I haven't read from them, but as a general thing, GoF research is very directional, so in practice the experiments will pressure a virus to gain a function, but the rest of the functions are usually impacted to a large extent due to the lack of evolutionary pressure.
So you may do selection on virions that target better certain receptors in certain human cells to infect them, and that's useful to know of possible evolutions of a wild virus, but in parallel it might be losing environmental resistance (temperature range, UV light), or maybe damage the expression of some vital protein, or become too pathogenic and die along with the host.
By all means, one could try to perform GoF in live humans to ensure there's no LoF, but that limits enourmously the speed of the research, plus it's usually forbidden to experiment in humans these days.
The link above is a fairly readable summary of a conference in which academics debated the need for gain of function research. As you can see, this was not a settled topic, and even some of the supporters of GoF research admit doubts about its utility.
To summarize the paper I posted:
1. Gain of function research, broadly construed, also includes adapting viruses to live "in culture", i.e. in a dish of cells. That's a fundamentally useful and necessary part of research, so a blanket ban could unnecessarily complicate basic research.
2. GoF is useful for evaluating the potential impacts of mutations observed in the wild. Like, we see a particular mutation circulating, but its significance is unknown, so we introduce it into a model virus in a lab to test what impact it has. This helps us decide which strains we should choose to develop vaccinations for. This can also be done prospectively, GoF can identify particularly nasty variants, which we can then prioritize for more intense intervention if they're observed in the wild.
3. There's a basic research interest in understanding the molecular details of how viruses infect humans. GoF allows researchers to probe this much more easily than the random sampling we get from wild viruses. This research has led (in part) to basic insights in virology, like the role of the furin polybasic cleavage site in coronaviruseses in increasing virulence.
It would not, but it would sure as hell reduce the risk of a lab leak. The whole idea of GoF research was to preempt evolution on bad viruses. If instead, the research is causing the evolution of bad viruses, it should be shut down.
I am going to go against the grain here and ask someone more knowledgeable than myself if the large number of changes in this variant is typical in virus evolution? Because as an outsider, it appears to me that studying the history of past pandemics would present a road map as to what must be modified to attenuate the damage potential in a virus. I suppose my question really is, why are we chancing GOF research, if not to use in this situation?
It's not my definition. And I can't tell what experiments you're referring to, so it's not reasonable to comment. But the experiments done at BU had the potential to produce new viable virus sequences that could display a phenotype that included increased pathogenicity. The researchers had no way of knowing what the results would be in advance. They followed all safety protocols -- that's not being questioned. But their experiments would qualify as GOF experiments under a variety of definitions.
That's not really the case here. Gain of function research can not be justified using this argument.
There are so many potential mutations that putting specific evolutionary pressure on a virus in order to "prevent" only those specific effects has such low efficacy considering the size of the problem space.
GOF research has provided very little in terms of benefits, and many argue it's simply been a way to disguise bioweapons research after the Geneva convention.
Suppose that a lab created a novel virus, which then leaked and killed 2 million people, including making you very sick so that you had difficulty breathing for a month and killing someone close to you. If that happened, might you conclude that maybe we shouldn't mutate deadly human viruses in the lab? Or at least, that the burden of proof that that research is worth millions of lives should be very high?
A lot of people died from Covid; there's a good chance it was due to virus research; even if it wasn't it certainly could happen in the future; I don't want them to have died in vain.
Here's another way of looking at it: Many mutations are going to happen in the wild, but only a few will make the virus more viable in some host or hosts. Most of the mutations will be dead ends, or jump to another species and then mutate away. Only rarely could one emerge and jump all the way to humans, spread across the globe and cause a pandemic. Ebola couldn't, and SARS1 as well due to speed of mutation. (The only original SARS1 around any more is in laboratories, except when it has escaped.)
In GOF you speed that process up by orders of magnitude. You arrive at the viable mutation sooner, possibly infinitely sooner if random mutation would never have arrived. If you engineered part of it, there's a good chance it would never have emerged naturally. It might have come into the world in a few decades or centuries, or it might never have. But you have it now, and have to guard it perfectly as long as it remains in your lab.
Bottom line, it probably won't escape, but it probably never would have emerged naturally either. IMO, to make GoF a beneficial trade-off, it should be focused on viral species that are close to emerging naturally and do not need their genomes to be artificially manipulated in order to become dangerous.
