A LINE IN THE TEST TUBE: The Debate over Stem Cells

Monday, September 20, 2004

Proponents of embryonic stem cell research proclaim the potential of the research to find cures or treatments for many diseases such as Parkinson's and Alzheimer's. Opponents say the use and destruction of human embryos in the conduct of this research are immoral. In 2001, President Bush announced a ban on federal funding involving any new lines of embryonic stem cells. But calls to lift the ban continue, as do movements to increase funding at the state level. Which side of the debate is right? Is embryonic stem cell research ethical or not? Peter Robinson speaks with Ramesh Ponnuru and Irving Weissman.

Recorded on Monday, September 20, 2004

Peter Robinson: Today on Uncommon Knowledge: should we stem the tide on stem cell research?

Announcer: Funding for this program is provided by the John M. Olin Foundation.

[Music]

Peter Robinson: Welcome to Uncommon Knowledge, I'm Peter Robinson. Our show today: the debate over embryonic stem cell research. In 2001, President Bush declared a ban on federal funding of stem cell research that would require the destruction of new or additional human embryos. There have been calls to lift the ban ever since and more recently there have been efforts to fund stem cell research at the state level. Proponents of stem cell research argue that it holds unique potential for the cure of a vast range of diseases, including Parkinson's and Alzheimer's. Opponents argue that research involving the destruction of human embryos is in and of itself wrong. Is embryonic stem cell research ethical or is it not?

Joining us today, two guests. Ramesh Ponnuru is a senior editor of National Review magazine. Irving Weissman is director of the Institute for Cancer and Stem Cell Biology and Medicine at Stanford University.

Title: A Line in the Test Tube

Peter Robinson: President George W. Bush in his address to the nation on August 9, 2001, "More than 60 genetically diverse stem cell lines already exist. I have concluded that we should allow federal funds to be used for research on these existing stem cell lines where the life and death decision has already been made. This allows us to explore stem cell research without crossing a fundamental moral line by providing taxpayer funding that would sanction or encourage further destruction of human embryos." Did the President make the right decision? Irv?

Irving Weissman: I think it was a dramatic decision. It was an important move forward but as we learn more, it wasn't enough.

Peter Robinson: Wasn't enough. Ramesh?

Ramesh Ponnuru: I think the President made the right decision and respected a very important ethical norm of not killing human embryos.

Peter Robinson: All right. What I'd like to do is go from issues where as I make it out, there's greater consensus, to the heart of the issue where there's less consensus--the sharper disagreements. So let's begin where there's greater consensus. I just want to sort of check this off and see that the two of you are sort of with the consensus in this one. In its April 2004 report, the President's Council on Bioethics, led by Leon Kass who became famous for writing and speaking about all this--issued its report. They said that although they like the country itself were divided on embryonic stem cell research, it had reached consensus on two related issues. And I want to check with you and see if you're with the consensus. One is cloning. I'm going to quote Leon Kass, the Chairman of the Council, the council recommends, "barriers against some radical reproductive practices. These include the conception of a child in any way other than by the union of egg and sperm. This recommendation would effectively prohibit cloning." You're with that?

Irving Weissman: That's called reproductive cloning.

Peter Robinson: Go ahead and tell us what it is.

Irving Weissman: Yeah, it's reproductive cloning. That is what they're trying to ban. That is, putting the nucleus from a body cell, the genetic information from a body cell into an egg, stimulating it to divide and then implanting that, the last stage, the blastocyst stage, into the uterus of a prepared woman with the intent of making a full organism. I was head of a National Academies panel…

Peter Robinson: Which preceded this Kass commission.

Irving Weissman: …which preceded it. We came out with a report in 2002 and we found that in all animal species where that was attempted--reproductive cloning--although we all think of Dolly as being an outcome and maybe an easily obtainable outcome…

Peter Robinson: Dolly the sheep. Wasn't it a sheep?

Irving Weissman: Dolly the sheep. 99.2% of the fetuses that develop from those implanted blastocysts died in utero and those that died in the uterus mid-gestation, late gestation, often killed the mother. So without a doubt, without having to go to any moral arguments, just medical, ethical arguments…

Peter Robinson: It doesn't work.

Irving Weissman: It doesn't work…

Peter Robinson: It's unsafe and it doesn't work.

Irving Weissman: …and it's dangerous and it's against the Nuremberg Code which says human participants in experimental research should never be submitted to such a dangerous possible outcome.

