A New Era in Biosecurity Risks

Dangerous games

The Omicron coronavirus variant was likely the fastest-spreading virus in human history. It swept the world like a firestorm.

In October 2022, researchers at Boston University described a chimeric virus made by splicing the spike gene from Omicron into an ancestral SARS-CoV-2 strain, in order to test how much of Omicron’s mildness is attributable to spike. In transgenic mice engineered to express human ACE2 receptors, the chimera killed eight of ten, while Omicron killed none.

The number that travelled was “80% kill rate”. The number that did not travel is the comparator: the ancestral strain they started from killed all of the mice it was given to. The chimera was therefore substantially less lethal than its parent, which is precisely the finding the experiment was designed to produce — that spike is a major determinant of Omicron’s attenuation. Boston University said plainly that the work had not made the virus more dangerous, and the headline that drove the story was subsequently flagged as misinformation. The strongest version of the biosecurity argument does not rest on any single scary study.

Here is that stronger version.

The experiment still drew federal scrutiny over whether it should have been reviewed before it proceeded, and that question — who decides, and when — is the real one. Work of this general character continues in many places; reported plans to modify orthopoxviruses at a US government laboratory drew similar objections around the same time. The issue is not whether one particular chimera was more or less lethal than its parent. It is that a global research enterprise is routinely constructing and manipulating pathogens under a review regime that activates late, inconsistently, and often only after publicity.

The record on containment is not reassuring. The past few decades include multiple laboratory escapes of serious pathogens, which is what one would expect: containment is a human process, and human processes fail at some non-zero rate. Multiply a small per-year probability across many laboratories and many years and the question stops being whether and becomes when. Meanwhile the distributed nature of the pandemic means highly transmissible platforms are now widely available, and advances in synthetic biology are making it possible to construct agents unlike anything shaped by natural selection — which cuts both ways, offering new safeguards and new hazards in the same breath.

The origin of SARS-CoV-2 itself remains genuinely unresolved, with a laboratory-associated accident among the hypotheses still on the table and honest people disagreeing. I state it that way deliberately. The governance argument does not require the lab-origin hypothesis to be true; it requires only that we cannot currently rule it out, which is itself an indictment of how little visibility we have.

Decades of gain-of-function work have yielded improved general understanding of viral biology, but no protective breakthrough proportionate to the tail risk being run. If there was ever a case for leadership by intergovernmental bodies, this is it. Manipulation of transmissible pathogens towards greater harm should carry the taboo we attach to human reproductive cloning. Supply chains for key equipment should be cryptographically tracked, including decommissioning and breakage. And dangerous sequences should be as difficult to print as banknotes are to photocopy — screening at the synthesis step, where the chokepoint actually is.

That last proposal has aged into policy. Screening of synthesised nucleic acids, once treated as a niche preoccupation, is now a recognised instrument of biosecurity governance.

None of this is easy, and it is considerably harder than nuclear non-proliferation, because the material is information and the equipment is dual-use and increasingly cheap. It will frustrate a great deal of legitimate research, and that cost is real and should be acknowledged rather than waved away. But the alternative is to keep running an uncontrolled experiment on the assumption that our containment record will improve for reasons we cannot name.

Critical biosecurity lessons have not yet been learned. We tend to repeat those until we understand them.