Part 1
EUGENE MICHELS, MA
The problem of biomedical research and human rights is reviewed from the perspectives of current issues, historical events, and other sciences. Govern ment control of research, reactions to and possible consequences of that control, and the concern for consent from members of vulnerable populations are examined. The nature of research is discussed and the origins of opposing ethical views are described in an attempt to clarify the issues within the prob lem.
Under the byline of "News and Comment," the November 1, 1974, issue of Science presented a report titled "GraveRobbing: The Charge against Four from Bos ton City Hospital." At the foot of the page appears the terse, boxed announcement: "Recent advances in biomedical science are raising important problems of ethics and public policy. This is one of a series of occa sional articles planned for News and Com ment on the conflicts involved." More specif ically, the problem is one of human rights in biomedical experimentation. 1 Judging by the recent actions of federal lawmakers- and funding agencies, 3 - 4 the reactions in both the professional 3 and lay ( i press, and the issues involved, I have reason to believe that the re cent advances in biomedical science serve as only the means for drawing our attention to the problem of research and human rights. Now that our attention has been obtained, each of us might find it both easy and right eous to choose a side and advocate what should be done for the good of either biomedical science and research or the rights
Mr. Michels is Associate Professor of Physical Therapy, School of Allied Medical Professions, University of Penn sylvania, Philadelphia, PA 19174. Adapted from a paper presented at the Fifty-First An nual Conference of the American Physical Therapy Associ ation, Anaheim, CA, June 16-20, 1975.
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of human beings. My intention is not to choose a side and advocate what should be done. Instead, I will attempt to do what Albert Jonsen of the Health Policy Program, Univer sity of California, suggested in a letter to the readers of Science in April of this year: to define the issues in terms suitable for public debate, to analyze the moral arguments, and to examine the presuppositions and the logic of debate. 1 Serious moral choices are posed to society by experimental medicine. The choices and their consequences are not simple. We in physical therapy are part of both society and medicine. To give the topic of research and human rights careful thought, we must look at the problem in its current and historical sense, we must see the parallel problems in other sciences which are of interest to us, and we are obliged to consider just what research and human rights are and how they have been viewed historically. In this way, I believe that we will see that the underlying issues are enduring, that they likely will not be decided once for all time, that resolution of the issues may itself yield other problems and issues in the cauldron of human affairs, and that the current concern may have far-reaching con sequences for a profession which, in the im age of medicine, is moving toward becoming both a science and a practice.
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Research and Human Rights
THE PROBLEM IN RECENT FORM
In July 1974, the National Research Act was signed into law. Among its provisions affect ing research and research training, the act placed a moratorium on experimentation with the living human fetus, before or after in duced abortion, and created a National Com mission for the Protection of Human Subjects of Biomedical and Behavioral Research. 2 The commission, which is advisory to the Secre tary of Health, Education, and Welfare, re cently studied the issue of fetal research and submitted its recommendations to the Secre tary who is likely to adopt the recommenda tions as written. 7 The recommendations gen erally are that the ban on fetal research be lifted, that proposed experiments be carefully evaluated for medical and ethical soundness, and that the informed consent of the mother, and in certain cases the father, be required. The commission is to have a life of only two years, but the act provides for metamorphosis into a permanent council. 2 One month after the National Research Act became law, the National Institutes of Health issued two announcements 3 , 4 which, while unrelated both to that act and apparently one to the other, represent the latest regulatory steps taken by a federal agency concerned with the rights and welfare of human subjects who participate in research projects funded by public monies. The earlier of the two an nouncements, addressed to the criteria for the clinical investigative use of therapeutic devices under research contracts with the National Heart and Lung Institute,'* is narrow in scope, detailed in statement, and quite possibly precedent - setting — a possibility which appears not to have excited the aca demic-research community. The later an nouncement, addressed more broadly to the protection of the rights and welfare of human subjects in all research, development, and related activities under grants and contracts with the National Institutes of Health, 4 seems to have elicited a widespread allergic reac tion. Instead of describing these regulations in detail, the more useful approach taken is one of looking generally at the kinds of concerns
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Government Action
for human rights which are embodied in the requirements to be met by researchers who seek federal funding. Risk and risk-benefit ratio. Potential risk is broadly conceived to include physical, psy chological, and social injuries which may arise from the subject's participation in any activity which departs from established and accepted methods necessary to meet his needs or which increases the ordinary risks of daily life. The departure from established and accepted methods, that is, the manipulation without which there is no experiment, may consist of either a method which is not yet established and accepted or the withholding of a method which is established and ac cepted. The potential risk is not limited to the harm which may arise from an experimental procedure or device but includes, as well, the public embarrassment or humiliation which may occur through the variety of forms in which information is recorded and subse quently used by the investigator or other per sons. In brief, the risk to the subject is seen as a risk to his body and to his person. The likelihood and seriousness of potential risks are viewed