Peter Robinson: Ramesh, you're with the consensus on this?

Ramesh Ponnuru: Well, what the Kass Council recommended is a ban on creating the human embryo using cloning with the intent to implant it in a woman's womb and create a child that way. I am in favor of that ban, although I would also say that we should have a broader ban on cloning, the creation of the new human embryo through cloning to begin with.

Peter Robinson: All right. Here's the second point of agreement on the Council on Bioethics. I'm going to quote Leon Kass once again, "Regarding embryo research in earlier stages, the nation and the council are divided but everyone on the council agrees that research on embryos at the later stage, after ten to fourteen days, is either wrong or imprudent and should be prohibited." So whatever else is at issue as this discussion continues you'd be opposed as would everybody on the Kass Council to work on embryos that are older than two weeks?

Irving Weissman: Yeah. That's what I said. That's so close to the line that I would draw that I'm not in favor of that kind of research.

Peter Robinson: All right. And that's an easy one for you?

Ramesh Ponnuru: There are no limits now. I'd like to start imposing that limit. Eventually I'd like to make it a zero day limit but fourteen days is better than nothing.

Peter Robinson: Let's establish why stem cell research matters in the first place.

Title: Having a Blast(ocyst)

Peter Robinson: Having narrowed the discussion to embryonic stem cell research, not reproductive cloning, and limiting it to embryos that are younger than fourteen days, tell us why it's important?

Irving Weissman: First let's distinguish quickly…

Peter Robinson: All right.

Irving Weissman: …between embryos that are created by sperm-egg fusion which happens in in vitro fertilization clinics and in our bodies and which the President allowed the previous destruction to create embryonic stem cell lines and the issue of transferring the nucleus say from your skin into an egg that had its own genetic material removed with the intent of producing what's called a pluripotent stem cell line. Now a lot of people call that cloning--scientifically it's not cloning because the egg brings its own genetic material and mitochondria. So I'll just say if you're a quibbler on science, the word cloning is not appropriate for that.

Peter Robinson: All right.

Irving Weissman: But the real issue here now is what will happen if you can't do research more than with the cell lines that were allowed. And that leads to what we now know from mouse experiments that's very, very important. If you take the skin cell from a mouse let's say that has a genetic disease, the most celebrated and proven example is immunodeficiency and put that into a mouse egg, make a pluripotent stem cell line from it, what we now know is that cell line develops the same disease as the skin cell from the donor. It opens the door that people who have genetically determined diseases, very common diseases, type I and type II diabetes, Lou Gehrigs disease, most Alzheimers, a few Parkinsons and on and on and on and on, that one could develop pluripotent stem cell lines which recreate those diseases in a test tube which can be passed around to every investigator who is eligible to work on them…

Peter Robinson: Right.

Irving Weissman: …to try to understand and treat these dread diseases. Now we're not talking about orphan diseases. We're talking maybe thirty, forty percent of the patients that come to, for example, Stanford Hospital.

Peter Robinson: Right. Let me ask you this. Ron Reagan addressing the Democratic National Convention said, "Imagine that you develop Parkinsons ten years from now. You go to a doctor, instead of prescribing drugs, takes a few skin cells from your arm, the nucleus of one of your cells is placed into a donor egg whose own nucleus has been removed. These cells will generate embryonic stem cells containing only your DNA. These stem cells are then driven to become the very neural cells that are defective in Parkinsons patients and finally those cells are injected into your brain. In other words, you're cured." Ten years from now, is that holding out false hopes? Is that what you as a professional researcher would consider within the realm of possibility if stem cell research is permitted to go forward in a completely unfettered way?

Irving Weissman: If it goes in an unfettered way, if there's enough funding to bring the best and the brightest into the community, I would be surprised if in ten years, you're not at the point of at least doing clinical trials if not clinical examples. It's been done in mice.

Peter Robinson: Ramesh, do you grant the science? Do you grant all that Ron Reagan claims and that Irv has just explained?

Ramesh Ponnuru: Well, I think that there have been a lot of hyped claims made for the potential of this research and you keep hearing expanded estimates of the number of people who are supposedly going to be able to derive some kind of therapeutic benefit from this research down the line. So I am inclined to be skeptical. At the same time, you do have to say that a lot of scientists do think that there is some potential here for cures and I would not gainsay that. As I said though, I do think when I hear numbers like 100 million Americans, 125 million Americans who are going to benefit from this research being thrown around, I'm very skeptical of those claims.

