28th March 2002
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Medicine & Biology



Turned on by Danger: Programme Notes

Dr Polly Matzinger is a sheep-dog trainer, former bunny girl, and one of the world's foremost immunologists. Four years ago she had a blinding moment of insight that led to a most extraordinary idea, the Danger Model. This film tells the story of how a high school drop out became a scientist, and had an idea that's reshaping the way people think about organ transplants and cancer.

Polly Matzinger left school under the cloud of being voted by her fellow students, "the person least likely to succeed in life". She spent ten years drifting, as a jazz musician, a dog trainer, and then a Playboy bunny. One evening she was serving drinks to a couple of scientists who were discussing their experiments. She asked a few incisive questions. One of the scientists was so impressed that he started a nine-month campaign to persuade her to go back to school to do science. Twenty years later she is chief of an immunology lab at one of America's leading research centres, the National Institutes of Health in Washington, and the main proponent of a radical theory.

For half a century doctors have been taught that the body's immune system attacks anything that's foreign. Not so, says Polly. The idea that the immune system operates like a rampaging skinhead, indiscriminately attacking foreigners, does not explain how we tolerate the millions of "good" bacteria that colonise our gut, nor does it explain why pregnant women do not reject their "foreign" babies. Instead, Polly Matzinger argues that the body will attack anything that attacks it. Our immune system responds, not to foreigness, but to danger.

Her theory points the way to a revolution in transplant surgery: it suggests ways of doing transplants without the fear of rejection and the need for immunosuppressive drugs. Horizon has filmed something that has never been done before: a mouse with a transplanted rat's heart inside him. Such transplants are so foreign they should be immediately rejected. Yet this mouse, on no drugs and with a completely normal immune system, has accepted the rat's heart as part of himself. Her "Danger Model" has also inspired novel cancer therapies; 32 year old Briton, Geoffrey Allen, has advanced cancer that has spread to his bones. At one of London's leading teaching hospitals he is being injected with bacteria in the hope that this will trigger a danger response, arousing his immune system to attack his cancer. And it does appear to be responding.

Her assault on long established beliefs has provoked a passionate debate. Polly Matzinger tells the moving story of her own, very unusual life and the extraordinary moment when it all came together.

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