as human cost factors which are to be outweighed by potential benefits. The idea of a risk-benefit ratio is both prag matically and ethically sound. The wording in both documents, however, poses either a di lemma or a restriction on the kind of research which will be funded. The requirement that a proposed research project offer potential benefits to both the individual subject and society in general poses the entirely practical problems of 1) either demonstrating in what way the normal subject (the nonpatient) may benefit from some biomedical manipulation or restricting the subject population to only patients, 2) devising adequate control condi tions which are as likely as the experimental condition to yield benefits for individual sub jects, 3) purporting to investigate the effect of some biomedical intervention, the benefit of which is already demonstrable, and 4) dis carding entirely so-called basic or nontherapeutic research. Informed consent and special popula tions. The requirement that the subject give his informed consent to participate in the ex periment requires at the minimum that he un derstand the nature of the experiment, the
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the number of nonfunded projects carried out each year, the number of experimental proce dures for which patients are billed, the extent to which actual practices conform to re search protocols, and the frequency with which consent is honestly obtained. 1 0 The second flaw in the argument posed above is the unstated assumption that all searchers for knowledge will accept the ethical restraints and will not use grantsmanship skills to get around the barriers to inexpensive, nonprotesting patient populations. My intent here is not to conjure up images of doctor scientists gone wild in their laboratories and luring un suspecting victims into Frankensteinian ex periments. On the contrary, we must consider the objections which have been raised to the ethical safeguards and to the federal govern ment's role in regulating this matter. The ob jections may or may not be warranted but in either event they suggest a continuing con frontation between opposing views which might affect compliance with the existing regulations and the shape of future regula tions. Reaction to Government Action Before 1974 ended, the academic-research community responded in a largely negative way to two elements of the regulations: 1) the protection of rights of subjects from special, vulnerable populations, and 2) the review process. 5 Complaints that some aspects of the regulations are equivalent to returning to the Dark Ages, or make scientists sound guilty until proved innocent, deserve little se rious consideration. On the other hand, one should not dismiss charges that the regula tions are cumbersome, costly, unnecessary, and either destructive of, or stifling to, medi cal or scientific progress. Many of these im mediate reactions could have been antici pated because the debate over ethics in re search and the role of government in regulat ing research has raged for some time. Many of the earlier arguments are as timely today as when they were first raised and some of these earlier arguments appear to have been more carefully considered than the recent reflexive responses. Morality and necessity. Arguments about researchers voluntarily controlling the ethics
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risks to his body and person, and the poten tial benefits to himself, to society in general, or to both, and that he voluntarily agree to participate under conditions which he under stands and accepts. Using language with which most of us are familiar, informed con sent requires that the subject and the experi menter enter into a contractual agreement which, however, is never binding on the sub ject. Members of special populations such as the mentally deficient and the very old or very young may not be able to understand suffi ciently well to make their own determination of consent. Others, such as the poor and pris oners, may be easily induced to consent be cause of financial or other rewards. By requir ing the rationale for using subjects from these special populations and a description of the consent procedures to be used, the regulations provide at least some assurance that the protection of human rights is equal ized for the not-so-equal members of our so ciety. Research question and design. As is the practice with other granting agencies but perhaps more rigorously so, the National In stitutes of Health demands that the proposed research project be designed to answer im portant questions in a scientifically sound manner and that the project produce maxi mum research information at minimum haz ard to the patient. Another way of stating the matter is to say that human subjects are a precious resource to be used only in sound research which seeks answers to important questions. In this sense, the research ques tion and design do pose ethical implications for the use to which human subjects are put. 8 - 9 The concerns for human rights in research are enforceable to the degree that honesty prevails in actual research settings, as well as throughout the multiple review process which is required. If one assumes that only those projects are funded in which human rights are protected and that most or all biomedical research requires outside fund ing, then one might be correct in concluding that biomedical research from this time for ward will be both scientific and ethical. The argument has two flaws. The information is simply not available on
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the scientific community agrees with the ar guments reviewed above. Some have no con fidence in voluntary control by researchers who are no more able than the lay public to distinguish among their ethical and unethical colleagues. 1 7 Others are a bit more stinging in their assertions. In what must be one of the more extensive chronicles of unethical exper iments culled from the published literature of mostly the 1950s and 1960s, Pappworth made a strong case for his accusation that modern medicine is dominated by antihumanism. 