Peter Robinson: Now let's turn to one of the arguments in favor of stem cell research.

Title: A Cold Case

Peter Robinson: Let me set this one up by quoting your colleague at National Review magazine, Jeffrey Hart. "There are about one hundred thousand fertilized cells now frozen in maternity clinics." I actually have seen figures that are much higher, 400,000. That's more like it. All right.

Irving Weissman: Well, that's what I've heard.

Peter Robinson: All right. "These are the inevitable byproducts of in vitro fertilization. Such embryos are deliberately destroyed all the time and such destruction arouses no public outcry." Embryos are destroyed all the time anyway. Why not use them?

Ramesh Ponnuru: Well, I think we ought to reconsider prevailing practices towards human embryos. But let's look at those numbers again. We have 400,000 embryos in fertility clinics, human embryos, around this country. Now less than 5% of those are not claimed or owned by their parents. Now parents of these embryos have the right to have them destroyed under current law or to have them stored. The vast majority of them choose to keep them stored or to donate them to other people. In 3% of the cases, these embryos are donated for research purposes. In less than 5% of the cases, as I said, are they unclaimed. So this number that 500,000, 400,000, however many embryos are there doesn't mean that they are all available for research. They have claims made on them by their parents.

Peter Robinson: Now but take the small percentage that is unclaimed. What would be wrong with using that small percentage which would still be in absolute terms what some tens of thousands I think, right, if my math is right, some low tens of thousands. What would be wrong with using those for embryonic stem cell research?

Ramesh Ponnuru: If you take seriously the idea that the human embryo has a right not to be killed, is a living human being, then you can see the problem right away. Right? You wouldn't say that because a death row inmate at the end of his appeals is going to die anyway, then therefore you can take their organs out, you know, maybe inject them so that it's painless and so forth. We'd all see the ethical problem there. If you see that the embryo's a human being, then this whole argument about it being unused becomes a grossly inappropriate way of talking about it.

Peter Robinson: Irv?

Irving Weissman: But the question just to answer him first.

Peter Robinson: Sure.

Irving Weissman: Do you therefore believe that we should shut down in vitro fertilization as a medical option in the United States because it is inevitable that embryos created--real embryos that have a 25%-50% chance if implanted, becoming real human beings. Those are being destroyed now because of in vitro fertilization. So do you think we should stop the practice of in vitro fertilization?

Ramesh Ponnuru: There are clinics that offer parents who are seeking this treatment, the option of only generating as many embryos as needed, not trying to go beyond it, not generating extra embryos. I think that is the practice that we ought to see more of in in vitro fertilization clinics.

Irving Weissman: But, in fact, if you talk to obstetricians who are trying to do this, they need to get that access just to have a chance of having a real child.

Ramesh Ponnuru: Well look, whether or not it is appropriate to create conditions in which you have a large number of human embryos being stored, that's a separate question from whether once they have been created, it's appropriate to kill them. And I just think that the ethical norm against killing them is a strong norm in a way that the ethical norm against creating them isn't. Right. That it's just a separate analytical question.

Peter Robinson: Now we're at the sort of the central ethical question here.

Irving Weissman: Sure but could I just…

Peter Robinson: If you're still unsatisfied, go right ahead.

Irving Weissman: I'm not satisfied because I find it to be a real curious disconnect that an in vitro fertilization real embryo, which has a high chance of giving rise to a human being, it was permissible to destroy that whether it's the in vitro fertilization clinic can't keep it, the parents choose not to keep it or for whatever reason. That's ethically acceptable in the United States, legally acceptable. But a nuclear transfer, blastocyst, which one would have to say is even begging the possibility it could be an embryo since it's been tried and never worked for full embryogenesis or fetal development in primates and which we know in all other species 99.2% of the time, it can't make it all the way through pregnancy. That is what is being banned. So…

Ramesh Ponnuru: It's not banned. There's no ban on that.

Irving Weissman: Wait, wait, wait, wait.

Peter Robinson: Go ahead.

Irving Weissman: That's what the Bush Administration in backing Brownback and Weldon and in the U.N. called for a worldwide ban and a local criminalization, a million dollar fine, ten years in jail. That's a ban.

