I looked at other articles on that author's site and found a topic that was discussed here more than once that I would be interested in hearing opinions about:
Quite a few other potentially interesting links, even if only to check some things more deeply. Also, https://guzey.com/fiction/hntop1/ ("How I got to #1 spot on Hacker News and why you should never try doing the same")
There seems to be a tension between “all ideas come from PIs who direct slaves to do experiments” and “students and postdocs came up with their ideas and did everything, PI just paid salaries and equipment”.
My experience is that all labs fall somewhere between these two extremes, and within labs people are spread along this axis.
I felt a contradiction where the author states all ideas and execution comes from lab members, while quoting Boyden on the early days of expansion microscopy.
Nice article. I love hearing podcasts with scientists as guests (eg Boyden quote on expansion microscopy).
Even better is when the hosts are themselves working scientists.
Recently I got really into this podcast by Itai Yanai and Martin Lercher that tries to find how scientists navigate “day science” (eg formal papers and grants) vs “night science” (mucking about in the lab). Highly recommend if one wants to hear discussions by biological scientists talking about creativity.
>I am confident that somewhere between 10% and 50% of papers published in good journals are wrong, meaningless or fraudulent.
This is entirely unsurprising to me. On top of this, reporters will see something interesting in a big name journal and report on it yet that usually adds a whole 'nother layer of incorrectness that the general public picks up as "fact"
having been there (last was in the fray 7 years ago now... geeze time flies) here are my thoughts:
1. These are all technological developments, not scientific developments. Even MRNA-vaccines leading edge stuff was being built when I was in grad school (20 years ago). So judging by what technical developments are coming out now, may be a lagging indicator on science.
2-1: Absolutely correct. Out of 10 years in science I only did 1 "officially on what we were funded to do". The other nine were on sneakily independent shit, or on fully independent (hard money) experiments.
2-2: No comment either way, have no experience with 'methods development' at least in the sense that he's talking about.
2-3: correct in the short term but wrong in the long term. If you are foolish enough to be a postdoc that puts everything into the science, you won't get promoted, so your track record of being a good scientist ends on the vine.
3. Correct in the short term but wrong in the long. I did exactly this but couldn't keep going because being a postdoc was terminal for me.
4. Correct. I tick off at least four of these bullets, including "unwelcome demographics".
5-12. All correct, without much else to add. Well said!
The biggest problem in sciences (biological) in the US is that we let the good quality scientists burn out and quit, and those who advance are mostly people who are playing the game (with a negative selection for those who are actually good scientists, because playing the game is so competitive at this point that it burns time effort and brainspace). This is a leadership defect. We don't give professors instructions on how to groom, including putting time, effort, and political capital into their grad students and postdocs to become lab leaders in their own right (if that is what they want)
One thing that the author does not (and cannot) address is deep knowledge, or thinking about things from first principles, a la feynman or musk. I think as we have more and more interdisciplinary scientists jumping in at the interdisciplinary level, we're already in an era where diletanttery (especially in trendy science mashups like biophysics) is high. This will further dilute expertise and make it hard to separate the wheat from the lemons. Once had a coworker grad student think you could drop a bacterial plasmid into a mammalian cell and get protein expression. I told him I would do it for him, but "I did not think that would work". He then confidently reported a positive observation (which, thank god, did not make it into any sort of publication). Dude is now a associate professor of genome sciences at university of washington.
> as we have more and more interdisciplinary scientists jumping in at the interdisciplinary level, we're already in an era where diletanttery (especially in trendy science mashups like biophysics) is high
Once heard a bioinformatics (CS) PhD candidate say "natural selection would remove a region of the genome if it didn't have biological function". They graduated with a thesis having to do with genome evolution.
This has to be true over geological time doesn't it? I know about "junk" DNA but as I understand it much of that probably is functional, though it's not expressed in protein. Natural selection is what stops DNA from becoming non-functional. If a goven sequence stops working that means either something breaks and the organism gets sick(er) or a workaround is developed or redundancy is used up. If something is non-functional there are many more ways for it t be non-functional in the same way than one so mutation is far lesss constrained than if it's expressed so over the very long run we should expect non-coding regions to disappear though there will always be quite a few.
