Reprinted from ANNALS OF INTERNAL MEDICINE, Vol. 67, No. 3, Part II, September, 1967 Printed in U.S. A. A Geneticist Looks at Contraception and Abortion JosHuA LEDERBERG, PH.D. HE PAST 15 or 20 years have seen the "TD rrancmutation of genetics into bio- chemistry and the emergence of a new sci- ence of molecular biology. This discipline has greatly illuminated some of the most fundamental issues of human nature. It inevitably raises questions for that time when we modify the genotypes of human beings by principles already commonplace in the experimental genetics of microorgan- isms. Originally it had been my intention to discourse on these questions to contemplate how we might be able to cope with the issues that this awful knowledge which man has acquired might bring us. But in con- templating how I might discuss molecular human biology, it occurred to me that to dally on such questions would be an amus- 25 ing and engaging futuristic escapism. We might then have to chide ourselves for using these issues to avoid facing up to some very cogent and very present problems about which physicians and biological sci- entists are still not sufficiently outspoken * and which result in an untold amount of human misery. And further, unless we are able to deal with these contemporary issues in a humane way, we will never in the future be able to cope with the subtler problems of qualitative intervention in the finer points of human reproduction. We have been through an era in which mystical conceptions of human nature have discouraged the distribution of information about contraception and family planning. The earth is laid open to an unprecedented crisis of misery because of the reticence 20 or 30 years ago of many informed individ- uals to speak out soon enough, vigorously enough, demandingly enough to reach the position and policy we take with respect to family planning today. I would like to remind you that not very many years ago “contraception” was a dirty word; it was impossible to refer to contra- ceptive devices in public media. Yet I don’t have to remind this audience what the total, miserable consequences of the delay in the imparting of knowledge of quanti- tative control of conception have meant and mean now throughout the world. It is even possible that the world will not survive as a habitat of the human species simply be- cause of our reticence, because of our pusil- lanimity, in coming to face an issue about which every one of us here has long had all of the moral and biological facts. * This material was presented before the AMA’s. endorsement of abortion-law reform. 26 JOSHUA LEDERBERG Now we are approaching an era of reason- able policy with respect to family planning; contraception is no longer a dirty word or a furtive action. It is even respectable for the President of the United States to refer to it as an issue of public and social policy. These advances may barely rescue some part of the situation but only with extra- ordinary efforts in food production and economic adjustment to cope with the population pulse. The next issue of this kind is, I believe, in a state of transition quite comparable to the biomedical approaches to questions of family planning of 20 years ago. I refer now to voluntary abortion. I believe all of you are acquainted with the legislative crises that are cropping up throughout the coun- try over attempts to reform the savage laws that now concern this practice. As you know, there are at least 1 million unsanc- tioned abortions in this country each year at the present time. I am still dumbstruck that we countenance such a bootleg system, a facility available particularly to the well- to-do, the sophisticated, the well-informed, whereby they are able to evade the law, and the hypocrisy of the law, in dealing with this issue. This hypocrisy lies in the fact that doctors are sporadically brought to the bar of justice for the admitted prac- tice of abortion and in the medical hazards and the psychological strains that are so unfairly imposed on so many women in consequence of the present status of the law on this question. We do need the most con- troversial discussion of the law of gestation from the standpoint of public policy. This is not a simple issue. The consequences of drastic reforms of the law on this subject need to be very thoroughly worked out from the point of view of their impact on the quality of life of the community. I do protest, however, against allusions to the absolute right of the life of the un- born (which implies some absolutely unique quality of the fertilized egg compared to other tissues) and that this point is abso- Annals of Internal Medicine lutely definable as the start of human life. In fact, all of our fundamental knowledge of the main roots of biology, evolution, and development processes opposes this cata- strophic theory of human personality. The question “When does life begin?” is held to be a premise for a legal construction about when it is permissible to interrupt the proc- ess of development. There can be no an- swer to this question separate from the pur- poses for which the question is raised; you will get back exactly the answer you had already prejudged. For life is a continuum; if life had a be- ginning at all, it was an event that occurred some 3 billion years ago. About this we must be quite vague, lacking a precise defi- nition to separate the first living macro- molecules from the inorganic molecules that led to them. Since the establishment of effective deoxyribonucleic acid (DNA) molecules, there has been a continuous transmission of the spark of life from cell to cell, from DNA molecule to DNA mole- cule, with gradual changes during the evo- lutionary process. No more than a small percent of the total nucleotide composition of the diploid human nucleus differentiates the human being from the ape, or the monkey, or other primate species. During the evolution of the species there was no sudden emergence of human personality but the gradual accumulation of those ge- netic alterations controlling the develop- ment of the brain that in turn permit the development of humanity. We see the same process during develop- ment: The fetus is by no measurable cri- terion nearer to being a human being than the unborn ape or chick. Even the new- born infant must undergo further develop- ment to achieve the full measure of hu- manity. An operationally useful point of divergence of the developing organism would be at approximately the first year of life, when the human infant continues his intellectual development, proceeds to the acquisition of language, and then par- Vol. 67, No. 3, Pt. IE Suppl. 