Category: Entrepreneurship

If Switzerland Is “Capitalist to Its Core,” Where Are Its Breakthrough Innovations?

If Switzerland is the premier capitalist country in the world, as Ruchir Sharma argues in the puzzling passages quoted below, what breakthrough innovations has it nurtured in the last half century? I can think of none. (Swatch may have been successful, but was it a breakthrough?) If I am right, what is Switzerland missing?

(p. 5) Capitalist to its core, Switzerland imposes lighter taxes on individuals, consumers and corporations than the Scandinavian countries do. In 2018 its top income tax rate was the lowest in Western Europe at 36 percent, well below the Scandinavian average of 52 percent. Government spending amounts to a third of gross domestic product, compared with half in Scandinavia. And Switzerland is more open to trade, with a share of global exports around double that of any Scandinavian economy.

Streamlined government and open borders have helped make this landlocked, mountainous country an unlikely incubator of globally competitive companies. To build wealth, a country needs to make rich things, and an M.I.T. ranking of nations by the complexity of the products they export places Switzerland second behind Japan, well ahead of the Scandinavian countries, whose average rank is 15.

. . .

Die-hard admirers of Scandinavian socialism overlook the change of heart in countries such as Sweden, where heavy government spending led to the financial crises of the 1990s. Sweden responded by cutting the top income tax rate from nearly 90 percent to as low as 50 percent. Public spending fell from near 70 percent of G.D.P. to 50 percent. Growth revived, as the largest Scandinavian economy started to look more like Switzerland, streamlining government and leaving business more room to grow.

For the full commentary see:

Ruchir Sharma. “The Happy, Healthy Capitalists of Switzerland.” The New York Times, SundayReview Section (Sun., November 3, 2019 [sic]): 5.

(Note: ellipsis added.)

(Note: the online version of the commentary has the date Nov. 2, 2019 [sic], and has the same title as the print version.)

Innovative Project Entrepreneur Mike Wood Helped Children Leapfrog the Reading Skills Taught at School

In my Openness book I argue that the kind of entrepreneurs who matter most in changing the world are what I call “project entrepreneurs,” those who are on a mission to bring their project into the world. Mike Wood, discussed in the obituary quoted below was a project entrepreneur.

I sometimes wonder how much formal education would be desirable in a world, unlike our world, that lacked creeping credentialism. Samuel Smile’s biography of George Stephenson says that he had zero formal education, but early-on paid someone from his meagre wages in the mines, to teach him to read. After that, the inventor and innovative entrepreneur read prodigiously to became an exemplary autodidact.

Today, Stephenson could learn to read through phonics technology like the LeapFrog pads developed by Mike Wood.

[By the way, Mike Wood, like Danny Kahneman recently, committed suicide at Dignitis in Switzerland in anticipation of declining health, in Wood’s case Alzheimer’s. As a libertarian, I believe they had a right to do this, but were they right to exercise this right? Harvard psychology professor Daniel Gilbert cites (2006, pp. 166-168) research showing that people generally underestimate their resilience in the face of major health setbacks. They can often recalibrate to their new more limited capabilities, continuing to find challenges they find fulfilling to overcome. If so, then maybe Wood and Kahneman were wrong to exercise their right to end their lives. (More than most of my claims, I very readily admit this one could be wrong.)]

(p. A21) Mike Wood was a young father when his toddler’s struggles to read led him to develop one of a generation’s most fondly remembered toys.

Mr. Wood’s 3-year-old son, Mat, knew the alphabet but couldn’t pronounce the letter sounds. A lawyer in San Francisco, Mr. Wood had a new parent’s anxiety that if his child lagged as a reader, he would forever struggle in life.

So on his own time, Mr. Wood developed the prototype of an electronic toy that played sounds when children squeezed plastic letters. He based the idea on greeting cards that played a tune when opened.

Mr. Wood went on to found LeapFrog Enterprises, which in 1999 introduced the LeapPad, a child’s computer tablet that was a kind of talking book.

The LeapPad was a runaway hit, the best-selling toy of the 2000 holiday season, and LeapFrog became one of the fastest-growing toy companies in history.

. . .

Former colleagues recalled Mr. Wood as a demanding entrepreneur who was driven by a true belief that technology could help what he called “the LeapFrog generation” gain an educational leg up.

