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John Gearhart

Stem Cell Research

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.
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John Gearhart

Stem Cell Research

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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John Gearhart

Stem Cell Research

"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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John Gearhart

Stem Cell Research

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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John Gearhart

Stem Cell Research

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."
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Frank Gehry

Award-Winning Architect

Frank Gehry: What got me excited in the beginning were the social issues. I come from a very lefty liberal family in Canada, and architecture looked like it was the panacea. You could make housing for the poor and make wonderful cities, city planning in the future and so on. That was the initial turn-on. That lasted me all the way through school, actually.
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Frank Gehry

Award-Winning Architect

Frank Gehry: I bought an old house, and I put a new house around it. I got interested in the dialogue between the old and the new and trying to sculpturally create a new entity, but that retained the qualities of the new as independent of the old. I set myself goals like that when I started. I kind of pulled it off. I also wanted it to be seamless, that you couldn't tell where it began and where it stopped, and that was very successful, and that was the power of it. In fact, critics would come in and would look at a rain spot on the plaster and say, "Is that on purpose or not?" They thought they were maligning me, and I thought that was just wonderful. That was exactly what I wanted them to worry about.
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Frank Gehry

Award-Winning Architect

There is a range of creativity possible, and I think it behooves us to explore that envelope and push at it. It comes out of an intuition, or a learned intuition, I guess. You study a long time 'til you can do it. But it's from looking around you, it's from understanding what's happening in the culture, what's happening in the world. It's a really big picture. Because there are no real rules. If you look at the world around us, and you think of all these adult and intelligent people who have gathered together over the years to create the biggest mess. It always looks like that, whatever period. It looked like that when I was a kid, it looks like that now. And yet, somehow we muddle forward and make things. So out of that comes inspiration, believe it or not, and leads to ideas. For instance, I've been interested in the sense of movement in architecture. Well, who cares whether a building looks like it's moving or not? Maybe they shouldn't, but that's something that interested me. Maybe it comes from the fast society, the fast world around me, that I'm trying to make some kind of connection to. So I think you've just got to keep your eyes open, keep your ears open and understand what's going on. And then play with it, and move with it, and make your expression grow from that.
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Murray Gell-Mann

Developer of the Quark Theory

I was able to create a chart of my theoretical scheme, and I noticed that there were holes in the chart. And I predicted the existence of the particles to fill the chart. And those all worked. But then the question was, was there some sub-unit out of which all of these particles were made. These strongly interacting particles. Well I tried it, and it came out that you could do it with a certain set of particles, and in a quite economical way. But they would have to have electrical charges, +2/3 and -1/3. And of course, all known particles had integral charges, in units of proton or electron charge. The proton is called +1, the electron is called -1. And all the known particles had charges of +1 or -1, or possibly +2 or -2, and so on. Nothing had a fractional charge. But these sub-units, that would give the most economical scheme for making what we saw out of hidden sub-units. These sub-units would have charges of +2/3 or -1/3. It was initially discouraged, but then I made a visit to Columbia University, and a colleague there, Bob Serber, asked me whether I had ever considered this economical way of making sub-units, considering what you then called triplet. And I said yes, I have considered it, but they come out to have fractional charges. And I showed him the fractional charges on a napkin in the faculty club in Columbia where we were having lunch. And then, thinking about it during the rest of the day, it occurred to me that if they were completely hidden, these particles, if they never came out, but they were permanently trapped inside the known particles, then it wouldn't cause any difficultly, any disagreement with observation or with any fundamental theoretical idea. And so I began to put it forward.
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Murray Gell-Mann

Developer of the Quark Theory

Murray Gell-Mann: Just a slip of the tongue. That's how I figured out the explanation of strangeness. I had come up with an incorrect explanation, which had some features in common with the correct one, but which was wrong. And I knew why it was wrong. And another fellow had gotten the same idea, and figured out that it was wrong, and had written a letter about it, which was published. I hadn't published anything. But he had published the idea, plus the reason why it was wrong. But in a very confused manner, so that it was extremely hard to follow. I hadn't even read it, but I knew what it was, because I had the idea, and I knew why it was wrong. And when I visited the Princeton Institute for Advanced Study, where I had been working a short time before, the theoretical physicist there asked me to explain how this worked, how the idea went and why it was wrong. And I said yes I can do that. So I went to the blackboard and I started explaining the idea, and explaining why it was wrong. Part way through I made a slip of the tongue and I realized that the slip of the tongue made it ok, the arguments against no longer were valid, and this was probably the right answer. That was how I found the strangeness theory.
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Murray Gell-Mann

Developer of the Quark Theory

Murray Gell-Mann: The study of complex adaptive systems cuts across archeology and linguistics, economics, physics, chemistry, math, immunology, and so on and so forth. It just goes on and on. Computer science. That's the kind of thing we're doing at the Santa Fe Institute, which I helped organize. It is devoted to giving people from virtually all fields the opportunity to work together to understand how complex adaptive systems work, and other complex systems as well, but principally complex adaptive systems. And we bring people from all of these disciplines -- psychology, mathematics, chemistry, anthropology, and so on -- together for meetings, and we allow them, or encourage them, to form research networks. It's very exciting. I do a lot of the recruiting for the Santa Fe Institute, for the science board which supervises the program, and also for individual researchers. Every time I phone somebody in some distant field, some famous, busy person, I know that person is going to say, "Well, what you're doing sounds interesting, but I'm already fully committed, but don't call me, I'll call you." But instead, in almost every single case, the person says, "When can I come? I've been waiting for this! I've been waiting all my life for something like this!" It's very interesting. It's apparently a real felt need.
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