Isegoria

Between 1970 and 1999, David Epstein explains (in Inside the Box), the National Heart, Lung, and Blood Institute (NHLBI) funded thirty large clinical trials that tested drugs or dietary supplements for the treatment or prevention of cardiovascular disease:

While more than half of the studies published before 2000 found a benefit, only two out of twenty-five published early in the twenty-first century did. It was as if some millennium bug had struck, and medicine stopped working.

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Beginning in 2000, “authors face greater constraints in reporting the results of their studies.” They had to restrict what has come to be known as “researcher degrees of freedom,” and that restriction caused a shift from mostly positive drug-trial results to mostly negative results.

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Wansink was a scientific star, making headlines and influencing policy—until a well-intended blog post he wrote in the fall of 2016 abruptly ended his academic career. It was titled: “The Grad Student Who Never Said ‘No.’ ”

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At the start of the post, Wansink mentioned a study in which diners at an all-you-can-eat buffet were charged different prices. He was disappointed that the study had “failed”—that is, had not supported whatever hypothesis he started with. But along came the industrious graduate student. Wansink handed her the data and told her to start looking for positive results. “There’s got to be something here we can salvage,” he told her.

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As Wansink wrote in his blog post: “Eventually we started discovering solutions that held up.”

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Because the grad student was doing such a good job at finding positive results, Wansink gave her data from other samples to work with. More headline-worthy results followed.

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Wansink’s blog post was openly explaining how he had encouraged the graduate student to do what is known as “HARKing”: Hypothesizing After the Results are Known.

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Since the year after his blog post, eighteen of Wansink’s studies have been retracted from scientific journals. In 2018, he resigned from Cornell.

Wansink’s work received coverage in the New York Times (and one of your favorite blogs).

I quite enjoyed David Epstein’s The Sports Gene and Range, so I went ahead and got Inside the Box the day it came out. It’s a light, Gladwellian collection of pop-sci bits exploring How Constraints Make Us Better.

“It is a myth — widely believed but not less mythical for that — that people are most creative when they are most free.”
— Herbert Simon

He opens with the famous story of Dmitri Mendeleev seeing the periodic table in a dream. There’s very little evidence of that, but there is plenty of evidence that he was struggling to fit the remaining dozens of elements into the second volume of his new chemistry textbook, and he needed a way to group them.

“He was boxed in by a book contract,” Epstein notes, “and that made all the difference.”

UCLA scientists have uncovered a harmful group of immune cells that quietly builds up in aging tissues and in the livers of people with fatty liver disease:

When these cells were removed in mice, inflammation dropped sharply and liver damage was reversed, even though the animals continued eating an unhealthy diet.

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They found that the combination of two proteins, p21 and TREM2, reliably marks macrophages that are truly senescent and no longer functioning properly, while still driving inflammation in nearby tissue.

Using this marker, the researchers observed a dramatic shift with age. In young mice, only about 5% of liver macrophages were senescent. In older mice, that number rose to between 60 and 80%, closely matching the increase in chronic liver inflammation seen with aging.

Aging is not the only factor behind this buildup. The researchers discovered that excess cholesterol can also push macrophages into a senescent state. When healthy macrophages were exposed to high levels of LDL cholesterol in the lab, they stopped dividing, began releasing inflammatory proteins and displayed the same p21-TREM2 signature.

“Physiologically, macrophages can handle cholesterol metabolism,” said Ivan Salladay-Perez, first author of the new study and a graduate student in the Covarrubias lab. “But in a chronic state, it’s pathological. And when you look at fatty liver disease, which is driven by overnutrition and too much cholesterol in the blood, that excess cholesterol appears to be a major driver of the senescent macrophage population.”

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To test whether removing these cells could improve health, the team treated mice with ABT-263, a drug designed to selectively eliminate senescent cells. The effects were dramatic. In mice fed a high-fat, high-cholesterol diet, liver size dropped from about 7% of body weight to a healthier 4-5% percent. Body weight also fell by about 25%, decreasing from roughly 40 grams to around 30 grams.

The treated livers appeared smaller and healthier, with a normal red color, compared to the enlarged, yellowish livers seen in untreated animals.

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Although ABT-263 worked in mice, it is too toxic for widespread use in humans.

Nuclear fusion is generally presented as the sci-fi energy source of the future, providing unlimited, clean energy, but, while listening to the audiobook version Atomic Adventures by James Mahaffey, I was reminded that the astronomical output of the sun comes from its astronomical mass:

At the center of the Sun, fusion power is estimated by models to be about 276.5 watts/m³. Despite its intense temperature, the peak power generating density of the core overall is similar to an active compost heap, and is lower than the power density produced by the metabolism of an adult human. The Sun is much hotter than a compost heap due to the Sun’s enormous volume and limited thermal conductivity.

Researchers at Kyushu University in Japan were seeking complex, expensive methods to extract hydrogen from methanol:

“In what can only be considered incredible serendipity, we found in one of our control experiments mixing methanol, iron ions, and sodium hydroxide, and then irradiating it with UV light, generated a considerable amount of hydrogen gas,” [Takahiro Matsumoto, lead author and Associate Professor at Kyushu University‘s Faculty of Engineering] added.

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The simple iron mixture produced 921 mmol of hydrogen per hour per gram of catalyst. That is a technical way of saying it works just as well as the most expensive, high-tech catalysts.

The process, known as alcohol dehydrogenation, releases the hydrogen stored in compounds such as alcohols, such as methanol.

