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Judah Folkman

Interview: Judah Folkman
Cancer Research

June 18, 1999
Washington, D.C.

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When did you know what you wanted to do with your life?

Judah Folkman: I knew when I was about age seven or eight. There were three children in our house.

Dad was a rabbi, and if we were well-behaved that week, you got to go with him on his Saturday afternoon calls to the sick at the hospitals. And he would pray through the oxygen tents, and we would sit in a chair and be very quiet. And I thought I would be a rabbi. And then, about age seven or eight, I told him that I noticed that the doctors could open the tent, and do things, and that I would become a doctor. And I thought he would be upset because he had expected me to be a rabbi, but he said, "So you can be a rabbi-like-doctor." And then I knew that he thought it was fine.

When you say "the doctor could open the tent," what did that mean to you?

Judah Folkman: I noticed that while dad was praying for the patients -- but they had heart attacks and they were in oxygen tents, and they were very sick, and it seemed that the doctors actually were doing things, starting the intraveneouses and had a more active role. So I thought I would go that route. It's still the service to people.

Was that what was going through your mind?

Judah Folkman: At that time. I remember exactly where it was. I remember making that decision in a hospital in Grand Rapids, Michigan.

What attracted you to medicine?

Judah Folkman: It's service, and it's taking care of people, and it's ministering. That's what my father did, and mother also. Both of them said that was the highest thing you could do. They thought making money and providing jobs for people was another way of service, but this was their service, one by one, personal service to people. When you couple that with my interest in science, the two made a very good match.

Did your father and mother have a great influence on you?

Judah Folkman: An enormous influence in the way that they helped people. They were always on call. People would call at three o'clock in the morning if somebody died in the family. And Dad would go and see them. If Dad was out of town, Mom would go and see them, as almost a substitute. As the rabbi's wife, she was respected in the community.

He did a lot of marriage counseling. He had a very big congregation. At least two marriages every weekend. Then in the late '40s and '50s, he began to notice that what was happening around the country was also happening in the Jewish family. He was seeing divorces for the first time, so he began to study it. He actually got a Ph.D. in sociology at Ohio State in his spare time, and became an adjunct professor of sociology. He was always doing marriage counseling and counseling of families, children that were going on drugs or families that were breaking up.

At dinner he would tell us about people's problems, and how he was trying to help them. When he would marry somebody, he would give a little ten-minute sermon to the couple. It was always very personal, and something they remembered. And then they had Alumni Day for the maried couples. So when they were five years out and ten years out, he invited the married couples back to our home. They would come back for a weekend, it was usually in July. He'd see all these couples who were five years married, and they all had the same problems. They were poor. Then at ten years out, they were making money but they couldn't get a baby sitter, and their children had all the little problems. He used that knowledge therapeutically. So we saw all the time that they were helping people. That was the message that came across all the time. All three kids saw that.

How do you think this affected your life?

Judah Folkman: It was of very high value to follow in those footsteps, to minister to people, and not to choose a career which was totally selfish, or totally self-centered. It was very clear what that message was. They didn't say it all the time, but it was clear from what they did.

What was your childhood like?

Judah Folkman: It was a very warm home with a tremendous sense of humor, and also an enormous value placed on learning. Every day, when we would come home for dinner, every day mom or dad would say, "Well, what did you learn today?" with great interest, like "Teach us." Not, not in the sense that you didn't learn anything. So no matter what, we'd say, "Well, we had geography. "So we'd tell them. They'd be so interested, as though they didn't know. So it was that for the whole time. I always remember. That's something we, all of us, remembered: "What did you learn?"

Would you say you were a gifted child?

Judah Folkman: I didn't think so because I always had to struggle with math and other things, but I always had a lot of ideas. Those ideas came very easily. And I liked to work in the laboratory.

Did you feel different from other kids?

Judah Folkman: No, I really didn't. I didn't feel different because I noticed I had to struggle with certain things, and other things came easy. The great physicist Richard Feynman wrote in his biography that he was so brilliant that he always felt that he was in a retarded institution. That's feeling different! No, I was just going along and my interest was in science. I was a good student, but there were other kids with scientific interests.

How did you get from this childhood interest in science to the kind of research you do now?

