[HN Gopher] The Kariko problem: Lessons for funding basic research
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The Kariko problem: Lessons for funding basic research
Author : hatmatrix
Score : 119 points
Date : 2022-02-03 20:21 UTC (2 hours ago)
(HTM) web link (www.statnews.com)
(TXT) w3m dump (www.statnews.com)
| ISL wrote:
| 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 wrote:
| > 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 wrote:
| 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 wrote:
| > 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.
| WaitWaitWha wrote:
| > 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 wrote:
| 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.
| xchaotic wrote:
| The way scientific papers are ranked - ie how many citations a
| paper gets, means consensus is rewarded and dissent is punished.
| sdenton4 wrote:
| 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.
| [deleted]
| RcouF1uZ4gsC wrote:
| > 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
| Kariko to come work in his lab.
|
| The government funding doesn't necessarily have to identify the
| Kariko's of the world, as long as it can identify the Weissman's
| of the world who can identify The Kariko 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 wrote:
| The problem, though, is then often people like Weissman get the
| credit, because they're the ones with the money, and the
| Karikos 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.
|
| Kariko, 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.
| mrjangles wrote:
| 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.
| sdenton4 wrote:
| "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 wrote:
| > 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.
| mrjangles wrote:
| >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.
| mattkrause wrote:
| 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.
| mrjangles wrote:
| 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).
| mattkrause wrote:
| I don't think that's necessarily true. Industry is mostly
| interested in things that are _almost_ ready to be
| translated into a product. Foundations can be very
| conservative (and the grant sizes are often much smaller).
|
| Anyway, mechanisms like what you're proposing do exist
| (MITACS in Canada, for example). However, the problem is
| the other end of the pipeline. How can you pitch investors
| on something that might not be a product for decades, if at
| all? Government R&D primes that pump.
| sampo wrote:
| > 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.
| bsmith89 wrote:
| 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?
| mrjangles wrote:
| >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.
| derbOac wrote:
| > 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.
|
| In my experiences, the current system has led to problems
| with a small number of people "sucking up credit" that's
| unwarranted, in the sense that they're very very good at
| taking credit from others and building up a CV that makes
| it look like they're at the center of things.
|
| In any event, I'm very skeptical of these things at this
| point based on my personal experiences. Usually progress is
| incremental and involves a lot of efforts from lots of
| individuals. Even bigger advances usually involve a
| confluence of things.
|
| Bibliometric studies are often flawed because they make a
| lot of false assumptions and ignore realistic dynamics,
| with corruption and gaming of metrics.
| jltsiren wrote:
| > 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.
|
| Grants like that are rare, because there is very little
| industry funding for basic research. Private funding
| usually comes from various trusts and foundations that
| operate in similar ways to government funding agencies.
|
| > 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.
|
| Alexander the Great didn't win battles on his own. He
| needed a lot of soldiers for that. Similarly, scientific
| breakthroughs are meaningless on their own. You need a
| massive amount of grunt work by ordinary researchers to
| connect them to the real world and make them useful.
| mattkrause wrote:
| "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).
| ummonk wrote:
| 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.
| epistasis wrote:
| 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 wrote:
| 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 wrote:
| 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.
| jvanderbot wrote:
| 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.
| throwawayarnty wrote:
| 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 wrote:
| > 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 wrote:
| 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]
| zozbot234 wrote:
| If you _could_ systematically predict Kariko 's, they would not
| be Kariko'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.
| derbOac wrote:
| 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.
| xyzzyz wrote:
| 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.
| mattmcknight wrote:
| I am not sure funding Kariko 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 wrote:
| > 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 wrote:
| 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.
| kragen wrote:
| The things that would most help with the Kariko 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 Karikos 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.
|
| 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.
| ISL wrote:
| 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.
| derbOac wrote:
| 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).
| [deleted]
| bglazer wrote:
| 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.
| kragen wrote:
| 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 Karikos. 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, 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.
|
| 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.
| ok_dad wrote:
| 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.
| zozbot234 wrote:
| Citizen science can definitely be a thing, but it's going
| to have very different comparative advantages than anything
| based around established institutions, i.e.
| universities/research labs. It might well be that _both_ of
| these are worthwhile problems to solve - they need not be
| exclusive.
| keithalewis wrote:
| 6. And a pony. A pretty one with fluffy hair you can comb.
| kragen wrote:
| 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 Kariko's.
|
| Except for ponies. Those are pleasant but they're too
| resource-intensive to be much of a force for advancing basic
| research.
| BlueTemplar wrote:
| 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 ?
| zozbot234 wrote:
| Your average Kariko 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.
| kragen wrote:
| The modal UBI recipient is not your average Kariko; 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.
| ok_dad wrote:
| That's a very negative view of humanity. Everyone I know,
| from phds to blue collar workers, have great things they
| aspire to, if only they had the time. You must hang out
| with real losers if that's what you think is reality, or
| you must be listening to the media representations of the
| worst of us.
| kragen wrote:
| I have great things I aspire to, too, that I'm not
| actively working on. Instead I'm wasting my time getting
| flamed on some toxic website. I guess I'm a real loser!
| But I don't think I'm much worse than average. At least I
| don't beat my kids.
|
| You can see what people do with total freedom by looking
| at retirees and the rich. Some of them do the great
| things they aspire to. Most of them don't. I still think
| more freedom is a net good.
| CamperBob2 wrote:
| 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.
| kragen wrote:
| Amusingly, I put UBI near the top of the list in part because
| I thought it was one of the less controversial points.
| dekhn wrote:
| i'd be really surprised if buying acetone gets you put on a
| list, do you have more details?
| kragen wrote:
| Be surprised:
| https://www.argentina.gob.ar/sites/default/files/renpre-
| inst... https://www.boletinoficial.gob.ar/detalleAviso/primer
| a/85089... https://www.ecofield.net/Legales/precur-
| quim/res535-14_SEDRO...
|
| 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?
| aeternum wrote:
| 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.
| kragen wrote:
| 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
| generationP wrote:
| 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...
| zozbot234 wrote:
| The Surgisphere papers were not "null" results. They found
| significantly higher risk of death after HCQ treatment,
| based on what turned out to be highly flawed data. The
| problem was with the original dataset. (Not to be outdone,
| the Surgisphere folks also contributed their data to a
| preprint which purported to show horse
| dewormer^H^H^H^H^H^H^H^H^H^H^H^H^H^H ivermectin could be a
| _successful_ SARS-CoV2 treatment).
| sampo wrote:
| > horse dewormer^H^H^H^H^H^H^H^H^H^H^H^H^H^H ivermectin
|
| You are not being truthful, labeling ivermectin only a
| "horse dewormer". Ivermectin is used as an antiparasitic
| drug also for people. And not only as a dewormer, but
| also against lice and mites.
|
| https://en.wikipedia.org/wiki/Ivermectin
| dhosek wrote:
| 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).
| noslenwerdna wrote:
| Interestingly, this isn't true in particle physics!
| Probably most papers published by ATLAS or CMS are a
| negative result.
| xiaodai wrote:
| This women deserves a billion dollars
| lucidrains wrote:
| not even. like those MasterCard commercials, you could say it
| is, priceless...
| neonate wrote:
| https://archive.is/oVyno
|
| http://web.archive.org/web/20220203202632/https://www.statne...
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