Interview: Bert Vogelstein
Cancer Researcher

How did you first become interested in medical research? Was this something you'd wanted to do since you were a child?

Bert Vogelstein: I don't think there was any simple path. My father was a lawyer and a lot of older people in my family were lawyers. No one was a physician, no one was a scientist. There was a strong background of scholarship in my family. I come from 13 straight generations of rabbis, all of whom were very well-known in Europe and had written books. So there was a very strong strain of scholarship, but nothing in medicine.

I guess when I was 10 or 11 I kind of wanted to be a lawyer like my dad. And, when I went to high school I got interested in science, and I was pretty good at it, I guess. And, it wasn't until I was actually in medical school -- even past medical school, about five years after medical school -- that I finally decided what I wanted to do. So, there was a lot of indecision. I knew I wanted to continue to learn things about science, and about eventually medicine. But, I had no formed idea of what I wanted to do until I was maybe 27, something like that.

What kind of a kid were you?

Bert Vogelstein: I was a very serious kid. I would not say that I was popular in the sense that that word is usually used. I always had a few what I considered close friends, and I like to think that I was popular among my few close friends. But, I certainly wasn't the belle of the ball. I was never very socially interactive. In fact, I was kind of shy and scared of interacting with other kids and going to parties and stuff like that.

I was pretty serious. I did a lot of things, in addition to going to school. I had a good time, I had a great family. I used to play a lot of sports, but I was pretty serious, and I always read a lot. I read because I enjoyed it, that's the only reason.

Was there a lot pressure from your family to excel academically, or was it your natural predisposition?

Bert Vogelstein: There was no overt pressure, there was covert pressure. Parents often do that to their children, either purposefully, or unintentionally. I was expected to do extremely well in school.

When I was asked to leave the second grade, because I wasn't behaving properly, my parents were not overjoyed. But, they tolerated it, and I had to switch to a private school. And, I lasted there for about eight years, in the private school, until the dean of the private school asked my parents whether I wouldn't be happier in a public school again, so I changed. But, the reason was not because I was a troublemaker, it was mainly because I didn't go to school much. Instead of going to school -- there was a public library right next to the school and I just, in the morning -- I used to go there and read all day and not go to classes. Not all the time, but a few days a week because I thought I'd learn more reading. But, my teachers didn't agree that that was the best way to get an education.

What did you read?

Bert Vogelstein: Everything. I'd just go to the library and look at the shelves. If anything looked interesting, I'd pick it up and read it. It was a little library, so after several years of doing that, I had read a good portion of the books that looked interesting to me. That was fortunate, because that's when they asked me to leave.

Is there a book that stands out in your mind from when you were younger?

Bert Vogelstein: One book whose contents I remember best was called Mrs. Pickerel Goes to Mars. Somehow this woman got on a spaceship that was going to Mars. She was going there with a scientist who appeared to be very absent-minded. They took off with this woman in the ship and he didn't seem to know what was happening. She was flabbergasted that he was so scatterbrained and he said, "I try to keep in my mind only the things that are important. I write all the details down, so I don't have to fill up my brain with these silly details." That stuck with me. In fact, that's what I try to do. For better or worse, people often times think I'm scatterbrained for the same reason. If they get in a car with me, I'm at least as likely to go somewhere completely different, as I am to go to where we're supposed to go. I try to keep my brain free for important stuff, rather than trivia. So that book actually had an influence.

Was medical school an obvious extension of your high school interest in science?

Bert Vogelstein: When I graduated high school I thought I wanted to go into medicine. Part of the reason was that Johns Hopkins was here in Baltimore. I grew up here and I knew a lot about Johns Hopkins. I was always reading about it and it seemed like a great place to be and to study.

When I went to college I initially thought I was going to major in pre-med kind of courses, but I took math courses and I found them much more intellectually stimulating than the standard pre-med courses. So, I decided to major in mathematics and, in fact, went to graduate school in mathematics for a year. I finished college early, so I had an extra year to kind of fool around, and I went to graduate school. I took graduate courses in math. And, I began to feel, even though math was incredibly intellectually stimulating, it didn't have the practical edge that I wanted. I wanted to be able to do something for people.

Maybe that comes from my 13 rabbi forbears. I thought math was great, but I felt like I was playing chess. It was a wonderful game, but I wondered whether I would ever be able to apply what I was doing to helping other people. I didn't really know much about medical science or biology, but I thought, "If you go to medical school, they'll probably teach you about that stuff." So I applied to medical school. I had taken the requisite courses in college, I got in, and enjoyed medical school. Soon after that, I recognized that research was what I really liked. I recognized that by doing it. I think it's very difficult and wrong for people to assume that they will like something just because they've heard about it or read about it. You really can't tell until you do it.

