Dr. James Thomson

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• SUSAN DENTZER:

  Let's go back to August 9th of 2001. The President comes on primetime television, makes his address, explains the executive order that he's going to issue.

  What did you think at the time?

• DR. THOMSON:

  I had very mixed feelings about it and prior to August, it was not clear in my mind whether this research would be supported at all in this administration and I thought there's a very good chance, early on in the administration, that there would be no funding at all in this area.

  So I was very grateful that a compromise was found where research dollars could flow in this direction, and at the time, although it is a compromise, I was fairly muted in the criticism of that compromise because there are a lotta people really working hard to see that this research gets funded and it resulted in that compromise and to criticize it too strongly really kind a stabbed them in the back.

  I was skeptical about how many cell lines were available, I was shocked that there was that many. It does not appear that there is that many.

  The importance of the compromise is that it did allow this research to go forward in an administration which is not very supportive of this research and I think that scientists now should feel that no matter how restricted things are in this administration, they won't get more restricted in the future and there are some important things we can do with this compromise.

• SUSAN DENTZER:

  So in fact this created a kind of safe harbor, or at least some amount of research to continue.

• DR. THOMSON:

  To start. I mean in the Clinton administration, for two years there was no federal funding for this research. And then for the first approximately year in the Bush administration there's no funding, because the actual effect of data compromise in December.

  So there were three lost years where essentially no research got done in this area, and that compromise allowed things to go forward but it's a compromise that is slowing the research.

• SUSAN DENTZER:

  Let's, before we go on to the ways in which it is slowing research, let's go back and talk about what you did and what resulted in the publication in Science in 1998.

• DR. THOMSON:

  Yes. You have to go back several years before that, and I'm a developmental biologist, and developmental biologists are interested in how that single fertilized cell becomes an adult human beings. It's a very fascinating process and it's involved in disease processes too.

  And developmental biologists study specifically animal models to answer particular questions.

  So some people study frogs, some people study mice, and most people that study this in mammals study mouse and the mouse is a mammal just like humans, so a lot of the processes are the same.

  But if you look at early mouse development and human development, they're just different, they're different in clinically relevant ways.

  So I started out my career in graduate student studies studying the mouse, but when I finished my PhD, I started to get more interested in primate development and when you attempt to study primates it's very difficult.

  They're very similar to humans in early development but the ethical considerations in working with them and the financial considerations means you really can't get access to the material you need.

  So in the early '90s I came to this university specifically to derive embryonic stem cells from nonhuman primates as a better model to understand early human development and we were successful in publishing one species of primate in 1995 and the second one in 1996, and were pretty confident that that experience would allow us to do the same thing for human embryos and in 1998 we published that.

• SUSAN DENTZER:

  And of course human embryonic stem cells had been isolated before. Your contribution was really to isolate them and grow them into the so-called line.

• DR. THOMSON:

  Yes. Just extracting cells from the embryo is pretty straightforward but to stably expand in the stem cell state is difficult and arguably, there's no such stem cell in the intact embryo because a stem cell is something that has to replace itself indefinitely and give rise to other things.Where in the intact embryo there's some precursor cells that quickly become, rise to other things, and they go away. So the idea that you could actually do this on a human embryo or primate embryo was not really clear when we started to do this.

• SUSAN DENTZER:

  Now just for the record, what is a stem cell?

• DR. THOMSON:

  So a stem cell is a generic term for a cell that can replace itself, that's called self-renewal, and it becomes other things.

  So, for example, in your skin, there's cells that lives at the base of your skin that re–whose job it is to replace your skin as it sloughs off. So it's a stem cell in that it can replace itself and it gives rise to all the differentiated cells in your skin.

  So there's stem cells in the blood whose job it is to replace blood and there's stem cells elsewhere in the body.But if you go back early, early in development, you can come to a cell who doesn't know what it wants to be when it grows up, it hasn't committed to become a particular thing, and it has the potential to form anything in the whole body, and if you culture those cells in just the right way, they will self-renew and replace themselves as far as we know, forever, and yet they maintain this important property of being able to give rise to everything in the whole body, and that's what an embryonic stem cell is.

• SUSAN DENTZER:

  Now again your contribution was to figure out what special "soup" those cells needed to grow in to maintain themselves in a totally undifferentiated state for a long period of time.

