[mikeyouse]

A general defense is that nature is a far better incubator and gain-of-function laboratory that we could ever hope to be. A few billion birds have caught bird flu in the past decade, so we're talking about trillions and trillions of viruses constantly undergoing mutation in close proximity with farm mammals and humans all over the world... If we know the genetics of what turns a bird flu into one transmissible to humans, it's probably better to "get in front of it" rather than just awaiting that mutation to happen somewhere in nature for the first time.

[adrianb]

Trillions and trillions of mutations and still the most dangerous H5N1 viruses were created a decade ago by Fouchier and Kawaoka. And how did that help us prepare for the inevitable natural evolution of the same virus?

[mikeyouse]

Sure, but that's only if you restrict it to H5N1 instead of looking at the history of Influenza A and things like the Spanish Flu, which was the most deadly disease in human history and derived from a mutated bird flu.

https://www.nejm.org/doi/full/10.1056/nejmp058281

Even still, H5N1 has repeatedly infected humans in the wild... the most famous case in Hong Kong infecting 18 people and killing 6 of those. So you can make the case that GoF is irresponsible given the stakes, but it seems important to acknowledge that you're basically just hoping these horrific viruses don't mutate as we predict them to.

https://pubmed.ncbi.nlm.nih.gov/11938498/

[gensym]

That would be the case if GoF research was necessary to defend against these viruses, but that’s not the case. AFAIK, GoF research played no part in the development of vaccines and treatments for Covid.

[mikeyouse]

Sure, but it took over a year, trillions of dollars of economic disruption and millions of lives to develop the vaccines — its all balance of probabilities and costs.

Some of the proposed research that was GoF adjacent (that was never actually performed) was to develop pseudo viruses more similar to hACE strains that would evoke an immune response in horseshoe bats, effectively vaccinating them. Would the small, but certain, risk of an accident from that research been worth it if it could’ve averted the last 3 years and every future sarbecovirus pandemic?

It still might be the case that we shouldn’t risk GoF - but the simplistic “hurr durr, greedy virologists just want their grant money and don’t understand the risk” takes are childishly simplistic. There is nobody on earth more attuned to the risk of pandemics than the people doing this research, it’s why they’re doing the research.

[taneq]

That’s a terrible defence. Evolution isn’t directed. Gain of function research is like trying to breed animals for specific features, it probably reduces the disease’s overall fitness but it sure could increase its fitness in humans because that’s what they’re breeding for.

[mikeyouse]

We’ve had dozens of zoonotic jumps with bird flu that we know about, and surely thousands that we don’t know about. The mere proximity of humans and birds (and birds and other mammals) means that you don’t need directed evolution. Random mutation + recombination with other strains of influenza already present in humans and animals means that a single “winning” combination will inevitably spillover again. And has trillions of opportunities to do so.

When virologists talk about the inevitability of pandemics, this is the exact mechanism that worries them.

Not doing the GoF work is absolutely no guarantee that you’ll avoid these strains. I’m not convinced it’s worth the energy either, but playing ostrich isn’t a viable alternative.