In 1960, Dr. Judah Folkman, a young surgeon assigned to a Navy research project to find substitutes for blood, noticed a remarkable phenomenon. Melanoma cells--potentially one of the deadliest human cancers--stopped growing and remained tiny, harmless tumors under certain conditions.
Eleven years later, he proposed an explanation in a New England Journal of Medicine article--that all solid tumors induce the growth of blood vessels. Folkman reasoned that once cancers were separated from the blood supply carrying nutrients and oxygen to their cells, the tumors would remain small and harmless, like Napoleon in exile.
His theory that substances secreted by tumors can turn on and off blood vessel formation met with disbelief and ridicule. Other papers he wrote were rejected by scientific publications. One critic went so far as to say that Folkman’s theories existed only in his mind.
Undaunted, Folkman decided to seek the chemical factors that promote blood vessel growth. If these proteins could be found, they could be blocked. The task was immense. Tumors manufacture hundreds of proteins.
Folkman and colleagues in his laboratory on the 10th floor of Children’s Hospital in Boston persevered. They succeeded not only in growing endothelial cells, which are the building blocks of blood vessels, but in isolating and purifying for the first time some of the molecules that stimulate or inhibit vessel growth.
Overnight, many of Folkman’s critics became competitors.
Folkman’s feat was a breakthrough. Now, nearly three decades later, the 63-year-old physician is the recipient of honors (including election to the National Academy of Sciences) and is widely credited with beginning a new field of biology--angiogenesis research--the study of what factors govern the formation and regression of blood vessels.
Currently, 26 companies are working on substances to inhibit the formation of blood vessels. Eight new drugs are in clinical trials. Scientists say a promising area of cancer therapy is beginning. Many of these trials are in the early stages, but anecdotal evidence of progress with patients is highly encouraging.
The other day, Folkman, a professor of pediatric surgery and cell biology at Harvard Medical School and director of the surgical research laboratory at Children’s Hospital, addressed a hotel ballroom filled with scientists and drug company executives at a seminar on angiogenesis.
“My wife always asks what took so long,” he said, evoking laughter.
The question is particularly relevant for young researchers starting their careers and contemplating whether to work on short-term projects or fundamental problems that may take decades.
Embedded in the question are issues of scientific self-confidence, the courage to tackle high-risk problems and the ability to persevere through failures in an era when many Americans expect answers in the space of a half-hour sitcom.
If anything, the research path is more difficult today than when Folkman began his scientific journey. A Tufts University study shows that since 1992, the cost of bringing a new drug from the laboratory to the prescription counter has climbed from $200 million to as much as $500 million. With such economics, pharmaceutical executives worry greatly about committing to patient trials that might end in failure.
It also is harder for young researchers--even with highly promising ideas--to get grants.
“When you walk into meetings, there are tables filled with huge piles of applications,” said Dr. Dawn Willis, the American Cancer Society’s director of research promotion and communication. “Total dollars are up, but . . . the costs of funding a research project have skyrocketed.”
In 1995, the American Cancer Society supported 18% of grant applications.
Even if a young scientist receives money, it is harder to keep a career going. Researchers often must apply for fresh money every two or three years. Fewer faculty positions are available at universities.
When there is nothing to show but struggle, as in Folkman’s case for many years, young scientists can be accused of being unproductive. The line between being perceived by faculty review committees as having persistence of vision or being stubborn is a tightrope.
“It’s hard to show thinking like it’s hard to show rain on television,” Folkman said. “It’s hard to show [progress] after five or 10 years when all the experiments have failed.”