Ethical considerations in biomedical research involving human beings.

Ethical Considerations in Biomedical Research Involving Human Beings JOSEPH FLETCHER I begin this essay with an ethical premise, namely, that as moral agents we all have a right and an obligation to restrict or prohibit any- body's freedom to harm others, unless it be for the sake of the general welfare or a propor- tionate good. SCOPE OF INQUIRY The qualifying clause in this premise fits discussions of most human problems, such as foreign or civil war, the punitive and preventive coercions of law enforcement, social security legislation, and the delivery of health care. In the present context, however, scientific re- search and clinical trials in medicine specifically will be in mind. The development and use of complex biological substances and agents (gobulins, serums, vaccines, antitoxins, anti- gens) are an important sector on the experi- mental front. Remarkable work is being done, even at such basic levels as on the use of interferon to combat viruses. Primary ethical concepts, however, apply broadly enough to cover synthetics as well as biologicals. There is no peculiar or ideomorphic system of ethics for research in biologicals alone. Furthernore, we ought to include the investigators themselves and prospective bene- ficiaries of the research as among the human beings who are involved, and who have moral claims to be considered along with the claims of research subjects (therapeutic and non-thera- peutic). These parties to the process are too often treated as faceless or actually non- existent. The moral principles of research and investi- gative medicine have loomed bigger since modem medicine got its start with a shift from the spirit of Galen, relying on "tried and true" remedies, to the spirit of Paracelsus, i.e., the philosophy (a cognition theory) that experience is more important than tradition. It was this shift that loosed pharmacology's genius for scientific inquiry and experiment. There are three models of medicine. The cult of the Dogmatists (Pythagoras and Empedocles) was based on metaphysics rather than empirical principles. Tis is what Hippocrates broke away from. The cult of Aesculapius saw medicine as a one-to-one, patient-physician activity. Witih its strictly interpersonal morality, it created a model that still largely dominates medical thinking. The cult of Hygeia, daughter of Aesculapius, stood for a social ethic and a public health goal; it sought prevention as well as therapy, the public Interest as well as private health. This third hygienic model is the one that best fits our present inquiry into the ethics of biological research. The imperatives of social ethics have first claim on us; that is my bottom-line contention. The Hippocratic Oath spoke only of a physi- cian's obligation to his patient. The Helsinki Declaration (1964) still held to the doctrine that "my patient's" needs get first considera- tion, although it then adds a vague duty "to safeguard the health of the people." Therein lies the problem. Usually the tension between personal and social interests can be compro- mised, but when there is an irresolvable conflict Visiting Professor of Medical Ethics at the School of AMedicine, University of Vtginia. and at the Institute of Religion and Human Development. Texas Medcal Center (Houston),- Professor Emeritus of Social Ethics, Episcopat 7heological School, Cambridge. Massachusetts; Fellow, Institute of Society, Ethics and the Life Sciences. Box 32S, University Medical Center, Charlottesville, Virginia 22903. 101 1. Fletcher or true dilemma (if one or the other must be chosen) we ought to prefer the good of the greater number., Such at leatsist4 baseline of this paper, even though it stands somewhat against the traditional JudC4Ctrbtian preference for the inviolability of tie individual. It is the same basic premise as in the military draft, sacrificial acts of heroism and martyrdom, confiscation by eminent doman, or traffic signals at inter- sections. "What can we. do about this agonizing dilemma?" Walsh McDermott once asked. "Ob- viously we canot convene a constitutional convention of t«e Judeo-Christian culture and add a few amendments to it. Yet, in a figurative sense, until we cm do something very much like that, I believe deeply that the problem, at its roots, is unslvgable and that [in biomedical ethics] we must continue to live with it." For the present, Dr. McDermott thinks, we are just coping with it by reciting our ambiguous Oaths and Declarations In the accents of hypocrisy, "that marvelous humrn invention by which we are enabled to adapt -to problems judged to be not yet ripe for swlution(l).'" Martin Arrowanith, the bacteriologist in Sinclair Lewis' nov01, went off as a disciple of Hygeia to an island in the Caribbean during an epidemic of plage, taking a new bacteriophage to test its safety and efficacy for preventive medicine. It was * unique opportunity; yet, in the situation, Arrowsmith ruined it because he felt he could not withhold the product from a randomized control group(2). Was his