Interview with Insoo Hyun

11 October 2005 by telephone; interviewer Marie Godfrey

Insoo Hyun , Ph.D., is an Assistant Professor of Bioethics in the Department of Bioethics, School of Medicine, Case Western Reserve University, in Cleveland, Ohio.

Insoo Hyun, Ph.D.He received his BA and MA in philosophy from Stanford University, and his Ph.D. in philosophy from Brown University. Most of his early training in philosophy focused on ethical theory and epistemology; under the direction of his dissertation supervisor, Dan Brock, he later came to develop a predominant interest in biomedical ethics.

Dr. Hyun wrote his doctoral dissertation on the philosophical conception of personal autonomy, and he has been able to transform his research in that area into a number of bioethics publications. As a philosopher, Dr. Hyun is trained to explore critically the core values that motivate and are implicit in many contemporary bioethics issues. His current research projects include ethical issues surrounding patient autonomy and cultural diversity, equality and priority among claimants of medical resources, international dynamics of human research cloning, and theories of patient well-being. Dr. Hyun’s primary research goal is to provide new ways of framing bioethical problems by reexamining the theoretical orientations that have become commonplace among many bioethicists. Recently, Dr. Hyun was awarded a Fulbright research award to begin qualitative research on the ethical, legal, and cultural dimensions of human cloning research in South Korea . During the summer of 2005, Dr. Hyun collaborated with Korean bioethicists and Dr. Woo Suk Hwang to identify the unique social issues that are raised in South Korea by this particular line of scientific research.. Having returned to the United States , Dr. Hyun's long-term goal is to use his findings to begin building collaborative research projects with bioethicists in Korea and the U.S. who share an interest in studying the international and cross-cultural facets of therapeutic human cloning and embryonic stem cell research. Godfrey: I was particularly fascinated by the fact that you combine biomedicine and ethics. Can you tell me how that came about? Hyun: I began as a graduate student in philosophy with a focus on ethical theory and theory of knowledge—both core areas in traditional analytic philosophy. During my graduate work with Dan Brock, a very prominent bioethicist and philosopher, my first big entry into bioethics was the cloning issue. Right after Dolly was cloned by Ian Wilmut in 1997, President Clinton asked his National Bioethics Advisory Committee to come up with two position papers on the ethics of human cloning: one a religious ethics paper and the other a secular ethics paper. Dan Brock, as a member of the President’s Committee, was picked to do the secular ethics paper, and I was his research assistant. I had been a pre-med major in college until I switched to philosophy, and what I saw at that time was that bioethics was a way for me to combine my interests in biomedicine and science with philosophy. So, I think my first big interest in bioethics came with cloning—human cloning. What do bioethicists do? Bioethics is an extremely broad field. You have people who work in professional or medical ethics, relating to clinical issues between doctor and patient and in the hospital setting; then you have people who do work in health policy, perhaps at the political level; and those in biomedical research.
  • In the clinical area, they seem to be somewhere between the role of a clergyman and a lawyer. They’re dealing with ethical issues that are not completely answered by the law, and are not purely religious questions, and they’re not medical questions exactly—they’re questions of value. So they serve a unique function.
  • Then, in health policy, a bioethicist is the voice of concern about the implications of health policy for society
  • And in biomedical research, they consider what implications come from biomedical technology. They sort of serve as the voice of social concern there.
