Is any means by which smallpox or any other disease be heritable?

I have heard that smallpox introduced by European colonialists affected (and reduced) a significant proportion of the native American population. How were the native Americans more susceptible to smallpox? Is disease susceptibility or immunity heritable?

  • $\begingroup$ Susceptibility to infectious diseases is most certainly heritable. Variola is specific case. I'm off to the airport, but will be happy to give you a thorough answer tomorrow. Let me suggest, though, that you edit your question and rephrase it to remove the unnecessary political angle. I can't see how it adds anything to the otherwise useful scientific question. $\endgroup$ – De Novo Jul 23 '18 at 4:51
  • $\begingroup$ So do you have an answer $\endgroup$ – user45026 Jul 23 '18 at 5:28
  • $\begingroup$ A naturally-occuring disease would not lead to genocide. Else it could equally well be claimed that the Black Death was genocide of Europeans by (probably) Chinese, or AIDS an attempt at genocide by Africans. $\endgroup$ – jamesqf Jul 23 '18 at 17:19
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    $\begingroup$ @jamesqf but there is evidence of intention in the case of the British and native Americans, "could it not be contrived to send the small pox among the disaffected tribes of Indians" Jeff Amherst books.google.com/… $\endgroup$ – DavePhD Jul 30 '18 at 13:01
  • $\begingroup$ I'm voting to close this question as off-topic because it calls for speculation and is presented in a provocative manner. Its main concern appears to be American social history. $\endgroup$ – David Jun 29 '19 at 16:05

TL;DR: Pre-Columbian Native Americans would have been much more susceptible to smallpox than the Europeans who spread it, because of non-heritable factors such as immunity and traditional knowledge, and also because of heritable factors. It's therefore completely believable that smallpox (and other diseases introduced by Europeans, such as measles) could have caused massive deaths among the American populations post-contact.

The title of the question makes an incorrect assumption. Resistance to smallpox would not have to be heritable to have a highly susceptible population. European populations were continually exposed to smallpox and there would have been both maternal immunity and acquired immunity in most populations, leading to a herd immunity effect that would both reduce viral spread and increase resistance among some infected people. (It's commonly believed that herd immunity needs to be very high to lead to protection, but that's a misconception -- the lower the contagiousness of the disease, the lower herd immunity needs to be to lead to protection.)

Smallpox apparently circulated as a childhood disease in northern England and Sweden, even where population densities were low and settlement patterns dispersed.

--The geography of smallpox in England before vaccination: A conundrum resolved

Cultural factors would also be important. Europeans had thousands of years of experience with smallpox, and knew that isolating victims was important to reduce spread.

We concluded that transmission was controlled in southern England by local practices of avoidance and mass inoculation that arose in the seventeenth and eighteenth centuries. Avoidance measures included isolation of victims in pest houses and private homes, as well as cancellation of markets and other public gatherings, and pre-dated the widespread use of inoculation.

--The geography of smallpox in England before vaccination: A conundrum resolved

That said, there is also evidence that European populations did have some innate resistance to smallpox that was lacking in the pre-Columbian Native Americans, and this innate resistance may be even stronger in Africa, which is (possibly) where smallpox originated:

Pathogens that diminish reproductive potential, either through death or poor health, drive selection on genetic variants that affect resistance; selection is likely to be most evident for pathogens with a long-standing relationship with Homo sapiens, including those that cause malaria, smallpox, cholera, tuberculosis and leprosy ... We noted that, for 32 viral isolates with documented mortality, death rates are lower in Africa (0.4−12%) than elsewhere (4−38%), even though all isolates were from a single phylogenetic clade. This is consistent with selection for resistance in Africa, where the smallpox virus is predicted to have evolved from a rodent-borne ancestor tens of thousands of years ago and where outbreaks of other poxviruses continue nowadays.

