Nobel Prize in Medicine awarded to Katalin Karikó and Drew Weissman
nobelprize.org
nobelprize.org
"Dr. Kariko’s struggles to stay afloat in academia have a familiar ring to scientists. She needed grants to pursue ideas that seemed wild and fanciful. She did not get them, even as more mundane research was rewarded. “When your idea is against the conventional wisdom that makes sense to the star chamber, it is very hard to break out,” said Dr. David Langer ... Leading scientific journals rejected their work. When the research finally was published, in Immunity, it got little attention. ... “We talked to pharmaceutical companies and venture capitalists. No one cared,” Dr. Weissman said. “We were screaming a lot, but no one would listen.[1]”
[1] https://www.nytimes.com/2021/04/08/health/coronavirus-mrna-k...
Almost every groundbreaking idea that surfaced went through a period of obscurity and dismissal.
So, its really difficult to judge a revolutionary theory. Crackpot theories are easier to judge however. They often have very provable falsehoods.
This is an interesting insight. Yeah, I think you are onto something here.
Groundbreaking ideas, as opposed to new technologies, tend not to have obvious real world applications/results for years. As such, they aren't easily distinguishable from random crackpottery.
We tend to validate ideas by their later applications, or, at the very least, a heap of corroborating evidence. Both takes a lot of time to aggregate.
Even if it was not easy pharmaceutical companies finally did invest.
No, it shows there are weaknesses in the government-funded research grants. But it is far from clear which other system would be better overall not just in this case.
We have learned a lot from experience about how to handle some of the ways we fool ourselves. One example: Millikan measured the charge on an electron by an experiment with falling oil drops and got an answer which we now know not to be quite right. It’s a little bit off, because he had the incorrect value for the viscosity of air. It’s interesting to look at the history of measurements of the charge of the electron, after Millikan. If you plot them as a function of time, you find that one is a little bigger than Millikan’s, and the next one’s a little bit bigger than that, and the next one’s a little bit bigger than that, until finally they settle down to a number which is higher.
Why didn’t they discover that the new number was higher right away? It’s a thing that scientists are ashamed of—this history—because it’s apparent that people did things like this: When they got a number that was too high above Millikan’s, they thought something must be wrong—and they would look for and find a reason why something might be wrong. When they got a number closer to Millikan’s value they didn’t look so hard. And so they eliminated the numbers that were too far off, and did other things like that. We’ve learned those tricks nowadays, and now we don’t have that kind of a disease.
There was some article a while back that talked about the fact that measurements from the oil drop experiment pretty much moved as the input data got better.
IIRC, the experimental value went in one direction, from Millikan's to the currently accepted value.
https://skeptics.stackexchange.com/questions/44092/is-feynma...
The linked SE question is relevant. https://hsm.stackexchange.com/questions/264/timeline-of-meas...
You clearly couldn't be bothered to put in even a minimal amount of effort to follow the citations that have existed for 12 hours prior to your useless post.
I will give your post as much consideration as you gave mine.
You cannot even realize how many people in academia are running for wild and fanciful ideas. Don't blame the scientists, they are probably the most open-minded to the new ideas. But filtering out bad ideas is a part of their job, and they grew thick-skinned from constant bombardment of fancy ideas, we cannot pursue them all.
So I'd say this story is pretty traditional in the history of revolutionary ideas (e.g. a similar story of John Snow vs. cholera -- how many years and lives it took).
The original article is gone!
Just an constantly evolving page that likely has things deleted for reasons other than accuracy (e.g., like narrative coherency).
Just write another article! Damn!
> On Monday, they were jointly awarded the Nobel Prize for Physiology or Medicine for their research.
And added "Long Overlooked" to the title.
Wiki tells me that she started publishing about mRNA in 2005. The first mRNA vaccine was not approved until Dec 2022. That kind of timeline is impossible for private investment to fund. It needs to come from gov'ts and non-profits.
She had a very interesting life, I hope she writes a memoir.
Edit: She has a memoir out 10th Oct: https://www.penguinrandomhouse.com/books/706251/breaking-thr...
i cant imagine how it must feel to have her own vaccine injected in her, and know she saved so many lives through her persistence and the rare few that believed in her through her lowest moments.
Some background: for many years, the flu vaccine has had what's called the "egg problem". The vaccine is cultivated in chicken eggs in a sterile environment. The US government pays billions every year to maintain these production lines. It takes about 4-5 months to go from choosing what flu strainsa are likely to be prevalent to there being a vaccine. The production line can't scale up quickly either.
Also, people who are allergic eggs can't generally take the flu vaccine. That's why they ask you.