  How did you do that?

• DR. THOMSON:

  A lot of it was based on analogy to the primate cells and mouse embryonic stem cells had been derived in the early 1980's and people had actually tried to drive human embryonic stem cells early in the 1980's in Britain but failed, and a lot of our experience with the primates was why we're successful in humans. More than coming up with particular growth factors and a particular "soup," it's just technically how you deal with the cells is a little bit different and it takes some getting used to, and because we had that early primate experience it transferred quite directly to human experience.

• SUSAN DENTZER:

  So when you published this work, what did you think–what did you think was the promise of human embryonic stem cell research at that time?

• DR. THOMSON:

  Well, there are three basic areas and they haven't changed. One, which I still think is the most important, is that this is a important new research tool to understand the human body. It's been historically very difficult to get access to certain kind of human tissues. The heart's a very good example.

  There are no human heart cell lines that people can study. So people tend to study animal models and hope that that information goes over to the human heart.

  Well, it turns out that the human heart in these animal models are quite different and how they respond to drugs is quite different, but it's never been before possible to routinely get access to enough human heart cells to test drugs directly on human heart.

  Human embryonic stem cells give you good access to things like human heart, so that you could routinely study that in the laboratory.

  You know, it's not just the human heart that's difficult to grow and get access to but a lotta tissues in the body researchers simply don't get enough access to.

  So I think that human S cells, at one level, simply gives you better access to things in the human body that couldn't be studied before, and that as researchers more broadly have access, they will learn things about the human body that will be applied in the clinics, that have absolutely nothing to do with transplantation biology.

  But the second area–the first area is just basic science. The second area is drug testing. The third area is transplantation biology. Because these cells have the ability to form anything in the whole body, it's very possible we can use them to make cells that are defective in particular diseases, and use them to correct those diseases.

  Of the three that I mentioned, that has a huge amount of promise, but there's a great deal of work that has to done before we can direct it, bring it in the clinics.

  One other reason these cells are important is for drug testing and the human heart is the best example of that right now but it's true for any cell in the body.

  Historically, it's been essentially impossible for researchers to get access to a normal human heart. If you're in a university setting, what you did is you got access to biopsy material, very small amounts of material from diseased hearts, and they'd come in at, you know, 2:00 o'clock in the morning or something, and you couldn't plan experiments around it.There are no human heart cell lines and there's never been good access to direct human material.

  So people use animal models like the mouse and it turns out there's basically physiological differences between mouse heart and human heart. This is not surprising to nonscientists. I mean, mice and people are different.

  But the mouse heart, for example, is beating at, you know, several hundred beats a minute and the human heart's going 60, 70 beats a minute, and those differences are based on basic fundamental biological differences.

  Now when you test a new drug, you would like to actually test it in human material because its response is going to more accurately reflect what's it going to do in a patient, and prior to human embryonic stem cells, it was really not possible to routinely test drugs on human heart because it wasn't available.

  While this is true for any cell type in the human body, there's an awful lotta cell types in the human body you simply can't culture, and human S cells promise an unlimited supply of these cells so researchers can test drugs on it or just understand the basic physiology of those cells.

  And I really think that human embryonic stem cells will become a pervasive research tool that medical schools will use all over the country and all over the world, and the results of that research sometimes may have something to do with transplantation biology but in many cases it won't, and it re–it will result in basic changes in medicine, they don't make the headlines, but will be, in the long run, I feel, probably more important even than the transplantation aspects.

• SUSAN DENTZER:

  You've drawn an analogy between this and genetic engineering, gene splicing technology.

• DR. THOMSON:

  Yeah. I think there are a lot of analogies between human embryonic stem cells and genetic engineering, especially in the early days. I mean, both technologies was caught up in a, a large social debate. It wasn't clear, in the early days of genetic engineering, whether it would even go forward.

  But gradually, after the social debate sub–subsidized, compromises were put in place, safety measures put in place, and genetic engineering has moved forward.

  The other analogy I'd make is I don't think scientists were very good at predicting the specific outcomes of genetic engineering.

  They're very enthusiastic about the technology and there was universal enthusiasm for technology but when it came to making specific predictions, they weren't all that good at it.

