All of Dentin's Comments + Replies

What are the counterarguments to a Faustian Vaccine Hypothesis? ($2k charity bounty) I spent a bit of time looking at Geert Vanden Bossche's ideas about six months ago. I came away extremely unimpressed; he takes reasonable sounding things ("viruses mutate under selective pressure") and tries to extrapolate from them things that we don't actually see in reality. He describes a plausible sounding reality, that is not our reality. 2ndr16hI agree he paints a bad picture but he's short on actual, time-bounded, predictions to evaluate his claims. He shared some predictions [https://www.voiceforscienceandsolidarity.org/scientific-blog/predictions-on-outcome-of-mass-vaccination-during-a-pandemic-of-more-infectious-sars-2-cov-variants] in May, with a time frame of months/weeks to see some vaccine resistant variant. I think Omicron counts as variant that is vaccine resistant, even though there's no peak in vaccinated deaths rates (deaths may be, but not rates as far as I can tell). Some other people claim [https://twitter.com/EthicalSkeptic/status/1486176500042944514] Omicron does not descend from the Wuhan strain, so even this might not be the variant Geert Vanden Bossche predicted. Were you referring to some other prediction in particular? What are the counterarguments to a Faustian Vaccine Hypothesis? ($2k charity bounty)

I'd point out that vaccine designers are extremely aware of ADE, and construct vaccines to be resistant to it.  It's just something you wouldn't talk about, because it's second nature.

For a good discussion of what this looks like, there's a section on ADE in the RADVAC whitepaper; the section to look for is titled:

"possible mechanisms of vaccine-enhanced disease, vaccine-induced autoimmunity, and mitigation strategies"

Not only are designers aware of the risk, there are actually ways to mitigate/reduce it.

The counter argument is that we could never be completely sure; but that's as true about the covid vaccines as it is any other vaccine designed after ADE was understood.

1cistrane2dWhich is why the Wikipedia article says that ADE is definitely not a problem for the initial strain. All the vaccine trials looked for it and did not find it

The people at RaDVaC took measures to hit other targets then the spike protein as well for reasons to make the RaDVaC more effective with future variants. The officially approved one that just use the spike protein do not follow the ideas that RaDVaC advocates here.

I find his post incredibly uncompelling.  I believe he's arguing against a straw man; economists in the real world doing real work involving real dollars are painfully aware of the issues he brings up.

My guess is that his experience in economics is heavily influenced by his PhD work and that he's arguing against "economics as he experienced it at universities" as opposed to "economics as practiced by professionals in a real economy".

2Slider6moIf practioners need to go way beyond and above the theory that does underline how hollow the theory is

https://blogs.sciencemag.org/pipeline/archives/2021/06/07/ivermectin-as-a-covid-19-therapy is one of the better, current overviews of Ivermectin.  Basically, we don't have enough information.

Covid vaccine safety: how correct are these allegations?

One other thing to consider is that even small differences in replication rate might actually matter.  Consider that it takes a week for the virus to really ramp up, and that's a large number of doubling periods.  Even just getting a larger or smaller initial dose seems linked to how sick people get.  Even a few percent difference may allow the immune system to stay ahead in the arms race, and result in a nonlinear change in death rate.

Note that I'm not saying this happens; I'm saying that because this is an exponential growth attacker (the virus) versus and exponential growth responder (the immune system), even small differences in growth rates might have a large impact.

Looking for reasoned discussion on Geert Vanden Bossche's ideas?

Yeah, his second claim is bogus.  That's not how it works, and that's not what we've been seeing with existing mutations.

As an example, look at E484K - this mutation changes the amino acid polarity, so that antibodies trained against the E variant will have a much harder time attaching to the K variant.  If an antibody fails to attach, it doesn't 'crowd out' anything.

In the case where an antibody attaches but doesn't actually "inactivate" the virus due to a mutation, that's because the virus' attack surfaces are still present and exposed (otherwi... (read more)

2Lukas_Gloor8moThat makes sense; I was wondering about this exact thing. It seems like VB is painting a worst-case scenario where a bunch of things go wrong in a specific way. Perhaps not impossible, but based on what you're saying, there's no reason to be unusually concerned.
Looking for reasoned discussion on Geert Vanden Bossche's ideas?

#1 is where I would hinge a lot of objection.  Specifically:

"The vaccines are targeting outdated variants, and some vaccines are already only partly efficient. This creates the perfect conditions for further viral evolution."

