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Thursday, February 13, 2002

Session 2: Human Cloning 5: National Academies' Report "Scientific and Medical Aspects of Human Reproductive Cloning"

Irving L. Weissman, M.D.


CHAIRMAN KASS: All right. I have been asked by our audio technician to tell people that they should — when they speak, they should speak a little bit further back from the mic but still speak into the general direction. It should pick up very well.

We come to the second session of the meeting devoted to a discussion of the report by the National Academies of Science's Panel on Scientific and Medical Aspects of Human Reproductive Cloning. And we are delighted that Irv Weissman, who is the Chair of that panel, is here to discuss the report with us.

We want to do three things. I mean, Irv is going to make a beginning presentation. Council members will have an opportunity to discuss the findings of the report and then take up certain questions of either assumptions or questions of the reasoning. I am not sure that these distinctions are going to be able to be kept from one another. And, finally, we would like to have at least some discussion about Irv's view on the relation between what the Academies has done and what remains for us here in the consideration of these issues.

I would also, if I may, before we start, like to welcome and introduce Dr. Maxine Singer, who is the President of the Carnegie Institution of Washington, Distinguished Scientist at the National Cancer Institute and the Chairman of the Academies CSEPP Committee who oversaw and worked on this report.

Nice to have you with us, Maxine.

DR. SINGER: Thank you.

CHAIRMAN KASS: Irv, would you like to begin, please?

DR. WEISSMAN: Sure.

So let me introduce myself first because I think it is important to know where I come from. So my name is Irv Weissman and I am a professor of cancer biology, pathology, developmental biology and biology at Stanford. It just means that the field I am in is a new field and, therefore, it crosses into many disciplines and it has uses in many disciplines.

I work, especially in the last 20 years, on adult stem cells and it happens that we were the first to identify and isolate adult stem cells from any tissue from any organism and you should know that in the course of the research that began with mice in my laboratory I helped co-found two companies. One called Systemics, Incorporated. Another called Stem Cells, Incorporated. And at those companies I was a director or am a director, have an equity position or had an equity position, got consultant fees. Just so you know that there might be unconscious biases or not but you know that.

Now, I should say that none of my companies that I have been associated with, and no current plan of the companies, involves embryonic stem cell research. In fact, if there were an analyst in the crowd he would say, or she would say, what I am going to talk to you about, the permission of nuclear transplantation to produce stem cell lines, if it worked in the narrow sense of the term "therapeutic cloning," would create competition for any commercial effort I am in. So I have been advised of that, too, by people in the company.

So is that all clear so far? Adult stem cells, that is my expertise, it is what I work on but I certainly have worked hard on trying to understand embryonic stem cells.

Now, I am Chair of the panel, as you know, of the National Academies Human Reproductive Cloning Panel and Report. And, I think, the most important thing to say first about that report, both by the charge, by the way we carried out the investigations which were extensive and over a long period of time, and in the report we published we did not look at ethical issues or moral issues or religious issues or political issues. We never discussed them.

Our charge was to look at the scientific and medical, and if medical practice were to be involved, the use of human subjects or human participants in research issues only. Our objective was to try to report to society-at-large what are the facts about either human reproductive cloning or nuclear transplantation to produce human pluripotent stem cells to give you and Congress and others in society that data so that you would be informed about the debate.

Now I should say, since you mentioned that Congress has passed a bill, they passed a bill without the benefit of scientific or medical information. I am sure if you look back at the debate, it did not include what the two Academies' reports are. The first one headed by Burt Vogelstein on stem cells; the second headed by me on human reproductive cloning.

Now you will know if you look carefully at the report that we examined and heard testimony about all of the many animal experiments to produce reproductive clones; that is to produce whole organisms to be born. And what we learned is that in every animal species, whether it is the beginning of the trial or experiments done even most recently, that using nuclear transplantation to give rise to a blastocyst that is implanted in the uterus with the intention of making a living newborn or a living organism that that failed at virtually every step of the way.

Now, you also know that both by IVF and by natural reproduction that there are miscarriages that occur and usually they occur in the first trimester. These failed with a high rate throughout the pregnancy and the consequences of a failure late in the pregnancy did have some morbidity and mortality for the mother that carried it.

There were also defects in placentation, making of the placenta, and also large offspring that developed from it and each of these had morbidity and mortality. Of the blastocysts implanted, on average, 8/10ths to 9/10ths of a percent of them made it to parturition, birth. And even then, many of the newborns died because they lacked the ability to breathe or carry out other functions and those that lived for a long time are coming down with defects that may or may not be attributable to the nuclear transplantation method.

So given that what we learned in many species is likely to occur in man, we decided that that was not ready for prime time. So now I will read just the recommendation itself, not all the preamble.

"Human reproductive cloning should not now be practiced. It is dangerous and likely to fail. The panel, therefore, unanimously supports the proposal that there should be a legally enforceable ban on the practice of human reproductive cloning.

"The scientific and medical considerations related to this ban should be reviewed within five years."

Now, go back. "Scientific and medical."

"The ban itself should be reconsidered only if at least two conditions are met: (1) a new scientific and medical review indicates that the procedures are likely to be safe and effective and (2)..." which we did not do "...a broad national dialogue on the societal, religious, and ethical issues suggests that a reconsideration of the ban is warranted."

We did not recommend that if it was safe and effective that it should be instituted, that is unfortunately, as I see some of the questions, a misconception and maybe it is our miscommunication but I am going to clarify it here.

Next: "Finally..." this is still part of the recommendation. "...the scientific and medical considerations that justify a ban on human reproductive cloning at this time are not applicable to nuclear transplantation to produce stem cells. Because of the considerable potential for developing new medical therapies for life-threatening diseases and advancing fundamental knowledge, the panel supports the conclusion of a recent National Academies report..." that's the Stem Cell Report, the Vogelstein Committee "...that recommended that biomedical research using nuclear transplantation to produce stem cells be permitted. A broad national dialogue on the societal, religious and ethical issues is encouraged on this matter." And I should say, this also was unanimously approved — this recommendation approved by the committee.

Now I want to, therefore, say that from our point of view, we want — we recommend a legally enforceable ban, and that is really important because, like many laws, we expect the ban will have an effect on society and those who would attempt to break the ban, rogue scientists you might call them or rogue clinicians or other groups that want to do it, that they would face whatever penalties a legally enforceable ban no matter where they are. So we wanted to make sure that we were not limited to those people who were under the purview of federal funding or under the purview of the FDA. We wanted it to be in the United States and to be clean. It was the line in the sand.

I do not believe we could have moved on to the next recommendation if we did not draw that line in the sand.

Now, for me to get into the terminology issue, I want to get it a little bit into the science, and I am going to apologize. I am going to get up like a professor and show you a figure and talk you through it, and you do not have that figure in front of you but Debbie Stein has assured me that by this afternoon you will have a copy of that figure.

Right, Debbie? You do not have that figure?

DR. STEIN: It is very close.

DR. WEISSMAN: It is close but I want to use this to explain what is going on.

It is like Figure 2 but it is not the same. You could write in the notes what I am going to tell you.

Okay. This was Figure 1. So just so you know, and I am sure you know it better than I even by now that if you enucleate a human egg or in the animal circumstance an animal egg, so you move the chromosomal material, you can transplant into it a whole somatic cell or the nucleus from a somatic cell from some part of the body. And in some frequency when you electrically stimulate that egg, some of them go on to form the blastocyst stage of embryo development, the pre-implantation embryo.

Of course, the fertilized egg is an embryo. The two cell stage, the four cell stage. And if you implant that in the prepared human uterus, which is a complicated procedure to prepare the female who will be the recipient requiring medical treatment and medical personnel, in an operating room setting — and you will see why I am going to get there in a minute — if it implants, it can go forward.

At about the time organs begin to form in a very vague way definitionally, it transitions from an embryo to a fetus. The common perception, I will just say to you, and you know it, when you ask somebody in society to draw what an embryo is, they usually draw a fetus, not a single cell or a two cell or a four cell. So that is just a problem that we all have to deal with is that the popular conception of what an embryo is, is not necessarily even close to the facts that are at least defined by embryologists.

So now let's talk about the nuclear transplantation technology. So here now the nucleus can be from any somatic cell. Let me back up just for one second. President Bush's recommendation, edict, whatever you want to call it, on stem cell, embryonic stem cell research has given to the scientific community the possibility to do research on as many as 64 embryonic stem cell lines derived from blastocysts, over there, from spermate fusion, excess blastocysts in in vitro fertilization clinics. That does not represent genetic diversity of humans and if one is going to do even research based on this you would want wider participation by all elements of society, humans genetically so you would understand.

So, one reason to do nuclear transplantation into an enucleated egg to create the blastocyst stage of development from which you derive inner cell mass cells that grow as pluripotent stem cells is to have a broad representation of cells to understand normal human cellular decision making as you go from a pluripotent stem cell, which can make any tissue in the body but does not have the capacity to make a whole placenta or trophoblasts that are involved in the placenta. So this is the only totipotent cell that can make both placenta and embryo, placenta and the developing embryo but after you get this stage. It cannot do it on its own and so it is a pluripotent cells. It can give rise to germ line and to somatic line.

Now, we know next to nothing about the processes that a pluripotent stem cell will turn into say a blood forming stem cell or a nerve stem cell or a muscle stem cell or so on. So it is a legitimate avenue of research to understand those processes with human cells that you could get analogies in animal cells but in the very end to understand the real decision making ourselves, which are crucial to understanding a number of developmental defects that could occur, would be to use a broad diversity of human cells.

Now, if — and this is a very important point for at least the discussion. The nucleus could come from a normal person or the nucleus could come from somebody with a heritable disease. Everybody in this room, me included, contains genes which give a certain predilection for a human disease, and they are common diseases. Cancers, cardiovascular diseases, neurodegenerative diseases, both kinds of diabetes have a genetic component, and so on, Lou Gehrig's disease.

Now, the particular mutation that anybody found first, say for Lou Gehrig's disease, it is an enzyme called superoxide dismutase, when you have a defect in that, many, if not most people who have the disease, have that defect but not everybody who has a defect in that particular gene gets that disease. So if you want to have a real understanding of that particular disease or the other diseases I talked about, you would need to know all of the heritable components that come together to give rise to that disease.

