On Monday evening, renowned cancer researcher Judah Folkman, Harvard professor and director of the vascular biology program at Children’s Hospital Boston, died unexpectedly of a heart attack at the age of 74.
When I was in my junior year of high school, I saw “Cancer Warrior”, a Nova documentary on public television narrated by Alan Alda. The documentary was about Judah Folkman and his theory of angiogenesis, the process through which a tumor is able to generate its own blood vessel network. In order to grow beyond a certain size, tumors rely on their surrounding vasculature in order to obtain nutrients and excrete wastes. Folkman reasoned that if it is possible to cut off a tumor’s blood supply, a tumor could essentially be starved and maintained in a dormant state.
There was something magical about the way Folkman spoke. His electric energy, his grandiose ideas, and his enthusiasm for the way in which basic research can change the world was completely contagious.Listening to him tell his story about angiogenesis, I felt a passion and excitement for ideas that I had never known before. I remember at one point actually getting up from the couch and moving closer to the television in anticipation of the next turn of the unfolding story, as if I were watching an adventure thriller. Two aspects of the angiogenesis story captured my imagination: Folkman wasn’t ashamed to dream big and to share those big dreams - sometimes prematurely. Also, Folkman had a great, romantic story.
The major focus of cancer research in the 1970s was harnessing the new tools of molecular biology to study cancer cells themselves. No one was thinking about the tumor’s seemingly irrelevant normal environment. For decades Folkman’s ideas about the importance of a tumor’s environment were scorned and ridiculed. After all, he was a surgeon dappling in research in his free time. And he had the whole problem of his big ideas that he talked so freely about before he had any proof to substantiate them.
The work to prove angiogenesis was painstaking and slow because Folkman and groupies had to invent most of the tools and systems used to study angiogenesis themselves. Eventually, vascular endothelial growth factor (VEGF), a major stimulator of new blood vessel growth, was identified and in the years that followed a host of other stimulators and inhibitors of angiogenesis were isolated. With proof of such stimulators and inhibitors, tumor angiogenesis became a credible, accepted phenomenon. Overnight Folkman went from the quack with irrelevant, unprovable ideas to super science celebrity. The list of other diseases in which pathological angiogenesis is implicated keeps growing.
In 1998, two endogenous angiogenesis inhibitors, angiostatin and endostatin, were shown to cure cancer in mice, a study that made the front page of the New York Times and prompted co-discoverer of the DNA double helix, James Watson, to prophesize that “Judah will cure cancer in two years.” By the time I sat in my father’s downstairs study watching “Cancer Warrior” at the beginning of 2001, a whole new field of cancer research had exploded and a biography of Folkman, Dr. Folkman’s War by Robert Cooke, had just been published.
The next day I went to my high school biology teacher and I asked her if I could do an independent study reading about angiogenesis under her supervision in lieu of a regular course. She thought it was a great idea. I didn’t have Powerpoint, so for my end of semester presentation, I drew pictures of tumors in magic marker and color-copied them onto overhead transparencies. I loved every second of my independent study and by the end of my junior year, I decided that I definitely wanted to be like my hero Judah Folkman and become a scientist.
During my first year at Wellesley, I met a Harvard scientist who trained in Folkman’s lab and now had her own angiogenesis lab. I ended up working in her lab every summer during my time at Wellesley and also did independent studies in her lab during the school year. It was very lucky and special to actually become part of the research I first learned about in high school, especially since it was what inspired me to want to do science in the first place.
Every summer, Folkman would lead the annual surgical research department (later renamed vascular biology department) meeting at the Academy of Sciences in Cambridge. The meeting would consist of his own lab and the other collaborating labs in the department. Folkman was a pretty quirky guy (for instance, he drove a silver VW bug right into his 70s) and had very particular ideas about how this meeting should be run. For one thing, jacket and tie were required. The other rather interesting twist was that no Powerpoint or slides of any sort were allowed - “chalk talks” only. So you had everyone dressed in his or her finest garb in the middle of the day giving these very informal short talks with magic marker and chalk.
Every year Folkman would give a talk at the meeting that would more or less dictate the major themes of angiogenesis research for the next year. He’d get up there and be teeming with his electric energy and excitement and you’d know there was something special going on. It was just like watching the Nova documentary in high school all over again except it would be so much cooler, because I’d actually be in the room. It would set the standard for me of how I think all scientists should love their science and talk about their science.
The last time I saw Judah Folkman, he joked about his own death. Avastin (the first angiogenesis inhibitor to make it big which interestingly works more by normalizing the tumor’s convoluted vasculature to enhance deliverability of chemotherapy than by choking off the tumor’s blood supply) had just finished the last stages of clinical trials and had been put on the market. He said he was at a big press conference marking its release and one of the speakers commented, “If only Judah Folkman were still alive to see the results of his research.” Folkman then went up to the microphone during the question and answer session to say “This is the ghost of Judah Folkman!” (I think he really liked to tell this story).
I know that Dr. Folkman’s life and work affected thousands of other people very much like me and also very different from me and changed their lives forever - young people who were inspired to study science because of his story, scientists and physicians at all stages of their careers whose career paths and choices were impacted, patients in the death throes of cancer, some who lived and some who died, but all healed in some way whether by words or by drugs.
Now the patriarch of a whole new field, the man holding the light out front, is no longer with us. I am very, very sad. But I am pretty sure his boundless enthusiasm for ideas, his imagination, his creativity, and his unshakeable and stubborn pursuit of truth in the face of skepticism and adversity could reach from here to infinity. The stubborn rabbi’s son from the midwest turned surgeon “quack” scientist turned science superstar - you changed the world, Dr. Folkman.
Judah Folkman, cancer’s innovative enemy, dies at 74 Boston Globe