Respectful Insolence

i-0f6766ffc6a1bc0bda359ed19d60e0eb-folkman.jpg

Today is a very sad day around my lab.

I’ve just been informed that one of my scientific heroes, the man whose work inspired me to enter the research area that I entered, namely tumor angiogenesis, died last night. Yes, sadly, Dr. Judah Folkman reportedly died of a heart attack last night.

I had the honor of meeting Dr. Folkman on two or three separate occasions, one of which was for a laboratory meeting that involved discussion of our lab’s work. A self-effacing and humble man, he was a true scientist, always questioning, always thinking of new hypotheses to test based on answers that scientific experiments and clinical trials provided and, more importantly, the unanswered questions they left. Moreover, he was the consummate surgeon-scientist, a man equally at home in the operating room and clinic as in the laboratory, a member of a rare and unfortunately dying breed who was the true “triple threat” of being a great researcher, great clinician, and a great teacher. The last time I saw him was in October, when he gave one of the keynote addresses at the Breast Cancer Research Foundation in New York.

Few scientists can be said to have created a whole new and important area of investigation, but I can certainly say that about Dr. Folkman. Prior to his proposal in 1971 that targeting tumor angiogenesis (new blood vessel growth that tumors induce from the surrounding tissues in order to supply themselves with oxygen and nutrients) could be an effective new strategy to treat cancer, the idea that tumor blood vessels were an important component of how tumors grow and metastasize was not appreciated. Indeed, Dr. Folkman’s concept was greeted initially with skepticism and ridicule. Folkman didn’t whine or complain that he was misunderstood. Instead, he did what a real scientist should do: He went back to the lab. It was over two decades before Folkman’s patient, persistent research started to bear fruit with his discovery of angiostatin and then later endostatin. In the late 1990′s, due to some truly exciting results in mice, the media created a bit of a frenzy claiming that cancer was “cured” by this new therapy. Indeed, I was caught up in the excitement of the research at the time and ultimately ended up studying angiogenesis myself. Since then, although not unexpectedly the clinical results from angiogenesis inhibitors have been more modest that the hyperbolic claims of a decade ago, angiogenesis remains one of the more promising avenues for controlling cancer. Angiogenesis inhibitors have already been validated in clinical trials for cancer, macular degeneration, and other diseases, with many more in the pipeline. Later, when other investigators reported having difficulty replicating his results, he demonstrated once again what an exemplar of science-based medicine he was. Did he attack the scientists who questioned his results? No, he did what a real scientist would do: He offered advice, technical support, and even reagents, including the antiangiogenic agents themselves, until the reasons that replication was difficult were worked out and soon several labs were reporting similar results to his.

Characteristically, Dr. Folkman was very modest about this and very cautious about extrapolating the remarkable results in mice to humans. At the height of the angiogenesis media frenzy in 1998, he was known for saying in interviews, “If you have cancer and you are a mouse, we can take good care of you.” He’s also put it this way:

Folkman’s remarkable results in the laboratory set off worldwide speculation that he would be the man to cure cancer, but he was uneasy with the accolades because cancer is such a complex disease. “We never use the word ‘cure’ because it is far away,” Folkman said in one of his last interviews. “It may be that patients will have little tiny cancers that lie dormant for a long time.”

Dr. Folkman never lost his ability to inquire or to inspire. Without his example and his groundbreaking research, I can honestly say that I would not be the surgeon-scientist that I am today. It’s a shame Dr. Folkman never won the Nobel Prize. He definitely deserved it.

ADDENDUM: More on Dr. Folkman here and here.

Comments

  1. #1 Abel Pharmboy
    January 15, 2008

    This is absolutely terrible news – we have lost a giant and a role model for perseverance in scientific inquiry. I saw Dr Folkman twice last year where he provided evidence for the role of aberrant angiogenesis in more than a dozen tissues. His work extends far beyond cancer; I, too, share your sentiment that he was truly deserving of the Nobel Prize. We have lost a true gentleman.

  2. #2 daedalus2u
    January 15, 2008

    This is sad news. Angiogenesis is an extremely important physiological process and one that remains poorly understood, yet obviously must be involved in every tissue compartment that is vascularized. How anyone could think it wasn’t important in cancer, even 35 years ago, is not something I understand.

  3. #3 Jesse
    January 15, 2008

    My favorite quote from Dr. Folkman:

    “Science isn’t one success after another. It’s mostly one success in a desert of failure.”

    Truly a pioneer. I remember watching the Nova special about him and angiogenesis about a week before I decided to go to graduate school where I have been studying cardiovascular development.

  4. #4 Sigmund
    January 15, 2008

    That is sad news. I work at the Karolinska and know that he was very much admired by many on the medicine prize panel. I guess people assumed he would be around for quite a few years yet.

  5. #5 factician
    January 15, 2008

    I saw him give a talk once. It’s true, he was a scientist extraordinaire, in addition to having the rare gift of being able to give a truly exciting talk.

    This is truly sad news.

  6. #6 Sad One
    January 15, 2008

    Truly a sad day for all of us who knew Judah well and a major set back for humanity in the fight against cancer. My thoughts are with his wife and two children tonight as well as his colleagues around the world.

  7. #7 RJS
    January 15, 2008

    Wow, I’ve cited Dr Folkman numerous times, while knowing nothing about the man himself. A sad day indeed.

  8. #8 CanadianChick
    January 15, 2008

    I know next to nothing about his area of research and less about the man himself, but reading your tribute, I feel as though we have all lost one of the giants today.

    My sympathies for those of you who had a connection with this man…he sounds like the type of scientist we could use lots more of.

