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Making Vaccine
- timerol 6y agoSimilar to the author of the post, I'm surprised that I haven't seen or heard much about bio-hacking your own vaccine. Seems like an interesting trend to follow, though I will be waiting for an FDA-approved vaccine myself. I am a little worried that https://radvac.org/vaccine/ https://radvac.org/vaccine/ mentions that their vaccine has "the most extreme complication in some recipients of stuffy noses." I would expect a functioning vaccine to elicit an immune response. I would be more comforted if, like the mRNA vaccine, a sizeable percentage of people trying the DIY vaccine developed a short fever. Though according to them this is expected: "Intranasal delivery of chitosan-based vaccines have shown mild side effects and high levels of efficacy of both mucosal and systemic immunity, when delivered in a prime-boost regimen (in both animal models and human trials). "
- koeng 6y agoJosiah Zayner did one that looked fairly promising (believe it was either an mRNA or DNA vaccine), but unfortunately he got banned from a lot of media (like youtube) for it, so that may partially explain why you haven't seen or heard much.
- tomjakubowski 6y agoZayner's retrospective on the homemade vaccine experiment is interesting. He now thinks that testing vaccines is complicated enough to warrant large clinical trials. https://www.bloomberg.com/news/articles/2020-10-10/home-made-covid-vaccine-appeared-to-work-but-questions-remained https://www.bloomberg.com/news/articles/2020-10-10/home-made...
- koeng 6y agoJosiah is an interesting guy because it turns out his opinions hold quite a bit of nuance and he’s generally a good guy (not a snake oil salesman). I think he definitely had that perspective going in - the point of the experiment is partly inspirational to show it can be done.
- ampdepolymerase 6y agoBecause complying with GMP is tedious and expensive. One mistake and you could end up with blood poisoning or a brain-eating microbe. Lab grade material is not the same as pharmaceutical grade material. You can get a lot of expensive anti-cancer drugs too at bulk prices from lab suppliers. That does not mean they are rated for human consumption. What's good for the lab rat is not necessarily good for the homo sapien. https://en.m.wikipedia.org/wiki/Good_manufacturing_practice https://en.m.wikipedia.org/wiki/Good_manufacturing_practice Granted, more biohacking and bio experimentation is a good thing. Innovation should not be gatekept by institutions and the establishment. Here's a startup idea for whoever's interested: Take lab grade pharmaceutical drugs and turn them into human-rate drugs at a low cost.
- caveperson2102 6y agoYour comment made me think of something, I'll share it as a "PSA" in case it helps someone stay safe. Neanderthal DNA has been linked to severe outcomes from COVID.[0] To me that means I'll get vaccinated (and strain specific boosters that may have to happen), full stop. But if I have a choice of more than one type of vaccine available at the same time (unlikely? But still), then I will try to keep this in mind. Other than that it just means I will be extra careful. Disclaimer: not a scientist; and anything I say here is first-person (I'm in the demographic groups I'm referring to). My non-scientific speculation: there is a chance the stuffy nose could be a proxy for high neanderthal DNA. I say that because other sinus and nasal issues are among the things linked to genes inherited from Neanderthals. They had different anatomies in that regard. I've read it could have been an adaptation to cold. I've also read that the extinction of Neanderthals may have been related to viruses causing respiratory problems/diseases.[1] Anyways, the point is, that some of these genes could correlate with severe outcomes from coronavirus. If a reader knows their genetics, and/or knows people who have mentioned they have a relatively high amount of neanderthal DNA... You might want to think about it or mention it to them. Especially if they have other respiratory or sinus things going on. [0]: https://www.nature.com/articles/s41586-020-2818-3 https://www.nature.com/articles/s41586-020-2818-3 https://www.sciencemag.org/news/2020/12/neanderthal-gene-found-many-people-may-open-cells-coronavirus-and-increase-covid-19 https://www.sciencemag.org/news/2020/12/neanderthal-gene-fou... [1]: https://www.sciencedaily.com/releases/2019/09/190919080755.htm https://www.sciencedaily.com/releases/2019/09/190919080755.h... ---- [btw I accidentally posted this comment to the wrong thread then moved it. Not trying to spam or rant, I'm just bad at commenting because I rarely comment. Anxiety and so on...]
- Cogito 6y agoHey FYI looks like you got an auto ban, I've emailed the mods to get them to review in case it's a false positive. This was an interesting comment. I don't think it is particularly likely that Neanderthal DNA is associated with more stuffy noses, but who knows! An interesting hypothesis for sure.
- visarga 6y ago> bio hacking your own vaccine. Seems like an interesting trend to follow There's only one of you, no second chances if you mess up.
