Sickle Cell Disease, Malaria, and Human Evolution

Tony Allison grew up in Kenya. His father, a farmer, had relocated the family from England in 1919. As a boy, Tony went on long excursions with professional naturalists to observe and help collect birds for the Natural History Museum in London. He also visited the archeological excavation site of Louis Leakey, the pre-eminent anthropologist of his time, and became intrigued with human evolution and the relationships between the various tribes he saw in Kenya.

During one of the Allisons’ holidays on the beaches of Malindi in Kenya, Tony contracted malaria; he was only ten years old.  Malaria is a terrible disease and often fatal. It is caused by a protozoan, a simple single-celled organism and carried by a specific type of mosquito. When one of these mosquitoes bites a person, it injects this protozoan, P. falciparum, into the individual. These parasitic cells take up residence in the blood and destroy red blood cells, the cells that carry oxygen through the blood. There is currently no vaccine against malaria. Tony’s experience with malaria led him to switch gears: rather than becoming a naturalist, he decided to become a physician.

After earning his undergraduate degree in South Africa, Tony moved to England to finish his medical training at Oxford University. Although he enjoyed medical school, he had not lost his keen interest in human evolution. Tony was convinced that there had to be a way to measure human evolutionary relationships more precisely than anthropologists did by looking only at bones.

In 1949, when Oxford University sent a group of scientists to Kenya to survey and study plants and animals all over the country, Tony jumped at the opportunity to revisit the land of his childhood and to study human populations. He accompanied the expedition team on their travels throughout Kenya, and at each location he collected blood samples from individuals of each of the various tribes, including the Kikuyo, Luo, and Masai tribes. He tested the samples for red blood cell membrane proteins to see if there might be a pattern that would reveal genetic relationships. Tony also tested for the presence of sickle cells, a type of abnormal red blood cell, Prior to embarking on the trip, Tony had learned from other scientists that sickle cells, common in some areas of Africa and inherited, produced sickle cell disease—a painful and, in the early 20th century, generally fatal disorder.

To Tony’s disappointment, the analysis of red blood cell membrane proteins failed to reveal a pattern. In contrast, the sickle cell results presented an unexpected surprise. Tony observed the sickle cell trait in more than 20% of the individuals in tribes living along the coast or near Lake Victoria. Yet, fewer than 1% of people in tribes living in dry land areas or high altitudes exhibited the trait. Tony wondered why there was such a big difference in its prevalence and why it seemed to depend on where a person lived.

Sometimes a good idea comes like a bolt out of the blue. Tony knew that the density of mosquito populations varied in different locales as did the incidence of malaria. In lowlands and wet areas, the mosquitoes were abundant, malaria was prevalent, and the incidence of the sickle cells trait was high. In the dry highlands, mosquitoes were few and far between, malaria was not a problem, and the sickle cell trait was rare. Was there a relationship?  Tony hypothesized that possession of the sickle cell trait provided some resistance to infection with P. falciparum, the malaria parasite, but he could not test the idea because he had to return to England to finish medical school.

Tony completed medical school in 1952 and received the financial and technical support he needed to return to Africa in 1953. As Dr. Allison, his goals were straightforward: he wanted to see whether the inheritance of the gene that is associated with sickle cell disease would indeed confer resistance against malaria.

Dr. Allison designed three studies to address his research question. In the first study, he piggy-backed on to a drug trial being conducted by a pharmaceutical company. Scientists injected P. falciparum into healthy volunteers. When subjects developed malaria, the scientists administered their test drug to see if it was effective. Allison had access to all 30 of the individuals in the study. He took blood samples from all and looked for a relationship between those possessing the sickle cell trait and those who developed malaria. The results were dramatic. Fourteen out of fifteen infected subjects who did not have the sickle cell trait developed malaria. Only one out of fifteen subjects who had the sickle cell trait did so.


Allison was excited about these results, but he knew that adults living in mosquito-infested areas probably had been exposed to P. falciparum earlier in their lives. The results may have been due to immune responses remaining from previous infections. To address this possibility, Allison undertook a second study. He offered free medical check-ups to children at the local farmers’ markets. He administered physical exams and collected a small amount of blood from each child. He examined the blood samples for two things: the presence or absence of the sickle cell trait and whether P. falciparum was in the blood.

Eventually Allison collected data for 290 children. Once again, the results were dramatic. P. falciparum was present in only 28% of children who had the sickle cell trait. In contrast, 46% of children who did not have the trait were infected and the number of parasites present was greater than that observed in the children with the sickle cell trait.

In Allison’s final study, he traveled throughout Africa collecting blood samples from 5000 individuals representing more than 30 tribes. He observed that the frequency of the sickle cell trait ranged from 0% to 40%. In all cases, the sickle cell trait was rare or absent in locations where malaria was absent and common in locations where malaria was a serious problem.

Through his three studies, Allison demonstrated unequivocally that possession of the sickle cell trait afforded some protection against malaria. However, many questions remained. How does a person develop sickle cell disease?  What accounts for the relationship between sickle cell disease and malaria? For our purposes, let’s start with a simpler question: What exactly is sickle cell disease?

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