By Jocelyn Selim
The father of angiogenesis conceived an entirely new way to treat tumors
By Jocelyn Selim
In the late 1940s, Judah Folkman, a high school student in Ohio, became curious about a goldfish salesperson’s decree that the fish never stop growing. Most boys probably would have regarded this information as mildly interesting trivia, but not Folkman. He wanted to know why.
A student at Bexley High School in Columbus, Folkman decided to test the salesperson’s claim with an experiment—one that he hoped would win the prestigious Westinghouse Science Talent Search national competition. He and a friend rigged an aquarium with a measuring device—a sort of tape measure—so that when a fish swam by, they could record its length. Then, as the fish grew, they plotted the growth of the fish on a chart next to the tank. Many years later, Folkman would describe in an interview how he and his friend discovered that when they added two fish to the tank, the growth curve slowed down, and when they added four, it slowed down even more. At nine fish, all of the goldfish stopped growing. Remove some fish and the remaining fish would begin growing again.
The young Folkman was intrigued by the observations. The fish, he reasoned, must somehow be “talking” to one another, and he made plans to filter the water to try to track down the invisible biochemical signal that influenced their growth. But by that time, the Westinghouse deadline had rolled around, and the boys had run out of time to test their hypothesis. (They didn’t even get an honorable mention.)
Nonetheless, the experiment was a particularly apt foreshadowing. When Folkman died Jan. 14 at age 74, he was widely considered to be one of modern medicine’s great visionaries, credited with almost single-handedly ushering in the idea that tumors use invisible signals to “talk to” and recruit a nourishing blood supply. It would take years for Folkman’s ideas to be taken seriously, but eventually, other cancer researchers slowly realized he might just have hit on an entirely new approach to treating cancer.
A Serendipitous Discovery
Folkman seemed to always know he would become a doctor. “He started training very early,” according to his longtime friend and collaborator Steven Brem, who now heads the neuro-oncology department at the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Fla. “He was a little like the Tiger Woods of medicine.” When the young Folkman learned his grandfather was planning to buy him a Jeep for his bar mitzvah, the boy mentioned that he would much rather have a high-powered microscope. During high school, he apprenticed himself to a world-class surgeon, an experience that inspired him to continue on to Harvard Medical School and a career in surgery.
Graduating near the top of his medical school class, Folkman landed a particularly competitive position as a surgical resident at Boston’s Massachusetts General Hospital and was well on his way to his goal. But in 1960, in the middle of his residency, Folkman was drafted into the Navy. This much-resented interruption turned out to be his single most life-altering career experience. Instead of going to basic training, Folkman found himself shipped off to a laboratory in Bethesda, Md., to work on extending the shelf life of blood. Finishing the Navy’s assigned experiments months ahead of schedule, he and a colleague began devising their own projects to pass the time.
During angiogenesis, a tumor recruits a network of blood vessels to nourish itself and encourage growth. (Illustration by Nicolle Rager Fuller)
In the biography Dr. Folkman’s War, author Robert Cooke describes how the lab happened to be full of leftover rabbit thyroid glands from previous experiments. On a whim, Folkman and another researcher, Fred Becker, transplanted some melanoma cells onto the thyroids, which had been kept alive artificially. The cancer cells immediately began growing and dividing into small tumors, as they expected, but then the cell divisions abruptly stopped. Amazingly, all of the tumors were roughly the same size. Folkman and Becker knew this was unusual: Ordinarily, tumor cells divide into a large range of sizes.
Curious, the researchers took the tiny tumors and transplanted them into live animals. To their surprise, the tumors grew rapidly, nourished by a rapidly expanding bed of new blood vessels. They puzzled over the result. Could the tumors, like the goldfish, be somehow communicating to nearby blood vessels through invisible biochemical signals? Could they be calling in their own food supply, via the network of blood vessels? Were they unable to grow on the disembodied thyroids because the thyroids couldn’t form new blood vessels?