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The first human trial in Europe of a coronavirus vaccine has begun in Oxford (bbc.co.uk)
242 points by dustinmoris on April 23, 2020 | hide | past | favorite | 210 comments

My partner is taking part in the trial in Oxford. So far there was a bit of an anomaly on her blood work so they're bringing in her in for another round of tests but I'm happy to ask her to share (or allow me to share by proxy) her experience. Obviously she has no idea whether she is in the control group or not.

Are they receiving any compensation?

Here's the information sheet - https://www.covid19vaccinetrial.co.uk/participate-trial-oxfo...

> If you participate in the study until the end, you will receive a total payment of between £190-625, dependent on group.

My housemate hoped to take part but was not selected.

It'll depend how far she progresses but the range of £150-£600 is what we have been told

I don't think so. Travel expenses refunded I think.

From what I recall, its ~500 pounds

The thing i like most about this vaccine is that it's a T-cell vaccine.

Very broadly speaking, the adaptive immune system has two arms.

One arm, humoral immunity, is about detecting foreign substances in the spaces outside cells: B-cells make antibodies, antibodies inspect molecules floating around, a match triggers the B-cells to proliferate and make more antibodies, and then antibodies tell macrophages and various other brutal cells to destroy and eat everything in sight, resulting in inflammation, but hopefully killing the invader.

The other arm, cellular immunity, is about detecting foreign proteins inside cells: T-cells make T-cell receptors, T-cell receptors inspect peptides presented on the surface of cells through some amazing machinery culminating in the MHC I protein, a match triggers the T-cells to proliferate, and the T-cells themselves go round triggering self-destruction of cells presenting the foreign peptides.

(I'm leaving out MHC II and helper T cells here, let alone T-regulatory cells, gamma delta T cells and all sorts of other things i don't know about)

Both wings are useful in response to a viral infection, but ultimately, the cellular immunity is key. Viruses commandeer and replicate inside cells, so to stop an infection, you need to find and kill those cells. Cellular immunity does that.

Vaccines based on injecting proteins or dead viruses can only develop humoral immunity. Vaccines based on modified viruses, like this one, can also develop cellular immunity.

In theory. So far, there are no T-cell vaccines.

so, we can say that B-Cell vaccines are good enough coz they have already been working on other types of viral infection, right?

They are likely good enough yes, presence of strong antibodies pretty much means there's no way the virus can outpace the immune response, and it often is neutralized so strongly you wouldn't even notice inoculation.

Well, it's good enough for some diseases. And it's clearly not good enough for some others.

Bear in mind that there are lots of viruses we don't have vaccines for, and not for want of trying.

There is a strong argument for doing a challenge trial, using young people, on this candidate.

In a study like that would half the participants still be in the control group?

Infecting, or at least exposing, healthy, unvaccinated, people with the virus?

Pretty sure that would never make it past an IRB review.

Vox did a piece on this[1]. Basically, if you're young, the risk of death is about equal to a kidney donation, which is a procedure we allow.

Participating in a trial like this could save many more lives than donating a kidney. And, if you live in e.g. NYC, there's a decent chance you're going to get COVID anyway, trial or no.

Separately from that... y'know, there are currently lots of health care workers taking care of COVID patients—frequently without proper PPE—and getting sick from it. If we as a society have agreed this is worth the risk, why not a challenge trial to develop a vaccine?

I'm honestly a little surprised there's even a debate about this. The choice seems pretty clear to me.


[1] https://www.vox.com/future-perfect/2020/4/9/21209593/coronav...

> Vox did a piece on this. Basically, if you're young, the risk of death is about equal to a kidney donation, which is a procedure we allow.

I haven't seen the Vox article, but if that's what they said, it's total bullshit and irresponsible journalism, and I'd request that you do your part by not repeating that.

The first kidney donation was in 1954. We have 66 years worth of data--plenty of time for many kidney donors to live out their lives and have the problems caused by kidney donation, so we have a pretty good idea of what the long-term effects of kidney donation are.

We don't know what the long-term effects of coronavirus are because nobody has had it and then lived long term. The first case we know of was in November 2019--five months ago. Vox can't say that "if you're young, the risk of death is about equal to a kidney donation", because we do not know what the risks are. If scientists infected a bunch of 20 year olds with Covid in 2020 and by 2050, 40% of them die of lung cancer before the age of 50, is that something you'd be cool with? Because that might be reality--it's impossible to know.

To be clear, I'm not saying Covid-19 causes lung cancer. I'm saying we cannot possibly know ANYTHING about the long term effect of Covid-19. We shouldn't assume that it causes lung cancer, but we also shouldn't assume it's no more dangerous than a kidney donation. We shouldn't assume, period. So statements like, "if you're young, the risk of death is about equal to a kidney donation" are lies. And I would implore you to not spread that misinformation because it potentially has deadly consequences.

I take your point, but calling the comparison "lies" based on the possibility of long-term implications we know nothing about seems like a big stretch to me. We don't know the long-term effects of 5G either.

> If scientists infected a bunch of 20 year olds with Covid in 2020 and by 2050, 40% of them die of lung cancer before the age of 50, is that something you'd be cool with?

If it saves the lives of a bunch of nurses in the process? I don't know—I think I'm cool with a possibility of it, yes. Especially when those same people could also catch the virus naturally.

Also, I edited my original post to add a link to the Vox article. It's quite a bit longer / more expansive, and worth a read.

> I take your point, but calling the comparison "lies" based on the possibility of long-term implications we know nothing about seems like a big stretch to me.

I had gone through my post and removed all the places where I called it "lies" because I intended to say that this arose from ignorance rather than malice, albeit irresponsible ignorance from journalists whose responsibility it is to share information. I must have missed that one, my apologies for the accusation.

> We don't know the long-term effects of 5G either.

Geez, did you get this from Vox too? The bands used for 5G didn't just spring into existence: they've been around and used[1], albeit deployed on much smaller scales than 5G will be. We have long-term data on the effects of adjacent bands, and a few different ways of modeling how electromagnetic radiation affects the body. The data we have is certainly from much smaller deployments than 5G will be, so it's true we don't know all the long-term effects of 5G, but we at least have enough data to put some bounds on how horribly 5G could go wrong. For starters, we know that it doesn't have a 40% chance of killing everyone exposed to it in the next 30 years with lung cancer, because an effect that large would show up even in the more limited data we already have. And if it does turn out to cause some problem with even a minute fraction of that severity, we can turn off the 5G and stop the cause of the problem.

We don't even have a clear lock on the short term mortality rate of coronavirus and we can't stop the spread with the flip of a switch. Where, exactly, is your confidence coming from here?

> If it saves the lives of a bunch of nurses in the process? I don't know—I think I'm cool with a possibility of it, yes.

> Especially when those same people could also catch the virus naturally.

The worst-hit place in the US is NYC, with 141,754 confirmed cases currently. Even if we assume unconfirmed cases 5 times that, we're still talking single-digit percentages of the population infected. And cases are going down. So yes, people could catch the virus naturally, or, as is much more likely, they could not catch the virus, if we continue taking the recommended measures that are working.

