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In other words, how did human infectious diseases evolve in general, what were their sources, and what could account for the dramatic difference in disease prevalence in different human populations in particular? First issue to resolve is how human infectious diseases likely evolved in the first place.

Agriculture was a key inflection point in human infectious disease evolution

In 2006, Jared Diamond and Claire Panosian proposed (1) that major infectious diseases appear to have arisen predominantly in the Old World, i.e., Africa, Asia, Europe.

  • The first inflection point is ~11,000 years back, when agriculture first arose, allowing dense human populations to be sustained for the first time in human history.
  • According to this synthesis, burgeoning human population density was crucial in driving the emergence of many infectious diseases that didn’t exist pre-agriculture.
  • Wolfe, Dunavan, Diamond describe a five-stage process by which a pathogen exclusively infecting animals becomes transformed into one which exclusively infects humans (See figure below from 2).

Thus, majority of the 25 major human infectious diseases originated in the Old World.

  • Since the 1960s, this observation has set in motion the idea that many more Native Americans perished from Old World infectious diseases transmitted to them by the European colonists compared to deaths through war and violence.
  • The idea is European colonists had over evolutionary time developed both individual acquired immunity to survive these infections as well as some types of genetic resistance while the Native Americans had neither (3, 4, 5, 6).
  • According to Wolfe, Dunavan, Diamond, of these 25 major human infectious diseases, the only disease that can be clearly attributed to the New World is Chagas’ disease.

Why weren’t there any diseases (similar to small pox) that the native Americans had (& subsequently developed their immunity) but Europeans were not immune to?

Wolfe, Dunavan, Diamond argue the main reason for this imbalance between Old World and New World infectious disease origin stems from imbalance in domestication of animals (2).

Is there supporting data?

  • Thirteen of the world’s 14 major domesticated livestock originated in the Old World (4).
  • These include cow, goat, horse, pig, sheep, the five most abundant species humans come in closest contact, and which originated in the Old World (4).
  • The llama was the only livestock domesticated in the New World. Why isn’t it known to have transmitted any known pathogens to humans? Wolfe, Dunavan, Diamond (2) argue that it didn’t happen for the following reasons,
    • Geographic range confined to the relatively inhospitable Andes. Implicit in this point is the issue of human population density, i.e., that llama-associated human populations couldn’t and never did become dense enough to sustain evolution of human-to-human (direct) transmission of any hypothetical infectious disease agent from llama-to-human.
    • Llama wasn’t milked/ridden/hitched to ploughs.
    • Llama wasn’t cuddled or kept indoors, unlike calves, lambs and piglets.

These 25 major human infectious diseases include the 17 which currently impose the greatest global human infectious disease burden (7), i.e., the highest disability-adjusted life year scores (DALYs).

  • Eight of these are Temperate: Hepatitis B, Influenza A, Measles, Pertussis, Rotavirus A, Syphilis, Tetanus, Tuberculosis.
  • Nine are Tropical: AIDS, Chagas’, Cholera, Dengue, East and West African Sleeping Sickness, Malaria (Plasmodium falciparum and vivax), Visceral Leishmaniasis.
  • The remaining seven imposed heavy disease burden in the past but now modern medicine and public health have either eradicated them (Temperate Small pox) or greatly reduced their burden (Temperate Diphtheria, Mumps, Plague, Rubella, Typhoid, Typhus, and Tropical Yellow Fever).

The list of Tropical diseases highlights another difference between Old and New World infectious diseases since 8 of them arose in the Old World and only one, Chagas’, in the New World.

Wolfe, Dunavan, Diamond (2) have a two-fold argument to explain this discrepancy,

  • One, that genetic distance between humans and New World monkeys is ~twice that between humans and Old World monkeys, and many times more than that between humans and Old World Apes, implying that species jumping was more onerous in the New World.
  • Two, much greater evolutionary time (~5 million years) was available for animal-to-human infectious disease transfer in the Old World compared to the New World (~14,000 years).

Unresolved issues

Origin of major human infectious diseases needs major systematic surveys and review. Most studies examine specimens collected from a few domestic and wild animals rather than on systematic surveys of particular infectious disease agents across a spectrum of domestic and wild animals.

  • Syphilis and tuberculosis origins are unresolved (2).
  • Geographic origins of rotavirus, rubella, tetanus and typhus are unknown (2).
  • Unknown which major human infectious diseases came from domesticated livestock versus domesticated pets.
  • New archaeological evidence suggests human colonization of the Americas was much more complicated than surmised, with artifacts and bone tools dating back 30 to 45000 years back (8).

A counterintuitive take? Suzanne Austin Alchon argues that morbidity and mortality of New World humans to infectious diseases transmitted by Old World colonizers was similar to those experienced by the Old World inhabitants themselves (8). According to her, the major reason for sustained Native American population declines had more to do with European colonial practices, namely, brutalities associated with war, slavery, enforced migrations, and the resulting socioeconomic breakdown in their societies.


1. Diamond, J., and C. Panosian. “When Disease Makes History: Epidemics and Great Historical Turning Points. Hämäläinen P, editor.” (2006): 17-44; Wolfe, Nathan D., Claire Panosian Dunavan, and Jared Diamond. “Origins of major human infectious diseases.” Nature 447.7142 (2007): 279-283. http://www.com.univ-mrs.fr/~Boud…

2. Origins of Major Human Infectious Diseases. Nathan D. Wolfe, Claire Panosian Dunavan, Jared Diamond. pp. 349 to 362. In Choffnes, Eileen R., et al. Improving Food Safety Through a One Health Approach: Workshop Summary. National Academies Press, 2012.

3. Crosby, Alfred W. “Ecological Imperialism: The Biological Expansion of Europe, 900-1900 (Cambridge, 1986).” CrosbyEcological imperialism: the biological expansion of Europe (1820): 900-19001986.

4. Diamond, Jared, and Guns, Germs and Steel: The fates of human societies.” New York: W. W. Norton (1997).

5. McNeill, J. R. “When Disease Makes History: Epidemics and Great Historical Turning Points. Hämäläinen P, editor.” 81-111.

6. Ramenofsky, Ann Felice. Vectors of death: the archaeology of European contact. University of New Mexico Press, 1987.

7. Lopez, Alan D., et al. “Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data.” The Lancet 367.9524 (2006): 1747-1757.

8. Alchon, Suzanne Austin. A pest in the land: new world epidemics in a global perspective. UNM Press, 2003.