7, September 1967 ticipates in a meaningful, cognitive inter- action with his mother and with the rest of society. At this point only does he enter into the cultural tradition that has been the special attribute of man by which he is set apart from the rest of the species. I do not advocate a discussion of infanticide— a special intervention in the period between the delivery of the infant and the time at which he acquires language. We are all so emotionally involved with infants that this is in itself enough to create an inevitable and a pragmatically useful dividing line. To discuss the fetus during prenatal life as if he were a human being is merely to reflect the emotional involvement of that observer, according to a set of tastes not now shared by the majority. This should not be confused with any objective biologi- cal standard by which we can set up princi- ples of social order as criteria for the opera- tion of the law. If there were not such enormous in- humanity involved in the persistence of traditional points of view on this question, there might be little point in raising this issue. Tradition has to be given great weight. We have a reasonably successful social order based on our conceptions of the dignity of human life, and we must be extremely cautious about interfering with these. But I believe that the lay public is still not adequately aware of the facts and that the medical profession has simply not faced up adequately to the facts of which it is aware—that is, the hypocrisy that is rampant in the actual exercise of abortion in defiance of outdated law for a small, privileged segment of our population. I, therefore, submit it to you as a matter of conscience to help put this issue on the plane where it deserves to be discussed: What are the realistic consequences of re- vision of the law for human welfare in the light of your own knowledge of the con- A GENETICIST LOOKS AT CONTRACEPTION AND ABORTION 27 tinuity of biological development and evo- lution. The conditions of modern life are para- doxical: By sustaining impaired bodies medicine contributes to the postponement of the genetic load—the homage that must eventually be paid to natural selection as a means of eliminating deleterious muta- tions from the species. Natural selection can be a personal disaster if it entails the premature death or the incapacitation of a child or young adult. But differential mor- tality is merely the most grievous, not the most effective, avenue of constructive selec- tion. Differential fertility is perhaps the most innocuous, and contraception must play an important part of genetic policy here. When, however, a grossly impaired infant can be anticipated, genetic concerns for the health of the species concur with compassion for the mother and the other members of the family in supporting the need to make voluntary abortion available. New findings on the biological study of the early fetus open the way to the appropri- ate diagnostic tests and will surely play a large part in the rational control of human reproduction. Far from limiting efforts to have chil- dren, the availability of voluntary abortion should go a long way to encourage the gamble in risky matings, by putting the stakes under more effective anticipation. Such a policy represents the only humane reconciliation of the individual's rights of parenthood and social concern for the con- tainment of genetic disease. REFERENCES WituiaMs, G.: The Sanctity of Life and the Crimi- nal Law. Faber & Faber, London, 1958. Harpin, G.: Science and ethical values. Quart. Rev. Biol. 41: 47, 1966. LEDERBERG, J.: Experimental genetics and human evolution. Bull. Atom. Sci. 22: 4, 1966. Reprinted from ANNALS OF INTERNAL MEDICINE, Vol. 67, No. 3, Part II, September, 1967 Printed in U. S. A. Discussion (1) Medical ethics and etiquette—experimentation on humans—Federal clearance of drugs—self-experimentation—informed consent and legal lia- bility—stimulation of intelligence—“intellectual” drugs versus “mood” drugs—monstrous births and infanticide—genetic danger of nuclear testing —relaxation of natural selection—prisoners as experimental subjects. R. Leake: Now I come to the ques- D tions. I will try to keep one for each panelist as I go down the line unless we get into some kind of an argument, but I don’t think we will. Dr. McDermott: I must say that in pre- paring for this Colloquium I had occasion to read all those Declarations as well as the Hippocratic Oath. I was vastly entertained to see that “first things are first’ in the Hippocratic Oath in that the first part of it has nothing to do with the patient at all; it has to do entirely with the relationships of physicians to each other. Dr. LEAKE: It is important, I think, that we always make sure that we make the dis- tinction between medical etiquette—the subject of the older principles of medical ethics—and the fundamental moral prob- lems with which the public is concerned. We will turn, then, to Dr. Stumpf and his interesting discussion. The point that I’m raising here is in regard to the experimen- tation that he mentioned; he brought up the point that it is not possible to predict from animal experimentation what drugs will do in humans. Well, I’ve been working in this field for a long while, and my own feeling is that we can get a pretty good idea. But when it comes to experimentation on humans, I could ask, Isn’t a therapeutic procedure of any sort undertaken by any physician on any patient a form of experi- mentation in the sense that we can never predict absolutely what the outcome of the therapeutic procedure may be? 51 Pror. Stumpr: | agree that there is a dis- tinction between a patient and a subject, and I agree with your point that a physi- cian almost always is experimenting with a drug in relation to the particular patient. But the difference is that a physician is ex- perimenting on the patient with a drug that has been cleared, whereas (and this is the point that I have been raising) the sub- ject is being subjected to a trial with some- thing that has not been cleared. It may be that novel chemicals and drugs are used also in therapy, but the big distinction, I take it, is that, even in the case of using a drug that has not been thoroughly tested, the justification for it is the possible good it will do this patient in the context of a problem; whereas, when you give it to a subject, there is the question as to whether the possible side effects can justify its use. Dr. Leake: You have brought up a point, namely, whether the drug has been cleared. It is my opinion that judgment with regard to the use of any chemical agent for any purpose in medicine should be made by members of the qualified health professions and not by a group of bureau- crats. When we talk about clearance, I realize of course that it is necessary to have some consensus of judgment, but I believe that that consensus of judgment should be from the health professions. Pror. StumprF: I’m not aware that people who are unqualified are making judgments with respect to clearance. Now, I speak ob- viously as a philosopher who spends most 52 STUMPF, LEAKE, BURGER, KRECH of his time in a very delightful ivory tower, but the logic of it is rather clear. Two