People Helping People: James Thomson

By David Wahlberg  |  Wisconsin State Journal  |  Link to article
July 31, 2009

UW-Madison scientist James Thomson was the first in the world to grow human embryonic stem cells in a lab in 1998.

The discovery, which involved the destruction of five-day-old embryos leftover from fertility clinics, has transformed biology, politics and Wisconsin's economy. Stem cells are now a hot topic in the governor's race.

Thomson, generally media-shy, recently spoke to Wisconsin State Journal reporter David Wahlberg about his research and the controversy surrounding it. Following is a slightly edited transcript:

David Wahlberg: It's been eight years since you derivedthe first embryonic stem-cell lines. Are you happy with the progress that's been made since then, or did you think more would have been accomplished by now?

James Thomson: I think it's kind of a mixed track record right now. I'd say that the progress could have been substantially more. The political process has certainly slowed down the research. But nonetheless it's been a terribly controversial area, and it's understandable that society took a little while to catch up with it.

I have to say that the biggest progress has been in public perception over the last eight years. At the beginning, people didn't know what to make about it. They weren't very well educated about it. But we've gone from a situation of complete confusion to where most people support this research within certain boundaries anyway. I think that's the biggest win - that even at a national level, within the Senate and the House, both of those bodies support this research in a way that they didn't eight years ago.

Nonetheless, we are eight years in and because of the political controversy, things have gone much slower in this field than they could have. We do have a president that's not terribly supportive of this research. Even though there is a compromise that allows federal funding, there is not a substantial amount of federal funding for this area of research. So even though it's possible to apply for NIH research dollars - and we do that and we're successful with it - given the importance of this field and the general enthusiasm for it, there's not substantial funding for it.

The National Institutes of Health is very supportive in this area of research. But given that there's tight federal funding dollars, if you were an institute director, would you be pushing for this particular thing in your portfolio when you know that your boss ultimately doesn't support it? I think that changing the amount of federal support is fairly critical, and I think that's only going to happen when you have a change of president.

DW: What about the scientific progress?

JT: We've done remarkably well considering these kinds of roadblocks in our way. If you go back, in 1998, there was general confusion about what could and couldn't be done. This was during the Clinton administration. From then until the time of the Bush administration, there were no federal research dollars for this at all. From 1998 to 2001, when President Bush made that compromise, investigators effectively couldn't use these cells in the United States because everything is really driven by those federal research dollars. Even though private industry, in theory, could take up the gap there, they didn't. The research basically was stopped for those three years because of the lack of dollars.

At the time of the federal decision to allow research funding for existing cell lines - although that doesn't represent really sound public policy in my mind, I think it's kind of an odd compromise - it did open up research dollars for the very first time and that's a big deal. It opened up in a way that researchers did get into the field, and it took a while, and we're just now seeing the fruits of that. That was in 2001. If you hadn't worked with these cells before, it takes you a year or two just to figure out how to use them. It's only now that the research publications are really going up.

I haven't recently looked at how the research publications are doing, but they're going up exponentially now. It went from one in 1998 to one or two in 1999 and now it's dozens or hundreds or something. It's a period of growth. There's certain natural rhythms that occur in science that you can't really speed up. For example, if you're a graduate student, it takes four or five years to get a Ph.D. That's how long a training cycle is and you can't make that one year. It's just physically impossible.

There were only a few labs doing this in 1998 in the whole world. We've been very good at training people to grow the cells in Wisconsin; the WiCell Research Institute has trained over 300 investigators from all over the world to grow them. It takes a while to get that into publications. We can differentiate these cells into a variety of cells of clinical importance. Given the fairly limited amount of resources and the fairly limited number of people working in the field up until now, the progress has been pretty good.

DW: Many people, as you know, talk about using stem cells as treatments or cures for diabetes or Parkinson's disease or spinal-cord injury and other conditions. Is that where the most potential lies?

