 Thank you, thank you. Please listen to these announcements. After this session, coffee will be served on the Mall beyond the Union at the center of the campus. A nice area, please enjoy it. I remind the physicians of the continuing education credits and that they should sign up if they haven't done so. Again, I repeat an earlier announcement that people who have no banquet tickets tonight may still enjoy June Goodfield if they come to the three crowns room around 8 p.m. when she will give her lecture. The three crowns room is at the canteen end of the food service building, up the stairs and to the left. There have been some scattered requests about issues related to heroic treatment, medical care costs, and the immediate next morning problems that come up. I want to explain that we made a deliberate choice early on in our deliberations in the committee to focus on the beginning of life issues and not on the end of life issues. However, these are pertinent questions and immediate and difficult questions for many people in the audience. If you have and will be willing to write a specific question, we will take a look at them during the break after this session and spend some time in the closing panel on such issues. The focus on the beginning of life and on genetic engineering was deliberate, not exclusive of other beginning-of-life questions such as genetic screening and genetics counseling and the care of premies and so on. But we believe in our committee that ethics is an anticipatory discipline and that we need to look ahead before we get crushed by the difficulties. And so one of the reasons that we have been focusing on problems that look more remote is that we need to think ahead about them. And they aren't as remote in time as we sometimes think. So I want to explain why the focus was where it was. It's not an apology, just an explanation. I'm very happy now to present my colleague in the biology department from which so many of our questions are arising these days, as has been pointed out, Professor of Biology, Myron Anderson. And he will introduce Clifford Groobstein at this time. Clifford Groobstein is a Professor of Biological Sciences, which I was happy to see, and Public Policy, a title which may seem a little unusual to many of us. However, a brief look at the development of his career may make this combination a little more meaningful. He came on the academic scene in the first half of this century, completing his graduate studies in embryology at UCLA in 1940. At this time, his field embryology and another area of interest to him genetics were rather divergent, both in interest and methodology. However, some common ground was appearing and bridges between the two were forming in the areas of developmental genetics and biochemical embryology. Through some foresight on his part, he kept an active interest in both, apparently anticipating some reunion. It occurred in the late 1940s and 1950s with the beginnings of molecular biology and a description of the molecular basis of heredity, DNA, and led to numerous findings. Of course, some of those have been discussed in this conference. Building on some of these new methods, Professor Grobstein continued to develop an active research career in embryonic development that gained for him international recognition and respect, evidenced by his being selected for the prestigious Brachet Award in Developmental Biology in 1969. During a portion of his tenure at University of California in San Diego, which began in 1965, he was Dean of the School of Medicine and Vice Chancellor for Health Sciences. And it was during this involvement in biomedical administration that he developed a great interest in the role of science in the genesis of public policy. Two areas of special interest were the controversies surrounding recombinant DNA and external fertilization and implantation of human embryos. These formed the basis for his last two books, a double image of the double helix and from chance to purpose. In these, he deals with serious issues that have been raised as a result of the rapid generation of new knowledge and an increasing capability for deliberate and direct intervention in hereditary and reproductive processes. He states that in the past, humans have made many choices without awareness or concern about the consequences. Having long been an environment-creating species, we now face the issue of becoming a self-creating species. Should we be plotting long-term directions? Should desirable directions be defined and by whom? Is public health and welfare threatened? Does research itself need greater public regulation? These are just a few of the questions that he has addressed in his writings and that were used in the planning of this conference. Thus, he has been playing a significant role at the interfaces among advances in biotechnology, scientific discovery, and especially during recent years, the development of public policy. Another interesting thing for me is that each quarter, he shares this enthusiasm for the topics that we've just mentioned and others, usually in interdisciplinary courses taught at the undergraduate level. I present to you Clifford Goldstein, who will address us on the topic Manipulating Life with a God-Satan ratio. Thank you very much, Mike, for those kind and accurate words. I feel a little like the voice of anti-climax because after the erudite and sparkling discussion this morning of the grand themes that constitute the background of what we're discussing, I intend to refocus us on what I think is not altogether mundane, but nonetheless, the more specific kinds of questions that we face at the present time with respect to public policy in the area that we are discussing. This conference is devoted to the implications of manipulating life, particularly human life, manipulations that may arise out of advances in biomedical knowledge. The conference title calls special attention to our human responsibilities in connection with such manipulation or intervention. I shall focus on new and prospective reproductive interventions that have been the subject of recent agitated debate. Of course, the range of prospective reproductive interventions is far wider than I can cover in this brief talk. I've decided, therefore, to concentrate on external human fertilization, gene transfer, and the possible intersection between the two that has generated special concern. These matters, of course, have come up in earlier presentations. Let me first briefly recapitulate what we mean by these terms. External human fertilization is often referred to as in vitro fertilization, abbreviated IVF, meaning that the external process is carried out in glass laboratory dishes. Egg and sperm obtained from a couple unable to conceive naturally are combined under carefully controlled laboratory conditions. Fertilization and subsequent development of the egg are confirmed microscopically. And in the standard medical application, the early embryo is transferred back to the uterus of the egg donor. In more than one in 10 clinically reported attempts, pregnancy and normal birth ensue. It is estimated that well over 150 babies now have been born around the world as a result of the procedure. Gene transfer, on the other hand, is not known to have been successfully applied medically, but its clinical potential has been widely discussed, as you have heard. It is the possible outcome of the past decade of progress in molecular genetics. DNA segments containing a single