If there is one thing I certainly wouldn't just play around with it's the immune system. It's incredibly dangerous and easily capable of causing all kinds of harm to yourself up to killing you outright.
A vaccine is designed to produce an immune response of the right magnitude. Too low and it doesn't work, too high and it'll cause damage. At least one of the vaccine candidates in development was put back to the drawing board because the immune response wasn't strong enough. So this is not an area that is entirely predictable, you have to carefully test this to know if it works.
I'd also be very careful about the inhalation route. Inhalable insulin is a well-known failure, in part because of side effects due to the inhalation. And that is a protein that isn't designed to activate your immune system.
I also hope the synthesized peptides were carefully purified, you really don't want to inhale e.g. residual trifluoracetic acid.
I recall a researcher talking about previous attempts at creating coronavirus vaccines. How they resulted not in immunity, but in training the immune system to _over_ respond when a real infection came along.
> 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.
A recent attempt at a dengue vaccine faced a similar problem. The most dangerous kind of dengue fever happens when you are infected a second time, by a different variant than you were infected the first time. It turns out that the vaccine ended up having a similar effect as catching dengue for the first time. People who never had dengue and got vaccinated had a lower chance of catching the disease in the future. But if they did catch it there was a higher risk of it being the more dangerous version. The end result is that the vaccine is now only recommended for people who already had dengue before.
This is specifically mentioned in the Radvac paper in the section titled "POSSIBLE MECHANISMS OF VACCINE-ENHANCED DISEASE,
VACCINE-INDUCED AUTOIMMUNITY, AND MITIGATION STRATEGIES"
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.
The sites where the body evolves adaptive immune responses like antibodies and killer T cells aren't actually in the blood so that wouldn't produce any result. Rats don't have good ACE2 receptors for getting sick with Covid-19 but ferrets do so you could try testing this on them.
I said that the immune system can cause damage. Vaccines have a very high safety standard as they are given to large numbers of healthy people, so the tolerance for serious side effects is very low. So the development there is very careful, and anything that looks too dangerous is hopefully caught in animal experiments or at worst at phase I.
A well known example of how dangerous the immune system can be is the following phase I trial:
I have suspected for much of the last year that a lot of people are running on an unexamined "Only crazy people think vaccines cause autism -> Only crazy people think vaccines are ever dangerous in any way -> All vaccines are perfectly safe" psuedo-syllogism.
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.)
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?
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%.
>Right now, covid is the leading cause of death. It wasn't the case in 2020, but now, it is.
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.
>Covid is very deadly right now, it is the leading cause of death in several countries, including the US.
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.
The thing with covid is the younger/healthier you are, the less likely you are to die from it, but you are also less likely to die from anything. So the relative risk does not change much.
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.
>The thing with covid is the younger/healthier you are, the less likely you are to die from it, but you are also less likely to die from anything. So the relative risk does not change much.
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.
Probably the best example of this is the live oral polio vaccine. It's a bit risky (it occasionally reverts to being infectious) but in a population where polio is endemic it's much safer than letting polio keep circulating.
(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)
Another advantage of the oral vaccine is that it produces better immunity in the gut, which helps cut off assymptomatic transmission in places where polio is still endemic.
End of the day, we evolved and are bred to recognize patterns and project outcomes based in what we see. The problem in modern society is these instincts make us vulnerable to poor risk management.
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.
If you think carefully, you may realize that what you said is actually entirely unrelated to what I said.
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.
Yes you are right. I like to think im better than that, but in this instance i clearly wasn't.
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.
I personally know very intelligent and highly educated people who went to top universities who are convinced vaccines caused mental retardation in their children. They may be wrong, but I would not call them nutjobs.
> "very intelligent and highly educated people who went to top universities"
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.
Look I am not saying they are right. My point is these are not your average stupid uneducated person. The two families in question, the one parent has multiple PhDs from Columbia and Princeton, the other took their undergrad at Caltech. You don't get those degrees by believing any random crazy thing that crosses your path. Plus they have a first hand experience with their child that for some reason makes them believe the vaccine was responsible. If it were any other topic their background and experience would lend their viewpoint more credence than dismissal as "nutjobs". What makes this topic different? Why would they have any incentive to blame the vaccine besides some sort of convincing first hand experience? Why should we in this one instance distrust their rational capacities that have allowed them to acquire intellectual credentials the vast majority of the earth's population don't have the capacity to acquire?
I think it’s more accurate to say that intelligence is not adequate defense against trusting the wrong sources of information, and people are extremely resistant to changing their minds once they’ve placed a stake in the ground.
> 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.
Yup, and this is a few times worse than we're used to with widely used vaccines.
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.
Thankfully that's a rare side effect and one that the nurses giving the injection can recognize and deal with. No fun for the recipient but nobody has died or suffered lasting injury. This is, however, why we don't conscript people to give vaccine injections.
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.
I have no doubts about the safety of vaccines in healthy people. I have some harmless curiosity about people who are not known to be healthy. How do you actually determine if someone is "too immunocompromised" for a vaccine?
> I have no doubts about the safety of vaccines in healthy people. I have some harmless curiosity about people who are not known to be healthy. How do you actually determine if someone is "too immunocompromised" for a vaccine?