Ramesh Ponnuru: Right, yes. It's not banned now. There are proposals, which I endorse, to ban it. We have a widespread practice of these fertility clinics. And what you do with an accepted social practice that is morally questionable is a difficult matter. We don't have a widespread practice of cloning human embryos and it makes perfect sense for somebody who regards that as an evil to prevent it from happening in the first place by pushing for a national ban on it.

Peter Robinson: Now to the central question: What is and isn't a human being?

Title: I Think, Therefore I Am?

Peter Robinson: I'm going to quote Ron Reagan again. "It is," this is once again in his speech to the Democratic National Convention, "It is a hallmark of human intelligence that we are able to make distinctions. Yes these cells," he's talking about early stage embryos, "could theoretically have the potential to develop into human beings but they are not in and of themselves human beings. They have no fingers and toes, no brain or spinal cord; they have no thoughts, no fears. They feel no pain. Surely we can distinguish between these undifferentiated cells and a parent, a spouse, a child." To which Ramesh Ponnuru answers, how?

Ramesh Ponnuru: I would answer that yes you can distinguish it in many respects. Right? I mean you don't have the relationship with that cell that you have with your spouse or your father or so on and so forth. But you can see that that is a living member of the human species. It is an organism that is capable of directing its development according to its genetic template through the embryonic, fetal, newborn, adolescent, et cetera, stages of human life under the right circumstances.

Peter Robinson: Which is precisely what makes it valuable to the researcher, right?

Ramesh Ponnuru: He starts from the very beginning…

Irving Weissman: Not a nuclear transfer.

Ramesh Ponnuru: Well hold on a second. We're talking about both sets of questions here. Right? And we're talking about embryos taken from the fertility clinics and we're talking about the nuclear transfer question. So even if you were right about that, you'd still have the fertility clinic cases that you haven't dealt with and that Ron Reagan, Jr. is talking about.

Peter Robinson: Irv, let me ask you this question of distinctions. You said earlier in the program that you would agree with the Kass Commission that work ought not to be done on embryos older than 14 days. What's the distinction between--apparently there's a period there, 10-14 days is the phrase used--what's the distinction between an embryo at day 9 say and day 15?

Irving Weissman: So this is a personal opinion, not a scientific opinion.

Peter Robinson: All right.

Irving Weissman: But I'll just give you a scientific basis. I think that when you get to the point of making organs, including nervous systems, that you're getting close to the point where I become nervous personally because although many people think that humanhood or personhood exists in a ball of cells or at birth because there we have both ends of the spectrum, where I worry about it is when conscious thought is happening because that, to me, is self and that certainly requires an organized nervous system. So I would go very, very slowly if at all personally, beyond the time required to make a pluripotent stem cell line. The critical point is you can't make a pluripotent stem cell line after 5-8 days because the very next step starts the process of those cells differentiating and then they can't be made. We know that already.

Ramesh Ponnuru: I think when we're talking about which class of members of the human species we can and cannot kill; we need moral principles a little firmer than whatever happens to make somebody nervous. I mean, we need an actual moral principle that can be articulated. And I think that the trouble is as soon as you try to find anything, I mean, let's take consciousness as the criterion. You have to have consciousness, right? Well I mean, people are going to--you know, what's the threshold level of consciousness. People are going to vary in degrees. Are we going to say that the right to life is greater or lesser or that they differ in other fundamental rights according to the degree to which they happen to have this trait? You know, Ron Reagan, Jr. as you said, talked about fingers and toes. Well does that mean quadriplegics? You know, they're open season. Right, I mean, I think that we have to have a very firm moral rule that all members of the human species, it is impermissible to kill them.

Irving Weissman: You know, there's a problem here. You're acting as if this is an issue, should we proceed with this line of research or not and the only argument you're listening to--that I'm hearing at least--is is this a person? But I know lots of people having actually gone through an MD and treated patients and you and I have relatives that have these horrible diseases. I know that they're people. And I know now from a study of this research and participating in the research that this could take us much faster to an understanding and a series of treatments of all of these human genetic disorders. The principle has been established in animal experiments. So you end up with a situation here where you're calling for a ban on a particular kind of research, this kind of pluripotent stem cell research. So let's just ask when ever did the United States ban rather than regulate a line of research? And I think when you go medical research, okay, and I think that if you go back through it, it's never. So this is the very first time that a federal administration has said this promising line or any line of biomedical research should be banned rather than regulated.