  So, for example, gene therapy was one of the areas where people thought this would get to the clinics really quickly, make a large impact on human life. Well, there's been some success in that area but it's proven very difficult to get into the clinics, and I think there may be some parallels with the transplantation biology of stem cells, is that there's huge promise there but it's likely to be very challenging to actually get it into the clinics in a safe way.

  But the other parallel is genetic engineering has become pervasive through all of biology and through daily life in ways that was not anticipated and I think human S cells, in the same way, will become a basic experimental model that will be pervasive across medicine and make changes which are profound, that aren't anticipated right now.

  So, for example, in genetic engineering you can make better insulin, which is safer than it used to be, and that was anticipated. But the things like forensic DNA testing, that wasn't really anticipated, and the fact that your laundry detergent have enzymes, genetically engineered, is not widely known or anticipated.

  And I think the other thing is that some of the really big successes were also not anticipated, like the sequencing of the human genome.

  I don't think if you sat around in 1975 and asked people would this be done today, they'd say you're just dreaming about that.

  So I think human S cells have this tremendous potential, the specifics of that potential are difficult to predict, but scientists are very la–very rarely wrong when they–something this important comes along, we think is important.

• SUSAN DENTZER:

  In the abstract, you're saying, it's important.

• DR. THOMSON:

  Yeah. I think

  hat scientists will find ways that the science is important that they didn't predict, but they won't be wrong about the fact of how important this is.

• SUSAN DENTZER:

  Now the other night at the Democratic convention, one of the people who's risen to prominence is an advocate for embryonic stem cell research, Ron Reagan, Jr. said, as he was describing the potential, and emphasizing the transplant potential, said, How'd you like to have your own personal biological tool repair kit, staying behind, waiting for you at the local hospital?

  Is that overstating the case?

• DR. THOMSON:

  It is and it isn't. Some of the statements that have been made recently are somewhat overstating the case in the short term but not necessarily in the long term, and I think what people have to realize is that basic scientific research takes a long time and there's tremendous potential in the area of transplantation biology.

  But for most diseases, this is going to take a very long time, and I think that the expectation, given the hype in the press, is that things will be available for everyone in five years. I mean, that's not going to happen.

  There may be clinical trials within five years but it's going to take a long time for this to enter mainstream clinics.

• SUSAN DENTZER:

  What's a long time?

• DR. THOMSON:

  It's so hard to predict that I don't like doing that, but, again, I think it's, it's good to be cautious when we make these estimates and, you know, I see things being a decade out but if you asked me five years ago, I also said a decade out.

  So I think it's important to say that it's going to be longer than we anticipate but it's very difficult to put specific dates on it.

• SUSAN DENTZER:

  But a safer time frame would be 10 to 20 years then.

• DR. THOMSON:

  I believe for most diseases, that's true. I mean, there might be specific diseases where that's not true for it, but I think in most things I would too.

• SUSAN DENTZER:

  What about the advocacy community, the disease advocacy community? Are they also overstating this?

• DR. THOMSON:

  Well, I mean, in some ways they have to, to get their political message across. But I think that one of the worries I have is that where the funding really should be going to now is in basic research. The long-term implications of that funding will be greater if it's put into basic research.

  There's a large push for what's called translational research now and it's very important that we get better at going from the bench to the clinics. But if you put the money there right now in the human S cell community, I don't personally think the community's ready for it. I think we need to build up the basic science more and then start to push it more into the clinics, and if we try to put it the other way around, it's kind a putting the cart before the horse and I think in the long term we'll not benefit from it.

• SUSAN DENTZER:

  And some people might say, well, that's easy for you to say, you're a basic scientist. Of course you want that to be where the resources are–

• DR. THOMSON:

  Yeah, and I think that there's probably some truth in that. I am a basic science but I do firmly believe that unless you support that basic science in the long run, the progress will be less.

• SUSAN DENTZER:

  Let's talk about what has happened in the science of embryonic stem cells over the past three years. What would you say are the signal advances–

• DR. THOMSON:

  The major advance, say, in the last six years, even before the President's compromise, is that human embryonic stem cells have been derived by multiple groups and the basic properties of those cells have been confirmed, and it's repeatable across groups.

