Coffee Break: More on American Science, An NIH Grant Long Overdue, An Experimental Model, and Further Thoughts on AI

Part the First: Back to the Past in Science and Medicine.  The future of basic science in the United States looks grim for everyone from the aspiring graduate student to the full professor who has met her potential and has several graduate students, postdocs, and technicians working in her laboratory.  The precipitous and arbitrary Big Beautiful Bill lending limits placed on medical, nursing, and other healthcare students will only exacerbate the problem.  The numbers of students from previously underrepresented groups, including women and rural students, will collapse back to the baseline that was determined largely by family wealth and nepo baby connections (which is the plan).  The cancellation of programs to encourage students from underrepresented groups to consider a life in science will contribute further to our scientific decline:

The new data are being released in a political environment much less kind to such programs than when they began three decades ago. Over the past year, both programs, the Research Initiative for Scientific Enhancement (RISE) and Minority Access to Research Careers (MARC), were terminated by the Trump administration — as was the funding for the study itself.

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The RISE and MARC programs were created in response to the NIH Revitalization Act of 1993, which called for the agency to “increase the number of underrepresented minorities engaged in biomedical and behavioral research.” The RISE program provided funding to institutions to create educational and mentoring opportunities for students to prepare them for a career in biomedical research. The MARC program provided two years of funding directly to undergraduates to do research along with professional training.

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The paper matched students on 11 variables, which included their major, grade point average, their intention to become a scientist, and first-generation status. In total, the study included 608 students in the two diversity programs, and 135 students used as comparisons. The researchers found that 20% of the RISE students and 34% of the MARC students earned a Ph.D., as compared to 10% and 15% in their comparison groups.

These things are difficult to measure, but these results are positive.  I have worked several of these students, and for most of them the program was their only path into a career as a scientist.

Finally, a short note on women as a historically underrepresented group in science and medicine.  The scientist I worked for as a postdoctoral fellow was the first woman in a basic science department to get tenure at our top-5 medical school.  And this happened only after an external review of the department said that it was absurd she was still waiting, based on her history of discovery.  The department in which I did my long apprenticeship as a technician/research coordinator and then PhD student hired its first woman faculty member in 1978.  Medical school entering classes have tended to be 60/40 women/men over the past several years.  When I contemplated medical school in the late-1970s the ratio was closer to 25/75 women/men.

History is not as far in the past as people seem to think.  And a return to that past seems entirely possible.

Part the Second: The Essential Summary of the Current State of American Science.  U.S. science in chaos: How did we get here?

Countless scientists around the country are going through the same thing. Thousands of federal grants have been frozen or canceled, with perhaps 2,600 still in limbo—about $1.4 billion worth. The National Science Foundation and the National Institutes of Health are awarding three quarters of their usual number of grants. Fewer people are entering graduate programs. Nearly 95,000 scientists have left federal government employment. The NIH used to issue as many as 850 “Notices of Funding Opportunity” every year—requests for proposals that sought specific kinds of research. In 2025 the agency issued 120. By mid-March of 2026, the NIH had sent 14.

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Now, to be sure, the end product of science is supposed to be science, not grants or tenure. Applying for highly competitive grants with limited funding is what scientists have always had to do to carry out the science—a flawed process with few alternatives. But arbitrary cancellations and delayed disbursements are unprecedented. And justifying them on the basis of politics—prohibiting, for instance, grants that include language referencing diversity, equity and inclusion (DEI)—was unheard of until now.

The author correctly places the inflection point at the Bayh-Dole Act, passed during the one-term administration of our first neoliberal President, Jimmy Carter.  That is not a coincidence:

And in 1980 Congress passed the Bayh-Dole Act, moving ownership of the results of government-funded university research from the government to the universities. Now a blockbuster new drug or search algorithm could be a windfall for a university, and university administrations had common cause with venture investors. More basic discoveries started getting turned into dollars. But the alliance shifted the emphasis from state capacity to financial outcomes.

Read the whole article when you have time and bookmark it for future reference.  There is probably no other one-stop account that covers the issue better.

