Making Vaccine
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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.
A well known example of how dangerous the immune system can be is the following phase I trial:
https://www.nejm.org/doi/full/10.1056/nejmoa063842
That drug caused a cytokine storm in the participants in the phase I trial.
Allergies are another example of how dangerous the immune system can be if it is triggered against the wrong targets.
This is false.
Put another way, the very fact that we run such massive tests on them before deploying them is itself evidence that the wrong ones can be very dangerous. (Mostly, as I understand it, "very dangerous" to a small set of people who will have very large reactions, even if most people are fine. The ones that are very dangerous to everyone never gets past the initial phases at all, of course.) We're not doing that because vaccines are all perfectly safe under all conditions, but we just want to hold them back for a year for no reason. We're doing it because we need to be very careful with them.
Though I'd also observe a non-trivial component of that danger is also because we're injecting them. Bypassing the body's co-evolved with the environment's defenses is not to be done lightly. This sort of inhaled vaccine is likely to be much less dangerous. I won't say "safe", but less dangerous; the body already has to deal with essentially arbitrary small amino acid sequences being inhaled all the time. I'd still be a bit worried about sythesizing things that we haven't co-evolved with.
(If you don't know what co-evolution is, I'd suggesting taking a moment to learn about it: https://www.britannica.com/science/coevolution It's a very important part of understanding the disease landscape holistically.)
However, as the saying goes, science advances one funeral at a time.
Imagine trusting a "rocket scientist" to even weigh in on medical topics because they are "very intelligent" in their totally unrelated field. This is an unfortunate misconception that plagues conspiracy theory extremists who reference PhD graduates in their arguments against things like 5G brain control.... pointing to people with doctoral degrees in Music or something.
Perhaps you are not one of the people running on the unexamined assumption. I still say it's clearly operative in many people.
I call it "unexamined" precisely because once pulled up the conscious level, it is obviously false. Nevertheless, pulling such things up to the conscious level is not easy and usually takes effort. Or, to put it another why, while I cringe every time I adopt this terminology, Kahneman's System 1 is pretty sloppy about such things. System 2, when presented with a problem directly, can often see quickly that System 1 is being irrational... but it first must be presented with the problem directly.
If i can quibble though, i think "all" can be a bit of a loaded word in this context, because people often use it to mean, all well known ones or something along those lines and not all potential ones including random stuff people make in their backyards.
> The MHRA has received 101 UK spontaneous adverse reactions associated with anaphylaxis or anaphylactoid reactions with the Pfizer/BioNTech vaccination. All patients have recovered from the anaphylaxis episode. 13 reports of anaphylaxis have been received for the COVID-19 Oxford University/AstraZeneca vaccine to date.
> As of 24 January, an estimated 5.4 million first doses of the Pfizer/BioNTech vaccine and 1.5 million doses of the Oxford University/AstraZeneca vaccine had been administered, and around 0.5 million second doses, mostly the Pfizer/BioNTech vaccine, had been administered.
For a rare disease, this would be pushing the rate of side effects and risk that is acceptable. But you've got a huge risk of catching COVID, and COVID is many orders of magnitude more dangerous than the vaccine. At least for now: if COVID vaccination is required in the long term, vaccines may have to get better.
An issue here is that no one could risk the vaccine failing, with the limited time we had and the massive trial. In a normal process, it's likely that smaller doses would have been selected. But here it looks like both Pfizer and Moderna "rounded up" a bit from what phase 2 trials pointed to as doses. If I were in charge, I'd have funded a non-inferiority trial in December for 1/3rd dose, which would put us in a position in February-March to massively stretch supplies and reduce side effects.
The relationship between “crazy” antivax people and the actual attributes of a vaccine are not correlated. Antivax is a con game. Bad actors take advantage of natural instincts (ie protect your children), project false qualification and leverage ignorance to push their narrative, and usually product.
Covid is very deadly right now, it is the leading cause of death in several countries, including the US. If you catch covid, it roughly doubles your chances of dying for the year, and without a vaccine, it will happen eventually.
It means that even an "unsafe" vaccine, you are better off taking a shot.
On the other hand, a flu shot has to be extremely safe, because the flu is much less deadly, and the flu vaccine seems to be less effective than the covid vaccine. So most vaccines are pretty close to perfectly safe, the covid one, maybe a bit less so, but it is still worth it.
The thing is that we are biased. We will focus on the one person the vaccine has killed, but not the ten others the vaccine has saved. Just like with the trolley problem, will you throw someone under a bus if it can save five people?
(In places where polio isn't endemic, you get administered a totally inactivated vaccine by injection instead. They don't give everyone that one because it's more complicated to distribute, the oral one needs much less infrastructure)
This is misinformation.
Heart disease is the leading cause of death in the US, killing around 650,000 americans each year[1]. Also note that heart disease and obesity are extreme risk factors for negative health outcomes from covid, leading to potentially 3x the risk of hospitalization.[2]
Populations suffering from prexisting obesity epidemics, such as America and Europe, have had far worse health outcomes from covid than Asia and Africa, which have no obesity epidemic.[3][4]
>If you catch covid, it roughly doubles your chances of dying for the year
Do you have a source for this? I'm assuming this is not true for young and/or healthy people.
[1]https://www.cdc.gov/heartdisease/facts.htm
[2]https://www.cdc.gov/obesity/data/obesity-and-covid-19.html
[3]https://ncdrisc.org/obesity-prevalence-map.html
[4]https://en.m.wikipedia.org/wiki/Coronavirus_disease_2019#Mor...
In Africa, the population is much younger than in the US and life expectancy is lower. People die from other causes like malaria, malnutrition, violence, etc... much more often than in the US, so mechanically, the relative risk of dying from covid is lower.
In rich Asian countries like Japan, I haven't heard of a significant difference in infection fatality rate compared to western countries. They have less deaths overall because they have less cases, certainly because they manage the pandemic better. In poor Asian countries, it is essentially like Africa.
As for obesity, it is actually worse in northern Africa than in Europe, and closer to the US. And southeast Asia is getting close to Europe as these countries develop.
Exactly my point. Covid is a negligible risk to young healthy people compared to elderly, sick, obese people. This will have an effect on their risk calculations determining if they should take a vaccine which was rushed through safety trials or to take on a virus naturally which their immune systems can easily defeat, according to the data.