  These cells can be grown without apparent limit and they seem to have the development, the potential to form everything in the human body, and people now, in the last three years, are starting to show them differentiate to very specific kinds of cells.

  So a differentiation to blood, neural tissue of the brain, heart tissue, vessel tissue, blood vessel tissue, have all been demonstrated in the last couple years, and this increases the confidence that these cells are really what people said that they were originally.

• SUSAN DENTZER:

  They really are stem cells.

• DR. THOMSON:

  Really stem, really are embryonic stem cells with this remarkable development potential, and this repeatability across lab is very important. I mean, the people accepted that original publication quicker than anticipated because it's really important to have multiple groups be able to repeat such things.

• SUSAN DENTZER:

  Do we understand any more about what "stemness" is?

• DR. THOMSON:

  I think there's some progress in that area but I think that–in the long term, there's a very strong interest in being able to take an adult cell and transform that directly into something like an embryonic stem cell and I think we will ultimately be able to do that, but I think we're a long way off from doing that.

  But some of these studies, and trying to understand what stemness is are a good step in that direction.

• SUSAN DENTZER:

  And if we got to that point, of course we would get out of the debate about destroying embryos.

• DR. THOMSON:

  Yeah, and that's probably in the long term true but, you know, at least for now, if you don't have the embryonic stem cells themselves to study, then you don't know what you're aiming at. So it's very important to study these cells. That's actually a comment I should make, is that there's this debate between, in the press, between adult stem cells and embryonic stem cells, and that is entirely a political debate and a debate within the press.

  It's not a debate within the scientific community. Within the scientific community, there are a vanishingly small number of biologists that don't think you have to do both and when you do science, questions and the answer to those questions kind a slop between different model systems.

  So you think you're studying one thing in embryonic stem cells and you're actually benefiting people in adult stem cells and vice-versa.

  So it's very possible the fundamental discoveries we'll make with embryonic stem cells will be directly applied to the clinics, not with embryonic stem cells but with better knowledge of adult stem cells, and vice-versa.

  So the people in this field quite universally feel that both have to be pursued very vigorously and this idea that one is better than the other is not a scientific question because it'll be certain things that embryonic stem cells are good for and certain things that adult stem cells are good for, and, you know, people design their experiment about which is better about those particular applications.

• SUSAN DENTZER:

  What about differentiation? As you mention we've now established that you can in fact differentiate cells into various other cell types. But do we understand any more than we did three years ago about what happens–

• DR. THOMSON:

  Oh, certainly. It's a slow process and a lot of what's known in that process has to do with other model organisms when attempting to apply that to your embryonic stem cells. So in neural differentiation people know a fair amount about going from embryonic stem cells to specific nerves of the brain.

  For other tissues we know a lot less. So there's been considerable progress over the last three years in that area but it's slower than I like to see.

• SUSAN DENTZER:

  And when you say we know a lot, are you saying we know a lot about how to do it or we understand a lot about what goes on in the process?

• DR. THOMSON:

  A little of both and sometimes we're actually pretty good at doing it without knowing about the process. So, for example, in heart cells, it's actually quite easy to get these cells to differentiate to heart cells even though we don't understand the process very well.

  But there's easy ways to purify those heart cells and even though it's not very efficient, you know, it's very practical already.

  But there are other lineages, like the neural lineage, where we can understand it better and do it also.

• SUSAN DENTZER:

  What about things like cell cycle controlling, cause a critical issue's going to be knowing how to turn off the differentiation process, if you're going to apply the standing therapy down the line.

• DR. THOMSON:

  Yeah. So the question of safety in transplantation is a critical one and some people have said, for example, that because embryonic stem cells are so potent, that they could form everything, you have to turn off that potential and it, it's a critical problem for transplantation.

  I actually think that's a relatively minor problem compared to all the other problems that are out there and for transplantation there's several levels of challenges that remain.

  The first is developmental biology, and in developmental biology, I think that'll be the easiest one. I would guess that within a decade we'll be able to make most of the therapeutically relevant cells in the body in therapeutically relevant quantities.

• SUSAN DENTZER:

  We'll know how to differentiate–

• DR. THOMSON:

  We will, yes, within a decade, but what I would also guess within a decade, that there'll be very few routine therapies based on these cells because the hard part's going to be after having the cells and this is true for any stem cell-based therapy, is that when you're treating disease, those cells die for a particular reason in the first place, and if you, unless you correct that reason, simply putting those cells back into that environment won't succeed.

  So if you think about a heart attack, muscle cells die, but you have a heart attack because the vascular supply is bad, and if you simply put heart cells directly back into that environment, you wouldn't anticipate that they would live unless you can reestablish that, that blood supply.

  So I think that although we'll be able to make these cells and although there's great promise, actually getting them back into the body in a useful physiological form will be very challenging for most diseases.

• SUSAN DENTZER:

  And just to stay on that analogy in hearts, it would suggest you're still going to have to give people a stent and transfer new cells in, new stem cells–

• DR. THOMSON:

  Right.

• SUSAN DENTZER:

  It's not going to replace–

• DR. THOMSON:

  Yes, and most of the difficulty will be in repairing what was causing the damage in the first place.So if you think about diabetes, diabetes and autoimmune process, what kills eyelet cells, unless you change the immune system in some way that's going to happen again.So you have to treat the underlying cause of the disease in addition to replacing the cells, and I think for the most part treating that underlying cause is going to be the harder part.

• SUSAN DENTZER:

  So the stem cell therapy itself would not be a cure.

• DR. THOMSON:

  Well, it is if you understand the physiologic of the disease and I mean Parkinson's is another good example. There's hope that the transplantation of these cells could help Parkinson's patients.

  But the brain is a very complicated things and simply transplanting back in the brain and allowing them to reestablish function will be very challenging.

• SUSAN DENTZER:

  What would you say are the main things we need to learn in the next phase of stem cell research?

• DR. THOMSON:

  So I think there's several things that are going to happen in the next year or so in stem cell research which I think will also influence the political process. One is that when we derived the cell lines that we derived six years ago now, we derived them specifically for research purposes. We're very conscious of that.

  We figured that other people would derive more, very quickly after us, and there'd be no limitations on the derivation of these cells.

  So we made no attempt to derive them in specific conditions that would be appropriate for clinical trials. So, for example, they're derived in mouse embryonic fibroblasts. They're a cell type from a mouse that has the potential to introduce contaminants, and which could be harmful to people.

  They're introduced, they're grown in bovine serum, and bovine serum is another place where pathogens can be introduced.

• SUSAN DENTZER:

  This is a fancy word for cow serum.

• DR. THOMSON:

  Right. Cow serum; right. So there are products from animals that were not tested in a way that'd be appropriate for clinical trials. Now there–it doesn't mean that people can't do a lot of testing on the existing cell lines and still use them. There's precedence for that and people are trying to do that.

  But, clearly, as we get better at culturing these cells and we eliminate those problems, there's going to be a real need to derive more, and if I was a patient and had a choice between the cell lines that I previously derived and cell lines that others are, we will derive in these improved conditions, yeah, the new ones would be safer even though you might be able to use the old ones.

  So I think that improved culture conditions will really call upon the current administration or the next one to change the current policy so more cell lines can be derived.

  The second thing that will happen and is happening right now is people are deriving cell lines and derivative cells of clinical importance.

  So people are looking at neural derivatives for Parkinson's disease and multiple groups are having success in that area.So as people begin to derive these clinically relevant cell types, there's going to be a need to go back and derive safer cells because people are gonna start talking about clinical applications then. I think it'll happen within the next year or so.

• SUSAN DENTZER:

  And to be very clear about what we're talking about here, we–it seems to be the case that certain cell lines are better predisposed to become different types of cells than other types of cells; correct?

• DR. THOMSON:

  No.

• SUSAN DENTZER:

  Okay.

• DR. THOMSON:

  So–

• SUSAN DENTZER:

  What's the story?

• DR. THOMSON:

  So there is a concern that the existing cell lines might differ in their potential to form specific cell types. That's not well documented yet.

  But I think the need to derive more cell lines is more based on safety and genetic diversity of the cell line. So the existing cell lines are small in number and they don't, can't possibly represent the genetic diversity and ethnic diversity in the United States. It's simply not possible.

  In our own case, ours were donated in a blind fashion, so we actually don't know the genetic background of the donors, but given the small numbers, you know, it does not represent the genetic diversity.

