Unlike DNA, RNA Has “Catalytic Power”

(p. 8) In the early 1980s, when I was much younger and most of the promise of RNA was still unimagined, I set up my lab at the University of Colorado, Boulder. After two years of false leads and frustration, my research group discovered that the RNA we’d been studying had catalytic power. This means that the RNA could cut and join biochemical bonds all by itself — the sort of activity that had been thought to be the sole purview of protein enzymes. This gave us a tantalizing glimpse at our deepest origins: If RNA could both hold information and orchestrate the assembly of molecules, it was very likely that the first living things to spring out of the primordial ooze were RNA-based organisms.

. . .

RNA discoveries have led to new therapies, such as the use of antisense RNA to help treat children afflicted with the devastating disease spinal muscular atrophy. The mRNA vaccines, which saved millions of lives during the Covid pandemic, are being reformulated to attack other diseases, including some cancers. RNA research may also be helping us rewrite the future; the genetic scissors that give CRISPR its breathtaking power to edit genes are guided to their sites of action by RNAs.

Although most scientists now agree on RNA’s bright promise, we are still only beginning to unlock its potential. Consider, for instance, that some 75 percent of the human genome consists of dark matter that is copied into RNAs of unknown function. While some researchers have dismissed this dark matter as junk or noise, I expect it will be the source of even more exciting breakthroughs.

For the full essay see:

Thomas Cech. “Move Aside, DNA. RNA Has Arrived.” The New York Times, SundayOpinion Section (Sunday, June 2, 2024): 8.

(Note: ellipses added.)

(Note: the online version of the essay has the date May 29, 2024, and has the title “The Long-Overlooked Molecule That Will Define a Generation of Science.”)

The essay quoted above was adapted from the author’s book:

Cech, Thomas R. The Catalyst: RNA and the Quest to Unlock Life’s Deepest Secrets. New York: W. W. Norton & Company, 2024.

Subpoena Emails Between Wuhan Lab and U.S. Partners to Illuminate Origin of Covid

The passages quoted below are a very small part of a much longer essay that took up the space of a full page and a half of the SundayOpinion section of The New York Times.

(p. 6) On Monday [June 3, 2024], Dr. Anthony Fauci returned to the halls of Congress and testified before the House subcommittee investigating the Covid-19 pandemic. He was questioned about several topics related to the government’s handling of Covid-19, including how the National Institute of Allergy and Infectious Diseases, which he directed until retiring in 2022, supported risky virus work at a Chinese institute whose research may have caused the pandemic.

For more than four years, reflexive partisan politics have derailed the search for the truth about a catastrophe that has touched us all. It has been estimated that at least 25 million people around the world have died because of Covid-19, with over a million of those deaths in the United States.

Although how the pandemic started has been hotly debated, a growing volume of evidence — gleaned from public records released under the Freedom of Information Act, digital sleuthing through online databases, scientific papers analyzing the virus and its spread, and leaks from within the U.S. government — suggests that the pandemic most likely occurred because a virus escaped from a research lab in Wuhan, China. If so, it would be the most costly accident in the history of science.

. . .

(p. 7) The pandemic could have been caused by any of hundreds of virus species, at any of tens of thousands of wildlife markets, in any of thousands of cities, and in any year. But it was a SARS-like coronavirus with a unique furin cleavage site that emerged in Wuhan, less than two years after scientists, sometimes working under inadequate biosafety conditions, proposed collecting and creating viruses of that same design.

While several natural spillover scenarios remain plausible, and we still don’t know enough about the full extent of virus research conducted at the Wuhan institute by Dr. Shi’s team and other researchers, a laboratory accident is the most parsimonious explanation of how the pandemic began.

Given what we now know, investigators should follow their strongest leads and subpoena all exchanges between the Wuhan scientists and their international partners, including unpublished research proposals, manuscripts, data and commercial orders. In particular, exchanges from 2018 and 2019 — the critical two years before the emergence of Covid-19 — are very likely to be illuminating (and require no cooperation from the Chinese government to acquire), yet they remain beyond the public’s view more than four years after the pandemic began.

Whether the pandemic started on a lab bench or in a market stall, it is undeniable that U.S. federal funding helped to build an unprecedented collection of SARS-like viruses at the Wuhan institute, as well as contributing to research that enhanced them.

. . .

A thorough investigation by the U.S. government could unearth more evidence while spurring whistleblowers to find their courage and seek their moment of opportunity. It would also show the world that U.S. leaders and scientists are not afraid of what the truth behind the pandemic may be.

For the full essay see:

Alina Chan. “Why Covid Probably Started in a Lab.” The New York Times, SundayOpinion Section (Sunday, June 9, 2024): 6-7.