things have to be said here, and I don’t mean it to come out quite as abrasively as it will. In the first place, I’m not sure there would have had to be a bureaucracy if the issues hadn’t provoked it; and, in the second place, I have a feeling that Dr. Goddard * is, in fact, a doctor. Dr. Leake: He is, and he is an excellent man. But he is attempting, in my opinion, to regulate what I believe is an unsatistac- tory law or statute for this reason: that the law or statute implies that there is an abso- lute effectiveness or an absolute safety to every drug. There is no such thing. Pror. Stumpr: No, but the implicit drift of your argument would be that there should be no controlling of any kind; and I don’t think anyone in this room would want that. Dr. Leake: No, I didn’t say that. I ac knowledged the necessity for social control. Pror. StuMPF: Well, then, the goodness or the badness of it is yet a different ques- tion, but I think the issue that you have raised is whether there really should be technical organized supervision of this very delicate matter. Dr. Leake: And that is what I have advo- cated that it be—through the members of the health professions. The AMA abrogated their rights in the matter. Pror. StumpF: Are you suggesting that the government, as the government, ought not to have anything to do with this even though the government bureaucracy is staffed by physicians? Dr. Leake: No. Pror. Srumer: Then what is the issue? Dr. Leake: I feel that there is a reasona- ble way in between where it can be worked out without the difficulties that are arising now, especially in experimentation. But let * Dr. James L. Goddard, Commissioner, Food and Drug Administration. Annals of Internal Medicine me go on, if I may. How about self-experi- mentation. Pror. StuMpF: That’s a rather interesting thing in that the only code that I know of that touches on this is, to the best of my recollection, the Helsinki Declaration in which it says—I think in Section 5—that certain very dangerous experiments ought not to be undertaken except in those cases where the experimenter himself is the sub- ject. Dr. Leake: Remember, I tried to point out this is my own field, and, when one is dealing with chemicals for the first time, there is always a danger. I’ve had a lot of experience in this. In our laboratories out here we developed five useful drugs: divinyl ether for anesthesia, carbarsone for amebia- sis, Vioform® (iodochlorhydroxyquinoline) for amebiasis and bacterial enteritis, the amphetamines, and nalorphine, the antag- onist to morphine. In each case, no one of those drugs was ever used on anyone else first—on ourselves always. And I might say that in the experimentation in our labora- tory we have kept from coming to any use on any other human being except ourselves those drugs that did show in ourselves un- desirable effects. I think self-experimenta- tion is pertinent for those who are going to develop a new drug. Now to go on with my questioning. Turning to Judge Burger, may I ask a question that I think is of im- portance to all of us. What is the real sig- nificance of consent—whether informed or not? My point is this: Does consent absolve the clinical experimenter from liability for malpractice or for injury to either his sub- ject or his patient? Jupce Burcer: 1 know from talking to medical groups in the past and from long and intimate association with a great many members of the profession that it will never be possible for lawyers to explain really what informed consent means to doctors because it is a concept like that of the hypothetical “reasonable man.” That makes it difficult. The consent problem in experi- Vol. 67, No. 3, Pt. II Suppl. ?, September 1967 mental medicine, I would think, is not fundamentally different from the consent problem that the astronauts have with the U. S. Government. They're engaged in an enormous experiment, and recent events have shown how dangerous; the recent three deaths were ones that apparently were unpredictable. Yet it’s clear that these men knew the risk they were assuming, and that essentially settles the matter. If we could be clear on the disclosure, if the disclosure never holds back, and if it is articulated adequately, then the problem can be solved. Dr. Leake: Yes, but you haven’t an- swered my question. Does the consent ab- solve the experimenter from liability? Jupce Burcer: Well, I think what you're really saying is, does it prevent someone from suing you? The answer is no; nothing ever prevents anybody from suing you. Dr. Leake: I just wanted to make that clear, because a lot of physicians and a lot of hospitals think that once they have a consent signed by a patient everything is in order and they are not going to be sued; and they are surprised when they are. Jupce Burcer: This is a common atti- tude in the medical profession. But let me emphasize that there is nothing to prevent some of the ladies in the audience from suing anyone of us for breach of promise if we’ve smiled at them during the course of this session. You can always sue, but the adequately obtained consent with informed judgment—with the disclosure factor—will generally be an adequate defense in most of those situations. Dr. Leake: The point is that we should do everything we can to promote mutual trust and mutual confidence. JupGe Burcer: Right. Dr. LEAKE: This, then, is a matter of ex- treme importance in interpersonal rela- tions. I wish to turn now to Prof. Krech, if 1 may. He had a wonderful appeal to the hippy mystique, it seems to me. I think it’s important to consider this enriched psy- chological environment. We are certainly DISCUSSION (3) 53 in a tension-filed world. This does bring up plenty of problems. We all should get brains that will expand all over with this psychologically enriched environment that we're getting into. But I am interested in particular in some of the experiments that were quoted. I know something about ex- periments of this sort with rats and mice in maze learning. We did a lot of it when we were studying the amphetamines which are central nervous system stimulants, as are pentylenetetrazol and caffeine. The cen- tral nervous system-stimulating effects of many of these drugs have been studied quite exhaustively. I frequently used to tell my students, Certainly, caffeine is a central nervous system stimulant; it will promote association of ideas, but there is no guaran- tee that this association is ever more correct or accurate than that due to chance. One can say that coffee or caffeine tends to pro- mote a diarrhea of words and a constipa- tion of ideas. Now, when we were studying the amphetamines, we used pentylenetetra- zol as controls, and we could find no sig- nificant increase in rate of maze learning either with pentylenetetrazol or with am- phetamines or caffeine. All that I am point- ing out is that one can use all sorts of experiments, but one must evaluate those experiments. As has been