com- passion ethical? He himself was unable to say. His friends and fellow scientists, Gottlieb and Sondelius, were sure it was unethical. Here is a searching question. Is it susceptible of an answer? How are we,fthP, to relate such hypo- thetical situatioN toibstorically real situations such as the Tuskegee syphilis study? This long-term nves1tAQn of untreated syphilis in a group of black men in six Southem states started in 1932. It was conducted under the auspices of the U.S. Public Health Service, to determine the course of the infection. Even after both penicillin and heavy metals became available in the Forties this longitudinal study was not interrupted, nor were the subjects informed of the armamentarium. The affair was not uncovered until 1972. It was then promptly condemned by a panel set up by the Depart- ment of Health, Education, and Welfare, which included people from medicine, law, religion, labor, and government(3). As William Curran said, "It is difficult to quarrel with any of the substantive conclusions of the ad hoc panel(4)." Inquiry showed that the program had not provided for informed consent, that it lacked a written protocol, had no assurances of reliability, had no data base, and also was very questionably designed. This is an overwhelming indictment, both ethically and scientifically. But, we should ask, what if the scientific protocol had been acceptable, yet the efficacy of the antibiotic subsequently devel- oped had remained still undemonstrated? In this situation would silence as to the penicillin have been ethical (i.e., justifiable) in the in- terests of a double-blind experiment? (Asking "what if' questions is an important tool of ethical analysis and criticism, as it is of deci- sion-making theory.) Without getting bogged down in detail or being unnecessarily analytical, let me just list, by title only, some 17 distinguishable factors generally recognized, which enter into the total "mix" of the ethics of the research, develop- ment, and use of biologicals. The 17 factors are: risk (for both subjects and investigators), avoid- ance of harm (non nocere), reportage (profes- sional probity), pre-human tests (animal stu- dies), consent (competence as to freedom and information), benefit (proportionate good to be gained), avoidance of deception (of subjects), design (scientific standards), privacy (confiden- tiality), rnotivation of participants (both sub- jects dnd investigators), cost (part of risk- benefit calculations), duress, fraud, voluntary participation, in-course cancellation (by sub- jects or investigators), monitoring, and review (peer and public). There is a voluminous litera- 102 Ethical Cousaderations in Biomedical Researc Involving Human Bing0 ture extant dealing with the ethics of research; it shows a fairly impressive consensus on some scores and very little agreement on others(S). Manifestly, there are too many items on the conventional agenda to be explored here one by one; we will look only at "ethics" as such, in relation to biomedical research. ETHICS OFFERS LIMITED HELP In semi-scholastic circles reference is often made to a conceptual construct known as The Ideal Observer, originally put together by Roderick Firth(6). This idealist, ethicist, or moralist has five traits with which to weigh problems of right and wrong: he is omniscient- knows all the relevant facts; omnipercipient- can imagine all the human feelings involved; disinterested-is impartial and without self- interest; dispassionate-free of emotional bias; and consistent-uses generalizable principles to fit similar situations. But the most important thing about him is that he does not exist. All the rest of us are only fmiite creatures, in all respects. Two unusually candid papers on biomedical ethics have appeared in recent months, one by Daniel Greenberg(7) and the other by Danner Clouser(8). They both take a sharp look at some reasons for what is fairly obvitusly the "backlash" or negative reaction to the build-up ethics has had in the past ten years in science and medicine. Greenberg speaks of "that loose arnalgamation of anxieties and passions that comes under the banner of medical ethics." Clouser is the professional ethicist of the two, however, and therefore we will examine the way he treats the question. I endorse his analysis. Professor Clouser suggests at least eight things to be confessed about what the ethicist can or cannot contribute to moral decision- making. (a) Medical ethics is no "big deal" because it offers nothing new-only ethics attempting to function in a new area of interest. (b) It employs notions "we ordinarily aclmowledge in everyday life," and this is the case also with its "reasoning about the medical- ethical issues.. ." (c) We cannot expect the ethicist (ethician?) to be accepted as "the expert" since "what the professional ethicist does is not different in kind from what we all do in deliberating about a moral issue." (d) It is also noteworthy that "a serious limitation . . . is that ethics is a fairly blunt instrument; it does not cut finely." Therefore "it does not deter- mine