I am extremely bearish on this whole global situation, but given the gravity of the situation, we're going to see the world's best institutions and minds working on vaccines and treatments with essentially unlimited funding and top priority.
Even during our darkest times, we're going to see the most remarkable science and engineering capabilities exposed in the coming weeks and months, for the sake of humanity.
Reading about Russia sending rockets to Venus in the 1960-70s [1], then later watching a documentary about the Viking program [2], was one of the things that cheered me up the most during this whole thing.
Humans have done amazing things in the face of dire odds. Nothing brings them together like these sorts of challenges.
Since then I've been reading a book called "The Rise and Fall of Dinosaurs" and there's been so many extinction events, yet life still bounced back each time stronger than before. Looking at life on that timescale, what humans managed to accomplish in such a short one doesn't get enough praise. We've only scratched the surface on how much better we could be as a species.
I'm confident we'll be far better prepared for the next epidemic and at the very least hopefully China (and others like Vietnam) will eventually ban the wildlife trade for medicine as well, not just for food. Which is what early results by scientists are pointing to as the cause of this whole thing (Pangolins trafficked for Chinese medicine). Animal conservation plays an underrated role in epidemics, same with Ebola (monkeys) and SARS (bats). We don't need to be consuming any of this stuff.
> we'll be far better prepared for the next epidemic
I agree. Being in California, it's a standing recommendation to maintain extra supplies in case of impact from wildfire or earthquake. So, I thought I was pretty well prepared. I already stock and rotate extra water, toilet paper, n95 masks, canned food, etc. But, I discovered some holes in my preparedness that I will rectify when the stores are back to normal supply levels -- I will be even better prepared for the next state of emergency.
I'm sure the preparedness will go wide and deep across many government and private organizations. At a minimum, I hope the CDC ensures there are plenty more ventilators ready for the next one.
"At a minimum, I hope the CDC ensures there are plenty more ventilators ready for the next one."
My only thought here is that we don't know that "the next one" will require ventilators. While I'd certainly like to see our national stockpile of PPE and emergency equipment like ventilators improved, I'd like to see the CDC preparing to face a wider-set of the "next one".
I think we should be looking at our manufacturing infrastructure and ability to rapidly ramp-up the production of any life-saving hospital equipment in the face of a sudden need. With a national stockpile that's strong enough to cover the ramp-up period.
You make good points, but while the "next one" may not require ventilators, it's a good bet that ventilators will be needed again. This is not the first respiratory disease pandemic.
To quality as the next one, a disease would have to spread very easily from person to person. And that usually implies airborne. Which usually means it attacks the lungs, which usually needs ventilators.
Diseases that are differently transmitted like Herpes and AIDS can be widespread, but they’re unlikely to be the “next one” because they’re easier to contain.
Both influenza and coronavirus can cause severe respiratory distress. Both are subject to jumping the species barrier or mutation of existing strains resulting in higher mortality. Both are extremely infectious and very difficult to control. That's reason enough to have a few warehouses full of respirators ready to ship out. At the least we need a better plan for emergency bed space and resuscitation training for conscripted personnel.
> we don't know that "the next one" will require ventilators
Good point. How about, "the next one that needs ventilators". Either way, it is a concrete example of equipment that we can now add to the list of things we need more of to be better prepared next time, or the time after that, etc. There are certainly many more things that should be on that list too.
Specific equipment that we can buy and stockpile is one thing, but manufacturing capability seems even more important to have within our borders so we can keep making N95 masks not subject to foreign interference, in the event of a sustained epidemic.
One caveat though is that airborne diseases spread much more rapidly and are much more difficult to prevent than other forms of transmission.
Diseases that spread by skin to skin contact (smallpox, for instance) almost universally have visible signs before they're contagious. This makes quarantining easier.
Diseases that spread via contaminated drinking water (cholera) can almost always be stopped by boiling water or iodine tablets. And developed nations have well established ways of ensuring clean drinking water.
Diseases that spread via blood or other bodily fluids (Ebola, HIV) can be stopped by well established sanitary procedures.
Diseases that are not airborne simply don't have the potential to cause the damage covid has already caused, to say nothing of the total damage when it's all over.
Besides this, the world not just the US need standby health personnel in a similar fashion to armies. Soldiers do nothing unless needed, a "health workers" army can do the same.
This being more like a war than business as usual, the correct solution is more like the citizen armies that fought in the world wars, not a standing army.
I for one wish courses in first aid beyond the very basic save-a-life stuff were more widely available.
Here in the UK, there used to be training that anyone could take that was offered by the main first aid organisations, lasted 2-4 days, and covered significantly more serious but not necessarily life-threatening conditions. There were a few variations you could do, including things like common sports injuries, conditions you might encounter while in the wild outdoors and how to handle a situation as well as possible if professional help is going to take a long time to arrive, variations on first aid for children and babies, and so on.
Those courses for the general public seem to have all but disappeared now, presumably due to a lack of demand. This isn’t entirely surprising, as they weren’t cheap to do, but if you did have the means to afford it, what is the value of knowing how to help someone recover better from an injury, or preventing a serious condition from maybe becoming a life-changing one, or in extreme cases even saving a life? My wife and I did take a course specifically on first aid for little ones when we were about to become parents, but even finding that wasn’t easy.
The main ways to get more than very basic first aid training here now seem to be through either statutory obligations for first aiders at work (where the courses are widely available and longer but also have to cover the official paperwork you need to do as a first aider at work) or through becoming a much more serious amateur first aider (either joining one of the first aid organisations and in due course going out to work as a volunteer at major events and the like, or through things like sports coaching organisations that have the scale to make special arrangements for first aid training). That leaves quite a large gap in provision for “ordinary” people who just want to know enough to help out in a serious situation, but as far as I’m aware, there isn’t really anybody trying to fill that gap at the moment. I did ask the trainers on that last course I took if there was anything I’d overlooked in terms of more comprehensive general first aid training, and they said that unfortunately the above is about right at the moment.
I don’t know how much first aid training would really help with the current coronavirus situation anyway. It seems like what is needed in this case is more people with nursing skills and the ability to set up equipment like ventilators. But as a more general point, I would strongly support measures to increase general knowledge of first aid within the population, at least for anyone who is willing and able to help when they can. If nothing else, it might free up more of the fully trained professionals to deal with the most serious situations and so help reduce the strain on them.
The ones that I have done were through BASP [1], the focus was on what was needed for outdoor pursuits but there were people from a wide range of sports, they were not organized by the sporting body itself.
This was one of the things that was lost with the decline of scouting. I remember quite a bit of training between life guard training and first aid training for dealing with common injuries in the wilderness, dealing with shock, etc. Yeah I get the religious associations were a problem but there's no good secular counterpart or places willing to host (as most troops/groups met at churches), the organization is slowly changing but I don't think its the only reason its been in decline.
Just like a reserve army full of reservists has a serious cost (those people all have to spend weekends training, after all: time that could be spent doing other things), a "health care army" would require people to get regular training to stay up-to-date and in practice. Basic first aid can be useful for anyone, but for having people ready to jump in and become healthcare workers in a crisis, they need a lot more than a first aid refresher once a year I think.
You question contains an implication in it that all current other tax spending will not be reduced, and that "pandemic preparedness" will have to be added to the current load.
If this goes really badly in the next couple of weeks or months, that's not going to be a true assumption. A changed nation is going to be looking at its spending priorities and a lot of reassessing will be done. Predicting exactly what the result will be is difficult, but predicting that there could be a lot of change is not.
If we cross the logistic curve's inflection point today, then this may ultimately blow over and be remembered as an inconvenience (and, humans being humans, an overreaction). If this continues on for much longer and kills hundreds of thousands and (based on some of the nasty stuff I've read about) permanently damages the lungs of millions more or other such things, causing disability and long-tail mortality increases for the next 50 years, this will be a generation-defining event comparable to the Great Depression, and the usually-reliable "tomorrow will be mostly like today" prediction methodology will catastrophically break down in the next couple of months.
I guess the implication that the US military and also non discretionary fund won't be reduced based on the last 50 years of data is probably a status quo bet.
given that the US has spent[0] over $5,000,000,000,000 on pointless wars, redirecting even a fraction of that toward a necessary one should be a no-brainer.
We just added "Space Force" so ya, why not add "Health Force" while we're at it. Health Force could have a number of tasks during non-Pandemic times too. We might even be able to pay for Health Force, at least in part, out of some foreign aid budgets if we send Health Force as part of that aid.
Yeah! Some sort of Center who's job it would be to control diseases. We could call it the Center for Disease Control.
Snark aside, we had a similar situation with SARS. In the immediate aftermath, it's easy to say what needs to be done to prevent the next one. It's far harder to get everyone onboard with paying for something 5 or 10 years down the line when "there's no point" and "why do I have to pay taxes"?
Same as "Why we paying for backups?! We never had to use it!"