Certainly populations like health workers working directly with the infected are at much higher risk than the general population, but there's still a very significant chance they don't get infected. And even if the chance of them not getting infected were negligible, the solution would be to give them proper PPE, training, and other protections, not to say, "Hey you're probably going to get it any way, so let's just deliberately infect you to test vaccines that may not work."

[1] https://ethw.org/Millimeter_Waves

5G was, in hindsight, not the best example to throw in there. It came to mind because because I was having an orthogonal discussion on Hacker News a few months ago about 5G safety and radiation modelling. One commenter there said something like (heavily paraphrasing):

> You cannot tell me what effect 5G will have on the body in 50 years, because no one has tested it. Who knows what might happen?

And y'know what? Technically speaking, he or she is absolutely right: despite our best modelling, we can't really know what deploying 5G at this scale will do in 50 years, and we won't know until 50 years from now! All we can say is, this are what we've extrapolated from the models we have.

Is there specific evidence to suggest that COVID-19 will cause extremely high rates of lung cancer in 30 years? If not, we're just in the messy realm of "anything could happen," which is both true and not particularly useful.

I think you have to compare the (very real!) risks of a challenge trial with the risks of not doing a challenge trial. Maybe it does only speed up development by two months, and the number of health care workers and other members of the public who will die in that time is low enough to not be worth risking the lives of study participants. But that is a question we need to actually look at and consider!

> Is there specific evidence to suggest that COVID-19 will cause extremely high rates of lung cancer in 30 years?

Perhaps not "extremely high", but there are lots of other cases where viruses attacking human tissue much less severely are known to cause cancer. HSV causing cervical cancer is probably the most obvious example, but there are many others.

This is well outside my area of expertise, but what I've read leads me to believe that the way viruses reproduce is particularly prone to resulting in mutations in the human cells it attacks.

It would surprise me a bit if Covid19 didn't increase the chance of cancer at some level, although it might be a very small effect.

> I think you have to compare the (very real!) risks of a challenge trial with the risks of not doing a challenge trial. Maybe it does only speed up development by two months, and the number of health care workers and other members of the public who will die in that time is low enough to not be worth risking the lives of study participants. But that is a question we need to actually look at and consider!

That's true. No questions should ever be off the table.

But it didn't sound much like asking a question when you said upthread, "I'm honestly a little surprised there's even a debate about this. The choice seems pretty clear to me." That's why I responded the way I did.

I'm surprised there's even a debate about whether it's ethical in theory. As in, I see doctors overly attached to the "do no harm" mantra to the point where the alternative isn't being looked at.

I didn't mean to imply a cost-benefit analysis shouldn't be done.

> Even if we assume unconfirmed cases 5 times that, we're still talking single-digit percentages of the population infected.

Wasn't you point just that we shouldn't assume? I know that there are models looking at a possibility for only 1% of cases being confirmed. That's been in Sweden and not NYC, but just throwing a 5 out there doesn't make a lot of sense.

Okay, what number do you think is the worst possible case? Is there a reason to believe that there's a nearly 100% chance that people will get infected?

It's true that 5 was just a number out of a hat, but I think you'd have a hard time picking a big enough number that it invalidates my point. Even if you pick 100 as you're claiming, you're still looking at a double-digit percentage chance of not getting infected, which you're taking away from people by deliberately infecting them.

Incidentally, saying "If we assume" is different from saying "We can assume". I'm not assuming that number, I'm merely highlighting it as one of the many possibilities.

> Okay, what number do you think is the worst possible case? Is there a reason to believe that there's a nearly 100% chance that people will get infected?

Based on the number of people testing positive for the antibodies ([0] something like ~21% of random tests in New York), and given that the average estimated R0 is really high, I think ~100% of people being infected by this time next year is a pretty reasonable assumption. This also indicates that the death rate we previously estimated is much lower in reality. Infecting a few more young, healthy people and supervising their health seems a pretty good deal for the world at large.

[0] https://www.livescience.com/covid-antibody-test-results-new-...

Well, I'd love to see that actual study and peer reviews of it. A previous study saying something similar turned out to be done by a hedge fund manager who used it to argue for reopening businesses, and while peer review is still pending, preliminary reviews by other scientist have called it bullshit (only in nicer terms). So you'll excuse my skepticisim here.

Well that settles it, we better wait 30 years before we start testing a vaccine because otherwise it may be dangerous. And then wait 30 years again before releasing it.

Or, you know, test the vaccine the same way we test the flu vaccine every year, which takes a few months, and doesn't require abandoning basic medical ethics.

There are actually steps we can take to speed this up without abandoning medical ethics. It certainly makes sense to have the first human trials be on medical workers, because it has the highest chance of producing benefit for them, and the results will be clearer in populations with a higher infection rate.

But we're not talking about those because you guys would rather talk about injecting people with coronavirus based on a poor understanding of both risk and medical ethics.

It would be curious to see the Vox piece and I do hope someone drops a link in here. It would be most interesting to know if they were comparing it to the initial procedure (surgery + complications) or lifetime experience (Additional risk of death due to the remaining kidney failing).

That said, I feel like your points are a bit overstated. We now have 66 years worth of Kidney transplant data to show it's safe for both parties, but a lot of people needed to participate in what was a new, risk, experimental surgery to get us to this point.

At some point people have to be willing to take a little bit of risk to get data that could save untold lives and relieve unquantifiable suffering.

Additionally, if COVID-19 does indeed have some horrible long term effect, the cost us having less data or less valuable data now will have a much larger consequence than could ever be suffered by these volunteers.

> We now have 66 years worth of Kidney transplant data to show it's safe for both parties, but a lot of people needed to participate in what was a new, risk, experimental surgery to get us to this point.

Uh, technically that's true, but the risks are not the same. The first successful kidney removal (nephrectomy) was in 1869. It wasn't for a donation, it was for a woman suffering an uncloseable fistula which, without the operation, would have killed her. So what exactly was she risking? By the time someone was allowed to volunteer to donate a kidney in 1954, nephrectomy had the better part of a century's worth of data and refinement of technique.

Compare this to the risk you're proposing: With current measures which seem to be working, there's a good chance that most people don't get infected. So you're proposing that healthy individuals who would likely not contract the virus, be intentionally infected with a disease which he only have an approximate mortality rate for, and that we have no idea of the long-term effects of.

Surely you can see how the first risk fits withing "First, do no harm", while the risk you're proposing simply doesn't.

Good points. Only obvious solution is to give to the health care workers and you have your control group.

I'm sure that the Vox article said "from what we know so far", but even if it didn't say that, isn't it obvious? We can only talk from current knowledge.

> but even if it didn't say that, isn't it obvious?

If it's obvious then it should be equally obvious that a comparison with something that has long term knowledge is nonsensical.

1. Part of current knowledge are the facts that a) we don't know the long-term effects, and b) those long-term effects might be horrific.

2. It's apparently not obvious, because people on this thread seem to not have thought of it, and when I pointed it out, they've argued vehemently against it.

I'd happily volunteer to participate.

By the same argument, we also don't know the long term effects of drugs and vaccines that haven't been in use for a very long time

>If scientists infected a bunch of 20 year olds with Covid in 2020 and by 2050, 40% of them die of lung cancer before the age of 50, is that something you'd be cool with?

