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    Meeting Transcript
    July 11, 2002

    Ritz-Carlton Hotel
    22nd Street, N.W.
    Washington, D.C. 20037

    Thursday, July 11, 2002


    COUNCIL MEMBERS PRESENT

    Leon R. Kass, M.D., Ph.D., Chairman
    American Enterprise Institute

    Rebecca S. Dresser, J.D.
    Washington University School of Law

    Daniel W. Foster, M.D.
    University of Texas, Southwestern Medical School

    Francis Fukuyama, Ph.D.
    Johns Hopkins University

    Michael S. Gazzaniga, Ph.D.
    Dartmouth College

    Robert P. George, D.Phil., J.D.
    Princeton University

    Mary Ann Glendon, J.D., L.LM.
    Harvard University

    Alfonso Gómez-Lobo, Dr. phil.
    Georgetown University

    William B. Hurlbut, M.D.
    Stanford University

    Charles Krauthammer, M.D.
    Syndicated Columnist

    Paul McHugh, M.D.
    Johns Hopkins University School of Medicine

    Gilbert C. Meilaender, Ph.D.
    Valparaiso University

    Janet D. Rowley, M.D., D.Sc.
    The University of Chicago

    Michael J. Sandel, D.Phil.
    Harvard University


    TABLE OF CONTENTS


    SESSION 1: HUMAN CLONING (FINAL): COUNCIL'S REPORT TO THE PRESIDENT

    CHAIRMAN KASS: Could we get started?

    Welcome to this, the fifth meeting of the President's Council on Bioethics, actually the fifth meeting in a grueling six months, and I want to welcome council members back after a short hiatus. And we're very grateful to you for being here.

    This is a regular meeting, and we have a full agenda after this session, including return to the discussion of the patenting of human organisms.

    This afternoon we will have a report from Dr. Wendy Baldwin from the NIH on the implementation of President Bush's stem cell policy of last year.

    At the end of the day, the last session, we have Dr. Ted Friedmann, who will be discussing with us the possibilities for genetic enhancement of athletic performance.

    And then tomorrow morning we will return to what we call in-house search for a richer bioethics and pursue with the question of the relation between human identity and the body, using a wonderful short story by Richard Selzer called "Whither Thou Goest."

    And we will finish with a discussion of our future plans and have time for our usual public comment.

    The first session this morning is devoted to the release of our report to the President, "Human Cloning and Human Dignity: an Ethical Inquiry." Here is the text, and I hope all of you have them at your place.

    This is a pre-publication copy, not the final copy, made available for the first time officially today. No copies were distributed in advance. They are available at least until the supply is exhausted on the table outside, and after the supply is exhausted for anybody who is interested, there will be extra copies of an executive summary.

    The text of the report will be available if the promises are kept on line in HTML form by 10:00 a.m. this morning. The Web site is www.bioethics.gov.

    I want to begin by expressing my personal thanks to the members of the Council for your superb efforts at meetings, between meetings, and in your comments, your critical suggestions to the multiple drafts made by the staff.

    You were selected not to be some rubber stamp body, but to be the heterogeneous and thoughtful and articulate group that you are. Our opinions in this room have been keenly held and in sharp disagreement, but they have been well articulated, and this is perfectly appropriate because the issues are vexing; the passions are high; and it is very, very hard to think one's way through this.

    Nevertheless, it seems to me that we have done exceptionally well in proceeding in the spirit of goodwill and collegiality and with respect, even some appreciation for the viewpoints which are not our own. And I thank you very, very much for proceeding in that spirit.

    I also want to express my deep gratitude to Dean Clancy and wonderful Council staff for your monumental efforts under very trying circumstances to produce this document.

    We've had three weeks since the last meeting, and this document is some 145 pages, plus personal statements, plus bibliography, plus glossary. And the staff is to be commended for just heroic work.

    The procedure this morning is as follows. I will make an opening presentation of the report. Then there will be time for brief comments, ladies and gentlemen, up to two minutes from those members of the Council who have notified the Chair in advance that they wish to speak. And then we will take some questions from the media.

    There is a microphone there, and if you will step forward when the time comes.

    I'd like to begin by putting the report of the Council in its context, and to begin by reminding everyone of the mission of this Council according to the Executive Order that was used to create us. This is in the preface.

    "The Council's purpose is to advise the President on bioethical issues related to advances in biomedical science and technology, and in connection with its advisory role, the mission of the Council includes the following functions: to undertake fundamental inquiry into the human and moral significance of developments in biomedical and behavioral science and technology; to explore specific ethical and policy questions related to these developments; to provide a forum for a national discussion of bioethical issues; to facilitate a greater understanding of bioethical issues; and to explore possibilities for useful international collaboration on bioethical issues."

    This is, to begin with, an ethics council, and our first questions will not be simply will it work, is it safe, and how much does it cost. But is it good, right, just, noble, wise, and prudent?

    And first, even before getting to that question, the first task is: what does all of this mean? The first assignment is to explore the human and moral significance of these developments, and that is the spirit in which we have been proceeding.

    Second, why the subject of human cloning? Why was this our first project?

    First, because there have been steps moving fairly rapidly beginning with mammalian cloning over the last five years, and there was the announcement last fall of perhaps the first successful attempt at the cloning of human embryo, and there are reports that some fertility specialists are, even as we speak — unsubstantiated reports, that there are efforts undertaken to produce a cloned child.

    This has been the subject of intense public debate, and it is a debate which has been complicated because of the discovery of human embryonic stem cells which hold enormous promise for regenerative medicine, and therefore, the question of the promise of cloned stem cells emerges as an issue in this discussion.

    This was not a topic of the discussion when the National Bioethics Advisory Commission had to take up this report, this topic five years ago.

    Nevertheless, it seems to me the reason that we have taken this up is because the power to clone human beings is not really just a new tool for overcoming infertility, nor is it just an adjunct to the treatment of disease, but it seems to involve a crossing of the line between sexual and asexual reproduction. It might possibly represent an early step toward the genetic control of the next generation.

    And lots of people sense that in this issue are things even beyond the importance of cloning itself, that this might be something as a first instance of something quite momentous.

    The group process, I will just sort of make it clear how we have proceeded. We have met now — this is the fifth meeting in which we will have met to discuss human cloning. We have had 12 90-minute conversations on this subject.

    We've heard presentations on the recent cloning report of the National Academy of Sciences; presentations on stem cells, embryonic and adult. We've had a presentation on the ethics of embryo research and on the international systems of regulation of embryo research and assisted reproductive technologies.

    We've had a great deal of public comment, both oral and written, and we have done a fair amount of reading and discussing amongst ourselves.

    I want to say before turning to highlights of the report proper, say something about some of the principles that have guided us.

    First of all, we didn't begin simply with the technique and its impact, but chose in all cases, wherever we went in this report, to discuss things on the plane of the human goods that these technologies could either serve or threaten.

    In the first case, the importance of human procreation, individuality, questions of the relation amongst the generations, the importance of human healing and the adjunct, the great importance of its allied biomedical science and technology.

    And finally, the treasured, but delicate relation between science and society, which offers science the freedom to progress to serve humankind, but also always within the moral limits and social norms of the community.

    Second, we have not striven here for consensus. It will be reported that this council failed to reach consensus. That would be a deep misunderstanding. There was no desire to produce consensus here in the first place.

    There was from the beginning the recognition that these are hard questions, that there were competing views. We wanted them forcefully presented, and just as President Bush did when he tried to reach his decision on embryonic stem cell research, when he consulted as widely as possible and heard from as many different viewpoints as he could, we have decided and we were charged in a way from the very beginning not to be guided by an overriding concern to reach consensus, but to develop these positions in as strong a way as possible so that the President and everyone else would understand what would be gained and what would be lost in choosing A rather than B or B rather than A.

    Finally, I want to say something about the relation between the inquiry and its conclusion. Today's news will be entirely about the result. I've learned since coming to Washington that the thing that people care about is the bottom line and are you for it or against it.

    We've come to a bottom line, but I don't regard the bottom line as the most impressive thing about our achievement. I think that the more lasting value, I hope, will be in the arguments, the reflections, the reasoning of this report.

    The issues are going to be with us long after whatever decision is made on the current topic, and it is my sincere hope that what we've done here could be of some help to people who follow in thinking about these questions.

    I now want to hit just some of the high points of the report. I won't read the executive summary except in a few paragraph where I think I can't improve upon what the staff has done there.

    But first of all, in the first chapter, which I think is somewhat distinctive of what we have done, we have placed, as I already said, the subject in the larger human context, the context of human procreation, like entity individuality and the like, in the context of the moral meaning of health and the value of biomedical research, in the context of the tacit moral contract between science and society, and lurking behind this, the context of the nature and worth of human life in all its stages.

    This is what we lead with in the opening chapter, and it sets the stage.

    There's a chapter on the history which touches only very lightly on what has transpired from the time when cloning was science fiction until the time when it is fact at least in mammals and perhaps, perhaps, in humans to come.

    Third, a chapter on terminology, and here I think we have something of considerable importance to contribute. Our first effort, and a difficult effort it was, was to clarify the confusing terminology that confounds the public discussion beginning with the term of human cloning itself.

    And for people who are interested in the results, what you need to know is the terms that we are adopting here will be cloning to produce children, cloning for biomedical research, and we regard the immediate product of somatic cell nuclear transfer for whatever use as the cloned human embryo.

    Whatever the purpose for which cloning is undertaken, the act that produces the genetic replica is the first step, the creation of an embryonic clone. Accordingly, we mean by human cloning the production of cloned human embryos, the earliest stages of developing human life, with the intention of either transferring them to a woman's uterus to initiate a pregnancy or taking them apart in order to procure embryonic stem cells.

    The first use of cloning has come to be known as reproductive cloning or just cloning. The second has come to be called therapeutic cloning, research cloning or nuclear transfer or stem cell research.

    The Council has chosen for reasons articulated in the analysis in Chapter 3 to call them instead cloning to produce children and cloning for biomedical research. We think these terms accurately describe the two activities involved and allow us then to debate the moral arguments without euphemistic distortion.

    Whether we favor or oppose cloning to produce children, whether we favor of oppose cloning for biomedical research, we must acknowledge that both uses of cloning begin with the same act, the production of cloned human embryos.

    Next, in the fourth chapter, which I will not review, is scientific background which touches quite a number of things that are relevant at least in the continuing consideration of our report. We have drawn very heavily on the marvelous report of the National Academy of Sciences on the scientific and medical aspects of human reproductive cloning, and that report was a great blessing to our efforts.

    Next, to now turn to the ethical discussions, the rest of these remarks will be about the ethical discussions, and then finally the policy recommendations.

    In Chapter 5 we deal with the ethics of cloning for biomedical research. We do consider the case for cloning. Excuse me. Sorry. I misspoke.

    The ethics of cloning to produce children, and we do consider the case in favor of cloning to produce children from the treatment of infertility to the replication of a loved one or even of individuals deemed to be superior. But we are not persuaded by this argument.

    And we make a case against human cloning that builds on, that goes beyond the case that has been made by our predecessors. We concur that cloning is unethical at this time because it is unsafe both to the prospective children to be, as well as to the participating women who are either egg donors or carriers.

    But we try to extend the discussion of the safety question into an abiding moral concern grounded in our duty not wilfully to put at grave risk the children to be who would be the products of this activity, and we raise serious questions as to whether the safety concerns are merely temporary or whether they might be enduring and even permanent.

    Second, we go beyond the discussion of safety to undertake the broader ethical critique that was recommended both by the National Bioethics Advisory Committee report and by the National Academy of Sciences, and there by means of a primary discussion of the nature of procreation, we mount a larger critique of human cloning, raising questions about issues of identity and individuality, concerns about steps leading toward manufacture, questions of the possibility of an opening here to eugenics in this primary and initial decision that would involve the genetic modification, the genetic preselection of the genotype of the next generation, questions of troubled family relations, and also certain concerns about the effect on society that has become a cloning society even if it is practiced only on a small scale.

    All members of the Council find all of these reasons equally persuasive, but we've put them before everyone for their serious consideration. The conclusion in that section is not only is human cloning unsafe, but it is also morally unacceptable, and it should not be attempted. There the Council is unanimous.

    Coming to the difficult topic, much more difficult topic, on the ethics of cloning for biomedical research treated in Chapter 6 of the report, here I would like to read a paragraph from the executive summary on page 18.

    "The ethical assessment of cloning for biomedical research is far more vexing. On the one hand, such research could lead to important knowledge about human embryological development and gene action, both normal and abnormal, ultimately resulting in treatments and cures for many illnesses and disabilities.

    "On the other hand, the research is controversial because it involves the delivered production, use, and ultimate destruction of cloned human embryos, and because the cloned embryos produces for research are no different than those that could be used in attempts to produce cloned children.

    "The difficulty is compounded by what are for now unanswerable questions as to whether the research will, in fact, yield the benefits hoped for and whether other promising and morally nonproblematic approaches might yield comparable benefits. We simply do not know."

    The Council, reflecting the differences of opinion in American society, is deeply divided regarding the ethics of research involving cloned embryos, but — and this point I want to stress — we all agree that the parties to this debate have concerns vital to defend, vital not only to themselves, but vital to us all.

    No human being and no society can afford to be callous to the needs of suffering humanity or cavalier about the treatment of nascent human life or indifferent to the social effects of adopting one course of action rather than another.

    What we've done in Chapter 6, and this is an experiment, we have put together in one document not a search for consensus, but in fact, two or two and a half briefs made in the first person plural by proponents and opponents of cloning for biomedical research.

    Both sides have been asked to consider what is owed to the embryo. Both sides have been asked to consider what is owed to those who suffer. Both sides have been asked to consider what is owed to the entire society.

    And the conclusion, I think, just to simply state the conclusion and allow me to read the rest, the moral case for cloning for biomedical research is powerfully stated. It rests on our obligation to try to relieve human suffering, an obligation that falls most powerfully on medical practitioners and biomedical researchers.

    We, speaking for that group, who support cloning for biomedical research, all agree that it may offer uniquely useful ways of investigating and possibly treating many chronic debilitating diseases and disabilities, providing aid and relief to millions.

    We also believe — I'm now speaking from the mouth of the proponents — we also believe that the moral objections to this research, though genuine, are outweighed by the great good that may come from it.

    At this point there was a division in that group. Some see much greater moral concern in the risks of going too far and other moral hazards and would argue that this research needs to be extremely carefully regulated.

    A small number of Council members do not believe that the very, very early embryo has that kind of moral standing, would favor this research with enthusiasm, but both of those groups are absolutely in agreement on the importance of the research and give it their ethical approval.

    The second group presenting the moral case against cloning for biomedical research acknowledges the possibility, though still speculative at the moment, that medical benefits might come from this particular avenue of experimentation, but we, now speaking for that group, believe it is morally wrong to exploit and destroy developing human life even for good reasons, and that it is unwise to open the door to many undesirable consequences that are likely to result from this research.

    This group finds it disquieting, even somewhat ignoble to treat what are, in fact, seeds of the next generation as near raw material for satisfying the needs of our own, and they make various kinds of moral arguments which I will not here research.

    In short, what we've tried to do in that chapter is not reach a conclusion, but to present full throated defenses of the two sides, each side also having to address the other side.

    Perhaps one word with respect to the second position, which acknowledges that they must pay heed to the voices of the suffering and will accept the burden of perhaps saying no to things that might be beneficial to claims that they want to leave to our children, a world in which suffering can be more effectively relieved, but also a world in which one wants morally to live.

    Next, in Chapter 7 we discuss the various public policy options. Mindful of the importance of scientific freedom and the need for moral boundaries and mindful of the way in which human cloning in other countries has not been dealt with in isolation, as we have largely done it here, but in the context of embryo research, reproductive technologies, and genetics, and we outline and discuss the strengths and weaknesses of seven different policy options from no legislation and self-regulation to a permanent ban on everything.

    In the final chapter, the Council, having thought about those seven options, coalesced around two recommendations, which we put forth as alternative recommendations flowing from this Council, and these are as follows.

    The majority recommendation — this is in the executive summary on page 21 if you are following — ten members of the Council recommend a ban on cloning to produce children, combined with a four-year moratorium on cloning for biomedical research.

    We also call for a federal review of current and projected practices of human embryo research, pre-implantation genetic diagnosis, genetic modification of human embryos and gametes and related matters, with a view to recommending and shaping ethically sound policies for the entire field.

    And there follow then, and the hour is late, a whole series of arguments in defense of this proposal, the most important of which is the claim that there is a need for ongoing public moral debate before one decides to cross this grave moral threshold, which the proponents of this view believe either should not be crossed or should not be crossed as yet without further deliberation.

    And some members supporting this position support the moratorium because they would like this temporary ban to provide the incentive to develop schemes of regulation that, should the ban be lifted, might allow this research to go forward, and they also want cloning to be considered — all of us want cloning to be considered — in the larger context.

    I should say that the Chair belongs to that party.

    The other recommendation supported by seven members of the Council and on page 23 recommend a ban on cloning to produce children, but — sorry — and recommend with regulation the use of permission to use — this looks like there's a typo here.

    They recommend that there be a ban on cloning to produce children, but support, approve now the use of cloned embryos for biomedical research, but with regulation.

    And here the argument is clear, again, that the permitting cloning for biomedical research now, while governing through a prudent and sensible regulatory scheme, is held by this group to be the most appropriate way to allow the important research to proceed, while insuring that the abuses are prevented.

    This group does worry about some of the dangerous consequences, but believes that a system of careful, strict federal regulation could prevent those untoward effects, and they want to lend their support to allow this research to go forward at the present time.

    That is the main body of the report. There is a bibliography, and in keeping with the spirit of our enterprise and in order to contribute to further public discussion and to continue to allow individual members here to speak in their own voice, you will find at the back of the report an appendix of personal statements in which individual members who have chosen to do so have added their own statements, and we commend them for your attention.

    There should be two supplements. There was error in the version of Dr. Foster's statement that was included in the book and Dr. Rowley's statement is available as an insert. I hope it's in the volumes that you picked up. If not, it's available in the back.

    Finally, let me just say since the newspapers are already speaking about what the legislative implications are here, and let me say that I would say that as I understand what it is that is being recommended by the two sides, the view of the majority is that there should be no legal human cloning of any sort at this time, and that pending the necessary debate and review both of cloning and of the whole area, that only a moratorium could make possible that no law should now be enacted that would authorize or approve human cloning, that would give the green light to it.

    The other position, the minority position, argues that cloning for biomedical research should now be approved legislatively in principle, but it should not proceed in the absence of an enforceable system of federal regulation. That I take to be the gist of what this means for people who want to know what does this matter to the debate that goes elsewhere.

    That is it. I'm sorry to have been a little long winded, but I'd rather err on the side of thoroughness.

    I have six people who have asked to make short personal comments beginning with Rebecca Dresser.

    PROF. DRESSER: Thank you for this opportunity. Settling on our final recommendations was difficult for me and for others on this Council, but as a teacher and student of bioethics, I'm proud to have played a role in shaping this report.

    The report, of course, is not perfect, but I think it is a full and fair examination of the issues, and I believe that it will advance the public and policy examination of human cloning.

    As a member of this Council, I believe I have a responsibility to consider not just my own views, but also those of others with interests in our national policies addressing research using human embryos. I do not think we have sufficient agreement in this country about the morality of producing embryos for research to adopt the regulation approach that Proposal 2 endorses.

    Going forward at this point could be divisive and could reduce the chance for developing an oversight approach that would be acceptable to a majority of citizens.

    Proposal 2 could actually be criticized for going too far in labeling cloning for research permissible, but it could also be criticized for not going far enough in that it really doesn't address the federal funding question.

    Without federal funding, little of the basic research that scientists want to do is likely to go forward. For many years Congress has prohibited federal funding of any research that destroys human embryos. With time for further deliberation and further scientific work to indicate whether it is necessary to create embryos to develop stem cell and other therapies, it is possible, I think, a consensus will emerge on the appropriate national policy to govern this very contentious issue.

    Now, that consensus might be to go forward and to provide federal funding for the work, or it might be to refrain from permitting production of research embryos because of the moral objections and because there are alternative research approaches to developing therapies.

    The issue of whether to approve cloning for research is not ripe for policy resolution. It's not ethically ripe, and it's not scientifically ripe. It's too early to know whether or not people in this country believe that possible gains to patients justify the risks and losses that could come from creating embryos for research, and it's too early to know what we would be giving up if we refrained from taking this step.

    Possible benefits to patients are not the only ethical consideration bearing on research policy, and studying stem cells from cloned embryos is not the sole avenue to delivering benefits to patients.

    In the next four years, there will be many other research opportunities to investigate the potential benefits that stem cell studies could produce and many other opportunities to benefit patients through better delivery of existing health care services.

    These alternatives will, I hope, be pursued during four years of continued deliberation over the creation of embryos for research purposes.

    Thank you.

    CHAIRMAN KASS: Thank you.

    Paul McHugh.

    DR. McHUGH: Thank you very much, Leon.

    I wanted to comment on this report and my position on it in relationship to my views of SCNT, or somatic cell nuclear transplant, that I have articulated at this table and have put at the end of the report.

    As you know, I believe that SCNT is an issue of wonderful new discovery in cellular biology and it represents a form of biological engineering that, at least at its onset, produces cells and not human beings, and that those cells, therefore, are licit to be used in various ways.

    I don't want to further that discussion right at the moment, but I do want to draw from that why I then choose to speak about a moratorium here, as our country thinks further about the implications of the use of this form of biological engineering and study.

    I believe that there are three problematic aspects that still remain unresolved even if you accepted my position of SCNT, and these problems need to be worked out and thoroughly discussed as to their implications for the future by the American people, and I believe only a moratorium that calls attention to these three problems — by the way, there are many other problems, but these three problems, one an immediate problem, one an imminent problem, and one an ultimate problem.

    Two of them have been discussed before in this Council. An immediate problem is that the requirement for SCNT, human SCNT, is to find human oocytes. If this research is to go forward, there are going to have to be hundreds, maybe thousands of human oocytes, quote, harvested from women.

    I fear and see the turning of some women into egg factories, and no man or woman can look at that with ease and comfort.

    We should be talking about what that means both practically and morally.

    The second, less immediate, but an imminent problem comes out of my opinion that SCNT at first produces cells, and that those cells are suitably used. My colleagues and others have pointed out to me that this phase is just one phase in the potential of these cells, and that these cells could be put into some artificial or real uterus and developed further for the production of organs; that if the cells of the SCNT could be harvested, why couldn't the organs be harvested?

    And I believe that we should be talking about what that would imply, using a fetus for the production of organs, and again, I think a moratorium would help to see that.

    But then there's an ultimate problem, and it's a problem that relates to the existence of this technology and the potential ultimately of producing a child. And this, of course, is the issue that we want to address by banning human reproductive cloning.

    Now, I don't feel that anything that has been said in here or in the National Academy of Sciences has really come to some of the ultimate issues that relate to human cloning for reproduction that our beginnings could permit.

    Let me remind you that Charles Krauthammer's favorite animal is Dolly, and I've been looking at it since he's called that to my attention, and a recent ad has shown Dolly with her lamb, and that really drove home something to me and, I think, anyone who looks at this picture and imagines it in human terms.

    That is, that a human cloned would then be able to reproduce, and the reproduction would go through and produce a lineage of genes from that cloned product.

    Now, I do not know that anybody can assure me that the process of scrubbing the genome that is represented by SCNT will not in some way produce delicate but important changes in the genomic structure that would then pass into a lineage forever.

    I work with Huntington's disease patients. Huntington's disease is an extremely interesting disorder at one level in that it represents the expansion of a trinucleotide repeat in the genome of a human being.

    We have many trinucleotide repeats in our genome, but very few of them — fortunately, none of them tend to go critical and expand and, thus, produce a condition like Huntington's disease, which passes on generation after generation.

    Diseases like Huntington's disease, fragile X syndrome, some forms of muscular dystrophy, and others represent lineages from trinucleotide repeats that went critically in some family.

    I think it's an ultimate and perhaps enduring question as to whether the manipulations of this human genome may not in some way produce a lineage of disorder. Some of them that we know of, like Huntington's disease, are some of them that might be new pathologies that would then go generation after generation produced by the science of today.

    And I'm concerned about that to the point where I think that we should be discussing it as also a third issue in a moratorium and heading towards regulation.