Now in the human that has that disease, the components came together. So having a body nucleus cell would allow you to make pluripotent stem cell lines to study that disease process.

Some diseases, almost certainly all cancers, have something that goes beyond what you inherit. You have what is called "somatic mutations." Janet Riley is famous for finding somatic mutations that cause human leukemia or at least are involved in an important process. We also studied that in animal models and I can tell you that there are many successive mutations that have to occur. Only in that disease cell, only in that patient do you have the life history that led to that disease. There is no animal model close to this. And understanding how that nucleus, making a pluripotent stem cell line, could lead to the differentiation of cells, for example breast cancer, colon cancer and so on, would be a boon for science. There is no doubt about that.

Now, once these kinds of cells are allowed to differentiate, in many cases you can transplant them into a mouse and show in the context of normal development what goes right or what goes wrong. So the full uses, therefore, of nuclear transplantation for this kind of biomedical research includes normal subjects, heritable disease body cells and the nucleus of the disease cell itself.

If that is permitted, I can tell you that many, many of the best and the brightest will want to study that because it gets you closer to the truth of what is going on rather than the other reductive processes that one uses to try to get at the truth of what is going on. It allows you to look directly rather than by correlation.

Now, since these cells can be made and shown to be made in the tissue culture, many people, and of course companies, say that nucleus coming from that person has the same genetic material and, therefore, could be transplanted to repair defective, degenerated tissues. That is called "therapeutic cloning." That is the only place that therapeutic cloning, the word, fits in. That is why even though I agree completely with you about the popular sense of this, we need to come to the right terms because after a while what this group does, what the government does, what the national societies do to change the terminology will lead to a terminology that will be learned by the popular group but to say this is the only use is to, I think, skew the understanding of the broad importance of this kind of science if it is permitted. Okay.

And I should say even if these cells were here tomorrow, a lot of research would need to be done to make them transplantable entities. And in the — for full disclosure, I should say that when you put the nucleus in from a somatic cell, the mitochondria still come from the host.

Mitochondria in every species so far are genetically diverse so that between two individuals, Janet's, for example, a particular enzyme like cytochrome C will have maybe one or two different amino acids by mutations that are still functional but our immune system, especially the so-called T cell components of our immune system, look — scan those small peptides as they are presented on the surface of a cell to make an immune response.

And in mouse studies it is clear that those genetic differences can lead to a mild but certainly effective transplant rejection and so immunosuppression, mild though it is, will be required for that.

So, I think I have given you all the provisos that science can put in and I want you to know that if a ban or a moratorium occurs that blocks the fundamental research in understanding human disease development or therapeutic cloning, clearly promising avenues of medical research will be closed down. And, although I will get to it again in a couple of minutes, this group has a unique responsibility.

On the one hand, as you say, this might be a blastocyst with a tenth percent probability. Right? And that you are judging for various reasons whether that should retain the capacity to stay alive if it was created or in that case when it was naturally created or by in vitro fertilization. So you have a responsibility there. One that my committee did not even address but there is another responsibility that all physicians have taken an oath, and that is to try to be able to treat their patients.

And so I want to say that I believe, and I will give you an argument in a minute, that this is an equal awesome responsibility. Those who make the judgment that this research is banned take the responsibility of whatever medical treatments could have derived from it. There is no escaping this. All of us have that same responsibility. Just so we are all on the same page for that.

I will just take another minute to finish.

So what will be lost if there is a ban? I am going to use only one example, which was a hotly debated example in the '70s, as my precedent and you will find your own precedents. As you know, in the '70s the ability to put two pieces of DNA together became possible. Recombinant DNA. And it was hotly debated for many of the same reasons and, in fact, by many of the same people that this was creating life. It was creating a life form that had never existed before and the kinds of issues, I am sure, you are dealing with came up then.

The scientific community, notably Maxine Singer and Paul Berg, had a conference in Asilomar in 1975, I believe it was, I was there, where the scientific community said, "Let's wait for a minute and let's look at the possibility that something bad could happen from this at least that we could assess directly."

And from that a regulatory agency, the Recombinant Advisory Committee, was developed that looked at and regulated and, in fact, passed on all the plans to do recombinant DNA research.

There is probably not a person in this room who does not know somebody whose life has been made better or saved by the products of that recombinant DNA research. Erythropoietin, all kinds of cancer patients, dialysis patients, GCSF, the way to make stem cells come out of the bone marrow into the blood and do transplants which inarguably have saved lives by prospective analysis and clinical trials, the interferons, the antibody Herceptin for breast cancer, retuximab, and so on.

So I do not think it is arguable that if there had been a ban on recombination DNA research that there would not have been a loss of lives and many of them that could have been saved. Now I know that is going to be on my committee but I am just trying to say to you these are the facts. These are what you must know because the responsibility you are going to take to block a line of research could have that outcome and, of course, it can and probably will go forward in other countries. And then physicians here and the government here will be placed in a very unusual situation of what do you do when a cure comes from that kind of research and they want to import the cure to Americans?

What do you do as a physician, as a practicing physician? Would you deny your patient that treatment? I think you are going to have to consider that. I am not going to come down on it other than what seems to be apparent.

Now, many times the issue has come up that if you make the blastocyst in a research laboratory, what is to stop a rogue scientist from secretly putting it in the uterus of a woman?

That is what you said to me, Charles.

So I am going to try to deal with that issue. It was the reason that we needed to have a legally enforceable ban to stop that because we recognized we had testimony from three groups, two or three of which were going to go ahead no matter what we said and that was a fear.

So let me just say for those who have not participated in the isolation of eggs, the implantation of the blastocyst into a woman, this is not a single person's job. So for the safety of the person who is going to receive the eggs, of course, the — I mean, the blastocysts, the blastocyst has to be grown in a sterile environment. The transplantation involves a medical team. It involves a woman who has to have been prepared hormonally for it. It is a surgical procedure to put it into the place that will go into the uterus and it involves anesthesiologists, nurses, doctors and so on. It is not something that a single rogue scientist can do in hiding.

Now, to the extent that one is governed by law, there are a lot of people and a lot of places that would then fall under the jurisdiction. It would be a hospital or a clinic or whatever. It would be very difficult, I would say, to do this and, I still say from my point of view, if you have covered it by law, you have covered it. We could argue, and you will argue long after I am gone, what about that rare rogue one who will just go all the way?

So that is my prepared remarks or actually unprepared remarks of my reflections of what the committee did. If you would like, I could go to some of the questions you have or we could just stop here and have open questions and then come back to the questions that you have written.

CHAIRMAN KASS: Let's — Michael Sandel and Jim, let me make the suggestion — I mean, Irv has — you do not mind my saying have gone beyond the findings to speak about additional things towards the end, so even a way maybe to provoke comments about that as well. But I think if at least the beginning part of the discussion we could try to get some help such as we need it about the findings of the report proper and then move on to other things but I do not want to prevent people from going with it like Michael I saw and then Jim Wilson if I am not mistaken.

PROF. SANDEL: I have a scientific question and then a terminological one. The scientific question is could you tell us, based on what is currently known in the scientific community, what are the advantages of embryonic stem cell research as against adult stem cell research and how do those compare with this technique that was written up recently in the paper where an egg has been made to divide with our fertilization such that it might generate stem cells but does not have the potential for life?

DR. WEISSMAN: So let me go to what is known. And here I am going to try to adhere to a standard that journalists have recently, not all but many have crossed the line. Usually when scientists want to evaluate something scientific to know whether it is true there are two preconditions. One, of course, is that it is published in a peer reviewed journal so that other scientists can look at it with different viewpoints and look for holes in it and look for different interpretations and so on so that it has really gone through the wars before it gets published.

And then I still do not believe it, and most scientists do not believe it, until it has been independently verified by at least another laboratory as being something true.

Given those, we have nothing that adult stem cells, human or otherwise, would match the requirements here and I know that New Scientist magazine, not a scientific journal, reported unpublished results from a laboratory in Minnesota that would give all of us great hope that you might be able to get cells for therapeutic cloning. I will just say, first, it is not published yet.

CHAIRMAN KASS: You do not mean therapeutic cloning?

DR. WEISSMAN: Not cloning. Excuse me.

CHAIRMAN KASS: Yes, for therapy.

DR. WEISSMAN: Therapeutic outcomes — I am sorry — from adult cells. Thank you very much for the correction. All right. See what happens when you shut off, just all the natural words come by and then — I will try not to shut off the brain while I talk.

So anyway — and just to make sure, even though it was not published, I asked the inventor, the scientist, whether it would do everything that we described here. And I have a letter, which I do not know if it is published, she sent it to three senators say that it would not — and I could read it to you if you like but what I am trying to say is that —

PROF. SANDEL: What are you referring to here?

DR. WEISSMAN: That there is no — as yet, no fully pluripotent human cell taken from adults that will allow you to study normal development, heritable disease development, somatic mutation disease development or perhaps even therapeutic intent of transplantation. It might happen and it might come out, that part of it, but the scientist said, "You cannot fulfill all of these research objectives with that kind of a cell line."

So, I know every day you read in the media, you know, does umbilical cord do this, do placental cells do this, and are hematopoietic stem cells, the guys I study, can they do everything? And the answer is it is not there. It may come out to be there and all of us would be happy if we could do that but it is not there and so one should not make policy on the basis of those kinds of reported findings or unpublished findings.

PROF. SANDEL: And what about the other one, the parthenogenesis one, the unfertilized that has been —

DR. WEISSMAN: Sure. The parthenogenesis will only give rise to cells, of course, from that genetic origin, the mother. So, quite clearly, it will not cover any of those research objectives that I told you and it would limit the therapeutic intent to that mother. So if you needed to have it, you do not have a chance from that. You cannot do parthenogenesis. Okay.

CHAIRMAN KASS: Jim Wilson?