If the vaccine works then we'll all be dying of lung cancer in 30 years.

You, and the vox article, seem to assume that the risks are all associated with COVID19 in the trial as similar to those normally associated with COVID19 in the human population..

One of the issues with vaccine development is that vaccines can result in worse infections [1].

If the issue was just “this might not work, but it won’t cause any harm”. You would obviously give this to healthcare workers immediately. But that does not appear to be the case.

[1] https://www.pnas.org/content/117/15/8218

Well, I assume the challenge trial would be done to test efficacy after you've tested safety. Is this aspect substantially different than with any other vaccine trial?

The difference is right now healthcare facilities and providers are overloaded, so if there are adverse effects of a trial that require treatment, people could end up dead. Normally you would have hospitals ready to handle such cases, but there's zero guarantee of that today.

I'm sure we can all agree that trials with the potential to require medical intervention shouldn't take place in areas with overloaded hospitals. But most areas of most countries don't have overloaded hospitals right now.

All phases will be testing for safety to varying degrees.

So... a challenge trial at phase III will still have risks. Right now, I don’t think we have any vaccines ready to enter phase III?

COVID19 does seem to be actively spreading in the population currently. So I don’t think there would be an issue finding participants for a phase III trial.

At the point that we’re ready for phase III trials. If there is no population where COVID19 is actively spreading, perhaps challenge trials could be considered?

How do you test vaccine safety in a month? Shouldn't we be concerned with long term effects too?

Yea. I'm not an antivax person. I got my meningitis shot in Uni, tool all the ones I needed when going overseas like Typhoid ... but I know about Vioxx and I am weary of stuff rushed to market. I'm not in a high risk group, so I would want to wait a year or two personally.

I realize for many that won't be an option. But with the way things are going in America right now, I'm afraid it might not be an option for anyone; it may be a requirement just to get a job or go to school. That frightens me.

Long term, vioxx has actually been somewhat vindicated as all other nsaids have been shown to cause equal rates of heart attacks. That is, your ibuprofen is just as dangerous, but no one is demanding it be recalled.

Yes. Last time we rushed a vaccine during a pandemic we got pandemrix.

That was approved in Europe but not the US.

1 in 55000 people who took pandemrix got narcolepsy.

The risk is small, but the outcome is a severe debilitating illness that requires constant care for the rest of their life.

We may decide that risk is acceptable, but we need to know about it.

Thanks for the reference. Reading the wikipedia article on the topic, I get the impression that side effects that develop slowly (e.g. more than 3 months post vaccination as in this case) will either not be detected at all or it will be almost impossible to attribute them to the particular vaccine (esp. if you get a different one each year). What is really bothering me is the overall "debuggability" of the vaccines/medication. I mean, people developing them simply have no clue about the different mechanisms by which they can cause harm to the body. Let alone any adverse effect when combined with e.g. over the counter drugs or supplements.

I'm not disagreeing with your logic. The risk would be reasonably low if the subjects are young and healthy.

However, you can still get similar information by just dropping the control arm in this trial. Give a bunch of people the vaccine and exposed them to the virus. Sure it's not as good as having an untreated control arm, but you're also reducing the risk of someone in the control group dying.

The data is of very little use without a control. You could compare it to overall Coronavirus death rates, but those numbers are biased in all sorts of ways (for instance, fully asymptomatic cases).

I would disagree with "very little use". Uncontrolled trials are done all the time. You basically collect "nature history" data and compare it to that.

In addition, the mechanism of vaccines is very well know. You can vaccinate and measure antibody formation.

You could still develop a vaccine without a control and have confidence that it works.

Pretty sure uncontrolled trials are common at the latest stages of drug development. It's called a single-arm trial.

Source: I once participated in a phase III open-label single-arm trial.

They exist, but are usually not sufficient to support a drug or vaccine approval.

The standard is two well controlled studies, but additional open label trials may be used to address specific health authority concerns.

If you are interested, you can look up the other trials the drug may have gone through.

But if you donate a kidney, then you’ll now have a pre-existing condition. Which means you’ll be denied access to health insurance.

In which country?

Take a guess.

Not sure. Definitely not the USA, as pre-existing conditions no longer disqualify you for insurance.

As with bizarrely restrictive FDA regulations on, e.g., face masks, the famous conservatism of IRB committees is another thing that the COVID19 story should motivate us to re-examine.

But a large majority will be exposed to the virus eventually anyway, if things keep going as they are. So what's the added risk if you're exposed earlier rather than later?

That you are exposed while there is no known working treatment yet. Many attempts are in the works out even trials, but nothing proven. In the near foreseeable future, there might be one.

One reason to have the lockdowns.

No, the reason for the lockdowns was to increase the chance that people will find care in the hospitals.

I shudder at the thought of a government locking people up because a treatment might, at some point in the future, be found.

It is of course besides the point but I find it extremely optimistic to expect that a treatment can be found that will significantly reduce deaths when deaths mostly occur in patients of very advanced age or with significant underlying conditions.

Is there anything promising at the treatment front right now? My impression is that there was an initial group of candidates for repurposing that have on closer investigation all turned out to be not quite as helpful as hoped.

Are you sure? Challenge studies have been conducted in recent years for Norovirus[1] and Whooping Cough/Pertussis[2]. Admittedly, less is known about Coronavirus, but both those two can be dangerous.

1. https://www.ncbi.nlm.nih.gov/pubmed/25210140

2. https://clinicaltrials.gov/ct2/show/NCT03751514

Do you know the death rate of an american submariner in the Pacific?

I don't think they are going to infect people intentionally. They are giving the vaccine and control to healthcare workers who are naturally very likely to be exposed throughout he course of their work. They will then compare the infection rates between the two groups.

I don't think they are exposing them in any way different to how they would be exposed without taking the vaccine.

It's just vaccinate then let them do normal UK life.

It would have to be done outside the US.

Yes, how else could you know its efficacy?

Even though I am not that young, I might sign up for that. If there is already evidence in vivo of the vaccine’s effectiveness, IMHO the risk would be tolerable.

I too would sign up; I signed up here: https://www.thecovidchallenge.org/ to support the effort.

Remember there would be a control group.

Does there need to be a control group? Can we not detect if the vaccine is working or not without one?

Not to the standards required to show its safety and effectiveness, no

I think it's ethically unacceptable. We're basically throwing everything we've learned with drug safety out of the window.

If your country is invaded, is it unethical to let young, healthy volunteers form an army and fight back, even at some risk to themselves? It shouldn't be illegal to let people take reasonable, calculated risks for the good of everyone.

The british army tested nerve agents on un-knowing Army recruits and accidentally killed people.

The Australian army tested anti-malarials with good intent and caused huge mental harms (they are pretty psychologically active and can trigger suicide ideation)

The US army has form for testing on recruits without adequate consent or information

Overall, the whole "for the good of humanity" story here is that the consent is weak, the support is weak, the costs are not borne equally. I would not advise any young person to be guilt-tripped into volunteering for this.

The track record here is very poor

No one is talking about anything else than consenting, fully informed adults participating.