Judah Folkman: I began laboratory experiments in junior high school and high school. Science Club experiments. There were two extremely good teachers, a geometry teacher and a chemistry teacher at Becksley High School in Columbus who had a major influence on me. I began to do experiments, and they would allow more and more advanced experiments, beyond the lessons. They would say, "Come back after school and try this, try that."

You mentioned some teachers. Could you tell us why they were important to you?

Judah Folkman: In high school, there were a number of outstanding teachers, but two were really critical. One was a teacher who taught geometry and solid geometry. John Schott his name was. And he would allow you to solve problems. So you'd get the problem solved, like in the book. Then he would say to some of the students, "Can you do it another way?" And we always thought there was only one way to solve a problem. He said, "No, try it another way." And then when you'd get it that way, he would say, "Can you do it another way?" And then you began to learn that there were a whole series of ways to solve the same problem but the book only had one way. And he would say, "Can you make a model of it." So instead of drawing a graph, he would say, "Can you make a three-dimensional model." And he had all kinds of pieces of tools and things around in his geometry class. And so it was extremely interesting, because he made you solve problems that weren't written anywhere. So then I first got the idea you could do that.

The second teacher was a chemistry teacher. His name was Smith. After the first semester of chemistry, he would give these exams in which he would hand you a tube that was an unknown. You would add copper to it, and see if it precipitated as red. You would then know the answer was copper sulfate, and on and on. And every time you got it right, he'd give you another one. The more you got, the higher the grade. When you got it wrong, that's when you stopped. Pretty soon everybody had left, there were just two of us, and he was still giving us unknowns.

So he gave me something that was crystal clear, and none of the tests worked. I put everything in it. No precipitate came down. So I said to him, "This could be water. Just plain water." And he said, "Okay. Prove it." He had given us still water, just to see how we would handle that, because that's something you'd never test for.

About a month before, in physics, they showed us that if you have a light bulb with two wires going to a battery, and you cut one wire and put it in water, the current is broken because electricity can't go through water. But if you added a small amount of salt, the bulb would begin to glow, because now the water conducted. Pretty impressive experiment. So I told him about that experiment, and said that would be a way to test it. He said, "Why don't we go up to the physics class?" Instead of saying, "Okay, that's right," he said, "Show me." So we went up to the physics room. It was now five o'clock in the afternoon, and there was nobody there. We got that apparatus and he put the sample in and the bulb would not light up. So that meant there was water. If it was any other salt, it would have lit up.

-It was very impressive. I remember going home that day, thinking that you can cross fields. You can solve problems by crossing a whole lot of fields. We had always thought that you did chemistry and you used chemistry books, you do physics in the physics books, and English is English. That they didn't cross over. That lesson was a very important one. These teachers really went out of their way. He could have just said, "Look, it's five o'clock. Okay, it's water."

As a young person, what person do you think most inspired you?

Judah Folkman: A lot of inspiration came from father and mother, and then there were the teachers I mentioned. There were also two members of the congregation who had a big influence.

While I was in high school, I always seemed to have to work much harder at math. I mentioned that. It seemed to come hard. So there was a mathematician in the congregation named Ben Eisner. His hobby was mathematics, but he was in business. But he was a terrific mathematician. And he decided that every Saturday afternoon, whenever -- he would call every Saturday morning, say, "Are you free?" and if I was -- it was about once a month -- he would come out for about three hours, both my brother and myself, and we would just do problems, but only -- no paper. He would say, "Do it in your head." So he would just sit there and he'd say, "Now let's see, this train is going this fast, this train's coming this fast," and, and then, tell us something. And I would say, "Well, I need a piece of paper." He said, "No, you don't." And he would say, "Just imagine a track that's one foot, and another track that's a half-foot, and then imagine the velocity is such and such, and how fast will you traverse that?"

Then he went into statistics. All kinds of practical mathematics. Wind speed, air speed, everything. It lasted about two years. He did it totally voluntarily. I never knew why. Dad must have mentioned something to him, and he offered to do it.