DR. WILSON: Thank you very much, Dr. Weissman. I would like you to clarify for me, a complete nonscientist, some aspects of your report. To be precise, these: You have spoken about nuclear transplantation and described it on your second chart here. Cell — adult stem cells can also be derived, as I understand it, from fertilized eggs in in vitro fertilization clinics. In your judgment, are there important medical differences or are there likely to be in the future important medical differences between cells produced by nuclear transplantation and cells derived from fertilized eggs in IVF clinics?

DR. WEISSMAN: Yes. And part of this I probably did not explain it clearly enough first. The IVF clinics have people who come there for fertility problems. It is a very limited part of human genetic diversity. There are not nuclei there that I could go to and say if I want to study Lou Gehrig's disease or cardiovascular disease where you get a heart attack from the result of particular genetic defects, that is not there. So in a very important way those cell lines are only really able to tell you about the normal development from those cells and they will not allow you to do any of the other research objectives. And, of course, if you believed in the therapeutic transplantation, they would only be useful by having the same genotype as nobody who exists.

CHAIRMAN KASS: Stephen Carter and then Frank and Rebecca.

PROF. CARTER: Well, first, I want to thank you for what I think has been a very informative and in certain respects a very enlightening presentation. I am — I have a question about — I just want to make sure I understand something clearly about the presentation. I have a question — I hope this, Mr. Chairman, is in order — about the recommendation of the panel. Is that something I can ask now?

CHAIRMAN KASS: Sure.

PROF. CARTER: I just want to be absolutely clear that although I recognize the reasons for the different terminology that you chose for the processes you are talking about that up to the blastocyst stage these are identical processes; is that correct? This is the same process.

DR. WEISSMAN: Oh, you mean between this and this?

PROF. CARTER: Yes, this is the same process up to that point.

DR. WEISSMAN: Without a doubt.

PROF. CARTER: There is nothing — nothing is different up to that point.

DR. WEISSMAN: Nothing is different.

PROF. CARTER: All right. I just wanted to clarify —

DR. WEISSMAN: Except perhaps the choice of the nuclei but there is nothing different between nuclear transplantation with the intent to create a blastocyst to be implanted from nuclear transplantation to create a blastocyst from which you get pluripotent human stem cells.

PROF. CARTER: Okay. Now, I have a question also about the recommendation. In the recommendation the panel unanimously proposed a total ban, a legal ban on what you called human reproductive cloning. It should be — in five years we should reconsider the medical, that is the scientific basis for the ban. If the scientific evidence tells us at that point the process is likely to be safe and effective, then we should reconsider the ban itself only if there has been a dialogue, a national dialogue that also points to the same direction on the societal, religious and ethical issues.

DR. WEISSMAN: Exactly. A body like this.

PROF. CARTER: Now — so the point is the ban itself is not based on those issues. You did not consider them. The ban itself is based on the question of whether it is — the technique is safe and effective. It is not based in any way on these other issues that should also be considered. And so even if it becomes safe and effective, the ban should continue in place in your recommendation until such time as this dialogue has taken place. Is that — I do not want to misstate it. I want to make sure this is correct.

DR. WEISSMAN: Yes, and I will look around for Maxine or Debbie. That is exactly my reading of our recommendation.

PROF. CARTER: So would it then also be the case that one could plausibly say that a ban on the second form of technology should remain in place until such time as the societal, religious and ethical issues have been addressed since in the first instance even if it is safe and effective medically you still think there ought to be time for a conversation about these other issues. Is that also the case with respect to nuclear transfer that is not intended to create a born human being?

DR. WEISSMAN: Here is where I will differ with you in words but not in the outcome. Since we did not recommend a ban for nuclear transplantation to produce pluripotent stem cells, there is no recommendation for a ban to be in place. Nevertheless, we said clearly, and I think it is the last sentence, a broad national dialogue on societal, religious and ethical issues is encouraged on this matter.

So what we are reporting to you is that human reproductive cloning is dangerous. It is a dangerous medical practice. It contravenes the Nuremberg Code clearly. It contravenes everything that we gave our oath as physicians but there is no such evidence for a nuclear transplantation to produce these cells but as we are scientists and medical, people were not going to impose our personal opinion, which we do not even know. We never polled the panel what their personal opinions were. What we said is we are reporting to you, we are reporting to Congress, we are reporting to NIH, and we hope that this is going to be useful information in your dialogue.

PROF. CARTER: Let me — I do not want to press much more. I guess, the point — the question I was trying to ask another way is this: That with respect to human reproductive cloning, the way I read the recommendation of the panel, the question of safety and effectiveness does not conclude the matter.

DR. WEISSMAN: That is true.

PROF. CARTER: Okay. Thank you.

CHAIRMAN KASS: I have Frank —

DR. WEISSMAN: Or of responsibility for those who make the decisions.

PROF. CARTER: Yes, of course.

CHAIRMAN KASS: I have Frank, Rebecca, Gil and Robby at the moment.

PROF. FUKUYAMA: Thank you very much. That was quite helpful. I have two questions. The first is my understanding is that by either of these processes once you get to the blastocyst stage, in a certain sense, strictly speaking, is actually not cloning because the mitochondrial DNA always inherits from the mother's side and you mentioned that that might in some cases lead to the immune system rejection.

Are there other implications of that at further developmental stages? I mean, what —

DR. WEISSMAN: You mean in terms of the transplantation study in the animal models and in vitro ?

PROF. FUKUYAMA: Either. Or in terms of reproductive cloning. I mean, will the difference in the mitochondrial DNA lead to different outcomes in terms of —

DR. WEISSMAN: Well, we discussed the issues about normal embryos are born that have a fit between the nuclear gene products and the mitochondrial gene products, and in some experimental systems there are implications.

PROF. FUKUYAMA: Right.

DR. WEISSMAN: But these are by no means, at least from a scientific point of view, the major cause in reproductive cloning in animal systems that cause the demise of the animals. Many other — and really not understood — genetic changes in expression are probably involved in that.

PROF. FUKUYAMA: The second question is I am a little unclear as to what kind of research will happen after the somatic cell nuclear transfer produces the blastocyst and you say you want to study various disease models and then normal development and so forth.

DR. WEISSMAN: Sure.

PROF. FUKUYAMA: Does that invariably involve just harvesting the stem cells from the blastocyst and then doing things with them or does it involve actually allowing the blastocyst to develop, you know, to further stages?

DR. WEISSMAN: Right, right. In my view, and I believe in the panel's view, you are only harvesting the cells from the inner cell mass of the blastocyst. We would be pleased if it were so efficient that you could harvest one cell from the inner cell mass of the blastocyst. That is not here today.

There is no research that has been proposed by members of the panel or that I think are out in society to implant that into a woman that has been prepared for the purposes of harvesting cells or tissues. In my own personal view that would require — that would also be medical research and would have risks not just for the embryo or fetus that develops from it but for the woman who went through the procedure.

So that is my personal view but certainly everything I have told you here is only done with the pre-implantation blastocyst.

PROF. FUKUYAMA: Would it be possible to develop a blastocyst, you know, outside of a womb?

DR. WEISSMAN: I have heard people say that that is an object for research. I have not myself, and I — if anybody else has any information — I have not myself seen an extrauterine development of a complex organism like a vertebrate or a primate beyond the blastocyst stage, although I could conceive it could happen but I think — our report, by the way, did not go into enforcement that you might want, regulations that you would want.

The California report did and, I think, you ought to look at that report and other people's reports because I firmly believe that the Recombinant DNA example tells us how that should go forward through strict regulation but it was not part of our report.

CHAIRMAN KASS: There are several people, I think, who want in on this point.

Janet, were you going to go somewhere else or do you want on this point?

DR. ROWLEY: It will not be this direct point.

CHAIRMAN KASS: Then I think both Michael and Bill —

DR. KRAUTHAMMER: Could I just ask one question in the follow-up? Could you implant it in an animal and grow it beyond a blastocyst stage?

DR. WEISSMAN: I do not believe — I certainly do not know of an experiment where a successful full-term pregnancy has occurred from xenogeneic transplantation. I do not even know myself if any have been done but if it came from a human then I think it falls under human reproductive cloning, which I think —

DR. KRAUTHAMMER: I do not mean to bring it to birth but to go beyond the blastocyst stage to a stage where you might get differentiated organs that you could use.

DR. WEISSMAN: Right. As far as I know, that experiment has not been done and I do not know.

DR. KRAUTHAMMER: But under your recommendations it would not be banned since it would not involve harm to any human.

DR. WEISSMAN: Just a minute. How far are you talking about going?

DR. KRAUTHAMMER: I am just assuming you go a few months beyond the blastocyst stage in an animal model. You would not have the problem of the harm to the woman.

DR. WEISSMAN: But you would have harm to the fetus.

DR. KRAUTHAMMER: So that would be your criteria for saying —

DR. WEISSMAN: It is my personal criteria. It is not included in the report.

DR. KRAUTHAMMER: Okay.

DR. WEISSMAN: That is why I think you need to think hard about these issues and put in regulations that are clear.

CHAIRMAN KASS: I think we should — there are several people, I think, who want in on this same point. Let's see, Michael, Bill, Alfonso and I have one on the same — because I think this is important to get this sorted out.

Michael, please?

PROF. SANDEL: Just to understand how long the blastocyst would have to exist in order to achieve these scientific effects, the blastocyst is at the five to seven day stage, is that we are talking?

DR. WEISSMAN: Yes.

PROF. SANDEL: How long —

DR. WEISSMAN: In the animal models they are to achieve that stage where you have anywhere from probably 80-200 cells and have fully formed the inner cell mass. There may be a possibility of doing embryonic stem cell before then. I do not know if anybody has but I know clearly that Richard Gardiner has looked in mouse models and if you let it go beyond that stage you can no longer get pluripotent stem cells.

PROF. SANDEL: So that is how many days, that stage?

DR. WEISSMAN: In humans, I imagine it is a few days if it is implanted.

PROF. SANDEL: So if there were regulation that limited in terms of days beyond which you cannot grow the blastocyst either in a lab or by — no implantation in a human or in an animal, and that you cannot let the — work with the blastocyst beyond a certain number of days.

DR. WEISSMAN: Let's go with the first one because we know that the blastocyst needs to be implanted to go through the next stages because there are signals that it receives from the uterus itself, from the prepared uterus. And I think if you had a regulation no implantation in human or animal at all, you would cover that.

