Discoverer of Catalyst Role of mRNA Had Trouble “Getting His Work Published”

(p. B12) Sidney Altman, a molecular biologist who was awarded the Nobel Prize for Chemistry for sharing in the discovery that ribonucleic acid, or RNA, was not just a carrier of genetic information but could also be a catalyst for chemical reactions in cells — a breakthrough that paved the way for new gene therapies and treatments for viral infections — died on April 5 [2022] in Rockleigh, N.J.

. . .

HAs seems to happen so often in science, Dr. Altman stumbled upon his discovery. “I wasn’t looking for what I found,” he said in a 2010 interview with Harry Kreisler at the Institute for International Studies at the University of California, Berkeley.

He had studied how a small RNA molecule, called transfer RNA, carries genetic code to make new proteins. Some of the code is not necessary, so an enzyme cuts it out before it is used.

Then, in 1978, Dr. Altman began studying an RNA-cutting enzyme from E. coli bacteria that was composed of an RNA molecule and a protein. He managed to separate the two pieces and test them to see how they reacted in the enzyme process. Much to his surprise, he discovered that the protein did not perform as an enzyme without the RNA molecule. He later discovered that the RNA molecule could be the catalyst, even without the protein.

The finding ran completely contrary to what at the time was established theory, which held that it was the proteins that were the catalysts in enzymes.

The discovery of what are now known as ribozymes was so radical that Dr. Altman had trouble getting it accepted.

Joel Rosenbaum, a professor of cell biology at Yale and a colleague of Dr. Altman’s, told Chemistry World magazine that when Dr. Altman first tried to get other scientists to accept his research, “the community of molecular biologists, including several at Yale working on RNA, did not want to believe the work.”

“He had a hard time obtaining invitations to speak at scientific meetings and, indeed, getting his work published,” Dr. Rosenbaum said.

For the full obituary, see:

Dylan Loeb McClain. “Sidney Altman, Who Stumbled on a Breakthrough in Genetics, Dies at 82.” The New York Times (Saturday, April 16, 2022): B12.

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

(Note: the online version of the obituary was updated April 18, 2022, and has the same title as the print version.)

Buffalo Stadium Subsidy Is Corporate and Union Welfare Pork

(p. A11) It’s bad enough that the budget agreement announced Thursday night by New York Gov. Kathy Hochul will shower more than $1 billion of the public’s money on a new stadium for the Buffalo Bills, a billionaire-owned football franchise that competes in the world’s most profitable sports league. But Ms. Hochul has attached conditions to the deal that will drive up the construction cost by roughly 20% and assure that a big chunk of the subsidy will be wasted. That contradicts her claim that she sought to negotiate the “best deal for taxpayers.”

Ms. Hochul is the first New York governor to hail from Buffalo since Grover Cleveland. Her husband is general counsel of Delaware North, the chief concessionaire at Highmark Stadium, the Bills’ current home in suburban Orchard Park. The new 60,000-seat facility is to be erected nearby, on the site of an existing stadium parking lot. Ms. Hochul says it’s a good deal for residents, who are rightly suspicious. So too are economists, whose strong consensus is that taxpayers almost always come out losers in publicly funded stadium projects, which chiefly enrich owners.

In this case, the corporate welfare pork is greased with a costly handout to unionized labor. That’s because of the state’s so-called prevailing-wage law, which effectively mandates that contractors on public construction projects such as schools, roads, bridges and subways pay union-level wages and benefits. Last year, a “source familiar with the negotiations” told the Buffalo News that the project’s $1.4 billion price tag was driven in part by “prevailing wage and union workforce requirements, among other rules.” Exactly how much the prevailing-wage law adds to the stadium deal is hard to know, but it’s likely in the hundreds of millions.

For the full commentary, see:

Peter Warren. “CROSS COUNTRY; The Buffalo Bills’ Stadium Subsidy Is a Hand-Off to Unions.” The Wall Street Journal (Saturday, April 9, 2022): A11.

(Note: the online version of the commentary has the date April 8, 2022, and has the same title as the print version.)

