Interview: John Gearhart
Stem Cell Research

We understand you grew up in an orphanage in Philadelphia. How did that come about?

John Gearhart: This was a decision that my mother had made following the death of my dad, who was a coal miner in Western Pennsylvania and I was placed in an institution called Girard College, which is sort of a strange name, but it was one that was set up by Steven Girard who was a banker and merchant and mariner, who funded the War of 1812 almost solely by himself, which is interesting. A very wealthy man and he had set up an orphanage, and so I was placed there for ten years.

I spent ten years in the inner city in Philadelphia from 1950 to 1960.

What ages were you then?

John Gearhart: From six to 16 or 17, from first grade through high school.

Did you have brothers or sisters?

John Gearhart: I have two brothers, one older and one younger. The older one was sent away as well and the younger one remained with my mother for that period.

What was it like in the orphanage? What sort of education did you get there?

John Gearhart: I was in an accelerated group within the class in 12th grade, and all of my classmates were going to college. It was a very good place to learn academically.

It was a regimented school kind of a thing and they had control of you for 24 hours a day. So you were up at study hall at 5:30 in the morning, then you would have breakfast, then you would go to school, and the academics were very rigorous and everyone did extremely well as you can imagine. I mean, in the evening you had another long study hall so you really learned some good kinds of habits which I would say I carry toady. I get up extremely early in the morning -- at 4:00 o'clock -- and I study and I read.

This is when I do most of my stuff, so there are some good things that came out of that.

What person inspired you most as a young person?

John Gearhart: I don't know. My heroes were all athletes at that time. I lived in an all male institution. Testosterone levels were extremely high. Athletics was the big thing.

Who were your sports heroes? Any particular athletes?

John Gearhart: Oh sure. There were always the Mickey Mantles and any baseball or football stars, that kind of thing. No real heroes though.

We were disconnected, I mean from the world, in the sense that this institution had -- a remarkable place -- it had a wall that was 12 or 15 feet high. It was up the street from the Eastern State Penitentiary. It looked every bit like it. We were only allowed outside these gates for brief periods of time so it was really like a little, you know, sequestered -- although there were a thousand kids in there. It was a very isolated kind of a thing.

Were there any books you read when you were young that meant a lot to you?

John Gearhart: We had an English teacher at Girard by the name of Caswell MacGregor, who gave us a very classic English kind of literature and vocabulary, as part of our academic foundation. We were exposed to a lot of the English literature you would expect to see coming out of Eton or Rugby, this really hard-lined, institutional, all-male kinds of literature. I remember some of these things having an impact.

Was there any particular book that influenced you?

John Gearhart: No, I can't say there was any particular book. I think it was that whole genre of stories of male interactions and life in these kinds of institutions. At that time I wasn't into reading. My real reading didn't begin until I was actually a post-doc years later, so I had a lot of making up to do, going back and reading a lot of the classic things. I'm an intense reader now. I read everything. I don't do TV. Whenever I have time, I read a lot of books.

What about that post-doc period, were there books that were particularly meaningful?

John Gearhart: Oh yes. Milan Kundera's books, H.L. Mencken, Mark Twain. Everything interested me to be honest. Arrowsmith was very important, Sinclair Lewis's book. This was a very important book because Arrowsmith paints a very good picture of being in science and medicine. It is one of the very few books in fiction that really makes a very positive presentation of what it's like to be in medicine or science.

If you look at the scientists in literature, it is always very negative. It's -- you know, manipulating, always mucking around where they shouldn't. You know that kind of thing, the Frankenstein portrayal. I mean, this is what scientists were about. But Arrowsmith I really, really appreciated and I still do, and I urge my students. Now that we are now on this cutting edge of reproductive technologies and clonings and stem cells -- which are all thrown together now -- I find myself before groups trying to talk about the scientist and the responsibilities of a scientist in our society.

The perception of the scientist has been so negative for such a long time, and it still continues to be when you see someone saying we should be cloning humans, and the stuff that's going on in in vitro fertilization clinics and things. You get people saying, "Wow! What are these people about?" So I am very responsive now to arguing for the role of the scientist and what it should be, to bring credible and accurate information to the public, to be very candid about the social implications of our work, to be involved in the whole process of policy determination.

When did you first become interested in science?

