16 ms·

The Karikó problem: Lessons for funding basic research

286 points by hatmatrix 5y ago

misslibby 5y ago
She was demoted because she never got government funding, so privately funding science still sounds like a good idea. She was also working for a private company when Covid hit.
yosito 5y ago
As a Hungarian and an American, my reaction when reading that we should avoid the Karikó problem by funding more diverse people, my first thought was how Hungarians are often not considered “diverse” in the US because they have white skin, and the US has a very binary view of what makes someone a minority.
- selimthegrim 5y ago
  Have you ever been to the Midwest?
  - nulbyte 5y ago
    Not GP, and not expressing agreement or disagreement with GP, but those of us of Hungarian descent make up less than 1% of the population nationally according to 2018 census estimates, and 1% or less of the population throughout much of the Midwest according to data from the American Community Survey as recent as 2019. https://en.m.wikipedia.org/wiki/Hungarian_Americans https://en.m.wikipedia.org/wiki/Hungarian_Americans
    - selimthegrim 5y ago
      I am not disagreeing with him, but Cleveland (where I grew up) and Pittsburgh nearby had vibrant Hungarian communities.
      - jltsiren 5y ago
        I think the issue is the tendency to group "X" and "Americans with X ancestry" together. I can't speak for Hungarians, but someone born to Finnish parents in the US is culturally not Finnish, if they have lived their entire life in the US. Their ancestry may be Finnish, but they have missed all the shared experiences and key events that have shaped recent Finnish culture.
        inglor_cz 5y ago
        Oh, definitely. I am half-Bulgarian, but for all practical purposes I am a Czech, though none of my grandparents actually were (the rest were Slovak).
- sz4kerto 5y ago
  This is something that bothers me often about the US-centric view about DEI. I got lectured by a white guy from the US a couple of times wrt. not focusing enough on skin color and gender/sex when e.g. hiring, but somehow he was totally blind to the fact that e.g. a black woman from New York or London is not necessarily disadvantaged compared to a white male who grew up in rural Romania for example. But nobody really cares of the latter. The same person explained that a 5% wage gap between women and men in a certain field needs immediate action but it's 'fair' that there's a 70% wage gap between his salary and the salary of someone from Eastern Europe (working in the same role at the same company). Oh well.
  - Al-Khwarizmi 5y ago
    As a white-skinned male, but non-native English speaker from a small university that doesn't appear in the ARWU ranking and their ilk, in a small city, in a country that is mediocre in research and far from the US, this really makes me cringe. I needed to master a foreign language for reviewers to not reject my papers because "bad English". I have had applicants to PhD positions reject my offer and go to objectively worse US groups with less productivity by any metric because "my parents want me to study at a US university" or "your group is good but I think that I need to go to a high-ranked university to improve my prospects" (not to speak about how many applicants I get vs. how many an US professor with equivalent track record would get). I spend a lot of hours on things like grading that US professors have TAs do for them. I have several times seen people cite "Person from Stanford/Google/etc. (2013) proved..." when I actually proved that in 2011 and that person was just citing my result. And still, I have to listen to female, white, native-English-speaking professors from elite US universities, lecturing me about how they are discriminated because some study said that women get cited less often, etc. and keep a straight face.
throwawayarnty 5y ago
It's difficult to systematically predict Karikos. Probably impossible with very low success rates. A possible way forward is to simply give out grants randomly to all those that pass some minimum score. After enough filtering, all grants are essentially indistinguishable in quality.
- tsumnia 5y ago
  > those that pass some minimum score The issue though becomes that the score gradually stops being minimal as more and more requirements get added in over time
- sxg 5y ago
  I think this is an underrated idea in many domains. So many different things, including grant funding, university admissions, etc. should use a minimum threshold criteria with acceptances randomly granted to those meeting the criteria. The problem right now is that there are too many qualified people, leading to a rat race in which everyone's working for that extra 1% to set them apart from everyone else. But in reality, the standardized exams/scoring systems we use aren't sensitive enough to reliably differentiate people precisely. This leads to unneeded stress and wasted energy on trying to game the system to get that extra 1%. Definitely a controversial idea and would pose huge challenges to the system we have now. We'd have to confront the idea that a Harvard pedigree or an R01 NIH grant aren't quite the strong indicators of success that we think they are. We’d also have to consider that brilliance can be found in places we haven’t looked more often than we think.
  - deleted 5y ago
    [deleted]
  - ImaCake 5y ago
    I wonder if not randomly selecting after applying a quality filter is actually leading to worse outcomes? It is a well known in stock markets that it is often better to just randomly drop money in than to try and time the market. Maybe the politiking and bias of grant selection committees is picking the wrong half of the standard normal distribution?
WaitWaitWha 5y ago
> non-tenure-track research assistant professor at the University of Pennsylvania. But she was demoted in 1995 because, no matter how many times she applied for NIH funding for her mRNA research, she never got a grant for it. The author is misguided if this is consider to be 'discussed in hushed tones as a cautionary tale for young scientists'. There are a myriad of applications for NIH funding and vast majority are rejected, repeatedly. It is unnecessary to embellish to make the next point. > Yet she persisted. This is indeed, the minority of 'non-tenure-track research assistant professor', most will get discouraged and drop out. (&, 712 out of 2,005)
- jvanderbot 5y ago
  A 30% success rate is not bad. Actually, that's much better than my field. Ostensibly "no matter how many times" means "p<0.01 this was random chance" or something.
epistasis 5y ago
Before CRISPR came along, I remember talking to someone working in archaebacteria who went on and on about these arrays of sequences in archea that seemed really fascinating to him, but I never quite got the implication of what this would eventually develop into before it actually did become CRISPR (by other people working in the field). I remember ~20 years ago hearing about nanopore DNA sequencing, and wondering if it would ever work (it does!). I would have definitely funded both of these people, but I wouldn't necessarily have funded the projects. I knew they were brilliant, but I didn't know exactly where it would lead or if it would work. The key really is to break out of the current "big famous lab" approach, IMHO. Or at least have two tracks of funding. I'm not sure about how to fund people not projects in a systematic way, but we definitely need more random shots on goal and more stochastic exploration of the space of possible research areas.
- mattkrause 5y ago
  Why not both? It's astonishing that we have, essentially, a single "one-size-fits-all"[0] mechanism for funding biomedical research. We should have a bunch, ranging from "trust me, I'm a genius" to "you've never heard of me, but the data suggest this will work." There should be mechanisms where tons of preliminary data are required, but also mechanisms to generate that prelim data. There should be mechanisms for trainees, but also to keep experienced people in the field. [0] Essentially, the NIH's R01. Even that needs work because inflation has chipped away at what one modular budget can support.
  - epistasis 5y ago
    Yes, I think I'm suggesting both! I also agree with how R01 has changed as they become more and more competitive with lower funding rates. There's also been a rise in "but science" projects in bio, starting with the human genome project, that mirrors some of the big science that happens in physics. So adding in that track of funding there are kind of three funding tracks that are necessary.
- bsder 5y ago
  > Before CRISPR came along, I remember talking to someone working in archaebacteria who went on and on about these arrays of sequences in archea that seemed really fascinating to him, but I never quite got the implication of what this would eventually develop into before it actually did become CRISPR (by other people working in the field). >I remember ~20 years ago hearing about nanopore DNA sequencing, and wondering if it would ever work (it does!). These two things are very different to my eyes. Nanopore sequencing seems obvious to me as an electrical engineer. The basic problem was noise and control--which you could probably solve with computes and Moore's law. You can fund it, but it feels like something you could leave to industry as it seems like it's engineering more than science. CRISPR is non-obvious. It's more in the realm of Taq polymerase--it's interesting but, so what? Well, Taq polymerase would become the keystone to PCR about 15 years later. I'm much more interested in figuring out how to fund the things that later become building blocks rather than pouring money on something that industry is likely to do anyway.
jvanderbot 5y ago