He had “famously fluffy hair,” Chris D’Angelo, LeapFrog’s former executive director of entertainment, wrote of Mr. Wood on The Bloom Report, a toy industry news site. “When stressed, he’d unconsciously rub his head — and the higher the hair, the higher the stakes. We (quietly) called them ‘high-hair days.’ It was funny, but also telling. He felt everything deeply — our work, our mission, our audience.”

. . .

A shift in reading pedagogy in the 1990s toward phonics — helping early readers make a connection between letters and sounds — drove interest in LeapFrog’s products among parents and teachers.

. . .

In 2023, his daughter-in-law, Emily Wood, posted a TikTok video of Mr. Wood teaching her daughter to use a forerunner of the LeapPad. The video received 391,000 likes and thousands of comments.

“I owe him my entire childhood,” one viewer wrote. “I spent hours on my LeapFrog with my ‘Scooby-Doo’ and ‘Shrek’ books.”

“I sell books now because of him,” another viewer wrote.

“I’m learning disabled and have a stutter,” wrote a third. “This man helped me learn to speak.”

“I’m 25 and I loved my LeapFrog,” a fourth commented. “Coming from an immigrant family, reading made me have so much imagination. I never stopped reading.”

For the full obituary, see:

Trip Gabriel. “Mike Wood, 72, Dies; Taught a Generation With LeapFrog Toys.” The New York Times (Monday, April 21, 2025): A21.

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

(Note: the online version of the obituary has the date April 19, 2025, and has the title “Mike Wood, Whose LeapFrog Toys Taught a Generation, Dies at 72.”)

My book mentioned in my initial comments is:

Diamond, Arthur M., Jr. Openness to Creative Destruction: Sustaining Innovative Dynamism. New York: Oxford University Press, 2019.

Smiles’s biography of Stephenson is:

Smiles, Samuel. The Locomotive: George and Robert Stephenson. New and Revised ed, Lives of the Engineers. London: John Murray, Albemarle Street, 1879.

Daniel Gilbert’s book that I mention in my opening comments is:

Gilbert, Daniel. Stumbling on Happiness. New York: Alfred A. Knopf, 2006.

Fraudulently Doctored Images and “Suspect Data” in Many Leading Cancer Research Papers

Charles Piller in his Doctored paints a damning picture of doctored images and suspect data rampant in the leading scientific literature on Alzheimer’s disease. Not only were leading scientists guilty of fraud, but the key institutions of scientific research (journals, universities, and government grant-making agencies) failing their oversight duty, and when outsiders stepped in to provide oversight, delayed and minimized their responses. Practicing and turning a blind eye to fraud matters, since Alzheimer’s patients are depending on this research. And researchers who do not commit fraud suffer because they appear to have worse research records than those compiled by the fraudsters. So the honest get worse academic appointments and fewer grants.

After reading Doctored I was depressed, but I at least hoped that this pathology was limited to this one (albeit an important one) area of medical research. But in the article quoted below, evidence is presented that there is substantial similar doctored images and suspect data in the field of cancer research.

A side issue in the quoted article is worth highlighting. In the absence of credible oversight from the institutions tasked with oversight, oversight is being done by competent volunteers, with the aid of A.I. These volunteers do not receive compensation for their work, and in fact are probably pay a price for it, since they alienate powerful scientists and scientific institutions. But if science is a search for truth, and truth matters for cures, they are doing a service to us all, and especially to those who suffer from major diseases such as Alsheimer’s and cancer.

On the connection with the Doctored book, it is worth noting that the article quotes Dr. Matthew Schrag, who is the most important source in Doctored. The article also quoted Elisabeth Bik, who does not have an MD like Schrag but has a PhD in microbiology, and who is another important source in Doctored.

(p. A1) The stomach cancer study was shot through with suspicious data. Identical constellations of cells were said to depict separate experiments on wholly different biological lineages. Photos of tumor-stricken mice, used to show that a drug reduced cancer growth, had been featured in two previous papers describing other treatments.

Problems with the study were severe enough that its publisher, after finding that the paper violated ethics guidelines, formally withdrew it within a few months of its publication in 2021. The study was then wiped from the internet, leaving behind a barren web page that said nothing about the reasons for its removal.

As it turned out, the flawed study was part of a pattern. Since 2008, two of its authors — Dr. Sam S. Yoon, chief of a cancer surgery division at Columbia University’s medical center, and a more junior cancer biologist — have collaborated with a rotating cast of researchers on a combined 26 articles that a British scientific sleuth has publicly flagged for containing suspect data. A medical journal retracted one of them this month after inquiries from The New York Times.