The first summer after medical school I did some research in a lab with a gentleman named Howard Densis, and I immediately knew that this was fun. This was exciting, this was something you could really apply your innovative skills and your creativity to. And, that's the way I continued through medical school. Whenever I had a chance in the summers, I would take off quarters or semesters to do research. And that's kind of when I decided to probably concentrate on medical research.

I still didn't know whether I wanted to be a physician, too. That was a very difficult decision. They're very different careers, and I didn't decide that until later.

What event was a turning point for you?

Bert Vogelstein: There were two turning points that decided for me what I eventually wanted to do. The first one was after I had finished medical school. I was an intern, learning how to take care of patients.

One of my first patients was a little girl who was diagnosed with cancer. Actually, I diagnosed her cancer. Her parents brought her into the clinic because she looked pale and she was bruising, and a few simple tests showed that she had cancer. The little girl was only four at the time, and the look on her parents' face is something that has indelibly etched in my mind. It was terrible in the sense that I couldn't tell them anything about their daughter's disease. I couldn't tell them 'why' or 'what.' I could offer some encouraging words about some therapies that may potentially help, but what they really wanted to know was, "Why?"

The father of this little girl was a mathematician and I related to him quite a bit from my college days. And, he just wanted to know, why "my little girl" got this terrible disease, why her, and why this plague? And, I just shook up my hands. "I don't know, nobody knows." It's just this total black box, this thing that just struck people randomly, when they shouldn't be struck. And, right then and there it became clear to me that, if I wanted to spend my life on a puzzle, on a problem that I could apply my skills towards, that was going to be a good one.

I knew it would be hard, and I knew I'd probably never get there. But, I thought, that's something you could spend your life doing and feel like you're trying to do the right thing, and trying to make a real contribution. And, if you're successful at all, you could obviously feel very good about what you've done.

That was one turning point, but I still had to decide whether I should continue to see patients and practice medicine, or devote all of my energies to research. It was not something that I intellectualized about. Those kinds of decisions have to be made through experience. I tried doing both.

I found myself during the days seeing patients and during the nights going to the lab and trying to do a little bit of research. And, I found at night I was really happy. I felt stimulated. I couldn't wait to get to the lab at night so I could start experiments. I found them very intellectually challenging, and I liked playing with the toys. And at that point, I decided that this is what I enjoy doing best. And, this is probably the best way to be able to ensure, if I am going to make a contribution, that I will, by spending all my time doing one thing, research, rather than trying to treat patients and also do research. Those were the two events that most clearly shaped my future.

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.

In difficult times, 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.

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.

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.

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.

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.

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.

You also play music as a sideline, or hobby. Do you feel it's important to have another outlet in your life?

Bert Vogelstein: Our laboratory has a band, we play music. I play the keyboard, and Ken, the scientist who co-directs my laboratory with me, plays the drums. Students play guitars, and do the vocals. We have a blast.

It's a great diversion. We work hard all the time, cancer is a very serious disease and we're very serious about what we do. It's rejuvenating to do something completely different, and it takes your mind off the problems. It gives you a sense, after you've done it, that you can start again.

Even if all the experiments today didn't work, at least your music worked. That's the nice thing about music or sports. When you're doing science you can work for months or years without any real success. When you do something like music, or sports, or virtually anything that's a hobby, you get immediate satisfaction, because it works. You can hear it, it sounds good. That's very important, design some things that work into your life. I think it makes you feel good about everything else.

The other reason, of course we do it is that it's a lot of fun. Everyone likes to have fun, scientists are no different.

How do you balance your commitments to work and family? Is there a conflict?

Bert Vogelstein: That's one of the lessons I've learned from talking to people who are very accomplished, and have done more for mankind than anyone else. Legendary people, and not so legendary people, just good people, ask them what regrets they've had. Uniformly, across the board, they will all say, "I wish I had spent more time with my family."

I've never heard anyone say, "I wish I had spent less time with my family and more time with my work." It's the one constant theme that emerges from every wise person who's had that experience. I think it's important to learn that lesson before you're 60 or 70, and to try to put it into your life. When you get to be 60 or 70, you won't look back. You'll probably still say, "I wish I could have spent more time with them," but you'll know you spent as much time as you possibly could with your family.

Can you describe the potentially positive effects of cloning?

Bert Vogelstein: Cloning is used to describe numerous scientific areas. We clone genes all the time, but that's not the kind of cloning that people are talking about now. They're talking about cloning whole organisms, like sheep, which was done recently. And in particular, they're talking about taking a cell from a person, like taking one of your cells, and making a genetically identical copy of you from that cell.

That is obviously an incredibly intriguing idea. Unfortunately, people have largely thought about only the ethical problems associated with that line of research. Non-scientists have only recently started to realize that there are many potential benefits of that kind of research.