What is the point of doing actual GOF research? We already know viruses can gain function. We already know that bat viruses can infect humans. Is this backdoor bioweapon research framed to avoid breaking the letter of treaties banning it? But if that's the case, outsourcing it seems totally insane.
Like you say, we couldn’t even do GoF when HIV and pandemic influenza became a thing. Why take seriously the feeble efforts of humans to recreate evolution in a lab when the real thing has demonstrated it’s terrifying effectiveness many many times?
Your idea sounds nice, but it doesn't really make sense. Consider that terrorists can easily do GoF and release the product - no research necessary. On the other hand, when scientists do GoF research, our virological knowledge may be furthered, possibly with applications to making new vaccines and similar.
I 100% disagree, GoF research produces viruses as natural as selective breeding. The conditions that researchers expose various animals and humanized mice to infect each other would never happen in nature. This type of research only produces did not help predict the current pandemic, nor did it help with the fight against it, but it may have caused it!
Virologists competing with each other on who can produce the most infectious virus does not make us safer. Pursing research to prove that small pox can indeed mutate to be infectious via airborne aerosols is reckless, it creates a super charged version of a virus that never evolved naturally despite being a common disease for millennia.
Derek Lowe expresses a narrow definition of GOF to make his point and defend the research. Interestingly, using his definition, no proposed experiment could be classified as GOF because his definition depends on a successful outcome where a more pathogenic virus is produced which can only be determined after the fact. He misses the point that there are various definitions of GOF, and more importantly, that the people concerned about the experiments aren't concerned about the precise definition of GOF -- they are concerned with experiments that might reasonably generate successful GOF mutations.
"In other words, any selection process involving an alteration of genotypes and
their resulting phenotypes is considered a type of Gain-of-Function (GoF)
research, even if the U.S. policy is intended to apply to only a small subset
of such work." [0]
"...experiments that encompass all influenza viruses, SARS-CoV, and MERS-CoV
that can be reasonably anticipated to increase pathogenicity or transmissibility
in mammalian species" [1]
It matters. Zoonotic viruses that jump to humans naturally tend to be less well adapted to human biology, and thus less contagious. That potentially gives us more time to respond before they evolve really dangerous human adapted variants. Whereas GoF research using human tissue or transgenic animals can produce viruses that are perfectly adapted to humans right out of the gate.
I'm a layperson, but AFAIU GoF research in principle is a good thing. It helps us anticipate future viruses, study how they impact humans, and prepare for an eventual outbreak.
It's obviously very risky to do, but we should focus on adopting and enforcing better security practices to minimize the risks, not ban GoF altogether.
It's a bad idea (regardless of whether it's how COVID originated or not), but there are theoretical benefits. Make a GoF virus, observe how it interacts with humanized nice, see how different therapeutic agents work.
The issue is that it's unlikely that any knowledge gained from the GoF research meaningfully accelerates the delivery of treatments or a vaccine, which is the hypothetical benefit that makes up for the increased risk of escape.
The core argument of your Reddit post addressing gain-of-function research is that GoF research causes the sugars on the surface of the virus to be lost.
But that doesn't address the recombination event / recombinant virus, which is what the proponents of the lab-leak hypothesis seem to be arguing (spike protein from one virus combined with backbone from another virus)
The research described in the pre-print aimed to understand the mechanism of action behind the decrease in pathogenicity observed with Omicron strains, and specifically, whether mutations in the Omicron spike protein can account for that decrease. The experiment they carried out is about the most straightforward one you could draw up to begin to answer that question, and I would never even think to characterize it as
a "gain of function" experiment. If you want to classify this study as GOF then you might as well do the same with any study of a virus where even a point mutation is made - good luck doing any virology under those conditions.
So you may do selection on virions that target better certain receptors in certain human cells to infect them, and that's useful to know of possible evolutions of a wild virus, but in parallel it might be losing environmental resistance (temperature range, UV light), or maybe damage the expression of some vital protein, or become too pathogenic and die along with the host.
By all means, one could try to perform GoF in live humans to ensure there's no LoF, but that limits enourmously the speed of the research, plus it's usually forbidden to experiment in humans these days.
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