Chance and Necessity

If you free-associate the word “chance,” you may arrive at “I’ll take my chances” before potentially arriving at Thomas Bayes’ “Doctrine of Chances”. Jacques Monod was an early explorer of the collision of probability and chance in biology.

THE PRINCE OF CHANCE

Jacques Monod grew up just down the coast from Monte Carlo in Cannes, France, another town famous for its casinos and, later, its film festival. Graced with movie star looks—one prominent French journalist described him as a “prince” who resembled Hollywood icon Henry Fonda, as well as considerable musical talent, and an exceptional intellect, Monod struggled to decide on a career path through his twenties. After distinguishing himself in the French Resistance, Monod rose to fame not as an actor or musician, but as a brilliant biologist. He shared the 1965 Nobel Prize in Physiology or Medicine for seminal discoveries about how genes work.

A pioneer in the field of molecular biology, Monod was privy to the blizzard of discoveries in the 1950s and early 1960s about the molecules that determined the characteristics of living things—what Monod and others dubbed “the secrets of life.” He kept close company with a relatively small international community of leading researchers. For example, when James Watson and Francis Crick cracked the structure of DNA (deoxyribonucleic acid) in 1953, Monod was one of the first with whom Watson shared the breakthrough.

But as a Frenchman steeped in his culture’s deep philosophical traditions, Monod was interested in science for more than just science’s sake. After the war, Monod befriended France’s leading philosopher-writer Albert Camus, and the two men pondered questions of human existence in Left Bank cafés. Monod felt that the public misunderstood the principal purpose of science as being the creation of technology. Rather, Monod believed technology was merely a by-product. He said, “the most important results of science have been to change the relationship of man to the universe, or the way he sees himself in the universe”—a relationship of equally intense interest to his friend Camus.

Monod thought that there were profound philosophical implications of the new molecular biology, particularly in the realm of heredity, which had gone largely unnoted in the broader culture. Several years after his Nobel Prize and Camus’ untimely death, he decided to write a book to try to bring the meaning of modern biology to laypersons.

“[T]he ‘secret of life’…has been laid bare,” he wrote.

“This, a considerable event, ought certainly to make itself strongly felt in contemporary thinking.”

Monod used several chapters to describe the insights that had very recently emerged from the study of DNA and the deciphering of the genetic code. He understood this knowledge would be unfamiliar to most readers, so he included an appendix with chemical structures of proteins and nucleic acids, and a primer on how the genetic code worked.

In a matter-of-fact style, he explained genetic mutations as accidental alterations—substitutions, additions, deletions, or rearrangements—in the text of DNA, in the sequence of the long strings of chemical bases (ACTTGATAA, etc.) that make up genes.

Then, almost without warning, he turned to the broader implications of how mutations arise in DNA. It is worth quoting him at length for after 111 pages of background, he delivered one of the most powerful ideas in five centuries of science (all italics are original):

“We call these events accidental; we say they are random occurrences. And since they constitute the only possible source of modifications in the genetic text, itself the sole repository of the organism’s hereditary structure, it necessarily follows that chance alone is at the source of every innovation, of all creation in the biosphere.

“Pure chance, absolutely free but blind, at the very root of the stupendous edifice of evolution: this central concept of modern biology is no longer one among other possible or even conceivable hypotheses. It is today the sole conceivable hypothesis, the only one that squares with observed and tested fact. And nothing warrants the supposition—or the hope—that on this score our position is likely ever to be revised.

“There is no scientific concept, in any of the sciences, more destructive of anthropocentrism than this one.”

In essence, heretofore obscure discoveries in biochemistry and genetics (largely studied at that time in simple bacteria) had upended two millennia of philosophy and religion that put humans at the center or apex of creation. “Man was the product of an incalculable number of fortuitous events,” Monod wrote. “The result of a huge Monte Carlo game, where our number eventually did come out, when it might not well have appeared.”

Le Hasard et la nécessité (Chance and Necessity) appeared in France in October 1970. It was a fairly technical book with several chapters on philosophy and genetics, and those appendices full of chemical diagrams. A first-time author, Monod did not know what reactions to expect.