gene plus its control elements can be isolated and inserted into laboratory-cultured cells. Under suitable circumstances that are still subject to further study and clarification, the inserted genetic material is combined with that of the recipient's cell and is passed on to daughter cells. The incorporated gene can be expressed in the formation of its normal products. That is, it introduces new hereditary properties into the recipient's cell. In a few instances, such genetically altered cells have been returned to whole animals of the species of origin, thus conferring on these whole animals the altered cellular traits. The clinical application that is most clearly seen for such transfer of hereditary defects is to sickle cell anemia and other diseases due to genetically abnormal hemoglobin. Afflicted individuals have two defective hemoglobin genes in their blood-forming cells. Since normal human hemoglobin genes can be isolated and transferred, the idea would be to introduce these into the blood-forming cells of a patient's bone marrow. If successful, the modified bone marrow cells would give rise to normal blood cells rather than defective ones, hopefully curing the disease through gene therapy. With this to work, it would cure the disease in the afflicted individual, but would not change the chances of passing the disease onto offspring. This is because the cells that normally give rise to eggs and sperm become a segregated lineage, early, very early, in development. Changing the heredity of bone marrow cells does not alter heredity in the cells that give rise to a new generation. If the objective is fully to eliminate the disease, not only in an afflicted individual, but in descendants, the change must be made in germline cells that give rise to the gametes, eggs, and sperm. Now, this is the point at which the paths of in vitro fertilization and gene transfer may intersect. In the IVF process, early human embryos are, for the first time, accessible to observation and intervention. In fact, mouse embryos of a similar early stage have been subjected to gene transfer, and in very early and still limited results. The transferred gene has shown to be present and working, not only in the adult mice that are derived from the treated embryos, but in a small percentage of the generation they give rise to through reproduction. The objective of this line of research is not clinical application, as it is carried out in mice. But the production of mouse strains in which gene operation and control can be more effectively studied. Nonetheless, if fully validated and raised to the levels of effectiveness and safety demanded for human application, these efforts could lead to a first direct human hereditary intervention in the intergenerational sense. Commentators on these developments and their implications have frequently raised the question whether the physicians and scientists who are involved are playing God. This is not only because of possible conflict with some religious teachings, but because of the unprecedented aspects of the interventions in previously inaccessible and little understood processes. I share with these commentators their sense of the profundity of the issues. However, I believe that the image conveyed by invoking the concept of playing God is not helpful as a guide to solution of the serious policy questions raised. It exacerbates differences among us and makes more difficult the pluralistic accommodation that is essential in a society that respects and protects religious and other individual freedoms but seeks consensus in its public policy. Before saying more about the topic itself, I should like to recount some personal history that bears on my own perspective with respect to these matters. I have been involved in some degree in three of the major scientific, medical, and policy currents of this century. The first is the explosive development of the biomedical sciences, of which the new potential for human reproductive interventions is part. My activities as a bench scientist were dominated by this biomedical explosion from the time shortly after the Second World War, when I joined the staff of the National Cancer Institute as one of the very early NIH postdoctoral research fellows. The second major current is the development of nuclear weaponry based upon advances in atomic physics. Nuclear weaponry was the subject of bitter controversy in Washington circles when I arrived in suburban Bethesda in the late 40s. I was fresh from helping train combat crews for B-29 bombers, the delivery vehicles for the two primitive fission bombs that devastated Hiroshima and Nagasaki. My military station for much of the preceding years was within easy drive of Los Alamos and Alamogordo, of whose operations I knew little at the time. However, in post-war Washington, I found myself on the fringes of the climactic policy debate over whether to develop the super, the hydrogen bomb. Like many scientists of my generation, whether or not participants in actual weapons development, I regard the bomb as a constant and overwhelming moral and political challenge to scientists and non-scientists alike. Nothing else rivals this challenge to national and international security. The third current to which I'd like to refer is the tightening circle of interaction among science, technology, and public policy, an interest of mine that andedated the Second World War and has become my focal academic activity in the past decade. The sharply enhanced capability for purposeful manipulation of human reproduction is but the latest of the dilemmas presented to public policy by advancing scientific knowledge and derivative technology. Only through understanding of the close linkages among science, technology, and policy can measures be found to meet our human responsibilities in manipulating life. I want to examine the concept of playing God from this policy perspective, beginning with the meaning it appears to have for those who use it as an expression of concern. What is referred to, of course, is the scope of the human role relative to the role of God in governing the human experience. Conceptions of the nature of God's role vary widely, both over cultural history, among existing religions, and in secular society. The common religious assumption is that the human role is far more limited than that of God with a distinct delimitation between the two. Human activities that penetrate the boundary are not only sacrilegious in themselves, but pose a risk of bringing down unanticipated and unwanted consequences. Thus, the general secretaries of the National Council of Churches, the Synagogue Council of America, and the United States Catholic Council in a joint letter to the president on June 20, 1980, said, quote, we are rapidly moving into a new era of fundamental danger triggered by the rapid growth of genetic engineering. New life forms may have dramatic potential for improving human life, whether by curing diseases, correcting genetic deficiencies, or swallowing oil slicks. They may also have unforeseen ramifications, and at times the cure may be worse than the original problem. History has shown us that there will always be those who believe it appropriate to correct our mental and social structures by genetic means, so as to fit their vision of humanity. This becomes more dangerous when the basic tools to do so are finally at hand. Those who would play God will be tempted as never before, end of quote. The intent of the general