Coffee Break: End-of-the-Week Thoughts on Science and Other Matters Arising

Part the First: NIH cancels funding for landmark diabetes study at a time of focus on chronic disease (paywall).  As part of the defenestration of Columbia University, the National Institutes of Health has cancelled a long-term, multi-institution study on diabetes that has been managed for the past few years by Columbia.  Nearly 40 million Americans have diabetes.  Diabetes is the very definition of chronic disease, whether Type 1 (autoimmune, insulin dependent, previously called juvenile diabetes because of its usual early onset) or Type 2 (acquired usually as a concomitant of obesity and metabolic syndrome, insulin insensitive).

Since 2022, Columbia has been managing funding for the most recent phase of the program, which is focused on tracking the development of Alzheimer’s disease and related dementias among participants.  But over 90% of the current funding, which amounts to more than $80 million spanning five years, is ultimately distributed to over two dozen other research sites across the U.S.

This is the kind of work on chronic disease that falls precisely in line with what health secretary Robert F. Kennedy Jr. has advocated for as part of his “Make America Healthy Again” movement.  Diabetes is one of the most prevalent and costly chronic conditions in the U.S., and the study has been assessing the effects of lifestyle interventions, such as changes in diet and exercise, which Kennedy has shown a preference for over medications.

Researchers continued to follow participants to understand the long-term effects of the initial lifestyle interventions, the cost-effectiveness of such interventions, and patients’ risk factors for developing diabetes and related conditions like heart disease. The project has resulted in over 200 publications.

Diabetes is a risk factor for developing dementia and cognitive impairment, and the study’s researchers are uniquely positioned, with a “treasure trove” of data and long-term relationships with patients, to probe what biological mechanisms may explain this risk and how cognitive impairment affects health outcomes.

Studies of this kind cannot be restarted after they are stopped.  Momentum is destroyed, Scientists and staff disperse, participants feel their efforts have been wasted and decline a second invitation.

Part the Second. WHO issues starkest warning yet on fallout from U.S. withdrawal of aid for global health. The World Health Organization is one more whipping boy of the moment, but that does not make the headline untrue even if some of this work has been sponsored/funded by USAID.  But that is no reason to cut off funding for research and prevention of horrific infectious diseases.

Several WHO officials recounted the impact the U.S. funding cuts are already having on disease control efforts in multiple countries, including the rollout of promising malaria vaccines and mass campaigns to vaccinate against measles at a time when the incidence of the highly infectious disease is surging.

Over the last two decades the U.S. has been the largest bilateral donor in the fight against malaria…work that has helped to avert an estimated 2.2 billion cases and 12.7 million deaths.

As the richest nation on Earth, one would think we can afford this.  When my father was a boy in Louisiana in the 1930s malaria was endemic.  Autochthonous cases of malaria have been documented recently in the United States, and in a warming climate we can expect more cases of malaria in the future.  Dengue fever and other mosquito-borne diseases are probably next.  As for measles, see West Texas and New Mexico today.

Part the Third.  Speaking of measles, no the measles vaccine does not routinely cause deaths, despite what the Secretary of Health and Human Services fervently wants the people to believe.  On the contrary:

Measles is itself a killer. Before the measles vaccine was introduced in 1963, it was a near-certainty that children would be infected before the age of 15 – about three or four million cases occurred every year. Most children had no complications, but a little more than 1 in 1,000 would die after developing pneumonia or encephalitis. That equates to 400 or 500 deaths a year.

A 2024 study in the Lancet estimated that measles vaccines prevented 93.7 million deaths globally between 1974 and 2024 — a number equivalent to a quarter of the U.S. population.

I remembered having had the measles in the first grade, and this confirmed by my Report Card, found in a box after my mother died.  It showed twelve consecutive absences when I often went the 180 days without a single absence.  Measles (rubeola; I also had rubella as a child, which was called the German measles or 3-day measles at the time) was an unpleasant two weeks in a dark room, because the light sensitivity that accompanies measles was thought to be damaging.  The vaccine, not yet available, would have been better.  It is true that a live attenuated vaccine given to an immunocompromised individual can result in a bad outcome.  The shot commonly only causes a fever with other symptoms are extremely rare.  But that is not what the Secretary of Health and Human Services is talking about.  Moreover, even in this country, measles can be a killer (see Texas, again).

