Posts

Astrobiology IV: Photosynthesis and energy 2016-10-17T00:30:46.138Z
Astrobiology III: Why Earth? 2016-10-04T21:59:57.716Z
Astrobiology, Astronomy, and the Fermi Paradox II: Space & Time Revisited 2016-03-10T05:19:29.263Z
Astronomy, Astrobiology, & The Fermi Paradox I: Introductions, and Space & Time 2015-07-26T07:38:53.498Z
Irrationality Game III 2014-03-12T13:51:00.555Z

Comments

Comment by cellbioguy on Prediction: The Defense Department Will Blame Trump for the Slow Response on Jan. 7, 2021 · 2021-01-11T04:23:59.805Z · LW · GW

There is also the fact that the top of the DOD was stuffed with loyalists in the immediate aftermath of the election and it would be in the president's perceived interest to allow a mob to scare the crap out of or harm the legislature at that time.

Comment by cellbioguy on New SARS-CoV-2 variant · 2020-12-21T20:57:33.569Z · LW · GW

Yeah I was going with my quick and dirty numbers from earlier.  Way I see it what's probably happening is that doubling time for Britain as a whole has been ~2 weeks both about a month ago and recently (eyeballing graph from worldometer), and you are probably talking about a new doubling time of ~1 week for this variant under identical conditions.

Redoing math for a two week starting doubling time and the stated change in doubling time you get a R value going from ~1.25 to just under or circa 1.5, so basically similar order.

News sources do not use precise language, and precise language matters here.

Comment by cellbioguy on New SARS-CoV-2 variant · 2020-12-21T20:41:54.977Z · LW · GW

Taking an effective R value from ~1.2  to ~1.8 would WAY more than double the growth rate.  I really don't think that this makes sense, and that number for an increased R value seems like it should be referring to the unmitigated R0 value that is then reduced by behavioral interventions.

EDIT: doubling time would go from 17 days to 4 days (!) with the above change of numbers. This doesn't fit given what is currently observed.

An R0 going up by ~0.4-0.9  also fits well with my imputation of a ~15% increase in infectiousness, as estimates of an unmitigated R0 range from circa 3 to 5.

I think this is what happens when people don't show their work.

Comment by cellbioguy on New SARS-CoV-2 variant · 2020-12-21T19:18:26.501Z · LW · GW

The spectrum and rate of excess mutations (assuming they all came in one step) is similar to what has been recorded elsewhere in immunocompromised people chronically infected for a month or two straight, in which there's more time for multiple lineages to coexist in the same body and compete with selection against each other and a longer time with high viral numbers without transmission bottlenecks.

Comment by cellbioguy on New SARS-CoV-2 variant · 2020-12-21T05:21:15.556Z · LW · GW

I've become enough of an arrogant SOB evolutionary biologist poking his nose where it doesn't belong over the last year that I believe I have answers to all of these, and a few other important things to say.  WHILE MAKING IT CLEAR I AM NOT A VIROLOGIST OR IMMUNOLOGIST OR EPIDEMIOLOGIST AND THAT I COULD EAT MY WORDS IN THE FUTURE, though I have been pretty good so far.

How likely is it that the spread of this new strain was caused by a few superspreaders, and that most of the above is blown out of proportion

That would make sense if the frequency was rising in early introductions or when spread was thin on the ground.  Increasing fraction of the total infections while spread is already thick makes me think that there is more likely to actually be an actual effect on contagiousness.  They report a decent detectable increase in genome copy number as measured by PCR and sequencing in upper respiratory samples which makes me think this is likely.  More on the virology later.

What, uh, does the "71% higher growth rate" mean

TLDR: I think that it's probably barely 15% more infectious and the math of spread near equilibrium amplifies things.

I admit that I have not read all available  documents in detail, but I presume that what they said means something like "if ancestor has a doubling time of X, then variant is estimated as having a doubling time of X/(1+0.71) = 0.58X"

This can only be related to a parameter like R0 in relation to how much R0 has already been reduced by behavior changes to its effective actual R since the math gets really nonlinear and I presume I am either missing their math or there will be more detailed documentation in the future.  In the mean time let's run through an example.

I have seen estimates of 'generation times' for SARS-2 clustering around 5 days in the presence of all the stacked up behavior changes.  Doubling time is related to the generation time and the effective replication number Re, by the equation:

doubling time = ln(2) * generation time / (Re-1)

If you have reduced the Re to 1.1 with a 5 day generation time then you get a doubling time of 35 days.  If you have reduced it to 1.2 then you get a doubling time of 17 days.  In the former case, if you take 35 days to 0.58*35 = 20.1 days, you get Re going from 1.1 to 1.172, only 7% higher infectiousness.  In the latter case, if you take 17 days to 10 days, you get Re going from 1.2 to 1.34, a 12% increase.  Presumably the base R0 increases by a similar factor.

