The price of 'pudge'

In the current mood of public suspicion about the activities of scientists, it may not be long before publishers of book reviews follow the example set by science and medical journals and demand that their authors provide a statement of conflicts of interest. Anticipating this move, I confess that many years ago, during a medical examination for life insurance to obtain a mortgage, I was found to be "moderately obese", and the policy was weighted accordingly. Nearly 40 years later, and many pounds (sterling rather than avoirdupois) lighter, there seems little to change my original view that the population norms on which underwriters based these calculations were derived from studies of the inmates of concentration camps after the second world war.

Despite this personal bias, there is no doubt that obesity and the ills that accompany it, particularly cardiovascular disease and diabetes, are becoming a major global health problem. The World Health Organisation estimates that in the US and Europe alone they account for more than 2 million deaths each year. Things are even worse in many of the developing countries, in which there is a major epidemic of obesity and diabetes, affecting from 5 per cent to an astonishing 70 per cent or more of some populations. Although there is still much to be learnt about the reasons for this frightening situation, it is already clear that both nature and nurture play important roles.

The US geneticist James Neel popularised the concept of the "thrifty genotype", which has it that in the short period, in evolutionary terms, since our days as hunter-gatherers there has not been time for our genetic make-up to adapt to the environment in which we now live, with its sedentary lifestyle and high-energy, low-residue diet. But although there have been some spectacular successes in discovering the genes in mice and humans that are involved in rare forms of severe familial obesity - work that has already told us a great deal about the genetic and biochemical basis of appetite - the search for genes that may be involved in the more common forms of obesity has been less rewarding. Furthermore, other research, particularly germane to the developing countries, has suggested that babies with low birth weights are more likely to develop obesity and cardiovascular disease in middle life, pointing to the potential importance of maternal nutrition in the evolution of some of our major killers.

Since there may be many evolutionary routes to our thrifty genotypes, and numerous environmental factors in addition to our state of nutrition in foetal life that can stress our fragile genetic make-ups, it may be a while before we really understand the basis of obesity, which could differ between ethnic groups. But there is no lack of incentive to solve these problems. Every pharmaceutical company would dearly love a piece of this potentially lucrative action; hopes for a safe and effective appetite suppressor remain unfulfilled. And, more important, a true appreciation of the genetic and biochemical basis of obesity may lead to a much better understanding of the mechanisms of some of our major killers - heart disease, diabetes and even some forms of cancer.

But while further research in this field will shed light on these questions, it is clear that our indulgent lifestyles and the bad habits that we export to the rest of the world are playing a major role in making us fat. During a recent visit to a developing country, the local paediatricians painted a picture of the life of children in their urban communities. They leave home in the morning with no breakfast, consume a large meal of westernised "junk food" at about 11am, return home in the afternoon for an identical feast, and then spend the rest of the day sprawled in front of the television, where they are regaled by advertisements from the fast-food industry. Their exercise is limited to climbing on and off the school bus and fiddling with their television controls.

In The Hungry Gene , Ellen Ruppel Shell tells the story of the search for "obesity genes" set against the background of the societal changes that have done so much to generate the current epidemic of obesity. She begins by reminding us that obesity, or "pudge" as she prefers to call it, is not a "new" disease; its dangers were clearly set out in the works of Hippocrates and Galen, and the 18th-century Dutch physician Malcolm Flemyng, in his forward-looking A Discourse on the Nature, Causes and Cures of Corpulency , suggested that it might reflect an inherent predisposition.

After a lurid description of some of the hair-raising surgical procedures used in the past to help the obese - an account that if read widely should sound the death knell for the cream-cake industry - she goes on to describe the frenetic search for obesity genes on the part of individual scientists and the pharmaceutical industry. And she rounds off her tale with some insightful personal observations of the effects of obesity in some of the developing countries and a vivid picture of the extraordinary antics of the fast-food industry in selling their wares, particularly to children.

The messages of this excellent piece of scientific journalism go far beyond the problems of fat people. While emphasising the extraordinary potential of the genomic era for the understanding and control of disease, they remind us of the stresses generated for today's scientists in an environment in which scientific discovery and personal gain are entwined.

They also point to the dangers of scientific short cuts in a field in which the possibility of commercial gain is so enormous. And they raise worrying questions about the ethical behaviour of the fast-food industry that are at least as pressing as those that involve tobacco manufacturers.

Minor inaccuracies in the account of the history of modern genetics apart, this witty and thought-provoking book can be thoroughly recommended to anybody who is interested in how present-day science works and how our lives and those of our children are being changed by manipulation of the media and commercial greed.

Sir David Weatherall is emeritus regius professor of medicine, University of Oxford.