There was another member of the congregation who worked in a varnish factory. He was the chemist, the analytical chemist for a varnish factory, and he said -- this was in high school -- "If you have time on Thursday afternoons, if you could, want to come by?" And then in the summer -- so in the summer I worked for him, and measuring mixed ratios of solvents to paint and everything, and he was always doing the quality control. But he had a big chemistry lab. And so I learned a lot from him about what chemistry was like on a practical way, and how you had to be very careful about the numbers. So you did a little experiment on a bench, but if you were off three decimal places and it went to a 100,000 gallon production, the company'd go bankrupt. So he said, "What I'm doing is very important. The decimal places are important." So that was a good lesson about accuracy.

What books influenced you as a young person?

Judah Folkman: There were always books in the house. Dad had something like 4,000 books. There were books everywhere, by his bed, by our bed. Arrowsmith by Sinclair Lewis was a very important book to me. It was about a physician who saw the disease process, and saw that it could be improved, and actually took on the task himself, of trying to make improvement. And the book by Paul DeKruif, The Microbe Hunters, which I read in junior high, about physicians trying to improve things, 'cause at that time, like today, in certain areas, medicine is really primitive.

Medicine seems very advanced now, but not if you have a brain tumor. It's as primitive as it was then. And not if you have leukemia and other kinds of disease. So those books were very influential.

You were very focused. Did you have other activities or hobbies?

Judah Folkman Interview Photo
Judah Folkman: Well, yes. I worked as a caddie on a golf course, and was in a chess club, and a lot of things. I didn't have sports as a hobby, as most do. To me, the science seemed to be a hobby. There was a Science Club. There were six of us, and we made radios, and did experiments, and we all entered the Westinghouse Science Talent Search. We never got anywhere but we tried it. There was an experiment that I did with another friend, Dick Wolfe. His father owned the Columbus Dispatch, newspaper. He was well-off and he could pay for experiments.

We found that when you bought a goldfish they never stop growing, which was fascinating. The goldfish person told us they always grow. So we had it in an aquarium at school, and we had built a measuring device on the side, so when the fish went by we could get a reading of his length, and every day we plotted it, and every day it grew, and it was on the wall. And the other students would come by just fascinated. It looked like the stock market, it was always going up.

And we changed the water on a regular basis and added the food in excess. Then we added two more fish, and they had plenty of food, but they all dropped down to a slower growth curve. And then we added four, and when we had nine fish, I think it was, they stopped growing. Yet we were changing water as fast as we could, and adding new food, so it was not lack of food. So it became clear that they were talking to each other about crowding. We'd take five fish out and the others would start to grow. It took all the school year, but it was quite interesting.

That's the one we sent in for the Westinghouse Science Talent Search. We had just gotten to the point of saying maybe if we take the water and put it through a cellophane bag in a dialysis, and see if we can find whatever this thing is, is big or small, we hadn't finished that, and I think that's why we didn't even get an honorable mention. But it was an exciting experiment.

In high school, I began to work just briefly, in the hospital, first in the clinical labs, but then as an orderly in the operating room, to see if I wanted to be a surgeon. And so while I was doing that in about junior year in high school, the Chief of Surgery at Columbus, the University Hospital, Robert Zollinger, a very famous surgeon, stopped me, and he knew the family, and he knew me. He said, "You're wasting your time doing this. If you want to be a surgeon, why don't you go to school at Ohio State and come and work in my surgical laboratory where they're training surgical residents on operations on dogs." That's a standard, that was the standard. "And you can work in the afternoon and help them." And his idea was that he'd always been looking for somebody who knew that they want to be a surgeon, very early. He felt that surgeons should, like violinists and pianists and dancers, start early, instead of waiting till 25 years old. And he said you can learn the anatomy later; do the skills.

So I went to Ohio State, and for three years, every afternoon, about one o'clock, I would go from classes to his laboratory and operate as a first assistant for his resident surgeons. After a while, I got good enough that they would call up and say, "I'm late, get started." We would do a gastrectomy, or whatever operation they were working on. And then they'd call up and say, "I can't get there, finish up. Do the whole operation." And I was able to do that. So that was a terrific beginning.

How old were you?

Judah Folkman: I was a junior in high school. I started as a orderly in junior high school, but then all the way through college, for three years at Ohio State University, I was in the dog lab in the afternoons.