For decades the US government has funded research to get away from this system and that resulted in the mRNA vaccine. It doesn't require chicken eggs to produce and the lead time for producing a vaccine goes to almost immediate. we saw this with Covid where the candidate vaccines were produced in days. This fed into conspiracy theories about it being unsafe because it was rushed but it was nothing more than the culmination of decades of research where fast vaccine turnaround was the entire point.
In future years we'll see mRNA vaccines turned to diseases that have thus far we've been unable to produce vaccines for.
> This fed into conspiracy theories about it being unsafe because it was rushed but it was nothing more than the culmination of decades of research where fast vaccine turnaround was the entire point.
That's one interpretation. I wonder if you'd apply that same interpretation to the first few viable aircraft. Surely flight was studied for millennia at the point that the wright brothers got their plane flying. Would you hop in and try to cross the Atlantic on one? Or would you fall prey to conspiracy theories that maybe they hadn't worked out all the kinks yet?
edit: I suppose I'm being downvoted for spreading Big Wheel's antiwinger talking points.
No, for an absolutely abysmal analogy.
How long have we studied the fountain of youth? The cure for baldness? Penis enlargement pills? Would you trust any of today's solutions to those problems?
Research time is necessary but not sufficient. What I and many others care about is time in production usage.
What's so abysmal about this line of thinking?
We don't seem good at knowing that it doesn't also cause Z, A, B, C, etc, and by the time you figure any of that out, the checks have already been cashed and spent.
I don't think lay folks being able to regurgitate some terminology says much. Lay folks could tell you that birds flap their wings long before we had controlled manned flight.
> This fed into conspiracy theories about it being unsafe because it was rushed but it was nothing more than the culmination of decades of research where fast vaccine turnaround was the entire point.
Some people want to count all of the research time that went into mRNA tech as part of its "age" as a technology, like when it was being first tested on mice, or still failing small scale human trials. Others (like me) start the clock at the point when it started being rolled out in people en mass.
That has nothing to do with conspiracy theories (everyone's favorite mental shortcut). It has everything to do with not wanting others foisting their risk calculus on my medical decisions. It was somewhat understandable when everyone was being blasted with the propaganda about killing grandma, but we should be clear now that it was never actually appropriate to be trying to force this thing on anyone, and that was one of the bullshit arguments used to do so.
This only becomes a problem try to rationalize their fears and make them seem logical. Again, if that's purely an internal struggle that's fine. But if your fear of flight led you to push policy and legislation to outlaw planes and airports using junk science about noise, pollution or safety then your fear of flyijng has become a problem that needs to be addressed. And you need to be ignored.
Which brings us to mRNA vaccines and the "evidence" of them being unsafe. Trust me when I tell you that what motivates you here is your feelings, not anything rational. I would strongly encourage you to figure out why that is.
Who said anything about that? Wrong thread maybe?
Perusing your comments confirms this pretty quickly eg [1][2][3][4][5][6].
[1]: https://news.ycombinator.com/item?id=37669756
[2]: https://news.ycombinator.com/item?id=37579999
[3]: https://news.ycombinator.com/item?id=37579906
[4]: https://news.ycombinator.com/item?id=37525788
Though I guess for the record since you're throwing labels at me, I am no such thing by any reasonable definition of the word. Keep fighting the good fight though.
I downvoted you for complaining about being downvoted.
About Dr. Kariko:
"But for many years her career at the University of Pennsylvania was fragile. She migrated from lab to lab, relying on one senior scientist after another to take her in. She never made more than $60,000 a year"
It's just a culture of self-improvement.
Improving involves blood, sweat, tears, and defeat. Only to come back ever stronger.
People in the 99th percentile aren't super happy and satisfied that they've outcompeted 99% of the participating population who look at them with awe and envy. They're comparing themselves to the 99.9th percentile who leave them in awe and envy.
I think it's important for any high performer to occasionally step out of their narrow perception of the world and really grok how far ahead they are compared to everyone else. This is definitely something a lot of my high income tech friends could learn to appreciate when they get caught up feeling like a loser for only making $250k total comp.
A (pre-Putin) Russian proverb goes it’s better to be first in the village, than it is to be last in the city.
Individuals focused on real discovery and not publishing much until they really have something significant to say don't fit into this well.
Charles Darwin, for example, was born into wealth and doesn't really need to work for a living.
Even ones that are not all that prosperous per capita achieve things like moon landings.
You can have the monarchy without being a colony - several former colonies do.
Basic science funding seems sparse though. Investments tend to favor commercial entities.
This is still true, although to a lesser degree, because everyone is much better off. 500 years ago, you could only pursue some things if you were born rich. Today, the field has greatly expanded, to everyone's benefit.