  That's important for two reasons. One is the place of drug testing. The response to drugs is different between people based on their genetic background and if you wanted to test a new drug to show that it's safe, you would want a good genetic panel of cell lines to test it on.

  The second reason is that if you get to the point of wanting to transplant these cells, there are a lot of strategies for trying to get around immune rejection, but you would want at least a close match between the embryonic stem cell and the patient you're going to donate to, and without having multiple more cell lines it's not gonna be possible.

• SUSAN DENTZER:

  I want to get to some of the reasons to change the policy but just to stay on the question of what do we need to understand about the basic science about embryonic stem cells, that won't repel our ability to use them in the various ways you describe. Is there anything that stands out as the next burning question we have to answer?

• DR. THOMSON:

  Not a specific burning question. Again, the people that will want to use this will be broadly distributed across the biomedical research community and each of those will have their own questions, and which of them are more important and which are less, it's hard for me to say. I'm interested in very specific questions in my own laboratory.

  But as these cells are more broadly used, a lot of things we don't predict will be answered. So in terms of very specific things, yes, we're going to get better culture in these cells and that'll facilitate more people using them, for example.

  We'll get better at differentiating the very specific early lineages but it's hard to point to one specific thing that needs to be done now.

• SUSAN DENTZER:

  Tell me about the work your lab is engaged in currently.

• DR. THOMSON:

  We're asking what's special about these cells. How come they have this potential to form everything in the body and what are the basic molecules that make them decide to become themselves versus something else. So, the focus of our lab is really trying to understand this special cell in a kind of basic science sort of way.

• SUSAN DENTZER:

  What makes a stem cell decide to become a stem cell?

• DR. THOMSON:

  Right, versus something else, so self-renewal. A cell, when it divides, it has to come with a decision. It will either die; it will become itself again or it will become something else. And we want to understand at a basic level how it makes that decision.

• SUSAN DENTZER:

  Any thoughts?

• DR. THOMSON:

  Oh, I'm working on it.

• SUSAN DENTZER:

  When would you have something to publish on this?

• DR. THOMSON:

  Oh, we're publishing all the time on it. It's just, you know, continuing and expanding our ideas on how it works.

• SUSAN DENTZER:

  What do you think has been the impact of the President's policy?

• DR. THOMSON:

  Well, it, it's multifold. The biggest impact is the one of perception. And the perception in the scientific community is that, these cell lines are not widely available; that they're too expensive; that it takes too long and that we live in an administration that's very restrictive.

  So, if you're a young investigator thinking about what kind of science to go to, that's a big hurdle to go over. And I think, either a young investigator, even an established one is looking at this as being something too controversial to get in right now, because of those restrictive policies.

  So, I think that the biggest impact of removing those restrictions is that a lot more scientists will simply choose to enter the field because of perception.

• SUSAN DENTZER:

  And therefore, the science will progress, although faster?

• DR. THOMSON:

  Right. I, I strongly believe that if the existing restrictions are in place for another four years, they'll have a very impact on the field. I believe that the compromise to allow research to get started and given the politics involved, it's really the best we could hope for. So, I haven't been very vocally against it, you know, publicly anyways.

  But I do feel that if the same policy goes forward for another four years, it will seriously impact this research and people will suffer because of it.

• SUSAN DENTZER:

  There are various proposals, as you well know, to change the policy, one of which is at least not fund the derivation of new lines from embryos that are discarded by IVF clinics, but at least to allow federal dollars to used to do work on those lines once they are derived. Is that an appropriate middle step?

• DR. THOMSON:

  It certainly helps a lot. So, that people currently deriving cell lines, those are useful cell lines to a very small number of people, because nobody can work on them. And there are people set up to drive new cell lines and as long as there is a share to the scientific community, the fact that federal dollars didn't go in their derivation wouldn't hurt too much. But it does seem a little bit kind of disingenuous to me that we're going to take the fruits of this research and kind of wash our hands of the initial steps of it.

  And it seems to me that, better public policy would actually provide the appropriate oversight for the initial derivation and the funding, but I realize politically, that would be very difficult in the foreseeable future.