>In rich Asian countries like Japan, I haven't heard of a significant difference in infection fatality rate compared to western countries.
If you look at the data, you'll see the significant difference.
The US has 139.30 deaths per 100,000 people from covid.
Japan has 4.88 deaths per 100,000.[1]
>As for obesity, it is actually worse in northern Africa than in Europe, and closer to the US. And southeast Asia is getting close to Europe as these countries develop.
Indeed, if you look at the obesity map and the covid map of the world, you'll see the same correlation of obesity and larger relative covid risk in northern Africa.
[1]https://en.m.wikipedia.org/wiki/COVID-19_pandemic_death_rate...
One good thing about living in this time is that facts are trivial to look up. All the stastistical data is publicly available.
The leading cause of death in the US is still heart disease, then cancer.
> If you catch covid, it roughly doubles your chances of dying for the year
Not according to the CDC statistics, unless you mean some specific group, such as those aged 85+.
How many people even knows what chance it is they will die this year?
Right now, covid is the leading cause of death. It wasn't the case in 2020, but now, it is.
For the "roughly doubles", it is, as I said a rough idea in a high income country, something I forgot to mention. It is probably less overall but not by a huge amount. It is relatively consistent with a 1% IFR. It is age dependent but surprisingly not by that much, simply because older people are more likely to die of any cause.
> How many people even knows what chance it is they will die this year?
That question is meaningless. The nature of probabilities is that you don't know. For example, if you are playing Russian roulette, just before you press the trigger, you can estimate your chances of death quite accurately to be 1/6. But there is no intrinsic value to that number. To someone who can see the bullet in front of the hammer, it is closer to 100%, and to someone who knows the gun is jammed, it is closer to 0%.
Are you implying you think covid will kill more americans than heart disease in 2021 based on this incomplete data set?
>>How many people even knows what chance it is they will die this year?
>That question is meaningless.
It is not meaningless for people who care to take personal responsibility for their own health, and who want to make informed decisions based on a data driven risk analysis.
However, most Americans do not care to take personal responsibility for their health, so you're right that such people are not concerned with such information.
Vaccines that go through proper testing have a very high bar for safety but nothing is 100%.
This is simply not true. I've talked to a psychologist who treated kids with autism about this. Autism is usually diagnosed at a young age when children develop and also get vaccinated. This leads to bias in some of their parents who are looking for someone or something to blame for their misfortune. Combine this with the fact that in the last two decades diagnostic for autism was extended to other less severe disorders such as Asperger's. If adults would develop autism after getting vaccinated, then it would support this crackpot theory, but they don't.
This must be a question with no good answer.
My understanding is that being too immunocompromised for a vaccine happens in two different ways:
1) the vaccine contains live virus and so there's danger that the weak immune system couldn't fight this off
2) the vaccine isn't live, so it's not dangerous on its own, but the immune system is too weak to recognize it, so it doesn't build any immunity to the real thing. (One doctor I was talking to said the mRNA ones should be good here, because your own body produces so much of the lookalikes that even a weak immune system should notice it - and then you're much better prepared to fight the real thing off faster.)
Only the first is immediately dangerous, so the standard seems to be to just stay away from those.
I'm not sure if much is commonly done for the second, in terms of looking for response, but you can get tests for measles antibodies and such, so that would probably be how?
I imagine for this article the biggest risk is you make something other than you expect and poision yourself, or you just make something that does nothing. (IANAexpert)
Now the real virus shows up, your body goes "Aha! I've seen this before let me make those antibodies." But it wasn't trained on the real virus, so the antibodies it makes aren't actually effective against the real thing. The virus replicates and your body makes more and more antibodies but they do nothing to stop it. Meanwhile the the antibodies are running rampant in your body causing inflammation and blood clots.
This has happened before with vaccine candidates, and is analogous to what goes in on severe covid. The body tries to respond to the invading virus but does so ineffectively and causes potential deadly damage.
Maybe the explanations are simplified but I don't quite understand how the immune system could fail to recognise permutations of proteins or any other differentiating factor between COVID-19, its variants and mRNA vaccines; nor what makes this specific example of vaccination riskier.
The reason the second infection is so bad is exactly as outlined above: your immune system 'recognises' the second variant and produces antibodies that it learnt when fighting off the first variant you recovered from. Unfortunately, these antibodies are useless against the second variant, and you have a bad time.
This exact same issue happens with the current vaccine for dengue, which is why it is only given to people who have already had dengue of some kind, or in populations where most people have had it before. For a situation where this did not happen see the section titled 'Phillipines controversy' in the wikipedia article.
There is currently a lot of work being done to produce vaccines that protect against all 4 variants at the same time, with some promise for the years ahead as trial results come in!
That's not even getting into the issues that may arise from skipping all the GMP/GLP guidelines. They can be tedious but exist for a reason.
If I may - perhaps one alternative question is "Can an unapproved vaccine product cause harm?". With that re-wording, the answers become a bit more clear. Yes, chemicals used in the formulation maybe toxic, or the final vaccine might give rise to an auto-immune response, or could induce anaphylaxis in certain people. There could be cell debris/endotoxins that a purification process doesn't remove properly and causes problems. Maybe the vaccine contains an attenuated pathogen that can "revert", etc, etc.
After a bit of digging I found this: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3335060/
> An early concern for application of a SARS-CoV vaccine was the experience with other coronavirus infections which induced enhanced disease and immunopathology in animals when challenged with infectious virus
I didn't dig deep enough to see if any experimental vaccines caused similar issues, but it definitely appears to be a concern.
So yeah, I'd be _very_ cautious with any homebrew vaccine. You might accidentally train your immune system to self destruct when you get exposed to a real SARS-CoV-2.
That said, I have little to no experience with biology, so it's entirely possible that radvac based vaccinations have already been demonstrated not to have this particular problem.
Trying it is IMHO a risk calculation once you've jumped the "is this credible" bar.
Might be a nitpick, but the immune system destroying itself would be a different, still possibly dangerous outcome of probably losing your defenses.
An over-sensitized response would be a hyper-sensitive trigger-happy paranoid all-hand-on-deck general-mobilization fight-or-die this-is-the-end immune response, of various scale, possibly similar to but not exactly the same as a bad case of covid.
Good thing that's not what the article author has done, ey?
If your experiment is not falsifiable, you are not doing science.
