How Hard Would It Be To Make A COVID Vaccine For Oneself?
post by johnswentworth · 2020-12-21T16:19:10.415Z · LW · GW · 9 commentsThis is a question post.
Contents
Answers 31 eillasti 8 ChristianKl None 9 comments
I always assumed, without investigating, that vaccine-making was the sort of thing which required highly specialized experts and equipment. But I've been hearing that the Moderna vaccine was designed in two days, which strongly suggests that it's simple. So I'm at least asking the question: how hard would it be to make such a vaccine?
The main question is what's involved in designing and synthesizing a vaccine. Subquestions:
- What information is needed for design, and is any non-public?
- What skills are needed for design (other than general bio/bioinformatics know-how), and how does one design a vaccine?
- What equipment and supplies are needed for synthesis?
- Does the equipment require any unusual skills (other than typical wetlab stuff, e.g. how to use a pipette or prevent contamination)?
- Perhaps most important for a non-professional effort: what quality assurance steps are typically used? How can one verify that the thing one intended to produce was actually produced?
These are the main things I'd like to know about.
There's also a cluster of secondary questions around exactly what one could do with such a vaccine, beyond using it oneself. Presumably the FDA would shut down any effort to sell it to others as a vaccine, but which part of that is the problematic part? If someone gives away a homebrew vaccine for free, is that ok? If it's advertised as not-a-vaccine (but with a technical explanation of exactly what it is), or even as "not for human use" (since of course humans never use things not fit for human use), is that ok? To what extent can barriers be circumvented by loading all the equipment in an RV and taking a weekend trip to Canada/Mexico/whatever the equivalent is for Europe? I'm imagining e.g. a small group in Berkeley decides to put in the effort to learn how to make vaccines, buys $10k of equipment and supplies, then gives away vaccine to most of the Berkeley rationalist hub (with a clear "not approved by FDA, not fit for human consumption" warning accompanied by an implicit wink). Where does the FDA draw the line between "a group of friends doing stuff they shouldn't be doing" vs something which needs to be shut down?
I expect any viable plan would take quite a lot of effort, but there's an awful lot of value to be had here - even just immunizing oneself and a handful of friends could plausibly be valuable enough to justify the effort and expenditure. Also, this seems like the sort of thing where someone could learn the skills and acquire the equipment in advance, as preparation for future pandemics - possibly including diseases much more dangerous than COVID. Given how well this episode has gone, that could provide even more value.
Answers
The closest real life example that I know of is RaDVaC. They are professionals in this area, but they are a group of enthusiasts, not a big institution. You can read their white paper to get a basic understanding regarding what was needed to make their vaccine. The rest of the answer is for a peptide vaccine, specifically RaDVaC vaccine, this is the only class of vaccines that I know about in details.
What information is needed for design, and is any non-public?
The most crucial information is the amino acid sequences (peptides) of the virus that are 1) crucial for its functioning, 2) immunogenic, 3) would likely look the same way alone without the neighbours, 4) possible to synthesise. As far as I understood, they got 1 and 2 from public sources (preprints and journal publications), you can follow the references to check if those are actually public. 3 probably requires some special knowledge, but even then you end up with trial and error, so you can probably do without special knowledge. Predicting 4 again requires special knowledge, but there are labs who would synthesise a custom peptide for you for $300 in 4-5 weeks. If they fail to do so, you can probably work with the lab to try some special tricks (amino acid substitution, left/right isomers).
What skills are needed for design (other than general bio/bioinformatics know-how), and how does one design a vaccine?
I am no even sure that you need bio/bioinformatics know-how beyond the stuff that you can read up in the wikipedia.
What equipment and supplies are needed for synthesis? The only complicated ingredient is peptides. You can order their synthesis in a special lab for around $150-$300 per peptide, 4-5 weeks delivery time. The other ingredients you can also buy somewhere. The equipment is trivial, you can buy the whole set for $400 and cook it in your kitchen if you wish.