Sound to me like you also have to have a very intense background—in this case, in biomedicine and law as well. You do. I think it’s interesting that you have to know a little bit about everything. It can be challenging. And it varies…you also need to be very good at realizing what you don’t know and when to seek expertise and counsel. Not a lot of bioethicists know where that point lies. How did your application for the Fulbright research grant come about? The timing of all this is really fascinating. The public’s interest in cloning had sort of cooled off a bit until February of 2004 when Hwang and his colleague Dr. Moon announced that they had cloned the first set of human embryos and had derived a stem cell line from one of these 32 cloned blastocysts. That was first big break, the first time that a team had done human cloning, and it made big news. Based on that, I was thinking it would be really interesting to see—if this line of research continues in Korea—what kind of an impact it may have on South Korea culturally, socially. I wondered what the legal developments were that enabled that kind of research to happen. One of my reasons for applying for the Fulbright was that I have a very sincere interest in this area of bioethics and I think that it could be possibly a very new area of research ethics—and, there were lots of personal reasons for me to want to go back to Korea, where I was born. So, I did it for professional reasons and also for personal and cultural reasons. I applied for the research grant and received it this past spring. As I’m packing and getting ready to go—in May—I hear that the Korean team has come out with another article in Science about how they had improved their efficiency and made 11 patient-specific stem cell lines from individuals that had all kinds of different medical conditions, both male and female, and of different ages. So, it was just perfect timing to have that huge development come out at that time. What were your expectations when you left for Korea? Well it’s interesting. I arrived in Korea and was thinking, “I hope I get to meet Hwang once or twice.” I arrived June 1, met him June 5, and then ended up spending almost every day there. He told me, “You’re the first bioethicist that I’m talking to…and over 200 tried to get an interview with me.” He really liked the idea of my being Korean-American and whenever Dr. Hwang and I meet, he speaks to me in Korean all the time. His English is very good, but he feels more comfortable speaking in Korean and he wouldn’t have been able to do that with the others. And, as far as I know, I’m the only Korean-American bioethicist in the U.S. Was Dr. Hwang interested in the bioethical implications of his work? At the beginning of the summer, he kept telling me that people like me should think about the ethics and just let him do his research. I suggested, “If you don’t think about the ethical issues, there will be a time when it will hinder your basic science research, like what’s happening in the U.S. A lot of people in the U.S. can’t do what you’re doing because the public dialogue about the ethics of this work hasn’t been going very well.” And I said, “You really need to be involved in the ethical discussion right from the start.” Now, after spending a considerable amount of time with him, I feel that he also recognizes this new area of research is extremely sensitive. I think I made some headway, because one of the components of the World Stem Cell Bank (the announcement of its formal open is expected October 19 in Korea) will be an ethics working group. In all, I’ve been quite impressed by Dr. Hwang and his team as well as with their willingness to accept the need for ethical discussion. Do you think scientists generally consider the moral implications of their work, or do they say, “It’s there, it has to be done”? If they give any sort of moral thought or moral reflection to what they’re doing, they really think they’re doing humanitarian work—the whole point of them trying to do the stem cell derivation and cloning is to find medical applications and—if anything, they’re kind of bewildered at why anyone would be against what they’re doing. But to another extent, I think that they may not fully appreciate how firm people are about the moral status of embryos. I mean, how deep those sentiments go. In Korea, there’s a small—but a very vocal—minority against Hwang’s research. I saw in some of the scientists an attitude that the group’s small enough, we can ignore them. We can’t change their minds, so there’s no point in engaging in a discussion with them. I think actually it pays to try to have at least some kind of discourse and to try to understand as much as possible why they have that kind of opposition. Recently, I saw an announcement that the Catholic church in Korea intends to raise large amounts of money to create a separate research facility for adult stem cells. An interesting aspect of the conflict—one that not many people realize—is that Dr. Ahn, whom Hwang calls his lieutenant and who is the one in charge of the clinical applications branch, is both female and Catholic. She is especially concerned with trying to reach out and address the religious concerns about their research. I guess Hwang is just a little more undecided and thinks this is a distraction. What I see is this dynamic of her constantly opening his views. This brings me back to a big question in this country and how that fits in with the work that Hwang has been doing—namely: Why do any embryonic stem cell research at all? Most often, we hear about the 65 diseases that can be cured with adult stem cells—the number’s always the same because it comes from the same site. Why do we need embryonic stem cells? I would say the main reason for wanting to pursue both kinds of research (it’s not an either/or situation) is that embryonic stem cells are pluripotent —they can turn into basically any kind of tissue. And adult stem