One Mosquito Bite Away from Colonization: Malaria Resistance in Africa due to Sickle Cell Anemia

One Mosquito Bite Away from Colonization: ENDNOTES Malaria Resistance in Africa due to Sickle Cell Anemia

In the early 1600s, Europeans successfully colonized the Americas. However, deadly diseases such as yellow fever and malaria stalled their conquest of Africa at the continent’s coast. While Europeans vindicated this anomaly with pseudo-scientific racism, modern science shows that high frequencies of the genetic disease sickle-cell anemia gave Africans a resistance to malaria that Europeans did not possess. It was not until the discovery of the antimalaria drug quinine that Europeans were able to survive malaria and move their colonization project further into the interior of Africa, demonstrating the importance of understanding the role of science in history.

In the eighteenth century an estimated thirty to seventy percent of Europeans died each year from various diseases while travelling to Africa; Europeans were quick to blame these high death rates on race.1 Diseases like sleeping sickness, worms, dysentery, yellow fever, and malaria were common to African regions.2 However, the eighteenth-century medical community struggled to rationalize the cause of the diseases. Ancient Roman and Greek philosophers created the miasma theory which hypothesised that tiny animals who dwelled in swampy places could enter the body via the air and cause illness. Through this theory “bad air” became an explanation for malaria epidemics, especially in swampy West Africa.3 Europeans noticed that malaria mostly affected white men to the extent that Sierra Leone became known as “White Man’s Grave,” and they began to attribute race as an explanation for infection.4 Pseudo-scientific racism emerged with the idea that different races of men were created by God as different species in a hierarchy topped by white men.5 This meant that white men thought black people were not susceptible to malaria because they were a different species, plagued by a different subset of disease. However, high malaria rates can actually be attributed to West Africa’s ideal environment for mosquitoes in the genus Anopheles (Figure 1), which are vectors for the malaria causing parasite, Plasmodium. 6 In a time before the microscopic causes of disease were known, Europeans wrongly believed that survival of malaria depended upon a person’s skin colour; however, modern population genetics and epidemiology have attributed African survival of malaria to the genetic disease, sickle cell anemia.

Unbeknownst to scientists of the eighteenth century, Africans have higher frequencies of sickle cell anemia than any other racial group. Sickle cell anemia is caused by a mutation in the gene that produces haemoglobin, the oxygen carrying component of red blood cells.7 A rendering of a genetic mutation is shown in Figure 2. *figure title in the comments on trello* When a human egg is fertilized, a copy of half of the mother’s and father’s genes are passed to the child. Individuals with two copies of the sickle cell gene (HbS), one copy from each parent, are affected with sickle cell anemia and are said to have an SS genotype.8 They have abnormally functioning sickleshaped haemoglobin, and present with fatigue, swelling, and frequent infections.9 Individuals with one normal copy of the gene (HbA) and one copy of HbS are said to have the AS genotype and are carriers for the disease.10 They are carriers because they can pass the affected HbS gene onto their own offspring but are not affected themselves. Children with the SS genotype for sickle cell disease have a low life expectancy; however, HbS carriers do not usually display sickle cell symptoms or deleterious side effects.11 The higher frequency of the HbS gene in African populations strongly correlates with the regions where malaria is endemic. A study in 2010 found that the HbS frequency was maximal at 18.18% in northern Angola, 9% in Ghana and Zambia, and 0.5% everywhere else in the world.12 These frequencies almost perfectly match the occurrence of malaria infections in the world as seen in Figure 3.13 This supports the hypothesis that Africans could better survive malaria because of this evolutionary adaptation and disproves the attribution to race which European colonizers held.

Figure 2: A single mutation in this strand of DNA can alter the gene and cause genetic diseases, like sickle cell anemia. (“What Happens When a Genetic Mutation Occurs.” Accessed March 21, 2022. https://pathologytestsexplained.org.au.)

Figure 3: A) The current percent frequency of the HbS allele across the globe compared to B) which shows the severity of malaria globally since 1900.

(Piel, Frédéric B., Anand P. Patil, Rosalind E. Howes, Oscar A. Nyangiri, Peter W. Gething, Thomas N. Williams, David J. Weatherall, and Simon I. Hay. “Global Distribution of the Sickle Cell Gene and Geographical Confirmation of the Malaria Hypothesis.” Nature Communications 1, no. 1 (December 2010): 104. Fair use.

Figure 4: Sickle-shaped red blood cells of a person with sickle cell anemia. The sickle shape prevents the malaria parasite from reproducing, giving people with sickle cell anemia a better chance of surviving malaria. (Correspondent. “Experimental Gene Therapy Reverses Sickle Cell Disease for Years,” The Daily Guardian blog, January 3, 2022.)

Africa experiences a balanced polymorphism, the paradox of a deadly disease-causing allele maintaining a high frequency in a population, because the malaria parasite cannot survive in people with sickle cell disease.14 Malaria begins with the Anopheles mosquito ingesting the Plasmodium parasite. As the mosquito bites, the parasite enters the human host and completes its life cycle within the liver and blood cells.15 The parasite develops in the blood cells and causes toxins to enter the blood stream, resulting in fevers and chills as the immune system fights the invader.16 Carriers of the HbS gene produce some sickle-shaped blood cells, shown in figure 4, that prevent the parasite from completing its lifecycle, but have enough normal blood cells that enable them to live unaffected by sickle cell anemia.17 Because sickle cell anemia protects against malaria, the genetic disease continues to be selected for within African populations. For Europeans to successfully colonize Africa, they had to circumvent the disease that was stopping them from penetrating the continent. While human motivations for wealth and power often shaped conquests in the Atlantic world, the way that malaria, genetics, and quinine shaped the colonization of Africa advocates for the role of science in historiography.

Europeans soon found quinine, a cure for malaria within the bark of a South American tree. They were able to exploit and mass produce quinine, giving them one of the defenses they needed to colonize Africa. It was well known to Indigenous Americans that the Cinchona

Figure 5: This glass bottle would have contained quinine sulphate to treat malaria. (Wellcome Collection. “Quinine Sulphate Bottle, London, England, 1860-1910.” Fair use.

tree’s leaves could abate fevers.18 Jesuit missionaries discovered the tree in the 1600s, leading to European exploitation of the tree for its medicinal properties.19 Traditionally, the bark was ground and mixed with a liquid that patients drank; this treatment was neither effective nor efficient as it required many trees.20 In 1820, Pierre Joseph Pelletier and Joseph Caventou extracted and purified the active chemical compound, quinine, from the bark. Figure 5 shows a bottle which would have contained the mass produced, synthesized quinine which became a more effective treatment for malaria.21 Quinine’s success is demonstrated by the thirty-three percent decline in deaths among the French military in Senegal in the mid1830s.22 Likewise, from 1849 to 1890, the British military death rate in West Africa dropped about twelve percent after the widespread introduction of quinine.23 With decreased mortality and increased military power, the European scramble to colonize Africa was finally successful in the late nineteenth century.24

Haley Friesen Biology major, Chemistry minor