Another opinion piece in Science on the Research Project Grant adds to the discussion, while pointing out that the archetype that was Bell Labs was a one-off thing killed when AT&T became anathema:

The reformers’ solution is elegant in theory. Rather than forcing scientists to write grants, give them stable institutional homes; rather than funding projects, fund people and organizations. Create a network of 10 or 20 institutes, each empowered by block funding (long-term, unrestricted institutional support) to pursue research programs the RPG cannot support. The promise is Bell Labs redux: the industrial lab that gave society the transistor, information theory, and the laser, none from a grant application.

The central confusion is that Bell Labs was not a government program, but the research arm of a regulated monopoly, AT&T, funded by captive ratepayers (was that so bad in hindsight?), accountable to no appropriations committee, free to operate on a time horizon no public agency could sustain. The true parentage of X-Labs is not Bell Labs but the continental model: Germany’s Max Planck Institutes (MPIs), France’s Centre national de la recherche scientifique (CNRS), and the US Department of Energy (DOE) national labs.

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What the RPG gets right is easily overlooked because it is built into the mechanism, not into the wisdom of any administrator. The grant follows the investigator; a scientist treated badly can leave and take their funding with them, giving the scientist real bargaining power vis-à-vis their institution. The system also offers multiple doors—NSF, DOE, the National Institutes of Health (NIH), and other agencies and private foundations—so that a paradigm out of favor at one agency may find support at another. NIH alone makes roughly 40,000 RPG awards a year, a portfolio that could support randomized experimentation and rigorous self-evaluation (this, from the author, is not a solution to anything) if agencies were so inclined, and that a handful of X-Labs could not. The bundling of research with graduate education that the RPG sustains is the commons from which any new institution would draw the scientists it proposes to redeploy.

I suppose the next administration, from wherever it comes, might reconsider how science is supported in the US, but a continued decline along with the dissolution of American Empire seems more likely.

Part the Third: Good News from NIH.  The United States is full of former industrial sites that are stews of noxious and dangerous chemical wastes.  The National Institutes of Health has funded an award to study several of these in one small area along the Georgia Coast:

After decades of pollution, Brunswick residents have a new resource for researching the link between area Superfund sites and their health.

A five-year, $15 million grant from the National Institutes of Environmental Health (NIH) has been awarded to Emory University to examine how environmental contaminants affect human health, following a 2023 pilot study involving approximately 100 Glynn County residents, according to the Emory University Rollins School of Public Health.

Emory will lead the research in partnership with university faculty from the University of Georgia, Georgia Institute of Technology, Morehouse School of Medicine, Spelman College, and Texas Tech University.

“By combining cutting-edge exposure science and health research with direct community partnerships, the center will translate complex environmental data into practical information that can support healthier decisions for families, clinicians, and policymakers,” said Dana Barr, a professor of environmental health at Emory University’s Rollins School of Public Health and director of the new Superfund Research Center.

I am very familiar with the two largest sites on the list.  They are evidence of our previous (and returning) disregard for Creation.  But this lack of care was normal back when the world was seemingly empty and therefore useful as a sink for industrial wastes.  Not so much as it turned out.  And while it might cause some cognitive dissonance, the first substantial recognition of this came during the Nixon Administration when the Environmental Protection Agency was established.  At least one of the four sites covered here may never be cleaned up, but the public health establishment will gain a better understanding of what has been done to the land, water, saltmarsh, and the people and what might be done to help in the future.

As one of thousands of supporters of 100 Miles, thank you to the scientists who will do the research and NIH for funding the work.  We look forward to your results that will undoubtedly reveal several “social determinants of health” inhabitants of the current administration believes are fictitious.  This research will be extendable to any number of similar sites around the country, including Cancer Alley, which is covered well in Strangers in their Own Land by Arlie Russell Hochschild.

Part the Fourth: Yeasts, Our Friends in the Laboratory.  One of my goals here has been to explain how biological and biomedical research is done in the lab.  I have used many unconventional experimental systems in my lab life, ranging from the single cell organism Thecamonas trahens (representative of the first step on the branch leading to animals) to jellyfish to mice.  By the time I got to them, yeasts were not unconventional but they were and are unusual, especially for the nonscientist.  The Scientist is primarily a magazine for advertisers, but it also publishes general interest articles that explain things well for the general reader.  The Rise of Yeast as a Model Organism in Biology is one of them:

For millennia, yeast has held a place at the table of history, transforming flour into bread, grapes into wine, and grain into beer. But yeast is much more than a building block for a good meal. It offers a glimpse into the fundamental questions about the inner workings of cells and into something much larger than itself—human biology.

