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I Melt My Laptop's CPU To Find No-one Knows The Definition Of 'Gain-Of-Function'
Wuhan Outbreak Investigation, Part 1
If you’ve been wondering why I haven’t kept to my schedule as of late, I am uncovering one of the biggest stories that will blow people’s socks off, the discoveries keep expanding like a mutant fungal creature, but organising that ever-expanding data in a way that is coherent is very difficult.
Case in point, I’ve had to write a custom OCR tool — which crashed trying to load the 360mb+ Fauci FOIA PDF (it ran out of memory) — complete with specified restart point so it doesn’t try to reconvert the same images again.
It had to first convert the PDF to a set of images, and then take the images and convert it to machine-read text so it becomes at least partially searchable. I plan to upload the text conversion in some format so others can use it.
At time of talking, 4 days later, the conversion is still ongoing (page 2685, out 3200+ pages). My tiny laptop struggles, and a cooling pad I got for it ages ago is helping prevent the CPU from melting itself.
The donations from paying subscribers helped on a major scale here. I upgraded my laptop’s tiny RAM so I am at least able to both do online research and process the images without crashing. Really I should be saving it for food, but I feel the story here is so important it warrants priority, and it is what I’m paid to do.
Usually, proper reporting says I break the main story first, and then discuss the “smaller” issues in an ‘after-report’. However the main story still isn’t complete due to complexity and there are connections I need to uncover, confirm or exonerate before I can truthfully present the situation. So we’re discussing one of the “smaller” issues instead.
No-One Truly Knows The Definition Of Gain-Of-Function
This might come as a surprise. You might point to a dictionary definition, but it turns out no-one knows what it actually means. When reading about the Wuhan outbreak, scientists give differing views on what they thought it was, so I opted to go straight to the source.
I asked National Institutes of Health (NIH) for comment on what their definition of gain-of-function (GOF) was. This was their response:
NIH describes it as something that which “increases the ability of a pathogen to cause disease”. Now, the definition of disease itself varies, but in medicine it is understood, in a simplistic sense, to refer to the symptoms. An infection, pathogen, refers to the ‘infectious agent’ that causes the disease (EG virus, bacteria, injected toxins).
So what NIH are saying here is gain-of-function is research that increases the ability of a pathogen to cause (worsening) symptoms.
NIH also pointed to a different definition for gain-of-function, by the 2022 Congressional Research Service report. Their ‘quotation’ is paraphrased, so I will be quoting from the January 19th, 2022 Congressional Research Service report directly:
The terms gain of function and loss of function refer to any genetic mutation in an organism that either confers a new or enhanced ability or causes the loss of an ability […]
A key area of GOF research is the study of both naturally occurring and experimentally induced changes in organisms to better understand the transmission, infection, and pathogenesis of viruses.
This is much broader than NIH’s definition. So the first part includes both the gain and the loss of an ability, with ability ambiguously undefined. And the second mentions ‘transmission, infection and pathogenesis’.
Tranmission is how well it spreads, infection is how well it can enter host cells, and pathogenesis is how it originates and develops within the host body — the ability to be pathogenic and cause disease.
NIH at the end commented — out of the blue, I didn’t ask for this — “In terms of the Covid-19 pandemic, the NIH continues to stand by this statement”, and linked to a statement by no-longer-NIH-director Francis Collins, which creates a third definition for gain-of-function:
[…] neither NIH nor NIAID have ever approved any grant that would have supported “gain-of-function” research on coronaviruses that would have increased their transmissibility or lethality for humans
Notice it now has become an ‘increase’ in ‘transmissibility’ (spread) and an ‘increase’ in ‘lethality’ (mortality), but only in humans specifically. Notice in neither custom definition by the NIH is the mention of loss of ability by Congress. It seems like the NIH don’t know what the definition of gain-of-function is.
NIH Aren’t The Only Ones
Peter Daszak, head of EcoHealth Alliance, declared his own research wasn’t gain-of-function, as he declared that it “has never been demonstrated to infect humans or cause human disease”.
Which is odd, because neither the NIH nor the Congressional Report specified a host species when defining the terms of gain-of-function, with the exception of former Director Francis Collins. Isn’t Congress supposed to decide?
National Institute of Allergy and Infectious Diseases (NIAID) — who reside under NIH, and therefore should know the NIH’s definition — concurred with Peter Daszak and replied “NIAID is in agreement that the work proposed under Aim 3 to generate MERS-like or SARS-like chimeric coronaviruses (CoVs) is not subject to the GoF funding pause”
The irony is NIAID should clearly know both MERS and SARS are human infectious diseases that caused ‘human disease’, so any work on “MERS-like” or “SARS-like” coronaviruses implies more of the same. After NIAID agreed with Peter Daszak, he expressed glee the pause on his not-gain-of-function gain-of-function research had been lifted: “We are very happy to hear that our Gain of Function research funding pause has been lifted”.
Another virologist — Ralph Baric — also working on “SARS-like” coronaviruses, co-authored a paper titled “SARS-like WIV1-CoV poised for human emergence”, where he declares it cannot be subject to the White House’s Office of Science and Technology Policy gain-of-function research pause on October 17th, 2014, because his study started before the ban.
Interestingly and oddly, he did not consider the ban to also apply to ongoing research involving WIV1 — a SARS-like coronavirus — even though there’s a media article report where he complains the ban stopped his ongoing research that started before the ban.
He goes on to say the NIH — again — greenlit the research:
This might have something to do with the fact Ralph Baric argued to the NIH back in November 2014 that a ban on GOF studies would impact his ability to do “vaccine design” studies. Ah, yes, risk human outbreak for the good of vaccine companies.