Over the extremely long run regions of the genome that have no biological function should disappear, no?
> Over the extremely long run regions of the genome that have no biological function should disappear, no?
I think the only argument you can make is that 'eventually a neutral deletion would delete it' but I don't think we have a sense of what the timescale of that should be, and anyways, that isn't 'natural selection', unless you have some sort of argument that there is some intrinsic burden to maintaining DNA. If there is such a burden, it's very low, and probably doesn't affect the reproductive fitness of most organisms (esp. not higher organisms).
I think maybe for a really small organism, like on the order of Mycoplasma, or viruses, the carrying extra base pairs burden can be real, but this is not a general rule across biology.
hypothesis: one purpose of "junk" DNA is to guard against viral disruption of coding regions.
even if they serve no purpose except to fill space, the added base pairs create "decoy" areas of DNA and decrease the likelihood of random mutations affecting vital functions.
> Natural selection is what stops DNA from becoming non-functional [...] Over the extremely long run regions of the genome that have no biological function should disappear, no?
If you have a sequence that's neutrally mutating with no corrective pressure it won't eventually disappear. At most it'll mutate into something unrecognizable [^1]
For example, your genome is littered with pseudogenes. These are mutated, ineffective shadows of what used to be a functioning gene. Nonetheless they're still close enough to what they used to be that you could reason about them in an evolutionary sense, eg: this one is also a pseudogene in other primates (i.e. it stopped mattering a long time ago), or this other one has a functioning homolog in non-primate vertebrates (i.e. it kept functioning in that lineage).
[^1] as a first order approximation. There are of course other structural events that can create much more change per event than your run of the mill single-point mutations that occur during every DNA replication.
>>>> 1. These are all technological developments, not scientific developments. Even MRNA-vaccines leading edge stuff was being built when I was in grad school (20 years ago). So judging by what technical developments are coming out now, may be a lagging indicator on science.
I'm not a life scientist, but a physicist developing scientific equipment. My impression is that every branch of "science" has a technological side, to an extent that varies from one branch to another. Making and testing new therapies has been undertaken under the umbrella of life science for a long time. I think one reason is that the same "hands" that are good at doing the basic science work are also needed for technology work in those fields.
Another is that the underlying science isn't robust enough to expect a scientific development to be handed off to an engineering department without needing to learn more science along the way.
It's not like physics, where a mainstream engineer working on a technology is highly unlikely to discover gaps in physics theory.
I think the "biology gonna biology" is often a bit overplayed. A friend of mine was a high level manager at a certain petrochem's biotech arm and they ran into a bottleneck that was erratic. My friend kept saying "hey guys it's probably this" but they refused to listen to her and they went on a year long saga to search for the problem, including a full DOE (design of experiments) analysis. It turned out she was right. And thn the petrochemical company lost a major lawsuit about an accident they had caused and so they didn't need a green washing campaign anymore, and the department was shuttered.
I'm concerned by #3 "Nothing works the way you would naively think it works (for better and for worse)" which seems to imply that all or most of life sciences is funded by the NIH. What % of life sciences funding comes from the NIH and what are the other big sources?
The vast majority of life sciences is funded by NIH. This is one reason why the nonstop "revelations" of crazy projects funded by gasp Anthony Fauci are really meaningless. NIH doles out an enormous bucket of cash year after year for all sorts of research.
>the nonstop "revelations" of crazy projects funded by gasp Anthony Fauci are really meaningless
I'm not really aware of any of those other than the gain of function research on bat coronaviruses by EcoHealth Alliance, which was only controversial beacause Fauci denied it in front of Congress and was technically not supposed to happen due to Obama's moratorium. What are the other revelations are you talking about?
Not gp, but there was another one that made the rounds about dogs being subjected to being bitten by desert insects. Iirc It turned out that this wasn't funded by the nih?
In the US the NIH funds the vast majority of life sciences ($30B/year), but NSF, DOD(IIRC at least a billion a year each), and private institutions also provide life sciences funding (several more billions). NIH definitely is the big gorilla, many young investigators are trying to get established by getting R01s and using them to publish papers at the start of their career.
Fascinating. I guess I am surprised because I had thought of NIH as focused on human/public health, and there is so much to life sciences that is non-human. I would have thought there would be more major sources of funding. For example, something around ag science.