Does the equipment require any unusual skills (other than typical wetlab stuff, e.g. how to use a pipette or prevent contamination)?
No. Not even wetlab stuff, more like high school chemistry lab skills.
Perhaps most important for a non-professional effort: what quality assurance steps are typically used? How can one verify that the thing one intended to produce was actually produced?
That’s the hard part. Probably not only for a non-professional effort. The simplest answer is you don’t. You just reason that it cannot hurt that much because you know what you have mixed and just try it.
You forgot the most important question: how do you verify that it works? The answer is that you don’t. You definitely cannot do a usual clinical trial with tens of thousands people. The challenge trial doesn’t make much sense if you are only going to use it for yourself and you friend. So probably you just say “ok, it is almost pure safe and there is a chance that it works, so I better make it and take it”. If a lot of people take it, you can have observational data. If people who take are high risk (e.g. doctors) and they don’t get sick compared to their colleagues, then you have some evidence.
There's also a cluster of secondary questions around exactly what one could do with such a vaccine, beyond using it oneself.
You can publish the recipe as RadVac did. Afaik, FDA doesn’t care or cannot do much about it. You can try giving it to other people for a minimal comp. There was another case in US where a guy tried to do so with his own vaccine. FDA sued him and I think it ended up in him having to return money to the “victims”. You can give it to your friends for free, I guess nobody would care (but I don’t live in US). You can sell it in the darknet.
↑ comment by eillasti · 2020-12-24T18:27:40.468Z · LW(p) · GW(p)
You can order online not only peptides, but also the antibodies. So if you get sick, you can theoretically inject yourself an antibody cocktail like the one that Trump received. This is obviously not a medical advice, I haven't even researched it in depth and don't have a plan to do so on my own.
↑ comment by eillasti · 2020-12-24T18:22:47.241Z · LW(p) · GW(p)
Regarding "how do you verify that it works?", specifically regarding the concerns whether the generated antibodies will bind to the virus and antibody enhanced disease concerns. , Right now there is a $600 test selling online (at a reputable source) that can verify whether the antibodies are neutralizing (=block the virus replication). It tests whether the generated antibodies bind to the RBD (Receptor Binding Domain) of the virus and block it from binding to the ACE2 receptor of the human cell (this is how the virus gets into the cell). It does so in a extremely simple way: it contains RBD and an ACE2 proteins plus some stuff to detect when they bind. There exist other ways to do so, but they are more expensive and not widely available. This is how advanced the science actually is, we can commercially create somewhat arbitrary parts of human cells and viral particles for a $600 price and <1 year of development.
So you can test whether the vaccine should work via antibodies IF it elicits a sufficient immunity response measured by high antibody titer. There are already widely available antibody tests to measure the antibody titer. So if you have a candidate vaccine, you order corresponding antibodies for it (also available online), test that they block the ACE2 binding, give it to humans once you are sure that it is kind of safe (peptide vaccines are) and measure the antibody titer. If it is high enough, it is very likely that the vaccine works.
You don't need challenge trials. You still need to check for safety, but after this is done, you can simply distribute it to people, measure their antibody response and monitor whether they get sick. If they do at a substantial rate and there are no explanatory circumstances (e.g. weak immune system, very high viral load), well, something went wrong... Otherwise, all good!
↑ comment by johnswentworth · 2020-12-22T00:54:52.977Z · LW(p) · GW(p)
Well, this is looking way better than I expected.
Looking at the RADVAC docs, I agree, this is dead simple. Required expertise is near-zero.
Regarding the cost: a few hundred dollars sounds like the right ballpark, and I'll point out that making more doses costs next to nothing once it's all set up. The protocol on the RADVAC site is for "10 to 15 doses", and peptide cost is more about how many amino acids are in the sequence than how much of it you want to order. Should be quite cheap to make a lot.