one or only one action that receives the moral seal of approval;" most commonly "all of the possible actions infringe on one moral rule or anotner, in which case it is a matter of choosing what one regards as the lesser evil." Clouser's confession continues: (e) Ethics helps "structure" the moral issues of medical science and treatment but this does not "neces- sarily mean making a decision on what to do in the situation." (f) Often "the field really is not narrowed down much by moral criteria, and frequently the decision is ultimately made on the basis of some belief, predilection, or matter of taste." (g) Ethics has to have "outside" help. Pivotal decisions "such as 'normal,' 'rational,' 'sick,' 'person,' 'competent,' and 'voluntary' need considerable conceptual analysis by a variety of specialties," as well as by empirical help with risks, the effect of drugs on judg- ment, physical and psychological reactions to infonnation, and the like. Finally, he concludes that (h) "for the most part" we have to work our morals problems out "by trade-offs, com- promises, convincing arguments. or whatever, so that the interests of all of us will be served as far as possible." (This "ethicist's confession," as 1 call it, is strikingly pragmatic, utilitarian, relativistic, and pluralistic.) So much for a professionally sophisticated assessment of the role of ethics in biomedical problems. There is, -however, a more positive side, even given all of Clouser's reservations. We may believe, as the editor of The New England Journal of Medicine does, that knowledgeable ethicists can sometimes help doctors and inves- tigators to grasp more fully the value altema- tives and spread of options between which they will have to choose, even though we rule out the onlooker-ethicists who are "more activists 103 J. Fletchei than philosophers" and "too ready to act as self-appointed judges in labeling this or that medical research. activity as 'unethical'." This he calls "the unethical in medical ethics(9)." We seem to be saying in effect that ethics is no more than informed common sense. Very well, let us say so; that is what it is. Ethics deals with what we happen to hold to be good, and right actions are wh.t conduce to the good-to what we "value." We approve human acts ("moral value") and things ("non-moral value") for personal and cultural reasons, for subjective as well as objective reasons. At the most we might justify them; we cannot verify them. Ethics is not a true-false discipline. There is no way to "prove" It iswrong to steal; we can only assert it is wrong (usually but not invariably being able to justify our judgment). The end product of the 9thical process, as of legal or judicial thinldkng is a judgnent, not-as in science-a concluion. Deciding whether some- thing is good or evi is not a problem in verification orjlsifcation. We can only ap- prove or disapprove ethical opinions. Speaking of ethics, values, and moral judg- ments, Ludwig Wittgenstein rightly despaired of objective and rational thinking in ethics. "'This is a terrible business-just terrible," he said. "You can at bst stammer when you talk of it(1O)." You sooner or later come to a point in ethical discourse where your argument becomes rhetoric rather than Mason. In saying that ethics is informed common sense we ought not to ignore the fact that common sense s not always so commonly come by, and neither is adequate information. Even if ethics deals with value determinations and preferences mibjectively, there are none- theless things to be known about options, about frequencies and likelihoods, and about the history of human experience with them. The only atem*e to this theory of ethics is to believe (a) that there is an objective moral order after al, and furthermore (b) that this moral order is kiotwn by special revelation (as in a religious ait system) or by reason somehow amenable to occult verification. Re- search scientists and medical investigators naturally prefer to be rational rather than metarational, to check their value perceptions against those of others, and to be as coherent and responsibile as possible when making their decisions. This is the ethics of common sense. CODES, REGULATIONS, GUIDELINES The research, development, and use of bio- logicals is inevitably and properly surrounded by regulations, established both from within and without professional circles. This is not, however, an unmixed blessing. In the world today there is a mood of suspicion and dislike for science and technology, in the affluent and developed countries rather than in the develop- ing countries. Its causes are probably a mix- ture of anger and fear because of various misuses of science and technology (especially of technology), combined with jealousy and envy of the leamed, training and competence behind them. Many of the ethical principles upon which the regulations are based explicitly or implicitly are contained in the Nuremberg Code, the Helsinki Declaration of the World Medical Association, and (in the United States) the American Medical Association's Guidelines for