Part the First: The Selfish Gene is 50 Years Old. The mid-1970s brought forth two biology books that have had a lasting impact. The first is Sociobiology: A New Synthesis (1975) by the ant biologist E.O. Wilson of Harvard. Sociobiology is a topic for another time, and it may require me to finally get some blood pressure medicine. The second book is The Selfish Gene (1976) by another freelance critic of all things, Richard Dawkins of Oxford. Both books were motivated by the desire to simplify biology down to the smallest, and therefore fundamental, parts and then give those parts a kind of agency that explains all.
As a molecular cell biologist with an abiding interest in evolution who did a long apprenticeship in an old-school biochemist’s laboratory before the revolution that was gene cloning and modern molecular biology, I understand the urge to get to the root of the matter, so to speak. But my cell and evolutionary biology tell me things are never so simple. A retrospective on The Selfish Gene was published in Nature earlier this week: The Selfish Gene 50 years on – it’s time for an update. Yes it is. And as the tagline of the essay puts it, “A focus on the gene alone has become outdated. Books that capture the complexity of life deserve center stage.” Yes, they do. From the author Daniel Comfort:
The idea at the core of the book, published in 1976, was thrillingly simple: that a living organism is just a gene’s way of making more organisms that can carry the gene down the generations.
Back then, The Selfish Gene seemed pretty harmless. Dawkins’s ideas tracked with mainstream sociobiology. It was a popular book that covered exactly the sort of ideas that my lecturers were already teaching.
Re-reading it now, with decades of scholarship in the history of biology under my belt, it seems less benign. The determinism baked into the “gene’s-eye view” in the book troubles me, as does the passivity of the organism in Dawkins’s telling — a “vehicle”, a mere “replicator”. The implication: that traits such as aggression are hard-wired into people. Fortunately, over the past couple of decades, new tools, fresh models and scholars in many disciplines have begun to embrace the complex reality of biology. Readers in search of an understanding of life on Earth today would do better to reach for books that take a broader view.
Dawkins later denied this, but the thrust of the book is that the gene is the unit of selection in evolution. Well, life without genes is unimaginable but they are not the unit of selection in evolution. The evolutionary biologist Stephen Jay Gould and the philosopher Mary Midgley, and others without physics envy, pointed this out. Now, fifty years later a more holistic approach to all of biology is bearing fruit. Although planet Earth came first (obviously, excepting some of the more outrageous speculations of Fred Hoyle; I read this when it was published so you wouldn’t have to now) biological organisms make the world as much as the world makes them. One of the first and most convincing statements of this is from the Richard Lewontin:
For years, a group of biologists, philosophers and historians has been calling for an extended evolutionary synthesis that accounts for phenomena beyond this isolated window of transmission. Heredity operates at many levels at once. For example, there’s some evidence that epigenetic changes — molecular modifications to the genome that can alter gene expression without changing DNA — are heritable. Ecosystems involve many life forms that adapt to one another, creating stability and developing a kind of homeostasis — the self-regulating process through which balance is maintained — that confers resilience against catastrophic change. Your body consists of more microbial cells than cells derived from your parents’ genes. The microbiome doesn’t participate directly in your genetic heredity, but you can’t live without it.
Comfort recommends the recent book Eco-Evo-Devo: The Environmental Regulation of Development, Health, and Evolution by Scott F. Gilbert and David W. Pfennig. I never recommend a book I have not read, but this one is on the list. Based on my previous reading and the success of Professor Gilbert in formalizing the discipline of developmental biology out of what had been embryology, I expect this to have a wide-ranging impact, including on the basic biology of cancer. I’ll get back to you if it pans out.
In the meantime, never pay attention to unitary explanations of any kind in biology. They are usually the handmaiden of eugenics. Sometimes this is obvious. More often the hand is hidden but it is still there. The same is true for unitary explanations in economics, but at least biology is a science.
Part the Second: What is Wrong with Big Medicine? Other than the fact that it is large, very large, and as unfeeling as Sue, the T. rex greeting visitors to the Field Museum in Chicago. While searching for something else a few days ago, I came upon this obituary of Arnold Relman, which I read at the time. Dr. Relman was editor of The New England Journal of Medicine. He is missed:
Relman was a towering figure in American medicine. He was a medical researcher, a clinician, a medical school professor and department head, the editor of two influential medical journals, and a prolific writer on health care. In 1977, he became editor of The New England Journal of Medicine, and it was in this position that he came to national prominence. Under his leadership, the NEJM’s standing as the world’s most prestigious medical journal grew, and it became a source not just of new research results, but of thoughtful analyses of important ethical and policy issues in medicine.
In 1980, he wrote a landmark article, “The New Medical-Industrial Complex,” in which he sounded the first warning that the American health system was becoming a profit-driven industry. For the rest of his life, that was his dominant concern: that health care in the US was increasingly treated as a market commodity, distributed according to the ability to pay, not medical need. It explained why the US, alone among advanced countries, leaves millions of its citizens with no or inadequate health care, even while spending about twice as much per capita as those countries, much of it on income-generating but medically unnecessary tests, overhead, and profits.
