Did smallpox emerge in 1580?

Question

Researchers compared and contrasted the 17th Century strain to those from a modern databank of samples dating from 1940 up to its eradication in 1977. Strikingly, the work shows that the evolution of smallpox virus occurred far more recently than previously thought, with all the available strains of the virus having an ancestor no older than 1580

Smallpox, once thought an ancient disease, may have emerged in more recent times / MCMASTER UNIVERSITY

I am skeptical. Is there evidence to support this?

Answer 1

Q Is there evidence to support this [ all the available strains of the virus having an ancestor no older than 1580]?

Yes.

What we think of when we say "smallpox" is a disease that did not exist in this form before and seems to be of quite recent origin. That disease is tied to a causative agent called virus that in this variant did not come into existence with these necessary genes and qualities before 1500.

Meaning, the disease caused by the apparently no-longer existing-in-the-wild Variola major virus, which has a definition of a:

… highly contagious and frequently fatal viral disease that is characterized by a biphasic fever and a distinctive skin rash that leaves pock marks in its wake. Because of its high case-fatality rates and transmissibility […] The disease is caused by the variola virus. The majority of patients with smallpox recover, but death occurs in up to 30 percent of cases.[…]
_{–– Medical Definition of Smallpox}

…is by the best evidence we have a post-medieval phenomenon.

A note on language usage: "1588" is in reality an inappropriate over-precision. Numbers like this used subsequently are to be read as estimated approximations that are used as a shorthand for ranges for convenience.

Historical, archaeological and genetic sources – so far – do not permit another conclusion.

_{Src: Duggan} Not only Duggan et al think that. Reading closely it becomes apparent that older descriptions of diseases are misleadingly 'identified' as (20th century!) smallpox.

They were mostly quite deliberately and sometimes desperately "identified" as "most probably smallpox" by believers ("believed, seems, plausible"), no matter how tenuous the connection. But in those historical cases were we now still would be certain to say that a described illness might reasonably fit with "could have been caused by a kind of pox-virus): that these cases were also quite benign in comparison. Much lower transmission, much lower death rate.

The first considered the antiquity of the disease itself, and whether it was in fact known to earlier civilizations and medical writers prior to its first clear description by Rhazes in the tenth century.

One might easily construct an argument that the medical profession was conservative and excessively dependent upon its authorities, especially on Avicenna, and so one might not expect to find contradiction of the Arabic picture of benign smallpox before the sixteenth century in its writings. But even if one turns to strictly non-medical accounts by chroniclers and diarists of Europe, sure instances of killing smallpox epidemics are very difficult to find. One cannot but wonder why a disease so lethal in the eighteenth century caused neither demographically appreciable losses nor much concern to those living before the sixteenth century.
_{(Carmichael, 1987)}

Well almost "benign". No one wants to be sick with any kind of virus. But whatever went around before, it was not as deadly as the 20th century definition and characterisation of smallpox makes one believe when looking back at "disease probably as old as 12000 years BP".

The first reliable description of one form of smallpox

Abu Bakr Muhammad ibn Zakariyya al-Razi, known to the Western world as Al Rhazes (864-930 CE), developed this fundamental philosophical paradigm shift in man’s understanding of a disease. Medieval medicine was based on clinical observations of the most prominent symptoms of epidemic diseases, particularly diseases with distinctive cutaneous eruptions, such as smallpox, plague, and measles. Rhazes opposed Hippocrates’ and Galen’s concept of the 4 humors. In his landmark “A Treatise on the Small-Pox and Measles,” Rhazes recognized that the 2 were separate diseases. Rhazes’ observations and conclusions were important in the genesis of the ontologic concept of disease (ie, distinct, specific disease entities exist, each with its own unique pathogenesis).