I'm happy I don't live in The USA right now. Even the worst hits, I don't have to be afraid of medical bills or if I lost my job. Both are covered by the tax I payed before.
I agree, it would make too much sense to have a program of national service where people were required to undergo training for medical emergencies and disaster response. Having practically every able bodied person qualified as a first responder would pay huge dividends.
This may come across as crass but I legitimately believe that there is a market for "emergency preparedness" as a service. It can deliver a set of basic necessities at sign up and perishable supplies at regular intervals customized for your geographic location, number of family members, storage space etc. While you can do the same by trawling through prepper forums and making monthly trips to Walmart or Costco, it's not as convenient.
I think there are much worse issues than just the wildlife trade. I think long-term we're gonna have a lot of issues with antibiotic resistance diseases as a result of overuse in the meat industry [1].
I see overuse of antibiotics around me all the time. Just the other day my friend's daughter had bronchitis and readily prescribed antibiotics. A couple of days later when it didn't get any better, she got a stronger shot of the same antibiotic. Then it still didn't get any better and another doctor just decided to change it to another kind. There wasn't any of the "let's wait it out and see if this is viral instead of bacterial" or any testing done. And this isn't a single case. It's the norm with 80% of doctors I hear about.
Part of that is viral things often weaken your body enough for a bacterial infection to come in as well. In some (not all) of the most deadly diseases the problem wasn't the initial infection is was secondary.
> ... there's been so many extinction events, yet life still bounced back each time stronger than before.
Nit: The Great Dying, c. 252MYA, took about 10 million years to 'recover' from (though it depended on region, maybe). And the species that came out were not the same that died. As in, they evolved to fill the old niches. The Great Dying was no joke, nearly everything that had more than one cell went poof, like, 96% of all species.
Not to rain on the parade, but we have to work at this. If we do, we are fine, but just posting internet comments is not going to cut it.
Call your congresscritters or other representatives, tell them what you think.
> Not to rain on the parade, but we have to work at this. If we do, we are fine, but just posting internet comments is not going to cut it.
I think posting online is a double-edged sword. On the one hand, "clicktivism" and posting hopeful messages soothes that person; on the other hand, if they are that easily soothed, they panic just as easily.
> Call your congresscritters or other representatives, tell them what you think.
This is important. Fortunately I've always lived in a district where my representatives were almost 100% aligned, but even then it is important to double down on the signal to noise. They love to hear positive feedback as well as negative feedback.
I'm with you on this. One of the not-so-physical wonders of the world we have is a lot of scientific, capable minds paired with high technology and rapid feedback on their efforts. The timing, though it could have been better, is on our side.
My one concern is once this whole thing is over there will be a long pause followed by a blame game.
There are already conspiracies floating out there being pushed forward by officials in various countries.
What would be really, really nice is if after the crisis passes the world's best institutions and minds continue to get a significant amount of funding to apply those remarkable science and engineering capabilities for the sake of humanity.
IMHO that is the real issue. We didn't need to be in this crisis in the first place : /.
I can’t find the source I saw the other day, but the CDC ran out of a good chunk of its budget September 2019. Right before all this started.
We, especially the US, keep treating CDC like they’re responsible for fixing diseases after they spread when their focus is prevention. This has been happening repeatedly for at least a couple decades.
Every time, it gets worse because we treat disease as a solved problem.
Darkest indeed, if you are more than 70 years or have other illnesses then you take every precaution not to get infected.
The rest of the population pray that the Corona quarantine will be scaled back as soon as possible, so we don't have a financial ruin to deal with the next decade or more.
I share your sentiment, this will be amazing and also a 'working together' time.
But - time - is the issue. It's medical. Stuff takes a long time to develop a test, there are real ethical rules that won't get broken I think even now.
50 years ago, there would be either some brave volunteers who would be willing to get infected or some poor souls somewhere who would be unwittingly infected to see the results. No more of this.
It's possible however the CCP may 'volunteer' some prisoners, or they may allow brave citizen volunteers. I can see that happening. (I can see brave volunteers coming from everywhere, but I don't see governments allowing such a program to go forward).
I dont think thats a problem. At the very least there will be doctors who are infected and there is nothing to prevent them testing the vaccine on themselves.
We need people who do not have the disease to act as guinea pigs for vaccines and other therapies, not just people who already have it.
Also, we need to test drugs and therapies that have excessive, even deadly consequences. Again, dilemma.
This is a huge ethical dilemma.
Up to a generation ago, drug companies would run trials in Africa, away from aggressive regulation.
During the Manhattan project, the US Army would run squads of soldiers right through the aftermath of test nuclear explosions, literally to see 'the effect of radiation'.
Many specialist jobs entailed levels of riks unthinkable today. Remember, this is in an era where cars didn't have seat-belts.
In 2020, things have changed, but it's possible totalitarian regimes will find 'volunteers'.
China has been engaging in harvesting the organs of political prisoners, at scale [1]. If they're willing to put people in prison for their ethnicity, and then 'have them die' so that a rich person can get a kidney through back channels ... then absolutely they can do medical trials on these people, it may not even need to be publicized.
I love that the 'tribunal' starts its conclusion with 'If the accusations are true'.
They can be true, but remember the Curveball dossier that helped to start a war.
In a February 2011 interview with The Guardian he [Rafid al-Janabi] "admitted for the first time that he lied about his story, then watched in shock as it was used to justify the war."
I'm aware of all that stuff, I was just saying there is no ethical dillema or procedure if you want to do medical tests on yourself. That's how Barry Marshall proved that Helicobacter pylori causes stomach ulcers.
How certain would the experts have to be to get such coordinated action?
With close approaches, it seems (as a layman) that there are always pretty large ranges of just how close they will be. I dont think you'd know "a comet is headed directly at us" until way too late. Instead you'd get some warning that there is a 10% chance or something. Over time that would go up to a near certainty. Maybe I'm pessimistic, but I would predict something more similar to climate change with deniers and paralysis.
This remark reminds me of the book, "Seveneves" by Neal Stephenson. He plays with a similar 'what if?' doomsday scenario. Around 80% of the book revolves around testing and pushing humanity at it's extremes.
I think it's worth noting that the corporation is trying to do the right thing, even as pushed by the US government to act unethically. Don't always expect that corporations are evil, or that governments will protect us from that.
The problem is the virus will already have done it's damage by the time the vaccine comes out. Mayhaps it will be useful for the next pandemic that comes out of Wuhan's wet markets.
Considering the actions of the US government in Germany, and most probably the actions of other governments, I'd say for the sake of national interests, not humanity.
I'd be happy to be proven wrong, though: When a vaccine is found I'm sure the government/company behind it will make available to the world for free...
Inside of governments and corporations are individuals making all of those decisions. There is a buck and it stops with an individual on a decision, or a couple of individuals at most.
That's how a national emergency gets declared. The President decides to go forward with it. If California declares a state of emergency, it's the governor that has the final say:
That news about him trying to buy exclusive from the German company was false news and even the company itself put out a statement that it’s false and it never happened. Media very conveniently didn’t report the correction.
That's not Trump-only propensity. German government has confiscated all 3M masks from 3M European distribution center (obviously they didn't literally confiscated them, they just said that they are the only one who can buy them), they didn't care that, say, Italy needs them more.
But I don't blame Germany at all, there came a time where people can see what is important and if economy of their country is healthy - it produces everything people need and if it really make sense to outsource all production elsewhere just to save a few bucks and if the government they elected is able to handle situation.
There's another new (as in just a few years old new) and fascinating technique for making vaccines that hasn't received much publicity. It's a general technique that can be quickly applied to any pathogen. It was recently used to develop a vaccine against Venezuelan Equine Encephalitis Virus (VEEV), was used to vaccinate mice against staph, and is also being tried against new strains of polio emerging in India.
Here's an excerpt from paper about VEEV summarizing the technique's mechanism:
...a disease-causing organism (pathogen) can be exposed to gamma radiation in the presence of a Deinococcus Mn complex, and rendered non-replicative (killed) by overwhelming genetic damage, but still maintain the shape of key surface proteins needed to mount a highly protective immune response.
I think this could have the potential to develop a cure but isn't receiving any attention from our (dysfunctional) government (who also happens to own the patents on it!).
The problem is not vaccine development - the bottleneck is TESTING.
The vaccine itself can be developed in literally DAYS (for most viruses). The problem is that it takes a YEAR to test it comfortably in humans. For something that you'll be delivering to otherwise healthy humans, the bar for safety is extremely high.
...now the modern counter-argument is that if 4% of people are going to die globally, then maybe the safety bar should not be so high (this time).
I heard that killed virus vaccines from corona viruses can actually lead to a cytokine storm and higher mortality rate in those innoculated with it. There's a reason we don't have general vaccines for the common cold. During some previous corona related outbreaks (SARS, MERS) there was an attempt at using this method, but it actually has a backlash effect when the person is exposed to the virus.
We do have a vaccine for the common cold. Problem is the common cold is really about 300 different viruses, and a vaccine for just one of them didn't make a statistical difference.