In the mid-1990s, the Institute of Medicine – now known as the National Academy of Medicine – did a careful review of reports from VAERS.  They concluded that except for (transient) allergic reactions and blood clot disorders, (both of) which were incredibly rare, there was no link between the MMR and deaths.

It should go without saying, but it must be said again: There is absolutely no connection between the MMR vaccine (Measles-Mumps-Rubella) and autism, whatever is floating around in the MAGA universe.

Part the Fourth.  Mice are still not a good experimental model for Alzheimer’s Disease, despite what a recent paper in an MDPI journal purports about a hair loss remedy, according to the New York Post:

A new study published in the journal Antioxidants has identified carnosic acid — a compound found in rosemary and sage — as a promising warrior in the fight against Alzheimer’s.

Rosemary sage chicken soup will not prevent me from getting AD or keep my hair from thinning, as it seems to be doing at my age.  No big loss except for feeling the raindrops hit my scalp.  My hair had a good run for a long time.  As for mice and AD, this has been reviewed here before.  The course of disease is completely different in mice compared to humans.  Symptoms of cognitive decline, such as they can be measured in a rodent, are reversible in mouse models.  Not so for a human with any treatment tried, so far.  Based on the utility of unconventional experimental models, I’m still betting on the turquoise killifish to tell us something useful about APP, the source of amyloid plaques in AD, and the aging brain.

Part the Fifth.  Contrary to Max Planck, science does not always advance one funeral at a time.  In this case we have lost a scientist for our time.  Elisabeth Vrba was a giant of modern evolutionary theory and practice and she will be missed, as explained in this appreciation by her peer in modern evolutionary theory, Niles Eldredge.  Back when I probably should have been in the lab working on my protein purification skills, I was often in the Science Library reading the evolutionary biology literature.  It was an exciting time with scientists such as Stephen Jay Gould, Richard Lewontin, Niles Eldredge, and Elizabeth Vrba rattling the cages of the establishment.

The theory of punctuated equilibria had been proposed by me (Eldredge) and Stephen Jay Gould in 1972. We argued that most species in the fossil record remain unchanged for long periods, with occasional branching events involving rapid change during which new species evolve.

Vrba found a way to squeeze insight from the barren lines of phylogenetic diagrams into our understanding of evolutionary processes. Focusing on fossil antelopes, she contrasted two evolutionary lineages. One, impalas, has had only two species in the past six million years, since the Miocene. The other, wildebeests, hartebeests and others, has contained at least 27 species in the same time span.

Impalas exploit a wide range of ecological conditions, whereas the wildebeest lineage contains numerous grassland specialists. Vrba argued that the width of the niche that a species can occupy drives rates of both speciation and extinction, with the environment being the main force underlying this evolution.  Her ‘effect hypothesis’ proposed that apparent directional trends in evolution are accumulations of increasing specialization inside lineages of narrow-niched species – a phenomenon she later referred to as species sorting – and are not necessarily manifestations of species selection.

Vrba solved a problem that had vexed Darwin throughout his entire career: how could the great diversity of species over vast stretches on continental areas have occurred in the absence of obvious barriers that would cause reproductive isolation? Elisabeth’s answer was that environmental change not only drives species extinct, but also through the fragmentation and rearrangement of habitats, can cause isolation and create opportunity for rapid speciation.

Biologists in the next few centuries, if there are any working biologists in the next few centuries, will have the proverbial field day with this kind of research.