On the FDA front, that sure sounds like they go after people who sell the stuff, but don't care when it's given away for free. So that's pretty much ideal for a "make a thousand doses and vaccinate a whole community" scenario.
You forgot the most important question: how do you verify that it works? The answer is that you don’t.
I didn't forget that, I guessed the answer. I could imagine the rationalist community scraping together a 200-person challenge trial, but that would be a big project. (At least the vaccine-making part wouldn't be too hard or expensive, though.)
Replies from: jmh, ChristianKl, TheSimplestExplanation, eillasti↑ comment by jmh · 2020-12-22T20:33:58.245Z · LW(p) · GW(p)
While I also find this an interesting idea I'm wondering if this exchange maybe suggest some additional complications.
When Estep reached out to him earlier this year, Siber also wanted to know if the team had considered a dangerous side effect, called enhancement, in which a vaccine can actually worsen the disease. “It’s not the best idea—especially in this case, you could make things worse,” Siber says of the effort. “You really need to know what you are doing here.”
He isn’t the only skeptic. Arthur Caplan, a bioethicist at New York University Langone Medical Center, who saw the white paper, pans Radvac as “off-the-charts loony.” In an email, Caplan says he sees “no leeway” for self-experimentation given the importance of quality control with vaccines. Instead, he thinks there is a high “potential for harm” and “ill-founded enthusiasm.”
Church disagrees, saying the vaccine’s simple formulation means it’s probably safe. “I think the bigger risk is that it is ineffective,” he says.
from https://www.technologyreview.com/2020/07/29/1005720/george-church-diy-coronavirus-vaccine/
Given it is from the end of July I might wonder if any evidence of the potential or making the disease worse by taking the home brew has been seen.
I am also not a big fan of the "'no leeway' for self experimentation" view as I tend to think more "putting your money where your mouth is" would be a better world. The concerns should really only be about significant negative externalities, such as you test on yourself and reduce everyone else's immunity type outcomes (not that I think that particular example would be possible).
Replies from: johnswentworth↑ comment by johnswentworth · 2020-12-22T21:09:31.021Z · LW(p) · GW(p)
Guess I'll read up on that too. My immediate impression is that I'd expect, a priori, for Very Serious People to have Concerns regardless of whether they're realistic, and these sound like about what I'd expect in that department. (Also, I have rather a lot more confidence in George Church than in the vast majority of biologists.)
↑ comment by ChristianKl · 2020-12-22T11:44:02.084Z · LW(p) · GW(p)
If you would start a 200-person challenge trial I would expect the FDA suddenly to care a lot because that's actually a challenge to the way they regulate drugs.
↑ comment by TheSimplestExplanation · 2020-12-22T10:35:45.980Z · LW(p) · GW(p)
I didn’t forget that, I guessed the answer. I could imagine the rationalist community scraping together a 200-person challenge trial, but that would be a big project. (At least the vaccine-making part wouldn’t be too hard or expensive, though.)
If only a few thousand people are ever going to get the vaccine a challenge trial doesn't make sense, especially not such a big one. Maybe you could have some animal trials instead though.
Replies from: johnswentworth↑ comment by johnswentworth · 2020-12-22T14:20:14.834Z · LW(p) · GW(p)
I agree this is the main potential failure mode of that plan. That said, the upshot of challenge trials is that we can get good data with very few people, so quite a bit less than 200 could suffice; I haven't run the numbers. More generally, it seems like the sort of thing where a bunch of folks on LessWrong would discuss it for a while and figure out a way to do it which gives maximum information for minimum risk.
Replies from: TheSimplestExplanation↑ comment by TheSimplestExplanation · 2020-12-22T16:34:27.414Z · LW(p) · GW(p)
Sure. Only in that specific scenario, DIY vaccine, for maybe a small community, very safe, scales well in that range; i would say the value of the information you could get from a challenge trial seems low. Instead i would just give it to everyone.