Don't confuse "I don't hear about it in my daily news for the general public" for "nobody has considered it". You are not receiving an unfiltered medical-professional-level summary of all efforts currently underway. You're receiving a chaotically chosen, filtered-through-reporters (who mostly don't understand any of this beyond the middle-school level) subset of the news, further skewed by PR people actively trying to promote their own stuff. There could be any number of complicated biochemical reasons why this approach won't work on this particular virus.
The rationale against mass inoculation with an untested vaccine stems partially from the botched 1976 Fort Dix swine flu H1N1 outbreak and vaccine. The volunteers of successive regular clinical trial phases play Russian roulette on our behalf, and this takes time.
The dengue fever vaccine disaster on the Philippines is another good example why one should be cautious. Dengue fever is the canonical example of antibody-dependent enhancement - someone who has antibodies against a certain strain of dengue fever will show a very serious reaction when he is infected with a different strain of the virus. That's why people who are given the dengue vaccine must have been infected with dengue previously.
On the Philippines, they gave the dengue vaccine to schoolchildren, a substantial number of whom were seronegative. The disease in that population was much more serious than it would have been otherwise, there were unnecessary deaths, and a good number of parents avoided the measles vaccine for their children, and a measles outbreak promptly followed.
>On December 16, a one-month suspension of the vaccination program is announced by CDC head Sencer. William Foege of the CDC estimates that the incidence of Guillain-Barré is four times higher in vaccinated people than in those not receiving the swine flu vaccine.
The rushed vaccine apparently substantially increased the risk of Guillain-Barré syndrome in those receiving it. The syndrome is fatal in up to 5% of those that contract it and can cause permanent damage to the peripheral nervous system.
Increasing the risks of catching the disease from 2 per 100,000 to 8 per 100,000 does not sound that bad. It’s an additional 6 cases per 100,000 and ~0.3 deaths per 100,000.
Clearly a significant issue, but less so if it was likely to prevent a serious illness. The real issue was the vaccine was administered for a disease that never gained a significant foothold.
I don't have any objection to developing and distributing a vaccine, but it's deployment without sufficient testing. Had the disease become widespread, as you note it would have been worth the additional risk, but in the event, it made the occurrence of any serious side effects seem more egregious. These kinds of things just feed into the anti-vaccination movement and if that overall hurts vaccination rates long term, rushing a vaccine that ends up having side effects could negatively affect public health.
I am not sure how you can catch something that’s at 6 per 100,000 without giving it to an very large group of people. There are so many unusual conditions that such problems are going to look like statistical noise until your distributing something to around a million people.
The vaccine was thought "likely to prevent a serious illness", but that didn't pan out. So that's why testing is important, to make sure that the cost is worth the benefit.
Only about 200 cases of swine flu and one death were ultimately reported in the U.S., the CDC said.
More than 500 people are thought to have developed Guillain-Barre syndrome after receiving the vaccine; 25 died
The cure was worse than the risk not the disease. If it had actually infected people and had 1 death per ~250 people x say 50% of the population that absolutely dwarfs 25 excess deaths.
Which is my point, the problem was mass vaccination for a non issue. Saving 500,000 lives at the cost of 100 lives is a really easy tradeoff to make. Costing 25 lives to save 0 is a problem.
Given the choice between contracting the disease or taking the vaccine you would take the vaccine. But, as the spread had stopped, it was a choice between taking the vaccine or having a 0% chance of catching the disease which had already died out.
Maybe in a truly utilitarian, rational society, but here in the USA, we expect the risk of a vaccine to be near zero, with no adverse consequences, before we give it to everyone.
This isn’t as irrational as you make it sound- I think it has to do with how we assign blame for actions. Less blame is assigned for failure to prevent hurt than blame for acting in a way that hurts someone directly. This reflects both the practical difficulty in assessing what harm could have been prevented vs what harm was direct caused by an action, and reflects our justice system’s role as a deterrent for people harming others, and less as a tool to compel helpful behavior.
From another practical concern, we need to preserve the public perception that vaccines are low risk to them, not just that they are lower risk to society than the hypothetical alternative, before healthy people will get vaccinated.
I meant rationality in the economic sense, where we would purely look at the cost-benefit of the decision, and where everyone else would look at it the same way. In that case, even a slight net savings in lives would be OK, even if that meant that administering the vaccine would cause some deaths.
I'm not saying that is how we SHOULD act. I'm definitely not saying that's how we DO act. Clearly, taking into account all of the factors that you mention, we have a very high standard for action, and that's a rational choice given the realities. It's still not a rational choice from the economics perspective, which strictly looks at cost/benefit.
And this comapny's particular approach to vaccination has never been approved for any indication. I can't imagine why this company would be considered a first-line relative to classical approaches to vaccination (inactivated, attenuated live, made by recombinant hen egg, etc., etc.) that we roll out regularly and successfully.
All approaches need to be considered at this time because we don't know which if any will work. We also don't know what the side effects of the ones that will work might be.
When we get farther along in testing we will have more information and should re-evaluate. Maybe something will prove to work well (we can do a new flu shot in a few months because we have approved the process to create a new one), maybe everything else will fail. Maybe this will fail. We don't have enough useful information to work with now though.
You say these things like you know something about the field. In fact, we're talking about a technology for vaccination that is far less likely to work than many tried and true ones. It has never been FDA approved for anything.
That doesn't mean that it won't work, or that the others will work. If the others turn out to work and because they are more tried in general great, but right now all approaches are worth exploring
Did you read the wikipedia article? The problem is not related to the virus being present in the vaccine- the vaccine caused a immune disorder that damages the nervous system.
Not to mention we already have a problem with anti-vaxxers causing outbreaks, and that's without any actual facts on their side. I shudder to think what they would do given any real reasons to distrust vaccines.
There are real reasons to distrust the safety of at least some vaccines. I did not get too much into it(it is tiresome as you are quickly in tinfoil hat territory), but what I took away is, that the procedures to check and regulate the safety of vaccines could definitely improved.
Even if initial safety tests go well, “you’re talking about a year to a year and a half” before any vaccine could be ready for widespread use, according to Dr. Anthony Fauci, director of NIH’s National Institute of Allergy and Infectious Diseases.
So even if these trials go well that suggests a vaccine is a long way down the road.
Given how serious the situation is worldwide I suspect that there will be at least an attempt to speed things out as much as possible. I would be surprised if it actually would end up being a year and a half.
1.5 years is already very fast for a clinical trial. The average duration of clinical trials for "breakthrough" drugs is 5.0 years [1], compared to 8.0 years for drugs without that status. Plus O(1%) of trials actually make it to approval [2].
As much as many people like to hate on the pharmaceutical industry etc, there is a reason clinical trials take time. Yes, this is a pandemic and we must move quickly, but it's important to ensure that we don't repeat the recent mistakes made with the dengue vaccine in the Phillipines [1].
That vaccine made dengue significantly worse for those who had not been previously exposed to it. Situations like this are especially bad because they erode trust in vaccines, perpetuating the idea that all vaccines are bad/malicious when in fact a properly vetted vaccine is very safe.
If these first trials succeed, yes, we might get a vaccine mass-produced fast. But you're not looking at the downside risk: if these trials fail, and the next trials fail. This is research; by definition we don't know what will happen. It could turn out to be really hard to make a vaccine for this particular virus. In that case, even with well-funded efforts trying everything, it could take many years.
I really hope people will take a more "effective altruism" approach to those 18 months with all the people dying. I'm guessing just with logistic and bureaucratic prioritizing we can shave 6 months (somebody mentioned above that it takes months just to set up testing with the large number of volunteers. Sure, normally it does, but definitely not today).
Beyond that we can probably cut another 6 months with judicious strategizing. Have certain populations defined that are high risk and high exposure - like elderly health care professionals - and start using the vaccine before the approval is complete. You might actually mix this with early testing and have the volunteers be actual beneficiaries. This way you get efficiency results from the field - it's trivial to implement a double blind and measure infection rates.
Lots of things can be done, if one is willing to look at the letter of the rule and re-think if it's applicable now.
You can't magically whish vaccine into working. The controls aren't there in order to maximize the delay for when vaccines can be deployed.
A bad batch could essentially equal to purposefully infecting people with the disease, for example.
Ed: i don't see it mentioned explicitly: while young people might reasonably volunteer to be vaccinated and exposed to the virus - we really need to vaccinate the elderly and at risk - who has a high mortality rate. We might get volunteers, but it's still different to sign up for a 50/50 shot at death, than the risk of two weeks of mild flu...
And we probably do need to test for adverse effects in the at risk population too.
> A bad batch could essentially equal to purposefully infecting people with the disease, for example.
