Breathless The Scientific Race to Defeat a Deadly Virus

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 that the next big disease outbreak might very well be viral, in particular RNA viruses such as coronaviruses.

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. 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.

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 hardback, not the updated 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.

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. Interested readers could do worse than first read Spillover. Anyway, those details.

Proponents of a lab leak have pointed to three virological details. Two features of the virus's spike protein, its receptor-binding domain and its furin cleavage site, could have been inserted in a lab. We are nowadays capable of gain-of-function research and Quammen 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. The third detail was that SARS-CoV-2 was initially not accumulating many mutations. Was it already well adapted by having been cultured in a laboratory? As Quammen points out, SARS-CoV-2 turns out to be a generalist virus readily infecting domestic, farm, zoo, and wild mammals. 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 with insufficiently 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. 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 endeavou, he refrains from asking whether this applies to any of his interviewees.

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 they can exist as swarms of strains in multiple hosts. This strongly reminded me of the concept of RNA viruses as quasispecies introduced in Cordingley's 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.

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 and concepts such as herd immunity and molecular phylogenetics. Quammen explains how COVID-19 risks becoming a forever virus by being introduced to new wild reservoir hosts, 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. 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.