But at first, scientists could not develop angiogenesis inhibitor drugs because there was no established test for the drugs' effects on the growth of blood vessels.

Three years after his initial discovery, in 1975, Folkman and colleague Henry Brem discovered the first angiogenesis inhibitor molecule in cartilage. Researchers, including Folkman, had to learn to culture blood vessels and try to test angiogenesis inhibiting compounds.

From Folkman's original work, study of angiogenesis and its medical uses has spread to labs across the globe.

Folkman says that of the 20 angiogenesis inhibitors now being administered to patients in clinical trials, seven have reached Phase III, the stage that comes immediately prior to obtaining approval from the Food and Drug Administration (FDA).

But endostatin, a compound discovered in Folkman's lab in 1997 by Michael O'Reilly, a researcher at the Dana-Farber Cancer Institute, has led the pack.

It has raced through tests on mice to the beginnings of human clinical trials so quickly that Folkman says "It must be a record."

After a report on endostatin was published in the science journal Cell in January 1997, the protein's crystal structure was described in the fall of 1998 by Loeb Professor of Biochemistry and Biophysics Donald C. Wiley and associate Wuan-Hua Ding in the Department of Molecular and Cellular Biology. Clinical trials with human patients are slated to begin at Dana-Farber, Brigham and Women's Hospital, and Massachusetts General Hospital in just a few months.

It was endostatin which brought Folkman to the front page of the New York Times.

Under the Microscope

Six months after the Nature report was published, the New York Times picked up the story and ran it--not in the Science section, where Folkman thought it would appear, but plastered above the fold on the front page.

Folkman and his colleagues were guardedly optimistic about transferring the positive results of treatments of mouse tumors--the experiment on which the Times had seized--to human cancer patients and were leery of the raised expectations such press coverage could bring.

The media's response to his work has been puzzling to Folkman, who stresses he never used the word "cure"--"only the New York Times did." He also says his positive results in trials with mice did not seem to warrant the front page of the Times, since the so-called "third generation" drugs used in his research--angiostatin and endostatin--have yet to be tested in humans.

To jump to conclusions about the drug's potential success in humans based on their observed effects on mice, says Folkman, is not right.

Folkman says he told the New York Times reporter who wrote the article that it was imperative to use the word "mice" in the headline and to make clear that cancer remission had only been documented in rodents, which the writer did.

"I asked them to print, up front, `If you are a mouse and you have cancer, we can take good care of you,'" he says, "but when it went out the next day [on television and in other newspapers] it was overlooked."