JT: Yes and no. I think in a long-term kind of way, there are likely to be transplantation therapies based on these cells. The political process and the press have so hyped expectations that people expect to see these therapies in the next couple years. (That's) not going to happen. When anything brand new like this wants to enter the clinics, it takes a long time.

I can't remember exactly how long it takes for, say, the drug industry to go from discovering a drug to getting it into clinics. But it's like 20 years; it's not a year or two. That's for a well-proven kind of therapy, a small molecule. For cell-based therapies, people should anticipate that they will ultimately work. But there's going to be a long, hard series of events that have to occur before we get them to work.

You should look at other kinds of brand new areas. Gene therapy is a good example. I think (the stem-cell) field will parallel gene therapy quite closely. If you go back to the early days of recombinant DNA or gene manipulation, in the early 1970s, there was a very similar kind of social uproar to what happened with human embryonic stem cells. It was followed ultimately by compromise and the work getting done. There are still certainly segments of the population that disagree with that research, but it's gone ahead very well and people have benefited dramatically.

But if you look at those early years of recombinant DNA, people knew how important it was, but they weren't terribly good at predicting where and why it was going to be important. I think human ES cells are going to be like that also. One of the things people hyped a lot back then was gene therapy. If you had a genetic disease, now that we could do recombinant DNA, we could just repair it. I think that ultimately that will turn out to be very important. But we're now about 30 years in, and it hasn't become a dominant, mainstream therapy. There's been some limited success in clinical trials, but very limited.

Nonetheless, recombinant DNA has completely revolutionized how biology is done in this country and the rest of the world. Because it simply gave you this wonderful new research tool that's been important in ways we didn't anticipate, whatsoever.

It's certainly important in mainstream medicine, for making things like insulin. But it's also important for forensics and criminology. If you think back to the O.J. Simpson trial, it was all about recombinant DNA. If you think about daily products, there's recombinant DNA products - the whiter white stuff in Tide is a recombinantly made protein. It's become this pervasive, basic research tool that's dramatically impacted human medicine. Nonetheless, that one particular application is taking longer than people anticipated.

It's my personal guess that that's going to be the kind of growth of human ES cells. What recombinant DNA was, it gave us access to genes in a way that we can amplify them and study them for the first time. Human ES cells does that for the human body. Where we used to not be able to study the human body directly because we didn't have access to the material, now these cells give you access to the human body.

Now, in some cases, they may be used for transplantation. I think ultimately they will be. But that access to the human body is ultimately more important because it will give us a basic idea of how the body works and how it doesn't work in disease.

[Slideshow] If you think about a disease like Parkinson's, some people believe it will be possible to transplant dopaminergic neurons into their brain and treat that disease. I hope that that's true. But I think it's good to be skeptical. The brain's a very complicated thing. If you have death of neurons in your brain, simply injecting cells back in and expecting them to connect up right might be a little optimistic. Nonetheless, there's people in the field who believe that's possible. So I think it's good to be skeptical about that.

We can make dopaminergic neurons from human ES cells already today. Su-Chun Zhang on this campus has accomplished that, and others on other campuses have done that. Although I think it's good to be skeptical about transplanting those cells, I'm not at all skeptical about studying the basic biology of those cells. For the first time, they're accessible. They've never been accessible before. We might discover why do they die in Parkinson's disease. Understanding that is more important than the transplantation.

Because if you understand why and how they die, you can either prevent it in the first place or you can catch an early Parkinson's disease and prevent the progression. If you think about it, trying to cure something after the fact by re-injecting the cells is a very crude thing to want to do. You want to understand how the damage occurs in the first place and never let it happen.

I believe that as a basic research tool, human ES cells are qualitatively different than everything that came before. It gives us access to the whole body.

They may well be used for transplantation some day. There's some things that simply should work, like diabetes. There's already a transplantation procedure. They're starved for material because you use cadavers and there's not enough appropriate matched donors. I do believe once the cells are made they're ultimately going to be used for diabetes. But it's going to take a long time, and safety issues are a very significant concern. This is not true about just embryonic stem cells; it's true about any cell-based therapy.