Both parts of the great grandparent's sentence are false. I don't think saying false things for rhetorical effect is good for the health of hackernews discourse.
I do think context and implication do need to be taken into account when evaluating the authors statements. The authors present this article as if they were making an actual vaccine. They talk about how you too can make one. With strong implication that its likely to do something. Admittedly, they do talk about follow up, but its follow up that by their own admission is not likely to show anything, and that's after having an incredibly rosy view of it, to the point where i don't believe anyone could reasonably call it a follow up.
As far as healthy discussions go, i would say that assuming the people you disagree with are arguing in good faith and while they might be mistaken, ultumately believe their premises and not simply intentionally making false statements to further their rhetorical point, is important too :)
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
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.
I didn't get this from the post at all -- they didn't invent the vaccine, they're just trying a protocol put together by some other biologists they seem to trust.
The certifications and testing is not for show, and no one serious is claiming that. Asking an entire population to vaccinate is a huge responsibility; if you're making claims to the public that an injection is safe you'd better be as sure as you can reasonably be that it's true.
If you're just experimenting on yourself, the bar is lower: as here, you just need to convince yourself that your risk of adverse outcomes is very low.
An individual may be willing to accept a 0.1% risk of severe adverse outcome. A society that asks 300 million people to take that risk will experience 300,000 severe adverse outcomes.
A homemade vaccine is both unlikely to be effective (and therefore do nothing for others) and probably more likely to harm me personally than covid. It’s certainly the greater harm for most people.
I can pretty easily avoid Covid for the couple more months it’ll take before I get a real vaccine, so it’s low danger for me. I’m also younger and healthier so my risk if I get it is quite small. High enough that I’m modifying my life to avoid it, but still pretty small.
And since I think the homemade Covid vaccine is unlikely to work, it is unlikely to decrease the odds of any of the things you mentioned anyway.
However squirting strange chemicals up your nose adds risk. People die from Neti pots and that’s just water.
If I’m currently faced with the choices of taking a homemade vaccine or not taking a homemade vaccine, the latter is clearly the less dangerous course of action. I think that’s the spirit of the comment to which we were all replying, and it’s the actual choice being discussed.
Now if I were an 85 y/o diabetic in a nursing home and there weren’t a vetted vaccine available that might be different.
Well, the actual content of the comment we’re all replying to is a mix of “it’s impossible for a non-expert to come up with an idea that’s worth experimenting with for anyone” and haughty derision about Rationalism and what the commenter perceives as the “hubris” that goes along with that.
What the original comment misses is that the people who came up with this protocol are not pitching it as anything other than an experiment for themselves and maybe others who are interested — they make no safety claims, no claims about the real vaccines, no claims that it’s a good idea, etc., and no one is arguing that taking a homemade vaccine is good or better than the real vaccines or other precautions, which seems to be the strawman you’re debating in your post.
That said, historically, a significant number of vaccines were demonstrated to work initially by the inventors trying them on themselves and then challenging themselves with live virus.
The fact that at it’s not a good idea for the average person to try a homemade vaccine (and to be clear: we are 100% in agreement here) does not imply that the original radvac authors here should not have put together their protocol.
It seems like it’s probably more likely to harm you, either directly because you’re shooting amateur-made chemicals up your nose, or indirectly because it might give you false confidence or make Covid hurt you more if you do contract it.
It’s an interesting idea to make your own vaccine, but clearly a bad one.
Does your opinion change if you assume the person making the vaccine has had lab training?
Several of the vaccine candidates from a year ago have failed. So even pros with virtually unlimited budgets fail a decent amount of the time.
Perhaps there’s a case where someone for whatever reason will not be able to buy a safe vaccine soon, is at real risk of contracting covid, is demographically at high risk from covid, and has enough knowledge and access to proper materials to make their own, and for that person it is a smart move. I don’t know. Anything is possible.
I’m also defining bad idea as worse than the alternatives. It’s like riding a motorcycle. I consider that a bad idea because you have a much, much higher chance of dying than in a car. But your most likely result is neutral. Most people who try to make a vaccine will probably just lose a little money and time.
And I should note I do things that are bad ideas sometimes too. If you’re doing it for fun or education or whatever else that’s fine, you should just be realistic about the risk you are incurring.
Of course in this case the systems in question are actually most definitely Turing complete on many levels; and much, much older.
'Life' is ultra-advanced (non-artificially) intelligent (non-alien) nano-technology. If that doesn't seem totally fascinating and something people might want to hack... what on earth does?
But someone said that your risk from covid was higher than your risk from a home made vaccine, and to me that’s almost certainly untrue for nearly everyone at best. That’s where the thread started. I was disagreeing with someone’s obviously poor risk assessment.
> When [an outsider] asserts an opinion, he has only one thing he's optimizing for - being right.
> When the Director of the CDC asserts an opinion, she has to optimize for two things - being right, and keeping power. If she doesn't optimize for the second, she gets replaced as CDC Director by someone who does.
This does sound good, though I have seen zero examples of this fairy tale coming true in the real life around me.
For sure you have to be a good doctor to become a head of CDC, but also you have to masterfully balance that with politics.
But be careful of taking the first one at face value. The outsider might be optimizing for being right. He might also be optimizing for looking good in his social circle, confirming some self-image in his own mind, establishing himself as a prudent person who holds sensible beliefs, or establishing himself as a daring person who holds antiestablishment beliefs. The process that brought him to your attention, might also have selected him for noteworthiness by all sorts of criteria, only one of which is being right; that counts as an optimization process in and of itself.
Which doesn't mean the outsider isn't right. Maybe he is. But be careful of just assuming it.
Organizations like WHO and CDC make their recommendations based on studies which are in turn based on evidence. If you compare that procedure to 2 bloggers who happen to be right about the same topic among 98 other bloggers who happened to be wrong, selection bias alone may make those 2 outliers appear like genuises. That doesn't mean or show anything.
Perhaps there is some context that you have elided, but as it stands, this is terribly cynical and almost certainly not true.
Being CDC Director is an entry on a resume, albeit a prestigious one. It can only come after outstanding achievement in medical and/or scientific pursuits. Assuming one does not leave in disgrace, it is followed by even more prestigious, and highly compensated appointments.
There is a strong analogy here with the obsession of finding "signaling" everywhere one looks. As if everybody is an automaton, or even a malicious actor, that behaves in a facile, self-serving manner.