cells are much more limited. Now, when I talk to stem cell scientists about these figures they always come back with a very interesting point. If you look at the amount of money spent towards adult stem cell research and how long that’s been going now—very good, we hope there have been some successes because if so, that would be very good news. But, please don’t compare that to the very limited funding and the extremely short history of research with embryonic stem cells. That’s an unfair comparison. You might try to equalize them by saying, “Let’s compare the first year or two years or three years of research with embryonic stem cells to the other”, and you’ll see that actually it’s not clearly a matter of adult stem cell research achieving superior results. We don’t know enough. It’s really a strange argument. What you’re really saying is, “We’ve been restricting embryonic stem cell research and, oh look, nothing’s happening! So therefore, we’re going to keep restricting and you’re never going to find out.” If that’s your attitude, you’re never going to learn the real applicability of this kind of stem cell research. There have been some incredible successes with animal models and embryonic stem cell research, so it’s not as if people have been working full time and not coming up with anything. It’s not that at all! Their hands are tied. It’s like saying, “There are two persons in a race and one person is able to run freely. See how far this person can go compared to the one who’s got his legs tied! Well, he must not be a very good runner.” The feeling I get from the adult cell research is that, first of all, about 55 of the 65 diseases cited have to do with recovery from intense cancer chemotherapy and helping to restore the blood cell lines. The only cells I’m hearing of now that are not blood related are the mesenchymal cells—cells that have a different plan. They’re not in the blood cell line. There’s also the push using umbilical cord cells in research. The interesting thing is that adult and embryonic stem cell research are not even targeting the same kind of conditions. They’re used for different purposes. Will the work in Hwang’s lab continue to be focused on embryonic stem cell research using nuclear transfer? Yes, and what’s interesting too is that so far they’re still the only team in the world that can pull it off. What’s happening is that basically others know how to do it. But it’s the manual manipulation they don’t seem to be able to do. Hwang is a hands-on PI [principal investigator]. He’s done thousands of nuclear transfers with cow eggs and he has developed considerable manual dexterity. This also means that the Korean team comes up with innovations faster, since he’s the one doing the work, rather than giving the task to a research staff and saying, “Here’s the recipe, the cookbook—go do it.” Do you envision him being one of the people who actually injects stem cells into a human for the spinal cord study? I don’t think it’s going to be him. What I was told while I was in Korea, was that the next phase will be working with animal models and working toward clinical applications. I think the person who will be the real leader will be Dr. Ahn. Nobody said this directly, but I got the idea that Hwang has sort of done his part, developing the technique, and he’s on to other things. He’ll continue to try to improve the conditions and everything, but the big next step is—what do you do with these stem cell lines? Okay, let’s go back to the World Stem Cell Bank. Is there a big public announcement coming out next week? I was at the meeting where they were discussing all the plans and everything, and we decided not to say anything about the details until the big announcement. So, there’s a lot I could say, but I’ll just save it for that day when they really want to make it public and then I can talk about it all I want. But it’s exciting. It’s going to involve more than one site. It’s very innovative. Hwang has compared the Bank to the Jackson Laboratories in Maine, where strains of mice are developed and shipped to the rest of the world. How will they be similar? That was the model thrown about during the meetings. And they’re really trying to model it like a place for research so it’s not just a bank. So, even the name is not confirmed yet. I’m not anticipating that it’s going to be a very large facility. Really as far as the scientists are concerned they don’t need a lot of lab facilities and they don’t need a lot of space, but basically it will be a place where they’re doing the stem cell derivations and making them available for applied research. In the U.S., because of the funding issue, the scientists are envisioning having to keep two separate sets of books because of having to separate federal funding and any other funding. They won’t have to worry about any of that in Korea, will they? No, because what they’re doing is legal. Hwang gets funding from the government. The planned funding for the clinical and bioethics groups will be separate, but also probably from the government. What about guidelines for the research? In the U.S. guidelines were proposed this summer by the National Science Foundation and the Institute of Medicine. Was there any talk about trying to implement those guidelines? No, but there are guidelines in place. For example, there are guidelines for what you can do with the cloned embryos—you can’t put them into a womb, or anything like that. But, as far as the kind of research they’re planning to do, there are no limitations. Will there be a hands-on oversight group, like the Embryonic Stem Cell Research Oversight Committee (ESCRO) recommended by the U.S. guidelines? We have three working groups. Hwang’s the head of the basic science. The head of the clinical applications group is Dr. Ahn. And I’m the co-chair of the bioethics group, with Dr. Jung, and we’re trying to make that kind of an international working group. My feeling is that