research; and we should add the 1969 Regulations of the U.S. Public Health Service. There are well-publicized instances of un- ethical practice. Not only the Tuskegee case already mentioned but the New York cancer cell study, the thalidomide disaster beginning in 1960, the hepatitis infection of soldiers in World War II from pooled human plasma in a live virus vaccine, even the Elixir Sulfanilomide affair back in 1937 (using untested diethylene glycol as a solvent). The full list would be a long one. As an ethicist I am sensitive to the seventeen different ethical "factors" I have listed above. At the same time, knowing that there are no "ideal observers" and no "moral experts" (vide Clouser), and that moral judgments are only blunt Instruments bringing ethical issues down in the end to "trade-offs" and "compromises" of a common sense kind, I am wary of carrying 104 Ethical Considerations in Biomedical Research Involving Human Beings too many ethical "principles" too finely drawn. There is much practical wisdom and ethical perception in the position of the Public Health Service in the Southam-Mandel cancer study debate. Agreeing positively that moral stan- dards and ideals are imperative, they still thought that "proper ethical and moral stan- dards are more effectively guarded by the process of review and criticism than by regula- tion(ll)." In other words, situational or case- by-case decisions are better than rigid a priori rules. Professor Wolfensberger's classi survey of research ethics unfortunately used the lan- guage of "rules" and "codes"-although his intention was certainly not to drag us from conscientious guidelines (principles) into moral- istic inflexibility and paralysis(12). Under pressures from powerful sectarian elements, the National Institutes of Health (NIH) in 1974 allowed their policy to be twisted; they fled (temporarily-for a year or so) into a taboo kind of ethics on fetal research(12). (Taboo ethics consist of general- ized prohibitions or "universal negatives.") This telltale episode combined politicization of medical science, similar to Lysenko's subjuga- tion of genetics in the Soviet Union, and doctrinization similar to the Galileo tragedy in the history of Italian astronomy. For the sake of both ethical and scientific integrity they would have been better advised to keep faith with the Livmgston Report of 1964: "NIH is not . . . to assume an exclusive or authoritarian position conceming the definition of ethical boundaries or conditions mandatory for clinical research(13)." We would all be immeasurably better off if investigators and their funding auspices. both public and private, would keep all rules based on moral values to a minimum, taking a laissez-faire stance toward research enterprises except when they hold both real and present dangers; the emphasis here Is on "both"- dangers that are simultaneously both real. rather than minor or petty, and present. not just "possible" as in a slippery-slope argument about what conceivably "might" happen in the future. And ."dangers" are dangers, of course, for all human beings-subjects, investigators, bystanders, present or prospective patient populations, and the general public. One editor of a medical joumal writes in warning terms of a growing "ethical bureau- cracy," to be discemed in the Federal Register reports: local institutional review committees, consent committees for certain research pro- grams (e.g., involving prisoners, children, ex utero fetuses, the mentally ill), an NIH Ethical Advisory Board to advise funding agencies, a new National Commission for Protection of Human Subjects of Biomedical and Behavioral Research to promulgate ethical regulations, and finally, of course. Congress itself. "The number of inspectors threatens to outnumber the in- spectees," with the possibility that "eternal ethical verities" will be determined by six to five votes(14). (One ethical issue was actually settled by the National Commission with a five to four vote-two members absent.) Setting aside "eternal ethical verities" as a presumably jocular reference, we can agree that each of these watch-dog bodies is appropriate in a democratic society, yet also sounding a waming that "etemal vigilance" is needed to protect science and medicine from the subvert- ing interferences of pressure groups, doctrinal sectarians. bandwagon agitators, and those whom Franz Ingelfinger calls simplistic "fimger pointers," too often mspired only by yester- day's gross misdeeds or ignorant of the benefits to be gained from an experiment today. Public policy tends, as Reinhold Niebuhr remarked, to be "a twilight zone where ethical and technical issues meet(15)." Science and medicine are only beginning to learn how to deal with "public ethics"-the hard way. empirically(I6). The heart of ethics is obligation. To whom is it owed and how is it to be rendered or fulfilled" Perhaps we need only to remark that valid moral claims exist not only for subjects but for investigators and society too, and therefore what we owe morally to any one of these three parties to medical research can