1. Government funded research
2. Private industrial research
3. Private personal research
Usually, those involved in #3 are made fun of constantly by the lumpenproles. Before someone in category #3 makes it they look like Bryan Johnson doing Blueprint. That's the defining characteristic, actually. If you were to look at Ms. Kariko before she was successful, the majority of HN users would have made fun of her.
I don't have any idea how to calculate those proportions, but it's an awesome puzzle.
And have their own internal politics - they want science that does not disrupt the VP/CEO's plans, or make the chief scientist look bad.
Hence patents. The new Hep C treatments are hundreds of thousands of dollars cheaper than older treatments, but were still researched and developed.
My point was only that (by the definition I think makes the most sense here) they are doing science to the exact extent they give up the intellectual-property monopoly, whatever that extent happens to be.
That does not mean that dissemination of new information has to work like it does now. The Republic of Letters was very different but quite successful. But if you have taken no effort to make your discovery available to others, I’d say you’re not advancing the cause of human learning; if you have taken effort to ensure it is not available, like what many patents aim for nowadays, I’d say you’re working against it.
On the other hand, those who at the same time were experts in, for instance, making shoes, made efforts to keep secret their techniques.
Fuck, even the head of the institution publicly announced that only quantity matters, not quality. Because the government funding for research also depends only on quantity.
Graduate school, MS at Harvard & MIT, PhD at UIUC.
Both my MS and PhD supervisors were brilliant and strongly believed in publishing only when they had something real to talk about, which I respected a lot. But it was clear this wasn't what the top professors were doing. They were running paper mills.
>> What fields in academia?
Elec engineering & CS.
>> Do you work there or have friends there
I don't work there, although I was offered several positions. This culture is pretty much why I chose industry. In the real world, most customers care about real achievements.
Lots of friends, yes.
Obviously, you then only get very incremental, low-risk, low-reward research, but high-profile scientists who mainly serve on the committees at the NIH and dole out funding get to keep their small business (err, I mean lab) going with minimal disruption in funding.
https://www.theguardian.com/science/2013/dec/06/peter-higgs-...
Institutions also often don't recognize researches that end up going nowhere. What we can say is that finding a gem is hard because of abundance of noise.
Unlike industry, where there’s no internal politics and everything is merit-based.
I know it's a dumb cultural cite, but I keep thinking of the "12th man" scene from the movie (book too?) "World War Z". The Israeli is explaining that his job is to disagree with the consensus. Just in case. Who is then given charter and resources to plan accordingly. Just in case.
I hope there's many buckets of research funds. With a modest bucket for long shots. And perhaps a smaller bucket for loonie tunes. Where by formalizing that model would preempt all the reactionary "omgherd golden fleece!?" outbursts.
As a taxpayer, I'd be thrilled if researchers, artists, journalists, musicians, and misc crazies got some kind of UBI, to do their work without starving. Considering the scale of all the usual waste and pork, genius grants wouldn't be more than a round-off error.
With a payout of 1:1000, it'd be a bargain for society. Smartest investments ever.
Kariko had a PhD from Hungary, was a post-doc at Temple U. - not an elite pedigree. At Penn, an elite school:
"It was a low-level position, research assistant professor, and never meant to lead to a permanent tenured position."
and after that boss left,
"Dr. Kariko was left without a lab or financial support. She could stay at Penn only if she found another lab to take her on. “They expected I would quit,” she said.
Universities only support low-level Ph.D.s for a limited amount of time, Dr. Langer said: “If they don’t get a grant, they will let them go.” Dr. Kariko “was not a great grant writer,” ...
Kariko was slotted into the non-tenure / adjunct role, and it didn't matter what they did. It happens in private industry too. The problem is elitism overlooking talent and production. It's a brazen, obvious flaw.
The US long had the culture - imperfect, of course - of an active rejection of elitism, class, etc. 'All men are created equal', 'every man a king', meritocracy, hard work, you can accomplish anything if you work hard enough, the land of opportuity, the American Dream, etc. That equality, the respect for others, is the foundation of voting - you respect everyone's right to have input and its value.
The dominant fashion, a sort of neo-reactionaryism, is to reject that, deride it, rather than aggressively moving it forward. Many people look for ways to justify prejudice, to exclude, to embrace personal ego and greed and to mock public good. I think that's because if you embrace universal rights, opportunity, equality, etc., you can't avoid 'liberal' ideals too, and those are the target of reactionaryism.
What really matters is if the elite is closed or relatively permeable, and how it treats the non-elite.