Nope, impossible. mRNA based vaccines don't use a weakened version of the virus to train the body:
> [0]The use of mRNA has several beneficial features over subunit, killed and live attenuated virus, as well as DNA-based vaccines. First, safety: as mRNA is a non-infectious, non-integrating platform, there is no potential risk of infection or insertional mutagenesis. Additionally, mRNA is degraded by normal cellular processes, and its in vivo half-life can be regulated through the use of various modifications and delivery methods
To use a bad analogy mRNA based vaccines train the body using a "signature" of the virus, essentially skipping the first step of actual infection and jumping to the second/third steps where the body's previously exposed to antigens are generated. It is an entirely new form of vaccine that has worked in trails before.
Which isn't to say it is 100% safe for other reasons. I'd say auto-immune reactions are the biggest risk (e.g. the body using the signature encoded to attack the body itself).
> Which isn't to say it is 100% safe for other reasons. I'd say auto-immune reactions are the biggest risk (e.g. the body using the signature encoded to attack the body itself).
Out of curiousity, why couldn't potential auto-immune response be simulated on a computer up to a degree of confidence, if nothing? Would quantum computers drastically rid of current computing related handicaps wrt to simulating a large search space typical of such simulations? What role might yet the recent resurgence in deep-learning play for immediate future?
"Out of curiousity, why couldn't potential auto-immune response be simulated on a computer up to a degree of confidence, if nothing?"
Basically every answer you could imagine to that question is true. We don't understand the system well enough to simulate it at that level of detail. We don't have the computational power to do it if we did. If we did have aliens from space deliver to us both the power and the simulation, we'd have a difficult time verifying the validity of the simulation!
Quantum computing is still not well-understood enough to know if it's helpful; there's a certain barrier of "what can it actually do" that we won't really understand until we have them, and we start raising up quantum programmers. No slam against the theorists intended, it's just the difference between "the halting problem is unsolvable" and "here's a program for calculating payroll" is small in theory but large in practice. We won't really know what they can do until we work with them for a while.
I work in computational drug discovery. With current hardware, we are basically limited to simulating single proteins for microseconds of time, and even that requires a lot of simplifying assumptions. So we can only simulate a small part of any given process. We can't develop high confidence about a complex cascading process this way.
Quantum computing would definitely help if we had it. And researchers are using deep learning in many parts of the process now.
Elderly might not be able to take the vaccine, which will make it much more important for everyone else to be vaccinated. Vaccines provide immunity in aggregate as well as in person.
Adverse effects need to be considered against risk. If .01% who get the vaccine go blind is that better or worse than then taking your chances without? Tough choice, and not one that can reasonably answered. (note the .01% number was made up on the spot, I have no idea what the risk is just third hand reports that there once was a vaccination that made some people blind)
As much as many people like to hate on the pharmaceutical industry etc, there is a reason clinical trials take time. Yes, this is a pandemic and we must move quickly, but it's important to ensure that we don't repeat the recent mistakes made with the dengue vaccine in the Phillipines [1].
That vaccine made dengue significantly worse for those who had not been previously exposed to it. Situations like this are especially bad because they erode trust in vaccines, perpetuating the idea that all vaccines are bad/malicious when in fact a properly vetted vaccine is very safe.
I'm not a professional vaccine researcher, but I can only imagine you want to validate 1. that the vaccine is effective and 2. that the vaccine doesn't cause everyone who takes it to get an aneurysm six months later. These things have to be pipelined. You don't want to inject 10k people with something you've only tested on 45. You don't want to inject 45 with something you haven't tested on animals. You don't want to stop the 10k person trial too early in case if there is a longer term side effect you missed. You don't want to start manufacturing billions of doses until your 10k trial is done. Etc.
As someone who works in the industry, you pretty much covered it.
If you dose people with a new vaccine, you’ll need to monitor them 6 months at a minimum. 12 months would be better.
It takes 3 months to nail down the protocol and for all the sites to be ready. Then you start recruiting and for a vaccine, you’d want a large population (reflects usage). So assume 6 months to recruit 1000 people. They don’t all start at the same time, so if you’re tracking for 6 months, it will probably take 9 monthsfor the last person to finish the trial.
Then you need to analyze all the data you collected, so another 3 months. Then the FDA takes 3 months to review and approve.
There is a TON of work that goes into running a clinical trial.
Any chance review and approval can take 3 days instead of 3 months? For example with the review process happening concurrently while monitoring the whole trial?
Sure, you could probably accelerate review from 3 months to a few weeks. The FDA is familiar with rolling submissions where you send data to them as it becomes available.
But it does sound like if there's priority and fear, much time could be saved. For example, "6 months to recruit 1000 people". I suspect in this case, a week can work.
> Then you need to analyze all the data you collected, so another 3 months.
Help me understand this. You vaccinate 1000 people. In 6 months, the number of them that get sick is 10% of the rate of the unvaccinated. 0.1% have a bad reaction. How much more analysis do you need?
> the FDA takes 3 months to review and approve
How much time if that is moved to the front of the queue and all hands work on it? Given how enormously disruptive the coronavirus is, we cannot afford to not have all hands working on it.
Let's tackle recruitment. I've seen trials recruit really fast and that took a month. It's not like someone says "hey I'd like to take part in this trial" and you give them a shot of drug. You need to screen everyone who comes in. Basic labs, then make sure they don't have some other disease that will mess up the results. That's just one part of it.
Then in terms of the trial, 6 months would be nice, but it wouldn't be ethical to actually expose them to the virus. You'd simply need to recruit a very large number of patients and see if the treatment groups has less disease than the non-treated group. With infection rates pretty low across the entire population, you'd need to recruit thousands, just to capture the handful that actually get exposed.
Then when it comes to analysis, you need to clean the data (yes, there will be errors), then you need to do a statistical analysis of not only efficacy but every possible side effect. You're probably measuring things like viral shedding, so that's another entire dataset. Oh, then you'll have missing data. Do you toss that patient's data out entirely? Or keep them? What impact does that have on your conclusion?
I could go on and on, but suffice to say it's a ton of work. And yes, you can speed up some parts, but other parts you just have to let them run their course.
If tens or hundreds of thousands of people were dying every day from the virus, might we find many volunteers willing to be intentionally exposed to the virus in order to rapidly test the efficacy of a vaccine? I imagine so.
I believe the magnitude of this pandemic will in time push us (rather violently) to think outside the box.
How do you test the efficacy if you don't know who you're injecting? Maybe it works really well on a certain population, and reacts harmfully to people with some pre-existing genetic trait or condition. You wouldn't know, because you took a random set of volunteers.
If you're going to counter and say "we'd still do the pre-analysis on the volunteers"... Well, that's what takes time.
Even if volunteers take the vaccine, this will not significantly change the timeline. Do you really want to cut short the observation time to e.g. 1 month, then greenlight the vaccine and administer it to millions or billions of people, only to find out that after 6 months it causes an aneurysm or whatever in 10% of them?
Start by 100 people, monitor for 1 month.
If it looks promising, add 1000 people, monitor for 1 month.
If it looks promising, add 10000 people, monitor for 1 month.
If it looks promising, add 100000 people, monitor for 1 month.
If it looks promising, add 1000000 people, monitor for 1 month.
And so on. The exact rate could be set according to the actual infection and death rates in the population. Given the current costs of curfew, we could create an entire government agency just to administer this, and still save trillions.
If you're testing a drug for a serious cancer, then there is a lot of tolerance for side effects - the alternative is death, so even if it causes things like nerve damage, it's an acceptable risk.
With vaccines, you're going to treat a huge percentage of the population and they'll be healthy when you give it to them. As such, the risk-benefit analysis is much different since there is a chance for serious harm.
> Let's tackle recruitment. I've seen trials recruit really fast and that took a month. It's not like someone says "hey I'd like to take part in this trial" and you give them a shot of drug. You need to screen everyone who comes in. Basic labs, then make sure they don't have some other disease that will mess up the results.
You could do that time-consuming screening after they get the trial vaccine, not before. After all, I suspect it is highly unlikely that a virus vaccine would give someone a bacterial disease or a genetic disorder.
Also, before the 6 month trial is up, you're still going to have data trickling in that will give a good indication whether it's working or not.
Source: I saw the movie "Contagion" and learned that a vaccine is considered safe and effective based on one monkey not getting sick. I believe everything celebrities tell me.
You could do that time-consuming screening after they get the trial vaccine, not before. After all, I suspect it is highly unlikely that a virus vaccine would give someone a bacterial disease or a genetic disorder.
Ok. So let’s say you give the vaccine and run the tests later. This person’s white blood cell count is way above normal.
Is that caused by the vaccine? Was it something else? Was it always there? You have no idea because you didn’t capture a baseline.
The challenge of clinical trials is you don’t know what to expect, and you’re measuring effects on top all the stuff that’s happening in the background with completely healthy people.
The goal is to capture as much data as possible so you can actually draw conclusions from it. Otherwise you’re left thinking “it’s probably the drug, but I’m not sure”.
Take your samples before giving them the vaccine, but do the actual screening later.