Ramesh Ponnuru: Any medical research that required the killing of 15-year-old human beings would be subject not just to restrictions and regulations but to a flat ban. It is simply the case that in general, we have a flat ban on homicide. The question here is whether that ban should be extended to this class of homicides.

Irving Weissman: I agree with you that we have a ban on homicide and I love that we have a ban on…

Ramesh Ponnuru: Whether or not it's done…

Irving Weissman: …homicide.

Ramesh Ponnuru: …for medical research.

Irving Weissman: Medical research has nothing to do with that. And I think you are pushing the statement to the point that you have now made a reasonable argument about a group of cells unreasonable because you extrapolate to 15 year olds or convicts. And that's just not what we're talking about.

Ramesh Ponnuru: To say it's unreasonable, you'd have to find a point and reason in which the argument does not work, and you have yet to identify one.

Irving Weissman: And I think society needs to wrestle with that issue.

Peter Robinson: Last topic: Just how should ethical issues be settled in a democracy?

Title: Majority Rule, Majority Right?

Peter Robinson: Let me quote Ron Reagan one more time. "It does not follow that the theology of a few should be allowed to forestall the health and well being of the many." The theology of a few?

Ramesh Ponnuru: Well, none of the arguments I've adduced in support of the propositions that this one-celled or several-celled organism is human rather than belonging to another species, is living rather than being dead or inanimate, is a being rather than being part of some other being. None of those are theological arguments. They're all eminently rationally testable arguments. And as for the question of, you know, what we do in a democracy, well I think one of the things we do is we do not force people to use their taxpayer dollars on research that they find ethically abhorrent. And that's what is being discussed when we talk about the President's policy on funding stem cell research.

Peter Robinson: What about that?

Irving Weissman: Well, look the President's…

Peter Robinson: There's a lot of private money available. The State of California may now pass an initiative to fund…

Irving Weissman: If the State of California does, there will be a lot of money available. But I was with a group of stem cell researchers who met with Elias Zerhouni, the Head of the NIH and Jim Battey, the Head of their Stem Cell Task Force, and I said look, right now we know from mouse experiments that getting these cell lines out from human genetic diseases, Alzheimer's, diabetes, Lou Gehrig's Disease, that we learn a lot. Now it's going to happen whether it's in Singapore or U.K. or South Korea or Israel, or in Doug Melton's lab at Harvard, that people will get human disease specific pluripotent stem cell lines out and want to make them available to the best and brightest. But Dr. Zerhouni, and I don't think he personally believes this but I can't tell you, said…

Peter Robinson: Director of NIH?

Irving Weissman: Director of NIH. I said will you allow NIH funded people to work on these cell lines because imagine, you're a Diabetologist; you take care of kids with type I diabetes. You want to defeat this disease. And now there's a cell line that recreates the disease for you in a test tube. Will you allow medical researchers in the U.S. at the NIH or elsewhere to be funded by NIH? He says I cannot. I cannot.

Ramesh Ponnuru: If Dr. Zerhouni said that, he was being imprecise because, in fact, NIH funded researchers face no restriction on being able to use foreign stem cell lines. They simply can't do it with federal money.

Peter Robinson: Give me your best bet about what you think will happen. Five years from now which takes us up into not the next administration but a year into the administration that will follow that one, will the federal government have relented and begun to fund stem cell research? Irv, what do you think?

Irving Weissman: What will happen is that this research will go forward somewhere, maybe in the State of California, maybe in a foreign country and maybe eventually in the United States. If the results are great, if new discoveries keep coming out, there will be a change in the opinion about whether you, yourself, want to accept the benefits of those discoveries or want to remain in a hard line position that the moral line was crossed once and for all.

Peter Robinson: Ramesh, what do you think?

Ramesh Ponnuru: Well, I think it's very much of an open question. I think there's a lot of misinformation and propaganda being put out by the people who want taxpayer funding for this research. They're saying there's a ban. There's no ban. They're hyping the benefits of the research and so forth. The question is going to be whether we have a responsible media that calls into question a lot of this disinformation. And I hope that one place it starts is in this California initiative where a lot of misleading claims are being made for a bond initiative.

Peter Robinson: Irv Weissman and Ramesh Ponnuru, we're out of time alas. Thank you very much.

Peter Robinson: I'm Peter Robinson for Uncommon Knowledge, thanks for joining us.