(Note: ellipses, and bracketed date, added.)

(Note: the online version of the essay has the date June 3, 2024, and has the title “Why the Pandemic Probably Started in a Lab, in 5 Key Points.”)

The essay quoted above summarizes and updates her co-authored book:

Chan, Alina, and Matt Ridley. Viral: The Search for the Origin of Covid-19. New York: Harper, 2021.

Gates’s TerraPower Breaks Ground on Small Nuclear Reactor

(p. A16) Outside a small coal town in southwest Wyoming, a multibillion-dollar effort to build the first in a new generation of American nuclear power plants is underway.

Workers began construction on Tuesday on a novel type of nuclear reactor meant to be smaller and cheaper than the hulking reactors of old and designed to produce electricity without the carbon dioxide that is rapidly heating the planet.

The reactor being built by TerraPower, a start-up, won’t be finished until 2030 at the earliest and faces daunting obstacles. The Nuclear Regulatory Commission hasn’t yet approved the design, and the company will have to overcome the inevitable delays and cost overruns that have doomed countless nuclear projects before.

What TerraPower does have, however, is an influential and deep-pocketed founder. Bill Gates, currently ranked as the seventh-richest person in the world, has poured more than $1 billion of his fortune into TerraPower, an amount that he expects to increase.

“If you care about climate, there are many, many locations around the world where nuclear has got to work,” Mr. Gates said during an interview near the project site on Monday. “I’m not involved in TerraPower to make more money. I’m involved in TerraPower because we need to build a lot of these reactors.”

Mr. Gates, the former head of Microsoft, said he believed the best way to solve climate change was through innovations that make clean energy competitive with fossil fuels, a philosophy he described in his 2021 book, “How to Avoid a Climate Disaster.”

Nationwide, nuclear power is seeing a resurgence of interest, with several start-ups jockeying to build a wave of smaller reactors and the Biden administration offering hefty tax credits for new plants.

. . .

In March [2024], TerraPower submitted a 3,300-page application to the Nuclear Regulatory Commission for a permit to build the reactor, but that will take at least two years to review. The company has to persuade regulators that its sodium-cooled reactor doesn’t need many of the costly safeguards required for traditional light-water reactors.

“That’s going to be challenging,” said Adam Stein, director of nuclear innovation at the Breakthrough Institute, a pro-nuclear research organization.

TerraPower’s plant is designed so that major components, like the steam turbines that generate electricity and the molten salt battery, are physically separate from the reactor, where fission occurs. The company says those parts don’t require regulatory approval and can begin construction sooner.

For the full story see:

Brad Plumer and Benjamin Rasmussen. “Climate-Minded Billionaire Makes a Bet on Nuclear Power.” The New York Times (Thursday, June 13, 2024): A16.

(Note: ellipsis, and bracketed year, added.)

(Note: the online version of the story has the date June 11, 2024, and has the title “Nuclear Power Is Hard. A Climate-Minded Billionaire Wants to Make It Easier.”)

Gates’s 2021 book, mentioned above, is:

Gates, Bill. How to Avoid a Climate Disaster: The Solutions We Have and the Breakthroughs We Need. New York: Knopf, 2021.

People Feel “Stuck” in Lives Lacking Freedom and Hope

People need more control over their lives to feel hopeful for a free flourishing future. Fewer government regulations and more innovative firm managers could allow more of us to be “unstuck,” working on challenging but doable projects that improve the world and allow fulfilment. (I discuss these issues in more depth in Openness to Creative Destruction.)

(p. 9) The hallways on the television shows I watch have been driving me mad. On one sci-fi show after another I’ve encountered long, zigzagging, labyrinthine passageways marked by impenetrable doors and countless blind alleys — places that have no obvious beginning or end. The characters are holed up in bunkers (“Fallout”), consigned to stark subterranean offices (“Severance”), locked in Escher-like prisons (“Andor”) or living in spiraling mile-deep underground complexes (“Silo”). Escape is unimaginable, endless repetition is crushingly routine and people are trapped in a world marked by inertia and hopelessness.

The resonance is chilling: Television has managed to uncannily capture the way life feels right now.

We’re all stuck.

What’s being portrayed is not exactly a dystopia. It’s certainly not a utopia. It’s something different: a stucktopia. These fictional worlds are controlled by an overclass, and the folks battling in the mire are underdogs — mechanics, office drones, pilots and young brides. Yet they’re also complicit, to varying degrees, in the machinery that keeps them stranded. Once they realize this, they strive to discard their sense of futility — the least helpful of emotions — and try to find the will to enact change.