Yes, the vaccines are targeting outdated variants, and yes, the vaccines are only partially efficient.  But the mRNA vaccines, even partially efficient, are still hugely overkill.  From previous posts here on LW, even partially effective mRNA vaccines likely cut transmission by a factor of 100 between the reduced infecti... (read more)

4ChristianKl8moWhen it comes to Sinovac it's worth noting that given that it's a inactivated-virus vaccine it creates different selection pressure then all the spike protein vaccines.
1Lukas_Gloor8moI agree, if all of this was only about argument (1), then it's clear that the ongoing mass vaccinations are best. But Vanden Bossche wants us to look at both arguments together, (1) and (2). His point is that having the antibodies from an outdated vaccine will soon be bad for you, because the types of antibodies set off by the vaccine will "get in the way" of innate antibodies. Are you specifically saying that it takes too long for viral evolution to escape vaccine-generated antibodies so much that they go from "suboptimally useful" to "actually harmful because they get in the way?" I think that's plausible based on the observation that every vaccine in circulation so far is overwhelmingly net positive to have, and we've already vaccinated 50%+ of the population (at least in some fortunate countries) and could continue "keeping up" with booster shots. So all of that makes sense and makes me feel reassured. However, I wonder if we're maybe underestimating the selection pressure from "virus evolves in unvaccinated population" and "virus evolves in population vaccinated by an outdated vaccine." The Delta variant evolved in India where only few people were vaccinated. Somewhere there (or in the vicinity, e.g. Nepal), it apparently acquired a mutation that's been studied in the Beta variant [https://twitter.com/jcbarret/status/1400487135828918273], which gives the virus better immune escape. This looks like somewhat fast virus evolution already, and the selective pressures will get even stronger. The UK has the Delta+ ("Nepal") variant already, and is reopening the economy. The selection pressure will strongly favor mutations that make the vaccine-generated antibodies less useful. Vanden Bossche is saying that the antibodies are targeted at the virus in a fragile way, so that once you dial up the selection pressure for vaccine escape, it could happen quickly. Therefore, I worry that the argument "virus evolution has been too slow so far" is not watertight because the
Looking for reasoned discussion on Geert Vanden Bossche's ideas?

The core issues I had with it are that the scenario he's envisioning just isn't playing out in the real world.  He has a mostly coherent model he's working with, and he's making the valid claim that "for some set of parameters and constants, terrible things happen!"  It's just that in real life, the parameters and constants are nowhere near what's needed for the badness he's claiming.

Specifically:

• His scenario requires a much higher mutation rate than we're seeing;
• His scenario assumes vaccine immunity isn't very strong, but what we're seeing is in

These extremely short responses discarding the bulk of my content feel less like you're attempting to understand, and more like you're attempting to get me to draw bright lines on a space I have repeatedly indicated is many different shades of grey.  Disconnecting from the discussion for now.

3JenniferRM9moI don't mean to butt in. Hopefully this interjection is not unfriendly to your relative communicative intentions... but I found the back-and-forth personally edifying and I appreciate it! Also, I do love bright lines. (I like weighing tests better, but only if the scales are well calibrated and whoever is weighing things is careful and has high integrity and so on.) In places, it seemed like there was a different gestalt impression of "how morality and justification even works" maybe? This bit seemed evocative in this way to me: Then this bit also did: For me, both of these feel like "who / whom" arguments about power, and exceptional cases, and how the powerful govern the powerless normally, and the justifications power uses, and the precedent of granting such power, and how precedents can cascade weirdly in black swan events, and how easy or difficult it is to resist seemingly-non-benevolent exercises of power, and to what degree appeals are possible, and so on. I read Jeff as trying to break the question of "ads" down into a vast collection of cases. Some good some bad. Some fixable, some not. Some he might be personally able to change... some not? Then he constructed at least one case that might be consistent with, and revelatory of, an essentially acceptable (and not unbenevolent?) exercise of a certain kind of power. One case could exist that was good for everyone in that one case... because it is full of puppies and roses for everyone (or whatever). The "power" here is basically "the power to choose at the last second what some parts of a website (that in some sense 'has been asked for by the person the website copy will be sent to') might look like"? If you object even to this one quickly constructed "best possible use" of such a website editing power, despite the puppies and roses... that would mean that it isn't "the results as such", but (groping here...) more like "who or how are the results decided"? Which... maybe who and how any economic even

Publisher, advertiser, the distinction does not matter.  The point is that the target does not get to decide.