John Gearhart: Probably when I was completing high school. I came from a farm family. Science interested me, the ability to manipulate science in a way that we could benefit from. I was very interested in crops, believe it or not. This was something of great interest to me, trying to provide healthier, faster-growing crops.

Where was the family farm?

John Gearhart: It was in Western Pennsylvania, in the Allegheny Mountains. I was there for a fairly brief time before I was placed in the orphanage.

A lot of kids would have felt a sense of lowered expectations in that environment, but it seems like you've always had high expectations about what you could achieve.

John Gearhart: Yes, but when I left there I had no idea what I wanted to do.

I know I didn't want to go back to Western Pennsylvania, a very depressed area. I mean, it was a -- but I really didn't -- and I sort of went along on this -- what I was saying is that the people in this group that I went with, there was 25 or 30 of them; they all went to college, so the thing to do was to go to college. And, I remember the counselor at the time saying, you know, essentially "You are not going to amount to anything." I mean, it was very -- a very hard kind of an institution. You know, "Why waste your money on college."

So he could tell that I was sort of a mediocre kind of a student. No real, you know expectations of anything. So I went to college and then did extremely well there because I had -- I mean, I had never had a glass of alcohol in my life. I had never had any association with females. These things we were taught were not good things, to be honest with you. I mean, it is bizarre but this was our teaching. And so I went through the first year or couple years of college just with the same kind of regimen that I had, and did extremely well. I thought college was a piece of cake. And then the third year I found these other things and you know, plunk! I mean, for quite a while I was in a tizzy and then came out the other end of this fine.

Other things meaning alcohol?

John Gearhart: The alcohol and the women. Yeah, that is right. Many of my fellow students from Girard found these things earlier than I did and they didn't survive college. They couldn't make up. They have these GPAs you are supposed to keep up, so many of them floundered and had a problem. I was fortunate that I had a base first before these things struck. Then in college I just fell in love with genetics. I was enthralled with genetics.

You have made such dramatic developments in science, do you now look back and see the seed of that scientist as a kid? Did you have a feeling you were going to achieve something considerable even when you were growing up?

John Gearhart: No, not at all. To be honest with you I just didn't know what I was going to do. I don't want to give you the impression I was just flopping around for decades and suddenly fell into something. Not true.

My dad had, before he died had actually -- He was one of the first people to sign up for Social Security, and this is what put me through college, was the funds that had accrued during that time. And I had gone to Penn State University with an interest dating back to those farm days of wanting to do something in agriculture and horticulture.

I went into an area of horticulture and of plant breeding which was the real hot genetic area at that time, trying to improve on corn, wheat, all kinds of crops. But crops weren't fast enough; it took years to develop something.

When I started in college I wanted to be the best pommologist in the world, to grow apples and pears and peaches and things like this. Breeding was the thing to do to improve those crops, but it takes decades, as you can imagine, to breed an apple tree and see what is going to happen. This led me into other areas of plant breeding and into floriculture. I was breeding snapdragons and geraniums, and things like that. I actually got some All American selections out of these things. That was fun; I had a good time with that.

I got interested in animal genetics, and particularly the model system, which was this fruit fly drosophila, melanogaster. I got my Ph.D. actually studying that and then I wanted to extend it immediately to humans if I could. Now, this is an era where the genetics of human beings was in its infancy, but I decided to go through the mouse as a model system. The model, the mammalian model at that time, of course, was the mouse, and then 30 years later I am finally into humans, where I wanted to be many, many years ago, and having the resources and having the environment at Hopkins now, where I am Director of Research in Obstetrics and Gynecology. My interests are still in human development and what controls it, what regulates it. I am very interested in the basises of congenital birth defects, what is the cause of them, and then how we can ameliorate the problems with them.

Were you in contact with your mother after you left the orphanage?

John Gearhart: I saw her (my mother) a couple of times a year but for fairly brief periods, and didn't really get to know her until she developed breast cancer and came down to Baltimore and was admitted as a patient, and so sort of in her terminal several months of life I spent a lot of time with her trying to find out who the family was, who she was. Anyway that's what happened.

Was there a point when you went back to see your mother and told her you were going to be a scientist?

John Gearhart: Oh yeah. She had remarried, and it wasn't until after her death that I really got to know my stepfather, who is still alive. They thought I should return and work on the farm. They wanted help on the farm and it was almost as if they thought too much education is not good for you. This was in the era of the hippies. To return home at this point with long hair down the middle of your back in that culture! I remember one time I drove home. I had purchased a little foreign car; it was the only thing I could afford. The fact that it was a Japanese car and everything, that was just the wrong thing to do in this community in Western Pennsylvania. It was a cultural thing.