Research funding should be wider-spread, perhaps, but it should not be spread wider by finding show-horses that stand out for appearances. The validity of ideas is only born after a decade or more, so we should prioritize diversity and persistence of ideas and funding streams.
neonate 5y ago
https://archive.is/oVyno https://archive.is/oVyno http://web.archive.org/web/20220203202632/https://www.statnews.com/2022/02/01/kariko-problem-lessons-funding-basic-research/ http://web.archive.org/web/20220203202632/https://www.statne...
kragen 5y ago
The things that would help most with the Karikó Problem are: 1. Open access to research. Wikipedia, Sci-Hub, PLoS, Library Genesis, GitLab, MDPI, arXiv, PubMed, GitHub, BitTorrent, medRxiv, bioRxiv, and Tor. It's unconscionable that today professional societies like ACM and IEEE are using copyright to impede access to knowledge as if they were for-profit corporations. 2. Universal basic income, so today's Karikós don't have to choose between research and food. Conceivably some kind of reform is needed to prevent landlords from skimming off the UBI and returning us to zero, as the Georgists claim. 3. Reducing the cost of apparatus through initiatives like Foldscope and Paperfuge. We need not just one Manu Prakash but ten thousand Manu Prakashes, because Edmund Scientific is just never going to fulfill the needs of shoestring labs in Ghana. 4. Freedom from persecution for researchers. For example, where I live, buying acetone gets you Put On A List, and the hardware stores now label their lye simply as "drain opener" to evade the same regulations. California recently prohibited the sale of basic supplies like xylene under an extremely far-fetched interpretation of anti-air-pollution laws. Only recently did Texas repeal its prohibition on sales of lab glassware to unlicensed individuals. Hennig Brand discovered phosphorus by isolating it from a massive amount of his own urine; in South Carolina today you can get arrested for possessing a bottle of urine: https://www.avvo.com/legal-answers/a-friend-was-charged-with-having-a-bottle-of-urine-5082892.html https://www.avvo.com/legal-answers/a-friend-was-charged-with.... Critical Art Ensemble founder Steve Kurtz was famously arrested for "bioterrorism," then indicted for wire fraud and mail fraud, because he and his wife were culturing non-pathogenic bacteria in Petri dishes. This sort of thing should be unthinkable. This will probably require ending drug prohibition; I don't see a reasonable way to protect researchers' freedom to synthesize arbitrary materials while prohibiting the possession of a large and constantly growing list of materials. But I don't think it's reasonable to prioritize the needs of drug addicts, drug traffickers, and empire-builders in law enforcement over the needs of innovators. 5. Going beyond freedom from active persecution, it's important to cultivate a social attitude that basic research is not only not harmful, but an important and worthwhile activity. This is the opposite of the attitude cultivated by Hollywood, which considers anything scientific to be inherently scary and antihuman.
- keithalewis 5y ago
  6. And a pony. A pretty one with fluffy hair you can comb.
ISL 5y ago
As an admittedly-biased basic-researcher (who is no longer doing basic-research as a day-job in part due to constrained funding), the big lesson here is that funding basic research can yield very large returns. There will always be people at the margins of funding, no matter where those margins are. Sometimes those people will hit it big for reasons that span persistence, cleverness, collaboration, serendipity, luck, and more. There are some arenas in which widespread funding of small actors works well and others in which decades of focused investment can yield huge breakthroughs. Overall, though, if you like the outcomes from basic research and want more of them, fund it.
- zozbot234 5y ago
  > the big lesson here is that funding basic research can yield very large returns. It can also be somewhat wasteful, depending on what gets funded. Research that generates "very large returns" is probably quite rare and special, in a way that makes the whole notion of "basic research" somewhat less than meaningful as a target for funding.
  - derbOac 5y ago
    But that's the rub. I think almost by definition big discoveries will often be unpredictable, because if they were predictable you'd not have trouble finding them and they wouldn't be big. So if you just fund things that are popular, you're kind of stuck because although sometimes things that are popular are popular because they work, sometimes they're just rehashing what's already known. Part of the problem I think is that there needs to be some healthy acceptance of risk in research. I'm not sure how you draw the line all the time between "things that are just bad ideas" versus "things that are unusual" but if you're always funding the sure bet you're not going to get anywhere.
    - zozbot234 5y ago
      > So if you just fund things that are popular, you're kind of stuck The principled approach is to correct for that by looking for things that ought to be popular by current standards, but are nonetheless underfunded. Yes, this is hard - it's literally trying to beat all other grantors at their own game. It's also supposed to be hard. There was no reason to expect that "funding good work in science" would have an easy, painless solution.
mrjangles 5y ago
The solutions to this problem are completely obvious, and right in front of everyone's faces. The problem is it doesn't fit people's ideology so they simply refuse to see it. But anyway, the article states clearly that Kariko floundered for years until Drew Weissman working at the _privately_ funded University of Pennsylvania picked her up. You wouldn't have even needed to look up if the University of Pennsylvania was privately funded, because just about every important breakthrough in science in the last 30 years occurred at a privately funded American university. There is a reason why something like 10 privately funded American universities make more scientific breakthroughs than the 10,000 publicly funded universities around the world put together. It's right in front of everyone's faces, and no one is talking about it. It is seriously and elephant in the room. Then the article comes up with a "solution" like this >My answer? Bend over backward to fund a more diverse range of people and ideas, even deliberately including ideas that are currently perceived as unpopular, unworkable, obscure, and the like. After all, many scientific discoveries can be traced back to origins that didn’t seem promising Seriously, is this the best you can do? Regardless, this idea would be impossible in the first place at a government funded institution so why even bother mentioning it.
- mattkrause 5y ago
  "Privately-funded" is not a particularly meaningful distinction when the NIH pays for the vast majority of academic biomedical research--including most of the researchers' salaries. (UCSD, Berkely, UMich, and University of Utah, among others, are research powerhouses too).
- sdenton4 5y ago
  "There is a reason why something like 10 privately funded American universities make more scientific breakthroughs than the 10,000 publicly funded universities around the world put together." Messenger bias?
- LeanderK 5y ago
  > There is a reason why something like 10 privately funded American universities make more scientific breakthroughs than the 10,000 publicly funded universities around the world put together. It's right in front of everyone's faces, and no one is talking about it. It is seriously and elephant in the room. this is just not true. They just hire the best of the best but if one deep-dives into any kind of research one can see an ocean full of universities producing valuable research. And most of the time the basic breakthroughs came from universities you didn't think of or you didn't even know.
mattmcknight 5y ago
I am not sure funding Karikó would have worked out. She was using all of her experience in synthesizing mRNA in pursuit of gene therapy. Not being funded led her to run into Weissman, who was interested in using RNA for vaccines and had run several successful experiments (he co-authored several papers with Fauci the 1990s). It was that serendipity which led to the innovation. Funding her directly may have led to nothing. It seems more notable to me that two people working in the same university were unaware of their mutual interest in RNA. However, I have seen similar things in large companies. When I was analyzing R&D for a 1000 person company, there were several similar projects unaware of their mutual co-existence.
- zozbot234 5y ago
  > She was using all of her experience in synthesizing mRNA in pursuit of gene therapy. Not being funded led her to run into Weissman, who was interested in using RNA for vaccines If your work gets funded and published, it's easier not harder for people working on tangentially-related stuff to hear about it and start cooperating with you. "Interdisciplinarity" is a big draw.
  - mattmcknight 5y ago
    Or she could have been funded to pursue gene therapy and not wanted to spend time on vaccines. If the objective wasn't realistic, it still wouldn't have gotten published.
RcouF1uZ4gsC 5y ago
> A couple of years after her embarrassing demotion, she ran into immunologist Drew Weissman at the office copy machine and struck up a conversation about mRNA. Weissman was intrigued, and asked Karikó to come work in his lab. The government funding doesn't necessarily have to identify the Karikó's of the world, as long as it can identify the Weissman's of the world who can identify The Karikó at the ad-hoc meeting. This is one of the areas where "fund people not objects" really works. The people that are really productive are the first to know that they are heavily dependent on having a good team, and often those people are really good at finding hidden talent.