In short, the closer you are to equilibrium when measuring the effect the larger the effect a small change in contagiousness will have.  Given that compared to unmitigated situations we are pretty close to Re=1 and I never see cases doubling recently in Britain in less than two weeks, I doubt that the total factor of increase of infectiousness is actually all that large.  You get a huge nonlinear effect as you move the numbers around near one, even when the total factor of increase is not huge, but mitigation increasing by only a small factor can counteract it.

Prepared to eat this, hard, if I am misinterpreting what has been said.

Is there any reason to suspect this new strain might have an impact on vaccination plans? Are the currently approved vaccines (pick a country of choice to decide what this means) possibly better/worse/other against this strain?

It is almost certain that the vaccines (all of which present exactly the same piece of the virus to the immune system) work a bit less well on this variant, but at the same time I think it changes absolutely nothing important of substance for the near future.

For now, ignore EVERYTHING except the spike protein.  This lineage bears several mutations in this gene, responsible for fusing the virus to target cells and the main target of antibody responses (and a good fraction but not all of the T cell response).  They are, separated thematically:

deletion 69–70
deletion 144


 N501Y
A570D


D614G
P681H
T716I
S982A
D1118H

Deletion 69-70 and deletion 144 are in what's called the N-terminal domain.  This is not quite the business end of the spike but is near to it and is involved in invasion to some degree via mechanisms that are not well understood.  The double deletion has appeared independently several times, and seems to be helpful in becoming more invasive to human cells to some degree and also may help escape a subset of antibodies possibly as a side effect. Bit of a loooong story there I won't quite get into here.  Anyway, these are in a domain that constitutes about 20% of human neutralizing antibodies and are quite possibly somewhat immunologically relevant.

N501Y& and A570D are particularly interesting because they are in the receptor binding domain that actually sticks to ACE2.  In particular, N501Y has already been identified as a mutation that increases the strength of binding to the ACE2 receptor.  It also functions as a known escape mutation, and the other one could as well.

An escape mutation is a mutation that causes a subset of antibodies functional against the ancestor to become inert.  However, vertebrate immune systems generate a small quantity of a large number of antibodies against their targets, so generally speaking when an escape mutant comes along there are other antibodies around to take up the slack.

I  have seen papers exposing large numbers of recovered human serum samples against various escape mutations.  When one at a time was presented, only the weakest ~7% of responses (presumably consisting of the fewest antibody types) were affected at all and only a subset of those dropped below likely having an effect.  When two escape mutations were added, it went up to about 20%, still biased strongly towards the weaker responses.  But again, not all those responses dropped to zero, some just got weaker.  Of note, natural responses to the virus vary in strength by a factor of TWO HUNDRED, and a weak response is very different from a strong response.

I would expect that each escape mutation you add makes the fraction of responses that have a problem go up, and the size of the problem to go up.  We are talking 2-4 escape mutations here, so there is likely some immunological impact.

D614G is one of the first mutations  in the history of this virus from January and is likely associated with a mild increase in contagiousness to humans, via a slight change in the geometry of the trimer that is completely immunologically irrelevant.  

The rest of the mutations are in parts of the spike that are a lot less likely to be immunologically relevant, even if maybe one or two of them changes something about the arrangement of the three spike monomers  in the trimer that could theoreticaly affect binding or synergize with others to affect binding efficacy or shedding of the S1 domain from the protein or any number of other things, but dont necessarily and a bunch of them are probably just silent.

Given the sheer strength of responses created by immunization so far, as strong or even stronger than the very strongest natural responses, I find myself doubting that even multiple escape mutations will be able to break through the response to the vaccines.  I would presume they would make the speed with which immunization immunity decays increase, and mean that fewer additional mutations on top of this base would be needed to properly evade it.

But we will have do deal with this anyway!  It is now known that the human coronaviruses do evolve on a timescale of circa a decade to be able to escape previous antibody responses, we just constantly get exposed to these  new changes as they barely break through into us.  Over a timescale of somewhere in the single digit years, I would presume that this virus would evolve to escape immunity be it natural or vaccinated.  And there is a hell of a difference between getting infected when you are completely naive and have never seen anything like it, and when you just barely can be broken through into and you are still generating antibodies and T cells that both are still reactive, even if it can slip past well enough.  A vaccination rolled out to prevent this first burn through a naive population is vital, and we will see if we can keep ahead of eventual evolution with later boosters or if we just live in equilibrium with another respiratory virus which will not be like the current situation.