1 1 He argued that the right to be treated with de cency is an individual right which supersedes every consideration of what may benefit sci ence or society in general and, further, that no physician investigator has the right to choose martyrs for the general good. Pappworth's conclusion was that voluntary codes were not sufficient to curb the unscru pulous and that legislative regulation was necessary. The arguments for placing curbs on scien tific freedom and the activities of researchers stand in stark contrast to those offered in defense of scientific freedom and trust in the researcher. The question of choosing be tween the two sets of arguments is not a scientific question to be answered by looking at the evidence. The choice hangs upon an ethical dilemma which is probably older than the recorded history of man; namely, the di lemma of which has the greater value, the individual or society in general. Biomedical research, on the scale and at the intensity with which we are familiar, is a fairly recent innovation; indeed, the point might be made without stretching it that research is the latest social institution devised by man. So we have an old, enduring ethical dilemma surfacing in the center of our latest social invention. As efforts are made to resolve the dilemma, we may anticipate certain consequences which also need to be considered. Possible consequences. The mere reading of the policies and procedures laid down by federal agencies and one's own institution 1 8 to regulate research on human subjects forces the conclusion with which even the proponents of governmental regulation agree; namely, that the necessary review pro cedures will delay research. 1 1 , 1 7 Whatever one's persuasion about the slowing up of rePHYSICAL THERAPY
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of their own research, that is, arguments about the need for governmental regulation of research ethics, are themselves ethical ar guments. Extensive documentation of abuses notwithstanding, 1 1 even the definition of abuse requires certain a priori ethical as sumptions in order to be operational. With this caution in mind, consider the arguments which have been brought to bear upon the issue. The scientific community has been advised to view with caution the governmental regula tion of the use of human subjects in research. Not only are the abuses said to involve a minority of researchers who presumably would be driven out of business by voluntary control mechanisms but the specter is raised of authorities imposing restrictions on the freedom of inquiry. 1 2 Some say that in accept ing the challenge to understand nature man should accept no handicaps, no artificial limi tations of tools or subject matter. Scientific freedom, the freedom to be intelligent, is es sential; the imposition of restraints on this freedom betrays a fear of the unknown and of man himself. 1 3 Scientific freedom, like aca demic freedom, is an acquired right which society in general accepts as necessary for the advancement of knowledge from which society itself may benefit. Some experiments are justified even if they involve great risks. 1 4 Even though the advances of science may sometimes threaten life, the quality of life, or our self-respect as human beings, these haz ards are unforeseen consequences and not the intentions of wicked scientists. Scientists, on the whole, are amiable and well-meaning people. 1 5 These arguments for scientific freedom and trust in the researcher come down to main taining that the unfettered or relatively unfet tered pursuit of knowledge is both a good and a right, and that such harm as does occur amounts to an infrequent risk which is justi fied for the ultimate good of society. As an aside, one might wonder if the ethical prob lems would disappear were all researchers to abide by the Golden Rule. Not surprisingly, George Bernard Shaw has a ready-made an swer: "Do not do unto others as you would that they should do unto you. Their tastes may not be the same." 1 6 Obviously, not everyone in or familiar with
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only the question. Finally, before leaving the possible conse quences attached to the problem in its recent form, consider the possible ultimate effect of biomedical research given the current and foreseeable state of federal funding and con trol. Data on the 10 leading causes of death in 1900 and in 1967 show that the conquest of infectious diseases was the major accom plishment of research in that period. 2 4 Much of that conquest was achieved before World War II at which time research of all kinds started to receive massive financial support from the federal government. Much of that support went to basic research — research into basic processes-which should be vital to the eventual conquest of the neoplastic and degenerative diseases which came to be among the 10 leading causes of death. In the mid 1960s, the priorities for funding were shifted to so-called targeted research, the fundable research was increasingly shaped into project and contract form, and the enter prise of research became increasingly bureaucratized. By the end of 1974, research had also become politicized. When the enemy was specific organisms, the research enterprise was neither heavily funded nor heavily encumbered with regula tions, proposal deadlines, and reviews. In deed, before the 1960s, few federal or state laws existed on medical research and its reg ulation. What may have been the first legal recognition of clinical investigation occurred as a court decision in 1935. 2 5 Prior to that time, clinical investigation was essentially an "outlaw" activity. Yet, experimentation on human subjects was done, the risks were high, individuals lost their lives, and genera tions of people who followed lived longer as a result. Perhaps we can never go back to those simpler, but more brutal, days. Perhaps we do not wish to return to the days of absolute experimenter license but somewhere be tween then and now we appear to have backed science into a corner where 1) basic research on animals must precede research on human subjects but that basic research is either not possible or not fundable, 2) an ex perimental treatment must be effective before it is tested, 3) the experimenter must tell the subject what will happen when the experi menter does not know what will happen, and 411
