Origins of Malaria

Agriculture and Malaria

In July 2001, The Economist notified its readers of two articles in Science published that month concerned with the origins of malaria. Both articles, the news magazine noted, employed studies in genetics to explore a hypothesis put forth more than forty years earlier by Frank B. Livingstone in American Anthropologist. In “Anthropological Implications of Sickle Cell Gene Distribution in West Africa,” Livingstone suggested that the development of agriculture in western Africa brought Plasmodium falciparum as a parasite into human populations, and “the spread of this agriculture is responsible for the spread of the selective advantage of the sickle cell gene” (555). He concludes:

The agricultural revolution has always been considered an important event in man's cultural evolution, but it also seems to have been an important event in man's biological evolution. … [Disease became a significant limiting factor in population growth.] Two results of the agricultural revolution seem to account for this change in the role of disease in human evolution: (1) the great changes in the environment, and (2) the huge increase in the human population. Both of these seem to be involved in the development of holoendemic malaria. First, when man disrupts the vegetation of any area, he severely disrupts the fauna and often causes the extinction of many mammals, particularly the larger ones. When this happens, there are many known instances of the parasites of these animals adapting to man as the new host. It is thus possible that the parasitization of man by P. falciparum is due to man's blundering on the scene and causing the extinction of the original host. Second, concomitant with the huge increase in the human population, this population became more sedentary and man also became the most widespread large animal. Thus, he became the most available blood meal for mosquitoes and the most available host for parasites. This change resulted in the adaptation of several species of the Anopheline mosquito to human habitations and the adaptation of many parasites to man as their host.
Livingstone, “Sickle Cell Gene Distribution,” 556.

One of the Science articles presented research by the Harvard-Oxford Malaria Genome Diversity Project. Sarah K. Volkman, Alyssa E. Barry, and the others on the team analyzed “25 introns from eight independent isolates” (482) which they found deficient in single-nucleotide polymorphisms (SNPs). Their data led to an estimated age of 3200 to 7700 years for the most recent common ancestor (MRCA) of extant P. falciparum, and 9500 to 23,000 for the age of MRCA when two “suspect SNPs” are included.

[T]he establishment of slash-and-burn agriculture in the African rainforest less than 6000 years ago … could have provided suitable expansion conditions for the mosquito vectors of P. falciparum and adequate human population size to maintain transmission.
Volkman, et al., “Recent Origin of Plasmodium falciparum,” 483.

The other article examined “genetic defense mechanisms … for resisting infection by Plasmodium” (455). Estimating the ages of two glucose-6-phosphate dehydrogenase (G6PD) alleles that “are restricted to specific geographic regions,” Sarah A. Tishkoff and her co-authors note the ages correspond with the development of agriculture. They estimate that G6PD “A- mutation arose in the past 3840 to 11,760 years” (459) and the Med allele 1600 to 6640 years ago. They note that the age of the A- allele partly supports the hypothesis of Frank Livingston, but that “an increase in both temperature and humidity between 12,000 and 7000 years ago” in Africa may have contributed to malaria’s spread earlier in the Sahara and east Africa (460). They note that malaria had been present in human populations much longer, but that “more severe malaria did not become hyperendemic until the past 10,000 years” (460). They also state:

It is possible that the recent and rapid spread of the Med allele across a broad geographic region may correspond with the spread of agriculture during a Neolithic expansion and migration across Europe from the Middle East 10,000 to 5000 years ago.
Tishkoff, et al., “Haplotype Diversity and Linkage,” 460.

These two articles were not published without skepticism from other researchers in genetics, epidemiology of malaria, and related subjects. In “Malaria's Beginnings: On the Heels of Hoes?” in the same issue of Science, Elizabeth Pennisi outlined some aspects of the controversy. The “prevailing view has long favored ancient origins,” she notes, but several studies in recent years have supported the “link between malaria and agriculture” (416-417).

Two years after the flurry of articles in Science in 2001, another article offered additional support both for the ancient origin and for the more recent expansion of P. falciparum. Deidre A. Joy and her co-authors “reject the claim that the parasite originated 6000 years ago,” but suggest that the population of the parasite likely remained small for a long period. Their data “provide[s] strong evidence for a recent and rapid population expansion in Africa followed by migration to other regions” (321).

Historical Significance

If P. falciparum, the parasite that causes the most virulent form of malaria, expanded in concert with agriculture, it joins many other maladies that have made gatherings of humans into towns and cities unhealthy places for most of human history.

As the development of agriculture made possible the rise of cities, food became cheaper but often less varied. The rise of towns and cities with the expansion of agriculture reduced the overall health of human populations. Deleterious effects of the Neolithic revolution included sedentary lifestyles, repetitive physical tasks (swinging a scythe, for example, or pounding grain into flour), ecological degradation, and new illnesses. Cities were terribly unhealthy abodes for humanity until the twentieth century developments of modern water and sewage treatment, plumbing, and garbage disposal. These themes are central to the arguments in The Backbone of History: Health and Nutrition in the Western Hemisphere (2002), edited by Richard H. Steckel and Jerome C. Rose, and of Jared Diamond, Guns, Germs, and Steel: The Fates of Human Societies (1997).

In general, the healthiest populations were hunter-gatherers, and the least healthy lived in large settlements supported by systematic agriculture. Our statistical analysis of the health index identifies settlement size and use of domesticated plants as the two most important factors associated with the long-term decline in pre-Columbian health.
Steckel and Rose, “Conclusions,” The Backbone of History, 587.

Sedentary farmers became surrounded not only by their own feces but also by disease transmitting rodents, attracted by the farmers’ stored food. The forest clearings made by African farmers also provide ideal breeding habitats for malaria-transmitting mosquitos.
Diamond, Guns, Germs, and Steel, 205.

Civilization made us sick, but it also made us more numerous so we could impose our will on those otherwise more fortunate. The maladies that afflicted Europeans contributed in significant measure to their global expansion.