Posted on by rjonakait

Whither Biomedical Science? (Guest Post by the Spouse)

Starting out as a small federally-funded Laboratory of Hygiene in 1887, the National Institutes of Health (the NIH) has become the largest and, arguably, the most prestigious biomedical institution in the world. It has fueled virtually all of the advancements in the treatment of heart disease, cancer, stroke, multiple sclerosis, AIDS, other infectious diseases, and much more. It can be considered the jewel in the crown of scientific excellence. It funds a cadre of in-house scientists as well as academic scientists across the United States and around the world. Explain to me, then, why the Trump administration is trying to hobble it…no, destroy it.

Beginning in February 2025 the administration terminated 2,300 ongoing research grants, amounting to cuts of almost $4 billion. Most of the cuts were at medical schools and hospitals, but they reached into other institutions — mostly universities — as well. More than 60% of these terminations were aimed at research and development, but an alarming 38% targeted research training and career development. Most of these were Post-doctoral Individual National Service Awards. Is this a problem? Yes. Emphatically, yes.

Training to become a scientist is time-consuming and expensive. It usually begins (in the U.S. at least) at the 4-year undergraduate level. Graduate training (course work and hands-on laboratory experience) can consume another 4-6 years. A written thesis and its defense are required for completion of the doctorate. Attainment of the PhD, however, is only the beginning of the ending point. It’s followed by another 2-4 years of post-doctoral training. When one finally takes her place as an assistant professor with a research lab of her own, she needs microscopes, centrifuges, PCR machines, supplies (glassware, chemicals, paper towels, for heaven’s sake), computers, animals, and a helping hand to get things underway. NIH often provides a good deal of the funding for this extensive training. Moreover, those recipients of NIH training grants at the graduate and post-doctoral level provide established laboratories with essential intelligent labor. Experiments that would not get done without trainees get done with them. Explain to me, then, why the Trump administration is cutting the very training that leads to the health of a scientific future.

One answer is a sad one. Over the years it had become clear that the scientific work force was almost exclusively white and male. Surely there were women and minorities out there who could be recruited to this important enterprise, and it just might be in the national interest to find them. So the NIH (and other scientific agencies) began to actively recruit from these populations, and sometimes, even to insist on the inclusion of them.

Then came Executive Order 14281, issued in April 2025 just months after Trump took office. It was the opening salvo of the Trump administration’s assault on Civil Rights legislation. This EO direct all agencies (not just scientific ones) to “deprioritize” enforcement of statutes and regulations imposing “disparate impact liability.” In everyday language this meant that agencies could not take into account the fact that certain groups had been discriminated against, and that they should not give priority to these so-called “underrepresented minorities.”

This injunction was elaborated more specifically for scientific grant funding in EO14332 later that year. “Discretionary awards” it states, “must…demonstrably advance the President’s policy priorities.” One has to assume that some of those policy priorities were enumerated in EO14281. So, in short, no priority is to be given to minority groups.

The Office of Management and Budget (OMB) is given the task of implementing Executive Orders, and it has recently promulgated its new rules that will apply to scientific grants funding. It includes the language of EO14332, but goes further: A “federal award is not to be used to fund, promote, encourage, subsidize, or facilitate ‘diversity, equity or inclusion’ (DEI)….This includes racial preferences or other forms of racial discrimination used by the recipient”[Emphasis added]. Technically, awards are granted to institutions, not to individuals. This means that even if a scientific study has nothing to do with DEI, funding can be withheld if the formal recipient of the grant (e.g., a university) engages in something that is determined to be in violation of the administration’s DEI policies. This appears to be designed to punish institutions that are in presumed non-compliance at the expense of what might be relevant and meritorious science.

Moreover, and more insidiously, the OMB regulations would give final approval authority not to a scientific advisory council, but rather to a political appointee whose job it will be to ensure that grant applications are consistent with administrative priorities, do not espouse “anti-American” (undefined) ideas, and are in the “national interest” (undefined). This can and will lead to decisions based on political considerations (undefined), not scientific merit. It is ironic that the EO14281 is entitled “Restoring Equality of Opportunity and Meritocracy.”

Another provision of EO14332, the order underpinning these new OMB rules, is that funded grants must not “compromise public safety.” This, too, is ironic. Because some of the current administration policies are demonstrably anti-intellectual and anti-scientific (anti-vaccine rhetoric that has undermined public confidence in vaccines that have been in use for decades, quashing anti-mRNA research, decimating the Centers for Disease Control, removing the U.S. from the World Health Organization, canceling studies examining effects of global warming, etc., etc., etc.), the administration itself poses threats to national safety thereby violating its own prohibition. Political appointees of this administration cannot be considered qualified to determine what is a threat to national safety.

There are other egregious aspects to the new OMB regulations (they log in at 238 pages of single-spaced type). Many of them handicap researchers sometimes to maintain accountability (not necessarily a bad thing), but often to punish them and their institutions for perceived grievances — grievances defined by political appointees, not scientists. The most troubling rules allow an authoritarian overreach that can have a chilling effect on creative and necessary scientific endeavor. These proposed regulations taken together do not advance the scientific enterprise. American scientific know-how and ingenuity used to be the envy of the world. The Trump administration is rapidly darkening that sparkling reputation.