What the founding generation of America rejected, was inheritance of elite status, but I don't think they were completely egalitarian either. After all, people like Jefferson and Washington were highly regarded by their peers.
You could also ask, 'is there any elitist country out there?'. There is no perfectly elitst or non-elitist. The differences are matters of degree.
Some countries have castes and royalty that last forever. Others at least advocate social mobility and work at it.
> people like Jefferson and Washington were highly regarded by their peers
'Highly regarded' and elitist are very different.
I particularly enjoyed the unreasonably effective antivirus bypass achieved by slight modification of the payload by introducing pseudouridine (Ψ), which the antivirus had never seen before and therefore ignored. Such a bypass definitely deserves a Nobel Prize!
mRNA tech is just cutting out a lot of cruft and mass-producing and delivering tiny mRNA strands directly.
Edit: I stand corrected.
mRNA/viral vector/attenuated all involve some degree of "code execution."
Yes they do. They are live viruses, and they attack cells and hijack their protein-making machinery for making more viruses. But the attenuated vaccine viruses are not capable of causing a severe disease, so in time the body's immune system cleans them out.
The real question is now: When will it be used in doping? Honestly, I suspect it might be already.
Not the other way around...
I often wonder if, as a lay person, I would be capable of understanding the significance of really technical papers like this if I were to randomly start reading. Probably not without the right foundation.
I read this as an undergrad and had a blast (inside joke lol). I am considering starting a YouTube channel explaining such breakthroughs while going through the original research. If you’re interested I’ll ping you as focus group when I have some!
This is an example where even citations fail to recognise significant papers.
The Doudna Charpentier paper, by contrast, has been cited 17k times and publishes only 12 years ago.
As a fun exercise, the journal immunity should provide the reviewer comments to see how things have changed in light of 20 years.
Like a recruiter rejecting screening you out without an interview.
basically a judgment call by the person in charge of a journal that the paper is not interesting or impactful enough to warrant going through with the rest of the review/publishing process
on the other hand you have the pay-to-publish journals that have a financial incentive to push as many papers through peer review -- these thrive on sub-par papers that are technically just barely 'good enough', but the upside is that the real good ones will also make it through. however, they inevitably face reviewer fatigue, and the most valuable ones will quit reviewing if they often send them low-quality papers. so basically once in a while they'll publish top notch research without being aware of it.
i'm not aware of any middle-ground solutions out there and it certainly feels like a tough problem to solve.
Imagine a world where all papers start their life as preprints. Researchers read these preprints (like arxiv) and comment on them (like PubPeer). Journal editors then search for the best papers (or hear via word of mouth within their field) and journals compete for the rights to publish the most interesting papers. When an agreement is reached, the journal organised reviewers and asks for any changes to the paper.
I may be missing something critical but I dream of a day when the actual people producing academic output have power over journals who produce nothing but fees.
Historically journal controlled peer review didn’t exist and science still progressed perfectly well.
I do suspect that this would strengthen the winner-takes-all dynamics in academic publishing. Like whoever has the biggest twitter following gets all the attention, then gets Nature and Science competing for their paper, which allows them to get funding to hire a publicist, who increases their profile.
In my utopia, publication success would be driven by interest within a field which means lesser known researchers who haven't had breaks in high impact journals are more likely to break through, because the community acts as the gatekeepers, not a small group of journal editors.
The couple are billionaires, so I'm sure they're doing just fine, but that's gotta hurt to be overlooked for such a major prize when they did so much for that discovery and technology.
I worked in a lab with “Nobel winning lineage” and the ego fights always come up so I get kind of tired of it coming up lol. Sorry I responded so harshly.
You might not believe this but I actually forgot to put on my nicotine patch this morning.
Personally, it seems like everyone's contribution is important, but we as humans irrationally want to point to a single thing/event/team and say "this was the cause" rather than stand back and notice how interdependent the whole thing is. In the end I think things like Nobels are pretty silly.
But the original discoverer of CRISPR, Francis Mojica, was not awarded the prize. That's because, in my opinion (as well as the Nobel Committee), Doudna and Charpentier played the greatest individual roles in the process of turning the original discovery of CRISPR into a powerful tool (CRISPR/cas9), that is much more general than CRISPR the process that occurs in bacteria. I still think Mojica should have been given the prize, and if 4 recipients were possible, also Zhang.
[1] -https://genotopia.scienceblog.com/573/a-whig-history-of-cris...
Yes, Robert Malone could be seen as initiating the journey in 1987 [0] but there are a lot of landmark contributors who refined it to the mass-produced mRNA platform of today.
As with other Nobel Prizes, it is a far outdated award of the late 19th/early 20th century in which honoring single individuals made some sense.