5ChristianKl9moThere are a lot of decisions I can make to influence the ads I see. On facebook I can give quite detailed feedback. In the Google ecoystem I can tell google the interests for which I want to see ads. In many cases I can decide whether an app gets access to an identifier to give me customized ads or random ads.

You might find it unpleasant, but it's it the job of Simurgh Followers to spread the Truth Of The Endbringers to everyone!  Surely if people just watch enough of it, they will be converted.

The point is that the target gets to decide what's acceptable and what isn't, not the advertiser. The current system makes the advertiser the judge, and that's not ok, even if we have managed to construct a sorta functional system that mostly takes care of the worst abuses.

5jefftk9moYou mean the publisher, right?

I'm not convinced I fully understand your distinction, let alone that we could codify it sufficiently to make it into law.

Regarding 'codify into law', that's not an excuse, and it disregards how the US legal system works.  If we can codify slander, if we can codify "harm", if current advertising companies can codify "unacceptable ad", we can codify this.

If you visit a model railroading site, are ads for model locomotives push or pull?

Firm push, but only because of the physical realities of the current system.

The fact of the matter is that by default, ... (read more)

2jefftk9moI'm still confused about what you consider to be pulled. If I click on a link within the model railroading site to their page about locomotives, would locomotive ads in the response be push or pull?
Fractal Conversations vs Holistic Response

For bulk exchange of information and state, holistic is really good.  I strongly prefer the holistic approach, but I've found that it only works for entirely friendly conversations.  If it's adversarial, I find that branches get aggressively pruned to just the things that the opposing side can most easily attack.

And if you think about holistic being optimized for "exchange of information and state", this makes perfect sense:  adversarial conversations are rarely if ever about information exchange; they're about "winning".

It's also perhaps wo... (read more)

2abramdemski9moThis is a good point. The holistic approach can come off as really adversarial if the conversation is just a little adversarial, because my blindsight guess can be pretty ugly, or at least, can come off that way. I have witnessed a fairly friendly seeming conversation where a holistic-responder responded to a decision theory point by bringing up trauma and abuse (bringing up episodes in the past of both conversation participants which you'd normally expect to be really sensitive) and offered a perspective which could at least very easily be confused with "it's your fault you were abused". If the conversation hadn't been very friendly, this could have gone extremely poorly. Holistic responses have a tendency to Yeah, I often find that I have to prune less-important threads preemptively, out of concern that my response on branch X might seem like an easy target and thus cause branch Y to get pruned by the other person, when I think branch Y is more important. To be honest, I probably do not do this as much as I ideally should. (I want to respond to all the threads!) So a level of non-adversarialness is also required to really maintain good branching conversations.
Let's Go Back To Normal

Given the current vaccination rates in the US, and the fact that supply is already beginning to exceed demand, I'd recommend full open in approximately a month.  That gives most of the remaining unvaccinated people time to go get at least their first shot, and should allow us to get below exponential growth nationwide, even though we're likely to have it in sub-populations.  IMO the target should be 'not overloading hospitals'.

After that, let it burn.

From the interviews and things I've seen so far, literally the only way to change a vaccine denie... (read more)

1[comment deleted]9mo
Let's Go Back To Normal

I'd just like to point out that while "facing these tradeoffs is stupid and avoidable" (which I agree with), it's much, much more accurate to say instead "facing these tradeoffs is effectively impossible to avoid even though it's stupid and avoidable".  We might not like reality, but it's not going to go away no matter how much we call it stupid and avoidable.

6Zac Hatfield-Dodds9moI think it's a valuable post, and agree that as an individual in the USA in 2021 it's worth thinking carefully about these tradeoffs. In Australia though, it's trivial to avoid facing these tradeoffs, because of the different policies we followed through 2020. (I will never claim they were great policies, but they were good enough) My broader point is that the policy playbook we learn from COVID should be how and why to avoid such situations, not about how to live with R0≈1 for extended periods. Just do the proper lockdown for four-six weeks at the start instead of the end, and it's over! We wouldn't even need vaccines, let alone masks!
Alzheimer's, Huntington's and Mitochondria Part 3: Predictions and Retrospective

Having an overarching model (or several competing models) of which different parts can be tested independently seems like a structure which is very amenable towards different scientists, so I am disappointed none of the biological/medical community has started doing something like this.

This is actually done, quite a lot in fact, it's just really hard and the search space is huge.  Kudos to you for your analysis; it's unlikely to be a major step forward, but given that idea search space is effectively exponential, it's also entirely possible that it's ... (read more)

> its entire purpose is to alter people's mental state without their permission

I think that's the core of our disagreement?

