Knowing Humans

Study their behaviors. Observe their territorial boundaries. Leave their habitat as you found it. Report any signs of intelligence.

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Thursday, June 17, 2021

Why Did We Fumble COVID-19 Therapeutics?

A variety of reasons, in roughly descending order of guestimated importance:

  • The early focus was on "flattening the curve" to preserve hospital and ventilator capacity, and so insufficient attention was paid to early-stage therapeutics.
  • Hydroxychloroquine was unsuccessfully tried as a late-stage therapeutic, and this politicized episode made the healthcare establishment afraid of an embarrassing replay.
  • Therapeutics don't appreciably reduce R0 compared to a vaccine. Treatment is super important, but curtailing exponential spread is super-duper-important.
  • Risk-averse government bureaucrats didn't think to waive the rule that Emergency Use Authorization for vaccines is only allowed if no therapeutics are available.
  • Risk-averse medical bureaucrats are indoctrinated to oppose any therapy that hasn't been proven effective, particularly in randomized control trials.
  • The pharmaceutical industry has no profit incentive to re-purpose off-patent drugs for new indications.
  • The Orange Man was promoting therapeutics, and we can't give him a win.
  • It was harder to recruit early-stage trial subjects because 1) they're not in hospital beds and 2) the pandemic ebbed in summer.

Tuesday, June 15, 2021

COVID-19 Heterogeneity

A list of possible factors for why COVID-19 has affected different regions differently, in decreasing order of my guestimated importance. 

Beware the political agenda of anybody selling a monocausal theory.

  • geographic/travel connectivity, incl. travel bans
  • vaccination curve
  • efficacy of vaccine(s) used
  • population age structure
  • population density
  • hemisphere (summer vs. winter)
  • co-morbidities: obesity, heart disease, hypertension, smoking, asthma, diabetes/kidney, sickle cell, cancer
  • vaccine demographic targeting
  • elderly clustering e.g. nursing homes vs. multi-generational domiciles
  • super-spreader opportunities
  • under-/over-reporting of COVID-19 deaths
  • domicile ventilation
  • air conditioning
  • temperature
  • humidity
  • ultraviolet incidence
  • prior culture of mask use
  • advanced contact tracing
  • cultural acceptance of lockdowns
  • compliance culture (e.g. Italians racing to trains against lockdown deadlines)
  • vitamin D use
  • anti-parasite Ivermectin use
  • anti-malaria hydroxychloroquine use
  • use of mass transit
  • blood type
  • prior experience with SARS/MERS
  • greeting culture: kiss, handshake, bow
  • nursing home return policy
  • South Asian Neanderthal haplotype (Zeberg, Paabo 2020) makes hospitalization 2X likely
  • chromosome 12 Neanderthal haplotype (vs RNA viruses, 2021) makes hospitalization 22% less likely

Wednesday, May 26, 2021

Covid Vaccine Safety and Efficacy In Israel

The anti-vax group America's Frontline Doctors are promoting an article by HervĂ© Seligmann claiming that "the Pfizer vaccines, for the elderly, killed during the 5-week vaccination period about 40 times more people than the disease itself would have killed". The article makes a basic mistake that invalidates its main claim.

First, Seligmann makes an apples-to-oranges mistake by comparing Israeli vaccinations from Dec 19 to Feb 11 with a baseline of "death rates per day for unvaccinated are estimated for the 303 days from March 1 to December 20". (Ignore his mistake of saying "death rates per day", he meant "per-day death rates".) A big problem with that baseline is that the vaccinations were just getting started as Israel suffered a third wave of deaths that dwarfed the deaths from March 1 to Dec 20. That's like saying that aiming firehoses at a burning building must be the reason why more people trapped in the burning skyscraper died after the fire trucks arrived versus before.

The first drop of water from a firehose doesn't immediately extinguish a fire, and it's well-known that it takes several weeks for COVID-19 vaccines to reach full efficacy. During that time, it's expected that just-vaccinated people will be more vulnerable to COVID-19 than when the 2nd dose has been given its two weeks to fully kick in. 

Also, note that the earliest vaccines in Israel were given to the most vulnerable populations -- just as the third wave was heading for its peak. Seligmann's data conveniently ends at Feb 11, just as COVID-19 deaths per million in Israel were about to plummet. Israel reached 50% fully-vaccinated on Mar 16, and the data since Feb 11 indicate the exact opposite of the increased COVID-19 death risk that Seligmann claimed.

