[FRIAM] whackadoodles go mainstream!

Mon Apr 20 20:32:55 EDT 2020

This was my read, too, Roger, exactly.  He is willing to make a call that he doesn’t think protein designers are sophisticated enough to solve that complicated a problem that cleanly, yet he thinks it is not improbable in large, diverse-population evolutionary dynamics.

I have a friend who once made the observation “terrorists seem to be very stupid.  Why did it not occur to them before the early 2000s, when the fancy avenues had been cut off, that they could drive rented trucks into crowds and create a big disruption that way.”  I don’t credit this friend with a profound insight, but to me this is indeed a thermodynamic argument.

In ordinary thermodynamics, we don’t minimize an internal energy, but a free energy, which is an internal energy most-likely to be found by a sampling process with a lot of randomness.  I have assumed the way to think of malicious-actor bioterrorism is something like that.  Very very one-in-the-world-genius best practice would be very hard to reproduce, if you were also working under cover, with potentially murderous management, maybe on a limited budget, in a hurry, etc.  So one expects that a lot of what is done will be a trade-off between what would work very effectively, and what is off-the-shelf manageable in the presence of other limitations. How to compute the relevant sampling processes, and the relevant entropy concept, is something I would enjoy getting some clarity on somehow.

Eric

> On Apr 21, 2020, at 9:23 AM, Roger Critchlow <rec at elf.org> wrote:
> 
> I found the assertion weak that the simple presence of these previously unreported sequence features (the binding domain ACE2 specificity, the (I think) detaching spike adaptation of the glycan collar) in wild type populations is evidence against purposeful engineering.  Maybe the glimmer of a natural evolutionary path does absolutely beat any protein engineering budget that anyone has ever seen, I think that's the gist of the argument, and if I state it that way I start to believe the argument more.  I found the absence of any protein/gene engineering scaffolding a fairly persuasive argument, too.  These sorts of manipulations leave lots of pencil marks in the sequences, marks which you would not waste time erasing until you were sure you had what you wanted, so if you accidentally released something that was under development, it would almost certainly look like something a bunch of monkeys had been hacking at with machetes.
> 
> It's funny that the core of conspiracy theory is an unbounded faith in human ingenuity, and the core of anti-conspiracy theory is experience of large budgets and clever, motivated people never getting anywhere close to their goal.
> 
> -- rec --
> 
> On Mon, Apr 20, 2020 at 7:36 PM uǝlƃ ☣ <gepropella at gmail.com <mailto:gepropella at gmail.com>> wrote:
> It's unclear to me whether we'd expect the virus to evolve faster or slower, depending on where it "originated". It seems to me that if it first appeared in a species that was dissimilar, then when it finally landed in a more optimal host type, it would evolve quickly (at least in non-critical regions) to thrive in that host type. On the other hand, if it lands in an almost already optimal host type, then it shouldn't evolve much at all. And only if it's under some sort of pressure to evolve (e.g. the immune system) would it do so quickly.
> 
> What *would* you people who can read all this stuff *expect* to happen?
> 
> On 4/20/20 3:57 PM, Marcus Daniels wrote:
> > As a ballpark the receptor binding domain is 211 residues, so 20^211, however only a small part of it seems to be actively evolving. [1]  (see Table 1)
> > 
> > https://www.biorxiv.org/content/10.1101/2020.03.10.986398v1 <https://www.biorxiv.org/content/10.1101/2020.03.10.986398v1>
> > 
> > *From: *Friam <friam-bounces at redfish.com <mailto:friam-bounces at redfish.com>> on behalf of David Eric Smith <desmith at santafe.edu <mailto:desmith at santafe.edu>>
> > *Reply-To: *The Friday Morning Applied Complexity Coffee Group <friam at redfish.com <mailto:friam at redfish.com>>
> > *Date: *Monday, April 20, 2020 at 3:49 PM
> > *To: *The Friday Morning Applied Complexity Coffee Group <friam at redfish.com <mailto:friam at redfish.com>>
> > *Subject: *Re: [FRIAM] whackadoodles go mainstream!
> > 
> >     https://www.nature.com/articles/s41591-020-0820-9?fbclid=IwAR1vyx1SqreXoeVgFVKBIayEWGOgZn5IbXmx3-V4nsrWiIlrYvYHQW2TuLA <https://www.nature.com/articles/s41591-020-0820-9?fbclid=IwAR1vyx1SqreXoeVgFVKBIayEWGOgZn5IbXmx3-V4nsrWiIlrYvYHQW2TuLA> 
> > 
> > There is discussion in here about the kind of mosaic it is, and the nearest identified variants for different parts.  I find this interesting as a question in evolutionary dynamics of either convergence or recombination.  The question of how “hard” an engineering problem it is to find non-local optimizers for various biding problems if you happen not to have templates in the same basin of attraction is an interesting question to me in methods of protein biochemistry.  The question of what level of sophistication we currently imagine is in use around the world is a potentially interesting question of sophistication versus availability of method, also practical if one works in threat defenses.
> 
> -- 
> ☣ uǝlƃ
> 
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