Occam's Razor should be your north star here.
Actually, that's a net negative for me: whatever benefits the community may create some warm happy feelings (kumbaya!) that may reduce the correctness of my decision.
Check out what I think is called the depression correctness hypothesis (at least IIRC): clinically depressed people cast more accurate judgements and evaluations.
I want to use the full power of that by taking decision that have the potential to increase my future utility (or the sum of its present value) in the most clear minded way possible, so with as little warm fuzzy feelings as possible
The Depression Correctness Hypothesis experiments, incidentally, said nothing about depressed people's ability to achieve better outcomes; they simply concluded that in experiments where humans were asked to estimate their level of control over the outcome, depressed people were more likely to correctly reason they didn't have [much] control. cf predictions for future utility in studies of cooperative behaviour, reciprocal altruism etc...
I do not generally avoid that - only when it comes to serious decisions. For a pandemic not seen for the last 100 years, I think this precaution is warranted.
Last time I did was when I was receiving conflicting signals - LW was strongly pro crypto, HN strongly against. HN generated warm fuzzy feelings (if crypto succeed it's extreme selfishness, they can't be right because as a community we find it wrong, deflation is good and more generous to newcomers, etc). I waited a bit too long to my taste to get in. A lot of LW people just didn't. It was quite a fiasco - the calculations clearly made sense, but a lot of people didn't act on the advice they were freely given. The reason is still unclear. Personally, I think it's due to these warm fuzzy feelings - or the lack of thereof.
I vowed "never again!", and now I apply a discount factor to questions that appeal to sentiments.
> in experiments where humans were asked to estimate their level of control over the outcome, depressed people were more likely to correctly reason they didn't have [much] control
Good enough for me! In the case of covid, we have little control - if only about the vaccine formula and access. A homemade vaccine allows me more freedom.
I see that as buying an option for a deadly 2nd wave driven by a mutant selected by the evolutionary pressure of everyone being vaccinated against the same antigens.
$1k isn't much for such a deadly scenario: I estimate the odds at 1%, and the lifetime cost at 1M (average cost of a human life), which means the homemade vaccine option is interesting up to $10k.
The title is misleading. He didn't really make the vaccine. The peptide sequences were designed by people with real biology credentials [1,2]. He ordered the peptides online. All he did himself was mix the peptides with some liquids [3] and spray his nose.
[2] e.g. https://en.wikipedia.org/wiki/Preston_Estep, https://en.wikipedia.org/wiki/George_Church_(geneticist)
[3] Ok, now I am misleading. There is also chitosan, vinegar, activated charcoal, and more steps than just mixing proteins with liquids.
Definitely not like that.
This is like the Galileo complex, where people think their ideas are right because they are rejected by the establishment, forgetting that by the time Galileo started promoting heliocentrism, he'd already been one of the most respected, well established scientists in Europe, and, in fact, his views were accepted by the majority of establishment scientists. It was the non-experts who rejected him.
You don't have to "wait", but you do need to trust. These people exist, and nearly anyone can join their ranks.
It is indeed hubris to suggest expert-level ability is possible without the experience to back it up. Expertise in one domain does not confer expertise in another.
Side note: expertise is surprisingly hard to define. And I don't believe that "only the experts can speak". All voices bring something.
It's more evident in the comments on that page. From the author:
"I heard that the Moderna vaccine was designed in two days... 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."
He seeks to demonstrate that an individual can 'operationalize' a vaccine i.e. manufacture personal doses. He describes his motivations: "we've all been complaining about how 'we' (i.e. society) should [make vaccines and tests], yet to a large extent they’re things which we can do for ourselves unilaterally" and says he hopes his efforts are "enough to go out, socialize, and generally enjoy life without worrying about COVID."
There's little consideration of 'should' only 'can'. Is it desirable to have people self-vaccinating then socialising? What might go wrong, and how might issues be mitigated? Are there broader issues with showing how to order items from Amazon then snort them in the name of self-vaccination?
I'm also unclear of the evidence supporting his assertion that these are things "we can do for ourselves".
His other motivations include this being "a fun project" and "build[ing] the habit of Doing This Sort Of Thing, so next time I hopefully do better". His self-awarded "D" grade is assigned on the basis that he is "embarrassed" at taking 4 months to notice radvac. He refers to this as poor "performance", but I'm not sure what performance is being measured: reading a news-feed or developing lab-skills?
He draws a lineage from "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" through to himself, in the name of "Rationalism".
He describes his experience of the pandemic as "a near-perfect real world equivalent [of Jesty's experience] on super-easy mode with most of the work already done by somebody else". This makes his detailed description of the process he followed feel like a bald-faced humble-brag to me: here's all the juicy detail; I consider this to be 'super-easy mode'. I recognise that it might be self-deprecation and a recognition of standing on the shoulders of giants, but that just doesn't come across for me.
To be frank, and I recognise how subjective this is, the entire exercise whiffs of self-aggrandisement. A less contentious approach might have been to do the work anonymously and post on a pre-print server that permits anonymous papers, then optionally de-anonymise once results are collected.
The whole approach just rubs me the wrong way, and the "Rationalist" declaration exacerbates that.
At least he does mention the problem with expertise: "you need some level of expertise yourself before you can distinguish real experts from fake. There is no substitute for learning at least some amount oneself".
He's just trying out something an actual expert has made to see if it works when he tries to do it. So far it hasn't worked, as he admits, but it certainly could. Sure, it's probably with greater cost, higher risk and less effectiveness than the mass produced vaccines I expect (and the author would likely agree). But it's certainly not the case thay a layman can never do what an expert can do, particularly if they are following expert instructions, they just shouldn't expect to do it as reliably or well as an expert (for example, with a bit of reading up you can wire your house and it'll probably be ok, but the expert is far less likely to electrocute himself and has a much lower chance of doing something that will lead to your house burning down).
Are you so offended by someone spending $1000 and a few hours on a hobby that may have some useful results that you must assume bad things about them?
Theoretically this might be true, but in practice it seems obvious that this will fail. I can think of so many ways in which this could be subtly invalid and I am in no way an expert. I would expect someone with commercial lab experience or vaccine production experience to be able to point out a hundred ways in which this won't work.