be determined only relatively to the other two. So 105 J. Fletcher called "rights" are paired with commensurate "duties." It is true that scientists and society owe subjects care and concern, but subjects owe it to investigtors and to society to help. We must reject the moral opinion of Hans Jonas, that "no one, not even society, has a shred of a right" to ask anybody to take a risk for research-that volunteering is absolutely "gratia gratis data(17)." Investigators and sub-jects, both, owe it to society to leam how to save life, but soiety owes them, each in his own role, financial and legal support, and protection of their results from abuse by business and yellow joumalism. Investigators in particular are morally obliged to serve societal priorities, to minimize risk and harm, to wel- come evaluation and review, to report fully, to accept monitorigg by their peers-but not by incompetent "public watch-dogs" who are not equipped to watch intelligently. As a parenthesis, in spite of the admission above that in this short paper we cannot canvass specific ethical factors, 1 suggest that in a full-dress appraisal of medical research we ought to take a hard look at one much neglected side of risk. It would be easy to wax cynical about the virtual absence in the litera- ture of any discussion recently of the obligation of investigators to volunteer themselves as experimental subjects. The silence is remarkable when we recal Walter Reed in his yellow fever studies, the way J. B. S. Haldane and his father before him frequently acted as their own subjects, how Carri6n inoculated himself with Bartonella bacilli to find a cure for verruga peruana. Pettenkffer and Emerich swallowed cholera bacilli, Bergioni and Wameri and Linde- mann submitted to injections of syphilis organ- isns(18). Sir John Eccles and his students self-tested in New Zealand between 1944 and 1951(19). If we speak of moral obligation, what of this one? We can be sure that a rigorous analysis here would go a long way towards ethics in depth on the problem of research with human subjects. There are three fundamental questions in ethics which need to be squarely faced by every one of us before we can make much headway with the questions at stake in research ethics. They have to do with (a) what we hold to be the highest good, (b) what method of conscien- tious decision-maidng we should use, and (c) how we are to balance the individual in- terest versus the common interest. Let me take them up briefly, in a down-to-earth fashion, and in the order given. The highest good or fmt-order value In current rhetoric we speak of value and values rather than of "the good" and particular goods. In either lexicon we mean what is regarded as desirable, among moral and non- moral entities. Without being arbitrary or too reductive can we not say that science and medicine are committed to humanism-the ethical first-order value of human survival and wellbeing, both individually and collectively; this is their summum bonum and their highest or "ultimate" cnrteron of what is worthwhile. For some people humanism is theistic (having a divine sanction), for others it is naturalistic (no supematural reference), but all are commited to the humanist standard. From this follows our obligation to protect subjects, to volunteer for tests and trials, to make choices maximizing or optimizing human health, to investigate and know how to do so. It is sometimes said, somewhat abrasively, that science as such has "truth" as its highest good and its only obligation. (Science deals with truths, not with the truth.) Yet the search for knowledge is for the sake of human beings-not the other way around. Human interest has the first-order priority(20). It was for this reason that a committee of the National Academy of Sciences in 1974 called a moratorium on research with recom- binant DNA molecules or plasmids, as a bio- hazard, because a drug-resistant carcinogenic construct might get loose and threaten both scientists and society at large. Only when the Asilomar conference agreed on various contain- ment procedures did the research get a renewed "proceed with caution" signal. For this same 106 Ethical Considerations in Biomedical Research Involving Human Beings reason work on bacterial warfare at Fort Detrick, Maryland, was shut down. It would seem there could be "forbidden experiments," rejecting "dangerous knowledge," if the dangers were found to be both real and present enough to justify suspending the scientific "habit of truth.." The work of ethics, then, in biomedical research is critically to evaluate all investiga- tions by the measure of the humanist principle, a humane or humanitarian yardstick, checking them out for the values of health, happiness, professional vocation, scientific discipline, and social wellbeing. These are the parameters within which to evaluate a protocol on the 17 scores of "factors" we have listed. Be it noted, however, that in this world of relativities, decision means having to choose between values. Looking at the risk problem, Walter Model once pointed out that "as there