Except these things have a habit of not being what anyone is "talking about" but about what they actually do.

That's a false equivalence. We are not talking about not testing vaccines at all or not, but how.

You are simply ignoring the responsibility of the vaccine maker of potentially not going through the adequate steps.

A better equivalence would be the question, how should your hypothetical army be equipped and trained. And would the people doing/deciding that be responsible for the choices made. I would understand you saying, it doesn't matter we are under attack.

No, a better equivalence would be how long you let the invading army plunder before you start handing out spears and shields, because if you wait another month the shields might work better.

That metaphor sounds nice but conjurs the wrong image. The vaccine could very well be worse than a Covid infection, i.e. you grab your shield, but that newsly invented shield has spikes on the inside.

> A better equivalence would be the question, how should your hypothetical army be equipped and trained.

Agreed. And if standard training takes 12 months and you're being invaded now, what do you do?

Hunker down and hide from the invading army until enough of them go home that it's possible to capture and isolate the remainder?

IMO, institutional review boards in charge of trials would not let this pass, for a good reason. Especially because you can't (obviously) use a control group.

It's different from a phase 1 study when you are testing on healthy volounteers. This would mean deliberately infecting people with a largely unknown virus after vaccination with a vaccine whose efficacy is still not yet determined fully (in fact, it would be to determine its efficacy).

Oh yes you can use a control group. I would volunteer for such a trial if success would mean approval of a vaccine.

Of course it involves some risk. But the alternative is that millions of others, many older and with compromised immune systems, would get the virus involuntarily because the vaccine trials took longer to run. Is it ethical to ban research that saves thousands of lives?

You don’t know that the research will save thousands of lives, or kill thousands, until it’s done.

What proportion of vaccine trials are successful usually? Could the probability of efficacy be estimated and used to judge if the study goes ahead?

There needs to be a reasonable amount of risk taken in research, otherwise we will find it impossible to make progress.

We should just use prisoners as the test subjects. Leave it up to and IRB and they will sit on it until we’re all dead...

If you ask under-40y/o non-violent offenders with >10yr sentence and say a $10k payout and guaranteed presidential pardon upon completion of the trial I’m sure there would be some takers.

Yes that’s crazy and I do know the governments history of shady vaccine testing, but we are facing a pandemic and each day sooner that we have a vaccine will be many lives saved.

There was an early experiment with variolation tried on someone sentenced to death, where he agreed to be variolated, then challenged with smallpox infection. his sentence was commuted after he survived.

the highest-profile prison experiments in the US were Project MKUltra, in which prisoners were injected with high doses of LSD, the Stateville Penitentiary Malaria Study, and some experiments with radioactive isotopes.

offering prisoners their freedom in exchange for participating in dangerous or harmful trials was widely viewed as coercive, and contrary to the Nuremberg code of medical voluntary consent established after the horrors of Nazi experimentation.

why should it be better to use prisoners than young, healthy volunteers? are their lives cheaper and expendible because they committed non-violent offenses? no IRB would sign off on that, and if you're bypassing IRBs anyway just use young people who think they're invincible..

That seems to raise more ethical questions than just letting willing volunteers do it.

It is absolutely unacceptable, that's why 2/3 answers to this comment so far use martial metaphors. It violates not the liberty of young men, who have every right to be reckless and volunteer, but integrity of the scientific community.

If the Oxford researchers made trials on Syrian kids in a refugee camp, in exchange for $100, I suppose more people would see a problem here.

I'd be willing to do it. It could save thousands or lives. Which part to you object to? Enthusiastic volunteers being able to choose to take a risk? The world has become far too nanny state and arse covering in my opinion.

I find the attitude puzzling that people are willing to value vague abstractions like "integrity of the community" over thousands of lives.

I agree with everything you say. If a rogue MD in a nanny state will talk you into a challenge trial, - by all means, let him do it and face the consequences (hopefully, tough). But let's not pretend, that it would be an informed consent.

The reason for the vaccine research protocol we're settled on, is the ubiquity of wanna-be Pasteurs, and dearth of the real ones.

On a separate note. We have deprived ourselves of basic human rights under the premise, that lives are worth any economic outcome of shut down. Where I live, premeditated spreading of the Covid is considered by law an act of terrorism. Officially vetted challenge trials just don't add up.

Yeah I'll give you you need informed consent and some common sense about the whole thing.

How is the integrity of the scientific community harmed?

Refugee kids can't give informed consent.

Well, kids over 18 can give consent. And no one can give an informed consent to a challenge trial at this point. If you and I stole the vaccine, injected it, and would try to get infected, as an amateur scientific endeavor, it would be perfectly ok. If an MD would inform us, that she "feels optimistic", in order to get a consent, she has no business being a researcher.

It's going to harm the integrity of the scientific community a lot more once the world starts counting up the lives human challenge trials could have saved.

They are volunteering and the risks are small to zero or negative. Do you think it's unethical to let people choose take any risk at all in their lives?

Every time you tell a doctor to go to work treating COVID patients, you're doing a challenge trial, except he has no chance of being vaccinated, and the risk he's taking doesn't contribute to the most important thing for the world, which is a working COVID vaccine.

We are allowing "essential" workers to be exposed to COVID. Who could be more of an essential worker than a vaccine trial participant right now?

This is exactly why you wouldn’t need a challenge trial: lots of people are already regularly exposed to the virus. Immunize some of them and see if the infection rate is lower in that group vs a control.

Except failed vaccines can induce a response that makes you more susceptible to the disease and with worse symptoms. It’s called antibody-dependent enhancement:


Just about the last people you’d want to risk that kind of vaccine trial on are healthcare workers, who are already in short supply.

I didn’t say healthcare workers.

I said that there’s plenty of incidental exposure already: healthcare workers, yes, but also nearly everyone who’s leaving the home too. It is literally a pandemic!

This point is actually made in the article itself: they want to get it done while and where there’s community transmission to avoid the ethical fraught ness of a challenge trial.

For similar reasons, challenge trials also weren’t done for AIDS PrEP, since there were groups with enough lifestyle exposure to power a study.

Sinovac (which is testing an attenuated vaccine) published some data on a preprint[1] claiming it does not cause ADE.

[1] https://www.biorxiv.org/content/10.1101/2020.04.17.046375v1

We ask young people to risk their lives often, it's called 'The Army' (and other groups).

Also - this would be less risky than going to space.

My instinct says >50% of soldiers between 20-30 would instantly volunteer for this. Probably much higher, like 80%. Especially those unmarried.

There would be no lack of fit volunteers.

Its ethically problematic obviously, but so is asking grocery store workers to stock shelves as 'essential workers' during a pandemic when they have no PPE.

I think probably there's a 100% chance that so-called 'essential workers' who are not medical staff will die from Coronavirus due to the pandemic.

The rate of death among the 'very young' is exceedingly low, and I think there were always complications.

If we can narrow it to 19-26 year old, super healthy, without complications ... I think the 'possibility of harm' would be quite low.

It's not beyond the realm of ethical consideration.

Now - remove some ethnical barriers - such as what drug companies used to do by testing drugs in Africa, or what authoritarian governments do all the time (aka China) and you'll have this done in a heartbeat.

