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Op-Ed: Why Redfield Is Wrong on SARS-CoV-2 Origins

— Scientific data simply don't support the former CDC director's claims

MedpageToday
A photo of CDC director Robert Redfield, MD, next to a photo of the Wuhan Institute of Virology

Recent comments by former CDC Director Robert Redfield, MD, on CNN have helped push the question of the origins of SARS-CoV-2, the virus that causes COVID-19, back to the forefront of public discussion. Two theories have emerged: one, favored by most virologists, is that SARS-CoV-2 was transmitted in the wild from an animal – a bat or intermediate host species – to a person before exploding in Wuhan. The other, pushed by a vocal minority, holds that the virus was being secretly researched at the Wuhan Institute of Virology, a major research center, before escaping the lab through the accidental infection of a lab worker. Right now, we still don't know enough to be certain which route the virus took from its natural host to humans, though there are compelling reasons to believe the first scenario is far more probable. Redfield is suggesting more than an accidental version of the latter scenario though – he's saying that human action made SARS-CoV-2 the virus that it is.

Unfortunately, Redfield's comments don't advance the discussion of SARS-CoV-2 origins, as they are unrooted in any evidence (by his own admission) and plagued by an apparent faulty understanding of basic virology. Broadly speaking, Redfield finds it implausible for a virus to jump from a bat to humans and immediately be as contagious as SARS-CoV-2. Rather, he thinks the virus was manipulated in the lab through a process called serial passage and became better adapted for human transmission.

It's often stated almost as a truism, and apparently accepted by Redfield, that a virus crossing from animals into people has to undergo rapid adaptation to become transmissible in humans. While that may often be true, it doesn't have to be. We know SARS-CoV-2 itself can jump seamlessly between hosts – it's gone multiple times from humans into minks and spread like wildfire. It transmits perfectly well among hamsters and ferrets in the lab. If a human virus can transmit among mink, there's no basis to assume a bat virus can't transmit among humans. Us humans may think we're very special – but to a virus we are just another mammalian host.

That said, it's undoubtedly true that any virus finding itself in a new host will adapt to new surroundings, and SARS-CoV-2 is no different. And maybe Redfield is right that this is an instance in which the virus circulating in animals wouldn't have been immediately efficient at human-to-human transmission. In that case, the virus would have to adapt quickly in humans and it would have had to do so before it was discovered by Chinese scientists in late December 2019. Did it have the chance then? A powerful in Science estimated that SARS-CoV-2 first started circulating in Wuhan between mid-October and mid-November 2019, one or two months for it to circulate at a low level and adapt to a new host – us. But did it adapt? Another , not yet peer-reviewed, identified a single mutation in the SARS-CoV-2 spike gene that probably occurred in those one to two months. These seemingly missing evolutionary links that led Redfield down the road to a lab accident are being filled by real scientific data in front of our eyes.

Redfield's more sinister claim – that Chinese researchers passaged this virus repeatedly to make it grow better and thus adapted it to human transmission in the lab – simply doesn't hold up. A from late 2020 in PLoS Biology demonstrated that the ability of SARS-related coronavirus spike proteins to bind to human cells is naturally evolving in the viral milieu, and a more recent not-yet-peer reviewed found that SARS-CoV-2 isn't even unusually good at doing so; the spike of a closely related virus found in pangolins initiates infection of human cells much more effectively. SARS-CoV-2 is still adapting though. The spike protein from the B.1.1.7 variant acts a lot more like the pangolin virus spike protein. Evolution never stops.

More fundamentally, adaptation to human transmission and virulence is exactly the opposite of what we'd expect from serial passage in cells or animals. This exact process is a classic way of weakening a virus to make a vaccine – the oral polio vaccine developed by Sabin and the yellow fever vaccine have used this approach, among many others. That's because viruses evolve virulence and transmission in a complex host system. If you extract them from that system and force them to evolve in a different context (like in cells outside a body) they "de-adapt" to the "real world," precisely the opposite of what Redfield suggests. Frankly, it's hard to understand why he wouldn't know that.

Zooming out a bit, Redfield's comments landed just before the World Health Organization (WHO) SARS-CoV-2 that designated a lab-release origin of the pandemic as "extremely unlikely." Extremely unlikely is a long way from impossible, and WHO Director-General Tedros Adhanom Ghebreyesus, MD, appropriately, in my view, urged the undertaking of a more comprehensive examination of this possibility. It is possible that a worker, in the course of say, attempting to grow a new virus from an animal sample, became infected and transmitted the infection.

There are ample reasons, however, that most scientists view this as the less likely scenario. The biggest reason, exhaustively detailed in the WHO report, is that the intensity of infection surrounding the Huanan wildlife market and other animal markets in Wuhan in December 2019 is simply staggering. Amazingly though, if one looks at the landscape of human interaction with bat coronaviruses in China (and the closest viruses to SARS-CoV-2 are all from bats), it's amazing we've made it this far without a pandemic emerging from the wildlife trade. A in Virologica Sinica found that 2.7% of people living near bat caves in southern China tested positive for prior infection with a SARS-related coronavirus, suggesting millions of infections that don't turn into anything. A step closer to the markets, a conducted by the WHO and Chinese CDC found that 13% of animal traders tested positive for previous infection. It shouldn't be any surprise to have a contagion erupt from within this viral milieu. The surprise is that it doesn't happen more often.

Questions are undoubtedly going to persist about the origin of SARS-CoV-2 until, and if, a definitive answer is uncovered (and perhaps beyond). Until then, it's imperative that leaders in science, public health, and government continue to call for rigorous study and stick to the science of viral evolution and viral ecology in their public commentary. One of the fundamental principles of a life in science is to admit what you don't know, and never be afraid to look it up. That's where Redfield falls short, unfortunately on a big stage.

is a postdoctoral research associate at the University of Utah, studying viral evolution and genomics. Previously, he received his PhD from the University of Pennsylvania, where he studied MERS-CoV and its interactions with the host immune response.