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?
The MMR vaccine has live virus, and before injecting the kids the nurse make a few additional questions about the health of the children and IIRC about the people that live with the children. (Like: Does someone in the family have cancer or is immunosuppressed? I don't remember the details.) It's safe, but they must check that the nearby persons are healthy.
That's true in general but I'd be very surprised if an inhaled rather than injected vaccine that didn't use any adjuvants or live virus was going to cause a serious problem.
The goal of the vaccine is to train the immune system to recognize the real virus when it shows up. If you get it wrong, the vaccine may not simulate the virus very accurately which can lead to a number of issues. You may not mount an immune response when the virus shows up, or worse the vaccine may have improperly trained your immune system and you create antibodies that are ineffective against the virus but wreak havoc on your body. This has happened before with vaccine candidates like RSV or Dengvaxia. It can be deadly.
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.
Well, a vaccine is a rather vague and generic term. Are you talking about an FDA approved product? An experimental vaccine? A vaccine whose use is contra-indicated for certain people? etc. etc.
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.
For vaccines in general, i imagine it depends on the type a lot. Live vaccines for example have the obvious risk factor of maybe giving you the disease, but i dont know much about the topic.
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)
You can actually do much worse than nothing with antibody dependent enhancement. Let's say you make something that at first glance appears similar to the virus but is a little off. Maybe you chose the wrong proteins, or maybe you used an inactivated virus and the inactivation step damaged some key part of the virus. You inject the vaccine and your body learns how to make antibodies for this particle.
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.
Isn't it possible your body would have the same response if it was exposed to a variant of a virus that it already has antibodies for?
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.
For a real-life example look into dengue fever. There are multiple variants that - to our immune system - look very similar, but antibodies for one do not protect against the others. This means that if you recover from one variant and are subsequently infected with a second you can have a really really bad time.
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!
Your immune system is not intelligent. Through natural selection it has evolved to be able to handle some things, but it can't see permutations like that, as they are not something it evolved for, it's all chemical/physical matching.
Those people tested their theories, did experiments. They didn't just stick something up their nose and assumed it worked with no further investigation.
But it is. The author has made no attempt to test whether he is immune to covid as of this writing. He talks vaugely about future blood tests, but its unclear what test specificly, if a positive result would actually mean he is immune, if a Negative test would mean he is not, so its basically a test that tells us nothing, and he hasn't even done it yet.
If your experiment is not falsifiable, you are not doing science.
He explicitly has not "assumed it worked", nor has there been "no further investigation" (there has been some and will be more).
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 maintain my statements are neither false nor are they being made purely for rhetorical effect.
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 :)
This is an impressive amount of hubris. Does the author assume that all the certifications and testing stages were for show?
I don't hold the highest view of LessWrong and the whole rationalist shtick. This post exemplifies why. Underneath this post is the assumption that the author is so much smarter than everybody else because they are Rational with a capital R and can therefore harness the power of science to make a vaccine[^1]. Again, that's an incredible amount of hubris. If there's one universal truth about science, it's that it is extremely specialized. Just because someone knows a lot about chemistry doesn't mean they're qualified to talk about biology. There is no magic Rationality that can have amateurs making vaccines a good idea. Unless you are an expert in vaccines a priori, you cannot suddenly become one in a few weeks.
Heck, I'm skeptical of doctors who are not infectious disease experts giving advice. I still hear a lot of "well my sister's neighbor's brother is a pediatrician and he said XYZ". Doctors are certainly more educated than the average person, and if this was a minor medical problem I'd certainly take a random doctor's advice. But this is a pandemic with a novel disease. Listen to the infectious disease experts.
[1]: Quite honestly this feels like a plotline from Harry Potter and the Methods of Rationality
> 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
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.
I would say your risk in taking a homemade vaccine is greater than your risk from Covid if you don’t take the homemade vaccine. The homemade vaccine is unlikely to work so it won’t decrease covid risk much to you or others. The expected value is low.
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.
I guess there would clearly be some people who would be much more likely to be successful than others. I can’t imagine it’s a good idea in our current situation, in which there are very effective vaccines that have gone through extensive testing that will soon be readily available.
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.
It's so strange to see people switch to the other side in an open source/hacking debate, when it comes to hacking systems that are not 'traditional' computers.
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?
Yeah it’s interesting. I read the article and enjoyed it. I’ve really got no problem with someone doing it. I’m not suggesting people shouldn’t be able to so I don’t feel I’ve switched sides.
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.
So? I’m not worried about the effects on others if I squirt peptides and chitosan up my nose. I’m worried about the effect on me.
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.
The risk of permanent smell changes, possible neurological changes, and a chance of hospitalisation and death from COVID is unlikely to be smaller than ingesting a microscopic quantity of a peptide.
Disagree because you’re looking at it as if my options are get Covid or take homemade vaccine.
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.
> 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.
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.
This is obviously false in the case that an error is made in the process. E.g. someone vaccinates themselves with a live virus, or possibly accidentally engineers an even more virulent strain.
If you are making your vaccine from artificial peptides that are a hundred times shorter than a live virus, this seems unlikely. There was no way for live virus to be introduced into this process.
The parent said "Homemade vaccines are not contagious (just stating the obvious). ", they didn't say "homemade vaccines made from artificial peptides are not contagious".