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search, the old adage that "time is money" suggests that more extensive review of re search proposals will cost somebody more money. The cost in dollars of slowing up research is of peripheral interest. More serious is the possibility that extensive review to protect the rights of subjects will delay providing to the public the benefit of a new therapeutic or immunizing agent. 9 The individual and soci ety are pitted one against the other in such a way that the cost to one purchases the benefit to the other. Regulations governing the use of human subjects may be so stringent that certain kinds of research, or research on certain kinds of subjects, may be impossible. 1 0 , 1 9 The initial use of a therapeutic or immunizing agent in human subjects is that unique form of experimentation in which the subjects and society in general stand to benefit. This ini tial-use research is one area which is particu larly vulnerable to arbitrary ethical stand ards. 2 0 Some diseases occur only in man, and initial-use experiments, with unknown conse quences, must be done in man. Regulations may be threatening as well as restrictive. Some institutions may be so concerned with protecting themselves from criticism or legal risk in the research activities which they ap prove that they may take no risks at all, a response which is hardly in the interest of the public. 1 0 I have found not one objection to the regu latory requirement to protect the confiden tiality of medical records and other forms of data collected on human subjects. 4 If any thing, that requirement may be too-little toolate to protect untold numbers of us from the unauthorized use of medical data already centrally stored. 2 1 The computerization of data has unlocked a treasure chest for re searchers and a Pandora's box for their sub jects. 22 - 23 As the issue of confidentiality inten sifies, and as increasing regulatory control over experimental data emerges, the question of just what constitutes research will receive increasing attention. We may even ask now about the conditions under which a case study might be construed as research, and, if there are such conditions, whether publica tion of the case study might constitute a breach of confidentiality. I offer no answer,
Institutes of Health. His words describe a view of the current state of affairs which we cannot ignore:
Research means going out into the un known, which demands a pioneering spirit. This spirit is now strangled by the way in which the main federal biomedical granting agency, the National Institutes of Health, dis tributes its grants. The unknown is the un known because one does not know what is there. If one knows what one will find in it, then it is not research any more and is not worth doing. 2 6
REFERENCES 1. Jonsen AR: Letter. Science 188:98-100, 1975 2. National Research Act: Restores training, bans fetal research. Science 185:426-427, 1974 3. US Department of Health, Education, and Welfare: Cri teria for Clinical Investigative Use for Therapeutic De vices under Contract to the National Heart and Lung Institute. NIH Guide for Grants and Contracts 3 (11): August 7, 1974 4. US Department of Health, Education, and Welfare: Re search Projects Involving Human Subjects. NIH Guide for Grants and Contracts 3 (12): August 26, 1974 5. Boffey PM: Research on human subjects: Proposed safeguards assailed by scientists. Chronicle of Higher Education, November 11, 1974 6. Brown C: Use of humans in medical testing a dilemma for doctors. Philadelphia Inquirer, March 30, 1975 7. Fetal research: Ethics commission votes to end mora torium. Science 188:811-813, 1975 8. Piatt R: Ethical problems in medical procedures. In Wolstenholme G, O'Connor M (eds): Law and Ethics of Transplantation, A Ciba Foundation Blueprint. Lon don, J & A Churchill Ltd, 1968, pp 149-153 9. Rutstein DD: The ethical design of human experi ments. In Freund PA (ed): Experimentation with Hu man Subjects. New York, George Braziller, Inc, 1970, pp 383-401 10. Mechanic D: Risks and benefits. A book review of Research on Human Subjects by Barber B, Laily JJ, Makarushka JL, et al. Science 181:255-256, 1973 11. Pappworth MH: Human Guinea Pigs: Experimentation on Man. Boston, Beacon Press, 1968 12. Etzioni A: Regulation of human experimentation. Sci ence 182:1203, 1973 13. Percy Bridgman, quoted in Runes DD (ed): Treasury of Philosophy. New York, Philosophical Library, 1955, p 186 14. Edsall JT: Scientific freedom and responsibility: Re port of the AAAS Committee on Scientific Freedom
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and Responsibility. Science 188:687-693, 1975 15. Medawar PB: Science and the sanctity of life. In East man AM, Blake CR, English HM Jr et al (eds): Norton Reader: An Anthology of Expository Prose (rev). New York, W. W. Norton & Company, Inc, 1965, pp 371-381 16. Shaw GB: Man and Superman. New York, Bantam Books, 1959, p 215 17. Capron AM: Letter. Science 183:797, 1974 18. Research Administration, University of Pennsylvania: Human Beings in Research: University of Pennsylvania Policies and Procedures. Philadelphia, University of Pennsylvania, 1974 19. McCormick RA: Proxy consent in the experimentation situation. Perspect Biol Med 18:2-20, 1974 20. Moore FD: Therapeutic innovation: Ethical boundaries in the initial clinical trials of new drugs and surgical procedures. In Freund PA: Experimentation with Hu man Subjects. New York, George Braziller, Inc, 1970, pp 358-378 21. Spingarn ND: No more health secrets. Philadelphia Inquirer, June 8, 1975 22. Scientific Conference on Computers and Confidential ity in Medicine: Summaries of Papers. Pressedrucksache nr III. Generalversammlung des Weltarztebundes, Munchen, October 16-20, 1973 23. Curran WJ, Laska EM, Kaplan H, et al: Protection of privacy and confidentiality. Science 182:797-802, 1973 24. Chase A: The Biological Imperatives: Health, Politics and Human Survival. New York, Holt, Rinehart and Winston, Inc, 1971 25. Curran WJ: Governmental regulation of the use of human subjects in medical research: The approach of two federal agencies. In Freund PA: Experimentation with Human Subjects. New York, George Braziller, Inc, 1970, pp 402-454 26. Szent-GyOrgyi A: Research grants. Perspect Biol Med 18:41-43, 1974
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4) new knowledge about topics or population types is to be obtained by not studying them. Confronted with important problems which are more complex than those undertaken at the beginning of the century, can the biomed ical research of today solve those problems in timely fashion and still keep both feet in the corner to which we have confined it? I sup pose we will learn the answer to that question in time. Meanwhile, each of us should feel just a bit uneasy over a prominent re searcher's public announcement that he will not again apply for a grant from the National
EUGENE MICHELS, MA
The problem of biomedical research and human rights is reviewed from the perspectives of current issues, historical events, and other sciences. Govern ment control of research, reactions to and possible consequences of that control, and the concern for consent from members of vulnerable populations are examined. The nature of research is discussed and the origins of opposing ethical views are described in an attempt to clarify the issues within the prob lem.
