The conventional view is that smallpox has been around since antiquity, but more recent evidence has suggested it's actually only around 500 years old.

So I have a research/rationality question: how conclusive is the "500 years old hypothesis"? I don't really have the expertise to evaluate it.

The wikipedia entry briefly notes the new findings, but doesn't seem to have rewritten the overall history section:

The earliest credible clinical evidence of smallpox is found in the smallpox-like disease in medical writings from ancient India (as early as 1500 BC),[54][55]Egyptian mummy of Ramses V who died more than 3000 years ago (1145 BC)[56] and China (1122 BC).[57] It has been speculated that Egyptian traders brought smallpox to India during the 1st millennium BC, where it remained as an endemic human disease for at least 2000 years. Smallpox was probably introduced into China during the 1st century AD from the southwest, and in the 6th century was carried from China to Japan.[26] In Japan, the epidemic of 735–737 is believed to have killed as much as one-third of the population.[14][58] At least seven religious deities have been specifically dedicated to smallpox, such as the god Sopona in the Yoruba religion. In India, the Hindu goddess of smallpox, Sitala Mata, was worshiped in temples throughout the country.[59]
A different viewpoint is that smallpox emerged 1588 AD and the earlier reported cases were incorrectly identified as smallpox.[60][61]

Paper: 17th Century Variola Virus Reveals the Recent History of Smallpox

The paper arguing the 500 years hypothesis is here.


• Variola virus genome was reconstructed from a 17th century mummified child
• The archival strain is basal to all 20th century strains, with same gene degradation
• Molecular-clock analyses show that much of variola virus evolution occurred recently


Smallpox holds a unique position in the history of medicine. It was the first disease for which a vaccine was developed and remains the only human disease eradicated by vaccination. Although there have been claims of smallpox in Egypt, India, and China dating back millennia [1, 2, 3, 4], the timescale of emergence of the causative agent, variola virus (VARV), and how it evolved in the context of increasingly widespread immunization, have proven controversial [4, 5, 6, 7, 8, 9].
In particular, some molecular-clock-based studies have suggested that key events in VARV evolution only occurred during the last two centuries [4, 5, 6] and hence in apparent conflict with anecdotal historical reports, although it is difficult to distinguish smallpox from other pustular rashes by description alone.
To address these issues, we captured, sequenced, and reconstructed a draft genome of an ancient strain of VARV, sampled from a Lithuanian child mummy dating between 1643 and 1665 and close to the time of several documented European epidemics [1, 2, 10]. When compared to vaccinia virus, this archival strain contained the same pattern of gene degradation as 20th century VARVs, indicating that such loss of gene function had occurred before ca. 1650.
Strikingly, the mummy sequence fell basal to all currently sequenced strains of VARV on phylogenetic trees. Molecular-clock analyses revealed a strong clock-like structure and that the timescale of smallpox evolution is more recent than often supposed, with the diversification of major viral lineages only occurring within the 18th and 19th centuries, concomitant with the development of modern vaccination.
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Dec 11, 2018


There is genetic evidence discussed in Hopkins' "Princes and Peasants: Smallpox in History," which implies ancient existence of variola viruses, as you note from the Wiki article. The newer paper overstates the case in typical academic fashion in order to sound as noteworthy as possible. The issue with saying that earlier emergence is not the "current" disease of smallpox is that we expect significant evolution to occur once there is sufficient population density, and more once there is selection pressure due to vaccination, and so it is very unsurprising that there are more recent changes. (I discuss this in my most recent paper, )

It's very clear that a precursor disease existed in humans for quite a while. It's also very clear that these outbreaks in thin populations would have continued spreading, so I'm unconvinced that the supposed evidence of lack due to Hippocrate's omission, and the lack of discussion in the old and new testament is meaningful. And regarding the old testament, at least, the books aren't great with describing "plagues" in detail, and there are plenty of times we hear about some unspecified type of plague or malady as divine punishment.

So the answer depends on definitions. It's unclear that there is anything like a smallpox epidemic as the disease currently occurs in a population that is not concentrated enough for significant person-to-person spread. If that's required, we have no really ancient diseases, because we defined them away.


Curious if you could explain molecular clock analysis like I’m five? Your argument here sounds plausible but I’d still be interested to get a better handle on that.

I'm definitely not the best person to explain this, since I'm more on the epidemiology side. I understand the molecular clock analyses a bit, and they involve mutation rates plus tracking mutations in different variants, and figuring out how long it should take for the various samples collected at different times to have diverged, and what their common ancestors are.

By "really ancient" you mean bronze age, right?

Classical antiquity definitely has plagues in the modern sense, like the Antonine plague. Indeed, in your paper you endorse the fairly standard claim that it was smallpox. That seems to me worth mentioning here, more than the negative claim about Hippocrates.

Yes. But to clarify, I don't think the Antonine plague is quite the same as modern ones, for the simple reason that it could only spread over a fairly limited geographic region, and it could not become endemic because of population density constraints. Smallpox evolution is driven by selection pressure in humans, and the "500 years old" claim is about that evolution, not about whether it affected humans at any time in the past. That said, it absolutely matters, because if the original source of smallpox was only 500 years ago, where did it come from? The question is how smallpox evolved, and what variant was present prior to the 1500s. It's plausible that Horsepox, which was probably the source for the vaccine strain, or Cowpox, spread via intermediate infections in cats, were the source - but these are phylogenetically distant enough that, from my limited understanding, it's clearly implausible that it first infected humans and turned into modern smallpox at recently as the 1500s. (But perhaps this is exactly the claim of the paper. I'm unclear.) Instead, my understanding is that there must have been some other conduit, and it seems very likely that it's related to a historically much earlier human pox virus - thousands of years, not hundreds.