    In fact, when I think about it, I'm sorry. I depend in my clinical work, of course, on very much basic science, and am very sorry to speak for anything that hinders and slows science. But I do think that this is a situation that calls for that in these three ways.

    And I'm disappointed, in fact, that the scientific community hasn't come forward to say that there would be a voluntary moratorium while they considered these matters and discussed them thoroughly as to their implications for the future.

    Thank you.

    CHAIRMAN KASS: Thank you. Michael Sandel.

    PROF. SANDEL: Thank you, Mr. Chairman.

    Some may be surprised that this Council is not recommending a ban on cloning for biomedical research. Neither of the policy recommendations this Council has put forward endorses the ban on research cloning passed by the House of Representatives last year.

    Some members of this Council, a sizable minority, have argued powerfully for such a ban. Although they did not persuade a majority to accept their view, their position is worthy of the utmost respect.

    Among those of us who hare rejected an outright ban, most would permit the research to go forward subject to regulation, whereas some favor a moratorium.

    These positions are laid out clearly and candidly in the report in the table on page 129. Seven members favor a ban, seven favor permitting the research subject to regulation, and three favor a moratorium.

    When the membership of this Council was first announced, some critics complained that President Bush had stacked the Council to insure a particular outcome. I believe that this report, if carefully read, will put that charge to rest.

    The President could easily have stacked this Council to guarantee support for a ban on cloning for biomedical research, but he didn't do that. He wanted a group of independent minded people who would wrestle honestly with hard ethical questions so that the best arguments on all sides could be placed before him and before the American people.

    The President deserves enormous credit for that choice, which I believe will serve him and the country well in the long run.

    And our Chairman, Leon Kass, deserves great credit and appreciation for leading these discussions with integrity and fairness.

    CHAIRMAN KASS: Thank you.

    Alfonso Gómez-Lobo.

    PROF. GÓMEZ-LOBO: It has been a great honor and a deeply felt responsibility for me to contribute to the deliberations on human cloning of the Presidents' Council on Bioethics.

    After much thought, much difficult thought, it seems to me that human cloning, if carrier out, will represent a major step towards a radical instrumentalization of human life. It would be the ultimate transformation of a growing and developing human being into mere research for experimentation.

    That a human life begins shortly after fertilization or of somatic nuclear transfer is neither a matter of subjective opinion nor of religious belief. And I want to insist on this point.

    By itself, that is, without the contribution of science, none of our major religious traditions is equipped to decide the issue. When our life begins is a matter to be decided not by faith, but rather by reason in light of contemporary embryology.

    As a recent article in the journal Nature, July 1st, the journal Nature shows, the mammalian body plan with its diverse functions starts being laid down — and I literally quote from the Nature article, from the moment of conception, unquote.

    To claim that a human embryo cloned or naturally conceived is a clump of cells is like describing a car as a bunch of wheels. This expression totally misrepresents the structure and nature of an automobile.

    Likewise, an embryo is much more than a heap of cells. It is a unified organism, a self-moving whole programmed from the start to go through its natural stages until she becomes, if given the appropriate conditions, an adult like us.

    An embryo does not yet have a functioning nervous system or a brain, but if nurtured properly and not wilfully deprived of her natural surroundings, will have them within a short time. Sentience and thought are natural outcomes of the earlier stages.

    The very idea of cloning for biomedical research rests on the assumption that the internal genetic program of the embryo is at work and will lead to the blastocyst stage, and at this point stem cells will be extracted.

    It would be a euphemism to say that the embryo is then lost. It is, of course, intentionally dismantled.

    The recent advance for research cloning, of course, is the promise of cure for numerous illnesses. My family and I, I must confess, are among those who would benefit tremendously from those cures.

    But — and I pose the question to myself ?- does this admirable and desired end justify the questionable means? And after much thought, I have to answer no.

    As a result of all that I have learned from my colleagues and from the material provided by the excellent staff of the Council, I would like to make two exhortations.

    One is an exhortation to all Americans to familiarize themselves with embryology and the real nature of research cloning. It is not simply a procedure directly to produce stem cells. It is a procedure that entails producing human organisms, letting them grow according to their own devices, and then destroying them.

    Any suggestion that this can be done in a morally permissible way before 14 days is, in my opinion an illusion. There is no bright or dim light at that point. We were already before 14 days the human beings we are now, and this, above all, should be a deep concern to our legislators.

    My second exhortation is to those members of the community who have devoted their lives to science and medicine. We admire you; we support you; and we depend on you for our own well-being and that of our children and grandchildren.

    But we urge you to be mindful of the ethical implications of dealing with human subjects who cannot give consent and are going to be treated as mere instruments for the benefit of the rest of us.

    We urge you vigorously to pursue truth and healing, but in strict observation of the principle that commands us never to treat a fellow human being, no matter how young, merely as a means towards our ends.

    Thank you.

    CHAIRMAN KASS: Thank you.

    Let me see. Janet Rowley. Mike, do you want to go first?

    I want to alternate. We have two new additions, and I'd like to bring you in. Mike, would you like to go?

    DR. GAZZANIGA: Sure.

    CHAIRMAN KASS: Mike Gazzaniga.

    DR. GAZZANIGA: I think Mike Sandel stole my notes. I echo completely his sentiments and his statement that this committee has worked fairly and in the open, and every time one would call with a suggestion, the answer always was, "We'll put it in there."

    There never was any sense of override. There never was any blocking of any point of view. And for those of you who actually read the report, every viewpoint that the individuals of this committee have is represented in the report.

    I do want to remind that this is a committee not of scientists, but of professionals looking at ethical questions, and echoing Mike Sandel's point, on page 129 the majority of the committee actually has no problem with the bioethics of biomedical cloning, but we vary in the extent and speed with which we want to go forward.

    I would just conclude with the thought that it is our great intellect that finds many of us at this table still alive from prior biomedical advances, and I think the objective of biomedical cloning is have us alive and healthy during these aging years. So I hope the process will go forward.

    Thank you.

    CHAIRMAN KASS: Thank you, and a long life to you, Mike.

    Let's see. Gil Meilaender.

    PROF. MEILAENDER: I wanted to say just a few words about the policy a majority of our Council has recommended with respect to cloning for biomedical research, a policy that I support.

    That recommendation, a four-year moratorium, is in some ways not the very best policy that I can imagine. The best would be simply to try to say a lasting no to all human cloning for reasons one can find set out in detail in parts of Chapters 5 and 6 of our report.

    Not all Council members agree, but some of those who do not yet agree — note the hopeful tone there — some of those who do not yet agree share many more reservations about proceeding with research cloning now. Our partial agreement is, I think, a considerable achievement, given the circumstances under which we've forged it in a rather short time.

    Were it enacted into law, it would prohibit all human cloning whether publicly or privately funded for four years. That is to say for that period of time, we would have the best policy in place, and our deeply divided society would have continued opportunity to think, to talk, and even to argue about the morality of human cloning, opportunity to take seriously the limits on our own wisdom and goodness, opportunity to question even our most praiseworthy motives.

    Beyond that, I make three observations, each very brief, about the worth of a moratorium.

    First, some might describe our four previous meetings of a day and a half each over a half year as six months of searching ethical and scientific inquiry. I think that sets the bar too low, lower than I'd want to set it anyway.

    I think, on the contrary, that neither this Council nor our society has really yet fully plumbed the depths of the moral issues in human cloning and embryo research. There's much more to be done, some that we haven't done, some that we've hardly been willing to do, and we can use a moratorium to think more deeply and fully.

    Second, I used to think that I could never care about any child the way I did my own children. then I spent a decade as a foster parent, and I learned I was wrong. My feelings and my moral sensibilities had not been a very sound moral guide. They needed to be reshaped and redirected, and that really took years.

    Perhaps the feeling of those like myself who see an industry of research cloning as abhorrent are wrong. Perhaps, on the other hand, the feelings of those who see relatively little moral problem with cloning for biomedical research are an unsound moral guide.

    It will be good for our moral health to take more time to think this through.

    Third, Oscar Wilde is famous for having described the cynic as the man who knows the price of everything and the value of nothing. We're engaged; we have been engaged in an attempt to think through some very important questions about the value of things, questions that cannot be reduced simply to costs and benefits.

    I believe it will serve the moral health of our society to take additional time to do so.

    Thank you.

    CHAIRMAN KASS: Thank you.

    Now Janet Rowley, please.

    DR. ROWLEY: I, too, want to echo the compliments of my colleagues around the table both for Leon specifically as well as for the staff for the openness of the discussion that we have had in these last months, and many of you in the audience have been here and sat through a day and a half of discussions, and I salute those of you who were in attendance because I think it was a surprise to me to see that all of our deliberations would be conducted in this kind of goldfish bowl, but I think it's a very strong and important statement for the country to see the discussions and the meeting of intellects, if not the coming to agreement of individuals trying to deal with very, very serious issues.

    And I think that it is important to emphasize that those of us in the scientific community who would espouse more progress certainly recognize the very sensitive issues that we are dealing with at this particular time. It's been raised both in the report by Dr. Kass and by others that we have asked many questions during this time, and we've found answers.

    I want to focus on why we have so few answers to the questions, the critical questions, that we have asked. And for me the answer is shockingly clear. Most American scientists have been prevented from working on these very critical problems because of a ban on any federally funded research using cells from human embryos, and this ban has been in existence since 1994.

    We're not proposing that we stop active research now. We're saying that we should continue this prohibition on research by federally funded scientists, which really has been the engine of all biomedical progress in the past.

    And I have to say why continued ignorance is a wise public policy escapes me.

    It is clear that in addition to wanting to move ahead with funding research, that as I've already said research using these cells requires great sensitivity and careful thought.

    And as a matter of fact, all academic institutions have an institutional research board in place where the research that is proposed, particularly that involving human subjects, is very carefully reviewed by the institution before grants can be submitted to any agency.

    In fact, in 1998, NIH had a working group developed that proposed guidelines for pluripotent stem cell research, and this was approved after extensive public comment. More than 50,000 comments were received in response to the announcement, firstly in the Federal Register, in the final report, and guidelines were published in the Federal Register in August of 2000.

    And at that time, there was a proposal for the establishment of the human pluripotent stem cell review group. In fact, this group was constituted, but because of the election never met.

    The group consisted of — broadly represented the American public with consumers, ethicists, lawyers, as well as scientists.

    And so despite the claims in part of our report, there is no evidence that I'm aware of that scientists oppose the formation of such a research board. In fact, as I've already said, members of such a board were already selected.

    The proposal, again, in our part of our report, to exclude knowledgeable scientists from the review panel will, I think, perpetuate the serious handicap under which our own Council has labored in not having experts as members of the Council who are constantly available to inform us in our discussions.

    We are dealing, as we've all discussed with competing moral goods, and we spend a great deal of time, of paper, many pages discussing the moral rights of a single cell.

    There's very little discussion of the moral rights of patients and the potential benefits to humanity of this research. Again, part of this is because of our ignorance, and our ignorance is due to the fact that we cannot do the science that's required to answer these questions and to spend four more years in ignorance, I think, is extraordinarily distressing at least to me.

    So I think that Congress should lift the ban on human embryonic research and should establish a broadly constituted regulatory board now.

    CHAIRMAN KASS: Thank you very much.

    The last comment is from Charles Krauthammer.

    DR. KRAUTHAMMER: Like Professor Meilaender, although for possibly different sets of moral reasons, I oppose all cloning, reproductive and research. I would like to see them banned.

    But I live in the real world, and in the real world there is no consensus either in American society or on this Council for such a permanent ban right now.

    And I might say in echoing the remarks of Professor Sandel that the fact that the pluralism on this issue in the country is reflected by the pluralism on this issue in the Council gives lie to the impression widely disseminated that this Council was stacked to produce an ideological result.

    The fact that we have produced this variety of opinions and this kind of division, I think, gives light to that. Not only have the members of the Council with differing opinions shown respect for each other's positions, but they have both in our discussions and in the report recognized the valuable goods represented by the other side, and that one necessarily forfeits in proposing ones own position.

    Given this pluralism, I think that recommending a moratorium as the majority of this Commission has now done is more than a compromise. It's an achievement.

    And the reason it is an achievement is because the creation of human embryos solely for the purpose of experimentation is a significant moral barrier, and by proposing a moratorium, we recognize the significance of the barrier and the importance of it not being crossed.

    Creating embryos solely for their exploitation and research and therapy is new. It's dangerous, and I believe that we will live to regret it were we to allow it to go ahead.

    The reason the moratorium is so critical is because without any such action today it will go ahead. We already know that the Jones Institute has created human embryos using sperm and eggs for experimentation. We know that Advanced Cell Technology has attempted to create human embryos solely for experimentation using cloning techniques.

    In the absence of any action here, in the absence of any action by the Congress, this barrier will be breached.

    I think the importance of what we have done is that a Council of people drawn, as Michael Sandel pointed out, from the different perspectives, reflecting different points of view, that such a Council has come together and recommended in the majority that this barrier not be breached is extremely important. It represents a recognition that the country needs, and I think it is a significant contribution to the debate and to the moral health of the country.

    Thank you very much.

    CHAIRMAN KASS: Thank you very much.

    As a matter of personal privilege let me say that I am just thrilled with the comments that have just been made around the table and not simply for their kind words for the Chair. People who are with us for the first time have just gotten a taste of the kind of discourse that we've been having here.

    I can't say I'm sorry we're finished with human cloning, but this was a very nice way for the Council to finish its discussion, and I thank you all for the thoughtfulness and high moral principle behind all of the statements, and I'm very grateful.

    We now invite people from the press to come to the microphone and ask questions. We have another session beginning at 10:45. So this will be brief. We'll take a break, and then people can speak in the interim.

    But please step forward to the mic and identify yourself and ask whatever questions you might have.

    There will be a session tomorrow for public comment. This is not the occasion for editorial complaint, but really for questions.

    MR. VERGANO: My name is Dan Vergano. I'm with USA Today.

    CHAIRMAN KASS: Could you speak up better or could we get the microphone a little —

    MR. VERGANO: My name is Dan Vergano. I'm with USA Today.

    CHAIRMAN KASS: Thank you.

    MR. VERGANO: What I'm wondering is did any of the Council members change their original opinions or notions about this topic as a result of this process.

    CHAIRMAN KASS: This has been a roller coaster of a conversation. I mean, there are some people who probably remain at the end where they were at the beginning, and other people have wrestled very hard and, as best I can tell, may have changed their minds certainly if not exactly about the morality of the question, at least about the right way that we should proceed as a society.

    But it seems to me personal confessions might be in order if you want to buttonhole people around the table, but, no, I think from where I sit it seems to me there has been some movement in some places, and we're not all simply dug in where we began.

    And certainly there has been movement in which the power of the other point of view has been clearly recognized in ways in which the heated debate in Congress and other places rarely does. So that, I think, is certainly movement.

    MR. VERGANO: Thank you.

    CHAIRMAN KASS: Thank you.
    Please, Mr. Palca.

    MR. PALCA: I'm Joe Palca from National Public Radio.

    My question is if at least half the Council and possibly more favor this four-year moratorium where people can work out the proper regulations that would make cloning for biomedical research ethically acceptable or at least done in an ethical manner, who do you recommend derive those regulations?

    I mean, are you stepping out of the discussion now and saying others should do it, or are you saying we will continue and come up with what we feel are a set of ethical guidelines?

    CHAIRMAN KASS: No. Thank you very much.

    First, I'll just correct the facts. I mean, the ten-member majority group that favors a temporary ban on all human cloning, a four-year moratorium on all human cloning, comprises individuals who, as you heard from Gil Meilaender, would like to use those four years to persuade Paul McHugh (a) that this product is really an embryo and shouldn't be used.

    There are others who see this not as a down time, but as an opportunity not just to devise the regulations for this, but to locate this in the larger context the way the Canadians have and the way the British have, and to think through this entire area.

    This Council has been created with a lifetime of two years by executive order. We go out of business at the end of November of 2003.

    We have already begun our discussion of regulation in this whole area, and not just about human cloning in particular. Frank Fukuyama has taken the lead with his book The Post-Human Future to call for such things. We've had several sessions on them. We will have more.

    And we will give our best thought to suggestions for either supplementing the regulatory mechanisms that now exist or if we have anything useful to suggest to talk about others, we stand ready to participate in this process.

    But we are an advisory body with no decision making authority, and it seems at least to some of us that what this area needs is a consideration that goes beyond mere safety and efficacy, but to some of the deeper moral questions that we're considering and to be able to do so in some kind of an effective way, issue regulations, and enforce them.

    At the moment we have, it seems to me, a very partial solution, and that's why we were very interested in the last meeting to learn something about what's being done in other countries. We will continue to do so, but mindful of the differences between the United States and other places.

    But thank you very much.

    Ms. Stolberg, please.

    MS. STOLBERG: Hi. I'm Sheryl Stolberg from The New York Times. I have three very simple questions. First, why four years?

    Second, it appears that Professor Carter didn't vote, and I wanted to know why not.

    And third, have you been asked or do you intend to present this report in any way to Congress?

    CHAIRMAN KASS: Thank you.

    Four is a number less than some wanted and more than others wanted.

    Professor Carter has not been able to make any meetings since, I believe — I think he was there part of the February meeting. He was not present with us in April. He was not present with us in June, and he has been unable to comment and, therefore, has chosen not to participate in this report.

    It's not correct to say that he's abstained. It is, I think, more correct to say that he has just not participated in this report. We regret that very much.

    And we are responsible to the President. And late last night — we just got these copies yesterday — late last night a copy was delivered to the President. We will be glad, I think, to make copies available to members of Congress, but there aren't at the moment immediate plans for such distribution.

    Thank you.

    Ms. Meckler, welcome.

    MS. MECKLER: Hi. Laura Meckler from the Associated Press.

    My question is you've said that you hope that this report outlines the arguments, the powerful arguments, on both sides of the issue.

    CHAIRMAN KASS: Right.

    MS. MECKLER: From a practical point of view, as Congress and, more particularly, the Senate is grappling with this issue, what specifically do you see them doing with this report?

    Obviously, one thing that may happen is people will use the arguments that they like to reinforce their points of view. Do you see anything beyond that? Do you think this will change people's minds? Do you think the majority opinion, albeit a small majority, will carry some weight with those who might be undecided?

    Could you just talk about the practical impact?

    CHAIRMAN KASS: Well, the truth is it is not for this body to hazard many guesses as to what other people are going to make of it. The Senate is a large, powerful, independent body, and you'd, I think, probably have to give them time and ask them what they will say.

    I would say only two things. If somebody reads carefully, they will see that the two proposals that have come from this Council are neither of them explicitly represented in the alternatives that are present before the Senate. The more permissive proposal does not call for the prior establishment of strict regulations, and if you look at the document, what the minority is calling for are things that are really quite, quite strict and extensive.

    And I commend you to Chapter 8 for the details.

    The majority recommendation calls for not a permanent ban, but calls for a permanent ban on cloning to produce children, but a four-year ban on all human cloning so that this debate can continue, so that those who want to seek for regulations can do so, so that there will actually be an incentive for people to continue to carry on this conversation because the green light will not have been given.

    Some of the members of the Council — this political debate was swirling around us all the time we were working. It made life interesting, but we tried to follow our own line on this, not to be unduly influenced by what was there.

    On the other hand, at least some of us have been distressed or at least concerned that after much public debate both in 1998 and in the current session of Congress, that the result might be simple acquiescence in whatever Dr. Antinori and other people do, and that we regard that as regrettable.

    If the Senate would be interested in adopting this proposal, you'll have to ask them, but it might be a way past this impasse.

    Please.

    MS. BOYCE: Hi. I'm Nell Boyce with U.S. News & World Report.

    I wondered if the panel, those who were in favor of a moratorium in terms of giving time to produce adequate regulation and oversight over research use of cloning, if they considered or it was discussed what impact it might have if one of these groups working on human cloning for children actually came forward with a successful birth of a child through somatic cell nuclear transfer.

    I wondered. You know, four years is a long time, and I wondered if that was something that was discussed in terms of giving this time period to develop regulation.

    CHAIRMAN KASS: Yeah, I think I'm speaking fairly that we were not — the time wasn't somehow dictated by the chances of a successful creation of a cloned child. In fact, the Council, I repeat, is unanimous in recommending that this be proscribed permanently.

    And everybody understands that even permanent bans — permanent bans, first of all, can be altered. One can revoke them. And permanent bans do not prevent rogues from violating them, but they can't violate them with impunity and certainly they can't violate them and be praised by the community that regards this as a deep violation of the moral norms.

    So I don't think the call for the moratorium of four years was somehow affected by what Dr. Antinori or Dr. Zavos might be planning, but rather by, as you've heard around the table, the believe that there's an important moral boundary here to be crossed, and that we need time to debate that thoroughly to decide whether we should cross it, and if so, what the costs are both of crossing it and of not crossing it.

    One last question, please, and then we will take a break.

    MS. LEONARD: Hi. I'm Mary Leonard with the Boston Globe.

    CHAIRMAN KASS: Hello, Ms. Leonard.

    MS. LEONARD: The position that you've laid out today is not President Bush's position. You said the report has been delivered to him. I wonder, first of all, if you had had any conversations with the President about this; whether you will be urging him to adopt this position and, I suppose, whether you're prepared for him to reject your recommendation.

    CHAIRMAN KASS: Well, thank you very much for that question.

    No, I have not discussed this with the President. I will not be urging this on the President. He has the reflections and recommendations of this Council, and I'm confident that he is a man who will consider the various issues and reach his own conclusions, as he has done on so many occasions before.

    The only one thing I would correct slightly. I'm not sure it's fair to say that the majority of the recommendation is not the President's position. It's not the President's position, if I understand it, that called for a permanent ban on this, but it does not somehow violate.

    If it were given effect, namely, that there would be no human cloning of any kind for a time, I'm not sure that that is a contradiction of the President's position, but I think I'd have to leave it to the President and his spokes people to answer for themselves.

    Thank you all very much. We are adjourned until a quarter of 11, when we will return to discuss the patenting of human organisms.

    (Whereupon, the foregoing matter went off the record at 10:22 a.m. and went back on the record at 10:55 a.m.)

    SESSION 2: REGULATION 5: PATENTABILITY OF HUMAN ORGANISMS

    CHAIRMAN KASS: On the record. Would Council members please return to their seats so that we can get started. All right. This is the Council's third session on the topic of patenting human organisms on which we had two sessions at the last meeting and from which the staff has prepared a working paper in your briefing book.

    Just to review the bidding at the June meeting #150 we began to explore the potential problem of the patenting of human organisms and we had five guest presenters who tried to provide us with a sense of the issues at stake, the history, the state of the present law, the interests and needs of the biotech industry and the moral questions surrounding the matter.

    The factual question for us is this: Are human organisms patentable subject matter under the terms of the U.S. Patent Code as interpreted by the courts and the applicable question is should they be? According to staff's understanding of what happened at the last meeting, it looks as follows: under the present and in the light of several important court decisions over the past two decades there is no explicit barrier to the patenting of human organisms; and that this is a troubling circumstance but any attempt to address it must take careful note of the needs of the biotechnology industry and should not be a backdoor effort to address the large moral issues raised by embryo research, genetic manipulation and other morally charged developments in biomedical science and technology.

    The presenters all urged us to focus very narrowly any kind of inquiry on the patent in question. Many of the people said that this was an inappropriate way to get at those larger moral issues, and one can concur. But that seemed to imply that the Council's only interest in taking up the question of patenting living organisms was in fact as a backdoor means of getting at those other issues. The suggestion is that this might not be true.

    Patenting might not be the route to those questions but it is the only route to answering the question of patenting human life itself which might be a significant ethical concern of some real importance to us. There is a moral aspect unique to the patenting question itself.

    So the point of this meeting is to have a discussion amongst ourselves to see how after several weeks of opportunity to think further about it whether this is something that we think is important and important enough to become some kind of Council project.

    Do we want to include human organisms at whatever stage of life, embryonic, fetal and child under the subject matters that might be patentable? If so, why has there been a reluctance to do so? And to what does this reluctance point? What could it teach us?

    What would it mean to grant quasi-property rights patent protection over human organisms over body or body parts? How does this relate to larger concerns what some people expressed about the commodification of human life? What does this actually say about the topic that we'll be discussing tomorrow, the relation between ourselves and our bodies? Patenting isn't the backdoor to these questions. It seems to lead to them directly.