If you think about diabetes, you live a long, productive life with Type I diabetes. Nonetheless, at the end of your life, there's fairly significant complications and your life expectancy is much reduced, even with the best therapy today. Nonetheless, if you introduced a cancer to a person, so that they got pancreatic cancer, that kills you pretty quickly. You want to be really, really sure that the thing you introduce doesn't create a worse condition than what you're trying to cure. In the case of diabetes, I believe this will be ultimately successful. But there'll be an awful lot of safety testing required before this actually gets into patients.

DW: If the basic research about human development is as important as the potential for cures, at least in the short term, how do you respond to those who say it's even more problematic to destroy embryos for research if it's not going to lead to cures?

JT: It is going to. It just won't make the front pages. There's an analogy which I'm always uncomfortable making. But it's unfortunately a fairly good one - because I think fetal tissue research and human ES cell research get confused in people's minds a lot, and they're actually quite separable, but some of the ethical concerns do overlap.

In the case of fetal tissue research, people have done transplants for Parkinson's in the last 10 years or so. I think it's fair to say they haven't been terribly successful. I think the average person receiving them hasn't had a dramatic improvement in quality of life. There's a little bit of argument about what the level of improvement is or isn't. But I think there is a general agreement on that. So the people that oppose the research would say, "See it has to be stopped, it hasn't helped anybody." The only reason is that's what makes the front pages.

But in terms of a basic research tool, there's a cell line called WI-38 which was devised at the Wistar Institute. I think it was in the 1960s, by Len Hayflick. That cell line has been used in the production of most, if not all, of the major vaccines in the United States since that time.

MMR - measles, mumps, rubella - polio, rabies, those are the ones that happen to come to the tip of my tongue. All of those were developed by that particular fetal-cell tissue line. Everybody in the United States who has been vaccinated has received a very significant health benefit because of that research. Vaccination is one of the most cost-effective ways to impact the health of the population.

It made a tremendous impact and yet nobody knows about it because it's kind of lost in the background of basic research. Human ES cells will be very similar, in that we won't be able to point and say, "Gee, that human ES cell was transplanted." But the basic knowledge, I have complete confidence, is going to change human medicine. I think that's a good thing and I think it justifies the work we're doing.

DW: If treatments or cures aren't developed within a few years, do you think opposition to embryonic stem cell research might increase? Might there be sort of a backlash?

JT: Yeah, I worry about a backlash predominantly because the field has been so overhyped. The people who support this research have made exaggerations in the (same) way that people who are opposed this research (have). There might be some early successes, and I hope that there will be. But for most diseases I anticipate a long, hard fight to get it to work. I think there could be, sometime in the next five years, a backlash to that.

But I'm not entirely sure that there will be. Scientists really try to communicate these problems. There certainly are some people who over-exaggerate, but most people are pretty honest about it. If they keep plugging away and explaining it better, I think realizations might settle down more gradually to where it's really going to go.

DW: Researchers have recently reported on new methods of obtaining embryonic stem cells without destroying the embryos. What do you think of these methods? And do they indeed remove the need to destroy embryos to get embryonic stem cells?

JT: Not really. That's a little disingenuous. It now appears to be possible that you can take, say, an eight-cell embryo, take one cell out, make an embryonic stem cell and not kill the other embryo ... It likely works. It's good if somebody repeats it, but it likely works.

[Audio] It has a very limited applicability. If you think about where these embryos are coming from, it's from couples that had a problem with infertility and they underwent in-vitro fertilization because they want to have children. For those couples, the most important thing is nothing jeopardizes that process. You don't want to even inflict a little bit of risk into the embryo. These procedures, while they can be done fairly safely, there's risks involved. You can damage the embryo. You can decrease the probability that it will result in a successful pregnancy. For the couples whose only goal is to have children, it doesn't make a lot of sense for them to subject their embryos to this process.