brought out very clearly in this discussion, what applies at an animal level can be carried over to the human level only with careful considera- tion. Dr. Krecu: I venture to take the risk. I agree that man—and his brain—is bigger and perhaps even better than a mouse. The experiments that I cited were just two of McGaugh’s experiments—only two out of a whole series of about 10 years of experi- mentation over a whole range of drugs. But, despite his very positive and very exciting results (and, of the controls that you indi- cated should be taken, many have been taken), despite all the progress, I suspect that we are still in the Stone Age of this kind of experimentation. Add to that all 54 KRECH, LEAKE, MC DERMOTT, LEDERBERG Annals of the experimentation on the deleterious ef- fects of inhibitors of protein synthesis, the ribonucleic acid (RNA) experiments, and so on, and J think you can’t avoid the feel- ing that we are close to the verge of an important breakthrough (awful word!). I just want to try to anticipate what we're going to do when the breakthrough comes. I know that already several of the pharma- ceutical houses have on clinical trial a num- ber of drugs intended to speed up or facili- tate memory. These trials are being made on patients who are mentally retarded or senile. What the results will be, no one knows. But I would not bet against the project. Dr. Leake: This is all very important. In general, insofar as the central nervous system is concerned, it is much easier to find chemical agents that will inhibit in one way or another the activity of the cen- tral nervous system than ones that will im- prove or accelerate its activity. But very recently, as you know, magnesium pemoline was introduced by a former student of mine for the purpose of increasing RNA forma- tion. It works, apparently, in experimental animals; it has been tried in humans, not too satisfactorily. Dr. Krecu: It doesn’t work too satisfac- torily in animals either. I might make just one point here. I find in general that phy- sicians are familiar with mood drugs— they have been on the front pages. Physi- cians are not familiar with what might be termed “intellectual” drugs, and most of the exciting experimental work that is going on (as far as I am concerned) is with intellectual drugs. Now, it is important to understand that, to evaluate the signifi- cance of the current work with these drugs, one has to be sophisticated about psychol- ogy and behavioral measurement as well as about pharmacology. And I regret to say that most physicians and most pharmacolo- gists are naive and ignorant about the sci- ences of behavior. Internal Medicine Dr. Leake: Surely I will admit all this, but I also want to remind you that I did emphasize the distinction between mood and behavior; nothing exemplifies it more fully than the attitude or the way in which our hippies go about—their mood is ex- alted and wonderful; you can judge their behavior. Dr. McDermott: I gather that Dr. Krech has made the point that he likes it when the investigator is at least as smart as the drug. Dr. Krecu: By the way, we seem to be of the happy opinion that we can’t do any self-experimentation on mental retardates! Dr. Leake: No. Speak for yourself, Dr. Krech; I can’t. Dr. McDermott: Order! Dr. LEAKE: Now I'd like to ask Dr. Leder- berg an important question. This has to do with the matter of voluntary abortion and the right to die. Let me ask, Is infanticide justified in the case of monstrous birth? Dr. LEDERBERG: What I spoke to was not a moral judgment about the consequences of reforms in our law or in our attitude but to plead that they be examined in terms other than so-called “absolutes” with respect to the objects in question. The ques- tion of whether infanticide is morally jus- tified, I think, can only be answered by an inquiry as to the consequences of the intro- duction of this practice into contemporary society. I think it is possibly true—and this is the point that I believe should be de- bated—that to make it easier to kill a live- born infant may knock down other im- portant barriers to misbehavior on the part of our population. I think that before I would advocate killing even monstrous births, I would want to inquire what the effect might be on the standards of care of other infants, on the attitude towards child beating, and so forth. I hope I did not leave the impression that I regarded our tradi- tional attitudes or our traditions of care for human life in any casual fashion. Vol. 67, No. 3, Pt. II Suppl. 7, September 1967 Dr. Leake: No, not at all. I was not quite correct, perhaps, in emphasizing the posi- tive aspect of infanticide. But how about letting the monstrous birth die? In other words, how about making no positive effort to keep it alive? That also is a moral problem. Dr. LEDERBERG: J can only express now a judgment that is personal and one that I would not advocate strongly but that might provide the point of departure for a discus- sion of the issue rather than a conclusive statement. This would be that I would very much prefer that we anticipate as many of these events as possible, that we improve our scientific technique for prenatal identi- fication of monstrosities, that we do as much as we can to bring about the earliest possible detection of aberrations so that these genetic deaths can be made to occur at that period where they would have the least strenuous consequences for the other members of our society. That would still leave some monsters that are not detected before birth; my inclination with respect to them is that they may be such interesting objects for humane observation and experi- mentation that it may very well be worth making very great efforts to keep them alive once they have started to exist. But I think that one ought to do more than just lock them up in a warehouse or inflict them on an unfortunate family that doesn’t know how to keep them or how to deal with them. They ought to be regarded as exactly what you’ve described—monsters—careful study and observation of whom under the most humane conditions could teach us more about human nature. We have not taken this approach. Dr. Leake: Could I ask you one more question? What actually is the genetic dan- ger of nuclear energy? We’ve had a lot of conflicting statements recently. Dr. LEDERBERG: Well, I don’t think there is much conflict about the facts despite the DISCUSSION (i) 55 complexity of the subject. The issue that was raised 10 years ago was that, if nuclear testing into the atmosphere were to continue at the existing rate, there would be a gradual accumulation of radioactive effects on ge- netic material that would begin to match to a considerable percentage the already existing load. There is already an existing background of spontaneous mutation of es- sentially unavoidable exposure to cosmic rays and disintegration of potassium-40 in granite and so on, and this has been used as a commonsense