secretaries was to have their concerns explored within the federal government. Two years later, the president's commission for the study of ethical problems responded in its report entitled, Splicing Life. The commission noted that, and again I quote, while religious leaders present theological bases for their concerns, essentially the same concerns have been raised by many thoughtful secular observers. The examination of the various specific concerns need not be limited therefore to the religious format in which some of the issues have been raised, end of quote. Having examined the several meanings that might be attached to the notion of playing God, the commission concluded that none justified prohibition of continued research in the area, but that the issues are consequential enough to warrant a mechanism for continuing oversight. Several months later, however, a broad group of prominent religious leaders specifically called for prohibition of genetic transfer into human germline cells. That is transfers that might have consequences in future generations. What these activities clearly do is to indicate that there continues to haunt us the issue of genesis or creation. Bible-based religious groups generally view God as the creator of natural order. Humans are part of the creation, but are transgressing when they seek to intervene in the inner workings of the natural order. In particular, they are transgressing when they intervene in human beginnings, nature, or destiny, because these are matters of God's special concern. In fact, of course, there has been steady nibbling at the edges of this religiously defined sacred province. People have been meddling in natural processes since they became people, meaning that the human sphere for intervention in the natural order has been enlarging relative to the divine one. Along the way, they have been recurring anxiety and controversy with repeated admonitions and dire prophecies from the protectors of the divine role that each new transgression goes too far. Nor have the warnings been without support in experience. Many human interventions in the natural order, undertaken with the most beneficent intentions, have had unanticipated unfortunate consequences. There has been much dispute in recent years over the net gain of our environmental health and even economic interventions. Many voices call for a respite, for time to draw breath, to evaluate, to adjust to what already has been wrought, even permanently, to let well enough alone. It is in this context that the charge is heard that scientists are now finding new ways to play God. And at this very time, in some of the most deeply sacred and private processes of human existence, the charge was heard in the middle 70s when expanding knowledge of the nature and hereditary role of molecular DNA gave clear indication that a potential was being created to alter the heredity of human cells. It was repeated at the turn of the decade in the clinical success of external human fertilization. Itself, an unprecedented intervention in a previously sacrosanct area opened a window for still further interventions in human development. Between the two, a model was presented in laboratory animals for limited alteration of succeeding generations. The advent of this potential new age of intervention seemed close to the ultimate in arrogant encroachment on divine prerogative. It was this that led the general secretaries to call upon the president of the United States to provide careful assessment of the morality of new biomedical technologies that might be on the horizon. Clearly, a charge of playing God is less heinous than a charge of playing Satan. To play God is by intention at least to seek benefit. It would not be God-like to be malevolent. Foolish arrogance, not malevolence, is what biomedical scientists are charged with displaying. But what of their colleagues, the physicists, who produced the atomic bomb in the 40s with full understanding that the purpose of the effort was military? Were they not playing Satan? J.R. Oppenheimer himself acknowledged that the physicists had come to no sin. Was the whole episode not typically satanic, with its early rationale of benefit by beating the evil Hitler to the punch, followed after the collapse of Hitler without resort to atomic bombs, by the unleashing of the holocaust upon the Japanese? Is the scenario not now obviously satanic when possessors of nuclear weapons, weapons grown mightier and more numerous, hold the entire world hostage on a knife edge of mutual deterrence? Were the physicists of mid-century not playing Satan? At some point, however, one must ask whether such dramatic but simplistic portrayal of complex social decision-making really is useful. Albert Einstein and Leo Zillard played key roles in getting the attention of President Franklin Delano Roosevelt, an essential step to the launching of the Manhattan Project. Both were peace-loving men who labored mightily after Hiroshima and Nagasaki to constrain further development and use of nuclear weapons. What do we gain by regarding such men first as agents of Satan and then of God? Is it not more to the point to say that they were human beings, seeing the matter first in one context and then in another as circumstances changed? Did the travail of JR Oppenheimer stem from his being a double agent of God and Satan or from the conflicted structure of his own ambiguous, self-chosen role? What understanding of any of these people or of the great issues they face is provided by portraying them in the rhetoric of a medieval morality play? Do we not strike closer to human responsibilities by facing as our own the choices between moral alternatives? Casting aside masks culturally created to displace responsibility to some benign or malign higher authority and power, is it not time, past time, to accept that it is we who should improve the God-Satan ratio of our own behavior? The central fact is that our growing options and powers have increased to levels that force attention to human responsibilities that once were assigned to the gods. We as human beings have altered the face of our planet. We unleashed and in some measure now control the primordial power of stars. We have dispatched vehicles and messages beyond the solar system. We may now be approaching capability to manipulate the substrate of our own genesis. What hangs over us as a new millennium nears is not so much sacrilege as anxiety, the dread that we, or more especially others of our fellows, may not be able to match knowledge with wisdom. It is indeed an epical challenge. I submit, however, that a calm retrospective look at the events of the past decade provides some evidence that we are beginning to beat out a path to wisdom in this area. For example, we have moved through the acute anxiety attack that followed the advent of DNA recombination in the early 70s. The anxiety then fixed on biohazard, the possibility of generating new plagues and pestilences through inadvertent release of altered organisms from the laboratory. Thanks to the principled approach of scientists most directly involved and then to others, risk mitigating measures were adopted that allowed for political and social adjustment to the new realities. The process is still going on with broader and broader issues that earlier were avoided, now being seriously addressed. There is no better example of this broadening than the matter of possible deliberate clinical application of gene transfer. How difficult