- buildstatements 6y ago> though I will be waiting for an FDA-approved vaccine myself. If it was July, and this post popped up, heck even November pre-US election when we were told the vaccine was months away, would that change the equation? I feel like there are two questions here: 1. is this safe? If so, how safe? 2. Is it worth trying? Question 1 is quantitative and verifiable, whereas question 2 is one of risk preference.
- aqme28 6y agoI'm amazed at the price here. $1k for 500 doses, and the author stated in the comments that they could have saved a lot more per dose if they bought in bulk. It seems like a failure of the system that no one is trying for FDA approval or industrialization.
- goatcode 6y ago> FDA approval Of what? Edit: I get it now, sorry. I think FDA approval would bump up the price quite a bit.
- palcu 6y agoThis Lesswrong thread has a good discussion about the subject. https://www.lesswrong.com/posts/niQ3heWwF6SydhS7R/making-vaccine?commentId=JvegGTbGe28q868yG https://www.lesswrong.com/posts/niQ3heWwF6SydhS7R/making-vac...
- fredgrott 6y agoit's not you are implying.. they use peptide..real vaccines use mRNA thus more effective than this one at say about 10% effectiveness.. Sorry for being brief as it would take a more in depth hour explanation of why the difference in effectiveness.. CDC had a recent article on the differences between this approach and the approach they and pharms chose namely mRNA
- raylad 6y ago>real vaccines use mRNA thus more effective than this one at say about 10% effectiveness.. Not true. Novavax is just peptides and is 96% effective against the original Wuhan covid-19 strain.
- sct202 6y agoNovavax is growing whole modified spike proteins and sticking a dozen of them on to a nanoparticle. The article mentions their peptide is only a small fraction of the size of the spike protein.
- 6y ago
- goatcode 6y ago> In principle one can run a similar antibody test on a mucus sample, but <reasons> I'd really like to know what those reasons are. It seems like a pretty important detail.
- pas 6y agotl;dr a partial/localized immune response just in the nose; and to confirm the vaccine worked you want to be sure It seems "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". Which I guess means a false positive for post-vaccination verification. (The sentence you have copied is shortly after this: "The key problem is how to check that the vaccine worked.") If your question is why it's possible to have a partial immune response, then it's because the immune system was not activated fully. The immune response might only consist of "sIgA antibodies in nasalwash and saliva", sIgA is secreted IgA, and IgA "is an antibody that plays a crucial role in the immune function of mucous membranes". So if mucous membrane successfully "handles" the vaccine, then -- layman speculation -- it's possible nothing [not enough] gets into the bloodstream/lymph.
- goatcode 6y agoI took what the author wrote to indicate that there was no available test to do what he'd wanted to do. I really wish people would drop the whole "because reasons" thing, especially when writing something meant to be read by many other people.
- deleted 6y ago[deleted]
- kneel 6y agoCurious whether short peptides are sufficient to generate a formidable immune response. Looking at the paper cited, it's not trivial to detect T-cell immunity so I'm not sure a general antibody test would be able to pick up an immune response. It's probably better than doing nothing, but it's not clear whether it's even in the same ballpark as a Pfizer vaccine. edit: I'm not sure about t-cell vs b-cell responses in immunoassays, can anyone with experience point out what is going on with these peptides?
- jfjrkrkfjf 6y agoNot an expert, but I've read that the antigen presenting cells break down the antigen into short peptides too (8-20 amino acids) when creating antibodies. One might however still ask if the body is better at selecting exactly which portions are cut and chosen than however these were selected. Also, if the antigen is small from the start, that might have implications too (like being ignored).
- crazydoggers 6y agoThey’re not sufficient without an adjuvant. Peptides by themselves usually aren’t enough to be recognized as pathogenic. If any peptide by itself could kick off an immune response, you’d be getting sick with everything you eat and smell. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494216/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494216/
- Kim_Bruning 6y agoThe protocol white paper uses Chitosan. They do discuss use of Alum and other adjuvants, starting on page 12. ( https://radvac.org/wp-content/uploads/2020/12/White-Paper-SARS-CoV-2-vaccine-ver-3-3-1.pdf https://radvac.org/wp-content/uploads/2020/12/White-Paper-SA... )
- tim333 6y agoI rather doubt snorting some peptides as described will do much. There are some attempts to make actual nasal covid vaccines and I think they use chimpanzee adenovirus vectors. Ie you get a virus that gives chips colds and add some covid bits on. See the Indian one for example https://indianexpress.com/article/explained/explained-understanding-bbv154-bharat-biotechs-single-dose-intranasal-covid-19-vaccine-7160945/ https://indianexpress.com/article/explained/explained-unders... I think they also were talking of trying the AstraZenca one nasally which is also a modified chimp virus.
