Diets do not work for many people

Wall Street went mad and the patent for leptin was purchased by a biotechnology company for millions of dollars.

Others working in obesity research shared that same sense of excitement. "As one read it, the dawning realisation that this was a seminal discovery came upon one," recalls Professor Stephen O'Rahilly from Addenbrooke's Hospital in Cambridge, UK.

"What went through my mind was that may be we had got our first handle on understanding what the molecules are that control body weight. It was wonderfully exciting."

Complicated picture

However, researchers quickly discovered that many fat people had high levels of leptin and giving them more would have little effect. Even when O'Rahilly successfully treated a nine-year-old child weighing 95 kilos (15 stones) whose body, like the fat mice, could not make its own leptin, scientists knew the problem in front of them was a very complicated one.

Leptin is produced by the fat cells. It travels through the blood where it reaches a part of the brain called the hypothalamus - it carries a message to stop eating. The signal is picked up and passed along a network of neurons, killing those pangs of hunger.

However, it is now clear that the message can be corrupted - just one faulty gene can block the pathway. New research has focussed on the brain chemicals - neuropeptides - which also play a role in regulating the desire to eat.

Just before Christmas, American researchers announced the first thin mouse - an animal predisposed to lose weight because it lacked the gene that coded for a neuropeptide called melanin-concentrating hormone (MCH).

The mouse did not want to eat even though the low levels of leptin in its body must have been telling the brain it was hungry. There was clearly a short-circuit in the messaging system.

Research revolution

Although the initial excitement over leptin has not delivered a wonder cure for obesity, the importance of its discovery should not be underestimated. For the first time, it showed there are genetic reasons why some people become very fat.

Fatty food: Western societies cannot resist it

Obesity does not necessarily equal greed and laziness. There are some men and mice who cannot help the way they are. "It's quite obvious to me that there must be some individuals who are born with a more intense or less intense appetite than others and put in the right situation or the wrong situation - abundant access to food - those individuals born with greater appetite drive are much more likely to become obese," says Professor O'Rahilly.

Leptin has led to a revolution in the study of why some of us are fat and others of us are thin. And this new approach really does open up the prospect of more effective means of weight control than those pointless yo-yo diets. "The excitement of the last four years in obesity research can't be exaggerated," says Professor O'Rahilly.

"As a physician, I think we will be able to identify specific types of obesity that we may be able to actually treat. And I think on a societal level, the understanding that obesity can have fundamental genetic causes and is not always due to moral failing may permeate society and we may treat obese people differently."

The story of leptin is told on the BBC Science programme Horizon. Born To Be Fat is broadcast on BBC Two at 2130 GMT on Thursday, 7 January, 1999.