Did you stay close to either of your brothers?

John Gearhart: No, I didn't. It was only years later that we began to forge a relationship. I'm still trying to get to know them. My older brother is 58 or so, and my younger brother is about 50.

Did they go into any similar fields?

John Gearhart: No. My older brother went to work in construction immediately and he has been doing that ever since. He's worked his way up and now he's the president of a construction company in Western Pennsylvania. My younger brother went into the service, which is the normal thing people in that area did, and then took a job in one of these huge energy producing stations, with coal, and has worked there ever since.

Was there a teacher that was really important to you?

John Gearhart: Yes. Absolutely. A person by the name of Jim Wright, who was a southerner, who taught the introductory course in genetics.

To this day -- I mean, I've written him, I've seen him in meetings and things, and he -- I'll never forget it -- when I took this course I didn't understand anything about genetics and I did very badly on the first exam because I just couldn't get into the vocabulary, into the concepts. I was really having difficulty, and then it just opened up to me and I just completely understood. I mean, it was never again a problem. Jim Wright, just a dynamic, dynamic individual. And from then on in I was stuck on this, but I applied it more to plants. You know, I was still in this mode in plant breeding. I did my honors thesis on looking at the pigmentation that you see in flower petals and the pinks and the -- particularly the pinks and the purples and reds -- and I figured out the genetic pathway that went through these different colors. They are called Athysanuses. And that was my honors thesis as an undergraduate.

When I finished that honors thesis I was still trying to figure out what I wanted to do with my life; I still didn't know. My thesis advisor at the time -- a person by the name of Dick Gregg who was another very important person in my life -- said, "Why don't you go to spend some time with Owen Rogers at the University of New Hampshire." I said, "The University of New Hampshire? I've never heard of this place." It was far away. I had never been further than ten miles from any place that I'd ever lived. He said, "Rogers is a wonderful person. Go and just spend some time with him." He was just a very laid back really wonderful person. So I enrolled in the master's program at the University of New Hampshire and went up there and I became a world's expert on lilacs. It's the lilac state, so the plant breeders all worked on lilacs. I was a big hit at garden clubs where I would come in and I'd identify all these different lilacs. That was fun.

The advice I had gotten from my undergraduate thesis advisor was the best advice I could have. He told me to go and just hang out with this guy in New Hampshire. It gave me an opportunity to think of what I wanted to do and put my plan in place. I knew out of that that genetics was what I wanted to do and I applied to the best genetics program in the country, which was at Cornell University, a long history in genetics, powerful programs, and was accepted there. From that time on I knew what I wanted to do. I had made the commitment. The interest was there. I got a great deal of excitement doing the genetic experiments, trying to figure out how these genes actually controlled or regulated the development of a plant or an animal. I'm still at it. The excitement from this comes in two parts. Not only in achieving an endpoint.

I think for most scientists the fun is in the journey. You know, what I mean? Of being in the laboratory, of knowing that you can do whatever experiment you want to do, but it has to come from you, and you have to think about what the problem -- what the questions are, how you plan that experiment, how you execute it, what controls you use. You know, interpretation. This to me is the excitement.

And the end, in reaching a goal, yes. Since then I have been on track going from drosophila in this little fruit fly, which still is a model genetic system without exception. I wanted to take this into something that I thought was more relevant, which was the mouse. A mammal, closer to humans. Gosh, we could understand this! When I finished my doctoral work I took a post-doctoral position looking in the genetics in development of the mouse. A lot of the genes that we know about in the mouse, we know about in humans, so I worked in the mouse for a number of years. This was a very important transition.

I was interested in identifying genes that were important at the very early embryonic stages in the mouse. In other words, right after fertilization when all of your body -- or when all of the mouse's -- body plan was being established, and what were the key genes here for doing this, and I worked for years on this. And I had a little ancillary problem going on in the lab. I was interested in Down's Syndrome. Now this is a very complex chromosomal disorder. It's the largest known genetic cause of mental retardation we know about. Every day in the United States there are 12 children born with Down's Syndrome. It's a major clinical problem as you can imagine, but I was interested in it from the standpoint of saying, "What if you have extra genes in your genome? What is this whole genetic dosage business, this balance of genes? How does that impact on development? I began a project in the mouse looking at this, but in the interim I was doing all these other things that were my main interest, NIH funded, et cetera. Over time this ancillary thing became the main thing. For years I published [research] using the mouse model to recapitulate in the mouse what was seen in humans, what we understand about mental retardation. I'm still very actively involved in this.