. . .

We’re not stuck in our circumstance. We’re stuck in the ways of living that perpetuate it.

If enough of us give up the sense that things are inevitable — that we’re stuck — it’s possible that we can course-correct humanity, or at least nudge it toward a hopeful path.

There’s another more realistic option that offers a thrill and reward of its own. If we don’t let the stucktopia keep its hold on us, if we rebuke it, maybe we shift ourselves ever so slightly toward optimism, and give the system whatever small hell we can.

For the full commentary see:

Hillary Kelly. “It’s Not Your Imagination. We’re All Stuck.” The New York Times, SundayOpinion Section (Sunday, July 7, 2024): 9.

(Note: ellipsis added.)

(Note: the online version of the commentary has the date July 6, 2024, and has the title “Welcome to Stucktopia.”)

Monarch Butterflies Thrive on Poisonous Milkweed

(p. D5) The caterpillar of the monarch butterfly eats only milkweed, a poisonous plant that should kill it. The caterpillars thrive on the plant, even storing its toxins in their bodies as a defense against hungry birds.

For decades, scientists have marveled at this adaptation. On Thursday [Oct. 3, 2019 [sic]), a team of researchers announced they had pinpointed the key evolutionary steps that led to it.

Only three genetic mutations were necessary to turn the butterflies from vulnerable to resistant, the researchers reported in the journal Nature. They were able to introduce these mutations into fruit flies, and suddenly they were able to eat milkweed, too.

Biologists hailed it as a tour-de-force that harnessed gene-editing technology to unscramble a series of mutations evolving in some species and then test them in yet another.

“The gold standard is to directly test mutations in the organism,” said Joseph W. Thornton, an evolutionary biologist at the University of Chicago. The new study “finally elevates our standards.”

For the full story see:

Carl Zimmer. “MATTER; How Monarch Butterflies Evolved to Eat Poison.” The New York Times (Tuesday, October 8, 2019 [sic]): D5.

(Note: bracketed date added.)

(Note: the online version of the story was updated Oct. 3, 2019 [sic], and has the title “MATTER; These Butterflies Evolved to Eat Poison. How Could That Have Happened?”)

The article in Nature mentioned above is:

Karageorgi, Marianthi, Simon C. Groen, Fidan Sumbul, Julianne N. Pelaez, Kirsten I. Verster, Jessica M. Aguilar, Amy P. Hastings, Susan L. Bernstein, Teruyuki Matsunaga, Michael Astourian, Geno Guerra, Felix Rico, Susanne Dobler, Anurag A. Agrawal, and Noah K. Whiteman. “Genome Editing Retraces the Evolution of Toxin Resistance in the Monarch Butterfly.” Nature 574, no. 7778 (Oct. 2019): 409–12.

The “corresponding author” (often considered the primary author) of the article is Noah K. Whiteman, who has published a book that extensively discusses cases such as the monarch butterfly, where a creature has evolved the ability to consume or make use of chemicals that are poisonous to other creatures:

Whiteman, Noah. Most Delicious Poison: The Story of Nature’s Toxins―from Spices to Vices. New York: Little, Brown Spark, 2023.

Tax Universities to Offset Their Negative Externalities?

(p. A11) What can we do about the corruption of American higher education? Milton Friedman had an idea 20 years ago: Tax the schools rather than subsidize them. That reflected a change of heart. In “Capitalism and Freedom” (1960), he argued that college education had enough “positive externalities” to justify subsidies. But when I was researching a book in 2003, I emailed him (then 91) and asked if he still believed that.

He replied: “I have not changed my view that higher education has some positive externality, but I have become much more aware that it also has negative externalities. I am much more dubious than I was . . . that there is any justification at all for government subsidy of higher education. The spread of PC”—political correctness—“would seem to be a very strong negative externality, and certainly the 1960s student demonstrations were negative externalities. . . . A full analysis along those lines might lead you to conclude that higher education should be taxed to offset its negative externalities.”

For the full commentary, see:

Richard Vedder. “Harvard Should Pay Its Fair Share.” The Wall Street Journal (Saturday, Dec. 23, 2023): A11.

(Note: ellipses in original.)

(Note: the online version of the commentary has the date December 22, 2023, and has the same title as the print version.)

Friedman’s book mentioned above is:

Friedman, Milton. Capitalism and Freedom. Chicago: The University of Chicago Press, 1962.

Dick Nunis Was Resolved That Walt Disney’s “Dreams Would Live On”

(p. C3) When Disneyland opened in 1955, it was, in many ways, a disaster: There were rides out of service, restaurants that ran out of food, soft asphalt that consumed the heels of women’s shoes—all of it broadcast on national television.

