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Recently, two highly informative articles served as eye-openers on the issue — Nicholson Baker’s ‘The Lab Leak Hypothesis’ in New York magazine, and Nicholas Wade’s ‘The Origin of Covid’ in Bulletin of the Atomic Scientists. Then, last week, 18 experts from universities like Cambridge, Harvard and Stanford sought a ‘transparent’ probe in a letter published in Science. In their view, pending more data, a lab accident and zoonotic spillover are both ‘viable’ theories.
Scientists generally concur that Sars-CoV-2 moved from bats to an intermediate host — possibly pangolins — before infecting humans. But the hypothesis lacks solid evidence so far. With Sars (2002-03) and Mers (2012), civets and camels were named the likely go-betweens. Sars-CoV-2’s intermediary remains elusive, prompting another surmise: the bat-borne virus jumped straight to humans and lurked around for an unsuspected duration.
Chinese authorities predictably repudiate the escape-from-Wuhan scenario. But, elsewhere, there’s renewed focus on WIV’s experiments with bat coronaviruses aided —wittingly or otherwise — by some US scientists and funding sources, including the US National Institutes of Health. ‘Gain-of-function’ (GoF) research, particularly, has reignited debate.
GoF research probes the biology of microorganisms. It investigates pathogen-host interactions and the spillover potential of diseases by enhancing the pathogenicity of emerging infectious agents, so that vaccines and therapies may be found. What makes it controversial? Certain GoF studies involve creating, in epidemiologist Marc Lipsitch’s words, ‘novel, highly virulent and transmissible pathogens against which there is no human immunity’ — in short, ‘potential pandemic pathogens’ (PPPs).
Here’s one example. In 2011, lab-induced mutations made the avian H5N1 influenza virus airborne among ferrets. The aim, said virologist Ron Fouchier, was to determine if H5N1 could infect mammals and, hence, humans. The unintended fallout, warned critics, could be accidental release or bioterrorism.
Baker and Wade narrate how scientists have worked on making coronaviruses jump species. This research got a boost in 2014-15 when University of North Carolina’s (UNC) Ralph Baric, a renowned virologist, tied up with WIV’s Shi Zhengli, an authority on bat viruses well-known for collecting coronavirus samples from bat-rich sites in Yunnan province.
These scientists, one imagines, had impeccable motives for collaborating. One result, nonetheless, was their creation of hybrid viruses by inserting bat virus spike proteins into human Sars virus backbones. These so-called ‘chimera’ sickened mice genetically engineered to harbour human ACE2 protein, that cellular receptor facilitating viral entry now much-discussed in relation to Sars-CoV-2. They also infected and thrived in cultured human airway cells. Citing experts, Wade suggests that Sars-CoV-2’s ‘prototype’ might well have been here.
Significantly, a Yunnan-sourced bat coronavirus closely studied at WIV, RaTG13, is Sars-CoV-2’s nearest genetic kin. Also, unlike other Sars-linked beta-coronaviruses, Sars-CoV-2’s spike protein has a ‘furin cleavage site’ with an ideally located, infectivity-boosting cluster of four amino acid units. This unusual feature helps the virus breach human cells, and its origin is a subject of furious speculation.
Many scientists view Sars-CoV-2 as suspiciously primed to target humans or, in Baker’s words, seemingly ‘selected for infectivity’. Certain experiments deepen such doubts. One is the UNC-developed ‘no-see’m’ technique of making viral clones: you can’t detect they’re lab-made. Another ingenious method, serial passage, involves repeatedly infecting a series of cell cultures or animal hosts to observe how pathogens evolve and adapt.
Finally, it’s said WIV studied bat viruses in not-so-stringent biosafety level-2 conditions and, at times, operated a BSL-4 lab with inadequately trained staff. The risk: in-house infection. Going by a January 2021 US State Department document, some indisposed WIV researchers apparently showed Covid-like symptoms in autumn 2019. Coincidentally or otherwise, many of the first Covid-19 cases weren’t related to the Huanan wet market, located near WIV and the Wuhan Centre for Disease Control and Prevention.
Clearly, the lab leak theory won’t disappear. So, Chinese authorities must allow unencumbered, if belated, access to all relevant records and Wuhan’s labs and wet market. Also, whether Sars-CoV-2 is natural or man-made, the well-documented history of lab mishaps worldwide warrants a global relook at the ever-present threat PPP-linked GoF research poses. As experts warn, countless labs handle dangerous pathogens, not always vigilantly, multiplying the chances of leaks by accident or design.
Dr Anthony Fauci once called nature the ‘worst bioterrorist’. His highly disputable contention has an obvious counter: should humans deliberately arm this ‘bioterrorist’ against themselves? What are the unforeseen consequences of trying to play god with nature? Pursuit of knowledge is noble, for sure. But science needs a better reason for spawning killer-microbes than just to know if they can kill.
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