I think China/CCP wouldn't think twice about trying this on young men in jail. Is my cynical take.

US soldiers knowingly volunteered to test all manner of chemical horrors in the Edgewood Arsenal experiments, from BZ to VX. you're completely right.

Edit: I should add, I don't want to leave out other groups of individuals (and non-groups) who would gladly sign up for such an opportunity to help even with some risk. Healthcare workers, Police, probably most veterinarian staff and civil servants as well (!) if they were young and fit. And so many others.

WHO publishes a list of the vaccine landscape here - https://www.who.int/blueprint/priority-diseases/key-action/n...

As of April 20 2020, there were 5 in clinical evaluation and 71 in preclinical evaluation. I'm a layperson, but very interesting to see the different techniques and testing methodologies used.

I get that everyone like to put "we're the first" in their press release but there are already a number of trials, eg house the day before a German company was reportedly starting trials


The news reported in the BBC article is that the first patients have been injected in a UK vaccine trial, and that they are the first such patients in Europe.

The New York Times article discusses vaccine trials that have been approved, or which are planned pending regulatory approval, in Germany, China and the US. If a vaccine in the German trial has already been administered to patients, then the claim in the BBC article about the Oxford trial being the first to inject patients in Europe would be incorrect, but the New York Times article doesn't state whether or not patients have been injected in the German trial — it only states that the trial has been given the 'green-light', and that it 'will be initially conducted on 200 healthy people'.

Another comment here contains a link to an article discussing a World Health Organisation trial, in which the first patient will be Norwegian. That trial will test non-vaccine treatments (specifically hydroxychloroquine, remdesivir, lopinavir and interferon-β 1a), and at the time of publication, the participants had not yet received treatment.

It doesn't seem to me that any of the statements in these articles are in conflict with the BBC piece.

The author of the BBC article is Fergus Walsh; he's a senior medical correspondent for the BBC who will be familiar to anyone who has been watching UK television news during the pandemic. He is one of the most measured and scientifically literate voices on the BBC, and he is not prone to sensationalism or exaggeration. Anything he has written for the BBC's website is very likely to have been worded carefully, and to be reliably-sourced and well-researched, but if there are any errors, either he or the BBC should be contacted so the piece can be corrected. The BBC publishes corrections at https://www.bbc.co.uk/helpandfeedback/corrections_clarificat...

I have no connection to Walsh or the BBC, but I thought this should be noted.

And trials started weeks ago in Norway as well: https://www.regjeringen.no/en/aktuelt/who-global-corona-stud...

(I don't speak Russian, yet)

Given how politicized this has gotten, in general for treatment of this virus, I'm not optimistic that we'll be sharing information. Praying I'm wrong.

Basically on 11 of April they started a trial. Up to today WHO approved for trial 9 potential vaccines made in Russia.

The new vaccine is good but arcticle title is not.

The trials in Norway are about treatment, not vaccines.

Maybe there will be a vaccine for SARS-CoV-2, but the one lesson to take away from all this is that if a truly terrible pandemic hits (eg more contagious than SARS-CoV-2 but with a 10%+ mortality rate) a vaccine won’t save us. I’m not sure what will. Relying on the source country to quickly identify an outbreak and raise the alarm obviously isn’t going to work...

We never have been here before in almost everyone’s lifetime; there are a few over 100 year old people who did ofcourse, but that is it.

As with wars on your own soil, people forget fast. In Asia my HK colleagues got stressed in january as they did see this before and they (the people without the gov) already automatically took more care.

If this occurs ‘soonish’, I think a lot of people and countries will act differently; I know I will. I was still travelling as, silly me, trusted my gov to warn me; big mistake. I would have wanted to self isolate a month earlier to make sure; next time that will happen. I hope there will not be a next time.

Obviously the issue is, as with everything that relates to the effectiveness of education on most people, how to teach future generations to not be so lax. I am not sure how that would work. It does not work generally or with a massive delay; exactly like the parent trying to save the child from making the same mistakes as she did but the child having the need not to listen (old people, what do they know he, world changed and such!) and experience all the crap themselves instead.

I think, even with a far worse virus, if all countries would’ve shut all borders with china and self quarantined immediately begin january, nothing would happen. Just everyone, every gov and person, thinks and many keep thinking it is all blah and nothing will happen to them. Apparently only the firsthand experience of ‘something bad’ (like Boris Johnson) will actually give them perspective. I think this prepared us well for a worse virus for the coming 20 years; however I think after that, it is will drop off and you will be right; most people will be screwed.

> We never have been here before in almost everyone’s lifetime

That's not really true. 1957 "Asian Flu" resulted in > 1 million deaths, and 1968 "Hong Kong Flu" resulted ~1 million deaths. Difficult to compare viruses directly, but I would say those were in the vicinity of something like covid-19, which has not yet resulted in even 200k deaths, but certainly had the potential to kill millions of people. (and may yet...)

> which has not yet resulted in even 200k deaths

It's almost certainly resulted in a larger number than that already.

Estimating the true number of people who have already died of COVID-19 is difficult.

I've seen estimates ranging from 15% more to 4x more than the "confirmed" figure, which itself has increased from 100,000 to ~190,000 over the last 2 weeks.

That's the number of "confirmed" deaths, by some meaning of confirmed. Some of the contributing figures only counting people in hospital at the time of death, and even that with a significant time delay.

I have an 80yo friend who lived though both of those pandemics and says that the 1957 one was terrifying in the UK. It hit nursing staff very quickly and hard, many hospitals were running below half-staff. It was the first pandemic of the air-travel era and spread like wildfire.

But until this latest pandemic arose he hadn't even mentioned his experience, it was just considered part of life. And unless you know to look for it, it's barely mentioned in modern history.

Yeah, I'm surprised how little these are mentioned, especially in the context of the current pandemic.

Yes, but apparently that is already too far gone for anyone to remember and not hard enough to hit all history books...

I think another factor is that there wasn't the internet back then. Information about the viruses would've been spreading a lot less rapidly than information about covid-19 has been. Overall, I think even at the time people were probably less informed about what was going on (and the global context of it) than we now are.

I'm not any epidemiologist, so if someone knows more please correct me, but I read that viruses with a high mortality rate are much easier to contain. Mainly because the virus more naturally dies out as it kills its hosts. That was one of the reasons that SARS didn't reach pandemic scale with its 10% mortality rate.

I have to wonder if Covid-19 is in the 'sweet spot' of dangerousness, as it has a mortality rate that doesn't hamper its ability to spread but still kills a lot of people.

I suppose that if the incubation period is long enough the virus can have an arbitrary mortality rate and still spread.

Incubation period and lethality are usually correlated, afaict.

Or, imagine a HIV-esque virus. Super long incubation period, lethal in that it attacks your immune system, and super different than anything we've seen before to effectively find a cure or a vaccine faster than usual.

Now imagine if such a virus was airborne and was already spreading... Who'd know?

> but I read that viruses with a high mortality rate are much easier to contain

Only if all other parameters remain the same. There could be much worse viruses than SARS-Cov-2 (e.g. that are similar in eventual mortality but have symptoms lag behind start of shedding even more). A virus could be just as species-ending as a large rock hitting the earth, they are just both very unlikely or else we wouldn't be here.

