoria to Dysfunction, Department of Health,

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Education, and Welfare, Publication No. 80-553,Washington, D.C., 1977; Wyse, D. G., “DeliberateInhalation of Hydrocarbons—A Review,” CanadianMedical Association Journal 108:71-74, 1973;another relevant reference is: Commission of In-quiry into the Non-Medical Use of Drugs, FinalReport, Ottawa: Information Canada, 1973, seeespecially app. A-9: “Volatile Substances: Solventsand Gases. ”The Effectiveness and Costs of Alcoholism Treat-ment, Health Technology Case Study 22, part ofthe OTA Assessment of Medical Technology andCosts 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 Alco-hol,” Washington Post, Aug. 26, 1983, p. A13.Nicholi, A. M., ‘(The Nontherapeutic Use of Psycho-active Drugs, A Modern Epidemic)” New EnglandJournal of Medicine 308:925-933, 1983.Terenius, L., “Characteristics of the Receptor forNarcotic Analgesics in Synaptic Plasma MembraneFraction From the Rat Brain)” Acta Pharmacolo#”aToxicologic 33:377-384, 1973; DeWied, D., andJones, J., “Neuropeptides Derived From Pro-opio-cortin, Behavioral, Physiological and Neurochem-ical Effects,” Physio)ogica) Review 62:976-1059,1982; Marx, J. L., “Synthesizing the Opioid Pep-tides, ” Science 220:395-397, 1983; Rossier, J., andChapouthier, G., “Brain Opiates,” Endeavor, NewSeries 6:168-176, 1982.Taste, D. L., et al., “Stanford Research Institute:

31

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Shift Work Practices in the United States,” Depart-ment of Health, Education, and Welfare DocumentNo. 77/148 available through the National Techni-cal Information Service as PB-274-707, March 1977;Moore-Ede, M. C., Czeisler, C. A., and Richardson,G. S., “Circadian Timekeeping in Health andDisease: Part 2, Clinical Implications of CircadianRhythmicity, ” New England Journal of Medicine309:530-536, 1983.Hearings before the Subcommittee on Oversightand Investigations, House Committee on Scienceand 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 DisruptSleep Are Improved by Applying Circadian Prin-ciples, “ Science 217:460-463, 1982.Commercial Biotechnology: An International Anal-ysis (Washington, D. C.: U.S. Congress, Office ofTechnology Assessment, OTA-BA-218, January1984).

34. Pharmaceutical Panel, Committee on Technologyand International Economic and Trade Issues, Of-fice of the Foreign Secretary, National Academyof Engineering, and Commission on Engineeringand Technical Systems, National Research Coun-cil, The Competitive Status of the U.S. Pharma-ceutical Industry (Washington, D .C.: NationalAcademy Press, 1983).

35. Brown, G. L., et al., ‘(Aggression, Suicide, andSerotonin: Relationships to Cerebrospinal FluidAmine Metabolizes, ” American Journal of PSuV-chiatqy 139:741-746, 1982.

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

37. Benbow, C. P., and Stanley, J. D., “Sex Differencesin Mathematical Ability: Fact or Artifact?” Science210:1262-1264, 1980.

38. Gilligan, C., In a Different Voice: PsychologicalTheory and Women’s Development (Cambridge,Mass.: Harvard University Press, 1982).

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

40. Gonzalez, E. R., “Premenstrual Syndrome: An An-cient Woe Deserving of Modern Scrutiny, ” Jour-nal of the American Medical Association 245:1393-1396, 1981.

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

42. “Mathematical Ability: Is Sex A Factor?” letters toScience 212:114-121, 1981.

43. Ross, A. O., “Behavioral Therapy With Children,”

36 . /rnpacts of Neuroscience—Background paper

Handbook of Psychotherapy and BehavioralChange: An Empirical Analysis (2d cd.), S.L. Gar-field and A. E. Bergin (eds.) (New York: Wiley,1978), pp. 599-602.

44. Bazelon, D. L., “Statement Delivered at Workshopon Impacts of Neuroscience,” Office of TechnologyAssessment, July 27, 1983.

45. Bazelon, D. L,, “Governing Technology: Values,Choices, and Scientific Progress, ” Technology inSociety 5:15-25, 1983.

46. Gutheil, T. G., and Appelbaum, P. S., “SubstitutedJudgment: Best Interests in Disguise,” The HastingsCenter Report, June 1983, pp. 8-11.

47. The President’s Commission for the Study of Ethi-cal Problems in Medicine and Biomedical and Be-havioral Research has issued several reports re-lated to topics influenced by neuroscience. Theseare listed, and are available through the Govern-ment Printing Office: Summing Up, DefiningDeath, Making Health Care Decisions (covering in-formed consent), Screening and Counseling forGenetic Conditions, Implementing Human Re-search Regulations, and Protecting Human Sub-jects.

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

49,

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chotic Medication, ” Journal of the AmericanMedical Association 249:2784-2785, 1983.American Psychiatric Association, statement on theinsanity defense, December 1982.Mercer, J. R., Labeling the Mentally Retarded(Berkeley, Calif.: University of California Press,1973).Gomberg, I. L., and Atelsek, F. J., NeurosciencePersonnel and Traitu”ng (Washington, D. C.: Ameri-can Council on Education, 1983).Matthews, W., Director, Budget Office of the Na-tional Institute of Neurological and CommunicativeDisorders and Stroke, National Institutes of Health,personal communication, June 1983.National Research Strategy for Neurological andCommunicative Disorders, National Institutes ofHealth publication No. 79-1910, June 1979.Matthews, W., Director, Budget of the National In-stitute on Neurological and Communicative Dis-orders and Stroke, National Institutes of Health,personal communication, September 1983.General Accounting Office, U.S. Congress, Multi-year Authorizations for Research and Develop-ment, Publication No. PAD-81-61, 1981.

nw