With smallpox eradicated, vaccine response is used as a crude phenotypic proxy for studying host resistance. Two GWASs that included European, African American and Hispanic populations identified 37 SNPs associated with cytokine response to vaccination179, 180 (P < 1 × 10−8). Most of the significant associations (65%) were found in African Americans, even though their sample size was half of that of the European cohorts, which is consistent with a larger effect due to selection in Africa.

--Natural selection and infectious disease in human populations

Some resistance alleles have been tentatively mapped:

However, when examining the population post-contact and into contemporary times, variants of the HLA-DQA1 gene experience a marked frequency change. ... Although we were unable to precisely identify the selection coefficient necessary to drive the allele frequency change (since the likelihood surface is relatively flat, Supplementary Fig. 8), it is likely that relatively strong negative selection occurred. Such strength would be expected under a time frame of less than seven generations and correlates with the high mortality rates associated with the regional smallpox epidemics of the 1800s, which reached upwards of 70%

--A time transect of exomes from a Native American population before and after European contact

The CCR5 Δ32 mutation is a good example of an advantageous allele with a well-characterized geographic distribution. ... The mutation is found principally in Europe and western Asia, where average frequencies are approximately 10% ... Bubonic plague was initially proposed as the selective agent [2], but subsequent analysis suggested that a disease like smallpox is a more plausible candidate

--The Geographic Spread of the CCR5 Δ32 HIV-Resistance Allele

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  • $\begingroup$ This is good, but I wonder why you would say that immunity to an illness that requires T-cell involvement (and thus antigen presentation on the MHC) is not heritable? (top of your post, in the tl;dr summary) $\endgroup$ – De Novo Jul 23 '18 at 17:53
  • $\begingroup$ Adaptive immunity is not considered heritable, even though of course it has heritable components to it. If you know enough to comment on MHC, you must have noticed the link with HLA-DQA1, which is of course an MHC allele. $\endgroup$ – iayork Jul 23 '18 at 17:57
  • $\begingroup$ I've upvoted your post, but I'd encourage you to read Casanova's excellent inaugural PNAS article. You may not consider adaptive immunity to be heritable, but as an infectious disease doctor, I can tell you it certainly is. MHC loci are among the most variable in the entire genome, this variability is heritable, and contributes a great deal to host susceptibility. There are plenty of other examples. $\endgroup$ – De Novo Jul 23 '18 at 18:14
  • $\begingroup$ And yes, I noticed and appreciated the link. I was making a suggestion that you edit your statement in the tl;dr summary, where you classified immunity (in general) as non-heritable. That is a false classification. You could narrow it down to antibody response and be less wrong, but again, with class switching, it relies on T-cell involvement. It's a good post overall. I was just remarking on the one error. $\endgroup$ – De Novo Jul 23 '18 at 18:21
  • $\begingroup$ @user45026 So basically yes. If you need further clarification, please spell out what's confusing you. $\endgroup$ – iayork Jul 23 '18 at 18:44

As usual, @iayork has a great answer. Let me add some additional context.

Host-pathogen interactions

Pathogens are not disease. The result of an interaction between, e.g., a virus and a host is variable. This is a fundamental and extremely important concept in understanding infectious disease. You can read more about it in Chapter 286 of Cecil Medicine and Chapter 119 of Harrison's Internal Medicine. The clinical outcome of a host-pathogen interaction is as much dependent on the host as it is the pathogen.

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Host effects are variable and heritable

There is great interindividual and interpopulation variability in host factor side of this graph, the susceptibility/resistance to specific infectious diseases. Much of it is heritable. Sickle cell trait is an excellent example. We refer to it so often to illustrate genetic principles, that the key lesson about host-pathogen interactions is often forgotten. It was not unnoticed in the original paper. This genetic variation in susceptibility is not an exception, see Jean-Laurent Casanova's inaugural article in PNAS for an excellent discussion.

Comment on @iayork's answer

I did enjoy the discussion of the non-genetic (but certainly vertically transmitted) traditional knowledge in the susceptibility of a population to smallpox, as well as the references to single gene associations. Host susceptibility and resistance is certainly heritable, but as s/he points out, there are important non-heritable contributions to consider.

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