Scientific Research and the Unforeseen World: Why Basic Research is Essential

Yves here. I’m old enough to remember when both the American government and some major private companies did a lot of basic research, such at the old Bell Labs. Per Wikipedia:

Researchers working at Bell Laboratories are credited with the development of radio astronomy, the transistor, the laser, the photovoltaic cell, the charge-coupled device (CCD), information theory, the Unix operating system, and the programming languages B, C, C++, S, SNOBOL, AWK, AMPL, and others. Nine Nobel Prizes have been awarded for work completed at Bell Laboratories.

Now it seems to be quaint to be interested in science for the thrill of discovery or even of making a fundamentally important contribution. It’s so much easier to get rich making an app or hawking a designer dietary supplement. And the rest of us wind up poorer for this misuse of potential.

KLG makes a key point below: the way that research is funded now further impedes potentially pathbreaking inquiries moving forward.

By KLG, who has held research and academic positions in three US medical schools since 1995 and is currently Professor of Biochemistry and Associate Dean. He has performed and directed research on protein structure, function, and evolution; cell adhesion and motility; the mechanism of viral fusion proteins; and assembly of the vertebrate heart. He has served on national review panels of both public and private funding agencies, and his research and that of his students has been funded by the American Heart Association, American Cancer Society, and National Institutes of Health

During the final summer of World War II Vannevar Bush, who was leader of the Office of Scientific Research and Development in the White House, wrote a report for President Truman that he called Science, the Endless Frontier.  The report was recently republished with an introductory chapter by Rush Holt, Jr, a physicist and was an 8-term congressman from New Jersey from 1999 to 2015.  Although Vannevar Bush was primarily an engineer, he appreciated that science, engineering, and technology are not one and the same, but that each is dependent upon the other.  Science, the Endless Frontierwas a thoroughgoing brief for basic scientific research, explaining why government support of science was an essential component contributing to the wellbeing of all.

A major result of the Bush report was the establishment of the National Science Foundation (NSF) in 1950, followed by the transformation of what began as the Hygienic Laboratory in 1887 into the National Institutes of Health (NIH) we know today, with its 27 separate centers and institutes and a budget of $42B in 2020. While the Cold War tended to subvert certain priorities, a topic for another time, the Golden Age of American Science from the 1950s through the 1990s was real.  Although there were ups and downs associated with budgetary constraints and politics, and there has always been some logrolling among the chosen, both agencies funded what Karl Popper would have called “good science” that was directed at answering interesting questions of what was once called “natural history.”

I am a biologist by temperament and vocation, and in this post, I will briefly tell a story of biological research that would be characterized today by reviewers and program officers at funding agencies using the killer epithet “descriptive,” but nevertheless resulted in knowledge that revolutionized cell biology in remarkable and entirely unforeseeable ways.

Bioluminescence, the emission of light by living organisms, was described by Aristotle and subsequently appeared often in the literature of natural history through the 19thcentury.[1]

Throughout the 20thcentury, this fascinating aspect of natural history yielded to biochemical approaches, as scientists in the United States, Europe, and Japan developed an understanding of the chemical nature of “cold light” and explained “how” of bioluminescence works in bacteria, protists, fungi, and animals[2].  The evolutionary “why” of bioluminescence is not as well understood across the web of life and is still mostly an outstanding question, though it is clear that deep sea anglerfish use their lures filled with bioluminescent bacteria to attract prey in the darkest ocean depths.

At the biochemical level, bioluminescence is most well understood in bacteria, fireflies, and marine invertebrates, including various Cnidaria (coelenterates, including hard and soft corals and jellyfish) and Ctenophora (comb jellies).  The latter are considered to be among the earliest diverging animals, with a current nod to ctenophores, so bioluminescence is likely to be an ancient attribute of animals, though restricted in distribution among extant organisms.  Here we will concentrate on the jellyfish Aequorea victoria and the sea pansy Renilla reniformis, because the mechanisms of bioluminescence in these organisms are similar and have been described in detail.

Without getting too far into the biochemical weeds, the key points, which were worked out in a series of papers from the late 1950s through the 1980s primarily from the research groups led Milton J. Cormier(Renilla) and Frank H. Johnson and Osamu Shimomura (Aequorea), are

  1. A chemical (substrate) called luciferin is acted upon in the presence of oxygen by
  2. An enzyme (protein) called luciferase
  3. With the production of blue light

This blue light is produced in the test tube with purified components.  In each organism, however,

  1. The emitted light is green

And for a long time the question was, “How does that work?” To make a long story short, another protein is required for light emission in the organism: Green fluorescent protein, or GFP.  The energy released during the oxidation of luciferin is passed directly to GFP, which then emits green light.

After the biochemistry and biophysics of coelenterate bioluminescence were worked out using components purified the old-fashioned way from the sea pansy and the jellyfish collected at marine laboratories, the biochemists doing the research did the next thing – they became molecular biologists and cloned the genes for Renillaluciferase, AequoreaGFP, and aequorin (here and here). Aequorin is the pre-charged luciferase-luciferin-oxygen complex triggered to emit light upon binding to Ca2+ions.

The availability of these recombinant versions of each protein led to their use as tools in molecular and cell biology.  Recombinant luciferase was soon used to measure gene expression in real time in cells in which a chimeric luciferase/gene-of-interest simply by adding luciferin to the culture medium and measuring light output under experimental conditions.  Aequorin purified from the jellyfish had long been used as a calcium indicator in studies of muscle contraction and the propagation of signals in nerve cells, but the availability of recombinant aequorin made it possible to extend the reach of this technique without the necessity of purifying the native protein from the jellyfish and then microinjecting it into cells manually.  As with Renillaluciferase, it became possible to prepare cells expressing recombinant aequorin and measure calcium fluxes without microinjection.

These benefits from research on coelenterate bioluminescence were important advances.  Light emission is easy to measure, and to a first approximation, the localization of the light-emitting molecule (aequorin or a chimeric aequorin/protein-of-interest) in a cell, tissue, or organism can be determined.

But AequoreaGFP was unexpectedly destined to be the most important result of this research. Shortly after publishing his work on the cloning and sequence of the GFP gene, Doug Prashermet Martin Chalfie and shared his GFP clone.  Chalfie then expressed AequoreaGFP in the bacterium Escherichia coliand nematode Caenorhabditis elegans, and the rest is history.  From the abstract of that article:

A complementary DNA for the Aequoreavictoria green fluorescent protein (GFP) produces a fluorescent product when expressed in prokaryotic (Escherichia coli) or eukaryotic (Caenorhabditis elegans) cells. Because exogenous substrates and cofactors are not required for this fluorescence, GFP expression can be used to monitor gene expression and protein localization in living organisms (emphasis added).

GFP, prosaic name that it has, is quite simply a wonder of nature.  The protein folds into its native three-dimensional conformation spontaneously.  Moreover, the protein is remarkably stable.  Thus, a recombinant gene-of-interest containing GFP at one end or the other is easily expressed in cells of all types, from bacteria to human stem cells, and the location of this GFP-containing protein can be identified precisely using a fluorescence microscope, in real time in living cells.