PROF. SANDEL: And what about a limit in terms of days, not beyond 14 days?

DR. WEISSMAN: In vitro, we are treading on ground where I do not think we have, that I know about, good animal experimentation but I think you could come up with either a stage of development or a time in which it would develop. It would be riskier for you to say a stage of development — I mean, a time simply because techniques might improve and it might move faster by that time than you would want it so I would, if I were advising you, try to think out at what stage you think the blastocyst turning into a fetus should not be allowed in vitro.

CHAIRMAN KASS: Bill Hurlbut, still on this matter?

DR. HURLBUT: You mentioned a second ago that — I cannot remember your exact words but you said something about the concern for the fetus which was not part of the Academies report, and as I read the report I noted that in Finding 1 you left any reference to the fetus out completely, and I will read it.

"The scientific and medical criteria used to evaluate the safety of reproductive cloning..." and here one might include this in all your considerations of nonreproductive cloning also. "The scientific and medical criteria used to evaluate the safety of reproductive cloning must be the potential morbidity and death of the woman carrying the clone as a fetus and of the newborn..." this is ES2 "...of the woman carrying the clone as a fetus and of the newborn and the risk to women donating the eggs."

So what was missing in that, it struck me right away, was any reference to safety issues or dignity issues to the fetus.

Now no one is arguing at this point for reproductive cloning, which has a lot more weight on that particular score, but here is my question: We are debating this not because you would deny the tremendous medical benefits that might come out of this kind of research, and I would like to hear more of that because I am very convinced by your arguments that great good could out of this, we are here because we are worrying about its moral — the moral meaning of what we are doing.

So the question is what does this — what is this entity that you have created and what could it become and what uses could it be put to? Is this entity created somehow different in character or kind from that which can become a — which is the early process of a natural human life? Can you convince us in some way that you could do this in a way that would not raise the moral question for anybody who believed that human life started from its earliest initiation at fertilization or zygote production?

In which case, what I guess I am suggesting is could — can this be done in such a way that there is only partial generative potential so we could look at this as a part apart from the whole? In that sense could it be seen as not quite an embryo and could you do it in such a way that it would render it from the onset not quite fully potential so you satisfy this concern?

Because what strikes me as the problem here is that even if you say you do not want to go beyond the blastocyst that what you have created could be taken beyond the blastocyst. Now I have not read the original papers but there is a lot of reference out there to gestation of a mouse to the point of a beating heart.

And I spoke last week with a professor at Cornell who is working on an artificial endometrial lining that she says she can implant, the hatching takes place, she implants the embryo into it. And she says she is working on a 3D scaffolding that she believes — and I know this is just anecdotal personal projection but so is most of what we are working on here, Irv. In a sense, we do not know where this is all going in science. I know you will get me on that but the point is we have to think in anticipation of what could happen.

I mean, I would think by reasonable study we could take the embryo beyond the blastocyst stage and wouldn't there — having made all these arguments for good uses of this blastocyst — wouldn't there be good arguments for the use of further developmental stages of developed life so that if it did not involve implantation into a woman but into an artificial medium or an animal and so forth that you might gain great benefit beyond the 14 days you have talked about?

What about the development of limb primordia or organ primordia? I have personally seen in the bottom of a test tube a human hand that was taken from human primordia. Wouldn't you possibly have potentials here that you could take this — what I am getting at is where is your moral stopping point if the science were able to stretch the time you could keep it?

DR. WEISSMAN: So, Bill, I think there is about 15 or 20 questions in there.

DR. HURLBUT: Yes, but they are all about the same thing.

DR. WEISSMAN: Maybe they are, maybe they are not so let me try to at least dissect the few that I remember. First, what you are reading was about the human reproductive cloning part. That is what the finding was relevant to. You know, we tried to stick to what was relevant to us and what we could report to you with assurance because that is what you want your National Academies to do.

Second —

DR. HURLBUT: Was there no concern for morals in that — for the morality —

DR. WEISSMAN: There was absolutely no discussion because we felt we were not by ourselves competent to discuss the issue that vexes you most. That is morals and ethics of what this is. We did not do that because we knew we would not be the people who made the decision.

DR. HURLBUT: But you made a recommendation to continue it.

CHAIRMAN KASS: Irv, could I intervene? I think you are overstating on that point in the light of what you, yourself, have said. You did take into account, and rightly, as part of what it means to do medicine the — that aspect of the moral question, which concerns the ethics of research and, in fact, that is really what —

DR. WEISSMAN: Ethics of human subjects in this particular research.

CHAIRMAN KASS: Human subjects research, right.

DR. WEISSMAN: Yes, we certainly did.

CHAIRMAN KASS: Yes, and I think — if I understood Bill's question, it was — it could have been framed to ask why when you are taking up the questions of the ethics of human subjects research does or does not a fetus come under that as a subject where it, in fact, does come under that as a subject in the canons of research on human subjects and IRBs, and other places.

DR. HURLBUT: Yes, that is right.

CHAIRMAN KASS: It was not the big broad global moral questions.

DR. WEISSMAN: That is right.

CHAIRMAN KASS: But in terms of the research.

DR. WEISSMAN: And we did not do the big broad moral question because we were not a body constituted to even address those questions, Bill, and although personally people may have wanted to address them we felt it was more important to get the science as straight as possible.

Now as to your conversations with reproductive biologists at Cornell, maybe that is published, maybe not, I do not know but I would just advise you be — try very carefully when you are going to make policy that will ban or not ban what is going forward that you at least try to adhere not to anecdote but studies that have been done that show clearly the way to go.

CHAIRMAN KASS: Could I — I think this is an important question not because it bears on the question of the ban but because it bears upon the logic and reasoning that the Academy itself uses and is encouraging us to follow.

I am going to try Bill Hurlbut's question again. It seems to me that the powerful — it is, indeed, a moral argument of the importance of learning about these disease processes because there are human lives on the line that we want to do these kinds of studies for which stem cells created from — let me not beg the question — stem cells obtained following nuclear transplantation offer opportunities not available from stem cells created by IVF and you have made a powerful argument for what we can learn from that.

But then Bill asks, look, what if one wanted, both for the sake of understanding development and also for the sake of maybe obtaining even better tissues for transplantation, to go beyond the blastocyst stage. No one has done that to this point in humans though Michael West's group put the cloned cow embryo back in and took primordial renal cells at a later stage. And we do know that there are immune deficient hosts in which one could, in fact, do cross species — even intrauterine placement.

So it is not a question about the ban. The question is, is the logic of defense that has been given for the nuclear transplantation to produce stem cells, isn't the logic — wouldn't it actually countenance the taking of the blastocyst further if it were possible? Not with reproductive intent but with the intent to learn more about pathological development, with the intent of trying to find therapies without — not going through stem cells but perhaps getting organs and tissues.

I think that was the force of the question. Not should we ban this but did the Academy itself consider other further uses of blastocysts beyond just extracting their stem cells because it is certainly conceivable.

DR. WEISSMAN: So we were asked to look at the scientific, medical and human subject participation in research aspects of human reproductive cloning and how this applies in general to the issue of pluripotent stem cells so it was not part of our charge. We were not constituted in a way that we could have answered that. And, as I said at the beginning, in the middle and at the end, we cede that to broader societal discussions. On a case by case basis as science advances you and other groups must look at these issues again. What we were dealing with are the two issues we bring to you and not other issues.

CHAIRMAN KASS: But speaking now as a scientist, and we will not have you again next time we meet —

DR. WEISSMAN: How do you know? The way that this discussion is going on, I am just about to book an apartment here.

(Laughter.)

CHAIRMAN KASS: Thank you very much.

DR. WEISSMAN: Okay. Go ahead.

CHAIRMAN KASS: Are these thoughts of the further development of blastocysts either on artificial endometria or with implantation, wouldn't that produce interesting new knowledge that would help cure disease?

DR. WEISSMAN: It may or may not.

CHAIRMAN KASS: And wouldn't we want to do it?

DR. WEISSMAN: It may or may not. It was not covered in our report.

CHAIRMAN KASS: I understand.

DR. WEISSMAN: But I would argue to you that if this other issue is one that you need scientific data on and good scientific and medical advice then commission the Academies or NIH or somebody to do that. We did not do that.

CHAIRMAN KASS: I have Janet, Gil and then Robby. I skipped Rebecca. I am sorry. Janet and Rebecca.

DR. ROWLEY: Rebecca was first.

CHAIRMAN KASS: Sorry.

PROF. DRESSER: I have a few questions. One is in the Cloning Report you talked about one ethical concern being the number of oocytes that would have to be obtained for reproductive cloning but you did not really talk about the number of oocytes that would be needed for biomedical research purposes so I wonder — it seemed to me — I mean, this Michael West group tried once and they did not get very far so it seemed to me that there would be a number of oocytes required and I know this was not your — well, I guess it was your — if that was an ethical concern with this cloning, whatever it is, to produce a baby, isn't it an ethical concern in the research context not only the risks that women would be exposed to but the probability that there would have to be some payments attached? In some sense "competition with fertility clinics," a whole set of issues there. So I wondered why you thought it was important with the one type and not with the other.

DR. WEISSMAN: Sure. So if you look, for example, on B12 of the appendix, the figure — and I will just describe it for you, you could look at it or not — the number of eggs required to make the numbers of blastocysts by nuclear transplantation to implant in the uterus with the intent of reproductive cloning to get a single human is massive but the number of eggs required to get to the blastocyst stage from which you could extract cells that would be producing pluripotent stem cells is at least — I want to get the number right — at least 100-fold less.

So we pointed out from a scientific and medical point of view that you would need to have a source of eggs to do so and we pointed out that there are syndromes that women have, hyper stimulation syndromes, which I believe have morbidity without mortality but I would have to cede to the gynecologists on that.

So going into the numbers game and understanding the regulations and the institutional review boards that must approve it are all part of what we think should go on from there before it could happen but just from a strict scientific point of view it is orders of magnitude fewer eggs required to create a blastocyst for producing the stem cell lines than from producing blastocysts in sufficient number to have even a viable birth.