The merde hit the fan.

The book received dozens of reviews across France and quickly became a bestseller—second only to the French translation of Erich Segal’s Love Story (this was France after all. After it was translated into English, reviews and interviews with Monod were featured in several of the most prominent British and American newspapers and magazines.

Many commentators immediately recognized the threat chance posed to traditional ideas of humanity’s origins and purpose. To Arthur Peacocke, a British biochemist turned prominent theologian, Monod had put forth “one of the strongest and most influential attacks of the century on theism.” A flurry of articles and books appeared with titles such as Anti-Chance: A Reply to Monod’s Chance and Necessity, Beyond Chance and Necessity, and God, Chance, and Necessity. Monod was invited to debate philosophers and theologians both in France and abroad, on television, radio, and in print.

American Calvinist theologian and pastor R.C. Sproul summed up the high stakes posed by chance in the first page of his book Not A Chance:

“It is not necessary for chance to rule in order to supplant God. Indeed, chance requires little authority at all if it is to depose God; all it needs to do the job is to exist. The mere existence of chance is enough to rip God from his cosmic throne. Chance does not need to rule; it does not need to be sovereign. If it exists as a mere impotent, humble servant, it leaves God not only out of date, but out of a job.” More than two hundred pages later, Sproul concluded:

“Chance as a real force is a myth. It has no basis in reality and no place in scientific inquiry. For science and philosophy to continue to advance in knowledge, chance must be demythologized once and for all.”

Sproul and other critics argued that what scientists perceived as chance merely reflected a lack of knowledge of true causes. Perhaps that was the expression of hope to which Monod alluded—the hope that as scientists learned more, our position on the role of chance would somehow be revised.

A SECOND CHANCE

The ensuing fifty years have not played out as either Monod or his detractors hoped. The Frenchman thought that the new insights from molecular biology should be a turning point for modern society-away from traditional beliefs about causes in the natural world toward one that embraced randomness and our chance existence.

Ha! Fat chance. The excitement and fuss stirred by Chance and Necessity simmered down, and Monod passed away a few years later. Surveys reveal that the majority of Americans, for example, continue to believe that everything on earth happens for His reasons.

But Monod’s critics should take no comfort. The province of chance in the biosphere and human life has been revised, although not at all in the scope or direction that they hoped.

The domain of chance has expanded into realms neither Monod nor anyone else imagined.

As we have learned much more about the history and workings of the planet, we have been startled to discover how the course of life has been buffeted by a variety of cosmological and geological accidents—without which we would not be here. As we have explored human history, we have seen how pandemics, droughts, and other civilization-changing episodes have been triggered by random, singular events in nature that easily might not have happened. And as we have probed human biology and the factors that impact our individual lives, we have caught chance red-handed, reigning over the often-thin line between life and death.

This book tells the stories that Monod could not—of astonishing discoveries from the planetary to the molecular scale, from great upheavals across the globe to the machinery of chance that operates within every cell of every creature, including ourselves. And while these discoveries vaporize the comforts of anthropocentrism, the story of chance, I hope you will come to agree, is much more than highfalutin philosophy or the refutation of theologians’ wishful thinking.

I hope that you are awed—awed by the power and the drama of asteroids slamming into the planet, of continents colliding, and of the rapid rising and falling of ice and oceans; awed by the realization that we live on (and are at the mercy of a planet that is far more unstable than our short lives perceive; awed by the knowledge of how random chance is at the source of all of the beautiful and wondrous creatures with whom we share the planet; awed by the unique invisible accidents that made each one of us; and awed by the fact that we humans, recent descendants of bands of hunter-gatherers who persevered through a period of exceptional chaos, have in just the last fifty years or so, figured all of this out!