Although the concept of contagion was known to ancient physicians, smallpox was not recognized to be contagious. Indeed, most diseases were thought to be of a humoral (related to the 4 humors: blood [sanguine], yellow bile [choleric], black bile [melancholic], and mucous [phlegmatic]) or miasmatic (acquired from bad vapors) etiology. Recognizing the skin as a window into, and a mirror of, internal physiological disturbances, Rhazes identified the importance of early diagnosis of smallpox through recognition of its characteristic eruption. Furthermore, he believed that once the correct diagnosis was made, the physician could successfully treat and cure the patient. Most important, he noted that those who survived it were no longer susceptible.
_{– Isabelle C. Band & Martin Reichel: "Al Rhazes and the Beginning of the End of Smallpox", JAMA Dermatology, Volume 153, Number 5, 2017.}

But in any case, the clear historical evidence points to a much lower transmissibility and mortality in comparison. Making what we moderns define as smallpox a recent phenomenon.

Until recent centuries there is no firm historical, archaeological or genetic evidence for high-virulence Variola Major with the characteristics of the disease we "eradicated" in 1980 per official declaration. Viruses and diseases don't have the same definitions.

To quote from an outdated source:

The earliest writers on smallpox whose descriptions are now universally accepted – Ko Hung in China, Vagbhata in India and al-Razi in Asia Minor – describe smallpox as primarily a disease of children. This is a mark of well-established endemicity and was the result primarily of demographic factors. Alivizatos (1950) noted that smallpox was repeatedly imported into Germany by the Crusaders towards the end of the 12th century. It began to cause extensive epidemics only by the 14th century, eventually becoming a disease in which the majority of cases occurred in children (it was given the name Kinderblattern) only at the end of the 17th century. The change occurred more rapidly than this in more densely populated countries […], but in most places it probably took several human generations. Thus the classical early descriptions of smallpox as a disease primarily affecting children…
_{– Frank Fenner et al.: "Smallpox and Its Eradication", WHO: Geneva, 1988. Chapter5 as PDF}

Was the "Plague of Athens" really smallpox virus? Or Yersinia pestis? Was the "Antonine plague" in reality another variant of smallpox? We do not know for sure! But we like to know for sure! So; why not just believe it?"

For historical sources especially they are often open to interpretation and not definitive in conclusions. But reading closely they at least reveal that for European occurences of what was thought of as "perhaps smallpox, no more like: definitively!" the picture turned out a bit more complicated than those who like to write the hagiography for "the march of progress".

Either smallpox as we know it did not exist at all, or related strains of older origin were much more benign than the "evil killer" we are told about, and suddenly jumped host or suddenly mutated into much higher gear virulence in the 16th century:

[information reviewed suggests centuries or even millennia preceding 1600 AD virulent smallpox did not occur in Europe] Except for a few outbreaks in the fifteenth and sixteenth centuries, widely scattered in both space and time and quite atypical of the Variola major that would spread throughout Europe during the seventeenth century, most medical, epidemiologic, and literary evidence points to the presence earlier of only a relatively mild endemic form of the disease.
_{– Ann G. Carmichael & Arthur M. Silverstein: "Smallpox in Europe before the Seventeenth Century: Virulent Killer or Benign Disease?", Journal Of The History Of Medicine And Allied Sciences, Inc. Volume 42 pp I47–168, 1987.}

If the above sounds 'crazy', genetics confirm this historical conclusion:

… our data clearly show that the [smallpox] lineages eradicated during the 20th century had only been in existence for ~200 years, at a time of rapidly expanding human movement and population size in the face of increasingly widespread inoculation and vaccination.
_{– Ana T. Duggan et al.: "17th Century Variola Virus Reveals the Recent History of Smallpox", Current Biology, 26, 3407–3412, 2016.}

One might draw some conclusions about the strange effect of a relatively benign disease that was contained with 'crude but effective methods' and the disastrous effect the dangers of inoculation brought with them:

This was an impressive achievement, because southern England was more densely settled and urbanised than most of northern England and Sweden in particular, and would otherwise be expected to have sustained more rapid circulation of smallpox and higher mortality. Instead it appears that a high proportion of adults survived to adulthood without accidental infection (although after 1760 many may have been protected by deliberate inoculation).