Yes, and I think that would be a better path to attack my position.  There's two attack vectors in that quoted line - "alter peoples mental state without their permission", and "permission".  I would recommend avoiding the first attack vector; that will be an exceedingly difficult sell to me.

Permission on the other hand is already a partially open attack vector, and you're much, much more likely to change my mind by that r... (read more)

3jefftk9moI'm not convinced I fully understand your distinction, let alone that we could codify it sufficiently to make it into law. If you visit a model railroading site, are ads for model locomotives push or pull?

Here's another version of your example:  Some people aren't watching nearly enough snuff and torture videos. There are people who would like to watch them, but don't know it exists.  If I place ads for torture and snuff videos and some people decide to click on them while other people don't, is that a problem?

As I mentioned earlier, advertising is like weaponry.  Your example also reads to me like a classic justification for 'everyone having guns':  "but what if I'm attacked by a rabid dog?  If I have my gun I can protect myself! &... (read more)

5jefftk9moIn that case I expect users to find viewing these ads incredibly unpleasant, on average, much more so than either the example I gave, or advertising in general? (And almost all publishers would not be willing to work with an ad network that placed this kind of ad on their page)

As someone who also works on Ads at Google, I have to take the opposite stance; I view advertising as a blight upon the face of humanity, something to destroy if we can at all figure out how to do so.  I comfort myself knowing that Google Ads is arguably the best of what's an awful ecosystem, and that I work in what's arguably the 'least bad part of advertising', which is fraud and abuse protection.  At least the systems I work on make things less terrible.

its entire purpose is to alter people's mental state without their permission

I think that's the core of our disagreement? Here's an example I think is about maximally sympathetic: in non-pandemic times I help organize a contra dance. There are people who would like our dance, but don't know contra dancing exists, don't know that they would like it, or don't know about our dance in particular.

If I place ads, and some people see them and decide to come to our dance, do you have a problem with that? Or is it that you think most advertising doesn't work that way?

7JesperO9moAt least on the internet you could argue that people give their permission by choosing to visit the sites (as opposed to avoiding them, or paying for an adfree experience). But maybe people aren't giving their permission because they underestimate the power of ads and are not making a conscious choice? Curious what you think of JeffTk's argument about the counterfactual - would universal paywalls be better?
Best empirical evidence on better than SP500 investment returns?

I still have some remaining bitcoin, from the olden days when mortal man could mine it themselves.  My advice to everyone I've ever talked to regarding bitcoin is to avoid it.  I have been slowly divesting my holdings.

My rationale is that while both the dollar and bitcoin are fiat currencies, bitcoin is far, far less anchored to reality than most 'normal' currencies.  The dollar and the euro at least have people trying to keep monetary levels somewhat tied to physical economic value.  The value of bitcoin, meanwhile is largely driven by... (read more)

2Teerth Aloke9moI don't hold Bitcoin, friends.
1Jozdien9moWhat would your advice be on other cryptocurrencies, like Ethereum or minor coins that aren't as fad-prone and presumably cheaper to mine?
On Sleep Procrastination: Going To Bed At A Reasonable Hour

I've found lighting, melatonin, and caffiene regulation to be wonderful additions to my sleep regime.  I take melatonin pretty consistently at around 8:30 pm, and it seems like it helps make me sleepy ~45 minutes later.  As per SSC though, melatonin isn't particularly strong and the effect I'm noticing may very well be placebo.  I always have caffiene, but rarely after 2 pm, and typically not more than two cups of coffee per day.

That said, I suspect my lighting and light policy is having a much, much bigger effect.

The primary light source in... (read more)

1iamef9mo"I've found that even a few minutes of using the overhead lights after 7:00 pm breaks this; I both don't get as sleepy as normal, and find it harder to go to sleep if I go to bed anyway." Are the overhead lights orange / red-shifted? Have you tried blue-blocking glasses?

Quick comment:  I noticed that in all of your examples above, I chunk substantially bigger and fewer pieces.  For example, in the "15 different bold bits" clip, I chunk it into about 8 pieces instead.

This is likely experience/background dependent; I happen to have a relatively strong background in ML and have read a stack of research papers recently, so I probably have both stronger noise filters and more complicated primitives available.

2AllAmericanBreakfast10moThese are great points! The chunks I included are not personalized, so as you point out, they include information a skilled reader would filter out and use multiple chunks where a skilled reader might just see one.
How Should We Respond to Cade Metz?

