The Karikó problem: Lessons for funding basic research

https://www.statnews.com/2022/02/01/kariko-problem-lessons-funding-basic-research/

by hatmatrix • 4 years ago

286 155 4 years 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• 4 years 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• 4 years 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.

ImaCake• 4 years 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?

zozbot23413• 4 years ago

If you could systematically predict Karikó's, they would not be Karikó's. For all we know, any attempt to "solve" this problem might just be a fool's errand. At least in the absence of a meaningful argument to the contrary.

After enough filtering, all grants are essentially indistinguishable in quality.

I don't believe this. You can always soften incentives (and thereby prevent wasteful gaming) by adding random noise/dithering to your scoring function, but a threshold-only approach seems quite blunt to me.

derbOac7• 4 years ago

Actually, this model has been suggested by former heads of NIH and NSF, who have publicly expressed concern about the current funding paradigm.

The problem is that impact by reasonable metrics is correlated about 0.30 with grant score, so it's difficult to predict what will be successful. (Note that impact itself is controversial, given self-fulfilling fad dynamics in research -- FOMO popularity spikes and so forth).

One of the biggest predictors of grant success is having previously published with people on the review committees.

The idea is that you randomly fund research because it's difficult to know what will be important, but try to balance that against grants that might be poorly conceived to begin with.

cycomanic• 4 years ago

> After enough filtering, all grants are essentially indistinguishable in quality.
I don't believe this. You can always soften incentives (and thereby prevent wasteful gaming) by adding random noise/dithering to your scoring function, but a threshold-only approach seems quite blunt to me.

These assessments come from statistically investigating grant scoring and success. What you find that 90%of grants are essentially scored the same, within the noise. In these situations what typically happens is that previous grant success will determine current success, i.e. the person previously got a grant so what they are doing must be good (the "safe" bet). The problem that creates that you create empires of people who get a lot of grants based essentially on one luck of the draw.

The biggest issue is though not even that you miss some good people with good ideas, but the incentive structure you create. Because there is an expiry time on the benefit from previous success and it is research area specific, what happens is academics have to write grants constantly and you can't really change fields.

Academics spend 30% of their time applying for and reviewing grants. None (hardly any) of the people who are very successful with getting grants are doing research themselves any more. I suspect this is also the reason why most Nobel winning research is done in people's 30s.more senior academics don't have time to do the research (and can't take the necessary risks).

Al-Khwarizmi3• 4 years ago

I read this proposal of randomness often. It would work assuming researchers were robots, but I don't think it would really work with humans. It's just not aligned with basic human psychology and incentives. Why would a researcher strive to come up with a really good proposal if as long as it's somewhat decent, the outcome is random? Why would they strive to execute it well if it won't influence future outcomes? In fact, why would anyone want to be an academic researcher in the first place if funding depends on a lottery, and no matter what you do, you might find yourself without any funds to do anything meaningful?

I think a system where grants are only given to a small minority is defective and wastes everyone's time, no matter how the minority is chosen. The solution has to be to give some reasonable funding to anyone employed as a researcher - which, depending on how much you value science, can be achieved by increasing the funding or by decreasing the number of researchers (I'm an academic myself so I believe in the former, but I might be biased).

dariosalvi78• 4 years ago

All researchers know very well that grants are assigned somewhat randomly. I mean bad science is usually filtered out, then there is good marketing, which shouldn't count but it does, and the rest basically depends on some random evaluation from some random person. It's a lottery. I support the idea of having a sort of 3 tiers: crap, excellent and good enough. The third one could be, at least partially, be assigned randomly.

fuzzfactor• 4 years ago

Some people are just better at predicting the future than others.

kmonad• 4 years ago

Why even ask for a grant proposal? Require some evidence that the applicant is serious, and then let luck decide. You might be suggesting this already (but your last sentence read to me as if you're thinking of vetting proposals). Obviously not all funding should be allocated like this, but maybe a small fraction. Perhaps only to those without any grant support at the time. I think it could be a good hedging strategy for society.