The efficacy of the preventative measures used against smallpox in eighteenth century England supports the characterisation of smallpox as a disease of low infectivity, particularly given that one pillar of prevention, mass inoculation with live smallpox, carried the risk of engendering an epidemic.

The preventative practices identified here do not appear to be of ancient origin, but developed over the course of the late seventeenth and eighteenth centuries. We suggest that these practices were adopted in response to the emergence of smallpox as a major public health problem in this period, as claimed by contemporaries (Creighton, 1894: 435–441).

It is likely that smallpox was a rare epidemic disease throughout most of Britain in the seventeenth century, but as its incidence increased then a sufficient proportion of southern parishes responded with communal measures that prevented endemicisation, while northern parishes did not. These conclusions regarding the chronology of smallpox incidence are consistent with molecular-phylogenetic evidence for a relatively recent origin of modern smallpox strains. Analysis of smallpox DNA recovered from a seventeenth century Lithuanian mummy indicates that this smallpox strain was ancestral to all known twentieth century strains, suggesting that a new variant of smallpox emerged in the sixteenth or seventeenth century, and replaced any pre-existing variants… The curious geography of smallpox in England also confirms some of the more distinctive features of the smallpox virus: its capacity to persist at relatively low host densities, and its susceptibility to relatively crude control measures. These features, together with the possibility of the late emergence of a virulent subtype, complicate McNeill's model of historical smallpox as an ancient and classic crowd disease.
_{– Romola Jane Davenport et al.: "The geography of smallpox in England before vaccination: A conundrum resolved", Social Science & Medicine 206, pp 75–85, 2018.}

The disease from the 20th century we called "smallpox" seems to have been caused by a virus that existed in one identifiable form in the wild from ~1580–1977.

There were most probably other forms of smallpox or what was just called smallpox, misidentified as smallpox. Relatives of the strain in question, predecessors of which we have no real genetic clue.

The genetic predecessor for 20th century smallpox is quite young and gained its virulence only later:

Based on this evolutionary estimate, the time of the most recent common ancestor of the genus Orthopoxvirus was placed at about 10 000 years before the present. Cowpox virus was the species closest to the root of the phylogenetic tree. The root of VARV circulating in the XX century was estimated to be about 700 years ago, corresponding to about 1300 AD. The divergence between West African and South American VARV went back about 500 years ago (falling approximately in the XVI century). A rodent species is the most probable ancestral host from which the ancestors of all the known Orthopoxviruses were transmitted to the other mammal host species, and each of these species represented a dead-end for each new poxvirus species, without any further inter-specific spread.

The present study confirmed the previous hypothesis that the common ancestor of Old World OPVs was an ancestral CPXV-like virus infecting rodents which was capable of being efficiently transmitted to a wide range of susceptible hosts, including humans. The spillover event triggering the successful adaptation to humans may be dated back to between about 4000 years ago (when the common ancestor of the group VARV+TATV+CMLPV existed) and about 1000 years ago (when the radiation of the available VARV strains began in humans). The long evolutionary history of adaptation to new human hosts can explain both the loss of unnecessary genes and the subsequent extinction of strains with different levels of virulence.
_{– Gianguglielmo Zehender: "Bayesian reconstruction of the evolutionary history and cross-species transition of variola virus and orthopoxviruses", Journal of Medical Virology, 90, 1134–1141, 2018.}

Using genetics:

Paleomicrobiology dedicated to variola virus is restricted to few studies, most unsuccessful, involving ancient material. Only one recent approach allowed the identification of viral DNA fragments from lung tissue of a 300-year-old body excavated from permafrost in Eastern Siberia; phylogenetic analysis revealed that this ancient strain was distinct from those described during the 20th century.
_{– Catherine Thèves: "History of Smallpox and Its Spread in Human Populations", Microbiology Spectrum, 4(4), 2016.}

For the best we know: What exactly was supposedly 'killed' in 1977 seems to be a strain that came to 'life' only in the 16th century.