Let's be blunt here:  the NYT article is pure, unbridled outrage bait dressed up as journalism.  It's not trying to solve a problem, and it doesn't have any agenda other than to pack as much outrage as possible into the publication form factor so as to maximize eyeballs.  It simultaneously craps on EA, the tech industry, SSC, rationalists, MIRI, tech investors and a stack of others.  (I'm surprised that they didn't also include jordan peterson, because hey, why not?)  That's not the sign of someone being honest.

IMO the correct resp... (read more)

4kjz1yStrongly agree with your analysis. I also think a lesson to take away here is that, assuming we agree pseudonymity is generally considered a desirable option to have available, it falls on us to assert the right to it.
Speedrunning my Morning Makes the Coffee Taste Weird

I do a low-grade speedrun in the morning, every day.  If you make it a habit, it becomes less of a stressful "speedrun", and more of "how you do things".

Example:

• Roll out of bed, grab phones
• While walking through hallway flip on heat
• Wander to office, put phones on desk where they'll sit all day long
• Put on clothes and socks that were put on my chair the night before
• Bathroom
• Stumble to kitchen
• Fill teapot, put on stove
• Fill water purifier back up
• Put coffee grounds in mug
• Do a set of pushups
• Go to office, power up monitors, start catching up
• Go to kitchen after
2kithpendragon1yFor sure! In fact, I do some things in that mode all the time. For example, most of the cognitive load left in my workday is dedicated to routing the most efficient path on the fly so I can fit more tasks in less time (and therefore have a leisurely lunch time). The primary reason for deliberately making my morning routine less efficient is to make sure that when I need to save time, there's plenty of time to save. Some things are better done with great efficiency, while others benefit from having built-in buffers for when things go wrong. Also, I like my coffee brewed a bit longer. 🕐🕜☕😁
We got what's needed for COVID-19 vaccination completely wrong

I think this might be (very slightly) unfair to mRNA vaccines, as the comparison between them and peptide vaccines is pretty situation dependent:

• We have reason to believe that peptide vaccines will work particularly well here, because we're targeting a respiratory infection, and the peptide vaccine delivery mechanism targets respiratory tissue instead of blood.
• That said, mRNA vaccines are expected to elicit much stronger immune responses than peptide vaccines would.
• I suspect that the low efficacy of mRNA vaccines (only 95% - low is relative) is likely beca
3agc1yI should probably know this, but are any of the mass produced COVID vaccines peptide vaccines?
5brianwang7121yEh, I guess I'm skeptical that it's that easy, even now, to make changes to the mRNA vaccines that would bring us from 95% up to 100% protection (against symptomatic infection), without knowing more about what's happening to that 5%. The spike protein does have "high mutant escape potential" as we are seeing, but I'm not sure that's what's behind 95% vs. 100% efficacy, given that the clinical trial data was gathered mostly before mutants really started taking off. It could just be inherent variability in the strength of people's immune systems. Not that it matters a ton, it's not like those 5% are developing severe disease, and given that I think it's weird to call the efficacy low (even in a relative sense — relative to which more effective vaccines?).
7paragonal1yJust a minor point: by delivery mechanism, are you talking about inserting the peptides through the nose à la RadVac? If I understand correctly, Werner Stöcker injects his peptide-based vaccine.
2ChristianKl1yI agree that the main issue is regulation that makes vaccine testing and the rollout harder then it needs to be. We don't know at this point how often you can give someone polyethylenglycol-based mRNA without their body creating a serious allergic reaction against it. That's an open safety question that needs to be addressed before you can use mRNA treatments to address a host of different issues. We already have substantially more side effects for the second vaccine dose then the first.
Making Vaccine

In my case, I'd estimate that I've spent around two hundred hours over the last several months coming sufficiently up to speed on the topics that I can reason about them.  I started with about your level of biology (or possibly less), but probably a slightly stronger chemistry background.

For the basics, I started with cell biochemistry, DNA/RNA, mRNA and protein construction.  From the vaccine side of things, I just started looking up things I found in the whitepaper which I didn't understand, and once I understood all the terms I started looking... (read more)

How do you optimize productivity with respect to your menstrual cycle?

I have two data points for dealing with this successfully, and both amount to "make it stop" instead of "improve things":

• One of my sisters "doesn't have time for this crap" and one day just stopped taking the placebo pills from her normal birth control and stayed on the active hormones continuously.  This apparently suppressed her period.  After doing this for about ten years, she stopped and successfully conceived at almost 40 years old.  This is not medical advice, do your own research, etc blah blah.
• One of my female friends has had an IUD
3just_browsing1yAh, I actually also have experience with the first bullet point. From what I remember, these "long cycle" periods were less problematic than my periods are off the pill. But, the particular pill I was on had negative side effects so I eventually stopped. Increasing cycle length would definitely improve my situation (assuming I can find a pill with no negative side effects). I think it's good to consider but not exclusively focus on that option because: * The selection of pills that are compatible with long cycles seems to be relatively small (at least my doctor says so) * On a 1 month cycle one might be able to manufacture more "highs" than on a 3 month cycle
Making Vaccine

Making Vaccine

I believe that initial post is what got me going down the rabbit hole of peptides and proteins and dna and rna and transcription factors oh my!  It's been a long ride.

Making Vaccine

Sarah Constantin is confused, and likely has not spent significant time reviewing the vaccine design.  From page 32 of the whitepaper:

"Empirical evidence should dominate selection criteria. Here are some best types of evidence:

• Mapping of epitopes in blood and other samples collected from convalescent patients (ideally stratified by severity of illness). This can be accomplished by a few primary means:
• 3D structural studies and modeling of neutralizing antibody binding to a viral antigen (e.g. Spike protein)
• Mapping of linear B-cell epitopes by binding a
4henryaj1yI also don't understand her comments about the peptide 'not neutralising COVID in cell [culture]' - why would it? The peptide is just an antigen to get the body to raise an immune response; on its own it doesn't kill COVID.
5ChristianKl1ySpeaking about what are the best types of evidence is different from demostrating that this evidence exists for individual sequences. If we start with the list the first is Spike 802-823cir. They provide no citations to papers for this and changed the structure in a way the believe to be benefitial (likely based on in silico modelling).
Making Vaccine

Sorry about that; I believe I misread your comment as implying that if the moderator is ignorant, he won't have enough information to form a reasonable prior.  My disagreement was along that line, as it seems that misinformation, especially about medical things, is so prevalent that everyone's default prior should be 'fraud unless lots of evidence points the other way'.

A couple of minor quibbles:

1. The peptides did not "come from in silico studies"; they came from the antibody profiles of real patients, who really had covid, and really recovered from covid (ideally without having a Bad Time during recovery.)  So there's more than just computational reasons to believe they will be useful.
2. It's questionable to complain that radvac did not have a single "research study using any of the peptides in the RADVAC white paper that found they inhibited SARS-CoV-2 infection in cells, let alone animals or humans", when the pfizer vaccine (which we know works) was designed via the same process a year ago, when we had even less information about effectiveness.
3Daniel Kokotajlo1yHow minor are these quibbles? What's your overall estimate of the probability of the RADVAC vaccine working and how much did it change upon reading Sarah's post?
Making Vaccine

Yes.  The differential tradeoff is how one should evaluate this.  The only reason my evaluation came out in favor of trying the radvac vaccine is because I have a high-risk event coming up in the next few months, and I am extremely unlikely to be able to acquire a commercial vaccine before then.

Making Vaccine

In my case, yes.  My bio expert indicated that it was likely to be effective (more than 50%, but less than 90%) and that the risks were effectively zero in terms of serious complications.

Regarding the food grade versus lab grade question, as well as inaccuracies or mistakes in construction of the vaccine, this was a question I spent a reasonable amount of time on.  The TL/DR is that the engineering tolerances are incredibly wide; the molecular weight of the chitosan isn't that important, the mixing rate isn't that important other than it be fast ... (read more)

6Davidmanheim1y"the risks were effectively zero in terms of serious complications" Your expert said that the risk of putting unfiltered peptide strains into your body was negligible? This claim confuses me. Did you talk to someone who has a background in immunology, or an infectious disease specialist? (The former seems like the more important type of expertise.) And while this isn't my area of expertise, the claim seems wrong. Having your body develop immune reactions to sequences that aren't the full virus seems potentially really bad - because they could look like other things you don't want your body reacting to.

I wasn't sure what you meant by more dakka, but do you mean just increasing the dose? I don't see why that would necessarily work--e.g. if the peptide just isn't effective.

I'm confused because we seem to be getting pretty different numbers. I asked another bio friend (who is into DIY stuff) and they also seemed pretty skeptical, and Sarah Constantin seems to be as well: https://twitter.com/s_r_constantin/status/1357652836079837189.