    On the other hand, a biotech industry is a precious resource. The patenting is a terribly important instrument for encouraging innovation and any discussion that we would have about these matters has to keep firmly in mind that this is something to be treasured. Any attempts even to think about closing a loophole must keep the fundamental purpose of patenting in mind which is not to regulate but in fact to assist and encourage commerce and industry and the advancement of knowledge.

    That, by way of introduction and I simply was setting the table to see where your thinking is on this question. Whether you think there is something here of limited or perhaps not so limited scope that would make sense for this Council to take up. The floor is open for your comments and discussion.

    PROF. DRESSER: Well, if no one else wants to jump in I will. I guess I have a few thoughts on this although my head is still full of cloning. I guess there are things I think to be said for taking it up and questions I would have.

    One reason to take it up is that my impression is that people who are patent law scholars such as Professor Rai who was here with us before and I think she is not the most extreme example. But there tends to be a focus primarily on how should the patent law be designed so that innovation can be stimulated. That is the concern that they have.

    They don't really look at these broader ethical questions that we would be addressing in a project like this. I heard an interesting presentation in which someone was discussing this, Professor Boyle from Duke Law School. He said that it's like the top of the bus and the bottom of the bus. The scholars are up here talking about how do we foster innovation. On the bottom of the bus I don't endorse this hierarchy but there are democratic debates going on about what should be patentable subject matter. And we're not talking to each other.

    It's almost as though we speak in different languages. So I guess one thing that we could contribute would be an attempt to try to bridge that gap and to try to bring enough of the technical legal scholarship together with more democratic concerns. There I think we would want to try to get some good expertise in patent law scholarship because I certainly don't consider myself an expert on that.

    I guess a question I have is that I agree with Professor Rai and others that a patent is a property right. It's only one of the many property rights that exists. So is there a problem in treating patenting in isolation so that if we were to say well it's wrong to grant patents on human organisms wouldn't there still be a lot of other possible property rights that we might worry about, types of ownership and commodification. I think this leads to Michael Sandel's previous point at the earlier meeting about the question of whether we should just address the commodification more broadly.

    Then I guess another question I have is if we were to do this I think we would want to look not only at this question of human embryos and human life at various stages but what is a human organism. If there's a genetically modified creature how much of the human genome has to exist for us to consider it a human organism that would be encompassed in any policies that we might suggest?

    CHAIRMAN KASS: Thank you very much. Let me make a suggestion. There were about three or four meetings ago we decided not simply to do everything in queue in the hope that actually we might discuss one topic at a time. The group is also somewhat smaller. I'm sorry about that but we are somewhat smaller. Maybe we can actually discuss one topic at a time. Let me try to keep order and then let's try to stay with one thing and see if we can advance the ball.

    Rebecca has given us at least three things to speak on: building stairs on a bus; thinking about the relation between this property right and other property rights and the questions of commodification on them; the next question of all right if you wanted to say something about not cloning human organisms and what exactly does that mean. Michael, could I ask you to pick one of those things and whatever you pick we will discuss.

    PROF. SANDEL: That's a dangerous offer, Leon. I think we should take up the question of patenting life but my question is whether we would do it better if we took it up as part of a more general inquiry into the commodification of life.

    We found ourselves saying many times around the table over the past in the cloning debate that in many ways we wish that we could address cloning for biomedical research in the larger context of embryo research. Many times we found ourselves frustrated that we hadn't taken that broader view.

    I think that we might learn from that experience here. I think that might argue for taking up and I certainly think that's of importance and it's of great moral and intellectual interest, the question of the commodification of life in general. Patenting is troubling for reasons that I think are very hard to distinguish from the same reasons that make us worry about the commodifying of life in other ways.

    CHAIRMAN KASS: For example?

    PROF. SANDEL: For example, the buying and selling of eggs, sperm, fertilized eggs, stem cell lines, genes, commercially contracts for surrogate motherhood. I think that if we simply focused on that aspect of commodification or of property rights in life presented by patenting in exploring the ethics of that we would be driven to analogous cases about ownership of let's say in the sale of sperm and eggs or of surrogacy contracts or owning genes and —

    CHAIRMAN KASS: Organs.

    PROF. SANDEL: And organs. So if the moral arguments would naturally lead to closely analogous cases of those kinds I think we might regret restricting the bounds of our inquiry in advance. Now an inquiry into commodification might take longer but I don't see that as an objection to it.

    I think ethically and intellectually the issues raised are similar I think from the standpoint of focusing public discussion. It's as important to focus public discussion on these areas as it is on patents. So I'm all for discussing and examining the patenting of life but I don't see any compelling reason not to situate that in a larger inquiry into the commodification of life though it may be there are considerations I haven't thought about.

    CHAIRMAN KASS: Mary Ann, to this. Please. Would you put the mike on please?

    PROF. GLENDON: I agree with Rebecca and Michael that we ought to look at patenting in the context of the larger questions. But I want to throw out another idea about what the larger questions might be whether it be commodification which relates to the property is quite the right category.

    I think the patent language in the Constitution is a very interesting intersection between science and commerce. That whole set of questions about the relationship between science and commerce has been woven through our discussions and concerns about cloning and is likely to be woven through any subject that this Council might take up.

    It was interesting for example to read in this morning's Boston Globe of Ellen Goodman's column commenting on the recent controversy over the use of estrogen. It says that prescription of estrogen over the years represented the triumph of market over science. I think really that's the set of questions that we want to look at and just a few more words about that.

    We all agree around this table that free scientific research is of very value, something that we want to encourage, that patenting language of our Constitution wants to encourage. I think we all agree that the free market has great advantages but that both the freedom of science and freedom of the market somehow to work at their best have to be conducted within a moral and juridical framework.

    That's where the real hard questions are. Where does the moral framework come from? Internally? Self-regulation? Formation of citizens? Where does the juridical framework come from? That's really more in our province and I think that's the context in which we should situate our discussion of patenting.

    PROF. SANDEL: Could I just ask as a follow-up?

    CHAIRMAN KASS: Michael, please.

    PROF. SANDEL: I find that persuasive. Could you say just a little more about what in practical terms that focus which seems like a very good focus how might we structure that discussion? Can you say a little bit more about what you would have in mind?

    PROF. GLENDON: Michael, I think that's just the sort of thing that would take a period of preparing some papers and call some people in. But I think that would be a good general question to start out with. What should be the relationship between these two values that we pursue and believe in but both of which need some kind of a framework in order not to be self destructive. You can kill the geese that are laying those golden eggs of scientific advance and productivity.

    CHAIRMAN KASS: Directly to Mary Ann.

    DR. ROWLEY: Yes, it's directly to a comment that she made though. It's tangential to the discussion. I just want to point out your statement of triumph of marketing over science.

    You see what it really was was initial small scientific observations made concern conclusions because heart disease doesn't really increase dramatically until after menopause that estrogens might protect you from heart disease and other things. It was only when larger studies were done and good scientific data were obtained that it became clear that there are both benefits and disadvantages to a hormone replacement therapy.

    So that good science, well done science on a large scale was what was required to then clarify the good things for hormone replacement therapies such as reduction of osteoporosis and the bad things such as potential increase in heart disease and breast cancer. These are very small increases proportionately over the general risk so you have to have well done large studies in order to begin to get some of these data.

    CHAIRMAN KASS: Mary Ann please and then Gil.

    PROF. GLENDON: The phrase wasn't mine but nevertheless I think there are issues just on that particular problem that bear examination. Was estrogen therapy oversold to women who really didn't need it and what was the role of the drug companies? So it's again an intersection between science and commerce that we don't very often look at as closely as we ought to.

    CHAIRMAN KASS: Gil and then Dan. I'm just trying to keep us on track.

    DR. FOSTER: I want to respond to Mary Ann. There's another thing and I don't know these legal terms and I don't know whether commodification is the same thing but you hinted about the effect of the market here and we see it on all the advertisements on TV and everything for drugs right now we've talked about that in this conference before. I have a further concern and I don't know whether it ought to be part of yours and Michael's consideration but if you use the term you will understand what I mean if it's correct or not.

    There's a commodification of the scientists themselves which to me is in many ways deeply regretful. There is a powerful incentive to make money. I mean scientists didn't used to be too interested in money or academic people. I remember when I decided to go into academic medicine I told my wife when I decided to do that we're going to always be poor but that's what I want to do. She said okay I'm with you. But it didn't turn out that I was always going to be poor because I make a good salary and so forth.

    But the emphasis, the commodification that I worry about is that the power at least when the market was very high of making money in biotech companies and so forth no doubt influenced not only what one worked on which in one way is good. Many of the basic scientists are working on clinical things when they wouldn't touch it before. But it's also inhibiting.

    For example often times there are restrictions that would allow the graduate student or post doctorate fellow not to talk about the work that is going on or you don't talk in the hall. It used to be when you walked around the scientific institution people are jotting on boards in the hall and I'm happy to say that we still have a few boards at Southwestern where we jot in the hall regardless of somebody owns a company and I'm in no company.

    I have no restrictions. But I wonder if the commodification of scientists itself might — I think there are ethical issues there that we might want to talk not only about worrying about the market and other things but that might be something that we might want to include in your broader scope. The topic might be minor but I'd like to talk about it.

    CHAIRMAN KASS: Gil.

    PROF. MEILAENDER: When I told my wife that I wanted to go into academic life and teach ethics I said we will always be poor and by George nothing has changed.

    (Laughter.)

    DR. FOSTER: Now listen at this late time in your life, Gil, if you wish to be admitted to a medical school class I will try to see what I can do.

    (Laughter.)

    PROF. MEILAENDER: Thank you. Back to the patenting thing, whether we should proceed with this or not I don't know. I'm not sure it's at the very top of my list of questions to proceed with. Just thinking about how one might proceed if one did, I grant that the commodification issue is inevitably an important one there and the relation of commerce and research is important.

    But I must say that I'm leery for a body like this beginning with some kind of grand, large, philosophical starting point. If we start with commodification, we can spend a long time reading an amazing body of literature about the body and what it means to be embodied and so forth. If we start with commerce we can all read Tocqueville to think about what a commercial republic is.

    I think I might be more help to think about it if I started with something very narrow and precise and then waited to see how these larger questions which I agree are there came out of it. For instance when I read the staff paper I realized that I never actually read section 271(G) of this patent law.

    I think I would be more help to have that section in front of me and a proposed revision of that section by somebody who wanted to figure out a way to control patenting of a human organism and then listen to a couple lawyers argue about it. Perhaps a couple biotech researchers argue about how it worked. Then I'll see what big questions do or do not emerge from it. I know whether I think I have a very small project here that doesn't require much more than a letter to the President saying the Council has thought about this and recommends this or whether it requires something more like a report. At least for me I would rather start that way and see how the big questions fall out.

    CHAIRMAN KASS: This is really methodological. You don't dissent from the importance of the large questions but you worry about whether it makes sense for this body to tackle them in that global way.

    PROF. MEILAENDER: Right. I make my living thinking about large questions.

    CHAIRMAN KASS: You make your non-living.

    PROF. MEILAENDER: My non-living. My less-than-Foster living. But no I don't know for a group like us if it will work very well to start big.

    CHAIRMAN KASS: Frank.

    PROF. FUKUYAMA: I'm really with Gil on this. I think there were a lot of practical issues revealed in the discussion at the last session on patenting that really need some fairly nitty-gritty discussion. For example, although I think that Professor Rai was correct in saying that if you for example want a blanket ban on embryo cloning probably the best way to go about it is just to ban it and not try to get at it through patent law.

    There is something a little bit disingenuous about that because she was preceded by Mr. Holtzman who said well if we don't have property rights in these procedures you're not going to have any of this product. So obviously there's a relationship between whether the thing exists and whether those property rights exist. One alternative path towards regulating these activities is by controlling the property rights. It doesn't get at the ethical issue. I mean there is an ethical issue of commodification in addition but there also is a very important practical significance.

    The other thing that was quite clear from that discussion is that in fact the patent and trademark office does get into a lot of ethical issues where they have absolutely no institutional capacity for making decisions. It was clear from that discussion for example that some of their past decisions had amounted to asserting that life begins at conception because I believe in the materials we were given it clearly indicated that they had applied the rules about no ownership of human beings to basically an embryo which I think would probably surprise a lot of pro-choice people in this country that some patent lawyer tucked away in a obscure bureaucracy and Washington have made this decision on behalf of the American public.

    It's just such a minor — It didn't get particularly politicized but that's an important decision. It's very clear that as a particular matter that whole institution needs to have some scrutiny but also I would say put in the context of scrutiny of a lot of other institutions that we have that control biomedicine.

    CHAIRMAN KASS: Robby George.

    PROF. GEORGE: Yes, thanks Leon. If we go into the issue there will be good reasons to avoid making the issue simply replicate in large measure, the debate of the moral status of embryonic human beings. There will be a lot of pressure that we will apply to ourselves to avoid that. At the same time for the reasons that Frank has articulated and others, we will discover there will be in the end no avoiding that issue. The issue won't perhaps dominate the discussion because there's a lot more to the issue of commodification than the status of the embryo. But that's a very important issue and I think it's going to be difficult to avoid.

    But I wonder if we will find ourselves bumping up against that issue and against our disagreement on that issue and then constantly having to pull ourselves back from it but pull ourselves back feeling quite unsatisfied because in a certain way for the reasons Michael articulated to engage the issue of commodification fully, we have to engage that issue.
    I guess there are lots of reasons we are going to eventually have to engage that issue. I hope that eventually we will.

    CHAIRMAN KASS: I shall take that as a friendly warning. (Laughter.) Look. Let me try you out on this and let's shift from thinking about the embryos to something that I doubt no one is going to make an argument that an isolated organ is a human being. Right? One could imagine that with certain kinds of genetic alterations that would be the work of human art rather than of nature. In fact one has seen it with mechanical organs.

    One could imagine that one could find ways of altering fleshy organs as opposed to mechanical ones such that they would come under the category of patentable matter. I guess the question would be does one regard that with equanimity or does one say that there is something here that one wants to draw back on.

    In other words, I'm not sure that the issue about the patentability of human organisms and let me add their parts is simply going to turn on the vexed question of whether this one-cell creature is or is not a human being. I'm not arguing one way or the other. But Michael sent out a list of a whole series of things that I don't think he was simply trying to get us to avoid the focusing of all this but he believes that that's the right domain.

    PROF. GEORGE: Yes, I wasn't asserting that every issue is going to turn on the moral status of the embryo. But I think that there are going to be a number of issues that are central that will implicate the question of the moral status of the embryo. And we're going to bump up against them. Are we just going to draw back each time?

    CHAIRMAN KASS: But my point was and I guess I didn't make my point that just as one doesn't regard a human body part as a person so someone who didn't regard an embryo as a person might still find it regrettable that one is getting patents but doesn't necessarily turn on the judgement about whether the embryo is a full person or not, whether one thinks that this is an area that has an ethical dimension worthy of our attention or not.

    PROF. MEILAENDER: Leon, just could I intervene to say. I think you should eliminate the full person language in your exchange with Robby. I think that loads way too much. Use human being or something like that.

    CHAIRMAN KASS: I accept the correction. It was loose speech. Do you want to fix my sentence?

    PROF. MEILAENDER: I would never try to do that.

    CHAIRMAN KASS: Make my point for me here.

    PROF. MEILAENDER: I don't think it's a point that I disagree with. But I don't know if I want to make your point exactly. I think all Robby is saying and I believe I agree with it is that at some point in discussing this issue you're likely to end up talking about some things that the staff paper I think calls human organisms. The question is going to be what is their status.

    CHAIRMAN KASS: Right.

    PROF. GEORGE: And we're going to want to distinguish those things that are not human organisms from those that are. While some people are going to make undoubtedly arguments or at least will have concerns about patenting even in cases where they don't believe that you have a human organism in play. There will be others for whom that will be crucial and the trajectory and content of their arguments will be affected by that which I guess is just a long round-about way of saying let's do this. Let's do it knowing that as with cloning we aren't going to be able to simply separate out even if for other reasons it would be desirable to the question of the status of the embryo, and please at some point let us be the ones to lead or at least invite our fellow citizens into a national debate about the moral status of the human embryo.

    DR. KRAUTHAMMER: Could I make one point? I think you're right. You will have people agreeing and disagreeing about the moral status of the embryo but thereby for different reasons coming to the same conclusion about how we ought to deal with the patenting of human organisms or parts in the same way we this morning had people who disagreed about the status of the embryo who came together on recommending what we ought to do with cloning.

    So I'm not sure that it's going to be an impediment to reaching a serious proposal conclusion recommendation that we can make. I think you're right in highlighting that there's no getting away from this conundrum but I'm not sure in the end it will stop us from achieving a good result.

    PROF. GEORGE: I agree with that. I think the parallel with what we've done in cloning is pretty close. I know that it would have been nice in dealing with some important aspects of the cloning issue to be able to get rid of the question of the embryo if it could have been laid aside. It turned out that we were unable to do that. We can now understand why we weren't able to do that and we'll be unable to do it I think when we move on.

    But, Charles, I'm not making an argument for not moving on to this issue. I guess I just want us to have in mind that we're going to bump up against it as we did with cloning. But I hope at some point we'll really confront it directly.

    DR. KRAUTHAMMER: And I'm hoping that we don't.

    (Laughter.)

    CHAIRMAN KASS: I was going to say something but I think I'll let it sit. Robby's point is at least taken and for the record it should be noted that all parties to the discussion in the cloning report adverted to, made use of, based arguments on some tacit or explicit views of the status of the embryo.

    We had many abortive attempts to discuss that amongst ourselves. It is one of the large themes that is not thematically treated as a separate section of its own in this report. It was one of the things that struck me reading the whole report at the end. You dealt with procreation. We dealt with meaning of healing. You dealt with science in society. But there really wasn't some section with embryology and so on.

    Maybe if we had that we might not have been able to finish but it will come back insofar as we take up the question of embryonic stem cell research. Without making any promises, let's at least keep in mind the possibility of doing it better although I think it would also be very nice for the short run to have a little respite.

    I'm speaking simply from the chair that we find some topic in which that question doesn't get in the way of our making some progress on the thing that mattered to all of us. Then I think lots of interesting things could happen around the table. Mary Ann, was that a hand?

    PROF. GLENDON: Yes.

    CHAIRMAN KASS: Please.

    PROF. GLENDON: Well some topics since I'm a property teacher property suggests itself because of the topic. Maybe the way to think about the issues that Rebecca and Michael are raising and the patent is about the question why it is that we assume that certain things can be owned. In the history of property law over time, there has been great variation in notions of what is a proper subject of ownership and what is not.

    Also by the way I should say there have been great variations in what is the constellation of rights that we call property rights. Property is not a unitary thing. It's a bundle of rights. To have a patent on something is not necessarily to have the whole bundle of rights that one could possibly have. If you have a patent on an organism, it doesn't mean necessarily that you own that organism for all purposes or that you can do as we often say about property anything I want with it. That's not really what property is about in any legal system.

    But here's my concrete suggestion. There are more legal systems than not in the world that view the human body as not a subject of property rights and as not in commerce. I would think that if we are going to go forward with this it would be very interesting and helpful for us to have somebody from France or Germany, one of the Romano-Germanic systems somebody who has served on one of their Bio-ethics commissions, come and talk to us about what it means concretely as a practical matter to have a legal system in which that idea of outside of commerce, outside of property is deeply embedded and how they deal with all the problems that modern science poses.

    I would say that at the heart of our political philosophy there is a problem. John Locke at the very heart of the chapter that is the heart of his essay on liberty, the chapter on property, says his starting point is that we own our own bodies. He just asserts it. He doesn't have any argument. He just says we own our bodies.

    That poses a problem for him and for us immediately because if you own something, can you alienate it? Locke really never solved that problem. He didn't want to say that we can alienate our body but he wasn't able to really put together this idea that you can't really alienate your body with the idea that you own it. But that idea of owning bodies which is unique to the Anglo-Americans really bedeviled our legal system. So I'm suggesting that we take a look at how other legal systems approach this.

    CHAIRMAN KASS: Michael?

    PROF. SANDEL: I like that idea very much. I think that whether we undertake that or any broader inquiry we should in any case provide Gil with section 271(G) which he can read during or after any of these philosophical discussions. I think the idea of the human body and commerce(?) might be one way of framing this.

    It occurred to me thinking about this just as we've been discussing that one reason not to have a quickie narrowly focused study is and I haven't followed in detail or as much as I should the Senate debate and what Senator Brownback's fallback position is but as I understand he has gone for a moratorium and then for some legislation on patenting.

    I think there's the risk especially now since the Council has recommended a moratorium and now we're going to do a quickie, small, brief, narrowly-focused thing against patenting. It's really going to look like we're doing what we are committed not to doing, taking our agenda from a certain sector in the Senate and plugging ourselves into that.

    I think that's a further reason not to do this but as the report keeps saying time and time again and I kept wondering why I kept reading very small, brief, narrowly-focused and so on. For political reasons I think it would be a bad idea.

    I would just add to that the more fundamental reasons which are intellectual ones and ones having to do with the character of the moral inquiry. So I would very strongly urge that we adopt something like Mary Ann's formulation just now, the human body and commerce or ethical questions at the intersection commerce or science or commodification or even as Gil put it the question of the moral implications of being embodied cells and what implications that should have for policy and law in patenting and in buying and selling of organs, bodies, so on rather than the small, brief, narrowly-focused quickie.

    CHAIRMAN KASS: Bill Hurlbut.

    DR. HURLBUT: I basically want to ask a question of the legal experts here. My understanding of the whole concept of patents is that the right to make some commercial benefit from something. It does not hinge primarily or exclusively on a patent but rather that patents are a way of opening up the process of producing something.

    In other words, if I have the history of this right, originally patents were over technique for making a certain kind of leather and the idea was that the technique itself would be made public in order to foster alternatives and deeper uses of this as opposed to keeping it secret. Don't we have in our society a right to not ownership of something but commercialization of something that we just keep secret without having to grant a patent in the first place?

    PROF. GLENDON: Yes, as the people who came to our last meeting explained if you want to speak very precisely about what it is that a patent gives you it is the right to exclude others for a certain period of time from the process that you patented. The Supreme Court of the United States has said frequently that the right to exclude is the most important stick in the bundle of rights that composes property rights.

    But it's not the only stick. So to have that stick by virtue of a patent doesn't mean again that you can do anything you want with what you have. In other words, there is room for regulation.

    DR. HURLBUT: And then the other side of it being that there is a possibility for commercialization and commodification even in the absence of a patent. Is that right?

    PROF. GLENDON: Sure. All the patent does is give you the exclusive right to exploit process that you have patented for a period of time. So in a way it's a suspension of free market activity for the sake of another value.

    CHAIRMAN KASS: Question. Gil has mentioned for taking case studies and starting small not to do a quickie because he worries about our starting a large stratosphere. Is that the top of the bus or the bottom of the bus? I can't remember. It's the wrong metaphor but never mind.

    Are there other areas that strike you as just Michael sent out and gave us a list of things in which the question is property in the body and its parts. Mary Ann refers to other legal systems where that is somehow beyond the understanding of what can be followed. Are there other specific aspects of this that one might cluster together and see if they add up to something? Gil, do you have some thoughts for particulars?

    PROF. MEILAENDER: See, I don't know if I'm the person who is persuaded that they cluster so much and that's partly why I suggested starting where I did. We have a session tomorrow where we're going to talk about possible future work for example. I was going to raise that somebody needs to think about organ transplantation industry and the increasing number of arguments being put forward for some kind of commercial payment for organs because actually I think it has been for some time an important issue and if you pay attention you will see that it's really cycling back and there's a lot of attention on it.

    Now there's an example of another issue that relates. I'm just not sure that the and I can be persuaded but I have to think about whether the question about whether I ought to be able to arrange to have my organs sold after I've been in a car accident to benefit my heirs who need, Dan, all the benefiting they can get. I'm not sure how that notion of selling organs from someone who's essentially a corpse relates to the question about getting some kind of property right even if it's only some of the sticks in the bundle, Mary Ann, in a human organism.

    Maybe it does. I'm certainly open to being persuaded but I just don't off the top of my head see how it does. That's why I would rather take and I don't too much care what issue but if it were the patenting issue I would rather start with that and then see what connections I made.