is this issue in terms of appropriate policy? It falls into two parts with a transitional or gray zone between. The first part involves gene transfer to offset genetic defect in somatic cells, ordinary body cells. The scenario earlier outlined to deal with sickle cell anemia and other genetic effects involving hemoglobin. An abortive clinical effort in this direction actually is made in 1980, unsuccessfully, but demonstrating that policy currently exists to monitor and in some degree to regulate advance along these lines. Two separately developed policies were invoked. The first governing experimentation on human subjects, the second governing experiments involving recombinant DNA. At UCLA, a faculty member sought approval from the two institutional committees that must review proposals in these areas. The proposal was to remove bone marrow cells from patients severely ill due to defect of their hemoglobin gene to treat the bone marrow cells externally with normal hemoglobin genes produced by recombinant techniques and to return the hopefully normal bone marrow cells to the patient to produce normal red blood cells. When there was delay in gaining approval from the UCLA committees, the investigator elected to attempt the procedure abroad where approval had been provided. His efforts involving two patients, one in Israel and one in Italy, becoming known, both UCLA and the NIH, following investigation reprimanded and punished the researcher for violation of their required procedures. At issue in the background was the question whether therapeutic modification of human bone marrow cells was any different in policy terms if carried out genetically rather than by chemotherapy or hormone replacement. The informal consensus of commentators on the UCLA case is that gene transfer is not fundamentally different from other forms of therapeutic manipulation, assuming that the change benefits the individual patient and the altered cells terminate with the life of the treated individual. If this consensus were to hold, gene therapy is likely to be sanctioned at the appropriate time on a case-by-case basis under existing policy if rules for clinical trials are followed, including demonstration of probable safety and efficacy in animal tests. Although no further attempts at clinical application have yet been reported, several lines of laboratory investigation point toward achievement of necessary preconditions for clinical trials, very likely by the end of this decade. Evaluation and choice are distinctly more complicated for modification of human germline cells. Here we do face difficult questions and need to proceed with caution while we deliberate. Is there any convincing rationale for interventions in human beings if effects will persist into future generations? So far as consensus has yet been achieved, the following rationale might be acceptable. Patients who are afflicted with a heritable hemoglobin defect are not only sick in their blood-forming cells, but also in their gamete-producing cells. Their blood cell defect threatens the duration and quality of their own life, but their germline defect reduces their reproductive health by increasing the risk of defective offspring. If their somatic defect were corrected, the state of their germ cells would no longer be academic. Seen from the point of view of the individual patient, therefore, there appears to be as good rationale for treating the germline cells as the blood-forming cells. It can be argued against this patient-oriented view that subsequent generations are being simultaneously altered without consent. But if the change is regarded as beneficial to this generation, assuring them effective rather than defective hemoglobin, why should the next generation not be equally accepting? Under our existing model, medical model, it can be argued persuasively that genetic modification of germline cells should be sanctioned if it is oriented toward patient benefit and poses no serious harm to the offspring. Given successful application along these lines, however, would there be pressure to expand the sanctioned purposes? Might it be argued, for example, that not only individuals expressing the hemoglobin defect should be treated, but recessive carriers of the defect as well? Imagine a case of a couple who already has had a sickle cell or thalassemic child. Both carry the same recessive defect and they therefore are at 25% risk of producing an offspring with the actual disease. If either one were successfully treated, the couple's risk of having an actual defective offspring would drop to zero, although half of their children would be expected to be carried. If both were successfully treated, they would be assured in addition that none of their offspring would even be recessive carriers. Assuming that the treatment is fully effective and at zero risk, a very speculative assumption in terms of our current knowledge, treatment of one member of the couple fits the model of preventive medicine, intervention to reduce actual disease incidents as with vaccination, but in a succeeding generation, treatment of both members of the couple would further reduce actual disease incidents, but not until the second generation, that is in the couple's grandchildren. The additive effect of treating both members of the couple in terms of preventive medicine is quantitatively small and two generations removed. However, in terms of genetic medicine, including what is called negative eugenics, the cumulative effect of treating all recessive carriers over time could be elimination of the recessive defect from the population. This, however, would require a deliberate and sustained effort based on a formulated purpose that goes beyond the conventional medical model. It no longer is confined to benefit for an individual patient or couple and immediately succeeding offspring. It is motivated by concern about the human gene pool. Thus, in considering treatment of germline cells, there is a gray zone containing a possible divide for gene transfer policy. On one side of the divide, there is medical motivation to relieve affliction. On the other is eugenic motivation to improve the gene pool. Between is a zone of overlap of motivation in which it is difficult to draw a sharp line without reference to intent or purpose. A comparable gray zone exists for external human fertilization. As a means of overcoming sterility in married couples, this procedure now appears to have been accepted under the umbrella of previously developed biomedical policy that is to provide benefit to afflicted individuals or couples who cannot naturally produce a child. But the issue of freezing early embryos derived from this procedure has revealed another possible divide. Embryos have been frozen at some treatment centers. When more embryos were obtained from a hormonally treated patient than are usefully transferred to the uterus of that patient in a single attempt to achieve pregnancy. In several instances, such frozen embryos have been thawed and observed to be capable of continued development in vitro. In one instance, a thawed embryo continued development for several months after transfer to the uterus of the donor, although the pregnancy terminated prematurely. The primary medical rationale for freezing early embryos, thus it is to avoid their destruction and to give time for transfer back to a uterus for continued development. To transfer frozen thawed embryos to the uterus of the egg donor in subsequent cycles is a