Not disbelieving your account, just noting that we seem to be getting pretty different outputs from the expert-checking process... (read more)

Making Vaccine

Again, I have to disagree - misinformation is much more likely than information by default, and the moderator need only have a reasonable low-probability prior in order to reject unusual/uncommon claims without evidence.

7Yoav Ravid1yI agree with that. not sure what you think i meant that you disagree with it.. (or was it directed at the comment above me?)
Making Vaccine

Yeah, the pfizer vaccine looks like it just uses mRNA to construct the RBD (receptor binding domain) of the spike protein, which is about two hundred amino acids long.  None of the default 9 peptides in gen 9 radvac are for that domain.  See page 40 of the whitepaper for the full spike protein sequence; the highlighted blue is the RBD, and the short underlined sequences are peptides selected for the vaccine.

The moderna vaccine uses mRNA to construct pretty much the whole spike protein, including the RBD.  This has overlap with 3 of the 9 rad... (read more)

6johnswentworth1yHoly crap, the entire RBD!? These mRNA vaccines are a technical marvel, I'm amazed they can actually deliver that into a cell safely. I really hope you write up a post on your learnings, the comments have been amazing and way more in-depth than my knowledge.
Making Vaccine

Absolutely obviously yes.  I have some level of concern that this post will go viral (ha ha), get a lot of attention outside of lesswrong, and the company I'm working with will cancel my order because it's "covid misinformation" related.

The FDA might be slow and take months to approve safe things while thousands of people die per day, but they're perfectly capable of announcing an immediate and indefinite peptide ban in under a day because a news article crossed the wrong person's desk.

About the "viral" part. This post is currently at the top of HN: https://news.ycombinator.com/item?id=26022750

