https://www.lesswrong.com/posts/niQ3heWwF6SydhS7R/making-vaccine This website requires javascript to properly function. Consider activating javascript to get access to all site functionality. LESSWRONG LW Login Making Vaccine by johnswentworth5 min read3rd Feb 2021117 comments 404 CoronavirusDIYMarket InefficiencyPractical Frontpage Making VaccineThe ProcessThe PlanMotivations 117 comments Back in December, I asked how hard it would be to make a vaccine for oneself. Several people pointed to radvac. It was a best-case scenario: an open-source vaccine design, made for self-experimenters, dead simple to make with readily-available materials, well-explained reasoning about the design, and with the name of one of the world's more competent biologists (who I already knew of beforehand) stamped on the whitepaper. My girlfriend and I made a batch a week ago and took our first booster yesterday. This post talks a bit about the process, a bit about our plan, and a bit about motivations. Bear in mind that we may have made mistakes - if something seems off, leave a comment. The Process All of the materials and equipment to make the vaccine cost us about $1000. We did not need any special licenses or anything like that. I do have a little wetlab experience from my undergrad days, but the skills required were pretty minimal. [lta3rcoijw]One vial of custom peptide - that little pile of white powder at the bottom. The large majority of the cost (about $850) was the peptides. These are the main active ingredients of the vaccine: short segments of proteins from the COVID virus. They're all <25 amino acids, so far too small to have any likely function as proteins (for comparison, COVID's spike protein has 1273 amino acids). They're just meant to be recognized by the immune system: the immune system learns to recognize these sequences, and that's what provides immunity. [v88hftnaw1]Each of six peptides came in two vials of 4.5 mg each. These are the half we haven't dissolved; we keep them in the freezer as backups. The peptides were custom synthesized. There are companies which synthesize any (short) peptide sequence you want - you can find dozens of them online. The cheapest options suffice for the vaccine - the peptides don't need to be "purified" (this just means removing partial sequences), they don't need any special modifications, and very small amounts suffice. The minimum order size from the company we used would have been sufficient for around 250 doses. We bought twice that much (9 mg of each peptide), because it only cost ~$50 extra to get 2x the peptides and extras are nice in case of mistakes. The only unusual hiccup was an email about customs restrictions on COVID-related peptides. Apparently the company was not allowed to send us 9 mg in one vial, but could send us two vials of 4.5 mg each for each peptide. This didn't require any effort on my part, other than saying "yes, two vials is fine, thankyou". Kudos to their customer service for handling it. [cvehyfik1r]Equipment - stir plate, beakers, microcentrifuge tubes, 10 and 50 mL vials, pipette (0.1-1 mL range), and pipette tips. It& apos;s all available on Amazon.[j6o2kqnnwt]Other materials - these are sold as supplements. We also need such rare and costly ingredients as vinegar and deionized water. Also all available on Amazon. Besides the peptides, all the other materials and equipment were on amazon, food grade, in quantities far larger than we are ever likely to use. Peptide synthesis and delivery was the slowest; everything else showed up within ~3 days of ordering (it's amazon, after all). The actual preparation process involves three main high-level steps: * Prepare solutions of each component - basically dissolve everything separately, then stick it in the freezer until it's needed. * Circularize two of the peptides. Concretely, this means adding a few grains of activated charcoal to the tube and gently shaking it for three hours. Then, back in the freezer. * When it's time for a batch, take everything out of the freezer and mix it together. Prepping a batch mostly just involves pipetting things into a beaker on a stir plate, sometimes drop-by-drop. [v68crrhy53] Finally, a dose goes into a microcentrifuge tube. We stick the intake tube of a sprayer into the tube, and inhale. [guucarnodg] That's the process, at a high level. Multiple boosters are strongly recommended, so there's a few iterations of this, though only the "take stuff out of the freezer and mix it together" step needs to be repeated. See the whitepaper for the full protocol details, as well more information about each of the peptides and what the other ingredients do (summary: chitosan nanoparticles). The Plan The key problem is how to check that the vaccine worked. If it were injected, that would be easy: just get a standard COVID antibody test. Inhaling makes it a lot harder to hurt yourself, but also complicates testing. The whitepaper goes into more detail and half-a-dozen different types of immune response, but the basic issue is that immunity response in the mucus lining (i.e. nose, lung, airway surfaces) can occur independently of response in the bloodstream. Commercial COVID antibody tests generally check a blood draw. In principle one can run a similar antibody test on a mucus sample, but , so the commercial tests check blood. (Side note: in many ways immunity in the mucus lining is better than in the blood, since it blocks infection at the point where it's introduced. This is an advantage of inhaled vaccines over injected. So why do most commercial vaccines inject? Turns out logistics are a major constraint on commercial vaccine design, and injections are surprisingly easier logistically. One of the major relative advantages of radvac is that it's intended to be prepared on-site shortly before administration, so it can use techniques which work better but don't scale as well. That largely balances out the constraints of readily-available materials and simple preparation. As usual, the whitepaper goes into much more detail on this, including several other logistics-related relative advantages - multiple boosters, custom peptides, frequent design updates, etc.) The whitepaper claims that "over a hundred" researchers have self-administered the vaccine so far, but I have not been able to find any data on test results from any of them. The paper says that inhaled vaccine can induce immunity in the blood, but I don't have a quantitative feel for how likely that is, other than the usual assumption that more dakka makes it more likely. Meanwhile, I don't have a convenient way to test for immune response other than the commercial tests. So, the current plan is to search under the streetlamp. We'll just use the commercial tests. Both of us got an antibody test before starting the project, and both came back negative. My current model is: * If the vaccine induces an immune response in the blood, then it almost certainly induces one in the mucus lining, but the reverse does not hold. So a positive blood antibody test means it definitely works, a negative antibody test is a weak update against. * There's some chance that a few doses are more than enough to induce a blood response. * There's some chance that more dakka will induce a blood response, even if the first few doses aren't enough. So, we'll do (up to) two more blood tests. The first will be two weeks after our third (weekly) dose; that one is the "optimistic" test, in case three doses is more-than-enough already. That one is optimistic for another reason as well: synthesis/delivery of three of the nine peptides was delayed, so our first three doses will only use six of them. If the optimistic test comes back positive, great, we're done. If that test comes back negative, then the next test will be the "more dakka" test. We'll add the other three peptides, take another few weeks of boosters, maybe adjust frequency and/or dosage - we'll consider exactly what changes to make if and when the optimistic test comes back negative. Risks are very minimal (again, see the paper), so throwing more dakka at it makes sense. Consider this a pre-registration. I intend to share my test results here. Motivations Why am I doing this? I imagine, a year or two from now, looking back and grading my COVID response. When I imagine an A+ response, it's something like "make my own fast tests, and my own vaccine, test that they actually work, and do all that in spring 2020". We've all been complaining about how "we" (i.e. society) should do these things, yet to a large extent they're things which we can do for ourselves unilaterally. Doing it for ourselves doesn't capture all the benefits - lots of fun stuff is still closed/cancelled - but it's enough to go out, socialize, and generally enjoy life without worrying about COVID. I've written a blog post about Benjamin Jesty, the dairy farmer who successfully immunized his wife and kids against smallpox the same year that King Louis XV of France died of the disease. I explicitly use this as an example of what Rationalism should strive to consistently achieve. Yet when a near-perfect real world equivalent came along, on super-easy mode with most of the work already done by somebody else, it still took me until December to notice. The radvac vaccine showed up in my newsfeed back in July, and I apparently failed to double-click. That level of performance is embarrassing, and I doubt that I will grade my COVID response any higher than a D. So I'm doing this, in part, to condition the mental motions. To build the habit of Doing This Sort Of Thing, so next time I hopefully do better than a D. Of course, the concrete benefits are nice too. But at this point it's only ~4 months until I'd get a vaccine anyway, so the price tag is only arguably worthwhile. It's still a fun project in its own right, and it gets dramatically cheaper with more people (remember, $1000 bought enough supplies for ~500 doses). Concretely, the largest benefits are in risk reduction. If there's big hiccups in commercial vaccine deployment, this becomes much more worthwhile. If the South Africa strain turns out to evade commercial vaccines, this becomes much more worthwhile - the radvac design is frequently updated based on the latest COVID research, so we hopefully wouldn't need to wait around for approval of a new commercial vaccine. Finally, I'm curious whether it will work - or whether we' ll be able to tell that it works. It's a data point as to just how often large bills are left sitting on sidewalks just a little ways off the beaten path. Coronavirus9DIY7Market Inefficiency2Practical4 Frontpage 404 Pingbacks 70Covid 2/4: Safe and Effective Vaccines Aplenty 117 comments, sorted by top scoring Highlighting new comments since Today at 10:58 PM New Comment Submit Some comments are truncated due to high volume. ([?]F to expand all) Change truncation settings [-]gwillen2d 48 Do you have any thoughts on the risks/hazards involved here? To me that's a much more significant consideration than the price. Some thoughts / priors: * Snorting chemicals I got from the Internet / mixed up myself without really knowing what I was doing: Superficially, seems potentially pretty risky. * Snorting peptides (assuming that the stuff ordered online was what it claimed to be, was pure and not contaminated with anything hazardous, and that I didn't accidentally create anything hazardous in the process): Definitely not as risky as snorting arbitrary unknown substances. Seems unlikely to be directly poisonous (although that's without reading about the other contents of the vaccine.) * Snorting COVID-19 peptides, in particular: Should I be worried about things like antibody-dependent enhancement? Are there other possible hazards specific to experimental vaccine administration that I should worry about? I'm sure the paper talks about this stuff, but I'm not a biologist so I can't promise I'd understand it if I read it. * Is there a possibility that this vaccine is both ineffective, and interferes in some way with the effectiveness of subsequent administration of a different vaccine? ... (read more) Reply [-]johnswentworth2d 70 The main answer here is "see the paper"; there's a lot of discussion about this stuff. I'll summarize a few points, as I understand them, relevant to your particular thoughts. * The "snorting chemicals" aspect is generally not much of an issue, since every ingredient other than the peptides is food-grade, and the quantity in a dose is tiny (one dose is <1 mL, and most of that volume is vinegar and water). If you were eating this stuff in your food and coughed on it, you'd probably get a higher dose than what's in the vaccine. * Peptide synthesis services generally provide various quality control checks on the product (some free, some upcharge). So at least you'll know what you're getting. * Antibody-dependent enhancement is one of the main things the paper discusses. It's pretty rare to begin with, and the cases where it's happened have some patterns to them which can be avoided; the peptides are chosen to avoid those pitfalls. Reading between the lines, it sounds to me like historical cases were largely a by-product of historical vaccine techniques (e.g. attaching pieces of one virus to the backbone of another in the case of Dengvaxia) which aren't used here. * As I understand it, interfer ... (read more) Reply [-]Dentin1d 23 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) for posting this article; it tracks almost perfectly with my understanding, and I have no significant model conflicts with any of your observations. It raises my confidence in both my understanding, and the project, substantially. Reply 6johnswentworth1dI'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. [-]gwillen2d 15 Thanks, I really appreciate you taking the time to respond. I should probably have clarified my current views / epistemic status in my comment, since I think it sounded more skeptical than I actually am. I would say it's something like: "I expect this is quite possibly a good idea, and most probably at worst a neutral idea. I am interested in trying to elicit anything in the long tail of risks that could change that." (I guess I did also want to encourage other people to at least briefly consider risks before trying this themselves -- although given the complexity and expense, perhaps I shouldn't worry that anybody might rush to try it.) Reply [-]johnswentworth2d 12 No worries, these are the right questions to ask and I'm glad someone brought them up. Reply [-]lincolnquirk2d 25 I think a lot of these questions are answered in the radvac paper. I sent a copy of it to a biologist I know, and asked if he thought it was crazy to do this, and he read it and said "geez this looks safer than doing drugs". I don't have enough expertise to add anything beyond that. Reply 5gwillen2dThanks, that's helpful (and hilarious.) I am looking through the paper now, and it definitely at least purports to answer some of my questions/concerns. (I haven't had a chance to follow the references to see the details.) I would love to hear more takes from people expert enough to weigh in. [-]AllAmericanBreakfast2d 32 I double-cruxed this article because my "voice of caution" objected to it. I eventually realized the issue was that part of my decision-making process when I do something weird, potentially risky, or expensive, is to consult with friends and family. Yet I feel that the feedback I would get from them would be so thoughtless, negative, frustrating, and potentially damaging, that it's not worthwhile. And I don't want to ignore this "consult someone first" rule, because it seems like a generally good rule that loses its force if ignored. However, I do know some specific people who might be good to talk it over with. They're warm, open-minded, very smart, scientifically literate, unconventional, have my best interests in mind, trustworthy, and willing to discuss this kind of stuff at length. My next move is probably not to read the paper, but rather to discuss it with them. Reply [-]JenniferRM1d 21 I think what you have done here is re-invented the actual helpful version of a practice whose authoritarian bureaucratic cargo-culted version is called "anonymous peer review". It is easy (and maybe dangerously wrong) to come to the straightforward conclusion that peer review in general is simply evil bullshit... until one finds the place from which a benevolent truth-oriented human (like oneself) finds a reason to consult with an actual "epistemic peer" as a prudent and socially-embedded response to one's own uncertainty about things one cares about. Reply [-]Dentin2d 32 Speak of the devil. I literally just placed my peptide order a couple of hours ago. My experience (finding supplies, test runs of mixing the solution, safety profile, analysis, etc.) basically matches up with this post. Thanks a lot for posting it. Reply [-]JenniferRM2d 30 You have my admiration, and my hope that you are calculating the risks accurately! I have not read the RaDVaC paper so I don't have a good object level model of safety and risks. From a distance it looks like heroism, because from a distance it looks like taking a risk in a way that could provide a role model for many if it works safely! It reminds me a bit of Seth Roberts who was a part of the extended tribe who did awesome stuff over and over again (seemingly safely) but who also may have eventually guessed wrong about safety. I guess I just want to say: "This is so freaking awesome, and PLEASE be very careful, and also please keep going if the risks seem worth the benefits." If you get a positive antibody result, have you thought about a personal challenge trial? The big benefits to be gained from vaccination seem to be to be behavioral: going out, doing life similarly to the Before Times... which is similar to a partial/random/natural sort of "challenge trial". I wonder if 1daysooner can or would be interested in keeping track of people who have tried the RaDVaC option, to build up knowledge (based on accidental exposures or intentional challenges) of some sort. Reply [-]jsteinhardt21h 28 Have you run this by a trusted bio expert? When I did this test (picking a bio person who I know personally, who I think of as open-minded and fairly smart), they thought that this vaccine is pretty unlikely to be effective and that the risks in this article may be understated (e.g. food grade is lower-quality than lab grade, and it's not obvious that inhaling food is completely safe). I don't know enough biology to evaluate their argument, beyond my respect for them. I'd be curious if the author, or others who are considering trying this, have applied this test. My (fairly uninformed) estimates would be: - 10% chance that the vaccine works in the abstract - 4% chance that it works for a given LW user - 3% chance that a given LW user has an adverse reaction -12% chance at least 1 LW user has an adverse reaction Of course, from a selfish perspective, I am happy for others to try this. In the 10% of cases where it works I will be glad to have that information. I'm more worried that some might substantially overestimate the benefit and underestimate the risks, however. Reply [-]Dentin11h 14 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 enough, the quantities aren't that important, exact peptide quantities aren't that important etc. A lot of these can be off by not just percentage points, but integer factors, and the result will still be acceptable. It's also worth pointing out that unless you make serious, significant mistakes that dramatically impair effectiveness, you can always just use "more dakka" to overpower the variations. My plan is to mix each batch independently, such that at least some of the construction variations are expected to cancel. (Also, freezing the final vaccine is likely to impair effectiveness, from what little I've found on the topic.) Reply [-]benjaminikuta2d 28 I was banned from r/neoliberal for sharing this. "Spreading dangerous medical information" Reply [-]Yoav Ravid2d 25 I think deleting it was a fair response (though perhaps banning is a little over the top). assuming the moderator has no way of checking for himself whether this makes sense and he knows he doesn't, he's left with a bet about whether this is the real thing or just bullshit. he expects more bullshit than real things, and he expects the bullshit to be dangerous. so he removes everything that fits this class of things, knowing he might end up also removing something real. Reply 5jimmy1dI think this is inaccurately charitable. It's never the case that a moderator has "no way" to know whether it checks out or not. If "Hey, this sounds like it could be dangerous misinfo, how can I know it's not so that I can approve your post?" is too much work and they can't tell the good from bad within the amount of work they're willing to put in, then they are a bad moderator -- at least, with respect to this kind of post. Even if you can't solve all or even most cases, leaving a "I could be wrong, and I'm open to being surprised" line on all decisions is trivial and can catch the most egregious moderation failures. Maybe that's acceptable from a neoliberal moderator since it's not the core topic, but the test is "When confronted with evidence that they can correctly evaluate as showing them to have been wrong, do they say 'oops!' and update accordingly, or do they double down and make excuses for doing the wrong thing and not update". I don't know the mod in question, but the former answer is the exception and the latter is the rule. If the rejection note was "Medical stuff isn't allowed because I'm not qualified to sort the good from the bad", then I'd say "fair enough". But actively claiming "Spreading dangerous misinfo!" is rarely done with epistemic humility out of necessity and almost always done out of the kind of epistemic hubris that has gotten us into this mess by denying that there's an upcoming pandemic, denying that masks work and are important, and now denying that we can and should dare to vaccinate in ways that deviate from the phase 3 clinical trials. This kind of behavior is hugely destructive and is largely the result of enabled laziness, so it's really not something we ought to be making excuses for. 4Yoav Ravid18hI agree i was being charitable. and yes, i was talking specifically about my expectations from a neoliberal forum moderator (if this was a biology or medicine forum i would have higher standards). my point wasn't necessarily that the mod did that out of good epistemics, just that the decision is justifiable, whatever method he actually used to take it. (i don't know the moderator in question either). actually I'd bet the moderator didn't do it with good epistemics, since he overreacted and outright banned him rather than just deleting it. 4Dentin1dI 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. 4benjaminikuta2dEven with a Harvard professor as an author? [-]Yoav Ravid2d 13 It depends more on the ignorance of the moderator and on how much time he's willing to spend than on the quality of the evidence. there definitely are cases of of PHDs and maybe even professors advancing pseudoscience. so this doesn't guarantee trustworthiness. the moderator has to make a decision in a state where he can't trust himself to distinguish real stuff from bullshit. he goes for minimizing harm at the cost of deleting novel good ideas. seems like a sensible decision to me. Reply 2benjaminikuta21hHow often do scholars of such prominence promote dangerous pseudoscience? [-]jsteinhardt21h 10 Often, e.g. Stanford profs claiming that COVID is less deadly than the flu for a recent and related example. Reply 1Yoav Ravid18hInteresting question, i don't know. but it also doesn't matter here. if the moderator is ignorant he's also ignorant of this fact, and thus cannot take it into account or will have to spend effort finding a good answer for it - so we're back at square one. 5Dentin11hAgain, 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. 1Yoav Ravid10hI agree with that. not sure what you think i meant that you disagree with it.. (or was it directed at the comment above me?) 2ChristianKl1dI think there's a difference here between sharing a link to RadVac and sharing a link to a LessWrong post by someone without credentials doing something on their own. 5AI_WAIFU17hI wouldn't look too deeply into that. The selection process for moderators on reddit is essentially first come first serve + how good are you at convincing existing moderators you should join the team. As far as I can tell this process doesn't usually select for "good" moderation, especially once a sub gets big enough that network effects make a subreddit grow despite "bad" moderation. This applies for most values of "good" and "bad". [-]Raemon2d Moderator Comment27 Note: this post was frontpaged (despite a general policy of not frontpaging covid content) both because a) it seems pretty important, and b) the rationality life lessons seemed pretty timeless. Reply [-]jsteinhardt1d 23 Hmm, important as in "important to discuss", or "important to hear about"? My best guess based on talking to a smart open-minded biologist is that this vaccine probably doesn't work, and that the author understates the risks involved. I'm interpreting the decision to frontpage as saying that you think I'm wrong with reasonably high confidence, but I'm not sure if I should interpret it that way. Reply [-]johnswentworth1d 13 You should make a top-level comment about this. Chance that the vaccine works and the associated risks are object-level questions well-worth discussing. In general, frontpage decisions are not endorsements (though I don't know Raemon's thoughts in this particular case), and this comment section is not the place for a debate about frontpaging norms. This is definitely the place to talk about chance the vaccine works and associated risks, though. Reply 6jsteinhardt21hI don't think I was debating the norms, but clarifying how they apply in this case. Most of my comment was a reaction to the "pretty important" and "timeless life lessons", which would apply to Raemon's comment whether or not he was a moderator. 4johnswentworth20hYeah, I don't mean to say your comment was bad as-written, just preemptively heading off a potential thread. 4jsteinhardt20hAh got it, thanks! [-]AllAmericanBreakfast2d 21 Vaccines that are brought to clinical trials have a 33.4% approval rate, which seems like a reasonable estimate of the chances that this vaccine works if executed correctly. Note that this is from trials conducted from 2000-2015. I probably have a roughly 5% chance of catching COVID before I'm vaccinated. Given my age, COVID would put me at a 0.2% risk of death. Let's double that to account for suffering and the risk of long-term disability. If I value my life at $10,000,000, then an intervention that gives me a 33.4% chance of avoiding a 5% chance of a 0.4% chance of death is worth $668. So it seems like I'd want to be vaccinating at least one other person in order for this to be worthwhile. I welcome any further thoughts on this expected value calculation. In particular, I think it's possible that I'm dramatically underestimating the risk and potential severity of long-term symptoms . It doesn't take much additional risk to make this project worthwhile for a single person. Reply [-]Dentin1d 16 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 system and hope that the immune system guesses the right antibodies to deal with the live version." Both peptide and RNA vaccines are instead, "we have identified very specific antibodies which we know are effective both from the serum of recovered patients and from computational modeling, then use exactly the minimal protein sequences needed to generate those antibodies." Both the russian and chinese vaccines use chunks of proteins that are thousands (and likely tens of thousands) of amino acids long, in a mostly inactivated form. The immune system has no idea what to latch onto, what will be effective at stopping replication, ... (read more) Reply 4ChristianKl1dThat seems to me like a strange statement. In what way are amino acids sequences in the peptides "from antibodies"? 3TheSimplestExplanation1dIt's my impression that the peptides in question are the antigens to those particular antibodies. 4Dentin1dYes; sorry I was unclear. Those peptides generate the antibodies we care about, that are known to be effective against the full virus. 2ChristianKl1dIt'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. [-]Dentin11h 12 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 Reply 1TheSimplestExplanation12hDo you have doubts? It seems plausible to me? 8Chan Bae2dDo you value your life at ten million? As in, would you take a 50% chance of death for five million? If so, why are you not smuggling drugs or whatever? 4AllAmericanBreakfast1dWell, a couple of researchers estimated [http: //ftp.iza.org/dp8224.pdf] that drug mules made a median of $1313 back in 2014, so I'd need to smuggle a lot of cocaine to earn that much. Seems like it would take a while... 3Bucky1dSay my life expectancy from now is 50 years and I work at an hourly salary of $30 (~$60k yearly salary) then I implicitly value the remaining 310,250 hours of my waking life at something like $9.3m total. This breaks down if offered larger probabilities of death and larger amounts of money (e.g. opportunity cost) but $10m seems like a sensible place to start for a Fermi calculation. In this case we don't even have to worry about larger probabilities of death - the calculation here is essentially an expected gain of 1.2 days of life for $1000 which comes to about $50 per hour of waking life. Instead of making a vaccine only for myself I would be better just to take half a week unpaid leave and gain the same amount of time for a cost of only $600. Obviously this has some assumptions baked in (like that I don't value my job) but If It's Worth Doing, It's Worth Doing With Made-Up Statistics [https://slatestarcodex.com/2013/05/02/ if-its-worth-doing-its-worth-doing-with-made-up-statistics/] . 5Czynski3hThis is an inappropriate reference class. This has no in vitro testing conducted; it's entirely a computational model [https:/ /twitter.com/s_r_constantin/status/1357653234261884929]. ""Peptide" just means "sequence of amino acids." Would you conclude that, because some lines of code can navigate a rocket to the moon, that your code is pretty likely to navigate a rocket to Mars?" [https:// twitter.com/s_r_constantin/status/1357655025418444800]. A vaccine brought to clinical trials has already overcome many more hurdles than this has. Generally in vitro testing (I think both for safety and efficacy), in vivo safety testing (in rats! [https://twitter.com/ justsaysinmice]), and some scaled-up testing in other animal models. This isn't a vaccine candidate. This is a promising research lead for a vaccine candidate. 4AllAmericanBreakfast2hI agree with the point of your comment, that vaccines brought to clinical trials is a suboptimal reference class. However, I think that this is a locally invalid argument: A computational model plus grounding in theory, if done right, should increase our confidence in the the efficacy of a sequence of peptides taken from the virus above the efficacy we'd assume for a random sequence of peptides. How much? Can't say. As others have pointed out here, we on the other hand are comparing a new and perhaps much more effective means of designing a vaccine to the methods that were used from 2000-2015, which may be less effective. Hence, perhaps the reference class is suboptimal in the opposite direction as well. I have no way to know how to weigh these competing factors. So I think the best thing to do is to start with the basic formula I concocted above, then modify it based on our intuitions about these other factors. Alternatively, you could very justifiably stick with the rule "I don't take untested medications." Although as someone else pointed out, if you have that rule then perhaps you should also make sure to not use any drugs? I don't have the answer, but wanted to try and provide some clarity for people who are considering breaking the "take no untested medications" rule. 4johnswentworth3hI'm not sure what your level of background knowledge is, but I heard that the Moderna vaccine was designed in two days. Clearly they did not do any significant in vitro or in vivo testing in that timespan. Maybe they did some in-vitro before human trials, I don't know; that would support an argument against using "vaccine brought to clinical trials" as a reference class. But the deeper point which this is trying to operationalize is "vaccine design just isn't that hard", in the sense that we don't need to test many designs to find one which works. People basically-know-how-to-design-vaccines, maybe not to quite the same extent as people basically-know-how-to-design-bridges, but to enough of an extent that experimental verification just isn't necessary in order to get a >50% chance that the design works, especially for relatively-mechanical designs like mRNA or peptides. Under this view, the reasons we don't see nearly-every vaccine trial succeed are (1) commercial vaccines are harder than lab (especially if you want no boosters, easy logistics, etc), and (2) diseases which are harder-than-average will naturally end up with disproportionately many trials, and (3) out-of-date companies take time to die off. 5waveBidder2dYou're missing the very real possibility of long-term negative side-effects from the vaccine, such as triggering an auto-immune disease or actually increasing your susceptibility, both mentioned in the whitepaper (whose risk-assessment I would be pretty sceptical of). I would think of this as more a trade-off between risks of side effects and COVID risks, rather than whether or not you can afford it. 4Dentin10hYes. 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. 3cursed2dI don't follow. Don't vaccines have trials on cells, mice, primates, before clinical? So unless radvac has also done similar testing, this 33.4% isn't comparable. [-]Sniffnoy2d 15 Wow! I guess a thing that still bugs me after reading the rest of the comments is, if it turns out that this vaccine only offers protection against inhaling the virus though the nose, how much does that help when one considers that one could also inhale it through the mouth? Like, I worry that after taking this I'd still need to avoiding indoor spaces with other people, etc, which would defeat a lot of the benefit of it. But, if it turns out that it does yield antibodies in the blood, then... this sounds very much worth trying! Reply 8Dentin1dMy 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 the virus. Keep in mind that the commercial vaccines don't have 100% success rate in that some people still get sick, but the 'priming' of the immune response is still there. I believe this is why the death rate / severe complications rate is effectively zero for immunized patients, even though it's possible to get sick. (Again, my understanding. I would very much appreciate correction/clarifications here.) [-]u8k2d 14 My jaw dropped at "~500 doses". At $2 per dose... that's significantly cheaper than it's costing the companies to produce the official vaccine. What am I missing here? I know you're making a different thing than Moderna, but if the thing your making exists and is this cheap then why is Pharma leaving the money on the floor and not mass producing this? I think you're underselling the potential benefit here! Doing a batch of this and distributing it to 500 people may be unfeasible. I assume the FDA or something comes for you if you're trying to commercially distribute home-brewed vaccines. But say, to 20 friends? Why not. Which brings the price down to $50 per/person, which seems like it'd be totally worth it to have immunity even a month earlier than the official vaccine is available to me. And it potentially gives immunity to your whole social scene. I'll wait for your results, and then will strongly consider doing a batch of this myself. Reply [-]Dentin1d 24 Oh, it's far, far worse (better?) than $2 per dose. As a thought experiment, I price estimated buying enough peptide for a hundred thousand doses, and it only costs about ten thousand dollars. Ten cents a dose is closer to realistic if you buy in bulk. Which also brings to mind a question of civilizational inadequacy: if we really cared and it really mattered, why not have every university with a lab in the country crank out a hundred thousand doses per week to their local populace? Reply [-]ryan_b1d 11 I don't think this has ever been possible in previous epidemics, at least for at-home manufacture. That being said, I would strongly support compiling a list of low-risk interventions like this, so next time we can publicize them at the outset and try mitigating the problem while waiting for the low-risk&high-success solution to be developed. Reply [-]Silver_Swift1d 17 If the thing your making exists and is this cheap then why is Pharma leaving the money on the floor and not mass producing this? There are a number of costs that Moderna/Pfizer/Astrazenica incur that a homebrew vaccine does not. Of the top of my head: 1. Salaries for the (presumably highly educated) lab techs that put this stuff together. I don't know johnswentwort background, but presumably he wouldn't exactly be asking minimum wage if he was doing this commercially. 2. Costs of running large scale trials and going through all the paperwork to get FDA approval. I think I'm generally more in favour of organisations like the FDA than a lot of people here, but even I expect this to be a very non-insignificant number. 3. Various taxes and costs of shipping/storing the vaccine until it can get to customers. 4. Costs of liability and a desire for the company to make a profit on this (as well as to pay the salaries for the all of the people needed to keep a large company running). Given all that I don't think the gap between this and the commercial vaccines is that insane. Reply [-]Czynski3h 11 As someone else said, the logistical difficulties for this are much larger than the standard jab method, the production process doesn't scale well, and once prepared it doesn't last long even if you freeze it. Making this for 20 friends and distributing it to them is very plausibly net-harmful, because you need to gather in close quarters to hand off the prepared vaccine, do it within a fairly short window (1-3 days) for all 20, and then repeat all that, including the production of new doses, at least once per week and ideally 2-3x per week. Given that the only evidence for efficacy is in silico, none in vitro let alone in vivo or in actual humans, it's not at all clear that the benefits outweigh the increased risk of spread from all that close contact. Reply 8johnswentworth1dBoth the other comments here are on-point. The materials for large amounts of radvac would cost pennies per dose, because the cost-per-unit of the peptides drops very rapidly as you scale up (remember, we doubled our order for <10% extra cost). However, in general, people and logistics are a bigger expense than materials for most products these days, and I certainly expect that to apply to vaccines. 3Andrew_Clough2hThat's only for raw materials. Actual production seems to have involved a fair amount of skilled labor per dose which probably dominates the $2 figure. A commercial vaccine can automate that but then you've got lots of development costs as well as logistics and compliance to worry about. I wouldn't expect that this vaccine is especially cheap. [-]AnnaSalamon2d 12 Neat! Will you also use try commercial antibody tests on your mucus, or is that known to not-work? Reply 7johnswentworth2dThe way the tests we've used work is a nurse takes a blood draw, then ships it off somewhere for the antibody test, so there's not really an opportunity to use mucus in the test. If the next test comes back negative, then I might search harder for an at-home antibody test and a protocol for mucus. 3jmh1dWould an alternative (and possibly easier) approach be to simply take some additional doses -- it's my understanding that you really cannot make yourself sick with this type of vaccine -- over a week and then retest for antibodies? If that still fails then consider figuring out how to perform your own mucus testing. 8TheSimplestExplanation1dWasn't there something about to much antigen possibly reducing immune reaction in the white paper? 7johnswentworth1dYes, good job catching that. I'm currently using relatively low dose of each of nine different peptides, so there's a fair bit of elbow room before I hit a large dose of each individual peptide, and even more elbow room before I'd start worrying about tolerance. It is something I'll check if I start cranking up the dosage. Also, to a large extent, "more dakka" here is as much about more time as higher dose. In general, you have to wait a while for a vaccine to really kick in. 2johnswentworth1dYeah, more dakka is still the default plan right now if the next test comes back negative. [-]Czynski3h 11 Via Sarah Constantin's Twitter: I looked into this, because yay citizen science. I could not find one 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. and "Take a random peptide that has never been tested on any living thing" is not at all the same thing as "take a well-known, well-studied recreational drug", as far as risk goes. She doesn't explicitly state that this has never been tested on any living thing. Possibly because she wasn't confident enough in her research survey to claim that, possibly because she was drawing a starker contrast than applies to this instance. But all the COVID testing for RADVAC is purely in silico, so while the chemicals involved may be studied for safety in vivo, efficacy is completely untested even at the (much simpler than organism) cell level. So the EV of the benefits are low, and the risks are unclear. Reply [-]TheSimplestExplanation1d 10 From the white paper: Antibody can be measured in nasal wash, however this is less quantitative and reliable than measurement in serum. Reply [-]Daniel Kokotajlo1d 9 Related: This was discussed on LW in August 2020, someone claims to have done it in December: https://www.lesswrong.com/posts/ 62WuBbQpSwAbctGDP/ what-price-would-you-pay-for-the-radvac-vaccine-and-why Reply [-]johnswentworth1d 16 I'm afraid I'm not flexible enough to kick myself that hard. Reply [-]ChristianKl6h 7 If nasal application doesn't provide a blood immune response it might be worth testing whether anal application will lead to a blood immune response. Reply [-]korin4319h 7 FYI, there's a map of people working on this that you can add yourself to for coordination: https://radvac.org/researchers-map/ Reply 2Jayson_Virissimo6hDoes this add you to an email list where discussion is happening, or merely put you on a map so that others in the area can reach out to you on an ad hoc basis? 1korin435hI think it just puts you on the map. [-]benjaminikuta2d 7 How do you know this is safe? Reply [-]Dentin1d 36 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. Reply 3johnswentworth2dSee the answers to gwillen above, and also the whitepaper. [-]Adele Lopez1d 6 The cheapest options suffice for the vaccine - the peptides don't need to be "purified" (this just means removing partial sequences), they don't need any special modifications, and very small amounts suffice. Seems like partial sequences could contribute to the autoimmune disease risk since they would be much more likely to match to normal cellular proteins. Has this been considered? Reply 7johnswentworth1dJust based on general background knowledge, if autoimmune problems were induced by sequences short enough to show up frequently from random noise, then we'd have autoimmune problems all the time (since we're breathing in peptides - including partially-broken-down-peptides - basically every day). So I'd be very surprised if it were an issue. This is exactly the sort of question I love to see, though. Great thinking. 6Adele Lopez1dSo at what point does a peptide go from triggering an immune reaction, to being completely inert? Off the top of my head, I can think of three possible factors: 1. The length of the peptide matters. Presumably, your body wouldn't create an immune reaction to dipeptides under any circumstances. But in this case, how close are these peptides to the threshold length? If they're well above it, then it seems this risk is still relevant. If they're close to the threshold, then that would mitigate a lot of this risk. 2. The amount of the peptide matters. I'd expect that your immune system generally does not create an immune response to a single foreign peptide it detects, and that there's a certain amount (perhaps variable between different peptides) necessary to cause a reaction. That would explain why breathing doesn't create autoimmune issues. But in this case, we might still expect a particular partial peptide to have a significant population, especially since certain peptide-peptide bonds are weaker than others. So again, this risk is still relevant. 3. The peptide must be associated with some sort of damage. It's plausible that the immune system doesn't create a response unless it detects actual damage (irritation at the human level). In that case, the vaccine presumably works because snorting a spray is sufficiently irritating. This risk is clearly still relevant in this case. I suspect that the actual answer is likely a combination of all three, and maybe some other stuff is relevant. Also, I checked the white paper, and it says the partial peptides aren't an issue, but doesn't seem to elaborate. [-]Adele Lopez21h 12 Alright, so the thing that antibodies are "trained" to detect is called an epitope. On page 23 of the white paper, it says: 6. VED might arise through vaccine design-induced distortion of viral epitopes, as has been proposed to occur by formalin treatment of RSV. a. Our preferred epitope type is synthetic peptides. Such peptides are chemically well defined and have a high degree of structural integrity. So distortions of the epitope can cause an autoimmune reaction, and synthetic peptides are good because they're stable and you know exactly what you are getting. But if you have a bunch of partial peptides mixed in, then it substantially weakens this point. Re: 3. It does seem to be true that "damage" is required. Substances which provoke an immune response are called adjuvants, and the adjuvants in this vaccine are the Chitosan and the Tripolyphosphate. Reading the paper more closely, it says that the truncated peptides are fine because the peptides get chopped up by proteases anyway. This does make me feel a bit less worried about this, but it also implies that this would be a potential issue for purified peptides as well. ETA: I also did a spot-check to see at which point this woul... (read more) Reply [-]PatrickDFarley1d 5 Very impressed by this, I really hope it works. These are the kind of audacious efforts that I love to see in this community Reply [-]sarelbic2d 5 If anyone knows of anybody planning to do this in the Maryland/DC/ Virginia area, please let me know Reply [-]ChristianKl1d 4 Are there other nasal vaccines that are based on nanopeptides currently on the market and FDA-approved? Reply 2johnswentworth1dI don't know this, but the whitepaper does mention that this approach is quite common for research vaccines. [-]gojomo22m 3 Curious, are the peptides-as-ordered shipped in freezer packs? Reply 2johnswentworth15mNo, they ship dry. [-]andrewseanryan2h 3 Have you tried making at home rapid covid tests? I have often wondered if it is possible to make an at home version of the spit paper rapid tests. No clue what this would take but would be great since the government hasn't allowed them yet. Reply [-]Borasko1d 3 Thanks for posting this, I didn't know about radvac before and now I am excited. I will read the white paper and probably make some myself. If your results are good which I really hope they are, I will try to help my family members get some as well. I don't mind paying $1000+ for family safety, and with the delayed vaccine rollout I would feel better even getting the vaccine to them one month earlier. So thanks again! I hope all goes well. Reply [-]jmh1d 3 Thanks for the write up! I started to do this myself but quickly found I was a bit confused on how to even order the peptides. I was expecting to be able to search product lines but.... Not really possible. So...is the process to simply identify some suppliers (not hard to find with Google) give them the amino acid sequences in the instructions and ask for a quote? (Hit that initial speed bump and have not gotten back to looking for phone numbers or customer support chat windows.) Just a thought. So this doesn't scale well for storage and shipping it sounds... (read more) Reply 4johnswentworth1dThe one I used had an online "custom peptide synthesis" order form. I just pasted in the sequences, checked a few boxes, it autogenerated the price tag on checkout screen, and then I hit the order button. (It actually took a bit longer than that since both my girlfriend and I triple-checked the sequences.) I specifically avoided any suppliers which would have made me talk to a salesperson to get a quote - that crap is a strong sign of Maziness. Dentin had a comment on this somewhere in this rapidly-growing comment section, saying that the commercial vaccines use different epitopes and should therefore play well together with this one. 6Dentin11hYeah, 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 radvac peptides. This paper has one of the better lists I've found of commercial vaccine types: https:// www.sciencedirect.com/science/article/pii/S2319417020301530 [https:// www.sciencedirect.com/science/article/pii/S2319417020301530] From the list in that paper, it seems like pretty much all commercial products are using spike as the primary target; radvac is unique in that it also targets ORF and Nuc. ----- Amusingly enough, when talking about the commonly targeted spike protein RBD sequences, the radvac whitepaper lists on page 29: "Spike 450-500; ACE2 binding residues of the RBD (Zhang et al); low degree of conservation; probably moderate to high mutant escape potential". So they pretty much called it in regards to the new virus strains with mutations like E484K. Another radvac whitepaper quote, which seems to line up with my independent research: "It is important to note that most published neutralizing antibodies target Spike RBD, as do many vaccines in commercial development. However, given the high degree of mutability of the RBD portion of Spike, it is highly recommended to identify and select targets outside the RBD because of mutant escape potential." And lastly, more specific to why no RBD peptides were selected, page 34: "Therefore, rather than focusing on ACE2-binding epitopes in the highly mutation prone RBD to inhibit virus binding to the ACE2 receptor, we targeted these B-cell epitopes in the highly conserved 3johnswentworth5hHoly 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. 4ChristianKl1dHow about sharing the link? Besides different epitopes, if the RadVac vaccine gives you an immune reaction in the mucosal immune system and the other vaccines give you a immune reaction in the normal immune system you will want both. 8johnswentworth1dI don't want people giving the company crap if this post ends up very widely read. If anyone would like a link, PM me. 3ChristianKl1dAre we really living in times where "company helped people with doing something themselves against COVID-19" would be problematic PR-wise? [-]mingyuan21h 17 obviously yes? Reply [-]Dentin11h 14 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. Reply 8habryka2hAbout the "viral" part. This post is currently at the top of HN: https://news.ycombinator.com/item?id=26022750 [https:// news.ycombinator.com/item?id=26022750] [-]cursed2d 3 Props to you for taking action here, this is some impressive stuff. That being said, I'm extremely skeptical that this will work, my belief is that there's a 1-2% chance here that you've effectively immunized yourself from COVID. What do you believe is the probability of success? Why are established pharmaceutical companies spending billions on research and using complex mRNA vaccines when simply creating some peptides and adding it to a solution works just as well? Reply [-]Dentin1d 28 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 a bit of effort): * Shots are well understood and easy; people are used to them, people know how to give them, etc. Nasal spray is irritating and makes you want to blow your nose, which washes out a lot of it and reduces effectiveness. * You need multiple of these annoying doses in the nose, staggered a few days apart, to generate a 'good' response. * This particular nanoparticle vaccine doesn't have a long shelf life due to peptide degradation. Peptides don't last forever, and while they're more stable than the RNA vaccines, you'd have to ship them frozen as well. * Nanoparticle vaccines in general suffer from particle aggregati ... (read more) Reply 7dxu1dThis 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: This question inherently assumes that the situation with commercial vaccine-makers is efficient with respect to easy, do-it-yourself interventions, and the key point I want to make is that this assumption is unjustified even if you don't happen to have access to a handy list of bullet points detailing the ways in which companies and individuals differ on this front. (Eliezer wrote a whole book [https://equilibriabook.com/inadequacy-and-modesty/] on this at one point, from which I'll quote a relevant section:) The grandparent comment is more or less an exact example of this species of argument, and is the first of its kind that I can recall seeing "in the wild". I think examples of this kind of thinking are all over the place, but it's rare to find a case where somebody explicitly deploys an argument of this type in such a direct, obvious way. So I wanted to draw attention to this, with further emphasis on the idea that such arguments are not valid in general. The prevalence of this kind of thinking is why (I claim) at-home, do-it-yourself interventions are so uncommon, and why this particular intervention went largely unnoticed even among the rationalist community. It's a failure mode that's easy to slip into, so I think it's important to point these things out explicitly and push back against them when they're spotted (which is the reason I wrote this comment). -------------------------------------------------------------------------------- IMPORTANT NOTE: This should be obvious enough to anyone who read Inad 7Dentin1dWhile 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 that we don't see any commercial products based on this, which pushes my estimate down to 1-2%" I think this is a pretty reasonable place to start from. 1cursed21hI don't understand the argument about SAD. A simple Google search shows thousands of articles addressing this very solution. The first Google result I found is a paper from 1984 with 2,758 citations: https://jamanetwork.com/journals/jamapsychiatry/ article-abstract/493246 [https://jamanetwork.com/journals/ jamapsychiatry/article-abstract/493246] But taking a step back, the "Chesterton's Absence of a Fence" argument doesn't apply here because the circumstances are very different. The entire world is desperately looking for a way to stop COVID. If SAD suddenly occurred out of nowhere and affected the entire economy, you would be sure that bright lights would be one of the first things to be tested. Dentin addresses the 1-2% claim pretty well, so I won't repeat it. [-]dxu6h 10 A simple Google search shows thousands of articles addressing this very solution. The solution in the paper you link is literally the solution Eliezer described trying, and not working: As of 2014, she'd tried sitting in front of a little lightbox for an hour per day, and it hadn't worked. (Note that the "little lightbox" in question was very likely one of these, which you may notice have mostly ratings of 10,000 lux rather than the 2,500 cited in the paper. So, significantly brighter, and despite that, didn't work.) It does sound like you misunderstood, in other words. Knowing that light exposure is an effective treatment for SAD is indeed a known solution; this is why Eliezer tried light boxes to begin with. The point of that excerpt is that this "known solution" did not work for his wife, and the obvious next step of scaling up the amount of light used was not investigated in any of the clinical literature. But taking a step back, the "Chesterton's Absence of a Fence" argument doesn't apply here because the circumstances are very different. The entire world is desperately looking for a way to stop COVID. If SAD suddenly occurred out of nowhere and affected the entire economy ... (read more) Reply 1cursed21hYou 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. 3johnswentworth20hI wouldn't take 50/50. I do think it's much more likely than that to induce mucus antibodies, but not blood antibodies. I would take 3:1 odds. 2Dentin11hMy 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. [-]kjz2d 2 Crazy thought, and I doubt this is likely on large scale or it would have been in the news, but any chance this could explain the higher than expected percentage of nurses who have rejected getting the vaccine? Perhaps some have already vaccinated themselves under the radar! And therefore have no need to take the "real" one. Reply [-]Dentin1d 10 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. Reply 1kjz1dAgree 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? 5Dentin1dYes, 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. 9jayterwahl2dI predict that is an overly-optimistic reason for why they're rejecting the vaccine. 2ChristianKl1dGiven that this vaccine targets a different part of the immune system there's no good reason to reject an injection vaccine when you take this vaccine. 1kjz1dFor the average Less Wrong reader, I tend to agree. But a nurse in an area with a strong, vocal anti-vaccine community may face substantial social pressure to (at least publicly) reject commercial vaccines, for the reasons I stated above. 3ChristianKl1dThe average nurse in a anti-vaccine community is not going to make their own vaccines. I would also expect that most nurses will face some social pressure in their workplace to take the vaccine. 2Eigil Rischel2dThis seems prima facie unlikely. If you're not worried about the risk of side effects from the "real" vaccine, why not just take it, too (since the efficacy of the homemade vaccine is far from certain)?. On the other hand, if you're the sort of person who worries about the side effects of a vaccine that's been through clinical trials, you're probably not the type to brew something up in your kitchen based on a recipe that you got off the internet and snort it.