Since the cloning of AequoreaGFP, it has appeared in over 45,000 publications, such that cell biology without the use of GFP is scarcely imaginable.  After GFP was first used, Roger Tsien set out to produce GFP in different colors, and now we can use various shades of “GFP,” ranging from deep blue to red, often used in the same cell while studying the function of distinct proteins.  Thus, Osamu Shimomura first purified and initially characterized GFP from the jellyfish; Doug Prasher later cloned the gene and then gave it to Martin Chalfie, who showed that GFP could be used as a marker of protein expression in virtually all living cells.  Roger Tsien of the University of California-San Diego subsequently developed GFP in multiple colors.  Drs. Shimomura, Chalfie, and Tsien were awarded the Nobel Prize in Chemistry in 2008 in recognition of their work, which has revolutionized research in cell biology.

Why is this interesting, to me and other biologists and to those interested in scientific research as one of our methods useful for understanding the world around us?  Because the research upon which this revolution was based developed straight out of Vannevar Bush’s vision of basic research, which should be funded and supported in the absence of a particular goal.  This research had no instrumental justification, other than to understand an interesting puzzle of natural history.  There is no way that anyone could have pictured where the early funding from NSF to Osamu Shimomura, Frank Johnson, Milton Cormier and several others would take us.

That was indeed a different world.  Current guidelines from the NSF Cellular Dynamics and Function Cluster, which would be a likely source of funding for the research on bioluminescence are here:

The cluster seeks theory-driven investigations of diverse cellular and subcellular systems. Research proposals are encouraged that use multidisciplinary physical, chemical, mathematical and computational approaches to providenovel techniques and integrative insight into fundamental cellular functions. Innovative proposal using plants, microbes, and nontraditional model species are encouraged. Proposals that rely heavily on descriptive approaches are given lower priority.

The cluster encourages proposals in the following areas:

  • Predictive understanding of the behavior of living cells through integration of modeling and experimentation.
  • Evolutionary approaches to understanding the rules governing cellular functions.
  • Integration of function with emerging cellular properties across broad spatiotemporal scales, including ideas that consider cellular organization from the standpoint of soft condensed matter are encouraged.

The cluster recognizes that technological advancement can have profound and catalytic influences on the field of cell biology. These advances are often the result of technology in one scientific field being borrowed and applied to another in new and creative ways. The cluster encourages proposals to develop or adapt innovative tools with potential to enable new avenues of cellular investigation.

This is word salad of the worst kind, rivalling that of the typical American politician (which come to think of it, NSF has a .gov suffix).  The description at Systems and Synthetic Biology may be worse.  But let us unpack some of this.

Theory-driven investigations.  Theory is in the eye of the beholder, and theories in biology have an undistinguished past.  This in particular reminds me of the “axiomatic biology” developed by J.H. Woodger during the 1930s,[3]during one of Biology’s periodic extended bouts of physics and engineering envy.  Aside from the Gene Theory, the Central Dogma of Molecular Biology, and the Modern Synthesis of Evolutionary Biology, biology is too granular, i.e., biological molecules and cells have a meaningful evolutionary history of almost 3 billion years, for grand overarching theories of any kind.

Multidisciplinary. Interdisciplinary, perhaps, but then such collaborations and conflations, seldom work, especially when forced, although they are popular with politicians.  Novel techniques and integrative insights…innovative tools with potential to enable new avenues of cellular investigation. Anyone who proposes something truly novel or innovative in a grant proposal to NSF will be disappointed with an inevitable version of “she has not proved she can do this or that it will work” from at least one reviewer.  One is enough.  And it is usually Reviewer Number 3.

And now to my favorite: Proposals that rely heavily on descriptive approaches are given lower priority.  I think they forgot “incremental,” which is the twin of “descriptive” in the Program Officer/Proposal Reviewer universe of disdain.  I will simply point out that none of the solid research that led to the revolution in cell biology described here would have met the standards of the current NSF.  The objective of those scientists 50-60 years ago was to understand nature, at whatever appropriate level they pursued.

Because Biology is not amenable to “theory” except in the most trivial of contexts, virtually all biological research is primarily descriptive.  It is also incremental.  Leaps are few and far between, including the structure of DNA although James Watson in The Double Helix tried his damnedest to make it so for DNA and nearly succeeded.

Other major advances in biology in the past 50 years that were “descriptive and incremental” include our understanding of the cell cycle, which was worked out using yeasts and marine invertebrates as experimental organisms after the use of “higher” cells and models proved fruitless.  The first cell lineage map of a multicellular organism was accomplished using the nematode C. elegans, and this led to the discovery of programmed cell death (apoptosis), which is the objective of much cancer therapy.

Every high school biology student knows the importance of the fruit fly in the development of genetics, but the genes responsible for pattern formation in virtually every animal came out of research by a largely solitary, independent scientist who described fruit flies that looked strange. As Joram Pitiagorsky pointed out several years ago, those responsible for choosing the winners and losers in what has become the Great Grant Lottery, from policymakers to reviewers to Program Officers, should remember always that the answers to biological questions cannot be known in advance – there is no biological equivalent of the Higgs boson– and that the answers to these questions often lead to advances in scientific knowledge, and scientific practice, that are as unimaginable and unpredictable as they are revolutionary.

Is there a way forward for biology?  Yes, but things must be changed.  In my first two contributions to this series (here and here) I undoubtedly came across as one who is disenchanted with science.  Nothing could be further from the truth.

But I have seen good science, bad science, and indifferent science in a career that began as a dishwasher in a teaching laboratory.  I hope I have contributed to the first of these, and I have no doubt that I have been party to some of the latter.  Nevertheless, I am about to break Horowitz’s Law, named for my Introductory Sociology professor when I was a freshman many years ago: “Never generalize about your own limited experience!”

Horowitz was right, and his teaching has served me well for 40 years.  But my experience has now been extensive at every level of research in the biomedical sciences.  When the early work on bioluminescence described here commenced, grant review panels met to decide which applications not to fund.  This does not mean that obtaining grant support was ever easy. But there was a time when positive expectations were reasonable, when the word “grantsmanship” did not exist.

I have written and reviewed grant applications for more than 30 years, and more recently I served for 10 years as co-chair and chair for a national review panel of a prominent funding agency. During this time, it became clear to me that a review panel can (just possibly) decide which applications are in the top third of the pool and should be funded and which are in the middle third and should be funded upon revision.  A 67% success rate is about right.  Most scientists are serious minded and willing to work hard.  Preparing a research grant application is certainly hard work that can take a year or more.  Those in the bottom third will remain hopeless for the duration.

Believable success rates for major public funding agencies are hard to come by because definitions of research awards are sometimes incommensurate with one another.  But at NIH the recent pay line for extramural research project grants is ~20%.  Or as we should view it: 80% of all research proposals remain in purgatory.  In some institutes the success rate is in the single digits.  I have a close colleague doing some very promising research on cancer.  With the pay line of 8-9% at the National Cancer Institute, she, as someone who is not already a member of the club, she has virtually no chance.

The opportunity costs of such low success rates are not calculable, but they are large.  What are we missing by picking the winners ahead of time, ranking one grant in the top-5% while there is no difference between that application and one that ranks in the top-30%?  Had the current neoliberal project reigned in the 1950s would bioluminescence of obscure “primitive” animals have been funded?  Probably not.  Would someone have eventually figured out that GFP from a jellyfish could be used as the indispensable tool in cell biology?  Probably not.

So the solution to this problem is similar to the solution to so-called evidence-based medicine: Scientific research funded with an open mind and disinterested expectations.  Will some of the research yield indifferent results, or even no results.  Of course, it will.  But some if it will be revolutionary.  We cannot know which ahead of time. 

And in the long run, it will be less expensive to have an enlarged NSF and NIH (yes, we can afford both) fund the ideas that do not work while making sure that those that will work get the chance they deserve.