Maybe the more obvious problem though is that we can't know if it works either. Without a valid scientific study on the effectiveness it's all just a guess. To call it a vaccine is hubris because it is precisely this study that deems a concoction of ingredients to actually be a vaccine. I'd expect Less Wrong to be the first place to point out all the flaws in the idea of just getting an antibody test to decide if it's working.
Are you defining "vaccine" in a manner that makes those 19th century things called "vaccines" not actually vaccines?
Vaccines aren't magic that can only be done by a suitably blessed priest and aren't necesarily even very high tech...
https://radvac.org/wp-content/uploads/2020/12/White-Paper-SA... (be aware: there's 3 pages of warnings and disclaimers upfront. They are very clear that this constitutes self-experimentation.)
The paper does appear to assume that the reader is indeed an expert or at least a somewhat experienced amateur. If you sign up on their researchers map, they do ask whether you have a science degree and/or lab experience:
https://radvac.org/researchers-map/
I must admit I'm stymied by your implication that an antibody test wouldn't constitute evidence that the vaccine had been effective in that instance (n=1). What makes you say that?
If you think there’s something off about his protocol, then say what it is. But your criticism is just “this guy is reaching above his station”.
Sasha Shulgin synthesised plenty of compounds at home and tested them on himself. Did none of them work because he wasn’t working in a commercial lab?
https://radvac.org/a-homepage-section/
What you can do is conduct experiments, and report back what you find. If enough people do that, then together one can get usable n.
"Possible Risks and Uncertain Benefits
- Immediate allergic or other serious reaction
- Unforeseen long-term effects
- Instillation/administration of the vaccine in an inappropriate way or in an infected area might increase the risk of infection by enhancing viral entry into the body
- Benefits are uncertain. There are extensive published histories of the materials and procedures described on this site, but every novel vaccine should be considered experimental, with the possibility there will be no benefit.
- Even if there are signs of immune response there is no guarantee this response is indicative of protection from SARS-CoV-2 infection, or if protection is achieved, how long it will last.
- Even if the vaccine confers protection from the virus, certain methods for assessing protection–such as measuring antibodies due to previous infection–might not capture vaccine-induced immunity. In such cases, infection, and thus a positive test result, are unlikely to occur. Immunity passports and other privileges given to convalescents might be difficult to obtain for those with vaccine-induced immunity.
- Use of this vaccine may change the efficacy of any future vaccines you may take or that are administered to you, in unknown ways."
* "THERE IS NO WARRANTY [...]" and
* "IN NO EVENT WILL [...anyone...] BE LIABLE TO YOU FOR ANY DAMAGES [...]".
I will grant that seeing such a disclaimer in a text on something that you need to ingest is a little more scary.
I think a lot of people here probably think they're as smart or smarter than the average Google, Microsoft or Apple engineer. (Some readers are actually Google, Microsoft or Apple engineers, and some (others) may -indeed- be smarter).
Possibly some amount of hubris comes with the territory? ;-)
The story reminds me of Barry Marshall, but with less science behind it. https://jamesclear.com/barry-marshall
In many cases, the hard part isn't so much making a working vaccine, as proving it works, scaling manufacturing, etc.
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.
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.
The hard part isn't making a vaccine, it's making one that's safe and reliably effective. Using 19th century techniques will kill you an unacceptably high proportion of the time (well, unacceptable unless it's something like widespread smallpox or, debateably, covid) and also often won't work.
Early vaccines were made in the scientific equivalents of modern basements and worked adequately well. Influenza vaccines come out each year like clockwork. There are plenty of vaccines which just aren't rocket science, including for virtually all major historical viral diseases which wiped out or crippled large numbers of people.
And then there are ones like AIDS.
With COVID19, as far as I can tell, virtually all reasonable vaccine candidates DID work, and it was mostly a question of how quickly and how well. I'm much more excited about a 95% effective shot than a 60% effective one. The Moderna one was developed, quite literally, overnight. Once Moderna had the sequence, they had a (later proven working) vaccine candidate more-or-less instantly, in January, long before they'd seen the virus live, let alone had a way to check that it worked.
Did you see many /failed/ COVID19 vaccines? I saw a few /worse/ vaccine candidates. A couple failed in some populations (e.g. Sanofi worked well for younger people, but not older). Some didn't have competitive effectiveness (e.g. Merck, presumably, but they didn't release enough to know when I last looked). Some had side effects (UQ/CSL would cause people to fail AIDS tests later). Etc. I think all of these will compete for some of the logistics chains as the winners, so it doesn't make sense to push with /less effective/ vaccines.
My general impression is that COVID19, at least unmutated, is not hard to make effective vaccines for. There are questions about longevity and mutations, but for now, I can see the sticking-peptides-up-nose approach potentially working. I mean, compare that to early vaccine efforts like variolation (which worked), or the whole flu of 1918 vaccine effort (which didn't).
Disclaimer: Not an MD or biologist.
I think the reason they're (clearly) not first is because it appears they had to scale their people-network as well as actually work on the vaccine. It doesn't help that biology and genetics skills are -as yet- a bit more rare than programming or editing skills yet.
Given the constraints I think they've gotten impressively far within 1 year.
That said, the interesting bits are:
#1) Vaccine design at home. This is an application of what is known colloquially as "bio-hacking" and as a topic group is no less impactful than "computer hacking."
#2) You can do something for < $1000 which wasn't possible before because of the industry that will print you rna sequences.
Interesting stuff indeed.
I've TLDR'd most of them here for everyone:
-Immune tolerance: diminished immunity resulting from exposure to an antigen
-Vaccine-enhanced disease (VED): A small number of injected vaccines have led to enhancement of disease, meaning that infectivity is enhanced, or the disease is made more serious in people who have been vaccinated.
-Adjuvant hyperstimulation or toxicity: ..certain adjuvants have caused hyperstimulation and other serious side effects. For example, alum produces a robust Th2 immune response, but an unbalanced ratio of Th2:Th1. A Th2 polarized response, and alum in particular, have been implicated in immunopathology, including ADE. Adjuvants can also be toxic. As one example, the intranasal use of a detoxified mutant form of Escherichia coli Heat Labile Toxin has resulted in transient Bell’s palsy, or facial nerve paralysis.
The whitepaper then argues the following: "And it becomes clear why the formulation described here has not been used in a commercial product; it is not lack of safety or efficacy, but other factors.."