On the other hand, the couples might actually want to have a stem-cell line matched to their future children - in which case that risk is kind of balanced by the benefit to the future child because that embryonic stem cell line would be genetically matched with that child. There wouldn't be any problem with immune rejection. They could want to bank it away the same way people bank away cord blood. That does have a certain applicability, and some couples may choose to do that.

DW: But isn't this technique already used for pre-implantation genetic diagnosis? If the risk is already there, why not use it for something else at the same time?

JW: It's only done occasionally for people at high risk. If you have a familial background of a particular genetic disease you want to screen for ahead of time, there's a balance there. You're willing to accept it, whatever the risk is. I assume it's relatively small. But it is a risk, whatever it is. You have to have some possible benefit. For those people, they don't want these terrible genetic diseases to be in their children. So they do this genetic testing.

For the embryos themselves, unless you're saving a cell line particularly for that child, then there's no benefit to the parents for undergoing this procedure.

DW: What about some other methods that have been reported on somewhat, such as using so-called therapeutic cloning, or somatic cell nuclear transfer, and then altering the resulting embryo genetically so it could never fully develop?

JT: I know that there's a wide variety of people that find those methods promising. I find them somehow disingenuous. It's hard to articulate exactly why. But if you take just a few steps back, [Audio] my personal bet is that so-called therapeutic cloning will not be therapeutically useful in terms of applying those cells for transplantation. It's not that they couldn't be theoretically. I think there's no reason why the procedure won't work. It's more about cost and where the technology's likely to go in the next 10 years or so. I could be wrong because again my colleagues disagree with me on this.

But I believe that there ultimately will be other technologies to accomplish the same thing, that don't require a human oocyte. It's the cost of the human oocyte and the ethics of obtaining those oocytes in reasonable numbers. If you look at a population of Parkinson's patients in the United States with over a million people, there's such a mismatch between the availability and the demand that I think other technologies would be more suitable.

So that being said, there certainly are colleagues that believe that procedure should be pursued, and I could be wrong on this. But the genetic manipulation to avoid making something that somebody defines as an embryo ... I don't know, it just seems like sophistry to me. It just doesn't quite seem sensible.

DW: What are the other methods that you think would lead to genetically matched therapies quicker than therapeutic cloning?

JT: [Audio] The message of Dolly is not that we can clone sheep - or people for that matter. It's that the differentiated state is reversible. The only question now is understanding how that happened. Something in the oocyte is accomplishing that. There's a lot of groups around the world trying to understand what the oocyte is doing to accomplish th at reprogramming.

There's recently a paper out of Japan that showed that you could take a particular adult cell type from a mouse, and with a series of particular genes, transcription factors, you could revert it to something that was pretty close to embryonic stem cells. It wasn't exact. It's not quite there yet, but it was closer than I thought it would be this soon. Although it's not completely done, and the same transcription factors didn't work for human cells, it looks like it's a solvable problem within a reasonable timeframe - a decade, not tomorrow necessarily. So it's clear that it's a solvable problem.

If Dolly hadn't been cloned, we wouldn't have known this was even possible. But because Dolly was cloned, we know that there are sufficient things in the oocyte that allow this process to take place. It's just a matter of time before we figure out what they are and replicate it. That Japanese paper suggests to me that this will happen relatively soon rather than later.

DW: Since we're talking about therapeutic cloning, I just want to ask: is there a difference between therapeutic cloning and reproductive cloning?

JT: It's all a question of definition. The powers-that-be are trying to have scientists call it somatic cell nuclear transfer, because the word cloning is so emotionally loaded. Be that it may, therapeutic cloning is kind of in the mainstream and is used right now. (With) therapeutic cloning, the idea is that you're doing this procedure to make a stem-cell line and you don't use it to transfer to uterus to make a baby, which would be the other one. Yeah, there's a big difference.

DW: OK. The process is the same, but the application is different?