PROF. DRESSER: I see. Based on animal work because we have not even gotten to the —

DR. WEISSMAN: All on animal work.

PROF. DRESSER: — that stage with humans.

DR. WEISSMAN: Right. And we will not.

PROF. DRESSER: I guess the other observation I had was that — I mean, it really is — part of your statement finessed what we have to do. I mean, think of we could say, well, if we did not require consent from human subjects then we could learn a lot of important knowledge and if we decide to require consent and other countries do not require consent then other scientists might go to those countries. I mean, the real question is not whether there are important benefits available but on the other side what are the ethical considerations. And whenever we think about the traditional research ethics considerations, as well as some of the things we might think about here, we must accept that we might not be able to get certain knowledge.

DR. WEISSMAN: I certainly agree and the Nuremberg Code, with which I am in full agreement, outlines those kinds of things you would not do simply for the sake of knowledge that involve human subjects. I personally believe it is one of the most elegantly written documents I have ever seen and I adhere to it completely. So does that answer your question?

PROF. DRESSER: Right. It is just that it does not really address the kinds of questions we have to and so —

DR. WEISSMAN: That is right. That is why I do not envy you the responsibility you have.

PROF. DRESSER: Thank you.

CHAIRMAN KASS: Just on this? On the Nuremberg Code?

DR. GÓMEZ-LOBO: Yes.

CHAIRMAN KASS: Quickly then, Alfonso, and then Janet.

DR. GÓMEZ-LOBO: This, I believe, is tangential to the reference to the Nuremberg Code. I would like to understand the central part of Finding 4, which reads, "Participants in any human cloning research efforts require full protection as human research participants..." which I think is on the Nuremberg Code "...although it should be noted that as with fetal surgery, this protection cannot be extended fully to the cloned fetus." My question are what — how do we distinguish between full and partial protection and, second, why is in one case full protection demanded and in the second case not?

DR. WEISSMAN: Well, we recognize, as you recognize, that the fetus is not in a position to give informed consent. As you know, there are lots of intrauterine surgery to repair defects in human fetuses with the intent of keeping them alive even though they cannot have informed consent for the surgery and the risks of the surgery. So it is within that context I understand that it is partial rather than complete, that sometimes physicians, parents and so on must come together to make a decision that is in the best interest of the life of that fetus.

CHAIRMAN KASS: Janet? Thank you for your patience, Janet.

DR. ROWLEY: I have two questions. I think one of them comes back to your diagram Figure 1 and it has been brought by others in terms of times that these events are — over which they are occurring and you were obviously uncomfortable about putting a specific time but the blastocyst in the normal course of say IVF, of the time from the donor egg to the development of the blastocyst, that range is known and it is approximately —

DR. WEISSMAN: About five to seven days I am told.

DR. ROWLEY: — five days.

DR. WEISSMAN: I have not done those myself.

DR. ROWLEY: And I understand that some of the regulations in other countries, the U.K. for example, requires the disposal of embryos after 14 days. Why did they choose 14 days? I mean, I am asking you —

DR. WEISSMAN: I do not know.

DR. ROWLEY: — do you whether there is a reason to choose that particular time?

DR. WEISSMAN: I do not know why they chose that.

DR. ROWLEY: Okay.

DR. WEISSMAN: Could I just make a small point because I think it is an important point?

CHAIRMAN KASS: Yes.

DR. WEISSMAN: You have been very strong, I hear it, about whether nuclear transplantation with the intent of producing human pluripotent stem cells gives rise to a stage you would call an embryo that could become a human being. So would you believe if scientifically one made a blastocyst that had no possibility of implanting would be an appropriate research venue?

CHAIRMAN KASS: That was part of Bill's question. Could one incapacitate —

DR. WEISSMAN: Yes, I know, that is what I was getting back to.

CHAIRMAN KASS: Yes.

DR. WEISSMAN: So if it were possible to deny the formation of a trophoblast or remove a trophoblast so that there was no chance whatsoever that it could be implanted even by rogues even in that, I think, unlikely finding, do you think that that is fully permissible by this group?

CHAIRMAN KASS: We will have, I think, our first discussion — real discussion of the ethics of nonreproductive cloning. It is the tail that wags the dog of the discussion of research on embryos all together, which is part of our charge in the whole stem cell question.

DR. WEISSMAN: Sure, but that is the point that I — that we are discussing now.

CHAIRMAN KASS: I mean, people — the floor is open if anyone wants to speak to that. Janet, would you —

DR. ROWLEY: I need some more education. So you explained why the presently available ES cell lines are not suitable for some of the kinds of both investigation and potential therapy that you envision or that is possible — may be possible. And I am ignorant as we look at embryos that are presently in freezers in IVF clinics. It is my impression that some of those may well be used for somatic nuclear transplantation. Is that correct or is that —

DR. WEISSMAN: I do not think so.

DR. ROWLEY: — that is not —

DR. WEISSMAN: Because I think they have already passed beyond the stage where a somatic nucleus could develop into all the tissues that you want. It would be interesting if somebody had accomplished that, that is by putting a somatic nucleus into an inner cell mass cell that has been enucleated and actually succeeded in making a line. I asked Ian Wilmont and Austin Smith that question, who are the experts in that field, and they said they have tried many times and they cannot make it work yet.

DR. ROWLEY: Because it was my impression that some further attempts were being made to actually use discarded embryos to do just that and you are saying —

DR. WEISSMAN: To do nuclear transplantation?

DR. ROWLEY: — you are saying that that is not — as far as you know that is not possible.

DR. WEISSMAN: Certainly, as far as I know, it has not been accomplished and when I talked to the people who are at the leading edge of the field they have not been able to accomplish it, although they have tried.

DR. ROWLEY: Okay. So is it possible, though, to take these frozen embryos and develop ES lines from them comparable to the ES lines that are already available?

DR. WEISSMAN: They would be — yes, comparable to the ES lines that are available but in no way could they address the genetic diversity of the heritable disease and the somatic mutation issues that I raised.

DR. ROWLEY: Okay. So the reason I pursue this is because a number of individuals have thought, well, one out is to take — and we discussed this the last time — is to take the embryos that are currently in freezers around the country and around the world and actually do a number of the kinds of experiments that are — or the preparations that are illustrated in Figure 2 and that, in fact, we would not need to create new embryos for that because we might have them already and you are saying that, in fact, the nuclear transplant has to take place at a very early stage and, therefore, we do not at present, at least, have such cells available for that kind of research.

DR. WEISSMAN: That is right. That is right.

DR. ROWLEY: Thank you.

DR. WEISSMAN: You know, if you were trying to go the route of having so many human embryonic stem cell lines from these discarded IVF clinics, if you use the experience of bone marrow transplantation to get a probability of a histocompatibility match, that is a tissue match, not a perfect match, believe me, but just a match in the HLA locus. It is about 40,000 required so that is not realistic either.

CHAIRMAN KASS: Gil Meilaender, Robby. Let's see. Michael, Michael, Stephen and Bill.

Gil, it is for you.

PROF. MEILAENDER: Okay. I would like to think about the relation between the Academies report and sort of what we might do in our deliberations because actually I am increasingly confused about what that relationship might be. Let me come at it from a couple of angles. On the one hand, you said several times that there is — your report is sort of just the science and you abstain from moral or political issues and deliberations.

DR. WEISSMAN: As a group.

PROF. MEILAENDER: As a group, yes.

DR. WEISSMAN: But I am still an individual.

PROF. MEILAENDER: Oh, yes. Yes, I meant the report as a report.

DR. WEISSMAN: Right.

PROF. MEILAENDER: And yet the report recommends political actions like a legislative ban. It uses language with respect to the nuclear transplantation to do stem cells that it should be permitted. It concurs with the previous Academy report that it should be permitted. So that all looks like moral language to me. It appears to be drawing a moral or a political conclusion. That is — and, therefore, does not seem to me to be significantly different from the kinds of questions we might raise ourselves.

DR. WEISSMAN: Well, let me clarify it then if I can.

PROF. MEILAENDER: Okay.

DR. WEISSMAN: Because it is in the language of the recommendation. "Should be permitted" pending on scientific medical grounds alone the nuclear transplantation technology to produce stem cells. But we said clearly, and it is the last sentence again, that we are not the last word. We are delivering this to groups like you to make that judgment. We did not make that judgment. The only reason that we said a legally enforceable ban recommended, a legally enforceable ban for human reproductive cloning is that when we scanned the regulations that existed and the bodies that had authority to regulate it, we realized there was a gap and so we felt, and I think we felt pretty urgently, that since there were people saying they were going to do that very soon and in the United States, if possible, that we ought to recommend a legally enforceable ban.

Now, of course, what we are doing when we did that was very uncomfortable for scientists, of course, to say that you should ban any freedom of inquiry but we were so — the evidence was so compelling that a bad outcome would result if it was attempted that we recommend to society — because we have no power —

PROF. MEILAENDER: Nor do we.

DR. WEISSMAN: — to develop — you have more power than we do.

PROF. MEILAENDER: I would be surprised.

DR. WEISSMAN: I expect that you have more power than we do. At least you are talking to groups that could by executive action enforce a ban. We are not.

PROF. MEILAENDER: Okay. But let me just comment on that that it is nonetheless the case that as opposed to simply saying here are some real safety considerations that one might think about in connection with what we are calling reproductive cloning and the rest of you folks are just going to have to decide whether those risks are worth the possible gains. You did actually make a recommendation that I would call moral and political. I mean, I think that is important to see just in terms of thinking about the relation between the Academies work and whatever we might do so that we are not, in fact, doing two entirely different things but that whatever you do does —

DR. WEISSMAN: Yes. Our reading of human subject participant in research in light of the Nuremberg Code and the things that follow clearly stated that that would be something that would go against an agreed upon societal restriction. That is why we recommended it.

PROF. MEILAENDER: Okay. Good. And now may I pursue one other aspects on this?

DR. WEISSMAN: Sure.