Under the byline of "News and Comment," the November 1, 1974, issue of Science presented a report titled "GraveRobbing: The Charge against Four from Bos ton City Hospital." At the foot of the page appears the terse, boxed announcement: "Recent advances in biomedical science are raising important problems of ethics and public policy. This is one of a series of occa sional articles planned for News and Com ment on the conflicts involved." More specif ically, the problem is one of human rights in biomedical experimentation. 1 Judging by the recent actions of federal lawmakers- and funding agencies, 3 - 4 the reactions in both the professional 3 and lay ( i press, and the issues involved, I have reason to believe that the re cent advances in biomedical science serve as only the means for drawing our attention to the problem of research and human rights. Now that our attention has been obtained, each of us might find it both easy and right eous to choose a side and advocate what should be done for the good of either biomedical science and research or the rights
Mr. Michels is Associate Professor of Physical Therapy, School of Allied Medical Professions, University of Penn sylvania, Philadelphia, PA 19174. Adapted from a paper presented at the Fifty-First An nual Conference of the American Physical Therapy Associ ation, Anaheim, CA, June 16-20, 1975.
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of human beings. My intention is not to choose a side and advocate what should be done. Instead, I will attempt to do what Albert Jonsen of the Health Policy Program, Univer sity of California, suggested in a letter to the readers of Science in April of this year: to define the issues in terms suitable for public debate, to analyze the moral arguments, and to examine the presuppositions and the logic of debate. 1 Serious moral choices are posed to society by experimental medicine. The choices and their consequences are not simple. We in physical therapy are part of both society and medicine. To give the topic of research and human rights careful thought, we must look at the problem in its current and historical sense, we must see the parallel problems in other sciences which are of interest to us, and we are obliged to consider just what research and human rights are and how they have been viewed historically. In this way, I believe that we will see that the underlying issues are enduring, that they likely will not be decided once for all time, that resolution of the issues may itself yield other problems and issues in the cauldron of human affairs, and that the current concern may have far-reaching con sequences for a profession which, in the im age of medicine, is moving toward becoming both a science and a practice.
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Research and Human Rights
THE PROBLEM IN RECENT FORM
In July 1974, the National Research Act was signed into law. Among its provisions affect ing research and research training, the act placed a moratorium on experimentation with the living human fetus, before or after in duced abortion, and created a National Com mission for the Protection of Human Subjects of Biomedical and Behavioral Research. 2 The commission, which is advisory to the Secre tary of Health, Education, and Welfare, re cently studied the issue of fetal research and submitted its recommendations to the Secre tary who is likely to adopt the recommenda tions as written. 7 The recommendations gen erally are that the ban on fetal research be lifted, that proposed experiments be carefully evaluated for medical and ethical soundness, and that the informed consent of the mother, and in certain cases the father, be required. The commission is to have a life of only two years, but the act provides for metamorphosis into a permanent council. 2 One month after the National Research Act became law, the National Institutes of Health issued two announcements 3 , 4 which, while unrelated both to that act and apparently one to the other, represent the latest regulatory steps taken by a federal agency concerned with the rights and welfare of human subjects who participate in research projects funded by public monies. The earlier of the two an nouncements, addressed to the criteria for the clinical investigative use of therapeutic devices under research contracts with the National Heart and Lung Institute,'* is narrow in scope, detailed in statement, and quite possibly precedent - setting — a possibility which appears not to have excited the aca demic-research community. The later an nouncement, addressed more broadly to the protection of the rights and welfare of human subjects in all research, development, and related activities under grants and contracts with the National Institutes of Health, 4 seems to have elicited a widespread allergic reac tion. Instead of describing these regulations in detail, the more useful approach taken is one of looking generally at the kinds of concerns
408
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Government Action
for human rights which are embodied in the requirements to be met by researchers who seek federal funding. Risk and risk-benefit ratio. Potential risk is broadly conceived to include physical, psy chological, and social injuries which may arise from the subject's participation in any activity which departs from established and accepted methods necessary to meet his needs or which increases the ordinary risks of daily life. The departure from established and accepted methods, that is, the manipulation without which there is no experiment, may consist of either a method which is not yet established and accepted or the withholding of a method which is established and ac cepted. The potential risk is not limited to the harm which may arise from an experimental procedure or device but includes, as well, the public embarrassment or humiliation which may occur through the variety of forms in which information is recorded and subse quently used by the investigator or other per sons. In brief, the risk to the subject is seen as a risk to his body and to his person. The likelihood and seriousness of potential risks are viewed as human cost factors which are to be outweighed by potential benefits. The idea of a risk-benefit ratio is both prag matically and ethically sound. The wording in both documents, however, poses either a di lemma or a restriction on the kind of research which will be funded. The requirement that a proposed research project offer potential benefits to both the individual subject and society in general poses the entirely practical problems of 1) either demonstrating in what way the normal subject (the nonpatient) may benefit from some biomedical manipulation or restricting the subject population to only patients, 2) devising adequate control condi tions which are as likely as the experimental condition to yield benefits for individual sub jects, 3) purporting to investigate the effect of some biomedical intervention, the benefit of which is already demonstrable, and 4) dis carding entirely so-called basic or nontherapeutic research. Informed consent and special popula tions. The requirement that the subject give his informed consent to participate in the ex periment requires at the minimum that he un derstand the nature of the experiment, the