Part the Sixth. Life will always find a way: Blue-lined octopus Hapalochlaena fasciata males envenomate females to facilitate copulation.  Unfortunately another paywall, but this was irresistible to the sometime evolutionary biologist in me:

A variety of phylogenetically distant taxa, including flatworms, mollusks, amphibians, and fishes, use the deadly neurotoxin tetrodotoxin (TTX) for predation and defense.  A well-known example is the blue-lined octopus, Hapalochlaena fasciata (Hoyle, 1886), which uses symbiotic bacteria to sequester TTX in its posterior salivary glands (PSG). When it bites, the TTX-laden saliva immobilizes large prey and has caused lethal envenomation in a few incidents involving humans.  Female blue-lined octopuses are about twice the size of males, which bears the risk of males being cannibalized during reproduction. Surprisingly, we found that the PSG of males is roughly three times heavier than that of females.  Using laboratory mating experiments, we show that males use a high-precision bite that targets the female’s aorta to inject TTX at the start of copulation. Envenomating the females renders them immobile, enabling the males to mate successfully.

As a reminder, for some the thrill of eating fugu is said to be the tingling that is sometimes felt in the lips.  I would not know.  But I do know that fugu can kill you when mishandled or prepared improperly.

Part the Seventh.  More evolution, but after all, “Nothing in Biology Makes Sense Except in the Light of Evolution.” – Theodosius Dobzhansky.  The tools of phylogenomics continue to get sharper, as shown by a recent paper described here: ‘Mystery population’ of human ancestors gave us 20% of our genes and may have boosted our brain function.  The paper itself is heavy going, but well done, A structured coalescent model reveals deep ancestral structure shared by all modern humans:

Understanding the history of admixture events and population size changes leading to modern humans is central to human evolutionary genetics…We present evidence for an extended period of structure in the history of all modern humans, in which two ancestral populations that diverged ~1.5 million years ago came together in an admixture event ~300 thousand years ago, in a ratio of ~80:20%.  Immediately after their divergence, we detect a strong bottleneck in the major ancestral population…Moreover, we found a strong correlation between regions of majority ancestry and human–Neanderthal or human–Denisovan divergence, suggesting the majority population was also ancestral to those archaic humans.

A friend who pointed me to this paper asked if it is really possible to even do this using genome data.  The answer is yes, and it may be that this research can shed light on biological questions.  From the first author on the paper:

Some of the genes from Population B, “particularly those related to brain function and neural processing, may have played a crucial role in human evolution,” study co-author Trevor Cousins, a postgraduate student in genetics at the University of Cambridge, said in the statement.  In general, the genetic material from Population B reduced the ability of individuals to have children, Cousins told Live Science in an email, but “the genome is a complicated place, and regions outside of genes can still do important things.”

Speculation, yes.  But informed and potentially useful in explaining how humans as a sentient and (sometimes) sapient species emerged in the primate lineage during the last 200,000 years.  It is also worth noting that much of the research making this particular study possible was funded by the National Institutes of Health in the Institute of General Medical Sciences and the Human Genome Research Institute – which is why seemingly abstruse research is worth doing.  You never know what you don’t know until you look.  And you never can predict, except retrospectively, what will be useful in other contexts.

Part the Eighth.  In other matters arising, close reading can reveal hidden meaning.  The recent history of Palestine was covered somewhat discursively here about a year ago in a consideration of several books.  Adam Kirsch’s  On Settler Colonialism: Ideology, Violence, and Justice has received much attention since it was published in the summer of 2024.  Aviva Chomsky’s reading includes this:

Critics of the term, like the Wall Street Journal’s Adam Kirsch…argue…(that)…Because (settler colonialism) denies the legitimacy of existing states including the United States and Israel, it is inherently a call to violence and genocide.  Strangely, while Kirsch acknowledges that settler colonial scholars, from Rashid Khalidi to Mahmoud Mamdani to Lorenzo Veracini, all explicitly reject violence and genocide and advocate, for Palestine, either a two-state solution or one state with full and equal rights for Jews and non-Jews, Kirsch continues to insist that the concept inevitably leads people “into morally disastrous territory.”

I would just add here that Kirsch begins his Chapter 6, “Why Israel Can’t Be Decolonized,” by referring to the Palestinian Liberation Organization.  No.  PLO is the acronym for the Palestine Liberation Organization.  There is difference, mostly glossed over, and this explains much about our current world.

A thank you and apologies to those who responded thoughtfully to last week’s Coffee Break.  I have been away from my computer for much of the time since last Friday.  I hope to address many of your concerns in upcoming contributions.

See you next week.