    Even in some of the other things that Michael mentioned in this list like surrogacy for instance, people who disapprove of surrogacy have never been able really to agree on what the reason is. Some people think it's more for one reason. Some people think it's for another. So it's hard to sort out. I guess yes it's interesting. I agree with that. And if you were teaching a class where you had a semester to sort it all through I think that you might proceed in one way. If on the other hand, you were chairing a bioethics council which came together at most once a month for a day and a half to think about something, I believe I would start in a different way. That's all.

    CHAIRMAN KASS: Janet.

    DR. ROWLEY: I think there is an aspect of this discussion which is probably a practical aspect that should be considered. If you look at what is currently patented not patentable but patented related to humans, their genes and their cell lines. Both of these have utility both scientifically and commercially. They can be replicated so that you can use them, you can give them to somebody else, that other person can use it.

    The hypothetical question you were posing about taking an organ and modifying it in some way so that it might be different as you were discussing this I was trying to think well then it's a unique process that you've done unless it was a process that could be widely applicable to all sorts of organs. The heart for example you did something unique to it that made it more useful, made it less subject to rejection for example.

    Again coming back to something that I think Mary Ann was saying you can patent the process by which you make that organ more universally acceptable, you aren't actually patenting the heart itself. So I think that we should at least keep some of the perspective in mind as we discuss this issue.

    CHAIRMAN KASS: Yes, that's very helpful. Thank you. Mike.

    PROF. SANDEL: Here's one possible practical suggestion. We had a session late in our discussion of cloning for biomedical research where we invited people who could tell us about the experience in other countries. As it turns out in most of those other countries they did deal with the broader question of embryo research rather than cloning specifically.

    Could we maybe have a session along the lines that Mary Ann suggested where we would have people tell us about how other legal systems and regulatory systems deal with the question of commerce in the human body including patent law but not limited to patent law or other regulatory aspects. Then on the basis of such a session try to figure out whether we had a workable topic or one that we might define.

    CHAIRMAN KASS: Comments to that? Whatever we do on this, the purpose of this meeting was not necessarily to lead to the conclusion yes we should or should not do something right away on this but to see whether there is interest here. Even if there was enough interest to say this is important subject but it may not be important enough given the other things that are competing for attention from us and we'll be talking about that tomorrow.

    It seems to me fairly clear that if we wanted to pursue this some additional work behind the scenes has to be done by way of inviting in some outside consultants to enlighten us on one or another of the larger aspects of this the way we did get some help on the narrower question of the patenting last night.

    It might also would be good and maybe we can work this out by the end of tomorrow if the people on the Council who have a special interest either in the science-commerce end of this or the commerce-body end of this might constitute themselves a small working group.

    It's true, Gil, that we come together once a month or six weeks or so for a day and a half. And you've given very generously of your time in the interstices. We can't demand very much more of this body than you are already giving.

    On the other hand there is no reason why if there's real interest that that interest occupies three or four people only the staff and the group as a whole thought this was sufficiently worthwhile to allow some of us to explore and bring back to the group we could provide some staff help and support to that. So not everything has to be done always in the plenary the way we've tackled this. So unless there are some more substantive things. Charles?

    DR. KRAUTHAMMER: I would just like to make one practical suggestion from what Michael had said.

    CHAIRMAN KASS: Please do.

    DR. KRAUTHAMMER: I seems to me that the question of patenting the human organism is a subset of commerce of the human body which I think is a very interesting subject. Another subset is the sale of organs which is a very eminent practical and I think pressing issue. So perhaps we could address the larger issue of the commerce and the body by starting with a look at the sale of human organs. Then we can see whether we get a two-fer out of it by having principles or ideas deriving from that subject that would apply to patenting of the human organ.

    CHAIRMAN KASS: I'm not sure we can plate this out for the morning but how should I read these looks of silence? Fatigue? Hunger? Are there enough people here who think that there is topic not necessarily to put as a definite topic for us but to keep in mind as we go to work tomorrow and that what we really need to do is some strategic thinking about how it should be framed.

    I myself like the possibility of juxtaposing say a concrete matter on the sale of organs and the concrete question of the patenting as two ways and maybe the thing that concerned Paul McHugh in the comments this morning that has concerned Rebecca about the egg donors who are paid for their services but not for their eggs that is to say the way commerce functions in that area as well.

    But maybe there are three mini-pieces of something but then it becomes a very large project to be done right. I think some kind of help from how other people think about this legally and ethically would also be useful.

    It is with all due respect, Robby, not just the body. Gil in his early paper that he wrote for us when he talked about some of the large themes of bioethics raised up the question of embodiment and the question of the relationship between embodiment and identity. That is one of the relatively neglected topics in the field of bioethics commerce or no commerce and what is moving body parts around.

    I don't want to speak for Mike in his absence but I listen to him on some occasions. It sounds as if for him his identity is almost entirely cerebral and the rest is an apparatus that enables it to work. I don't mean to defend this. There's a distinguished pedigree to that idea, very distinguished. Yet here we are with hunger and we're endowed with a respiratory system that is so designed so that one can in fact be the rationale animal and speak with one breath.

    DR. FOSTER: Mr. Chairman, I don't want to interrupt you but let me make a couple of suggestions. I'm just going to suggest that we adjourn. I think we're in post traumatic shock from this morning. Secondly I do think there is an important issue for tomorrow about the priorities of things. For example, I believe that the natural movement would be to move from the cloning debate into gene therapy debate and particularly the more dangerous issue in my view that we have to discuss of germ cell therapy. Somatic gene therapy is an entirely different thing.

    But my view would be although I'm very intrigued by this and I don't mind moving that into the next place because you could do it that we could decide tomorrow because I do believe that the natural sequence would be into moving into gene therapy. There's where the enhancement and all those things are going to become so much more important. We will hear about more of that this afternoon with support. So my motion for you, Mr. Chairman, is that we now adjourn for lunch.

    CHAIRMAN KASS: I will do that only after the two guys who have had their hands up.

    DR. FOSTER: I believe that my motion trumps if I want to call for — No I'm kidding. Go ahead.

    CHAIRMAN KASS: We will exhort that the last two commentators take less than a minute or two. Bill and Gil and then we will adjourn.

    DR. HURLBUT: Well, it's an odd moment to make a comment after that. I just wanted to point out that what Janet said about process versus product is very important but the strange thing about all this is that now we're moving into the regime where organismal processes in a way are becoming patentable products. That I think we are going to have to confront. This relates to what Robby brought up but it relates more broadly to the issue of commodification of human beings and their embodiment.

    We are going to have to confront the question that was a little less complicated in past generations where it was parts apart from wholes. Now we're going to have to confront the question of partial generative potential apart from full organismal generative potential and that makes it somewhat more complicated and brings us close into the question of whether there is something about the human organismal process that is different in quality than the small significance that other organismal processes.

    CHAIRMAN KASS: Gil, do you still want to speak?

    PROF. MEILAENDER: Yes, although I hate to do it when someone has mentioned lunch. This may simply reflect my own lack of knowledge in a way but I just want to say again or ask again with respect to the patenting issue. I came away from our session last time thinking that at least for people who work on patent law which has a very long developed history in this country it's a realm from which moral considerations are largely excluded.

    It is quite technical in certain ways. Therefore it's hard to figure out how to drag into it these larger sorts of questions. That's really been the source of my reluctance of lumping issues here. I just wonder if it's not a sufficiently different issue because of that long technical and somewhat amoral history that makes it to some degree a world unto itself and a little less able to be lumped into some larger circle. That may just be ignorance but I just wanted to make that clear once more.

    CHAIRMAN KASS: Thank you very much. I remind Council members that owing to the exigencies of Dr. Wendy Baldwin's schedule we have to start at 1:00 p.m. Please as a courtesy to our guest be back promptly at 1:00 p.m. She will be speaking to us about the NIH implementation of the stem cell policy. The meeting is adjourned.

    (Whereupon, at 11:55 a.m., the above-entitled matter recessed to reconvene at 1:05 p.m. the same day.)

    SESSION 3: STEM CELLS 4: NIH FUNDING OF STEM CELL RESEARCH (IMPLEMENTATION)

    CHAIRMAN KASS: On the record. Thank you very much. I think we should start. We have a couple of stragglers, Dr. Baldwin. There are always a couple of stragglers. I think since your schedule is tight we should get moving.

    It's a great pleasure to welcome Dr. Wendy Baldwin who is the Deputy Director for Extramural Research in the Office of the Director of NIH. And who after President Bush announced his decision on stem cell research, he was finished and she was not. She has come to talk to us about the implementation of the President's policy on stem cell research. We've been looking forward to learning exactly what's happening. It's very good of you to come and join us and educate us this afternoon. Thank you.

    DR. BALDWIN: Thank you, Dr. Kass. I'm very happy to be here and to tell you how I've been keeping myself busy in implementing this policy. Let me go through a little bit. I don't have handouts of the overheads, but I'd be happy to leave the overheads if you'd like. I don't think I have to go into much detail with this group certainly about what the embryonic stem cells are, their unique properties, their ability to proliferate, and the capability of forming other kinds of cells. So that has importance for basic science understanding of what cells do as well as our anticipation of clinical application as well.

    There are many areas that we feel are major questions for us to think about where stem cells are going to influence how biology is done and what the importance will be. Our major activity right now has been to implement the policy that was put in place last August 9th. So the criteria for allowing research with federal funding on human ES cells is shown on this slide. I think we're probably all familiar with this.

    They had to have been derived from a blastocyst that was initiated prior to the President announcing his policy. The embryo had to have been created for reproductive purposes and no longer needed which means it came basically from IVF clinics. There had to be informed consent from the donors to use these cells with no financial inducement for the donation.

    The way we're implementing this is that having established these criteria our first job was to complete the documentation and ensure that we had documentation, that the available lines met these criteria, and then to post a registry. Once we did that then an investigator could go to the registry and identify a line that they wanted to use knowing that it met the President's policy. So this is front-loading if you will that review process.

    On November 7, 2001, we published the NIH Registry. I've given you minimal handouts. You must have 150 pounds of paper to carry back with you. Your handout from me is one single sheet of paper, two-sided. On the front, it shows you the registry. On the back, it shows the stem cell site on the NIH website that has every conceivable document. People are looking around like they don't have it. Do they have it?

    CHAIRMAN KASS: I'm afraid there's been a slip up.

    DR. BALDWIN: We will get it to you.

    CHAIRMAN KASS: Does anyone have these?

    DR. BALDWIN: It's a page.

    CHAIRMAN KASS: They're coming right now.

    DR. BALDWIN: Once you go to the stem cell section of the NIH website, basically all of our documentation, information, et cetera is there and is updated regularly. It took us a little while to get the registry up. We wanted to be sure that we had developed it in a way that would be user-friendly and that we had unique codes for the different stem cell lines. It went up November 7th. Then what we did was we started to put in place the things that would be needed for investigators to make use of the registry and actually obtain funding to do this research.

    The first thing we did was to realize that we had amissed the posting of the registry so that people could come in for our October 1 receipt date. NIH has three rounds of application receipts. So what we did is extended that receipt date so that anyone who was sitting there poised to do this research still had an opportunity to get an application in.

    We then moved on to issue and announcement for Infrastructure Awards so that we could reach out to the sources so we could help them be sure they were actually going to be able to provide stem cells for the researchers who wanted them. We moved on to Administrative Supplements. I'll go into these in a little more detail, but it shows you how almost week by week we were putting in place one or another element that was necessary for us to actually fully implement this policy and make it a reality for the research community.

    So Administrative Supplements, Training Potential, all of these pieces. The implementation job was really taking the policy and then saying what are all of the different steps that have to happen to make this actually really work. Let me go back to that one in a minute.

    The last one on there is we announced the procedures for how you could use the process that's in place for having research done on human embryonic germ cells. In May 20th, we had the first review of such an application. That's the companion to the embryonic stem cell activities.

    As of July 5th when the slide was done, we had made five of these Infrastructure Awards, 13 Administrative Supplements, and one Grant Award. That I think people can look at and say one award. How can this be? But there actually is a fair amount of time that takes place between submitting an application to us, going to scientific review, going to an advisory council, and an actual funding decision made, and an award made.

    What you're hearing here is our taking that policy and mainstreaming it in to how NIH does business. We have very sound principles as to how we do business of transparency and peer review. We're bringing stem cell research into that process. At the same time where we've identified what might be a gap or a hurdle or an impediment, we're trying to reach out to that as well whether it's a need for training or a need for infrastructure support.

    A few features of this registry. We are listing all of the cells that meet these criteria. You may be interested to know that we've added lines since the President's statement because we found six additional lines that met these criteria. The registry serves two very important functions. It provides a code for each of these and provides the contact information because an investigator that wants to do this research goes to the registry, identifies a line, and then gets in touch with them.

    This is the content of the registry. When you go to each one, this is what it looks like if you go to it on the web. You can't read that on the screen. When you click on any one of these sources, you go to a slash screen that's for that particular source. This one happens to be WARF. You'll see that it gives you contact information, e-mail information, their website, and the information about the cell lines that are on there. That is information we're asking the sources to keep up and keep current because it is their information.

    What have we found to be the issues for researchers? Well, first is the simple access to the line. Are there intellectual property issues, IRB issues, administrative ones, and ones relative to how they're going to actually get the skills to work with these lines? Let me take these one at a time.

    There have been questions as to whether these cell lines are actually available. I think it's important to realize that human embryonic stem cell work is relatively new. Because this was not an area available for federal funding prior to the President's statement, they are largely in foreign sources or commercial entities. So many of these groups were not at the outset thinking about supplying the scientific community. That's why we put infrastructure support out there, so that each of the sources can come to us and apply for funding to help them scale up, better characterize their cells, and make them available.

    These are the awards that we've already made. (Indicating.) It's on a rolling receipt date though. It's something that we'll continue to do as long as we have sources that need infrastructure support in order to make their lines available.

    There are of course many things that can affect easy access to these lines. In some cases, we have international issues. There's been a change in terms of whether biologic material can be shipped on a passenger airplane. I can't sit here and tell you that it's all simple. This is not Amazon.com where you can just click on it and it comes by FedEx the next day. There are things your investigators have to do in order to get access. They're not qualitatively different from other fields, but they are important in this case.

    All of these lines have intellectual property issues associated with them. As I said by enlarge they are either commercial sources or they are foreign sources. There is a U.S. patent on the derivation method. In fact, the sources have to work out their intellectual property agreements in order to make them available.

    NIH did something that's a little unusual here. We of course would have to negotiate a memo of understanding for our investigators to have access to these lines. We did the first one with Wisconsin with WARF. What they said was not only would these terms be available to the NIH investigators but they would make them available to other investigators.

    That's important to realize because the NIH doesn't get involved in the negotiations between a source and a user. That's their responsibility. But what this has done is made it much easier. In fact, you can go to the website. Those memos of understanding are all on the website. An investigator can just download that, click on it, read it, take it to their tech transfer office, and if they can accept the terms which are pretty straight forward, they're ready. They don't have to negotiate this from the ground up as it were.

    We now have four of the MOUs that are available on the website. I'm walking you through each of these steps because I think it's important to understand the different pieces of this puzzle that had to be put in place so that this whole area of research would actually take off. Some of these sources may initially want to start out doing collaborative arrangements, and others are further along in their development and are more ready to make them just generally available. That was clear at the outset that we would have that kind of variability.

    This is the flip side of the handout which is the stem cell information site which is absolutely essential if you're interested in this area of research. On it, you will see all of the MOUs are there. We run a Frequently Asked Questions section. We update that as soon as we have anything new to put out there. Background reports, background material, anything a potential investigator or a funded investigator would want to know. We're trying to make it one stop shopping so that it is all out there and pretty easily accessible.

    In terms of IRB issues, all of these lines had documented informed consent for the donation of the embryo. One of the follow-on issues though was do any of these lines include identifiable information or not or are they completely anonymized. We worked with the Office of Human Research Protections to clarify the guidance about when IRB review is needed if there is identifiable information anywhere. In fact, this document which of course again is on the website clarifies that there can be a firewall, either it's anonymized or the person receiving the line has no potential to get access to any identifying information then that streamlines what they would have to do within their own institution. OHRP, we would not be requiring IRB review of the use of that line. Grantee institutions may of course have some additional requirements.

    There were questions raised about administrative issues in terms of how to think about the facilities and administrative costs if there were eligible research and ineligible research going on to the same institution. Again, we felt that there are already very strong and existing policies about unallowable research. The institutions know how to handle financially unallowable research. Basically this just clarified for them how to do that, again to mainstream how this issue is handled relative to other areas of unallowable activity.

    We have this as an administrative issue. I'm not sure that it is. Most research when it comes in it goes through peer review. Reviewers are really looking for preliminary data. In a new field, that's particularly challenging. If it's a brand new field, you may not have preliminary data.

    We've taken two tacks there. One is to now just have Administrative Supplements available, but to really go a little further step to advertise their availability. What that means is if you're already a funded investigator and let's say you're working on mouse ES cells and within the basic scope of the research you could add on some work in human ES cells, you can come to the NIH for an Administrative Supplement. They're modest in dollar support, about $50,000. They're handled administratively. But it is a way for probably our most promising cadre of investigators to get started in this field and be able to help develop some preliminary data. We've also tried to deal with that at the stage of review in terms of reminding people that this is an area where it's much more difficult to have preliminary data when you first come in.

    One of the difficult issues for us is these are not necessarily easy cells to work with. We've looked at what the need is there. Everyone who has worked with human ES cells has pointed out the need for very careful, meticulous laboratory work and that there's a high degree of variability across labs and culture conditions. So again, we've looked at what would be the tools that we could put out there to help investigators develop those skills.

    In some cases, they will get them through the acquisition process. So a source might package some training along with acquiring the cells from them. If you go to them in return for the price of getting the cells, you would also get a couple of days of on-site training for maybe your Senior Lab Technician. But we're trying to look broadly at that. We have an announcement so that an individual investigator who really wants to specialize in this area could come in and apply for funding or an institution that wants to focus on doing some short term training activities that they would make available to others could apply to us for support.

    Again, this is really taking the tools that we already have. We already know how to work with a community to build skills when it's necessary. We're just focusing them and applying them to this particular area of science.

    The information has been very widely disseminated. Now, we think it's been widely disseminated. Just because we think it's widely disseminated doesn't necessarily mean that it is. I get 350,000 or 400,000 hits a month on my website where this is located. We get more on the NIH website. You can access it right from the nih.gov site.

    We know some professional associations have been pulling up those Frequently Asked Questions and sending them back out to their constituencies. One of the things you can certainly help me with is if you can think of any other strategies that we might use to make this information widely available. That appears to do it. I wanted to go through that fairly quickly so that you would have a chance in my time here to ask questions. If anything that I've gone through was either too quick or didn't make sense, please ask me now.

    CHAIRMAN KASS: Dan Foster and then Janet.

    DR. FOSTER: I don't work on stem cells. One of questions I think fairly broadly asked in the scientific community regarding the research is given now the 80 cell lines, how many of those are in some sense adequately characterized to be useful in research. You know much better than I do, there's been considerable skepticism about the adequacy of these cell lines for the research that we want to do.

    DR. BALDWIN: Well, it's a little difficult to give an exact number. It's certainly in excess of two dozen on there and are pretty well characterized and we know they're available. I understand the question. I understand the concern.

    I think that we're equally concerned to see that investigators do get started working with the lines that are available. That's going to be the best test of how good those lines are. We won't know until people use them and test them and compare two lines from different laboratories.

    There's a tremendous amount of basic work that simply has not been done. While that's certainly an interesting issue to pursue, I'm at the implementation side. I'm asking are the grant applications coming in. Are we funding it? Are we building up a base of knowledge about those lines? I think we really have to do that.

    DR. FOSTER: Well, I think that's probably the only answer you have. We oftentimes say the only way you can answer these questions is to do the experiments. We had been talking about that earlier today.

    DR. BALDWIN: Exactly.

    DR. FOSTER: I think just myself that you've done a wonderful job on this infrastructure so far.

    CHAIRMAN KASS: Janet, would you like to begin?

    DR. ROWLEY: Well, I'd like to carry on with the first question that Dr. Foster asked you. Backing up just a bit. Have you or have you in conjunction with the sources come up with a set of standardized procedures that you're going to do to characterize these lines? Is everybody karyotyping their lines and doing some molecular analysis of them and what kind of studies have they done for longevity of the lines, et cetera?

    DR. BALDWIN: First off, the next enhancement if you will of the registry is to encourage our sources to provide additional data. The sources vary as to how much information they have and how much they're posting on those websites. To encourage them to go ahead and site either their published articles or the research that's being done with their lines, that's the area of enhancement that I'm looking for next.

    The next area I think will be for us to bring those sources together. They really form a very unique network. It will be bringing them together really as a group that I think would be most valuable, for them to share their experiences as to the most valuable information or where their information appears to be discordant. We've just made those awards within the last 60 days, so it's just a little early for that. That would be the approach that I'd be inclined to pursue.

    DR. ROWLEY: In terms of the Infrastructure Awards that you have made to individuals, you indicated in your very brief overview that you are asking or providing financial support to the sources to do some things.

    DR. BALDWIN: Exactly.

    DR. ROWLEY: I guess the question is in your infrastructure grants is there some commonality of information that you are hoping that they will use that support for to provide answers to some of these questions. Or is it just you have X number of cell lines and it costs X amount to do something.

    DR. BALDWIN: No. It's not that. But the first way that you phrased it, I think it would leave the impression that we're saying here's a list of things we want to see, do each of these with each line. We really haven't done that. They have come forward, not just give us money and we'll do more, but to say what they will do and that goes through peer review to say is that an appropriate strategy and are they going to be useful tests.

    I guess my experience has been especially in a new field bringing those investigators together so that four or five of them sit down and say here's the way I'm going to do this and here's the information that would be valuable. Having them talk that out to drive it toward some common sense of what is the most appropriate or the useful measures is usually preferable to us saying at the outset the specific ones we want to see.

    I know that's a taste in preference. Some people like a little harder edge at the outset. I guess my experience has been I prefer to draw some of that out of our sources as opposed to imposing it on the outset. But I understand your question.

    DR. ROWLEY: You're aware of the article in Nature suggesting it be some of the cell lines. Presumably all of these are grown on mouse feeder cell layers or virtually, a number of the cell lines are grown on —

    DR. BALDWIN: Many, yes.

    DR. ROWLEY: So that the possibility that there are mouse-human hybrids is real. Those would obviously have limited or no usefulness for the kinds of investigations that many people are interested in. I guess I'm a cytogeneticist, so the first thing we do for cell lines is karyotype them.

    DR. BALDWIN: Yes.

    DR. ROWLEY: I would have thought that it would be an important early parameter for the study section to have required that each one of the grantees do.

    DR. BALDWIN: It is. I think what you're raising to me may be one of the things that we could do would be to extract from those Infrastructure Awards a little more of the vision of what the sources are proposing to do even in advance of them having the results and having the data to post. Obviously the abstracts are available. But we haven't thought about doing that as an extract to see where that common sense of the group as to the most useful activities would be.

    They have latitude under a grant application. It isn't that they're locked into doing one thing. If six months from now it's clear there's something valuable to do, they could add that to it. That would be a very useful suggestion for this. I think I see something to go back and do.

    DR. ROWLEY: Okay. Let me just pursue two other aspects of this. I think it's marvelous that in your dealings with the sources that you have made arrangements for other investigators to get some of the same kinds of expedited access to the lines under the memorandum of understanding. I think that's marvelous because certainly these material transfer agreements can be painful and to do each one for private investigators is difficult.

    You raised the question of cost. I wonder is there a fair variability. It seemed to me that as we were approaching WARF it was several thousand dollars to get a single cell line.

    DR. BALDWIN: Because of the network of agreements really, I think that's going to be pretty standardized, the $5,000 for access. I'm talking about academic researchers not anyone who is accessing for commercial purposes. Then you can't just download an MOU and go to work. That's very different if you're setting out to develop them for a commercial activity. My interest is here, what we can do for the basic research community.

    DR. ROWLEY: Now, also in dealing with WARF, the MTA did include statements that any discoveries we make with those cell lines the intellectual property reverts to WARF. I don't know whether in more recent memorandum of understanding whether that's —

    DR. BALDWIN: (Off the microphone.)