Gary Becker Foresaw a Cure for Obesity that Daniel Kahneman Wrote Was “Implausible”

I have found much of value in Daniel Kahneman’s Thinking, Fast and Slow. But the following passage is not included in what I value.

A famous example of the Chicago approach is titled A Theory of Rational Addiction; it explains how a rational agent with a strong preference for intense and immediate gratification may make the rational decision to accept future addiction as a consequence. I once heard Gary Becker, one of the authors of that article, who is also a Nobel laureate of the Chicago school, argue in a lighter vein, but not entirely as a joke, that we should consider the possibility of explaining the so-called obesity epidemic by people’s belief that a cure for diabetes will soon become available. He was making a valuable point: when we observe people acting in ways that seem odd, we should first examine the possibility that they have a good reason to do what they do. Psychological interpretations should only be invoked when the reasons become implausible—which Becker’s explanation of obesity probably is.

Source: Kahneman, Daniel. Thinking, Fast and Slow. New York: Farrar, Straus and Giroux, 2011, p. 412.

Gary Becker is vindicated again:

(p. A16) An experimental drug has enabled people with obesity or who are overweight to lose about 22.5 percent of their body weight, about 52 pounds on average, in a large trial, the drug’s maker announced on Thursday.

The company, Eli Lilly, has not yet submitted the data for publication in a peer-reviewed medical journal or presented them in a public setting. But the claims nonetheless amazed medical experts.

“Wow (and a double Wow!)” Dr. Sekar Kathiresan, chief executive of Verve Therapeutics, a company focusing on heart disease drugs, wrote in a tweet. Drugs like Eli Lilly’s, he added, are “truly going to revolutionize the treatment of obesity!!!”

Dr. Kathiresan has no ties to Eli Lilly or to the drug.

. . .

The Eli Lilly study lasted 72 weeks and involved 2,539 participants. Many qualified as obese, while others were overweight but also had such risk factors as high blood pressure, high cholesterol levels, cardiovascular disease or obstructive sleep apnea.

They were divided into four groups. All received diet counseling to reduce their calorie intake by about 500 a day.

One group was randomly assigned to take a placebo, while the other three received doses of tirzepatide ranging from 5 milligrams to 15 milligrams. Patients injected themselves with the drug once a week.

. . .

The medications are among a new class of drugs called incretins, which are naturally occurring hormones that slow stomach emptying, regulate insulin and decrease appetite. The side effects include nausea, vomiting and diarrhea. But most patients tolerate or are not bothered by these effects.

For the full story, see:

Gina Kolata. “Experimental Obesity Drug Produces 20% Weight Loss.” The New York Times (Friday, April 29, 2022): A16.

(Note: ellipses added.)

(Note: the online version of the story was updated May 1, 2022, and has the title “Patients Taking Experimental Obesity Drug Lost More Than 50 Pounds, Maker Claims.” Where there is a slight difference in wording between the online and the print versions, the passages quoted above follow the online version.)

Kahneman’s book is:

Kahneman, Daniel. Thinking, Fast and Slow. New York: Farrar, Straus and Giroux, 2011.

CAR T Therapy Is a Durable “Cure” for Some Leukemia Cancers

(p. A17) Doug Olson was feeling kind of tired in 1996. When a doctor examined him she frowned. “I don’t like the feel of those lymph nodes,” she said, poking his neck. She ordered a biopsy. The result was terrifying. He had chronic lymphocytic leukemia, a blood cancer that mostly strikes older people and accounts for about a quarter of new cases of leukemia.

“Oh Lordy,” Mr. Olson said. “I thought I was done for.” He was only 49 and, he said, had always been healthy.

Six years went by without the cancer progressing. Then it started to grow. He had four rounds of chemotherapy but the cancer kept coming back. He had reached pretty much the end of the line when his oncologist, Dr. David Porter at the University of Pennsylvania, offered him a chance to be among the very first patients to try something unprecedented, known as CAR T cell therapy.