The NSF funds basic science, including life sciences. NIH targets diseases. (and the NSF or NIH will not fund something if it better fits under the other) I certainly think it's a valuable thing to have a federal agency doing. If you want more basic life science, funding this area in the NSF more would be the way it's done in the system we have today. NIH has the cancer institute and the institute of mental health and so on. It is therefore really the domain of physicians. They want a path through mouse (or whatever) then human clinical studies, and want to see doctors as co-PI's.
The fact that this careful practical system still pumps out so much bs is very problematic. I think it's the same problem as other research areas, not the fault of the NIH system itself.
the NIH is awesome. we owe those civil servants a debt of gratitude for sacrificing higher compensation in industry and performing as well as they do given the constraints.
breakthrough ideas typically come from unconventional ideas, i.e., risky ideas or ideas likely to fail -- and thus waste taxpayer money.
yet the funding process is mostly about conforming to traditional assumptions, which naturally gates scientific breakthroughs.
the problem lies upstream. politicians don't allow the NIH to fund risky research and waste money.
>politicians don't allow the NIH to fund risky research
how about NIH funding those gain-of-function coronavirus experiments (which included human testing) in Wuhan? And when DARPA refused to fund as too risky the additional human targeting coronavirus genetic manipulations in Wuhan, it was NIAID (led by Dr. Fauci - the top politician in life sciences today) which funded it.
>how about NIH funding those gain-of-function coronavirus experiments (which included human testing) in Wuhan?
Politicians expressly disallowed those experiments. Don't stir stuff up just to stir. It was a non-political agency exec (Fauci?) who apparently sidestepped the typical review process where they would have been killed, and funded them anyway
to me transfer of the research to China is exactly a typical solution by politicians - maintaining the perception of prohibition while in reality scaling the research even more into risky territory.
you know what annoys me the most about this? I wanted to be an NIH researcher (US citizen, working in the US, on non-risky research and I couldn't get funding. That NIH is funding chinese institutes really bothers me, if legit us researchers can't get funding.
"You're doing it wrong" as SRCUM peddlers like to say :) If you look at EcoHealth NIH grant for Wuhan you'll see that only about 25% of the grant money actually went to Wuhan. I'd guess you in your grant application didn't have 75% allocated for general sales and administrative/whatever money black hole and thus for example couldn't hire as a visiting professor/consultant some useful people :)
Amusingly, after my first R01 was rejected, I kept an eye on that study section and several people submitted R01s with exactly my proposal the year after and got funded. Those were people that were likely on the study section the year before and saw my proposal.
I also learned from that if you want to get funded by a study section, you volunteer for that section for several years and then you know exactly what to say to get funded.
NIH likely funds 2/3rds of US biomedical research and ~1/3rd of global biomedical research by dollar value [0]. That link lists other big sources (ERC, MRC, US DoD, HHMI). My sense is that this landscape will change rather quickly with pandemic-inspired biomedical/defense initiatives and more private institutes in the US.
Moreover, NIH funding, due to its central role in supporting biomedical research, is often necessary for getting a tenured PI position. Many high caliber R1 schools require multiple R01 NIH grants for tenure. Often private funding sources are less valuable to universities because they pay lower indirect rates (<10% vs >40%) on sponsored research. As institutions are so dependent on NIH funding, the NIH can exert influence far beyond the research it funds directly.
Well for one, if anyone says "they weren't funded for X grant, so it didn't happen", it's implicitly encodes the idea that people don't do research before they get the grant money. They do.
Just like the trend with big news media in general -- they understandably care about popularity, not facts. Why do we listen to those journals then, for the topics we care about?
https://guzey.com/books/why-we-sleep/
The title is "Matthew Walker's "Why We Sleep" Is Riddled with Scientific and Factual Errors" and the contents is piece by piece refuting that book.
Checking google, it was discussed on HN actually: https://news.ycombinator.com/item?id=21546850
and in this sub-thread: https://news.ycombinator.com/item?id=21792342
Quite a few other potentially interesting links, even if only to check some things more deeply. Also, https://guzey.com/fiction/hntop1/ ("How I got to #1 spot on Hacker News and why you should never try doing the same")