My goal here is to be comprehensible without being comprehensive. It is almost trivial to claim that the world is the way it is or that we are here because of a long chain of chance, albeit fortunate, events. The explanatory power I seek comes from specificity. It is essential to unpack some of those events to appreciate how they shape the direction of life. The layout of the book follows a simple three-part logic. I’ll begin with inanimate, external chance events that have shaped the conditions for life (Part One, “Stuff Happens”), and then turn to the internal random mechanism within every creature that generates the adaptations to those conditions (Part Two, “A World of Mistakes”). Then, I bring the story to the personal level (Part Three, “23 and You”) and how chance impacts our natural lives, as well as our deaths. Our chance-driven existence shatters long-held beliefs about humanity’s place and raises challenging questions about the meaning and purpose of our lives. In the Afterword, I’ll offer some possible replies with the help of some special guests.

This is a relatively small book for a really big idea. Science has given us a handful of really big ideas over the centuries, but they have been received in funny ways. Darwin had a huge idea that was very simple to understand, and even though the evidence is massive and everywhere, many refuse to believe it. Einstein had a brand new idea, and even though few understand it or the evidence for it, most everyone seems to believe it. Monod had a great idea, but these days most people (other than scholars) have not heard of it, or of him.

My greatest hope, then, is that this short book might be chance’s second chance.

Sean B. Carroll, A Series of Fortunate Events: Chance and the Making of the Planet, Life, and You, Princeton University Press, 2020, pp. 6-12.

Modern biology as described by Monod pushes the linkage of probability, randomness and chance to the center. At the time, this was a very radical and profound way of looking at biology. If we combine Monod’s biology with theoretical physics like Lawrence Krauss’ A Universe from Nothing: Why There Is Something Rather than Nothing, we realize that accidentality is the bedrock on which our knowledge of the universe is built.

World-Watching: Science First Release, 10 July 2025

[from Science]

Accepted papers posted online prior to journal publication.

NASA Earth Science Division provides key data

by Dylan B. Millet, Belay B. Demoz, et al.

In May, the US administration proposed budget cuts to NASA, including a more than 50% decrease in funding for the agency’s Earth Science Division (ESD), the mission of which is to gather knowledge about Earth through space-based observation and other tools. The budget cuts proposed for ESD would cancel crucial satellites that observe Earth and its atmosphere, gut US science and engineering expertise, and potentially lead to the closure of NASA research centers. As former members of the recently dissolved NASA Earth Science Advisory Committee, an all-volunteer, independent body chartered to advise ESD, we warn that these actions would come at a profound cost to US society and scientific leadership.

[read more]

Spin-filter tunneling detection of antiferromagnetic resonance with electrically tunable damping

by Thow Min Jerald Cham, Daniel G. Chica, et al.

Antiferromagnetic spintronics offers the potential for higher-frequency operations and improved insensitivity to magnetic fields compared to ferromagnetic spintronics. However, previous electrical techniques to detect antiferromagnetic dynamics have utilized large, millimeter-scale bulk crystals. Here we demonstrate direct electrical detection of antiferromagnetic resonance in structures on the few-micrometer scale using spin-filter tunneling in PtTe2/bilayer CrSBr/graphite junctions in which the tunnel barrier is the van der Waals antiferromagnet CrSBr. This sample geometry allows not only efficient detection, but also electrical control of the antiferromagnetic resonance through spin-orbit torque from the PtTe2 electrode. The ability to efficiently detect and control antiferromagnetic resonance enables detailed studies of the physics governing these high-frequency dynamics.

[read more]

Scalable emulation of protein equilibrium ensembles with generative deep learning

by Sarah Lewis, Tim Hempel, et al.

Following the sequence and structure revolutions, predicting functionally relevant protein structure changes at scale remains an outstanding challenge. We introduce BioEmu, a deep learning system that emulates protein equilibrium ensembles by generating thousands of statistically independent structures per hour on a single GPU. BioEmu integrates over 200 milliseconds of molecular dynamics (MD) simulations, static structures and experimental protein stabilities using novel training algorithms. It captures diverse functional motions—including cryptic pocket formation, local unfolding, and domain rearrangements—and predicts relative free energies with 1 kcal/mol accuracy compared to millisecond-scale MD and experimental data. BioEmu provides mechanistic insights by jointly modeling structural ensembles and thermodynamic properties. This approach amortizes the cost of MD and experimental data generation, demonstrating a scalable path toward understanding and designing protein function.

