REDISCOVERING TONY ALLISON

Tony Allison2.JPG

Over 60 years, Tony Allison has made two major breakthroughs. Laura Spinney meets a scientist who should be better known ...

From INTELLIGENT LIFE Magazine, Spring 2009

Sixty years ago, a young graduate was kicking his heels in Oxford, waiting to embark on his medical studies, when he was invited to join an expedition to a country he knew well. Kenya was his childhood home, but this would be more than a nostalgia trip for him. His head stuffed with new-fangled notions about human evolution, he saw it as an opportunity to put his ideas to the test. Thus began one of the great unsung scientific journeys of the last century, whose impact continues to be felt in this one.

The young man, Anthony Allison, went on to demonstrate a link between malaria and the inherited blood disorder sickle-cell disease—showing for the first time that disease is a potent driver of human evolution. Decades later, he had an insight into the functioning of the human immune system that led him and his Argentine wife Elsie Eugui to invent the blockbuster drug CellCept, which prevents the rejection of organ transplants. “There were two occasions”, he says, “when nature lifted her veil and showed me her beautiful face.”

Today, at 83, he has the military bearing and energy of a young man. With his moustache, impeccable manners and blazer, one sleeve tucked into a pocket because his arm was damaged by a high forceps delivery, he still bears the stamp of colonial Kenya. He has no plans to retire and is working on an experimental molecule that he believes can reduce reperfusion injury—the damage caused to tissues when bloodflow returns after a period starved of oxygen. The primary indication for the molecule is organ grafts, but theoretically it could also be used to treat stroke, as well as his old foes malaria and sickle-cell disease. If so, he says, “it would bring my career full circle.”

Although Allison’s work has saved lives and changed the direction of scientific thought, his name is barely known outside the scientific world. The reasons go back 60 years, almost the span of living memory, and they provide a reminder that science is, after all, a human activity.

He grew up on a chrysanthemum farm at Gilgil, overlooking the Great Rift Valley. His father, a war veteran and keen polo player, left Britain in 1919 because, as his son puts it, “he realised he could live more gracefully beyond his means in East Africa.” As he grew up, his ears burned with the scandalous antics of the Happy Valley set, with whom his parents mixed at Nairobi’s Muthaiga Country Club. Life could have turned out very differently for him had his questioning mind not been drawn to a different valley, farther south.

At Olduvai Gorge in Tanzania, the palaeontologist Louis Leakey was busy sifting the volcanic soil for evidence of man’s extinct forebears. Allison visited him and their conversations came back to him later, at Oxford, where he absorbed what was then a novel concept: evolution is only possible against a background of genetic diversity. Leakey understood that diversity was the secret to human success and was searching for it in fossils of long-dead ancestors. Allison saw it all around him, in the living African tribes.

His plan, when he set out on that university expedition in 1949, was to create a map of African blood groups, based on the blood samples he would collect, and through it to stake out the long, slow trajectory of human evolution. As so often happens, however, he got distracted by a different question. On the eve of his departure, a haematologist alerted him to the puzzle then posed by sickle-cell disease. At the time, scientists could not explain why this disease remained in the African population even though it killed its victims before they reached puberty—in other words, before they were able to pass on the faulty gene.

Almost immediately, Allison noticed the odd distribution of the sickle-cell gene: it was much more common on the coast and around Lake Victoria than in the highlands. “Half the young children in the paediatric wards in Malindi and Mombasa on the coast, and in Kisumu near the lake, had sickle-cell disease,” he says, and it was usually fatal. He was distressed by what he saw, perhaps because it reminded him of his own bouts of sickness as a boy infected with malaria. But that reminder, too, was serendipitous, because now the various elements of the answer were floating in his subconscious. The eureka moment came during a party in the Ngong Hills to mark the end of the expedition: the sickle-cell gene, he realised, was most prevalent in the hot, humid areas where the malaria parasite thrived.

Allison knew that to have sickle-cell disease, a person must have two copies of the sickle-cell gene. Those who carry only one copy are mere carriers. It occurred to him that the gene might have remained in the pool because carriers had an evolutionary advantage over non-carriers—they were protected against that other African scourge, malaria.

He had to wait four frustrating years to return to East Africa to test his hunch, but return he did, as a qualified medic who had worked hard at his parasitology in the interim, travelling this time from the Semliki Forest of western Uganda, down past Lake Victoria and the highlands of Kenya and Tanzania to the coast—dropping in on Olduvai Gorge to pay his respects to Leakey. It was 1953, the year of the Mau Mau uprising, and in the highlands he slept with a revolver. He took more blood samples, comparing the parasite loads in carriers and non-carriers of the sickle-cell gene, and the fruits of his efforts were published in a now-famous series of papers in 1954.

The theory was greeted with scepticism at first, but by the time he was invited to present it at the prestigious Cold Spring Harbour Laboratory in New York later that year, it had the scientific establishment’s seal of approval. As the author of the theory, however, Allison’s troubles were only just beginning. Powerful members of the British scientific establishment, notably the Nobel laureate Sir Peter Medawar, said it was not original, and that he had stolen it from the geneticist J.B.S. Haldane.

In 1948, Haldane had publicly speculated that there might be a link between another blood disorder, thalassaemia, and malaria, but had produced no evidence. “Haldane’s was a brilliant piece of imaginative jumping,” says Sir David Weatherall of the Weatherall Institute of Molecular Medicine at Oxford, who later demonstrated the thalassaemia-malaria link, “but he left the rest of us to sort out the evidence.” There was a convergence of thinking at the time, Weatherall says, towards an idea which Haldane formulated and Allison demonstrated, leaving plenty of room for dispute over priority. Medawar, for one, remained implacably opposed to Allison until his death in 1987.

The result is an intriguing disconnect. Ignorant of the politics of his discovery, Allison’s younger admirers—respected scientists in their own right, like the infectious-diseases expert Jean-Laurent Casanova of the Necker Medical School in Paris—wonder why he isn’t better known. Meanwhile, his sickle-cell work goes from strength to strength. It is currently enjoying another spell in the limelight for two reasons. First, because it has helped revive an idea of Louis Pasteur’s, that susceptibility to infectious diseases is inherited. And second, because the relationship between man and mosquito is entering a new phase, as global warming drives mosquitoes into previously non-malarial zones. He gets invited to speak at conferences all over the world, where his audiences regard him with a mixture of curiosity and awe. He trails a certain mystery, as he himself acknowledges. “Every generation”, he says, “likes to rediscover me.”


Picture credit:
Martin Klimek

(Laura Spinney writes on science for The Economist.)