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the number of nonfunded projects carried out each year, the number of experimental proce dures for which patients are billed, the extent to which actual practices conform to re search protocols, and the frequency with which consent is honestly obtained. 1 0 The second flaw in the argument posed above is the unstated assumption that all searchers for knowledge will accept the ethical restraints and will not use grantsmanship skills to get around the barriers to inexpensive, nonprotesting patient populations. My intent here is not to conjure up images of doctor scientists gone wild in their laboratories and luring un suspecting victims into Frankensteinian ex periments. On the contrary, we must consider the objections which have been raised to the ethical safeguards and to the federal govern ment's role in regulating this matter. The ob jections may or may not be warranted but in either event they suggest a continuing con frontation between opposing views which might affect compliance with the existing regulations and the shape of future regula tions. Reaction to Government Action Before 1974 ended, the academic-research community responded in a largely negative way to two elements of the regulations: 1) the protection of rights of subjects from special, vulnerable populations, and 2) the review process. 5 Complaints that some aspects of the regulations are equivalent to returning to the Dark Ages, or make scientists sound guilty until proved innocent, deserve little se rious consideration. On the other hand, one should not dismiss charges that the regula tions are cumbersome, costly, unnecessary, and either destructive of, or stifling to, medi cal or scientific progress. Many of these im mediate reactions could have been antici pated because the debate over ethics in re search and the role of government in regulat ing research has raged for some time. Many of the earlier arguments are as timely today as when they were first raised and some of these earlier arguments appear to have been more carefully considered than the recent reflexive responses. Morality and necessity. Arguments about researchers voluntarily controlling the ethics
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risks to his body and person, and the poten tial benefits to himself, to society in general, or to both, and that he voluntarily agree to participate under conditions which he under stands and accepts. Using language with which most of us are familiar, informed con sent requires that the subject and the experi menter enter into a contractual agreement which, however, is never binding on the sub ject. Members of special populations such as the mentally deficient and the very old or very young may not be able to understand suffi ciently well to make their own determination of consent. Others, such as the poor and pris oners, may be easily induced to consent be cause of financial or other rewards. By requir ing the rationale for using subjects from these special populations and a description of the consent procedures to be used, the regulations provide at least some assurance that the protection of human rights is equal ized for the not-so-equal members of our so ciety. Research question and design. As is the practice with other granting agencies but perhaps more rigorously so, the National In stitutes of Health demands that the proposed research project be designed to answer im portant questions in a scientifically sound manner and that the project produce maxi mum research information at minimum haz ard to the patient. Another way of stating the matter is to say that human subjects are a precious resource to be used only in sound research which seeks answers to important questions. In this sense, the research ques tion and design do pose ethical implications for the use to which human subjects are put. 8 - 9 The concerns for human rights in research are enforceable to the degree that honesty prevails in actual research settings, as well as throughout the multiple review process which is required. If one assumes that only those projects are funded in which human rights are protected and that most or all biomedical research requires outside fund ing, then one might be correct in concluding that biomedical research from this time for ward will be both scientific and ethical. The argument has two flaws. The information is simply not available on
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the scientific community agrees with the ar guments reviewed above. Some have no con fidence in voluntary control by researchers who are no more able than the lay public to distinguish among their ethical and unethical colleagues. 1 7 Others are a bit more stinging in their assertions. In what must be one of the more extensive chronicles of unethical exper iments culled from the published literature of mostly the 1950s and 1960s, Pappworth made a strong case for his accusation that modern medicine is dominated by antihumanism. 