John Gearhart Interview (page: 4 / 8) Stem Cell Research	Print Interview

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.
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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.
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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.
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"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.
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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.
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