technical extension of the procedure that provides benefit to the donor patient. Embryos derived from a single hormonally stimulated cycle can be used for successive transfer attempts without additional laparoscopy, the procedure necessary to recover the eggs in the first place, a procedure that is the most uncomfortable step from the point of view of the patient. This use of freezing falls therefore within the medical model for improved patient care. However, two possible variants in the use of frozen embryos illustrate the gray zone that strains the medical model and even escapes from it altogether. The first variant is to use surplus embryos after meeting the needs of the donor couple for transfer to another sterile couple. Such embryo adoption, as it has been called, by the second couple is technically possible and pregnancy following transfer of an embryo from one woman to another has been recorded. The procedure is routine in cattle. It remains within the medical model in that it is an effort to overcome sterility but raises unusual social and legal issues about family relationships of the offspring that have brought expressions of concern from a number of commentators. A second imaginal variant is not known to have been attempted but seems technically feasible. It involves freezing of IVF embryos early in a marriage with delay of transfer to the donor uterus until some years later. It has been noted that many women are postponing pregnancy in their 20s for career purposes but seeking it in the middle to late 30s or even into the early 40s. By the natural process, such late pregnancies are more difficult to achieve than earlier ones and have a higher incidence of genetic abnormality presumably due to aging of OVA in the ovary. The imagined variant of banking OVA or embryos early in life might not only circumvent the aging process but also provide full control of family planning. Such options lie at the edge or beyond the boundary of the conventional medical model. They also clearly involve power in human decision making that exceeds traditional religious conceptions. What is our human responsibility in confronting such consequential technological options? Human beings have long been meddlers in the natural order but they also been contemplators and moralizers witness this conference. Clearly the new reproductive options call for deliberative contemplation and possibly for new moral principles. The experimental excesses of German Nazism brought the Nuremberg Code emphasizing individual human rights that has ever since strongly influenced clinical trials around the world. It is our human responsibility to formulate new principles if necessary and possible before rather than after excesses occur. The process has in fact already begun. Witness the voluntary scientific moratorium on certain kinds of experiments established by molecular geneticists in the mid-70s. The study and report on external human fertilization of the Ethics Advisory Board of the Department of Health Education and Welfare report that was never acted on. And the recent recommendations of the President's Commission on Ethical Problems in Spicing Life. One can discern in these and related activities both here and abroad an innovative mode of public deliberation to meet the new policy challenges we face. We appear to be in a period of improvisation and invention in mechanisms of policy formation to match the thrust of our scientific and technological advance. If the process has begun, what further steps are needed? What has characterized the new approach so far is first, an attempt to ensure full involvement of all relevant interests. And second, emphasis on ethical considerations. Wide involvement of interest is important because the issues raised may bear on the nature and future of humanity, obviously of concern to all human beings. In turn, this broad context focuses attention on values and on concepts of human nature and purpose, the crux of ethical discourse. If these characteristics are to be realized in a policy forming process for either in vitro fertilization or gene transfer, there must be the widest possible awareness and discussion of the new anticipated options and their implications. This conference clearly is a step in that right direction, but it needs to be magnified, perhaps a thousandfold, to accomplish anything near the requirements. Particularly important to the consciousness-raising effort is participation by young people who will make the individual and collective decisions and raise the resulting children. Colleges and university faculties, accordingly, must recognize a new agenda, not only for teaching, but for scholarly effort to clarify the naughty ethical and social dilemmas that are posed. Beyond this, there is need for continuing interactive public forums, hopefully of more than one kind, most often suggested as a national commission along the lines of the Ethics Advisory Board, the National Commission on Research on Human Subjects, and the President's Commission for the Study of Ethical Problems. Such a commission to exercise oversight on genetic intervention has been proposed in legislation introduced by Congressman Albert Gore, now pending in the House. The proposal does not include developmental interventions such as in vitro fertilization. It would be desirable for it to do so. But more important than questions of scope is the basic role of such a commission or of other forums that may be established to deal with the subjects under discussion. I suggest, as have many others who've addressed the matter, that what currently is needed is a deliberative forum and not a regulatory body. Definitive decisions in their implementation are not the prime objective. Clearer perspective, greater understanding, and wider public awareness are first needed. The commission needs to address itself to ensuring that these things will take place. What conclusions may eventually come from such a commission and from other deliberative forums? Two general models have been discussed for decision making in areas as complex as those we are discussing. First, case by case, and second, principle. In most extreme form, case by case conclusion implies that each case is unique. No precedent or generalization is established as each case is decided. Decision on principle, however, implies that generalizations, developed either a priori or out of synthesis of what is common in previous cases, are guides or even determinants of decisions about each new case. Because of the special character of this area, it seems to me that the decision is not one of choice between the two, but of a combination of the two. Both are likely to be needed. What sort of principles might be considered by such a commission and conceivably adopted? I will offer four examples as examples of the direction in which this might go. The first is that there is an extension of existing principles of human rights that include assurance that individuals will not be subjected to experimentation without informed consent. Such a principle might provide, I quote, no genetic or developmental intervention will be practiced on any human being that is intended or can reasonably be expected to restrict or reduce that individual's biological capability either within the individual's generation or in the production of offspring. The objective of such a principle would be to preclude such uses of genetic transfer as it is feared might be made to create subhumans or castes as a basis for a