"Gosh, we've isolated these! We've used them for targeting the mouse genome. We've used them in tissue culture. Wouldn't it be nice to have human embryonic stem cells?" So that ultimately -- and this is where we are going -- that in a laboratory setting we could have in a dish, just in dishes, control cells that are going to form muscle, nerve, whatever other tissues we want.

Virtually any tissue is affected by these extra sets of genes. So we're now getting down to the level where we can begin to measure this, rather than having to take biopsy material or something which just doesn't work very well. This is what got me into the area of wanting to get human embryonic stem cells, and we started on this in 1993. It took a couple of years to get approval, as you can imagine, to get access to tissue, and then to begin the actual experiments of trying to derive that tissue. I think this meandering career -- going from interest in plants to invertebrates, to vertebrate genetics, and then into humans and applying this to clinically relevant things -- I think this reflects as a scientist, the freedom that you have. The interesting thing here is that the thread of this is all the same and that is, how genes are regulating and controlling developmental processes? Whether you are looking at this in a plant or a fruit fly or a mouse or a human, these processes are all the same, but you have this ability and this freedom, if you will, to go from one system to another.

Where do you see as the next great frontier in this? There are so many medical implications of what you're doing.

John Gearhart: As you can imagine, the press has put us in a very awkward position. When we report scientific progress we are very conservative in what we're stating. We say, "Where are we right now?" Okay. Where we are right now is...

We have been able to demonstrate -- I mean, Jamie Thompson and myself using different procedures -- that you can isolate and have in culture these very important cells that have this ability of replicating in culture and then, under the right conditions getting them to -- what we call -- differentiate, or become specialized into different tissues. That's where we are. Where are we going right? Well, what we're trying to do right now is to identify the conditions under which you can take these cells and instruct them to only form one cell type. In other words, let's say you have a million cells in a dish of these embryonic stem cells and you say, "I want only dopaminergic neurons." Big term, but it's a specific type of a neuron and it's one that is clinically relevant because it's the one that's at risk in Parkinson's disease. Now how do we get all those cells in a dish to go in one direction? That is a difficult biologic problem. Or to form heart muscle? Or to form islet cells in the pancreas? Or anything else? So this is where we are going to be for the next ten years, figuring out the conditions under which you can take these cells that can form anything and saying, "But I only want this."

One thing we haven't touched on is some of the medical implications of your research. We've heard about your interest in Down's syndrome. Can you tell us a little bit about how HPSEs can be a factor in tissue transplantation?

John Gearhart: If you have a cell in a laboratory setting that is capable of forming a variety of cell types, this opens up the possibility of culturing large numbers of specific cells that are at risk in a number of diseases. Now what we're talking about here are cells. We're not talking yet about organs, body parts or anything like this.

But there are many diseases that affect a single cell type, and that cell type is destroyed, whether it's Parkinson's, Alzheimer's disease, diabetes. Stroke for example, which will wipe out a region of the brain. There are a variety of neurons there, but some type of tissue transplant therapy would work. Or tissue damage, when someone accidentally cuts something or is burned or something like this.

Where there are specific cell types involved, it is reasonable to assume now that we can take these cells from a culture setting and transplant them into humans. Now it's actually more than reasonable. Proof of concept has already occurred in the mouse system, where the same types of cells have been isolated. They've been grown in culture to form, for example, all the blood cells. These blood cells then have been transferred into a mouse in which the blood producing capacity has been destroyed by radiation or chemicals. These cells -- these animals once they've been reconstituted -- are normal. Cardiac cells grown in culture have been placed in damaged mouse hearts, physically damaged, where they have integrated and have formed normal junctions and these hearts have been repaired. In the mouse, neural stem cells from these embryonic stem cells have been transplanted into the brains of animals and they have integrated and functioned.

There's a very interesting clinical trial going on now in Pittsburgh in which these cells were first placed into an animal model of stroke and they ameliorated the effects of that stroke. Now these cells are being placed into stroke victims. So proof of concept is already there, so it will work. It absolutely will work, but when you start using it in humans you've got to be sure that all of the cells you have in that dish are the cell type that you want. So there are some other hurdles.