As a final note, while I was reviewing the literature referred to here, I noticed that the research groups who did the work were often small and the number of publications by the principal investigators not ridiculously large. There is something to this, alluded to by Karl Popper: “My own misgivings concerning scientific advance and stagnation arise mainly from the changed spirit of science, and from the unchecked growth of Big Science (certainly including Big Pharma), which endangers great science.”  This great science is often done by very small groups of committed individuals.

If we as a nation are serious about building back better, this is one of many good places to begin.

––––––––

[1]E. Newton Harvey, A History of Luminescence from the Earliest Times until 1990. Philadelphia: The American Philosophical Society, 1957.  Bioluminescence, New York: Academic Press, 1952.

[2]F.H. Johnson and Y. Haneda, eds. Bioluminescence in Progress, Princeton: Princeton University Press, 1966; P.J. Herring, ed.Bioluminescence in Action, New York: Academic Press, 1978.

[3]The Axiomatic Method in Biology(1937).  Yes, I read this to the extent that was possible.  It has been a long time, but the notation reminded me of Principia Mathematicaby Bertrand Russell and Alfred North Whitehead.  A library with open stacks in a major research university is a wonder of the modern world.

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68 comments

  1. kriptid

    Good post by KLG. Allow me to add my own personal views and anecdotes as a basic researcher in biology currently transitioning out of science.

    Science, has become like so many other things in life, narrative-driven. This seems counterintuitive, since the layperson and even most scientists claim that science is the opposite of narrative, that it is the pure pursuit of objective truth at the expense of all other interests. This objective truth is often ugly, messy, and unrecognizable when it appears in its initial form. However, that vision of truth will certainly not get you funded. In fact, the type of ‘truth’ that is favored is that which is neat, tidy, makes perfect sense, has no holes, no flaws to be seen. However, as any person who has spent years of their life toiling in a basic research lab and writing papers knows, these perfect narratives can never be based in reality, because reality, and biology, is very messy.

    ‘Descriptive’ research, as defined by the author here, is essentially the entirety of biological research up until the 1960s when the genetic code was untangled. I’m currently writing a review and perusing some papers in my field from this time. The tone was much different. Papers were very open-ended, the conclusions were soft, hedged, strictly confined to the evidence. Caveats are openly acknowledged, contradictory data from other studies presented and confronted. I contrast that with now, in which contradictory data is often ignored or uncited, conclusions are often sweeping and overbroad based on little evidence, every paper seeks to determine the next ‘molecular mechanism’ or ‘revolutionary method’ rather than focusing a simple question. Science is way, way out over its skis in terms of what it can deliver and promise.

    Why has science changed? Because biological science has now proven that it can be a major economic engine, especially in an unhealthy society with privatized healthcare. Publically-funded research has become the birthplace of private fortunes. Moderna is a great example of this. One day I will do a longer post about the massive bureaucratic incentives for Moderna’s success that relate to relationships and funding sources of the early principals involved, but that is for another time. What’s important for my point now is that science is no longer done for the sake of science, it is done for the sake of some future economic incentive that can be exploited for profit in healthcare.

    This has led to a massive gutting of basic research efforts, not by design, necessarily, but because nobody is interested in funding something that doesn’t promise to be a breakthrough. CRISPR is a phenomenal example of how this system fails, even better than GFP in my opinion, because it was rooted in basic research that seemed to serve little point beyond entertaining someone’s intellectual curiosity. GFP, at least, had more obvious utility in broader research at first glance. Now, CRISPR has completely transformed biological research. The problem is, the person writing the grants to study CRISPR at that time could have no idea how impactful CRISPR would be; this can only be realized a posteri. It is impossible to propose an analysis of cost-and-benefit when the benefit is not realized until the cost expenditure is made. And this model is anathema to one built on immediate economic incentives.

    Let me illustrate how this model works against you further, but from a completely different angle. The standards for publishing on Covid19 in the first six months of the pandemic went absolutely through the floor. You had thousands of labs all over the world working on viruses for the first time, with no prior experience. Not only that, but on a virus upon which no literature existed. Now, everyone knew that there was going to be a cash bonanza for Covid research, and so everyone piled on. This has led to the proliferation of so much bad research on Covid, that the truth about many things Covid-related will not be determined for decades. I’ll admit that I often cringe when I see how authoritatively bioRxiv and medRxiv papers posted in the Links are treated by NCers when I know that probably at least half (to be favorable) are just flat out bad science written by many people (because, let’s remember, that’s what scientists are) chasing the Covid19 gravy train for the money and for the career clout. This is not to call those folks out as immoral; they’re just doing as they’re trained in this system. No judgment here.

    I’ll close with this thought: nobody takes peer review seriously anymore. What I mean by that is, very, very few reviewers will take the time to thoroughly read and understand a paper when they have their own papers and grants to write. Peer review has become an absolute joke. The editors are often low-quality post-docs with no relevant scientific experience to the area they are assigned. Many papers are rejected by reviewers just due to time unless its the top journals, because reviewers think that volunteering to do reviews in a journal they want to publish in will help them. Lesser journals might have to e-mail a dozen reviewers to get a few to agree, and there’s no guarantee they’re very interested. They might spend 15 minutes reviewing a paper that took years to write. But since the editors are so starved for reviewers, they will say nothing. They grin and bear it and ask the authors to deal with the most ridiculous requests so the process can maintain the semblance of utility and legitimacy.

    I won’t miss it. I’ve spent the last five years of my life writing my own personal obituary for the modern scientific enterprise and I look forward to taking my talents to a field where I’ll be better compensated.

    1. lab_rat

      Thanks, kriptid. I just transitioned out of biology research, and I will never look back. Good luck with your transition!

      I agree with everything you said – the profiteering in scientific research, particularly biological or medical sciences, is just sickening. Every party of the game – granting agencies, researchers, reviewers, academic publishers, pharma companies – does their own calculations to maximize gain.

      Regarding narratives, I was once in the game of dissecting the so-called “molecular mechanism”. Every research article talking about molecular mechanisms tend to story-tell in a way that it seems the relationship between biomolecules are linear – that is, “neat and tidy”. It is also more acceptable to the human brain, which favors linear, causal relationships that requires less processing power. But the reality is that molecular mechanisms, as you said, are never neat and tidy – linear relationships do exist; but most likely, there are so many of such relationships that form a complex network. Just imagine packing all the proteins with different functions in a tiny cell – do you still expect simple linear relationships when many of these proteins can just randomly collide with each other? Oh and the establishment of causal relationship requires a lot of serious work. Many research articles, in my opinion, only perform experiments enough to establish a correlation but frame it as if it is a causation – again, for the sake of being neat!

      1. Antagonist Muscles

        This article and comment leaves me with trepidation as I embark on my next career. During the pandemic, I stayed home and did nothing except study medical papers. Specifically, I studied how and why I have an extraordinary ability to detect light and ultra sensitive hearing. This sensory augmentation has accelerated to the point of pain. Besides all the pain and fatigue I suffer, I was fairly impressed with all the highly specialized doctors I saw. I think the feeling was mutual when I presented my research, and we then agreed that I should apply to the PhD program, where I hopefully get to study my own rare disorder.