Um... are you reading the same post as the rest of us?
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?
The hubris is to expect that someone at home can manufacture something worthy of being called a vaccine if they're just smart enough to follow the science.
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.
> The hubris is to expect that someone at home can manufacture something worthy of being called a vaccine if they're just smart enough to follow the science.
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...
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:
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?
Note the long disclaimer, though, clarifying among many other things:
"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."
> can therefore harness the power of science to make a vaccine
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.
So what he effectively did is create chitosan nanoparticles loaded with protein/carbon nanoparticles. This, I would imagine, is to allow the proteins to help bypass every protease, lysosome, and other defensive mechanisms that your body and cells have to protect against non-self proteins. These antigens, would then need to be presented by major histocompatability complexes to induce an immune response.
I agree this is dangerous and wouldn't work in a large scale, but I abhor this attitude of "only the experts can speak". He did it on himself and showed what he did, how do you think things actually get made, by sitting around waiting for experts to show up? How did they become experts?
In this domain, in an ideal world, things "get made" through transparency, collaboration and scrutiny. Expertise is earned, not declared.
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.
In this context he was simply following a protocol developed by established experts. No hubris involved, unless you think the experts also have hubris.
I would go so far as to say it's precisely the ability to have a protocol designed by an expert in science work for a layman who follows it that separates scientists from which doctors.
I'd suggest the hubris is in the author identifying as a "Ratonalist", cherry-picking the others whom he identifies as being in that same tent, and identifying with them while simultaneously declaring their efforts trivial, and over-emphasising quantitative measures at the expense of social considerations.
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".
Did you miss the part that he'd become a doctor and observed patients for years before he started experimenting on himself to treat the very condition he was already an expert on?
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.
> 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.
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.
Exactly. The Rational movement is well optimized for signaling their intelligence. Everything from the fanfiction to the explicit partitioning of people into rational and non-rational groups is meant to signal how smart they are. Sometimes that means they encourage genuinely smart practices. Autodidactism is great. Learning math and computer science is great. But the game is fundamentally to appear smart, often via contrarian views. That doesn't always align with safe medical practices.
In the article, he was mentioning one specific outsider (Zvi Mowshowitz) that he trusts. I changed it to "[an outsider]" more generally since it didn't make sense without context.
This is a complete straw man, we’ve no idea of the complex layers and motivations of person one and two. The outsider could be a troll and the Director of the CDC probably got there on merit, looking after their power might not be an issue at all; people could just respect and like her as a talented leader. You just don’t know, but simplifying things like this does make “proving” yourself right a lot easier.
Okay so Elon Musk, Collison brothers, even people like Bezos (while immoral on the tax stuff) are all extremely effective. The management at the pension fund I work at are very good at their jobs too... there’s plenty of examples of one is willing to look.
The Director of CDC has to be right for the right reasons, not just by coincidence, and carries the whole weight of the responsibility about his decision, both politically and in drastic cases maybe even legally. That is a completely different business than voicing your opinion, and apparently the blogger you cite completely misses that point.
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.
> When the Director of the CDC asserts an opinion, she has to optimize for two things - being right, and keeping power
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.
Well, we are commenting on a site called "Hacker News"; so I guess you do have to expect and be tolerant of people who would try their hand at wetware hacking too.
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 truly rational (and ethical) way to get a vaccine early would have been to volunteer in an early-stage trial. You'd even get paid! The risk would be lower, and the likely efficacy would be higher, because even an unproven candidate is more likely to work than something you cooked up in your kitchen. In some early stages there isn't even the risk that you would be in the placebo arm. And of course there's the extra benefit that you would be helping the wider community, though I'm not sure how important that is to true Rationalists.
> And of course there's the extra benefit that you would be helping the wider community, though I'm not sure how important that is to true Rationalists.
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.
Many reasons - mostly that it makes you incorrectly discount the negatives, incorrectly assert some possibility, neglect some second or third order consequences etc.
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
But even if you are a unique human whose utility is entirely unrelated to the sum of warm fuzzy feelings they feel, arbitrarily avoiding stuff which makes you happy is an irrational cognitive bias which will often if not even usually (since warm fuzzy feelings evolved from preference for certain types of collaboration improving survival odds) lead to worse material outcomes.
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...
> arbitrarily avoiding stuff which makes you happy is an irrational cognitive bias
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.
If you are faced with a decision where one option gives you warm fuzzy feelings it doesn't mean that the appealing option is any more likely to be incorrect, just that you need to be more careful when deciding. Preferring the less enjoyable option is just as irrational as preferring the more enjoyable option. In fact, all things being equal, you should choose the enjoyable one because at least then you get some enjoyment from it
Have you tried? There were still single-arm, paid stage 2 trials recruiting in the UK in December (I can't remember which vaccine). I would've signed-up, but I'm already on the (placebo-controlled, unpaid) J&J stage 3 trial so can't take part in another. A stage 2/3 trial is still more likely to be effective than the homebrew approach, even after accounting for the 50% chance you've been given a placebo. As for how I got onto the stage 3 trial: I signed up here in the summer, and they contacted me in November: https://www.nhs.uk/sign-up-to-be-contacted-for-research
Sort of but not really. I'm an odd case as I had covid in April. I put my name with the NHS anyway in case they still want to try stuff on us survivors.
