Under The Microscope: The fight to make cancer survivable

THE DIFFERENCE A LONE VOICE CAN MAKE

WHEN I FIRST met Judah Folkman some 20 years ago, I was so excited by his ideas that I wanted to stop strangers in the street to tell them. I also started some new experiments under his influence. What was his novel discovery? How blood vessels develop, and their fundamental role in cancer.

Judah Folkman was a young paediatric surgeon working on cancer at the Harvard Medical School. Like cells, tumours can be grown in a culture medium in a dish. Folkman became puzzled as to why cancer cells in a dish stop growing when they form a small tumour, about the size of a pea. These cultured tumours are always tiny and quite different from the tumours that grow in the body, which can be several centimetres in diameter. He offered his research students a fortnight's holiday for two at the best hotel in Miami if they could get tumours in the culture dishes to grow any larger. Folkman's prize was safe, for what he demonstrated is that tumours need a blood supply in order to grow, and that this is why their growth is so restricted outside the body.

What Folkman then showed was that there is an intimate relationship between tumours and the blood vessels that supply them with nutrients. The tumours actually attract vessels to grow towards them, and if the blood vessels do not reach the tumour, it will remain tiny or die. The way tumours attract vessels is by secreting a substance which causes the fine vessels nearby to migrate towards the source of the substance. The vessel's cells can detect local concentration and will move towards higher and higher concentrations. Once the tumour has received a blood supply, its growth can be explosive - it can become 20,000 times its original volume in a few weeks.

It is this growth that makes tumours lethal. There is evidence that an individual with cancer may have many small tumours in the body that are hard to detect until they receive a blood supply and start to grow. Folkman devoted his next efforts to identifying the substances released by tumours that attract vessels, in order to find ways of preventing them from working and the tumours from acquiring a blood supply. His views were met with considerable scepticism - few believed that it might be possible to treat cancer by blocking blood-vessel development. He had to use considerable powers of persuasion to convince scientists to join him, as other professors actually tried to dissuade them from doing so.

But Folkman received a major boost in 1994, when his laboratory isolated a natural inhibitor of blood-vessel growth called angiostatin (blood-vessel growth is called angiogenesis). Two years later, they isolated another inhibitor, endostatin. When a mouse with a large tumour was treated daily with endostatin, the tum- our almost disappeared within 12 days. It is still not known how the inhibitors work, but tests using related substances to suppress vessel growth in cancer patients are due to start next year. And because of the publicity his work has attracted, his office already receives over 1,000 calls a day from cancer patients or their families, desperate for a life-saving treatment.

In an interview in the journal Science, Folkman was asked whether he thinks that his treatments will eventually cure cancer. His reply: that his inhibitors will not, but that he believes they will make cancer more controllable when used alongside standard treatments like chemotherapy. Folkman is now honoured by numerous prestigious awards. He is a wonderful example of a scientist who did not give up his ideas, despite initial opposition.

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