PROF. MEILAENDER: From a different angle, a way in which it just — you know, despite all the helpful information you gave, it still leaves me confused, it relates to our conversation in the first session this morning and that is that it appears, and I think you, yourself, said it in response to a question someone asked about the two diagrams up there that with respect to these two processes called "human reproductive cloning and nuclear transplantation to produce stem cells," it appears that the actual initiating act and the product are the same. The difference lies solely in the human will and choice, the purpose. And "will, choice, purpose" language is once again moral language.

DR. WEISSMAN: Yes. You know, what you are saying and what I could agree with is that an intermediate step of both is the same. The product is not the intermediate step in either. So the product is not the same and I certainly agree "will, intent and choice" we will rule in law — we will rule on whether one choice or another is permitted or not but stopping at any particular stage is not necessarily going to help us understand the real issues. You stopped it at the stage of the blastocyst because that is really important to you and I understand it. Okay. But that is not the product.

PROF. MEILAENDER: Well, may we pursue this or not?

CHAIRMAN KASS: Why don't you go ahead one more line, one more time?

PROF. MEILAENDER: Okay.

CHAIRMAN KASS: Because I think you are talking — I think there is some —

(Simultaneous discussion.)

PROF. MEILAENDER: Can we come around — what is important to me is trying to get clear on this. Can we come around to the question that I submitted — one of the questions I submitted in advance to you?

DR. WEISSMAN: Okay.

PROF. MEILAENDER: Which I will just read again. You have it. It was that the Academies report discusses two procedures which it says are very different from each other. First, human reproductive cloning and, second, nuclear transplantation to produce stem cells. Suppose we are shown externalized in the laboratory two cloned blastocysts X and Y. We are not told which is X and which is Y but we are told that X is the result of procedure one and Y is the result of procedure two, and we are asked to examine the blastocyst and determine which is X and which is Y. On what basis could we make that determination?

DR. WEISSMAN: Right. And so I would use an analogy, which is based on my background. I grew up in Montana and we grew up with rifles, which we used for many purposes. The rifle is the same as you know, whether you intend to use it to kill a person or for target practice the rifle is the same. That is not the crime. That is not the issue. So it is not visually what you can see or even by genotyping what you can see. The purpose is the important point here.

PROF. MEILAENDER: Well, I think it is a little more complicated than that. If you — there might be two cases, identical cases in which you shoot to kill someone for very different reasons. One, merciful motives and another different does not alter the fact that you shoot to kill in both cases.

DR. WEISSMAN: Right. And you use the rifle for other reasons, too. I agree with you and there are laws that we developed to protect society against one case and not the other, and we are subject to those laws and you are going to help advise on what laws should be present or what guidelines or what regulations or what bodies will regulate it.

CHAIRMAN KASS: Irv, if I may, it seems to me that — and maybe it is the fear of impending legislation or interference that colors to some extent the responses that you have made here and on other occasions. I thought — I thought Gil's question was not somehow intended to embarrass or, in fact, to invite that there is a kind of cryptolegal (sic) judgment that hangs on the back of this. It was simply to make sure that we are clear, whether we are clear about what the — what the product is (a) and (b) to indicate, and I think he is not wrong about this, to indicate that it is true that the Academy has — and I would want to say rightly — restricted its scope to what is within its area of expertise and has taken up those moral questions that belong to the proper understanding of the conduct of medical researchers that to be a researcher is not simply a technical activity but insofar as it deals with human subjects it is understood to be a moral freighted activity and it is, therefore, perfectly proper to do exactly, it seems to me, as you have done.

But I thought that Gil was pointing out that there — in the first part of his question he was trying to ask what is the relation really between the fact that you have — that whether you are willing to say so or not, you have engaged in a partial moral analysis insofar as you touched the question of human subjects research and insofar as you distinguish between two kinds of activities in terms of the human intent that also is to bring moral terms to bear on what are otherwise simply scientific or technical things.

I do not think — if I — I mean, I have listened to this guy a long time. I know when he is trying to make an argument for some additional purpose and where he is simply trying to explore certain things for clarification because it does really go to the question what is the relation between the kind of medical/moral analysis that you have done because when you do make recommendations or you do pronounce you are going beyond simply saying this is unsafe. This is unsafe as a scientific judgment. Therefore, it should not be done.

It is a judgment of a different sort and I do not think — there is no reason to be embarrassed about that. That seems to me a service here but the question then is what is the relation between the character of the moral discussion there and the kinds of things that we are doing here, and I think that is —

DR. WEISSMAN: Well, there is a huge difference in that you are charged with looking at all of the critical moral issues. We were charged to look only at in terms of the human reproductive cloning and cloning for the production of stem cells, to look at those issues that would apply to human subjects in clinical experimentation or clinical practice and we restricted ourselves to that and we needed to report to you and to Congress what would be lost if there was a ban also on stem cells and I reported that to you.

CHAIRMAN KASS: I have Robby and then the Michaels, and we will go from there.

PROF. GEORGE: Thanks, Leon.

Dr. Weissman, thank you for your presentation. I grew up in West Virginia and it was a similar sort of culture when it came to guns so I liked that analogy very much and I —

DR. WEISSMAN: And now you are going to use it and you want to stick with it, yes.

(Simultaneous discussion.)

PROF. GEORGE: Yes, I think we can communicate when we talking in these terms we can definitely communicate even though I am not a scientist.

(Laughter.)

PROF. GEORGE: At least where I grew up, and I bet it is true in Montana, people had guns for different reasons and that is part of your point, two of the reasons. One was hunting and the other was collecting. There were a lot of people who were interested in collecting but when someone assembled the gun, whether the goal was collecting or hunting, the product was the gun. The product of the assembly was the gun.

Do you agree with that? It is not a different product depending on the intention, whether it is hunting or collecting?

DR. WEISSMAN: Yes.

PROF. GEORGE: Now the nuclear transplantation is a procedure, right?

DR. WEISSMAN: Yes.

PROF. GEORGE: Okay. It aims to produce a product. Now let's not get hung up on the definition.

DR. WEISSMAN: I will assume that. Go ahead, yes.

PROF. GEORGE: Okay. Down the line that product might be a cure for a particular disease.

DR. WEISSMAN: Right.

PROF. GEORGE: But proximately is it the case that the product is stem cells as such or is the product the thing that has to be produced in order to get the stem cells, the blastocysts?

DR. WEISSMAN: In my view —

PROF. GEORGE: Or is it not settled scientifically?

DR. WEISSMAN: No, no, I will give you my view and then we will say it scientifically.

PROF. GEORGE: Okay.

DR. WEISSMAN: What I told you was that the product of recommendation — the second recommendation, nuclear transplantation, to produce stem cells describes the product, stem cells. You may choose to say that an intermediate step in your mind is the product, the blastocyst, that is your choice. I am just saying we tried to be as clear as possible what the product was and we said what the product of the first was, the intent to make a human live birth by implantation, and the second to make stem cells not by implanting but by extracting cells. So the products are different.

You may choose in your own mind, in your own description to take an intermediate step, the single cell, the two cell, the four cell, the eight cell, the morula, the blastula. You may choose that but that is not what we described scientifically or, I think, by our language.

PROF. GEORGE: If no blastocysts were brought into being, would it be possible to obtain stem cells?

DR. WEISSMAN: You are asking me is it possible that we could make something short of being a blastocyst? Theoretically, yes. I do not know anybody who has done it. We could, for example, enzymatically remove the trophoblast cells as they are formed or genetically prevent their development. That is not inconceivable. The experiments are not done and are not published but that is inconceivable so, yes, you could get to a point where you make something that nobody would call a blastocyst because it lacks the trophoblast. You could do that. Is that where you are going?

PROF. GEORGE: No, but you have brought me right to where I want to go, and this is the question of the something. You said something that no one would call a blastocyst. So one possibility is a blastocyst. Another theoretical possibility, and I take your point that we do not know, would be something else and it would be from that something else that stem cells would be harvested.

DR. WEISSMAN: Yes, if you could do that experiment, right.

PROF. GEORGE: Okay. But what that says to me, now tell me why I am wrong about this, is that it is unavoidable as a matter of scientific fact and not as a matter of definitions or how I choose to use words. It is a matter of scientific fact. There has got to be an intermediate step. A something from which stem cells are harvested. That something being brought into existence by a procedure called "nuclear transplantation."

DR. WEISSMAN: Mm-hum.

PROF. GEORGE: Yes?

DR. WEISSMAN: Absolutely.

PROF. GEORGE: Okay. When you referred to the — several times you referred to the blastocyst stage. Tell me if I am right, is that the stage in the development of a determinate organism?

DR. WEISSMAN: Yes.

PROF. GEORGE: Yes, okay. So that after the blastocyst stage if the environment is suitable there would be further development into other stages?

DR. WEISSMAN: Do you mean if by intent you put it into a uterus that is prepared for it?

PROF. GEORGE: Could be accidentally. I mean —

DR. WEISSMAN: I cannot believe it is accidental that you could put it into uterus. Let's be real, okay.

PROF. GEORGE: Well, could you —

DR. WEISSMAN: It is by intent that you put it into a prepared uterus with the intent of having the downstream effects of it, namely for a fertility clinic to make a child.

PROF. GEORGE: I am not interested in the issue of intent right here and I wonder if we can get at the problem without intent. Maybe you can show me that we cannot and intent is relevant to the scientific description but however it happened if the environment were hospital the blastocyst would continue to develop. Right, there is a stage that is the blastocyst stage. I take it this is what you mean by stage. If it is the stage, as you say, in the life of a determinate organism —

DR. WEISSMAN: Yes.

PROF. GEORGE: Okay.

DR. WEISSMAN: Correct.

PROF. GEORGE: Yes. All right. So looked at back the other way, Dr. Kass is now in an adult stage, as the rest of us around the table are, at an earlier point of his —

DR. WEISSMAN: Decrepit.

PROF. GEORGE: Hardly.

(Laughter.)

PROF. GEORGE: — existence he was in adolescent stage, before that —

CHAIRMAN KASS: Never, I do not believe —

(Laughter.)

PROF. GEORGE: He was wise before he was old.

(Laughter.)

PROF. GEORGE: And before that in an infant stage.

DR. WEISSMAN: Pick another subject.

PROF. GEORGE: Is that right?