↑ comment by eillasti · 2020-12-22T21:17:22.637Z · LW(p) · GW(p)
If you really want to know that it works for sure, challenge trials are not that hard. Of course, you should probably check for immune response (T-cells and antibodies) and do some animal studies before going for a challenge trial. You don't need to infect 200 people at once, you can do one-by-one from a healthy cohort with low infectious dose so that in the worst case it works as variolation. You can get volunteers from https://www.1daysooner.org/. You can do it anonymously. You can pay people in darknet with BTC/Monero for the experiments. You can only recruit people from countries where nobody cares about your small experiments (e.g. Africa or post-Soviet Union), in some countries, e.g. Russia, there is no criminal penalty for illegal human experiments, only general responsibility for causing harm (and Russian police and courts couldn't care less about some guy who took some stuff on his own initiative following an anonymous internet advice and ended up sick or even dead).
Replies from: Jayson_Virissimo↑ comment by Jayson_Virissimo · 2020-12-23T21:45:09.349Z · LW(p) · GW(p)
Are there any English language sources where I could learn more about the legal issues surrounding human experimentation in Russia such as the one you mentioned?
↑ comment by TheSimplestExplanation · 2020-12-22T10:13:16.102Z · LW(p) · GW(p)
You forgot the most important question: how do you verify that it works? The answer is that you don’t. You definitely cannot do a usual clinical trial with tens of thousands people. The challenge trial doesn’t make much sense if you are only going to use it for yourself and you friend. So probably you just say “ok, it is almost pure safe and there is a chance that it works, so I better make it and take it”. If a lot of people take it, you can have observational data. If people who take are high risk (e.g. doctors) and they don’t get sick compared to their colleagues, then you have some evidence.
I guess you could also test for antibodys, that should give you some evidence.
Replies from: johnswentworth↑ comment by johnswentworth · 2020-12-22T14:24:23.328Z · LW(p) · GW(p)
Oh yeah, I was wondering about that. If someone gets the RADVAC, would they pass existing COVID immunity assays (including antibody tests)? What different ways are there to test immunity, and which would we expect a vaccinated person to pass?
Replies from: ChristianKl, eillasti↑ comment by ChristianKl · 2020-12-22T17:11:41.018Z · LW(p) · GW(p)
The RaDVaC FAQ talks about this:
Unfortunately, this is a complex issue and there isn’t a simple answer. The most common measurement of immunity is an antibody test performed on blood. However, an intranasal vaccine is able to elicit immune responses of various kinds, and even though it might produce a robust and highly protective mucosal immune response, the blood antibody response might not be as pronounced. [more info at the FAQ]
↑ comment by eillasti · 2020-12-22T21:01:19.525Z · LW(p) · GW(p)
My bad, I forgot about testing for immunity. There are 2 testable types of immunity mentioned in the paper: antibodies and T-cells. They explicitly suggest testing for antibodies before and after. However, they say that it is going to be essentially tricky with their vaccine. Firstly, the biggest effect is expected to come via cellular immunity, not via antibodies, and testing for it is not as easy as for antibodies. Secondly, the biggest effect is expected via mucosal immune system, so even the antibodies testing should be done on a nasal wash and not on a blood sample and this is a bit tricky and less reliable. Thirdly, I guess that detection of antibodies by standard antibody assays strongly depends on a specific assay and it is hard to know if the commercial test that you have access to would detect the RaDVaC-induced antibodies. I think they mention that some of the people who took the vaccine had positive antibody tests and some had negative tests.
If you are willing to spend a bit more resources on it, you can actually test for both antibodies and T-cell response. You can create a custom ELISA assay targeted specifically at response to RaDVaC antigens. I think ordering it in a lab is a bit more difficult than peptides, but still possible as a standard service. As for the T-cells, there is ELISpot or smth like that, but it is not so easy as ELISA and much more costly as it involves collection and processing of specific T-cells.