hierarchical authoritarian society. Although technically, this is an unlikely scenario at the present time, it has been widely discussed and it generates much apprehension. It would be good to set it formally outside the boundary of acceptability to reduce the dread which it inspires in many people. The second example might be in relation to gene, excuse me, germline transfers, a human genetic modification that is intended or may reasonably be expected to alter germline cells shall not be undertaken without review and sanction by a body especially constituted to examine not only technical risks, but political, social, and moral considerations. The language is intended to cover two kinds of circumstances, inadvertent alteration of germ cells when the effort is to influence somatic cells and secondly, primarily eugenic use intended to affect the human dream, germ pool, and future generations. The proposal calls for a special review body that might either itself provide sanction for a particular application or make recommendation to an elected and responsible public official or group for final decision. A third principle that might be considered might go as follows, except as necessary to implement the preceding principles. No restriction shall be placed on research to increase understanding of human heredity and development. To do so might foreclose options that would otherwise be made available to future generations. A principle of this kind, sorry, that fly got me, must be a very interesting subject. A principle of this kind is essential if principles like the first two are adopted. In effect, the first two put legitimate constraints on innovation in the interest of human rights, both individual and collective. But if there is a constraint on innovation, there must also be a constraint on the constraint. Otherwise, research and innovation may be seriously curtailed. It is worth noting that new genetic capabilities have come contemporaneously with nuclear weapons and space exploration. Whatever our need for genetic therapy and modification today, it may be much greater if nuclear bombs are unleashed or extraterrestrial colonization is attempted. Our concerns of today should not cripple capability to achieve the aspirations of tomorrow. A fourth principle relates to the range of application of any principles that are adopted. Any principles governing human genetic therapy or modification should be incorporated not only into national law, but into international covenants. Moves in this direction have already begun in the European community and should be supported by professionals in other groups in the United States and the subject of new initiatives in U.S. foreign policy. Let me conclude with a response to a question put to participants in this conference by our chairman, Robert Aspiansen. He asked to consider what is meant by being human, specifically whether it is more human to live by the rule of survival of the fittest than to live by cooperation and caring. A biologist speaking professionally can give only a partial answer because the full connotation of being human is not confined to the province of biology. The broader and hopefully still expanding connotation of human should be viewed as a trajectory, perhaps beginning when our distant ancestors first conceived limited futures and judged them as to good and evil. The full course of the trajectory is probably less certain today than it appeared to be a century ago, largely because we have ourselves introduced uncertainty by assuming so large a role in determining the trajectory. Caring and deciding are as much human as blindly struggling for survival, just as dining at maxims is neither more nor less human than sucking a nipple. Each is a stage in the human trajectory retraced in each generation and controlled increasingly by human decisions made in a historical cultural matrix. Our expanding options for building upon our biological human quality are an opportunity to continue our trajectory with a growing necessity and responsibility to increase the God to Satan ratio. This requires us to be increasingly purposeful and to be increasingly participatory in formulating our purposes and in implementing them. Our human thrust as a community is to move outward to a wider existence, physically, intellectually and spiritually. Exactly what this means will not be fully defined except as it is achieved. And then it will only be a platform for a further step toward what lies beyond for better or for worse, for good or for evil. Whether divine or satanic, that is what it means to be human. Thank you. Thank you, Dr. Grobstain. While the panel is coming forward and some are leaving, I will tell you a question that was given to me. Would I please explain the parable of the jackpots? I think it's rather risky to add explanations to parables, especially after time passes and time has passed. So I refuse to give an explanation. Give your own. You think that wants to take your picture right after that, right up there. There's a high school delegation that would like your picture right after this. The six of you together. And they're coming up here to do it right away. Great. Put this thing where she's going. How are you doing down there? How are you doing down there? Thank you so much. Robert? Pardon? I have a comment. You know, all right. Okay. Okay. So I'm being traveled to the airport. And I have ordered a cashier to take my part in the construction work right now. Also, tonight on Caldwell, I think all of you are going to understand what it looks like if you don't do it at all. So be careful. I announce and invoke the cloture on private discussions. You have 25 seconds this time to settle down. I was talking to them, telling them to settle down within 25 seconds. They cut their time a little bit. Looks like they're going to do it. Yeah, all right. This is something you don't have to bear in mind, because you and I have been talking about it. The panel, nobody has managed to hear each other except for Rumble. The first Rumble was open. That's funny, because I can hear everybody. I wonder, I don't know what to do about it. Really? It's not something I can do. No, that's fine. Really? I don't know. I can't, I can't. It's the bunks and the rules. And you're getting three or four error. All right. That's, yeah, that's... See, where's the large people? Where's the large people? There's one down here, you see, and there's one here, there are two in the back. As well as, they have them all over the place. We'll start our conversation here, as we usually do, with comments from the panel. Is there anyone wish to open the discussion? June Goodfield will, women. I've got two comments for Dr. Groepstein. I want to refer first-cliff to the case of the investigator who went abroad to try the genetic intervention with, I am firmly convinced, the very best interest of his patients in mind. The protocols that are brought forward by concerned parties over these questions seem to me to have two prime functions. They seem to me to protect two things. The first thing that they protect is the human subject, the patient, or the subject of investigation, the experiment. And the second thing that they serve to protect is the public's trust in the social contract, the form of contract, the public's trust that the contract between the scientific community and society at large is in fact being maintained. Now, in the way you analyzed that particular situation, Cliff, I think you said that the