No offense, but you do sound a little triggered, and I completely understand why (in some sense). That being said, there are many different types of wrong/right, and the way in which the self-vaccinating Rationalist is "wrong"/"right" about the world is somewhat inverse to the way in which decorated science commitee can be wrong / right.
Experts are usually mired in procedure and politics (sometimes for good reason, sometimes not). A smart outsider who isn't constrained in the same way often has a pretty good shot at beating out the established experts. That's not hubris; it's just a viable strategy.
I don't disagree with the premise that outsiders are unconstrained. There is a notion that modern science lacks the frequent paradigm shifting leaps in progress due to bureaucracy and safety.
But... obvious issue: without the bureaucracy, how do we ensure safety? Vaccine trials do go wrong, people do die when that happens.
I hope we're living through the final years of the tension between population based evidence and processes, vs ultra-individualised medicine. Humanity just needs to keep its shit together for long enough, and learn to operate as a planet rather than as disparate factions.
#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.
The whitepaper also lists some possible short and long term side effects.
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.."
>as a topic group is no less impactful than "computer hacking."
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.
It's more difficult due to low observability of the system, low understanding of it, and long deployment cycle.
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.
I'll give biochemists all the time they need. I'll laugh in the face of anyone with a high school education in biology who injects themselves full of things they found online.
Dude, Pfizer can make a mRNA vaccine but that doesn't mean if I follow their directions I can.
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.
Ahh.. that’s what it’s for. Going on the radovac site there is no validation of nanoparticle formation? Just mix, shake a bit and it’s good?
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.
It's looks like this is an open source science project originating near Boston. The white paper looks pretty thorough. I think they progress by means of people contributing back with their findings.
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.
Because if all it took to make a vaccine for a respiratory disease was stick some peptides up your nose, we would havev a lot more vaccines (and i dont mean just for covid.).
Even if the other parts are harder (not sure if thats true. The reason proving things work is hard is because most initially promising candidates dont actually), it doesn't follow that every single vaccine candidate works.
Non-rhetorically, I'd encourage you to look at which vaccines we're missing and why. Do any of those apply to COVID19?
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).
Peptide vaccines do work - there's a very similar vaccine currently in limited use (EpiVacCorona, running phase 3 trials in Russia, with emergency use approval granted in two countries at time of writing). The inhalation based delivery mechanism is also not novel, but almost never used because you need a whole lot more spaced doses than intramuscular, and that's a massive pain logistics-wise when you are trying to run a public vaccination campaign. There is no clear reason this wouldn't work. That said, there are many reasons it can fail in practice without a GMP environment - peptide chains are fragile and contamination is a risk - with a contaminated substance inhalation is going to be a much safer mechanism than injection, but unless repeated multiple times it will be less effective. The thermal disinfection stage needs precise temp control to not destroy the peptides and in general there's a lot of handling steps that can go wrong. But that's a matter of process, not of principle - both intranasal delivery and peptide vaccines have individually been shown to work.
Vaccines are sufficiently easy to make that people in the 19th century could make them.
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.
If my life depended on having a self-driving car ready in a year to drive me to California, I'd have a self-driving car ready in a year. It could drive me to California with perhaps only a 25% chance of an accident.
I mean, it might be driving with the emergency blinkers on the whole time, at 10 miles per hour, and flashing the horn, or crazy stuff like that, but making a basic self-driving car just isn't out-of-scope for an amateur.
DARPA urban challenge was 2007, and 6 cars finished an urban course, with the fastest averaging 14MPH, and most developed mostly by students, with professor support. Today, I can get a lot of that stuff CoTS, open source, or read papers about what they did.
I couldn't sell millions of self-driving cars, because of edge cases, manufacturing, or what not, but it's not fundamentally different from biohacking. Technology moves forward.
Disclaimer: I'm not an MD, biologist, or similar, but I am pretty good at all the stuff that goes into a self-driving car. I'm not claiming a /typical serious amateur/ could build one. I'm claiming /I/ could build one.
Rough comments here... I admire the spirit of DIY in his project. He asked for and received good data, consumed the process and risk, and proceeded. He wasn't trying to save the world, he took a calculated risk on himself, and wrote a blog post about it. I'm most happy to have the process demystified for me. I don't think the world would be a better place if more people made their own vaccines unless there was some ubiquitous, reliable material testing procedure that we can't imagine yet. I do think I'd like a person like that to be my neighbor if society were to collapse, or maybe in general that would just be a good time.
The negativity might be warranted if they had encouraged other people to follow, or if they were trying to DIY-vaccinate others.
But that's not what happened here. These are two capable adults experimenting strictly on themselves and being transparent about it. That deserves respect. You might think "that seems like a stupid risk, I would never do that", and that's a fine take. But don't judge.
Where's the "hacker" in hacker news if everyone immediately reaches for admonishment and appeals to authority.
A lot of people in these comments overestimate how clean and linear and officially-sanctioned scientific progress is, especially in biomed.