Ancient DNA reveals pervasive directional selection across West Eurasia, Nature acknowledges:

Ancient DNA has transformed our understanding of population history, but its potential to reveal as much about human evolutionary biology has not been realized because of limited sample sizes and the difficulty of distinguishing sustained rises in allele frequency increasing fitness — directional selection — from shifts due to migrations, population structure, or non-adaptive purifying or stabilizing selection. Here we present a method for detecting directional selection in ancient DNA time-series data that tests for consistent trends in allele frequency change over time, and apply it to 15,836 West Eurasians (10,016 with new data). Previous work has shown that classic hard sweeps driving advantageous mutations to fixation have been rare over the broad span of human evolution. By contrast, in the past ten millennia, we find that many hundreds of alleles have been affected by strong directional selection. We also document one-standard-deviation changes on the scale of modern variation in combinations of alleles that today predict complex traits. This includes decreases in predicted body fat and schizophrenia, and increases in measures of cognitive performance. These effects were measured in industrialized societies, and it remains unclear how these relate to phenotypes that were adaptive in the past. We estimate selection coefficients at 9.7 million variants, enabling study of how Darwinian forces couple to allelic effects and shape the genetic architecture of complex traits.

A Japanese led team, working with international partners at Dalhousie University and University of Tsukuba, has described a microscopic archaeon called Candidatus Sukunaarchaeum mirabile that blurs the edge between living cells and viruses:

The story began when scientists sequenced DNA from marine plankton and noticed genetic fragments that did not match any known organism. Reconstructing those fragments revealed a circular genome of about 238,000 base pairs.

For comparison, the previous record holder among Archaea, Nanoarchaeum equitans, carries roughly 490,000 base pairs, so this newcomer has kept barely half the DNA of an already-minimalist relative.

Almost everything in this tiny genome is devoted to handling genetic information. The microbe keeps the core instructions for copying DNA and building the ribosomes that read it, yet the usual metabolic pathways for harvesting energy or making amino acids and vitamins are missing. It seems unable to produce most of what it needs and instead leans on its host for supplies.

The authors of the study describe it as a “cellular entity retaining only its replicative core”, a phrase that shows how close it comes to the line between a cell and something simpler.

Even so, Sukunaarchaeum is not a virus. It still builds its own ribosomes and messenger RNA instead of borrowing all of that machinery from its host. At the same time, its tiny genome and single-minded focus on making more copies of itself make its lifestyle look strikingly virus-like.

A report in Science notes that its DNA is “focused almost entirely on replication” and suggests it may sit on an evolutionary path between more conventional cells and fully-viral strategies.

Spider dragline silk is stronger than steel and tougher than Kevlar:

This type of silk is created inside a spider’s silk gland, where the proteins are kept in a dense liquid form called “silk dope.” As the spider spins its web, this liquid is transformed into solid fibers.

Although researchers have known that the proteins first gather into liquid-like droplets before turning into fibers, the precise molecular steps that connect this phase change to the final structure of the silk have remained a mystery until now.

The interdisciplinary team of chemists, biophysicists, and engineers used a combination of advanced computational and experimental tools — including molecular dynamics simulations, AlphaFold3 structural modeling, and nuclear magnetic resonance spectroscopy — to demonstrate that the amino acids arginine and tyrosine interact to trigger the initial clustering of the proteins.

Crucially, these same interactions persist as the silk fiber forms, helping to create the complex nanostructure responsible for its exceptional mechanical performance.

“This study provides an atomistic-level explanation of how disordered proteins assemble into highly ordered, high-performance structures,” added Lorenz.

Gregory Holland, SDSU professor of physical and analytical chemistry, who led the US side of the research, said one of the most surprising outcomes was how chemically sophisticated the process turned out to be.

“What surprised us was that silk — something we usually think of as a beautifully simple natural fiber — actually relies on a very sophisticated molecular trick,” Holland said. “The same kinds of interactions we discovered are used in neurotransmitter receptors and hormone signaling.”

He suggested the findings could therefore extend into human health research.

“The way silk proteins undergo phase separation and then form ?-sheet–rich structures mirrors mechanisms we see in neurodegenerative diseases such as Alzheimer’s,” Holland said. “Studying silk gives us a clean, evolutionarily-optimized system to understand how phase separation and ?-sheet formation can be controlled.”

Morgan Worthy explains (in I Have Known the Eyes Already) some independent research done at Pennsylvania State University by people he had never met:

They tested the reactivity hypothesis with human subjects by studying eye color and reaction time in a laboratory setting. They first found that simple reaction time is not related to skin color, but it is related to eye color. They found that dark-eyed blacks and dark-eyed whites have faster reaction times than do light-eyed whites. They then focused just on comparing dark-eyed Caucasians to light-eyed Caucasians on how quickly they could react to a visual or auditory stimulus. They did a number of well-controlled laboratory studies, and then did a meta-analysis of all those studies. Read this quotation which reports the results:

Thus, the findings across studies have consistently shown that dark-eyed subjects have shorter pre-motor time and simple RT latencies than light-eyed subjects. Considering that Worthy’s hypothesis has been experimentally tested seven times with seven different samples … a combined probability value would more accurately reflect the reliability of the eye color phenomenon. Using a z-transformation procedure … a z value was obtained that could not occur by chance any more than one time in 10 million. Worthy’s hypothesis, therefore, reliably predicts RT differences between eye color groups from one study to the next (Hale, et al. 1980, p. 61).

I can live with a probability of one in ten million that my hypothesis is wrong. I wanted you to read that in order to make it clear that the association between dark eyes and quick reactions is very well established in humans.

He concedes that the differences not large in absolute terms:

I had reached the same conclusion by studying performance records of professional and college athletes. Even small differences in the general population can matter when looking at a heavily selected group like professional athletes.