keywords: epidemiology, pandemics, virology
Back in March 2020, as the COVID-19 pandemic first swept around the world, I reviewed David Quammen’s 2012 book Spillover for background reading. It looked at the risk of zoonosis: the spilling over of an infectious disease from animal into human populations. Quammen warned, and gave voice to many others who similarly warned, that the next big disease outbreak might very well be viral, in particular RNA viruses such as coronaviruses. Other authors quickly wrote books within the first year of the pandemic (I reviewed some of them), but not yet Quammen: “early in 2021 I decided to keep quiet for a while and listen” (p. 282). Finally, in October 2022, his book Breathless provided us with his insights into COVID-19 and the virus SARS-CoV-2.
Subtitled The Scientific Race to Defeat a Deadly Virus, Breathless provides a well-informed look at the science behind the pandemic, in particular the contested question of its origins, with side-servings of virology and molecular epidemiology. Oddly, Quammen only declares this focus at the very end of the book and mentions his decision to leave out topics such as the political failures and the hardships faced by medical personnel. Given that he was hunkering down at home like many others, this time his investigative journalism relied exclusively on videoconferencing. The book is heavily informed by 95 long interviews, most of them done between January and July 2021, with the latest one done in February 2022. That also seems to be the point in time up to which he has covered developments. A long, 43-page credits section at the end of the book mentions all the interviewees and gives short biographies, plus short quotes and insights that did not make it into the main narrative. It is a section well worth reading.
Quammen has been covering the beat of emerging viruses for 20 years. Given that a key phrase in Spillover was “everything comes from somewhere” it is unsurprising that the origins question gets the most attention. This is also of particular interest to me, given that in February this year I reviewed Chan & Ridley’s Viral (for clarification: the November 2021 hardback, not the updated June 2022 paperback). Whereas Viral argued that we should take seriously the possibility of an accidental leak from a laboratory (the Wuhan Institute of Virology or WIV being the prime suspect), Breathless leans towards animal spillover as the likely origin. But this book is not a case-closed scenario in favour of zoonosis and against a lab leak. What both books share is scrutiny of the available data, though their conclusions complement each other in a yin-yang-like fashion. Both acknowledge that definitive data for either hypothesis are still lacking, which, in the words of one evolutionary virologist, of course results in “people strongly defaulting to their prior beliefs” (p. 304). As an aside, both books, and the scientific community at large, do not favour the idea that SARS-CoV-2 is a deliberately engineered bioweapon.
Given my review of Viral, it is interesting to follow Quammen into the weeds on some of the details. Breathless can get fairly technical in places. This is understandable: the question of a pandemic is no longer hypothetical, so now we have many relevant specifics to discuss. Interested readers could do worse than first read Spillover. Anyway, those details.
“[…] this book is not a case-closed scenario in favour of zoonosis and against a lab leak. What [it shares with Viral] is scrutiny of the available data, though their conclusions complement each other in a yin-yang-like fashion.”
Proponents of a lab leak have pointed to three virological details. Two features of the virus’s spike protein make SARS-CoV-2 particularly well-suited to binding to and infecting human cells: its receptor-binding domain and its furin cleavage site. The former does what it says on the tin: it binds to a protein in human cell membranes called the ACE2 receptor. The latter assists, changing the spike’s shape upon binding to allow injection of the virus’s genetic material. Importantly, the latter is not present in the SARS-like coronaviruses we knew up to that point. Some argue that this is evidence that the virus was designed in a laboratory. Why? Because we are nowadays capable of modifying the genetic code of viruses and adding features to it. This is called gain-of-function research and Quammen in particular mentions such work by Ralph Baric’s lab which has collaborated with the WIV. Then again, a near-identical receptor-binding domain occurs in pangolins, and furin cleavage sites have now been found in other coronaviruses circulating in bats. Bats are furthermore frequently co-infected by more than one virus. Lastly, RNA viruses are particularly prone to rapid evolution via mutation and recombination, the wholesale swapping of larger stretches of genetic code. Thus, these seemingly suspicious features can and do evolve naturally. Quammen thinks that “at this point we should stop thinking about the “origin” of SARS-CoV-2 and proceed by thinking about its origins, plural” (p. 247). The third detail was that SARS-CoV-2 was initially not accumulating many mutations. This led Viral‘s co-author Alina Chan to infer it did not need to evolve as it was already well adapted, e.g. by having been grown in a laboratory in cell lines expressing human cell receptors. However, as Quammen points out, SARS-CoV-2 turns out to be a generalist virus readily infecting domestic, farm, zoo, and wild mammals (e.g. cats, dogs, tigers, gorillas, rhinos, mink, mice, and deer). And, as we have seen, SARS-CoV-2 has done plenty of evolving in humans since, with new variants sweeping the globe.