- derbOac 5y ago
  The problem, though, is then often people like Weissman get the credit, because they're the ones with the money, and the Karikós are dismissed as "just implementing Weissman's ideas" or something like that, even when a lot of the time the Weissmans of the world aren't developing teams, they're attaching themselves to them. It's this sort of self-fulfilling prophesy: so-and-so has good connections -> goes somewhere with lots of resources and good fit for them -> does well -> people attribute success to them -> fund "the person" -> cycle continues; meanwhile someone else has poor connections -> can't get an "in" -> is dismissed -> struggles to do well -> isn't funded -> etc. Karikó, for example, at her stage couldn't develop or attract a team if she wanted to. I don't know Weissman so none of this is to comment on him. But I personally know many examples of this phenomenon (and have seen the Wizard behind the curtain when random events cause these cycles to get disrupted). It's that I think part of the problem the article is referring to is this kind of vicious circle and self-perpetuating funding and career cycles in certain areas of academic science. I'm all for funding people rather than projects; I just think that it's only a fraction of the problem with research funding today.
sdenton4 5y ago
There can be more than one answer! The New York Marathon has a number of different selection criteria to handle different kinds of priorities: getting the world's fastest runners (qualifying marathon results), getting local runners (provide proof of residency), and raising money (let some people just buy their way in via auction). Here's a nice podcast on their system: https://www.npr.org/2020/01/03/793488868/episode-962-advanced-fairness-at-the-marathon https://www.npr.org/2020/01/03/793488868/episode-962-advance... But we could certainly imagine similar for research funding; different paths for rewarding known-good horses, innovative project ideas, etc.
- deleted 5y ago
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xiaodai 5y ago
This women deserves a billion dollars
- lucidrains 5y ago
  not even. like those MasterCard commercials, you could say it is, priceless...
xchaotic 5y ago
The way scientific papers are ranked - ie how many citations a paper gets, means consensus is rewarded and dissent is punished.
- netizen-936824 5y ago
  Its possible to cite a paper that you disagree with
  - pvaldes 5y ago
    But if the peer is the author of this paper you could be suggested to rewrite this paragraph
    - netizen-936824 5y ago
      Are there examples of this happening? Perhaps it may be reasonable if someone misunderstands part of the research (if it did happen)
xyzzyz 5y ago
One serious problem with this sort of “Kariko argument” is that it fails to consider a counter factual. Imagine that Kariko actually dropped out of academia after unsuccessful postdoc, as most postdocs do. Does that mean we would never have mRNA vaccines? I don’t think so, I think that, at best, one could argue that we would have them later. How much later? The figure here most likely does not count in multiple decades. It is very typical for discoveries to be independently done by multiple researchers at roughly the same time. This is because many discoveries and inventions are made when “the time is ripe”, so to speak — when other discoveries and technologies set up the stage for the final leap. I do not mean to diminish the achievement of Kariko here in anyway — she was, after all, the first to actually do it in the real, non counter factual world. But, had it not been her, it would probably be someone else, somewhat later. Now, one can argue that getting discoveries earlier is of crucial value. After all, we did hugely benefit from mRNA vaccine technology being available just in time for 2020. I course, I fully agree here, but again, it is necessary to consider counter factual. With some alternative modes of funding, we might be able to get Kariko to invent mRNA vaccines earlier, sure. However, in this counterfactual, we would also probably get a bunch of other discoveries later than we actually did. Which ones would those be? Are these more or less important than mRNA vaccines? It is, of course, impossible to know, and impossible to figure out before you actually decide to change your funding processes, because the process of discovery is fundamentally highly unpredictable. Point here is that it really is not instructive to focus on a single anecdote when discussing making fundamental changes to the system, because the counterfactual world is way bigger and more complex than a single anecdote.
ummonk 5y ago
One thing that pops out there though is the underrating of non-Western universities. Hungary has a history of producing scientific / intellectual talent, and it appears that Szeged is ranked #3 in Hungary, yet it's 712th globally. It would seem that the ranking list isn't very reflective of intellectual talent. For an even more glaring example, even the best of the incredibly selective IITs don't make it into the top 500 in the US News global ranking list.
- nextos 5y ago
  Rankings like ARWU or US News are quite biased towards big research universities. Nature and others have released rankings that are a bit normalized by size, and many niche institutions such as Cold Spring Harbor or the Austrian IST are near the top. This was discussed in an old HN post, which is quite interesting to read through: https://news.ycombinator.com/item?id=20231432 https://news.ycombinator.com/item?id=20231432. ARWU subject ranking is pretty good, though. Rankings that are not subject based are hard to interpret. For example, many smaller Ivies have excellent departments in topic X but are not so good in topic Y. They can't cover everything. But if you trust the ranking and go there anyway to study topic Y, you might be disappointed. However, funding is really biased towards big or famous institutions. In my experience, it's really easy to get tons of grants from a place like Oxford or Cambridge. If you move to an excellent place that is less known, say a university in the top 30-50 of the world, it gets a lot harder even if your proposal is identical.
  - PeterisP 5y ago
    There's also a big implicit bias towards the concept that research is done in universities - in some places there's a distinction of institutions where universities focus on teaching and most of academic research is done outside of universities in separate research institutes (e.g. the Fraunhofer institute chain in Germany which employs many thousands of researchers and has resulted in a lot of high-impact science); a professor might be involved in both, but his research work wouldn't count for the university's rating (because it's not affiliated with the university) and the institutes are excluded from that rating because they don't teach undergrads.
Gatsky 5y ago
This example is kind of cherry picked. Life science research has no geniuses. Although it is not possible to run the counterfactual, if Kariko quit then it is almost certainly the case that someone else would have discovered the same thing within a reasonable time frame. Life science research is very forgetful, and new discoveries are often not actually new. If you look carefully it is not infrequent that your brilliant idea was had by someone in 1970. In my field I found a paper from 1922 which basically revealed the key point the field is based on, but it was forgotten for nearly 100 years. That paper was before modern statistics were even in use so they did no statistical tests, it was that obvious. None of the many other people in the field knew about this paper. Diveristy in funding sources is important and should be encourgaged. The main issue with these alt funding initiatives is that they lack scale and the sustainability is uncertain. I heard the head of research at a very large and storied biotech dissing Sean Parker's $500 million cancer immunology initiative as being a drop in the ocean, to give you an idea. Life science research is incredibly expensive and wasteful, like setting money on fire. Yet medicine is still so backward we need at least 10X more to really dent human suffering. If you disagree come to my clinic and see what you think.
- chpatrick 5y ago
  That's true in almost every field. Einstein was standing on the shoulders of Mach.
  - tomrod 5y ago
    And Riemann and Gauss. Non-euclidian geometry for the win.
- zozbot234 5y ago
  > If you look carefully it is not infrequent that your brilliant idea was had by someone in 1970. In my field I found a paper from 1922 which basically revealed the key point the field is based on, but it was forgotten for nearly 100 years This is common outside the life sciences, too, FWIW. It seems that we're doing a very poor job of organizing the existing body of research in ways that could benefit the field as a whole. Not to mention that older papers/monographs/etc. are generally not even digitized, which makes them essentially inaccessible by modern standards.
aaron695 5y ago
hyperpallium2 5y ago
Persistence is key. How could we possibly design a system, whereby persistence alone is enough - enough for a liveable income, facilities to do research, and contact with fellow researchers who might help with the next piece of the puzzle? Our concept of knowledge is ludicrously positivist - we tend to think we know where we are ignorant. I feel the reality is that we are surrounded by potential breakthroughs. The only problem is it might take your whole life - or longer - to make them work... and a specific one might not be there at all. So the answer is to let ten thousand flowers bloom, whereever they want (and not imprison them). The odds are not great for individual flowers, so it's disingenuous to encourage them; but the odds are great, collectively.