Is there a type of screening that requires you to do tests over a period of more than a week, because you need the results from some slow tests to order other slow tests? If you just exclude all the people that need unexpected additional tests, is that so many it will ruin the data?
Normally, yes. But this isn't normally - here the goal is to get a vaccine as quickly as possible.
For example, white blood cell counts. Draw the blood, set it aside, inject the vaccine. Then get around to testing the blood. You save what, a week that way? That's a big deal.
Based on your descriptions, it seems that a lot of time can be saved by doing things concurrently rather than serially.
"Although far behind, the United States did work hard to get a jet into the air during the war. Lockheed was engaged to build a jet fighter, using the British De Havilland Goblin engine. Speed was called for, and Lockheed gave Clarence L. “Kelly” Johnson full authority for the project. He set up his special unit, the famous “Skunk Works,” with 23 engineers and 105 shop men, and he did 96 percent of his own fabrication and all inspection. Lockheed's normal development procedure of engineering conferences was by-passed; only 700 drawings were made; sometimes parts were made from a drawing, and sometimes the reverse was done: simplicity was Johnson's keynote. The XP-80 cost only 63 percent of the XP-38 prototype, which had been made by the customary system of development. It was accepted by the AAF only 143 days after the start of development, even though the engine had not been on hand until the 132nd day. After General Electric had designed an improved Whittle-type engine, the 1-40 or J33, the XP-80A was designed around it: the United States had a jet fighter and one of the best aeronautical designs in its history by the end of 1945."
"The most telling criticism of massed-manpower engineering practices is the record of the “Skunk Works.” Starting with the XF-80, this technique has been used periodically by Lockheed's Kelly Johnson to produce the U-2, the JetStar business jet, and the A-11 (F-12). The XF-80, it will be recalled, used 23 engineers and was designed in 143 days; the U-2 also used 23 engineers and took 80 days; the JetStar used 41 engineers and took 241 days; Johnson used 135 engineers to build the A-11, which was designed to go over Mach 3 at 20 miles high. This contrasts with the 3,500 engineers used to build North American's XB-70, which went Mach 3 at 15 miles high. Although it must be acknowledged that none of these aircraft are large, the XF-80, the U-2, and the A-11 all pushed beyond the state of the art, and the repeated success of the “Skunk Works” shows that effectiveness of the system is no fluke."
"The Jetmakers" by Charles Bright (yes, my dad)
Think about it - 23 engineers and 80 days for the U2. Kelly Johnson knew how to get things done.
Though, if 1% of your planes have issue that causes them to stop working midflight after 1 year, at worst you'll lose a few pilots and fix the issue by inspecting rest of the planes.
Backtracking and fixing issues after giving a vaccine to millions of people is a bit more problematic. Not just technically, but also in gaining the trust back, etc.
Walter is completely right. Under extreme circumstances (worst pandemic in 100 years) our risk thresholds should obviously shift. You can't cut corners too much and there is an inherent serial component, because if you want to vaccinate potentially hundreds of millions or even billions of people, you need to have some confidence about the risks involved. Even if you accept higher numbers of adverse vaccination reactions than you normally would. This means several months of observation you really cannot avoid. But most of the other things that take months according to refurb seem like baroque excess in the current context. Three months to analyze results and six months to recruit? Seriously? Also you can basically run any number of trials in parallel with different thresholds and then pick where you want to be on the risk/reward scale based on the situation a couple of months down the line.
I probably wouldn't take a vaccine that was validated just by several months of observation on test subjects, especially if it's a novel[1] mRNA vaccine. Maybe a year later, after release, when the potential for harm is better known.
Other people may have a different risk/reward calculation.
I'm not sure how this would contradict what I wrote, I totally agree that the observation of the patients is the one thing where you can't really speed things up much. It's inherently serial, no matter how much money and manpower you shove at it, but I don't see how this is true of many of the other stages mentioned upthread. Do you?
I wonder if the downvoters fully understand that Covid-19 is a big deal. If we don't manage to eradicate it and it becomes as common as the (various strains of) cold, we will likely take a big hit to global life expectancy. It may also evolve to become more virulent and we may yet discover various unpleasant things about it. Even if it stays exactly as it is now and we just let it run it's course and get 70-80% of world population infected, before eradicating it in say two years time with a vaccine, we will eat a huge, multi-year dip in life expectancy in the developed world.
And clearly, we are not accelerating this yet in ways that are completely safe (e.g. would we have more and better volunteers faster and more regularly if we paid them more than $100 for each visit?).
I'm not trying to contradict you. Just saying that the kind of vaccine that can be perhaps ready relatively quickly is the kind that's not very common yet, and is in the stage of "new and exciting technology", atm. I'll exercise caution.
There were news today that first subjects are getting the experimental vaccines already. I don't know if it's fast enough or not. But I doubt people will not try to speed things up, at all levels.
Yes, it’s an emergency, but many parts of the process just take as long as they take. Throwing more people and money at the problem can ensure that we have many parallel solutions in the pipeline, but won’t get us there faster.
Not who you're replying to, but I imagine bad, immediate reactions will be easy to spot, but more subtle, chronic problems would be found only after analysis. A part of this work would be figuring out what is attributable to the vaccine and what is not.
If you rush a vaccine that causes 5% of patients develop a fatal complication in 1 year you've just killed twice as many people as COVID-19 would have.
Personally I'd rather take my chances with COVID-19 than risk injecting myself with an untested vaccine.
The Dengvaxia controversy, Dengvaxia issue, or Dengvaxia mess is an ongoing controversy about the use of anti-dengue vaccine Dengvaxia in the Philippines. In late November 2017, the Department of Health suspended a school-based vaccination program utilizing French drug-based vaccine maker Sanofi Pasteur's Dengvaxia vaccine because reports circulated that several children died from various complications allegedly attributed to the dengue vaccine.
best of luck to USA - Hopefully coronavirus situation gets resolved ASAP. I have a feeling as humanity battles this virus, we will see the best of every nation.
One of my biggest concerns is that they mean well and rush these vaccine trials as having a vaccine very soon would be IMMENSELY VALUABLE.
But the fear part is that they screw up, people get hurt, and the anti-vaxxers dominate the conversation which leads to broader fear of vaccines and a vastly worse outcome overall for the foreseeable future.
I would not envy anyone who has to make such decisions right now. And I would respect the process as it is, rather than be angry at it, because vaccines are overall some of the safest medicine in the history of medicine and that's really important to getting people to use them.
If nothing else let’s ramp up production in parallel with testing. If it doesn’t work out we lose some time and money which isn’t a big deal in a crisis.
That's assuming nothing needs to be changed in the formula (I'm no chemist, excuse my ignorance).
But logically, if these tests show that somehow it needs to be tweaked, you're practically throwing out funding that could otherwise go towards developing better candidates.
If funding for these projects is the problem, our society is even more short-sighted than I thought. We should be throwing money at them. I would be more worried about underlying physical constraints, like a shortage of manufacturing throughput.
Speculative production ramp-up must be part of the solution, as long as it's not binding equally or more important production capacity. But still, vaccines are hard because you can only test them on the healthy. But treatment drugs, their development scales with desperation. If patients with beginning pneumonia symptoms could be sent home with a drug that would put them on a painful but safe path to recovery and that drug was available at scale, concerns about medical capacity would be pretty much gone and you could basically "brit it out" the hard way. My money would be on scaling treatment candidates, not vaccines.
You do need to test them on the healthy, but there are a lot of healthy people who know they are going to be exposed to the virus in the coming months because they are part of the response. It should be relatively easy to recruit from that pool and given their increased exposure would require fewer people to see if the vaccine is effective.
But do we want healthcare workers, police and members of the fire service to be the ones taking the experimental vaccine? Short of students going to parties and getting drunk, most of the people at high risk of getting the virus are high risk because their occupations are essential. Probably not the population we want to test vaccines on right now.
Depends on what the expected risks are. If the expected risks are worse than the virus, then yeah, probably not a great idea, but if the most likely downside is just that it doesn't work...
Also, testing is not large scale. The whole point is to do it in a small amount of people who are already at risk of infection.
If there are about 100k infected in the US today and this number grows 10x per week, we are 1 month from the entire country being infected. With 20% requiring hospitalization, it will be a blood bath. There will be nobody to benefit from this vaccine.
The rate is increasing, it's slightly worse. It's looking really really really bad. The vaccine's purpose will be to stop this from happening yearly for the rest of human history.
At least in the US, there's a policy of 'creating' a market for vaccines for these potential outbreaks in order to incentivize industry to research and produce them.
"Public health officials say it will take a year to 18 months to fully validate any potential vaccine."
That makes a lot of sense for a vaccine against, say, chickenpox, or anything else that kills a hundred or a thousand people a year. For something that, at a 3% fatality rate, is about to kill nine million people in this country alone, it's suicidally slow.
If you can prove it will save more people than it will kill, yes. That's difficult when you have to prove a safety margin of 99.9%. Proving a safety margin of 97% is much faster.