In the 1980s, an Australian doctor suspected that ulcers are caused by a specific kind of bacterial infection. At the time, the medical consensus was that ulcers came from stress and diet. His ideas and evidence were ignored. So he drank a beaker of H. pylorii culture, got an endoscopy before and two weeks later, and demonstrated convincingly that he'd given himself ulcers this way.
My thoughts exactly. The level of contempt and tribe-bashing ("screw these rationalists who think they're smarter than us!") in this thread is depressing.
Similar to the author of the post, I'm surprised that I haven't seen or heard much about bio-hacking your own vaccine. Seems like an interesting trend to follow, though I will be waiting for an FDA-approved vaccine myself.
I am a little worried that https://radvac.org/vaccine/ 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). "
Because complying with GMP is tedious and expensive. One mistake and you could end up with blood poisoning or a brain-eating microbe. Lab grade material is not the same as pharmaceutical grade material. You can get a lot of expensive anti-cancer drugs too at bulk prices from lab suppliers. That does not mean they are rated for human consumption. What's good for the lab rat is not necessarily good for the homo sapien.
Josiah Zayner did one that looked fairly promising (believe it was either an mRNA or DNA vaccine), but unfortunately he got banned from a lot of media (like youtube) for it, so that may partially explain why you haven't seen or heard much.
Zayner's retrospective on the homemade vaccine experiment is interesting. He now thinks that testing vaccines is complicated enough to warrant large clinical trials.
Josiah is an interesting guy because it turns out his opinions hold quite a bit of nuance and he’s generally a good guy (not a snake oil salesman). I think he definitely had that perspective going in - the point of the experiment is partly inspirational to show it can be done.
Your comment made me think of something, I'll share it as a "PSA" in case it helps someone stay safe.
Neanderthal DNA has been linked to severe outcomes from COVID.[0] To me that means I'll get vaccinated (and strain specific boosters that may have to happen), full stop. But if I have a choice of more than one type of vaccine available at the same time (unlikely? But still), then I will try to keep this in mind. Other than that it just means I will be extra careful.
Disclaimer: not a scientist; and anything I say here is first-person (I'm in the demographic groups I'm referring to).
My non-scientific speculation: there is a chance the stuffy nose could be a proxy for high neanderthal DNA. I say that because other sinus and nasal issues are among the things linked to genes inherited from Neanderthals. They had different anatomies in that regard. I've read it could have been an adaptation to cold.
I've also read that the extinction of Neanderthals may have been related to viruses causing respiratory problems/diseases.[1]
Anyways, the point is, that some of these genes could correlate with severe outcomes from coronavirus.
If a reader knows their genetics, and/or knows people who have mentioned they have a relatively high amount of neanderthal DNA... You might want to think about it or mention it to them. Especially if they have other respiratory or sinus things going on.
[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...]
Hey FYI looks like you got an auto ban, I've emailed the mods to get them to review in case it's a false positive.
This was an interesting comment. I don't think it is particularly likely that Neanderthal DNA is associated with more stuffy noses, but who knows! An interesting hypothesis for sure.
> though I will be waiting for an FDA-approved vaccine myself.
If it was July, and this post popped up, heck even November pre-US election when we were told the vaccine was months away, would that change the equation?
I feel like there are two questions here:
1. is this safe? If so, how safe?
2. Is it worth trying?
Question 1 is quantitative and verifiable, whereas question 2 is one of risk preference.
> Doing it for ourselves doesn’t capture all the benefits - lots of fun stuff is still closed/cancelled - but it’s enough to go out, socialize, and generally enjoy life without worrying about COVID.
Yes, I look forward to having random people skirt the social distancing rules because they sniffed their own homemade vaccine over the weekend.
> 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).
I completely agree with fabian2k. It's incredibly risky to throw all random sequences peptides into the blood stream for evoking immune response. What happens if a sub-sequence of peptide matches with one of our own's body proteins and our immune system starts building antibody against it? That's what happens in most of autoimmune disease.
In addition, most of the peptides that can be synthesized from a protein structures are sequential epitopes. To ELI5, imagine a string with beads that starts with A-Z letters and we take a smaller sequence A-B-C-D or B-C-D-E and throw to system to build antibody against it. Yes, the immune system can make antibodies against it. But in real life, most of the protective or virus neutralizing antibodies comes from conformational epitopes. Imagine when the protein gets folded to its natural form then the beads with letter sequences are just jumbled sequences and finding a conformational epitope is key to raise neutralizing antibodies. That is only possible when a protein's structure is fully understood using x-ray crystallography. The article does not disclose how the author was able to get those sequences and how he was sure about its efficacy.
However, the author's bold step towards the experiment is praiseworthy. But extreme caution is needs to be taken as self administering an untested drug or vaccine may fall within the boundary of law and it can invoke regulatory actions against him.
> What happens if a sub-sequence of peptide matches with one of our own's body proteins and our immune system starts building antibody against it?
The peptide sequences are listed on the whitepaper, so it’s a matter of BLASTing[1] them against the human proteome to check for possible matches. I just did it and there doesn’t seem to be any statistically significant hit.
Ok great to know. But my intention here is to convey that it is dangerous to biohacking a molecule/compound that a user is going to put in his/her body. The peptides after synthesis needs to be rigorously tested(QC/QA) for the desired sequences and to make sure the absence of any undesired epiotopes mixed.
