Dr Judah Folkman: Cancer researcher who realised that tumours secrete a substance that stimulates their own blood supply

Judah Folkman was probably the world's most innovative, imaginative and productive cancer researcher. In a "eureka" moment, Folkman had the vision to see that a malignant tumour couldn't grow larger than a pinhead unless it has a blood supply tailor-made for it, and to postulate that the tumour must secrete something that generates this supply. This sounded like science-fiction to many scientists, but Folkman was proved right, and his findings underpin a huge swathe of modern cancer therapy.

He went on to identify and characterise the substances, which he called angiogens; the process is called angiogenesis. From there, Folkman also identified substances that inhibit angiogenesis; this is called angiostasis. Today, there are a dozen or more angiogenesis inhibitors that slow tumour growth. Some old drugs that inhibit tumour growth – including tamoxifen and thalidomide – have been shown to work by inhibiting angiostasis, and they are revolutionising cancer chemotherapy.

Folkman, a Professor at Harvard Medical School, published his hypothesis in the New England Journal of Medicine in 1971, after it had previously been rejected by several other journals. It is now one of the most widely cited papers of all time. Some critics at the time, however, said that Folkman's ideas were flimsy and his publications flashy. The prevailing view was that malignant tumours grew around and along existing blood supplies.

He did painstaking research to refute his critics' arguments. For example, some scientists claimed that angiogenesis was triggered by dying tumour cells. Folkman implanted a healthy tumour into a rabbit's eye, and a dying tumour into the other eye. Only the healthy tumour stimulated new blood-vessel growth. But his theory received a setback when other researchers implanted uric acid – which causes inflammation and gout – into the eye and found that it triggered new blood-vessel growth. They argued that the inflammation caused the blood vessels. After that, even Folkman doubted his own hypothesis, but he vindicated himself when he showed that the uric acid was removed by macrophages, and that the macrophages, like the cancer cells, stimulated angiogenesis.

The scepticism Folkman was greeted with made it hard for him to gain US government research funding, so instead he accepted drug-company money, including a 12-year grant from Monsanto, the largest Harvard Medical School had ever received. In 1983 his group made a major breakthrough when it identified a substance produced by tumours that caused angiogenesis. Since then, a dozen other angiogenic chemicals have been found. Two years later, they made another discovery when, by chance, an airborne fungus landed on a dish where new blood vessels were being grown. The blood-vessel growth came to a halt. The active substance was isolated and is now in clinical trial. It proved to be the first identified angiogenesis inhibitor and was effective in mice, though not humans.

By the mid 1990s, Folkman's team had isolated two inhibitors that totally blocked tumour growth in mice. However, his work remained little known until James Watson, who discovered the double helix of DNA, told a New York Times reporter at a dinner party in 1998 that "Judah Folkman is going to cure cancer in two years". Not surprisingly, this led to a front-page story.

After that, he was deluged by journalists seeking interviews, and by patients seeking a cure. He responded courteously to all of them, explaining to patients that his cure worked in mice but not humans. He also played down the New York Times story: "I don't think angiogenesis inhibitors will be the cure for cancer," he said. "But I do think that they will make cancer more survivable and controllable."

Folkman's ideas have also led to new treatments for diabetic eye disease and the macular degeneration of old age, conditions where new blood-vessel growth blocks vision. They promise to lead to treatments for endometriosis. Conversely, substances that encourage new vessel growth have proved useful in treating ischaemic heart disease; and this work too has grown from his research.

Folkman was a rabbi's son and often accompanied his father to visit the sick. For his bar mitzvah he asked for, and got, a top-of-the-range microscope. He set up a lab in his parents' basement and won a school prize for keeping a rat's heart beating for 30 minutes outside the body.

He graduated from Ohio State University when he was 20 and four years later got his MD, magna cum laude, from Harvard Medical School. He did a year as intern – equivalent to a UK house surgeon – followed by four years' specialist training in surgery at Massachusetts General Hospital. During this time he took part in designing an early implantable heart pacemaker.

Folkman interrupted this training to do his military service in the US navy, where he took part in research on artificial blood. As part of this, he put mouse cancer cells in a rabbit thyroid gland and added synthetic substitute. Tumours formed, grew for a bit, and then stopped when they were still the size of pinhead. The same cancer cells implanted in a live mouse continued to grow, convincing him that tumours needed constant blood in order to spread.

A year after qualifying in surgery he moved to Boston Children's Hospital. Because he had no specialist paediatric surgery training, he was sent to Philadelphia where he trained under C. Everett Koop (later the US Surgeon-General). He stayed in Boston for the rest of a long career and rose to professorships in paediatric surgery, anatomy and cell biology at Harvard.

In an interview he later said that surgery was rewarding, but left little energy for research, which is why there are relatively few surgeon-researchers. Research, on the other hand, often meant years of frustration when experimental results were negative, and things could be made harder by the scepticism and criticism of other researchers.

Folkman left the operating room for good in 1981, shortly before he was 50, to direct the surgical research laboratory at Boston Children's Hospital. He retired from this at 70 to become director of the vascular research program. He never stopped working.

Judah Folkman published 400 research papers and 100 book chapters, and gave many distinguished lectures around the world. He received dozens of honours and awards, and was the subject of a book, Dr Folkman's War (2001), by Robert Cooke and C. Everett Koop.

Caroline Richmond

Moses Judah Folkman, cancer researcher: born Cleveland, Ohio 24 February 1933; Instructor in Surgery, Harvard Medical School 1965-66, Associate Professor of Surgery 1967-68, Julia Dyckman Andrus Professor of Paediatric Surgery 1968-79, Professor of Anatomy and Cellular Biology 1980-94, Professor of Cell Biology 1994-2007; married 1960 Paula Prial (two daughters, and one son deceased); died Denver, Colorado 14 January 2008.

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