Thanks very much for writing this. Unnecessarily alienating people for stupid reasons like misusing terminology or not understanding their perspective seems like a clear mistake and hopefully this can help people avoid these pitfalls.

I was curious about your suggestion that a lot of researchers think that basically all biomedical research is gain/loss of function. My impression is that one of the key defenses that the Fauci/NIH/EcoHealth/etc. offered for their research in Wuhan was that it was technically not Gain of Function, even if some parts of it might sound like Gain of Function to the layperson, which seems in tension with this claim. Do you think they were wrong about this?

Your point about many researchers in this area feeling defensive was a good one, and it's important to take this into account when talking to people. It's not fun to be blamed for causing a global crisis, especially if its possible you didn't do it!

I do think there's a risk of a missing mood, however. Speaking as an outsider, the amount of regulation on what you refer to as ePPP (adding functionality to make diseases more dangerous) seems shockingly low. The article you link to tries to make it sound like there are a lot of safeguards, but it seems to me like virtually all the steps only apply if you are seeking federal funding. This is not a standard we accept in other areas! If you are making a car, or building a nuclear power plant, or running a bank or airline, you have to accept extremely intrusive regulation regardless of your funding, and for many things - like nuclear weapons or money laundering - US regulation has world-wide reach. 

For comparison, here are some of the regulatory approaches used in finance, another industry that was widely blamed for causing a global crisis:

• Monitoring of all electronic communications.
• Quarterly reporting of activities to regulators.
• Regulators placed inside your organization.
• Risk Management departments at every firm, making up a non-trivial fraction of their total size.
• Compliance departments at every firm, making up a non-trivial fraction of their total size.
• Mandatory compliance training for all employees.
• Novel regulatory bodies with broad mandate to find and punish things that seem bad.
• AML & KYC rules that impose stringent penalties for doing business with suspisious actors.
• Mandatory insurance.
• Direct government control over key areas.
• 'Voluntary' advice from regulators (100% adoption due to legal risks of disobedience).
• Multi-million-dollar whistleblower awards.
• Billion-dollar fines.
• Decades long jail sentences.
• Lifetime bans from the industry.
• ... and most importantly, if you mess up, you will probably lose a lot of money.

As far as I can, few if any of these approaches are imposed on Gain of Function research, despite the potential to directly cause the death of all of humanity.

Without getting too far into the specifics, I think that this is a good attitude to have across a wide range of policy concerns, and that similar issues apply to other policy areas EAs are interested in.

Hi Elika, 

Thanks for writing this, great stuff!  

I would probably frame some things a bit differently (more below), but I think you raise some solid points, and I definitely support the general call for nuanced discussion.

I have a personal anecdote that really speaks to your "do your homework point." When doing research for our 2021 article on dual-use risks (thanks for referencing it!) , I was really excited about our argument for implementing "dual-use evaluation throughout the research life cycle, including the conception, funding, conduct, and dissemination of research." The idea that effective dual-use oversight requires intervention at multiple points felt solid, and some feedback we'd gotten on presentations of our work gave me the impression that this was a fairly novel framing. 

It totally wasn't! NSABB called for this kind of oversight throughout the research cycle (at least) as early as 2007, ^[1] and, in hindsight, it was pretty naïve of me to think that this simple idea was new. In general, it's been a pretty humbling experience to read more of the literature and realise just how many of the arguments that I thought were novel based on their appearance in recent op-eds and tweets can be found in discussions from 10, 20, or even 50 years ago.

Alright, one element of your post that I would've framed differently: You put a lot of emphasis on the instrumental benefits of nuanced discussion in the form of building trust and credibility, but I hope readers of your post also realise the intrinsic value of being more nuanced.

E.g., from the summary 

"[what you say] does impact how much you are trusted, whether or not you are invited back to the conversation, and thus the potential to make an impact"

And the very last sentence:

 "Always make sure ‘you’re invited back to the table’." 

This is a great point, and I really do think it's possible to burn bridges and lose respect by coming across as ignorant or inflammatory. But getting the nuanced details wrong is also a recipe for getting solutions wrong! As you say, proper risk-benefit analysis for concrete dual-use research is almost always difficult, given that the research in question very often has some plausible upside for pandemic preparedness or health more generally.

And even if you know what specific research to draw red lines around, implementation is riddled with challenges: How do you design rules that won't be obsolete with scientific advances?  How do you make criteria that won't restrict research that you didn't intend to restrict? How do you avoid inadvertent attention hazards from highlighting the exact kinds of research that seem the most risky? Let's say you've defined the perfect rules. Who should be empowered to make the tough judgment calls on what to prohibit? If you're limiting access to certain knowledge, who gets to have that access? And so on, and so on.

I do think there's value in strongly advocating for more robust dual-use oversight or lab biosafety, and (barring infohazard concerns), I think op-eds aimed at both policymakers and the general public can be helpful. It's just that I think such advocacy should be more in the tone of "Biosecurity is important, and more work on it is urgently needed" and less "Biosecurity Is Simple, I Would Just Ban All GOF." 

Bottom line, I especially like the parts of your post that encourage people to be more nuanced, not just sound more nuanced.

1. ^{^}

   From Casadevall 2015: "In addition to defining the type of research that should elicit heightened concern, the NSABB recommended that research be examined for DURC potential throughout its life span, from experimental conception to final dissemination of the results."

Just wanted to give my hearty +1 to approaching biosecurity issues with humility and striving to gain important context (which EAs often lack!)

Thanks for this post! I agree with your point about being careful on terms, and thought it might be useful to collect a few definitions together in a comment.