Isn't there a concern about rejection?

John Gearhart: Yes, certainly. Any time you transfer cells from one human being to another they'll be rejected unless you use these immunosuppressive drugs. Another advantage of these cultured cells is that we can genetically manipulate them to alter what we call cell surface determinants that your body responds to when they are different than yours. We can genetically manipulate them so that your body won't respond as, or won't respond at all. These cells give us that ability, so this is a very active area of research.

I feel that this work will only be successful if we can come up with what we're referring to as a universal donor cell. In other words, we would have banks of cells where we've genetically manipulated those genes that are involved in the rejection process so that they're compatible with a wide variety of people. It's a single bank and if you need cells of a certain kind you don't have to worry about them being rejected by anybody.

You have probably encountered more dramatic road blocks to your research than most scientists because of the delicate nature of the material that you're using. Can you talk about the controversy and why some people are so upset?

John Gearhart: It's difficult to assess how many there are but they are very vocal, so it becomes an issue. I should tell you up front that we have received more support than opposition, and not just from patient's interest groups who have a real vested interest in this, but among scientists and a number of people.

Having said that, let's say what the controversy is. The cells that we use are derived from human fetal tissue. That tissue comes to us as a result of elective pregnancy termination, abortion. As I mentioned, it took us years to get the approvals in place that said we have justifiable research goals, that we are conducting this under ethical guidelines and legal guidelines that are established at the federal, state, local and institutional level. Our work is reviewed annually by all these committees so we are within all the guidelines.

There is an absolute wall between our use of the fetal tissue in research and any woman who is considering or electing to have an abortion. We apply for this tissue as other investigators do, for research purposes, through a number of committees. Our protocols are reviewed and approved. So we get in line, if you will, to get access to this tissue, but still it's the source of the tissue that is the controversy.

As you know, abortion is the law of the land. There's nothing being done illegally here to induce a woman to have a termination. We also feel that once we establish these cell lines in culture there's no need for additional fetal material. Remember these cells live forever -- not the cells themselves, but the cultures go on forever. So it's not going to be something where a lot of investigators come in and demand a lot of tissue. It's not going to happen.

One of the anti-abortion groups that has been vocal against your research went as far as to say that this could encourage abortion.

John Gearhart: It's not revealed where or at what hospitals we get this tissue. No one can predict ahead of time that this tissue would be used for this purpose. Although there is a consent form that a woman is given after she has made the decision to have a termination, that's very standard, if she wants to provide this tissue for research purposes, and it states what those research purposes are.

But there's no incentive for her, is there?

John Gearhart: No, none at all. There's no financial remuneration of any kind for this. There is no financial incentive in any fashion to anybody within this program. That is against federal law. Let me make one other point.

What is the fate of tissue that is collected following a termination? It is passed to a pathologist to make sure that the technician who did the abortion did it properly -- meaning that all of the material is there, there's no risk to the woman that anything has been left in situ -- and then the material is discarded. Discarded. So from an ethical standpoint I view what we are doing with this -- the benefit of this -- to far outpace the risk, if you will. The options are: the tissue is discarded, or it's used in a research purpose that could benefit many, many people. So it's important to keep in mind. That's the fate of the tissue. It's discarded.

Have you seen your stem cell work, not only as a mean to further research but ultimately to prolong life?

John Gearhart: Yes, I would agree with that. Absolutely. The benefits would be enormous. You'd be able to help a lot of people.

Has getting funding for you research been an important issue?

John Gearhart: Funding is always an important issue in any kind of research endeavor. Initially, for about a five-year period I used institutional funds, endowment funds coming to me as a division director at Hopkins in obstetrics and gynecology.

Towards the end of this we needed funding and we were approached by a corporation to see if we could partner. They have acted appropriately. They have the review boards. The interaction has been, to me, sound both scientifically and ethically. We went forward with this and it was a decision that Hopkins made to go forward, and we've had a very good working relationship with this corporation. So for the last two years we've been funded through corporate support.

Now our work using fetal tissue has always been eligible for federal funding. Always. There has never been a ban on this research federally, but I chose not to go that route simply because I have known many of my colleagues who have applied for federal funding for fetal tissue work whose applications, although not banned, have been sort of put on hold.

