Judah Folkman, "the father of antiangiogenesis," a way to starve tumors of their blood supplies, died yesterday from an apparent heart attack. He was 74 years old.

Folkman, director of the Vascular Biology Program at Children's Hospital Boston, served as the hospital's surgeon in chief from 1967 to 1981. During his tenure, he published a groundbreaking article in The New England Journal of Medicine, suggesting that tumors require angiogenesis, the formation of new blood vessels (from established ones) to provide the nutrients their cells need to grow beyond a certain size. He had first had this insight in the 1960s when he was serving as a Navy surgeon and was tasked with developing a blood substitute that could be a lifesaver during combat. (At the time, it was cancer research dogma that tumors did not need new vessels to thrive.)

For much of the next two decades Folkman was treated as a pariah by his peers, who dismissed his theory outright. He was criticized whenever he announced a finding. To continue his unpopular research after all other funding sources dried up, he was forced to take a hefty sum—$23 million—from chemical company Monsanto.

Convinced he was on the right track, he persevered in the face of adversity. By the mid-1990s the tide turned in his favor when researchers in his lab discovered that two natural proteins, angiostatin and endostatin, could effectively block angiogenesis. In 1997 Folkman's group published a paper in which they described experiments showing that endostatin had dramatically reduced the sizes of aggressive malignant tumors by choking off their blood supplies. But that wasn't all: he also inadvertently discovered that the therapy not only slowed tumor growth but actually stopped it in its tracks by targeting more genetically stable blood-vessel manufacturing endothelial cells rather than the highly mutable tumor cells; this prevented the tumor from becoming immune to or developing a resistance to the proteins

In 1998 Folkman became a media sensation when Nobel scientist James Watson, co-discoverer of the DNA double helix, declared on the front page of The New York Times that he was "going to cure cancer in two years." At the time, Folkman's antiangiogenic therapies had successfully shrunk enormous mouse tumors comparable two-pound (0.9-kilogram) masses in humans. And, almost overnight, angiogenesis inhibitors became the cancer therapy du jour.

"At the beginning I felt enormous pressure," Folkman said in a 2002 interview with Scientific American. "[The news] raised expectations and demand for angiogenesis inhibitors before these drugs had completed testing in clinical trials. … For any new type of therapy there is always a dilemma about when to inform the public. If it's too early, then physicians are besieged by calls from patients for drugs that cannot be obtained. If too late, then critics say that hope was destroyed for patients with advanced disease."

Antiangiogenic drugs have had mixed results in human clinical trials over the past decade, including one in which only four of 42 patients suffering from cancers affecting hormone-producing nerve cells who were given endostatin experienced long-term relief. Today, however, many successful therapies involve angiogenesis. In early 2004 the Food and Drug Administration (FDA) approved Avastin, a drug manufactured by Genentech, for use, along with chemotherapy, for colorectal cancer; another antiangiogenic drug, thalidomide, was okayed by the FDA in 2006 for the treatment of multiple myeloma (cancer of the body's plasma cells, white blood cells that make antibodies); a few antiangiogenics have also been approved to treat macular degeneration (a progressive vision-impairing disease that destroys the macular, or central portion, of the retina).

5 Comments

1. 1. AnnyeD 07:22 PM 1/17/08

   The Bible says once Israel comes into being that a generation, 70 years, would not "pass" until all the signs of Christs' return takes place. These include, eclipses, grand earthquakes, 100 lb hail--megacryometeors--a star falling into our ocean--Sedna, our waters turning to blood, becoming bitter--wormwood--and Christ return- shining brighter than the sun with a celestial city the size of America coming out of the heavens on a cloud, with fire going before him. "The stars will go black"--supernova, the moon turn "red"--lunar eclipses and our sun to go "dark"-- "before that great and notable day". Get to know the invisible Jesus now before its too late, you will meet him face to face in all his glory=light-- & power=fire. The Bible says God is light and their is no darkness in Him at all. The black hole model can not work. See GRB060614. Israel is 60 years old. Revelations predicts a final 7 years for Earth after we see these celestial signs. The seas will be on fire, the heavens melt.

   Reply | Report Abuse | Link to this

2. 2. Aubrey 09:41 PM 1/20/08

   Folkman may have made outstanding contributions, but the news reports failed to mention some seriously dodgy science along the way.
   
   The Memory Hole
   
   http://scientific-misconduct.blogspot.com/2007/10/memory-hole-19-october-harvard-paper-in.html
   
   Aubrey

   Reply | Report Abuse | Link to this

3. 3. lysdexia 10:16 PM 2/12/08

   AnnyeD,
   
   Cretin, learn how to spell. Those predictions expired 2008-33+4-30 years ago; the destruction of the temple at Jerusalem was even also later than GIiberish said. The profesy is dead.
   
   http://google.com/groups?q=Autymn+fast-food

   Reply | Report Abuse | Link to this

4. 4. kenneth ellman in reply to Aubrey 02:20 AM 9/11/10

   Thank you foryur

   Reply | Report Abuse | Link to this

5. 5. kenneth ellman 02:53 AM 9/11/10

   Although this is very old news, I was not aware of the disputed incident regarding the effectiveness of interferon alfa-2a in reducing large hemangiomas. The fact that Judah Folkman was one of the authors of the discredited report was unknown to me. It just never came to my attention. The fact that Judah Folkman was involved in this kind of error at Harvard is a reminder that nothing must be accepted without full evaluation and replication, no matter who is the source.
   
   However certain things remain clear:
   1. That this previous incident involving Judah Folkman and the other authors in no way impacts his research regarding antiangiogenesis, angiogenesis, angiostatin and endostatin.
   2. While the evaluation of interferon alfa-2a for hemangiomas at that time was confused by the Folkman article, the therapeutic consideration itself was not discredited.
   3. To my knowledge, no reasonable explanation for the errors in the interferon alfa-2a article were ever given. Harvard to its credit moved to disclose this errors. How and why the authors fell way below the expected standards remains a mystery.
   4. Perhaps this merely proves what we already well know that all research must be carefully weighted and replicated. After all the purpose of publication is to attract attention and evaluation. Peer review protects research and in this case as in many others the publication caused changes in the assertions.
   
   Kenneth Ellman
   email:ke@kennethellman.com
   
   

   Reply | Report Abuse | Link to this