DURC (Dual-Use Research of Concern)

DURC is defined differently by different organizations. The WHO defines it as:

research that is intended to provide a clear benefit, but which could easily be misapplied to do harm

while the definition given in the 2012 US government DURC policy is:

life sciences research that, based on current understanding, can be reasonably anticipated to provide knowledge, information, products, or technologies that could be directly misapplied to pose a significant threat with broad potential consequences to public health and safety, agricultural crops and other plants, animals, the environment, materiel, or national security

ePPP (enhanced Potential Pandemic Pathogen)

ePPP is a term (in my experience) mostly relevant to the US regulatory context, and was set out in the 2017 HHS P3CO Framework as follows:

A potential pandemic pathogen (PPP) is a pathogen that satisfies both of the following:

1. It is likely highly transmissible and likely capable of wide and uncontrollable spread in human populations; and
2. It is likely highly virulent and likely to cause significant morbidity and/or mortality in humans.

An enhanced PPP is defined as a PPP resulting from the enhancement of the transmissibility and/or virulence of a pathogen. Enhanced PPPs do not include naturally occurring pathogens that are circulating in or have been recovered from nature, regardless of their pandemic potential.

One way in which this definition has been criticized (quoting the recent NSABB report on updating the US biosecurity oversight framework) is that "research involving the enhancement of pathogens that do not meet the PPP definition (e.g., those with low or moderate virulence) but is anticipated to result in the creation of a pathogen with the characteristics described by the PPP definition could be overlooked."

GOF (Gain-of-Function)

GOF is not a term that I know to have a clear definition. In the linked Virology under the microscope paper, examples range from making Arabidopsis (a small flowering model plant) more drought-resistant to making H5N1 (avian influenza) transmissible between mammals. I suggest avoiding this term if you can. (The paper acknowledges the term is fuzzily defined, citing The shifting sands of ‘gain-of-function’ research.)

Biosafety, biosecurity, biorisk

The definitions you gave in the footnote seem solid, and similar to the ones I'd offer, though one runs into competing definitions (e.g. the definition provided for biosafety doesn't mention unintentional exposure). I will note that EA tends to treat "biosecurity" as an umbrella term for "reducing biological risk" in a way that doesn't reflect its usage in the biosecurity or public health communities. Also, as far as I can tell, Australia means a completely different thing by "biosecurity" than the rest of the English-speaking world, which will sometimes lead to confusing Google results.

On “learning from people outside EA and those who slightly disagree with EA views” I highly recommend reading everything by Dr Filippa Lentzos: https://www.filippalentzos.com/.

Also, subscribe to the Pandora Report newsletter:
https://pandorareport.org/

Global Biodefense was great but sadly seems to have become inactive: https://globalbiodefense.com/

I think it's quite sensible that people hoping to have a positive impact in biosecurity should become well-informed first. However, I don't think this necessarily means that radical positions that would ban a lot of research are necessarily wrong, even if they are more often supported by people with less detailed knowledge of the field. I'm not accusing you of saying this, I just want to separate the two issues.

 Many professionals in this space are scared and stressed. Adding to that isn’t necessarily building trust and needed allies. The professionals in this space are good people – no reputable virologist is trying to do research that intentionally releases or contributes to a pandemic. Biosafety professionals spend their life working to prevent lab leaks. If I’m being honest, many professionals in and around the biosecurity field don’t think incredibly highly of recent (the past few years) journalistic efforts and calls for total research bans.

Many people calling for complete bans think that scientists are unreliable on this - because they want to continue to do their work, and may not be experts in risk - and the fact that said scientists do not like people doing this doesn't establish that anyone calling for a complete ban is wrong to do so. 

As a case in point regarding the unreliability of involved scientists: your reference number 6 repeatedly states that there is "no evidence for a laboratory origin of SARS-CoV-2", while citing arguments around the location of initial cases and phylogeny of SARS-CoV-2 as evidence for a zoonotic emergence. However, a survey of BSL-3 facilities in China found that 53% of associated coronavirus-related Nature publications were produced by Wuhan-based labs between 2017 and 2019, and it is extremely implausible that Wuhan bears 50% of the risk for novel zoonotic virus emergence in all of China! (it's possible that the authors of that survey erred - the do seem ideologically committed to the lab leak theory). Furthermore, I have to the best of my ability evaluated arguments about the presence of the furin cleavage site in the SARS-CoV-2 genome and my conclusion is that it is around 5 times as likely to be present in the lab origin scenario (accounting the fact that the WIV is an author on a proposal to insert such sites into SARS-like coronaviruses; also, I consider anywhere from 1.1 to 20 times as likely to be plausible). One can debate the relative strength of different pieces of evidence - and many have - but the claim that there is evidence on one side and none on the other is not plausible in my view, and I at least don't trust  anyone making such a claim is able to capably adjudicate questions about risks of certain kinds of pathogen research.

(not that it's especially relevant, but I currently think the case for zoonosis is slightly stronger than the case for a lab leak, I just don't think you can credibly claim that there's no evidence that supports the lab leak theory)

A little bit of proof reading

stating confidentiality

confidently

You don’t likely don’t know more than professionals

You likely don't know

I'm not that knowledgeable on the biosecurity field, but from afar I've thought that working biosecurity EAs tend to be some of the more collaborative, professional, and respectful of non-EA contributions. And this post is an example of that, thanks for sharing.

Do you have any additional sources you'd recommend? Things you didnt add to the initial list for whatever reason? I'd like to read widely on this topic.

Great post! This matches closely with the lessons I've learned and advice I've given after working with virologists and biosafety professionals. I'd also give a plug for the book Biosecurity Dilemmas for anyone who wants to do a deeper dive in the trade offs in this space.