IMMUNOLOGIST Charles Janeway had an audacious idea. It was 1989 and most of his colleagues thought the immune system was primed solely to detect molecules it hadn鈥檛 seen before. Janeway thought he had evidence that novelty alone wasn鈥檛 enough to mobilise the body鈥檚 full defences. He proposed that a second signal was needed to tell if a foreign substance was a threat or not. That signal, he predicted, would come from cells pre-installed with receptors that lock onto specific molecules found on viruses, bacteria and the like.
Janeway鈥檚 idea bombed. It took another decade of work in his lab and elsewhere to prove him right. Many cells of the innate immune system, the first responders to infections, carry a selection of these receptors. Estimates suggest that this system handles 95 per cent of our defence. Yet just 30 years ago, it had barely been imagined.
This tale is from 鈥榮 highly readable book The Beautiful Cure. It is beautifully researched, backed up with notes, references and interviews by Davis himself, whose status as an immunology professor confers added credibility.
Advertisement
He believes that we now know enough about the major components and interactions of the immune system to begin manipulating them to cure diseases such as cancer. We stand, he predicts, on the threshold of a medical revolution.
Janeway is one of a dozen leading researchers from the recent past through whom Davis tells the fascinating story of the immune system. The life and work of Ralph Steinman is also striking. A researcher at Rockefeller University, New York City, in the 1970s, Steinman thought he had discovered a new cell, though colleagues said he was barking up the wrong tree.
Today, Steinman鈥檚 dendritic cell, also part of the innate system, is known to be a prime activator of the more familiar adaptive immune system, which develops B and T-cells to fight specific threats and guards us from future infections.
In the following decade, Shimon Sakaguchi, a Japanese researcher working at the University of Kyoto, found he could stop autoimmune disease in mice by inoculating them with healthy immune cells. It took him and others 20 years to discover why: regulatory T-cells, which prevent immune reactions from spiralling out of control.
鈥淒avis says we now know enough about the immune system to start curing diseases such as cancer鈥�
Finding the brakes on the immune system laid the ground for the development of cancer immunotherapy. In 1994, a receptor on T-cells called CTLA-4 was found to be an 鈥渙ff-switch鈥� for immune reactions. At the University of California, Berkeley, Jim Allison was wondering if blocking that receptor with an antibody would extend immune responses long enough to destroy tumours. It did 鈥� at least in mice.
Ten years later, Allison鈥檚 idea was tested in humans to treat advanced cancer, and in 2011 the US Food and Drug Administration licensed a CTLA-4 antibody to treat melanoma. This antibody has since been joined by others that block another off-switch, PD-1. While these drugs only work for small numbers of patients and can cause severe side effects, Davis sees them as heralding the coming revolution.
Taking excursions from his main theme, Davis explores an emerging field: how immunity shapes the microbiome. And he discusses the mind-body link, t鈥檃i chi and mindfulness, and why astronauts take a lot of antihistamines.
Most memorable, though, are those stories of pioneering scientists. When Steinman developed cancer, other immunologists created novel treatments for him, including three aimed at dendritic cells. These probably prolonged his life, but couldn鈥檛 save him. News of his death in 2011 reached the Nobel prize committee hours after it had announced his award. He remains the only person never to know he had won a Nobel prize.
Book details
Bodley Head
This article appeared in print under the headline 鈥淒efence strategies鈥�
