Currently spending time on derisking research (see derisked.org). Previously worked at BERI, EpiFor/FHI, CEA, IPA. Generally US-based.
Josh Jacobson
Karma: 569
An article published today on Reuters and elsewhere reads, “Israeli survey finds 3rd Pfizer vaccine dose has similar side effects to 2nd.” Buried within this article is the following:
About 0.4% said they suffered from difficulty breathing, and 1% said they sought medical treatment due to one or more side effect.
This seemed quite bad to me and like a worrisome result. I sought information on how many sought medical treatment after the second shot. I could not find this information, but I did find:
only 51 of some 650,000 people to have received the Pfizer shot sought medical attention for symptoms suffered
from a December 2020 article on Israeli vaccination. Comparing the 1% to 51⁄650000 = 0.008% I found that the current frequency of side effects requiring medical attention was 128x the level found after dose 1. This seemed like a bad sign.
I then sought out more information about side effects post dose 2 in Israel, which I did not find. But instead I looked at the CDC’s Advisory Committee on Immunization Practices’ Interim Recommendation for Moderna, and found the following:
The frequency of serious adverse events** observed was low in both the vaccine (1.0%) and placebo (1.0%) recipients
** Serious adverse events are defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, or results in persistent disability/incapacity.
I can’t believe that this was 1%! That seems surprisingly high (for either group). I expect the outside-of-trial data has not been nearly that magnitude.
This 1% matches the current Israeli data, and with a more restrictive definition, so the Israeli data no longer seems particularly worrisome in comparison, though I may dig in to this further. In general, I feel somewhat confused by the situation.
Sources: Reuter’s article from today—https://www.reuters.com/business/healthcare-pharmaceuticals/israeli-survey-finds-3rd-pfizer-vaccine-dose-has-similar-side-effects-2nd-2021-08-08/
Article from December 2020 - https://www.timesofisrael.com/1-in-1000-israelis-report-mild-side-effects-from-vaccine/
CDC’s Advisory Committee on Immunization Practices’ Interim Recommendation for Moderna: https://www.cdc.gov/mmwr/volumes/69/wr/mm695152e1.htm
EDIT: This article’s statistics contrast with those of Reuter’s, and show data very similar to the 1st shot: https://www.timesofisrael.com/of-600000-israelis-who-received-3rd-dose-fewer-than-50-reported-side-effects/
Gawande discusses institutions, practices, and evidence that points to an alternative vision — of nursing homes that provide more autonomy; of hospice care that does not prolong life at extreme costs to its quality;
I don’t understand this; my understanding of hospice is that life-prolonging treatment is absolutely not allowed while being in hospice care (you have to exit hospice).
~2 weeks ago, the FDA added a warning to the J&J Covid shot regarding increased risk of developing Guillain-Barré Syndrome.
Perhaps unsurprisingly, given the history with blood clots, my quick check of prevalence finds that reports of developing GBS following J&J vaccination are actually less than would be expected otherwise.
My very basic analysis: https://docs.google.com/spreadsheets/d/1wDFrDq0E6Q096E97XzU7ndP53mYC0Paf9Wyun-XxmWA/edit?usp=sharing
Numbers from: https://www.yalemedicine.org/news/covid-vaccine-guillain-barre-syndrome
EDIT: Analyzed another way, GBS cases may be 3-4x more common in J&J vaccine recipients than base rates (still highly uncommon, but I see the potential association).
Josh Jacobson’s Shortform
It’s not just about Vitamin D. An example:
Liu et al. 201487 found that hypertension is reduced by UVR-induced nitric oxide independent of vitamin D. They showed that stores of nitrogen oxides in the human skin are mobilized to the systemic circulation by exposure of the body to UVA radiation, causing arterial vasodilation and a resultant decrease in blood pressure independent of vitamin D, confirming the hypothesis of Feelisch et al. 2010.88 These results correlate with the findings of Afzal et al. 201477 that genetically low 25(OH)D levels were associated with increased all-cause mortality but not with cardiovascular mortality, indicating that a mediator other than vitamin D may be involved in cardiovascular mortality, and with the results of Tunstall-Pedoe et al. 201589 challenging vitamin D’s alleged role in cardiovascular disease.
https://www.tandfonline.com/doi/full/10.1080/19381980.2016.1248325
See responses to later bounty request on this topic as well, in particular the response linked: https://www.lesswrong.com/posts/fBGzge5i4hfbaQZWy/usd1000-bounty-how-effective-are-marginal-vaccine-doses?commentId=Rd3f3KiAMFNvpJAhu
I entertained a similar hypothesis, but I now feel comfortable not including that to a meaningful extent in my decision making.
There’s some evidence against this that I consider significant:
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I read ~3 doctors’ takes on this question regarding a third dose; they all thought this sort of potential negative effect was very highly unlikely. At least one of them had a detailed explanation as to why that sounded reasonable to me (I’m not a medical professional), and that made that take a bit more additionally meaningful to me than those takes without explanation.
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Anecdotally, I feel like I would have seen more indication that this is a concern in the clinical trials news or in the news regarding those who are receiving / have received third shots, if it were substantial.
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The pattern that you refer to hearing about with dangerous kinds of flu has seemed to be the opposite of general covid severity and death patterns by expected immune response (age).
I don’t have a particular likelihood to assign; this is the summary of the evidence I have.
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That’s awesome, thanks!
It seems valuable to LOUDLY NOTE that Microcovid.org has not been updated for the Delta variant https://github.com/microcovid/microcovid/issues/869 and that the adjustment should be quite significant.
I’d be interested in perspectives on what adjustment should be implemented.
Cryopreservation doesn’t have to cause damage. For instance, Aldehyde Stabilized Cryopreservation (on pigs) doesn’t https://doi.org/10.1016/j.cryobiol.2015.09.003
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I don’t think this is done at any of the main cryonics organizations, right? Their methods are damaging in perhaps less predictable ways than this mechanism.
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I think the statement
Cryopreservation doesn’t have to cause damage
is deceptive and I wouldn’t want it being shared without further context. I had a conversation with my expert-friend about this method and the type of damage it causes.
Quoting some parts of my text message conversation with this expert friend who wishes to be anonymous:
(Him) I had never seen this article before, but it’s pretty cool. The technique it describes supposedly preserves the brains ultrastructure (i.e. connections between neurons etc) for connectome mapping and neural research. However, the technique utterly fails at (and isn’t trying) to preserve viability. In this case, the cryopreservation isn’t causing “damage” to the structure of the brain, preserving it for connectome research....BUT they did that by obliterating any hope for brain viability post thawing by exposing it to extremely high concentrations of toxic chemicals.
(Me) Interesting. I’m not familiar with the connectome really, but to you does that mean that this is a method that sounds promising for e.g. future digital brain construction but sounds really bad for e.g. biological reanimation?
(Him) Yeah, that’s a good summary. The question with digital brain reconstruction will be whether the connectome actually has all of the information you need or if there are other issues (analogous to how DNA is mediated by epigenetics).
(Me) Yeah, I could be wrong but I’d thought most people were thinking that chemical movements in the brain contained significant information that would probably need to be recreated accurately to reanimate someone who was accurate to the person who had passed.
(Him) That’s my impression too.
(Me) How do the toxic chemicals obliterate hope of brain viability post-thawing?
(Him) I don’t know the exact mechanism....but they’re using extremely high concentrations of very toxic chemicals. I think the tissue is fucked from the toxic chemicals, but it depends on the exact type of toxicity (which I’m not sure about and the paper doesn’t go into). In a certain sense, anything toxic “physically” damages the tissue at a certain scale...it might cause osmotic swelling or shrinkage, damage DNA, damage cell membranes, block oxygen (which causes all sorts of other damage), etc. Importantly for this application, it’s not damaging the overall structure of the brain, so the connectome is still intact and can be studied. You could think of it like degrading the steel in a building. The overall structure will be intact, but it’s now structurally unsound and will collapse if exposed to anything. Something is wrong about the structure on small scales, but the large scale structure appears normal.
Regarding your second response:
Brain biopsies are performed in hospitals e.g. during brain cancer diagnostics. They should not be dangerous to perform
The first paper I looked at on brain biopsies (https://link.springer.com/article/10.1007/s10143-019-01234-w) says:
The mortality rate varies from 0.7 to 4%. Overall morbidity ranges from 3 to 13%. Most of the complications are revealed by the following symptoms: neurological impairment (transient or permanent), seizure, and unconsciousness. Symptomatic hemorrhage range varies from 0.9 to 8.6%, whereas considering asymptomatic bleeding, the range may be up to 59.8%.
That sounds like a high risk of being very damaging to me, and that’s from one biopsy by expert medical staff vs. your proposed multiple by non-experts.
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Makes sense; I think it’s nice for that to now be explicit.
It’s interesting to tie some thoughts in his writing to EA, but based on just the evidence here, I’d object to calling him an EA.
I’d like to see that someone did significant good with their actions before calling them an EA, especially someone in a position of power.
His words, particularly on nukes, sound a lot more like prediction or speculation than advocacy to me:
If to these tremendous and awful powers is added the pitiless sub-human wickedness which we now see embodied in one of the most powerful reigning governments, who shall say that the world itself will not be wrecked, or indeed that it ought not to be wrecked? There are nightmares of the future from which a fortunate collision with some wandering star, reducing the earth to incandescent gas, might be a merciful deliverance.
It’s fun to call a famous figure an EA, but to me, identifying a risk in your writing = futurist, taking actions in pursuit of doing the most good you can = EA. I think to some doing things like calling famous figures EAs could be seen as the movement being spurious and status seeking, so I have a particular sensitivity to it that makes me want to flag this here.
The Wait But Why article “Life is a Picture, But You Life in a Pixel” makes this same point and is what caused me to start explicitly focusing on evaluating jobs this way years ago.
A good read: https://waitbutwhy.com/2013/11/life-is-picture-but-you-live-in-pixel.html
What you call a “significant indication that a third dose of an mRNA vaccine has a good safety profile” seems to be mostly just statements by vaccine manufacturers. … Also, statements by vaccine manufacturers can obviously be important evidence (in a Bayesian sense) for the safety profile
I agree that statements by Pfizer and Moderna are important evidence. Additionally, the Moderna report I linked included “The frequency of any Grade 3 solicited local or systemic adverse events was 15% after the third dose of mRNA-1273 and 10.5% after the third dose of mRNA-1273.351. There were no Grade 4 solicited local or systemic adverse events. The most common solicited local adverse event was injection site pain in both groups. The most common solicited systemic adverse events after the third dose of mRNA-1273.351 or mRNA-1273 were fatigue, headache, myalgia and arthralgia. In general, mRNA-1273.351 had a lower reactogenicity profile than mRNA-1273 in this study.”
I agree with them that this indicates a similar safety profile to the first two doses, in which “15.7 percent experienced a severe “systemic” adverse reaction and 7 percent, a severe “local” reaction.” https://www.vox.com/22158238/covid-19-vaccine-side-effects-explained
Perhaps I should have been more explicit about this evidence not having been reviewed yet by other parties.
Furthermore, in your list of 8 “reasons to not pursue a booster vaccine now” you don’t directly mention anything about potential health risks from taking a booster shot (which I’m not aware of the FDA claiming to be safe).
In that list is:
Some, such as the CDC and FDA, don’t think a booster is currently warranted.
More data on safety, optimal timing, etc. will be forthcoming and may help you make a better decision.
Given the evidence for a good safety profile (which also does include evidence I didn’t cite in my post), I personally think that this was an appropriate degree to which I indicated that safety wasn’t as validated as it could be, although perhaps:
Some, such as the CDC and FDA, don’t think a booster is currently warranted.
would have been better as:
Some, such as the CDC and FDA, don’t think a booster is currently warranted; they also have not reviewed the safety of a booster dose.
Thanks for highlighting your concern!
For some, now may be the time to get your third Covid shot
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Cryopreservation causes lots of damage, always. What would this show?
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Brain biopsies, especially by cryo staff, sound dangerous.
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Is there any indication that cryo companies would comply with this? What would associated costs be?
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The cleaned version here resonates more greatly with me, answers some questions I think I hadn’t realized I had, and I just really highly appreciate your response to this.
I’m making a meaningful quarantine decision prior to visiting someone immunocompromised, so it’s really great to have your very different perspective from the other response to this.
I also want to ask if you have any standby arrangements? I think that’s a meaningful difference between signing up with CI vs Alcor, because as I said at some point in the sequence, ischemic time matters way more for preservation quality than what perfusion technique is used. (Like, if I lived in Ann Arbor, I would almost certainly sign up with CI no matter what.) Maybe this is just my intense risk-aversion showing again, but it seems to me that cryonics arrangements without standby arrangements might be nearly useless, and that’s something I would worry about with CI.
To me this didn’t feel like a meaningful difference between Alcor and CI when I signed up. CI is very closely aligned with Suspended Animation, which does standby and transport. I do believe you can sign up for CI without signing up for Suspended Animation, but by default everything is sent and obtained together seamlessly with CI as the sole/only needed point of contact (they work closely enough with SA that most will likely never explicitly interact with SA).
I hate to use an analogy involving bad, typically non-vegan food (for some reason I’m not quickly coming up with an alternative), but I think to me the difference was something like wanting vegan chicken and a vegan burger and going to an A&W+KFC that serves those (https://live.staticflickr.com/5057/5389457870_37d10fc914_b.jpg) vs. going to a single restaurant that itself serves both. Either way felt like pretty OK solutions.
(I also appreciate the rest of your comment and think that your hypotheses make sense!)
I haven’t fully understood why weight loss drugs are so little used in the US given the health effects of being overweight/obese either. I think it’s good that you’ve shined a light on this and your overview is helpful guidance to someone getting oriented. Many aspects of this feel aligned with my research on the topics.
That said, Plenity (https://www.myplenity.com/) is a non-drug option that looks particularly promising and should potentially be at the top of the list here.
I haven’t looked into the longevity effects of weight loss yet myself, but the treatment here seems pretty unsophisticated and strikes me as likely incorrect. The cited study appears to be correlational rather than causal (only read the abstract, could be wrong). Additionally I would expect that age at which you lose weight has an impact, for example, and last I read a BMI that was borderline healthy/overweight is actually what maximizes longevity. I think there’s significantly more work to be done before the longevity conclusions would seem well-substantiated to me.
That said, I think putting numbers on it is totally fine and a good thing to do as directional information, I’d just prefer their (seemingly high) uncertainty was highlighted.