*****

This is where I nerd out randomly on something else.  Almost nobody is commenting on the fact that this lineage also contains a nonsense mutation in ORF8!  

ORF8, the 8th identifiable reading frame in the genome, is one of the several tricksy accessory proteins that the virus uses to subvert and confuse the adaptive and innate immune system both - in particular, it gums up the MHC complex that body cells use to present viral protein fragments to the adaptive immune system, both to train it upon first exposure and to tag a cell for destruction by eventual trained T cells.  This and other accessory proteins are almost certainly a large fraction of why this disease is so immunologically weird and causing such messed up immune responses in severe cases.

A nonsense mutation is a mutation that turns one of the codons that codes for an amino acid into a STOP sign, preventing the production of everything downstream of that position in the protein.  This nonsense mutation is practically right at the beginning of the protein, so functionally speaking it is obliterated.

This protein has, in the various lineages around the world, accumulated less impactful mutations at a faster rate than almost any other position in the genome, indicating that it is not under a lot of selective pressure to be maintained.  The accessory proteins are probably needed to replicate in bats, whose immune systems are tuned  differently than ours - their antiviral interferon responses are on a freaking hair trigger and their inflammatory responses are damped incredibly low.  They are probably a lot less necessary in other mammals.  A similar protein literally fell to pieces over the course of the first SARS outbreak twenty years ago, and multiple lineages have been seen with big deletions in this gene over the course of the SARS-2 outbreak but none of them became particularly common, and indeed several are basically confirmed to have died out entirely.

If NOTHING else, this lineage proves that the loss of the tricky accessory proteins is not a death sentence for the virus and the possibility of them being lost over time in the future remains.  This may be a mechanism of eventual self-attenuation, if previous research in Singapore indicating that the ORF8-deleted lineages were significantly less likely to send people to hospitals pans out (there was not enough research for me to be confident of this buty there were some reports that really need to be followed up on).  It is possible that this utterly broken ORF8 basically 'hitchhiked' alongside the spike protein changes that are likely responsible for increased transmissibilty, even if it is mildly harmful to the virus.  This virus does not seem to be doing recombination in the human population, so such evolutionary hitchhiking can become an important force.

Comment by cellbioguy on How long till Inverse AlphaFold? · 2020-12-18T03:24:22.336Z · LW · GW

From what I understand the pipeline depends strongly on homology to existing proteins that have determined structures to use substitution correlations to create an interaction graph which it then allows to evolve via learned rules.

I strongly suspect that as such it will not be very good at orphans without significant homology, be it sequence to structure or the reverse.

Comment by cellbioguy on Some things I’m looking forward to in 2021: probable post-pandemic edition · 2020-12-18T03:18:01.254Z · LW · GW

Seeing my long distance boyfriend who is an ICU nurse

Not being in the lab nocturnally

The gym

More literature search time into evolutionary biology and SETI rather than immunology

Comment by cellbioguy on On the stagnation of energy technology and the Cabal of Scientists · 2020-12-17T18:37:33.386Z · LW · GW

Watts per unit of infrastructure machinery necessary, including ancillary things not in the actual engine.  Not joules per unit fuel.

Comment by cellbioguy on On the stagnation of energy technology and the Cabal of Scientists · 2020-12-14T04:35:39.390Z · LW · GW

Or, fossil fuels provide the greatest energy flux per unit infrastructure of any option in the whole past and future of humanity and are as good as it gets and until they run low there is no reason to use anything else.

Comment by cellbioguy on Pre-Hindsight Prompt: Why did 2021 NOT bring a return to normalcy? · 2020-12-07T18:35:47.844Z · LW · GW

Low grade smouldering domestic insurgency instigated by the de facto Shadow President In Exile.

Rural hospitals continuing to be overwhelmed after urban hospitals as vaccination is not taken up sufficiently in rural areas (see the rates of flu vaccination in urban versus rural areas)

Comment by cellbioguy on [Linkpost] AlphaFold: a solution to a 50-year-old grand challenge in biology · 2020-12-05T21:03:34.845Z · LW · GW

See this writeup

 

https://www.blopig.com/blog/2020/12/casp14-what-google-deepminds-alphafold-2-really-achieved-and-what-it-means-for-protein-folding-biology-and-bioinformatics/

Comment by cellbioguy on Covid 12/3: Land of Confusion · 2020-12-03T19:33:14.745Z · LW · GW

The ascertainment ratio right now seems very clearly a little under 1/3 consistent with Covid-19 projections.  We know that the infection to death ratio is about 0.7% to 1% for a population like the US from numerous studies of closely followed populations.  The lagged IFR is about 3%.  Close enough to 3 point something.

 

I am also pretty sure that every day of delay is only preventing a few hundred infections right now given the inevitable snafus about getting the vaccine out and that eventually manufacturing rather than jabbing will become the bottleneck, whereas being perceived to rush by the general population will probably decrease the number who actually get it more than that.

Comment by cellbioguy on Covid 12/3: Land of Confusion · 2020-12-03T19:32:08.597Z · LW · GW

The graph here is a weekly average, including several days of the thanksgiving week that basically didn't report half of what was happening.

Comment by cellbioguy on Open & Welcome Thread - December 2020 · 2020-12-01T20:56:18.000Z · LW · GW

My first first-author publication of my postdoc (long delayed by health problems) is now up on a preprint server, with several more incoming in the next few months.

The central thrust of this paper (heavy on theory, light on experiments) ultimately derives from an idea I actually had while talking in the comments here, but fleshed out and made rigorous and all the interesting implications for early evolution of life on Earth I would not have thought of at first worked through.

Hesitant to tie together my professional identity and this account...

Comment by cellbioguy on [Linkpost] AlphaFold: a solution to a 50-year-old grand challenge in biology · 2020-12-01T17:09:27.653Z · LW · GW

I would mostly be thinking of engineering novel proteins.  That field is pretty rudimentary (though the work of Michael Hecht at Princeton fascinates me).

Comment by cellbioguy on What is “protein folding”? A brief explanation · 2020-12-01T17:06:14.055Z · LW · GW

When you remove membrane proteins from the membrane without great care, they tend to either aggregate into amorphous hydrophobic goo which is impossible to measure well, or take on a shape that is not the shape they ordinarily take in this new different context.

Comment by cellbioguy on What is “protein folding”? A brief explanation · 2020-12-01T07:33:00.250Z · LW · GW

I very much look forward to analysis of this model, since what it is 'seeing' probably tells you something about that which is conserved that is deeper than sequence over very long evolutionary time scales.

Comment by cellbioguy on [Linkpost] AlphaFold: a solution to a 50-year-old grand challenge in biology · 2020-11-30T18:31:49.661Z · LW · GW

I can't wait to see how it works when you apply it to orphan proteins that don't have any evolutionary relatives in the training dataset.  At least some of this efficacy probably comes from effectively encoding an ability to see very deep evolutionary homology hidden in sequences, and variations around ancient motifs.

I also wonder if the system can be reversed, such that you give it a 3-dimensional backbone arrangement and it dreams up a sequence to fold into it.

 

EDIT:  See this writeup https://www.blopig.com/blog/2020/12/casp14-what-google-deepminds-alphafold-2-really-achieved-and-what-it-means-for-protein-folding-biology-and-bioinformatics/

Comment by cellbioguy on Why are young, healthy people eager to take the Covid-19 vaccine? · 2020-11-24T07:20:49.298Z · LW · GW

One 35 year old friend of mine was on oxygen for four months and out of work for six months.

Another's (31) autonomic nervous system is fried and needs to be on vasoconstrictor drugs so she does not faint every time she stands up.

Four more in their thirties fought it off like a horrible flu plus smell issues.

There is evidence that the immunity provided by the RNA vaccines is stronger and possibly more reliable than that produced by natural infection for 3/4 of the population.

There is evidence of very weird and interesting infection of cardiac cells early in infection with implications that are not understood and might have interesting effects forty years down the line.  Precautionary.

I also do not want to spread to people around me who are unvaccinated.

 

On another note, I remain flabbergasted and angry that very little research is going on in Europe and America about indomethacin and ivermectin.

Comment by cellbioguy on What risks from vaccines? · 2020-11-20T06:44:21.691Z · LW · GW

I've heard talk of an intermediate step of amplifying the relevant part of the plasmid up a couple trillion times via PCR to make purification easier, such that there's less material from the original bacteria present per unit DNA and hitting your stringent composition targets is easier.

Comment by cellbioguy on Covid 11/19: Don’t Do Stupid Things · 2020-11-20T06:18:07.264Z · LW · GW

Deaths are highly correlated with cases 21 days earlier.  When cases are rising precipitously, it temporarily decreases the naive CFR.  When you take into account that lag, the apparent CFR of documented cases has been a remarkably flat about 2-3% since the summer.

Comment by cellbioguy on Covid 11/19: Don’t Do Stupid Things · 2020-11-20T06:16:59.783Z · LW · GW

It was a rapid antigen test, which does have a very high rate of false negatives.  Depending on these tests without any barriers or isolation is how you got rolling White House outbreaks.

Comment by cellbioguy on Covid 11/19: Don’t Do Stupid Things · 2020-11-20T06:16:05.878Z · LW · GW

The next two vaccines that will get approved (1-2 months after the first ones) are themselves adenoviruses!

Comment by cellbioguy on What risks from vaccines? · 2020-11-16T04:07:42.888Z · LW · GW

There was a little of this from an early measles vaccine, where a small percentage of people who got it became extra sensitive to adult measles years down the line.  They revaccinated everybody who got that one with the newer, better one and it's been fine ever since.

Given that all vaccine candidates that are close to roll-out more closely replicate a viral infection than that one did, I am not terribly worried, and I will take that as a future possibility to watch for and possibly need to get revaccinated for over the known risks of getting infected and spreading it to vulnerable people.

Comment by cellbioguy on Covid 11/12: The Winds of Winter · 2020-11-14T04:03:07.495Z · LW · GW

It also sounds like a massive misinterpretation of what was said...

Comment by cellbioguy on Covid 11/12: The Winds of Winter · 2020-11-14T04:02:36.009Z · LW · GW

The rate of death is roughly proportional to the rate of natual death at a person's age, yes - but you MASSIVELY increase your rate of death when you get it.  

Comment by cellbioguy on Does BioNtech's vaccine result of 90% disease prevention mean that 90% of the vaccinated can't pass the virus to other people? · 2020-11-11T04:05:18.412Z · LW · GW

This being said, the challenge the monkeys were given was a massive dose of virus that is probably a good deal more than a human is ever likely to see.  Also, you can have replication without having as much competent virus, especially if free virions are being neutralized via antibodies.

Comment by cellbioguy on Covid 'Mink variant' · 2020-11-10T18:11:24.360Z · LW · GW

The data is finally available!

https://files.ssi.dk/Mink-cluster-5-short-report_AFO2

Analysis later, when I have time to read in detail.

Comment by cellbioguy on Does BioNtech's vaccine result of 90% disease prevention mean that 90% of the vaccinated can't pass the virus to other people? · 2020-11-10T17:55:40.014Z · LW · GW

That isn't an endpoint that this study is able to determine at this point, sadly.  The people were not being tested for RNA regularly, only if they became ill or concerned they were infected.

In about six months, we will know better - study participants are being tested for nucleocapsid antibodies every few months.  The vaccine does not contain the nucleocapsid protein, so nucleocapsid antibodies (which are utterly irrelevant to infection control) would indicate an actual infection.  If they don't get infected they can't spread it - but I will bet you ANYTHING that those who DO get infected are at least less infectious.

Comment by cellbioguy on Covid 'Mink variant' · 2020-11-07T07:32:14.307Z · LW · GW

This is where I stick my neck out and make a bold claim, thinking I am unlikely to be wrong despite very much NOT being an immunologist:

I am not worried and I think they're overreacting, which in the pandemic business is a GOOD thing and in the long run obliterating human contact with explosively susceptible animal reservoirs is a VERY good thing and I am glad they are doing this, but still.

Okay, here we go:

The so called 'mink strains' bear the following mutations in the spike protein:
D614G, just like the whole rest of the world at this point.
Y453F
I692V
M1229I
H69 deletion
V70 deletion

They are interested because this is an unusually large number of mutations to appear in the spike in a short period of time.  Let's look at them

I692V and M1229I are nowhere near the part of the spike where most important antibodies that can neutralize the thing are.  Could change the stability of the trimer or the S1/S2 boundary and thus the behavior/binding, maybe theoretically if they're just right, but I'm calling them as less likely to be immunologically relevant.  They're also not looking like HUGELY disruptive mutations in terms of changes to amno acid properties, maybe.

H69/V70 are in what's called the "n-terminal domain" at the start of the gene.  This domain is up near but not quite at the business end of the spike.  It is not the part that binds ACE2, but is right next door to it.  It is involved in invasion to some degree, and seems to bind to cell-surface sugars a bit while not being the strongest binding thing.  Some other viruses have this domain as their main binding domain but not this one.  About 20% of human neutralizing antibodies are directed against this domain.  Could be slightly immunologically relevant, or could be an adaptation to hit the mink better.

Y453F is actually quite interesting.  This one is in the receptor binding domain and is probably an adaptation to bind the mink or human ACE2 better.  It is also a known 'immune escape' mutant.  DO NOT PANIC at that name.

I will use another, better characterized immune escape mutant to illustrate what this means.  

https://www.biorxiv.org/content/10.1101/2020.11.04.355842v1

There is a mutation circulating in other European strains, N439K.  This one came about as an adaptation to better fit the human ACE2 protein, and has a mildly better binding affinity to the human receptor than the original.  It also is in the receptor binding domain.  Since most neutralizing antibodies attack the receptor binding domain, this renders a subset of antibodies generated against the RBD less effective - in particular, one of the two monoclonal antibodies in the Regeneron cocktail that the president got is rendered completely inert!

Thankfully, and for good evolutionary reason, vertebrate immune systems don't make huge amounts of one or two antibodies against something, they make small amounts of a diverse array of antibodies.  So when an escape mutant of something that's as large a target as this comes along, there's usually other antibodies around that are unaffected by it.  Researchers exposed the serum of hundreds of recovered patients to the original spike and this mutant spike.  They found that most people (~80%) didn't have an appreciable difference in the amount of antibody binding that occurred.  About 7% of the population had the binding ability of their antibodies decline by at least a factor of two, some down by a factor of sixteen - but these were almost exclusively people who mounted a very weak response to begin with, probably because they didn't make many different types.  So a subset of people who already mounted a weak response had their response rendered weaker by this escape mutant.

I should note that all the vaccines in phase three trials are generating immune reactions at least as strong as the strongest convalescent patients did, and some are up in the 2-3x as strong range.

Escape mutants will come along, but the fact that it's been a year and we are only just starting to see weak escape mutants tells me that this is gonna happen WAY slower than flu.

-----

So, they saw a spike protein in this secondary zoonotic strain with many mutations, and there is word that they tested it against monoclonal antibodies and it escapes a number of them.  Word floating around on virology twitter pre-publication is that upon exposure to actual patient serum, it again weakens response for some but is still very well neutralized by most.  I suspect they are being paranoid about a spike with multiple mutations being out there as as base for further evolution, and don't want more events like this happening in the future in this highly susceptible animal reservoir.  Could be that that deletion in the N-terminal domain is immunologically relevant even though that domain is less relevant than the receptor binding domain most of the time and thus that there's a double-escape floating around now.

I VERY much look forward to the actual publication of actual results.  And am prepared to eat my words.

 

EDIT:  The data is finally available!

https://files.ssi.dk/Mink-cluster-5-short-report_AFO2

Comment by cellbioguy on What is our true life expectancy? · 2020-11-07T07:06:06.490Z · LW · GW

Basically yes.  Though I suspect the ultimate form would probably be more like 'completely flat until 90ish then just kicking in with a consistent half life from then onwards'.

Comment by cellbioguy on Covid Covid Covid Covid Covid 10/29: All We Ever Talk About · 2020-11-07T07:04:34.782Z · LW · GW

This is what 'public goods' with strong positive externalities provided by governments paying the vaccine companies are for.

Comment by cellbioguy on Non Polemic: How do you personally deal with "irrational" people? · 2020-11-03T07:18:59.535Z · LW · GW

"When you think about it, because of the way evolution works, humans are probably hovering right around the bare-minimal level of rationality and intelligence needed to build and sustain civilization. Otherwise, civilization would have happened earlier,"

I actually profoundly disagree with this both empirically and theoretically.

Civilizations are not some kind of natural inevitable 'next step' that must happen when you have a smart animal.  They are a thing that CAN happen in the context of a smart animal that is capable of inventing agriculture.  But there are other prerequisites.

I find the argument that complex culture is a thing that can happen in dense enough human populations, running away as it further densifies the population, persuasive.  The idea is that in a low density human population ideas sometimes fail to percolate down the generations, while in a dense enough social network innovations stick down the generations more frequently because losses are less likely.  It is possible that you can reach a 'tipping point' in a dense enough population at which point the ability to pass on new innovations allows a denser population still and further accumulation of complex culture.

There is a bit of a case study in Tasmania.  The native Tasmanian population had continuity with the aboriginal Australian population before the end of the ice age, when the two landmasses were united.  Ten thousand years later, upon European contact, the Aboriginal Australians maintained oral culture of events and places tens of thousands of years back, and had kept and expanded upon the toolset that existed in the united landmass... while the Tasmanians, with a smaller social network and a less dense population on that land, had lost large numbers of tools and skills including the ability to produce fire de novo (while still being able to propagate it).  

I think Neanderthals are also likely evidence pointing in this direction.  Their brains were more or less the same size as ours, and they had a common ancestor a full 500,000 years ago with us.  But they lived in the frozen wastes of ice age Europe, in small isolated subpopulations if the homozygosity of the neanderthal paleogenomes is to be believed, with LOTS of small subpopulation bottlenecks.  That's a perfect recipe for repeatedly losing your complex material culture down the generations.

Empirically, human brain size has also been on a downtrend for the past fifteen thousand years as agriculture and civilization has spread.  It is a simpler environment with fewer complex things you need to interact with on their own terms and significantly worse nutrition, so we give up some small fraction of our highly expensive intelligence over long periods of time.

Comment by cellbioguy on Covid Covid Covid Covid Covid 10/29: All We Ever Talk About · 2020-11-01T20:17:31.427Z · LW · GW

Qatar is believed to have reached more than half infected.  Their median age is 30, however, which significantly mitigates the associated morbidity and mortality, as does the over 60 population being 2% of them compared to like 10% of the United States.

https://www.medrxiv.org/content/10.1101/2020.08.24.20179457v2

Same research finds only ~50 probable reinfections in a cohort of hundreds of thousands of followed individuals and all but one non-hospitalized and that one only out of caution.  

Comment by cellbioguy on Covid Covid Covid Covid Covid 10/29: All We Ever Talk About · 2020-11-01T20:14:48.676Z · LW · GW

Also, my boyfriend is an ICU nurse on the covid ward in a Southern state.  He says average ICU stays are half as long now but that the average ICU patient is younger, so take that for what it's worth.

Comment by cellbioguy on Covid Covid Covid Covid Covid 10/29: All We Ever Talk About · 2020-11-01T04:52:06.998Z · LW · GW

>We certainly are not going to allocate a scarce valuable resource according to ability to pay. That’s crazy talk.

Indeed, when talking about a vaccine that is crazy.

Comment by cellbioguy on Covid Covid Covid Covid Covid 10/29: All We Ever Talk About · 2020-11-01T03:48:48.321Z · LW · GW

There are small nations that have reached 60% infection...

Comment by cellbioguy on Covid Covid Covid Covid Covid 10/29: All We Ever Talk About · 2020-11-01T03:48:14.169Z · LW · GW

The numbers I have seen are suggesting that it's lower but only by say 30%?

Comment by cellbioguy on Covid Covid Covid Covid Covid 10/29: All We Ever Talk About · 2020-11-01T03:45:37.734Z · LW · GW

Trials of several of the adenoviral vectored vaccines for nasal inhalation have already begun.

Comment by cellbioguy on What is our true life expectancy? · 2020-10-25T04:53:38.760Z · LW · GW

So, I completely discount all the AGI stuff that so many here hang their hats on.

I similarly am pretty damn sure that there will be no silver bullet magic anti-aging in our future.

I am not involved in aging research so take this as the words of a vaguely interested amateur.

That being said, I noticed something interesting when I was playing with actuarial data a few years ago.  I downloaded a dataset of life expectancy at every age for every year since 1950 in the United States.  I was playing with it, looking for patterns, and I decided to plot life remaining at every age in 1970 versus life remaining at every age in 2000, and a striking pattern emerged.  

It was a remarkably straight line with a slope that was not one.  Life expectancy at every age had gone up, but it had gone up more at younger age than older age in a very consistent pattern.  I played with the data on more axes and the line crossed the 1:1 line of life expectancy equal to current age at approximately age 95, indicating relative lack of improvement above that age.  (I realize this description is a bit roundabout and hard to visualize and weird, but it is how I noticed the relationship.  I should really dig up these graphs again...)

I repeated this with other pairs of years.  Every time I did this with two years after ~1950, it produced a similar straight line, passing through the 1:1 line at age 95, only varying in the slope. 

As the years have gone  on, life expectancy at younger ages than 95 has continued to increase (at an ever slowing rate!), but life expectancy at older ages has not kept pace with those at younger, and the pattern is very consistent.

I don't have the graphs or spreadsheet or equations I did available right now, but what I ended up interpreting this as indicating is a progressive rectangularization of the mortality curve.  Rather than people dropping off at all ages over time, more and more of the mortality is being concentrated in a particular age band in a very consistent way for the past seventy years.  If the pattern were taken to its extreme conclusion, it would mean everyone having a life expectancy of reaching age 95 at all ages, and dropping off right then pretty reliably.