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A virus is a different thing than a disease it causes. If a virus causes a disease at one time, then jumps from elsewhere or mutates and causes a disease that is similar but different in its effects: in terms of quantitative transmissibility, survival rate, endemicity etc than it is this qualitative feature combination that is of interest here.

That a disease can change its very nature and even change from what it was once believed it was is not a revolutionary idea. Not many people today are diagnosed with 'too hot blood', 'dance mania' or 'hysteria'.

For the symptoms of smallpox, old vernacular forms of languages are of limited utility. A "pock" is just a blister or boil and a disease that fits this one-word description could be caused by chickenpox, cowpox, horsepox, vaccinia, measles, numerous bacteria, like in common acne… As a matter of convenience for this argument, the older any one medical text is, the less specific the descriptions get, often obviously because the authors were confusing the symptoms and diseases. And the horrors of 18th century smallpox are barely hinted at at best. But the expected wide-ranging demographic impact of 30% death rate of infected people in epidemics is measureable from the sources as: absent!

During its lifetime, smallpox was many things. […] a useful tool for making people obey the Scriptures and the lesson of nature that brought us vaccination.

‘Pocca’ is an Anglo-Saxon word meaning a pouch or blister, while ‘pocks’ or ‘pox’ were terms long used to describe any unpleasant skin eruption. The seemingly inappropriate ‘small pocks’ (later small-pox and then smallpox) was coined in the late fteenth century to distinguish the disease from the ‘great pox’ of syphilis, one of the bounties brought home from South America by Columbus’ sailors. Terrible though it was, smallpox was an established fact of life in Europe so the new curse of syphilis – mutilation, paralysis and a lingering death – may well have seemed a bigger threat.

German used the same root as English to name the disease: Kinderpocken, which also reminds us that smallpox targeted children. The French variole and the Spanish viruela come from the Latin varius, meaning ‘speckled’. This also gave rise to variola, the Latinised name of smallpox and now the scientific name of the virus that causes it. The original Italian vajuolo umano (nowadays vaiolo) comes from the Latin vacuola (‘cavity’), while one of the Mandarin Chinese words for smallpox, dou chouang, describes a bean-like eruption with ulcers.

Smallpox gave its name to the family of viruses to which it belongs – the poxviruses. Close family members include cowpox (Kuhpocken in German and variole bovine in French) and the mysterious vaccinia virus, the active ingredient of the smallpox vaccine (the mystery being that nobody knows where it came from). Chickenpox produces a rash that can be dif cult to distinguish from that of smallpox but is caused by the varicella virus which has nothing to do with poxviruses (or chickens).

Smallpox and mankind go back a long way together. *There are many gaps in its early history and attempts have been made to fill these in with, for example, pockmarks on the face of a mummified Pharaoh and reading between the lines in the Bible. The Pharaoh in question was Ramses V, whose death from an acute illness in his early thirties was recorded in 1157 BC.
[…] Surviving Ancient Egyptian medical papyri contain recognisable descriptions of diseases such as diabetes, but strangely make only passing mention of a skin eruption that may or may not have been smallpox.