issue was that at that time, whether genetic intervention was equivalent to chemotherapeutic intervention, and as this seemed to be appropriately so, then what the investigator did was okay. What I thought, quite frankly, as a member of public was at issue was something quite different in this case, was surely the question of the appropriateness of the investigator going ahead with this, even in a foreign country, when the form of the protocols had not been agreed upon by, sorry, by violating the formal protocols that had been agreed upon by his own peers, and therefore the violation was not a scientific violation, but it was a violation of the trust that exists between us and the scientific community. That's how I saw that issue, and that's why, though I would have been the first to applaud had that experiment been successful, the intervention being successful, I would also be the first to say that he shouldn't have done it at that time. If I understand you, Joan, you are raising the question whether to focus on the procedures that were actually followed, that is the expectation that any protocol would be approved by the Recombinant DNA Committee and by the Human Experimentation Committee, whether the basic violation, so to speak, was procedural in that sense, or whether the violation was in terms of some higher expectation in terms of the role of the scientific investigator? No, let me try and, I haven't got this, made this quite clear, Cliff, what I'm about to say. I'm having a little trouble, as you know, hearing. In hearing you, I think we're all having a terrible time in hearing each other. I'll try and speak in two directions simultaneously. That, you know, following the Recombinant DNA debates, following many of the issues where there have been ethical committees which have come together with scientific committees to lay down protocols for particular procedures, which, and these have been arrived at as a consensus of the scientists in question and the concerned other groups in question. I understood that operating on that investigator at that time was an obligation to get permission to do the procedure, and he didn't get the permission, there was delay, you use the phrase, and so he went to a place where permission was not necessary. And I am saying that in doing that, in not waiting perhaps, or taking the further steps to try to convince the very committee of which his scientific peers had taken part in establishing the protocols, such protocols which at one of the same time protect both the patient and society's trust in the scientific community, that in ignoring that and going abroad, he betrayed a contractual trust, and that to me is the issue that should be addressed, not the issue whether the chemotherapy is just as appropriate as the genetic intervention or vice versa. That is why that case continues to disturb me. Okay, then I agree with you that there isn't any question, but that there was a violation of trust as well as of procedure, and I think that that did play a part in the determinations that were made. It is not the case, however, just to correct as factually as I understand it, that he went ahead abroad without permission. He secured the permission of a comparable group in both in Israel and in Italy. So from his point of view, he had met, so to speak, the letter of the law. He did have permission, but I agree that it was the violation. Now my reference to the question which was in the background, that is whether or not the therapeutics and the policy relating to it are the same, whether or not you were using a chemotherapeutic agent or whether you were using radiation or whether you were using DNA. That was a background issue. And as a matter of fact, when Dr. Klein, who is the person we're discussing, testified before the Gore subcommittee, which he did six or eight months ago, he specifically addressed that question, that is whether or not it was appropriate to regard this as any different from any other type of approach. But I agree with you that the prior question was, did he follow the procedures and as an understanding that protected both the public and the scientific community and the patient, all three. I have no question in my mind that he was guilty of that. And he was guilty particularly given the fact that this was a precedent establishing situation and was bound to attract very considerable attention. But my citing the case was really not so much for that as to indicate that we already do have in place certain elements of policy that will enable us to deal with some of the issues that have been raised and reach some kind of decisions, hopefully, sound ones. Well, I've got you able to hear me. Could I just ask one more question further out of your thing, Cliff, which is the question of freezing embryos and freezing them early in a marriage and then implanting at some suitable stage when professional life is perhaps not so effective as before. Have you already got procedures in place for that to deal with such questions as to what happened, what happens to the frozen embryos if before that happy event, the parents decide to get divorced? Well, I would say that that's the kind of question that we want to present for deliberation to the commission that hopefully would be a point. Yeah, technically I would say not referring to humans but to other species. All of the elements to carry out that scenario are in place. There are some questions about safety and efficacy and so on, but the basic elements technically are entirely feasible. Well, Rick Galen, please. I wanted to make an observation strictly for the record and I wanted to draw no conclusions about it, but I think it should be noticed that at this conference, which deals with the perhaps the limits of man's reach or of human reach and potential arrogance, for the first time we're experiencing after 20 to 30 years of geneticists attacking flies, flies attacking a geneticist. I draw no conclusions. I must point out that I am being used as a fall guy because I am not a geneticist. Karen Lomax. I am very appreciative of this lecture for laying out some groundwork both with regard to the technologies and what they are and what they do and also the policy questions. You have suggested that we might have a national commission that would look at questions of principles as well as a case-by-case deliberation and in your own suggestion of the four possible principles, I really thought you were coming dangerously close to proposing regulation instead of principle. So I want to take up your challenge, the question of whether there are new moral principles needed and I am going to say yes, there are. And I say that as a former member of the National Commission for the Protection of Human Subjects of Research, which did outline the three basic ethical principles that have formed the basis for the very regulations that you think are already in place and operating to help protect us in some of these areas. I will take responsibility for some of the principles that we are currently using and I will also suggest that they are a bit limited. Let me propose as an additional principle that we ought to have a principle that requires a covenant between those who would do research and those who would be the recipients of the effects of that research for better or worse and that that covenant might require some very stringent kinds of responsibility for the outcome of the research and a bonding between those who do it and those who receive the