renewiltord 5y ago
This is not a Kariko problem. This is a success. The academic process will spit out those with novel science, and among those spit out will be those with economically useful novel science. So in some sense, academia is a trap for those who will, with great diligence, only do non-novel things for the pseudo-success that is being well known there. We can then use them for the plodding progress that is incrementality; while shooting the novel folk into the venture universe to gain great wealth for providing great utility. With that honey trap in place, the economy will prosper outside and reward the Karikos.
andrewflnr 5y ago
This is an unreasonable demand of any funding model. Lacking literal infinite money, funders must prioritize based on attributes they can observe. Since the future is not perfectly predictable, they will necessarily have a non-zero false-negative rate. There will always be people who could be said to deserve funding who slip through the cracks. Meanwhile, these new institutes don't have to solve every possible problem with funding research to be worthwhile. They should be judged on whether they're an improvement to the state of the art, not on whether they solve this one problem the author cares about.
auggierose 5y ago
I don't see how that problem can be solved, especially in fields where you need lots of money to do research. There are limited funds, and nobody knows what is good science and what is bad science by just judging the science in front of them, especially if it is new and original science. Even very good scientists, experts in their respective field, will not be able to tell great science from bad science when reviewing a grant application or a paper. Because usually, such a review would take too much time and effort. If the reviewed paper claims to solve a famous problem, and is done by a famous researcher, then reviewers can justify the resources for a proper review. Otherwise they most often will not. So in the end it is up to the researcher themselves to come up with the funds for their research by convincing someone with money. That can be the government, but doesn't have to be. Actually, it is probably NOT going to be the government, because they are just playing some sort of game in which they have no skin, and the money will go to people who play the game better. So it will be easier to find someone else who has some intuition about the problem, or about you, or both.
pbk1 5y ago
While we're talking about funding basic research - how come these independent institutes and government funding agencies don't get equity (warrants, options, whatever) in the entities that ultimately commercialize and patent this research? I reckon they probably take some cut as a licensing fee, but seems like participating in the upside would create significant incentives over the current regimes.
- lvs 5y ago
  See the Bayh-Dole Act.
- zozbot234 5y ago
  > how come these independent institutes and government funding agencies don't get equity (warrants, options, whatever) in the entities that ultimately commercialize and patent this research? Because if it was trivially easy to provide such "equity", the research would've been funded by non-government, private sources already. The whole point of public research funding is to deal with fields and scenarios where this is not really feasible.
Upvoter33 5y ago
It was enjoyable to read about the history of mRNA. It reminds me of the great story of CRISPr (see the Radiolab episode about that if interested). Both are stories of real science and how the most obscure of paths can lead to big breakthroughs. There isn't, imho, a great funding solution -- other than more funding for basic science. You never know which path might lead where.
abetusk 5y ago
I see, this article confuses "fund people, not projects" with "fund people from top tier universities with degrees, credentials and any other pedigree that would make them successful in the current system, not projects". Everyone has their own way of interpreting "fund people, not projects" but my take on it is that it would basically be "basic income" for scientists and engineers. Make a lot of small bets to provide the base level of comfort so that scientists and engineers can work with some piece of mind with the hope of having a few unicorn successes that make up for the rest. This seems like what's ostensibly happening in silicon valley to begin with so that's why I have this interpretation. The implementation details always matter but my view is that the Kariko story is precisely in favor of the "fund people, not projects". Ultimately the article comes to the same conclusion ("... fund a more diverse range of people and ideas, even ... ideas that are currently ... unpopular, unworkable, obscure ...") but I guess the assumption is that a "fund people" approach would be implemented to favor superstars at the exclusion of everyone else.
devwastaken 5y ago
What funding? We don't fund projects, nor people. The feds refuse to tax the largest companies their fair share, while those companies profit heavily from public education and refuse to give back. There are far too many U.S. uni's, very reputable names, that gobble up tuition money and it never sees a lab. No equipment, no expertise, overwhelmingly it's people sitting on a guaranteed government paycheck with their union guaranteeing they're going to sit there and do the minimum possible. Those taxes come out of my paycheck, not pharma, or silicon valley. Reminder if you attended a uni in 2010 the tuition has now doubled to tripled on average, and the quality of education has vastly diminished. Silicon valley is funding labs themselves because uni's have become freeloading institutions we have to defund but are too scared to.
subroutine 5y ago
So here’s the Karikó problem in a nutshell: Anyone can identify Karikó in retrospect, [Weissman could identify Karikó 20 years ago] Who is the better/safer bet to fund: Kariko or Weissman (MD PhD fellowship at the NIH under Anthony Fauci, full professor at UPenn)?
- deleted 5y ago
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inglor_cz 5y ago
Altos Labs, the current Bezos-and-other-billionaires-funded project to attack aging, got 3 billion dollars in order to recruit famous professors, give them 1 million USD year salary each and tell them "research whatever you want in the general direction of anti-aging and regenerative medicine". This might actually work, but they are already famous professors in the fields. What to do with the newbies, who often have interesting ideas, but no previous body of work to back them up with?
hamilyon2 5y ago
There was, as I remember, a curious observation, called goodhart's law or something similar stating that people will always try to affect outcome. When artificial rules of the funding game are known, people will game the rules and the just stop to be useful. For example, if we use "fund research at random", people will flood with research proposals. Or if HN upvotes will become measure of which research is funded, soon enough people will optimize research proposals for HN upvotes. I think, goodhart's law would not apply in certain situations, for example when signal is extremely costly to fake. In research world, some unquestionable proof of personal time of a researcher spent would suffice, I think. I.e three years in a row researcher comes in the same grant proposal and his colleagues say in writing, that yes, he is working only on it and nothing else for three years, no funny stuff.
SubiculumCode 5y ago
1. Top scientists are forced to become administrative salespersons begging for grants from people they've barely met. This is an imbecilic waste of time for our best talents. 2. Safe proposals are generally rewarded, risky ones less so...but not based on scientific merit. We know which institutions conduct science (i.e. accredited research institutions). NIH NSF should provide block grants to Universities, which would provide that to Departments, which would then fund the Department's scientists. This would: 1. ...create more heterogeneously funded science because you Departments judge on personal interactions with individual scientists, who will have more intimate knowledge of their research and strengths. 2. ...risky science is more likely to be funded, and less politically adept science can get funded. 3. departmental/university applications for funding are much less work than traditional NIH NFS applications...because the University has a vested interest in not wasting their scientist's time.
throwaway-3232 5y ago
Not all scientific work requires funding as huge as building a lab. You do not always need pricey reagents and equipment. What is required is 1) time 2) covering biological needs. Given modern productivity, the time required to cover biological needs is small, something like 2-4 hours/day. If I could work just this little time, I will have enough free time for scientific work and I will not need to depend on grants.
DrAwdeOccarim 5y ago
Of course these types of articles were bound to come out, but part of why Karikó and others like her are successful is because they did not get showered with funds and success. The grit is part of the recipe. It reminds me of Alex Danco's Scene discussions (https://alexdanco.com/2021/03/19/how-scenes-work-with-jim-oshaughnessy/ https://alexdanco.com/2021/03/19/how-scenes-work-with-jim-os...).
missionfission 5y ago
This is so true though, academia can be horrible for people, non motivating, and keen on rejecting incremental contributions

