Thread by @Ayjchan

I think that it is important for scientists & public stakeholders across diverse fields of training to convene and discuss the range of pathogen research occurring worldwide as we tweet.

I wouldn't raise this except in the context of a pandemic that has shut the world down...

We may not know for years or even decades, for sure, how COVID-19 / SARS-CoV-2 came to be.

In this situation, we just have to prepare for each of the plausible origin scenarios - natural spillover, lab leak, and unfortunately, for some subset of 🌏, cold chain #PopsicleOrigins

Before we set up another forum or advisory board (which mustn't just be scientists this time) to discuss how to evaluate the risks of pathogen research, it's important to look back on the past few years of this type of debate among scientists on Gain of Function (GOF) research.

Late 2014, biosafety incidents at federal US research facilities prompted a pause on -new- US gov funding for GOF research "reasonably anticipated to confer attributes to influenza, MERS, or SARS.. enhanced pathogenicity and/or transmissibility..."
obamawhitehouse.archives.gov/blog/2014/10/1…

Notably, "the research funding pause would not apply to characterization or testing of naturally occurring influenza, MERS, and SARS viruses, unless the tests are reasonably anticipated to increase transmissibility and/or pathogenicity."

Here's the actual doc titled "U.S. Government Gain-of-Function Deliberative Process and Research Funding Pause on Selected Gain-of-Function Research Involving Influenza, MERS, and SARS Viruses" phe.gov/s3/dualuse/Doc…

This was only a policy relating to new funding, not ongoing funding or even any research.

The document even says "we will encourage the currently-funded USG and non-USG funded research community to join in adopting a voluntary pause on research that meets the stated definition."

Basically it had no teeth regarding research that was happening anywhere, including in the US, even if it was funded by federal $.

You only needed to get around "reasonably anticipated" and "voluntary".

This was apparent in the reporting then: "it is difficult to determine how much mutation deliberately created by scientists might be “reasonably anticipated” to make a virus more dangerous — the point at which the White House states research must stop..." nature.com/news/us-suspen…

"... government says that this point will be determined for individual grants in discussions between funding officers and researchers."

If you were in a grey area of not knowing if your work could reasonably be anticipated to be GOF, you just needed to confer with your funders.

Not too surprisingly then, a fight broke out in 2015 over whether chimeric viruses were considered GOF.

"The NIH eventually concluded that the work was not so risky as to fall under the moratorium"
nature.com/news/engineere…

I'm not saying whether this assessment was correct or incorrect, just that it was what it was.

In 2015, building chimeric SARS viruses was not assessed as being risky enough to fall under the GOF moratorium.

If we don't like it, we should bring it up today on a clean slate.

This chimeric SARS work was criticized back then (2015) by experts including @R_H_Ebright who put forward that “The only impact of this work is the creation, in a lab, of a new, non-natural risk”

But the authors of the work and Peter Daszak said the findings of the work “move this virus from a candidate emerging pathogen to a clear and present danger” and "help indicate which pathogens should be prioritized for further research attention."

I'm going to refrain from judgment because the risk judgment in 2014 vs today are clearly different based on the new developments and information available to us.

If you look at the 2015 version of the grant awarded to EcoHealth, it did not fall under this $ pause or GOF moratorium: "receptor binding assays, and virus infection experiments across a range of cell cultures from different species and humanized mice."
grantome.com/grant/NIH/R01-…

(1) Because it was using natural viruses (see above in thread).

(2) Because it could be reasonably argued that these novel bat viruses were not likely to be both highly transmissible and highly virulent in humans.

Most importantly, (3), even if you're creating chimeric viruses, it would be up to a discussion with your funding person whether this could be reasonably anticipated to result in a pathogen with pandemic potential.

The work ultimately was not aimed at creating viruses that were more infectious. It was taking parts of natural viruses and studying them in well-characterized virus genome backbones.

I don't buy into the concept that scientists were intent on killing us all with risky business.

Roll around to 2017 when this pause on $ was lifted, actual US HHS Dept doc titled "Framework for Guiding Funding Decisions about Proposed Research Involving Enhanced Potential Pandemic Pathogens" phe.gov/s3/dualuse/doc…

I suspect, to ensure that the policy did not dramatically impact ongoing pathogen research, it was very carefully scoped to discuss only pathogens that are both (likely) highly transmissible and highly virulent. If it was only one of those things, it wouldn't be counted as a PPP.

Once again, the wording was: "Proposed research.. determined by the funding agency to be reasonably anticipated to create, transfer, or use enhanced PPPs must be referred for HHS department-level review."

Reasonably anticipated.

To use enhanced PPPs.

Scientists in 2017 pointed out this loophole: "weakness of the new framework is that surveillance activities involving potential pandemic pathogens (PPPs), including sampling and sequencing, aren't considered to be enhanced PPPs and would be exempt..."
cidrap.umn.edu/news-perspecti…

And probably half the people who encountered this thread are 😴 now, but you can see how the wording of these documents would exclude work on natural viruses, chimeric viruses you can convince your funding officer does not have increased transmissibility/virulence.

Scientists who were/are hunting viruses in the wild and in rural human populations could very reasonably say their work isn't GOF.

But we need to separate this fight about whether a particular project is GOF vs whether it has risk of lab accident + causing an outbreak.

I also want to take this opportunity to point out that scientists who hunt for viruses with pandemic potential don't always believe they're going to be exposed to/find one:

https://twitter.com/Ayjchan/status/1337416885143560192

Scientists who do this type of work could, reasonably, within the same grant application claim that they're predicting the next pandemic, while also not engaging in any risky pathogen (GOF) research activities requiring any additional review.

I know it is super tempting for people who think a lab origin is very likely for COVID-19 to look back at this GOF debate and wonder why these scientists didn't get the point.

But it's just hindsight. Otherwise we'd all be Apple, Bitcoin, and mRNA vaccine billionaires by now.

Even today, a considerable number of scientists are still pushing for more of this type of research so that we can continue to "prepare" for the next pandemic.

It's not a very straightforward issue with any kind of consensus among top scientists.