Thread
So here's my take on the BU experiments. I know you can't say this on Twitter, but it is my current state of understanding, possibly imperfect, subject to revision with better understanding, and trying to make sense rather than condemn opponents.
First, these are unquestionably gain-of-function experiments. As many have noted, this is a very broad term encompassing many harmless and some potentially dangerous experiments. GOF is a scientific technique, not an epithet. The wildtype "backbone" virus gains immune escape...
...from the insertion of the Omicron spike, in ways that the paper describes in detail. That is gain-of-function.
Second, there is scientific value to the study, as @florian_krammer and others have noted. Understanding which changes have which phenotypic consequences is valuable for science. This is a classic microbial genetics study to do that, and appears to do so convincingly, though
virology is not my field and others may find problems.
Third, as several people have pointed out in an email chain I've been a part of (I'm not naming names to avoid broaching private communications, but also not claiming this as an original thought), this is probably not the most dangerous kind of GOF study.
In particular, the antigenic properties of the virus created were those of Omicron, and assuming this was done recently (one rarely puts dates of experiments in papers, but these days perhaps one should), much of the world had been exposed to Omicron or some sublineage.
So this is not like enhancing the properties of a truly novel virus in humans.
Those are the points in which I am most confident. Now for some more difficult questions. What is the public health value of these experiments? The authors say they will help develop therapeutics. That is possible; understanding biological structure-function can do that.
I wouldn't put much of a bet on the value of doing so, but it's not an outlandish claim.
In general, GOF experiments in viruses that are already widespread may be -- though individual evaluation is needed -- both less dangerous because the virus isn't novel, and more valuable to health because the virus is a big problem.
On the other hand, the possibility of making a virus with the immune escape abilities of Omicron (or worse, since by the premise of doing the experiment we didn't know before where all the immune escape lies) and the severity and transmissibility of wildtype was real.
This goes unacknowledged in the paper and is essentially dismissed in the subsequent statements from BU
www.bu.edu/articles/2022/neidl-researchers-refute-uk-article-about-covid-strain/
www.bu.edu/articles/2022/neidl-researchers-refute-uk-article-about-covid-strain/
The statement from BU is disturbing in several ways. First, it denies that this is GOF. It is GOF. If meant sincerely, this is disturbing from the institution that did the research because it provides prima facie evidence that institutions are not equipped to self-regulate.
The wording is confusing, seems confused: " If at any point there was evidence that the research was gaining function, under both NIAID and our own protocols we would immediately stop and report."
Research does not gain functions; viruses (or other biological entities). Hard to know what is meant here but it seems confused.
Putting aside the research vs. virus gaining function, it seems maybe they are claiming that because the wt virus with Omicron spike was (slightly) less virulent to mice than the wt virus unmodified, there was no gain of function. But again, the function gained was immune escape
Second, the statement reflects a culture of compliance rather than responsibility: because the NIAID funding was for equipment rather than the specific experiments, BU states it doesn't need to report the research to NIH. I'm no lawyer but likely they are right.
One of the main shortcomings of the current US regime for regulating enhancement experiments to create potential pandemic pathogens is that it applies only to research projects funded by the Department of Health and Human Services. That's a mistake www.centerforhealthsecurity.org/news/center-news/2022-07-08-ePPP-sign-on-letter.html
In seeming contradiction to that, the BU statement says "If at any point there was evidence that the research was gaining function, under both NIAID and our own protocols we would immediately stop and report." Is there an obligation to report or no?
Finally, BU seems to be saying in that statement that high lethality is only for mice, not humans, so nothing to worry about. This is misguided and hard to know how one could say it. SARS-CoV-2 has caused havoc in humans with <1% infection-fatality rate.
High lethality in mice is used -- although the numbers are different -- as a proxy for severity in humans. Otherwise why do it in a mouse? No one cares if Omicron can kill a mouse, except as a marker for severity (>1 order of magnitude lower) in humans.
If not a proxy for human phenotype, spare the mice and stop doing those experiments. Same arguments were made in the H5N1 GOF studies, where claims about "mammalian transmissibility" (ie, it's a model) alternated with "it's only transmitting in ferrets, not people," no worries.
Bottom line: as to whether these experiments should have been done, I'm uncertain but think there is at least a reasonable risk-benefit argument in their favor, if done in proper biocontainment.
Did BU have a legal or regulatory obligation to get permission from NIH, I'm no lawyer but I bet not.
Has BU shown that they are capable of self-regulation, assessing both the real risks that might be created and documenting that they considered them and found them minor compared to benefit: no. They are in full denial mode from their public statements.
Did they consider whether safer experiments could answer some or all of these questions well enough to accomplish what was needed? If so, no evidence thereof.
My current take then is two things. First, this is one of many cases to come where -- unlike the 2014-era enhancement of H5N1 transmissibility -- there is a decent argument for public health benefit, and HHS funding was not required.
As @DavidRelman and I argued in 2015, the H5N1 experiments were an easy edge case for these and other reasons: marginal scientific and near-zero public health value, safe alternatives, government funding, etc. www.foreignaffairs.com/world/new-game-new-rules
The current study has greater scientific and public health value, did not directly get USG funding, etc. Much harder to regulate, though I think our suggestions go a long way toward laying out a path www.centerforhealthsecurity.org/news/center-news/2022-07-08-ePPP-sign-on-letter.html
Second, relatedly, this shines light on shortcomings in the current frameworks. Institutions seem to lack the understanding to effectively spot legitimately controversial research; US jurisdiction is limited and unclear; and we now have controversy without a clear resolution...
I agree with @florian_krammer that the current regulatory environment is confusing, but seems like it is confusing in a way that encourages recklessness rather than chilling work that everyone would agree with. Finis