• SUSAN DENTZER:

  So, given the political constraints–

• DR. THOMSON:

  Yeah and given the political constraints, I think that much of the value we need to go forward would be obtained by just changing that one thing. And that, you know, the actual funding the derivation would also have value, but nearly as much as just allowing new cell lines to be used with federal dollars.

• SUSAN DENTZER:

  I want to come back and give you NIH's response to a lot of the criticisms you raised. For example, on the question of the lines becoming, if you will, genetically fatigued, the karyotype disintegrating, they say, well, you can go back to the initial passage lines and grow them all over again. Not a problem.

  The second point they make on the issue of not enough young scientists coming into the business, they say, well, there's no cap on federal funding and look at all of the courses that you and others teach to teach people how to use these lines. Those are always over-subscribed. So, not a problem there.

  In essence, who's right about this? It sounds like it's a question of perception as much as anything else, how real these problems are.

• DR. THOMSON:

  Well, I do believe it's perception, but given the amount of scientific enthusiasm for this field–you know, we're six years in now. And, yes, we're making a good faith effort to share our cells with the community, but we ship them to maybe 200 groups, something like that.

  For something this important to have that level of interest, which is small relative to the need, there's something wrong here. And I think what's wrong is the perception, that it's a very restrictive field. It's hard to get into and that the Federal Government is not supporting it well.

  NIH is making a good faith effort to see this–you know, to live under those restrictions and to get it funded as well as they can. They're to be commended for it. But they live under those restrictions and have to abide by them.

• SUSAN DENTZER:

  One of the other things NIH now proposes to do is create a stem cell bank to eliminate some of the hassle factor that some researchers say they encounter in terms of having a one-stop shop to get these lines. Is that a good idea or a bad idea?

• DR. THOMSON:

  I think in the current political environment with our current president, it's a bad idea. And if the Federal Government funds a single place to distribute these cells and that single place is completely dependent on federal funds, it doesn't free up the research. It restricts it.

  So, a much better model is to allow a lot of research to drive these cell lines and compete with each other. And if some do it cheaper and better, then they will be the ones distributing it. If you put it in one place where it moves the competition and makes the Federal Government even more controlling than they are and, given the current administration that's not supportive of this research, I think it's a bad idea.

  So, if they were to do that, I would say it's important to do more than one; that a minimum of something like three, which are regionally distributed, especially since local politics gets in the way of this also and there are some states like California, Massachusetts that have been very supportive of this research, I think rewarding with such banks would be worthwhile.

• SUSAN DENTZER:

  They have also proposed to make substantial contributions to the translational side of this research as you've mentioned earlier. Why do you think this is?

• DR. THOMSON:

  Yeah, I don't think that, you know, putting investments in translational research, in stem cell research is bad. It's just that if it's done in the absence of really strongly supporting the basic research, the end result would be much less. So, I think that there is a great need for funding in this area. And again, I'm biased, because this is my area. But I think that something comparable to the War on Cancer in the Nixon administration, where really, serious federal investment was made–not just in human embryos and stem cells, but in the whole field of what's now called regenerative medicine, is needed. Human ES cells have a part to play in that, but it's not the whole thing.

  I think that centers of regenerative medicine that are aggressively funded that for right now, really focus on the basic research but make sure that everything is in place for the translational research would make a huge event. But if you put the money into the translational aspects now, I think that it would starve potentially the basic aspects and in the long run, you would be damaged for it.

• SUSAN DENTZER:

  Let me come back to ask, what if it's 2008, ten years after your science paper was published. What will be different? What will we have seen? Let's assume the policy has changed.

• DR. THOMSON:

  Yes and let's hope it's just not me by then because, you know, there are really a relatively small handful of labs working in this area. There are probably a couple hundred with the cells that are just beginning to work, but it's not thousands.

  And my prediction is that, if those restrictions are removed within four years, there will be thousands of investigators in the United States using them and aspects of biology we do not even predict and just unleashing that creativity will create things we can't even predict now, but it will be quite fun to see.

• SUSAN DENTZER:

  What would you do if tomorrow, the restrictions were lifted?

• DR. THOMSON:

  Well, personally, I'm not sure it would change us in our lab that much, because we have derived a certain set of cell lines and we use those cell lines in our own research. When we get to the point where we can culture better, we will drive more cell lines and it would make a big difference in our life if such cell lines were federally fundable.