        So now I have to convince the admissions committee that I have some super rare disorder, and they should pay me a tiny stipend to study it. I’ll say, “I study the intersection of (1) neuropathic pain and chronic pain, (2) circadian physiology and the health consequences of circadian desynchrony and insomnia, (3) addiction – substance abuse and behavioral addictions, and (4) neurodegenerative disorders, particularly retinal degeneration. These are my research interests because the rare and unnamed disorder that I suffer implies dysfunction in all these areas.” The admissions committee may respond with KLG’s criticism of heavily descriptive approaches. “Well, Antagonist Muscles, you have zero professional experience in medical science. You have zero academic experience. And your proposal is too descriptive.”

        If I get past the admissions, I may – in the distant future – have to beg a grant officer for money. Is there any chance this will work? “Dear Dr. Grant Reviewer. You should give me money to study this rare disorder that affects one in 50 million because it is interesting.” The grant office replies, “No, I need novel techniques and integrative insights.” Currently, my research is entirely descriptive and has no practical value besides satisfying my intellectual curiosity, as kriptid noted above.

        Am I doomed? Are the wiser people (kriptid, lab_rat) leaving while the fools (me) are just rushing in?

        1. kriptid

          Antagonist Muscles — you shouldn’t feel like you’re doomed, but you have to manage your expectations.

          I’m very sorry to hear about your condition. I can imagine that is a major motivating factor. I certainly think that going to graduate school and pursuing knowledge about your condition will be a reward in its own right.

          I’ll give you my own perspective. As a graduate student, I was given a project upon entering the lab. This project was very straightforward, had a predictable outcome, and turned into a very high profile publication with hundreds of citations in a few years. I wrote a follow up to that paper that I also published in a slightly smaller but still well-respected journal.

          I spent about half of my time on this work. The other half of my time, I worked on a completely obscure passion project that my advisor often discouraged me to spend time on in favor of the more ‘publishable’ project I described above. I didn’t listen.

          Eventually, when my committee decided I could graduate, I was in the middle of two different projects of my own and finishing up the project I had inherited.

          However, because of the progress I had made, those passion projects survived and were passed to other graduate students in the lab by my mentor.

          So, he spent all this time counseling me against using my time in a way that didn’t seem rewarding short-term, but ultimately because of my stubbornness and positive results, he had no choice but to push those projects forward after I left, simply because I had shown him it was in his interest to do so.

          These projects are now playing out to be bigger and more impactful than the project that I published in a so-called high-tier journal.

          I take a lot of pride in that, even more so than the big papers that I got. That work is giving birth to a new field; unfortunately, my old boss will get the credit for that, not me.

          All this is to say that there is a chance to do good science, but you basically have to do it under the cover of darkness, so to speak, and be realistic about what you can achieve vs. what you dream of. But good and stubborn scientists can drive research in the direction they want, often against the whims of the herd. You just have to be persistent and be willing to toil in obscurity until the tree bears its fruits (and this may come even after you’re retired, or dead — be warned).

          The easy and simple projects get funded. The deep, dark, mysterious projects happen with little to no funding. You have to prepare yourself to serve your paymasters half of the time, and to serve yourself and science as the majestic human enterprise it is the other half of the time.

          I definitely do not regret becoming a scientist; I learned an incredible amount, and I’ve learned a ton about the world and its cultures through the relationships I’ve formed. I wouldn’t trade that for anything. I’m just at the point where it has run its course in my life due to the reasons I’ve outlined in my post, but I would not tell people to avoid science; just go into it knowing the rules and the risks and temper your expectations accordingly.

        2. KLG

          No, you are not doomed but you must be prepared for what is coming. I didn’t know the jig was completely up until I had a grant reviewer write: “It is worrying that the applicant will be using so many kits in his project.” I am reasonably certain this is a direct quote, 18 years later. For the uninitiated, one of the wonders of molecular biology is that many small, independent companies did a very good job of marketing reagents, enzymes, plasmids, etc. to make molecular biology possible on a time scale that was ridiculously short to those of us who were cloning genes before PCR was a thing. I thought that the comment was odd, because I did not remember referring to any kits in the proposal. I looked. Nope, no kits. Ironically, I did write that I would be using the first series of enhanced GFP expression vectors developed by one of the best of the independents, now gobbled up. When I finally got the Program Officer on the phone, I told her that comment bothered me, since it was patently untrue, not to mention borderline silly. At least 15 seconds of silence ensued, until she finally said, “Well, sometimes the reviewers do not read the entire application.” Had I been more sure of myself, I would have replied, “No, shit, ya’ think! So why do you listen to them?” One thing is certain. If peer review were not anonymous, that kind of crap would be much rarer.

      2. KLG

        I was an apprentice in all but the name when Bayh-Dole passed. Everyone looked at me funny, which was not an uncommon event, when I raged that “Now we will have to pay for everything at least twice, the first time when NIH/NSF fund the research and the second when someone charges us much more for the benefits.” I saw how Bayh-Dole corrupted academic science up close in my own orbit, in which I was but a minor asteroid. It was ugly then and now it is simply grotesque.

    2. Questa Nota

      There is hope.

      Weaponizing the GFP for Ultraviolet Spectrum Analysis would provide untold benefits for future, uh, crowd control.

      Visualize, or not, detectable identifiers that allow tracking from space, or by your mail carrier. What are the odds that research has progressed well into field testing? That is a black budget item, so another grant a lot more grants and tax dollars will be needed to push the Spectrum to full dominance until there is adequate submission.
      /s, or maybe just 1/2 /s

    3. KLG

      It is obvious that Biology is losing one more scientist that we shouldn’t. My research has slowed to a crawl, but it is not dead. Yet. The funny thing about the utility of GFP is that I remember telling a scientist working on the project that GFP is likely to be the most interesting protein in the system. I thought aequorin would be the more useful, though. It took someone from completely “outside” to take the plunge. Regarding the “scientific response” to COVID-19, I have begun an analysis of that literature, such as it can be done, comparing it to the HIV-AIDS literature of 40 years ago. The internet has its uses, but the rapid publication of “science” is not one of them. For science. However, the phylogenomics I am doing now would be impossible without the web. The only way to rescue peer review is to make it public. This has been tried at the margins and now should go straight to the core, for all grants and all publications. When it became obvious that under current constraints the process really is a lottery, things would change. No, who am I kidding?

      1. kriptid

        Totally agree with you about peer review. One of the major issues is that the current system really benefits the big institutions who have thrived in it for years, and the folks from those institutions are the cultural drivers of science. So if the Big Science model works for them, it’s hard to overcome the inertia for making any real substantive changes, outside of the margins, as you say.

        I also think reviewer compensation and public ratings should be discussed. Editors and authors have no way of keeping reviewers accountable right now. A big revision of this relationship between editor-reviewer-author could go a long way to fixing some of the problems with peer review right now.

        Thanks again for your post, look forward to reading more of your stuff here.

  2. PlutoniumKun

    Fantastic overview, and some great btl comments below too. Very informative. My last direct contact with the world of research was in the 1990’s in the UK and it was obvious even then that the MBA mindset and neoliberalism was destroying the concept of basic research. What I find most disturbing now is not that the process has gotten worse, but that it is ‘normalized’. I know a few young very talented scientists/researchers who see absolutely nothing wrong whatever with focusing entirely on the lines of research that are most likely to allow them cash out quickly with a unicorn – it simply doesn’t seem to have occurred to them that there are other, better ways of organizing science. Every one of those is a loss to real scientific process.

  3. outside observer

    Also note decreased funding for science effectively amounts to paycuts of 25% for many university faculty members who are unable to win grants to fund summer salaries. That is the reward after pursuing professions that are already less remunerative than the parasitical fields.