The answer, he wrote, was two-fold: a single-payer financing system, like Medicare, with no investor-owned private insurance companies; and a nonprofit delivery system, consisting of multispecialty groups of doctors paid by salary within a set budget. He believed that the Affordable Care Act will ultimately unravel unless it is fundamentally reformed, because while it has the virtue of increasing access, it leaves in place the private insurance industry and the profit-oriented delivery system. Either costs will rise rapidly, he thought, or benefits will become too skimpy with excessive deductibles and copayments.
That about sums it up. And in the last twelve years things have gotten only worse. For the past forty years I have thought that, eventually, the United States would see the light and fix health care. Silly me. The entire system will have to hit absolute rock bottom before anything changes for the better. Current medical students are beginning to understand. Well, some of them. They could be the answer to the problem, and a few of their teachers try to get to them before the malign influence of Big Medicine takes over. ‘Tis a struggle.
Part the Third: Alternative Medicine in the Swiss Dock. Last week I briefly mentioned those medical clinics in Switzerland that cater to a rich clientele and cure them with various potions, poultices, and infusions that have little more than a placebo effect when things go right. In a nice example of synchronicity, Did an Alternative Medicine Guru Accidentally Kill Patients? by D.T. Max appeared in notification earlier this week from The New Yorker:
Thomas Rau is a prominent Swiss doctor of alternative—or, as he calls it, “biological”—medicine. He believes that in most cases the best way to cure disease is not to attack the ailment directly but, rather, to boost the body’s natural defense systems. In his eyes, most conventional medical practitioners are timid and overly literal-minded. (A patient of Rau’s remembers him calling specialist doctors “narrowists.”) Whereas most doctors give a standard battery of CT scans and MRIs, Rau uses a technique called dark-field microscopy. He takes a dab of a patient’s blood, places it on a slide, and observes the cells’ behavior over time. Do they clump up, or are they motile? The presence of toxins or inflammation—indicated, Rau told me, by irregular formations or “stacked rings” of cells—dictates specific treatment protocols, often including a change of diet. He has written, of dark-field microscopy, “Hardly any other examination leads so quickly to conclusions about dynamic processes in the body.” He performs the test at BioMed, a clinic that he owns, along with an adjoining hotel, in the picturesque town of Schwellbrunn, Switzerland. Guests often stay for several weeks and spend tens of thousands of dollars.
Rau believes that virtually anyone can benefit from his interventions, many of which he defines as preventive. But he told me that his specialty is treating people with what he calls “unclear” conditions. He estimates that eighty per cent of such patients—principally, sufferers of long COVID or chronic-fatigue syndrome—go home from his clinic “massively improved.” In 2024, he spoke at an event in Brooklyn called “The Future of Medicine,” in which he described himself as “the master in rebuilding cellular function.”
Rau’s tool kit includes colon hydrotherapy (irrigating the bowels with warm water), ozone treatments (infusing the blood with the gas), and hyperthermia therapy (placing a patient on a bed heated by infrared-A radiation to mimic a fever, which supposedly shrinks tumors). He isn’t concerned by the absence of studies confirming that the treatments performed at BioMed work. “I pay a lot of taxes,” he told me when I visited him in Switzerland, in 2024. “I pay scientists’ salaries.”
Red blood cells do “stack” when the fluid phase of blood is altered by any number of conditions, but these rouleaux are only nonspecific indicators that something may be out of balance. Moreover, contrary to Dr. Rau, red blood cells are not motile. They might move due to Brownian motion but that’s all. Red blood cells are biconcave bags of hemoglobin and glycolytic enzymes and little else. The only motile cells in the blood are white blood cells. As for this “test” being the best measure of dynamic processes in the body, hematologists would argue that point if the point were worth arguing. And if Dr. Rau really was the “the master in rebuilding cellular function” everyone would have heard of him, especially after his visit to Stockholm one December.
It goes without saying that being a specialist at treating people with what he calls “unclear conditions” will always have an “out” with his patients. So he really doesn’t have to be concerned that his treatments have not been shown to work. Colon hydrotherapy is little more than an enema, bubbling ozone into the blood is hazardous and has no known effect except perhaps damage to red blood cells and the lining of blood vessels, and infrared light does not shrink tumors.
I suppose it is easy to believe Dr. Rau, if you can afford it. The institution looks very comfortable, but not quite like this one. The article is long and the conclusion undetermined. But we can expect Dr. Rau and his clinic to be there as long as he is. What he does is not too different from alternative/functional medicine in the United States, except that he makes a lot of money at it. So far.
Part the Fourth: Whither American Football? We are in the middle of football season in the Land of the Free and the Home of the Brave™. Billions of dollars are to be made at the professional and collegiate levels (with college football being a most peculiar thing about American higher education). But how long will it last? How long can it last, since recent studies on chronic traumatic encephalopathy (CTE) show that it disables or kills so many players who play at the highest and fastest levels ?