  9. #9 Chris Noble
    January 16, 2008

    My favorite quote from Dr. Folkman:

    “There’s a fine line between persistence and obstinacy, and you never know when you’ve crossed it.”

  10. #10 Gregory D. Pawelski
    January 16, 2008

    Truly sad news for a great researcher, scientist and physician. Over the years, he had survived peer rejection of his theory and gone on to develop drugs that did what he predicted they would do. The angiogenesis-blocker boom is on. His ideas will be greatly missed. Nobel Prize posthumously!

  11. #11 JC
    January 16, 2008

    Orac I share in your sadness. MJF was a truly amazing man and he will be missed by so many. One of my favorite MJF quotes: “If you drain the Pacific Ocean, do not be surprised to find that the islands are connected.” His realization that aberrant angiogenesis connected so many different diseases was an amazing insight. The kind of insight that dreams are made of.

  12. #12 DLC
    January 16, 2008

    Always sad to see one of the pioneers die.

  13. #13 juliamd
    January 17, 2008

    I heard Dr. Folkman speak at PriMed in Boston in 2005(? I think it was ’05) and he was a wonderful speaker and a brilliant man. The scientific world is much poorer without his presence.

  14. #14 Barbara
    February 4, 2008

    Dr. Judah Folkman: Thank you for your inspiration

    Posted by Barbara Lavery — January 16, 2008 11:12 am
    Yesterday, Dr. Judah Folkman, the pioneering cancer researcher whose passion and commitment resulted in a whole new field of medicine, died. I was driving to work listening to his friends and associates on NPR talk about Dr. Folkman’s relentless pursuit of ideas and passion for learning. It struck me that even though I had never met Dr Folkman and even though I am not a scientist by training this man had been part of my life. When I joined Zoomedia in 1997 I was a theater designer who knew little about the Internet and even less about scientific research. Today, I am passionately committed to the advancement of science and the communication of those advances to the public. Without Dr. Folkman’s pursuit of ideas and innovative approach to cancer research I would never have started that journey of learning.

    In 1998, SUGEN, a biotech startup in Redwood City, asked Zoomedia to develop a corporate website that would help explain the company’s new approach to cancer therapy. My job was to work on an animated piece called “Angiogenesis Magnified”.

    “Hey Barbara, can you draw a few screens to show what happens when tumors grow and become hypoxic, and synthesize and secrete vascular endothelial growth factor (VEGF) and how this growth factor, or molecular messenger, sends a signal to nearby blood vessels that triggers the activation, division, and migration of endothelial cells that line the blood vessel walls and how that results in the sprouting of capillaries from the blood vessels and into the VEGF-secreting tumor…” “Oh and we need it by Tuesday…” “Umm, sure, no problem…” and so I began to learn.

    In 1998, the idea of communicating science to broad audiences on the Internet was an idea that Zoomedia was very excited by but we were limited by the Internet itself. Connectivity was slow, downloading images gave you enough time to go get a cup of coffee, and creating the work in the first place took hours of interviewing the scientists working on new research and then sketching, scripting and visualizing something that even they could not fully explain. The resulting animation had to be absolutely scientifically correct, easily understood, and delivered through a web browser. You can see the results of the “Angiogenesis Magnified” project below.

    Today, we are streaming Flash videos, creating 3D animations, working in virtual environments like Second Life, and pushing the limits of the Internet to deliver critical information to patients, physicians, scientists, the media,and investors. What we are capable of and what the Internet allows us to do is so far ahead of 1998 it’s hard to remember where we started. The things I have learnt and much of the cancer-related science we illustrate and communicate would not have been possible without Dr. Folkman. SUGEN meanwhile, was acquired by Pharmacia, Pharmacia was acquired by Pfizer – Pfizer’s drug Sutent (one of SUGEN’s original angiogenesis inhibitors) was approved in 2006 and was the first new cancer drug to be approved for two indications simultaneously – gastrointestinal stromal tumors and renal cell cancer (RCC).

    Dr. Folkman’s work has allowed many of my personal friends and family to benefit from drugs like Sutent, Thalidomid and Avastin that may not have been possible without his ceaselessly creative approach in seeking new paths to cancer treatment. The pursuit of new cancer treatments is far from over and the communication of how scientific advances impact our health and our future is ever more critical. Thank you Dr. Folkman for your inspiration.

    Barbara

  15. #15 Dr Aust
    February 4, 2008

    Really sad that Judah Folkman didn’t live long enough to get a Nobel, which would have been richly deserved. Sometimes those panels do seem to wait an awful long time – too long in this case.

    I remember seeing Folkman give a packed-out big lecture at the NIH (early ’98, I’m pretty sure it was before the famous Gina Kolata story in the NY Times), and the buzz in the Building 10 auditorium (500+ hard-core scientists and doctors) was really perceptible. People who can get that reaction from the trade are a rarity, in my experience – Francis Collins talking about the HGP back in the early 90s is another example I remember. Anyway, Volkman was very droll, as well as showing some amazing data – I distinctly remember him using the self-effacing line Orac quotes above about “If you’re a mouse with cancer, we can take good care of you – unfortunately people with cancer present a bigger challenge”, or something close. Another line I remember was a recurring jokey riff about how difficult it was to get an opthalmologist excited about anything. The final thing I recall about the seminar was him saying he had a whiteboard up in the lab with key unanswered questions written on it, and that “anyone who could figure out an experiment that would answer them got to be first author on the resulting paper”.

    Anyway, it’s a shame he’s gone. Let’s hope targeting angiogenesis really pans out as a tumour therapy. That would be a pretty good memorial to the man and his work.

The site is undergoing maintenance presently. Commenting has been disabled. Please check back later!