  4. The Rev Kev

    This is really bad this. Going forward we will need to have a science that is factually based to come up with the answers that we will need to solve our problems with climate change alone. I have read how the budgets are being cut for pure research and being diverted to research that promises and immediate economic benefit. But going by KLG’s great post on biological science alone – and reinforced by comments from kriptid and lab_rat – a lot of what we call science these days is actually just trash science. And you just know that there is going to be a reckoning for this. And it won’t be good. Not for anybody.

  5. Carolinian

    Thanks for this. I would say some of us of a scientific attitude of mind (if not actual scientists) would describe pure scientists as “heroes of truth” if truth is a matter of feedback from the natural world and not product of our own imaginations. Naturally this reputation for purity has led others to appropriate the science label to sell their own self serving activities. In fact truth itself can be controversial to those who make a handsome living out of untruth. Perhaps what we really need is a Bell Labs for human behavior–something which must be more fully understood before the misuse of pure science (for war, AGW etc) can be remedied. This, of course, would be the most controversial science of all.

    1. KLG

      Scientists are just people, and you learn quickly which are the kinds you keep at a distance. Incentives have become twisted, though, and that does bring out the worst in some.

  6. Dave in Austin

    An absolutely wonderful post about a guy I’d never heard of.

    Biological research doesn’t demand a 30 km-long particle accelerator. Funding large numbers of highly educated biological scientists to semi-blindly explore “What the elephant feels like” will elucidate both many dead ends and a few exciting new discoveries. And some of the dead ends will turn out not to be as dead as we originally thought.

    If scientific knowledge is something like an expanding sphere, the equation for the outside surface to be explored is Surface = 4 Pi Radius squared. So every time you double the radius of the sphere you get four times as much surface to explore. That takes a lot of biological scientist blindly feeling around to see what’s there. And considering how little we know about the biology of deep sea creatures and the fungi under our feet we still have a lot of unexplored territory.

    The US used to be good at this sort of thing. I knew a few people at Bell Labs and Lincoln Labs in the old days and they usually had no clue what they were looking for on their side-projects, but they knew terra incognita was fun to explore. Half the time the tools they needed to do the searching didn’t exist- so they made them. The C computer language at Bell is the perfect example of that process.

    In some ways the system of having a committee trying to determine who the likely scientific winners are mirrors the work of the arts committees that try to fund the “new” visual arts, dance and music that will inhabit the future.

    In music if you want to know the future give 14 year-olds some cheap instruments, a camera and access to Twitter and TikTok and you will find out. And occasionally be appalled.

    In visual arts leave the undergrads at the Rhode Island School of Design alone for a semester and see what shows up.

    At MIT the freshmen explore-and-built challenges routinely turn up “We never though of that” hacks.

    Biology grad students can do the same thing, and fairly cheaply. A lot of smart monkeys working at inexpensive typewriters shouldn’t be underestimated.

    1. KLG

      Yes, biology is relatively cheap. But the potential benefits are quite large. The Biology Clusters at NSF seem to be sorely afflicted with Physics Envy these days. I laughed out loud at “…ideas that consider cellular organization from the standpoint of soft condensed matter are encouraged.” And then looked up “soft condensed matter.” Biochemists, who were a new thing, were doing that 100 years ago, but called it colloid science. Pure genius like Joseph Needham devoted many waking hours to it, but he also published a very large 3-volume treatise called Chemical Embryology (also in that same Science Library) long before that could even be a legitimate thing, since he didn’t yet have a clue how genes and development were related. Anyway, in the 1970s and 1980s cell biologists figured out that the actin cytoskeleton reversibly domains converted the cytoplasm into a gel-like matrix, with one major protein getting the name “gelsolin.” “Soft condensed matter physicists” will just add a few spurious, complicated looking equations with a couple of capital Greek letter sigma, several exponents, and a few double integral signs to something already well understood and thoroughly investigated on an ongoing basis. But Oooo, the name! Soft condensed matter! Take that, you quantum chromodynamicists!

  7. Ignacio

    Well written KLG and good reply also by kriptid above.

    I would need some time to digest it all but would like to add a small contribution with what I perceived during my years on research (Some of it was quite basic research and the latest part was more, let’s say market or patent oriented research). During these years, what policymakers wanted was to spend less and less in basic “useless” research and more in market oriented research. Papers were less liked in curricula than patents and Research Centers were valued according to the proprietary knowledge they could generate in patent numbers rather than much more difficult to evaluate scientific relevance of their discoveries and scientific quality of the work done. Indeed, evaluating today scientific relevance and aptitude is very difficult and time consuming and the evaluation methods for grant proposals follow simplified methodology that may not yield best selective results.

    There is also something that is very much ignored and it is the idea of scientific diversity. You cannot predict who is going to produce the “great breakthrough” and in which field so planting diversity in research (including ‘peripheric’ players) probably seeds higher probability of success that betting always with the same (even if these are demonstrably excellent scientists).

    KLG, forgive me for not devoting the necessary time and effort to pile in with you in this interesting conversation. Again, thanks a lot!

  8. flora

    Until around the mid-1980’s, public uni funding was strong and provided by the state. Public uni’s and uni scientists had more leeway to pursue avenues and ideas while knowing there was a stable funding source not immediately tied to private profit demands. That all changed in the mid-80’s with state cuts to public funding and the uni desperately looking for grant funding (public/private don’t ya know), especially in the sciences. (The sciences and ramping up major sports programs for the TV revenues.)

    My uni used to be primarily funded by public dollars, over 60%. That’s now down to around 20% public funding; the rest comes from fees, licensing, royalties, private grants, National Science Foundation govt grants, corporate directed science research grants where the results become corporate property, not public property, etc. The only observation I have is this: long term research that might take years to yield something useful has been replaced by short term research, for the most post. Funders, grantors, want results sooner rather than later. (We joke that uni scientist jobs are becoming like attorney jobs – expected to generate “billable hours” for the firm… er… generate grant dollars for the uni. )

    Thanks for this post.

    1. flora

      Adding: It was in the 1980’s that the tax-cut mania took hold in states legislatures and at the federal level. The result was deep and deeper cuts in public funding for public purposes: schools, hospitals, health care, infrastructure maintenance, etc. took the brunt of the cuts.

      1. flora

        an aside: From Philip Mirowski

        The future(s) of open science
        Philip Mirowski

        Abstract

        Almost everyone is enthusiastic that ‘open science’ is the wave of the future. Yet when one looks seriously at the flaws in modern science that the movement proposes to remedy, the prospect for improvement in at least four areas are unimpressive. This suggests that the agenda is effectively to re-engineer science along the lines of platform capitalism, under the misleading banner of opening up science to the masses.

        Keywords: neoliberal science; open science; platform capitalism; radical collaboration; science and democracy.

        https://research.ncsu.edu/ges/files/2018/09/Mirowski-2018.pdf

        1. Susan the Other

          All the little land grant colleges were set up to do basic science and applied science. Most of them have grown into very high-tech labs for government funded stuff. Much of it for the military. We should do a little trust busting and free science up to take a fresh look. It’s not so much that science is monopolized – but the money certainly is. Which all fits in with KLG’s plea to consider good science for all sorts of fields, not necessarily connected, when we start to build back better. If economies can be brought back down to local reality, we should be able to do the same with science. There is good technology available for every little rural lab that pops up, so why not? I’d just imagine that the more dispersed science is allowed to be, the more practical, original (and even profound) it would be.