WaitWaitWha• 4 years 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)

jvanderbot2• 4 years 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.

epistasis3• 4 years 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.

mattkrause4• 4 years 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.

epistasis3• 4 years 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• 4 years 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.

zozbot23413• 4 years ago

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.

Industry will only ever fund things that are easy to monetize in the very short term. Translational research can be just as important as basic research, so both should be funded when they are plausibly in the public interest, regardless of any private returns.

epistasis3• 4 years ago

Both of those issues: 1) slowing down the DNA, and 2) finding enough change in current to be able to distinguish bases, did not seem that they could work out. You really have to solve the first before you know if the second is solvable, but getting tiny molecules to behave as they flit through protein pores is not a trivial task, particularly around ~2000.

The signal processing is still quite significant, and I hear that if you don't have a compute box that's set up correctly, you can't get data to and from the GPU quickly enough for base calling (no personal experience, just heard friends griping about early experiences). So even with todays compite tech, the signal processing is pretty heavy duty, 2000 era hardware and algorithms would have far far less accuracy.

Which is all to say that yes, now it works, and my uncertainty was perhaps unwarranted. I'm super impressed that it works, and I've learned a ton of humility about guessing what other people can figure out how to do. David Deamer is a visionary, and all the people that worked so hard on it afterwards deserve major kudos.

jvanderbot2• 4 years 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.

kragen19• 4 years 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.... 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.

keithalewis2• 4 years ago

6. And a pony. A pretty one with fluffy hair you can comb.

kragen19• 4 years ago

You seem to be saying that it's unlikely that we'll achieve all of this. And that's true: it's a lot of social change, and social change is very difficult. But every incremental step in the direction of these goals will improve the situation for high-risk basic research like Karikó's.

Except for ponies. Those are pleasant but they're too resource-intensive to be much of a force for advancing basic research.

BlueTemplar• 4 years ago

The pony problem is a tough one. Though maybe we can find a self-reinforcing loop by funding research into breeding prettier and fluffier poneys ?

pvaldes2• 4 years ago

So, we need vaccines to not die, and she wants a pony to comb its hair?.

Seems like a really easy decision to make...

"I will save you five million dollars, if you give me three hundred dollars?". Just take my money and the damned horse is a gift.

zozbot23413• 4 years ago

Your average Karikó would not benefit directly from Universal Basic Income. Not that solving extreme poverty/deprivation while preserving economic freedom and efficiency isn't a good idea for plenty of other reasons, but it's not a free lunch either. The modal UBI recipient will probably be expending their time and effort on training for productive work, not long-term research with no immediate benefits for themselves.

kragen19• 4 years ago

The modal UBI recipient is not your average Karikó; the modal UBI recipient will probably sit around beating their children and watching music videos on whatever the equivalent of MTV or YouTube is in 02039. No conceivable intervention will turn the majority of the population into inventors and scientists, so we shouldn't try unless it's a low-risk effort.

But we can certainly aspire to liberate science from bibliometrics, dollar-auction postdoc rat races, grantwriting, mandatory reporting requirements, and especially prosecution, so that the people who do want to spend their time on advancing human knowledge have the opportunity to do so. And we can work to change the public perception of innovation and research from Frankenstein and Walter White to Edison, Tesla, and Einstein.

aeternum• 4 years ago

Along with #1, a culture shift to promoting the publishing of null-results would also help quite a bit. Journal acceptance and funding is now incredibly biased towards finding a significant result. Every researcher will find p<.05 on average after 20 studies even if those studies are literally measuring random noise.

We need to have some incentive to at least share null-results and replications.

kragen19• 4 years ago

Agreed! Aside from the spurious results produced by publication bias, the amount of effort spent on trying things that somebody already knows don't work is staggering. The knowledge of what doesn't work is mostly passed on tacitly through apprenticeship rather than published, which means it can easily be lost.