is no drug without hazard there can be no testing of new drugs without risk(21)." This is why the law allows the dangerous Pasteur treatment for rabies; in the common law it is an "unavoidable" life-saving risk using an unsafe biological product. The Department of Health, Education, and Welfare allows "minor" but no "substantial" nrsks to subjects in research. These terms are (probably wisely) not spelled out, of course, and if there were a scale of risk it would have to be stepped alongside a scale of benefit to be ethically signiflcant. Decisions involve choices-less of this for more of that. The only realistic strategy of medical research is to reach a more favorable ratio between the probable adverse effect of experiment and treatment and the probable adverse effect of disease. Ethical codes are moal traps "A man must judge whether an action is ethical or unethical in advance," said Marshall Walker, "hence he must try to predict the consequences(22)." Walker went on to describe what an ethical decision maker does: "He extrapolates his knowledge of the past to predict the future. This procedure is the domain of science. His classification of acts as ethical or unethical is as reliable as his scientific predictions of future events, no more and no less. Some ethical judgments will be as certain as, The sun will rise tomorrow'; others will be as uncertain as, 'The probability of rain tomorrow is three out of ten'." There are two ways to conceive of right conduct. In one view it means obeying and following moral laws already promulgated (by gods or churches or governments or hospitals or guilds or some other rule-making authority). The other view is to examine altemative courses of action to choose the one with the most good consequences. This is the basic ethical issue- whether one is consequential about one's obli- gations or committed to a priori moral rules. Advocates (they exist) of a priori or before- the-facts morality, if consistent, will actually say they must follow a rule even if the foreseeable consequences are bad (i.e., hurtful to human beings). The ethics of most scientific workers, fortunately for mankind, are conse- quential throughout, yet with no expressed code morality or codified conduct. The survey of ethics and research with human beings by Professor Katz and his colleagues(S) is conse- quential throughout, yet with no expressed awareness of it(23). Professional ethical "codes," so called but misnamed, are actually quite flexible in the sense that they consist of guidelines and stan- dards without fixed rules that allow of no exceptions. For example, informed consent is set out as a standard in U.S. government guidelines for the investigative use of new drugs but there is no way to absolutize it if conse- quences and situational variables are taken into account; therefore the official full statement is "except where they deem it is not feasible or, in their professional judgment, contrary to the best interests of such human beings(23)." If no discretion was possible and "the right thing to do" was prefabnrcated (thus ruling out moral decision-making. in effect) there would be no responsibility-only obedience. Unable to be Kantian, with categorically imperative rules, 107 J. Fletcher science and medicine act consequentially, for the sake of humaine results. Instead of "commandments," then, medical science needs guideline principles, and only as many as ethical practice requires. '"e scientist escapes lightly-instead of ten commandments only four," said Bentley Glass. He gves them: "to cherish complete truthfulness; to avoid self-aggrandizement at the expense of one's fellow-scientist; fearlessly to defend the free- dom of scientific inquiry and opinion; and fully to communicate one's findings through primary publication, synthesis, and instruction(24)." I would add a fifth: to have concern for all persons involved, not only subjects but investi- gators and prospective beneficiaries. To repeat an observation made in another place, I agree with a past editor of The Joural of the American Medical Association who "advised us succinctly to decide moral ques- tions according to the case or situation, rather than by universaliling rules and laying down categorical prohibitions. The wisest ethical method is situatlofal; non-dogmatic, flexible, particularized, value-oriented(25)." It was with this conception of ethics that Dr. Ingelfinger complained, after a National Academy of Sciences meeting on "Experiments and Re- search with Humans: A Conflict in Values," that some of the ethicists were moralistic. "Some philosophers .