- lxe 6y agoJust to summarize for my own understanding/fascination: this person DIY's 500 doses of nasal-spray COVID-19 vaccine for $1000 using ingredients and tools off of Amazon and easy-to-source synthesized peptides with minimal skill?
- habryka 6y agoYes, though the vaccine is likely to have substantially less efficacy than current mRNA based vaccines from Pfizer and Moderna, though I think it's promising enough that some level of efficacy (like idk. maybe 50%, who knows) doesn't seem out of the question (whereas Moderna and Pfizer are likely 90%+).
- SahAssar 6y ago> 50% efficacy doesn't seem out of the question Is there anything at all to back up that figure? Like, seriously, anything at all? I'd be very interested to hear if there was, but again, are there any hard numbers from studies of success rates of this? Or even self-reported numbers?
- avs733 6y agono. the actual efficacy on this isn't 50% or 100% or 0% is is unknown. The value of the vaccines is in part that there is evidence to backup that they work, they aren't dangerous, they are formulated properly and consistently.
- habryka 6y agoI suggested 50% as more of an upper bound. My current guess is I would be very surprised if these have very high efficacy, based on a number of studies on kind of similar vaccines I remember reading. I think the most likely outcome is that these have 0% efficacy, though I also wouldn't put less than 10% probability on them having between 20% and 50%. But yeah, these are all just random guesses. Probably some biologists have better models here that could allow them to make better predictions, but there is no hard data.
- fabian2k 6y agoIf there is one thing I certainly wouldn't just play around with it's the immune system. It's incredibly dangerous and easily capable of causing all kinds of harm to yourself up to killing you outright. A vaccine is designed to produce an immune response of the right magnitude. Too low and it doesn't work, too high and it'll cause damage. At least one of the vaccine candidates in development was put back to the drawing board because the immune response wasn't strong enough. So this is not an area that is entirely predictable, you have to carefully test this to know if it works. I'd also be very careful about the inhalation route. Inhalable insulin is a well-known failure, in part because of side effects due to the inhalation. And that is a protein that isn't designed to activate your immune system. I also hope the synthesized peptides were carefully purified, you really don't want to inhale e.g. residual trifluoracetic acid.
- deleted 6y ago[deleted]
- zests 6y agoCan you provide more information about how vaccines can cause damage?
- dante_dev 6y agoI think he was referring generically to any bad crafted vaccine. Not the one approved by authorities. Indeed any improvised drug can be harmful.
- wiml 6y agoSome vaccines in the past have been withdrawn for causing autoimmune disorders, eg arthritis.
- recursivedoubts 6y agohttps://www.washingtonpost.com/history/2020/04/14/cutter-polio-vaccine-paralyzed-children-coronavirus/ https://www.washingtonpost.com/history/2020/04/14/cutter-pol...
- fabian2k 6y ago
- deadlyvaccine 6y agoI really hope no vaccine will work and all over-80 people will pay for all the suffering they have done for 98% of the population. People are living in conditions similar to jail second year in a row!
- deleted 6y ago[deleted]
- CivBase 6y agoNations have spent thousands of dollars per person on just mitigation efforts and economic stimulus. Meanwhile we have had the ability for months to vaccinate an entire household for a measly $1k? What's the catch? Is it significantly riskier than the Pfizer or Moderna vaccines? Is it easy to make a mistake while producing this and end up with something ineffective or harmful? Is it just not particularly effective?
- avs733 6y agoQuality control. Precision. Repeatability. Certification. Knowledge. Distribution. Efficacy. Evidence. It's like the difference between heroin and opioids
- xxpor 6y agoIt's kind of funny, pharmaceuticals have similar economics to software now that I think about it: extremely high upfront fixed costs, minimal marginal costs.
- kazinator 6y agoYes; there are similar risks. Working on something for years that might not work, or not pass clinical trials or whatever. The only difference is that the researcher's limit for not understanding the code might be 150,000 lines, but only 50 atoms for not understanding the molecule. :)
- asitov 6y agoAre you saying you wouldn't take the heroin version of a covid vax?
- avs733 6y agoI wouldn’t take the heroin version of anything unless the alternative was highly likely and extremely bad Would I drink murky water in the woods? Maybe? Am I about to die of thirst and have no other clean water sources? Would I take a vaccine made in a dude’s garage and posted on less wrong? Maybe? But only if there are no other options to keep me from a disease way worse than the horrors that covid actually is. But it’s worth recognizing that this fear and noise in the system is the same type of thing that gave us an Arizona couple dead from drinking fish tank cleaner.
- deleted 6y ago[deleted]
- angry_octet 6y agoEven if no one dies from this, he and the contrarian happy clappers on lesswrong deserve a special recognition for ingenuity at the Darwin Awards. The field is crowded for 2020, what with HCQ and ivermectin truthers, statistical frauds, denialists and blind optimists, but there is a chance they'll dominate the anti-vaxxers in 2021.