    DR. ROWLEY: Okay.

    DR. BALDWIN: I don't think so. I could have brought you a whole notebook of this material. But I don't think that's the case for the academic researcher. Again, the MOU is downloadable.

    CHAIRMAN KASS: Could I just ask a question because this is an important question to lots of people? Could I have Janet ask the question again and could I hear the answer again so I know what we've just had?

    DR. ROWLEY: Well, I was raising the question that it was my impression that as we approached the Wisconsin Alumni Research Foundation that were we to buy the cell line —

    CHAIRMAN KASS: Right.

    DR. ROWLEY: Which is $5,000 and we did research with it, any intellectual discoveries that we made then became the property of WARF, not of us. There are a lot of these MTAs that have what are called pass-throughs. This was the question. Whether I was mis-remembering or whether possibly your memorandum of understanding is maybe a bit different than I recall from maybe four or five months ago because I haven't paid attention to this recently.

    DR. BALDWIN: I don't think that has changed in that time. I do have a copy and I'd be happy to leave it with you. I think you may be thinking of when you're obtaining the cell lines for a commercial development.

    DR. ROWLEY: No, because this is strictly university research. That's an important issues as to whether as you are making new discoveries they're your intellectual property or reverts in some way to the source of the cell lines. The fact that's not part of this is I think excellent. I assume that as people come in with R01s that the cost of the cell lines and things can be included as costs within the grant.

    DR. BALDWIN: Oh, absolutely.

    CHAIRMAN KASS: Again, just for my clarification. I gather the answer to that question is that reversion applies only if these things are sold to commercial organizations and not to university researchers. Is that right?

    DR. BALDWIN: Yes.

    CHAIRMAN KASS: Okay. Thank you. Janet, are you complete for now?

    DR. ROWLEY: Yes.

    CHAIRMAN KASS: Thank you. Rebecca Dresser.

    PROF. DRESSER: I wanted to ask about a couple of things. First, I was interested in how you decided about whether the informed consent requirement had been made in some countries far away. Did you ask for just some documentation or how did you approach that?

    DR. BALDWIN: We had documentation from all of the sources. We also had visits to a number of the sources. All of the sources at the time the registry first posted had come and visited at the NIH, so we had discussed these things with them specifically. We also have had visits to many of these other labs. So it's not just a paper review. It's primarily a case of them presenting the documentation which is always the case. That's the heart of it. But we have gone further than that.

    PROF. DRESSER: Right. I understand. The other thing I wanted to ask about is a little bit off the track but I understand that Dr. Gearhart recently got an award to work on stem cells from fetal tissue.

    DR. BALDWIN: Right.

    PROF. DRESSER: And that it went through a review process under the earlier NIH guidelines for stem cells which applied to both embryonic stem cells as well as fetal stem cells.

    DR. BALDWIN: Yes.

    PROF. DRESSER: So I understand that it went through a review process, and all the very detailed requirements were met. I wondered if that was the same review group that reviewed that protocol as the one that was earlier put up during the prior Administration, the group the Janet Rowley mentioned this morning.

    DR. BALDWIN: You mean the composition of that review group.

    PROF. DRESSER: Right.

    DR. BALDWIN: No.

    PROF. DRESSER: How did that work?

    DR. BALDWIN: Let me explain what happened there. We had these guidelines that covered both derivation from germ cells, from fetal tissue to generate the embryonic germ cell lines and also for embryos. So the expectation had always been there would be more interest in the embryonic research at that point. A group had been put together, but it had never actually met and functioned.

    So when the President's policy came along that really superseded this whole section on embryo research. So we rescinded that portion of the guidelines. But the only rescinded that portion of the guidelines. We left in place prohibited. We left in place the fetal tissue side of it. Now we had a very different creature because we knew the scope of that would be much narrower than was originally construed.

    So we basically went back and rebuilt that process. I mean, we didn't change any of the elements of review. We didn't change any of the rigor. But we did make that an internal NIH review. Obviously dealing with appropriate conflicts of interest so that there was actually someone who would be on that group who would have been from the funding institute. We had them absented from that review because of potential conflict.

    But we took that group which was very mixed in terms of their science background, ethics background, et cetera, to review that proposal and to align it with the guidelines that were in place. They did meet. That was a public meeting. We announced that in the Federal Register. We did approve that project.

    That process only begins when there is an application ready to be funded. So someone comes in, we knew the Diabetes Institute was ready to make an award through their Beta Cell Consortium. That's what prompted that meeting. It happens in conjunction with the Center for Scientific Review Advisory Council meeting.

    PROF. DRESSER: So is the group all then NIH employees?

    DR. BALDWIN: Yes.

    PROF. DRESSER: I mean, one of the things we're interested in is if you're going to have review of some of these kinds of things who should be on the group. I was just curious about that. So you see this group more as going down the requirements and checking off to make sure everything was done as opposed to making some sort of ethical judgement about whether it's good enough to go forward.

    DR. BALDWIN: Well, they're explicitly not to review the science again.

    PROF. DRESSER: I understand that.

    DR. BALDWIN: The science is reviewed on a separate track.

    PROF. DRESSER: Right. So what is their role?

    DR. BALDWIN: Their role is to in fact look at the requirements which have many different components and to see whether the documentation that's presented to us is consistent with the requirements that we've put out there. If you go back to your first question, it's really not terribly different from the review that we've done now on the materials submitted on the embryonic stem cells where we basically had the President's policy and it was our job which was in fact an NIH staff-level review as to whether the documentation was appropriate.

    PROF. DRESSER: Right.

    DR. BALDWIN: We were trying to look for some parallelism there.

    PROF. DRESSER: But the initial proposal when this was going to cover both kinds of stem cells, I just know some people who I believe might have been put on the earlier group. I know it wasn't all NIH. It was more diverse.

    DR. BALDWIN: Oh, no. Right.

    PROF. DRESSER: So was that group seen more as making conceptual, ethical judgements more than this one is?

    DR. BALDWIN: That group really had a much larger task because that was where we were envisioning prospective establishment of embryonic stem cell lines.

    PROF. DRESSER: Right.

    DR. BALDWIN: So they were going to really be reviewing the proposals or the strategies for developing those lines. With the President's statement, that decision was made. No prospective work, only retrospective. It's only those lines that meet these criteria fixed in time and space. I think we felt from the beginning that was going to be the much more challenging area and likely to be the volume of work would come in from the embryonic side. But that was a judgement call on our part to bring that a little more in parallelism with what we were doing on the embryonic side.

    PROF. DRESSER: Thank you.

    CHAIRMAN KASS: Bill Hurlbut.

    DR. HURLBUT: Apropos of that question in a slightly different perspective. Are there provisions in the way things run now for opening to new apparent embryonic-type pluripotent stem cells that aren't from embryo sources? For example, suppose that something like Catherine Verfaillie cells are shown to be truly pluripotent or maybe even totipotent. Are there possible ways to review that which would allow new lines to be admitted if they didn't come from embryonic sources, either from above or below in the sense that by de-differentiating something that was differentiated or producing something that was slightly differentiated from below? Do you see what I'm saying?

    DR. BALDWIN: But de-differentiating from an adult cell is not covered by this at all. Maybe I'm not understanding your question.

    DR. HURLBUT: One of the hopes is that you'll be able to take an adult stem cell or maybe a somatic cell using the proper cytoplasmic factors and bring it down to pluripotency.

    DR. BALDWIN: But you could do that. That would not be covered by this because you're not starting with an embryonic or a fetal line.

    DR. HURLBUT: My point is there are going to be some potential ethical questions around that, and they will be the equivalent of embryonic stem cells in a certain sense. I know that they're sources not embryos, but they're potential is what's also in question. Isn't it?

    DR. BALDWIN: Well, that's —

    DR. HURLBUT: I mean, you or the current policies would not approve for example the artificial creation of a zygote from above if you will. You could add the cytoplasmic factors.

    DR. BALDWIN: I understood your question as to whether there would be specific requirements to generate an apparently pluripotent stem cell line starting from an adult cell. We would not have coverage over that. I think you're probably really asking other questions about what you would do with that cell after you got it, perhaps.

    DR. HURLBUT: Yes. I'm trying to get at the moral question of whether the current provision has possibilities for reviewing new creations that are being worked on at this time.

    CHAIRMAN KASS: Bill, I think if I understand what is here being implemented is something that is tied specifically to these authorized embryonic stem cell lines.

    DR. BALDWIN: Right.

    CHAIRMAN KASS: And that while there might be other things coming along that give rise to all kinds of myriad questions, that's not the bailiwick of this body. Am I misunderstanding?

    DR. BALDWIN: No, you're absolutely correct.

    DR. HURLBUT: So they were not principles put in place. It was the cell lines only.

    CHAIRMAN KASS: Yes. Here was for the first time authorization, permission to go ahead with these lines. Nothing was in place to make that possible. The NIH has had the pleasure and burden of making this happened as expeditiously as possible. That's not without its difficulties and bugs. That's partly what we are learning about I think. What happens with other things that come along, that would require different kinds of structures or might already belong to different kinds of places. But that seems to be not the issue before us here.

    Could I ask a question. It's probably too early to tell because the number of proposals is still few. But what are you hearing from the investigators who want to get up and running, granting that there might be the usual kinds of impatience between researchers and funding and assistant sources? But with respect to the procedure, with respect to the obstacles, what are you hearing from the investigators who say at last? Are there certain chronic obstacles at the moment? If so, what are they?

    DR. BALDWIN: Well, I'd say the obstacles are not big obstacles, but they are certainly issues to deal with. They are really the ones that I've mentioned. You do have to deal with the intellectual property issues. I mean, this is something and that's true for many products that are out there in research that you do have to deal with and MOU. You do have to think about the intellectual property issues.

    I haven't heard any particular concerns other than the anxiety around how much emphasis we'll place on preliminary data in a field that's going to be a little hard for them to develop preliminary data. When we know that there are more lines being shipped then we're seeing applications for, it says to me that probably what is happening or what I am speculating is happening is that some investigators are going ahead, getting the lines, lines they know will be eligible for our funding, but working on them some before they apply to us for funding. That's not anything we're imposing on anyone.

    Most researchers like to put the best application forward that they can and knowing the difficulty in working with these lines, knowing that it's not simple may want to buffer themselves with some time before they actually come in with an application that goes into peer review. That's really my speculation from bits and pieces that we've heard.

    I think we have six intramural labs that have now received cells. This is all really very new. I mean, I don't know how people's cosmic time sense here is but for me this is very fast for this much of a roll-out of a very new, exciting, difficult, and high profile area of science. I've been asked 100 times am I satisfied with the flow of applications, do I think there should more. You always want to see more good applications. Always. It's not been a flood. But given the circumstances, I'm not really all that surprised.

    CHAIRMAN KASS: Could I ask a follow-up? To pick up on Dr. Rowley's question before on the question of the characterization of many of these lines and also on the — Well, it really goes to the question of the purity of these lines as well. Is there anything further that can be done through NIH, either on that or on the access questions? Are you being asked by the investigators to lend a hand there? Is there a hand to be lent?

    DR. BALDWIN: Well, we're only partway through this implementation. I mean, we haven't stopped the helping hand out there to work with these sources or to put funding out there for training activities. This is certainly a high profile issue for us because we know that we're doing things that almost sound contradictory. Somehow, I don't think they are.

    One is we want to mainstream the process so the we stay connected to our fundamental principles and strategies of how we do business and use the tools. Applications still have to go through peer review. These things don't happen overnight. On the other hand because it is such an exciting area of science, there really has been a concerted effort. We have a contact group with all of the institutes involved. We're working very closely with them to use every tool that we do have.

    So we're trying to balance those two things. I guess our instinct is that's the right strategy, but we have to keep the pressure on and we have to keep it a high profile issue for the NIH. And we are.

    CHAIRMAN KASS: Thank you. Janet and then Frank.

    DR. ROWLEY: I'd like to follow on with two questions. One of which relates to your earlier answer to me that there are about two dozen cell lines that have been characterized and again, how you would define characterization.

    DR. BALDWIN: Well, I think part of the problem is I don't think there is that clear of a definition.

    DR. ROWLEY: Okay.

    DR. BALDWIN: There's not tab six that is the clear definition of what everybody would accept as characterized. That's the figure that we've been using of the ones where there is considerable information about the characteristics of the lines.

    DR. ROWLEY: But it's different probably for each one of the six.

    DR. BALDWIN: It is a little.

    DR. ROWLEY: So that there isn't a standard.

    DR. BALDWIN: But you're now challenging me to go back and see the extent to which we could line up some of that information and even use that network that we'll create with those sources as a way to drive it towards certainly some basic understanding. But I don't think that exists right now. I don't think we can say here are the six things you definitely should have done.

    I think the field is moving pretty fast. It's important for us not to foreclose anything. I think when you're working in a new field one of the riskiest things for us to do as funders is to inadvertently foreclose or tighten it down too soon.

    DR. ROWLEY: I certainly agree with that. As you say, it's as investigators use the lines they may also through their use find either additional features or additional problems that hadn't been appreciated before. So all of that is going to be important information. You indicated you were probably going to get at least some or all of the sources together to discuss these. What kind of timeframe do you see for that?

    DR. BALDWIN: I really don't have a timeframe on that. We've only made five of the Infrastructure Awards. We still have more to deal with. The new sources are very new to us. It's just too early for me to say.

    DR. ROWLEY: So it would be more like a year from now rather than say six months.

    DR. BALDWIN: Probably in between that.

    DR. ROWLEY: Okay.

    DR. BALDWIN: If you had prompted me, I probably would have said maybe nine months. But we do not have a specific date on that.

    DR. ROWLEY: Okay. I'd like to change gears if I can but also take advantage of your long association to senior level at NIH. If you could help and I think this is related to the question that Rebecca was asking, we are aware that when Harold Varmus was Director of NIH he had a working group under Shirley Tillman looking at pluripotent human stem cells and reviewing some of the procedures to use that. I think when you said that the focus of the present is narrowed down obviously the focus of that larger group under Shirley did include some derivation of embryo research using IVF.

    One of the concerns of this group as well as others is how you would see a somewhat broader group either of the pluripotent stem cell review group for example that was envisioned in 1998 to 2000 that group was composed of ethicists and lawyers as well as scientists. At least that's my impression. I believe the membership was appointed by the Secretary of HHS. I'm not positive about that, but that was my impression. Whether such a review group would be an appropriate regulatory body to actually give responsibility to if for implementing and reviewing certain aspects or setting certain guidelines for embryonic stem cell research.

    DR. BALDWIN: What kind of guidelines do you have in mind? Do you mean for areas of science that would be instituted?

    DR. ROWLEY: Well, my impression is that the working group under Dr. Tillman came up with a series of guidelines, some of which you've already incorporated or were incorporated into the embryonic stem cell lines that they had to be derived with donor consent and things of that sort. The guidelines also have prohibited areas of research.

    DR. BALDWIN: They're still in place. We did not rescind the prohibited areas of research.

    DR. ROWLEY: And our discussions here and the evolution of science in the last few years has really suggested that some of those prohibitions might be removed. Then whether a review body of such as a broadly constituted body would look at the prohibited areas. For example, the prohibition says no somatic cell nuclear transfer. That's now an area that's been supported by the report from the National Academy of Sciences amongst other things. Is that up to NIH and the Secretary to remove that prohibition or would there be a broader constituted group that might look at that?

    The other thing that's prohibited is actually developing embryos specifically for research. This is an issue that we've discussed back and forth. At least some individuals, members of our Council, believe that it should be allowed under certain circumstances and with certain guidelines.

    DR. BALDWIN: Well, you have certainly outlined a very difficult and evolving area of science and ethics. The current group, the human pluripotent stem cell review group is definitely not envisioned as a group that would be taking on issues such as you described. That is a group that is really there to address the adequacy of any plans to use fetal tissue. The prohibitions that were in place in the original guidelines are still prohibitions that are compatible with administration policy.

    So what we might do in the future is really not something that I could comment on here. I can say that's not the kind of issue that would be remanded to that advisory group. But we always have the capacity of putting in place other advisory groups if it's warranted. We don't have any specific plans at this time.

    Dr. Zahuni (PH) the current NIH Director certainly views this as a very important area of science and one that requires our due diligence and careful attention to what our steps should be. So it's certainly not something that's going to get any less attention. But I wouldn't be able to comment further than that.

    CHAIRMAN KASS: Frank Fukuyama.

    PROF. FUKUYAMA: A brief question. Is there any possibility of these approved lines any of them dying out as a result of mistakes and handling or inexperience? You said that they are very hard to keep going.

    DR. BALDWIN: That's very speculative. I don't know. Of all of the things I worry about in this line —

    PROF. FUKUYAMA: That's not it.

    DR. BALDWIN: That's not on my worry list. Maybe you gave me something new to worry about.

    CHAIRMAN KASS: Robby George.

    PROF. GEORGE: Just very quickly. A point of clarification. In reply to Dr. Rowley's last question about who would have authority to lift or alter the prohibitions that she discussed such as somatic cell nuclear transfer, can you tell us again who's authority would be exercised there? My understanding is that would require an action by the President or the Congress, not any advisory body. Am I wrong about that?

    DR. BALDWIN: No. You're not wrong.

    PROF. GEORGE: I'm right about that.

    DR. BALDWIN: Yes. Anytime an issue is up for discussion there's frequently a desire to have an advisory group's comment on them.

    PROF. GEORGE: Absolutely.

    DR. BALDWIN: And we don't have a group in place that is doing that. I'm not anticipating any changes in that.

    PROF. GEORGE: Right. But apart from discussion or advise the policy —

    DR. BALDWIN: That's why I said those prohibitions are compatible with Administration, with our current policy. So I'm not envisioning any changes.

    PROF. GEORGE: Is that your understanding as well, Dr. Kass?

    CHAIRMAN KASS: Yes. That's my understanding. This is perhaps a strange question to put to you. This group as you know has been asked by the President to monitor stem cell research and to think about offering guidelines for it. We have spent a fair amount of our time on human cloning as you probably know. But we have had presentations from Dr. Gearhart and Dr. Verfaillie. We are trying as best we can to keep up with what is going on through the NIH.

    From the point of view of your activities and what you hear from the researchers in-house and extramurally, are there things that you would like brought to this body that might deserve our special attention? We've been trying to learn really about the implementation policy and finding out how easily and well are things moving. Apart from the request that the President should become more liberal and allow more lines to flourish which I understand would be a perfectly natural opinion of the scientific community, within the policy as now stated or in relation to that policy that we would have to consider, are there not so much advise but questions and concerns that we would be remiss in not attending to from the point of view of the people that you speak with and the research that you're trying to help develop?

    DR. BALDWIN: I don't know whether this is a direct answer to your question. I think what I see most need for right now is scientists just getting down to work with the lines that are available. There are many questions that need an informed debate. I think that debate will be better informed if it can come from not a speculation about what might happen and whether this is a good enough line or those work are enough but really more concrete, empirical evidence as to what happens when researchers get in there and work with these lines.

    There are very different views out there as to are they enough, they're not enough, they're good enough, they're not good enough. But they're a little hypothetical for my taste right now. If they could be better grounded in experience we may find that people have terrible problems working with these lines. We may find all kinds of terrible problems. On the other hand, we may not.

    Certainly if you look at the mouse ES experience, it started out with a lot of lines and it shook out to where there were a few that seemed to be the most valuable, most useful. Will it be the same way in the human lines? I don't know. We won't know unless we get investigators willing to get in there and in the trenches and starting the work with them.

    We're trying to put every conceivable mechanism out there to help that move along, but we still have to get the applications in from the research community. I guess if you say what's the one thing that I most want to see happen, I think that's it because I just think it will just make the discussions the we could have six months, nine months, ten months, and 12 months from now so much more empirically grounded. That would be my issue right now.

    CHAIRMAN KASS: Well, thank you. Just a tiny addendum. We are also trying to plan our own agenda for the remaining 17 or 18 months of our existence under the existing Executive Order. I know there's no real answer to this question. But order of magnitude. If we wanted to be good monitors of this and of the research and how it's going along, do you think a year from now there would be stuff to monitor?

    I mean, are we going to be able to do what we're supposed to do or are we at the end of this time say let the research go forward, we'd like to know what's happening? And I'm not going to hold you to the answer. But it matters to us I think in thinking about how to plan our own agenda what kind of time table we ought to be expecting to have some kind of data coming in. I know it's absolutely unpredictable.

    DR. BALDWIN: Several things I do know. One is this all takes longer than anyone thinks it does at the outset.

    CHAIRMAN KASS: Right. Rowley's Law.

    DR. BALDWIN: If you had said anything less than 12 months to tap back in and see how implementation was going I would say I really think that's too soon. I mean, if you look at a timeline from when these agreements are in places or when we've actually started to move money to a source for infrastructure support, we're measuring things in matters of weeks and months here. Science just takes time.

    In a year's time I think we'll certainly have a better sense of the rate of applications. We'll have a better sense of some people's early experiences in working with these lines. But I would not want to over promise as to how definitive that will be. Less than a year, I wouldn't do it. In a year's time, I think it would be a fair question to say come back in a year or send someone back in a year and say how has it progressed and how many more investigators, what's the experience from those.

    We'll have 13 Admin. Supplements. Those are going to be experienced investigators who are probably our bellwether, our leading edge. In a year's time, I think we'll have a much better feel for how difficult this has been for them or how quickly the sources given infrastructure support have gotten more common information available about their lines and whether in fact we have any lines that turn out just to not appear to work at all. In a year's time, I think that would be a reasonable question to put to us. I would hope I have some answers for you.

    CHAIRMAN KASS: Well, thank you. Would you allow me one more?

    DR. BALDWIN: Sure.

    CHAIRMAN KASS: In connection with your own heavy responsibilities to this activity, is there someone as part of this project also keeping up with what is being done in the private sector on this activity to the extent to which that information is forthcoming? In other words, if one wanted to say is there somebody at NIH who sits really in command of —

    DR. BALDWIN: Asking the private sector to tell us about what they're doing with their own money and not ours? No.

    CHAIRMAN KASS: I don't mean that. But there are things that are published too.

    DR. BALDWIN: Yes, certainly. We have been attentive to the meetings that occur. We have staff at any of the national meetings or regional meetings, et cetera who are staying apprised of where the interesting work appears to be done. I just have to draw that little line. There's always work that's going on in the not federally funded sector that we don't always know about.

    CHAIRMAN KASS: Of course.

    DR. BALDWIN: There's nothing new about that. But no. We are definitely staying on top of where the developments are to the extent that we can.

    CHAIRMAN KASS: Thank you. Alfonso Gómez-Lobo.

    PROF. GÓMEZ-LOBO: This is an information question. Maybe it's out of your domain. I know that at NIH quite a bit is being done on adult stem cell research. Right?

    DR. BALDWIN: Yes.

    PROF. GÓMEZ-LOBO: Now, is there any way of comparing volumes? I mean, is there a lot more being done in adult stem cell research?

    DR. BALDWIN: Oh, yes. That's a much more established field, yes.

    PROF. GÓMEZ-LOBO: Okay. Thank you.

    CHAIRMAN KASS: Well, it looks like you have answered our questions for now very forthrightly, very fully, and very helpfully. We're very glad.

    DR. BALDWIN: I'm happy to take any other questions that you would like to probably channel them to me. E-mail them to me and I will try to get an answer for you if there is anything that I have not gone over. Again, virtually every piece of information that we have put out there, every announcement, every piece of guidance, every helpful hint all is accessible on the website. If you would prefer to receive that as hard copy, I'd be happy to pull together a briefing book and send it to you if the Members would like that.

    CHAIRMAN KASS: Well, we thank you very much. Dr. Lee Zwanziger, would you stand please? Lee is a research director on the staff and the person most interested in the stem cell aspect of our work. I'd like at least you and she to say hello. We can keep a communication open in that direction.

    DR. ROWLEY: I mean, I think that would be very helpful particularly to the extent that we would have some understanding of the cell lines that have been reasonably well characterized. For example, are most of them derived in the U.S.? Are most of them derived elsewhere? Issues like that would certainly be helpful.

    DR. BALDWIN: You sort of challenged me to do an update on that. So it gives me something to do.

    CHAIRMAN KASS: Thank you.