measure of potential hazard. The existing pattern of fallout at that time, I believe, was calculated to be approximately 10% of the natural back- ground of genetic effect. I believe it true that we would like to minimize this to the least possible value, and a 10% increase over the preexisting background would have begun to reach the level that I think we would not want to see continue and cer- tainly not to increase. On the other hand, I would also point out that there are many, many measures that we could contemplate taking, or to which research could be di- rected, that might be expected to have the effect of reducing the background rate of mutation due to thermal and chemical mu- tagens. So, on the one hand, I would not be frantic about attempting to vary the background incidence of mutation within that realm of some few percent, but, on the other hand, I would be alarmed if there were any great increase—as indeed might have happened if atmospheric testing of nuclear weapons had continued to have increased. Dr. McDermott: Dr. Leake, I’m very anxious to get Dr. Dubos into the fray. I wonder if you could approach Prof. Meda- war and Dr. Starzl at this time. Dr. LEAKE: Sir Peter, in connection with the relaxation of natural selection to which you referred, do you think that this will occur even in the face of the increased ten- sions of our overcrowded planet? 56 LEAKE, MEDAWAR, STARZL sir PETER Mepawar: I don’t quite under- stand that question. I referred to the re- laxation of natural selection in the context of preserving the genetically unfit, those people who are genetically obliged to live in more restricted worlds than the majority of us. What I mean by the relaxation of natural selection is the preservation of life and the propagation of genes in people and by people who would otherwise have died. I think that this is a purely technical point; nothing very emotive turns on it. Dr. LEakeE: Finally, I will ask Dr. Starzl a question in connection with the matter of choice of subjects for human experimen- tation and the use of prisoners or soldiers or other people of that sort. Now, we don’t want to coerce anyone to become a human subject for experimentation. But supposing the individual volunteers and honestly vol- unteers? Isn’t he more or less in the same position as the medic at the battlefront who volunteers to go out after the wounded on the battlefield? I don’t think that the prisoner who may volunteer honestly and fully should be denied the opportunity to serve the rest of us; he may be wishing to compensate. I remind you that in Walter Reed’s studies on yellow fever death did occur—as it did later with Stokes and No- guchi. These were volunteers, but they also were self-experimenters. I’ve worked on prison volunteers—actual volunteers—at Ohio where the prisoners asked if they could be permitted to serve as subjects in Internal Medicine testing new drugs. They came to us; we didn’t go to them. Dr. STARZL: I didn’t mean to suggest that we had ever used a penal donor who was not to our advance knowledge a legitimate volunteer. I think they were all strongly motivated, most for the very high-minded social reasons you have suggested. We know for certain that there were certain others or at least one other who was proved to be motivated by the thought that he would be able to more easily escape from the hos- pital than from the prison. This, in fact, he did. I think that the problem is not that there aren’t legitimate volunteers in prisons but that in the absence of their civil liberties they might not be really free to make a choice. I think a 16-year-old minor who donates a kidney to his identi- cal twin also probably wants to do so, but he does not have the requisite legal protec- tion to be able to make his decision freely. I think we made a mistake in accepting prison volunteers, and I suspect that you probably did so also when you were in Ohio. Dr. LEakeE: No, I deny that; we did pretty well on it, and I think the prisoners en- joyed it. But, Mr. Chairman, might I take the opportunity here to thank the members of the panel for responding so directly and so clearly to these nasty questions that I have raised. The panel is an excellent one. Dr. McDermott: And may we thank you. We will now turn to Dr. Dubos for his challenge. Reprinted from ANNALS OF INTERNAL MEDICINE, Vol. 67, No. 3, Part II, September, 1967 Printed in U. S. A. Discussion (it) Permanency of moral values questioned—change of attitudes with time— social control of research—speeding up the law by educating the public— individual conscience in research versus social control—extension of educa- tion to influence intelligence—hazards of drugs for intelligence—pay and insurance for experimental volunteers—doctrine of assumption of risk— social determinaton of the individual conscience—the researcher's social responsibilities—care for quality of human life, the permanent moral value —some wisdom from outside science—individual versus statistical morality, an artificial distinction—three permanent values—absolute versus absolute inferences—the application of traditional, immemorial morality—summing up. R. McDermott: Thank you, Dr. Dubos. Would any members of the panel like to volunteer to start attacking the morals of each other or of our community? Prof. Medawar, do you have a question that you wish to ask? Sik PETER Mepawar: I would like to say, if I may, just by way of starting off the discussion, how very much I agree with Dr. Dubos’s questioning the permanency of mora] values. We tend to strike moral atti- tudes that are actually obsolete or are out of date in relation to what we actually be- lieve at the time. I'd like to give you an example of such a change of attitude. The question of the justifiability of abortion is not a scientific question, but it is a question to which scientific evidence is highly rele- vant, and, as the scientific evidence enlarges, so in fact do our opinions change. For example, a hundred years ago it would have been perfectly reasonable for a mar- ried couple to think that the child they conceived on any one occasion was a unique and necessary product of that occasion. That is to say, they would necessarily have the child they actually did have, if they had a child at all. And the child himself 61 is apt to believe this automatically. A child does sometimes say, rather wonderingly, that if his mother and father had never chanced to meet and fall in love and marry then he himself would never have existed. He does, however, take it for granted that, as they did in fact meet and fall in love and marry, they necessarily had him—him uniquely and distinctively. One of the things that has changed is the reali- zation from Mendelian principles that the actual child conceived on any one occasion is one of a million possible children who might perfectly well have been conceived on that occasion if the luck of meeting of sperm and egg had been otherwise: So the child actually conceived by any one occa- sion is conceived as a matter of luck. Some- times it is cruelly bad luck: A phenylketo- nuric (PKU) child may be born in the 25% of cases that would be expected if PKU heterozygotes marry. Why should we be vic- timized by this process of luck? We now have a new understanding of the process of conception and the way in which luck enters into it. Why should we regard our- selves as morally bound by the laws of chance to put up with the birth, let us 62 MEDAWAR, KRECH, BURGER, LEDERBERG say, of a monstrous child if there were some humane and sensible way of preventing such a thing occurring? Our attitudes have changed. Pror. Krecu: I would like to speak to another of Dr. Dubos’s comments. I wonder if we all realize how radical one of his sug- gestions is. It is to this effect: that the choice of our research problems—not only biomedical but all basic research—is no longer to be determined by the interests and preferences of the research worker alone. Rather, this choice is to be controlled by social needs, social priorities, or social values. And this, for many research workers, does represent a radical reorganization of thinking. I happen to agree with you, Dr. Dubos, so J am proud to be associated with you in this revolutionary position. But it ts a revolutionary position and one to which I think researchers would object— vigorously and violently—raising against us the old standards of “freedom” of research. JupcE Burcer: I have a feeling that the medical profession has had a tendency to overreact to some of the fears about law and lawyers and judges and juries. Admit- tedly, they have something of a problem as to juries because they are unpredictable. But the fact is that over the years, as was pointed out, our progress in the law is not so terribly glacial at that. I was perhaps overstating its slowness. But I also coun- tered by pointing to the changes in atti- tudes, and another one comes to mind. A hundred years ago the dissection of human bodies was forbidden in many places. That's all gone; it’s part of mythology now. A de- cision of our court recently has made the world safe for the town drunk: He may no longer be arrested, because it is not a crime to be a chronic alcoholic. He has to be picked up and put away, but he cannot be prosecuted and put in jail. Probably in due course the same thing is going to happen with narcotics addiction. Only within the last 18 months Congress has passed an Internal Medicine enormously significant piece of legisla- tion calling for the treatment—compulsory treatment to be sure—but treatment as an alternative to imprisonment, of narcotics addicts. All I intended to point out was that the law cannot lead these things. It can only respond. You must lead them, and you must take your case to the public, either directly or through articulate lay people who can argue your case for you. And when you do, I think the consensus of the people in this country will respond. Just as your medical research has had this fantastic rate of speed in the last 20 years more or less, you have forced the law to speed up. You have brought about swifter changes in public opinion; and public opinion, in turn, is what leads congress- men and senators to act. So 1 would not be disheartened, and I would think that the medical investigators perhaps should lose some of the fears they have about going ahead just so long as the medical profession is prepared to control and denounce the irresponsible investigator and the irrespon- sible kinds of things that occurred in some of the disasters that I mentioned. Dr. Leperserc: At Dr, Krech’s request, I will add a point to the one I was previ- ously going to make and will comment on what he said. I didn’t take Dr. Krech’s re- mark as implying a large degree of social control of research; he was appealing to the social conscience of the individual investi- gator that he, the investigator, perhaps pay more attention to the requirements of his community in whatever way he could find it within himself to do. And this I heartily applaud. If Dr. Krech was stating that he agreed with the principle of social control of research—which I think he was saying— I would want to express my vehement dis- approval. I would regard this as an utter disaster and one from exactly the point of view of attempting to reach the same aims that he has in mind. The implication that social control or any rigorous effort to re- eee iliac + Vol. 67, No. 3, Pt. II Suppl. 7, September 1967 discipline research should be vested in regu- latory bodies such as the Councils of the National Institutes of Health would require a concentration of social wisdom in a few individuals in exactly the area where we can least expect it in terms of innovation and creativity.* No one else can possibly know what ideas I might have if I am left to the freedom of my own choice of investi- gation in an area whose social consequences are not yet apparent. In this matter I think there is an enormous distinction between an appeal to conscience and an imposition of control, (Applause.) I am beginning to wonder what was wrong in what I have said. I shared Dr. Krech’s amusement in the parlor game “what if” as applied to the ex- pected appearance of chemical innovations in the development of intelligence. And by the way, I fully agreed both with his ex- pectations of the occurrence of a break- through in this area and with his statement of the time scale on which it is likely to occur (assuming that psychologists do learn some of the tricks of proper behavioral con- trol in the conduct of their experiments). My only riposte is that the change in avail- ability of higher education is a social ex- periment that I believe to be strictly analo- gous to what he suggests may come about with the availability of chemicals to in- fluence intelligence. Until rather recently, higher education was a resource open only to a strictly limited segment of the popula- tion—the economically affluent. Its avail- ability to a wider variety of social groups and different countries represents exactly the kind of experiment that he was postu- lating would come from the introduction of drugs that influence intellectual compe- tence. I am not greatly alarmed about any of the possible outcomes of either of these two experiments. I believe there should be * Since the Colloquium was held, Dr. Lederberg has accepted an appointment to the National Insti- tute of Mental Health Council. DISCUSSION (ii) 63 the maximum availability of whatever re- sources we have that can augment man’s most human attributes for the use of his own intelligence and cooperativeness with other individuals. There is a “what if,” though, that we didn’t raise concerning, particularly, some of the drugs that have already been investi- gated, namely, their hazards. It seems to me very unlikely that we are going to have it so easy that a chemical will be found that will