The white paper lists the set of epitopes, why they were selected, and provides references to the original papers that found them; starting on page 27.
Whether it's governments or corporations, there is constant tension between "move safely" and "move fast and break things." One reason why tech companies managed to dominate many fields is that they are less worried about making mistakes than their institutional competitors. Especially in western society where our medical institutions are quite old with many safeguards, the time it takes to roll out a vaccine can seem maddening, especially to readers of HN who work in fields where software bugs don't kill people. For those people, what this author did could seem like an attractive means of cutting through perceived red tape.
As has been pointed out before on HN with roll-your-own vaccine stories, it takes a week to make a covid vaccine. It takes much longer to prove it's safe and effective. We rightly live in a free society where someone can do what they like with their own bodies, but - like buying GameStop stock - I hope the naive do not get the wrong idea and do something they'll regret.
Without any evidence of efficacy, this article doesn't strike me as much different from "I went into the woods and gathered up some herbs and made myself an elixir that cures covid". I guess it's neat that you did all that stuff, but unless it actually helps, who cares? Doing it with science-y ingredients instead of herbs and ordered them online instead of harvesting them from plants doesn't magically mean it actually works.
The difference however is that this article is based on the scientific method, and the go into the woods and gather herbs is based on mythology.
Now the reasonableness of experimenting on yourself, even in a scientifically "valid" way, is certainly arguable. But the elements are all there; Theory of the Immune system, Hypothesis that it can be trained in this way, experiment that trains immune system in a known with with the experimental training element.
As others have pointed out, the immune system is designed to kill cells it doesn't like. And it has been demonstrated in other scenarios that it can target cells that are vital to one's survival, resulting in death when the immune system targets and kills those cells.
Thus the risk in the experiment is that it will successfully invoke an immune response, it just won't be the one that was anticipated.
Not surprisingly, this is the whole point of animal trials to get a feel for what might happen.
I would grant that it has a lot of the trapping of the scientific method, and uses a lot of the terminology. But I think we're kidding ourselves if we pretend that there's much knowledge to be gained here. It's a non-controlled trial with n=2 using ingredients of uncertain purity and a loose experimental protocol ("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."). I'd certainly put the net contribution to scientific knowledge below that of someone who just signs up for a clinical trial.
It does not have a sample size. It was not sampled and one is not a size.
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.
Okay, I love "scientific method LARP"! Granted it is a bit elitist but still, conveys a solid point. As a counter point, was Edward Jenner[1] a LARPer or a scientist? Follow up question, was his net contribution to science "big" or "small"?
Jenner was living in the 1700s and was doing the best he could with the tools of the time. Still, his report included 20+ people, included challenge results in which subjects were exposed to smallpox to verify their immunity. If the role models for this exercise are all from the 18th century, that should ring some alarm bells.
He's not really Doing Science in the manner you are describing, nor is that the intent as far as I can tell. The aim is not to contribute to the body of knowledge but to inatead to experiment (yes, it is literally LARPing, but that's a perfectly fine hobby) and hopefully reduce chance of getting covid.
It's hardly the scientific method when the outcome isn't actually measured. It is entirely unknown whether this whole procedure has done anything at all.
The author said he is going to try to do measurements to the best of what is easily possible:
> So, we’ll do (up to) two more blood tests. The first will be two weeks after our third (weekly) dose; that one is the “optimistic” test, in case three doses is more-than-enough already. That one is optimistic for another reason as well: synthesis/delivery of three of the nine peptides was delayed, so our first three doses will only use six of them. If the optimistic test comes back positive, great, we’re done.
> If that test comes back negative, then the next test will be the “more dakka” test. We’ll add the other three peptides, take another few weeks of boosters, maybe adjust frequency and/or dosage - we’ll consider exactly what changes to make if and when the optimistic test comes back negative. Risks are very minimal (again, see the paper), so throwing more dakka at it makes sense.
> Consider this a pre-registration. I intend to share my test results here.
Pre-registration for this kind of thing seems pretty good, and I am looking forward to seeing the results.
I've taken a whopping one class about immunology, so I'm not even remotely qualified. But maybe I'm just qualified enough to call this nonsense.
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.
And yet he titled the post "Making Vaccine". Unless you make it all the way through to the end, you might assume that he actually did make a vaccine -- and judging by the comments on HN, it looks like some people are assuming this. It all seems a bit... irresponsible?
> 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.
Does "go into the woods and gather herbs" follow the scientific method if I write my observations neatly in a blog post?
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.
I think you misunderstand what "falsifiable" means. This hypothesis is absolutely falsifiable. He just doesn't have the resources to conclusively falsify this hypothesis, because he's working with a small sample size and doesn't have affordable access to testing for immunity in the mucus lining.
The hypothesis "my homebrew works at scale" is falsifiable. As you say, that really isn't under test, nor is it a hypothesis the author cares about.
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.
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.
> (But, yes, I think that writing hypotheses with 100% falsifiability, before challenging them practically, is quite a good definition of science)
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.
> there are no circumstances whereby the author has to accept that their hypothesis was False.
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.
Curious whether short peptides are sufficient to generate a formidable immune response.
