Bert Vogelstein Interview (page: 3 / 4) Cancer Researcher	Print Interview

What were some of the biggest obstacles you've had to overcome?

Bert Vogelstein: I joined the faculty of Johns Hopkins in 1978. Almost all biomedical research today is funded by grants from the government, from the National Institutes of Health. After I had worked for a couple of years, I applied to NIH for my first grant, which would have given me the funding that I needed to continue the experiments I was doing.

I was very disappointed that it did not get funded. Which means I didn't have the money I needed to continue in the way I wanted. There were some other sources of funding for my department that I used. And of course, I reapplied the next year. It takes about a year to reapply. I was very disappointed when I didn't get that one either. This was pretty serious, because it was twice I applied for funding and didn't get it either time. The reviews were critical. They thought that what I had in mind was not likely to be productive, or yield useful new information.

So I applied a third time, about eight month after that, which was the soonest I could do it. I was getting really worried, because there's only a limited time you can go in science without getting funded, or else you're going to be driving a cab or something. So this was really important to me.

I asked them to change the reviewers that were reviewing it, because I thought maybe I'd have better luck with another group of scientists reviewing my application. They say three times are a charm, and I was really excited about this one, and then that didn't get funded. That was a pretty trying experience.

I wanted to study human cancers. I wanted to identify and clone the genes that were responsible for human cancers. No one had done it at the time. The senior people who were reviewing my grant thought it wasn't possible to do it, and these in general were very smart people. I talked to many senior scientists at the time -- Nobel laureates included -- and people said, "You can't do this from humans. You might make some progress if you're studying animal tumors or test tube tumors, but you just can't do it in people, and you should use your skills to do something else." That's why my grants were all turned down.

But in my gut I felt that you could do it. With the new technologies that were just coming on board then, I believed I really had a chance of doing it. And that's what I wanted to do.

In fact, I didn't get a grant until I had actually done it, and proved to people that it was possible. That's part of the problem with granting systems. You almost have to prove that what you're trying to do is feasible before you can get funding to try it. Fortunately, there are lots of ways to get funding besides the standard way. People who are persevering enough, and dedicated enough, and really think that there's a light at the end of their personal tunnel will usually figure out a way to get there. Once you get there, funding usually isn't a problem anymore.

That was the most trying period of my life, because there were several points at which I thought I wasn't going to be able to do what I really wanted to do, just because I couldn't get the funds to do it.

At difficult times like those, what motivated you to continue with your research?

Bert Vogelstein: Until very recently, our laboratory was in an unusual and motivating geographical position within the medical school complex at Johns Hopkins.

Our laboratory was right above the radiation therapy unit. Radiation therapy, of course, is where cancer patients get x-rays treatments for their disease. And in order to get to our laboratory, I actually had to walk through the radiation treatment area. And, every day we'd come in and we'd see dozens of patients lined up waiting to get these treatments, and they were all very sick, many of them were in wheelchairs. You could see that they were just in terrible shape; most of them you knew were going to die relatively soon. And, you couldn't possibly walk through that room and not run up the stairs and start working. It just continually reinforced the idea that this is a disease, people are getting it, they shouldn't get it, we've got to do something about it.
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I saw that in my students. They'd go through there and literally run up the steps. It reinforced the importance of doing something for this terrible condition.

You spoke a moment ago about a gut feeling that you were right. How do you see the respective roles of intuition and analysis in making scientific discoveries? Is there a balance? A place for each?

Bert Vogelstein: That's been debated and written about for years. In my experience it's really pretty simple. It's not simple to do, but what makes a great discovery is simple. It's based on hunches. People have insights about processes that are sometimes unique.

When I was in college one of the things that one of my professors said, which only later I understood -- he was a math professor, and he was telling me that he started out in physics and he switched, and I asked him, "Why did you switch from physics? because it's a lot of fun?" And he said, "My insights into math were better." And I didn't really know what he meant because at that point I'd never had an insight into anything. But, now I know exactly what he meant. You have hunches. There's some gut feeling you have that something is right, or can be done, or is ripe for investigation.
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That's not methodical at all, or analytical. It's just something that is a spark in a person. A person will be able to connect two things that haven't been connected before.

We talk about creativity, but humans are not creative. I mean we're not God; we can't create anything. What we label creativity is really something quite different. It means we can connect two things that were not connected before. We can't create either of those two things, it's just we recognize a connection.

With artists, it's that same sort of creativity. When they draw or sculpt something, they're connecting reality with something they see that has not been seen before. When a scientist discovers something, it's not a creation, in a sense. He or she is just able to connect two observations that were made by two groups of people and say, "I see a connection here that wasn't previously observed."

That has nothing to do with math, or anything you learn that's analytical. It's a power of reason. It's logical, at least in terms of science. And it's something that really can't be taught. You can be educated to recognize and have the knowledge. If you don't know about thing one, you'll never be able to connect it to thing two. That's why accumulating knowledge is so important in science, probably more important than in art, but the processes are very similar.

The analytical part only comes later. Once you make that connection, once you have that hunch, that insight, then you have to prove it, or try to prove it. That's when analytical skills come in, but that's quite a different process. That's an execution process, rather than a discovery process, per se.

Do you find one part of the process preferable to the other?

Bert Vogelstein: They're different.

The best thing, clearly, is that initial hunch, is that feeling you get often, at least for me, it's early in the morning. I'm lying in bed thinking and I think of something that to me at that time, seems really neat, some connection. And, nine times out of ten, after I get up and think about it and talk about it with my colleagues or my students, it turns out that it was the stupidest idea that anyone every had. But, that few minutes when you think of it, and you think that you really have come up with something that's important, that's a great feeling. And, the fact that they almost all turn out to be nothing, doesn't really matter. It was fun for the moment.
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That's part of the fun. The other part, the experimentation, which you do to try and prove that the idea you had is right, that connection that you thought of is right, that's much different. That's a lot like playing with toys.

You have all these instruments in the lab, test tubes, and chemicals, and they're really just toys that scientists play with, that make it fun to do what we do. They're great toys. You have all these knobs, and it's just that we're all little kids who can fool around with these things and use them for interesting purposes. But, anyone who likes to play with toys has got to like to do science because they are the world's best toys.
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Where does your sense of humor come from?

Bert Vogelstein: No one has ever asked me that question before. There's a lot of humor in our lab, which I guess comes from failure, from a kind of pain. In science, you're always failing. Almost everything you try fails. The words that I like to hear best from the people in my lab are, "It works!" Those words are music to my ears. Because what I almost always hear is, "It didn't work." Then we have to figure out why.

Most things don't work, either because the idea was wrong -- the connection was wrong -- or because of execution. Trying to prove that the idea was right is very difficult. And the combination of those two things almost guarantees that somewhere between 90 and 99 percent of experiments will fail. And in order to cope with that, you need a sense of humor. You need to understand that, yeah, it didn't work, but there's got to be something good that came out of it. You must have learned something, or there's got to be something funny about how it didn't work, or something that we can be happy about that will stimulate us to try it again the next day.
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Bench scientists, people who work at the bench and do science with their own hands, generally have a pretty good sense of humor. It's a fun place to work.

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