Memorial Sloan Kettering Cancer Center, where Dr. Yoon worked when much of the research was done, is now investigating the studies. Columbia’s medical center declined to comment on specific allegations, saying only that it reviews “any concerns about scientific integrity brought to our attention.”

Dr. Yoon, who has said his research could lead to better cancer treatments, did not answer repeated questions. Attempts to speak to the other researcher, Changhwan Yoon, an associate research scientist at Columbia, were also unsuccessful.

The allegations were aired in recent months in online comments on a science forum and in a blog post by Sholto David, an independent molecular biologist. He has ferreted out problems in a raft of high-profile cancer research, including dozens of papers at a Harvard cancer center that were subsequently referred for retractions or corrections.

From his flat in Wales, Dr. David pores over published images of cells, tumors and mice in his spare (p. A17) time and then reports slip-ups, trying to close the gap between people’s regard for academic research and the sometimes shoddier realities of the profession.

. . .

Armed with A.I.-powered detection tools, scientists and bloggers have recently exposed a growing body of such questionable research, like the faulty papers at Harvard’s Dana-Farber Cancer Institute and studies by Stanford’s president that led to his resignation last year.

But those high-profile cases were merely the tip of the iceberg, experts said. A deeper pool of unreliable research has gone unaddressed for years, shielded in part by powerful scientific publishers driven to put out huge volumes of studies while avoiding the reputational damage of retracting them publicly.

The quiet removal of the 2021 stomach cancer study from Dr. Yoon’s lab, a copy of which was reviewed by The Times, illustrates how that system of scientific publishing has helped enable faulty research, experts said. In some cases, critical medical fields have remained seeded with erroneous studies.

“The journals do the bare minimum,” said Elisabeth Bik, a microbiologist and image expert who described Dr. Yoon’s papers as showing a worrisome pattern of copied or doctored data. “There’s no oversight.”

. . .

Dr. Yoon, a stomach cancer specialist and a proponent of robotic surgery, kept climbing the academic ranks, bringing his junior researcher along with him. In September 2021, around the time the study was published, he joined Columbia, which celebrated his prolific research output in a news release. His work was financed in part by half a million dollars in federal research money that year, adding to a career haul of nearly $5 million in federal funds.

. . .

The researchers’ suspicious publications stretch back 16 years. Over time, relatively minor image copies in papers by Dr. Yoon gave way to more serious discrepancies in studies he collaborated on with Changhwan Yoon, Dr. David said. The pair, who are not related, began publishing articles together around 2013.

But neither their employers nor their publishers seemed to start investigating their work until this past fall, when Dr. David published his initial findings on For Better Science, a blog, and notified Memorial Sloan Kettering, Columbia and the journals. Memorial Sloan Kettering said it began its investigation then.

. . .

A proliferation of medical journals, they said, has helped fuel demand for ever more research articles. But those same journals, many of them operated by multibillion-dollar publishing companies, often respond slowly or do nothing at all once one of those articles is shown to contain copied data. Journals retract papers at a fraction of the rate at which they publish ones with problems.

. . .

“There are examples in this set that raise pretty serious red flags for the possibility of misconduct,” said Dr. Matthew Schrag, a Vanderbilt University neurologist who commented as part of his outside work on research integrity.

. . .

Experts said the handling of the article was symptomatic of a tendency on the part of scientific publishers to obscure reports of lapses.

“This is typical, sweeping-things-under-the-rug kind of nonsense,” said Dr. Ivan Oransky, co-founder of Retraction Watch, which keeps a database of 47,000-plus retracted papers. “This is not good for the scientific record, to put it mildly.”

For the full story, see:

Benjamin Mueller. “Cancer Doctor Is in Spotlight Over Bad Data.” The New York Times. (Fri., February 16, 2024): A1 & A17.

(Note: ellipses added.)

(Note: the online version has the date Feb. 15, 2024 [sic], and has the title “A Columbia Surgeon’s Study Was Pulled. He Kept Publishing Flawed Data.”)

Piller’s book mentioned in my initial comments is:

Piller, Charles. Doctored: Fraud, Arrogance, and Tragedy in the Quest to Cure Alzheimer’s. New York: Atria/One Signal Publishers, 2025.