1 1 He argued that the right to be treated with de cency is an individual right which supersedes every consideration of what may benefit sci ence or society in general and, further, that no physician investigator has the right to choose martyrs for the general good. Pappworth's conclusion was that voluntary codes were not sufficient to curb the unscru pulous and that legislative regulation was necessary. The arguments for placing curbs on scien tific freedom and the activities of researchers stand in stark contrast to those offered in defense of scientific freedom and trust in the researcher. The question of choosing be tween the two sets of arguments is not a scientific question to be answered by looking at the evidence. The choice hangs upon an ethical dilemma which is probably older than the recorded history of man; namely, the di lemma of which has the greater value, the individual or society in general. Biomedical research, on the scale and at the intensity with which we are familiar, is a fairly recent innovation; indeed, the point might be made without stretching it that research is the latest social institution devised by man. So we have an old, enduring ethical dilemma surfacing in the center of our latest social invention. As efforts are made to resolve the dilemma, we may anticipate certain consequences which also need to be considered. Possible consequences. The mere reading of the policies and procedures laid down by federal agencies and one's own institution 1 8 to regulate research on human subjects forces the conclusion with which even the proponents of governmental regulation agree; namely, that the necessary review pro cedures will delay research. 1 1 , 1 7 Whatever one's persuasion about the slowing up of rePHYSICAL THERAPY
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of their own research, that is, arguments about the need for governmental regulation of research ethics, are themselves ethical ar guments. Extensive documentation of abuses notwithstanding, 1 1 even the definition of abuse requires certain a priori ethical as sumptions in order to be operational. With this caution in mind, consider the arguments which have been brought to bear upon the issue. The scientific community has been advised to view with caution the governmental regula tion of the use of human subjects in research. Not only are the abuses said to involve a minority of researchers who presumably would be driven out of business by voluntary control mechanisms but the specter is raised of authorities imposing restrictions on the freedom of inquiry. 1 2 Some say that in accept ing the challenge to understand nature man should accept no handicaps, no artificial limi tations of tools or subject matter. Scientific freedom, the freedom to be intelligent, is es sential; the imposition of restraints on this freedom betrays a fear of the unknown and of man himself. 1 3 Scientific freedom, like aca demic freedom, is an acquired right which society in general accepts as necessary for the advancement of knowledge from which society itself may benefit. Some experiments are justified even if they involve great risks. 1 4 Even though the advances of science may sometimes threaten life, the quality of life, or our self-respect as human beings, these haz ards are unforeseen consequences and not the intentions of wicked scientists. Scientists, on the whole, are amiable and well-meaning people. 1 5 These arguments for scientific freedom and trust in the researcher come down to main taining that the unfettered or relatively unfet tered pursuit of knowledge is both a good and a right, and that such harm as does occur amounts to an infrequent risk which is justi fied for the ultimate good of society. As an aside, one might wonder if the ethical prob lems would disappear were all researchers to abide by the Golden Rule. Not surprisingly, George Bernard Shaw has a ready-made an swer: "Do not do unto others as you would that they should do unto you. Their tastes may not be the same." 1 6 Obviously, not everyone in or familiar with
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only the question. Finally, before leaving the possible conse quences attached to the problem in its recent form, consider the possible ultimate effect of biomedical research given the current and foreseeable state of federal funding and con trol. Data on the 10 leading causes of death in 1900 and in 1967 show that the conquest of infectious diseases was the major accom plishment of research in that period. 2 4 Much of that conquest was achieved before World War II at which time research of all kinds started to receive massive financial support from the federal government. Much of that support went to basic research — research into basic processes-which should be vital to the eventual conquest of the neoplastic and degenerative diseases which came to be among the 10 leading causes of death. In the mid 1960s, the priorities for funding were shifted to so-called targeted research, the fundable research was increasingly shaped into project and contract form, and the enter prise of research became increasingly bureaucratized. By the end of 1974, research had also become politicized. When the enemy was specific organisms, the research enterprise was neither heavily funded nor heavily encumbered with regula tions, proposal deadlines, and reviews. In deed, before the 1960s, few federal or state laws existed on medical research and its reg ulation. What may have been the first legal recognition of clinical investigation occurred as a court decision in 1935. 2 5 Prior to that time, clinical investigation was essentially an "outlaw" activity. Yet, experimentation on human subjects was done, the risks were high, individuals lost their lives, and genera tions of people who followed lived longer as a result. Perhaps we can never go back to those simpler, but more brutal, days. Perhaps we do not wish to return to the days of absolute experimenter license but somewhere be tween then and now we appear to have backed science into a corner where 1) basic research on animals must precede research on human subjects but that basic research is either not possible or not fundable, 2) an ex perimental treatment must be effective before it is tested, 3) the experimenter must tell the subject what will happen when the experi menter does not know what will happen, and 411