You say that until the vaccine is given to everybody and turns out to cause lung failure a year latter in 10% of the people who go it - thus killing 30 million people in this country alone.
I don't think we'll give the vaccine to everybody. Well, a few years from now probably, but for this particular pandemic we'll target vulnerable populations (elderly and sick) and professions at risk (like health care).
Have you actually checked youtube comments in the recent months? The algorithms seem to be changing a lot and the top comments for most videos are actually very on-point, positive and non-abusive, even if somewhat skewed towards fun content and jokes.
If you watch the Viking video clips from the NASA office and see the group of nerdy 70s people who got us to space... you start to appreciate that it’s not always a uniform species for
inspiration, the crossover with the lowest common denominator is less interesting in practice, or worrying. Something I dont always remember every time I come across popular threads on Twitter and want to claw my eyes out. (And yes I know you’re joking.)
It has always been the case that 1% of humanity pulls the other 99% forward. We do not need everyone to be a genius. We just need one.
We do not need everyone to be Martin Luther King Jr. or Gandhi, or Michelangelo, or Bach or Einstein, or Shakespeare, or Newton or Galileo we just need to be smart enough to recognize when one of them is born amongst us. We've not always been good at that.. but we've been getting better at it.
> It has always been the case that 1% of humanity pulls the other 99% forward. We do not need everyone to be a genius. We just need one.
This is such a ridiculous hero praising statement. It's also completely wrong.
While we love to hero worship, none of these heroes worked in isolation or without correspondence with others. Be it their teacher, peers they were having letter relationships with, their partners, their students or other people.
You are entitled to your opinion, but I think you misinterpreted me there. I didn’t claim that they worked in isolation or accomplished it on their own. I was simply pointing out that the work, knowledge and understanding by the very few have always benefited the many. Look at the parent comment and you will understand the context.
It seems that the '1%' is symbolic, though. Just a round 'very small' number that sounds nice. Probably way less currently, orders of magnitude less.
It seems that the proportion of ground-breaking individuals is less a function of population than of the state of things. Meaning, it doesn't matter how many are trying if there are only ever X slots available for 'greatness' at a given time. E.g. when one Musk or one Gandhi arises, a thousand others might have just missed that spot for this life.
At the very least, there is a relation between the two — pushing population to extreme numbers obviously increases the number of exceptional individuals because there is more need; but I see a rather linear bottleneck here, whereas context dictates a lot of what you can and can't do. In that sense, the greatest are the most adaptive (evolution-style, applied to civilization), they find the 'correct formula' to solve in their own space and time. And execute on it.
I think it's more of a “few thousand people” worldwide at any given time in recorded history, maybe 10x or 100x more today than in Ancient times but... nowhere near the population growth ratio.
Obviously, it's all just my subjective perception. I could be so wrong it's actually not-not funny to think about it... ¯\_(ツ)_/¯
Individual doesn't need to be "ground-breaking" to push humanity forward. Just pushing a little bit helps as well. I think that for instance even majority of postdocs (in useful areas of studies) and significant part of open source developers pushes humanity forward. On individual level it might not be very significant, but take millions of such little pushes and it becomes huge.
That's what we'd think intuitively, but not what's demonstrated empirically in reality, history.
It seems that at some point, it takes more of us to crack the same amount of "scientific difficulty" as it were — hard to be a lone genius typically these days.
I don't know. But you definitely speak of a bias that I had and got almost unequivocally debunked by a colder, more statistical (retrospective, empirical) than logical perspective (models, thought experiment). I personally trust the former more ('facts' in layman terms).
It's not the same amount of scientific difficulty though. Low hanging fruit (relatively speaking) was already picked. Impact of even greatest geniuses toady is miniscule compared to geniuses of yesteryear. Andrew Wiles', Grigori Perelman's and Terence Tao's impact on humanity is not even one thousandth of Leibniz's.
It's pretty much just a tautology (which can't even be false). Of course it's true that only a small minority of people will ever have a major impact on many other people.
None? More research needed to discover Isaac Newton's buddy to whom we evidently owe so much. Then we can get to work on Proust, Emily Dickinson, Michaelangelo, Kubrick, Thoreau and Nietzsche. All presumably unfairly taking the fame.
It's actually quite a hard task. You'd have to figure out who - if their name had not been on the credit roll - would have made the difference between the movies being as good as they were and much less good. Talent isn't fungible, and great talent can make all the difference. Great talent still needs to be supported, so that's where the remainder of that credit roll comes in. But the third gaffer likely could have been anybody and the movie would have come out the same.
I agree. Everyone looks to the captain of a ship (Jobbs, Bezos, Obama, Armstrong, Trump) and they forget about the hundreds or thousands of people who all worked to actually make and implemented the things to make their voyage possible.
I was thinking about that fact yesterday, when I pondered on my disgust at people looking in my shopping cart, and one person telling his wife they should also buy tea.
I'm probably a bad person for feeling that, but I just wanted to punch the guy in the face, because I'm sure people like him buy all the toilet paper.
Then it dawned on me that if you can't be smart and innovative, evolution-wise, at least be nosy, insidious, envious and without scruples.
Let the 1% bright humans get you out of your mess(like elect Xenophon your leader in times of crysis) then strike them down once the danger has passed.
I worry that headlines like this will lead to complacency amongst certain parts of the population.
They'll think a vaccine will be here soon.
I imagine their thought processes would be like: what's the big deal with this virus, why do we need to mess up the economy by social distancing, if we're going to have a vaccine quite soon?
I don't know how you can look around and seriously worry about complacency right now. Yes, complacency is very bad, but so is panic. We need to find a healthy, productive middle ground. A trip to my local grocery store is all the evidence I need to confidently say the pendulum has swung too far the other way.
People are exhausting our supplies of essential hygiene products and cheap, non-perishable foods. Scalpers are re-selling the supplies online with huge markups. Hourly workers are loosing their incomes and parents are struggling to find means to take care of their kids who are suddenly without school for the foreseeable future.
We need public awareness. We need people to take this matter seriously. But we also need a balanced approach to ensure we don't cause even more devastation in the long term.
Frankly, I'm happy for anything that gets people to calm down for a second and just commit to good hygiene practices and avoiding crowds for a few months.
Complacency and panic aren’t the only two options.
Complacency is a massive problem right now. So many people are not taking social distancing seriously, and it’s going to have disastrous consequences, al la how things are currently playing out in Italy, in many countries.
And compared to that, the temporary exhausting of supplies is a trifling matter. (Wait until the real panic sets in when hospitals can’t keep up). But like I said, it’s not like we have to chose between complacency OR panic. We can take it seriously and take appropriate actions.
Unfortunately a vaccine is unlikely to work. This is probably being done more for optics. This virus likely has Antibody Dependent Enhancement. Same reason there's no vaccine for SARS or MERS. It's 4am and I should be sleeping but there's a paper floating around where a bunch of SARS candidates were trialed on multiple species. In ever case immunity was conferred but upon re-exposure the animals had autoimmune lung damage.
This virus is far more dangerous than most people understand now. The news media has been a month late in everything since they started reporting because all of this is evolving too rapidly to confirm to journalistic standards. You have to dig for this information yourself.
I disagree that this is being done for optics. Conspiracy theories rely on people being much better at keeping secrets than we know they are.
There does seem to be some evidence that other Coronaviruses may exhibit ADE but it's important to note that ADE is not well understood and that many viruses seem to display it in-vitro but non in-vivo.
In particular, vaccines and monoclonal antibodies targeted at SARS spike proteins seemed to cause ADE in some experiments but not in others.
There has also been at least one paper that speculated that the virus was deadlier in China than South Korea due to pre-existing exposure of the population so similar Coronaviruses and ADE cross-over from them. This was before the big spikes in mortality in Iran and Italy which would be pretty strong counter-evidence to this hypothesis.
I think it is best for us to treat our both our species-level understanding and our personal understanding of immunology and epidemiology (assuming that like me, you are reading papers but have not spent significant pre-existing time studying this field) with an appropriate level of epistemic skepticism. I would be careful of making statements like "a vaccine is unlikely to work" unless you have a high degree of confidence in your own understanding of the state-of-the-art.
(I haven't downvoted you and would encourage others not to do so as that mechanism is intended to remove noise and not to signal disagreement)
> Conspiracy theories rely on people being much better at keeping secrets than we know they are.
Most people have no idea WHY they are doing what they are doing! Like the actual true long-term business objective of a task etc. Successful task completion usually requires only technical details and immediate organizational ones. Fake goals are easy to sell to investors and board members by expert manipulator sociopaths (the kind of people explicitly hired and selected for top executive roles).
You can make immense progress towards a goal you know nothing about. You can't leak a secret you don't know.
That's kind of how human societal evolution works, only the bigger goals are evolved/emergent instead of envisioned by some dark conspiratorial cabal. But you can't rule out the latter.
As a society we need to maintain some "immune reaction potential" against nefarious manipulation by entertaining unlikely conspiracy theories too!