Thus, there are natural explanations for some of the suspicions raised by the lab leak hypothesis. Quammen stresses the need for critical thinking and humility in the face of so much uncertainty. Remarkably, he steers clear of addressing some issues raised in Viral that you expect him to be cognizant of. He quotes Chinese virologist Zhengli Shi on p. 62 about initially sampling bats merely wearing masks and gloves rather than full protective garb. But he does not address Viral‘s point that not all research on coronaviruses in China was done in laboratories of the appropriate biosafety level, BSL-4. Or how lab animals were being sold on markets. Similarly, he does not mention the database with hundreds of genetic sequences of novel bat coronaviruses that the WIV took offline in 2019 and has since refused to share with anyone. Though there is much-deserved admiration in this book for scientists and their work, there were points where I questioned whether Quammen was being too cautious in not wanting to cast suspicions on people. Despite a frank admission that science very much remains a human endeavour—hamstrung by blunders, career incentives, and personal pressures—he refrains from asking whether this applies to any of his interviewees.
“[Regarding] the uncooperativeness of the Chinese government. Is it not just as likely, asks Quammen, that they are trying to cover up an animal leak? Illegal wildlife trade is flourishing in China and poaching is rife.”
Quammen makes two further points on the origins question worth mentioning. One has been dubbed the circulation model by its authors and argues that RNA viruses are so genetically promiscuous “that swarms of loosely related viral strains can surge this way and that, exploring various niches and strategies. […] They are multi-host viruses” (p. 277). This strongly reminded me of the concept of RNA viruses as quasispecies that Cordingley introduced in his book Viruses. The other point regards the uncooperativeness of the Chinese government. Is it not just as likely, asks Quammen, that they are trying to cover up an animal leak? Illegal wildlife trade is flourishing in China and poaching is rife; law enforcement has been knowingly turning a blind eye to the sale and slaughter of wild animals on wet markets in Wuhan and elsewhere.
Let me also briefly highlight the healthy dose of accessible explanations on related topics that Quammen serves up. There are some great insights into viruses generally. Would it not be great if we could just rid the world of them? Not so quick: viruses are intimately involved in life’s evolution. Eliminate them “and the immense biological diversity gracing our planet would collapse like a beautiful wooden house with every nail abruptly removed” (p. 109). How did viruses evolve and are they even alive? Rather than excluding them from the domain of the living, “more fruitful is to grant viruses inclusion within the big tent called Life and then wonder about how they got in” (p. 112, some interesting answers are considered here). There are useful explainers about the concept of herd immunity or molecular phylogenetics (the building of family trees based on genetic sequences). Quammen explains how COVID-19 risks becoming a forever virus by being introduced to new wild reservoir hosts, entering a so-called sylvatic cycle in e.g. mice or deer. And then there is the story of vaccine development. Quammen only touches on this aspect here, and those wanting more information will have to turn to one of several recent books on the COVID-19 vaccines. However, he does clarify how mRNA vaccines could be developed so quickly: research has been ongoing in the background for years. This “is not one story, with one beginning [but more like] an epic, braided from a thousand threads” (p. 213). Finally, there are several interludes providing background stories to some of the scientists interviewed here. Quammen is keen to make the reader understand why he trusts them and why they are considered experts in their fields.
Technical as Breathless is in places, it is also eminently readable. Much like his previous books, it is written in the same style: numerous short sections of a few pages each that keep driving the narrative forward. So, where do I now stand on the matter of COVID-19’s origin? I am still on the fence, but where Viral made me lean towards seriously considering the lab leak hypothesis, Breathless has swung the pendulum back, highlighting why zoonosis is still a logical default position to take. If you read Viral, this is a must-read accompaniment. If you have not, I recommend you read both books to get the full picture of why people are arguing about the origins of this virus.
Disclosure: The publisher provided a review copy of this book. The opinion expressed here is my own, however.
Other recommended books mentioned in this review: