Posts

Astrobiology IV: Photosynthesis and energy 2016-10-17T00:30:46.138Z · score: 9 (11 votes)
Astrobiology III: Why Earth? 2016-10-04T21:59:57.716Z · score: 18 (18 votes)
Astrobiology, Astronomy, and the Fermi Paradox II: Space & Time Revisited 2016-03-10T05:19:29.263Z · score: 23 (24 votes)
Astronomy, Astrobiology, & The Fermi Paradox I: Introductions, and Space & Time 2015-07-26T07:38:53.498Z · score: 42 (43 votes)
Irrationality Game III 2014-03-12T13:51:00.555Z · score: 11 (18 votes)

Comments

Comment by cellbioguy on Covid 9/3: Meet the New CDC · 2020-09-06T05:14:03.063Z · score: 5 (2 votes) · 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 · score: 2 (3 votes) · 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 · score: 6 (3 votes) · 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 · score: 3 (2 votes) · 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 · score: 4 (3 votes) · 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 · score: 5 (2 votes) · 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 · score: 2 (1 votes) · 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 · score: 5 (3 votes) · 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 · score: 2 (1 votes) · 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 · score: 2 (1 votes) · 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

Comment by cellbioguy on What is the current state of knowledge around COVID-19 at-home remedies? · 2020-07-27T01:30:50.751Z · score: 2 (1 votes) · LW · GW

You can take NAC every day, it's basically an amino acid and acetate joined together in a peptide bond. Some people do take it every day. I would be hesitant taking it for very long times, since there are a few mouse studies in which mice that got a high dose constantly had higher cancer risks, but mice and cancer are a weird combo already and may not be representative. I would up the dose when actively sick.

Indomethacin is a 1960s NSAID that is used less these days because there are slightly safer NSAIDs for most indications - it has several times the rate of causing ulcers compared to advil for example, but I think that's mostly for chronic use rather than short term. They recommend you take it with an antacid, so I would definitely take it with... famotidine, a drug that blocks histamine receptors involved both in stomach acid production AND possibly involved in the inappropriate inflammation that COVID is causing, and which was associated with higher recoveries in some studies. These days I think indomethacin it is mostly used for gout, some types of arthritis, migraines, and some edge cases like helping premature babies rewire their hearts for breathing instead of using a placenta. It's DEFINITELY something you would only take while actively sick, 5-10 days. It's prescription-only in the US, but not exactly 'controlled', it's not like anybody takes it for fun.

Comment by cellbioguy on Covid 7/16: Becoming the Mask · 2020-07-17T14:36:40.020Z · score: 2 (1 votes) · LW · GW

No. It is already known that type O people are at lower risk of disease, with higher risk to type B then higher still to type A then highest to type AB, and that when you do a GWAS study for associations with disease the ABO locus is one of exactly two loci that fall out as very important. The question is, is that due to some intrinsic degree of resistance to disease brought on by the ABO locus or is it due to this sort of transmission incompatibility? To know you need to figure out actual pairs of people you know transmitted to each other and see if particular pairwise patterns of blood types are more likely than others (which has never been done), and test the virions themselves to see that they can be neutralized by anti ABO antibody levels that you find in mucous membranes (though this is highly likely given previous work on other viruses).

Comment by cellbioguy on Covid 7/16: Becoming the Mask · 2020-07-17T05:28:12.314Z · score: 7 (4 votes) · LW · GW

Important to note that the author suggests that the best fit from observed blood type disease risk differences to a model like this would indicate that getting a virus from someone with an incompatible blood type would be about 40% as easy as getting infected from a compatible blood type.

One might be able to make arguments about intra-familial transmission versus extra-familial transmission rates with more math than I have time for right now.

In this model, if you ignore secretion status, type O people would be hardest to infect but most likely to spread. In the US about 45% of the population is type O, about 40% is type A, about 11% is type B, and about 4% is type AB according to the first source I found. You get the following fractions of the population being easy to transmit to and receive from for each blood type:

O - to 100%, from 45%

B - to 15%, from 56%

A - to 44%, from 85%

AB - to 4%, from 100%

If you assume that you are 40% as likely to spread to someone of a noncompatible blood type, you get a ease-of-infecting-others score for each type of: O = 100%, B = 49%, A = 66%, AB = 42%. Assuming you don't know their secretion/nonsecretion status.

If you take into account non-secretors, then this is all slightly wrong and you actually have most non-O people slightly less infectious than that and some people who are A, B, or AB with their usual higher risk of getting infected but who transmit like type O. This is me - I am a type A nonsecretor and thus would be more vulnerable to transmission from a full 85% of the population, while being good at transmitting to 100% of the population. Such individuals might be more likely to be important nodes in the network.

If you look at the paper they show that the biggest result of this kind of an effect on an epidemiological model is that the more diverse the population is in terms of blood types - a more even distribution of A, B, and O - the slower spread happens, and the more homogenous a population is in terms of blood type the faster it happens regardless of which blood type is dominant.

Comment by cellbioguy on Covid 7/16: Becoming the Mask · 2020-07-17T05:11:05.809Z · score: 16 (5 votes) · LW · GW

No, I am talking about actual ABO antigen on actual virus particles, and specifically probably on actual spike protein.

The ABO antigen is not a protein, unlike the Rh antigen (the positive/negative factor - which is not empirically relevant for disease risk unlike ABO). It is a motif of a few sugars hooked together (three particular sugars in a chain for O, and two different branched 4-sugar motifs for A and B) that is used as a component of polysaccharide chains used to decorate proteins via glycosylation. It winds up attached to loads and loads of membrane proteins made by cells. In a nonsecretor it winds up on surface proteins of blood cells and endothelial cells only, in the other 80% of the population it winds up on surface proteins on all cells.

The spike protein is COVERED with glycosylation sites. They are places on the protein that polysaccharide chains defined by the particular enzyme milieu of the cell get added. Like many glycosylated proteins they're rather variable molecule to molecule and not precisely genetically predetermined by the protein sequence, though the protein certainly biases particular types of chains to wind up on particular pieces. In the case of the spike protein, these chains actually significantly help make sure that there's very few places on the protein that an antibody can bind without needing to bind to the sugars, since the sugars are the same sugars that you decorate your own cells with and you thus cannot generate an immune reaction against.

If you look at the references of the paper above, you will see it has been experimentally determined for SARS, measles, and HIV that the ABO antigen winds up decorating the spike/fusion protein and that anti-A antibodies can neutralize particles created in tissue culture that expresses the A antigen. It doesn't neutralize nearly as vigorously as antibodies raised against the protein proper, but a whole lot of the particles get neutralized in in vitro experiments. Presumably they bind to sugar chains near the receptor binding site and just physically block it from being able to touch its receptor.

So, virions made in your own body are effectively cloaked by glycosylation. But if an incoming inoculum includes a bit of glycosylation that you have antibodies against - an incompatible ABO blood type - antibodies might be able to bind to and neutralize a reasonable fraction of incoming viral particles before they are able to infect you and make virions that have your own ABO sugars.

---

I am quite aware that this is only modeling. The feature is that the risk factors of different blood types line up with what you would expect if there was this blood type incompatibility of spread in which getting the virus from someone with an incompatible blood type was only 40% as likely as from someone with a compatible blood type, and that this could explain a component of the extreme dispersion seen in which some people barely spread the disease and some spread it quite freely. Definitely requires in vitro and careful contact tracing work to follow up on and see if the blood type associations are somehow a fluke with a different mechanism.

Comment by cellbioguy on Covid 7/16: Becoming the Mask · 2020-07-16T17:59:03.305Z · score: 16 (7 votes) · LW · GW

Thought I would plug a really fascinating recent preprint. It is entirely a theory paper but it makes sense of several interesting things that have been seen about the fact that type A blood is a risk factor for infection, type O blood is protective, and only a fraction of infected people infect most new people. If you have the ability to read biomedical literature I recommend it wholeheartedly along with all its references.

"Modelling suggests blood group incompatibility may substantially reduce SARS-CoV-2 transmission"

https://www.medrxiv.org/content/10.1101/2020.07.13.20152637v1

Short version: it is possible that transmission of the virus from one person to another is substantially hampered by blood transfusion incompatibility. Type O blood individuals become 'universal viral donors' able to maximally infect most people, while being at substantially lower risk of infection from non-type-O individuals.

It has already been established that HIV, SARS-classic, and measles virions produced in tissue culture from cells expressing the type A antigen can be deactivated by serum containing anti-A antibodies, albeit at a lower rate than using antibodies specifically raised against the viral proteins. The ABO antigen is not a protein, but instead is a polysaccharide that is used to decorate many other proteins. If the viral spike protein incorporates an ABO antigen in its glycosylation it can be bound by antibodies, some of which will neutralize it. This would ONLY affect the incoming viral inoculum, not any virus produced in your own cells.

The data in the paper suggests a risk to type O inviduals of getting the virus from a type A individual of about 40% baseline.

This would also be complicated by 'secretor' status. About 80% of the European population puts the ABO antigen on proteins on all their cells rather than just blood cells, but 20% are 'nonsecretors' who only put it on blood cells. These people would fail to put the ABO antigen onto virions and transmit as if they were type O 'universal donors' but still get infected with heightened risk factors if they have non-O blood type status. This would also imply that the rate of getting infected by someone of an incompatible blood type who was a secretor would actually be only about 20% of baseline.

An implication of this work is that spread should be slower in populations with a greater *diversity* of blood types - a more even mix of A, B, and O - and that superspreaders should preferentially be nonsecretors and type O individuals.

Needs in vitro work and careful contact tracing epidemiology to back it up. But it makes way too much sense...

Comment by cellbioguy on What is the current state of knowledge around COVID-19 at-home remedies? · 2020-07-14T21:53:08.716Z · score: 8 (2 votes) · LW · GW

The big ones I think:

DON'T take dextromethorphan, the substance in a lot of cough syrup. Preliminary untested-in-animals results that it increases viral reproduction in tissue culture.

DO take N-acetyl cysteine (NAC).

Recharges glutathione, one of the primary reducing-agent intermediaries in cells (not involved in energy metabolism).

Several likely good effects. Mucolytic - breaks the disulfide bonds between mucous proteins to make it more fluid. Known to decrease the symptom strength of flu and other respiratory diseases. Believed to reduce pathological clots (while not really being a classic anticoagulant) via changing the disulfide bond status in some of the clotting proteins in capillary walls. Possibly an effect decreasing the amount of NET production by neutrophils in the inappropriate inflammation that's going on here.

Smaller ones:

For the same effect on NET production I also might suggest L-carnosine, there's mouse work to the effect that it reduces immune-mediated lung damage from a wide variety of different insults. Lots of people around here are also fans of niagen, and I would take it while actively sick based entirely on the fact that the virus has enzymes that cleave off NAD-generated tags from proteins as part of its actions against the innate immune system.

Agree with the things listed above.

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On a side note, I am appalled and flabbergasted that there are not multiple clinical trials ongoing for indomethacin, a prescription NSAID. There's in vitro data from SARS classic and SARS-2 that it dramatically suppresses viral replication via triggering the PKR pathway that senses dsRNA and makes ribosomes more selective against viral proteins. There's the fact that it's known to stop the cough that high doses of ACE2-inhibitors cause, suggesting something of the mechanism of this virus triggering cough and inflammation. There's in vivo data in dogs infected by canine enteric coronavirus that twenty four hours into the dose you give people for arthritis there's 1/100 the viral load. And there's anecdotal reports from large numbers of doctors in NYC and India of massive symptom relief in non-hospitalized patients, way above and beyond other NSAIDs.

Also still quite interested in the ivermectin trials when they come out.

Comment by cellbioguy on What is the current process for increases testing? · 2020-07-12T21:19:39.854Z · score: 2 (1 votes) · LW · GW

A crazy, inconsitant patchwork. The end result is that more people with lower amounts of symptoms are getting caught in most places that aren't exploding.

Comment by cellbioguy on Covid-19: Analysis of Mortality Data · 2020-07-12T21:18:26.550Z · score: 2 (1 votes) · LW · GW

Indeed, this was my assumption since April or so. Quantitative evidence is good though.

Comment by cellbioguy on Covid 7/9: Lies, Damn Lies and Death Rates · 2020-07-10T23:52:28.721Z · score: 8 (6 votes) · LW · GW

Oh my god... in the Florida data, the numbers of that 'not elsewhere classified' category are now twice the number of official COVID-coded deaths, and 4x baseline!

This would mean that they are mislabeling two thirds of the deaths. If you add up the excess deaths of that code and the covid deaths, the death rate did not actually decline in that state at all and instead has been in a plateau since April.

Comment by cellbioguy on Covid 7/9: Lies, Damn Lies and Death Rates · 2020-07-10T23:42:28.145Z · score: 2 (1 votes) · LW · GW

Here's a first-principles normalization - take national tests, and normalize the positives to the total number of tests performed. This assumes linear returns to testing which is wrong, but it produces a curve of the shape of ACTUAL infections (without telling you the true number, just its relative shape over time) that mirrors the death curve shifted by two weeks very closely:

https://twitter.com/econstatsnerd/status/1276629941384331264

Comment by cellbioguy on What are your thoughts on rational wiki · 2020-07-10T23:03:51.903Z · score: 7 (7 votes) · LW · GW

I love it.

Comment by cellbioguy on Covid-19 6/18: The Virus Goes South · 2020-06-19T13:53:01.427Z · score: 6 (3 votes) · LW · GW

I can report that at a major southern university we are starting to get plans sent out by administration for a return to in person instruction (!) in mid August (!). They are refusing to mandate masks for students and are planning for way too many in person classes. Another nearby university is forcing faculty to get medical justification for not participating in classrooms.

They've picked their priorities, they'll chew us up and spit us out.

Comment by cellbioguy on If the reproduction number is socially "controlled" to its inflection point 1, what are the ethical and predictive implications? · 2020-06-18T06:28:58.715Z · score: 3 (2 votes) · LW · GW

At first I thought that the soial system implicitly trying to control an exponential with a sensor lag longer than the doubling time would be simply impossible, and there would be wild swings between exploding cases and cratering cases. But then I realized that the dial that is being turned is the doubling time itself, such that near homeostasis the doubling/halving time is extremely long and the delays in the system don't matter as much.


That being said... South Carolina, man. They have entered a new exponential phase with a doubling time of much less than a week and we will get to see quite the excursion. These things still happen when people react faster than the delays in noticing people getting sick.

Comment by cellbioguy on Is a near-term, self-sustaining Mars colony impossible? · 2020-06-05T02:06:03.740Z · score: 5 (3 votes) · LW · GW

You drastically underestimate the difficulty of genetics.

Comment by cellbioguy on Should I self-variolate to COVID-19 · 2020-05-27T05:17:20.462Z · score: 2 (1 votes) · LW · GW

I would be worried about straight up lung, kidney, blood vessel, and heart damage in addition to the already stated chronic fatigue.

Comment by cellbioguy on What aspects of the world emotionally bothers you on an immediate personal level on a daily basis? · 2020-05-24T05:01:10.268Z · score: 6 (4 votes) · LW · GW

The huge amount of unnecessary pesticides around me and the paucity of insect life compared to my childhood. This is a disaster and won't end well.

Comment by cellbioguy on The Greatest Host · 2020-05-12T05:39:01.883Z · score: 7 (4 votes) · LW · GW

Bats sustaining viruses that rip our lungs and blood vessels apart isn't because of population structure, it's because their immune systems are tuned to produce different responses than ours in a way that causes bat viruses to frequently cause messed up responses in other mammals. For reasons that are only just starting to be figured out, their inflammatory responses are turned way the hell down and their interferon responses are turned way the hell up. This means that a virus that has evolved to replicate in them is able to basically completely silence the interferon response of other mammals, being overclocked for the job. If other factors let it actually replicate, this means the early disease goes nearly unnoticed by the innate immune system until viral replication has reached obscene levels and the adaptive immune system becomes involved, in a frequently poorly-regulated response. The viruses are also used to facing a strong innate antiviral response from the start, so they replicate much faster and with more fallout in the absence of that response than one that has reached equilibrium with us would.

---

On another note, the innate immune response of jawed vertebrates has been reshaped by interaction with the adaptive immune response over evolutionary time and cannot be considered in isolation.

Comment by cellbioguy on Nicotinamide riboside and SARS-CoV-2 · 2020-05-10T14:45:41.125Z · score: 2 (1 votes) · LW · GW

To be clear, the work I am speaking of is on enhancing the NAD salvage pathway preventing NAD depletion in stressed neurons. This treatment seems to drastically decrease neuron programmed cell death in response to brain injury, neurodegenerative diseases, and hypoxia.

The mose work showed great promise in brain injury and hypoxia and while it doesn't stop the neurodegeneration from ALS and the like (the underlying damage is being done) the threshold for individual neurons dying is raised, so the mice are healthy for a long time before suddenly falling apart rather than slowly declining.

This is work being done by Calico and by Dr. McKnight. I will provide links when I'm no longer on my phone

Comment by cellbioguy on Nicotinamide riboside and SARS-CoV-2 · 2020-05-06T01:02:15.514Z · score: 3 (2 votes) · LW · GW

There is a whole bunch of work on boosting NAD levels to suppress PARP effects on NAD depletion triggering neuron apoptosis...

Comment by cellbioguy on Nicotinamide riboside and SARS-CoV-2 · 2020-05-05T20:10:34.796Z · score: 5 (3 votes) · LW · GW

I will definitely be having my parents take it if they get sick, and this is just one of the reasons. I can't see how it would hurt acutely and there is a chance it will help acutely.

One of my parents got over cancer 10 years ago though so I am very uncertain about having them take it prophylactically on a chronic basis, especially since they are in a position to very easily nearly completely isolate. Given the biochemistry of NAD supplementation, encouraging nascent tumors to not kill themselves is one of the risks you may take with it.

Comment by cellbioguy on [Link] COVID-19 causing deadly blood clots in younger people · 2020-05-05T19:52:51.464Z · score: 3 (2 votes) · LW · GW

For the most part, all those labels are just labels for where on the tree of all sequences it falls. There is almost no evidence of widespread functional mutants. They're useful for tracking the spread of the virus around the globe.

There is one mutation in the S protein at the root of the European strains that you could *imagine* having an effect on the function of the fusion protein but there is no particularly strong evidence that it's doing much - a little equivocal difference in the measured PCR cycles required for detection from samples, but that could have to do with the fact that they happened at different times when people were getting tested at different disease stages or on different equipment. It is more common more recently relative to the other lineages in Europe and America, but that could very easily just be because it is the only lineage in Italy and once Italy exploded its shrapnel founded a lot of new transmission chains all over Europe and America. It could very easily just be a bottleneck effect having to do with breaking into a new area.

Much more interesting are a few small lineages that have actually lost whole accessory proteins involved in suppressing the innate immune response, but that's a total of like 7 patients found to have them.

Comment by cellbioguy on Should we be reassessing the argument for globalization? · 2020-04-29T16:53:15.338Z · score: 2 (1 votes) · LW · GW

I disagree profoundly with the last sentence.

The process continues when everything is perfect, but shocks undo it. If super-efficiency and super-specialization were optimal, the biosphere would have reached that point long ago.

Instead, everything is robust at the expense of efficiency at multiple levels, from individual cells to networks of ecological interactions. Super-optimized things do evolve, and sometimes spread explosively, but they are almost always shortlived and die out.

Comment by cellbioguy on Should we be reassessing the argument for globalization? · 2020-04-29T00:38:45.604Z · score: 6 (4 votes) · LW · GW

YES.

Smearing supply chains across the world and chasing them to the lowest labor costs and into very specialized locations produces a supply chain that while extremely efficient has zero surge capacity for unusual circumstances, is brittle and liable to lock up at a moment's notice, and requires far too many state actors to not be at cross purposes.

NOTHING in biology is optimized for efficiency. Everything is robust at the expense of efficiency. Everything too efficient yet brittle died off long ago. A potato manages 0.5% conversion of sunlight to starch, nowhere near the theoretical yield of its photochemistry. But if you move it from shade to sun, it doesn't burn up its electron transport chain (which is harder than you'd think for photochemistry!), and if you move it from sun to shade it gets by without starving. If a virus chews up your lungs, you have fat stores to draw on rather than only functional tissue and the capacity to get by on lower lung capacity until the crisis is dealt with and regeneration can happen.

Nothing that has stood the test of time is nearly so centralized and brittle and over optimized as the current global civilization. Regardless of the end effects, things that last will go away from that direction.

EDIT: This does not only apply to international supply chains. Over optimization and over centralization and giganticism of players of the food supply chain has resulted in a system within the US in which is untenable unless everything goes right. Closing restaurants has resulted in farms that only sell to specialized suppliers being unable to get their product into domestic supply lines leading to absurd waste and a few crowded nodes in the meatpacking industry represent both absurdly effective viral breeding grounds and critical points that are threatening to take down large fractions of the domestic meat supply. Other examples abound.

EDIT: One could make the counterargument about how everything on Earth functions as part of an ecology rather than being fully self-sufficient, but ecologies are systems with huge numbers of interacting parts that are interchangeable, not small numbers of super specialized but independent actors. Symbiosis exists but results in loss of individuation once it gets severe enough...

Comment by cellbioguy on [Link] COVID-19 causing deadly blood clots in younger people · 2020-04-28T15:59:02.534Z · score: 6 (4 votes) · LW · GW

NY is the place in America we have the most data, and are most likely to notice less common effects.


It fits with all the autopsy and clinical data that coagulation issues are a major cause of morbidity in severe cases, and the fact that children with non-severe cases are having an anomalously high rate of skin lesions in fingers and toes characteristic of circulation problems.

Comment by cellbioguy on [Link] COVID-19 causing deadly blood clots in younger people · 2020-04-28T13:26:52.038Z · score: 13 (4 votes) · LW · GW

The article seems more of a "this is a thing that's happening" article than a "this is a major cause of death" thing.

Still, it looks like it'll be important to follow recoveries for an increase in circulation issues going forward.

Comment by cellbioguy on Coronavirus: Justified Key Insights Thread · 2020-04-28T13:14:04.993Z · score: 6 (3 votes) · LW · GW

UPDATE as of 4/28/2019.

Others coming to this exact same distribution more rigorously.

https://t.co/51b3bJYg3e?amp=1

Compiling rigorous data, the compatible range is circa 0.5% to 1% with a central tendency of 0.8%.

Comment by cellbioguy on Coronavirus: Justified Key Insights Thread · 2020-04-28T13:10:23.152Z · score: 4 (2 votes) · LW · GW

The effects of measures on the spread take weeks to show up in the data.

If the doubling time hadn't cratered, the hospitalization rate would've remained exponential. At the time of posting it was comparatively flat, and I estimated.

The half came from the fact that it usually takes ~3 weeks to die, that the exponential spread had only stopped a few weeks earlier, and a drawing of a triangle and square representing a rise and flat that I drew a vertical line through.

Comment by cellbioguy on On New York’s Antibody Tests · 2020-04-26T21:13:33.001Z · score: 2 (3 votes) · LW · GW

This fits perfectly with the numbers I have been coming up with based on total deaths (~0.2% of NYC) and infection to fatality ratios that are coming out of many many MANY pieces of GOOD research (rather than the denialists and minimizers getting a LOT of airtime) - 0.5% to 1%.

Comment by cellbioguy on The Chilling Effect of Confiscation · 2020-04-26T21:12:01.504Z · score: 2 (4 votes) · LW · GW

Foolish, yes. This is what happens when parasitic short-term-focused elements take over and blow up a cooperative system. Happens all the time in symbiotic systems with parasites, cheaters, cancer.

Comment by cellbioguy on The Puzzling Linearity of COVID-19 · 2020-04-24T19:48:22.726Z · score: 2 (1 votes) · LW · GW

A constant level of testing, leading to a constant number of confirmed cases some of which die?

Comment by cellbioguy on My Covid-19 Thinking: 4/23 pre-Cuomo Data · 2020-04-24T14:55:11.890Z · score: 6 (4 votes) · LW · GW

The New York numbers are certainly interesting. I wonder if New York reached a no-longer-susceptible rate that means that it can no longer support long transmission chains in lockdown...

New study with claims of meaningful mutation in Covid-19
Claim is that European strain, which is also in New York (and I’m going to presume New Jersey and other surrounding areas as well, because physics), is deadlier than the strain elsewhere, generating orders of magnitude more viral load.

I am VERY VERY skeptical of this paper.

The mutations they show are TINY. And their methods section does not include any details at ALL of how they grew their viruses, or how they diluted them to a multiplicity of infection of 0.5. Short version, they were supposed to grow cultures of each of their 11 viral isolates, measure how infective each culture was, and then dilute them so there were 50% as many infective viruses as cells in the flasks they poured them into to make sure they all started from the same point. But they give no details of how they measured this and did the dilution.

When growing viruses, batch effects are a BITCH. Your virus culture might be a little differently diluted, they might be a different average age, or your culture might've been produced in a corner of the incubator that was a little warmer. The lines of each of the viruses bounce around over time, some higher and lower over time, and all I really see is a cloud of viral RNA levels that goes forward over time with some high and some low at any given time. They have four replicates of each virus and DO show that the replicates behave exactly like each other, but their methods section doesn't say if they took the same diluted virus stock and put it into four culture flasks, or made four separate stocks of each virus. It is QUITE QUITE possible that they are just seeing differences in the stocks they grew that have to do with their culture histories and dilution details, rather than genetic differences.

On another point, the cell line they grow them in isn't even human and doesn't really have an innate immune response, which would be by far the most important things regarding real-world infection. Their high viral replication lines were also not from their more severe cases.

They definitely did find ONE interesting thing - one of their isolates appears to have independently invented a particular missense mutation seen in another strain elsewhere in the pile of global sequences. Actually suggestive of selection. It's not in the receptor binding domain of the S protein though, so it shouldn't affect binding or immunity much.

Other papers have found MUCH more interesting mutations - there is a cluster of cases in Singapore that have up and completely lost one of the accessory proteins of the virus, which is involved in squashing the human innate immune response, and another case in Arizona has broken another such accessory protein beyond repair. This is presumably because this bugger evolved in bats, and their interferon response is on a freaking hair trigger. The anti-immune-system measures of the virus are overclocked relative to what you need to replicate in humans, and losing some of them doesn't really hurt them.

Comment by cellbioguy on Coronavirus: Justified Key Insights Thread · 2020-04-23T19:04:38.944Z · score: 12 (3 votes) · LW · GW

UPDATE as of 4/23/2020.

I'm so sick of being right.

Seroprevalence in NYC reported as 21%.

https://twitter.com/NYGovCuomo/status/1253353516803993600

There can be false negatives, but at this positive level false positives are less of an issue than at low levels. Also, they apparently specifically grabbed people out and about at grocery stores, so very sick people may have been excluded, pushing levels down. On the other hand, people shopping might be more likely to pick it up.

Pretty much right on the nose...

https://twitter.com/trvrb/status/1253398329766973441

" If we then take deaths as of today as 17,200 based on excess deaths (https://nytimes.com/interactive/2020/04/21/world/coronavirus-missing-deaths.html), we'd get an infection-to-fatality ratio of ~1%. " I suspect the true seropositivity is higher than the measured due to selection effects on the net, which would push this down a bit.


EDIT: Apparently this test also only detect IgG, which is the type of antibody that rises last and can take two weeks or more to be detectable in some people after symptoms develop.

Comment by cellbioguy on How likely is the COVID-19 apocalyptic scenario? · 2020-04-23T15:35:51.524Z · score: 3 (2 votes) · LW · GW

It is mostly just retroviruses that wind up entering the genomes of their hosts. RNA viruses leave a very different imprint: high rates of evolution of the proteins that their proteins interact with, as they race to deactivate their hosts immune responses and their hosts race to deactivate or evade the viral proteins.


There is also a constant, diversifying selection on the components of the immune system (HLA/MHC) that display viral proteins from within cells on cell surfaces for the immune system to be sensitized against. Viruses always evolve to take better advantage of the most common of these alleles, and the rarest of these genes are always selected for in populations as result. The end result is what is called 'balancing selection', where rare things become more common and common things become less common leading to the maintenance of great diversity. This is why tissue typing for transplants is so difficult - there is such immune system diversity that most people don't have the same alleles at these loci as each other. Of course, if something new enters the population that a subset of these alleles isn't great against, that set of alleles will become less common over time.

Comment by cellbioguy on Solar system colonisation might not be driven by economics · 2020-04-23T02:50:01.350Z · score: 2 (1 votes) · LW · GW

I'm still convinced that solar system colonization simply won't happen.

Comment by cellbioguy on How likely is the COVID-19 apocalyptic scenario? · 2020-04-23T02:46:57.893Z · score: 10 (6 votes) · LW · GW

Then after a few hundred years, the human population will have undergone enough selection that all the bad HLA alleles that make T-cell responses difficult are low in the population and all the formerly rare ACE2 alleles are widespread. Here, check out these papers:

https://elifesciences.org/articles/12469

https://www.biorxiv.org/content/10.1101/2020.03.18.997346v1.full

Looking at signatures of natural selection in the human population, by FAR some of the strongest signals in the past few tens of thousands of years is proteins that interact with viral proteins - the HLA alleles and all the parts of the interferon response and everything else that all those tricksy accessory proteins sequester and alter.

This is nothing new. We just have somehow decided that we expect better.

------

As for other things:

The virus apparently has a mutation rate which is on the high end, unexpectedly large rate of mutation. This makes the vaccine less probable. How much less? No idea.

This is simply not true. Coronaviruses actually proofread their polymerases unlike almost all RNA viruses. The only interesting mutations I am aware of in the current outbreak is two independent origins of a particular missense mutation away from the receptor-binding-domain of the spike protein (that thus dont affect neutralizing antibodies), and a few strains that have up and LOST whole accessory proteins that are part of how the virus evades the innate immune response (because they are so damn good at evading it in humans because the bat response is so absurdly fast that they don't need half of what they have).

Following the vaccine development scene, I am actually absurdly optimistic. All the stuff entering human studies are basically just repurposing already-researched SARS and MERS vaccines that work in monkeys, and swapping out the sequence. The preliminary data is already coming in in these animals and is good.

Comment by cellbioguy on Coronavirus: Justified Key Insights Thread · 2020-04-22T14:01:47.938Z · score: 3 (2 votes) · LW · GW

I think it's a horse, not a zebra. ACE2 is expressed on endothelial cells lining blood vessels. If you get bad viremia the inner sheath of blood vessels, especially in heavily infected organs, probably just gets all messed up.

Comment by cellbioguy on COVID-19: List of ideas to reduce the direct harm from the virus, with an emphasis on unusual ideas · 2020-04-19T02:51:42.292Z · score: 11 (4 votes) · LW · GW

See my answer of another link below. Short version:

  • Severe disease is associated with hyper-coagulation, and people experiencing breathing difficulties should be treated with anticoagulants.
  • Antivirals and anything believed to decrease viral replication should be given early, to the more moderate cases to decrease the odds of progressing to severe, rather than only to severe cases.
  • A case is likely to be followed by a period of immunosuppression, much like measles, so those who become ill should be prepared to be careful afterwards.

https://www.lesswrong.com/posts/nRX7uwT2wNvvmd2Yd/coronavirus-justified-key-insights-thread

Comment by cellbioguy on COVID-19: List of ideas to reduce the direct harm from the virus, with an emphasis on unusual ideas · 2020-04-19T02:45:07.284Z · score: 6 (4 votes) · LW · GW

There have been studies of soaking them in brine, so they have tiny salt crystals in the cloth that dessicate viruses that land on them. Had a positive effect!

Comment by cellbioguy on Coronavirus: Justified Key Insights Thread · 2020-04-19T02:43:31.562Z · score: 9 (3 votes) · LW · GW

New information. The Italian town of Vo was blanket-RNA-tested twice in late February and early March. A total of 3% of the town tested positive, and they were able to lock down this subset and shut down transmission from continuing in the town indicating they caught enough of the asymptomatic-but-transmissive carriers.

https://www.medrxiv.org/content/10.1101/2020.04.17.20053157v1

Here we have a detailed analysis of these positive-testing people.

43% asymptomatic all the way through.

~20% hospitalized. This means almost 40% hospitalization of people who were symptomatic. Critera for hospitalization is an interesting question, as is the age breakdown of the town.

One death, in a town in which a total of 82 people tested positive. That one death was what alerted authorities to the outbreak in the town, so we need to take it as a given rather than taking it as even weak evidence of an over 1% fatality rate.

No cases among hundreds of children, even in houses with symptomatic family members. Extra cases among the elderly (as in 1% of 20 year olds versus 6% of 70 year olds). Small numbers but significant. Unclear if that means they are not getting infected or are not producing long-lasting infection that is detectable or if social structure has something to do with it.

No obvious difference in symptomatic versus asymptomatic across the age distribution, subject to sample size.

More men took more than 2 weeks to clear the virus than women.

Definite confirmed asymptomatic people passing it on, and presymptomatic people passing it on.

3% of the town testing positive via PCR in the beginning of March is compatible with 15% of other towns in the area testing positive via serology a month later, as that would be less than 3 doublings. They find a 'serial interval' of only about 7 days in their contact-tracing data from before the lockdown, and 10 days after the lockdown, and a replication number before the lockdown of about 3 and 0.14 during the lockdown. That's a doubling time of well under a week before the lockdown. The rest of Italy's lockdown didn't include such good contact tracing and thus still was probably doubling a few times during that period.

Comment by cellbioguy on My Covid-19 Thinking: 4/17 · 2020-04-18T02:26:31.835Z · score: 7 (4 votes) · LW · GW

All the reports of people becoming ill (or testing positive) after only a month are almost certainly not 'reinfections', rather are some combination of false negatives and people with immune systems damaged by the infection having a bit of a relapse. There are also no documented cases of one of these relapses infecting even close family contacts. Shed viruses seem to be nonviable with much less of an immune response than is required to clear it from within the body.

It is definitely possible that the immunity could fade rapidly, but even if that is true I expect second infections to be much less severe than the first infection. Mostly because it looks like most of why this disease is so severe is that the virus escapes the interferon response allowing it to replicate up to an obscene level before the adaptive immune system notices it. Even a weak antibody response will allow the innate immune system to notice the fact that there is an infection, and it will probably have a harder time replicating up to such ridiculous levels.

This being said... we are definitely going to be living with this bastard for a while.