we’re sort of charged with giving them ethical advice and trying to develop international guidelines. So if the Hwang team has a connection to those guidelines it will be mostly through us. We’ll serve as a sort of representative for the multi-national guidelines. One of the key components of the Ethics Working Group is that our funding is going to be separate from Hwang’s, even though both may come from the Korean government. But our role isn’t supposed to be oversight, or policing. As they’re working on projects and issues start to come up, they come to us and immediately ask, “Well, what do you think of this or that? We’re more advisory in nature; and we’re definitely not the police. I think it’s better to have an open dialogue and have them raise the issues that we’re to address. Part of the challenge is to train them to see where some of the ethical dilemmas lie. And we’re learning at the same time; everything is so new. I’ve been very impressed. They’re doing collaborative research right now, and it’s actually a little overwhelming because they have so many questions coming up. “Well, what do you think about this….And we said, “That raises some issues we’d need to address.” And they said, “If you don’t think that it is a good idea, then we’re just going to scrap that one and do something else.” And we said, “Wow, if we tell you that it is ethically problematic, you won’t do it?” And they said, no, they wouldn’t. That sounds very good, because one of the concerns that I have been hearing from people that I work with through Geneforum was that some bioethicists were placed in a front man or “shill” position where they were told, “This is what we want to do, now go make it sound ethical.” Absolutely, that’s not what’s happening. That’s what was very fascinating about the experience. I think what’s happening is that they realize that there are so many different things they could be working on, that what they want is some guidance on where we think the landmines are and they’ll try their best to avoid them. Believe me, they’ve had criticism from groups in Korea, and they’re tired of it. What about informed consent and the egg and cell donors? Now the team’s efficiency rate is such that one normal egg cycle will produce 10 eggs and they take 10 eggs on average to get one stem cell line. There is no longer a need for lots and lots of egg donors. So I don’t think the challenge now will be to recruit people. Now the challenge is to make sure people understand what they’re getting into and the nature of the research. I’m especially interested in this aspect of the work—informed consent—because that’s been an important area of my research in ethics. I have a paper coming out in January related to the issues of informed consent in the somatic cell nuclear transfer process. Which kinds of clinical applications do you see happening first? Broadly speaking, the area of medicine that they are trying to develop is called regenerative medicine and they’re addressing injuries at the cellular level. The ethics working group as part of the World Stem Cell Bank, is called the Regenerative Medicine Advisory and Research Committee (ReMARC). Oh…we need a new name. Regenerative sounds to me like trying to look for the fountain of youth. Not the way we understand it; we’re talking about regenerating tissues and their functions. So, we’re not talking about aging. There are aging implications, but one analogy would be an antique car—if anything goes wrong, you can replace the defective part. Generally, there are two different categories of therapeutic applications—one where you use cells directly and one where some sort of genetic manipulation will be necessary. For spinal cord injuries or myocardial infarctions [heart attacks], harvesting cells is no problem. What they do is take a tiny skin sample just below your navel. The donor—who’s also going to be the recipient of the stem cells—doesn’t even need to be extremely healthy. Not like the many stabs the donor may have to endure for a bone marrow transplant. Then what they do is take the nucleus out of an unfertilized egg and then put the entire donor body cell into the egg. When you apply a slight charge, the rest of the body cell except for the nucleus basically dissolves. This new process is much faster than the old one of extracting the nucleus from the body cell. [The stem cell line developed in this way is patient-specific, so there are no concerns about rejection or graft-versus-host disease.] Now, if it’s a condition such as juvenile diabetes, you’re going to have to manipulate the cells. Because you can’t develop embryonic stem cells that have the same genetic defect and just put them back into the donor. Is cell banking involved? With injuries, you can use the cells right away. With the other conditions, you will still have to do the genetic manipulation, and then banking might be used, if a supply of cells is needed over a period of time, or will be used for another person. In the future, are you going to have to be in Korea to serve on the ethics group? No, we’re making it international. We’re going to do most of the work by conference call and we’re probably going to have to meet only once or twice a year, when I’ll have to be Korea. Initially, they were saying, you’re going to have to come to Korea every other month. But I think it will be more like 3 or 4 times a year. I assume that Case is extremely supportive of this venture because of the ethics work Case has been doing. Yes, and my department is very excited about the work I’ve been doing and am going to continue doing. It’s kind of an endless supply of ethical issues that I can think and write about. It’s actually a lot to analyze and, it’s funny—because I’m in this role as sort of an advisor, I’ll get something and think I want to sit on it and think about it. and they will say, “We need some kind of analysis by such-and-such a date.” So, the work is fast-paced and exciting.