As a simple example, we've known how to make transparent glass for 1900 years, but it took Ben Krasnow two months to achieve it himself despite having money, libraries, and glass experts at his disposal, and being generally competent at making things, having built, for example, his own electron microscope: https://www.youtube.com/watch?v=mUcUy7SqdS0

dhosek• 4 years ago

This is true in all fields. I was playing with an idea that factors of Fermat non-primes (2^{2^n}+1 for n > 5) could be expressed in terms of products of the complex factors of the polynomial x^{2^n}+1 with x=1 with the idea that it might lead to a proof that for all n > 5, F_n is composite. I spent a bunch of time working out the exact expressions for these roots and playing around with their products (which ended up having a connection to Chebyshev polynomials), and then it occurred to me to try exhaustively trying the possible products of the complex roots of x^{64}+1 with x=1 to see if it turned up the factors of F_6 and it turned out it was a dead end. A compilation of false hypotheses in different fields of mathematics could make for interesting reading (and perhaps lead to eliminating multiple people getting stuck in the same cul de sac).

generationP• 4 years ago

As the Surgisphere affair has showed, publishing null results opens its own can of worms: No one will bother replicating them. Surprising positives at least have a kind of target drawn on them, but a negative result that matches people's expectations is really not something anyone disinterested would want to replicate -- there is no fame in that. Fraudulent non-results will be blocking fruitful directions.

I wish I had a panacea for these things...

CamperBob2• 4 years ago

So frustrating when someone makes four good points yet throws in a controversial outlier, seemingly at random, that makes me feel awkward about upvoting the rest. I don't necessarily disagree with the concept of UBI, but geez, WTF does that have to do with this conversation?

I guess 80% is good enough. Consider the advantages of focusing on your core theses, though.

kragen19• 4 years ago

Amusingly, I put UBI near the top of the list in part because I thought it was one of the less controversial points.

dekhn2• 4 years ago

i'd be really surprised if buying acetone gets you put on a list, do you have more details?

kragen19• 4 years ago

Be surprised: https://www.argentina.gob.ar/sites/default/files/renpre-inst... https://www.boletinoficial.gob.ar/detalleAviso/primera/85089... https://www.ecofield.net/Legales/precur-quim/res535-14_SEDRO...

They reformulated all the nail polish removers using ethyl acetate instead of acetone.

That said, the listings I'm finding on MercadoLibre right now don't have the requirement that you send them your DNI or your Sedronar authorization that I used to see, so maybe the policy changed recently?

derbOac7• 4 years ago

The attitude isn't cultivated by Hollywood. It's the media and business. And that attitude is that successful, worthwhile ideas, and the persons generating them, are the ones who are successful at climbing the grant career ladder under current funding regimes.

Not saying that what you're referring to isn't also a problem, but the immediate problem with reference to the paper is the meritocracy-funding-complex that underlies modern biomedical academics (and by extension, other areas of academics that are held up to it as a profit source by universities).

bglazer• 4 years ago

Points 1-4 seem to be promoting a vision of individual researchers working independently with low cost instruments. A sort of yeoman farmer model of research?

Why not aggregate those independent researchers into a single place so that they can share ideas and the cost of high quality instruments? Like a university.

Also, I don't disagree with any of these ideas, I just don't think they're relevant in a university setting, at least in the US. Most universities have good libraries with access to all the luxury journals. They have core facilities with high quality equipment. There's some red-tape but you can study just about any chemical in a university lab.

Edit: I should note that the current journal publishing system is a terrible fucking scam and should be immediately dismantled. That said, it's not currently limiting my research because everyone at my university shares in the extortion fees charged by publishers.

ok_dad2• 4 years ago

The literal problem in the article is that those who might make the largest contributions are currently excluded from university organized research due to politics (entrenched and powerful researchers and inflexible policy), discrimination (not just the standard forms of race or sex, but also based on education), or other arbitrary reasons! You’re just saying “the current way is the most efficient” and discarding the entirety of the GP comments 5 points above you.

kragen19• 4 years ago

Oh, universities are great! I'm not saying universities should stop existing or that they aren't important. They're very important! But we can't expect them to provide unlimited resources for free to anyone who is curious about something. They have to pick and choose who they fund, which means excluding the majority of possible Karikós. Perhaps just as bad, the mechanism consigns many of the most promising researchers to administrative tasks like grantwriting and personnel management instead of science. If you're a PI supervising 30 RAs you aren't going to spend a lot of time at the bench.