In 2010, he became the second of three patients to get the new treatment.

At the time, the idea for this sort of therapy “was way out there,” said Dr. Carl June, the principal investigator for the trial at Penn, and he had tempered his own expectations that the cells he was providing to Mr. Olson as therapy would survive.

“We thought they would be gone in a month or two,” Dr. June said.

Now, a decade later, he reports that his expectations were completely confounded. In a paper published Wednesday in Nature, Dr. June and his colleagues, Dr. J. Joseph Melenhorst and Dr. Porter, report that the CAR T treatment made the cancer vanish in two out of the three patients in that early trial. All had chronic lymphocytic leukemia. The big surprise, though, was that even though the cancer seemed to be long gone, the CAR T cells remained in the patients’ bloodstreams, circulating as sentinels.

“Now we can finally say the word ‘cure’ with CAR T cells,” Dr. June said.

Although most patients will not do as well, the results hold out hope that, for some, their cancer will be vanquished.

For the full story, see:

Gina Kolata. “Potential Leukemia Cure Leads to New Mysteries.” The New York Times (Thursday, February 3, 2022): A17.

(Note: the online version of the story has the date Feb. 2, 2022, and has the title “A Cancer Treatment Makes Leukemia Vanish, but Creates More Mysteries.”)

Most Journalists No Longer Aspire to Objectivity

(p. B1) In 1979, two journalists got into an argument. More than four decades later, they haven’t settled it.

The subject of their disagreement was journalistic “objectivity,” a notion that goes back at least to the 1920s, when some of the more high-minded newspapers and magazines were trying to distinguish themselves from the scandal sheets and publications led by partisan and sometimes warmongering publishers.

In one corner, Alan Berger. In 1979, he was a 41-year-old media columnist for the Real Paper, an alternative weekly that had emerged from a rift at its predecessor, Boston Phoenix. Before he started watch-dogging the press, Mr. Berger had grown up in the Bronx, attended Harvard University and taught a class at M.I.T., in French, on the poet Charles Baudelaire.

His target in the debate over objectivity — which has come roaring back to life in the political storminess of recent years — was Tom Palmer. Back then, Mr. Palmer was a 31-year-old assistant national editor of The Boston Globe, meaning he belonged to the establishment and was thus a ripe target for the Real Paper.

. . .

(p. B4) His former protégé, the national correspondent Wesley Lowery, argued in a widely circulated New York Times opinion essay that objectivity mirrored the worldview of white reporters and editors, whose “selective truths have been calibrated to avoid offending the sensibilities of white readers.” Mr. Lowery, who ended up leaving The Post for CBS News, suggested that news organizations “abandon the appearance of objectivity as the aspirational journalistic standard, and for reporters instead to focus on being fair and telling the truth, as best as one can, based on the given context and available facts.”

That same argument has found an embrace at some of America’s leading journalism schools, as well.

“We focus on fairness and fact-checking and accuracy, and we don’t try to suggest to our students that opinions they have should be hidden,” said Sarah Bartlett, the dean of the City University of New York Craig Newmark Graduate School of Journalism. “We embrace transparency.”

. . .

Mr. Palmer also never quite let the argument go. He appointed himself a kind of genial in-house watchdog at The Globe, eventually known for his persistent emails to reporters and editors he thought had allowed their liberal views to infiltrate their copy.  . . .

Needless to say, he remains unpersuaded by the arguments against his cherished ideal. They “were dead wrong back then,” he emailed me, “and I believe are dead wrong even more so today.”

“Journalists are simply not smart enough and educated enough to change the world,” he continued. “They should damn well just inform the public to the best of their abilities and let the public decide.”

He also said, ruefully, that he believed his side was losing. The notion of objectivity “was declining before Trump, and that era removed it from the table completely,” he wrote. “I have doubts it will ever come back.”

For the full commentary, see:

Ben Smith. “A 1979 Fight Over Ideals Is Still Going.” The New York Times (Monday, October 11, 2021): B1 & B4.

(Note: ellipses added.)