It's way less impactful. An amateur playing with computers might not achieve what a pro can, but it obviously has some effect. Computer programs are rarely a placebo.
Little these so-called bio-hackers do is known to be effective. That's almost by definition.
Still, it's hacking molecular nanotechnology. Possible developments are far more interesting than what we do with computers now. Let's give it some time.
Justin from The Thought Emporium created a fairly durable treatment for his own lactose intolerance https://youtu.be/J3FcbFqSoQY
quite effective at getting themselves on FBI watchlists
Pretty sure George Church is a "formally trained scientist"!
This guy is a total amateur. He bought some proteins, diluted them then shot them in his nose. That's not science.
And I also question his methods. Simply shooting a small peptide into your nose is unlikely to elicit any major immune response. Cells in your respiratory tract excrete proteases. I'm guessing those peptides get chewed up pretty quickly. You need to develop and validate some sort of delivery mechanism.
This is so far from any resemblance to an actual therapeutic vaccine it’s just scary. Reminds me of the recipes for making meth on the web. Sure, it theoretically works, but nobody seems to check the final product.
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.
I am a little worried that 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). "
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.
https://www.bloomberg.com/news/articles/2020-10-10/home-made...
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.sciencemag.org/news/2020/12/neanderthal-gene-fou...
[1]:
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...]
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.
There's only one of you, no second chances if you mess up.
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.
Yes, I look forward to having random people skirt the social distancing rules because they sniffed their own homemade vaccine over the weekend.
> 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).
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.
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.
https://radvac.org/wp-content/uploads/2020/12/White-Paper-SA...
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.
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.
> 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.
The author is planning to take a "test". What test? The standard lab tests are some proprietary qualitative test looking for antibodies to a specific synthetic antigen. For a (new, untested!) vaccine, this is a dubious experiment at best. The vaccine could produce an amazing antibody response that doesn't trigger the test, or it could produce a tiny, useless response that happens to trigger the test. And the test is unlikely to give numbers.
But this vaccine is using short-ish peptides. There are two (at least? I think just two) different types of T-cell receptor, and they are sensitive to different lengths of peptide. Testing for those is complicated and expensive.
I don't know how one would find a lab to do the relevant tests, but it's probably not so easy.
> 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.
> 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.
It's like a scientific method LARP.
Self experiment, not in order to generalize conclusions to the rest of the world, but to find useful conclusions for own use.
The most basic cases of statistics run on point estimate evaluations. With one datum you just have a point, not an estimate, and you cannot evaluate anything.
The author says they will accept that their homebrew worked if they get a positive antibody test (yet, plenty of people will get a positive antibody test without any administration of homebrew or vaccine); but will not accept that it failed if there is a negative antibody test.
As such, their hypothesis is not falsifiable and it is not science.
The hypothesis "my homebrew has worked on me" is what the blog asks ("I'm curious whether it will work - or whether we'll be able to tell that it works."). That is not falsifiable.
If he ends up getting COVID-19 in a few months, he'll have pretty strongly falsified that hypothesis.
You cannot dismiss a hypothesis as "not scientific" simply because it's likely that your search for evidence will be inconclusive.
I know you used "pretty strongly" as sarcasm, but falsifiability is absolute - and this is not.
(On your later point about my claim that this is not scientific, we are back to the comparison with gathering roots and berries - either both are, or both are not)
> I know you used "pretty strongly" as sarcasm, but it's not falsifiability is absolute - and this is not.
I'm having a very hard time parsing what you're saying. At this point, it looks like you're trying to make an argument that "falsifiability" must mean that it is both possible and practical to reject a hypothesis with 100% certainty, and if you can't then you're not doing science. Would you care to explain more clearly why the position you're taking is less extreme and absurd than that?
(Additionally, I did not use "pretty strongly" in any sarcastic way. I used it to acknowledge the possibility of confounding factors that I did not care to enumerate, which mean that even the experimental outcome of getting COVID-19 after inoculation with the homemade vaccine would not be a 100% certain rejection of the hypothesis that the vaccine conferred some protection against COVID-19. But if you're operating in a mindset of 100% certainty being achievable and necessary for science, then I can see how you would misunderstand me.)
This is equally science as going into the woods, picking some berries and roots, grinding them and put them up your nose, doing an antibody test, and writing your conclusions up in a blog post. There's no difference.
(But, yes, I think that writing hypotheses with 100% falsifiability, before challenging them practically, is quite a good definition of "scientific method", based on Karl Popper's work. You can compare with what Wikipedia has to say.)
Edited to respond to your edit: The word falsifiability is deliberately used to distinguish that we are talking about False, the Boolean state. The confounding factors are important - the confounding factors here mean I can't prove it False; there are no circumstances whereby the author has to accept that their hypothesis was False.
It seems like you're still not making the necessary distinction between whether it is possible for an experiment's outcome to falsify the hypothesis, vs whether it is guaranteed that the experiment will falsify the hypothesis if it is in fact wrong. The latter is an unreasonable requirement to make part of your definition of science.
The author described such a circumstance, but then explained that he did not have access to the necessary lab testing to actually do so. The hypothesis is falsifiable in principle even if the researcher does not expect to have the equipment necessary to measure falsification by that outcome.
> The author described such a circumstance, but then explained that he did not have access to the necessary lab testing to actually do so.
In the parent article? Could you quote that part?
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?
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).
( https://radvac.org/wp-content/uploads/2020/12/White-Paper-SA... )
I think they also were talking of trying the AstraZenca one nasally which is also a modified chimp virus.
> 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.
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.
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?
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
1. No, it won't be a massively important result. It might have been important a year ago, but now it will be completely and utterly useless. Testing a vaccine takes a long time. It maybe kind of working and maybe kind of being safe is irrelevant when we have already started mass vaccinations.
2. The author has no good way of testing it. He will take an off-the-shelf antibody test, but no one will know how to interpret those results.
It won't be an important result, at all.
Vaccines are tested on the thousands, one person having a positive response isn't interesting at all, especially when you already have effective vaccines rolling out globally.
By chemically synthesizing naked (non-glycosylated) protein fragments, you likely end up with the wrong antigen.
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?
It's like the difference between heroin and opioids
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. :)
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.