-. . insisted that the care of patients should be the result of categorical absolutes, that a balance of risks and beneflts should play no role. How abysmally ignorant of medical practice is such a position! It was all very disheartening(26)." The one-and-the-many tenson The so-called Nuremberg "Code" set out after the trials of ihe Nazi prison-camp experi- menters has supplied the core of current ethical considerations; ten baic pnrnciples-on consent, results otherwise unattainable, proportionate risk and benefit, animal pretesting, avoidance of harm, avoidance of' fatal effect, professional qualifications, the right of subjects and investi- gators to withdraw, termination if subject is in jeopardy, and stopping if fatal consequences are foreseen (except when the experimenters are also subjects). At the hearings of United States versus Karl Brandt(27) an American physician was asked: If a city is dying of a plague and you have a drug you believe could save the populace, yet it has never been tested in a human subject, and the Mayor says, "Here is a prisoner condemned to die and here is a man dying of cancer; try it out on them," would you do it? The doctor replied, "No," he would not. If he had agreed would he be right? If the prisoner and the cancer patient refused to be subjects could we justify "using" them anyway; can a cost-benefit or proportionate-good case be made for it? How weighty ethically is "the greatest good of the greatest number?" Obviously this utilitarian theory lies behind most of our legislation; it is the moral principle of legislation and laws in democratic societies. When we stop to think carefully we know that we cannot approve of sacrificing the many for just one, or even for only a few. Experimental science is risking "some lives to save more lives," and, in doing so, it does better than public safety policy, which knowingly sacriflces lives rather than spend the money for pre- ventive measures(28). When we are told in a parable that the Good Shepherd abandons the ""ninety and nine" sheep to the ravages of wild beasts in order to go off and hunt one lost lamb, it is obvious to all but those who absolutize all lives regardles of the consequences that this is immoral, unfair, unjust. It has no sense of proportion. (Unless, of course, the abandoned flock is in no danger, in which case the parable Is pointle.) Ivan in The Brothers Karamazov wonder If it would be justiflable to make all men happy at the cost of torturing one little baby to death. If, in the hypothetical case (What if. - .), the diseases and deaths of countless people hang in the balance (trade-off) then of course trading one for many would be right-a preponderance of good or evi, of benefit over cost, measured in terms of relative human values. 108 Ethical Conuidertions in Biomencal Research Involving Human BDingp To be "impersonal" in the sense of counting heads is not in any sense to be anti-personal or non-personal. It is being multi-personal. It is preferring severral or many persons over one or a few. Randomization of research subjects is still a very personal, very "human" procedure. The trees are not at all lost in the woods because every tree in the woods is a tree. To sacrifice the one for the many is to save many ones. The "greatest number" is not an abstraction; it is the sum and count one by one of real, particular, and personal individuals. Counter to Edmond Cahn's judgment, if the Pharaoh was wrong to spend the lives of many workingmen (slaves?) to build the pyramids it was not the loss of life that made it wrong; it was the poor balance of human life aginst piled stone(29). Walsh McDermott saw the tension of the one-and-the-many this way: "When the needs of society come in head-on conflict with the rights of an individual, someone has to play God . . . But the hard core of our morality will not yield to the approaches of 'Declarations' or 'Regulations,' for as things stand today such statements must completely ignore the fact that society, too, has rights in human experimenta- tion(30)." The ethics of medical care and medical research should see its problems broadly, social- ly, through a telescope-not just a microscope. We will have to stop the myopic and often irresponsible escape from the agony of ethics, which we try to do in shibboleths like "my patient comes first" and "first come first served," and "medicine is not a social service." These unethical gambits are based on the Aesculapian model, not on the model of Hygeia which is so much more appropriate to our highly interdependent modem world. It is perfectly plain that ethical judgynents are not simple; not black-or-white, either-or choices. It is also plain that decision makers, like it or not, are moral agents; value (ethical) considerations enter into decisions in every- thing, including research and investigative medi- cine. Ethics is a process carried out by which a chooser, according to perceived values, comes to a decision about what he ought to do in a certain choice situation. The more we know the better we can choose. Furthermore, if we are not radical egoists and individualists we will try to choose the good of the greatest number, the social interest. Our moral decisions then become matters of distributive or allocative justice-as in triage judgments. We have to calculate, count, measure. Just as Paul Samuelson and other economists use the tern econometrics, we can coin the term "ethometrics" (ethometry?)