They would come and go, but I was always there as the assistant. I was helping the surgeons, and I worked very hard at trying to learn how to tie the knots fast and do all that. There was a point at which one of them said, "You have good hands." That's the way they say it. I remember that, because you never know if you can do anything. Then you get a single compliment that can last for years, because you get self-confidence that maybe you can actually do this. I've learned to do that with young surgeons that I'm teaching, or young scientists who are in our laboratory. Their self-confidence is pretty shaky, but you can build it up so that they keep going.

What kinds of frustrations and setbacks have you suffered in your career? How do you deal with them?

Judah Folkman: Many setbacks. Most of the most difficult ones have been in the experiments that I've been doing for the past 30 years, because there it's very clear. And always the problem is knowing when you should give up or not. That's the big problem, I always found, is how long should you persist?

There's a fine line between persistence and obstinacy, and you never know when you've crossed it. So mostly, as I observed other scientists and read about them, many of them had given up. Fleming gave up on penicillin. He discovered it in the late '20s, tried to purify it, failed, and wrote in 1932, "I give up." He said, "This will never be useful because it's too unstable." And so it waited until 1941 till Florey and Chaine could figure out how to purify it. All three got the Nobel prize. So had he persisted, he might have had it many years earlier. There are many, many, many examples in science.

The obstacles mainly were in the very beginning, in the late '60s, when we proposed the idea that tumors need to recruit their own private blood supply. That was met with almost universal hostility and ridicule and disbelief by other scientists. Because the dogma at that time was that tumors did not need to stimulate new blood vessels, they just grew on old ones. And that even if they could, after we showed it, the next disbelief was it didn't make any difference; it was a side effect like pus in a wound. So if you said you were studying wound healing and you found pus, they said you were studying a side effect, it's not important. And then after we showed it was important, which took us about five years (and we said there would be specific signals, molecules that would stimulate this, everyone said -- pathologists, surgeons, basic scientists -- said, "No, that's non-specific inflammation. You're studying dirt." They used to say, "You're studying dirt. There will be no such molecules." And then when we actually proved that there was -- that was now 1983 (starting in the late '60s), we had the first molecule. They said, "Well, but you'll never prove that that's what tumors use." So it was each step.

Now it's not only well accepted that tumors are using specific molecules, they're actually made now, manufactured. When we said, "You should be able to turn off this process," everybody said, "It's impossible. Once angiogenesis is turned on, once they recruit their blood supply..." In other words, now they were using our own theories against us. They said, "Once they recruit their own blood supply." That's all accepted now. Every article now, a thousand articles a year, start out with, "It is well accepted that tumors are angiogenesis dependent."

You didn't just meet setbacks; you ran into actual hostility. How did you persevere?

Judah Folkman: Oh, yes. Ridicule. A lot of people would walk out of my presentations. There were many critics, very great experts who kept saying this couldn't be. I had one advantage. I kept saying, "I'm pretty sure they're wrong." And the reason is that I had been a surgeon for years. I was surgery chief at Children's Hospital.

When you operate on cancer, it was different than any other thing. It never stopped bleeding. You could operate on a kidney, a liver, or do any other surgery, and if you lost blood, the organ would stop bleeding. It would turn white. All of the vessels would clamp down and the anesthetist would say, "Stop, we've got to give a transfusion." But in a tumor it would never bleed, and if they could just keep bleeding and bleeding, and there was massive bleeding, and you would use up pints of blood, and all surgeons know that. I knew there was something different about these blood vessels. And the pathologists who were criticizing for example, had never seen the blood, because once we hand them the tumor, it's white, and so to them it's bloodless. And the oncologists, a further step away, had never come to the operating room, so they were looking at x-rays. And the basic scientist has only seen cancer in a dish. And it began to dawn on me that they were missing something, and I said, "These people are wrong."

I never said it to them, because you waste your time battling like that. You just keep doing the data. I remember a second thing. I was in my lab at Children's Hospital.

We had ten years of really tough ridicule. I was sometimes very upset. And John Enders' lab was right next door, and he had won the Nobel prize for polio virus, a very quiet, reserved person. He also had a pipe. And he said, "This is just..." when grants would be rejected, he said, "This just proves that there are no experts of the future. There are only experts of the past, and they sit on the study section." So he said that you just have to take this in stride.