286 points by hatmatrix 5y ago

She was demoted because she never got government funding, so privately funding science still sounds like a good idea. She was also working for a private company when Covid hit.

yosito 5y ago

As a Hungarian and an American, my reaction when reading that we should avoid the Karikó problem by funding more diverse people, my first thought was how Hungarians are often not considered “diverse” in the US because they have white skin, and the US has a very binary view of what makes someone a minority.

selimthegrim 5y ago
Have you ever been to the Midwest?
- nulbyte 5y ago
  Not GP, and not expressing agreement or disagreement with GP, but those of us of Hungarian descent make up less than 1% of the population nationally according to 2018 census estimates, and 1% or less of the population throughout much of the Midwest according to data from the American Community Survey as recent as 2019. https://en.m.wikipedia.org/wiki/Hungarian_Americans https://en.m.wikipedia.org/wiki/Hungarian_Americans
  - selimthegrim 5y ago
    I am not disagreeing with him, but Cleveland (where I grew up) and Pittsburgh nearby had vibrant Hungarian communities.
    - jltsiren 5y ago
      I think the issue is the tendency to group "X" and "Americans with X ancestry" together. I can't speak for Hungarians, but someone born to Finnish parents in the US is culturally not Finnish, if they have lived their entire life in the US. Their ancestry may be Finnish, but they have missed all the shared experiences and key events that have shaped recent Finnish culture.
      - inglor_cz 5y ago
        Oh, definitely. I am half-Bulgarian, but for all practical purposes I am a Czech, though none of my grandparents actually were (the rest were Slovak).
sz4kerto 5y ago
This is something that bothers me often about the US-centric view about DEI. I got lectured by a white guy from the US a couple of times wrt. not focusing enough on skin color and gender/sex when e.g. hiring, but somehow he was totally blind to the fact that e.g. a black woman from New York or London is not necessarily disadvantaged compared to a white male who grew up in rural Romania for example. But nobody really cares of the latter. The same person explained that a 5% wage gap between women and men in a certain field needs immediate action but it's 'fair' that there's a 70% wage gap between his salary and the salary of someone from Eastern Europe (working in the same role at the same company). Oh well.
- Al-Khwarizmi 5y ago
  As a white-skinned male, but non-native English speaker from a small university that doesn't appear in the ARWU ranking and their ilk, in a small city, in a country that is mediocre in research and far from the US, this really makes me cringe. I needed to master a foreign language for reviewers to not reject my papers because "bad English". I have had applicants to PhD positions reject my offer and go to objectively worse US groups with less productivity by any metric because "my parents want me to study at a US university" or "your group is good but I think that I need to go to a high-ranked university to improve my prospects" (not to speak about how many applicants I get vs. how many an US professor with equivalent track record would get). I spend a lot of hours on things like grading that US professors have TAs do for them. I have several times seen people cite "Person from Stanford/Google/etc. (2013) proved..." when I actually proved that in 2011 and that person was just citing my result. And still, I have to listen to female, white, native-English-speaking professors from elite US universities, lecturing me about how they are discriminated because some study said that women get cited less often, etc. and keep a straight face.

throwawayarnty 5y ago

It's difficult to systematically predict Karikos. Probably impossible with very low success rates. A possible way forward is to simply give out grants randomly to all those that pass some minimum score. After enough filtering, all grants are essentially indistinguishable in quality.

tsumnia 5y ago
> those that pass some minimum score The issue though becomes that the score gradually stops being minimal as more and more requirements get added in over time
sxg 5y ago
I think this is an underrated idea in many domains. So many different things, including grant funding, university admissions, etc. should use a minimum threshold criteria with acceptances randomly granted to those meeting the criteria. The problem right now is that there are too many qualified people, leading to a rat race in which everyone's working for that extra 1% to set them apart from everyone else. But in reality, the standardized exams/scoring systems we use aren't sensitive enough to reliably differentiate people precisely. This leads to unneeded stress and wasted energy on trying to game the system to get that extra 1%. Definitely a controversial idea and would pose huge challenges to the system we have now. We'd have to confront the idea that a Harvard pedigree or an R01 NIH grant aren't quite the strong indicators of success that we think they are. We’d also have to consider that brilliance can be found in places we haven’t looked more often than we think.
- deleted 5y ago
  [deleted]
- ImaCake 5y ago
  I wonder if not randomly selecting after applying a quality filter is actually leading to worse outcomes? It is a well known in stock markets that it is often better to just randomly drop money in than to try and time the market. Maybe the politiking and bias of grant selection committees is picking the wrong half of the standard normal distribution?

WaitWaitWha 5y ago

> non-tenure-track research assistant professor at the University of Pennsylvania. But she was demoted in 1995 because, no matter how many times she applied for NIH funding for her mRNA research, she never got a grant for it. The author is misguided if this is consider to be 'discussed in hushed tones as a cautionary tale for young scientists'. There are a myriad of applications for NIH funding and vast majority are rejected, repeatedly. It is unnecessary to embellish to make the next point. > Yet she persisted. This is indeed, the minority of 'non-tenure-track research assistant professor', most will get discouraged and drop out. (&, 712 out of 2,005)

jvanderbot 5y ago
A 30% success rate is not bad. Actually, that's much better than my field. Ostensibly "no matter how many times" means "p<0.01 this was random chance" or something.

epistasis 5y ago

Before CRISPR came along, I remember talking to someone working in archaebacteria who went on and on about these arrays of sequences in archea that seemed really fascinating to him, but I never quite got the implication of what this would eventually develop into before it actually did become CRISPR (by other people working in the field). I remember ~20 years ago hearing about nanopore DNA sequencing, and wondering if it would ever work (it does!). I would have definitely funded both of these people, but I wouldn't necessarily have funded the projects. I knew they were brilliant, but I didn't know exactly where it would lead or if it would work. The key really is to break out of the current "big famous lab" approach, IMHO. Or at least have two tracks of funding. I'm not sure about how to fund people not projects in a systematic way, but we definitely need more random shots on goal and more stochastic exploration of the space of possible research areas.

mattkrause 5y ago
Why not both? It's astonishing that we have, essentially, a single "one-size-fits-all"[0] mechanism for funding biomedical research. We should have a bunch, ranging from "trust me, I'm a genius" to "you've never heard of me, but the data suggest this will work." There should be mechanisms where tons of preliminary data are required, but also mechanisms to generate that prelim data. There should be mechanisms for trainees, but also to keep experienced people in the field. [0] Essentially, the NIH's R01. Even that needs work because inflation has chipped away at what one modular budget can support.
- epistasis 5y ago
  Yes, I think I'm suggesting both! I also agree with how R01 has changed as they become more and more competitive with lower funding rates. There's also been a rise in "but science" projects in bio, starting with the human genome project, that mirrors some of the big science that happens in physics. So adding in that track of funding there are kind of three funding tracks that are necessary.
bsder 5y ago
> Before CRISPR came along, I remember talking to someone working in archaebacteria who went on and on about these arrays of sequences in archea that seemed really fascinating to him, but I never quite got the implication of what this would eventually develop into before it actually did become CRISPR (by other people working in the field). >I remember ~20 years ago hearing about nanopore DNA sequencing, and wondering if it would ever work (it does!). These two things are very different to my eyes. Nanopore sequencing seems obvious to me as an electrical engineer. The basic problem was noise and control--which you could probably solve with computes and Moore's law. You can fund it, but it feels like something you could leave to industry as it seems like it's engineering more than science. CRISPR is non-obvious. It's more in the realm of Taq polymerase--it's interesting but, so what? Well, Taq polymerase would become the keystone to PCR about 15 years later. I'm much more interested in figuring out how to fund the things that later become building blocks rather than pouring money on something that industry is likely to do anyway.