And most women who get a Ph.D. sacrifice the chance to have kids in their 20s in the process, which is a big deal for many of them; life isn't easy for "nontraditional" postdocs.

And 95% of people don't live in the US.

Finally, universities aren't omnipotent. Gang Chen, David Gelernter, Aaron Swartz, Steve Kurtz, Star Simpson, and Majid Shahriari were all affiliated with universities, and they were persecuted for their research anyway, resulting in their deaths in two cases.

Also, many of the measures I suggest would substantially ease the path of researchers who want to form a new institution to pool resources, such as a hackerspace or a mail-order DNA synthesis company.

So, I think giving people more freedom to pursue research as they see fit would substantially increase the amount of research that gets done, and so would placing more social value on it.

netizen-9368243• 4 years ago

Good luck studying things like cocaine, MDMA, or DMT without a bunch of paperwork and likely denials by the DEA for arbitrary reasons. I hope you like waiting if you want to apply to use these compounds. It should be noted that MAPS had to sue because the DEA was dragging their feet.

https://maps.org/news/media/marijuana-moment-another-scienti...

ISL2• 4 years ago

On point 4: As a scientist who normally chafes at those prohibitions, I'll point out that responsibility for the consequences of ones' research is also important.

For example, it is extremely easy, with both household and scientific chemicals/tools, to create a hazardous waste problem that is a problem for neighbors or a community. I imagine it could be the same for some biological experiments. One of the key advantages of garage experimentation is the freedom from the strictures of a laboratory, but one cannot lose sight of the impacts on others.

kragen19• 4 years ago

I agree! Also, aside from hazardous waste, it would be easy to accidentally create a small-scale version of the PEPCON disaster, the Bhopal disaster, the Enschede disaster, the defoliation surrounding early alkali plants (from HCl emissions), or just a public nuisance. I think there are a couple of things we can do to improve this situation:

1. Create an environment without fear of repercussions for hazardous waste training and services. In much of the world today if you show up at a hazardous waste collection site with 50 kg of poorly characterized organic molecules dissolved in acetone, you can expect an investigation of whether you're running a meth lab.

2. Scale down the hazardous waste regulations to something realistic. A return to Victorian-era nonchalance about things like lead acetate and mercuric chloride would be counterproductive, but we've somehow gotten to a point where people call in hazardous waste teams if they break a mercury thermometer, which is totally out of proportion to the actual risk from metallic mercury, and I've literally seen a news report about sulfur spills where adult anchors who presumably went to college solemnly warn that sulfur is very toxic and can cause severe skin burns. Due to totally implausible concerns about toxicity, borax has been prohibited for most uses (fertilizer, flame retardancy, etc.) in the EU now, though it fortunately remains available in pharmacies. And I already mentioned California's restrictions on aromatic solvents on the absurd pretext of "air quality".

3. For chemistry in particular, focus on developing microfluidics and miniaturized apparatus, because a nanoliter of pyridine is much less of a nuisance than a liter.

jpeloquin2• 4 years ago

Everything on this list is nice in general; my favorite is #5. I suspect that UBI would not make any difference to the "Karikó problem" though. Labs are almost always desperate for people who can get things done. If you don't mind not being a PI and are ok with a relatively small paycheck (but still much greater than what UBI would provide), it's fairly easy to maintain scientific employment that still allows you to pursue your own side projects. Perhaps we should call persisting as an individual contributor, not in a PI / management role, the "Karikó solution".

kragen19• 4 years ago

Labs don't have much funding. Remember 95% of people don't live in the US.

neonate• 4 years ago

https://archive.is/oVyno

http://web.archive.org/web/20220203202632/https://www.statne...

ISL2• 4 years 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.

zozbot23413• 4 years 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.

derbOac7• 4 years 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.