Looking at the paper cited, it's not trivial to detect T-cell immunity so I'm not sure a general antibody test would be able to pick up an immune response.
It's probably better than doing nothing, but it's not clear whether it's even in the same ballpark as a Pfizer vaccine.
edit: I'm not sure about t-cell vs b-cell responses in immunoassays, can anyone with experience point out what is going on with these peptides?
I rather doubt snorting some peptides as described will do much. There are some attempts to make actual nasal covid vaccines and I think they use chimpanzee adenovirus vectors. Ie you get a virus that gives chips colds and add some covid bits on. See the Indian one for example https://indianexpress.com/article/explained/explained-unders...
I think they also were talking of trying the AstraZenca one nasally which is also a modified chimp virus.
Not an expert, but I've read that the antigen presenting cells break down the antigen into short peptides too (8-20 amino acids) when creating antibodies.
One might however still ask if the body is better at selecting exactly which portions are cut and chosen than however these were selected.
Also, if the antigen is small from the start, that might have implications too (like being ignored).
They’re not sufficient without an adjuvant. Peptides by themselves usually aren’t enough to be recognized as pathogenic. If any peptide by itself could kick off an immune response, you’d be getting sick with everything you eat and smell.
Many of the negative comments here seem to have missed something important:
> Consider this a pre-registration. I intend to share my test results here.
How about, instead of totally dismissing this - in classic HN fashion - with "this can never work" or "this is magical thinking", we let the guy share his results?
If it works, that will be a massively important result. If not, it won't be surprising, but _at least he will have tried_. I for one think the expected value leans overwhelmingly in favor of at least one person actually trying.
> 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.
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.
>If it works, that will be a massively important result.
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.
> How about, instead of totally dismissing this - in classic HN fashion - with "this can never work" or "this is magical thinking", we let the guy share his results?
Sure. How about instead of sharing wishful thinking covered in "this will work because science" OP waits until there are actual results before posting?
Anyone can make a vaccine candidate. Few can make a vaccine. Even fewer can make a safe vaccine.
> How about... OP waits until there are actual results before posting?
It seems to me there's value in posting the details before the results are in:
- Helps prevent publication bias, by encouraging posting negative results
- Elicits comments from knowledgeable people who may be able to help
- Discourages doctoring the story after the results are in
> Even fewer can make a safe vaccine.
I don't know, the article, whitepaper, and comments seemed to make a pretty convincing case for the nasal vaccine attempt here to be not very dangerous - probably useless at worst. Do you have a more substantive counterargument?
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
Besides the obvious safety concerns, I also have some serious doubts about the efficacy. It's quite well known that the glycosylation of the spike protein ("decorating" sugar structures) contributes significantly to immunerecognition (see e.g. https://www.nature.com/articles/s41598-020-71748-7).
By chemically synthesizing naked (non-glycosylated) protein fragments, you likely end up with the wrong antigen.
That’s a good point. In this case the spike-derived peptides have no known N-linked glycosylation sites[1] and the paper you mentioned showed that at least some of those epitopes are accessible even when taking glycans into consideration.
Nations have spent thousands of dollars per person on just mitigation efforts and economic stimulus. Meanwhile we have had the ability for months to vaccinate an entire household for a measly $1k?
What's the catch? Is it significantly riskier than the Pfizer or Moderna vaccines? Is it easy to make a mistake while producing this and end up with something ineffective or harmful? Is it just not particularly effective?
They could not even test themselves to see whether they developed immunity against SARS-Cov2. All we know is that someone sprayed something up their nose and hoped that it actually had the effect that they wanted. This is the catch.
But the point is, even if there's a 1% chance that this plausibly works, the government should be throwing money at bio-hackers like this. Or at the very least exempting them from the regulations that stand in their way. Very likely these moonshots won't work. But they're still dirt cheap relative to the economic impact of Covid. If there's a way to disrupt the current slow approach to vaccine production, we should be exploring it.
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.
If they have total immunity from FDA regulations, how are you going to be confident it actually works and is safe at scale? The regulations are there for good reasons.
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.
> 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.
Err.. why not? Not sure how asserting this without explaining why helps. From my understanding, Moderna made their vaccine in a day in early 2020 (https://nymag.com/intelligencer/2020/12/moderna-covid-19-vac...) and HCT basically means deliberately infecting people. One day to make the vaccine, four weeks for it to take effect, infect everybody, four weeks to see who gets sick - that's 2 months to make and test a vaccine with HCT. It took us 11 months without HCT.
You still need the phase I trial to determine that it is somewhat safe, the phase II trial to determine that it is somewhat effective for some people, and the phase III trial to see if it is safe and effective on a large diverse population and to characterize side effects.
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.
Everyone loves an underdog but I can not imagine that this could possibly work. Why do you think bio-hackers could come up with something that thousands of smart people in the industry could not? The money would almost certainly be better spent on upgrading production facilities in advance and starting vaccine production long before approval. This has the risk that they might need to trash everything if the trial is not successful but in the case it is, production has a headstart.
Your argument may be too strong - you're suggesting that big companies or the professional class of responsible people always does things better. But HN is founded on many examples of that not being true.
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.
The mRNA vaccines were completed within a week or two with modern technology. It took nearly a year to test: prove that it was safe, prove that it was effective (preventing deaths, preventing hospitalizations, preventing symptoms).