(Note: the online version of the commentary was updated October 11, 2021, and has the title “Two Journalists Started an Argument in Boston in 1979. It’s Not Over Yet.”)

New York Times Columnist Finds that Trump’s “Truth Social” Platform Is “Less Restrictive than Twitter”

(p. B1) Truth Social, Mr. Trump has said, would “stand up to the tyranny of Big Tech.”

The app’s surge in popularity this week caught the attention of Mr. Musk, a self-proclaimed free speech absolutist. In several tweets, the billionaire noted that Truth Social was “beating Twitter & TikTok on the Apple Store” and blamed Twitter’s rules on (p. B6) speech for birthing the alternative apps.

. . .

To test the app’s claims about political ideology, I published a Truth with a New York Times Opinion article that was critical of the Republican Party, and other posts with news articles about the Jan. 6 riot and how Truth Social’s prospects could be hurt by Mr. Musk’s takeover of Twitter. None of the posts were flagged as problematic. That suggested the app wasn’t discriminating based on politics, just as it had said it wouldn’t.

I also found some accounts that were not allowed to post on Twitter — like The Babylon Bee, the right-wing satire site that was suspended for misgendering a transgender Biden administration official — posting regularly on Truth Social. It was another sign that the app was less restrictive than Twitter.

For the full commentary, see:

Brian X. Chen. “Upgrade Frees Trump App, But Glitches Hold It Back.” The New York Times (Thursday, April 28, 2022): B1 & B6.

(Note: ellipsis added.)

(Note: the online version of the commentary has the date April 27, 2022, and has the title “Truth Social Review: Trump’s Uncensored Social App Is Incomplete.”)

Stereotyping Older Adults May Shorten Their Lives

(p. D3) Dr. Robert N. Butler, a psychiatrist, gerontologist and founding director of the National Institute on Aging, coined the term “ageism” a half-century ago. It echoes “sexism” and “racism,” describing the stereotyping of and discrimination against older adults.

Among the mementos in Dr. Levy’s small office at Yale is a treasured photo of her and Dr. Butler, who died in 2010. One could argue that she is his heir.

A psychologist and epidemiologist, Dr. Levy has demonstrated — in more than 140 published articles over 30 years and in a new book, “Breaking the Age Code” — that ageism results in more than hurt feelings or even discriminatory behavior. It affects physical and cognitive health and well-being in measurable ways and can take years off one’s life.

. . .

Another memento in Dr. Levy’s office is a card on her bulletin board that reads, “Ask Me About 7.5.” The souvenir came from a Wisconsin anti-ageism campaign and refers to her 2002 longevity study, which for two decades followed hundreds of residents older than 50 in a small Ohio town. The study found that median survival was seven and a half years longer for those with the most positive beliefs about aging, compared with those having the most negative attitudes.

. . .

We absorb these stereotypes from an early age, through disparaging media portrayals and fairy tales about wicked old witches. But institutions — employers, health care organizations, housing policies — express a similar prejudice, enforcing what is called “structural ageism,” Dr. Levy said. Reversing that will require sweeping changes — an “age liberation movement,” she added.

But she has found reason for optimism: Damaging ideas about age can change. Using the same subliminal techniques that measure stereotypical attitudes, her team has been able to enhance a sense of competence and value among older people. Researchers in many other countries have replicated their results.

For the full commentary, see:

Paula Span. “How Ageism Can Take Years Off Seniors’ Lives.” The New York Times (Tuesday, April 26, 2022): D3.

(Note: ellipses added.)

(Note: the online version of the commentary was updated April 28, 2022, and has the title “Exploring the Health Effects of Ageism.” Where there is a slight difference in wording between versions, the passages quoted above are from the online version.)

Levy’s book mentioned in the commentary above is:

Levy, Becca. Breaking the Age Code: How Your Beliefs About Aging Determine How Long and Well You Live. New York: William Morrow, 2022.

More Than Six Million Have Died From COVID-19 Worldwide

(p. A13) Though many global coronavirus trends are rapidly improving as countries emerge from surges driven by the highly transmissible Omicron variant, the grimmest metric hit a tragic milestone on Monday [March 7, 2022].