Making Vaccine

My estimate for whether or not I would test positive on a blood test was only about 50%, since blood isn't the primary place that the response is generated.  I'm already betting a substantial amount of money (peptide purchases and equipment) that this will be helpful, and I see no reason to throw an additional $50 on a break-even bet here. I would, however, be happy to commit to sharing results, whether they be positive or negative. ... and now it occurs to me that if Lesswrong had a 'public precommitments' feature, I would totally use it. Making Vaccine A lot of people have been working really hard for the last year to discover, understand, and know these things. It's the foundation for how the mRNA vaccines work. Perhaps take a look through this: https://www.sciencedirect.com/science/article/pii/S2319417020301530 -1ChristianKl1yI seems my intuition is well-founded here. According to Sarah Constantin [https://twitter.com/s_r_constantin/status/1357653234261884929]the peptide here are selected in silico and not based on antibodies developed by infected people. Making Vaccine While I generally agree with the concept, I'm going to push back a little here. I read the 1-2% chance as less being about "why aren't companies doing it" and more about lack of information. My initial reaction to seeing it was that it was a combination factors along the lines of: • "there's a lot of fraud out there, and by default my prior for things like this being valid is very low" • "factoring in that a couple of lesswrongers seem to think it's ok that only pushes my estimate up into the handful of percent range" • "but there's also evidence against, in t ... (read more) Making Vaccine Yes, I still plan to get the commercial vaccine once it's available to me (likely some time in august.) As I understand it, the commercial vaccines hit different areas of the virus from the ones that radvac selected, improving protection even further. There is actually an optional peptide for radvac which does cover one of the same regions as the commercial vaccines. I elected not to include it under the assumption I'd be getting it from the commercial vaccine. Making Vaccine Yes; sorry I was unclear. Those peptides generate the antibodies we care about, that are known to be effective against the full virus. 2ChristianKl1yIt's unclear to me to what extend we know this and your description looks to me like it asserts that we know things that are very hard to know. Making Vaccine Regarding the 33.4% approval rate: based on what I've learned about traditional vaccine development and production in the last few months, I am not at all surprised. Both peptide and RNA vaccines are effectively "state of the art" technologies compared to traditional vaccine techniques. It's like comparing modern non-invasive out-patient surgery to the 1970's equivalent. You need look no further than the russian and chinese vaccines - those use the rather crude technology of "throw big chunks of inactivated virus particles at the immune sy... (read more) 3Creutzer1yThe Russian vaccine, unlike the Chinese one, is not an inactivated virus. It uses an adenovirus vector for delivery of genetic material that makes the body's cells synthesise antigen material, much like the AstraZeneca/Oxford vaccine. 5ChristianKl1yThat seems to me like a strange statement. In what way are amino acids sequences in the peptides "from antibodies"? Making Vaccine My understanding is that it helps a lot. The biggest benefit seems to be that the immune system is primed in at least some fashion; it knows what to look for, and it has readily available tools that should be effective. It doesn't have to take a day or a week to try random things before it finally discovers a particularly effective antibody and gets the production chain ramped up to start a proper immune response. Instead, your immune system will very quickly get a signal it understands as bad and can immediately start ramping up when it does detect th... (read more) Making Vaccine I agree as well. It takes a non-trivial amount of knowledge and research to evaluate the the whitepaper and its claims, and I wouldn't expect the moderator of a "neoliberal" group to have that expertise. We have options with a known risk profile (the commercial vaccines), and there's a spot of fraudulent "cures" out there. The safe thing for a moderator to do is blackhole potentially dangerous claims they don't have the time and/or experience to evaluate. Making Vaccine Regarding the final paragraph, "you need some level of expertise yourself before you can distinguish real experts from fake": that has been the number one reason I didn't beat johnswentworth to the punch and post first with my experience. I have learned more about biochemistry in the last three months than in my entire prior life combined. It has taken me three months of research, asking questions, and conferring with experts to get sufficient confidence in my understanding to commit to the project. I'm incredibly thankful to you (johnswentworth)... (read more) I'd be very interested in a post on what you learned! I relied mostly on general bio background from undergrad, it sounds like you probably went into more depth in areas specifically relevant to this. Making Vaccine My personal estimate is that the the percentage of nurses who have done this is effectively zero (less than one in a thousand with high probability, less than one in ten thousand with moderate probability.) Further, those who did do it are likely to have read through the whitepaper, and therefore are also likely to get the commercial vaccine, as it covers different epitopes than the radvac vaccine. 1kjz1yAgree it is extremely unlikely that many nurses have done so, and your probabilities seem quite reasonable. I think the main reason why many nurses have declined the vaccine is social signaling - either to maintain their social status within a mostly anti-vaccine peer group, or to maintain credibility with their anti-vaccine patients, who may be reluctant or outright refuse to be treated by a nurse who has been vaccinated because such a nurse is on "the wrong side" and can no longer be trusted. However, a nurse could self-administer the radvac vaccine and get some protection, while still being able to honestly claim they have no plans to get the commercial vaccines. I hadn't read the whitepaper yet before my initial post, and after a quick scan it looks like you are correct that radvac covers different epitopes than the commercial vaccines (I haven't done my own detailed analysis yet). Are you and others planning to take radvac still planning to get a commercial vaccine once you are eligible? Making Vaccine The whitepaper is a good source, but like johnswentworth, I also contacted a medical professional to evaluate it. The response came back quickly and confidently, and was along these lines: "Oh, yeah, this is safe. Nasal vaccines are safe. The biggest worry is that it might not work, so make sure you get the commercial vaccine too. I'd be interested in doing this with you as a joint project and giving it to my family, and I also have a colleague who might be interested in doing it." The biggest point of disbelief on their part was that it's possible to order all the equipment and peptides online and have them shipped to your door. Making Vaccine My rough guess is that there's a 75% probability of effectively full immunity, and a 90% probability of severity reduction. This is a pretty well tested and understood vaccine mechanism, and the goal isn't "perfect immunity" as "prime the immune system so it doesn't spend a week guessing about what antibodies it needs to combat the virus effectively". As to why established companies don't do it, I believe it's partially logistics, and largely red tape. Logisitics first (though it should be noted that at least some of these could likely be tackled with... (read more) 9cursed1yYou can buy nasal sprays over-the-counter [https://www.walgreens.com/store/c/nasal-sprays/ID=361393-tier3], while I can't think of a single injectable medicine that you can buy legally without a prescription. I don't think the "stab people in the arm" argument is very strong. Would you like to make a friendly wager? (Either Dentin, or johnswentworth, or anyone else making their own vaccine). We can do 50/50, since its in between our estimates. If you have two positive back-to-back anti-body tests within 2 months, you win (assuming you don't actually contract covid, which I trust you'll be honest here). If not, I win. To start off with, I'm willing to put down$100, but happy to go up or down.

This is a very in-depth explanation of some of the constraints affecting pharmaceutical companies that (mostly) don't apply to individuals, and is useful as an object-level explanation for those interested. I'm glad this comment was written, and I upvoted accordingly.

Having said that, I would also like to point out that a detailed explanation of the constraints shouldn't be needed to address the argument in the grandparent comment, which simply reads:

Why are established pharmaceutical companies spending billions on research and using complex mRNA vaccine