DR. WEISSMAN: I did not hear the last —

PROF. GEORGE: But before the adolescent stage and infant stage —

DR. WEISSMAN: That is right.

PROF. GEORGE: — all the determinate life — the life of a determinate organism, before that in a fetal stage. Now I do not want to use the term "embryonic" because I know it was problematized, as my colleagues in English literature insist on saying these days, in the earlier discussion but would it be fair to say that before that Dr. Kass was in a blastocyst stage?

DR. WEISSMAN: For sure.

PROF. GEORGE: Okay. Good. Then the only other question that I have —

DR. WEISSMAN: So we have linked him up with all the other vertebrates now.

(Laughter.)

PROF. GEORGE: Okay. And the other question that I had is on this question that both Steve Carter and Gil Meilaender have raised about the relationship between ethical considerations in the scientific and medical ones, I take your point entirely and understand it that there were certain extra medical scientific considerations that you rightly took into account in making that first determination because we have certain international legal and medical standards that have been agreed to and there is nothing controversial in that at all, and it would be irresponsible not to take those into account as providing the necessary ethical premise to be joined with the scientific premises about the danger of this —

DR. WEISSMAN: And it was part of our charge.

PROF. GEORGE: Fine. That leaves me with the second one and that is the one that I am not sure about. It looks to me as though to reach the conclusion that nuclear transplantation to produce a blastocyst for stem cells or however you want to say it should be permitted, and I think I am quoting this accurately, should be permitted. That is to say not forbidden. That is to say not banned. So it is the reverse of what is being proposed with respect to what you are calling reproductive cloning.

It looks to me as though that requires, in addition to whatever scientific information we have about the possible cure for diseases and development of therapies, it requires the ethical premise, the extra scientific premise that the destruction of the blastocyst is not sufficiently of more weight to justify a conclusion other than the conclusion that the nuclear transplantation procedure should be permitted.

DR. WEISSMAN: Not at all.

PROF. GEORGE: Okay. Can you explain that?

DR. WEISSMAN: What we said, and if we read the whole paragraph, it says, "The scientific and medical considerations that justify a ban on human reproductive cloning at this time are not applicable to nuclear transplantation to produce stem cells." That is the first point.

So we are reporting to you that what we saw as a problem with human reproductive cloning from a scientific and medical and human participation point of view does not apply to this method of producing pluripotent human stem cells. Then we mention, of course, because of the considerable potential, which I have now gone into much more depth than you probably wanted about the diseases, we said and recommended that "biomedical research using nuclear transplantation produced stem cells be permitted." And the very next sentence we say, "A broad national dialogue on the societal, religious and ethical issues is encouraged on this matter."

We ceded the responsibility for the ethical and the moral determination of that research not to us but to broader bodies and we said it not just in that wording of the language but everywhere in the report, and you and I could go through it. Maybe 10 or 15 times, you know, we said it over and over and over again.

PROF. GEORGE: It looks to me like you have got two recommendations here and they are in successive sentences. The first is a recommendation "that biomedical research using nuclear transplantation to produce stem cells be permitted." That is a recommendation. I realize you do not have authority, nor do we, to make that a legislative matter. It is a recommendation.

And then there is a second recommendation in the immediately following sentence, and that is "A broad national dialogue on societal, religious and ethical issues be encouraged on the matter."

CHAIRMAN KASS: Counselor, may I help you out?

PROF. GEORGE: Please.

CHAIRMAN KASS: I was over that paragraph several times because it does look at first glance to be something like — and one could rewrite it to take the ambiguity out. I think what that really says is that we find no grounds here as we find with reproductive cloning to recommend a ban because the safety considerations obviously do not apply for obvious reasons. In addition, we think there are perfectly good reasons to do this.

Nevertheless, there are other ethical considerations which we would recommend the broader society take up. "Should be permitted" seems to be a strong moral conclusion. I think it should say "should not be banned on these grounds." I think that is what —

DR. WEISSMAN: We are not going to go back and —

CHAIRMAN KASS: No, but I think that is —

(Simultaneous discussion.)

DR. WEISSMAN: What I would like you to see is the rest of the report where we stress where our responsibility and recommendations end and society's responsibilities begin.

PROF. GEORGE: Oh, yes. Well, I am not asking you to redraft it and that is a very helpful explanation of Dr. Kass'. I mean, is Dr. Kass right that what you are saying here — I mean, the proper translation of that is we see no reason on scientific and medical grounds not to permit nuclear transplantation? Is that what it means?

CHAIRMAN KASS: And they see positive reasons to do it.

PROF. GEORGE: And there are positive reasons for it.

CHAIRMAN KASS: There are positive reasons compatible with the moral character of medical research.

PROF. GEORGE: I mean, if that is what it means, it seems to me, fine.

DR. WEISSMAN: It is my personal opinion that that is a reasonable interpretation of what we say but I cannot —

PROF. GEORGE: Speak for the group.

DR. WEISSMAN: — speak for the group.

PROF. GEORGE: Okay.

DR. WEISSMAN: Because I would have to go get a vote.

CHAIRMAN KASS: Thank you.

PROF. GEORGE: Thank you.

CHAIRMAN KASS: Look, we are at the time where we said we would break. I, with your indulgence, since there are a number of people in the queue, if we could take — steal say 15 minutes from an hour-and-a-half lunch, I think it would be fruitful and I will try to keep — I think this back and forth is sometimes useful but we now have Michael Sandel, Michael Gazzaniga, Stephen, Bill. Which Bill? Was it Bill Hurlbut? Alfonso and Charles. And if you can make it, all six of you, within 15 minutes, let's try.

Michael Sandel, I guess.

PROF. SANDEL: I would like to restate a worry that was voiced by Charles and Leon and maybe others but to reformulate it and to get your own view of it not speaking for the Academy. One way of reformulating the worry, and I do not want this to be on their heads so it is my formulation, it is one thing to create, to clone or to create a blastocyst of five to seven days and to extract stem cells from it to do potentially wonderfully things of the kinds that you have described.

But if we do not ban that potentially very promising thing then there is the real danger that the scientists now or in the future will be tempted to go further beyond the five to seven day blastocyst and to develop it, to grow it to some further stage of development, not because they are crazy rogue scientists who want to create a baby but because there will be other wonderful medical research possibilities that will come later, whether that means implanting it in a cow or in a pig or developing something in a laboratory where they do not have to implant it.

And if it really is tempting medically, not just a crazy rogue thing for some weak purpose, where do we draw the line?

Your answer to that before was, "Well, this was not part of the charge of the Academy." And your second response was, "Well, the science — there is no evidence that this can be done."

And so the way I want to reformulate — well, so I want to put that question to you again. Where do we draw the line if there are very tempting, attractive possibilities of developing going way beyond this five to seven day, 64-200 cell stage, to have a much more fully advanced thing that begins to look more and more like a fetus? What about that? Can you just respond to that?

DR. WEISSMAN: So long as you say in this conjecture that it could all be done in a test tube, that it does not require a human subject because I am very clear about the use of human subjects.

PROF. SANDEL: Okay. Suppose there is a way of doing it. They are worried about ways of doing it without a human — without implanting it into a woman.

DR. WEISSMAN: Right, so it —

DR. KRAUTHAMMER: Without a human subject because otherwise it is easier to reject.

DR. WEISSMAN: Right.

PROF. SANDEL: So what do you say —

DR. WEISSMAN: What I am trying to say is, just so that we are all clear, that — so we do not go into pure science fiction — that to carry it beyond that stage at an institution, say like mine, I want to do that experiment. Let's say I am going to try to find a way to carry it in vitro or put it into a mouse uterus.

PROF. SANDEL: Right.

DR. WEISSMAN: Okay. So with a purpose of going on.

PROF. SANDEL: Right.

DR. WEISSMAN: That is clearly covered by my institution by its institutional review board and the use of any materials from humans and so if I were to do it personally I would have to get approval from a group that includes ethicists, lawyers, da, da, da, da. And so individually if I try to go beyond the bounds of the experiment as a responsible scientist who wants to keep his job in my institution I have to go before a review board and I would be kicked off the faculty if I tried to do that on my own.

So let me just go forward. So now that now relegates it to those who are not in institutions that have a requirement of an institutional review board and, as I said before, although we did not consider that, and this — and our findings do not project to that — that I think it probably is an important question for you to get medical facts on and scientific facts on, and we did not do that for you.

PROF. SANDEL: Could I put the question from another angle, which is suppose — never mind your review board and what standards they might or might not use or should use — it would bother you — and now here I just mean you and not the Academy group — it would bother you as a scientist if there were a federal ban on nuclear transplantation to produce stem cells because it would foreclose important scientific and medical research.

DR. WEISSMAN: Right.

PROF. SANDEL: Would it bother you as a scientist if there were a law that permitted nuclear transplantation to produce stem cells provided that there were no implantation and that were also a time limit, say 14 days, on how long the thing could live? Would that bother you?

DR. WEISSMAN: It would not bother me at all with the implantation ban. Not at all.

PROF. SANDEL: What about the 14 day limit?

DR. WEISSMAN: The 14 days, I am just worried for you and for me that that — putting a time limit on it rather than a stage limit on it is not precise enough to do what you or I may want to do.

PROF. SANDEL: Put a stage limit on it then.

DR. WEISSMAN: Well —

PROF. SANDEL: Suppose this case —

DR. WEISSMAN: — I think that it would be reasonable for you to try to go into the question of what kinds of regulatory bodies could be set to look at these questions as a requirement for that kind of research just as the Recombinant DNA Committee, as a requirement, regulated commercial, public, private use of recombinant DNA and not to anticipate on a case per case basis ahead of time what would be permissible or not but to give clear enough guidelines and include people on that paper, ethicists, lawyers, scientists, so that on a case by case basis we can understand where it should or should not go forward given the context of the science and the medicine and the society at that time.

Is that sufficient?

PROF. SANDEL: Yes. I want to let others. Go ahead.

CHAIRMAN KASS: Michael Gazzaniga, please.

DR. GAZZANIGA: Pass.

CHAIRMAN KASS: Stephen Carter and then Bill.