improve intelligence and will have an unambiguously favorable effect or a neutral effect on every other aspect of human per- formance. In fact, there are some individ- uals in whom the very increase of intelli- gence represents a hazard, sometimes even to themselves. But that is not quite what I had in mind. I think any drug that has this kind of effect on the central nervous system will almost certainly have a risk at- tached to it for some individuals. We then face the nice question, Is an increase in humanity, a general increase in IQ, worth taking some risk with respect to the per- formance of this individual? I would like to make a general remark on the whole issue of medical experimen- tation. I think the law is properly alarmed at a situation where individuals face the risk of becoming “bamboozled” into giving up, without evidence of appropriate con- sideration, an important value, namely, their life or health. And this is why, of course, one has to be so touchy about in- formed consent because it seems unreason- able to expect that an uncompensated individual or an individual whose compen- sation is ambiguous will in fact respond so altruistically. The law is suspicious of al- truists and properly so. I have an answer that I think deserves to be explored. Then why don’t we pay medical volunteers? Why don’t we establish some level of compensa- tion for risks incurred in the same way that, to a degree, we pay firemen and police- men because of the risk they take on our 64 LEDERBERG, BURGER, KRECH, ELKINTON, STUMPF behalf in their hazardous occupations? To a certain extent we grossly underpay them; we even pay our servicemen for the risks that they undertake on our behalf in mili- tary engagements. You may think that this would be an economic burden that we cannot afford to pay. But if we paid medi- cal volunteers at actuarially sound rates and if we bought insurance against the hazards that might accrue to them, this could only have a humane effect. I think we should consider the whole question of whether, if there has been an ample ex- change of information between the physi- cian or the hospital and the subject of research, we would not have a much better precedent and an understanding that a fair contract had been made. I would like to open this question for legal and lay con- sideration. Jupcr Burcer: There is historical prece- dent, as I suggested earlier; for lawyers, you know, can always find precedents for some- thing cushioning the unhappy consequences of medical research. A couple of hundred years ago people who worked in the mills and the mines were subject to what was called the “doctrine of assumption of risk.” They took the risk, and if they got killed or maimed, they were on their own and often went to the county poorhouse whether it was in England or in early America. Dr. Lederberg has suggested money payment for taking the risk. Perhaps this should not be compensation in terms of paying a sub- ject for undergoing the experiment but rather in terms of providing a broad-based fund, financed in any one of a dozen ways and geared to the NIH grants for medical research, by which the victim of the un- successful experiment—the person who is maimed or injured or killed—is covered just as is a coal miner or another workman who is paid a compensation when he is injured, without reference to negligence. This would take this whole area of experi- mental medicine out of the realm of negli- Internal Medicine gence and malpractice. This is a possibility that some of your fertile:minded medico- legal people might do well to think about. Pror. Krecu: In the first place, we do have a precedent. We have a fund now, do we not, for the victims of a poor experi- ment—our economic society; this fund is called “social security.” But that is not what I really wanted to discuss. I want to go back to Dr. Lederberg and his unhappiness at the applause he drew. I think I know, Dr. Lederberg, what was wrong with your statement that drew the applause. It was your easy distinction (which I find very dif- ficult or impossible to make) between “so- cial control” and “individual conscience.” I think that there is nothing so socially determined as a man’s private conscience. Now, one speaks of the doctor’s “personal” conscience and his attitude towards his pa- tient. But these very attitudes and ethics were built up from the doctor’s very first day of medical school. He was taught what were the “correct” attitudes. The doctor's “individual conscience” was very much so- cially shaped and is very much socially controlled. There are various ways of so- cially controlling the basic researcher also. What do we teach our research people? Do we teach them to seek truth for its own sake and to pay no attention to the effects of our research on society? Do we teach them that society will somehow take care of the effects and that it is none of the scien- tist’s business anyway? He must merely dis- cover the truth? If we teach that, then we are inducing one set of social attitudes or personal conscience or “scientific ethics.” But this is a set of attitudes that I find, at this stage of the game, to be medieval at best. Another position would be deliber- ately to teach the basic researcher that when he goes into the laboratory he continues to carry with him all of his social responsibili- ties. When he takes off his “civilian” coat and puts on a laboratory coat he does not shed these responsibilities. If we taught him Vol. 67, No. 3, Pt. I Suppl. 7, September 1967 this, as deliberately as the medical student is taught his ethics, we would produce sci- entists with a different (and in my opinion, a better) set of “personal” values. That is one form of using social control—inducing the proper attitudes. Let me now mention another kind of social control. We all apply for money from the federal agencies. Money has been the greatest invention for the pro- motion of research in the last 30 or 40 years—government money. And who gets the government money? Obviously someone makes decisions about that, and his deci- sions are not based purely on chance. This is another area of social control that has been made without much thought. Perhaps we should do some thinking about this form of social control, too. But in any event, Dr. Lederberg, I fail to see the dis- tinction between ‘“‘an appeal to conscience” and an “imposition of social control’—a distinction that, when you merely stated it, brought down the house with approving applause. Dr. ELKINTON: I can’t quite let Sir Peter and Dr. Dubos go unchallenged over their delineation of moral standards as shifting sands without making a comment. And I think that this comment applies both to individual morality and to social morality. It seems to me that what we have been talking about, and what we all are inter- ested in, is enhancing the potential quality of human life. This is so whether we are talking about the human life of one