Thread by @kesvelt

I'm deeply worried about future pandemics & nastier agents. Nature doesn’t try to kill us; humans will. This e-print details a universal early-warning system: a “Nucleic Acid Observatory” (#NAO).
arxiv.org/abs/2108.0267
1/20

All catastrophic bio-threats grow exponentially
All bio is made of nucleic acids
To detect all threats, deep sequence wastewater + rivers & look for exponentially growing fragments (k-mers)
arxiv.org/abs/2108.02678
#NAO
2/20

Why a Nucleic Acid Observatory? @EricLander46: “to keep future viruses from becoming pandemics… (we need) early-warning systems to spot new biological threats anywhere in the world soon after they emerge” washingtonpost.com/opinions/2021/…
3/20

When you’re fighting something that grows exponentially, every day counts: there will be exponentially fewer of the enemy. A universal early warning system would give us the best possible chance to control invasive bio-threats.
4/20

#NAO would use unbiased deep metagenomic sequencing to detect all new threats, then targeted amplification/enrichment to find each threat at all other sites + go back in time w/ stored samples to learn how it spread.
5/20

For example, SARS-CoV-2 can show up in airport wastewater before cases. Wastewater detection works for flu and other viruses too. Sequence & spot new pandemics early.
nature.com/articles/s4158…
6/20

It’s not just pandemics. I’m responsible for CRISPR-based #genedrive systems, which can spread exponentially in wild populations. Gene drive favors defense, but only if you look. #NAO would look everywhere.
elifesciences.org/articles/03401
7/20

Neat fact: sequence a river, and you pick up genome fragments from most species in the watershed, even terrestrials. besjournals.onlinelibrary.wiley.com/doi/full/10.11…
8/20

Sufficiently deep sequencing of rivers could also pick up invasive species, be they pandemic viruses, fungi, agricultural blights, weeds, murder hornets, or whatever.
9/20

Why not PCR or @cambearon & @Blaineylab’s CARMEN? 1) we don’t know what nature will throw at us, & 2) any competent adversary will engineer a weapon to evade probes. First ID the threat, then target. nature.com/articles/s4158…
10/20

What about clinical sequencing a la @AndyWeberNCB? We should do that too, but it has privacy and legal issues that environmental sequencing avoids: everything is mixed together. 80000hours.org/podcast/episod…
11/20

Would a #NAO be expensive? Not compared to a $10t pandemic or military budgets. Sequencing wastewater from all 328 U.S. Ports of Entry would be just ~$450m up front and ~$325m/yr. Fund as infrastructure!
economist.com/finance-and-ec…
12/20

Adding 378 water basins would ~double the cost. Add all big international airports, and all U.S. towns or cities, and it’d be ~$10 billion a year, which may pay for itself by controlling invasive pests.
pnas.org/content/113/27…
13/20

Even a pilot waterway #NAO would teach us a ton about biology. We’ve barely tapped nature’s bounty in terms of useful biomolecules; this would give us much of the rest. The full version would give us most everything.
14/20

As for conservation, comprehensive deep sequencing could give us data on the comparative abundance of most species over time. We could spot problems and address them early.
15/20

Crucially, the cost of sequencing has been falling faster than Moore’s Law, and that looks set to continue. So whatever we build today will just get better. And sequencing tech favors defense.
16/20

Once we build a #NAO, we simply won’t have to fear any creeping bio-threats like polio, nor worse engineered agents. The entire category of subtle bio-attacks would be off the table; no one would try.
#BioDefense
17/20

The very existence of a #NAO providing early detection and tracing capabilities would deter malevolent folks from trying to make exponential weapons, and improve our response vs natural threats. As this preprint concludes...
18/20

“A #NAO would tell us when to act when we are confronted with an emerging pandemic or other exponentially spreading biothreat. The time to build it is now.”
arxiv.org/abs/2108.02678
#BioDefense
19/20

I’m just one of a global team that came together to sketch out #NAO; I can’t claim a major role. Building one is what matters. To help prevent future pandemic-class events, please retweet this thread and/or reach out to them: Nucleic.Acid.Observatory@gmail.
20/20

Humility check: my typo in the link in the very first post underscores the need for robust and layered defenses: someone will make mistakes/misuse increasingly powerful technologies. If you RT post 1, please quote+include the correct link: arxiv.org/abs/2108.02678. Thanks.
21/20