          1. Jeremy Grimm

            I believe what you say in your comment — that much of the research in college and university labs is devoted to defense concerns remains true — but I also believe the larger proportion of research is devoted to developing products for commercial purposes. The highpoint for u.s. funded basic research was the period when the DoD used blue-sky research grants — NOT contracts — to fund research for both defense and to build knowledge capital for the u.s. Industry — back when the u.s. still had Industry. Consider this — I believe the Space Race, with its ample COTS offshoots of new products, processes, and entire technologies — was in no small part a defense program. And for another example, DARPA paid for the concepts and technology that effectively invented the Internet. The DoD kept Chomsky funded for his research in language theory — would the contemporaneous GE or ATT have funded Chomsky’s research?

            The u.s. is long past due for more than a little trust busting, but to me, the most pressing question hinges on the attempt to Pareto optimize ‘investments’ in science. Science should never be approached as a potential profit center. The research ‘contract’ must be replaced by research grants and if there is some waste … sobeit! The u.s. has tolerated colossal wastes in DoD spending. Why the reluctance to admit that Science is much more than some business venture MBAs can optimize for returns? Is it a crucial chink in the Neoliberal armor protecting so much stupidity and waste?

          2. kriptid

            I really like your comment Susan.

            I totally think that science is too centralized in general.

            The NSF/NIH often seems to me like a secular Vatican trying to control its flock.

        2. Jeremy Grimm

          If I am not mistaken, the Neoliberal coup by Corporate interests co-opting Science was Phillip Mirowski’s initial study interest. I believe most of his early monographs and papers are studies of Science and the history of economic theory. As I recall, Science provided his introduction to the concept of thought collectives. Though I must regret too little familiarity with Mirowski’s full corpus of work, I believe his studies of the Neoliberalization of Science and Knowledge and … ‘truth’ motivated his very angry — to me — writings about science and the predations of Neoliberalism in the larger worlds of our economic lives.

          I have worked with university research centers and seen firsthand how public-private research at major universities works. I have read the patents of Corporate powers like Qualcomm and marveled at how much publicly funded research served to build private fortunes. I have seen first hand how the drive to gain $$$$ has shriveled curiosities and any inclination to take risks in exploring the unknown. The u.s. does not practice Science. The u.s. practices the science of exploring certainty for greater profits.

          1. kriptid

            Thanks for your mention of Philip Mirowski; my first time hearing about him. Interesting stuff.

        3. KLG

          I have looked into this very thing; it is all published in the yearly Fact Book available online (for now). When I was an undergraduate student at a large state university in the 1970s, tuition accounted for 10% of the university budget. This had been a “rule” for many years before and into the 1990s. The remainder was contributed by the state and federal governments in the form of resident instruction, grants, and contracts. Now, tuition contributes nearly 40% of the budget IIRC, which has significantly outgrown enrollment, adjusted for inflation. This is not a tax increase, however. And yes, Mirowski is very good.

  9. DJG, Reality Czar

    KLG: Thanks for this. I especially appreciate your starting with something “charismatic” like bioluminescence. How many of us as kids kept wondering, How do lightning bugs do that?

    There are many other events and things appearing in nature that provoke that same sense of how and why (which leads to investigation, which is science): Color changes among octopodi, squid, and cuttlefish. Flying fish. The structure of a bird’s feather. The amazing “spinners” that fall from maple trees.

    Which lead to “theory,” and I am glad that you took a good whack at that overused word. “Theory” is now being stretched to cover what used to be called (politely) unfounded opinions.

    As you mention, biology doesn’t have many theories. There’s the theory of evolution, which has gobs of data to hold it together.

    There’s the theory of gravity, which has held up well since Newton. Biologists can use it.

    There’s number theory. Someone has to explain how numbers work.

    Just about all other theories are flimsy. In the social sciences, “theories” aren’t even theories. They are clusters of data strung together into Rube Goldberg Contraptions and into Departments of Economics.

    And then there are all of those “theories” that Trump is a narcissist and such that are truly no more than Facebook posts. I notice that Darwin, Newton, and Alfred Russel Wallace aren’t much in evidence on Facebook.

    1. KLG

      Bioluminescence is fun! Both as a kid and as a scientific worker. Plus, sea creatures are collected at some very beautiful sites.

  10. scott s.

    Everybody knows Eisenhower’s warning about a military-industrial complex, but they don’t consider his other warnings:

    “Today, the solitary inventor, tinkering in his shop, has been over shadowed by task forces of scientists in laboratories and testing fields. In the same fashion, the free university, historically the fountainhead of free ideas and scientific discovery, has experienced a revolution in the conduct of research. Partly because of the huge costs involved, a government contract becomes virtually a substitute for intellectual curiosity. For every old blackboard there are now hundreds of new electronic computers.

    “The prospect of domination of the nation’s scholars by Federal employment, project allocations, and the power of money is ever present and is gravely to be regarded.

    “Yet, in holding scientific research and discovery in respect, as we should, we must also be alert to the equal and opposite danger that public policy could itself become the captive of a scientific-technological elite.”

    In Wisconsin, the state designated its university as its land grant college. In the progressive era progressive Gov La Follete developed what came to be called “The Wisconsin Idea”, which meant that the role of the university was to advance the progressive policies favored by the state thus becoming a political arm of government.

    1. KLG

      Dwight Eisenhower gets a lot of credit for his farewell speech, but it contained nothing he had not known since 1942 and before. Easy to say it while on the way out the door to a farm in Gettysburg and a golf course in Augusta.

    2. Anthony K Wikrent

      Seems to me the obvious solution is to ensure there is a “culture of improvement” similar to that embodied by the great scientist Benjamin Franklin: the greatest good a person can do is to help other people. This “culture of improvement” was a key principle of the ideology of republicanism which dominated the American founding era. Unfortunately, republicanism has been replaced by liberalism, of which the key part is economic liberalism, allowing for the development of unchecked predatory capitalism in which another key principle of republicanism — civic virtue, the notion that the public interest of the entire community is often more important than an individual’s self interest — has come to be almost entirely ignored.

      It is important to note that if you look at the institutions Franklin helped establish, such as the American Philosophical Society, you can see the seed of almost the entirety of USA 19th and 20th century industry. For eaxample, the American Philosophical Society was founded by Benjamin Franklin in 1743. Nearly a century later, Samuel Vaughan Merrick became a member of the American Philosophical Society, Merrick was the founder of the Merrick and Towne Foundry in Philadelphia, In 1839, the Merrick and Towne Foundry built the steam engines for one of the first two US Navy steam frigates, USS Mississippi. This experience in steam power – gained “on the government dime” – led six years later to Merrick becoming
      the first president of Pennsylvania Railroad Co.in 1847. Merrick hired Thomas A. Scott to be general superintendent of the Pennsylvania Railroad. In 1853, Scott hired an 18 year old kid as clerk for the railroad. The kid’s name was Andrew Carnegie.

      In 1824, Merrick partnered with scientist William Keating to establish in Philadelphia The Franklin Institute of the State of Pennsylvania for the Promotion of the Mechanic Arts. Merrick served as president of the Franklin Institute from 1832 until 1854.