One time I wrote this big grant in the '70s that outlined the whole field as it almost is today. That there would be inhibitors and stimulators, and you could turn off blood vessel growth, and there wouldn't be drug resistance, and you shouldn't attack the tumor so directly. Laid it all out. And then I got cold feet, and I went to him and said, "I think I'm giving away too much." And he looked at it and he said, "No, it's theft-proof." He said, "They're never going to believe this. You'll have to ram it down their throat and it will take you ten years." He said, "Very interesting." And then also my wife Paula, many, many times. It would be very upsetting to get rejections from journals many, many times, and rejections from grants and things, and you think that the work is really -- I remember one time in the study section, "Haven't we funded this work long enough?" It didn't seem to be going anywhere. It was hard work. They were going to just stop all the funding. And Paula would always say, "Well, what do you care? If you really think it's right, you should go on."

It's easier now because it's all accepted. In about 1983 there was a big experiment that we published, which overnight converted most of the critics to competitors. So we had And now the principles are established, we have hundreds of competitors. There are hundreds of labs. There are 90 companies working on this. But...

The nay-sayers keep coming. There are always nay-sayers. And now they say, "Well, it works in mice, but it won't work in people." So I say, "So what? Should we not test? Should I stop because you know for sure?" And people come up, stand up at meetings, "I'm very perturbed. It cannot work in people, must not work in people. This only works in mice." So I do two things. I say, "Will you sign?" I have a little book that I carry. I say, "Will you sign for me? Because you're so sure, I can just publish your remarks directly and save a lot of government and taxpayers' money, and we won't do the experiments. We won't test in humans. We'll just say it won't work." And then you get this body reaction. And then I also have -- there's a slide that I have for occasional -- I don't get this so much any more, but the slide is the New York Times, and it's 1903, and it's two Harvard professors, on the front page, have shown the exact mathematics of physics -- these professors of physics -- of why it is impossible for man to fly, because you can't build a motor that could lift its own weight. And three months later they took off at Kitty Hawk, or four months, something like that.

People who make these predictions can slow down a field, but they can still be wrong. There's still a lot of nay-sayers. They're all over the place. I also have begun to notice that the same nay-sayers -- and I never mention their names -- call me at home at night when they have prostate cancer. So they do believe something. It's being tested now and being validated in the clinic. We have seen it ourselves. We have children who are alive and well today from therapy at Children's Hospital, who would be dead because every other therapy failed. One at a time, by using experimental angiogenesis inhibitors, getting permission from the FDA, compassionate approval, one case at a time, because there's not enough of the drug to do big trials. And they've done beautifully. So we have a forecast of what's to come.

There must have been dark moments, moments of self-doubt, fear of failure?

Judah Folkman: Right. Very early in the '70s, there was a time when all of our grants were turned down, so we didn't have any funding. In a university laboratory, if you don't have funding, they cannot carry you. So you must close your laboratory, and you have to stop. Now once you stop, you can't get started so easily because they say, "Well, there are lots of people. These ideas didn't turn out." And there was another time.

In the '70s, there was post doctoral fellows who would apply, who were told not to come to our laboratory. They said, "That's very controversial, very controversial," and so nothing scares a young post-doc worse than "very controversial," because he doesn't want to commit his two years of his life, three years. And I remember it turned around with a couple of people. One was Michael Gimbroni, but another one was Robert Langer. Robert Langer came from MIT, number one in his class in chemical engineering in 1974. And we really needed help in chemical engineering, because we were trying to get these molecules to diffuse like tumors. And Langer said he had offers from everywhere, from MIT, from Shell Oil, from everywhere. And he was interested in biomedicine, and he was just going to stop in and say hello, but he said, "I have to warn you, I've been told by four professors at MIT don't come here, and never go to a medical school anyhow because they'll treat you like a technician if you're a chemical engineer." And I remember saying, "Why don't you come for six months and make up your own mind?" And that appealed to him, and he came and stayed two years, and within six years was a professor at MIT.

He was the youngest member of the National Academy of Sciences. He's very famous now.

There had to be something beyond the courage of your scientific convictions. It takes a certain inner strength. What did it take for you to ignore the nay-sayers? Ordinary people would have given up somewhere along the line.

Judah Folkman Interview Photo
Judah Folkman: When you're a surgeon, you can take somebody through surgery and take care of them, but if anything happens to them it's your fault. It's not the team. And you see what cancer is like.

