Dr Armand Leroi is obsessed with size. Why has life evolved to produce such physically different organisms as 7ft basketball players and 5ft Chinese men, or bijou chihuahuas and statuesque Great Danes? “We simply don’t know the genetic programme required to make a whale or a mouse,” he says. And so, for the past five years, he has been tweaking genes in worms in the hope that one day he will elicit the secrets of the very big and the very small.
Leroi, 35, an evolutionary biologist at Silwood Park, Imperial College’s outpost in Berkshire, will reveal his latest, remarkable findings in a Scientists for the New Century lecture entitled The Size We Are on March 28 at The Royal Institution in London.
The 6ft Dutchman, who heads the wonderfully named Worm Lab at Silwood, cannot yet tell me why I have failed to progress beyond the unsatisfactory height of 5ft 2in. However, his work with freak C.elegans worms — by knocking out certain genes selectively he can produce giants and dwarfs — suggests that size really matters. Why? Because the genes that control size also appear to govern life and death.
The research has guided him to a startling hypothesis — it is possible that, all other factors being equal, short people are genetically primed to live longer than tall people.
It is already known that if mice have their growth deliberately stunted, they live up to 75 per cent longer than their normal-sized neighbours. Leroi knows of researchers who have created dwarf flies that survive much longer than normal. So he decided to do a test to explore the link between size and longevity.
“Take a look at this,” he says, pointing to a graph of dog breeds and their lifespans. “Any dog owner will tell you that Great Danes have a propensity to die relatively young, and smaller dogs tend to live relatively long. We trawled through the data on 400 breeds of dog, looking at height, weight and longevity.
“You see a striking negative correlation. You can explain 50 per cent of the variation in a breed’s longevity by its body size.” Even to an untrained eye, the graph is convincing — the taller the dog, the shorter its average life. One of the important differences between dogs of differing size, he says, is the levels of growth hormone circulating in their bodies. Even accounting for body size, large dogs have proportionally more of a hormone called IGF (equivalent to growth hormone in people). IGF is also found in worms and mice — if scientists disable the genes that manufacture IGF, the animals live longer. It appears that turning off IGF production delays death. Since the development of human beings is partly controlled by growth hormones, does this mean that shorter people live longer than their loftier counterparts? “For humans, it’s increasingly evident that our notion that big is good is not necessarily right,” he says. “There are real costs to being big. Traditionally, because of the association between socioeconomic status and height, there is a long association between tallness and health. As Western society comes to a socioeconomic equilibrium, it is no longer the case that people are short because they are malnourished. It is becoming clear that shorter people tend to live somewhat longer, and that tallness is not necessarily a good thing.
“It is not clear why that is. If we look to dogs, Great Danes get a particular kind of bone cancer. It is known that relatively tall children are more at risk of getting a similar bone cancer. It is a very small risk, and there has been controversy over it, but this appears to be a cost of getting big.”
For Western countries at least, the worst socioeconomic extremes have been pretty much ironed out since the war. But young people in the West keep on growing. Leroi says: “I’m 6ft but if I go to Holland, there are these blond giants who crowd me out in the trains — even the women are taller than me. It’s predicted that by 2005 the average Dutchman will be another inch taller.”
The northern European countries have genetically taller populations, but height has also been linked with milk consumption: “The Dutch are the tallest people in the world, and it has been suggested that it’s because they drink a lot of milk. The tallest people in Africa worship cows and drink vast amounts of milk. In effect, we are super-fuelling our bodies and growing too tall.
We are giving our bodies a diet to which we are not adapted.”
Leroi, a Dutch diplomat’s son who was born in New Zealand and educated in Canada and the US, is turning his attention to another problem — he has observed that removing the gonads of some worm species makes them grow to double their normal size, and makes other species live longer. Fascinatingly, eunuchs and castrati — boys castrated before puberty to preserve their high singing voices — have been observed to be substantially taller than their peers. A survey of eunuchs carried out in the Sixties shows that they lived longer.
Biologists have explained this phenomenon in terms of resources — there is a trade-off between reproduction, growth and ageing, and removing the organs of reproduction diverts more resources into physical growth and longevity. Leroi suggests, instead, that the gonads are the source of molecular signals for growth and ageing. “The gonads are the source of the death signal,” says Leroi. “This upsets this vague idea of resource allocation, but we have yet to find out exactly which genes are producing which signals.”