jvanderbot 5y ago

Research funding should be wider-spread, perhaps, but it should not be spread wider by finding show-horses that stand out for appearances. The validity of ideas is only born after a decade or more, so we should prioritize diversity and persistence of ideas and funding streams.

neonate 5y ago

https://archive.is/oVyno https://archive.is/oVyno http://web.archive.org/web/20220203202632/https://www.statnews.com/2022/02/01/kariko-problem-lessons-funding-basic-research/ http://web.archive.org/web/20220203202632/https://www.statne...

kragen 5y ago

The things that would help most with the Karikó Problem are: 1. Open access to research. Wikipedia, Sci-Hub, PLoS, Library Genesis, GitLab, MDPI, arXiv, PubMed, GitHub, BitTorrent, medRxiv, bioRxiv, and Tor. It's unconscionable that today professional societies like ACM and IEEE are using copyright to impede access to knowledge as if they were for-profit corporations. 2. Universal basic income, so today's Karikós don't have to choose between research and food. Conceivably some kind of reform is needed to prevent landlords from skimming off the UBI and returning us to zero, as the Georgists claim. 3. Reducing the cost of apparatus through initiatives like Foldscope and Paperfuge. We need not just one Manu Prakash but ten thousand Manu Prakashes, because Edmund Scientific is just never going to fulfill the needs of shoestring labs in Ghana. 4. Freedom from persecution for researchers. For example, where I live, buying acetone gets you Put On A List, and the hardware stores now label their lye simply as "drain opener" to evade the same regulations. California recently prohibited the sale of basic supplies like xylene under an extremely far-fetched interpretation of anti-air-pollution laws. Only recently did Texas repeal its prohibition on sales of lab glassware to unlicensed individuals. Hennig Brand discovered phosphorus by isolating it from a massive amount of his own urine; in South Carolina today you can get arrested for possessing a bottle of urine: https://www.avvo.com/legal-answers/a-friend-was-charged-with-having-a-bottle-of-urine-5082892.html https://www.avvo.com/legal-answers/a-friend-was-charged-with.... Critical Art Ensemble founder Steve Kurtz was famously arrested for "bioterrorism," then indicted for wire fraud and mail fraud, because he and his wife were culturing non-pathogenic bacteria in Petri dishes. This sort of thing should be unthinkable. This will probably require ending drug prohibition; I don't see a reasonable way to protect researchers' freedom to synthesize arbitrary materials while prohibiting the possession of a large and constantly growing list of materials. But I don't think it's reasonable to prioritize the needs of drug addicts, drug traffickers, and empire-builders in law enforcement over the needs of innovators. 5. Going beyond freedom from active persecution, it's important to cultivate a social attitude that basic research is not only not harmful, but an important and worthwhile activity. This is the opposite of the attitude cultivated by Hollywood, which considers anything scientific to be inherently scary and antihuman.

keithalewis 5y ago
6. And a pony. A pretty one with fluffy hair you can comb.

ISL 5y ago

As an admittedly-biased basic-researcher (who is no longer doing basic-research as a day-job in part due to constrained funding), the big lesson here is that funding basic research can yield very large returns. There will always be people at the margins of funding, no matter where those margins are. Sometimes those people will hit it big for reasons that span persistence, cleverness, collaboration, serendipity, luck, and more. There are some arenas in which widespread funding of small actors works well and others in which decades of focused investment can yield huge breakthroughs. Overall, though, if you like the outcomes from basic research and want more of them, fund it.

zozbot234 5y ago
> the big lesson here is that funding basic research can yield very large returns. It can also be somewhat wasteful, depending on what gets funded. Research that generates "very large returns" is probably quite rare and special, in a way that makes the whole notion of "basic research" somewhat less than meaningful as a target for funding.
- derbOac 5y ago
  But that's the rub. I think almost by definition big discoveries will often be unpredictable, because if they were predictable you'd not have trouble finding them and they wouldn't be big. So if you just fund things that are popular, you're kind of stuck because although sometimes things that are popular are popular because they work, sometimes they're just rehashing what's already known. Part of the problem I think is that there needs to be some healthy acceptance of risk in research. I'm not sure how you draw the line all the time between "things that are just bad ideas" versus "things that are unusual" but if you're always funding the sure bet you're not going to get anywhere.
  - zozbot234 5y ago
    > So if you just fund things that are popular, you're kind of stuck The principled approach is to correct for that by looking for things that ought to be popular by current standards, but are nonetheless underfunded. Yes, this is hard - it's literally trying to beat all other grantors at their own game. It's also supposed to be hard. There was no reason to expect that "funding good work in science" would have an easy, painless solution.

mrjangles 5y ago

The solutions to this problem are completely obvious, and right in front of everyone's faces. The problem is it doesn't fit people's ideology so they simply refuse to see it. But anyway, the article states clearly that Kariko floundered for years until Drew Weissman working at the _privately_ funded University of Pennsylvania picked her up. You wouldn't have even needed to look up if the University of Pennsylvania was privately funded, because just about every important breakthrough in science in the last 30 years occurred at a privately funded American university. There is a reason why something like 10 privately funded American universities make more scientific breakthroughs than the 10,000 publicly funded universities around the world put together. It's right in front of everyone's faces, and no one is talking about it. It is seriously and elephant in the room. Then the article comes up with a "solution" like this >My answer? Bend over backward to fund a more diverse range of people and ideas, even deliberately including ideas that are currently perceived as unpopular, unworkable, obscure, and the like. After all, many scientific discoveries can be traced back to origins that didn’t seem promising Seriously, is this the best you can do? Regardless, this idea would be impossible in the first place at a government funded institution so why even bother mentioning it.

mattkrause 5y ago
"Privately-funded" is not a particularly meaningful distinction when the NIH pays for the vast majority of academic biomedical research--including most of the researchers' salaries. (UCSD, Berkely, UMich, and University of Utah, among others, are research powerhouses too).
sdenton4 5y ago
"There is a reason why something like 10 privately funded American universities make more scientific breakthroughs than the 10,000 publicly funded universities around the world put together." Messenger bias?
LeanderK 5y ago
> There is a reason why something like 10 privately funded American universities make more scientific breakthroughs than the 10,000 publicly funded universities around the world put together. It's right in front of everyone's faces, and no one is talking about it. It is seriously and elephant in the room. this is just not true. They just hire the best of the best but if one deep-dives into any kind of research one can see an ocean full of universities producing valuable research. And most of the time the basic breakthroughs came from universities you didn't think of or you didn't even know.

mattmcknight 5y ago

I am not sure funding Karikó would have worked out. She was using all of her experience in synthesizing mRNA in pursuit of gene therapy. Not being funded led her to run into Weissman, who was interested in using RNA for vaccines and had run several successful experiments (he co-authored several papers with Fauci the 1990s). It was that serendipity which led to the innovation. Funding her directly may have led to nothing. It seems more notable to me that two people working in the same university were unaware of their mutual interest in RNA. However, I have seen similar things in large companies. When I was analyzing R&D for a 1000 person company, there were several similar projects unaware of their mutual co-existence.

zozbot234 5y ago
> She was using all of her experience in synthesizing mRNA in pursuit of gene therapy. Not being funded led her to run into Weissman, who was interested in using RNA for vaccines If your work gets funded and published, it's easier not harder for people working on tangentially-related stuff to hear about it and start cooperating with you. "Interdisciplinarity" is a big draw.
- mattmcknight 5y ago
  Or she could have been funded to pursue gene therapy and not wanted to spend time on vaccines. If the objective wasn't realistic, it still wouldn't have gotten published.