In the latter half of the 20^th century, researchers relied on mammalian systems, including mouse and human cells, as representatives of higher eukaryotes. Yeast had not yet become a widely recognized model organism for studying fundamental biological processes.

One researcher, however, would begin to question this approach. In 1964, Leland Hartwell was a postdoctoral fellow in virologist Renato Dulbecco’s group at the Salk Institute working with polyoma virus-infected mammalian cells to study how the infection influenced cell growth and induced DNA synthesis. However, Hartwell remarked, “I felt like I wasn’t going to get anywhere with human cells…There just weren’t technologies to allow us to really ask fundamental questions.”

Hartwell eventually left the Salk Institute for a position at the University of California, Irvine, where he had received a grant to study the control of cellular DNA synthesis. Determined to pursue a different approach, he decided not to continue working with mammalian cells. “I spent a lot of time in the library looking for a eukaryotic organism that had [facile] genetics, because I was impressed by the success that had been made in studying gene regulation (the locus classicus on gene regulation) in bacteria and bacterial virus reproduction both using genetics.” His search ultimately led him to yeast.

Why are yeasts so useful?  They are small, cheap to culture, genetically tractable, and most importantly they are our sisters among opisthokonta at the cellular level.  Without yeasts, we might still not understand very well how our cells regulate cell division.  Leland Hartwell initially identified many of the genes responsible for the control of cell division.  Paul Nurse showed later that a critical protein in another very divergent yeast does the same thing.  But more than that, he showed that human and yeast proteins did the same thing:

Looking for (the budding yeast) CDC28 homolog in (the fission yeast) S. pombe, Nurse took a budding yeast library, put it onto a fission yeast cdc2 temperature-sensitive mutant, and cloned a DNA sequence from budding yeast. Upon further investigation, his team later determined that cdc2 in fission yeast was the homolog to CDC28 in budding yeast; it was necessary for (progression through the cell cycle and cell division).

While these yeast findings excited him, Nurse wanted to look for the human homolog of this gene. The idea seemed far-fetched, as yeast and humans probably diverged about 1.5 billion years ago. “Obviously, most people thought we were crazy, and we probably were,” said Nurse, who at that point worked at the Imperial Cancer Research Fund. Undeterred, Nurse and his team used a human cDNA library and inserted the entire catalog into S. pombe with a defective cdc2 gene. Nurse described it as “the dirtiest experiment you could imagine,” because he wasn’t sure it would even work—but it did. They observed that a human gene functioned similarly to yeast cdc2, effectively rescuing it and restoring its function: Could this be the human homolog they were looking for?

Well, yes, it could be and it was.  The human protein worked just fine in yeasts.  In one of the most remarkable results I ever read in a journal:

It took them a few more months to confirm the result using Sanger sequencing (this would be an overnight automated task today). When the computer printed out the results on the ticker tape, Nurse couldn’t believe his eyes. The findings revealed that the human and yeast proteins were over 60 percent identical. Because of these similarities, the mechanisms controlling the cell cycle were likely to be conserved in eukaryotes. They had found the human homolog: cyclin-dependent kinase 1 (CDK1)

Shortly after this work, which led to a Nobel Prize in 2001, I used what the late Ira Herskowitz originally and somewhat tongue-in-cheek called “the awesome power of yeast genetics” to get my PhD by characterizing another cell cycle mutant.  It was fun!  And “the awesome power of yeast genetics” was repeated with a smile by every “yeast person” giving a talk, or those with a sense of humor, which most of them had.  We also used Ira’s simple style in preparing our slides, pre-PowerPoint.  My project could not have been done using any other system.

So, when people wonder why someone gets grant support to work on yeast, tell them that many cancer chemotherapeutics were designed to attack proteins that were first identified in our fungal relatives.  And finally, if you will indulge a personal comment, the highest moment of my scientific career may have been having the one and only Ira Herskowitz talk to me for thirty minutes about my work and its importance while we were at a scientific meeting in Seattle.  That kind of thing lasts a long time, as in, to this very day.  As Jasper Rine put it in the link to his eulogy for Ira, he was our Larry Bird and Tiger Woods (before his successive and precipitous falls from grace).