Little wonder, then, that there was trepidation as the Walt Disney company approached the 1971 opening of the far more ambitious Walt Disney World, especially as the word spread that it might not open in time. So, when Dick Nunis, the head of operations at the parks in Anaheim and Orlando, took control of the project, he was given carte blanche to do whatever it took to open the gates on Oct. 1.

. . .

Nunis, who died Dec. 13 [2023] at the age of 91, fired contractors who got in the way, held meetings at 5 a.m. and put signs up all over the property that said the park would open on Oct. 1. He made sure construction workers knew that their families were invited to the park a week before opening. He flew palm trees in on helicopters the night before the gates opened.

Not only did he understand the logistics of what it would take to hire thousands of employees, motivate construction workers and oversee the myriad details of opening a resort, he had worked closely with Walt Disney for a decade and knew how the company’s founder and creative visionary—who had been dead for almost five years—would have wanted it done.

“He understood the culture that Walt wanted there,” said Sandy Quinn, who started as marketing director of the resort years before it opened. “Walt didn’t want employees, he wanted a cast. He didn’t want customers, he wanted guests. They weren’t uniforms, they were costumes. And it was a mindset.”

Nunis didn’t just get the Magic Kingdom and the first phase of Disney World open as planned. He spent his 44-year career at Disney opening and overseeing parks around the world, and acting as a steward of Walt Disney’s philosophies as the company grew in the decades after his death in 1966.

. . .

“I had no idea at the time, but in those early years with Walt, he was looking for someone he could mentor by nurturing, challenging, and testing, to ensure that his ideals and those dreams would live on,” Nunis wrote in his memoir. “He was looking for an ‘apprentice.’ As that apprentice, my role and my life expanded beyond what I had ever imagined.”

. . .

Mary Nunis said that although the couple visited Walt Disney World on occasion after he retired, he didn’t walk the park as he had for the more than 40 years he was with the company, which she believed was because he wouldn’t be able to handle seeing something he wanted to change and not be able to change it. But he remained fiercely loyal to Walt Disney and his ideas.

“He just loved Walt Disney,” Mary Nunis said, “and knew that dream was what he wanted to try to maintain.”

For the full obituary, see:

Chris Kornelis. “Dick Nunis Got the Magic Kingdom Open.” The Wall Street Journal (Saturday, Jan. 6, 2024): A10.

(Note: ellipses, and bracketed year, added.)

(Note: the online version of the obituary has the date January 5, 2024, and has the title “Dick Nunis, Walt Disney’s ‘Apprentice’ Who Got the Magic Kingdom Open, Dies at 91.”)

Nunis’s memoir, mentioned above, is:

Nunis, Dick. Walt’s Apprentice: Keeping the Disney Dream Alive. Los Angeles: Disney Editions, 2022.

Mountains Are Not Sublime if You Need a Plain to Survive

(p. 13) Most of the people who have lived on this planet since the invention of agriculture have been peasants.

. . .

The cultivators, it is often assumed, are dreadfully uncultivated. And this alleged lack of sophistication has made them fair game for every kind of depredation. The food they produce has been expropriated by their overlords, by marauding armies and by totalitarian states. They have been conscripted as cannon fodder; entangled in debt and dependency as sharecroppers and serfs; starved, sometimes deliberately, in famines and prisons; forcibly converted to their masters’ religions; herded onto collective farms and slaughtered mercilessly when they revolt.

. . .

. . . very few of the countless millions who have eked a living from the land left enduring accounts of their own lives.

“This,” Joyce wrote, “is a world of a very ancient form of silence, peasant silence, something enmeshed in cultures that are largely oral in nature.”

. . .

“The wild as our sublime,” he writes, “makes no sense to the peasant.” (Joyce cites a Polish peasant interviewed in the 1960s who said, “I like it where the plain is; when I was in America I saw a mountain, and this was an awful view.”)

. . .

Joyce shows how the supreme value of the peasant is generational survival: The great task is to hand on to the child the land the peasant has inherited, making one’s own existence a kind of interlude between past and future.

For the full review, see:

Fintan O’Toole. “Fanfare for the Common Man.” The New York Times Book Review (Sunday, March 10, 2024): 13.

(Note: ellipses added.)

(Note: the online version of the review was updated Feb. 28, 2024, and has the title “A Love Song to His Roots.”)

The book under review above is:

Joyce, Patrick. Remembering Peasants: A Personal History of a Vanished World. New York: Scribner, 2024.