The number of known Covid-19 deaths around the world surpassed six million, according to data from the Center for Systems Science and Engineering at Johns Hopkins University.

“Six million is really unfathomable,” said Beth Blauer, the data leader for the Coronavirus Resource Center at Johns Hopkins. “These are real lives.”

. . .

Public health experts agree that six million is a vast undercount and that the true devastation will never be precisely known. In Yemen, where a civil war has been raging for years, the government has reported only 2,100 deaths since the start of the pandemic while its population of 30 million is 99 percent unvaccinated.

“There’s a lot that we don’t know in places that don’t necessarily have the same infrastructure for fundamentally understanding the pandemic and reporting,” Dr. Blauer said.

. . .

. . . the United States, with ample vaccine supply, has suffered the highest known total — more than 950,000 deaths — and failed to inoculate as much of its population as other wealthy nations.

. . .

. . . stark vaccination disparities between countries remain, leaving the entire world vulnerable to the threat of a new, deadly variant. Vaccination rates continue to lag in low-income countries, where only 14 percent of the population has received at least one dose of a vaccine. In high- and upper-middle-income countries, 79 percent of the population has received at least one dose.

For the full story, see:

Adeel Hassan. “Number of Known Coronavirus Deaths Surpasses 6 Million Globally as Omicron Recedes.” The New York Times (Tuesday, March 8, 2022): A13.

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

(Note: the online version of the story has the date March 7, 2022, and has the title “The pandemic’s official global toll surpasses 6 million known virus deaths.”)

BioNTech Is Running Clinical Trials for mRNA Cancer Vaccines

(p. C2) Scientists are . . . advancing mRNA vaccines and therapies to treat cancer, which poses a particular challenge because tumor cells arise from the body’s own cells and can easily deceive the immune system into thinking they are normal. Cancer patients today receive varying types of treatments, but they involve therapies manufactured outside the body. The mRNA researchers believe that the body’s own immune system can be used against cancer if it’s given the right tools.

BioNTech, now a household name for its Covid-19 vaccine with Pfizer, was founded in 2008 to pursue mRNA cancer treatments. The German company says that even at a low dose, a strong enough mRNA treatment can be developed to prompt immune cells to make certain proteins and to train the rest of the immune system to recognize and target tumor cells that express these same proteins. “It needs to be louder and more aggressive for cancer because the immune system needs stronger persuasion to attack something that appears to resemble a normal cell which it should respect and not attack,” said Özlem Türeci, BioNTech’s chief medical officer.

The company’s pipeline includes at least 10 cancer vaccines in human clinical trials using mRNA for skin, pancreatic, ovarian and other tumors. Two of its most advanced programs in mid-stage clinical studies, one for melanoma and the other for head and neck cancer, harness mRNA to make specific proteins seen with these cancers that will prompt a vigorous response from the patient’s immune system. Research from BioNTech published in 2020 in the journal Nature showed that the treatment caused the lesions of melanoma patients to shrink.

Some of BioNTech’s other cancer treatments are tailored to individual patients. A tumor is removed surgically and then shipped to the company’s laboratories, where researchers sequence the DNA and search for proteins, using machine learning to decide which ones are needed for that individual’s therapy. To address how quickly cancer can spread in the body, BioNTech designs and develops these clinical-trial treatments in just four to six weeks—a potentially lifesaving turnaround time for more pressing cases.

For the full essay, see:

Jared S. Hopkins and Felicia Schwartz. “Can the Technology Behind Covid Vaccines Cure Other Diseases?” The Wall Street Journal (Saturday, February 5, 2022): C1-C2.

(Note: ellipsis added.)

(Note: the online version of the essay has the date February 4, 2022, and has the same title as the print version.)