- flr03 6y agoI'm not suprised to see this post so popular on Less Wrong/the rational community. I can easily imagine the fascination they have for crazy scientists doing experimentations on them selves, cutting all the corners and operating at fair distance of ethical concerns. I'm not very convinced by the "Motivations" section of the article by the way, but that's a nice stunt nonetheless, and quite fascinating indeed.
- angry_octet 6y agoThey've romanticised the stories of scientists self-testing and mixed it with the stories of Jenner and Fleming, misinterpreting their unethical (Jenner) and credit grabbing (Fleming) ways as brilliant contrarianism.
- shuckles 6y agoThis is unnecessarily dismissive. IIRC, Josiah Zayner home brewed a vaccine which led to a positive antibody test, which is in and of itself a pretty impressive outcome given the resources he had available to deploy.
- throwaway2245 6y agoThe Bloomberg link posted above states he had a positive antibody test before administering the home brew.
- shuckles 6y agoThat link seems to be quite incomplete. For example, it never mentions that there were two other people involved, at least one of whom didn’t have the same confounding issues. Here are the results: https://docs.google.com/document/d/1WTuRBuy74KlaBzLrd0aTZl852nhPNCWL06aB7wY1JKk/edit https://docs.google.com/document/d/1WTuRBuy74KlaBzLrd0aTZl85...
- 1970-01-01 6y agoTLDR: I attempted to make a COVID vaccine. It was cheap. I have no proof that it worked. Other risks are unknown. The story reminds me of Barry Marshall, but with less science behind it. https://jamesclear.com/barry-marshall https://jamesclear.com/barry-marshall
- bawolff 6y agoHonestly i'd be pretty shocked if this actually worked.
- wegs 6y agoWhy? In many cases, the hard part isn't so much making a working vaccine, as proving it works, scaling manufacturing, etc.
- bawolff 6y agoBecause if all it took to make a vaccine for a respiratory disease was stick some peptides up your nose, we would havev a lot more vaccines (and i dont mean just for covid.). Even if the other parts are harder (not sure if thats true. The reason proving things work is hard is because most initially promising candidates dont actually), it doesn't follow that every single vaccine candidate works.
- visarga 6y agoKind of like self driving cars, so many edge cases, so many unknowns in deployment. Got to test the shit out of it.
- wegs 6y agoIf my life depended on having a self-driving car ready in a year to drive me to California, I'd have a self-driving car ready in a year. It could drive me to California with perhaps only a 25% chance of an accident. I mean, it might be driving with the emergency blinkers on the whole time, at 10 miles per hour, and flashing the horn, or crazy stuff like that, but making a basic self-driving car just isn't out-of-scope for an amateur. DARPA urban challenge was 2007, and 6 cars finished an urban course, with the fastest averaging 14MPH, and most developed mostly by students, with professor support. Today, I can get a lot of that stuff CoTS, open source, or read papers about what they did. I couldn't sell millions of self-driving cars, because of edge cases, manufacturing, or what not, but it's not fundamentally different from biohacking. Technology moves forward. Disclaimer: I'm not an MD, biologist, or similar, but I am pretty good at all the stuff that goes into a self-driving car. I'm not claiming a /typical serious amateur/ could build one. I'm claiming /I/ could build one.
- jiofih 6y ago> 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. Yes, I look forward to having random people skirt the social distancing rules because they sniffed their own homemade vaccine over the weekend.
- Aachen 6y agoThey spent a thousand bucks on this and many weeks and blood tests. I agree with your general point but do give them some credit.
- jiofih 6y agoNo mention of blood test results in the post.
- Aachen 6y agoYeah, the results aren't in yet. > Consider this a pre-registration. I intend to share my test results here. Of course, without checking/testing this would be a completely useless exercise. Or if you test in the wrong way, like a nose swab after doing nose spray vaccination. OP instead will do blood tests and does seem to have thought this through to an extent that I find reasonable. However, henceforth considering yourself safe indefinitely and normalizing socializing during the pandemic and normalizing the homebrewing of vaccines... that's where I'm not certain about the conclusion (iff it proves effective in the first place - e.g. I also see no mention of false positive rates in the test they'll use).
- devilduck 6y agoWhy am I supposed to take this seriously? LessWrong is not exactly known for being a sane place (as much as many of them would love to believe they are smart) and this guy states it as a "fun project" which make it sound extremely suspect.
- Imnimo 6y agoWithout any evidence of efficacy, this article doesn't strike me as much different from "I went into the woods and gathered up some herbs and made myself an elixir that cures covid". I guess it's neat that you did all that stuff, but unless it actually helps, who cares? Doing it with science-y ingredients instead of herbs and ordered them online instead of harvesting them from plants doesn't magically mean it actually works.
- ChuckMcM 6y agoThe difference however is that this article is based on the scientific method, and the go into the woods and gather herbs is based on mythology. Now the reasonableness of experimenting on yourself, even in a scientifically "valid" way, is certainly arguable. But the elements are all there; Theory of the Immune system, Hypothesis that it can be trained in this way, experiment that trains immune system in a known with with the experimental training element. As others have pointed out, the immune system is designed to kill cells it doesn't like. And it has been demonstrated in other scenarios that it can target cells that are vital to one's survival, resulting in death when the immune system targets and kills those cells. Thus the risk in the experiment is that it will successfully invoke an immune response, it just won't be the one that was anticipated. Not surprisingly, this is the whole point of animal trials to get a feel for what might happen.
- fabian2k 6y agoIt's hardly the scientific method when the outcome isn't actually measured. It is entirely unknown whether this whole procedure has done anything at all.
- habryka 6y agoThe author said he is going to try to do measurements to the best of what is easily possible: > 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. Pre-registration for this kind of thing seems pretty good, and I am looking forward to seeing the results.
- fpgaminer 6y agoI know some people object to biohacking like this, but I'm not convinced that we should be concerned. In general I believe that, in a free society, people should be allowed to do as they please as long as their actions don't endanger or harm others. There's a lot of nuance and caveats there, though. Perhaps this is one? I guess I don't see an inherent problem with vaccine hacking. I'm reminded of the person who biohacked their lactose intolerance by doing gene modification on their gut. Even though it's not something I'd experiment on myself with, I was happy to learn from someone else's experience. And they're only endangering themselves; that experiment didn't pose a threat to anyone else or society. There's perhaps an argument that these kinds of things do have an impact on others, because it might convince others to follow the author's footsteps. Well I highly doubt any joe or jane shmo is going to homebrew a vaccine. This is so niche that only a scarce few would even have the capability to do it. And again, if someone wants to do something stupid to themselves, who am I to stop them? The only real danger is these homebrew vaxxed people mixing with herd immunity. But that's easily handled by only recognizing government approved vaccines. You're welcome to vax yourself, but if you want access to restricted public activities you'll need an official vaccine. Or if we mandate vaccination (for example the required immunizations at school), again you need an official vaccine. But if you want to homebrew vaxx yourself against the yearly flu, or even want to homebrew vax COVID-19 and get the official one later when it's more available, I don't see the problem with any of that. I'm mostly curious for rebuttals to this logic. Are there serious concerns about biohacking like this that I'm missing? Or is this one of the caveats where, even though it doesn't pose a danger to others, it's a serious enough danger to self that we should intervene? P.S. As a side note, while reading this article I couldn't help but imagine a future where every hospital has a "vaccine machine" which gets fed raw materials and spits out the vaccine de jure on demand. That seems doable with this radvac protocol. It can download the latest approved peptide sequences, assemble and purify the peptides and mix up a vaccine. A vaccine 3D printer of sorts. Or maybe mRNA vaccines can be made this way? You come in once a year, the machine looks up your records and downloads a list of virus genomes from the past year that you hadn't been vaccinated against. Prints out the custom set of mRNA sequences, mixes it up, and you inject it. That's the future I'm far more interested in than a future where everyone biohacks themselves with instructions downloaded from vaccinebay.
- 6y ago
- spoonjim 6y agoWhat is the rationale for doing this?
- trash_cat 6y agoThis is actually super exciting. However, there is literally 0 evidence that this works. Am I missing something?
- gregwebs 6y agoAll the current vaccines being rolled out give non-sterilizing immunity. This means the vaccinated still get infected in the upper respiratory tract and still transmit the virus (but perhaps 50% less transmission). The vaccine protects them from developing a severe infection (COVID). The implication of this is that we will still be dealing with this virus for many years to come. I hope the drug companies are working on a vaccine similar to the one in the article that has the potential to provide sterilizing immunity since it works in the upper respiratory tract.
- maxerickson 6y agoThey did not study it, there is not data to make conclusive statements. There really isn't data to state a quantified reduction in transmission (None!).
- karmicthreat 6y agoThis seems to be a form of magical thinking cloaked in science. It might even screw up them getting the real covid vaccine later.
- namesbc 6y agoThis is like a person writing a 100 line python program to search a text file, and claiming they finished a competitor for Google.
- sirsar 6y agoMany of the negative comments here seem to have missed something important: > Consider this a pre-registration. I intend to share my test results here. How about, instead of totally dismissing this - in classic HN fashion - with "this can never work" or "this is magical thinking", we let the guy share his results? If it works, that will be a massively important result. If not, it won't be surprising, but _at least he will have tried_. I for one think the expected value leans overwhelmingly in favor of at least one person actually trying.
- airstrike 6y ago> How about, instead of totally dismissing this - in classic HN fashion - with "this can never work" or "this is magical thinking", we let the guy share his results? Sure. How about instead of sharing wishful thinking covered in "this will work because science" OP waits until there are actual results before posting? Anyone can make a vaccine candidate. Few can make a vaccine. Even fewer can make a safe vaccine.
- sirsar 6y ago> How about... OP waits until there are actual results before posting? It seems to me there's value in posting the details before the results are in: - Helps prevent publication bias, by encouraging posting negative results - Elicits comments from knowledgeable people who may be able to help - Discourages doctoring the story after the results are in > Even fewer can make a safe vaccine. I don't know, the article, whitepaper, and comments seemed to make a pretty convincing case for the nasal vaccine attempt here to be not very dangerous - probably useless at worst. Do you have a more substantive counterargument?
- airstrike 6y ago> - Helps prevent publication bias, by encouraging posting negative results That's not what we're really seeing here, is it? The article is lowkey touting success when it's just an early experiment. OP is not "making vaccine" as the title states. > - Elicits comments from knowledgeable people who may be able to help Also not the case here. > - Discourages doctoring the story after the results are in Not really. One thing doesn't prevent the other from happening. > I don't know, the article, whitepaper, and comments (...) Do you have a more substantive counterargument? Yes, the scientific method and bona fide peer review
- gwittel 6y agoWhile interesting, even if anti-bodies are detected in the end we have an N=1. The average random person doesn't get this. A single result is not generalizable. It kind of reminds me of the @justsaysinmice twitter account [1] which replies to relevant studies with "IN MICE". So many factors can confound this type of work. Some big ones: 1) Does this work in general population? 2) How long does the antibody response last? 3) Does this work on variants? 4) Are there cases when this should not be used? I remember a reference to one of the early SARS vaccines. It was promising, until they found it caused immune responses resulting in lung damage on people who had SARS (can’t find the exact paper but [2] highlights some of the concerns then and now). [1] https://twitter.com/justsaysinmice https://twitter.com/justsaysinmice [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318931/#!po=2.00000 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318931/#!po=2....
- madrox 6y agoWhether it's governments or corporations, there is constant tension between "move safely" and "move fast and break things." One reason why tech companies managed to dominate many fields is that they are less worried about making mistakes than their institutional competitors. Especially in western society where our medical institutions are quite old with many safeguards, the time it takes to roll out a vaccine can seem maddening, especially to readers of HN who work in fields where software bugs don't kill people. For those people, what this author did could seem like an attractive means of cutting through perceived red tape. As has been pointed out before on HN with roll-your-own vaccine stories, it takes a week to make a covid vaccine. It takes much longer to prove it's safe and effective. We rightly live in a free society where someone can do what they like with their own bodies, but - like buying GameStop stock - I hope the naive do not get the wrong idea and do something they'll regret.
- subrat_rout 6y agoI completely agree with fabian2k. It's incredibly risky to throw all random sequences peptides into the blood stream for evoking immune response. What happens if a sub-sequence of peptide matches with one of our own's body proteins and our immune system starts building antibody against it? That's what happens in most of autoimmune disease. In addition, most of the peptides that can be synthesized from a protein structures are sequential epitopes. To ELI5, imagine a string with beads that starts with A-Z letters and we take a smaller sequence A-B-C-D or B-C-D-E and throw to system to build antibody against it. Yes, the immune system can make antibodies against it. But in real life, most of the protective or virus neutralizing antibodies comes from conformational epitopes. Imagine when the protein gets folded to its natural form then the beads with letter sequences are just jumbled sequences and finding a conformational epitope is key to raise neutralizing antibodies. That is only possible when a protein's structure is fully understood using x-ray crystallography. The article does not disclose how the author was able to get those sequences and how he was sure about its efficacy. However, the author's bold step towards the experiment is praiseworthy. But extreme caution is needs to be taken as self administering an untested drug or vaccine may fall within the boundary of law and it can invoke regulatory actions against him.
- flobosg 6y ago> What happens if a sub-sequence of peptide matches with one of our own's body proteins and our immune system starts building antibody against it? The peptide sequences are listed on the whitepaper, so it’s a matter of BLASTing[1] them against the human proteome to check for possible matches. I just did it and there doesn’t seem to be any statistically significant hit. [1]: https://blast.ncbi.nlm.nih.gov/Blast.cgi https://blast.ncbi.nlm.nih.gov/Blast.cgi
- subrat_rout 6y agoOk great to know. But my intention here is to convey that it is dangerous to biohacking a molecule/compound that a user is going to put in his/her body. The peptides after synthesis needs to be rigorously tested(QC/QA) for the desired sequences and to make sure the absence of any undesired epiotopes mixed.
- selimnairb 6y agoIs this a joke?
- cromwellian 6y agoThis article could have been written by Gwyneth Paltrow and it would have had the same level of authority. There's a reason vaccines require staged trials. This seems play playing not with fire, but with nitroglycerin or maybe Nitrogen triiodide.
- optimalsolver 6y agoNow you mention it, I do wonder how this exact same article would have been received on HN if it had been written by Gwyneth Paltrow.
- JunkDNA 6y agoIt’s not a vaccine if you don’t have efficacy data. You can go snort all kinds of peptides all day long, that doesn’t mean you’re going to actually have something useful happen. Do you know why we’ve developed all these complex rules about how to test whether drugs and vaccines work? It’s because humans have reliably demonstrated over and over that we have no friggin’ clue how our bodies actually work. I worked in drug discovery. The one thing that all failed drug candidates had in common was that they all looked like surefire bets right up until the point where the data came rolling in. The reason all these complex studies and checks and balances are in place is because ~200 years of human experience making vaccines and medicine has given us some small amount of humility.
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- headgasket 6y agoThe impure peptides is the part that scares me. What could be in there ? Could you end up moredead? The nasal pathway is quite direct I gather. Stay safe ! Cheers
- crazydoggers 6y agoInhaling peptides is not a vaccine unless they are using an adjuvant. You need something to kick off the immune response and recognize the peptides as associated with a pathogen, otherwise you’d be getting immune responses to everything you inhale in the environment (like when you cook). And if they are using adjuvants, well then as others have posted.. autoimmune issues can be real. It’s not that it’s not possible... just something you might want to try on a mouse before up your nose. Why oh why experiments on yourself or suggest this to others without lots of warnings?
- crazydoggers 6y agoSo much downvoting on HN for factual content that simply isn’t what people want to hear. It’s getting sad.
- visarga 6y agoOrder peptides they say? Won't scale in a pandemic. And in regular times we can get vaccines no problem.
- hardwaregeek 6y agoThis is an impressive amount of hubris. Does the author assume that all the certifications and testing stages were for show? I don't hold the highest view of LessWrong and the whole rationalist shtick. This post exemplifies why. Underneath this post is the assumption that the author is so much smarter than everybody else because they are Rational with a capital R and can therefore harness the power of science to make a vaccine[^1]. Again, that's an incredible amount of hubris. If there's one universal truth about science, it's that it is extremely specialized. Just because someone knows a lot about chemistry doesn't mean they're qualified to talk about biology. There is no magic Rationality that can have amateurs making vaccines a good idea. Unless you are an expert in vaccines a priori, you cannot suddenly become one in a few weeks. Heck, I'm skeptical of doctors who are not infectious disease experts giving advice. I still hear a lot of "well my sister's neighbor's brother is a pediatrician and he said XYZ". Doctors are certainly more educated than the average person, and if this was a minor medical problem I'd certainly take a random doctor's advice. But this is a pandemic with a novel disease. Listen to the infectious disease experts. [1]: Quite honestly this feels like a plotline from Harry Potter and the Methods of Rationality
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- centimeter 6y agoExperts are usually mired in procedure and politics (sometimes for good reason, sometimes not). A smart outsider who isn't constrained in the same way often has a pretty good shot at beating out the established experts. That's not hubris; it's just a viable strategy.
- austinjp 6y agoI don't disagree with the premise that outsiders are unconstrained. There is a notion that modern science lacks the frequent paradigm shifting leaps in progress due to bureaucracy and safety. But... obvious issue: without the bureaucracy, how do we ensure safety? Vaccine trials do go wrong, people do die when that happens. I hope we're living through the final years of the tension between population based evidence and processes, vs ultra-individualised medicine. Humanity just needs to keep its shit together for long enough, and learn to operate as a planet rather than as disparate factions.
- hyko 6y ago“The key problem is how to check that the vaccine worked” The first rule of DIY vaccine club is that you have no fucking idea what the key problems are.
- reilly3000 6y agoRough comments here... I admire the spirit of DIY in his project. He asked for and received good data, consumed the process and risk, and proceeded. He wasn't trying to save the world, he took a calculated risk on himself, and wrote a blog post about it. I'm most happy to have the process demystified for me. I don't think the world would be a better place if more people made their own vaccines unless there was some ubiquitous, reliable material testing procedure that we can't imagine yet. I do think I'd like a person like that to be my neighbor if society were to collapse, or maybe in general that would just be a good time.