experi- mental subject or one patient or a whole population. Perhaps we have acquired some wisdom down through the ages from out- side the boundaries of science—wisdom as to what constitutes, and what kind of action Jeads to, goodness, truth, and beauty in human life. At the core of this wisdom lies the general concept that to care for oneself alone is not as likely to enhance the quality of one’s own life as is activity directed out- side oneself, that is, care and consideration for the quality of life of others. These are DISCUSSION (ii) 65 moral insights that we tend to look on as old-fashioned but that I think we cannot write off entirely. Let us realize that, as our knowledge and insights accumulate in both science and the humanities, we should be much better able to predict what actions on our part, as individuals or as a society, are going to affect the quality of life of that as yet unborn fetus or of that over- expanding population in an underprivi- leged country. I do believe that there is an absolute common denominator underlying our moral judgments, namely, concern for the quality and dignity of human life. Pror. STUMPF: In that connection I want to comment on the distinction that Dr. Dubos made between individual morality on the one hand and statistical morality on the other. I think I saw the spirit in which he said this, but I genuinely feel that this is an artificial distinction because, in the last analysis, when you talk about the great- est good for the greatest number, you are still left with the question, In the name of what is this called a good for anyone? It has to be defined as a good for someone in order to be a good for many. I am sure you recall that this was a nineteenth century philosophy that was worked out mathematically by Jeremy Bentham and later on by John Stuart Mill. This is the utili- tarian philosophy, and it usually is stated in terms of the greatest happiness for the greatest number. Then you have to define what you really mean by happiness. So finally you are driven back to some inter- pretation of what it means to be a human being and what is good for each individual. And in this sense I have some concern with your stating that probably we should have had a theologian speaking here today and at the same time saying there are no moral absolutes. This in itself is rather an in- teresting combination of ideas primarily be- cause I think that we are not all that much in the dark regarding morality, whether it be individual or social. 66 STUMPF, MEDAWAR, MC DERMOTT, WRIGHT My comments are made on the assumption that there are at least three virtually univer- sal and permanent values. The first major value is truth telling and, with it, every- thing that is involved with respect to what we think of another person. I remind you that the possibility of a lie depends on giv- ing the impression that you are telling the truth. It’s a rather interesting point—you can’t lie unless you affirm the value of truth. The second permanent value is ex- pressed in the saying that we ought not to willfully injure someone; the third is that we should not take what is another man’s. And this, of course, is especially pertinent to our discussion here today, for what be- longs to a person more than himself—his body and his consciousness? I want to underscore your comment— which bears on many other comments here —-that medicine is not autonomous. This is the moral point I would want to make. I think the drift of the discussion, the drift of your comments particularly as well as of mine, is that science will not generate its own values, that somehow we have to bring to them the consciousness and de- liberate power of the human mind. I feel much happier in dealing with simple moral insights than with a system for the reason that you mentioned, namely, that there is a shifting complexion to our problem as we get more information. I take it that one of the reasons for the Vatican Council is to discover ways of getting out of the box formed by absolutes, or getting out of a commitment to a certain formulation of an absolute. I believe in some absolutes and I think you do too, but I think that what we feel uncomfortable with are absolute inferences from these absolutes. Sir PETER Mepawar: I wanted to make a comment on Dr. Elkinton’s point: his warning that we must not make too much of the changing standards of morality. Cer- tainly we cannot neglect what one might call traditional, immemorial wisdom. I do Internal ‘Medicine indeed agree with him. I think we ought to remember traditional wisdom more often than we do when we strike moral attitudes about problems like the problem of abor- tion. The fact is, we do treat the fetus quite differently from the way we treat the newborn child. For we don’t in fact bap- tize miscarriages; we don’t in fact hold fu- neral services for them. We do not regard every menstruation as a culpable depriva- tion of human life. I think that over mat- ters like this we should revert to a tradi- tional and common-sense morality that does in fact make a distinction between the fetus —-particularly the early fetus—and the new- born child. Dr. McDermott: I shall now proceed to close. Interestingly enough, particularly in this last three quarters of an hour, there has been a very constant thread running through the discussion to the effect, first, that morals are a reflection of culture, that culture is in constant evolution, that one cannot have laws until the attitudes of the society are there to back up the laws, and that there is something called a public good. Whether that public good is no more than the sum of the individuals “goods” is a point that Prof. Stumpf and I could hire a hall and debate. But this is obviously a public good of some sort for, if there are no social priorities, there is no ethical justi- fication for clinical investigation or other biomedical research that conceivably might put an individual at risk. 5o much for this common thread. But above all, I return to a comment made by Prof. Lederberg at the beginning that struck me as being really the text of our Colloquium today. His phrase, “known the pain of the consequences of his actions,” is the text that is running through everything that everyone has been speaking about. And our problem is that today we are so very much more able to see this linkage between our actions and their con- sequences that we can never really free our- Vol. 67, No. 3, Pt. IL DISCUSSION (ii) 67 Suppl. 7, September 1967 selves from anguish whether we act or choose not to act. I am convinced that it is this that has given rise to this extraordi- narily fine presentation this morning for which, on behalf of us all, I wish to thank the participants very much. Dr. Wricut: On behalf of the American College of Physicians I should like to ex- tend our deep gratitude to those who have contributed so generously to this remarka- ble intellectual experience. Thank you all very much.