RcouF1uZ4gsC 5y ago

> A couple of years after her embarrassing demotion, she ran into immunologist Drew Weissman at the office copy machine and struck up a conversation about mRNA. Weissman was intrigued, and asked Karikó to come work in his lab. The government funding doesn't necessarily have to identify the Karikó's of the world, as long as it can identify the Weissman's of the world who can identify The Karikó at the ad-hoc meeting. This is one of the areas where "fund people not objects" really works. The people that are really productive are the first to know that they are heavily dependent on having a good team, and often those people are really good at finding hidden talent.

derbOac 5y ago
The problem, though, is then often people like Weissman get the credit, because they're the ones with the money, and the Karikós are dismissed as "just implementing Weissman's ideas" or something like that, even when a lot of the time the Weissmans of the world aren't developing teams, they're attaching themselves to them. It's this sort of self-fulfilling prophesy: so-and-so has good connections -> goes somewhere with lots of resources and good fit for them -> does well -> people attribute success to them -> fund "the person" -> cycle continues; meanwhile someone else has poor connections -> can't get an "in" -> is dismissed -> struggles to do well -> isn't funded -> etc. Karikó, for example, at her stage couldn't develop or attract a team if she wanted to. I don't know Weissman so none of this is to comment on him. But I personally know many examples of this phenomenon (and have seen the Wizard behind the curtain when random events cause these cycles to get disrupted). It's that I think part of the problem the article is referring to is this kind of vicious circle and self-perpetuating funding and career cycles in certain areas of academic science. I'm all for funding people rather than projects; I just think that it's only a fraction of the problem with research funding today.

sdenton4 5y ago

There can be more than one answer! The New York Marathon has a number of different selection criteria to handle different kinds of priorities: getting the world's fastest runners (qualifying marathon results), getting local runners (provide proof of residency), and raising money (let some people just buy their way in via auction). Here's a nice podcast on their system: https://www.npr.org/2020/01/03/793488868/episode-962-advanced-fairness-at-the-marathon https://www.npr.org/2020/01/03/793488868/episode-962-advance... But we could certainly imagine similar for research funding; different paths for rewarding known-good horses, innovative project ideas, etc.

deleted 5y ago
[deleted]

xiaodai 5y ago

This women deserves a billion dollars

lucidrains 5y ago
not even. like those MasterCard commercials, you could say it is, priceless...

xchaotic 5y ago

The way scientific papers are ranked - ie how many citations a paper gets, means consensus is rewarded and dissent is punished.

netizen-936824 5y ago
Its possible to cite a paper that you disagree with
- pvaldes 5y ago
  But if the peer is the author of this paper you could be suggested to rewrite this paragraph
  - netizen-936824 5y ago
    Are there examples of this happening? Perhaps it may be reasonable if someone misunderstands part of the research (if it did happen)

xyzzyz 5y ago

One serious problem with this sort of “Kariko argument” is that it fails to consider a counter factual. Imagine that Kariko actually dropped out of academia after unsuccessful postdoc, as most postdocs do. Does that mean we would never have mRNA vaccines? I don’t think so, I think that, at best, one could argue that we would have them later. How much later? The figure here most likely does not count in multiple decades. It is very typical for discoveries to be independently done by multiple researchers at roughly the same time. This is because many discoveries and inventions are made when “the time is ripe”, so to speak — when other discoveries and technologies set up the stage for the final leap. I do not mean to diminish the achievement of Kariko here in anyway — she was, after all, the first to actually do it in the real, non counter factual world. But, had it not been her, it would probably be someone else, somewhat later. Now, one can argue that getting discoveries earlier is of crucial value. After all, we did hugely benefit from mRNA vaccine technology being available just in time for 2020. I course, I fully agree here, but again, it is necessary to consider counter factual. With some alternative modes of funding, we might be able to get Kariko to invent mRNA vaccines earlier, sure. However, in this counterfactual, we would also probably get a bunch of other discoveries later than we actually did. Which ones would those be? Are these more or less important than mRNA vaccines? It is, of course, impossible to know, and impossible to figure out before you actually decide to change your funding processes, because the process of discovery is fundamentally highly unpredictable. Point here is that it really is not instructive to focus on a single anecdote when discussing making fundamental changes to the system, because the counterfactual world is way bigger and more complex than a single anecdote.

ummonk 5y ago

One thing that pops out there though is the underrating of non-Western universities. Hungary has a history of producing scientific / intellectual talent, and it appears that Szeged is ranked #3 in Hungary, yet it's 712th globally. It would seem that the ranking list isn't very reflective of intellectual talent. For an even more glaring example, even the best of the incredibly selective IITs don't make it into the top 500 in the US News global ranking list.

nextos 5y ago
Rankings like ARWU or US News are quite biased towards big research universities. Nature and others have released rankings that are a bit normalized by size, and many niche institutions such as Cold Spring Harbor or the Austrian IST are near the top. This was discussed in an old HN post, which is quite interesting to read through: https://news.ycombinator.com/item?id=20231432 https://news.ycombinator.com/item?id=20231432. ARWU subject ranking is pretty good, though. Rankings that are not subject based are hard to interpret. For example, many smaller Ivies have excellent departments in topic X but are not so good in topic Y. They can't cover everything. But if you trust the ranking and go there anyway to study topic Y, you might be disappointed. However, funding is really biased towards big or famous institutions. In my experience, it's really easy to get tons of grants from a place like Oxford or Cambridge. If you move to an excellent place that is less known, say a university in the top 30-50 of the world, it gets a lot harder even if your proposal is identical.
- PeterisP 5y ago
  There's also a big implicit bias towards the concept that research is done in universities - in some places there's a distinction of institutions where universities focus on teaching and most of academic research is done outside of universities in separate research institutes (e.g. the Fraunhofer institute chain in Germany which employs many thousands of researchers and has resulted in a lot of high-impact science); a professor might be involved in both, but his research work wouldn't count for the university's rating (because it's not affiliated with the university) and the institutes are excluded from that rating because they don't teach undergrads.

Gatsky 5y ago

This example is kind of cherry picked. Life science research has no geniuses. Although it is not possible to run the counterfactual, if Kariko quit then it is almost certainly the case that someone else would have discovered the same thing within a reasonable time frame. Life science research is very forgetful, and new discoveries are often not actually new. If you look carefully it is not infrequent that your brilliant idea was had by someone in 1970. In my field I found a paper from 1922 which basically revealed the key point the field is based on, but it was forgotten for nearly 100 years. That paper was before modern statistics were even in use so they did no statistical tests, it was that obvious. None of the many other people in the field knew about this paper. Diveristy in funding sources is important and should be encourgaged. The main issue with these alt funding initiatives is that they lack scale and the sustainability is uncertain. I heard the head of research at a very large and storied biotech dissing Sean Parker's $500 million cancer immunology initiative as being a drop in the ocean, to give you an idea. Life science research is incredibly expensive and wasteful, like setting money on fire. Yet medicine is still so backward we need at least 10X more to really dent human suffering. If you disagree come to my clinic and see what you think.

chpatrick 5y ago
That's true in almost every field. Einstein was standing on the shoulders of Mach.
- tomrod 5y ago
  And Riemann and Gauss. Non-euclidian geometry for the win.
zozbot234 5y ago
> If you look carefully it is not infrequent that your brilliant idea was had by someone in 1970. In my field I found a paper from 1922 which basically revealed the key point the field is based on, but it was forgotten for nearly 100 years This is common outside the life sciences, too, FWIW. It seems that we're doing a very poor job of organizing the existing body of research in ways that could benefit the field as a whole. Not to mention that older papers/monographs/etc. are generally not even digitized, which makes them essentially inaccessible by modern standards.