- dcposch 6y agoThe negativity might be warranted if they had encouraged other people to follow, or if they were trying to DIY-vaccinate others. But that's not what happened here. These are two capable adults experimenting strictly on themselves and being transparent about it. That deserves respect. You might think "that seems like a stupid risk, I would never do that", and that's a fine take. But don't judge. Where's the "hacker" in hacker news if everyone immediately reaches for admonishment and appeals to authority. A lot of people in these comments overestimate how clean and linear and officially-sanctioned scientific progress is, especially in biomed. In the 1980s, an Australian doctor suspected that ulcers are caused by a specific kind of bacterial infection. At the time, the medical consensus was that ulcers came from stress and diet. His ideas and evidence were ignored. So he drank a beaker of H. pylorii culture, got an endoscopy before and two weeks later, and demonstrated convincingly that he'd given himself ulcers this way. He ended up winning a Nobel prize. https://en.wikipedia.org/wiki/Barry_Marshall https://en.wikipedia.org/wiki/Barry_Marshall
- PoignardAzur 6y agoMy thoughts exactly. The level of contempt and tribe-bashing ("screw these rationalists who think they're smarter than us!") in this thread is depressing.
- wimagguc 6y agoIf the goal is immunity to Covid-19, isn't it simpler to just: catch it? To be on the safe side, they could have lowered the risks of a bad outcome by things like (1) catching a smaller viral load (2) actually prepare for it and catch it at a convenient time etc. (Someone who's actually interested would research this longer.) Surely it's safer than the home cooked vaccine, and surely the favorable option on a risk vs potential benefit analysis. Would make for a boring blog post though.
- andai 6y agoThis is my perspective. (No luck yet!) From what I am hearing it doesn't matter though, I will need to get vaccinated anyway to be allowed to travel etc.
- ianlevesque 6y agoEnjoy your round two with a variant though.
- dmichulke 6y agoI believe the unstated secondary objective is staying alive (or at least optimizing the probabilities). Not the author though, so take it with a grain of salt ;-)
- folli 6y agoBesides the obvious safety concerns, I also have some serious doubts about the efficacy. It's quite well known that the glycosylation of the spike protein ("decorating" sugar structures) contributes significantly to immunerecognition (see e.g. https://www.nature.com/articles/s41598-020-71748-7 https://www.nature.com/articles/s41598-020-71748-7). By chemically synthesizing naked (non-glycosylated) protein fragments, you likely end up with the wrong antigen.
- flobosg 6y agoThat’s a good point. In this case the spike-derived peptides have no known N-linked glycosylation sites[1] and the paper you mentioned showed that at least some of those epitopes are accessible even when taking glycans into consideration. [1]: https://science.sciencemag.org/content/369/6501/330 https://science.sciencemag.org/content/369/6501/330
- lovemenot 6y agoIf a vaccine is tested in the wild, does it introduce an additional unique risk to society? It's an infectious disease that mutates. A vaccine may be partially effective in the treated person, but also increase the risk of viral mutation leading to increased infectivity or virulence. I have no authority or evidence, just a hunch. But if correct it seems that we cannot adford to just shrug and say "it's your funeral, mate"
- willyt 6y agoIt’s interesting that you can order custom made DNS sequences so easily, I didn’t know that. But, vaccination is something we have to do as a society. It’s fundamentally a social action taken across a population. He says that after taking the vaccine, he will be able to go out and socialise again, but the vaccines only make you immune from severe disease, not the people around you. So if you are vaccinated you can still catch Covid again and spread it to your grandparents, or the overweight person working on the supermarket checkout, or your neighbour’s sickly child. If your homemade vaccine has worked you’ll be ok, but they wont. This is why we have to vaccinate as a society and we all have to wait until there’s enough people vaccinated to ensure herd immunity. It’s also why you can’t take any risk at all that the vaccine that you give to the whole population could be harmful because if people lose trust in the vaccine or vaccines in general then as a society we will lose access to this tool for protecting us from disease, and the death toll from that would be far higher than a few more months of Covid.
- moonbug 6y agough, computer people are the worst
- littlemtman 6y agoWell done you will deliver faster than all the other companies with the regulatory overhead.
- seanwilson 6y ago> 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). I know nothing about making vaccinations, but what would happen if you made a vaccine with a huge number of random protein segments? Would it prime your immune system to make you immune to several yet to be discovered viruses? Or it's just useless and/or dangerous to do this?
- wombatpm 6y agoChances are your random sequences don’t match up with any protein sequences that are externally accessible for real viruses. Worst case, your random sequences matches a surface protein of your heart or liver and you trigger the immune system to attack an organ you can’t live without
- h2odragon 6y ago"Hubris" etc in the comments; no one agrees with "my body my choice" anymore?