“Troublemaker” Finally Convinced Peers That Hub Trees Distribute Resources to Kin

(p. C7) Over the years, Ms. Simard encountered no shortage of pushback. Government bureaucrats were reluctant to spend money on her recommendations. Her managers resisted changing their forestry models and perhaps “couldn’t listen to women,” labeling her a “troublemaker.” Fellow scientists challenged her research methods. This last may have originated in envy, but ultimately is an important part of the scientific process—after all, without stringent vetting, we might still believe that Vulcan is, indeed, a planet. Today Ms. Simard’s research is widely accepted. We now know that through fungal networks trees share resources, that mature trees (what she calls “hub trees” in her research, and “mother trees” when speaking to popular audiences) support seedlings, favor their kin and distribute resources, even in death. It’s a radical new understanding of plants.

For the full review, see:

Eugenia Bone. “Seeing the Forest.” The Wall Street Journal (Saturday, May 8, 2021 [sic]): C7.

(Note: the online version of the review has the date May 7, 2021 [sic], and has the title “‘Finding the Mother Tree’ Review: Seeing the Forest.”)

The book under review is:

Simard, Suzanne. Finding the Mother Tree: Discovering the Wisdom of the Forest. New York: Knopf, 2021.

Non-Drug Treatments Are Under-Studied Because They Are Hard to Patent, and Hard to Test in Randomized Clinical Trials

(p. C3) In particular, decades of research show that mental, physical and social stimulation is one of the potential ways to ward off Alzheimer’s disease.

. . .

All of these findings come from observational studies that look at people’s existing lifestyle and cognitive health, as opposed to providing them with a “lifestyle treatment” and then assessing cognitive outcomes. The gold standard in modern medicine is randomized, blind, placebo-controlled trials, which are more quantifiable and objective, and there have been few such trials of lifestyle treatments for dementia and Alzheimer’s.

Those that exist have shown disparate results. For example, a study published in the journal Applied Neuropsychology in 2003 found that while mental drills could train people to do better on specific tasks like recalling words from a list, the effect didn’t translate into overall cognitive improvement. Clinical trials on social engagement are currently lacking.

One reason why the cognitive benefits of lifestyle enrichment haven’t been sufficiently studied is that nonpharmacological treatments such as physical exercise can’t be easily patented, so pharmaceutical companies aren’t interested in investing. It’s also difficult to use placebos. In drug trials, a look-alike sugar pill and a test drug are randomly assigned to participants, but there’s no equivalent of a sugar pill for enrichment activities. Instead, the control group either receives no intervention, a fact that can’t be easily hidden to avoid bias, or they receive some other interventions that may have effects of their own and muddle trial results.

For the full essay, see:

Han Yu. “An Active Lifestyle Can Help To Ward Off Alzheimer’s.” The Wall Street Journal (Saturday, Feb. 27, 2021 [sic]): C3.

(Note: ellipsis added.)

(Note: the online version of the essay has the date February 25, 2021 [sic], and has the title “Can an Active Lifestyle Help Ward Off Alzheimer’s?”)

The essay quoted above is adapted from Yu’s book is:

Yu, Han. Mind Thief: The Story of Alzheimer’s. New York: Columbia University Press, 2021.

Chernow Channels McCloskey’s Index Card Advice

In her wonderful paper on how to research well and write clearly, Deirdre McCloskey suggests that we always carry with us a pack of 4 by 6 cards, so that we have them handy when we are hit by an epiphany or hear a relevant quote. (The suggestion probably also appears in the later book versions of her wonderful paper, but I do not have a copy handy to check.)

(p. C11) Mr. Chernow usually spends about twice as much time researching a book as writing it. He types up his research on a computer, so that he has it backed up, and then prints out the individual entries on paper with perforated edges that he can tear into 4-by-6-inch cards. (He was inspired to use index cards by Vladimir Nabokov, who wrote his novels on them.) He then files the cards chronologically and indexes them. His research on Grant fills some 25,000 cards packed into 22 boxes, all stacked up in the office of his Brooklyn brownstone under a big abstract painting.

For the full interview, see:

Alexandra Wolfe. “WEEKEND CONFIDENTIAL; Ron Chernow.” The Wall Street Journal (Saturday, Sept. 16, 2017 [sic]): C11.

(Note: the online version of the interview has the date Sept. 15, 2017 [sic], and has the title “WEEKEND CONFIDENTIAL; Ron Chernow’s New Chapter: Ulysses S. Grant.”)

The main Chernow book discussed in the interview is:

Chernow, Ron. Grant. New York: The Penguin Press, 2017.

McCloskey’s wonderful paper, mentioned above, is:

McCloskey, Deirdre. “Economical Writing.” Economic Inquiry 23, no. 2 (April 1985): 187-222.