    DR. BALDWIN: Thank you.

    CHAIRMAN KASS: We are finished a little early. Thank you very much, Dr. Baldwin. Is Ted Friedman here? If we started a little earlier, people could finish a little earlier. I don't want people who are coming from out of town just to hear you talk miss the beginning. But we are now ten after. What if we reconvened at 2:30 p.m.? Then we just finished a little earlier. Would that be all right? We'll take a break until 2:30 p.m. Off the record.

    (Whereupon, the foregoing matter went off the record at 2:09 p.m. and went back on the record at 2:36 p.m.)

    SESSION 4: ENHANCEMENT 2: POTENTIAL FOR GENETIC ENHANCEMENTS IN SPORTS

    CHAIRMAN KASS: Let's come to order. It's, if I may so, a special pleasure and privilege for me to welcome Dr. Friedmann to this meeting of the President's Council. We go back a long way, but we don't see much of each other. And in looking through the bibliography, I just checked to make sure I was right on the date. I had it right.

    We met long ago in relation to what became a paper called Gene Therapy for Human Genetic Disease?, Science 1972, co-authored with Dick Roblin, who is the Scientific Director of the Counsel. These are old colleagues and friends. Dick here, and Ted has been a man of science and a physician who, before it was fashionable is not the right word. Before it was even conceivable was giving an immense amount of attention to the large ethical issues related to biomedical advance.

    Ted is Professor of Pediatrics at the University of California - San Diego Medical School, and also the Whitehill Professor of Biomedical Ethics at the same medical school. He's the Chairman of the Recombinant DNA Advisory Committee, and a member of the Medicine, Health and Research Committee of the World Anti-Doping Agency. Also, has been the Chair of the AAAS Committee on Germ Line Modification, and a member of the California Commission on Human Cloning. We could use you, and we're very grateful to have you with us this afternoon to take us our next step in our discussion of questions of enhancement.

    We've had a couple of meetings ?- we've had one meeting on this before. For some of us, we are even more interested in what these new powers are to be used for, than where they come from, which is part of the reason that this is a specially interesting topic. And I'm looking for the title of this. I lost my agenda. I don't want to get it wrong. I'll leave the title to you. It's on the use of ?- potential use of genetics for the enhancement of athletic performance, or something close to that.

    DR. FRIEDMANN: Something like it.

    CHAIRMAN KASS: Very good to have you here.

    DR. FRIEDMANN: Thank you very much, Leon. It's really a very great pleasure to be here. I'm grateful for the opportunity, and to see so many familiar faces, it's great to have the chance to talk with you.

    First of all, I should give a caveat. I do not sit here sort of in an official capacity as Chairman of the RAC. I may let some RAC kinds of things slip by, but please don't take that as policy from the RAC. What you'll hear is my own opinion.

    Much of what I'd like to cover briefly has already been presented to you in your background paper, Number 7, I guess, that you've had a chance to look at over the past ?- and I will reiterate some of the points there, and make a few additional points. And then at the end, I hope leave you with some questions that I think may be germane to the function of this Council.

    I should allow apologize in advance for some of the Power Point features. This is the first Power Point presentation that I've prepared, and you'll see titles flying in, up and down, and I apologize for that. If any of you get motion sick, it's not my fault.

    All right. So let me start by posing three questions that I'll come back to toward the end of my presentation, and that has to do with these questions. Is genetic enhancement feasible, and is it likely, and is it desirable under some conditions? Two, what have we learned from the world of gene therapy that may instruct us about the potential for genetic enhancement? And three, does sport and athletics represent a kind of scenario which might be a useful springboard for discussing the opportunities for genetic enhancement. Is it, in fact, feasible in sport? Is it likely, and under some conditions is it maybe even considered desirable? So I come to these issues from three backgrounds, and I'll try to be a little bit personal about some of this if it's all right with the Council.

    These come from three interests that I've had for a very long time. One, obviously in genetics and gene therapy, which is my day job. Biomedical ethics, which is kind of my afternoon and early evening job, and then a background in sport, which I don't have personally, but which comes to me through my family. So this is my family connection. These are medals that my father won as an athlete in sort of Central European athletics pre-war. And it was in the context of this kind of view of sport and all its beauty, and all of its sort of effort that I grew up thinking that sport was a beautiful and lovely endeavor, and one that ought to be protected.

    The other part of the background that I bring to these issues is an experience that comes from my early sort of post-doctoral time. After a stint at the NIH, I went to the Salk Institute, ostensibly for a year to learn something about viruses and virus vectors, and came under the influence of Jacob Bronowski, who was there at the time as the head of the Council for Biology and Human Affairs. And the Council was interested in directions that science was going, the directions that genetics, molecular biology was going at the time.

    You'll recognize from the years that that was before the era of Recombinant DNA technology, but the people at the Salk were wise enough to know that it was coming, and Jacob Bronowski asked me and one of my colleagues to look into the issue of where molecular biology was likely to take medicine in the near future. And that was based on the presumption, on the intuition that the approach to genetic disease at the time was flawed.

    Now I won't be able to point at anything, but this is kind of a scheme of genetic disease, and the ?- well, it does point. Okay. A scheme of genetic disease and directions from which one might approach treatment and understanding of genetic disease. And you can see here, so there is the DNA with the X indicating a mutation response for disease. That gene, that mutant gene is responsible for making this gene product, and that gene product has the role of driving a metabolic step here. If that metabolic step is defective, then one induces a state of disease by either producing too little of a gene, of a metabolic product, or accumulation here of Product B. And it suggests a number of ways in which disease can be understood and treated. And you'll recognize that this is the scheme - for those of you who are interested in medical history and the history of science - this is the scheme that comes directly to us from Sir Archibald Garrett at the beginning of the 20th Century and his rediscovery of Mendel's Principles in 1900.

    You'll notice that, and I think if you think about this scheme, and you think about what it implies about therapy, you'll recognize that everything that happened essentially during most of the 20th Century in terms of therapy, is aimed at sites of this pathogenesis scheme everywhere except where the defect is. The defect is here in the gene at X, here in the DNA, and all therapies have been aimed, from time zero have been aimed everywhere other than for the site of the defect. And it became clear in the late 60s or so from work from many places, that the opportunity was going to arise in the reasonably near future to begin an attack on the mutant gene itself as an approach to treatment, so that takes the form of this cartoon.

    The cartoon says, "You fix what's broken." On the left side is a broken dam, representing a mutuant gene. That results in a metabolic flood downstream and a mess, and all therapy until sort of the end of the 20th Century took the form of cleaning up the mess, and it began to be apparent to a number of people, sort of in the mid-60s, early 70s, that the opportunity would come to fix the dam, to fix the gene.

    So here is the paper that Leon kindly referred to, and you'll recognize two things about it, three things about it. One, the date, 1972. Two, that one of the authors of this is Richard Roblin, who's your Science Director, I guess his title is. And three, there's a question mark at the end of the title, which meant that we really didn't know what we were saying, but we thought it was all going to come true, and so we published this in size at the behest of the Council for Biology in Human Affairs, and Jacob Bronowski's invitation to prepare this initially as a white paper for the council.

    And what Dick Roblin and I sort of envisioned at the time was not only is this an option for treatment of genetic disease, but it really is a requirement finally for designing rational therapy of human genetic disease. It was a necessary new step, a necessary next step in the treatment of disease.

    We envisioned that the approach would be to introduce functional therapeutic genes into cells to correct genetic defects, to correct mutations. And then we envisioned the use of viruses to do this. We did that because we were working, both of us, in a laboratory of virology with Renato Dulbecco, who had just established the mechanisms by which viruses cause cells to become cancer cells. And we thought well, if a virus can cause a cancer by introducing its own gene into cells, maybe we could fool the virus, use it as a trojan horse to carry therapeutic genes into defective cells, so we liked the idea of viruses. They were efficient and they did the right thing.

    We thought that in order to move ahead with such a procedure, one needed a very profound understanding of pathogenesis. We were worried a little bit that this field would lend itself to premature use, and to the use of immature technology in the name of therapy. And were concerned about when and if this would really move to human clinical application.

    We saw a number of ethical and policy dilemmas, including the potential for germ line modification, and the use of gene transferring to modify traits that were not obvious to everybody, obvious disease traits, but rather traits that were other sorts of human capability. That, of course, is the subject for today. And we thought that all this was so important, and so likely to be a difficult area of the confluence of technology and policy, that there was going to be a very ?- a need for heavy local and federal review and regulation of the technology, including FDA and local hospital committees.

    The paper appeared at a time, first of all, before recombinant DNA was available, and also before any vectors were available to move genes around, but those virus vectors became available over the next decade or so. And the details of this aren't important, but simply indicate two approaches to introducing genes into humans.

    Here is a patient with a human genetic disease, a woman at six o'clock. She might be treated genetically in one of two ways. She might donate some cells to a tissue culture plate, which would then receive a virus, or some other gene transfer vector in vitro. Those cells would then be genetically modified and returned to her to compliment some genetic defect that she had. That's call the ex vivo approach to gene therapy. In contrast to that, of course, is the in vivo approach, and with this virus vector here on the left side of the picture, is introduced directly into the patient to correct the defect, so that's the in vivo approach.

    I hope this doesn't make you dizzy. This now ?- the elaboration of this concept really came first in a most clear fashion from LeRoy Walters some time later, who developed this matrix for understanding gene therapy, and it took the form shown here. So the initial approach was obviously to use somatic cell modification to correct a disease phenotype, so for real therapy of a disease trait.

    LeRoy was concerned also about eventual use of a germ cell as the target for genetic modification, and envisioned that that could also be used for therapy, for prevention of disease or for therapy, but he also assumed sooner or later that somatic cells would be targets for the introduction of genes designed to enhance traits, rather than correct disease phenotypes. And the same thing to be done at the level of germ cells, so he had this four-way matrix, somatic cell, germ cell, therapy, enhancement, as four areas in which gene transfer was likely to become feasible in the human being.

    In terms of disease targets, very early the initial disease targets tended to be in-born errors of metabolism, single gene defects because they had a single gene missing, rather easy genetics to try to sort out. And in principle, all one had to do was to put the gene into the right cell at the right time, and you've got a cure.

    Not too long after that, of course, it became clear to many people that other kinds of diseases ought to represent targets for genetic modification. Complex diseases in which many genes talk to each other. Cancer is a gene in which many genes are ?- a disease in which many genes are involved. Neurological disease, psychiatric disease, cardiovascular, all those things became very popular targets for gene transfer kinds of studies. Even infectious disease, so non-in-born errors, non-genetic diseases, but diseases which had available genetic targets that one could manipulate to modify the disease process.

    And I won't go through the history of the 80s, late 70s, 80s, and early 90s, only to show you that all these concepts grew very rapidly at the beginning of 1990s, the last year or so of the 80s, `89/90, and the concept was that all you need is a gene, a target cell, and that therapy would be rather straightforward and rather easy.

    In 1989 was the first clinical study, human gene transfer study. 1991 was the first potentially therapeutic study, and you can see what happened over the next some years. Many proof of principle studies have been done in animal systems. Those animal systems look very promising, and by 1990, I can't see the date, `98/99, there was an enormous amount of optimism ?- well, by 1995 there was an enormous amount of optimism that this job would be really quite easy.

    In `95, you can see a little dip there from 44 to 28. In 1995, a series of papers appeared which showed for the first time that the job was going to be more difficult than we thought. There were a number of rigorous studies which, for the first time, showed failure, rather than this sort of exaggerated over, hyper-expectant field that had come to develop, which we thought things were going to move very quickly. In `95, things obviously became much more difficult. And the field of gene therapy kind of began to be more introspective, and to emphasize more rigorous hard basic science. But that also began to grow, and by 1991 ?- sorry, by 1998/99 things were growing again.

    And then, of course, in 1991 came the disaster in Philadelphia with Jessie Gelsinger's death, and another pall was cast on the field, indicating again that there were many surprises, and many unexpected reversals that we should be on the look-out for. That field was, in fact, going to be far more difficult than we had anticipated, and that it was filled with traps, and with potential pitfalls that only careful clinical experimentation would eventually clear up for us.

    However, what's happened since 1999, and since Jessie Gelsinger, is rather impressive. You can see now by March of this year, there are more than 500 clinical studies being carried out in many countries in the world, most of them in the U.S., but many studies in Europe, and Sweden, and Japan, China and others. Most of those studies are for cancer for a number of reasons. A number of diseases are, in fact, common genetically complex diseases, cardiovascular, neurodegenerative disease, arthritis.

    The first clinical success after 30 years after the Roblin-Friedmann paper, finally after all that promise and all that expectation, came what looks to be a real success over the past two years, a study in France carried out by Dr. Alain Fischer in Paris, showing, I think quite convincingly, and only time will tell if it's a cure or not, but quite convincingly, a phenotypic cure of children with an immunodeficiency disease, X-linked SCID. That's now been repeated in another form of immunodeficiency, and it looks as if we've turned the corner now. The field exists, it's a reality, it's a clinical reality, and poised to move into other clinical situations.

    At the same time, there's been no overt enhancement studies reviewed or approved by the local or federal regulatory review process. So again, June of this year, very impressive apparent success by Alain Fischer in Paris. The ADA SCID model, which is a similar disease, seems now to have been cured. The paper last week in Science indicates a very similar approach, with similar results.

    Interesting, and probably real results are being obtained now with coronary artery disease with injections of agents designed to induce new blood vessel formation in the heart, and also in peripheral tissues. There is a continuing slowly advancing number of studies in cancer showing some response of some cancers in some patients, and a very promising approach now with Factor IX Hemophilia, which seems to be poised on the edge of showing some clinical efficacy.

    So what do we conclude from all that? That the field is real. That it's beginning to show clinical effect. However, we know better than ever that the field is faced with many unknown, and many known dangers and problems. We learned that in spades from the Philadelphia study. The gene therapy studies have to be considered clinical research in the strictest form of that word, and therefore, require all the local and national regulatory review processes that clinical research needs. That the wish to do good, of course, is not on its own enough, to undertake studies, and that the studies have to be designed properly, a result that also came from the disasters in Philadelphia and a number of other places in which clinical design was possibly not as rigorous as it ought to have been. And that any applications of gene transferring outside of this realm of review and regulation recognizing the hazards and difficulties, and problems would be inappropriate, hazardous to the patients and to the participants in the study, and therefore, probably unethical for reasons, at least, based on safety.

    All right. So we get to the point we're back to LeRoy Walters' matrix. Therapy of somatic cells, treatment of somatic cells with foreign genes for the purpose of therapy seems now to be a reality, and that takes us then in the next step to the potential for using exactly the same methods to modify traits that are not disease traits, but at least farther out on this disease/non-disease spectrum, and begin thinking about enhancement.

    That doesn't come as a surprise to us because we already accept and seek enhancement in our society in many ways. And that was, of course, also reviewed very well in your document number 7, and I won't repeat all of that. Just simply to say that cosmetic surgery is with us, and we accept it, we seek it out. Recreational drug use is with us, and we accept it and seek it out. Psychopharmacology, an exploding area, a very important area which obviously comes initially from the need to treat psychiatric disease, but also to treat the rest of our neuroses and behavioral deviations. And, of course, the use of anti-depressants, tranquilizers and serotonin reuptake inhibitors, things of that sort, are ubiquitous and universal in our society, and we hardly question their use any longer.

    Attention deficit, hyperactivity disorder, a very popular and very important potential area. I don't know what the figure is now, but it must be 30 percent of children in this country on Ritalin, requiring 50 percent of the teachers to go on Prozac, I guess. But it's a situation that we accept, and we know, and we don't question it very much at a societal level. The area of aging offers major new areas of socially acceptable enhancement. Again, that was covered in your document number 7.

    There was a very interesting review in the New York Times last week on the use of anti-depressants to sort of underscore what I've just said, and indicating that social phobias and generalized anxiety, premenstrual distress and many other behavioral issues are targets, and probably legitimate targets for drug therapy. And in that article, a quotation as given below, "Psychiatrists argue that such conditions are real illnesses, but others say the impression is often conveyed by commercials."

    It's clear, almost everybody could benefit from them. Symptomatology is so broad and vague that any one of us could say yeah, that's for me. And we all know that. We watch the commercials and we think maybe that would help me.

    Well, if we accept enhancement, how far are we from accepting ?- if we accept pharmacology-based enhancement, how far are we from accepting genetically-based enhancement? The pressures for that come from, obviously, from the general acceptance of enhancement, in general from drugs. The indistinct line between disease and non-disease, what is one person's Alzheimer-based memory deficit is another person's desire for a slightly sharper memory, to memorize a role that he needs to enact on a stage, or learn a piece of music, or something of that sort.

    The Genome Project, and other advances in genetics, is dumping into our lap all kinds of genes involved in personality and cognition traits. You all remember probably the early days of the century, again the work of Archibald Garrett at the Cold Spring Harbor Genetics Record Office, in which everything was considered to be genetically determined, including love of the sea, thalassophilia, slovenliness and things of that sort. Those kinds of traits were based ?- were presumed on the basis of poor science to be genetic, at least partly genetic in origin, but those days of genetics are no longer with us. But we're now, of course, coming to realize that genes do play an important role in personality and cognition. And those genes are coming to be identified slowly but surely. And will, therefore, eventually be targets for manipulation. And, of course, the increasing pace of clinical efficacy in gene therapy is providing tools which are likely to be useful in an enhancement setting.

    All right. So if that's true, then on might begin to wonder about what kinds of approaches in the therapeutic sense may open doors inadvertently to enhancement. And I would like to just remind you of a number of studies, protocols that have been reviewed by the federal regulatory agencies, by the RAC, which are therapeutic in intent, but which have implications for non-therapeutic use for enhancement kind of applications. So these are a series of studies that have been proposed to the RAC for therapy.

    The first one here is the use of IGF-1, insulin-like growth factor for treating a muscle wasting disease in a peripheral nerve entrapment syndrome. It's called the Cubital Tunnel Syndrome in which a nerve gets entrapped, leads to muscle wasting. The proposal reviewed by RAC was that a non-viral vector of plasmid would be injected into the muscle around this blockage to stimulate nerve regeneration, muscle re-innervation. That would be directly injected in the muscle. And because the vector in this case is not a virus, but rather just a piece of DNA, its affect would be transient, but it would stimulate local muscle repair and maybe nerve regeneration, as well. Clearly, this is therapeutic in intent, but again clearly, the injection of IGF-1 into muscle has other implications. We'll get to that in a moment.

    Another study proposed to RAC in 2000 had to do with the production of Erythropoietin, to increase hematocrit levels in patients with chronic renal disease. These patients have difficulty with maintaining adequate blood production, and one way to treat that, other than for injections of Erythropoietin, is to introduce the Erythropoietin gene into the smooth muscle cells of these patients in vitro in the laboratory, and then use those genetically modified cells that are now producing EPO to line an artery-vein dialysis graft that these patients have implanted. Those cells would sit down on the graft, and produce a constant supply of EPO, which would then increase the blood production in these patients.

    Still another study reviewed earlier this year by the RAC, a very important study, suggested the use of growth hormone as an approach to treating Cachexia in cancer patients, have this terrible wasting syndrome very often, and one doesn't know what that's due to, but one potential approach to treating it is to introduce growth hormone, or things that will produce growth hormone into those patients. And this study, in fact, proposes exactly to do that, to use a hormone called "Growth Hormone Releasing Hormone" to stimulate the pituitary of a patient with cancer to produce its own growth hormone. That would then ?- to increase body weight, and to prevent parts of this Cachexia Syndrome from developing. The amount of growth hormone could be regulated in this system by the administration or removal of an oral drug, in this case, RU-486, which has the property of turning on or off the gene in this case.

    Again, it's not a therapy for cancer, but it's the therapy for something that comes with the cancer, and that's the Cachexia. This has the implications, of course, of developing methods for introducing something that will turn on or off growth hormone in a conditional sort of way, and has applications that we can get to in a moment, as well.

    You can't see that very well. Two weeks ago at the RAC meeting, we reviewed still another proposal, which is therapeutic in intent, but which also begins to sound potentially enhancement-related. This is a proposal from Dr. Melman in New York, to treat erectile dysfunction, not with drugs but rather with genes, introduced directly into the corpus cavernosum. This is a potassium channel gene that has the property of modifying blood flow in and out, and therefore ?- and that gene becomes active only during sexual stimulation. And therefore, in animal studies, has shown to produce reasonable results. And like Viagra, of course, has the potential for treating a real problem in some men, but also to go the direction of some Viagra use, and that is an enhancement sort of use.

    Well, okay. So if we accept enhancement, is sport an area in which enhancement is likely to find a home? You won't recognize this person here, but that man is Arne Ljungqvist, who is the Chairman of the ?- who was President of the Swedish Cancer Society, but in this era, he was Olympic high-jumper for Sweden in the 1952 Olympics. And he's the Chairman of the World Anti-Doping Agency Committee on Health Science and Research.

    So the question is what, of course, determines performance in sport. At least three things do. One, talent and drive. Those tend to be not terribly manipulable, but are innate and learned, and partially genetically determined. Of course, there's training, manipulable kinds of training, what equipment you use, what opportunities you have to train. And, of course, then physiological manipulation, performance-enhancing drugs, environmental changes. You train at altitude if you're going to be an endurance athlete. And now the question of new genetic functions becomes pertinent.

    It won't surprise you to learn that doping is extremely common sport, in some sports more than others. I won't reiterate all that, just simply again to remind you that it happens, and the sport profession considers it a problem. Some people do, at least. There was a question in the L.A. Times several days ago by Jerome Holtzman, who is the major league baseball historian, and his attitude was I don't care if guys are taking steroids or not. If they're taking these drugs, and if they want to risk their bodies so they can hit 20 homers a year, that's their decision, so that's kind of the official statement from baseball.

    You all know from the tests that U.S. screening agencies have had sort of a love/hate relationship with screening, and in screening for Olympic athletes, the U.S. committees have not always been as effective as they would like to be.

    You all know, of course, the response of the U.S. population to Mark McGwire's homerun hitting feat some years ago. That was not met with universal disdain or disapproval. It was really quite welcomed by most sports fans in the country. And, of course, the recent revelation of baseball use of — probably much more ubiquitous baseball use of steroids and the response that that's had. So sports organizations look down officially on the use of these kinds of agents. There's a list of banned substances. That list is evolving all the time, but tends ?- but includes things like Erythropoietin as drugs, not as genes, as drugs, growth hormones to improve strength, anabolic steroids, stimulants and narcotics are banned. Diuretics and plasma expanders are used commonly to hide the use of other drugs by athletes, and those are also banned. Beta blocks are banned.

    Medical exceptions are permitted under some conditions by the sports authorities. And recently, a revision of some of these lists of banned substances has begun to exclude things like caffeine and marijuana, which are universally used. Alcohol, which are universally used, but which have not been shown to be sports enhancing, and therefore, they no longer sit on lists of enhancing drugs.

    The sports world tests for drugs and screening in a number of ways. The International Olympic Committee and other international bodies have had screening methods in place for some time. National Athletic Associations similarly.

    In 1991, the IOC and the member nations established the World Anti-Doping Agency, the World Anti-Doping Association, funded by IOC, which has a three-part program to screen both in and out of competition, to educate athletes, and to do research on detection and screening. And then the member nations have their own versions of the same kind of agency, in this case, the U.S. Anti-Doping Agency.

    So why does one think that genetic approaches to athletic enhancement are inevitable? First of all, athletes are risk-takers. They're young healthy athletes who think nothing is ever going to happen to them. And they are known to accept all sorts of risks. Polls have been taken of young athletes asking if I were to guarantee you a gold medal in the next Olympics at the risk of losing 20 years of your life would you do it? And universally, they say yes. They will take that risk for the reward of gold medals.

    There are enormous financial pressures and national pressures to push athletes to perform and to win. We know that they use pharmacological approaches to enhancement. WE know that they're aware of gene transfer technology, and we know that that technology is still immature, but it's advancing rapidly. And we know that many of the studies in gene transfer technology, in fact, use the genes that are of particular interest to athletes, Erythropoietin, growth hormones and other relevant genes.

