The discovery of angiogenesis inhibitors: A new class of drugs: Transcript: Introducing Judah Folkman
Bill Speck:
Can I have everybody's attention please? It is a great privilege for me, Bill Speck, to introduce tonight's speaker, which begins our Friday night lecture series for the year 2001. For those of you who may not know who I am, I am the new director of the Marine Biological Laboratories. Part of the job of the director is to introduce the first speaker of the first Friday night lecture series, and it is a privilege to introduce Dr. Folkman, although he needs no introduction and therefore my remarks will be very brief.
As I thought about what I would say to introduce this very famous person, I really was struck by a quote by Szent-Gyorgi, who was one of our own [and] had been associated with the Marine Biological Laboratory for a long time. I think this quote, if you listen to it, really captures the essence of Dr. Judah Folkman. The quote of Szent-Gyorgi is, "Discovery is to see what everyone has seen and to think what nobody has thought."
For years, we physicians had taken care of patients with cancer. We had removed solid tumors and we had seen them surrounded by blood vessels that were deteriorating and eroding the tumor. And for years we thought this was a non-specific inflammatory response to the tumor invading the blood vessel.
Dr. Folkman looked at the same tumor&looked at the same blood vessels, and he thought what nobody else had thought. He hypothesized in 1970 that these solid tumors were angiogenesis dependent; that is, that these tumors were actually attracting these blood vessels. And that was startling. People thought he was mad. It was a heretical idea at the time because we had all been taught that tumors move out, follow blood vessels, invade the blood vessels, and then spread throughout the body.
Here was this "Alice in Wonderland" guy who thought just the opposite. He thought that the tumors created some substance that attracted blood vessels, and everybody really thought he was mad!
And here we are today--2001. Everybody now recognizes that angiogenesis is an important biological [inaudible]. People now recognize and understand that if we control angiogenesis, that is, the proliferation of endothelial cells and capillaries and blood vessels, we have the opportunity to preserve dead or dying tissue.
We also now know that if we inhibit angiogenesis in certain kinds of morbid states like tumors, we can actually deprive these tumors of their blood supply. All over the world today, people are working on the concept of angiogenesis--promoting it to save damaged organs and damaged tissue, inhibiting it in order to prevent the proliferation of malignant tumors.
But when he first said it&when he first thought it&people thought he was really crazy. And what is amazing to me, having followed his career, is that he has focused on this hypothesis, and he has spent his entire professional career trying to prove what he thought was true in 1970 and now, the truth be known--he was right.
Dr. Folkman was born in Cleveland, son of a rabbi, a brother and a sister in the family. And they moved to Michigan where the father ran a congregation, then subsequently settled in Ohio--a state in which I lived in for many years--at Cleveland, at Case Western University. He attended Ohio State University, a "Buckeye."
But one of the things that was interesting about him is that he hooked up early on with the leading academic surgeon of that time, Dr. Zollinger. This young undergraduate worked with Dr. Zollinger in an animal laboratory trying to understand the association between non-islet to islet cell tumors in gastric ulcers. It eventually became known as Zollinger/Ellison syndrome. But the most important thing was that this undergraduate student from Columbus learned how to work in an animal laboratory--surgical techniques that were really unheard of.
He went to Harvard Medical School after 3 years at Ohio State, and once again he worked with an academic surgeon, Dr. Gross. Dr. Gross was the Chief of Surgery at the Children's Hospital in Boston and Dr. Gross' main interest at that time was trying to figure surgical correction for children with congenital heart disease. He embraced Dr. Folkman, in part because he was a friend of Dr. Zollinger, but also he needed somebody who understood how to work skillfully in an animal laboratory. At the time they were working on ways to surgically repair congenital defects in cyanotic infants. They began to understand the importance of the cardiac conduction system, which is often damaged during surgery, and came up with the ideas of external and internal pacemakers.
He graduated from Harvard at the top of his class and immediately began internship and a residency at the Massachusetts General Hospital. Two years into that, he was drafted into the United States Navy, but he was fortunate in that he was sent to the National Naval Medical Center. His initial assignment at the National Naval Medical Center was to come up with a blood substitute-- something other than blood that could be used to treat war casualties until such time as blood was made available.
They worked on that, he and his colleague, for a number of months and improved the methods. But during that period of time, he became interested in other things, moreover he had some time to kill before he went back to his internship and back to his residency and that was the time he began to work with malignant cells, melanoma cells.
He made the observation early remember, this is a guy 24 or 25 years old-you could grow melanoma cells in tissue culture, they would grow to a certain size, these highly virulent, highly malignant cells, and they would stop their growth. Once they got to be about the size of an eraser, they would stop their growth. He would then transplant them into animals and they would grow and proliferate and kill the animal. He could transplant them into animals, into organs that didn't have normal blood supply, and again they would remain static. So at that time, he recognized that there was something about tumors that attracted blood vessels and allowed them to grow and thrive and prosper at the expense of the host.
He finished two years in the Navy, and he went back to Mass General--Senior Resident&Chief Resident&and then went on to join the Harvard Faculty as an Assistant Professor at the old City Hospital at Boston City Hospital. He was there two years, assistant professor, doing his research&an adult surgeon&when he was recruited to be Surgeon and Chief of the Children's Hospital of Boston. We in pediatrics were shocked. Here was an adult surgeon who was being made Chief of Surgery at a Children's Hospital!
On the other hand he dropped out of sight for a while and spent six months with C. Everett Koop--who was at the Children's Hospital of Philadelphia, and went on to claim fame as the Surgeon General--and he was Dr. Koop's chief resident. He operated on every single case that came to Children's Hospital in Philadelphia for a 6-month period of time. So, in 1967 he was made Surgeon and Chief at the Children's Hospital in Boston and continued his research until 1981.
In 1981 things were moving up in the angiogenesis field. He decided a time had come for him to relinquish his academic responsibilities for the department, having been a great teacher, a great patient care provider, and a great investigator, in order to focus all of his efforts on angiogenesis.
There is nothing I can say about his awards--[the list] covers 3 to 4 pages--and his curriculum vitae. The societies that he is a member of, including the National Academy of Sciences, go on for 1 to 2 pages and his publications are 4 to 5 pages.
He is a great person, a great man, and people who know him like him. He is "meshpucha," he is the kind of person we would all, I think, like to be. He developed a hypothesis, he focused on it, and he doggedly pursued it. And all of the skeptics now say he was right. He was able to look at something that we had all looked at and see something very different. And what he found had a dramatic impact and will even have a greater impact on human disease and suffering.
Dr. Folkman, it is a great pleasure to welcome you to the Marine Biology Lecture.
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