The Bible might also be expected to refer to such an obvious and lethal condition, especially as other diseases such as leprosy and plague figure prominently. The Ancient Hebrew terms yallepheth (an eruption or scab) and ga–ra–bh (an itch, scab or festering sore) would both have fitted the bill for smallpox but nasty skin eruptions merited only a couple of brief mentions…

Returning to Europe, the classical Greek and Roman medical traditions followed the biblical example and gave surprisingly little attention to smallpox. There is no specific mention in the writings of Hippocrates (c. 440–c. 340 BC), the father of the Oath which still embodies the aspirations and ideally the actions of the doctor. Five hundred years later, his compatriot and conceptual successor Galen (AD 129–216) referred only briefly to a lethal sickness that made the skin bubble up, turn black and ulcerate. Galen was physician to the Roman Emperor Marcus Aurelius Antonius, and the brevity may be explained by his hasty departure from Rome where this ‘Antonine Plague’ was beginning its 15-year reign of terror. Scholars have agonised over whether smallpox caused this and other catastrophic diseases that struck the Greek and Roman Empires, notably the horrific ‘Plague of Athens’ reported in 430 BC by Thucydides. On balance, they were probably not and perhaps significantly, there was no specific word for smallpox in either classical Greek or Latin.
_{– Gareth Williams: "Angel of Death The Story of Smallpox", Palgrave Macmillan: Basingstoke, New York, 2010.}

Since only German seems to be the one true language of scientific precision, let's look at the dictionary:

__ Pocke f. Blattern, (pus) blisters, pustule'. Mnd. pocke, nd. In the 16th century Pocke penetrates the Hd. and displaces early. (md.) poche, (obd.) pfoche. As guttural extension it belongs to the root like English poc, English pock, mnl. pocke, nl. pok (with intensifying geminination) in the sense of 'swelling, tumor'. *b(e)u-, *bh(e)u-, *b(h)ū- 'inflate, swell'. Plural Pocken smallpox becomes (17th century) the name of a dangerous, infectious disease;

For the word Blattern:

__ In the beginning the singular describes the single blister, the plural especially the 'rashes' of infectious diseases like plague, measles, syphilis, afterwards especially the smallpox. The plural Blattern serves at the same time as a disease name, but is today pushed back by smallpox.

To conclude: Yes. In the sense of: what we think of when we say "smallpox" seems to be of quite recent origin.
That previously other illnesses existed that were also called smallpox or thought to be the same or just looked like that is no reason to not acknowledge that a qualitative change occurred that changed not only the understanding and description of the disease – coinciding with a new linage of the virus family that emerged.

The strongest evidence for a historical and ecological interaction that changed quite fundamentally is found in the by now ample evidence that previously the associated diseases were not of the magnitude they became in early modern times. Whether genetically inherent features of the virus itself changed and dominated the outcome, or things like supposed changes in population density, travel, hygiene, nutrition etc is another argument to discuss (probably in favour of virus genetics?).

Closer relatives from the virus lineage died out, mostly on their own, and not in the least because most of them just couldn't establish themselves from self-limiting zoonotic diseases to a self-sustaining endemic variant of specialised human host dependence.

That one quite recent strain of virus seems to have been the only survivor branch of the lineage – being much more ferocious than his predecessors – is an important distinction to observe. That this last one of its kind was a qualitatively different beast compared to what Ko Hung or Al-Razes described, when it was eradicated doesn't touch the heritage of this linage. But it also doesn't allow for the entire linage to be equated with the exact number and qualities that last incarnation produced in its few hundred years of its existence.

Duggan, A. T., Perdomo, M. F., Piombino-Mascali, D., Marciniak, S., Poinar, D., Emery, M. V., et al. (2016). 17th Century Variola Virus Reveals the Recent History of Smallpox. Current Biology, 1–7.

Biagini, P., Thèves, C., Balaresque, P., Géraut, A., Cannet, C., Keyser, C., et al. (2012): "Variola virus in a 300-year-old Siberian mummy", The New England Journal of Medicine, 367(21), 2057–2059.

McKenna, Maryn (8 Dec 2016) Child Mummy Found with Oldest Known Smallpox Virus. National Geographic.

Carmichael, A. G., & Silverstein, A. M. (1987): "Smallpox in Europe before the seventeenth century: virulent killer or benign disease?", Journal of the History of Medicine and Allied Sciences, 42(2), 147–168.

