Stem Cell Pioneer

Text by Tim Hyland
John Gearhart, IRM director, and research teamPhoto credit: Candace diCarlo

Penn’s Institute for Regenerative Medicine was created for the sole purpose of encouraging groundbreaking discoveries in stem cell biology.

So it’s hard to imagine there could be anyone more qualified to lead this center than John Gearhart—the scientist widely credited with creating the very field on which the IRM is built.

Formerly the director of stem cell biology in the Division of Developmental Genetics at the Johns Hopkins University School of Medicine, Gearhart became a science superstar on Nov. 10, 1998. That was the day he published a paper in the Proceedings of the National Academy of Sciences revealing that he and his research team had become the first group to identify and isolate human embryonic stem cells. Gearhart’s breakthrough, which was considered a important first step toward development of a whole new generation of drugs and therapies for all manner of diseases, was instantly hailed as a milestone in modern medicine. It also quickly became one of the most hotly contested issues in American politics. It remains so today.

Though Gearhart has worked tirelessly in the ten years since his groundbreaking study to inform policymakers about the work, federal regulations continue to limit research on human embryonic stem cells. There also remains some misunderstanding about just what Gearhart and other stem-cell researchers are doing—as well as unrealistic expectations for what is really possible, at least in the short term.

Which is not to say work is at a standstill. As the director of the IRM, Gearhart will lead the effort here at Penn to encourage research that could open up new understanding about the very basic workings of human cells and, eventually, help scientists find new ways to attack disease.

Gearhart’s research is currently focused on the role of genes in regulating the formation of human tissues and embryos, especially as it relates to mental retardation, Down syndrome and other congenital birth defects.

Q. Looking back on 1998 for a moment, the release of your paper, and the reaction it drew must have been a very interesting experience. What do you remember about that?
A. It was one of those stories where, all of a sudden, it got bigger than the science, if you know what I mean. Everyone was captivated by the issue of using these cells for therapies, and we were more realistic about what we were doing. We were saying, ‘We’re really more interested in the basic biology here, and if in the end either the use of these cells or the information we obtain from those cells can be applied to new therapies, that would be great.’ And since then we’ve been working from both the basic science side and then perhaps trying to apply some of this information we’ve gathered to so-called cell-based intervention or therapies.

Q. Generally speaking, where is your research focused today?
A. From the basic science side, we’re looking at the development of the nervous system … and some of the major neurological diseases for which we have no therapies. We’re very interested in the heart and some other tissues as well. We’ve done some very nice gene discovery studies and we’ve also been able to develop protocols for generating cell types that are appropriate for cell-based interventions. In two minutes, that’s sort of what our focus is and what our interests have been in a scientific sense.

This [kind of research] really is a very powerful tool. But I’m also very concerned about the public perception of this. That initial reaction was, ‘OK, now that we have these special cells, therapies are right around the corner.’ But we know certainly that, even regardless of the political atmosphere, it’s really going to take a while to get to that point.

Q. How much time do you spend dealing with the political issues around your work?
A. I’ve made, I don’t know, 140 or 150 trips to Washington based on these cells. I’ve lost count. We have some more hearings coming up in the fall. It was clear from the beginning that we had a lot of issues on the table and [we had to do a lot of political work] if we wanted this work to go forward in an unfettered way, and in a way in which you would have appropriate oversight, but also have these cells eligible for funding. Well, we still haven’t reached that point. Here we are ten years almost to the day from my paper, and we’re still striving for that. And yet I believe very strongly still that we have to get out there. We have to play a role in not only having our policymakers understand what these cells are about and the importance of them, but also the reality of them. It was always very difficult, for example, to be at news conferences, where senators and representatives and their staff would be touting how important these things are and how soon we’ll have cures, and you’re sitting there like, ‘What?’

Q. How have you dealt with that?
A. I have become very much engaged in the policy end of things, at not only the national level but also the state level. I’ve traveled extensively. I’ve talked a lot. I’ve worked with the states and their policymakers and some of what I’ve done has been successful. Then there’s the international stuff as well—going to different countries and explaining what we’re doing. This is the policy end of things, and for me—I had been a lab-bench scientist—it was very different all of a sudden being thrown into this debate. But after a while you begin to recognize some issues within our society—the lack of understanding of science, or the attitude among scientists that we ‘deserve’ to have this funding even if we’re going to make very little effort to help people understand what the heck we’re doing.