Posted on by rjonakait

Ozempic Triumph vs. Scientific Defeat (Guest Post from the Spouse)

It has become clear in recent weeks that the “humanoid alien beings” (as a friend calls them) who run the White House have less than zero understanding of the way medical, biological, or chemical science works. It isn’t that they don’t understand scientific facts (okay, not all of us love the minutiae of alkaloid biochemistry), but they don’t understand the sociology, economics, methodology, or history of science. In particular, they don’t seem to know how scientific knowledge accumulates — tiny steps over long periods of time. As a result, the proposed layoffs and drastic funding cuts in the National Institutes of Health and the National Science Foundation threaten to bring scientific progress, particularly in medical science, to a halt.

Elon Musk may think that the design and construction of his electric car sprang full-blown from his brilliant mind. It didn’t. It was the result of incremental increases over time in the understanding of combustion engines, mechanical and electrical engineering, and so on. Similarly, most of us don’t appreciate where life-saving drugs come from, and even those of us who work or have worked in science don’t know the history of most of the drugs we take every day. I certainly didn’t. We don’t know the many, many hours of research and the many years of effort that culminate in these drugs seeing their way into the clinic. So I took a shallow dive into the history of the well-known drug Ozempic to see how it came to be.

This story goes back to research that began in the 1920’s. But, before going there, some basic human biology:

Blood sugar (glucose) levels are carefully regulated in the healthy human body. When blood sugar levels are too high, the pancreas produces insulin to encourage cells all over the body to take up that sugar and either use it or store it. When blood sugar levels are too low, the pancreas produces a different hormone, glucagon, that tells the liver that it’s time to release some of that stored glucose. It’s an important biological yin and yang. Insulin and glucagon are on two ends of a physiological seesaw, keeping sugar levels steady. If the system gets out of whack (as it does in Type 2 diabetes), too much blood sugar threatens the body with myriad catastrophes including organ failure, blindness, immune system dysfunction, etc. etc. etc. The importance of the seesaw to human health and the distressful increase in Type 2 diabetes have meant that interest in insulin and glucagon have been keen since their discovery in the 1920’s.

In the early 1980’s (more than 40 years ago and some 60 years after the discovery of insulin and glucagon) researchers at the National Institutes of Health who were interested in diabetes (already identified as a disease of the pancreas) began screening venoms for possible effects on guinea pig pancreatic cells, the insulin producers. (These days such a study would be called “a fishing expedition” and would be an unlikely candidate for funding.) It was tedious work. Nevertheless, after looking at venom from bees and wasps and snakes and such, the researchers found that venom from gila monsters (those ugly black and yellow reptiles of the US southwest) had a unique effect on pancreatic cells; the cells became enlarged and started producing lots of insulin. In short order they determined that the venom — or something in it — regulated blood sugar levels in animals. 

Around the same time, an American biologist at Massachusetts General Hospital and a Danish physiologist (working separately) were intrigued by glucagon. Reminder: Glucagon is made in the pancreas and promotes glucose release from the liver, thereby increasing blood sugar levels. However, a small piece of the glucagon molecule, which they called glucagon-like peptide-1 (GLP-1), triggered pancreatic production of insulin and…and…and seemed to suppress appetite and trigger weight loss in laboratory mice. Could this be a drug to treat diabetes and curb obesity? Side bar: the technology they used to identify this molecular “fragment” had taken its own sweet time in coming to fruition.

It was a short-ish step to determine that the substance found in gila monster venom was very like GLP-1. In the early 1990’s John Eng at the VA Center in the Bronx found a molecular look-alike to GLP-1 and named it Exendin-4. Later, a researcher at the National Institute on Aging, working with a pharmaceutical company, obtained FDA approval in 2005 for its use in Type 2 diabetes. Side bar: the technology used to purify and get the DNA sequence of this molecule had been developing on a separate track, but they couldn’t have identified the molecule without it.

But there was a problem with both GLP-1 itself and Exendin-4. They had to be injected (bad enough), but they disappeared quickly from the blood, not hanging around long enough to be very effective. Importantly, chemists at Novo-Nordisk came up with a method for changing the molecule so that it stayed active in the bloodstream. Side bar: you get the picture.

But what about obesity? This effort took a different track and gets murky in part because obesity was not yet considered a “disease” or even an eating disorder. Obesity was long considered to be the personal failure of individuals to limit their food intake and/or their refusal to exercise. Another line of research was being done leading to the realization that for many, obesity was a physiological abnormality that just might succumb to drug treatment. And so it is. In short, the same drug (semaglutide, a GLP-1 look-alike) is indicated for both Type 2 diabetes (Ozempic) and obesity (Wegovy).

People are still a bit unsure how these drugs work to increase weight loss and suppress appetite. They just know that they do. There are hints, though, that it involves direct actions in the brain. This observation, in turn, has led to the hypothesis that there could be a link between metabolic imbalance and neurodegenerative diseases such as Parkinson’s disease, Huntington’s, and/or Alzheimer’s. Clinical trials using Exendin-4 on Alzheimer’s-prone patients have begun. However, those trials and this promising line of research will be stopped when NIH research funding is stopped…as it is now.

In short, Ozempic is the result of almost 100 years of research involving incremental discoveries in physiology, chemistry, molecular biology, neuroscience, and research methodology. That’s a long time, but sometimes science takes a long time. These sorts of breakthroughs will take longer or not even occur if research funding is brought to a halt…as it is now.