The ability to obtain financing much more rapidly through this private side was certainly an incentive to go towards the private side. It was immediately available.

What do I see for the future? Well, there are two aspects to what I see for the future. I think it's absolutely essential that federal funding be available for this type of work. What has made biomedical research so great in this country has been funding from the public sector. It enables a number of investigators of high caliber, peer reviewed, you know, research applications, et cetera, to have access to these cells and to really make the advances that are necessary to bring this to clinical utilization. We need this. We need it desperately. Secondly, and to me as important, it provides an oversight to the work that I think the public demands. I mean, you know, there's this concept -- or this perception -- that if something is funded only from the private side that there's no regulation, that they're going to do whatever they want to do, et cetera, which isn't exactly true.

No publicly traded company is going to do something stupid in an area that's as sensitive as this. They're just not going to do it, but nonetheless this company has been in full support of having public financing, public oversight.

Harold Varmus, the Director of NIH, has been extremely supportive of getting public funding into this. He sees the same benefits coming: the speed of the work, and having the oversight, which I think would make the public feel that there aren't thousands of investigators going after every bit of fetal tissue that's available. There will be so many of these cell lines established and then they'll become available to investigators. Not only what the priorities would be with this--establishing this research but also the endpoint.

Another ethical argument which is brought up is, "Who is going to benefit from this? How much money is it going to cost for a patient to get access to these cells?"

There is a strong feeling among patients who have any type of disease that drug companies manipulate unfairly what it costs to get access to any type of therapy. Drugs are so expensive people think it's a conspiracy, so there's a feeling that if the private side owns this research and is so deeply involved and there's no public support that they're going to control who is going to have access to the therapies and what costs are going to be involved.

If NIH or the Federal Government comes in there's certainly going to be an oversight of this. I have spent a good deal of my time since our results and Jamie Thompson's results were announced lobbying, meeting with anyone who wanted to talk about supporting the public's role in this.

We have a responsibility as scientists to give you the facts, the implications of our research, but by the same token we feel that the public should be involved, from the standpoint of oversight, funding, the whole works.

There have been some pretty wild reactions to this research, including discussions of cloning humans, designer babies, mixing humans and animals and so on. Could you help us separate the real potential of this research from the fiction?

John Gearhart: Absolutely. I want to preface this with what my experience over the last six months has told me about how the public sees this. In the different forums that I have been in it is clear that to the public all the issues of sequencing the genome, cloning humans, stem cells, assisted reproductive technologies get thrown into the same barrel. They're trying to ferret out where the lines are. Is this all part of the same program? How are these connected? I find myself answering questions in all of these areas although very little of it applies to stem cells.

Another element that leads to this confusion is that at the national level, unlike in Great Britain and other countries, our country doesn't have a policy that applies to most of what's going on. There have been commissions and ad hoc panels to review and make recommendations that would become national policy. Virtually every one of these has been thrown out for political reasons, so we don't have any base of policy to build on. I think this adds to some of the anxiety of what's going on.

How do I see these things tied together? Let's talk about cloning and the stem cell issues. The stem cell work that I am promoting is not involved in any way in cloning.

We are taking cells that can form any kind of a tissue, and we are saying we want to grow these -- learn how to grow them in culture so that we can provide cells for therapy and that they will not be rejected. I mean, it's very straightforward. How did this get involved in cloning? I mean, what was the link? Well, I'm as guilty of this as other investigators. We proposed a number of months ago, when the issue of immune rejection came up, that one of the things we could do would be to take a cell from a patient and through this nuclear transfer -- you know, this is the term that everyone jumps -- that we could take that nucleus out of that cell and establish stem cell lines that have the nucleus in it. Now what is the purpose of this? Well, the purpose is just for the stem cell lines, so that those lines would match the patient so that you could, say, take these cells now that have the same genome as the patient, put them back, no rejection, everything would be fine. There's no interest here in making an embryo in that cloning step. These cells are incapable of making embryos. Embryonic stem cells and embryos are not synonymous. So there's this confusion.

There is no ban on what you're doing. Is that because your cells cannot create a baby?

John Gearhart: That's right. These cells are not what we call "totipotent." Now we learn the power of a word. "Totipotent" has two biologic meanings. In one it means that a cell or a nucleus can form all other cell types that are found in an animal. An alternative term is "pluripotent" which means it can form most cells.

