After having watched and listened Rand Paul as a senator for a number of years, I’ve come to the conclusion that the only way you can tell if he’s lying is if his lips are moving. Truly, he is one of the most ignorant, disingenuous members of the Senate.
This article was published clear back in 2013.
He reminds me of a toddler who never tires of playing with his own feces.
In a contest of honesty, it’s not even a yawn to determine who is telling the truth and who is lying.
I was really hoping to avoid this sliding over into “did COVID come from the lab?” because I am actually interested in the narrower question.
I’ve read a bunch more, but some things are still not clear to me.
As far as I can tell, it’s generally agreed the Wuhan lab did research with viruses which initially could not infect humans, but in their research they modified those viruses so they could (or at least so they could infect human cells, which may not be the same thing).
From reading various definitions of Gain-of-Function, that sounds like it fits, but Fauci says not, as well as many others.
Can anybody provide a layman’s definition of Gain-of-Function viral research, and explain how this research doesn’t fit the definition?
That’s why I just wished it. I also wish for a pony that poops skittles.
I guess the best we can hope for is a statement from the DOJ along the lines of “We do not conduct frivolous investigations based on false accusations from random senators trying to score political points.”
The FactCheck.org story linked by beowulff in the first reply to your original post includes a pretty straightforward definition that a layman (like me) should be able to understand:
Gain-of-function research in this context means that it would reasonably be expected to result in a virus becoming more virulent or contagious.
While there can be a debate about what constitutes a “reasonable” expectation, the EcoHealth Alliance grant was clearly not intended nor expected to create a virus that is more deadly or transmissible.
Can I have a cite where this is “generally agreed”? As far as I have read, most scientists think zoonotic transmission is, by far, the most probable explanation (as it’s happened with the majority of novel viruses throughout history). They are only keeping an open mind regarding the lab escape hypothesis.
Looking at the original paper, it seems that they were interested in the origin of SARS, and how it was able to infect humans. They found several predecessors to SARS that occurred naturally, but did not have the machinery necessary to enter human cells, so they were unable to see which of them were the likely precursor to SARS. So in order to study them they took part of the SARS virus that allowed it to enter human cells and plugged it into these viruses, and looked at what they did to human cells. They found that those that had a certain genetic sequence in common with SARS did infect the human cells, while those without it did not. This allowed them to draw the conclusion that that particular sequence was important in SARS’s ability to infect humans.
Note that there was no effort to select and propagate the versions that were particularly infectious or to create a super virus. They already had a super virus, it was called SARS. It is unlikely in the extreme that any of the new combinations would be any where near as virulent or deadly as the full SARS version.
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?
It would be nice if Rand Paul could gain the function of intelligent thought. At the moment, there are several bacterium that have him beat in this department.
I didn’t say anything about SARS-CoV-2, and as hard as it may be to believe I am not trying to get to any sort of political gotcha. I’m honestly just trying to understand GoF and what we know about research that was done.
Thank you, that sounds like exactly what I said:
And then there is this:
But that’s where the rubber meets the road. Using this definition from Dahnlor, and the above description of the research from Buck_Godot, it sounds for all the world like they did exactly this. They took viruses which were known to not infect humans, and “took part of the SARS virus that allowed it to enter human cells and plugged it into these viruses” then how is that not more virulent or contagious?
Is it because:
The reviewers who determined it was not GoF used a different definition?
The fact it can infect human cells doesn’t count as “more virulent or contagious” because it’s not infecting entire humans?
Question: If it turns out that it came from a lab, wouldn’t that pretty much show that the lab was doing gain of function research? Or are we to believe that a virus that did not infect humans spontaneously mutated into one that did inside the lab with no intervention?
I’m confused about this, It seems like the lab leak hypothesis has a lot of traction, but the idea that they were carrying out gain of function research does not. How do you have one without the other?
I think the point is that this was a necessary prerequisite to do the research. If this counted as GoF then virtually everything virologists do would be, and “GoF research” wouldn’t be a useful term.
I would agree though, that to the layman, it might seem like gain of function. But fauci didn’t lie and the point is a bit of a red herring, that is useful politically even though (as Paul did concede), no virologist considers it a serious possibility that covid was engineered.
(Also, as you say, there is some distinction between the virus being able to infect individual cells in the lab versus being human infectious in general, although IANA virologist, so I’m not clear on what that distinction is).
Good point, and I think part of why the lab leak has such traction is that people simply haven’t thought through such implications. And for politicians, it’s important to be seen as getting tough on China, and it’s irrelevant what scientists are saying.
Let me be clear, I am not saying, nor have ever said, that the lab leak hypothesis should be ruled out. And of course I support more investigations and greater transparency from the Chinese government. But the hypothesis has gained a lot more support than it should have at this point, and a lot of that support is based on nothing more than “Sneaky China…stands to reason, dunnit?”
Could be. I am agnostc on both issues. But do we agree that the lab leak and GoF are linked? That if this came from the lab, they were almost certainly doing Gain of Function? The only other way I can imagine it working is if they found naturally-occurring SARS-COV2 and were studying it. But they never made that claim, and despite lots of searching no one has yet found this virus in any wild bat or pangolin populations.
If Wuhan was doung GoF research, that still doesn’t mean Fauci funded it. As I understand it, that lab got funding from lots of places for lots of work. They may even have been doing secret work for the Chinese military, for that matter.
On the other hand, Fauci is a big fan of GoF research, and if he wanted to continue it despite the U.S. ban, finding an intermediary to fund which in turn would hire a Chinese lab to do the work strikes me as exactly how he would do it. And his lawyerly, tightly parsed responses to the question made me a bit suspicious.
I suppose that one might describe that as gain of function on the SARS precursor viruses that they were studying… but then again, you could equally well describe it as loss of function on SARS itself. The engineered viruses you would produce in this process would be a combination of SARS and one of those other viruses, and so would be expected to have a virulence somewhere between them, as well.
No it’s not. I didn’t hold it up as some truth or proof of a conspiracy. I just meant that the narrow way he responded did not close out the issue. I’ve watched enough politicians to kmow when they are equivocating or trying to squeeze through a narrowly parsed loophole. That doesn’t mean he’s guilty, just that his denials didn’t seal the deal for me. It’s called being skeptical.
For that matter, Rand Paul also sounded to me like he was demagoguing.
Okay, fair enough. I thought you were specifically talking about the origins of SARS-CoV-2.
Absolutely. In fact, as I read the paper, they weren’t even combining bat viruses with human SARS. They were combining bat viruses with other bat viruses (eg. WIV1) that already can infect human cells. They simply swapped the S region of the WIV1 viruses with that of each novel virus to see if one of the novel bat viruses could “rescue” the ability to infect human cells, not make a new virus that binds better to human cells. By the way, if SARS-CoV-2 arose from this type of experiment, you’d be able to see it right away.
This experiment is NOT the official definition of GOF research that was paused by the Obama administration. That definition is as follows, "Gain-of-function (GOF) research involves experimentation that aims or is expected to (and/or, perhaps, actually does) increase the transmissibility and/or virulence of pathogens.
Again, it’s possible that they are doing true GOF research, made a mistake, and are now hiding their tracks. By the way, the Chinese don’t need US money to fund their research. They have plenty of their own. It is better that we collaborate with them on these types of things so that we at least have some idea of what they’re doing.