I don’t know much about the subject - when one of these institutions discovers a vaccine, do the rest just give up and settle the loss of having come second in the race? Do the private companies then automatically switch to producing as much of the successful vaccine as possible to meet demand and turn a profit?

I imagine they keep going since side effects could be better, or it could be more effective.

A handful of the first SARS vaccines “worked” (in that they led to antibody production), but also had nasty side effects.

It's like how there's a cure for HIV that you really don't want.

You mean death? Or am I missing something?

I would assume they mean the CCR5 stem cell/bone marrow thing.

A handful of patients (2?) have undetectable viral loads after being treated for leukemia. In these cases, the bone marrow or stem cells were from donors with a mutation in CCR5 that confers some resistance to HIV. The mechanism isn't completely understood, AFAIK, since people with the CCR5 delta32 mutation have partial, but not complete, resistance to HIV normally.

It's not a very viable treatment yet: the transplant procedure is brutal (a friend went through it) and you need to be unlucky enough to need a transplant, yet lucky enough to find a donor that has the right mutations (which again, are not completely known) AND is otherwise compatible with the patient.

Still, very exciting for a possible mechanism, but also probably not coming to a hospital near you this decade.

Here's one of the studies: https://www.nejm.org/doi/10.1056/NEJMoa0802905

HIV is curable but the treatment is generally worse than just management with antivirals.

Derek Lowe gives a good overview of how different kinds of vaccines work here: https://blogs.sciencemag.org/pipeline/archives/2020/04/15/co...

The short answer is that there is a bunch of different types of vaccines, and each type has different constraints on their production. Someone who makes an mRNA vaccine isn't going to be able to easily switch to making a live attenuated vaccine instead, for example. Also, first does not necessarily mean best: again, with so many approaches, a vaccine using a different approach can have wildly different side-effects and risk factors. So being second (or even, say, tenth) isn't necessarily a loss.

That said, there are so many projects pushing forward that many of them are bound to fail early. Given the history of cooperation already in this crisis, some of those companies who find their coronavirus vaccine efforts going up in smoke may well choose to help scale out other, more successful efforts--or instead help by taking on more of the current vaccine production efforts, as polio and the flu aren't going away just because coronavirus is here.

Even if we have one, the larger problem will be scale. Having more than one type of effective vaccine available may actually be useful, since our existing manufacturing capacity for the different manufacturing processes can be used.

That is also why all the major players with vaccine development already in humans (including but not limited to this one) have already started making manufacturing deals with large pharmaceutical corpoprations.

Vaccination on large scale will likely require tens of millions of doses, if not more (and let's not forget you may need more than one inoculation).

The vaccine manufacturing point needs way more attention. We were talking about ventilator manufacturing weeks after there was no chance they'd be done in time.

The economic benefits to distributing a vaccine quickly would be huge, but I haven't heard world leaders talking about how to do it--they're still on the last war. Luckily, Bill Gates is spending on it, but this needs way more attention because this is our chance to be ahead of the virus for once.


Where do you derive the “tens of millions” of for the number of doses required?

That wouldn’t even be enough to vaccinate a mid sized EU country.

I originally wrote "billions", thought I was exaggerating, so I edited the post. Probably off on the other side of the interval.

The Chief Scientific Advisor to the British Government, Patrick Vallance (who is a clinical pharmacologist, and formerly president of research and development at GlaxoSmithKline, a pharmaceutical multinational), said this in a Government press conference on 17 April:

'The vaccine could come from anywhere. We've got a domestic vaccine discovery programme in the UK which is being supported, absolutely, as fast as we can go, but the vaccine can come from anywhere. GSK and Sanofi have announced they're doing a vaccine together, which is fantastic news. Most of the big companies are doing vaccines. This is going to come from somewhere, we just need to back lots of horses at the moment, and to make sure we're in a great position to access a vaccine when it occurs. And that's why organisations like CEPI are so important as well; to make sure that the world sees this as a way to get a vaccine, and we all need to be part of the same approach to trying to get as many vaccines as we can. And we may need more than one vaccine.'

Link to the press conference: https://youtu.be/jWOCpmjdHiw?t=1430

Some other comments have referred to the Gates Foundation's contribution to developing vaccines; the foundation's involvement in establishing CEPI (the Coalition for Epidemic Preparedness Innovations), which Vallance referred to, is a significant part of this.

not really, usually there is less competition for developing vaccines as the timelines are more relaxed and it would be a waste of money to have several groups discover the vaccines to the same disease

Multiple different vaccines could (and probably will) be discovered. These may have different mechanisms and tradeoffs and those too will be taken into account when scaling up to population.

Now who owns what, who gets it first, and who gets paid and in what way, those are thorny issues that have not yet been worked out.

It's likely that by the time they know this works (or doesn't work) and is safe (or isn't safe), many others will be in an advanced state of development. Totally plausible that there'll be a few available at some point.

This is a government funded university project, so "losing the race" is likely not a primary concern; I'm sure if someone else came out with a magic vaccine fully tested and ready to mass manufacture tomorrow the researchers on this project would be pretty happy about that.

The Sabin polio vaccine continued to be developed after the Salk vaccine was already deployed for various reasons.

No, in fact I think Bill Gates has fronted the money to develop several candidate vaccines fully to shorten the time to widespread introduction as much as possible.

Likely all of them would be developed anyway as some might end up failing (either during testing or during mfr) and I imagine demand is going to be high.

no, there’s still IP which plays a role and different vaccines have different pros and cons and logistically it might also be easier to scale multi different vaccines to the demands of the world population than a single one.

I imagine that what is discovered trying to develop a vaccine for this will be readily applied to other viruses.

The comments on that article are something else!

Reading comments on any mainstream news site inevitably brings total loss of faith in humanity. This goes double in a country where tabloids dominate public discourse.

I think comments tend to attract certain people. The vast majority of people don't say anything so you are left with the squeaky wheels. But because when you read it it feels like a overwhelming amount of people that are seemingly very ignorant it does feel quite disheartening. I've personally limited my exposure to comment sections of most news these days.

The problem with reasonable people withdrawing from the most popular online forums is that you end up with a vicious circle of the most unreasonable people arguing with each other and influencing public opinion.

Add a real name policy to the mix and you will only retain the absolute elite of squeaky wheels.

There used to be a website dedicated to the ludicrous nature of BBC Have Your Say comments (of which these are the contemporary equivalent), but unfortunately I can't remember what it was called . They've always been ... out there. I can't deal with reading them because I can literally feel the brain cells dying off when I do.

Speak You’re Branes. Sadly even the archive is gone now.

https://pointless-letters.tumblr.com/ is probably the closest modern substitute.

Indeed, I couldn't find a boring one. So much for the famed understated-ness of the British

I think we've gradually been Americanised. I don't recognise their behaviour as British, I find it all a bit embarrassing really.

They tried corona virus vaccines already after the first SARS outbreak. When patients were re-exposed to the virus they had severe auto-immune lung pathologies. Sounds super problematic.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3335060/ https://jvi.asm.org/content/85/23/12201 https://www.newscientist.com/article/dn23563-threatwatch-cou...