- moral responsibility requires a pair bond of value-determinations (classical ethics) and mathematics. Morality with a telescope, quanti- fying qualities. Determining risk ranges is an everyday prac- tice in medicine. Biological estrogen for post- menopausal treatment and synthetic estrogen in the oral contraceptive both carry a statistical margin of risk (of thrombo-phlebitis, pul- monary embolisms, breast and endometrial cancer). With the "pill" the figures are like this: 14 deaths per one million users compared to 228 deaths per million of non-users, from causes related to pregnancy and birth. This is a 17 times higher death rate for pregnancies than for prevention of pregnancy by means of estrogen. If these "metrics" are anywhere near correct, the estrogens offer a good trade-off of competing values, just as in severe cases good medicine uses antibiotics even though a marginal number of patients die of gram. negative bacterial infections. As for ethicists, they are not like the old-time doctors with a bag full of specific remedies; they do not have a "system" or armnwnentarium of specific moral rules, impera- tives, comnandments, prohibitions, and the like for specific questions of conscience. Their role, when moral problems arise in medicine and medical research, is more lice the con- sultant's or the monitor's or the "friend of the court." They can be asked in to see if they can find or think of anything else that ought to be taken into account besides what is already 109 110 J. Ptcet perceived by thou engaged in the work under wcrutiy. The) no toiOorce people for decision maks; queatlt askers rather than answr givers. But good quhtlor.askiang s the key to mswdr'gotting Nd dbeislon-mAing in medical rseutch and probably In anything else. 1. McDermott, W.: Opening Comments on the Changing Motrs of Biomedical Research, Annals of Internal Mdcine, 67, Supplemeht 7:39-42, 1967. 2. Lewi, S.: Afre*Iftilthi New Yotk, Harcourt, Brace and Company, 1924. 3. Final Report of the Tuskegee Syphilis Study Ad Hoc Advisory Pnel, Washington, D.C.: United Siates Depafthebht of lIealth, Education, and Welfare, 1079. 4. Curran, W.: LaU4edlcine Notes, The New England J;w of Medicime, 269:730-731, 1973. 5. Katz, J. et L: Expermentation with Human Beings, Ne' York: Russell Sage Foundation, 1972, pp. it".' 6. Flrth, R. Ithka Abovlutism and the Ideal Observer, PMsOupy and Phenomenological Research, 12a336-341, 1952. 7. Greenberg, tl.: Ethics and Nonsense, The New England Joutab of Medicine, 290:321-322, 1975. 8. Clouser, K.: Medice Ethics: Soen Uses, Abuses, and Limitatos, The New England Journal of Medicine, 293:384-387, 1975. 9. Ingelfinger, F.: Ethics and 14igh Blood Pressure, The New Eiug1and Journal of Medicine, 292:43-44, 1975. 10. Quoted in Waddft, C., SclnCe and Ethics, London, Goo. Alien and Ulnwin1942. 11. Langer, E.: Human Experinentation-New York Verdict Affirms Patietit's Rights, Science, 151:666, 1966. 12. Wolfensbeget, W.: Ethical Issues in Research with Humafabj.oI, Slenod, 135:47-51, 1967. 13. LIvingston, L Ppigtam Report on Survey of Moral and Ethical Aspects of Clinicl Investiga- tion, Mensorendum to t)itector, National institutes of libsth, 1Ioveinber 4, 1964. 14. Ingelflnser, F.: The Unethical i" Mdedicl Ethics, Annals of Internal Medicin, 83:264-269. 1975. 15. Niebuhr, R.: Mori man and IMmoral Society: A Study in Etics and Politics, New York, Scribners Sons, 1960, p. 171. 16. Jonsen, A. and Butler, L.: Public Ethics and Policy Ming, The Hastings enttt Report, 5:17-31, 1975. 17. Jonas, H.: Philosophical Reflections on Experi- menting with Humaxl Subject, Daedalus, 98:222, 1969. 18. Veresayev, V.: The Memoirs of a Physician, New York, A.A. Knopf, 1916, pp. 365.366. 19. Ecdes, J.: Animal Experientation versus Human Experimentation, IN: Definng the Laboratory Animal, National Academy of Sciences (ISBN 0-309-01 862-5), Washington, D.C., 1971. 20. Fletcher, J.: The Ethics of Genetic Control, New York, Doubleday and CQmpany, 1974, pp. 111-112, 188-202; V. Potter: Bioethics: Bridge to the Future, Englewood Cliffs, N.J., Prentice- Hail, Inc., 1971, pp. 69-82; 3. Bronowski: Science and Human Values, Rev. Ed., New York, Harper and Row, 1958, pp, 51-71. 21. Modell, W.: Hazards of New Drugs, Science, 139:1i80, 1963. 22 Walker, M.: The Nature of Scientific Thought, Englewood Cliffs, N.J., Prentice-Hall, Inc., 1963, pp. 153-156. 23. Federal Register, 321 :8753, 1967, and Code of Federal Regulations, 21:130-37, 1971. 24. Glass, B.: The Ethical Basis of Science, Science, 150:1258, 1965. 25. Fletcher, J.: Fetal Research: An Ethical Appraisal, Washington, D.C.: A Consultant's Report to the National Commission on the Protection of Human Subjects of Biomedical and Behavioral Resarch, National Institutes of Health, February 1975, p. 7. 26. Utr spra (14), 269. 27. Trials of War Criminals Before the Nuremberg Tribunals, Vols I and I1. The Medical Case, Washington, D.C.: U.S. Gdvermnent Printing Office, 1948. 28. Calabresi, G.: Reflections on Medical Experi- mentation on Humans, Daedalus, 98:387405, 1969. 29. Cahn, E.: Drug Experiments and the Public Conscience, IN: P. Talatay, ed., D)rugs in our Society, Baltimore, The Johns Hopkins Press, 1964, p. 255. 30. Utsupra(1),42.