Back in the day when I played it from grades 3-12, American football was called a “contact sport.” I remember two probable concussions, one from contact with another football helmet and the other from contact with the ground. But at the highest levels even then it was a “collision sport.” And it turns out those collisions have effects that lead to serious brain damage later in life. The evidence accumulates and it is undeniable. The Scientific American summary article states that Landmark study finds three in four NFL players die with CTE:
American football can be brutal. Scientists have long known that the hits, tackles and other collisions that are central to the sport come with health risks, but what these impacts do to the brain has been less clear. What we do know is that many footballers have died with brains that have shown evidence of chronic traumatic encephalopathy (CTE), a disease associated with symptoms such as mood swings and dementia. But because a diagnosis requires that investigators look for damage in a person’s brain after they die, it’s unclear just how common CTE is among current or former athletes.
But now, in a study published in JAMA Network Open, an analysis of medical records from thousands of deceased former NFL players—including hundreds who donated their brains to science—estimates that about 75 percent of these players likely died with CTE.
“No other environmental or occupational exposure ever studied is known to have increased dementia risk at death by that amount,” says Yorghos Tripodis, senior author of the paper and a professor of biostatistics at Boston University.
The study is based on records of 2,362 former NFL players who died between 2008 and 2023 and played in the league for an average of five years. Among those who donated their brains—almost 400 players—a stunning 93.5 percent had CTE. Signs of CTE in the brain can include atrophy, or tissue wasting, as well as clusters of tau protein—a symptom that is also linked to Alzheimer’s disease.
…
For comparison, among the general population, fewer than 1 percent of brains in community-based brain banks show signs of CTE, Tripodis says.
Correlation is not causation. But when there is a mechanism that can explain the correlation, the evidence from statistics can be strong. The underlying paper at JAMA Network Open is convincing, largely because the authors controlled for bias in their sample: Bias-Adjusted Prevalence of Chronic Traumatic Encephalopathy Among Deceased National Football League Players:
Main Outcomes and Measures. The main outcomes of this study were bias-adjusted prevalence of CTE neuropathology and all-cause dementia among the target population, both of which were measured in donors prior to this study. A cognitive symptom–related brain donation selection ratio (probability of donation given CTE divided by the probability of donation given no CTE) was estimated using Poisson regression and was applied to adjust donor-observed prevalence of CTE neuropathology at death and all-cause dementia during life. The prevalence estimates were adjusted for bias using the estimated selection ratio.
Results. The cohort consisted of 2362 deceased former NFL players (mean [SD] years played, 5.1 [3.9]; 971 [41.1%] aged ≥80 years at death), of whom 396 were brain donors and 1966 were nondonors. Of 387 donors, 362 (93.5%) had CTE. The median selection ratio was 4.97 (95% CI, 4.72-5.26). Bias-adjusted population prevalence of CTE at death was 74.5% (95% CI, 69.6%-78.3%), with a conservative lower-bound analysis estimating 63.7% (57.2%-68.9%). Bias-adjusted population prevalence of all-cause dementia history during life was 27.2% (95% CI, 22.6%-31.6%).
Conclusions and Relevance. The findings of this cross-sectional study suggest that selection bias materially inflates donor-based prevalence estimates but is unlikely to fully explain the high burden of CTE neuropathology among this population. Further research is required to understand the clinical impact of this disease.
Further research will show that repeated acceleration of the brain so that it collides with the skull causes cumulative damage that leads to dementia that can only be diagnosed only postmortem. At the moment the National Football League will probably use the “died with CTE” dodge instead of the “died of CTE” cause. One might ask: If the former player had occupational dementia during the last years of his life, what does that matter? We are seeing the same “died with/died of” obfuscation with measles right now. I do wonder how the National Collegiate Athletic Association (NCAA) will react? Can they justify putting their “student-athletes” at risk of dementia later in life because the branding opportunities for college football are so lucrative? Yes. By the way, “student” is a meaningless descriptor when a college football quarterback can be paid $5M a year and more, out in the open, and the players are free agents. Being on the side of labor, I have no significant objection to that. Still, the entire edifice is likely to crumble as legal prop bets inevitably destroy sports.
Eventually, this is likely to be beside the point. My poll is totally unscientific and anecdotal, but I have yet to have a young mother say “yes” when I ask if her son will be playing football when he gets old enough. My daughter has made it perfectly clear that I will not be teaching my grandson proper technique in blocking and tackling. Part of me will miss that, because technique even at the highest levels has degraded over the past fifty years as the athletes have gotten stronger and faster. But given what we know now, I couldn’t do it anyway. One of my high school football coaches played for a major college football power in the early 1960s after he graduated from our high school twelve years before I did. He later played defensive back (lots of collisions involved) in the NFL for five years. When he died last year his daughter asked that contributions be made to the CTE Research Center at Boston University. When the pipeline dries up, football will wither.
Now, should I watch one of the fiercest college rivalry games this weekend, a game that has been on the calendar for a hundred years? No. I do need to keep telling myself that…
Thank you for reading! Stay safe and I ask my American readers to remember to vote next Tuesday. Our Democracy™, so beloved by the faux-left wing of the Uniparty, may be moribund but hope, it springs eternal. My father always told me, from the first time I voted on the way to work with him at the chemical plant, “If you don’t vote you can’t complain.” I have a feeling that we seldom voted for the same candidate over the next thirteen years of his life, but that doesn’t matter. Then or now.