PeterisP2• 4 years ago

The whole concept of basic research is that it is inherently wasteful, as the vast majority of decent (as far as anyone can tell before funding) projects will not yield anything with practical short-term benefits. The projects with large returns can't be seen as rare and special before they are done, it's kind of ordinary and natural for projects which have actual scientific ambition and the potential to yield very large returns to be risky and uncertain; and it's also overwhelmingly common (if we look at historical examples) for the major benefits of the basic research to be impossible to know or describe before that research was done or funded.

If you want non-wasteful research, doing only "safe" projects with a clear path to expected results then you are simply committing to never fund any of the research that has the potential to yield very large returns, and not getting those returns. That is the key point - that attempting to eliminate wasteful research is counterproductive and results in throwing out the baby with the bathwater, so to say. It has a lot of parallels with VC funding, as with basic research just as with startups you can't tell which projects will "strike gold" before the work is done; you can and should do some basic diligence but if you throw out uncertain projects, then you throw out all of the really good ones as well; all the projects where you are quite sure about the results and can know that they won't be bad are the same projects where you can also know beforehand that they definitely won't be groundbreaking.

derbOac7• 4 years ago

Part of the problem is that a lot of basic funding mechanisms have sort of broken down, or we've lost sight of certain things, or aren't open enough or supportive enough as a society of diverse research funding mechanisms.

Just to take one example: at one time, you had a university, someone applied for a tenure-track job. The idea was, if they passed the tenure hoops, had the approval of their peers, etc. the university was essentially "funding the person". That was the idea: the public (or private benefactors) trust a university to appoint faculty who will identify people who are successful with worthwhile research. That is the idea behind tenure at a university, at some level. You as the public entrust the state to fund research, with the idea that there is some benefit and risk attached to that benefit.

Now, though, this idea has broken down, in that the current paradigm is for the university to find people who will get funding from the federal government, to fund their projects. The university is no longer "funding the person" at some level, it's passing that buck on to the federal government, and letting the federal government decide. So while, at one time, we had a very decentralized "fund the person" model (in the form of individual states and universities deciding who to fund), that's started to fail, in favor of a very centralized funding model where we basically rely on the federal government for funding everything.

There's just not enough options for people wanting to do research; it's too homogenous and too narrow in terms of incentive structures. It's like anything else: if you set up a system where there's one way to do it, you're going to incentivize taking advantage of that system.

mrjangles5• 4 years 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.

mattkrause4• 4 years 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).

sdenton42• 4 years 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?

LeanderK2• 4 years 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.

mrjangles5• 4 years ago

if one deep-dives into any kind of research one can see an ocean full of universities producing valuable research

This is simply untrue. When on deep-dives into any kind of research on sees an ocean full of universities polluting the sea with absolute crap. The more bureaucratic and government funded, the worse. For example, I know researchers who simply will not bother to read anything written by anyone working for a Chinese university.

bsmith893• 4 years ago

The outright falsehood of this statement:

just about every important breakthrough in science in the last 30 years occurred at a privately funded American university.

Really makes it difficult to take the rest of this comment seriously.

In case the ways it is "not even wrong" need to be detailed:

1. Drew Weissman's research was (almost certainly) majority funded by public money doled out by the NIH, NSF, and other national organizations. The public/private status of the university has little bearing on that, as most university research funding comes through these agencies, with something like 50% generally going directly to the universities themselves. Research at "private" universities as it currently exists would not survive without this mechanism.

something like 10 privately funded American universities make more scientific breakthroughs than the 10,000 publicly funded universities around the world put together

2. Also very false, although arguably hard to prove one way or the other. How do you define breakthroughs? Press releases from university PR departments? Patents? Either way (or by some third—hopefully measurable—way that I'll allow you to define for us) I guarantee that you need to go much further down the list of private universities before you match the output of "all publicly funded universities around the world put together".

I imagine that you have in mind important (and/or well publicized) advancements from MIT/Stanford/Harvard and are forgetting about the enormous amount of research output from public universities (which include but are not limited to Berkeley, CalTech, U of Michigan, Georgia Tech, Virginia Tech, U of Texas, Ohio State, etc.)