In today's scientific enterprise the high-frequent collaborative effort of different teams all over the world is the norm, so over time it becomes pretty hard to single out individual scientists.
The prize winners of today are just widely recognized representatives (and therefore mostly older folks) of a particular successful scientific endeavor so that the public can still relate to the achievements via a personal story what would be otherwise a history lesson involving a lot of important people - and in this case I think Karikó's extraordinary perseverance throughout her science career fits this bill very well without ruffling up some too many feathers.
I wonder if she would have survived today’s even more competitive academic environment. If not then we must wonder how many future Karikos have been silenced by our current academic system.
>Using an event study approach and data from 43 countries and all U.S. states, we measure changes in excess deaths following the implementation of COVID-19 shelter-in-place (SIP) policies. We do not find that countries or U.S. states that implemented SIP policies earlier had lower excess deaths. We do not observe differences in excess deaths before and after the implementation of SIP policies, even when accounting for pre-SIP COVID-19 death rates.
In 2020 it clearly was higher. Denmark, Finland and Norway avoided the spring 2020 death wave, whereas in Sweden mortality was 20% to 50% (well, 48%) higher during the weeks of April and May 2020.
https://ourworldindata.org/grapher/excess-mortality-raw-deat...
https://ourworldindata.org/grapher/excess-mortality-raw-deat...
https://ourworldindata.org/grapher/excess-mortality-raw-deat...
https://ourworldindata.org/grapher/excess-mortality-raw-deat...
After the first two devastating waves during the Spring and Autumn of 2020, Sweden in fact 'locked-down' in some ways more restrictively than our nordic neighbors - all of which made timely interventions that meant their restrictions on meeting en-masse in public were for shorter periods and less intrusive on people's everyday lives.
The narrative that it was a 'free-for-all' in Sweden has been fostered retrospectively by neo-liberal groups that placed economics above human lives. In their eagerness to be 'proved right' after the fact, most Swedes now embrace this historical revisionism.
The statistics that show that Swedish "excess deaths" were low or even lower than other countries were cooked-up by a journalist from a right-wing newspaper in Sweden (SvD), who noticed that if one discounts the downward trend in excess death for the last 25 years in Sweden, together with dispensing with demographic weighting, and then averaging the 3 years from 2019 onwards (which includes the period after vaccination), then miraculously you can squeeze the numbers you want from the raw figures.
If you go to:
https://ourworldindata.org/covid-stringency-index
take away the default countries, and instead add Denmark, Finland, Norway and Sweden.
Then make sure you also click "Align axis scales" you will see that Sweden only had fewer restrictions than its neighbors during a very short period at the beginning of the pandemic (during the first wave).
After that, Sweden had both more stringent restrictions than all its neighbors, and had those restrictions in place for a longer period of time.
The narrative - the historical revisionism, the myth that a very large number of people want to promote, and which has even become some sort of amnesiac 'reality' for many Swedes - should not be mistaken for what really happened.
/edit I actually found this in my bookmarks fyi: https://archive.ph/7y7gF
But Tegnell is the architect and main proponent of the historical revisionism that I'm talking about. He is the man at the center of the controversial policies.
Even while they were being enacted, Sweden was fed a narrative of exceptionalism by Tegnell and the mainstream media, who never mentioned the comparative liberality of the other Nordic states' policies, and maintained the fiction that we were still following the most liberal strategy (even to this day).
Tegnell is massively popular in Sweden. In fact, as deaths accumulated and it looked more and more like he was following a disastrous path, his popularity increased exponentially.
Criticism or even mildly questioning Tegnell was (and for a large part, still is) totally off-limits: there is absolutely no way I'd mention my doubts about him or his policies to my fellow Swedish colleagues or friends.
edit: Incidentally, for those who can read Swedish (or use Google Translate), this series of contemporary articles is a really great overview of the events in Sweden seen from a skeptical perspective:
https://floderochtekoppar.blogspot.com/2021/09/sveriges-hant...
And yes there is definitely a weird "Swedish exceptionalism", which interestingly Swedes from all sort of political persuasion exhibit.
None of the international discussions about restrictions has been about restrictions around elderly care. Sweden did actually issue some, which some described as prison-like for those impacted, but that was about a year into the pandemic. It was also seen as too late, with vaccine and proper staff/gear/protocols being more effective tools.
Sweden had negative excess mortality from Jan 2020 to Spring 2021, so fewer people died than expected in this period. These COVID waves just weren't devastating in any way, and yielded virtually no deaths "of" and not "with" COVID. It's strange that you are so convinced that Sweden's data doesn't disprove the effectiveness of lockdowns...