Rampant Fraud in ‘Skin’ Bandages Paid by Medicare

A “quirk” in the Medicare law allows ‘skin’ bandage firms to charge, and have Medicare pay them, exorbitant prices. Are such quirks accidents or intentional? Medicare rules are so voluminous and obscure that few have an incentive to look carefully at the details. But the firms selling ‘skin’ bandages had an incentive. Entrepreneurs within these firms saw an opportunity and seized it. But they are what William Baumol called “destructive entrepreneurs.” Their energy and talent works against the general good.

Since patients are not paying, they have little incentive to reveal the fraud. So the taxpayers are robbed. In a system where the patients are the payers they would have an incentive to reveal fraud, and to seek alternatives to over-priced medical therapies.

But what of the poor, you ask? Susan Feigenbaum proposed an insurance system where patients would receive lump sum payments for different ailments. Then poor patients could be payers, and have the incentives of payer.

(p. 1) Seniors across the country are wearing very expensive bandages.

Made of dried bits of placenta, the paper-thin patches cover stubborn wounds and can cost thousands of dollars per square inch.

Some research has found that such “skin substitutes” help certain wounds heal. But in the past few years, dozens of unstudied and costly products have flooded the market.

Bandage companies set ever-rising prices for new brands of the products, taking advantage of a loophole in Medicare rules, The New York Times found. Some doctors then buy the coverings at large discounts but charge Medicare the full sticker price, pocketing the difference.

Partly because of these financial incentives, many patients receive the bandages who do not need them. The result, experts said, is one of the largest examples of Medicare waste in history.

Private insurers rarely pay for skin substitutes, arguing that they are unproven and unnecessary. But Medicare, the government insurance program for seniors, routinely covers them. Spending on skin substitutes exceeded $10 billion in 2024, more than double the figure in 2023, according to an analysis of Medicare data done for The Times by Early Read, a firm that evaluates costs for large health companies.

Medicare now spends more on the bandages than on ambulance rides, anesthesia or CT scans, the analysis found.

. . .

(p. 19) . . . experts in health care costs said the spike had been driven . . . by sellers and doctors taking advantage of Medicare’s pricing rules. The government will reimburse any price that a company sets for brand-new skin substitutes, even if it is far above the market average. The higher the price, the larger the doctors’ cut.

And the bigger the bandage, the more they can charge. For one patient in Nevada, Medicare spent $14 million on skin substitutes over the course of a year, according to billing records reviewed by The Times. The wound of a patient in Washington State persisted after Medicare paid $6 million for the coverings. A man in Texas got $1.3 million of bandages despite having no wound at all. Health executives trying to ferret out suspicious spending identified these patients and shared their stories with The Times.

As the Trump administration — and particularly the new Department of Government Efficiency run by Elon Musk — aims to shrink the federal purse, profligate Medicare spending is a ripe target, experts said.

Companies have billed Medicare for hundreds of thousands of urinary catheters that doctors never ordered. Other schemes have peddled urine tests and knee braces. In 2023, a federal watchdog agency flagged skin substitute spending as wasteful for both taxpayers and Medicare enrollees, who ultimately pay the costs with higher premiums.

“It’s the patients, it’s the taxpayers — unfortunately everyone is footing a part of the bill for this outsized spend,” said Dana Rye, an executive with Duly Health and Care, a Chicago-based medical group where payments for skin substitutes have risen 1,400 percent since 2022.

. . .

Five years ago, the most expensive skin substitute cost $1,042 per square inch, while some were as cheap as $45. Today, the three most expensive products on the market each cost more than $21,000. (Samaritan Biologics, a company in Memphis that sells the three products, did not answer questions about why they cost so much.)

Companies can set such high prices because of a quirk in Medicare pricing rules, industry experts said. For the first six months of a new bandage product’s life, Medicare will set the reimbursement rate at whatever price a company chooses. After that, the agency adjusts the reimbursement to reflect the actual price paid by doctors after any discounts.

To circumvent the reimbursement drop, some companies simply roll out new products.

In April 2023, Medicare began reimbursing $6,497 for every square inch of a bandage called Zenith, sold by Legacy Medical Consultants, a company in Fort Worth, Texas. Six months later, Zenith’s reimbursement fell to $2,746.

That month, October 2023, Medicare began reimbursing $6,490 for a new Legacy product, a “dual layer” bandage called Impax.

Marketing materials for the two products use identical photographs and similar language. The company describes both products as providing “optimal wound covering and protection during the treatment of wounds.”

Since 2022, spending on Zenith and Impax has exceeded $2.6 billion, according to Early Read’s analysis.