I hate credentialism like this. It's anti-intellectual.
There are many smart people on HN who are perfectly capable of reading and understanding research literature in an area that is NOT their primary expertise, and who can make half-decent arguments and deductions.
Reply to the points he raises (if you can). Don't belittle him.
> There are many smart people on HN who are perfectly capable of reading and understanding research literature in an area that is NOT their primary expertise
Most of those people know that reading papers is far from enough to understand the issues at hand and making such stark statements. I've seen this issue a lot in HN: people who have no experience at all in a field, who think they are very smart, reading something on a paper or Wikipedia and then making these broad statements, specially without any sources. Intellectualism implies being humble and recognizing when one is not an expert in the matter, in order to avoid spreading misinformation and doubt.
>Most of those people know that reading papers is far from enough to understand the issues at hand and making such stark statements
Some of us people know that grad school literally consists of learning potentially exclusively from papers. These papers represent the cutting edge of human knowledge and for someone familiar with scientific literature they are not that hard to parse. Doctors and scientists are humans like you and me.
I'm not making policy here, I'm posting on a forum where unusually intelligent people from all disciplines gather and casually speculate on any number of topics. Though I guarantee at this point that I understand the problem at least as well as some 90% of our politicians...with or without sources.
> Some of us people know that grad school literally consists of learning potentially exclusively from papers. These papers represent the cutting edge of human knowledge and for someone familiar with scientific literature they are not that hard to parse. Doctors and scientists are humans like you and me.
Doctors and scientists are humans that, like you and me, spend years and years of study, practice and research on their own specific topic, with knowledgeable people by their side to guide, question them and answer their doubts. Parsing a paper is very different from actually understanding it, specially if you don't have the context they have.
> I'm not making policy here
You're right, but we have already enough disinformation as it is. We all have a certain responsibility towards not sharing unfounded statements in this situation.
> a forum where unusually intelligent people from all disciplines gather
HN is an echo chamber of programmers, mostly from the start-up world. A constant issue in this forum is programmers thinking that they can solve any problem (I still remember some discussions on sheet music that were extremely out of touch with actual music practice).
Also, "unusually intelligent"? Really?
> Though I guarantee at this point that I understand the problem at least as well as some 90% of our politicians...with or without sources.
Credentialism aside, there were no sources provided.
I do find the point about no SARS vaccine compelling, however. Is that true?
I know the flu vaccine gets updated every year or so with new viruses that are prevalent, so if there is no SARS vaccine then I wonder if that is true and if it is true it couldn't be developed.
Again, multiple things thrown out there without sources which are not common knowledge, followed by "you can look this up yourself".
I've only quickly searched, and to be honest it's a bit thick with foreign terminology for me to quickly glean much from it, but seems like this might be the paper the top-level commenter referred to:
Please don't tell people to do a search. If you're going to provide information provide sources, otherwise you're no better than Russian disinformation bots. This is exactly the kind of tactic they use. If you have a claim, provide a source. You are currently spreading unhelpful misinformation.
by your admission the person you are referring to is an engineer in a highly specialized field and is likely to be skilled at probabilistic inference as well as dissecting (certain types of) scientific publications.
I do have some special knowledge in biological research, from seven years of post-doc work at the Max Planck Institute for Computational Biology. We're the group that created the standard of care software for HIV treatment, and for a time we hosted the global influenza database. In other words, viral disease was a specialty of ours.
In my view, as someone with some high level expertise in the field, is that the original poster is correct in their assessment.
Oh my God yes I'm glad to see someone understand. Especially if you have a generalists background. ML is incredibly powerful because deep neural networks, as we're discovering, are extremely powerful, extremely general function approximators. We're inching toward a new type of mathematics.
I've been reaching out to prominent people and I'm getting interest in some kind of collaboration with funding. People are onto the tech and it's myriad applications. There's a reason ML engineer was ranked #1 be demand growth (300%) on indeed last year!
You don't understand. I am making this assertion as a former physicist. We have stumbled upon extremely general function approximators.
Effectively the same way that we can use equations to make inferences about reality - but because of the nature of mathematical notation and the limitations of human ability, though powerful, math has limitations. E.g. you can write out the idealized equations for heat propagation in a conductive medium, but solving them for a real object requires empirical simulation.
Deep neural nets are the next step. Now you can essentially train these neural networks to infer not just the general idealized behaviors, but specific details, discrete values for X and Y on a fine grid that are beyond the practical limits of applied math.
But this is much bigger. It turns out that, much in the way that idealized equations apply to many problems (e.g. exponential growth arising from diff EQ), neural nets generalize to all manner of real world problems, provided the training data is appropriately curated.
These neural networks excel at learning human like heuristics, with machine level precision. You can make inferences for both continuous and discrete probabilistic systems. This is a major development and it's just starting. We've finally assembled the pieces in the last few years.
I thought that no vaccine was developed for SARS and MERS because the diseases disappeared, so : not enough volunteers to test the vaccines, and also companies lost interest.
from an npr interview[1] :
BRIGHT: Unfortunately, when the virus disappeared, the funding tended to disappear with it. And the companies that were making a SARS virus vaccine lost interest and shipped it back to their more profitable vaccines.
Hmm... ADE shouldn't happen with natural immunity post-infection since the body tends to produce a cocktail of different antibodies and either some or the combo would have some virus neutralizing effects. But it's known to happen in-vitro and with vaccine generated antibodies (always less diverse than the ones generated naturally).
Natural-ADE shouldn't thwart development of a live/innactivated-virus vaccine though. But would immensely slow the dev of RNA or protein ones since you'd have to test through a lot of candidate variants until you find one that is not ADE-inducing...
Otoh, a population of naturally-immune survivors is a living library of antibody cocktails that are know to work. If I were more conspiracy-theory inclined, I'd say the UK gov. has knowledge along these lines and they are willing to sacrifice some of the gen. pop. knowing that (a) it will take a looong time to a good vaccine, so better for the economy if they get natural immunity faster than everyone else, also lots of arbitrage opportunities on international markets once they're first to recover, and (b) they bet their "living library" of good antibodies will maybe make them a leading producer of safe vaccines.
Now, if this COVID bugger does ADE with naturally induced immunity... that's BAAAD! Natural evolution would have no reason to optimize in that direction, and genetic lottery is probably not likely to produce this. You get the conclusion and geopolitical consequences... it's something something about that doomsday-clock striking a certain hour...
DISCLAIMER: I'm not an expert on the topic, or any other topic in general. Just another expert-generalist currently doing mostly software thinggies but having some old and rusty biomedsci background...
The virus is subsiding in China because they took massive preventative steps to prevent the spread of the disease. Not all countries are taking such extensive steps.
As far as I understand it, both companies use the same basic approach and are roughly comparable. But the issue, as soon as a valid working vaccine is found, will be production capacity: you cannot produce vaccine for 330mil people overnight; none of these companies can do that by itself. Hence securing eventually-needed production capacity has its value, especially if you need the vaccine to be broadly available before a certain election date happens, because otherwise you die a political death.
CureVacs vaccine can be produced in HUGE doses almost immediatly.
Their rabies vaccine CV7202 requires only two doses of 1 µg mRNA, and they hope to replicate that with the corona-virus. If corona needs approx. the same doses they claim to be able to produce billions of them soon.
I am skeptical of their 1mcg claim. The only way to get to 1mcg for an mRNA-based vaccine is through even newer and untested technology: self-amplifying mRNA, some undisclosed delivery technology/chemistry, or some undisclosed improvement to their adjuvanting technology. In general, they have been far behind Moderna and BioNTech for years, so I'm not sure we should be hitching our wagon to them.
This is their most recent clinical publication showing their adjuvanting technology (2019) https://www.sciencedirect.com/science/article/pii/S0264410X1... which in general is needed to make-up for their lack of potency in their mRNA vaccine technology. A problem neither BioNTech nor Moderna have with their mRNA and delivery technology.
What they don't say there is how long it takes to scale up and produce those "billions" of doses. I found documented claims of 10 million doses until this summer (https://www.chemistryworld.com/news/rna-vaccines-are-coronav...) with the existing production capacities.
I don't think CureVac's technology is the right choice, though we should fund everyone at the same time to scale-up at risk IMHO.
Moderna and BioNTech could scale-up to hundreds of millions of doses by EOY without expanding capacity. If the US and German governmetns really hit the gas, we could expand both companies manufacturing at risk and get to hundreds of millions doses in 6 months. Then, if the clinical trials look good, we already have the material ready to go.
That is probably the best approach: start manufacturing at scale as soon as the risk profile of a vaccine candidate offers a minimum of confidence for it to be working. And doing that with as many companies in the field as possible in parallel to increase probabilities of success.
As a retail investor living in Germany, this confirms my decision to put a little bit of money into Moderna stock. I would have done the same with CureVac, but they aren't listed at any stock exchange unfortunately.