Let me give you a couple of examples. Two people married, and they had genetic diseases circulating through their families. They were very scared of having a child who would be very sick and probably die from diseases that other people in their family had. Or worse, suppose they already had two children, both of whom had a genetic disease inherited from their parents that had killed them.

The child was born, the parents got to love them. Two or three years later the child got sick, they went through a terrible course of hospitals, the whole thing, and then the child died. That is the worst tragedy that ever happens to anyone. The parents still want to have a child of their own, which is the most natural and uniform desire of all people on earth.

If cloning were possible, they could take one of their cells, say the father's if they want a male, and clone that into a child that would be their own and that they would raise just as any other child. They would know that that child was genetically okay, because he would have exactly the same genes as the father. It's only the mix of the father and the mother's genes revealing recessive conditions that resulted in the genetically defective children that they had before. That's a very practical way to use the technology to help that family.

Here's another way, which is a little farther off, but could involve the same technology. Suppose a woman 40 years of age has a heart condition, and her heart is not working properly any more. The only way to save her is to transplant a new heart. The best heart to put in would be her own. You can get heart transplants now, but they're very difficult and they're often rejected.

If you could take one of her cells and grow it as an embryo, or a partial embryo until a heart forms, and use that heart to replace her own existing heart, then she could presumably live out a normal life span.

There are, to be sure, certain ethical questions that have to be very carefully considered before doing things like that, but I personally think it would be wrong to dismiss those possibilities automatically as ethically wrong, or to put a ban on the kind of experiments that might lead to advances in that regard. I think we have to be sensitive to the patients, not just to the public.

Let me give you a personal example that's not something 50 years in the future. Cloning of humans, if it's possible at all, will take decades to work out. So this is kind of a theoretical argument, but let me give you something that's here and now.

In some cases, we can identify individuals at risk to develop colon cancer. We know with 100 percent accuracy, just from looking at their genes, that they're going to develop colon cancer by the time they're 30. We can do that by taking a blood sample from a child. We can do it prenatally. We can take a sample from a developing embryo and tell with 100 percent accuracy whether that child is going to develop colon cancer.

Is it right to do prenatal testing for cancer predisposition? When I present that question to a public audience, It's interesting the response you get. Because remember, even though this child will develop cancer, they won't do so until their 30s. They'll have a very normal life up until they're 30. Even once they develop cancer, with appropriate surveillance, the cancer can be removed, they can be cured, they won't die. They may get very sick, they'll need to have a lot of medical examinations, periodic checks, but they're likely to live a normal life span, although with some significant sickness.

So is it ethical to do prenatal testing, with the idea that if the child has the mutation, you're going to abort it? Is that ethical for a disease that won't necessarily kill the person, and if anything, won't kill the person until they're at least 30 and have lived 30 good years? The response that I get from an audience of several hundred people at a lecture is, "No, that's not ethical. You really shouldn't do prenatal testing for that. You should do prenatal testing for diseases that you know are going to kill children in the first year of life, that we understand. But for this kind of disease, it doesn't seem right. What happens, happens."

Now, if I'm talking to a different group of people, a group of patients and their families who've had hereditary colon cancer, I get a much different response. They say, 'This disease killed my mother, and killed my sister, and made my brother really sick, and now you're telling me that you have the technology to tell me whether I can make sure I won't give this bad gene to my child. I can spare my children and my family from having to go through this incredibly painful process, and you're telling me that I can't have it? Is that fair? Is that ethical, to withhold that possibility from me?"

I agree with them. If they want access to this information and we've had the good fortune to be able to provide it to them, who am I to say that we can't, because others, who have been spared this, think it's wrong? My inclinations are to go with the patients. If something can help people, I'm much less inclined to put much stock in completely theoretical dangers to society. I see benefits to people, and those, to me, are very meaningful.

What would you like to accomplish in the future?

Bert Vogelstein: What I would like to accomplish in the future is simple. I would like the things that we have learned about cancer, and about the genes that cause cancer, to be applied to people, so that we develop methods to diagnose cancers early when they can be cured, and eventually develop new treatments, based on what we've already learned, and what we're going to learn in the future.

That's one thing I'm very intense about doing, and I hope that we'll have some success. I'm not foolish enough to think we're going to cure cancer in my lifetime, but I'm optimistic enough to hope that we'll make some strides in that direction.

The second thing that's very important to me professionally, is that all of the students that have worked with us over the years, and there have been dozens, will be able to continue doing their work. And that they will continue to make discoveries on their own that will advance the field, and eventually help people with cancer. Those are my goals for the next 20 years.

I hope you achieve them. Thank you very much for your time.