This blogpost completely ignores the difficult proof issue.
We could have tested it in two weeks with paid volunteers.
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 could test that it's safe, yes. Effective, no. You have to have the people out in the community, for both the vaccinated group and the control group, and then compare who gets infected in each group. The testing actually took less time than they expected due to the unfortunately-high prevalence of COVID-19 in the community.
No, the testers would be directly exposed as part of the trial, which is why they'd be compensated -- as opposed to waiting around for 9 months for some percent of people to be exposed.
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.
Not forcefully. He said paid volunteers. Why does the idea of challenge trials cause a furious reaction? Let's compare it to the space shuttle: 135 missions with 2 missions in which everyone died. That's a case fatality rate of 1.5% -- in the neighborhood of the Covid CFR. And I'd expect a challenge trial on young healthy volunteers to have a much lower CFR. Why is risking people for the shuttle OK, but risking people for a vaccine that benefits all of humanity not OK?
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.
For this age range, the survival rate for everyone is 99.98%. It'd be even higher if your screened aggressively for comorbidities / general health and provided everyone with top notch healthcare knowing in advance they have been exposed.
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.
So 2 person out of 10 000 dies. You would be a local hero and you would probably feel good for the rest of your life which is 2 weeks time. Also, let’s talk about long COVID. Nobody knows how long is it stay with you or if you even recover from it. You are a hero but you cannot climb the stairs anymore. And you will be forgotten in months.
Would it be immoral if they were offered a million dollars?Honest question, because it feels like the philosophy might not match up with common experience. It feels like an interesting question. People voluntarily risk worse for less pay in other fields, e.g. the military.
And if it wasn't immoral, what is the dollar limit?
Money is worth different amounts to different people.
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.
Good points. It's obvious that the potential for ethical problems in such a situation is huge.
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.
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.
[1 Day Sooner](https://www.1daysooner.org/) is an organisation pushing for these trials, that's found 38,000 informed volunteers who would be willing to do these trials. Force is completely unnecessary, there are enough altruistic people who are willing to do trials like this
Remember that in, say, a cancer treatment trial, patients are signing up to potentially not receive the treatment depending on the run-in and randomization phases. I'm not suggesting these patients are forced into that decision; rather, I'm just pointing that controlled, randomized trials have some ethical fuzziness around them.
But until treatments/vaccines were developed, everyone on Earth had the disease-equivalent, sometimes-fatal status of "no prior immunity to COVID".
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.
Do separate branches then. Use challenge trials to accelerate deployment to under 30s (or whatever) and natural infection for other age brackets.
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.
That's circular. If the challenge trial is successful, start deploying it to the groups tested using that method and then shift to the at risk groups as data justifies it.
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).
There is no reason to expect a challenge trial would slow down the standard branch of the trial. If it gave an earlier result, the differences would be good ones! The production would have worked through initial scaling and a bunch of people would be vaccinated.
Do you think the vaccines being distributed right now were manufactured more than a few weeks ago or something?
Maybe, or you developed and scaled up production of a vaccine that only worked on young healthy adults who don't need it that much, and kills or maims everyone else. Wasting a ton of time, resources, and good will that could have been better spent saving lives instead of getting 20 year olds back to bars.
Remember it wasn't a given that mRNA vaccines were going to work, we were lucky.
Disregarding a way to accelerate vaccine development by months, and save literally hundreds of thousands of lives along the way, because one thoughtlessly applies cliches like "you are supposed to not make people ill", even though the people who you make ill are all volunteers, well aware of the risk, and handsomely compensated for it, is the real total ethical failure.
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.
2,000,000+ people are dead because we didn't take this path.
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.
> The risk to testers under 40 would have been negligible.
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.
"One person died" isn't a refutation, it's just an appeal to emotion.
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.
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.
It lists the total population for each age group. Just the 35 to 44 age group is above 99.98% (given the death counts in younger age groups it's obviously still true if you include them in the calculation):
(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.
Why is it immoral to allow people to take a risk that they explicitly consent to (ensuring they have full knowledge of the potential consequences), but not immoral to let hundreds of thousands or millions more people die that you could have potentially saved if you undertook the challenge trials?
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.
I don't think that's true. You still need to study the testers over a period of time. With a human challenge study you can get by with fewer testers and a little less time, but it won't be that different.
> 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?
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.
It's kind of funny, pharmaceuticals have similar economics to software now that I think about it: extremely high upfront fixed costs, minimal marginal costs.
Yes; there are similar risks. Working on something for years that might not work, or not pass clinical trials or whatever.
The only difference is that the researcher's limit for not understanding the code might be 150,000 lines, but only 50 atoms for not understanding the molecule. :)
I wouldn’t take the heroin version of anything unless the alternative was highly likely and extremely bad
Would I drink murky water in the woods? Maybe? Am I about to die of thirst and have no other clean water sources?
Would I take a vaccine made in a dude’s garage and posted on less wrong? Maybe? But only if there are no other options to keep me from a disease way worse than the horrors that covid actually is.
But it’s worth recognizing that this fear and noise in the system is the same type of thing that gave us an Arizona couple dead from drinking fish tank cleaner.
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.