There are two other things that helped. A lot of credit goes to the Harvard Medical School. They gave me tenure very, very early. Dean Hebert was the deana at the time. I finished my chief residency in 1965 at Mass General, so my surgical training was complete and I was an instructor on the faculty. That's the lowest you can be, and the next level would be assistant professor in six years, associate professor in four to six years, and then tenure at Harvard is given to very few people. The joke at Harvard is that more people die waiting for tenure than for a liver transplant. That's because it takes a long time.

I was only 33 and I was offered the position of professor. I jumped. I was never an associate. They had a position open which was chief surgeon at Children's Hospital. I was told by the dean that this work was very controversial, but that if we were right, Harvard would get the credit, and it would be a new field. And I remember him saying, "The purpose of tenure is not financial security. The purpose is so that you can pursue a wild idea and not lose your job." So that really helped.

There was another time in the mid-'70s. The National Cancer Institute has supported this work virtually uninterrupted for 30 years, so they deserve enormous credit, but there were times when the peer reviewers, who are colleagues, just said, "Don't fund it." There was one time where they turned off all the grants.

The executive secretary came up to Boston and said she didn't think that the study section had been fair. She said she was going to take it all the way to the top, and she did. She took it to the Science Advisory Board. Mary Lasker was on the board and overruled the study section and we got the grant so we could keep going. So there were lots of people involved.

Another one has been Collette Freeman. She's been the executive secretary of our grants for about 15 or more years, and she's known as the mother of angiogenesis research. She made sure that these things were fair. If they were turned down, she would tell us why, and how we had to improve it. Very helpful.

Reading about what you discovered, it seems so simple.

Judah Folkman: The idea is simple, but the figuring it out was extremely complicated. For example,

Clotting of blood, going from liquid to clotting, is a very simple process when you look at it. But it has 40 proteins. They each have their own genes, receptors, signal transduction, and it's taken 40 years to figure it out. Many, many careers have failed and many have succeeded. And the angiogenic process, just making a capillary grow, is astoundingly complex as you get into it. And if you don't get into it, you can't turn it off, because you've got to know the wiring and the logic. But just how to make a tube, just making a tube, is an incredible set of genes. Then making a branch is an incredible set of genes. And if you look at this system, for example, in the embryo, in a fetus, in a chicken embryo where you can see it. Day one: the heart is not beating, the heart is forming, and all of the blood vessels are forming. But by day two, all of the blood vessels, far out in the limbs and everywhere are all formed, and the whole system is connected, and everything is sealed. And then a signal is sent that the heart can start.

Now that's all a genetic program. In a few percent of all cases, the signal comes early. The heart starts and there's bleeding in some far out place, and the animal dies, and that's the most common cause of miscarriage. Now figuring out how that works is one part of it, and then figuring out what are the chemical signals that a tumor makes that normal cells don't make, and what turns that on. Why?

In colon cancer, can you have that little tumor for 10, 15, we now know 20 years, and then one day it starts to bring in blood supply, and then you have blood in the stool, and then you have metastases. And then you only have two years left, or three years. That switch now is understood, is being worked out. And turning it off, because it's relentless when tumors turn it on, is incredibly complicated.

The biggest surprise of all, I think, was O'Reilly's discovery with us in 1993, when we found proteins in the body, hidden inside of other proteins, that by themselves, single protein angiostat, can turn the whole process off completely. No matter what the tumor was putting out, all of its angiogenic stimulators, this protein, if you gave it in high enough amount, would just shut it off with no side effects. And then the tumor would come down. It's a big shock, those kinds of things.

What makes your work so exciting for you?

Judah Folkman: What is exciting about studying just this process, it's a process called angiogenesis, how blood vessels grow, is that it continues to lead to fruitful discoveries. These come every -- they come over long periods of time, sort of an "Aha!" moment. When you find out, for example, that the same molecules that you were studying that the tumor has made in excess, one of them is the one that completely is the cause of diabetic retinopathy, of the millions of people who have blood vessels in their eye. And that this one is also the cause, in a different regulation, of macular degeneration. 15 million Americans who have that -- blood vessels again in the back of the eye -- elderly, and 200,000 blind from it. No drug at all exists, nothing, and even laser doesn't work. And that's primitive because they burn away the retina and then it doesn't work, so people go blind. And now you realize that you have -- in fact -- you understand it enough to turn that off.