Note that in the reports mentioned, the ‘patients’ are mice and ferrets.

So 2 days ago, we received the news that the first human trials on a vaccines by a biotech firm from Mainz have gotten approval by the Paul Ehrlich Institute [1] as well in Germany. Good news, let's all work together to kick this things ass!

Source [German News]: https://www.sueddeutsche.de/gesundheit/coronavirus-impfstoff...

Main source [PEI, English]: https://www.pei.de/EN/newsroom/press-releases/year/2020/08-f...

[1] a federal institute for vaccines

How exactly are vaccines made? Like how do you make a brand new one? For smallpox, the first vaccine came from cowpox (or possibly horsepox). People didn't know what viruses were, but horsepox happened to be similar enough to generate the same antibodies, but not kill people.

But I've never seen a good documentary on how vaccines are made for diseases today. YouTube just seems to be filled with professor's lectures from introclasses. Are live viruses used and, if so, how are they made inert yet cause the immune system to generate the same antibodies?

Anyone have a documentary with the technical details of any of the modern vaccine generation techniques?

Basically, there are three primary approaches to safely introducing antigens to the immune system: you can inactivate (or kill) a virus through methods such as heat treatment; you can attenuate it (make it less well-adapted to humans) by introducing it into foreign hosts until its adaptive mutations make it safe for humans; or you can synthesize molecular antigenic subunits and introduce those on a viral carrier or with chemicals to stimulate an immune response. Experience with inactivated SARS vaccines suggests that protection is incomplete and, worse yet, the vaccines trigger immunopathic responses that can cause serious damage. Most focus is on subunit vaccines, but s-protein-based vaccines in feline coronavirus have been shown to actually worsen the effects of reinfection, so researchers are understandably cautious.

Maybe not a documentary but I remember seeing some discussions on Reddit

But basically it's more complicated than the usual "attenuated live virus/dead virus".

Tou can have synthetic vaccines, targeting different parts of the virus. Also there are several ways of attenuating pathogens (look up the bcg vaccine for one interesting example)


Doesn't answer your question but hints at the complexity.

I'm about far from anti-vaxer stance as its possible to be, so please don't think this is where this is coming from, but isn't this crazy quick compared to how long vaccines usually take?

Is the long time to create vaccines not usually to make sure they are safe? What is different now that it can be done quicker? Is it just the sheer amount of effort and cash being thrown at it?

Coronavirus shares 90ish percent of its genetic material with SARS. So they had a head start.

We share 99% of our DNA with chimps, I don't think it's a helpful measure.

We use chimps in biomedical research precisely because of that overlap, why do you think it's not a helpful measure?

We...don’t actually.

The NIH started phasing chimp research out in 2013 and USFWS declared them endangered (and thus off-limits for anything invasive or distressing) in 2015. Great apes can be used for observational studies (like kids), but I think even drawing blood for non-vet reasons is now pretty regulated.

Other primates, especially rhesus monkeys and, increasingly, marmosets, are important model animals for lab experiments but are less closely related to humans.

Sources for the down voters: https://www.nih.gov/about-nih/who-we-are/nih-director/statem...

You’re being downvoted for utterly missing the point.

Care to explain?

The point is that we use genetically similar test subjects because it is helpful that they are genetically similar.

The point was not to demonstrate which exact subspecies of primate that is used.

Here's my counterpoint.

I do this stuff for a living. I know that primates are a valuable translational model, which is why I've spent the last 15 years working with them in neuroscience labs.

On the other hand, I also know that it's an ethically-tricky form of research too[+]. Public support for research depends on people understanding what we're doing and why. Conflating chimps with marmosets (which are still primates, but much less "human-like") or rhesus monkeys risks eroding that support. For example, I'm fine with genetically engineering marmosets; I would have serious misgivings about doing the same thing to generate autistic or Parkinsonian chimps.

Therefore, I think this is an important distinction and not being careful about it puts the benefits of primate work--that you're trying to champion!--at risk.

[+] For what it's worth, we do take excellent care of them.

Still missing the point. The argument against chimps is ethical, not scientific. Chimps would still be better because they are closer.

Not necessarily.

Along with the ethical issues, the Institute of Medicine concluded that it wasn’t scientifically warranted. Data from chimps would be slightly closer to humans, but it’s also hard to get: they are dangerously strong (much more so than macaques, which are already terrifying), grow very slowly, and need tons of care and space—-and therefore money—-to thrive. Those trade offs, made starker by ethical issues, lead them to wind down chimp research. As a tech analogy, writing a browser in assembler is closer” to the hardware and could theoretically result in faster code, but in practice nobody does it because it wouldn’t be worthwhile.

Fairly little research is done in monkeys for the same reason. Mice are faster, easier, and offer more tools. This isn’t always a good thing; in fact, my last few projects have made a big deal about the value of a monkey data over rats. Nevertheless, I have zero desire to spin up an ape version.


I only just saw this.

Personal attacks will get you banned on HN, regardless of how wrong someone else is or you feel they are. No more of this, please, and please don't post in the flamewar style to HN generally. It's not what this place is for.


Okay, how’s this?

Tell me one major biomedical discovery, not comparative anatomy or physiology, that we learned first or best from chimp research. I have a PhD in this and can’t think of one.

I agree that they're very genetically similar to humans. I agree that this, in some ways, would make them a good model organism. Where I disagree is that it's true we productively use(d) chimps in biomedical research for this reason. Instead, I would argue that the limited amount of biomedical research that's been done on chimps is because of the genetic similarity, which is the other way round.

So, to be clear, you are saying that we use(d) chimps for research because of their genetic similarity to humans?

That, my friend, is the point being made. We've come full circle.

There are two different things going on.

If you need a realistic model of a human for (say), preclinical or toxicology studies, chimps are almost never used. Rhesus monkeys are. Dogs, sometimes, or pigs. Ferrets work pretty well for respiratory stuff. Models are sometimes picked based on genetic similarity, but functional or anatomical similarity also guide the choice. Pig hearts are a go-to model for cardiac stuff, even though a primate heart is obviously closer.

Very occasionally, people will study chimps qua chimps. This is indeed because they're close to humans, but it's not usually aimed at improving human health. Moreover, this was never particularly popular and is now incredibly rare. Primates account for like 1-2% of vertebrates used in biomedical research; chimps can't be more than a tiny fraction of that.

If you said "software is written in assembler because it's close to the machine", I think most people would agree that it could be, but also that it is, in practice, not. That's exactly how I feel about this. Chimps could be used for biomedical research--and for that reason--but in practice, they're not.

Go back and read the thread but imagine I said "We used chimps in biomedical research for decades precisely because of that overlap, why do you think it's not a helpful measure?"

Let's simplify so you have another way of looking at it:

    OP: COVID shares 90% DNA with SARS so the vaccines would be similar.
    OC: We share 99% DNA with chimps, so what?
    Me: We use chimps in research because they are so close to us.
    You: Well actually we don't anymore because of ethical concerns
For the record, I think sentient creatures should have rights and I'm glad testing on chimpanzees has ended. Have they all been released to sanctuaries yet?