JT: Right. It's where you stop. Simply based on safety reasons, trying to actually clone an individual is not a good thing to try to do.

DW: Many people prefer to support research on adult stem cells, which can be taken from blood and in some tissues in children and adults. Umbilical cord blood also contains such cells. How useful are these cells compared to embryonic stem cells?

JT: [Audio] This again is more a product of the political controversy and the press. If you look within the scientific community, the perception is very different. There's no real battle between, "Is adult stem cells better than embryonic stem cells?" It's all kind of a continuum.

When you're a scientist, you pick a model based on the questions you want to ask. Sometimes you pick model organisms like fruit flies, or mice or rats, and you pick the model based on what's the best one for the particular question you want to ask.

For some scientific questions, embryonic stem cells are simply better. If you think, for example, (of) blood. When you have bone marrow transplants, that's a hematopoetic (adult) stem-cell transplant procedure. It's cured thousands of people. People have studied these hematopoietic stem cells for three, four decades now. It's by far the most widely used stem-cell therapy at all. It's very successful.

Nonetheless, people have never figured out how to grow hematopoietic stem cells. There's been some progress in recent years. But you can't simply take a hematopoietic stem cell out of the body, put into tissue culture, and let it divide and grow a lot of them. People have failed for the last 30, 40 years of doing that. There's a lot of clinical reasons why you'd like to do that.

Already we can take embryonic stem cells and differentiate them into blood. We and other groups study that process. At the end of the day when we have the knowledge from that process, it's not clear whether it'd be applied to adult stem cells or embryonic stem cells because there's no dividing between the two.

 

 

 

But if you want to study adult hematopoietic stem cells today, you've got to go to a patient or get a placental sample, you take this little elusive stem cell into your lap, and Poof! it goes away. Then you gotta go back to your patient again and get another one - and Poof! it goes away. With embryonic stem cells, it simply gives you a continuous source to study this particular lineage.

At the end of the day, I don't know whether that knowledge would be more fruitfully applied to adult stem cells or embryonic. It remains to be seen. But the knowledge is what the important thing is.

DW: California has started a $3 billion stem-cell research initiative. Other states, including Connecticut and New Jersey, are also contributing state money to this research. Is Wisconsin still a leader in this field? Is the state in danger of losing its prominence?

JT: [Audio] We're already losing people. The person from WiCell (Ren-He Xu) moved to Connecticut to assume a lab directorship to get access to that state money. The first person to actually show hematopoietic differentiation from human ES cells in my lab (Dan Kaufman) took a faculty position in Minnesota instead of Wisconsin. I suspect that pattern will continue. Nonetheless at the moment we are the leaders in this field. If you look at the total number of publications of this institution versus, say, Harvard, for example, we're way ahead of them. But other people are starting to outspend us. California is only one. Harvard has a program to get $100 million for their stem-cell institute as do some other institutes.

We need real research dollars if we're going to compete with those other places. Right now we're largely dependent on federal dollars. We've been very successful in competing for those. But as these 300 other labs we've trained to grow the cells go out and start writing applications and the amount of the pie doesn't increase in Washington, even if we're very successful, our percentage of that is going to go down. It's just going to happen. So, yeah, I am worried about that. The California one in particular, that's a lot of money. That's $300 million a year. There's a relatively small number of stem-cell researchers currently in the state of California. But even if there's a hundred, and there's not, that would be $3 million a lab. There is no comparable investment in this state.

DW: Do you think federal funding for embryonic stem cell research will be expanded after President Bush leaves office?

JT: Yeah, I think it's pretty inevitable. Especially as the field really starts to accelerate. There is a mismatch between public perceptions and when the therapies are going to come out. But there's not a mismatch in terms of what can be done in basic research with these cells. As more and more labs start to do good basic research, there's eventually pressure on the federal government.

