GOF research has been used for decades in yeast and bacteria to study molecular structure or cellular pathways. They usually knock out a gene so that the yeast or bacteria doesn’t grow under certain selective circumstances. Then they reintroduce some kind of DNA library that answers their question of interest. Let’s say that some other gene complements the gene they knocked out. Well, the yeast or bacteria that received the complementary gene will grow. It will gain (or regain) the function.
Another GOF type of research would be if you put some kind of selective pressure that would kill or inhibit growth of your organism unless it mutates to survive that pressure. Or you again, introduce pieces of DNA to create different clones that will make survival proteins. You sequence the DNA of the survivors and say “hey, this mutation or gene allowed them to survive”.
Likewise, GOF research can be used with viruses. Let’s say the gain of function is binding to the ACE2 receptor. You could create a library of viruses that have mutations in the spike protein through a variety of methods. These would likely have engineering tags that would be flagged as being made in a lab. Since the SARS-CoV-2 has high spike protein similarity to the pangolin virus and other parts to the bat virus, you could take out the spike protein from the bat and splice in the pangolin. The engineering tags would be apparent unless you did shitloads of work to hide it because the SARS-CoV-2 genome shows pretty complex evolution from both the bat and pangolin viruses (this means it’s not just an accident). Or you use a random mutation method (harder to trace, I suspect) which would be forcing “evolution in the lab”.
Then you can test the viruses’ binding affinity to cells that have the ACE2 receptor in tissue culture. You isolate the viruses that bind best and propagate. That wouldn’t be easy but much easier than testing on whole animals. If you weren’t specifically going for the ACE2 receptor, you’d likely be working with whole animals and testing whether or not they get infected. Since SARS-CoV-2 virulence depends on a lot more than binding to cellular receptors (like very complex immune evasion), the GOF research would be extremely involved and, perhaps, very inefficient in animals.
Taken together, it’s clear to me that the GOF research that would have created a SARS-CoV-2 without genetic engineering tricks and prior knowledge on transmissibility and immune evasion is much less likely than what happens in nature. This is expensive, time-consuming research. Much more than the little subgrant money that they received. I’ve said this before, if you’re doing the “evolution in the lab” approach, the best evidence would be frozen sample of several stages of the “evolution” that led from a bat strain to a SARS-CoV-2. Even if you raided the lab, they could claim that these came from nature too.
Rand Paul is an evil person. Grant applications have to include exactly what kind of experiments are going to be performed and they get reviewed. So that information is available. If it doesn’t say anything about experiments that describe GOF, how is Fauci supposed to know?