That's going into clinical trials. It takes years. But as you pursue understanding this process, you suddenly understand how psoriasis works: blood vessels. How arthritis works: blood vessels grow in the joint and just destroy the cartilage. Now for example, every week brings an article on endometriosis in women. The lining of the uterus sometimes backs up and grows in their abdominal cavity, especially in professional women, women who have delayed childbirth. It's a poorly understood disease. Now we really understand it. Hemangiomas in children in the brain, which we never understood, we can now treat.

So all of these rules are coming out. You have a map suddenly, and as you understand the rules of this process, you suddenly understand a whole lot of diseases. This isn't just in our laboratory; they're making these discoveries all over the world. Every week you pick up a journal, Science or Nature, and there's a new discovery. There's one out today, Science, reporting an incredible new discovery coming out of Regenerize , a company, about angiogenesis and tumors, that never occurred to us. It's very fruitful if you keep doing it.

What do you see as the next great challenge, the next great frontier for you?

Judah Folkman: There are two big areas. We want to see validation in the clinics.

We want to see proof of principle in humans, that you can take an angiogenesis inhibitor, these normal proteins, and you could add it to chemotherapy, or add it to radiotherapy, or add it to any current immunotherapy, and improve it, or add them to each other, and improve the care of cancer. Proving means, "Can you lower the terrifying toxicity?" That's what scares patients. Can you make it more of a -- nuisance? Like if you look at bleeding ulcers in the 1950s, if you had that, there were no drugs except Maalox. You went right to the operating room. That's all we could do to stop it. I was there in the '60s, that's what we did. And then when the drugs came in, Tagamet, and now the antibiotics, it's a nuisance, and we don't ever operate, or almost rarely. Can you do that? That's the question.

We'd really love to see that validated over the next five, ten years. And secondly, can you begin to use these principles to turn off other diseases? Can you have a drug for diabetic retinopathy? Can you use that for the other diseases that cause blindness? That's one area. The other area is very basic. Can we really understand why the body makes these proteins in the first place, and why it's using them under normal conditions? For example...

In both ovaries there about 400 potential follicles, but every month a woman turns out only one, and it gets a huge amount of blood vessels for four or five days, and then the ovum comes out. But the other -- when those vessels go on, the others are turned off, prevented from having vessels, so you never have two ova at the same time. Now suddenly -- nobody's ever understood that. It's called the dominant follicle, but it's turning out to be the same process by which a big primary tumor will suppress blood vessel growth and its metastasis. You take out this tumor and these grow up. It's the same process. It's just in a different setting. So it's exciting to understand that suddenly, because when you understand something, you can predict and you can control it.

What do you understand about achievement now that you did not understand when you were younger?

Judah Folkman: If you were told all the obstacles you face when you started, you'd probably never start. But once you're under way, you don't want to give up.

How would you define the American dream? What does it mean to you?

Judah Folkman: I've talked to people who can tell you better, because they've come to this country. They see it in a much different light.

There's a freedom to pursue ideas and jobs and kinds of work that fit you, that you like to do, freedom to express yourself, to write. It's not freedom from responsibility, but most places in the world you're told what you can't do, by the government, by the police, I mean, very few places like this country. And even in places like in Europe, great countries in Europe, after five o'clock, it's not so good to be working past five. It's frowned on. You are told, "That's not the way we do it here." There's a style. So there's enormous freedom here to do -- that just doesn't exist in other parts of the world. And I think that's what's so great about this country.

A few minutes ago I was taking a cab to the airport, and there was a Russian cabdriver who had been here only two and a half years, so he's just barely speaking English, but he had four cell phones going, all pasted on his dashboard, and they were ringing, and he was answering them. He was dispatching, and he was driving, and I said, "What are you doing here?" He said, "Well, I own a cab company. I have four other Russians working for me, and we do not make enough money. We make money, but we don't make enough money to rent a place to have a dispatcher." So he's the dispatcher. So he was saying -- I can't remember his words -- saying, "What a country!" Because he could never have done this where he was. And he was about 30, and he was working 18 hours a day. It's amazing.

Thank you so much, Dr. Folkman. We really appreciate it.




This page last revised on Sep 21, 2010 20:19 EST