• SUSAN DENTZER:

  And so, that's essentially something you would do in the next couple of years?

• DR. THOMSON:

  Yes.

• SUSAN DENTZER:

  We're here in the midst of a presidential election and one of the seminal issues appears to be embryonic stem cell research.

• DR. THOMSON:

  There's a significant difference between President Bush and John Kerry on this issue. And in that sense, I support the Democrats for making this an issue and pushing it forward.

  What I'm worried about is that, some of the key people who have really pushed to have this research center supported are Republicans. And some of the real champions in this area, like Arlen Specter, have been, you know, even in the Clinton administration, pushing to see this research get better funded. And they've kept to it for six years now.

  So, what I'm worried about is that, it becomes so deeply partisan with this election, that good public policy is going to need Republicans and Democrats crafting that policy. And if it becomes part of–more partisan and bickering, that may not happen.

  And I think what people don't understand is how broad the support for this research is, not within the White House, but within Congress and within the Senate and how it completely cuts across political boundaries. So, I, I don't follow individuals and politics very much, but when I was graduate student, I was in Philadelphia and that's [Senator] Arlen Spector's home state. So, I was familiar with him. And I used to enjoy listening to the Judiciary committee hearings, and he was a member of that committee. And what struck me about that committee is that, if you listened to Teddy Kennedy, he kind of counter-balanced everything that Orrin Hatch said and they never actually said anything you didn't anticipate. You didn't learn very much. But if you listened to Arlen Spector, he consistently asks very tough questions and he managed to piss off both the left wing and the right wing at various times, but he always asked those really tough questions. And he's been doing that for six years now, for human ES cell research.

  And I think that if it degenerates in simply partisan bickering, that some of these really good efforts on the part of Republicans could go by the wayside and it could damage the field. But if you think back to that committee with Teddy Kennedy and Orrin Hatch, all three of those people now are strongly supportive of this research, including Orrin Hatch, who is quite a conservative Republican. He is very much against abortion, but he took a very personal, hard look at the issues and he decided that he could support this research and that a series of other very conservative Republicans have done a similar soul-searching and have come out in support.

  So, the people that I personally respect are not the people that simply have a knee-jerk reaction to this research, you know, that make the predictable response…The people I respect are those who took a personal, hard look at it and some people decided a different point of view from mine, but they took the time to take a look at the issue.

  And some people, like Orrin Hatch, who at one time supported a constitutional amendment banning abortion, took a hard, personal look at it and he came out politically saying this was important in a way that certainly didn't help him politically in his home state. And there's a number of people like that and I'm concerned that, you know, when we have another president, that if it gets too nasty during the election, it will be difficult to craft new public policy because of it.

• SUSAN DENTZER:

  What do you say to people who believe that in doing the work that you've done, you are destroying embryos, you are aborting human life, you are a "baby killer"?

• DR. THOMSON:

  Yes, I think it's very important to take that point of view seriously and I don't think enough scientists do. But the question about whether you should support this research can be answered on several levels. And could take myself back to, say, 1995, where I considered whether I was going to start this research.When I was starting the primate work, I was not planning to derive human embryonic stem cells. I kind of presumed other people would do it, because I had not done that work before. So, I read the various commissions and ethical reports on human embryo and stem cell research and embryo research. I mean [all of us had to] sit and talk long before we'd done this.

  And again, there [are] several levels you can answer that question to your own personal satisfaction. But the one that's sufficient for me is that, there are now a few hundred thousand frozen human embryos from IVF clinics. Most of them will be used for fertility treatment, but a significant number of those will be thrown out. And I do not think it's an ethically superior decision to throw those embryos out when you can actually help people with them.

  And I think you can come to that conclusion, regardless of what you think the status of those embryos is, because if they're simply going to be thrown out and no good comes of it, why wouldn't you want them actually to help people. And that's the level I answer to and people disagree with that. But the more people personally think about it, it's remarkable how many people come to the same conclusion.

• SUSAN DENTZER:

  It is a very utilitarian perspective.

• DR. THOMSON:

  Well, it is, but it doesn't change the outcome about those embryos being discarded. And you know, it's kind of hard to say, well, if they are going to be discarded, why don't you want good to come of it.