Regardless, this idea would be impossible in the first place at a government funded institution so why even bother mentioning it.

3. As you hardly cite any evidence for this, I'll point out that private money can go to diverse people at diverse institutions (including government funded universities).

So my question to _you_ is whether this comment is motivated by a knee-jerk anti-government reaction, or if I'm entirely misunderstanding where you got these ideas?

mrjangles5• 4 years ago

1. Drew Weissman's research was (almost certainly) majority funded...

At least where I live, many government grants are only available to people who have also managed to get private industry funding for their work too. These grants are usually very successful. This does not disprove my point in any way, in fact, it _is_ my point

2. Also very false, although arguably hard to prove one way or the other.

You have to understand that it is in the interest of the tens of thousands of people doing work doing non-sense research to pretend their research is important. Just because you hear about them telling you how important their worki is in the media, doesn't mean it is.

Anyone who has actually worked it research knows every field is filled with 10's of thousands of garbage research papers that are of no value, and that all the key work is produced by just a hand full of people. I remember also reading some researchers that looked at dozens of fields and breakthroughs and found the same thing. All the real work in any breakthrough is done by just 2 or 3 people at most. so this is incorrect, what I said is actually very provable.

I'll point out that private money can go to diverse people at diverse institutions (including government funded universities).

Yes, that is my point...? You are calling my comment a knee jerk reaction yet you have responded without seeming to understand any of it.

selimthegrim3• 4 years ago

Caltech is and always has been a private institution even when it was Throop College of Technology. To my knowledge the only public institution ever privatized in the US was Tulane (for reasons having to do with Jim Crow).

sabas123• 4 years ago

Side note, looking at patents to identify #breakthroughs doesn't really work as

1. It requires quite a large investment which disfavors smaller institutions

2. The distribution of patents that actually make money is so incredibly skewed that university patents should considered such a bad investment, that it wouldn't be a good metric anymore.

mattkrause4• 4 years ago

I think this section is calling for a more diversified portfolio of ideas.

There's certainly a lot of fad-chasing in biomedicine. There are strong incentives to flock to the latest technique (RNAi, optogenetics, single-cell-seq, organoids) or stick close to an established hypothesis (beta-amyloids for Alzheimer). It might better if there were some countervailing incentives to stick with older techniques, or break away from established dogma. For example, optogenetics has been a very powerful tool for understanding the brain, but it also means that we've moved away from many animal models in favor of mice, where the tools are most tractable. As a result, we know more about brains that are, in some ways, less relevant to human health. A-beta, on the other hand, has been an absolute tire-fire and the field should have shifted ages ago.

The NIH tends not to 'steer' the field in particular directions, but they could. DARPA programs, for example, sometimes explicitly fund several competing ideas to see if a clear winner emerges.

On top of all that, we should also be building a workforce of diverse researchers.

mrjangles5• 4 years ago

I think my point is that private money already goes to diverse ideas. A system where the government will only provide money if there is already private money involved would work well.

e.g., the government will match any private money 2 to 1. Then, for example, the government can take a cut of patents that result (to prevent grants simply subsidizing research that would have occurred anyway).

sampo2• 4 years ago

something like 10 privately funded American universities make more scientific breakthroughs

You are mistaking privately owned universities for privately funded. Scientists in privately owned American universities still mostly apply and receive funding from public (federally owned) funding agencies.

mrjangles5• 4 years ago

Yes, yes! Your comment actually clarifies my point. I'm not saying money touched by the government gets evil magic attached to it that corrupts everything. I'm saying government money is allocated badly and corruptly by default. Except, America does a much better job, why?

In America these privately owned universities use their own money to hire the best people. Private money does an infinitely better job of selecting the best people than government money.

Then the government notes the historical success of these private institutions and sends funding their way, which the excellent individuals they chose can use to create excellent research. This system has made America produce orders of magnitude better science than the rest of the world put together.