    There's a general perception among the athletic communities that these manipulations genetically would be less detectable than pharmacological intervention. That's not at all clear, but that's what the athletes seem to think. So how does one enhance athletic performance genetically? One can increase oxygen carrying capacity with Erythropoietin. One might enhance skeletal and cardiac muscle function growth hormone, IGF-1, and other forms of growth hormone. One might imagine increasing blood flow to a particularly stressed muscle with agents designed, as in the cardiovascular therapeutic setting, to increase blood vessel production to that organ. One might imagine altering energy utilization by the tissue to raise pain threshold of injury, and to prevent injury, or to accelerate healing by genetic means.

    So let me give you now several examples of the way in which preclinical, therapeutic preclinical studies have used relevant genes to convince people that use in athletes is possible, and probably inevitable.

    The gene in this case is Erythropoietin, and it's been transferred into Baboons with this vascular graft approach that I described before. In this case, cells from the Baboon are injected with a virus that expresses Erythropoietin. Those cells then are used to line this vascular graft. And here you see the affect on the blood production of the Baboon over more than a year. The top closed circle curves represent the levels of red blood cells in this Baboon after a single injection, a single introduction of the smooth muscle cells into the graft. The lower curves represent the control animals, and you can see that the manipulated animals develop hematocrit levels, red blood cell levels well over normal, and up to the 70 percent level. That can be good, or it can be bad. And obviously, it's very dangerous if it goes too high because that predisposes to strokes, and to other cardiovascular disasters.

    Here's the use of another cell line to introduce Erythropoietin into animals, again the same affect. In this case, carried out over a shorter period of time. But again, you can see a prolonged elevation of Erythropoietin using a muscle cell to deliver the gene. Here's a different virus, an adenovirus vector. Adenovirus is used commonly in gene therapy studies, and on the right panel you can see a very prolonged elevation of hematocrit levels in, I guess in what animal? This is Baboons, as well. Prolonged increase of hematocrit levels after a single injection of a virus into the muscle of these animals.

    Here again is the single injection of a different virus into non-human primates. The lower right curves show you the persistence of increased hematocrit levels in these animals, despite the fact that the serum Erythropoietin levels in the very far lower right curve drops after a while, the hematocrit level stays up for more than a year.

    So a single injection of a vector carrying the Erythropoietin gene works. It increases hematocrit levels. And in some other of these, this can be turned up and down at-will, so you can take this animal and treat it with a small drug orally that will turn off this affect. The hematocrit level comes back down to normal. You can then turn it back on at-will, and you can bounce back and forth many, many times to modify and to titrate the amount of red blood cells that you want.

    With respect to muscle, very impressive studies by a number of workers, Sweeney in Philadelphia, and Goldspink in London have taken IGF-1, this insulin-like growth factor, and similar muscle growth factors, injected them into mice. Those mice then develop much bigger muscles, stronger muscles. If you tie little weights to their tails and force them to climb up a little pole, the injected ?- the mice with injected muscles climb higher, and faster, and carry more weight than the controlled mice, so it works. The muscles get stronger, they get bigger, and they also show improved muscle repair properties.

    I'll just skip that. That's more of the same. One might even, in fact, look upon this as a preventive procedure. Here is a study by people interested in preventing or treating joint injury, again with IGF-1, with insulin-like growth factor. In this case, cells from a joint were treated with a virus carrying IGF-1, and then put back into the joint. And on the left, you can see the thickness of the synovial membrane, the membrane in the joint that protects the joint from injury on the left, and on the right. The same cells now treated with a virus producing IGF-1, you can see the thickness of this synovial system, synovial tissue is much greater, and this joint is less likely to be injured, and is more likely to recover more quickly.

    So is application of these experimental kinds of approaches feasible in sport? To remind us all again, some of the properties, the lessons that we learned from gene therapy, so gene therapy is feasible in humans. It can be therapeutic. It can correct and treat disease. All present approaches to gene transfer must be considered experimental. The current methods are still immature, and many unknown dangers, and known dangers. Methods for gene transfer into humans all must, at the moment, go through this process of local and federal review. And I would suggest that rogue use, or illicit use in athletics or any other area, which circumvents that process, that is, the gene transfer into humans for other purposes, whether it's therapeutic or whether it's enhancement, which circumvents the review and regulatory process is dangerous to the subject, as unacceptable. And, therefore, I would posit, is unethical.

    Well, you can say that, but that may or may not convince athletes, and enormous pressures exist in athletics which make this kind of direction very likely, and inevitable. And the reasons are the following, the athletes, and their handlers, and federations know about gene therapy. They know vaguely what's happening, and they know that the field now thinks that it's turned this corner of efficacy. What they don't know, and what they don't appreciate is the safety concerns and the dangers lurking behind every corner.

    If this application to athletics is to be done, it probably will be done in a private setting, and private setting studies do not require review by the RAC. They do need to go through FDA, but certainly don't require RAC review. And that private and governmental funds are available to accumulate the kind of molecular expertise that would be required to make these vectors, to solve the rather trivial problems of delivery to the appropriate tissue, and simply to take the published data from gene therapy world and apply it in an enhancement setting in athletics.

    Regulatory structures largely are silent on the issue of enhancement, and that might be, in fact, a question that this Council might like to pose. Is continued silence on the issue of enhancement a wise thing to tolerate?

    We come back to the caveat that Dick Roblin and I sensed in our initial paper; and that is, the likelihood that immature science is going to be used before it's ready for real application. It happened in gene therapy. It's likely to happen in athletics. So faced with that issue, a number of agencies have tried to provide a shot across the bow of those who might want to circumvent these concerns. In 2000, a couple of years ago, the World Anti-Doping Agency incorporated into its Medicine, Health and Research Committee an effort to identify the potential for gene therapy as an approach to ?- for gene transfer as an approach to doping.

    Last year, the International Olympic Committee, taking that cue from WADA, had a one-day meeting in Lizon (phonetic), which began to identify the potential dangers to sport, and this year, several months ago, that the World Anti-Doping Agency sponsored a meeting at Cold Spring Harbor, a three-day meeting which was designed really to look in some detail into the potential for genetic modification in athletics.

    That meeting urged a number of things. It urged the publication of the proceedings for general promulgation to the scientific and sports community. It also called for dialog in the public sector, position statements from professional societies such as the American Society of Gene Therapy, to look at the issue and examine whether this is a real concern and what, in fact, one might do to head it off.

    Also, this spring the American Society of Gene Therapy held a symposium at its annual meeting on potential applications of gene transfer in sport, and next year AAAS is going to have a similar symposium.

    So back to the original questions that I posed, and I am going to wind up now, back to the original questions: Do advances in human gene therapy affect the potential for genetic enhancement? I think the answer to that is a clear yes. Is genetic enhancement feasible, likely, and desirable? I think it is certainly feasible and likely. Questions of its being defensible and desirable is something that deserves your careful consideration.

    Finally, is the enhancement of athletic performance feasible, likely, and desirable? I think it is certainly feasible. Attempts will be made soon, and its desirability again is not clear.

    So let me leave you, then, finally, with some questions that might be interesting for your Council to consider. These questions are difficult, and we certainly have not been able to answer them even in the context of the World Anti-Doping Agency.

    So one question is, of course, what is sport and what is it that we are trying to protect in identifying genetic approaches to modification? There is a classical view of sport I call the romantic view of sport, the kind that I grew up with at home, that says it is the effort and the triumph over adversity that makes sports so beautiful. We know that sport is more than that. Sport is entertainment. Now it is an economic force. Therefore, it is a different beast from what it was some years ago.

    As an undergraduate I studied a little bit and took a course with a man named Paul Schrecker at Penn, who had developed a principle of work and history looking at the features that make a society. He identified six major areas that define societies: development of the state, science, religion, the aesthetic province, economy, and language. He did not include sport. Sport, to whatever extent he discussed it, was included the aesthetic province. But it may be that sport represents something more aboriginal than that and very basic human instinct, and may, in fact, represent a completely different province of society.

    Sport is a technology which is manipulable in terms of material science. We make better swimsuits. We make better skis, more flexible pole jump poles. But it also represents now an area of biotechnology and bioengineering. It is not quite as clear to me and the WADA Committee whether that is a good thing or a bad thing. You might want to ponder that.

    Does sport offer a useful arena for — I guess I shouldn't have used the word "arena" there — does sport offer a useful area in which to examine this intersection of technology, in this case genetic technology, with public policy? Where do they clash? Finally, if we accept, as a society accept, enhancement in general, what is it that makes sport different, if anything, and why?

    On no particular subject, I just wanted to make one plea to your Council based on things that I heard this morning. There's no question that this march of technology, both in therapy and in enhancement, is going to continue and accelerate. You need and we need an enlightened public policy, an enlightened discourse.

    It seems to me a terrible thing that the U.S. has relied on very few stable bodies to continue a discussion of technology and public policy. The OTA was one such body, but we don't have that any longer. All the previous bioethics councils have come and gone. They have been too transient to keep up institutional memory and a momentum.

    I would certainly hope that this body, in whatever way it can, can make the point that it is an ethical issue, a bioethical issue, to have a national body to continue to advise our policymakers on what is coming next and how to prepare for it.

    So let me stop there and thank you very much for your attention. I would be more than happy to try to expand on any of this, if you would like.

    CHAIRMAN KASS: Thank you very much.

    Could we have some lights and this machine turned off?

    I think the presentation makes very clear how developments intended for therapeutic purpose can acquire a life of their own and are used for things that are beyond therapy, not necessarily making them either undesirable or wrong, as really beautifully documented here. Other people may want to weigh in with different questions.

    Granted that you and colleagues have concerns for the area of genetics, and therefore the uses of genetic technology. The question of a genetic means of delivering performance enhancement would be an obvious new question for you. But I guess, could you help on this question: Why in a world of steroids and epo available by injection and orally — what if someone said, look, this is really rather precious and very highly sophisticated, but how is this different, or is it different, and why is this likely to be a much larger problem than the one that is now faced, if it is a problem?

    What about the genetic angle makes this special? That is the less interesting question, I guess, as to what we should think about this, and if we should think ill of it, how to proceed. But just on the narrow, technical question, why is the fact that this is genetically-delivered enhancement special?

    DR. FRIEDMANN: I am not sure that it raises any new issues. It raises issues — the interest in this area seems to come from the general perception in the athletic community that this can be done more surreptitiously, and, therefore, less likely to be detectable, if in fact you can do it with a one-shot administration of something, turn it on and off at will —

    CHAIRMAN KASS: With small molecules?

    DR. FRIEDMANN: And, therefore, not so easily subject to out-of-competition testing. I think that is a misperception because what is detectable, of course, is the physiological effect of the introduced gene, and that is going to be presumably as detectable as if you had injected yourself with the protein itself, rather than the gene.

    So I don't think that there is a new kind of ethical issue that separates genetic doping from pharmacological doping. It is a challenge more, I think, to the athletic community because they are going to have to devise different kinds of methods of screening and detection. It is also a challenge, I think, to the gene therapy community because the applications in athletics, when they come, if and when they come, will come outside of the realm of current standard review and regulation. It seems to me that that is clear.

    How, in fact, to be on the alert for that and how, in fact, along the lines of this shot across the bow, how do we warn people, athletes, first and foremost, because they are the ones who are in most danger of being injured by such a manipulation, which is, after all, maybe less easy, less redeemable, and less easy to reverse than simply stopping taking a drug.

    The genetic manipulation is probably going to be less forgiving, maybe less manipulable and less titratable, but also less easy, more difficult to reverse. That increases the danger to athletes. That danger is not being advertised by the sort of between-the-lines support that one is beginning to see in these rogue athletic communities for this approach.

    So I think the fairest answer is there's nothing ethically new here, except from the gene therapy point of view, and the insistence that, if and when these kinds of manipulations are done, they must be done in the context of clinical research and not in the context of sort of East German approach to swimming as of some years ago.

    We need to be sure that the athletes are aware of that and know that, if they are being attracted by promises of surreptitious and less detectable approaches to doping, that they need a high level of suspicion. So the work of the Vardon, and you saw at the moment, is in fact to provide that shot across the bow.

    CHAIRMAN KASS: Robby?

    PROF. GEORGE: Thank you, Dr. Friedmann, for that wonderful presentation. I wanted to ask a couple of questions by way of clarification, and then I have a more substantive question.

    On clarification, one of your slides identified a list of stimulants that have become socially acceptable, and they included caffeine and marijuana and LSD.

    DR. FRIEDMANN: I don't think I had LSD on there. I hope I didn't.

    PROF. GEORGE: Okay, I'm sorry.

    CHAIRMAN KASS: No, he didn't have that, either; just caffeine and marijuana, unless you were taking something.

    (Laughter.)

    PROF. GEORGE: By socially acceptable, you simply, I take it, mean that it is widespread in its use?

    DR. FRIEDMANN: Widespread, and those agents have been on the list of proscribed drugs in the past, but a recent list developed by WADA now has removed them because they have not been shown to be performance-enhancing. They are lifestyle kinds of drugs, lifestyle agents, that are common, but which the athletic community no longer sees, or may no longer see itself in the need to proscribe because they are not performance-enhancing.

    PROF. GEORGE: Okay. I was wondering if socially acceptable there refers to accepted in the broader —

    DR. FRIEDMANN: In the broader sense, sure.

    PROF. GEORGE: In the broader society?

    DR. FRIEDMANN: Wider used; therefore, a lot of people accept it.

    PROF. GEORGE: But while it would seem to me caffeine is socially acceptable, cocaine and even marijuana is in a sense not, if we consider that we are now more than 30 years into a pretty aggressive campaign to legalize marijuana, and the national public polling, public opinion polling, seems to show that it hasn't really moved public opinion on that issue very much at all, although there are significant regional and even local differences. I bring this up only to say that, as we are thinking about this, maybe we are keeping in mind that, even where there is widespread abuse, some taboos along these lines, but not others but some, have been maintained, and in part reinforced, by countervailing social pressures.

    DR. FRIEDMANN: I tried to finesse that a little bit by putting "acceptable" in quotes. I hope that it was still there.

    PROF. GEORGE: I did notice that.

    DR. FRIEDMANN: But, also, I hope I didn't have cocaine. But the point is that widespread use indicates something.

    PROF. GEORGE: I agree.

    DR. FRIEDMANN: And ours, of course, is not the only society that's faced the use of those agents, and others have been more willing to buy into them. So "acceptable" in this case means widely used, but heavily debated still, and probably on their way to wider use.

    PROF. GEORGE: Well, I stay with the point because I think an interesting dimension of the problem is the question of inevitability, which was raised at various points in your presentation. Obviously, if something is inevitable, then thinking about how it can be restrained is a waste of time, although it might be that you can think about how its use can be channeled in certain ways or maybe even limited in certain ways. But that is why I was interested in that problem.

    Similarly, and I guess the answer is going to be the same thing, on a couple of occasions you used the term "universal," and I think I interpret what you meant by that as, again, being widespread, the universal use of drugs or the universal opinion among athletes that it would be worth giving up a certain number of years of life —

    DR. FRIEDMANN: I used that word it was wrong, about universal.

    PROF. GEORGE: Now to the substantive matter, am I thinking about this correctly? We have the health sets of issues when it comes to possible attempts at enhancement; that is, the attempts themselves could end up damaging the health of people who undergo the enhancement techniques.

    Then separated analytically from that is the question of the ethics of people, even if they are safe — so laying aside their safety — the ethics of undergoing these enhancements or availing oneself of these enhancements to be better athletes or to perform at a higher level. Am I right to think that the ethics of that depends on the concept of sport that is in play, on the, I think what you referred to, if I remember correctly, as the old romantic version or concept that you grew up with, you really do have an ethical problem, because the enhancements have driven out what seems to be central on the romantic understanding, which is drive, effort, perhaps natural talent in some sense.

    But then on a different conception that puts the focus on, say, entertainment, rather than the romantic conception, it doesn't seem to be undergoing — the enhancements techniques doesn't seem to be an issue because the goal is to entertain the public. Mark McGwire, or whoever, hits 70 home runs; the public likes that. Nobody has done anything ethically wrong. Am I right so far?

    DR. FRIEDMANN: I agree, yes.

    PROF. GEORGE: Okay. Then I guess we get to this interesting question — I remember the quotation you had up there from the basically baseball historian who said, "Well, look, if somebody wants to give up their certain number of years of their lives or damage their health to hit 20 home runs, that's a private individual decision."

    I think something in most of us wants to agree with that, that that is a private individual decision, but I wonder if we ought not to agree with that, not only the health question, but because it is not a private individual decision what sport is going to mean in a culture. The question whether the sport will have some substantial element of the old romantic notion or be entertainment will itself, in a certain sense, be the product of a lot of individual choices, but it is going to be a social reality, for better or worse, a social good, if you will, that all of us, whether we like it or not as individuals, are going to live with. Is that right, too?

    DR. FRIEDMANN: So far you're perfect.

    PROF. GEORGE: Okay. Well, that's all I wanted, the only —

    DR. FRIEDMANN: I mean, that is why I raised the question at the end. I am not so sure any longer what sport is. What is sport, and, again, the question of, what are we trying to protect from people's individual choice to use performance-enhancing anything? It is not fair for me to insist on my view of sport to the point where I say that it is improper for Mark McGwire to use what he uses. I have a view of sport; he and many other millions of Americans have a different view of sport.

    But to the point where it begins to suggest the ways in which areas of our society move from one realm to another and become entertainment or become technology, if sport is going to move to the position of being bioengineering —

    PROF. GEORGE: This is what I find interesting.

    DR. FRIEDMANN: — then it is a different world, and you may say, well, that's too bad; goodbye sport and hello bioengineering. I would find that sad, but I am not so sure on what basis I rail against it.

    PROF. GEORGE: Let's, just for the sake of argument, say that human life is enhanced, where the romantic conception of sport prevails, just for the sake of it. Let's say you did believe that we could, then, explore what the argument would be for that, but let's just say that that is a good thing, and therefore, it would be reasonable for me to want that to be available to my children.

    DR. FRIEDMANN: As athletes or as spectators?

    PROF. GEORGE: Well, both. Both. I want them to live in a world where the benefits to them as athletes and spectators, of participating and viewing that kind of human achievement, that kind of activity, are available to them.

    It looks to me like that gives me at least a reasonable basis for rejecting the kind of strong individualism or ethic of choice in these matters that would line up with what the baseball historian is quoted as saying in your presentation: that it's really nobody's business if this one guy, or every single individual athlete, decides that he would rather have 20 home runs than another three years of life. Because that set of decisions is robbing everybody else of the opportunity to make available to their children, let's say, probably starting all the way down in Little League, this conception of sport, since it turns out that sport is itself a kind of social reality. And if it is a good thing, if there is a conception of it that it is a good thing, it is a social good.

    DR. FRIEDMANN: I think one has to have faith in one's idols. When I was growing up, I lived down the street from the Philadelphia Phillies player who was one of the neighbors and just another person. I admired him. He was an athlete, but he was another one of us.

    I must say that in watching the Wimbledon tournament recently and watching baseball games, I no longer know what I am seeing. In a way, I feel a little bit robbed by not really have faith, not as much faith as I had in my old idol of the reality that I am now seeing bioengineering more than I am, and pharmacology more than I am sport. Maybe that's inevitable. I use that word again, but sport is not what it was, and it may be that we simply have to recognize that nothing is what it was.

    PROF. GEORGE: You have a couple of children. When they were small, you probably would have directed them or encouraged them into sport or not into sport, depending on what it was that was being offered in sport, right, whether the future was, if they wanted to get serious about it, enhancements, whether pharmacological or genetic or not?

    DR. FRIEDMANN: Well, one of them went into sport because he loved the effort.

    PROF. GEORGE: On the romantic conception?

    CHAIRMAN KASS: I have Janet. There is something of a queue, and if it begins to wander in every which direction, I am going to try to maybe stick to some topic, but please, Janet, and then Gil.

    DR. ROWLEY: Well, I am going to wander in a direction, but I am going to take up on your last point of the last slide, which is enhancement in other areas. This is a topic that we have talked about off and on here in this Council, using examples like one which is germane to just what you have been talking about. If somebody wants to have a child with the skills of Michael Jordan, then you can start doing germ-line therapy for enhancement for that child, or beauty or intelligence.

    I guess I would like your opinion, because it has seemed to me that these areas of enhancement involve complex genetic interactions about which we are pretty ignorant, and that at least at the present time those kinds of enhancements for overall athletic ability or intelligence or beauty are not likely to be immediately a concern. But I would very much appreciate your comments.

    DR. FRIEDMANN: Let me make sure I understand the question. So the question is genetic sort of germ-line modification for enhancement purposes?

    DR. ROWLEY: Yes, and have a superintelligent child. So is this something that we are going to be able to do germ-line treatment for in the next 5 years, 10 years, 20 years? I mean, enhancement for sports is one aspect, but I think many members of the Council are concerned about these other areas of enhancement. So what does your crystal ball say?

    DR. FRIEDMANN: I think nobody knows better than this group the difficulties in even imagining how one's going to do that. All the factors that go into defining one's intelligence and sportability and everything else, they are imponderable at the moment. We know they are genetic to some extent. We know there are non-genetic and environmental and upbringing issues. We all know that one is not going to get a Michael Jordan or a Beethoven or a Michelangelo who's going to care a wit for what his genetic destiny might seem to suggest.

    I mean, you make a Michael Jordan and he will probably hate sport. He may be very tall, but he may turn out to not have the opportunities to have learned basketball, not have the coordination which comes from conversations among lots of other genes. I think that is a non-starter at the moment because we are far too ignorant. There is just no question about that.

    This nonsense, I must say, about Ted Williams, of course, another destruction of one's image of romantic sport, the nonsense of Ted Williams being frozen so one can sell his DNA, so that one can produce lots of other Ted Williams, it is absolutely "klatsch," as the Germans would say. It doesn't make sense, but, of course, that is not going to happen. There is no scientific defensibility for that. I think that is a non-starter.

    CHAIRMAN KASS: Gil Meilaender?

    PROF. MEILAENDER: Yes, as someone who could tell you what the Chicago radio stations that do sports talk all day are, I think you are too quick to assume a certain kind of tacit acceptance on the part —

    DR. FRIEDMANN: I'm sorry?

    PROF. MEILAENDER: — to assume some kind of tacit acceptance on the part of the public of, well, most recently, the steroids in baseball, for instance. I think it is pretty far from that.

    I wonder if I can get you to just try to help me think a little farther than your presentation, which was very good and helpful. There are certain kinds of things, certain kinds of advances we make in sport. You pointed to them. So we start to use better tennis rackets, for instance, or bigger baseball gloves, or something like that. Maybe for a little while, if I have a better tennis racket and you have an old wooden one, it advantages me, but then pretty soon nobody uses wooden tennis rackets any longer, and all is well.

    There is a sense, I suppose, in which you could say the same might be true with some of these possible, in-the-future ways of genetically enhancing performance. For a little while, if I have had access to it and you haven't, you know, it is unfair, but then it evens out.

    So if the issue is simply kind of a level field of play and competition, if that is the issue, then probably, although there may be difficulties in the short run, in the long run it might not be a big issue.

    So what I want to know is, if that's not the reason that people, just intuitively, seem to be concerned, and maybe they're wrong, maybe their intuitions are just wrong, can we think a little bit more about it? Because I don't think it is just the issue of health. Indeed, if it were just the issue of health, I might actually be with Jerome Holtzman; you know, if you want to give up 20 years of your life in order to be a star, God bless you, sort of.

    But is there any difference between using genetic-altering approaches to enhancing my performance and using a bigger baseball glove or a graphite squash racket or something like that? You know, these could all be thought of as accomplishing the same thing in some ways, but do you think about them all in the same way or do you distinguish between them?

    DR. FRIEDMANN: I think they are the same if your endpoint is, how far can you hit a baseball or how fast can you come down a ski slope, and how fast you can run 100 meters. If that is the endpoint, just sort of the measure, the quantitation, then you could say there's no difference. On the other hand, if you are saying that there is a difference between modifying the equipment and modifying the user of the equipment, then I think there certainly could be a difference, that it is engineering, sort of materials engineering versus bioengineering.

    PROF. MEILAENDER: Well, I mean I understand that, but your sentence was that there's no difference if you are only interested in how far you can hit a baseball, but who is the "you"? See, when you went on to your second distinction, the issue was precisely who the "you" is in a way, you know, a bioengineered you or not.

    So the sentence, "There is no difference if you're only interested in how far you can hit a baseball" is systematically ambiguous, I mean, because it cloaks the crucial question, doesn't it?