      In “Benjamin Franklin’s Vision of a Republican Political Economy for America,” (The William and Mary Quarterly, Oct, 1978, Vol. 35, No. 4, Oct, 1978),Drew R. McCoy writes that in

      “America this classical conception of virtue—as consistently intensé, disinterested self-abnegation—gradually merged into a more modern meaning that emphasized the productive industry of the active citizen…. Virtue played an important role in Franklin’s republican vision for several reasons. First of all, virtue was necessary to prevent a tragic waste of America’s tremendous potential for the production of wealth. Since industry and frugality were Franklin’s “Way to Wealth,” it followed that virtuous men were always ”necessary in a Nation for its Prosperity.” Righteousness, or justice, Poor Richard once explained, was the most fundamental virtue and ”the surest Foundation on which to erect and establish a new State,” but the two “humbler Virtues, Industry and Frugality,” tended “more to increase the Wealth, Power, and Grandeur of the Community, than all the others without them.”

      In Philadelphia’s Philosopher Mechanics: A History of the Franklin Institute 1824-1856 (Baltimore: The Johns Hopkins University Press, 1974), Bruce Sinclair writes

      “the majority of Americans in those years placed their faith in democratic ideals and the applications science. They saw in that combination the potential for political freedom, the end of class privilege, and a basis for equal economic opportunity…. science also had ideological implications for Americans of the early nineteenth century. Science was almost always thought about in terms of education, and there it became intertwined with democratic ideals. Science was “useful knowledge,” a term widely popular in the 1820’s and used consciously in opposition to that idle learning which characterized the aristocracies of the Old World, where education was restricted by class lines. If it were made widely available, useful knowledge—training in science and its applications—would give any individual the chance to advance as far as his talents would take him. That was not only democracy’s goal but its best warranty for survival. Since useful knowledge was also the key to the country’s natural abundance, it would become America’s mission to the world to demonstrate that democracy was the political system best designed to produce wealth and freedom for its citizens. Technology, as Hugo Meier has persuasively argued, “proved to be a catalyst, blending the ideas of republicanism with the rising democratic spirit in the early national period.”

      I would argue that the crass commercialization of science and technology is not worst damage caused by neoliberalism. The worst damage is the destruction of the ideals of republicanism such as civic virtue and a culture of improvement.

  11. Jeremy Grimm

    Before attempting a comment to the body of this post I felt it important to call attention to a brief statement in footnote #3: “A library with open stacks in a major research university is a wonder of the modern world.” I might append to that — notice that the stacks included copies of older sources like the 1937 monograph referenced. Funding for libraries and physical books, especially older books has withered along with the funding for basic research. Newton could not stand on the shoulders of giants if he lacked access to their writings. This offers another perspective on this statement from the post: “virtually all biological research is primarily descriptive. It is also incremental. Leaps are few and far between…” I suppose this is a different way of saying that the quest for exponential growth — a mantra for investing in the 1980s which seems to have become dogma — is at least as unsuitable a strategy for ‘investing’ in research funding as it is for investing in securities.

    1. KLG

      Technology transfer is all the rage. This was pioneered by MIT 100 years ago, and Vannevar Bush was involved IIRC. Now, a few other universities try but most fail as badly as Biotech startups failed after Bayh-Dole. I watched one of those from very close range. It was particularly ugly. I remember the one outside business advisor telling the principal scientists that if they wanted to succeed, they each needed to go to the bank, borrow $50,000 (the bulk of the salary of the younger scientists involved), and put the borrowed money into the company. They all looked at him like he was crazy. Instead, they used money contributed by local investors (marks) to lease and renovate new lab space containing new Herman Miller furniture. This, when the university was prepared to provide incubator space in a repurposed textile mill for basically free. What could happen? $6M from people who couldn’t really afford to lose it was flushed down the drain. And on the library, exactly! I recently walked through it on an emotional archeology field trip with my better half, and it still looks great, except for the plastic tables that have replaced the solid wood versions. The other Wonder of the World was the New Journals table. Now paper copies are passe, and no one seems to be able to read more than 280 characters at a time. Incidentally, all the CIA really had to do to figure out that while the Soviet Union could indeed blow up the world, but was not a threat otherwise, was to read the Soviet science journals in translation that were delivered every week. They were simply sad.

  12. Will

    Thank you for this post. I join with other commenters in hoping for a better day when we can return to research just for the sake of knowing and scratching that basic human itch.

    Indeed, the several quotes from Popper in the post had me itching all day. Then I finally remembered this essay, How Popperian Falsification Enabled the Rise of Neoliberalism.

    I think this essay is relevant to KLG’s post because it points out that Popper’s theory of science as a process of falsification has been disproved yet is still widely believed among scientists. As KLG notes in his post, biology is too granular to support grand theories. Presumably “falsifiable” grand theories required of grant proposals. Do other disciplines also suffer from this “flaw”? More generally, does a general belief among scientists, grant reviewers and program directors in Popperian falsification foreclose “incremental and descriptive” research in favor of “theory driven investigation”?

    The essay’s larger point about Popper’s role in enabling the neo-liberal project is interesting, and I suppose also bears on KLG’s post inasmuch as he seems to believe neoliberalism has contributed to the sorry state of scientific research.

    In other words, Popper and his disproved, yet still widely believed, theory of science would seem to have played a large role in getting us to this sorry state of affairs. Perhaps any attempts to return to a better yesterday requires not only a reformed funding model but a more fundamental examination among scientists of what science is?

    1. KLG

      A lot can and should be laid at the feet of British Analytic Philosophy, writ large. Popper was a principal component of that movement. His Logic of Scientific Discovery has never held much allure for me, as I noted in the first post of this series on “The Illusion of Evidence Based Medicine.” The authors of that excellent book love Popper, largely for the reason that the “science” of Big Pharma can never fail or falsified. It can only be failed. They are right about that. My evolutionary biology professor was also enthralled by “falsifiability.” He is a pioneer in molecular population genetics and is a member of the National Academy of Sciences. I think he was so enamored because evolution is still considered hinky by much of the lay public and was trying too hard to prove to his advanced undergraduate students that evolution really is a science, which wasn’t necessary. Regarding falsifiability, all that means to a practicing scientist is that she does the proper controls that can and often will render her hypothesis null and void. But the good scientist simply refines the hypothesis and includes even more exacting controls so as not to fool herself. Now? Controls are for wimps…not the Big Pharma marketers in lab coats and the young scientists looking to cash out with that unicorn. Economics is not a science, despite the mathematical apparatus, but rather the political economy divisions of history and sociology, so it cannot be falsified. One of the funniest things I ever saw in a textbook was a supply and demand curve with the axes of the graph unlabeled. I want to say it was Samuelson, but surely not.

    2. Paula

      We know too little enough already but continue like we “know.” For instance, much of the ocean studies are quite new in that only 30 years ago or less we understood 70% of atmospheric oxygen came from the ocean. Yep, we are killing what we know so little about because of “hubris” or something akin to that. I do not like scientists but I like science. The latter seem to think they know it all, like doctors who don’t listen to you when you tell them how your body reacts to the world. Sorta same thing.

    3. Paula

      Isn’t what science is, is just a guess and a hypothesis with limited knowledge? I mean, if you tend to think in interconnected terms, the connections become complicated either because we do not see them, or we simply can’t because we ourselves, as humans, are not connected enough to see what is right before our eyes. If we could remove some of the hubris from science, science would be more beneficial to us.

      1. flora

        er… um… science is not “a guess” about the natural world, science is a method of inquiry about the natural world. My 2 cents. / ;)

        1. flora

          And to repeat in a too long and boring fashion for any who skimmed over the point; science is a method of inquiry. A method of inquiry. (OK, I’ll stop now. ) / ;)

  13. Sub-Boreal

    I work in a somewhat quieter area of science which doesn’t quite have the glam factor of the hypercompetitive biomedical realm, but KLG’s account rings pretty true. Which is why retirement is looking better every day!