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search, the old adage that "time is money" suggests that more extensive review of re search proposals will cost somebody more money. The cost in dollars of slowing up research is of peripheral interest. More serious is the possibility that extensive review to protect the rights of subjects will delay providing to the public the benefit of a new therapeutic or immunizing agent. 9 The individual and soci ety are pitted one against the other in such a way that the cost to one purchases the benefit to the other. Regulations governing the use of human subjects may be so stringent that certain kinds of research, or research on certain kinds of subjects, may be impossible. 1 0 , 1 9 The initial use of a therapeutic or immunizing agent in human subjects is that unique form of experimentation in which the subjects and society in general stand to benefit. This ini tial-use research is one area which is particu larly vulnerable to arbitrary ethical stand ards. 2 0 Some diseases occur only in man, and initial-use experiments, with unknown conse quences, must be done in man. Regulations may be threatening as well as restrictive. Some institutions may be so concerned with protecting themselves from criticism or legal risk in the research activities which they ap prove that they may take no risks at all, a response which is hardly in the interest of the public. 1 0 I have found not one objection to the regu latory requirement to protect the confiden tiality of medical records and other forms of data collected on human subjects. 4 If any thing, that requirement may be too-little toolate to protect untold numbers of us from the unauthorized use of medical data already centrally stored. 2 1 The computerization of data has unlocked a treasure chest for re searchers and a Pandora's box for their sub jects. 22 - 23 As the issue of confidentiality inten sifies, and as increasing regulatory control over experimental data emerges, the question of just what constitutes research will receive increasing attention. We may even ask now about the conditions under which a case study might be construed as research, and, if there are such conditions, whether publica tion of the case study might constitute a breach of confidentiality. I offer no answer,
Institutes of Health. His words describe a view of the current state of affairs which we cannot ignore:
Research means going out into the un known, which demands a pioneering spirit. This spirit is now strangled by the way in which the main federal biomedical granting agency, the National Institutes of Health, dis tributes its grants. The unknown is the un known because one does not know what is there. If one knows what one will find in it, then it is not research any more and is not worth doing. 2 6
REFERENCES 1. Jonsen AR: Letter. Science 188:98-100, 1975 2. National Research Act: Restores training, bans fetal research. Science 185:426-427, 1974 3. US Department of Health, Education, and Welfare: Cri teria for Clinical Investigative Use for Therapeutic De vices under Contract to the National Heart and Lung Institute. NIH Guide for Grants and Contracts 3 (11): August 7, 1974 4. US Department of Health, Education, and Welfare: Re search Projects Involving Human Subjects. NIH Guide for Grants and Contracts 3 (12): August 26, 1974 5. Boffey PM: Research on human subjects: Proposed safeguards assailed by scientists. Chronicle of Higher Education, November 11, 1974 6. Brown C: Use of humans in medical testing a dilemma for doctors. Philadelphia Inquirer, March 30, 1975 7. Fetal research: Ethics commission votes to end mora torium. Science 188:811-813, 1975 8. Piatt R: Ethical problems in medical procedures. In Wolstenholme G, O'Connor M (eds): Law and Ethics of Transplantation, A Ciba Foundation Blueprint. Lon don, J & A Churchill Ltd, 1968, pp 149-153 9. Rutstein DD: The ethical design of human experi ments. In Freund PA (ed): Experimentation with Hu man Subjects. New York, George Braziller, Inc, 1970, pp 383-401 10. Mechanic D: Risks and benefits. A book review of Research on Human Subjects by Barber B, Laily JJ, Makarushka JL, et al. Science 181:255-256, 1973 11. Pappworth MH: Human Guinea Pigs: Experimentation on Man. Boston, Beacon Press, 1968 12. Etzioni A: Regulation of human experimentation. Sci ence 182:1203, 1973 13. Percy Bridgman, quoted in Runes DD (ed): Treasury of Philosophy. New York, Philosophical Library, 1955, p 186 14. Edsall JT: Scientific freedom and responsibility: Re port of the AAAS Committee on Scientific Freedom
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and Responsibility. Science 188:687-693, 1975 15. Medawar PB: Science and the sanctity of life. In East man AM, Blake CR, English HM Jr et al (eds): Norton Reader: An Anthology of Expository Prose (rev). New York, W. W. Norton & Company, Inc, 1965, pp 371-381 16. Shaw GB: Man and Superman. New York, Bantam Books, 1959, p 215 17. Capron AM: Letter. Science 183:797, 1974 18. Research Administration, University of Pennsylvania: Human Beings in Research: University of Pennsylvania Policies and Procedures. Philadelphia, University of Pennsylvania, 1974 19. McCormick RA: Proxy consent in the experimentation situation. Perspect Biol Med 18:2-20, 1974 20. Moore FD: Therapeutic innovation: Ethical boundaries in the initial clinical trials of new drugs and surgical procedures. In Freund PA: Experimentation with Hu man Subjects. New York, George Braziller, Inc, 1970, pp 358-378 21. Spingarn ND: No more health secrets. Philadelphia Inquirer, June 8, 1975 22. Scientific Conference on Computers and Confidential ity in Medicine: Summaries of Papers. Pressedrucksache nr III. Generalversammlung des Weltarztebundes, Munchen, October 16-20, 1973 23. Curran WJ, Laska EM, Kaplan H, et al: Protection of privacy and confidentiality. Science 182:797-802, 1973 24. Chase A: The Biological Imperatives: Health, Politics and Human Survival. New York, Holt, Rinehart and Winston, Inc, 1971 25. Curran WJ: Governmental regulation of the use of human subjects in medical research: The approach of two federal agencies. In Freund PA: Experimentation with Human Subjects. New York, George Braziller, Inc, 1970, pp 402-454 26. Szent-GyOrgyi A: Research grants. Perspect Biol Med 18:41-43, 1974
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4) new knowledge about topics or population types is to be obtained by not studying them. Confronted with important problems which are more complex than those undertaken at the beginning of the century, can the biomed ical research of today solve those problems in timely fashion and still keep both feet in the corner to which we have confined it? I sup pose we will learn the answer to that question in time. Meanwhile, each of us should feel just a bit uneasy over a prominent re searcher's public announcement that he will not again apply for a grant from the National