Q. There has been some concern in the academic community about lagging federal research funding. What’s your impression of the situation?
A. Talking to very senior policymakers on strategy, it’s very interesting. From the outside, you might think health funding and whatnot is guaranteed. But it’s a struggle just like anything else. And that’s not just funds for stem-cell biology. You also learn how conservative some people can be. They’ll be up there damning you, but after [a hearing] they’ll sidle up alongside you and say, ‘My wife has this disease … what can do you for us?’ That happens all the time. … The very first question I think I was asked in a congressional setting was something like, ‘Dr. Gearhart, how does it feel to be killing the littlest Americans?’ So you have to learn to roll with the punches, and you have to give as good as you take. These people aren’t gods.

But I think the important issue is one of informing [the public]—of trying to spend as much time as you can with business organizations, garden clubs, churches, synagogues. I’ve done all of those things over time. And I think one reason why, in Maryland, our state didn’t have much trouble putting money into this … is because people began to realize where we were. I even went on a retreat with the National Convention of Catholic Bishops. That may be a losing venue, but the points still have to be made, and you also have to understand their concerns.

Q. Have you been surprised at the strong, ongoing reaction to your work?
A. I was surprised, yes. I wish I could sit here and say I saw it all coming. But I didn’t.

I guess I was looking at this as a research tool. But as we look back on the events of November 1998, there were some floods in Southeast Asia, you had Newt Gingrich announcing his resignation, but there was a gap, too, into which all of this stuff got dumped out. And I think the issue became that people were thinking we finally had a source of cells that could provide anything one would ever need [for therapies], without appreciating all of the issues involved.

In the days after these papers came out, we got thousands of emails from people in desperation [looking for cures]. I felt it was necessary to take an active role in the public side of things, and we’re still doing it. No matter who is asking [for information], if people ask for help, let’s at least provide them with whatever factual information you have that could be helpful for them in making a decision.

Q. How does this ongoing public relations responsibility impact what you’ll be doing here at Penn?
A. I think all of this impacts on the role of this new institution, the Institute for Regenerative Medicine. I look out at what we have here and, yes, the primary purpose of this institution is to really facilitate research and develop therapies. I don’t know if they’re going to come from embryonic stem cells. They may come from our knowledge of embryonic stem cells. But that’s our main charge—to try to organize research programs that would really facilitate getting some of these things into a clinical setting.

But with that comes this other responsibility, of helping policymakers understand us, of education, of talking to your colleagues and saying, ‘Look, we have to take a more proactive role in selling science and getting as many people as we can to understand what’s going on in science.’

Q. You’ve talked a lot about dealing with policymakers. What has your experience been with patients?
A. The only time I’ve really been harassed has been talking with patient groups. They came to hear me speak, and they still do, but when I do … they want to hear this ‘savior.’

But the message I deliver is a realistic one—that I don’t know whether what we’re learning now will ever be applied to them, but that we would hope we would have something for their children. We’re trying to put this research in a context of reality, but many people don’t want to hear this.

I also still get a ton of email. Somebody will write and say, ‘My daughter has a brain tumor’ or something else, and when you write back, you try to use conventional medicine. I’ll ask, ‘Have you really talked to some good people about what the best current interventions might be?’ And many people, maybe [because of where they live], will say, no, they haven’t. But then being realistic about [cell-based therapies] you have to say there’s nothing available.

The follow up question is then, ‘I heard there’s a clinic in the Caribbean or Beijing or someplace that uses cells to fix spinal cord injures,’ and you have tell make it clear that you should avoid these things—that it’s not real medicine. And they get angry, but there’s nothing you can do about that.

Q. Since so much of what you talk about seems to be about managing expectations, I have to ask: What can we really expect from cell-based research? Are cures possible?
A. First, I’d like to say, I do put more weight on the information we’re getting out of these cells—discoveries about how cells specialize, for example. These are tremendous resources, just tremendous. And it’s really this information that will allow us, ultimately, to be able to instruct our own cells to do what we want.

You can put some cells in there to help maintain other cells longer. We’re already seeing some evidence of this. We’ll be able to use this for better outcomes and better treatments. But the other issue people don’t understand is that it’s going to take teams of people. It’s not going to be some little lab coming up with a cure for whatever—it’s going to take resources.

I mean, we can right now grow in two weeks enough neurons to provide everyone in the world suffering from Parkinson’s to have enough cells for a graft. You can do tons of those things. But that’s not the answer. Because how do you shut down a process that is ongoing? You can imagine us putting some cells in there, but so what? They’ll be subject to the same pathological processes.

We have to understand those processes, we have to understand how to graft cells, we have to understand the safety issues—on and on and on. It’s going to take big groups of people to move these kind of things into a clinical setting.

But you have them here at Penn. It’s a major medical institution. And I think we’ve got to be involved in the private sector, too. … And I think the message I would have is that … what we want to know how to do is this: How do we get our cells to do want we want them to do?

Originally published Sept. 4, 2008

Originally published on .