Furuse Y, Suzuki A, & Oshitani H (2010): "Origin of measles virus: divergence from rinderpest virus between the 11th and 12th centuries", Virology journal, 7 PMID: 20202190

Taubenberger, J. K., & Morens, D. M. (2005): "1918 Influenza: the mother of all pandemics", Emerging Infectious Diseases, 12(1), 15–22.

Catherine Cameron, Paul Kelton, and Alan Swedlund ()Eds: "Beyond Germs: Native Depopulation in North America", University of Arizona Press, 2015.

Answer 2

The claim -- based on this paper[1] -- is not wrong, it is talking about the most recent common ancestor. That is not to mean that the disease spontaneously "sprang into existence" at that point, just that older variants of the disease have died out -- or that the smallpox as we know it today is a result of a predecessor's mutation.

Smallpox itself (as a contagious disease symptomized by fever, skin lesions, and high mortality) is much older than 1580. Quoted from Stefan Riedel: Edward Jenner and the history of smallpox and vaccination. In: Proceedings (Baylor University. Medical Center). Volume 18, Issue 1, January 2005, p. 21-25, PMV 1200696, emphasis mine:

The origin of smallpox as a natural disease is lost in prehistory. It is believed to have appeared around 10,000 BC, at the time of the first agricultural settlements in northeastern Africa (3, 4). It seems plausible that it spread from there to India by means of ancient Egyptian merchants. The earliest evidence of skin lesions resembling those of smallpox is found on faces of mummies from the time of the 18th and 20th Egyptian Dynasties (1570–1085 BC). The mummified head of the Egyptian pharaoh Ramses V (died 1156 BC) bears evidence of the disease (5). At the same time, smallpox has been reported in ancient Asian cultures: smallpox was described as early as 1122 BC in China and is mentioned in ancient Sanskrit texts of India.

I would also recommend this paper[2] for reading. It goes into great detail on the evolution of the various variants of variola virus (VARV). It also contains this passage (emphasis mine):

The earliest unmistakable description of smallpox first appears in the 4th century A.D. in China, the 7th century A.D. in India and the Mediterranean, and the 10th century A.D. in southwestern Asia.[6]

Whether you would still call that "smallpox" in the future remains to be seen. That paper by Duggan et al. adds some interesting findings, will probably spawn some more research into the subject, and might result in a different understanding of the disease emerging.

But what it does not allow for is the authoritative statement that "smallpox emerged in 1580" (with the implied, "and did not exist before that time").

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Referenced Sources:

1) Duggan et al., Current Biology 26, 3407–3412; 2016. 17th Century Variola Virus Reveals the Recent History of Smallpox.

2) Li Y, Carroll DS, Gardner SN, Walsh MC, Vitalis EA, Damon IK (2007).On the origin of smallpox: correlating variola phylogenics with historical smallpox records

3) Hopkins, Donald R. Chicago: University of Chicago Press; 1983. Princes and Peasants: Smallpox in History. [Google Scholar]

4) Barquet N, Domingo P. Smallpox: the triumph over the most terrible of the ministers of death. Ann Intern Med. 1997;127(8 Pt 1):635–642. [PubMed] [Google Scholar]

5) Lyons AS, Petrucelli RJ., II . New York: Abradale Press, Harry N Abrams Inc; 1987. Medicine—An Illustrated History. [Google Scholar]

6) 2. Fenner F, Henderson DA, Arita I, Jezek Z, Ladnyi ID. In: Smallpox and Its Eradication. Frank Fenner., editor. Geneva: WHO; 1988. [Google Scholar]

Answer 3

What the statement "the evolution of smallpox virus occurred far more recently than previously thought" means is not that it evolved into existence, what it means is that it evolved at all.

Today's smallpox strains are not all the same. 1580 was when they diverged from each other. Before 1580, there were other strains too but none of them except the direct ancestors of today's smallpoxen are known and observed to have survived (in other words, if they did, they are unknown).