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Agent provocateur pursues happiness

Clare Thompson and Abi Berger profile James Watson, one of the Nobel laureates who discovered the structure of DNA

While the rest of the biological world were anxiously awaiting the announcement of the sequencing of the human genome, James Watson, one of the discoverers of the DNA double helix and one of the original instigators of the genome project, was busily engaged in his new obsessionthe pursuit of happiness.

From a man who graduated from college at the age of 18, began his graduate career at the age of 19 at Indiana University, and spent the next six years trying to understand the gene (arriving at the structure of DNA at 25, with a resultant Nobel prize at the age of 34), such an esoteric goal might seem trivial. Still, Dr Watson seems to be tackling the subject with the same passion and sweeping mode that characterised the book The Double Helix, one of the most widely read scientific books of all time and named by the literary committee behind Random House Modern Library as number seven of the 100 most important books of the century.

Dr Watson unveiled his new theory at London's University College Hospital last week when he gave the prize lecture in clinical science. His latest theory revolves around the action of melanocyte stimulating hormone, which is responsible for skin pigmentation and hair colour.

He became interested in the subject two years ago while talking to a taxi driver in Tucson, Arizona. The driver happened to be a part time scientist studying the effect of stimulating the production of melanocyte stimulating hormone in mice, and his team's eventual aim was to produce a synthetic "natural" tan (to be called melanotan). But melanotan seemed to have a side effect that could be classified as adverse or favourable depending on a person's view. One of the team had injected the hormone into himself and found that he was the recipient of an eight and a half hour erection.

Dr Watson's interest was aroused, he said, because he is the product of Anglo-Irish parentage that has resulted in very pale skin and a basal cell carcinoma that sits on the top of his head and has to be removed once every three months. For him the idea of melanotan, presumably without the erection, would be a good thing. But the side effect intrigued him into the exact workings of the hormone. Could the hormone be responsible for some aspects of happiness? Is this the explanation for the term "Latin lover," and can it explain why the pale faced British descend on Spain in the summer? Does it explain why people from Scandinavian countries seem to enjoy nudist camps?

It is fair to say that at this point in the lecture most of the audience began to prickle at the tone of the argument. Dr Watson, however, who has had little to prove since the age of 25, never strayed from the maxim he adopted early in life: "offending someone is always preferable to avoiding the truth."

To influence skin colour, melanocyte stimulating hormone binds to a G protein coupled receptor, mutations in which cause pale skin, with two mutations in particular causing ginger hair. The hormone also binds to several other receptors, and one of these, human melanocortin receptor 4, is a key target for the drug companies because it also turns off appetite. The receptor works via the hypothalamus, which produces a neuropeptide called pro-opiomelanocortin, which in turn switches off the appetite. It is also under the control of leptin. Unfortunately, although the idea of turning off the appetite was a good one, the mechanism again turns on sexual activity. As a commercial product, mused Dr Watson, "it could be perfect, but [the manufacturer] will probably get sued."

These findings prompted him to think about other mechanisms. If you are heavy, you are probably producing more leptin and more melanocyte stimulating hormone, and so you might be more sexually active. Could this, he said, "explain the renaissance paintings where heavy women were associated with sexuality?" And, moreover, when melanocyte stimulating hormone breaks down, it can stimulate levels of b endorphin. As mood is controlled by internal endorphins, says Dr Watson, do people who are fat produce more endorphins? Could this explain why Father Christmas is cheery and fat? And why high profile fashion models may be unhappy and turn to drugs to stimulate their internal endorphins?

Can the decrease in crime in New York city be linked to increasing obesity in the United States, he asks.

As one of the audience observed, melanocyte stimulating hormone is much more complicated than depicted in Dr Watson's idea, and he conveniently left out mention of the neurotransmitter serotonin and gave only a passing mention to dopamine. But as Martin Raff, professor of biology at University College London, said, Dr Watson tends to be quite prescient in outlining mattersway ahead of his time. He refers specifically to an essay in James Watson's latest book A Passion for DNA, in which he discusses the potential of cloning 20 years before Dolly the sheep was a twinkle in her creator's eye.

But if James Watson's happiness theory comes to fruition, then his closing slide featuring Julius Caesar might ring some alarm bells. As Shakespeare's Caesar said: "Let me have men about me that are fat; Sleek-headed men, and such as sleep o'nights; Yond' Cassius has a lean and hungry look; He thinks too much; such men are dangerous."

Such characterisation may strike more than just a chord. James Watson is still, at the age of 72, thin and driven, and to his many detractors continues to suffer from the "crime" of thinking too much.

(Credit: A BARRINGTONBROWN/SPL ) James Watson (left) and Francis Crick with their model of part of a DNA molecule in 1953. Their discovery that DNA exists as a double helix structure won them the Nobel Prize for Physiology or Medicine in 1962.