Obituaries

Anthony Allison

BMJ 2014; 348 doi: https://doi.org/10.1136/bmj.g2243 (Published 24 March 2014) Cite this as: BMJ 2014;348:g2243
  1. Laura Spinney, Lausanne
  1. lfspinney{at}gmail.com

Showed link between sickle cell disease and immunity from malaria

I vividly remember the day I learnt about balanced polymorphisms in biology class. The teacher illustrated the concept with the classic textbook example—the case of the carriers of the sickle cell trait, who are protected from malaria.

The lesson stayed with me because of its pleasing symmetry—that beautiful bell curve that describes so many things in nature. The sickle cell mutation—lethal in homozygote individuals before they reach puberty—maintains itself in the gene pool because people with only one copy don’t get the disease, and are less likely to contract malaria too.

Tony Allison saw the distressing tail ends of the curve: the children’s wards in Mombasa on the Kenyan coast, and at Kisumu on Lake Victoria. Here half of the young patients were suffering the agonising crises of sickle cell anaemia—pain that penetrates the bones and brings fever with it. He himself represented the opposite tail, having often been confined to bed with malaria while growing up in Kenya.

It may have been the unhappy memories of those episodes—combined with the bone rattling cold of the British winter of 1947-48—that drove him to take a break from his medical studies in Oxford. In 1949 he joined an expedition to east Africa to look for evidence for ideas that were circulating at the time—that humans have innate immunity, and that disease drives selection for the genes that encode that immunity.

Human evolution fascinated Allison. His Kenyan upbringing had brought him into contact with Louis Leakey—then digging at Olduvai Gorge in Tanzania—and his anatomy teacher at Witwatersrand University in South Africa, Raymond Dart, was among those who discovered the first Australopithecus fossils, in 1924. Rather than look for diversity and selection in fossils, however, Allison intended to search for it in the blood groups of living people. On the eve of his departure a conversation with a haematologist sowed another seed in Allison’s mind—the outstanding mystery of why sickle cell disease hadn’t bred itself out in Africa.

Straight away he noticed a pattern—sickle cell disease was more common on the coast and around Lake Victoria than in the highlands. It occurred to him that it might not be a coincidence that these low lying areas were also malarial zones, but by then he had run out of time to investigate further. He returned to Oxford and it wasn’t until 1953 that he was able to go back to Africa and test his theory. He travelled through Uganda, Kenya, and Tanzania, comparing the parasite loads in blood samples from those with and without the sickle cell mutation.

The result was a series of papers published—one of them in this journal1—in 1954. There were disagreements about whether Allison deserved the credit for the discovery and this confirmed his sense of standing outside the British scientific establishment. It also goes some way to explaining why he isn’t better known.

In the 1970s, at the Medical Research Council’s Clinical Research Centre in London, he worked on the problem of deficiencies in innate immunity which left some children permanently vulnerable to infection.

Having identified an enzyme, inosine monophosphate dehydrogenase, that is important in those immune pathways, he speculated that a small-molecule antagonist of that enzyme might help to prevent the rejection of organ transplants, and in treating some autoimmune diseases. The molecule was mycophenolate mofetil, better known as the immunosuppressant drug CellCept. Allison and his wife, Argentinian biochemist Elsie Eugui, developed the drug at Syntex Corporation—a pharmaceutical company in Palo Alto, California—and it went on to make a substantial amount of money for Roche after it bought Syntex in 1994.

In the years leading up to his death, despite having interstitial pulmonary fibrosis, which progressively restricted his movements, Allison threw himself into a new project: developing a pharmacological strategy to reduce reperfusion injury to tissues following ischaemia. If it fulfilled what he considered to be its full potential, it would help in the treatment of both malarial and sickle cell crises, bringing his long and productive career full circle.

Allison leaves his second wife, Elsie Eugui, and two sons from his first marriage.

Notes

Cite this as: BMJ 2014;348:g2243

Footnotes

  • Anthony Clifford Allison (b 1925; q Oxford University 1952), died 20 Februrary 2014.

References

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