The Daily Beagle approached Ralph Baric with a simple question asking him what his perceived definition of gain-of-function was. At time of writing, no comment was received. Perhaps he does not know?
Politicians Have This Problem Too
It is all well and nice pointing to people with conflicts of interest and saying they got it wrong, but it turns out neither the public — who when polled said they thought it related to spread (infectibility) — nor the politicians, know what the definition was.
You might remark that politicians are perhaps ‘dumb’ or ‘stupid’, however you might have to pause for thought here. Politician Dr. Rand Paul — for he actively practices medicine — who had been grilling Anthony Fauci for lying to Congress over funding gain-of-function research, also gave another two definitions for gain-of-function:
"[…] and continually defending against the use of American taxpayer dollars in funding gain-of-function research, which aims to enhance the infectiousness or severity of a virus."
"The amendment defines gain-of-function research as “any research project that may be reasonably anticipated to confer attributes to influenza, MERS, or SARS viruses such that the virus would have enhanced pathogenicity or transmissibility in mammals.” This is the same definition the NIH used when implementing a funding moratorium on gain-of-function research in 2014-2017."
The first is research that aims to ‘enhance the infectiousness (spread) or severity (disease) of a virus’, even though the Congressional report includes the loss of ability, and includes all pathogens (a pathogen can be a virus, bacterium, toxin, spore or similarly), so the Congressional Report’s scope is much broader than Rand Paul’s.
The second he narrows to mean ‘influenza, MERS, or SARS viruses such that the virus would have enhanced pathogenicity or transmissibility in mammals’, which is a very narrow definition, and obviously ‘influenza, MERS or SARS’ is a much narrower subset of viruses.
He also narrows it to ‘enhanced pathogenicity’ (increased disease) and ‘enhanced transmissibility in mammals’ (increased spread), which would include things like humans, monkeys and mice, even though no species is defined in the 2022 Congressional Research Service report.
For completeness, The Daily Beagle also asked Rand Paul what his perceived definition of gain-of-function was. Yes, we know it is on his 2021 blurb page, but between then and now, he, like Ralph Baric, may have changed his mind. Naturally, no comment was received at time of writing.
Rand Paul Wasn’t Far Off
His perception isn’t entirely off the mark, because the 2014 pause does say something similar, albeit it tacks on another definition:
[…] the U.S. Government will institute a pause on funding for any new studies that include certain gain-of-function experiments involving influenza, SARS, and MERS viruses. Specifically, the funding pause will apply to gain-of-function research projects that may be reasonably anticipated to confer attributes to influenza, MERS, or SARS viruses such that the virus would have enhanced pathogenicity and/or transmissibility in mammals via the respiratory route.
It adds the line “via the respiratory route”. Not the biggest difference on Rand Paul’s part, but still a crucial detail to include.
This would mean both Peter Daszak and Ralph Baric’s work with respiratory viruses being used on “humanized mice” — a species of mammal — would mean both NIH and NIAID’s assessment of their work as not being gain-of-function is incorrect, and thus would mean Francis Collins’ claims they were not financing gain-of-function is false.
It’d also mean Peter Daszak’s argument it doesn’t infect humans as proof it wasn’t gain-of-function was irrelevant, as he worked with mice that are a species of mammal and thus caught under the original 2014 definition.
What’s interesting is, this reveals within government and within science, there is not one single used consistent definition used for gain-of-function. And finally…
The Daily Beagle Didn’t Know, Either
I was confident I understood the definition of gain-of-function - I was of the view it referred to either increased lethality (disease) or increased infectability (spread). Good journalism requires you do due dilligence, and I decided to double-check my assumptions. Over-confidence in knowledge without evidence is usally a surefire sign you’re wrong.
I tried to read several online definitions for gain-of-function and found they all gave inconsistent statements. How can I explain to the audience what it is if I don’t know? So I asked the NIH and found they also gave inconsistent explanations. I dug around and found pretty much everyone offered differing examples.
The cause is ultimately the fact gain-of-function, as a term, is ambiguous. That, and people didn’t check the original prohibition. What is a ‘function’? How can it ‘gain’? Sometimes viruses lose one function (lethality) that makes them better at another (spread). Is that a ‘gain’ of function?
The 2022 Congressional Research Service report doesn’t seem to know and leaves it undefined, and such wide leverage allows for malicious exploitation by those trying to skirt the law, and promotes confusion in the public.
I would propose explicitly defining the ‘function’, so it becomes ‘gain-of-infectibility’, or ‘gain-of-harm’. I also argue against ‘loss of function’ being thrown under ‘gain’ because it is counter-intuitive and error-prone. ‘Loss-of-infectibility’ and ‘loss-of-harm’ are distinct and clear. If you want to specify both loss and gain, I’d propose ‘change-of-function’ as a defining term.
Further, I’d argue against defining harm purely on the individual level, which is what the NIH, Francis Collins and Peter Daszak are trying to argue, and instead consider the much bigger picture of consequences.
Infectibility is a type of harm. So even if the virus only produces a mild cough, if it can spread very rapidly, it is more of a hazard — disrupting world economies and health systems — than a virus that kills but can’t spread at all.
I also think the wider list of pathogens as suggested by the 2022 Congressional Research Service report should be adopted, as focusing on such a narrow subset means people can experiment with other dangerous pathogens unimpeded.
Hopefully this article will help inform people on the wildly differing definitions on ‘gain-of-function’ and help inform wider debate.
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