Find a few thousand smart, maybe insane, biohackers. Give them each a $100k grant. Give them total immunity from FDA regulation. Free them from all the bureaucratic and ethical shackles that slow down establishment science. At a cost of $300 million, even a 1% chance that one of them figures out a way to double the rate of vaccination, constitutes a 1000%+ return on investment.
I haven’t heard of a single one of the available vaccines being held back by regulations, only the speed at which they could go through human trials.
The vaccine trials were drastically slowed down by the regulations against human challenge trials.
If you were dealing with a disease that is rare so that it might take a long time for enough people in phase II or III to get exposed to it naturally, an HCT might be able to cut the amount of time you need for phase II and maybe phase III.
With COVID, there should be enough people getting exposed naturally to make that unnecessary in phase III and probably in phase II.
What an HCT might do for a COVID vaccine is let you figure out early that your vaccine does not work. That might let you abandon an ineffective vaccine during phase II instead of not finding out it doesn't work until after you have spent a lot of time and money on phase III.
i.e. if your argument applies word for word against Semmelweis (who advocated hand-washing) or doubters against other earlier amateur vaccines, it it will fall victim to what we now know about those older cases, when the at-the-time experts were wrong.
In this case I wouldn't say that the reason this kind of research is valuable is anything related to medicine per se - but more that it can show the value of the much lower liability level he operates in, and how it means that amateurs can make massive cuts in preparing and defending from lawsuits. Example: if a company realized that only food-quality ingredients were required, not lab-quality, would it be worth it for them to justify that to the FDA and spend millions on it? probably not. My hypothesis for what's going on in general in medicine is this effect times a thousand, at every stage of development.
(a) The ability to produce hundreds of millions of doses.
(b) Tests that prove (as convincingly as we can) that the vaccine are safe.
I don't see any evidence that anyone has any idea how to do better at either (a) or (b).
This blogpost completely ignores the difficult proof issue.
The pay for brave vaccine testers could have literally been $1m and we’d have saved several trillion bucks and potentially over a million lives. Hell, make it $10m or $100m and you'd still save a ton of money.
We've done this for several other viruses: https://en.wikipedia.org/wiki/Human_challenge_study
You're really going to force testers to potentially pick up the placebo, and then inject them with COVID19 forcefully? I mean yeah, it'd work, but its generally considered immoral under today's philosophy of science.
It would be quite possible for it to clearly be informed consent also, at least to the extent the disease was characterized at that point in time.
The reason people keep bringing it up is that the consequences of the pandemic have been much worse than the consequences of allowing a few thousand people to intentionally expose themselves to an infection in a controlled setting¹. It's not guaranteed that challenge trials would have mitigated the pandemic, but it's weird to just outright circumscribe the possibility when the ongoing downside is huge.
1. I use the odd phrasing here because lots of people pretty much choose to expose themselves to the infection anyway; maybe not explicitly, but close enough.
And if it wasn't immoral, what is the dollar limit?
Bill Gates or Jeff Bezos will never risk their life for "only" a million bucks. Find a depressed + suicidal dude somewhere else, and they may be personally willing to risk their life for just $100.
Making an industry of people who are willing to harm themselves for money is... probably not the business we should be encouraging. And that's assuming everyone is "playing nice". At a minimum, it means that we'll be inclined to start experimenting upon the poor and depressed (and then shedding away moral qualms because they signed a piece of paper).
Historically speaking in the USA, we have legacies like the Tuskegee Syphilis Study, where African Americans were chosen as the control group and lied to about getting a Syphilis treatment: leading to a generation+ long distrust in science.
Yeah yeah, we can't "assume" scientists will be racist jackasses today. But... we still have to account for what happened in our history and why certain testing methodologies have become taboo.
I've thought for similar questions that a required baseline would be to at least have a society that provides a viable minimum social safety net, as well as free healthcare. When external conditions compel people to risk their health for survival, it is impossible to ensure sound ethics.
The point about ensuring that science and scientists can be trusted in the future is also an excellent point.
What's being proposed here is for people to sign up and then inject a potentially deadly disease into them.
Sure, the scale is massively different for a young healthy person: "susceptible to COVID" would mean a moderate chance of catching the disease (growing over time), and then a small chance of death or previous complications. But the "susceptibility" is also a "health condition" with nonzero risk-of-death.
And for society as a whole, COVID passed cancer as a cause of death last year, and in January 2021 has been killing about twice as many people as all cancers combined.
So "diagnosed-with-cancer" versus "susceptible-to-COVID" shouldn't be that different in terms of the kinds of risks we'd let informed people take to address that danger.
1) death is but only the worst outcome. Being on the space shuttle does bring risk, yes, but not a 50/50 chance of a significant impact to your general health.
2) you'll end up testing the vaccines largely on marginalized population and people with heavy financial problems, misrepresenting the population at large and showing biased result.
I would sign up for this in a heartbeat. Not only for the cash payment -- but you'd be a local hero and you could feel good for the rest of your life about taking a small risk to save the lives of many ill or elderly people.
The alternative that we chose was hundreds of thousands of more deaths and millions of more cases. From people who didn't sign up for it.
The risk to testers under 40 would have been negligible. I'm not being flippant about other peoples' lives -- I would have signed up myself if the compensation was high enough.
Luke Letlow (age 41) says otherwise, since he's dead. Okay, he's above 40, but he's high-profile and easy for me to remember. Plenty of sub 40 year olds have died.
Even among the survivors... plenty of young and healthy 20-30 year olds are having month-long recoveries, unable to breath at their old capacity.
Purposefully damaging the control group (who by definition, must NOT receive the vaccine) is immoral. Whether people in the control group believe in the potential harms of the disease or not.
Under 40 the survival rate is 99.98% for everyone -- including the already ill. If you screened for comorbidities and gave people great healthcare, you could get that 99.999% or higher. And save millions of lives (and trillions of dollars) by doing so.
I doubt that. But I'm not entirely sure how to calculate the numbers you just said.
https://www.cdc.gov/nchs/nvss/vsrr/covid_weekly/index.htm
I realize this page changes, so I've taken a screenshot here: https://imgur.com/0iM5FHC
This is the chart of who died in January 2021. Yes, most deaths are aged 65+, but there's been deaths in all age categories. I doubt its 99.98% as you suggest (especially since the current case-mortality-rate is ~2.5%, at least for my state)
The official CDC numbers are stratified from 35 to 44, I'm not entirely sure who you are citing to get "below 40" age groups.
