65. A small percentage of Europeans are HIV resistant because of genetic mutations caused by the plague of the Middle Ages
We're now discussing the topic of mutations in my genetics class. Mutations are not all bad, and this Fact is a great example. A mutation is just a change in DNA sequence. Sometimes these changes are good for the recipient, sometimes they make no difference, and sometimes they are bad.
I've had my ear to the ground about HIV resistance since I was a research technician at Fred Hutchinson Cancer Research Center years ago. One research group was working on HIV transmission. Another lab was interested in host-virus co-evolution. For example, mutations in human DNA can reduce the ability of viruses to invade and infect our cells. But, I was unfamiliar with the claim in this Fact. So, I was eager to see what sources that my students would uncover in their research.
Student Responses
Students identified a variety of peer-reviewed research literature that supported and contradicted this Fact. Not surprisingly, there is considerable interest in the topic of HIV resistance, and there is a lot of literature to wade through. So, I'll summarize:
If we abbreviated the published Fact to "A small percentage of Europeans are HIV resistant," then students would agree this is a fact supported by research. There is a mutation, named CCR5∆32, that involves the CCR5 protein, which is present on the surface of cells that are part of the human immune system. HIV can bind to the CCR5 protein as a first step in entering and infecting these cells. The ∆32 mutation (∆, or delta, meaning a deletion of a part of the DNA that encodes the CCR5 protein) prevents HIV from being able to stick to those immune cells, thus preventing infection.
However, the remaining phrase in the Fact, "because of genetic mutations caused by the plague of the Middle Ages," is its downfall.
First, if the CCR5∆32 mutation had been "caused by the plague," then we can reason this mutation would not have existed before the plague ravaged Europe in the Middle Ages. However, at least one study (Hummel et al. 2005) found that human remains from the Bronze Age (before the Middle Ages) also contained the same CCR5∆32 mutation. These data support the counter-argument that the plague did not cause this mutation, because the existence of the mutation preceded the plague.
Speaking of the plague, it is also not entirely clear what organism(s) caused the Middle Ages plague in Europe. Debate still exists over whether that plague was bacterial or viral in nature (Zajac 2018). Some suggest that the plague might have involved an early HIV exposure of the human population (Cohn and Weaver 2006). However, if the plague was caused by bacterial infections, then it would not make sense that the CCR5∆32 mutation, which prevents viral entry into immune system cells, would be related to exposure to the plague in the Middle Ages.
Other scientists have debated the identity of the virus (if any) that might be related to the prevalence of the CCR5∆32 mutation. As an example, it could be that smallpox, and not HIV, killed Middle-Ages Europeans that did not already have the CCR5∆32 mutation (Galvani and Slatkin 2003).
Finally, some students noted a critical semantic distinction. The Fact asserts that "mutations caused by the plague" conferred resistance. This is the most damning rebuttal. Indeed, few (if any) infectious agents cause mutations like CCR5∆32. Instead, evolutionary geneticists would argue: humans that already contained DNA mutations that helped them overcome viral infection (like CCR5∆32 preventing viral invasion of immune cells) would survive challenges like a viral plague. Humans that did not have such mutations would more likely die. Thus, although a viral plague might not cause (or induce) resistance mutations in humans, the exposure of a genetically diverse human population to a viral plague could cause the mass death of humans that did not already have the rare and randomly-occurring mutation (e.g. CCR5∆32) that would have made them less susceptible to viral invasion.
Student Decision: Fact or Fiction?Fiction! (but, once again, this outcome resulted mainly from the wording of the Fact. The intent of the Fact is, as has often been the case, strongly supported by research)
Literature Cited
- Cohn and Weaver (2006) "The Black Death and AIDS: CCR5-Delta32 in genetics and history" QJM
- Galvani and Slatkin (2003) "Evaluating plague and smallpox as historical selective pressures for the CCR5-Δ32 HIV-resistance allele" PNAS
- Hummel et al. (2005) "Detection of the CCR5-D32 HIV resistance gene in Bronze Age skeletons" Genes Immunity 6:371-374.
- Zajac (2018) "Evolutionary view of the AIDS process" J Int Med Res 46(10):4032-4038.