    DR. FRIEDMANN: I don't know if I see that as a crucial question. Maybe I don't understand it too well. If the only measure of the manipulation, a wooden bat or a fiberglass pole, or whatever, if the only measure is the end result, then you can say there is no difference. But if you are looking at the way you got to that point, if it is because the athlete himself has changed in fundamental engineering sorts of ways, then having hit a ball 500 feet is one thing. If he's got there by using a far better designed bat, then that is something quite different.

    The problem with Holtzman's analysis, Holtzman's comment, it seems to me, is that that certainly is true, if the athlete, or if people, subjects, whether athletes or not, are provided with full and complete information on what is likely to happen. If their information, if the available information is inadequate or is obfuscated or is not clear, and yet they are being offered, just in the case of the East German swimmers, offered long periods of pharmacological intervention based on the promise that they are going to have athletic success, and yet at the risk of their health, you can say to them, it doesn't matter what they choose. If they choose to win over protect their health, that is up to them. But it is only up to them legitimately if they've got correct information, if they have been educated, if they know what the options are, what true options are for them.

    In this case, I think the option is that genetic modification is too immature a technology to assure the subjects that they will not be harmed, that the issues are far too immature and the techniques are far too immature, technology is too young, to know, in fact, what is going to happen in 20, 30 years. That is a level of ignorance that you have to be aware of if they, in fact, according to Holtzman, decide that they would accept that risk.

    PROF. MEILAENDER: May I continue for one minute or not?

    CHAIRMAN KASS: Well, I was going to come to you, if I might.

    PROF. MEILAENDER: Okay.

    CHAIRMAN KASS: Because I think I might clarify this. I take it your question is really not about the safety question or the health risks. Your question is whether there is somehow a fundamental difference between alterations, like I say, in one's equipment and alterations in, which I guess is the debated question, in yourself, and if that is a difference, whether we should care about it, I take it is where you're going.

    Let me try something with you, because in the article that was distributed, Malcolm Gladwell's essay from The New Yorker — I won't get it right exactly — but, in effect, he is suggesting that some of these performance-enhancing drugs might, in fact, be a way of correcting for the accidents of natural endowment, and that if the romantic view of sport is based upon striving and effort, rather than on the basis of some ideal of excellence as such, then it seems to me, why wouldn't you want to say, "Look, what really counts is what you make of your talents and you can't take credit for your talents because those are gifts."?

    Then why say, "Look, what you really want to do to have real sport is to equalize talent and then what you really want to see is, what are each of us going to make, what is everybody going to make of the talents, on the basis of who you really are, which is not the gifts that you were given, but your discipline, your effort, your aspiration."?

    Why wouldn't you then want to say, "Look, body engineering is the possibility of really leveling the field in terms of gifts, so that we can then find out who's who when it comes to what's in the salt."?

    PROF. MEILAENDER: There are some complicated questions there. Remember, I began with a question. I wasn't making an assertion.

    But why do you think that who I am has only to do with the soul and not the body? Why do you think that who I am has nothing to do with the body that I have and the natural endowments, and so forth?

    Well, just, you know, hang in there. Is it not, therefore, possible that we can conceive of certain kinds of alterations of the body that seem to alter the who I am? I mean that is the issue. And I don't have an answer here, but I am not just prepared to accept the disjunction.

    CHAIRMAN KASS: But then your view of sport is that it is not — then the excellence isn't just in the striving.

    PROF. MEILAENDER: Why, no. I coached kids, baseball teams, for years, and I never told one kid that it didn't matter whether you won or lost. I wouldn't tell a kid that at all.

    DR. FRIEDMANN: I'm not so sure I buy the issue that you quote in the article about sort of leveling the playing field to make up for people's innate differences, innate differences in talent or ability, because that assumes that there is kind of a finite and defined normal for that. We all know, of course, that that, like everything else, sits along a very long wide spectrum of human capability, human traits.

    People at the low far end of the normal curve are going to have very different traits from people at the high far end of the normal spectrum. So is that fair? Is that just, that they have got to compete with each other? So why not, in fact, imagine getting everybody to precisely the same level and have no curve, have just sort of a single point which is acceptable? That's not going to happen. So the level playing field concept, get everybody to the same level of capability and then see who runs the fastest, I think that is not going to be feasible.

    CHAIRMAN KASS: Frank, Charles, Michael, and Paul are in the queue. Frank?

    PROF. FUKUYAMA: Two separate points. With Gil, I think the health — I mean, I just find it hard to believe that health is the only ethical issue. I am wondering if there is actually any empirical polling data about why people oppose doping.

    DR. FRIEDMANN: Why they oppose?

    PROF. FUKUYAMA: Yes. You know, at the beginning of "The Prime of Miss Jane Brodie," she is a school teacher and she sees a sign on her wall that says, "Safety first," and she rips it down and she says, "No, honor, virtue, courage first. Safety second." That's the choice. Like Gil, I'm with the athletes, but that is just one issue.

    But the second one is, I wonder if you could speculate a little bit with me. Supposing that you moved sport from the romantic version completely and made it more like auto racing, where it is a team effort of a bunch of doctors and medical people, to enhance the abilities of the athletes, that we kind of accepted that that is the ground of the competition, like the America's Cup or something, and it is a kind of open-ended competition.

    What would happen in that kind of world over time? Would you move asymptotically simply to a kind of natural limit and just get there quicker than you would by normal training and the kinds of things that have traditionally been done in athletics or would it lead to a world, basically, where you would have, for example, an increasingly freakish number of body types?

    I mean, already it is the case where football players and Sumo wrestlers and basketball players are look physically quite different, but you could imagine that, with the kinds of biomedical technologies that we're going to have in the next generation, you could push those somatic types in really, really far so that, instead of slam dunks, you would basically have basketball players that are dropping basketballs downwards into hoops.

    But what does that world look like? Have you given any thought to ?- I mean, do all athletes become Sumo wrestlers, kind of grotesque Sumo wrestlers, in a sense, or is it just a kind of convergence on a natural limit that —

    DR. FRIEDMANN: I must say I haven't given it more thought than your very perceptive question indicates. You have the same intuition that I have, that the second option isn't very pretty. If one wants to go there, then I keep thinking again of Schrecker, what does that make of sport? What is an athlete at the end of all that, if not just simply another byproduct of a piece of engineering?

    It is not sport, I presume. I am not an athlete, and I am new to the anti-doping world. But I have had trouble, as you have, understanding — and that is why I put it on one of the slides — what it is that we are so worried about. What are we protecting sport, for its own best interests, or are we protecting sport because we have the view of sport as we remember it growing up that we would like to see never change?

    I don't like looking at a sports competition wondering what I am looking at. If I am looking at the highly-engineered body, then that is one thing, but if I am looking at an athlete, I would like to see something else.

    That is my problem, I think. It is not the athlete's problem. It is not the society's problem.

    CHAIRMAN KASS: Charles?

    DR. KRAUTHAMMER: Let me try to address the problem, the question that you just raised, what are we worried about and why are we concerned about this? I don't think our concern is about sport. We are not a commission on sport; we are a Council on Ethics. Sport is very useful. Your presentation was very enlightening because it is such a clear sort of pure culture of the question. Things can be measured. We know that enhancement is possible. We know that enhancement has already occurred. So it allows us to look at the larger issue through a window that we can understand.

    But I am not sure that the aesthetics of sports is the critical issue. I think the real critical issue is, why does enhancement somehow bother us? As I look at it, I think there are three possible reasons: safety, fairness, and character. Safety is obvious, and that is sort of a given. We are a society that protects people from themselves and the use of drugs or other areas; it would carry over into here. I don't think it is a very interesting question.

    The more interesting issue, I think, is the issue of fairness. Gil raised it. I think he gave one explanation, which is that we ought not be that worried about the fairness because, as in the mechanical technology, as in tennis rackets, in the end if all the competitors are using the same enhancement, the fairness is retained. What's unfair now is that you've got doping being illegal; some know how to cheat and some don't. If you lived in a world in which it were either completely abandoned and enforced perfectly or allowed and universally used, you would end up in a situation where everybody is using the better tennis racket or the better body. The fairness issue, I think, would not be the major issue.

    The other aspect of the fairness issue was raised by Leon. In a sense, I think he is right; the enhancement can be seen as a corrective for the unfairness of natural endowment. It is not quite clear why we honor people with great talent. It is useful in a competitive society, but why it is honored, if the talent, in and of itself, is innate is an interesting question. If enhancement is a way to level the field, I am not sure it offends our sense of fairness.

    In the end, I think the reason that we object to this enhancement, or at least have some initial — why we recoil from it initially has to do with character. I think it is a sense that that is not the way to get from A to B. I mean, the ultimate enhancer was Rosie Ruiz. Do you remember Rosie Ruiz? She won the New York Marathon one year by riding the subway for the 18 miles in the middle. She started the race, got on the subway, waited a while — that was smart — and then rejoined it for the last mile. Her crown was only temporarily held.

    (Laughter.)

    But it offends us because that's not how you do it. In the end, I think when we discuss enhancement and make recommendations, or at least raise issues about it, not in sport but in life, because I think that is really what is important, is going to be this issue of character, that it is a cheap way to achieve what ought to be achieved by other means.

    I am not sure how defensible that objection is, but I think in the end it is what underlies our objection. It is not safety. I am not sure in the end it is fairness. In a sense, it is character, I would say.

    CHAIRMAN KASS: Michael?

    PROF. SANDEL: Well, I think Charles has advanced the discussion. He has partly stolen some of what I was going to say, but I think that this is onto something important to separate safety and the fairness considerations from some other objection that we have, but find difficult to articulate.

    During the last Olympics I was speaking to someone. He works in the biotech-industry. He said he wasn't watching the Olympics. I asked him why, and he said, well, he didn't really know what it was for, what it was about. Here were these people lifting huge weights, and there was all this discussion about enforcing anti-doping regulations, but if the purpose of the competition was to press the limits of human achievement to see what the people could do with the human body, then the logical thing to do would be to allow people to use whatever enhancements were available because that would be the way of pressing the limits of human achievement: how much weight could be lifted, how fast a hundred meters could be run.

    But, given the inconsistency about the forms of enhancement, rigorous training regimes, okay, but pharmacological or genetic interventions, not okay, given that inconsistency, there was an incoherence introduced into the nature of the sport. Therefore, he didn't watch it.

    I thought this was a bizarre reaction, a bizarre view, but I think he was onto something, just as I think Charles is onto something. I don't think it is true that the classic or romantic idea of sport is based on striving or effort. That misdescribes it.

    In fact, I think there are two ideals that coexist uneasily in the classic conception of sport. One of them has to do with effort and striving, but the other has to do with achievement and excellence. Different people, maybe as a matter of temperament, admire more the one or more the other.

    People who greatly prize and honor effort and striving will say that Pete Rose was the greatest baseball player who ever lived. He wasn't blessed with great natural gifts, but he was gritty and determined and, through sheer expenditure of effort and will, managed to be a great baseball player.

    Whereas, others are drawn more to Joe DiMaggio, who was blessed with great gifts and grace, and part of what people admired about his play was precisely its effortlessness and the grace that went with those gifts.

    So the second ideal, the one that's in tension with striving and effort, has to do with gifts, the great gifts that we admire when, of course, they are properly cultivated and displayed by great athletes. We saw the tension between these two stances, these two dimensions, of the ideal of sport in the celebration of Ted Williams. They told the story time and time again about how he practiced hitting until his hands bled. That was effort. That was striving.

    But, at the same time, he was celebrated and valorized for having such terrific eyesight, 20/10 eyesight. They said again and again, that he could read the signature of the League President on the ball as it came forward. That had nothing to do with striving or effort. It had to do with a gift, but the gift and the way it was deployed in the excellence is something that we admire wholly independent of the striving. But that raises the question, because now we have laser eye surgery that many athletes go in for, Tiger Woods famously among them, that can change and correct and improve the eyesight that sports figures have.

    So if we have, then, these two ideals and tension in sport, the question, an interesting question going back to the technological intervention, the enhancement, is, what exactly is threatened? What dimension of the ideal of sport is threatened insofar as we are uneasy, for reasons that go beyond safety and fairness in the case of sport?

    Our first instinct, I think, is to think it is effort and striving. Because of someone goes and gets a technological edge or takes a drug, then they are doing something that they really don't have to strive for and train for. It's training on the cheap.

    But I don't think that is really what bothers us about the biotech. enhancement. It is more deeply a threat to the second, not the first. Because what it displaces or confuses in what we honor and admire in sports is the appreciation of the gift, the gift of the great athlete which, when cultivated and deployed, leads to an excellence that we admire.

    In fact, the intervention, the enhancement of genetic or pharmacological enhancement is in some ways a ratcheting-up of the element of will, the first thing. It is carrying the idea of will to a kind of logical extreme, and so it threatens to crowd out the sense of gift, the great athlete a gifted. There it seems to me it is in crowding out the sense of gift that this deep, independent, morally-troubling threat consists.

    Now it is a further question, and Charles raised it very well, why we are so interested in using sports as a metaphor or as an analogy for trying to understand objections we might have to enhancement in the wider society. I think that is a question we need to think about, but here's just one speculation:

    Sports has become increasingly a metaphor for life, as the allocation of rewards and honors in our society, as we search for a rationale. We like to think of ourselves as a meritocracy, but a meritocracy is at odds with the idea of honoring or rewarding gifts or giftedness. So we tend to describe the system of social rewards as it is rewarding effort; if you try hard, you have an equal opportunity, you can get ahead and be rewarded. That is what we honor.

    So, if anything, we have kind of refashioned — and we saw it in the discussion here — we have refashioned the ideal of sport to fit the image of the society, that we have this meritocratic one based on effort, and yet we know with another part of ourselves, I think, that the distribution of honors and rewards in our society can't wholly be made sense of in terms of effort alone. That makes us uneasy, and it may get all the more complicated when we imagine a kind of genetic or pharmacological arms race, not only in sports, but also overlaid on a meritocracy, where we are not quite sure to what extent we are honoring effort or honoring achievement and gifts for which we can claim no credit.

    CHAIRMAN KASS: Thank you.

    DR. McHUGH: I always come after Michael, and I am so impressed by what he said, I have lost my track a little bit. I want to simply go along exactly with what Charles and Michael have been alluding to, but to make some simpler points along the way. I think, Dr. Friedmann, you have made some of them as well.

    But, fundamentally, what we are all concerned about is that which we are going to permit is going to have to be required eventually. I had a dear friend of mine who is a wonderful psychiatrist, who is a wonderful person, and he was involved with the professional football team in San Diego. He discovered that all of the defensive players were on amphetamines, and he wanted to get them off of the amphetamines. They all said to him, "Doc, can you imagine what it's like me going out into that field with those guys who are drooling with their amphetamines? You've got to help me to get through."

    The problem for my dear friend, and he is a wonderfully gifted person, is that he tried to help them, and help them reduce their amphetamines, and at the same time kind of keep them in play, and eventually hurt himself in the process, very much hurt his reputation. But that was the first example to me of what is permitted will eventually all be required.

    I agree also with what is being said, that one advantage of looking at sport — I mean we are not here to talk about sport, but sport does give us a little opportunity to look at what could happen in other arenas. One of the things that is being left out of discussion here is just the plain word "cheating," you know. Doesn't cheating perhaps apply here, just to get to the groundrules?

    Now take another game that takes very little athletics —

    DR. FRIEDMANN: But you can have that and have achievement at the same time.

    DR. McHUGH: Yes, that's right, and I want to talk about exactly that. There's a game that we know in America, and we know what constitutes learning about the odds and playing it well and folding when you ought to. We also know that if somebody spends a lot of time learning how to slip cards up his sleeve and play that way, that we shoot those guys because that's wrong. It takes away the whole idea of the game and what it is.

    I very much, with you, believe that the thing that has gone wrong for lots of people is that we have an immature science that we are telling them, nobody can get — everybody is going to have to join up. What's given is required. Yet, the science is so poor, we can't tell them exactly what's going to be lost in their health.

    But, ultimately, it does come down, well, for me, and I suppose I do have a romantic view of sport; I certainly spent an awful lot of hours in my life talking about sport. When Ted Williams died, I burned up the phones spending dollars talking to many people all around the country about what a terribly sad day it was and how I saw him hit the Eephus pitch and all of this. Because I thought, and still think, that part of the thing that sports gives to us is that it enhances our capacity to appreciate excellence in others and their character as they use what God gave them to achieve all the things that they have achieved.

    If we permit all this genetic enhancement to go, that there will be not only a loss in physical things, but we will lose the sense that there is a place where character counts. If we lose that, then in the boardrooms of the country and lots of other places, where character ought to count again, it will be lost there, too.

    PROF. SANDEL: Of course, cheating is what we are against.

    DR. McHUGH: Yes.

    PROF. SANDEL: But isn't the issue raised here, what counts is cheating? For example, if we go to the wider society, apart from sports, when kids who can afford it take courses to prepare them for the SATs, is that cheating?

    DR. McHUGH: Well, as I am saying, I am not sure exactly where cheating ends and where cheating begins, but I know it when I see it.

    (Laughter.)

    Consider poker. That's one of the reasons I wanted to talk about that.

    PROF. SANDEL: I didn't know what game you were referring to, so I'm glad you named it.

    DR. McHUGH: Yes, you were wondering, I'm sure. But you can consider games of that sort.

    No, I agree with you that there are ways in which you might wonder that we are not a completely equal society in lots of ways. Some people can have, just the case of baseball, some people can offer their kids a batting cage and a batting machine, a pitching machine with which to play early on, and they don't have to do like Ted did, go out into the dusty fields of San Diego and get somebody to pitch to them. I appreciate that.

    On the other hand, I think that we should be able to say at some point that certain forms of enhancement just go beyond what is, and I think lots of things that are happening in genetics go beyond there. Although there are gray areas, there are still areas of black and white.

    CHAIRMAN KASS: We are going to wind up shortly. I have Bill and then Frank, and I want to give Ted a final comment. Then we will stop. Bill Hurlbut.

    DR. HURLBUT: So cueing off of what Michael said, I want to suggest that we institute a third kind of Olympics. We have the normal Olympics and the Special Olympics. Maybe now we need the Bio Olympics.

    DR. FRIEDMANN: That is not as facetious as you may imply. There is already talk for sort of an enhanced weight-lifting set of events.

    DR. HURLBUT: Well, I, for one, will be much more interested in watching the normal Olympics, if they do it, as I am now more interested in watching Little League than professional baseball.

    I think when you mentioned the — I have to confess I am a romantic on all this, but I think that might not be so cultural as it is more deeply universal, picking up on what Robby said earlier. I teach at Stanford. We have a lot of Olympic athletes, and I have had them in my classes. It seems to me that there's something important going on here that we've kind of touched on, but maybe not quite completely.

    Obviously, there's something entertaining about watching eccentricity and novelty and extreme, but this is kind of — I don't know, I see this as almost a societal auto-digestion, where we are deriving entertainment from things that are destructive, a kind of nourishment from our own destructive deformation, rather than what I think sports is about, which is something that has to do with something profound and noble and moral, quintessentially moral.

    It is not health that strikes me. I think about, what would you approve using enhancing drugs for or even entering into territory of danger for? I think, for example, about a hand surgeon, I mean an eye surgeon doing an operation on a child. You wouldn't mind him using beta blockers to calm his hands for that, even if it was a little bit of a health risk to him. We send people out into space with NASA, and we don't mind the health risk of that. It seems to me it has something to do with serious purpose.

    Even with my students, I talk to them about all this. When it comes to things like cosmetic surgery, they feel okay moving kids with deformities up to the norm, but when you start moving beyond that mean, they are uncomfortable with it. They feel like something has changed.

    When it comes to sports —

    DR. FRIEDMANN: Is it the mean or —

    DR. HURLBUT: Or the norm.

    DR. FRIEDMANN: Yes.

    DR. HURLBUT: I mean whatever you call it, in the middle. They are okay if you move a kid with cleft palate up to looking normal, and they are okay even with taking a person with ears that stick out or a recessed chin or something, but when it starts to become a competitive action, they feel like it is no longer medicine, that it is somehow strangely moved into the realm not of social coherence, but of competition.

    It seems to me that that is what is going on in sports enhancement that bothers me personally. Maybe this is more universal than me; I think so. Sports is a kind of symbolic combat, but it seems to be a moral combat fundamentally. You spoke of an aboriginal impulse.

    If you go back and you look at Murdoch's human relations files — do you know about those? They did these ethnic studies across all cultures, and every culture has something in the way of a sports ritual. Often they are tied in with the rites of passage.

    I wonder if maybe at this particular age group that sports involves, primarily this risk notion has something to do with confronting the real world as it is, confronting danger, confronting infantile impulses and all the persuasions of pleasure, and in the constellation of that we gain control over ourselves.

    In that sense, when I watch an athletic event and I see somebody manifesting self-mastery, that seems to me to have a moral element to it that is quintessentially the essence of morality in the first place; that human beings exist in a world of striving and struggle within their open possibilities and indeterminacies, and they move in a moral direction when they move for serious purposes against the natural quality of giving in to the easy or the obvious.

    In that sense, it is not just effort that we care about. Ultimately, it is what is done. That is why to me all the things that we are talking about in terms of enhancement seem like they might be more okay at least, and maybe okay, when done for serious purposes. But the problem with sports is, instead of being a communal matter, it becomes a purely individual competitive matter then. It changes its character from being a place where we come together as a society to being a place where we lose the essence of what it is to be moral.

    Does that make any sense?

    DR. FRIEDMANN: I think that's a good analysis, but it flies in the face of the analysis of sport having multiple characters. One is striving and effort; the other is achievement. If achievement, in fact, is achievement and excellence or, in fact, the calculus by which sport is measured in a society, then it seems to me you don't have much of a leg to stand on.

    DR. HURLBUT: Doesn't it become boring when it is just about achievement?

    DR. FRIEDMANN: Well, of course, it's boring, but we presume that, to some extent, effort and striving — or at least how do I get to Carnegie Hall? Practice, practice, practice. No one ever said, take something to help you get there. In fact, most violinists probably take beta blockers to keep the quiver down.

    So I think that the question really, again, is, what is sport and what are the goals of sport? I don't mean in any way to say that this is the moral problem of our time, but I think it is an opening to the issue of what do we take for being normal; what do we take for being acceptable? And those things that we want improved, what is it that enhancement is designed to do for us? What kind of enhancement do we want, and what kind of enhancement is morally repugnant to us?

    That, of course, all depends on what we think sport is. If it is a paradigm, that is one thing. But the issue of enhancement outside of sport is still a major concern.

    CHAIRMAN KASS: Frank, absolutely the last; I've kept everybody after school.

    PROF. FUKUYAMA: Okay, well, very briefly, I thought Michael's distinction between gifts and effort was a very good one, but it does seem to me that the concept of gift and reveling in the excellence of that gift has to be related to some concept of what it means to be a human being. It is a human gift.

    What you find remarkable is that a human being can do this in a human way. If you're born as a freak, you know, nine feet tall and you can play great basketball, I don't think — and then, similarly, we don't revel in cheetahs because they can run faster; they can run the mile faster than human beings because that's what cheetahs do. So there does have to be, I think, a specific notion of what it is to be a human being, and the gift is in relation to our expectations of that.

    CHAIRMAN KASS: The hour is late. I usually teach in the afternoon, when I used to teach — it is a life for which one longs — from 2:30 to 4:30. I taught at 2:30 to 4:30 because, if I wanted to run over, nobody wanted the room.

    I have done it to you again. I promised an early start, but, Ted, you have provided the foundation for what is in some ways, I think, one of the most interesting conversations that we have had here as a group. For the illumination and the stimulus, we are in your debt and thank you very, very much.

    We will meet tomorrow morning at 8:30 for the discussion of the Richard Selzer story. I have good news for the wonderful people who have sat with us through this day. Whether you come back tomorrow or not, if you do, you will have a chance — the text of the story we are going to discuss is out there. So you can take it home, read it, and at least be in on the conversation. That is the gift of our appreciation for your endurance here and participation. We thank you also. Thanks to Council members, and the meeting is adjourned.

    (Whereupon, the foregoing matter went off the record at 4:42 p.m., to reconvene the following day, Friday, July 12, 2002.)


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