. . .

A cottage industry of doctors and nurses make house calls to treat wounds. Some skin substitute companies pitch themselves to wound care doctors by offering a cut of the rising bandage prices.

Dr. Caroline Fife, a wound care doctor from Texas who often writes about industry excesses, shared on her blog last year an email she received from an undisclosed skin substitute company. The company boasted that other doctors had developed “a healthy revenue stream” from its bandages and that a patch smaller than a credit card “would generate a little over $20,000 for your practice.”

Some companies offer doctors a “bulk discount” of up to 45 percent, according to doctor interviews and contracts reviewed by The Times. But doctors then collect a Medicare reimbursement for the full price of the product.

For the full story, see:

Sarah Kliff and Katie Thomas. “‘Skin’ Bandages Cost Medicare, And Doctors Get a Cut of Billions.” The New York Times, First Section. (Sun., April 13, 2025): 1 & 19.

(Note: ellipses added.)

(Note: the online version was updated April 14, 2025, and has the title “Medicare Bleeds Billions on Pricey Bandages, and Doctors Get a Cut.”)

The article by William Baumol praised in my initial comments is:

Baumol, William J. “Entrepreneurship: Productive, Unproductive, and Destructive.” The Journal of Political Economy 98, no. 5, Part 1 (Oct. 1990): 893-921.

The article by Susan Feigenbaum praised in my initial comments is:

Feigenbaum, Susan. “Body Shop’ Economics: What’s Good for Our Cars May Be Good for Our Health.” Regulation 15, no. 4 (Fall 1992): 25-31.

“A.I.s Are Overly Complicated, Patched-Together Rube Goldberg Machines Full of Ad-Hoc Solutions”

A.I. can be a useful tool for searching and summarizing the current state of consensus knowledge. But I am highly dubious that it will ever be able to make the breakthrough leaps that some humans are sometimes able to make. And I am somewhat dubious that it will ever be able to make the resilient pivots that all of us must sometimes make in the face of new and unexpected challenges.

(p. B2) In a series of recent essays, [Melanie] Mitchell argued that a growing body of work shows that it seems possible models develop gigantic “bags of heuristics,” rather than create more efficient mental models of situations and then reasoning through the tasks at hand. (“Heuristic” is a fancy word for a problem-solving shortcut.)

When Keyon Vafa, an AI researcher at Harvard University, first heard the “bag of heuristics” theory, “I feel like it unlocked something for me,” he says. “This is exactly the thing that we’re trying to describe.”

Vafa’s own research was an effort to see what kind of mental map an AI builds when it’s trained on millions of turn-by-turn directions like what you would see on Google Maps. Vafa and his colleagues used as source material Manhattan’s dense network of streets and avenues.

The result did not look anything like a street map of Manhattan. Close inspection revealed the AI had inferred all kinds of impossible maneuvers—routes that leapt over Central Park, or traveled diagonally for many blocks. Yet the resulting model managed to give usable turn-by-turn directions between any two points in the borough with 99% accuracy.

Even though its topsy-turvy map would drive any motorist mad, the model had essentially learned separate rules for navigating in a multitude of situations, from every possible starting point, Vafa says.

The vast “brains” of AIs, paired with unprecedented processing power, allow them to learn how to solve problems in a messy way which would be impossible for a person.

. . .

. . ., today’s AIs are overly complicated, patched-together Rube Goldberg machines full of ad-hoc solutions for answering our prompts. Understanding that these systems are long lists of cobbled-together rules of thumb could go a long way to explaining why they struggle when they’re asked to do things even a little bit outside their training, says Vafa. When his team blocked just 1% of the virtual Manhattan’s roads, forcing the AI to navigate around detours, its performance plummeted.

This illustrates a big difference between today’s AIs and people, he adds. A person might not be able to recite turn-by-turn directions around New York City with 99% accuracy, but they’d be mentally flexible enough to avoid a bit of roadwork.

For the full commentary see:

Christopher Mims. “We Now Know How AI ‘Thinks.’ It Isn’t Thinking at All.” The Wall Street Journal (Saturday, April 26, 2025): B2.

(Note: ellipses added.)

(Note: the online version of the commentary has the date April 25, 2025, and has the title “We Now Know How AI ‘Thinks’—and It’s Barely Thinking at All.”)