effects of it. That seems to me to be a principle that has been thus far left out from most of the regulations on which we operate and one that is consonant not only with Judeo-Christian tradition but I think with a number of other religious traditions and world perspectives as well. I would respond by saying first of all I want to acknowledge your pulling of rank and I salute you as a former member of the Commission on Human Experimentation because certainly I think that commission was groundbreaking both in its impacts within its own field and in terms of what I referred to, namely how we should handle this kind of matter and I think that it will always be cited as the beginning of a new trend in deliberation and policies of this kind. Now with respect to the principle that you suggest I would say that in principle I would agree with it. I foresee some rather grave difficulties if by a covenant among those who do the research and those upon whom it impacts whether for good or for bad. I find it rather difficult as I quickly think about this to imagine how certain kinds of research, for example the first demonstration of recombination in DNA, how you would have a compact between the doers of that research and all of the people who are likely to be impacted by it. The only way I think it could be done would be to make specific what is frequently been called an implicit covenant between researchers and the public that supports them and that certainly might be specified in somewhat greater detail and made explicit in ways that it has not yet been done and I would certainly think that that suggestion would deserve consideration by any groups that are attempting to deal with this matter. Dr. Ankenstein, did you? Yeah, well I have, I could say a few words. I won't say too many words because I came to St. Peter with a very simple-minded message, namely A, that it's unlikely we'll ever be able to stop scientists from doing what they want to someplace or other. B, that the human animal continues over the history of man to make a lot of boo-boos and this will probably also continue and C, that the rest of the people on the panel are much more likely to work out a system of controls than I possibly could. I don't think they'll work for a long time but it has to be done. So, once again, standing up for the gloomy people, the work will go on. It will become what we see now will be child's play with what we'll see 10 years from now in the potential of application to human evolution and so on. Bad things will happen. We have codes of ethics all over the place. You still have bank robberies and people cheating on construction projects and that's just the way us people are and some good, strong, clever sets of rules will have to be devised by others besides myself. Whatever became of sin, I guess it's still around. There are several questions about governments and about how we control those who control, especially through funding. Questions are asked about such matters as the relationship between government funding and the power of government either to direct or to control and sometimes with negative results, these new abilities. Would you consider the government, Plain Satan, Dr. Grobstein, is the government, there's a lot of suspicion of the government out here, I gather. Well, our government presumably consists of people as well as traditions and restraints and so on. And to the degree that anything involves people, they will inevitably, as far as I'm concerned, play both sides of the God to Satan ratio, some more on one side, some on the other. So government is not by any means, as far as I'm concerned, free of the necessity of doubt and concern as to what government will do. With respect to government funding and control, I think it is important to recognize that in our system of funding of science, government operates pretty largely through scientists in many of its funding operations. Certainly the fact that the funding comes from government and under the usual rules and expectations of governmental activity means that there are certain characteristics of funding in relation to possible control that would not exist if funding came from other sources. But particularly in the biomedical area, the decision-making about directions of research and about the application of new knowledge have largely been made within investigator communities in interaction with other elements, including patients, trustees and so on and so on. With, I would say, very little, except in the choices as to what areas will be funded and what won't, very little control by government. Dr. Thomas, please. With, I think it needed to be added that if we are to worry about individual investigators undertaking experiments of the kind that we would all agree should not be done on human beings of the kind that was cited earlier by Dr. Rosting, there are some sanctions that can be imposed on scientists. I suppose one rather severe one is to sew his fingers together. Another one more severe is to hang him, but the worst of all is to take his grant away. And that's power. Thank you. I would like to allow one more question that relates to government. We live in a global society where there's some risk in unilateral actions and several questions present this problem to us. When we live in a world where Soviet Union and other countries may have a different approach to these things, is there a danger from this? Would we be able to develop any kind of global regulations in the present political climate? Anyone? Well, I think my answer to that would be that number one, we're probably not in any position to talk to other nations until we have set our own house in order in this particular area. And I think we have a little way to go. If and when we clarify our own policies and put them into effect, and it's clear that we have reasonable consensus on what we're doing, then I think it would be appropriate to begin serious efforts to establish some kind of international consensus on the matter. Now, of course, it isn't the case that we're the only ones concerned about these matters. In relation to in vitro fertilization, the fact is that both in Australia and in England, they are further ahead than we are in formulating effective policy. If anything, we will have to learn from them rather than the other way around. So that a number of countries are giving attention, people in a number of countries are giving attention to the matter. Just as in the case of biological warfare, where an international covenant was achieved where it was very difficult to achieve it in other areas, leaving aside the question of its effectiveness, the degree of observation of it and so on, but it was recognized to be of such broad scope in terms of human interest that it was possible to do something in that area that was not possible, for example, in the area of control of nuclear weapons, nearly as far. So that I would hope that in this area, perhaps it might be possible to push ahead of some of the other areas where there doesn't appear to be the broad kind of consensus-making situation that exists here. I obviously cannot speak for the possibility or the interest on the part of the Soviet Union in such a covenant, but I think this is as likely as anything else to be a subject in which it would be possible. Thank you. It's time for a break, for a coffee on the Mall, or whatever you wanna do at all. Where's your St. James's version? I'll hold you. Have you graduated out of your front hall? No.