[Audio] The Nixon war on cancer resulted in the cancer centers. If you think about the history of medicine, we've kind of tackled infectious disease early on. And antibiotics, we were very successful with that. But some things like AIDS are coming back to haunt us. Nonetheless, we've had a huge amount of success as a society with infectious diseases.

Then there's been a very large investment in cancer since the 1970s. It's starting to pay off, although it's been fairly slow. What's left over is all these degenerative diseases, which are becoming increasingly important in society because of our aging population. In the same way that Nixon started the cancer centers, I think there's a real need for something along the lines of regenerative medicine centers. Embryonic stem cells are not all of that. They're an important little niche of that. But I'd love to see somebody from the top up push that kind of agenda. Given the current administration, it's not going to happen now.

I don't know if it'll happen after that. But I have to be optimistic that as the administration changes, they'll be increased funding for this.

DW: Given the ability you and others have had to make accomplishments with private funding, how much does it matter if federal funding is expanded?

JT: Oh, 80 percent, probably, I don't know exactly, of my lab is federally funded. We have not received an awful lot of private funding in this lab. It's unfortunate because part of it's perception.

The governor has announced this $750 million (biotechnology initiative, including the $150 million Wisconsin Institutes of Discovery to open in 2009 at UW-Madison). It's a good thing, but none of that's going to research. Everybody assumes it's getting flowed into embryonic stem-cell research, but it's not. It's mainly buildings and infrastructure, which are things that need to be invested in. But it doesn't allow us to compete in the short term with a place like California, where they're predominantly putting it into basic research. We haven't had a lot of private funding relative to our federal funding. Our federal funding is critically important.

DW: What impact might the outcome of the governor's race in Wisconsin have on stem-cell research in this state? Are you worried that Mark Green might make it more difficult to do the research?

JT: I want to stay away from politics as much as I can. Clearly I have my own personal opinions on this matter. I would say that the two candidates appear to have strongly different opinions on the subject. It would behoove somebody that's going to cast their vote to educate themselves on what their positions are on this subject. I think I'll leave it at that.

DW: Are there any specific obstacles you're concerned about that could be brought into play in Wisconsin? For example, are you concerned that Mark Green says he would want to ban therapeutic cloning?

JT: [Audio] Mostly I'm concerned about perception. We have major competitors out there, and the state is not currently investing in this research. They hope to make some buildings, and that's very nice, and that's very positive. If they go beyond that and make it sound restrictive here, it's going to be really hard to recruit people to the state of Wisconsin. It's hard already just because of the dollars. But if you make it even worse, it's going to be very, very difficult to get talent to come here. At the end of the day, the talent is more important than the dollars. The dollars follow the talent. But if you can't get them here somehow, it's a problem.

DW: Would a ban on therapeutic cloning be that kind of (obstacle)?

JT: Yeah. We don't plan to do that. I don't know anybody in the state of Wisconsin that plans to do that. So people could say, "Well, what's it matter?" It matters because of the perception.

It also seems to me that since it's not a problem, nobody's planning on doing it, couldn't we legislate some things that are a problem, that we actually need? Spend your time on something else because it's not helping anything. It's just grandstanding. It sends a very specific message to the rest of the country. It looks like we're anti-science here.

DW: Is the United States still leading in stem-cell research, or have other countries taken over?

JT: I'd still say the highest quality publications have come out of the United States. Britain has had very liberal legislation, and they're finally kind of kicking in. But their research dollars aren't as high as here.

But it's going to be California against the rest of the world with that amount of money. On a per capita basis, we'd have to be investing about $50 million a year to be equal to California. We're not doing that.

DW: What about places like Singapore?

JT: Yeah, I think Singapore might ultimately make important contributions. But they haven't done a whole lot yet. Certainly they've published some things, but most of the significant research has been dominated by the United States. There's exceptions to that. It's not absolute.

Certainly Britain's making a lot more, and Israel's published a lot and Singapore has published. But I would think that ten years from now, if the dollars flow as they're currently set, California will be the dominant researcher in this area.