PROF. CARTER: I will be very brief. We have given you, Dr. Weissman, kind of a hard time and you have been very gracious in — and very patient with us. We have talked a lot about areas of potential or implied disagreement. Now I want to ask you briefly about something, which I suspect there is widespread agreement around the table, and with — and which you also agree, and that has to do with the ban on what you have called "human reproductive cloning."

It will come as no surprise to members of the Council that whatever my view of a particular matter, I am an extreme skeptic of regulation. Extreme. Your report suggests that there ought to be a legal ban nationwide, and I suppose this would not preclude the possibility of negotiating international treaties that would include a ban and an international ban with very substantial penalties. You are talking about putting scientists in jail basically who attempt various procedures of this kind.

Are you worried at all that a ban like that enforced and developed with the consent, in effect with the enthusiasm of the responsible scientific community, could open a kind of Pandora's box? That is what lawyers like myself refer to as slippery slope arguments that, well, the next thing comes along; well, we banned reproductive cloning, what is the big deal if we ban this too; we will have to lock up scientists for that, why not lock them up for this too. I mean, I realize that is not within what the committee would have thought about but for you as a scientist isn't this worrisome, this very proposal you have made that there is a slippery slope character to it?

DR. WEISSMAN: I will try to answer that. Of course, this is personal. This has nothing to do with the committee.

PROF. CARTER: Right.

DR. WEISSMAN: Right, Maxine, Debbie?

PROF. CARTER: Just from your heart.

DR. WEISSMAN: Okay. And you will help me on it in a second. So I will say it and then if I could ask for Maxine to respond also.

I am very worried, and I have been lobbied by a number of scientists that this is a dangerous thing to do, that is to have a legally enforceable ban, and I always go back to the precedent of what is legal for human research based on the Nuremberg Code and what follows because that, I understand, has been well thought out. It has been discussed. Virtually all the cases that we could have considered were in that.

Now, if other groups in society, in Congress, in the House, the Senate wish to now extend the argument and use that as a precedent, I hope that they would go through the same sort of deliberative process to understand what is gained and what is lost. I do not usually buy slippery slope arguments because you have got to see it happen for a scientist before you believe that was a slippery slope rather than an assent or impossible barrier. You know what I am saying?

PROF. CARTER: Sure.

DR. WEISSMAN: So personally I am worried about it but I have some trust that deliberative case by case analyses hopefully will not make this a slippery slope where there is a huge wholesale ban on science. I think that a ban on nuclear transplantation was proposed and passed in the House because of the conjunction of the terms "cloning and human reproductive cloning" without such scientific knowledge and certainly without deliberation.

Now, Maxine, could you please respond?

DR. SINGER: You will find it on page 63.

DR. WEISSMAN: Oh, good. See, she knows this better than I. So you could read it or I could read it to you.

DR. SINGER: You read it.

DR. WEISSMAN: "There is concern that legislation or regulation that would ban reproductive human cloning would set a troubling precedent with respect to the restriction of innovative experimental research and medical procedures. Modern scientific research proceeds rapidly and its findings are unpredictable and often surprising. It is probable that at least every five years there will be significant new information regarding the issues of the safety and applicability of human cloning to medical practice. The above concern can be ameliorated by including in any legislation or regulation a requirement for an updated evaluation of the scientific, medical and societal issues within five years. Such a requirement for periodic reviews would allow for extensive public debate regarding reproductive human cloning and the consideration of modifications to the legislation."

PROF. CARTER: Let me say that I read that finding and, in fact, that is what generated the question.

DR. WEISSMAN: Okay.

PROF. CARTER: Because surely the five year review does not answer the fundamental problem. I mean, because, after all, if one is worried about the slippery slope, and I am glad you are not too worried about it but I am worried about it a little bit, if one is worried about slippery slope I assume that the next problem, whatever it may be, to come along that one — that some say nonscientists — it could be a scientist — wants to regulate, we just say, "Well, we will also include a five year sunset provision or a five year review provision. That will take care of any concern about..." because clearly it would not because clearly if there is something that where you as a scientist felt unjustifiably hemmed in or I, as a skeptic of regulation, worried the government was simply doing too much, that the fact that we say we will not do it for five years would not change either your sense of being hemmed in or my sense of the government doing too much.

DR. WEISSMAN: "Within five years" was the —

PROF. CARTER: Within five years. I understand that.

DR. WEISSMAN: Sure. A legislature could do that but if they did it in the way outlined in Finding 8 there would be a process by which the information could be gathered and delivered to the legislative body. So even though they could do it and can do it and have done it, you know, what we are insisting here is that they ought to do it with full knowledge of what is going on.

PROF. CARTER: Thank you.

CHAIRMAN KASS: I am going to urge people to be more succinct.

Bill, Alfonso, Charles, and then we will break.

DR. HURLBUT: Irv, drawing on the sense of the previous question, we spoke of the rapid pace of research and the undesirability of restriction so I am asking this question in the spirit of trying to keep open as much possibility in the scientific arena as we can morally do. Our mandate as a Council is to consider not just the immediate but what could come from immediate decisions and what seems reasonable to project in the way of scientific process.

So I want to return to that unpleasant subject of use of this entity beyond the blastocyst stage and I want to try and get at the heart of the question that is really beneath the moral issue here, and that is the status of developing life.

You, yourself, have said that you do not favor an implantation of this developing organism.

DR. WEISSMAN: With a restriction.

DR. HURLBUT: You can live with a restriction, okay, and I took it from that that you did not like the idea of implantation.

Others might say, "Get your laws off my body. I have a good reason to do this." And one might make a good scientific argument that you could get cells, as I mentioned earlier, limb primordia, organ primordia, from the harvesting of a fetus at a later stage that would be, indeed, useful.

Now I am not trying to suggest scare scenarios. I am trying to find a moral way that we can keep open these wonderful possibilities. When I said that I had seen a human hand in the bottom of a test tube, when I saw that I had two conflicting thoughts. One was that that was going to be a human hand had it not ended up as an abortion and then grown in a SCID mouse but my other thought was fantastic. Maybe some day we can generate hands for people with amputations.

My point here is can you help us, and this is my question, can you help us as a Council with any scientific information or perspective you have to gain some grip on this question of the moral status of developing life?

I had a conversation with Ian Wilmont, a long one, which he said, "Look, we do not know when moral status emerges but it is like the difference between midnight and noon. Somewhere in that process there is dawn." But that has a metaphor behind it and that is that there is an accrued, accumulated or maybe even earned moral status in the process.

Is there anything you know scientifically that can help us think clearly about where we should assign moral status to this developing life? And here I am thinking not just of the improbability of it successfully going forward, which is a quantity argument, not just the size, and this is all we are talking about roughly, eight cells on the top of a sharp needle so it is very small, but something like individuation, twinning. Can you give us some scientific thoughts about what the moral — what bears on the moral status of this entity?

DR. WEISSMAN: Let me answer that by saying a couple of things. That certainly, I know, for years is an issue that vexes you and it vexes each of us in our own individual way. We, as scientists, bring no more knowledge than anybody else about that particular moral question. I could, and Michael could do much better than me, describe to you when the possibility of thought — not just the possibility but the actual function of thought, mind consciousness, those human characteristics come about, but it is not going to be a moral argument and it should not impinge on the moral argument that you are trying to deal with.

It is a very vexing, and it is a personal issue. Scientists have no better and no worse prior knowledge from science about where to go with that argument but you must recognize that there will not come out of even this body a common agreement about when that moral issue comes about because we each bring our backgrounds to it.

I doubt, you know, if I would give you the precise stage or days after implantation that one would say when thought begins that you would have that or that you would have a common agreement in this group as to when it has "the moral dignity that you are trying to apply to it." I just cannot participate in this in any way that is more informative than you can or anybody else around this table. So I just — you know, that is an argument and we cannot settle that argument in this way.

DR. HURLBUT: A tiny subquestion?

CHAIRMAN KASS: Very quickly.

DR. HURLBUT: Do you think that this issue of when twinning can occur early, the early inchoate qualities that have been assigned to the embryo, should bear on our thinking on this?

DR. WEISSMAN: You would have to explain more to me about where you are going with that because I do not see it as an issue that is relevant to what I have presented to you.

DR. HURLBUT: The argument being if it does not have individual personhood should we consider its moral status different than after — than at a date in which twinning can no longer occur. Do you think there is any reasonable scientific basis for such an argument?

DR. WEISSMAN: All I think is that the twins I know are two different individuals every time.

CHAIRMAN KASS: Charles?

DR. KRAUTHAMMER: I think we are all hungry and I will pass.

(Laughter.)

CHAIRMAN KASS: First of all, Irv, thank you very, very much for making a special trip just to be with us on this occasion. Thank you for — first of all, thank you, and I think I speak for everybody, for the work of your Academy committee in preparing this report. There are things that you have left for us to do but you have done a huge amount of work that we now do not have to do in documenting the evidence on the safety of this research and, also, for exploring and, to some extent, raising some questions that are not generally raised in the media about so-called therapeutic cloning and the way in which it has been touted, and also for showing us how things that are generally not talked about, namely the kind of research that you have elucidated here, is, in fact, maybe even more important to the scientist's interest in proceeding with the nuclear transfer to develop stem cells.

We may have occasion to consult with you again. If you would be good enough to — there are some questions that were submitted to you in writing, many of them we have dealt with, if we might take the liberty of sending some further questions on to you as they occur, either now or down the road, we hope you and your colleagues might be obliging and help —

DR. WEISSMAN: I would certainly be happy to and I could provide you written responses, if you wish, for the questions already because I already wrote them.

CHAIRMAN KASS: Right.

(Laughter.)

CHAIRMAN KASS: Very good. One further thing, I mean, there were suggestions in the early discussion that the conversation about terminology would be vastly improved if we heard from Irv Weissman first. We have now heard and I think it would be incumbent upon us to spend at least ten minutes or so at the beginning of the afternoon session to revisit the terminological question to see whether that is, in fact, the case.

We are adjourned until 1:30. The Council members will have lunch in the room, whose name of which I cannot remember but it is where the continental breakfast was served.

(Whereupon, at 12:20 p.m., a luncheon recess was taken.)



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