Indeed, thanks to Israel's data-intensive healthcare system, we now have detailed data on how COVID-19 differentially impacts unvaccinated people there. Studies published in Nature and the New England Journal of Medicine confirm the success of the Pfizer vaccine in Israel.

P.S. Table 1 in Seligmann's article strangely labels the first column as "community". Maybe this is a language/translation problem, but nowhere does he explicitly say that this column counts COVID-19 cases among people who have received vaccine injections but are not fully vaccinated. So for his denominator, he chose

  • a vaccine-recipient population that is known to be skewed toward the most vulnerable, and
  • systematically excluded its members once their vaccine reached effectiveness, and
  • ended his data window just as Israel's death rate was about to plummet.
The meaning of his "community" column was only clarified after I finally found this detailed debunking of Seligmann written in German. (The Google translation is amazing, and actually reads more like native English than Seligmann's own paper.)
Update 12pm: Who debunks the debunkers? The German article makes a false claim here:

But ratios obviously matter more here than absolute numbers. The death rate among vaccinated COVID-19 victims was 709/54588 = 1.3%, while the rate among unvaccinated during the same period was 1566/368826 = 0.425%. However, note that the Pfizer vaccine efficacy in the 21 days between doses 1 and 2 is 52%. So to make the comparison fair, the denominator for the vaccinated case should include all the cases that the vaccine averted. This doubles the denominator, making the relevant 1-dose COVID-19 death rate be 0.65%.   That's only 50% higher than the unvaccinated COVID-19 death rate. That could potentially be explained by the fact that in Israel the vaccine was targeted early to the most vulnerable populations.
Israel's COVID-19 death graph above, with 2.5 months more data than the table above, shows that vaccines do not lead to more deaths from COVID-19. Some anti-vaxers have made a different claim: that vaccines will cause a spike in non-COVID-19 deaths. However, that claim is so far similarly contradicted by the excess-death data from the three countries that are making the most use of the most efficacious vaccines:

In the U.S., U.K., and Israel as of April 11, 156M distinct people had received a vaccine so far, while the population-weighted excess deaths among them had already become negative (as Israel's population is only 9M). As of yesterday, a total of 207M distinct people in those 3 countries have received a vaccination. When will all those "death jabs" ever cause the de-population that some anti-vaxers say the vaccine is engineered to do?
My prediction: in 2021-2023 there will be hysteresis pressure toward negative excess deaths in the U.S. because many of the pandemic deaths were among Americans likely to die in the coming years. Any spikes in excess deaths will be traceable to new variants that might develop, especially in the virus playground consisting of the world's unvaccinated people. But such spikes should be manageable, as emerging data suggests that the existing vaccines have some efficacy against variants. And since our most effective vaccines are based on the new nimble mRNA technology, it will be straightforward to create booster vaccines for problematic variants.

Tuesday, May 11, 2021

What Have Your UFO Aliens Been Doing?

Assume for the purposes of this post that we believe (as I don't) that at least some UFOs involve alien technology. If so, when did this alien technology reach our solar system, and what can we infer it would do during its tenure here?

By "alien technology" I am indifferent about whether the technology is "manned". I assume that aliens are at least millions of years more advanced than humans. So I assume that aliens have long since traded biological substrates for technological ones, at least for expeditions like a mission to Sol. I also assume that they can imbue their expeditionary technology with alien intelligence and values.

We infer that the aliens aren't grabby, because 1) they haven't grabbed Sol's energy or material resources, and 2) they haven't grabbed the energy resources of our galaxy. Reasoning from the Fermi Paradox, we specifically assume that the aliens

  • were the first technological intelligence to start expanding in our galaxy;
  • are applying a Zoo Policy to not only our solar system but to nearly all of the exploitable resources of the galaxy;
  • are somehow able to coordinate and enforce their Zoo Policy across thousands or tens of thousands of light-years.
Note that this model applies even if the aliens are a federation of civilizations with independent origins, though of course Zoo Policy enforcement then becomes more problematic. (If the first civilization are adamant Zookeepers, they have to ruthlessly enforce their policy on any new civilizations they allow to federate with them.)
How long ago did they have reach Sol? We assume no exotic physics allowing FTL travel or communication. Expanding from some random point in the galaxy at 1/10 to 1/1000 of c, we estimate they arrived here between 500Kya and 50Mya.
We infer that if they forego the exploitation of our solar system's resources, it is because they value any local biosphere's evolutionary investments and achievements. So it's plausible that they would want to protect local biospheres from extinction events. Do we see evidence of this?
Venus and Mars became suddenly unfriendly to life roughly one and four billion years ago, respectfully. Neither was due to impacts, and both happened long before the aliens are estimated to have arrived. Too late to help.
It would be trivial for aliens to protect Earth from the impacts that have regularly confronted Earth with mass extinctions. (We ourselves are at most a century away from being able to do so.) So what recent catastrophic impacts should they have stopped if they were on duty at the time?
  • 66Mya in the K-Pga extinction an object a few tens of km diameter took out the dinosaurs and all tetrapods >25kg. 
  • 35Mya the E-Og extinction was perhaps caused by the Popigai impactor.
  • 800Kya the enormous Australasian strewnfield was created by an impact whose crater has not yet been found. It's unclear why this event is not associated with any mass extinction or climate catastrophe.
It's easily plausible that the aliens arrived after E-Og and so couldn't stop it. But it's only barely plausible that the aliens arrived so recently that they could not stop the Australasian strewnfield event. (And no, the strewnfield is not because the aliens blasted the object to pieces. You prevent impacts but nudging the impactors, not by turning them into shotgun blasts.) If we count the strewnfield as alien Zookeepers not being here yet, that makes it suspiciously coincidental that the aliens have arrived so recently. 
(Many UFO believers speculate that aliens arrived due to our atomic testing. These speculations are some combination of fantastical and scientifically illiterate. The physics just doesn't work. If aliens are here, they've surely been here for millions of years.)
Aside from protecting local biospheres from catastrophic impacts, what else would the aliens be up to? 
Monitor the Zoo inhabitants? When you set up permanent zookeeping in a solar system, do your monitoring missions use large easily-observed craft with spaceship-like acceleration capabilities? Or do you instead use small, stealthy, camouflaged devices, to allow close-up and loitering observation? If I were hunting alien observation tech, I wouldn't look in the skies for spaceships. I'd instead look in the trees, for birds and insects that are suspiciously hard to catch. Again, we humans are less than a century away from creating a never-ending plague of privacy-invading disguised surveillance drones. No human in 100 years will be using a flying saucer to spy on anybody. So why would aliens use them? (cf. "teasing", below.)
Abduct the Zoo inhabitants? That of course depends on Zookeeper ethics. Zoo Policy doesn't tell us whether aliens value individuals like they value biospheres. If an alien values secrecy but is willing to kidnap and probe an individual human, that alien seems more likely to euthanize the test subject than to return it to spill the beans. So no flying saucers, and no returned abductees. 
Tease the Zoo inhabitants? Some say the aliens tease us with UFOs to test our reactions and prepare us for "Disclosure". But these are aliens with a monastic devotion to leaving the galaxy undisturbed in the eyes of anyone with optical and radio telescopes. So why would they reveal themselves only a few decades after we first noticed their millions of years of self-denial?
Protect Zoo inhabitants from each other? If Mars has remnants of independent life, the aliens would know it and might very well want to protect it from Earth. There have been a lot of failed Mars missions, but Elon Musk hasn't gotten the memo. Shouldn't we expect the aliens to protect Mars? If not now, when? (In Arthur Clarke's 2010, the Monolith aliens told humanity to leave Europa alone.)
Protect Zoo inhabitants from themselves? If you think nuclear weapons give humanity the ability to extinct itself, you might expect the aliens to disarm us. Note that through most of the 1960s, a large fraction of U.S. Polaris missile warheads were inoperable. And there are claims that UFOs have deactivated nukes. So yes, if you believe in alien flying saucers, you probably believe that aliens have the ability to deactivate most nukes if launched. (But aliens surely know that nuclear war could not extinct H. sapiens, and in fact would set us back a century at most. As horrible as that prospect would be to us, the Zookeepers might consider nuclear war to be growing pains -- a minor incident in one of the zoo cages.)
Cooperate with the Zoo inhabitants? Most UFO believers say aliens are secretly cooperating with human governments. Such behavior would be strongly at odds with the Zoo Hypothesis. Recall that ZH says the galaxy looks uninhabited only because the Zookeepers are maniacally committed to not letting knowledge of their presence interfere with the advanced development of other biospheres. So again: why bother keeping the galaxy looking uninhabited if you're going to start working with the local primates around the same time that a Fermi notices you're absent? Oh sure, they're cooperating "secretly", but millions of UFO believers claim it's easy to see through the "secret". If these advanced aliens can't fool the History Channel, they're not very advanced.
Bottom line: most alien-UFO claims and theories are nearly impossible to square with what we can infer from 1) how long aliens would have to have been here, and 2) what they would and would not do once here.