    The granting processes which KLG describes are oriented to individual projects, but there are other ways of doling out research money. The Canadian NSERC Discovery Grant (DG) system supports the researcher rather than a specific project, and typically run for 5 years. It has a much higher success rate (66% in 2022), but necessarily gives out smaller awards. Researchers’ host universities can’t deduct overheard from these awards, but there’s a separate program for covering some of the indirect costs of research.

    Despite the modest size of awards (average in 2022 ~ $CAD 37K), researchers put a ton of work into their proposals. That’s because the money is flexible – you don’t have to do exactly what you described in the proposal, as long as you produce publications and graduate students. And, although nobody will admit this, getting and holding a DG is taken as a de facto requirement for getting tenure in some Canadian universities if you’re in the sciences.

    So the DG process – both preparing and reviewing the proposals – is a vast time sink. You can always tell who’s up for renewal this year, because they disappear from sight in September and October except for showing up to teach.

    Because of this huge burden and the relatively high success rate, about a dozen years ago a couple of dissidents pointed out that you could just give everyone in an eligible field a modest basic operating grant, and skip all this bother. This idea was too sensible to go anywhere, plus it would mean that NSERC could get by with fewer staff, so it sank from sight. But they made an interesting argument, which can be seen here, along with some additional discussion.

    1. KLG

      Yes! I spent a significant part of the summer of 2011 at the Marine Biological Laboratory in Woods Hole, where one program in molecular evolution was led by a scientist from Dalhousie. Had I been younger, I would have started working on Canadian citizenship! NSERC makes the science that most of us want to do possible and rewarding. But IIRC, NSERC grants are not the source of funding for graduate students, and therein lies the rub for most American scientists. Canadian universities probably do not take an additional 50-75% in addition to the direct costs made available to the scientists. My last NIH grant was large at $189,000 per year for a lab with 6-8 people, graduates, technicians, and undergraduates included. They paid my institution about $287,000. Had I been at one of the large private research universities that would have been about $331,000.

      1. Sub-Boreal

        DGs can be used to pay grad students, but given their modest size, you can’t support very many. But the flexibility means that you can fill gaps in other student funding when needed. For example, you could give a student a stipend for the summer, and then they could support themselves from teaching assistantships during the fall / winter semesters.

        Having this degree of flexibility is why people sweat their DG applications so much. It really is remarkable that something so sensible has survived so long. However, NSERC also has an increasing array of smaller, targeted (flavour of the month?) programs which make up an acronym alphabet soup. If you ask grassroots research folk, most would just say to put the bucks into DGs and ditch the others. But that would probably remove a lot of job-justifying administrative activity at NSERC, so it’s unlikely ever to happen.

        1. flora

          How can one know what people a century or two from now will regard as “beneficial to all humankind” ? You posit an impossible benchmark for current scientists to imagine whatever their current work might appear to viewers centuries in the future. Impossible benchmarks are, to me, nonsensical efforts to stop any current scientific efforts to gain understanding.

        2. Lambert Strether

          Your comment misses the point of the post, which (I will crudely summarize) is that the benefits of basic research cannot be known in advance, but turn out to be (arguably) greater than research whose benefits can be (more or less accurately) known in advance, but which do not, by definition, advance science as such.

          It’s like asking was Kepler’s work on astronomy “ethical and would benefit all mankind’? Only “ethical” if you regard basic research as ethical (which I do. “The augmentation of the complexity and intensity of the field of intelligent life.” –Ursula LeGuin, The Left Hand of Darkness).

    2. Paula

      When is comes to doling out research monies, isn’t it all the same in the sense that only what has potential to make money is what gets researched and not science in hydro fueled cars, for instance, that might help save the planet?

      1. flora

        No. You conflate the latest political neoliberal stuff with the longer term, apolitical govt regard toward science, sans politics. (Although I accept the current neoliberal reining govt paradigm wanting to honor neoliberal ‘because Markets’ stuff is the current thing.) My 2 cents.

  14. Polar Socialist

    While I’m all for basic research and hate the current funding and “publish or perish” culture in the academia, from my point of view (computational research services) theoretical approach has scored some pretty geeky successes even since Fibonacci and Malthus.
    The huge names in Information Theory, Claude Shannon and Alan Turing both wrote about biology. Shannon’s thesis was about Mendelian genetics (suggested by Vannevar Bush himself) and Turing published a theoretical paper about morphogenesis.
    To me these are, and will remain, examples of how great scientific minds set out solve problems by using just their intelligence – no labs, no computers, not even knowing about genes yet.

    There also has been a lot of interesting work done by people like Gregory Chaitin in formalizing evolution, or John Baez in biological entropy and biodiversity studies. I find the information and category theoretical approach to biology extremely delicious, even if a lot if goes over my head.

    Caveat: I was a bioinformatician at one point of my life.

    1. Paula

      A volcanist wrote a book called “Hothouse Earth, An Inhabitant’s Guide by Bill McGuire. Check it out. I always believed the science and the plants and everything else in natural world trying to speak to us. Build underground to stay cool is not a new idea, but if I could build, that’s what I’d do. As well as many other things to keep our planetary temperatures down.

  15. Paula

    Was a hydro car, not hydrogen. Ran on water. Inventor ran out of restuarant where he was meeting with interested investors and brother witnessed him running out of restaurant claiming he’d been poisoned. Simply do not put it past what fossil fuel industry will do and wish someone had the cajones to investigate. Water saving our planet. What a thought and how disruptive to all the other players in the game of energy sources.

    1. drumlin woodchuckles

      Really? Ran on water? Even though dihydrogen monoxide is an extremely stable chemical from which no further energy of oxidation can be extracted?

      How did it “run” on water?

  16. Altandmain

    It’s interesting that this article was published, there was as recent Japanese study saying that China had surpassed the US in scientific research.

    https://www.theguardian.com/world/2022/aug/11/china-overtakes-the-us-in-scientific-research-output

    A lot of this comes down to culture and funding. A neoliberal culture that emphasizes short term profit will inevitable neglect research, especially of the “Blue Skies” variety. Likewise, a “fiscally conservative” government that is kept small simply will not do this for ideological reasons as well, because it is seen as something to be left to the “superior” private sector and free market to do.

    Of course, in the long run, this will mean that one of the pillars of American leadership will be gone and with it comes a lot of opportunities for Americans. New technologies can create new jobs, better standards of living, etc. In the long run, if the “hawks” are crazy enough to want a Cold War, then they are going to find themselves facing many “Sputnik” moments.

  17. drumlin woodchuckles

    While Bayh-Dole was certainly the expression of a broader deeper ideology, it was also a particular piece of social engineering ( a particular “law”) which gave actual permission and encouragement for researchers of every kind at every level to take a particular approach to research. (And most especially within the Research Univerisities which were thereby redirected to make all their research monetizable and to forbid and suppress basic research as much as humanly possible.)

    If Bay-Dole were totally and simply repealed and wiped from existence, and “patents” on “gene-sequences” and “life” were outlawed and every such patent now existing were forcibly voided, would the pure basic researcher-wannabes find the research-brainwar battlespace tilting or at least tiltable in their favor and against the “research for monetizable discoveries” community?

  18. drumlin woodchuckles

    What if the only thing a particular piece of basic research does is to make the people who do it and who learn about it smarter and more interesting people?

    Well . . . . smarter and more interesting people is a good thing too.

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