Part the Fifth: Another Response to Our Impending AI World.  Lately the well that is Front Porch Republic has been full of good things, with commentary on so-called Artificial Intelligence leading the way.  Teddy Macker has written In Defense of Our Country: On the Need to Resist AI and AI Data Centers.  Phillip Sherrard is less well known that most of the other writers Macker begins with, but he shouldn’t be:

The physical world, regarded as so much dead stuff, becomes the scene of man’s uncurbed exploitation for purely practical, utilitarian, or acquisitive ends…This is why the application of science—which is not really the application of science at all but the application of an unbelievable ignorance—has produced such disequilibrium, ugliness and even destruction not only in the natural world but in human life as well.

Harsh.  One does not have to be an Orthodox Christian to appreciate this, but it can be difficult to get a scientist, heathen or heretic, to understand any of it.  Mr. Macker begins:

Thich Nhat Hanh loved telling the story of a man riding a horse. The horse gallops along as if the man is on a mission of great consequence. Another man sees the rider tearing down the road and shouts, “Where are you going?” The rider yells back: “I don’t know! Ask the horse!”

This teaching came to mind while thinking about artificial intelligence. One might say that our country is riding a horse, and we have no idea where it is taking us. But after reflection, I see that this is not quite right. We do have an idea where this new technology is taking us.

Because Gandhi didn’t have an expert’s sense of economics, it allowed him—some claim—to see economic arrangements with fresh eyes. Because he didn’t get lost in the endless niceties of complexity, he was able to see the big picture, as we say now, and this big–picture vision enabled him to suggest and sponsor healing, hidden-in-plain-sight reforms. We should perhaps remember this claim about Gandhi when it comes to AI. We don’t have to be podcast-hosting experts with “150 IQs” fluent in tech-speak to shape the general welfare of our country. We don’t have to use phrases like “inflection point” and “preference cascade” and “effective accelerationism” to stand up and be counted. In fact, in order for our country to be our country we need to stand up and be counted, for we are, as Thomas Jefferson says, “the safe depository” of this country’s “ultimate powers,” no matter what the cynics and the understandably demoralized might believe.

So far, what has AI brought us that we did not have before?  Deep fakes that have rendered our world of information suspect, all the time.  “Cognitive surrender” of students and teachers, readers and writers, with many “books” listed in the Bezos Bazaar being the products of one large language model or another, it doesn’t matter which.  Artists put out of work; ditto for musicians.  At least 156 people killed, 120 of them children, in Minab during an unnecessary war.  Mass unemployment to come, except for those who do not have to actually work for a living:

We hear how some AI creators are openly suspicious of democracy and sympathetic to eugenics. We hear that some are building elaborate “doomsday bunkers” and planning “sovereign colonies” free of government regulations in our oceans, in foreign countries, and in space. And we hear that the president of Argentina wants to completely deregulate AI in his country and help create something called the “non-human corporation,” a legal entity owned and operated completely by AI robots. Says Forbes of such a corporation: “Imagine a company with no CEO, board or human employees—just artificial intelligence making every decision, signing contracts and owning assets in its own name. That scenario once felt safely hypothetical—ripe subject matter for SciFi movies and novels for years.”

Will AI “discover” cures for cancer?  Maybe, and that is a good thing but not something that it can do on its own.

Finally, Mr. Macker gets it right in my view when he quotes Teilhard de Chardin, Jesuit priest and scientist:

We can no longer afford to isolate our deepest understandings—apprehension of the holy and of the “hidden wholeness,” that fundamental unity underlying reality—from the affairs of our communities, of America, and our Earth. Putting these deepest understandings front and center (understandings that are so important, so central to our lives, yet can never be adequately and finally conveyed) prompts in one humility and loving care. The most important thing, the wise remind us, is to remember the most important thing. “In our hands, the hands of all of us,” says Pierre Teilhard de Chardin, “the world and life—our world, our life—are placed like a host.”

Whether one is religious or not, the words and concepts “holy, whole, and health” come from the same root.  And this should never be forgotten.

Thank you for reading! See you next week!