aaron695 5y ago

hyperpallium2 5y ago

Persistence is key. How could we possibly design a system, whereby persistence alone is enough - enough for a liveable income, facilities to do research, and contact with fellow researchers who might help with the next piece of the puzzle? Our concept of knowledge is ludicrously positivist - we tend to think we know where we are ignorant. I feel the reality is that we are surrounded by potential breakthroughs. The only problem is it might take your whole life - or longer - to make them work... and a specific one might not be there at all. So the answer is to let ten thousand flowers bloom, whereever they want (and not imprison them). The odds are not great for individual flowers, so it's disingenuous to encourage them; but the odds are great, collectively.

renewiltord 5y ago

This is not a Kariko problem. This is a success. The academic process will spit out those with novel science, and among those spit out will be those with economically useful novel science. So in some sense, academia is a trap for those who will, with great diligence, only do non-novel things for the pseudo-success that is being well known there. We can then use them for the plodding progress that is incrementality; while shooting the novel folk into the venture universe to gain great wealth for providing great utility. With that honey trap in place, the economy will prosper outside and reward the Karikos.

andrewflnr 5y ago

This is an unreasonable demand of any funding model. Lacking literal infinite money, funders must prioritize based on attributes they can observe. Since the future is not perfectly predictable, they will necessarily have a non-zero false-negative rate. There will always be people who could be said to deserve funding who slip through the cracks. Meanwhile, these new institutes don't have to solve every possible problem with funding research to be worthwhile. They should be judged on whether they're an improvement to the state of the art, not on whether they solve this one problem the author cares about.

auggierose 5y ago

I don't see how that problem can be solved, especially in fields where you need lots of money to do research. There are limited funds, and nobody knows what is good science and what is bad science by just judging the science in front of them, especially if it is new and original science. Even very good scientists, experts in their respective field, will not be able to tell great science from bad science when reviewing a grant application or a paper. Because usually, such a review would take too much time and effort. If the reviewed paper claims to solve a famous problem, and is done by a famous researcher, then reviewers can justify the resources for a proper review. Otherwise they most often will not. So in the end it is up to the researcher themselves to come up with the funds for their research by convincing someone with money. That can be the government, but doesn't have to be. Actually, it is probably NOT going to be the government, because they are just playing some sort of game in which they have no skin, and the money will go to people who play the game better. So it will be easier to find someone else who has some intuition about the problem, or about you, or both.

pbk1 5y ago

While we're talking about funding basic research - how come these independent institutes and government funding agencies don't get equity (warrants, options, whatever) in the entities that ultimately commercialize and patent this research? I reckon they probably take some cut as a licensing fee, but seems like participating in the upside would create significant incentives over the current regimes.

lvs 5y ago
See the Bayh-Dole Act.
zozbot234 5y ago
> how come these independent institutes and government funding agencies don't get equity (warrants, options, whatever) in the entities that ultimately commercialize and patent this research? Because if it was trivially easy to provide such "equity", the research would've been funded by non-government, private sources already. The whole point of public research funding is to deal with fields and scenarios where this is not really feasible.

Upvoter33 5y ago

It was enjoyable to read about the history of mRNA. It reminds me of the great story of CRISPr (see the Radiolab episode about that if interested). Both are stories of real science and how the most obscure of paths can lead to big breakthroughs. There isn't, imho, a great funding solution -- other than more funding for basic science. You never know which path might lead where.

abetusk 5y ago

I see, this article confuses "fund people, not projects" with "fund people from top tier universities with degrees, credentials and any other pedigree that would make them successful in the current system, not projects". Everyone has their own way of interpreting "fund people, not projects" but my take on it is that it would basically be "basic income" for scientists and engineers. Make a lot of small bets to provide the base level of comfort so that scientists and engineers can work with some piece of mind with the hope of having a few unicorn successes that make up for the rest. This seems like what's ostensibly happening in silicon valley to begin with so that's why I have this interpretation. The implementation details always matter but my view is that the Kariko story is precisely in favor of the "fund people, not projects". Ultimately the article comes to the same conclusion ("... fund a more diverse range of people and ideas, even ... ideas that are currently ... unpopular, unworkable, obscure ...") but I guess the assumption is that a "fund people" approach would be implemented to favor superstars at the exclusion of everyone else.

devwastaken 5y ago

What funding? We don't fund projects, nor people. The feds refuse to tax the largest companies their fair share, while those companies profit heavily from public education and refuse to give back. There are far too many U.S. uni's, very reputable names, that gobble up tuition money and it never sees a lab. No equipment, no expertise, overwhelmingly it's people sitting on a guaranteed government paycheck with their union guaranteeing they're going to sit there and do the minimum possible. Those taxes come out of my paycheck, not pharma, or silicon valley. Reminder if you attended a uni in 2010 the tuition has now doubled to tripled on average, and the quality of education has vastly diminished. Silicon valley is funding labs themselves because uni's have become freeloading institutions we have to defund but are too scared to.

subroutine 5y ago

So here’s the Karikó problem in a nutshell: Anyone can identify Karikó in retrospect, [Weissman could identify Karikó 20 years ago] Who is the better/safer bet to fund: Kariko or Weissman (MD PhD fellowship at the NIH under Anthony Fauci, full professor at UPenn)?

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inglor_cz 5y ago

Altos Labs, the current Bezos-and-other-billionaires-funded project to attack aging, got 3 billion dollars in order to recruit famous professors, give them 1 million USD year salary each and tell them "research whatever you want in the general direction of anti-aging and regenerative medicine". This might actually work, but they are already famous professors in the fields. What to do with the newbies, who often have interesting ideas, but no previous body of work to back them up with?

hamilyon2 5y ago

There was, as I remember, a curious observation, called goodhart's law or something similar stating that people will always try to affect outcome. When artificial rules of the funding game are known, people will game the rules and the just stop to be useful. For example, if we use "fund research at random", people will flood with research proposals. Or if HN upvotes will become measure of which research is funded, soon enough people will optimize research proposals for HN upvotes. I think, goodhart's law would not apply in certain situations, for example when signal is extremely costly to fake. In research world, some unquestionable proof of personal time of a researcher spent would suffice, I think. I.e three years in a row researcher comes in the same grant proposal and his colleagues say in writing, that yes, he is working only on it and nothing else for three years, no funny stuff.

SubiculumCode 5y ago

1. Top scientists are forced to become administrative salespersons begging for grants from people they've barely met. This is an imbecilic waste of time for our best talents. 2. Safe proposals are generally rewarded, risky ones less so...but not based on scientific merit. We know which institutions conduct science (i.e. accredited research institutions). NIH NSF should provide block grants to Universities, which would provide that to Departments, which would then fund the Department's scientists. This would: 1. ...create more heterogeneously funded science because you Departments judge on personal interactions with individual scientists, who will have more intimate knowledge of their research and strengths. 2. ...risky science is more likely to be funded, and less politically adept science can get funded. 3. departmental/university applications for funding are much less work than traditional NIH NFS applications...because the University has a vested interest in not wasting their scientist's time.

throwaway-3232 5y ago

Not all scientific work requires funding as huge as building a lab. You do not always need pricey reagents and equipment. What is required is 1) time 2) covering biological needs. Given modern productivity, the time required to cover biological needs is small, something like 2-4 hours/day. If I could work just this little time, I will have enough free time for scientific work and I will not need to depend on grants.

DrAwdeOccarim 5y ago

Of course these types of articles were bound to come out, but part of why Karikó and others like her are successful is because they did not get showered with funds and success. The grit is part of the recipe. It reminds me of Alex Danco's Scene discussions (https://alexdanco.com/2021/03/19/how-scenes-work-with-jim-oshaughnessy/ https://alexdanco.com/2021/03/19/how-scenes-work-with-jim-os...).

missionfission 5y ago

This is so true though, academia can be horrible for people, non motivating, and keen on rejecting incremental contributions