[read more]

Negative capacitance overcomes Schottky-gate limits in GaN high-electron-mobility transistors

by Asir Intisar Khan, Jeong-Kyu Kim, et al.

For high-electron-mobility transistors based on two-dimensional electron gas (2DEG) within a quantum well, such as those based on AlGaN/GaN heterostructure, a Schottky-gate is used to maximize the amount of charge that can be induced and thereby the current that can be achieved. However, the Schottky-gate also leads to very high leakage current through the gate electrode. Adding a conventional dielectric layer between the nitride layers and gate metal can reduce leakage; but this comes at the price of a reduced drain current. Here, we used a ferroic HfO2 – ZrO2 bilayer as the gate dielectric and achieved a simultaneous increase in the ON current and decrease in the leakage current, a combination otherwise not attainable with conventional dielectrics. This approach surpasses the conventional limits of Schottky GaN transistors and provides a new pathway to improve performance in transistors based on 2DEG.

[read more]

Coronavirus Update: Fall Boosters Could Have Bits of Omicron

[from ScienceNews Coronavirus Update, by Erin Garcia de Jesús]

For all the coronavirus variants that have thrown pandemic curve balls—including alpha, beta, gamma, delta—COVID-19 vaccines have stayed the same. That could change this fall.

Yesterday, an advisory committee to the U.S. Food and Drug Administration met to discuss whether vaccine developers should update their jabs to include a portion of the omicron variant—the version of the coronavirus that currently dominates the globe. The verdict: The omicron variant is different enough that it’s time to change the vaccines. Exactly how is up in the air; the FDA still has to weigh in and decide what versions of the coronavirus will be in the shot.

“This doesn’t mean that we are saying that there will be boosters recommended for everyone in the fall,” Amanda Cohn, chief medical officer for vaccine policy at the U.S. Centers for Disease Control and Prevention said at the June 28 advisory meeting. “But my belief is that this gives us the right vaccine for preparation for boosters in the fall.”

The decision to update COVID-19 vaccines didn’t come out of nowhere. In the two-plus years that the coronavirus has been spreading around the world, it has had a few “updates” of its own—mutating some of its proteins that allow the virus to more effectively infect our cells or hide from our immune systems.

Vaccine developers had previously crafted vaccines to tackle the beta variant that was first identified in South Africa in late 2020. Those were scrapped after studies showed that current vaccines remained effective.

The current vaccines gave our immune systems the tools to recognize variants such as beta and alpha, which each had a handful of changes from the original SARS-CoV-2 virus that sparked the pandemic. But the omicron variant is a slipperier foe. Lots more viral mutations combined with our own waning immunity mean that omicron can gain a foothold in the body. And vaccine protection isn’t as good as it once was at fending off COVID-19 symptoms.

The shots still largely protect people from developing severe symptoms, but there has been an uptick in hospitalizations and deaths among older age groups, Heather Scobie, deputy team lead of the CDC’s Surveillance and Analytics Epidemiology Task Force said at the meeting. And while it’s impossible to predict the future, we could be in for a tough fall and winter, epidemiologist Justin Lessler of the University of North Carolina at Chapel Hill said at the meeting. From March 2022 to March 2023, simulations project that deaths from COVID-19 in the United States might number in the tens to hundreds of thousands.

A switch to omicron-containing jabs may give people an extra layer of protection for the upcoming winter. Pfizer–BioNTech presented data at the meeting showing that updated versions of its mRNA shot gave clinical trial participants a boost of antibodies that recognize omicron. One version included omicron alone, while the other is a twofer, or bivalent, jab that mixes the original formulation with omicron. Moderna’s bivalent shot boosted antibodies too. Novavax, which developed a protein-based vaccine that the FDA is still mulling whether to authorize for emergency use, doesn’t have an omicron-based vaccine yet, though the company said its original shot gives people broad protection, generating antibodies that probably will recognize omicron.