> neo-liberal groups that placed economics above human lives
Ah, I see.
According to this, Sweden had quite bad excess mortality in 2020 in April and May, and some in June. And then again from mid-November 2020 to mid-January 2021.
https://ourworldindata.org/grapher/excess-mortality-raw-deat...
There are many different ways different sources have tried to estimate cumulative excess mortality. Depending on the calculation methods, different sources have ended up with quite different results.
What is your source, and what method did they use?
It can be debated what model should be used and governments don't always have consistent methods of baselining. With different models you can compute some excess mortality in Sweden but those have their own flaws.
But it's worth calling out here that the reason you have to dive into the details of what precise baseline model you use is because the number of deaths was so very tiny on the scale of a country. A simple graph showing the absolute numbers puts it in perspective:
https://www.statista.com/statistics/525353/sweden-number-of-...
Alternatively, a graph of deaths per 100k people shows how surprisingly normal 2020 was in Sweden:
https://i0.wp.com/swprs.org/wp-content/uploads/2023/04/swede...
It looks initially dramatic but that's only due to the massive drop in 2019. In reality 2020 had the same number of deaths per pop as in 2015! Nothing special happened in 2015.
Given that 2019 was an abnormally low year, 2020 would have been a bit higher than normal anyway even with no pandemic. But we're still looking at numbers pretty much within the realm of normal variance. If somehow you'd never heard of COVID, then someone had shown you that graph and asked "did something catastrophic happen in this decade" you'd probably have said no. Although 2020 is a bit higher, it's on the order of a few thousands of people, not something you could have noticed in a country of millions short of saturation-level media coverage.
That's why it's hard to say but important to hear: these levels of death simply do not matter. How do we know? Because some countries have had high and persistent levels of excess death since the end of the pandemic, but as COVID isn't the explanation hardly anyone cares. There's just no link between levels of death and severity of reaction, in our society.
Many European countries have an ageing population, and thus the number of yearly deaths increase year to year. For example Finland in 2010–2019 had about 0.8% increase in yearly deaths every year. If the deaths followed this model and thus there was absolutely no excess mortality (and no random variation), the simple method you cite would compare 2020, 2021 and 2022 to the average of 2015–2019, and would estimate 2.4%, 3.2% and 4.0% excess mortality for years 2020, 2021, 2022 for Finland.
Whereas Sweden doesn't have an ageing population structure, due to lots of immigration in the past 20 years. And Sweden didn't have an increasing trend in yearly deaths in 2010–2019.
This simple method overestimates the excess mortality for many countries, if they have an ageing population structure. Then you end up comparing overestimated values to Sweden's value that it not overestimated.
I'm happy to grant a different baseline though. It goes from being a really small number to a really small number. Remember that everything that happened was justified by claiming a 3.something% IFR and 100% infection rate in a single giant wave. That never came close to happening and the places that used very light touch approaches had no different outcomes to places that went full totalitarian. That's the important thing here.
Many factors: different demographics, population density, culture, what does "locked down" mean in different countries / areas, what does "significantly higher" mean...
One important point though is this probably confuses correlation and causation. Areas that were hit harder tended to lock down harder.
> Overall there's no evidence that lockdowns actually reduced mortality
People post this occasionally, and I'm going to keep calling bullshit. What happens is someone posts a fringe paper that supports their view whilst conveniently ignoring the large body of established scientific orthodoxy that supports the obvious conclusion: that restricting human interaction slows down transmission of a respiratory disease that transmits through human interaction.
I must admit this belief mostly comes from the claim Sweden did better, and the fact that where I live had almost no lockdowns and did better than the rest of my country.
Do you know of any good evidence that lockdowns were effective, or are you calling bullshit based on intuition?
Lockdowns were absolutely harmful - I don't think anyone is claiming otherwise. They were effective in stopping health systems collapsing, which is why pretty much everywhere implemented them when it looked like their health systems were about to be overwhelmed. (cf Italy in early 2020). That would have been catastrophic compared to the harms of lockdown.
In terms of suicides specifically, the evidence is not clear. I've seen studies that indicate suicide rates did not increase or actually fell during the pandemic, e.g. https://www.thelancet.com/journals/eclinm/article/PIIS2589-5... . There were also fewer deaths from road traffic accidents etc. However, there were lots of other harmful effects such as secondary effects from the economic impact.
> Do you know of any good evidence that lockdowns were effective, or are you calling bullshit based on intuition?
There have been a number of studies concluding that lockdowns were effective. I doubt digging them up will convince any of the sceptics in this thread.