DW: Your lab recently announced the creation of the first stem-cell lines known not to contain animal products, which could make them safer for use in humans. What's the latest on this development?

JT: There's no real change. The Bush compromise doesn't allow federal funding for that, although we do have some private funding to actually allow the derivation. All this nice equipment we have around us is intermingled with private and federal funding. We haven't done a lot with those cell lines. They're in the freezer now.

We did that as a proof of principle. It shows that it can be done. We would like to be able to expand those efforts. But given the realities of federal funding, we probably won't be doing a lot of research on those cell lines for a while.

DW: What else are you focusing on at your lab and at your company, Cellular Dynamics?

JT: They're very separate things. Within my lab, I'm interested in the basic biology of these cells. There's something very special about why one cell can give rise to everything else and most cells can't do that. It's called pluripotency. I'm very interested in how that's regulated and how that works. If you really understand that, then this reprogramming thing that Dolly does might become possible.

In one way or another my lab is either studying this basic concept of pluripotency or how the cells decide to become something else or sustain themselves - self-renewal versus differentiation - and that balance and how that balance works. We've kind of stepped back from some of the practical issues to look at this somewhat more basic biology issue. We continue to collaborate with some of the MDs on campus that have particular lineages of therapy with importance. But I didn't want to get so spread thin. I decided, this is the thing I think is kind of cool, and we'll concentrate on that.

CDI is very separate from my lab. We're going be a service toxicology company. In particular, we're going to focus initially on cardiomyocytes. Human heart cells don't divide in culture, so you can't make a human heart-cell line. It's almost impossible to study human heart cells because if you have a normal heart it goes to a donation program. What researchers are generally restricted to are just biopsy samples. They come at odd hours of the night, and very little material, and so it's almost impossible to directly study the human heart.

Human ES cells already differentiate to human heart cells at a very reasonable frequency. We've published on that as have others. Craig January is an investigator here, who is a cardiologist, who a number of years ago developed a particular assay for a particular kind of toxicology of the heart. It's called a HERG assay. The electrophysiology of the heart is altered when this particular channel is blocked.

There has been a whole bunch of drugs that just by chance happen to block this channel. I think it's called prolonged QT polarization. Things like antihistamines have caused blockage of this channel. They've had to have been withdrawn from the market. Something you take for the sniffles ends up killing people. It's really important to be able to screen for that early in the process rather than later. Because the physiology of animal hearts and human hearts is different, it's not been very easy to screen for these things.

He developed a very specific assay to look at this HERG blocker. It's become the gold standard internationally. We will start doing HERG screening not on human ES cells, just on his standard assay because he's good at it. We will migrate to doing comparable assays and cardiomyocytes derived from embryonic stem cells. Because there is no other source of human heart cells. There's been a real big need to (toxicology/pathology) on human heart cells. That's coming along well.

DW: What do you think the state of embryonic stem cell research will be in another eight years?

JT: What I hope it will be is that it will no longer be on the front pages. It'll simply be an accepted, general research tool. When's the last time you've seen headlines about recombinant DNA? You haven't, right? It's been couple decades now. Yes, (genetically-modified) organisms come up and things, but for the most part it's accepted, mainstream science.

I look forward to the day when this is accepted, mainstream science. Every single medical school in this country will be doing this research. Most of them will not call them stem-cell researchers. Because they'll simply use it as a tool in whatever their day job is, whether it's cardiology or studying the pancreas or whatever. This fad of calling yourself a stem-cell researcher will go away. But the basic value of the tool will not go away. The same way with recombinant DNA; everybody uses recombinant DNA now. Early on, they made molecular biology institutes. They're still around. But basically people just incorporate it into their day-to-day research now, and everybody uses it.

I think eight years from now, that will either be a reality or close to a reality. I hope that there are such things as regenerative medical institutes. There'll be adult stem-cell research and embryonic stem-cell research in a kind of collaborative environment. It will just simply be an accepted, everyday tool.