BioNTech is also public (BNTX), so you should add some there too. But maybe wait for them to come back to Earth (up ~50% premarket from announcements!)
Thanks for the tip, will keep an eye on them. Though I wonder why they shot up 50-60% while Moderna keeps trading normally. It does appear from the outside as if both of them were comparable from a liquidity standpoint and also with regard to their progress towards a working vaccine.
They announced a collaboration with a Chinese company to start trials in April. So that news is the catalyst for the move. I am surprised Moderna isn't moving higher on news that they actually dosed, you know, a real live person. shrug the market seems to enjoy hating on Moderna. Oh well, they raised $500mil in January and are sitting on $1.9b so it doesnt' really matter what the stock does in the near/mid term.
Compared to Moderna and BioNTech, CureVac uses an older nucleotide chemistry, an older delivery technology, and a riskier adjuvanting idea. Both Moderna and BioNTech have GMP production capacity and process know-how to get this done in short-order. CureVac is a distant third place overall.
> The Welt am Sonntag story spoke to an anonymous German government source as saying Trump was trying to essentially buy the work from the scientists for a vaccine, “but only for the United States.”
Bareknuckle and self-interested as Trump's foreign policy may be at times, I have a hard time believing he'd go so far as to deny the world a vaccine for this, though I do see the sense in attempting to acquire promising research teams in order to avoid the overhead of multi-organizational collaboration.
If the last four years have taught me much, it's that anonymous government officials say a lot of things. I can't read German, does the original article do anything to validate this claim?
Unless there is a new set of information out there, there has been no confirmation on the exclusivity as part of the negotiation, only the outlandish statements of a socialist politician who is pushing for a top to bottom overhaul of the German health care system. The same sources have been getting a lot of the basic facts wrong (such as the company already being partly owned by the bill and melinda gates foundation, and a large portion of their research happening in Boston).
I suspect that this is the same xenophobia that is resulting in the same rumors floating around the US that China has a vaccine that they are denying the rest of the world.
Regardless, it might make sense to wait a bit for facts to come out.
In this case do you mean the world's xenophobia of the states? I find it hard to believe that this message somehow stokes the United States to xenophobic sentiment.
> "I have a hard time believing he'd go so far as to deny the world a vaccine for this"
It's hard to imagine anyone would think like that, but keep in mind that Trump sees everything as a zero-sum game. For him to win, others have to lose. If he's losing due to Corona, he assumes others are profiting from it somehow. That's probably where the hoax talk came from.
It's a bizarre and harmful way to view the world, but all evidence suggests that this is how he really thinks.
He's desperate to stay president, probably because next stop is prison (or maybe not, the rich and powerful get away with everything). I can imagine his thinking was, "If I can cure Americans, I can brag, 'I fixed the problem here first, no other country could manage a vaccine as fast as us!', and that will guarantee my reelection.".
As a non-USAian, I can really see that he doesn't give a shit about the rest of the world, because the rest of the world can't vote him to stay in or out of office, but can be used as a base for his performance, for him to brag "Look how I delivered".
> There’s no chance participants could get infected from the shots, because they don’t contain the virus itself.
So ... what's in the vaccine? Is it just saline? Without a viral load I don't think we could call it a vaccine in the traditional sense; if this is some crazy new technology that enables the immune system to process the virus without introducing some viral material, that's neat and all, but deserves some deeper explanation.
Many vaccines only use parts of the virus (such as proteins from the exterior of the virus). These vaccines can't cause infection because only certain parts of the virus are included, not whole viruses.
Why develop a vaccine for a disease that is now non-existent? We still have the research from that and that's why we already know about some of the workable treatments like HIV and Malaria drugs.
There's a number of Zika vaccines that have been developed years ago that still aren't close to regulatory approval.
SARS-COV-1 infected people for 2 years, then it was gone. There's certainly a chance that SARS-COV-2 disappears before a vaccine could make it to market.
Also - epidemics are tail risks. You cannot just leave them to the market to be priced on the expected value basis, that will leave them grossly underpriced.
> Why develop (a vaccine for a disease that is now non-existent?)
Unless there's somehow infinite amounts to spend on research that's not viable whatsoever and actively diverting away funding from more pressing needs.
> SARS-COV-1 infected people for 2 years, then it was gone.
As someone not well-versed in virology, would you know what happens to the germline the virus leaves permanently in the infected host? Or, am I drastically on the wrong line of thinking here when someone says the "virus has disappeared"?
> Why develop a vaccine for a disease that is now non-existent?
I think the idea here is since both SARS and Covid-19 are part of the coronavirus type, a vaccine for SARS would make modification and rapid deployment of a Covid-19 vaccine significantly better.
Really, any existing coronavirus vaccine would have helped research efforts tremendously.
> SARS-COV-1 infected people for 2 years, then it was gone. There's certainly a chance that SARS-COV-2 disappears before a vaccine could make it to market.
Highly unlikely. SARS ended up infecting an order of magnitude less people _in its entire 2 year run_ than Covid-19.
We will have this virus around for at least 5+ years, possibly forever.
> I think the idea here is since both SARS and Covid-19 are part of the coronavirus type, a vaccine for SARS would make modification and rapid deployment of a Covid-19 vaccine significantly better. Really, any existing coronavirus
vaccine would have helped research efforts tremendously.
do we know that's the case? It seems to me that the bottleneck is testing, which need to be done specifically for each vaccine.
- Sars-1 and Sars-2 (COVID-19) are related enough to bear the same name, thus having researched a virus for the former would be incredibly informating to finding a virus for the latter.
- As it stands, we know so little in that regard that we do not know if there is a possible vaccine for COVID-19. If I take an average between 3-10 years (the range of guesstimates floating around in some circles apparently), that's 2026-7 to have a definitive answer on that (it also depends a lot on the behavior of the virus, and we are only 10 weeks into this mess, we just don't know).
- human testing on Sars-1 may have been impossible or rather unethical, but models on animal species are just about the way we do it for everything all the time, so having a 15-year body of research + associated datasets would have been the reasonable, cautious thing to do. Having a vaccine for e.g. mice on Sars-1 available now would help a lot.
- There is no valid reason to have stopped Sars-1 vaccine research, especially given the fact that numerous experts were certain that new coronaviruses would cross again to the human race in the future (this is still true today).
- Because of all this, we are now forced to rush tests on "best guesses" for vaccines, with nowhere near enough data to make a really "educated" guess, far from the usual. Meaning, increased risk to the patients in those trials, but most dramatically for all: we have cornered ourselves into making moonshots in a hurry in the quest for a vaccine.
There is a possibility that we've gotten so good at molecular biology and modelling that we'll actually overcome these obstacles that we've created for ourselves, but the gist is that had we been a little more forward-thinking (including hoarding stocks for medical supplies, etc), the ultimate death count could have been orders of magnitude smaller, possibly anecdotal.
There is a valid reason to stop Sars-1: the researchers working on that could go on other other things. On hindsight we know differently, but there was no reason to expect this even 6 months ago.
Up until late January I was saying I want a vaccine for the common cold which was more impact on my life and something these researchers could switch to. (I'd like a better treatment to prevent heart attacks even more, but it is unlikely the researchers could switch)
> “there was no reason to expect this even 6 months ago.”
You might want to re-think that perception.
I've recently heard Ralph Baric, an epidemiology Professor from UNC School of Medicine[0]. He's arguably one of the world's foremost experts on the topic — which makes it easy to at least listen to the man, you'd think... Have a look at his publications:
- Dec 2015 ⇒ A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence.[1]
- Mar 2016 ⇒ SARS-like WIV1-CoV poised for human emergence.[2]
Few sentences from the abstract of the latter:
> Outbreaks from zoonotic sources represent a threat to both human disease as well as the global economy. Despite a wealth of metagenomics studies, methods to leverage these datasets to identify future threats are underdeveloped. [...] Focusing on the severe acute respiratory syndrome (SARS)-like viruses, the results indicate that the WIV1-coronavirus (CoV) cluster has the ability to directly infect and may undergo limited transmission in human populations.
I mean... What more is there to say?
You may listen to a (great but rather technical) podcast[3] featuring him, among other experts, and there's even a layman-friendly companion post made by a listener[4] (whom I fully credit and thank for sharing the knowledge).
Joe Rogan interviewed Michael Osterholm (an American public-health scientist and a biosecurity and infectious-disease expert). he mentioned that he can create a vaccine within 24 hours for the coronavirus. The issue is not creating a vaccine, its creating one that won't hurt the humans who have to take the vaccine. So it's vaccine-able in a general sense. We just have to make it consumable for human usage. Just pointing out this little nugget of information, not trying to start an argument.
I'm not sure we can wait 12-18 months... Everybody will have to put all resources onto this, because if the virus comes back in autumn, it's going to be worse according some predictions. Hope it's not tho.
Even during our darkest times, we're going to see the most remarkable science and engineering capabilities exposed in the coming weeks and months, for the sake of humanity.