Comment by cellbioguy on Covid 9/3: Meet the New CDC · 2020-09-06T05:14:03.063Z · LW · GW

Housing prices are only partially controlled by supply and demand for HOUSING. They have been financialized into speculative assets to a ridiculous extreme that is highly destructive to their primary function. The price is driven up by investors which have access to huge amounts of freshly created money loaned into existence, such that as long as there is the expectation that the price can go up, speculative demand is almost literally infinite and prices are driven above the ability of those who need housing and lack access to that sort of financing to pay. The situation is highly untenable in the long term.

Comment by cellbioguy on Covid 9/3: Meet the New CDC · 2020-09-06T05:11:53.410Z · LW · GW

Currently living in the South, I can tell you that most states here are not actually responding to their situations and are ideologically incapable of doing so.

Comment by cellbioguy on Open & Welcome Thread - August 2020 · 2020-08-25T18:42:40.331Z · LW · GW

And now two more in Europe, both of which are reportedly mild and one reportedly in an older immunocompromised patient.

This will happen. Remains to be seen if these are weird outliers only visible because people are casting a wide net and looking for the weirdos, or if it will be the rule.

However, the initial surge through a naive population will always be much worse than the situation once most of the population has at least some immune memory.

Comment by cellbioguy on Money creation and debt · 2020-08-15T01:36:40.928Z · LW · GW

Correct. Keep in mind that private banks ALSO create money whenever they lend money out too. Then the asset and the liability are both contained within the private sector.


In the absence of sufficient federal deficits that make their way spent into general circulation, the private sector is obliged to become perpetually more indebted to the banking subsector. Welcome to the last forty years.

Comment by cellbioguy on What's the evidence on falling testosteron and sperm counts in men? · 2020-08-12T18:11:10.189Z · LW · GW

You will run across many orders of magnitude more plastic lechate, pesticide, and herbicide than you will of pharmaceutical estrogens unless you are taking them. They don't even double the quantity excreted by women taking them as contraceptives, so the main exposure route is barely affected.

Comment by cellbioguy on What's the evidence on falling testosteron and sperm counts in men? · 2020-08-10T20:11:28.763Z · LW · GW

I STRONGLY suspect it has a lot to do with xenoestrogen and endocrine disruption effects from plastic and rampant pesticide/herbicide use.

Comment by cellbioguy on What is filling the hole left by religion? · 2020-08-09T02:38:18.009Z · LW · GW

So-called 'civil religions'. They are manifold and varied and spring up repeatedly across history. Now is no different.

Old-school 19th century nationalism flared as the Christian religion began really losing its grip. Modern political mythologies hinging on national/ethnic/party purity or personality cults or idealizing moral progress have similar roots today.

Marxism was blatantly postmillennial Christian eschatology with the nouns swapped out, and a grand purpose presented for the faithful. Ayn-Randian fantasy is the satanist-equivalent inversion of this religion, uncritically accepting its flawed framework of the way the world works while inverting the value judgements in a way that very much does not lead to anything more functional.

Singulatarianism is similarly a blatant rehash of Christian eschatology, doctrines of redemption form original sin, and afterlife mythology, with different currents within it with isomorphisms to different schools of thought within Christianity. It is of course a far more niche interest than any of the aforementioned civil religions. Softer versions of talking about the Grand Destiny of Humanity Among the Stars are also related and more common.

Eventually all civil religions fail as they are limited by the rigors of the physical world and fail to provide the transcendence contained within mundane history they implicitly promise in the absence of more explicitly theological religions, which have more long-term staying power.

Comment by cellbioguy on New Paper on Herd Immunity Thresholds · 2020-07-31T07:31:57.713Z · LW · GW

There are neighborhoods in Indian cities that are already over 60%.

This doesn't empirically hold up.

Comment by cellbioguy on What is the current state of knowledge around COVID-19 at-home remedies? · 2020-07-27T04:33:09.250Z · LW · GW

Unfortunately this is not a direction I have done a lot of looking, sorry.

Comment by cellbioguy on What is the current state of knowledge around COVID-19 at-home remedies? · 2020-07-27T04:24:54.178Z · LW · GW

Apparently I am still consistently a month or two ahead of the curve.


https://www.sciencedirect.com/science/article/pii/S0306987720314973

https://www.sciencedirect.com/science/article/pii/S1521661620306513