Covid Policy Should Have Taken Account of Costs of Lockdowns and Mandates

(p. A17) Reducing the incidence of disease isn’t necessarily desirable if excessive prevention, in the form of lockdowns or school closures, is more costly to society than the damage done by an illness. We don’t close highways to minimize accidental deaths, despite the existence of dangerous drivers. Yet this is exactly what we’re doing when the government intervenes to limit the spread of communicable diseases by, for instance, mandating vaccines that don’t prevent transmission.

. . .

In early 2020, University of Chicago economists estimated that about 80% of the total damage from Covid came from prevention efforts that hindered economic activity, and only 20% from the direct effects of the disease itself. This analysis motivated me and others to recommend that initial efforts to stop the spread should focus on older people, who are at higher risk of severe illness and not as active in the economy as younger people. This would allow younger people to keep the economy going while limiting the spread of the disease among those most at risk from it. Some in the public-health community, like the signers of the Great Barrington Declaration, eventually saw the light.

My Chicago colleague Casey B. Mulligan has found that total monthly Covid-related harms fell from 2020 to 2021, even as the number of deaths rose. In tax terms, this is an effect not unlike that of the Laffer curve—a lower rate may increase revenue because of growth in the tax base. Similarly, vaccines and treatments reduced the costs associated with getting sick—call it the “disease tax”—but also increased social and economic activity, allowing the infection to spread. Even if the disease tax is paid by more people, the costs are outpaced by the overall benefit derived from the subsequent tsunami of economic activity.

For the full commentary, see:

Tomas J. Philipson. “An Economic Evaluation Of Covid Lockdowns.” The Wall Street Journal (Saturday, January 20, 2022): A17.

(Note: ellipsis added.)

(Note: the online version of the commentary has the date January 19, 2022, and has the same title as the print version.)

Some Venture Capitalists “Act as Mentors,” Some Install Seasoned Veterans as C.E.O.s, and Some Are “Founder-Friendly,” Allowing Genius “to Do Its Work”

(p. C4) . . . Mallaby never quite settles on the story he wants to tell. He introduces the book by laying out what he intends to do: “to explain the venture-capital mind-set” and “to evaluate venture capital’s social impact.” This mind-set, he says, revolves around the “power law” of his title — the idea that the distribution of phenomena is not “normal” but skewed. Instead of a bell curve, picture a long tail, where “winners advance at an accelerating, exponential rate.” Adapt or die, sink or swim — there’s no middle ground. This is why V.C.s like to talk about “grand slams” and “moon shots”; Peter Thiel says that a fund’s top investment should generate returns so spectacular that it will outperform everything else in the fund put together.

This, clearly, isn’t the kind of logic that has much use for steady, incremental growth, to say nothing of a flourishing middle class. You might therefore wonder about the “social impact” of venture capital, which Mallaby deems to be, on the whole, good. He concedes that “V.C.s as individuals can stumble sideways into lucky fortunes,” or can sometimes do unhelpful things. But he is ultimately bullish on what they have to offer: “Venture capital as a system is a formidable engine of progress — more so than is frequently acknowledged.” That engine, Mallaby reminds us, has funded such ventures as the development of synthetic insulin and, more recently, plant-based alternatives to ecologically damaging meat.

. . .

He gives examples of the different kinds of funds, with their various personalities and philosophies. There are V.C.s who see it as their role to act as mentors and coaches to inexperienced founders. There are V.C.s who insist on installing seasoned outsiders at start-ups to serve as C.E.O.s. There are also “founder-friendly” V.C.s, who promise to be hands-off, allowing genius, no matter how unorthodox or weird, to do its work.

For the full review, see:

Jennifer Szalai. “BOOKS OF THE TIMES; A Funder-Friendly Look at Venture Capital.” The New York Times (Tuesday, February 1, 2022): C4.

(Note: ellipses added.)

(Note: the online version of the review has the date Jan. 31, 2022, and has the title “BOOKS OF THE TIMES; ‘The Power Law’ Is a Funder-Friendly Look at the World of Venture Capital.”)

The book under review is:

Mallaby, Sebastian. The Power Law: Venture Capital and the Making of the New Future. New York: Penguin Press, 2022.