Pfizer and Moderna both updated their vaccines using a version of omicron called BA.1, which was the dominant variant in the United States in December and January. But BA.1 has siblings and has already been outcompeted by some of them.

Since omicron first appeared late last year, “we’ve seen a relatively troubling, rapid evolution of SARS-CoV-2,” Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research in Silver Spring, Maryland, said at the advisory meeting.

Now, omicron subvariants BA.2, BA.2.12.1, BA.4 and BA.5 are the dominant versions in the United States and other countries. The CDC estimates that roughly half of new U.S. infections the week ending June 25 were caused by either BA.4 or BA.5. By the time the fall rolls around, yet another new version of omicron—or a different variant entirely—may join their ranks. The big question is which of these subvariants to include in the vaccines to give people the best protection possible.

BA.1, the version already in the updated vaccines, may be the right choice, virologist Kanta Subbarao said at the FDA meeting. An advisory committee to the World Health Organization, which Subbarao chairs, recommended on June 17 that vaccines may need to be tweaked to include omicron, likely BA.1. “We’re not trying to match [what variants] may circulate,” Subbarao said. Instead, the goal is to make sure that the immune system is as prepared as possible to recognize a wide variety of variants, not just specific ones. The hope is that the broader the immune response, the better our bodies will be at fighting the virus off even as it evolves.

The variant that is farthest removed from the original virus is probably the best candidate to accomplish that goal, said Subbarao, who is director of the WHO’s Collaborating Center for Reference and Research on Influenza at the Doherty Institute in Melbourne, Australia. Computational analyses of how antibodies recognize different versions of the coronavirus suggest that BA.1 is probably the original coronavirus variant’s most distant sibling, she said.

Some members of the FDA advisory committee disagreed with choosing BA.1, instead saying that they’d prefer vaccines that include a portion of BA.4 or BA.5. With BA.1 largely gone, it may be better to follow the proverbial hockey puck where it’s going rather than where it’s been, said Bruce Gellin, chief of Global Public Health Strategy with the Rockefeller Foundation in Washington, D.C. Plus, BA.4 and BA.5 are also vastly different from the original variant. Both BA.4 and BA.5 have identical spike proteins, which the virus uses to break into cells and the vaccines use to teach our bodies to recognize an infection. So when it comes to making vaccines, the two are somewhat interchangeable.

There are some real-world data suggesting that current vaccines offer the least amount of protection from BA.4 and BA.5 compared with other omicron subvariants, Marks said. Pfizer also presented data showing results from a test in mice of a bivalent jab with the original coronavirus strain plus BA.4/BA.5. The shot sparked a broad immune response that boosted antibodies against four omicron subvariants. It’s unclear what that means for people.

Not everyone on the FDA advisory committee agreed that an update now is necessary—two members voted against it. Pediatrician Henry Bernstein of Zucker School of Medicine at Hofstra/Northwell in Uniondale, N.Y., noted that the current vaccines are still effective against severe disease and that there aren’t enough data to show that any changes would boost vaccine effectiveness. Pediatric infectious disease specialist Paul Offit of Children’s Hospital of Philadelphia said that he agrees that vaccines should help people broaden their immune responses, but he’s not yet convinced omicron is the right variant for it.

Plenty of other open questions remain too. The FDA could authorize either a vaccine that contains omicron alone or a bivalent shot, although some data hinted that a bivalent dose might spark immunity that could be more durable. Pfizer and Moderna tested their updated shots in adults. It’s unclear what the results mean for kids. Also unknown is whether people who have never been vaccinated against COVID-19 could eventually start with such an omicron-based vaccine instead of the original two doses.

Maybe researchers will get some answers before boosters start in the fall. But health agencies need to make decisions now so vaccine developers have a chance to make the shots in the first place. Unfortunately, we’re always lagging behind the virus, said pediatrician Hayley Gans of Stanford University. “We can’t always wait for the data to catch up.”

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