One way to get through our political turmoil is to read but not listen. Trump Derangement Syndrome, something I am not willing to fully understand, is definitely aggravated by listening. I stopped watching television news (and listening to NPR), for the most part, during the election of 1992 when it dawned on me (slow on the uptake yet again) that most politics of that level was purely performative. Bill Clinton was quite a performer. As was Ross Perot. Except for a few duds, the performers have kept coming. Their acts have worn thin.
It was still possible to keep up, though. Newspapers were still a going concern and I read the Atlanta Constitution every morning, beginning with the Sports Section, for twenty years beginning in the mid-1970s. Back in those days the Atlanta newspapers circulated in every county (all 159 of them) in the State of Georgia. Local and regional coverage was good. National and international, too, with very good writers, columnists, critics, and cartoonists all around. A few remain but their reach is shorter.
The Sunday New York Times was available for $1.50 back in the day after a pleasant walk to the newsstand downtown that was also an unusually good source of little magazines, from The Public Interest on the Right to the Monthly Review on the Left and everything in between – I must stop and note that only one of these little magazines remains. Thank you, John Bellamy Foster. The newsstand is long gone and the newspaper does not circulate outside Greater Atlanta. I am convinced our civic culture is dying, or has died, with the daily newspaper. Still, there are a few sane places left, on both the Right and the Left.
Part the First: If a Research University is Destroyed by Abject Shortsightedness, Does Its Fall Make a Noise? And now reading the news has become more of a chore as the attack on science proceeds apace. Yes, while I can understand the misunderstanding because my colleagues are by and large the worst sort of navel gazers, I take this personally. The Wall Street Journal story on the $800 million in grants cancelled at Johns Hopkins University hits home. It is hard to know what the brain geniuses of Trump II are thinking, but if and when the first research university in the United States is destroyed by their actions, it will not come back. I do wonder what Hopkins alumnus and chief benefactor Michael Bloomberg thinks about all this. And what will come of the Applied Physics Laboratory?
A few comments on the FB post attached to the link a friend sent me were typical in their obtuseness: “Hmm so they can’t make it without handouts from the government and taxpayers?” Handouts? To determine how HIV hides out in the body for years? Plus, the answers to a thousand other important questions, at one institution? Anyway, Big Pharma will not replace the thousands (just at Johns Hopkins) of scientists, physicians, biomedical engineers, public health experts, medical fellows, postdocs, technicians, staff who maintain OMIM, graduate students, and undergraduate students, and other national research institutions that are the source of essentially every medical advance. Virtually all this research in the United States is funded by the National Institutes of Health, which dwarfs the funding levels of equivalent organizations. Can NIH be improved? Of course, but the edifice in not a tear-down.
Part the Second: An Alzheimer’s Disease Animal Model with Promise (especially compared to the mouse). The Amyloid Cascade Hypothesis has not yet explained the pathobiology of AD. The amyloid plaques that have been associated with AD are bundles of fragments of a protein called (after the fact) amyloid precursor protein (APP). The exact functions of APP remain a mystery. But in a recent paper:
Dario Valenzano, an evolutionary biologist (my favorite variety of this type of nerd) at the Leibniz Institute on Aging in Jena, Germany, and his colleagues have found that knocking out the appa gene, which makes APP, in turquoise killifish (Nothobranchius furzeri) reduces signs of ageing…“We found that there is probably an overlooked role of amyloid precursor protein in normal brain ageing,” says Valenzano.
The turquoise killifish is a good model of ageing research because:
They tend to live no more than about 9 months and exhibit rapid age-related brain decline. Valenzano’s team looked inside neurons of aged fish — those about 6 months old — and discovered an accumulation of APP derivatives, including a damaging type of amyloid-β, that aren’t present in 6-week-old fish.
Using CRISPR (the explanatory pdf at this link is very good; CRISPR is the product of basic biomedical research on bacteria) Valenzano’s research group at the Leibniz Institute on Aging in Jena, Germany, produced a strain of turquoise killifish that don’t have the appa gene:
Brain tissue studies showed that this slowed cell death and decreased brain inflammation in ageing fish. It also improved the age-related decline in neuronal activity and capacity for learning. “We see quite remarkable rescue of learning in elderly fish,” says Valenzano. “They learn in a way that’s more like younger fish.”
Can a strange little fish that lives a short life in transient puddles tell us something important about AD? I am asked such questions all the time. My answer goes something like this: Without research using the yeast responsible for bread and beer, our understanding of the cell division cycle, dysregulation of which is usually the first step in cancer progression, would have been much slower to come. The same is true of the cell and molecular biology of learning, where pathways were worked out in the fruitfly and a marine mollusk. The paper is here as a preprint (caveat emptor) but I expect this work to be very productive, if it continues to receive adequate support from funding agencies.
Part the Third: Who Funds the Research that Provides the Foundation of Our Healthcare? From 2023, but still germane: Comparison of Research Spending on New Drug Approvals by the National Institutes of Health vs the Pharmaceutical Industry, 2010-2019:
Funding from the NIH was contributed to 354 of 356 drugs (99.4%) approved from 2010 to 2019 totaling $187 billion, with a mean (SD) $1344.6 ($1433.1) million per target for basic research on drug targets and $51.8 ($96.8) million per drug for applied research on products.
This was covered previously in Patents and Intellectual Property in Biomedical Science: A History in Two Tales.
Part the Fourth: NIH has paused patenting of discoveries, slowing their use in developing treatments. The article with that title is here; apologies for the paywall but I could not get around it after logging out. Or one could point out that the Bayh-Dole Act of 1980 is the source of much of our distress as basic biomedical science has been underdeveloped throughout the course of the Neoliberal Dispensation that began in the late-1970s. Yes, I remember “before” and “after.” I do not live in the past, but remembering it can be a comfort at times. Those who are fascinated by natural history also serve while not waiting.
Part the Fifth: Health Insurance Is a Category Mistake and Workarounds Never Work. Georgia publicly touts its Medicaid experiment as a success. Numbers tell a different story. Key passage: “As of the end of 2024, the Pathways program has cost federal and state taxpayers more than $86.9 million, three-quarters of which has gone to consultants.” That may have been the goal all along…this $65.2 million to the consultants?
Part the Sixth: Public Private Partnerships Always Advantage the Private. Also from The Current, Hyundai fails wastewater standards. Salaries to be paid at this megaplant for the assembly of electric vehicles were also apparently exaggerated as Hyundai courted the State of Georgia – more advantage to the private.
Part the Seventh: An Interesting Gloss on AI. From Front Porch Republic. Everyone needs a front porch or its equivalent, just as everyone needs a Third Place to live a good life. FPR has probably never appeared here, but it often addressed our puzzlements from the other side, as in this essay from Austin Hoffman, Artificial Intelligence for the Artificially Intelligent.
Thus, the AI question reveals what is truly valuable. If there is work that we truly do not mind replacing with artificial intelligence, perhaps it was not worth applying genuine intelligence in the first place. That is, if it is only worth doing by AI, maybe it is not worth doing. If an AI can replace teams of HR delegates answering pointless questions and regurgitating bureaucratic obfuscation, then maybe the HR department is a distraction from human relations. If the president or CEO can outsource all of his emails, communications, and decisions to a robot, what are you really paying him for?
AI in medical education has become an irresistible force while I find myself not to be the immovable object I had hoped. But I am still unmoved, so far. I live within walking distance of work, so I have a hard time not thinking about the energy hog that is generative AI. How unmovable can I remain? That remains to be seen. Especially if and when I begin using AlphaFold in my research. ‘Tis a puzzlement.
See you next week. Happy St. Patrick’s Day!