[HN Gopher] The Kariko problem: Lessons for funding basic research
       ___________________________________________________________________
        
       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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