In my case, I've prepared the vaccine only for a few people and verification looked too costly and unreliable to be justifiable, so I decided not to do it. I hope that RaDVaC guys did it and received antibody and T-cell immune response at least in some people, but they cannot publish the positive results, because this would be tricky on the legal side. If they did it, received negative results and still recommend the vaccine, well, then they are bad guys.
↑ comment by Jayson_Virissimo · 2020-12-23T21:43:10.664Z · LW(p) · GW(p)
What explains the 4-5 weeks delivery time for special lab peptide synthesis?
Replies from: eillasti↑ comment by eillasti · 2020-12-24T17:49:21.363Z · LW(p) · GW(p)
I don't know, this is simply what they state for all peptides and this is what actually took them to deliver.
Replies from: Jayson_Virissimo↑ comment by Jayson_Virissimo · 2020-12-24T21:20:49.910Z · LW(p) · GW(p)
I asked around about this on the ##hplusroadmap irc channel:
15:59 < Jayson_Virissimo> Yeah, sorry. Was much more interested in the claim about peptide sourcing specifically.
16:00 < Jayson_Virissimo> Is that 4-5 weeks duration normal? How flexible is it, if at all?
16:01 < yashgaroth> some of them might offer expedited service, though I've never had cause to find out when ordering peptides and am not bothered to check...and it'd save you a week or two at most
16:02 < Jayson_Virissimo> What would you guess as to the main cause? Does it really take that long to manufacture or is it slow to ship, or is there some legal check that happens that isn't instantaneous?
16:04 < yashgaroth> the legal check isn't an issue, though I'm sure all the major synthesis houses are aware of the Radvac peptide sequences and may hassle you about them - especially if you're not ordering as a company...shipping's not a problem since overnight is standard, so I'd say manufacturing time combined with the people ahead of you in the queue
16:04 < yashgaroth> and manufacturing includes purification, which is an important step for something you're ingesting, even if you're just snorting a line of it
16:07 < Jayson_Virissimo> yashgaroth: do the labs have any legal risk of their own if you are ordering something like Radvac sequences as a private person, or are they "hassling you for your own good"?
16:09 < yashgaroth> nah they're usually okay legally on their end, though most of them won't risk selling a small quantity to an individual since 'plausible deniability' wears a little thin on their end when you're buying sequences that match the Radvac ones
But I've been hearing that the Moderna vaccine was designed in two days, which strongly suggests that it's simple.
The word designed doesn't mean the same as produce. Here it just means deciding for the RNA sequence and that's not a big issue. The sequence for the spike protein is well known and it's basically about chosing a sequence for the spike protein while following a few heuristics about choosing coding that's robust and easily read so that you get a lot of protein production in the cell.
Moderna took 25 days to actually produce their first clinical batch.
Previously they spend 10 years developing know how about how to build the RNA delivery platform.
The fact that CureVac didn't manage to get a vaccine candidate as soon as Moderna/Biontic illustrates that the mRNA vaccine producing step is highly nontrivial.
On the other hand, there are simpler methods to produce vaccines like the one persued by RaDVaC.
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comment by MarcelloV (aram-baghdassarian-1) · 2020-12-21T18:20:36.196Z · LW(p) · GW(p)
This seems to be almost exactly what you are suggesting. At the end of the article he seems to offer an open invitation to receive their vaccine. While there is no mention of their vaccine's efficacy in the article, the article was written in late July so the team may have more updates by now if you reach out to them directly.
Replies from: PeterMcCluskey↑ comment by PeterMcCluskey · 2020-12-21T18:35:12.452Z · LW(p) · GW(p)
The RADVAC website has more information, possibly enough to tell experts how to do the same for other viruses.
Replies from: johnswentworth↑ comment by johnswentworth · 2020-12-22T00:46:56.935Z · LW(p) · GW(p)
Well now I'm kicking myself, because I saw the tech review article back in July but assumed this would require a lab. But looking at the RADVAC docs, this is dead simple. Looks like I can do it myself, no problem, it's mostly just a matter of ordering the peptides and taking the time to read through everything.