It is written in our federal law that if a cell is totipotent it also means it can form a whole organism or a whole being. Embryonic stem cells are not totipotent. There are certain cell types it cannot form. For example, if you took an embryonic stem cell and placed it into the uterus of a woman nothing would happen. These cells are incapable of forming the extra embryonic cells that are critical for organizing an embryo and having it implant into the uterine wall. It won't do it. So what you get are just a variety of cell types that are not organized into an embryo.

So our cells are pluripotent. They can form virtually any cell type you find in the adult, but they can't form some of the essential cell types that you find in embryos or fetuses. That is are important terms you see in the literature, and people are arguing about that. Anyway, the cloning issue came up because of this nuclear transfer step to match an embryonic stem cell to a potential host.

Are you cloning that cell in a sense then?

John Gearhart: Yes, cloning cells. You're not cloning individuals. Cloning has so many meanings now, but to the public it only means one thing: producing a genetically identical individual.

Now am I opposed to human cloning? Two thoughts on that. I'm not opposed to this. This may be startling to you but I'll tell you why in the long-term. We'll get to the short-term.

Every day in this country there are at least 30 clones born. Okay. Do people get upset about this? No. And these are identical twins. Okay. People say, "Well, they resemble each other," blah, blah, blah. But these are individuals, totally different as you could imagine.

And what the public doesn't understand is that you're not cloning individuals. You're cloning what we call a genome. DNA. That not an individual. An individual is something that arises from all of the interactions and environmental things that happen along the way to establish individual identity.

Do I care in the long-term? This isn't going to be done in any mass scale in any way.

In the short-term human cloning does bother me and I'll tell you why. Whether you want to talk about Dolly the Sheep, whether you want to talk about the cattle cloning, or whether you want to talk about the mouse cloning, these are the species in which cloning has been done.

There are clearly problems with these cloned animals. Dolly has shortened telomere cells. Now this is a big term for saying that it seems that this animal is aging more rapidly than normal.

In not only the sheep work but in the cattle work it's clear that animals are being born and they're dying mysteriously. Or if you look along the fetal period of the ones that are lost, you find that there's some birth defects in there.

The frequency of success here is so low by these procedures, --one in hundreds -- that this just isn't time to apply this to humans in any fashion, in any way. We have a lot of questions that we've got to work through. That's my take on this at the moment.

There's sort of a hysteria around this subject anyway?

John Gearhart: Yes. I think there should be. I think there should be a real concern about the biology and the outcome of this. No, this shouldn't be done. I don't care. Whatever.

There are ethical issues, aside from any of the biological concerns, which I think we have to deal with.

And then there's this final little issue over here that we've talked about which is called therapeutic cloning. The other things are reproductive cloning, where you want an individual.

We've introduced this new concept of therapeutic cloning, which is getting stem cells with the same genome in them. This is the area that the public doesn't understand as well. You can't blame them. I don't think we've done a very good job of informing them.

One question that we ask all of our subjects concerns the American dream. What does the American dream mean to you?

John Gearhart: That's a very deep question as far as I'm concerned. I think of the freedom that I've had in my life to do what I wanted to do, and when I wanted to do it, without having to worry about a class consciousness, without having to worry about a number of other issues. There's nowhere else in the world that I could have done or can do what I want to do.

And to have the support at the federal levels, the environment of having access to colleagues, of having opportunities. To me this is part of that American dream, and very important to me, as you can tell by my bio in a way. You can come from nowhere and not have any additional obstacles placed in your way that would have prevented you from getting to where you want to go. That is what I view as the American dream.

What to you is the most significant contribution that you have made so far to your field? What are you most proud of?

John Gearhart: What I'm most proud of, I think, are the students and the post-docs and fellows who have come out of my laboratory. I've followed their careers. I think my main contribution will come through them ultimately. As I said in the beginning, I think as a scientist it's really the journey, and sometimes when you achieve the goals of the journey, you do it with your students and your fellows.

Through mentorship you get very close to these individuals. They put all of their trust in you at least for a while. It's like a family. Then when they get mature enough they turn around and say, "Yeah, we know, old man." But that's okay. This gives me the most delight and I think it would probably be the lasting contribution.

Science and scientific findings are ephemeral. What makes a headline one day is gone, and the half life of a research paper is extremely short, so I think it's these kinds of connections that are critical. It's the students and the fellows.

Thank you so much for speaking with us.