My very next sentence agreed that we use other primates for that reason.

Yes, this is an additional reason you are being down voted.

You "well actually"ed my point WHILE agreeing with my point.

I was trying to add some clarifying details about something I know well. That's half the charm of this website.

It's the difference between "Yes, and we stopped ... " and "No, actually we don't". One is clarifying the second is distracting, appears to be disagreeing with facts, comes off as arrogant AND missed the point.

Just admit you were wrong, dude.

I give up -- inject your bleach, UV your veins, everything's a chimp, and facts don't matter.

I will cop to being short-tempered with the sheer amount of rubbish science floating around (generally and for covid-related things specifically), and for that I apologize. Wasn't shooting for arrogant so much as "you may not know that..."

Well this has been a fascinating journey.

It's pretty clear you don't realize this, but I don't think anybody in these threads have been arguing with your science. We also agree that experimenting on chimps is wrong.

What everybody has been doing, with various degrees of hilarity, is try to get you to see that your disagreement with my original point; we use(d) chimps in biomedical research because of their genetic similarity so using genetic similarity as a rebuttal to the SARS/COVID vaccine link makes no sense.

Facts matter and you're choosing to ignore the original fact that you disagreed with and make up some straw man fact that you can tilt at.

The reason I'm frustrated is that your comment is that it is "truthy." The general idea is true (you can learn a lot from genetically similar organisms) but the specific example is misleading.

Chimps are not--and weren't ever--a major part of biomedical research. I just looked on PubMed, which indexes pretty much all biomedical research. "Chimpanzee" returns twelve thousand articles; "monkey" returns 18.5 million.

I don't disagree that we can learn interesting things about evolution or anthropology from chimp research; I have lunch with a comparative anatomy lab all the time. At the same time, chimp research is mostly very basic science-focused. I can only think of one counter-example, which is the development of Hepatitis B vaccine. This was done in chimps and because of their close similarity to humans: other animals appear not to get Hep B. While this sort of proves your point, it's a singular exception rather than the rule.

Guns are effectively at killing both chimps and humans.

A lot of labs were researching MERS and SARS already.

So according to In The Pipeline[1] they essentially modified their existing MERS vaccine so that it worked for SARS-COV-2. Their original vaccine had already gone through phase 1 trials and had shown efficacy and no harmful side effects.

[1] https://blogs.sciencemag.org/pipeline/archives/2020/04/23/a-...

Derek Lowe is terrific in communicating complex ideas in the field to concerned lay observers like me; he's been a great resource for reliable information about the science of this thing.

Just to clarify; the ChAdOx1 MERS prospect hasn't proceeded to a trial demonstrating efficacy in human subjects (as yet).

That's a particularly important distinction here, given the nature of the novel delivery mechanism[1] and prior observation of complications in SARS-CoV-1 vaccine development[2]

[1] https://en.wikipedia.org/wiki/Viral_vector#Adenoviruses

[2] https://www.hkmj.org/abstracts/v22n3%20Suppl%204/25.htm

> Just to clarify; the ChAdOx1 MERS prospect hasn't proceeded to a trial...

Looks like it has (for SARS-CoV-2 instead): https://www.genengnews.com/news/astrazeneca-joins-u-of-oxfor...


Parallel processing. Normally a few labs would work on a particular vaccine. If a potential vaccine fails they have to retry something else and this whole process can take a long time. Now, pretty much all virus labs in the world are rushing to create a vaccine. There are 70 potential candidates last time I've read, so there is a high change one them works.

This is a very early step (phase 1). They are giving the vaccine to small number of healthy people to make sure it is safe in that population. From there they have to go on to larger trials that look at both safety and effectiveness. The phase 2 and phase 3 trials will take much longer.

Is this really a phase I? 800 people seems absolutely massive if it is—and I don’t think they’d bother with a placebo arm for safety.

Edit: Found the registration. It’s a weird combined Phase I and II: https://clinicaltrials.gov/ct2/show/NCT04324606

Well, it is complicated by the reality that this disease is widespread.

I was rejected because I had cancer (years ago but they don't need any extra factors) but this is mostly like a normal Phase I in that the primary question is: Do humans tolerate this vaccine? Roughly half those recruited (at random) get a different vaccine, an irrelevant one, that protects against Meningitus but we've no reason to think would make any difference to a coronavirus - and half get the new one. You can't tell what it was they stuck in your arm, so they can compare the two groups to see if any side effects were significantly more common for the new vaccine.

Because this coronavirus is widespread in the community they will also unavoidably get to collect information that would usually be the purpose of Phase II/III trials - did the group who got the "real" vaccine get COVID-19 symptoms less often that the other group? Or if they did, were they less severe?

You normally don't do this, and if you tried an ethics committee would stop you - it's unethical to expose patients to a novel risk when you haven't even figured out if the treatment you're trying is safe first. But in this case the risk is already there, for absolutely everyone, so you aren't making anything worse by just measuring if your treatment helped.

Right, but for those same reasons, a Phase I trial is usually much smaller and has “safety and tolerability” as an endpoint rather than disease-related outcomes (as this one does). I don’t think those usually have randomized control groups; see the example below.

In this case, it looks like the Oxford group had previously used the same ChAdOx platform to make a MERS vaccine, and they’re leveraging that data (here: https://www.thelancet.com/journals/laninf/article/PIIS1473-3...) to move more quickly into a combined Phase I and II trial.

And I think there are also some 4 or five vaccines in phase 1. See report https://www.nature.com/articles/d41573-020-00073-5

Other coronavirus vaccines have been developed before, though not brought through the full process. And this is really pretty early in the process; this is the start of human trials. Even if everything goes wonderfully there won't be mass manufacture of this for a while.

Germany started trials on April 22nd using a vaccine named BNT162. Apparently with non-infected people first.

If one had strong reasons to suspect a mechanism by which a vaccine could actually be deadly or fatal, but this mechanism had not been verified explicitly in literature, would they be ethically obligated to warn participants in advance?

If there is reason to believe it presents a material risk to their health and well-being. Yes.

Is this a rhetorical question?

COVID-19 is a retrovirus, much like HIV. They both have similar s-protein as well. When discovered in 1983 that HIV is the sole cause of AIDS, it took 12-years for an antiviral to reach the market. In the past 37-years, no vaccine has panned out against HIV. As for COVID-19 "Houston, we have a problem."

I believe you are correct. I believe COVID 19 IS in the category of RNA based retroviruses. No one here is saying it is the same thing as AIDS! That's silliness. But tests being rolled out on COVID 19 contain a reverse transcriptase polymerase chain reaction (RT-PCR). I believe the virus does fall into the retrovirus category; like malaria, AIDS and ebola.

COVID-19 is not caused by a retrovirus.

Our inability to develop a vaccine for HIV is not very relevant as they are very different viruses.

The development of this vaccine has not been from a standing start. From the article: "The Oxford team has already developed a vaccine against Mers, another type of coronavirus, using the same approach - and that had promising results in clinical trials.".

HIV, as I understand it, is a really difficult virus in general because it attacks the immune system. Our typical vaccine playbook doesn't really work well against it because our whole playbook depends on a healthy immune system.

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