Replies from: Benito, RedMan↑ comment by Ben Pace (Benito) · 2020-12-22T00:50:29.691Z · LW(p) · GW(p)
what
maybe the lw team should make itself vaccines
↑ comment by RedMan · 2020-12-22T08:22:46.531Z · LW(p) · GW(p)
I have not made the specific radvac vaccine, but have read the prep. I've done all of those steps for other projects, can confirm, extremely simple and straightforward.
I have had an open offer to my friends to go in halfsies on materials if anyone wants it, but no takers thus far.
As far as QC goes, 'trust the vendor to mail you the correct peptides' is the easy route, screwups in that industry are rare and shocking. If you really want to check, raman or IR spectroscopy is probably the way to go--I've only ever used 'the spectrum looks like this, which matches the spectrum in the authoritative source', I've never learned anything about actually reading them. So I couldn't do that myself...an ELISA assay or something (easy to do if you have it, but idk if one is readily available for those peptides) would work too (take sample of peptide, apply elisa test, if pass, it's the peptide)
No real reason not to trust the adjuvant or DI water suppliers either.
The actual final product is a kind of crude mixture, and it's just going up your nose, so you would need to deviate from the procedure pretty severely (like, adding toxic ingredients) in order to really hurt yourself by doing it wrong. It's not like a drug where microgram differences in dose are the difference between ineffective, effective, and lethal
comment by kithpendragon · 2020-12-21T17:11:03.007Z · LW(p) · GW(p)
I think you may be interested in learning about Homebrew Medicine or Open Source Medicine. I've never looked too deeply into it, but I remember reading a few years ago that somebody got fed up with the healthcare system as it stands and decided to research the very path you seem to be eyeballing. If memory serves, anybody with half a clue can make rather a lot of medicines with a fairly modest investment in equipment. The hard part is doing it with replicable safety. I think somebody had recipes for making insulin and birth control pills of some kind, and probably lots more besides.
Replies from: chlorophos↑ comment by chlorophos · 2020-12-21T20:53:03.443Z · LW(p) · GW(p)
I've personally looked into DIYing modafinil. The process itself actually seems pretty straightforward organic chemistry -- all the reagents are available online, and the synthesis is clearly described in patent filings. I also found that the hardest part would be "what quality assurance steps are typically used?".
But that's just chemistry, and while my knowledge of the subject is shaky I can get by going slowly and looking things up. Vaccines and biology feels like a much scarier black box, amounting to "something something mRNA???", but I'd guess it's probably much more achievable than the average person would guess.
Replies from: RedMan↑ comment by RedMan · 2020-12-22T08:38:28.469Z · LW(p) · GW(p)
Don't do this in the USA, modafinil is a schedule IV controlled substance. Manufacturing a controlled substance requires a license, and a bunch of other stuff. Use requires a prescription.
If busted, you'd probably be the only 'modafinil lab' the local cops have seen, and it's anyones guess whether the judge and prosecutors treat it like a meth lab or ignore you like a weed farm in a legal state.
Obviously this isn't legal advice, but I'd be unsurprised if making your own modafinil and using it would be treated like a felony akin to making your own DMT or meth and using it ('officer I was making that meth for personal use!' is hilarious, but I doubt a lawyer would let you try it in court). Since you're posting about this on a forum, it's probably safe for you to assume that you wouldn't avoid scrutiny from the law...so yeah, while I definitely feel what you're proposing in principle (why do I need a medical mafia member and the pharma-industrial complex between me and my nootropics????), you'd probably be taking a legal risk you don't need. Idk what the law is outside the US, but I'd assume it isn't sane
comment by Felix Karg (felix-karg) · 2020-12-22T22:25:10.886Z · LW(p) · GW(p)
Thank you for asking, I was wondering about exactly this myself earlier today - how much effort would it require creating something vaccine-like myself?