But since you ask... how about this Royal Society report? https://royalsociety.org/topics-policy/projects/impact-non-p...
Are there any particular papers in the report that you think are evidence that lockdowns prevented health system collapse and were beneficial overall?
I had a preliminary skim of it and decided to check the first relevant citation for lockdown effectiveness. It has the same problems as most of the studies I have seen: it does not include any of the second order effects. Of course virus transmission is reduced by limiting interactions but this is only one part of the story. This may be answered in some of the other references but I need to put it aside for now.
It's three years later now and the numbers are in. There is plenty of high quality data from all Western countries.
However data driven policy decisions should be much more fine grained than that. We should instead identify specific situations where different type of lockdowns would make sense.
But the data is clear. Prolonged periods looks bad, at closing schools were clearly the wrong decision on every time scale.
What made a difference in Sweden was that vaccination rates were really high and they were administrated quickly.
Had the anti-vaccine ideas spread more Sweden would be much, much worse off.
I could cite the most objective sources and statistics, but if you haven't figured it out by now, you don't want to. You're on the level of flat-earthers. The only difference being there's way more of you than of those idiots. And if you think the number of people believing in something somehow gives it credibility, then you should start preparing yourself to meet Allah in the afterlife.
Brief summary:
Goal of vaccine is to get antigens in body in order to stimulate immune response to antigen, ideally at a lower risk than via infection from associated pathogen.
- "Traditional" vaccines inject a dead or weakened pathogen. Protein subunit vaccines inject just the antigen(s). Antigen directly put in body
Both mRNA and viral vector vaccines, however, are genetic vaccines. Rather than injecting your body with the antigen directly, they inject your body with code (mRNA and DNA, respectively), with the goal of having your own body produce the antigen(s).
- mRNA vaccines deliver a snippet of mMRNA via lipid nanoparticles to your cells' cytoplasm, where your ribosomes pick it up and produce and express the antigen themselves
- viral vector vaccines deliver a snippet of code via living virus (in the case of COVID vaccines, a living adenovirus delivering a DNA payload) to your cells' nucleus, where your cells reads the DNA, produces mRNA in your cytoplasm, after which it behaves the same as the mRNA vaccines
Basically, both the mRNA vaccines and viral vector vaccines are genetic in nature and rely on delivering code to your body rather than antigens. The analogy I've used before is that traditional vaccines are SSR, and the genetic platforms are SPA. I'm just curious as to why mRNA as a platform has been so much more hyped than the viral vectors; they're novel in fundamentally the same exact way.
But my question is more related to the pop-science perception of mRNA vs viral vector. mRNA were presented as new technology, but on media publication after media publication, the viral vectors were presented as the "old"/"traditional" way of doing things. 9/10 people have that understanding of the mRNA vs vv vaccines. The truth is that both are radical departures from existing technologies and they're both genetic platforms very similar in nature, and both completely novel being deployed at this scale.
One is that the mRNA vaccines were brand new, while VV was old enough that most people have already taken a few shots using it. The media has a very non-linear response to novelty.
Another one is that the most profit-seeking laboratories were working with it. And they are the ones with closest relation to the media.
Finally, it may be some reflection of the experts hype. People were very rationally hyped due to the lack of restrictions, easiness to ramp-up new vaccines, and the bare beauty of the idea. It's possible that journalists perceived that, even if they couldn't understand or explain the reasons.
In particular, the delivery of the mRNA payload is done via lipid nanoparticles that are not in any way targeted to a specific cell type.
The European Medicines Agency released a report on the distribution of the mRNA found in various organs:
https://www.ema.europa.eu/en/documents/assessment-report/spi...
> "Besides injection site [muscle] and lymph nodes [proximal and distal], increased mRNA concentrations (compared to plasma levels) were found in the spleen and eye. Both tissues were examined in the frame of the toxicological studies conducted with mRNA-1273 final vaccine formulation. Low levels of mRNA could be detected in all examined tissues except the kidney. This included heart, lung, testis and also brain tissues, indicating that the mRNA/LNP platform crossed the blood/brain barrier
A similar 2017 study was conducted using mRNA coded for luciferase as a tracking mechanism:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5475249/
And it, likewise, found the protein was produced in the muscles, lymph nodes, spleen, liver, heart, bone marrow, kidney, lung, stomach, rectum, intestines, testes, and brain.
One of the main draws of using the lipid nanoparticle as a delivery mechanism for other payloads in the past has specifically been that the lipid nanoparticle can readily cross the brain-blood barrier (BBB). And the EMA paper/quotation referenced above seems to verify that this is, in fact, the case.
