Opportunity Killer
A new study suggests that, like other pandemic pathogens, SARS-CoV-2 did not require a special evolutionary adaptation to spread to humans but simply needed the right opportunity.
The question, “What causes epidemics and pandemics?” has long perplexed students of infectious disease.
Following an outbreak of influenza in 1789 in Hartford, Connecticut, the American lexicographer Noah Webster scoured the historical literature for accounts of epidemics and found that they tended to coincide with earthquakes, volcanic eruptions and other natural phenomena such as the appearance of comets in the night sky.
Speculating that these phenomena ignited subterranean fires and that these fires caused subtle electrical changes to the Earth’s atmosphere, Webster concluded that “the cause must be the action of fire, the most energetic principle in nature” and its effect on “the general properties of the air.”[1]
Fast forward one hundred years and the advent of bacteriology and modern epidemiological methods had done little to dispel these superstitions, hence the way that in 1889-90 medical authorities blamed the pandemic of “Russian influenza” on the flooding of the Yellow River in China the previous winter and the “burning heat” of the following summer. According to no less an authority than E. Symes Thompson, Gresham Professor of Medicine and expert on respiratory disease at London’s Brompton Hospital, the sun’s rays had acted on the corpses of Chinese flood victims buried in the mud, sending “countless of millions of organic spores” into the higher atmosphere”. Once there, all it took was the trade winds to spread influenza to every corner of the globe.
Today, armed with modern virological and genetic techniques, we know better. Sure, earthquakes and floods may spark epidemics but only indirectly through, by example, the destruction of sanitary systems that keep pathogens like cholera from contaminating water supplies, or by displacing rats that carry diseases like plague and hantavirus from their burrows.
Indeed, from serological sampling in areas where bats and other virus-carrying wildlife live cheek-by-jowl with humans and comparative phylogenetic analysis, we know that 70 percent of new human infections originate in animals. However, in the absence of hard virological evidence, in practice it has proved very difficult to identify the progenitor animal viruses of pandemics. Thus, we still do not know precisely where the 1918-19 influenza pandemic originated or whether it was first transmitted to humans by a pig, chicken or wild waterfowl. Nor do we know how or where HIV, which is closely related to simian viruses that circulate in the Congo and other parts of Africa, made the jump to humans.
This question is nowhere more important than in the case of Covid-19. Six years on from the biggest pandemic of modern times, we still do not know whether SARS-CoV-2 came directly from a bat or an intermediate animal host, such as a pangolin or racoon dog, or whether it was the result of laboratory experimentation.
Little wonder then that the same superstitions and racist Asiatic tropes that attached to previous historical pandemics have attached to Covid-19, not least the idea that it must all be the fault of the Chinese because of supposedly reckless experiments conducted at a laboratory in Wuhan.
Like other pandemics, the origins of Covid-19 are unlikely to ever be settled. That would entail retrieving an identical virus from a bat or some other intermediary host and showing that this virus was the first to exhibit the key mutations that enabled SARS-CoV-2 to spread efficiently between humans.
But now, a new study in Cell has called into question one of the central planks of the “lab leak” hypothesis: namely, that when SARS-CoV-2 emerged in Wuhan in December 2019 it was already suspiciously well-adapted to people.
By analysing viral genomes from previous outbreaks of influenza, Ebola, Marburg and SARS 1 and 2, researchers at the University of California San Diego were able to demonstrate that none showed evidence of special evolutionary adaptation before spilling over into humans. Instead, across these diverse viruses, investigators found that selection pressures prior to zoonotic emergence were indistinguishable from those acting during routine circulation in animal reservoirs, and that measurable changes in selection typically appeared only after sustained transmission had begun in people.
“Rather than requiring rare, finely tuned adaptations in animals, many viruses may already possess the basic capacity to infect and transmit between humans,” explains Joel Wertheim, senior author and professor of medicine in the Division of Infectious Diseases and Global Public Health at UC San Diego School of Medicine. “What matters most is human exposure to a diverse array of animal viruses.”
In other words, pandemic viruses do not require prior adaptation in order to jump species. They just need the right opportunity.
Investigators found just one exception to this rule: the 1977 Russian influenza. Unlike the other viruses they studied, the 1977 H1N1 strain showed both unusually limited genetic divergence from similar 1950s viruses and a clear shift in selection consistent with viruses that had been propagated in cell culture or in laboratory animals. The finding is consistent with the long-held suspicion that the 1977 Russian flu escaped from a lab as a result of an accident – perhaps a vaccine trial that had gone wrong in the Soviet Union or China.
By contrast, investigators could find no evidence that SARS-CoV-2 was shaped by selection in a laboratory or prolonged evolution in an intermediate host prior to its emergence in 2019. Instead, it steadily acquired mutations as it spread between bats, just like other SARS-like bat coronaviruses. And it was only after the virus emerged in humans that it underwent a marked genetic shift, resulting in radically new variants with mutations that made them well-adapted to humans.
(For a detailed account of this process, see my earlier Substack post putting the case for a natural origin for Covid-19).
As every schoolboy knows, absence of evidence is not evidence of absence. But in this case, argues Wertheim, the study’s findings are “exactly what we would expect from a natural zoonotic event – and it represents another nail in the coffin for theories invoking laboratory manipulation”.
No doubt proponents of the lab-leak theory will disagree with that verdict. But then they’ve long been reluctant to look at Covid within the context of other spillover events and pathogens that sparked pandemics long before scientists had the means to enhance their transmissibilty in a lab.
As a group of experts assigned by the World Health Organization to examine Covid’s origins pointed out in a study last month, most of the peer-reviewed scientific evidence supports the theory that SARS-CoV-2 originated in a natural bat reservoir from where it passed to animals that were being sold at a market in Wuhan.
Unless and until evidence emerges to suggest otherwise, that remains the most parsimonious explanation.
[1] Noah Webster, A brief history of epidemic and pestilential diseases, two volumes. Hartford: Hudson & Goodwin, 1799.