My point is that the question of how the government can best direct money has already been solved. Let the private sphere decide who is the best.

mattmcknight2• 4 years 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.

zozbot23413• 4 years 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.

mattmcknight2• 4 years 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• 4 years 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.

derbOac7• 4 years 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.

sdenton42• 4 years 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-advance...

But we could certainly imagine similar for research funding; different paths for rewarding known-good horses, innovative project ideas, etc.

xiaodai• 4 years ago

This women deserves a billion dollars

lucidrains• 4 years ago

not even. like those MasterCard commercials, you could say it is, priceless...

xchaotic• 4 years ago

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

netizen-9368243• 4 years ago

Its possible to cite a paper that you disagree with

pvaldes2• 4 years ago

But if the peer is the author of this paper you could be suggested to rewrite this paragraph

xyzzyz• 4 years 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• 4 years 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.

nextos2• 4 years 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.

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.

PeterisP2• 4 years 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.

derbOac7• 4 years ago

Hungary is an interesting example because it's been pointed to in recent years as adopting the "funding the person" model and trying out different funding approaches.

The broader issue you're mentioning is spot on, though: what are we incentivizing, really?

Things are so broken in academics, at least in the US. I'm not sure what is better but the current system just isn't working.

sfifs• 4 years ago

The thing is many of these rankings put a great deal of emphasis on research program quality and impact. For IITs at least, the research programs are nowhere as good as many top western universities.

I studied undergrad in an IIT faculty that's considered the top in its field in India by reputation of the professors and I worked on two research projects with PhD candidates there. I also spent one summer working on a research project at KTH in Sweden. I must say the experience in terms of research quality, capabilities of the PhD students, facilities, support systems etc was night and day. Due to this in the IITs, the top undergrads leave the country to pursue post-grad and the folks left behind are often the ones who didn't get admits with financial support outside. Very often I observed the undergrad students assisting with the research understood things better than the PhD candidates themselves and all these makes a difference in the research quality and impact.

Now, if you rank university programs in terms of % change in life circumstances, IITs will very likely come at the very top. Because the entry is entirely meritocratic with minimal reservations and even reservations are held to academic standards - seats go vacant rather than being filled with less qualified students - a lot of students from poor families get boosted solidly into upper middle class with an IIT education including many of my own batch mates.

alksjdalkj• 4 years ago

The US News ranking is known to be totally garbage, I really wish people would stop citing it. csrankings.org, which tries to be more objective, has Szeged tied with a number of other schools for at 432 globally (of course that's only considering the CS department).

(FWIW I think ranking schools like this is generally harmful, and even "objective" rankings will still have plenty of biases baked in)

Gatsky2• 4 years 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• 4 years ago

That's true in almost every field. Einstein was standing on the shoulders of Mach.

tomrod• 4 years ago

And Riemann and Gauss. Non-euclidian geometry for the win.

zozbot23413• 4 years 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.

twic• 4 years ago

During my PhD i not only found a paper from thirty years earlier describing exactly what i had discovered, but a footnote in that paper noting a paper from thirty years before that describing the same thing!

codekilla2• 4 years ago

Which field, and which paper? Genuinely curious.

Gatsky2• 4 years ago

Breast cancer immune microenvironment.

https://pubmed.ncbi.nlm.nih.gov/17864583/

hyperpallium2• 4 years 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.

misslibby• 4 years 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• 4 years 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.

selimthegrim3• 4 years ago

Have you ever been to the Midwest?

nulbyte• 4 years 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

sz4kerto• 4 years 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-Khwarizmi3• 4 years 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.

renewiltord• 4 years 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• 4 years 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• 4 years 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• 4 years 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• 4 years ago

See the Bayh-Dole Act.

zozbot23413• 4 years 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• 4 years 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• 4 years 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• 4 years 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• 4 years 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)?

inglor_cz3• 4 years 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• 4 years 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• 4 years 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• 4 years 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• 4 years 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-os...).

missionfission• 4 years ago

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

The Karikó problem: Lessons for funding basic research

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