A question that both platforms have to contend with is: "what, if any, risks are associated with having your cells producing and expressing a pathogenic antigen that your immune system is to identify and attack?" But one that the lipid nanoparticle delivery system has to contend with is the same question, but in the context that it has very little differentiation WRT where it is going to be deployed and expressed.
With the viral vector vaccines, the delivery mechanism is a living virus, and has much more predictable infection pathways. For one, our bodies have millions of years of evolution for dealing with viral infection, and particularly safeguarding the parts of our body least desirable for infection. Viruses have a very hard time crossing the blood brain barrier, whereas lipid nanoparticles do not.
There are, meanwhile, concerns associated with the viral vector vaccines which are not associated with the mRNA vaccines, but I've yet to see this sufficiently addressed as a major shortcoming of the mRNA platform. Targeted delivery is a very important topic in the world of gene therapies, and seems to have been completely neglected in the available platforms.
E.g. the target patient might already have a good immune response to the vector hull. I.e. the patient's immune systems would destroy the vaccine before it can do its work. One of the vector vaccines against covid did use two different vectors because of that. But repeated usage of the same vector might decrease its effectiveness.
"Producing whole virus-, protein- and vector-based vaccines requires large-scale cell culture. This resource-intensive process limits the possibilities for rapid vaccine production in response to outbreaks and pandemics."
Lobotomies also won the Nobel Prize because they were a cultural phenomenon of the day. JFKs sister got a lobotomy.
So even if these one and a half year old treatments prove to have significant long-term side effects there's still the recognition of the cultural and historical significance.
I wish I’m alive to see the day when we have cheap DNA compilers and molecular assemblers. Design in CAD and a machine grows it out from a mixture of molecules in water.
That's even more crucial when you're trying to vaccinate literally billions of people. Even for extremely safe vaccines (like these are), very low percentage bad outcomes can mean a lot of people willing to sue.
Billions of people also means a lot of cranks willing to call conspiracy theories in a lot of jurisdictions.
But leaving aside pragmatics, you're assuming that the manufacturers wouldn't be liable. If they'd e.g. hid bad results from some study, they'd presumably still be criminally liable.
Like, pretty much everything has some side-effects, and if (for example) you have the choice between doing nothing and having a million people die and doing something for which everyone is certain that that will save that million people but on average might kill ten other people, then asserting liability effectively means saying that you shouldn't do that thing, because you won't be liable for the former million deaths but will be liable for the latter ten ones. So if the society wants people to choose the former option, they shouldn't be liable for such consequences.
But it's a big leap to go from "Pharma is driven by profits, therefore they should be put under more scrutiny" and "Pharma is driven by profits, therefore they are injecting us with 5G-enabled nanobots to enable mind control by the Council of Rome"
They are put under way more scrutiny than other industries. Or where is the FDA equivalent demanding phase I, II, and III trials for so-called self-driving? Or imagine a pharma company embracing the slogan "Move fast and break things."
That’s exactly why the idea was to get the government to pay for it and then force everyone to take it.
If you want an evil corporation, it's the small ones that are usually the worst.
During the pandemic, however, governments gave financial guarantees that allowed vaccine trials to go forward right away, so SARS-CoV-2 is the first human virus with an approved mRNA vaccine.
> how much more complex was it to create a vaccine for COVID-19 specifically?
It's not necessarily more complex. A number of different approaches ultimately worked, including one of the oldest technologies: growing virus in eggs and then chemically inactivating it. However, mRNA vaccines worked the best, and had less side-effects than most other approaches.
people always assume that landmark discoveries are immediately obvious but really it only appears so after the accumulation of numerous research built on top of it.
thomas kuhn wrote that knowledge builds up to a tipping point where the collective intelligence begins a paradigm shift and realize that "oh yea... that was a major discovery"
I'm not convinced that the vaccines are 100% bad but they were a novel technology and I'm not sure we're far enough along to judge them objectively yet.
Regardless of how good they are, they were definitely over-sold.
The number of deaths due to COVID has been estimated at over 5 million. The fact that it didn't get much higher, and we can stroll about like nothing happened, is already a miracle.
Edit: didn't finish...
So what is your worry? Sure, there is the possibility of abusing the tech, like any tech. But healthwise?
I think that there is enough "noise" over COVID vaccine side-effects that we don't yet know whether long term it is safe. I also think that given the politicisation of COVID (for instance even discussion of the lab leak theory was gas-lit), I don't think politicians would admit to an issue even if there was one.
If that understanding holds up against scrutiny in the future, mRNA vaccines are an extremely safe and capable platform to deliver vaccines.
The only scenario in which you have better chances not taking the vaccine is by making sure you never get exposed to the virus, for years.