(1-7057/41659144)*100=99.983%
I expect the individual probability of surviving infection is not that high for each member of the group though. It's not clear if that meaning is intended anywhere above.
That's the total population of all 35 to 44 year olds in all of the USA.
> 99.983%
That's 0.02% of all 35 to 44 year olds have died, including those who never had COVID. IN ONE MONTH, not including the people who died two months ago, or 3 months ago.
It's for the entire period of the pandemic.
You are correct in pointing out that it isn't looking at deaths/infection.
A few bad cases and deaths that were consented to, versus hundreds of thousands to millions of cases and deaths from people that didn't consent. This morality scale doesn't make sense.
It's as if when there are some "professional" ethicists in the area who give "professional" ethical guidance, people lose their natural moral sense, and defer to their "professional" guidance no matter how silly it is if you apply even modicum of scrutiny.
This means you are choosing people to murder.
People can decide for themselves to take risks. You may not agree with the choices they make and that is your problem. Not theirs.
I honestly haven't thought deeply about the ethics, but it's really concerning that it has become such a hard rule that preventing people from injuring themselves in a particular way (we don't prevent lots of other forms of injury) is somehow obviously superior to letting tens of thousands of people die for lack of information.
It won't hurt the at risk groups to start up high volume manufacturing earlier (it will likely help them), and there is a benefit to everyone each time anyone is vaccinated (the reduction in transmission efficiency).
Optimizing deployment of the virus to bored 20 year olds may be popular among bored 20 year olds, but it isn't the best public health strategy.
Do you think the vaccines being distributed right now were manufactured more than a few weeks ago or something?
Remember it wasn't a given that mRNA vaccines were going to work, we were lucky.
What proportion of approved vaccines in general have such radically different responses in different age groups or demographics?
It might work or it might kill you. Please don't go snorting it until we know which.
Yes, yes and yes. This is all good fun, but isn't a super novel vaccine. The vaccines that are currently being delivered were mostly developed within weeks of Chinese researchers sharing the genome sequences in January 2020. The bits that took the time were the safety and efficacy trials, which is what this is skipping. And it's not like $1000 for a household is cheap: the Oxford/AZ vaccine costs about $3.
I'd really like to know what those reasons are. It seems like a pretty important detail.
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.
It seems like a failure of the system that no one is trying for FDA approval or industrialization.
Of what?
Edit: I get it now, sorry. I think FDA approval would bump up the price quite a bit.
https://www.lesswrong.com/posts/niQ3heWwF6SydhS7R/making-vac...
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
Not true. Novavax is just peptides and is 96% effective against the original Wuhan covid-19 strain.
There are also efforts for some simple to produce vaccines underway, it's just not the ones you'll likely see used widely in industrialized countries. An example is the chinese Coronavac vaccine.
Though keep in mind making vaccines isn't just producing them, it's also running trials. It pretty much doesn't matter how cheap your production is, it will hardly affect the cost of the trial. And after all they're there so you actually know whether your vaccine works - and that part certainly shouldn't be skipped.
The big problems with COVID vaccines is making sure they are safe and effective, and logistics. The author doesn't do any of these. There is a scale difference of 7 orders of magnitude compared to what we need. And he is taking risks that would be unreasonable for a commercial vaccine and efficiency is "let's see if it does something".
It is an experiment and it has scientific value, maybe some of the mainstream vaccine candidates started out like this. But it cannot be compared to current widespread vaccination efforts.
As for the money, it is a common fallacy to think that throwing money at a problem will solve it. Same as an often seen argument "it will take $X billion to end world hunger". World hunger is solved with food, not money, people don't eat money. On a small scale, you just have to go to the grocery store and spend money to feed a starving person. On a large scale there simply not enough food available unless we do some major changes regarding agriculture and distribution, throwing in money will just cause price inflation. Same thing with vaccines.
Vaccines are similar: vaccinating the world will be logistically very very hard. But vaccinating first-world countries is a lot easier, and supply of vaccine in rich countries absolutely is a problem that can be solved with more money and resources. The fact that we've had so much trouble solving it is a political problem.
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.
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.
Not the author though, so take it with a grain of salt ;-)
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?
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
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.
But as a starting point, I've thought the same in the past and I don't think it's bad. Just that crossing a red light, even if no one was harmed that particular instance, may still be judged to be reckless and fineable, and even if it's only about your own dead body (let's say you didn't run in front of a cyclist), that's still an impact in the way described above. Nevertheless, if you use "don't bother others" as a general rule for what should probably be legal and then define exceptions for particular situations and reasons, or even if you just look for those side effects, it might be useful.
What a tremendous coincidence that two people not only love each other, but also share the same interest in a specific area in science, and above all share the same amount of willingness to take these risks.
Somehow I believe that one of them is doing this not because he or she is convinced that this is the way to go, but because it pleases the partner. Might even have been manipulated to believe that this is good.
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"
The first rule of DIY vaccine club is that you have no fucking idea what the key problems are.
Stay in school, kids. Or at least don't get your wisdom from a guy whose magnum opus is the world's worst Harry Potter fanfiction.
I don't understand why, but that insult apparently smells correct to a guard dog in my brain.
Do you have an ELI5 for what the insult means?
ELI5: a cult that believes that they know the secrets of the world and everyone else is dumb.
Reality shows that’s not always true, witness for instance the death of the irreplaceable technologies Internet Explorer and Flash.
Argue all you want but these vaccines have been taken by hundreds of people with no ill effect already. So for the people in the article the risks are not worse than the people in the trials for the commercial vaccines.
I don’t know about the scarcity of the ingredients in this vaccine but if I was in government I’d have directed an institute to run a report on theoretic safety and then a trial on volunteers. That’s a better option than locking up the population for over a year while we wait for the commercial vaccines.
Commonly known as “pre-clinical development” and “clinical trials”
Given Covid's lethality, comparing not taking a vaccine at all to making a batch following expert instructions (in addition to taking the standard mass produced vaccine) seems unreasonable to me.
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?
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.
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.
You could call it an inoculation. I think it is okay to reserve 'vaccine' for something a bit more fine tuned and tested.
Want a good laugh? Here's the research team: https://radvac.org/researchers-map/
See how many obviously fake identities you can find.
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.
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?
Stay safe ! Cheers
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 [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318931/#!po=2....