A conference draft of the paper that Vafa co-authored on A.I.’s mental map of Manhattan is:

Vafa, Keyon, Justin Y. Chen, Ashesh Rambachan, Jon Kleinberg, and Sendhil Mullainathan. “Evaluating the World Model Implicit in a Generative Model.” In 38th Conference on Neural Information Processing Systems (NeurIPS). Vancouver, BC, Canada, Dec. 2024.

Health Freedom Is a Right AND Can Yield More and Faster Therapies

The headline of the article on the front page of the NYT says “No Evidence for Healing Powers,” and goes on to slam unsophisticated right-wingers as irresponsibly pushing ivermectin as a therapy for cancer. In the article the NYT publishes a ludicrous picture from a right-winger’s Facebook page where he has spread veterinary ivermectin cream on his tongue and says “tastes like dead cancer.”

But this is unfair and tendentious caricature. A friend recently sent me an Instagram post by a chiropractor suffering from glioblastoma who has taken ivermectin and mebendazole. He briefly sketches the hypothesized mechanisms for activity of the two drugs, consistent with research published in scientific papers.

Glioblastoma is a serious, often fatal, brain cancer. He had surgery, but knows that surgery often does not cure, so he threw a Hail Mary and took ivermectin and mebendazole. These drugs have long track-records for safety, having been tested and approved for other uses. Doctors can, and have, prescribed drugs for off-label uses for decades.

Decades ago minoxidil was approved as an blood pressure medicine. I asked my then-doctor to prescribe it for me for its rumored effects as a hair loss cure. He did, so I crushed the tablets and somehow applied them to my scalp, which proceeded to itch, but not grow hair. It was a low-risk, modest-chance-of-success experiment. I think I had a right to try it, and that no government or expert had a right to forbid it. (Eventually minoxidil was approved for hair loss and branded Rogaine–which still didn’t work for me.)

In a free country adults should have wide latitude to make decisions about what risks they take; to scuba dive, to drive NASCAR, to go into space, and yes to take ivermectin and mebendazole. And the ludicrous right-winger? Hey, maybe even he has rights.

The NYT headline says there is “no evidence” for ivermectin. Below I cite a survey article that identifies 24 articles published in scientific journals identifying mechanisms by which ivermectin may be effective against cancer. There’s plenty of evidence, just not from randomized double-blind clinical trials (RCTs). But as long-time readers of this blog may remember, I have posted many entries giving useful actionable evidence that takes forms other than RCTs.

“No evidence”? Maybe the NYT was seeking plausible deniability by running its article on April 1st.

Oh, and by the way, allowing health freedom might sometimes result in better and faster therapies. I am currently reading Rethinking Diabetes by Gary Taubes. He tells the story (pp. 346-356) of Richard K. Bernstein, an engineer with Type 1 diabetes who was suffering from various serious ailments from his diabetes, in spite of the doctors saying it was being well-controlled by insulin. In his 40s, he was only expected to live another 10 years. Well he bought a new device that was not supposed to be bought by patients. The medical profession thought patients could not handle the information. (His wife was an MD, so he ‘bought’ it by asking her to buy it for him.) The device allowed him to get frequent readings of his blood sugar, and thereby to better control it, ultimately through changes in diet. When he tried to share what he had learned, he had trouble finding anyone who would take him seriously, so in his 40s he enrolled in medical school, and started publishing papers and books describing his results.

Richard K. Bernstein died on April 15, 2025 at age 90.

[Below are some relevant quotations from a NYT companion piece to the front-page article. The companion piece provides only slightly less tendentious background information on ivermectin.]

(p. A21) . . . there is not evidence to support people taking ivermectin to treat cancer.

. . .

Scientists do not dispute that ivermectin is powerfully effective — against parasites. The drug was such a breakthrough in the fight against tropical parasitic diseases that two scientists who studied it won the Nobel Prize in 2015.

The Food and Drug Administration has approved ivermectin tablets to treat certain parasitic infections, and the agency has authorized ivermectin lotions to kill lice and creams to help with rosacea. Veterinarians also use the drug to prevent and treat parasitic diseases in animals.

. . .

Studies in human cells suggest that the drug may kill certain types of cancer cells in a way that triggers the immune system, said Dr. Peter P. Lee, chair of the department of immuno-oncology at Beckman Research Institute of City of Hope in Duarte, Calif. In mouse studies, Dr. Lee has seen that the drug, on its own, does not shrink breast tumors. But it’s possible that the drug may have benefits for breast cancer when used alongside existing cancer immunotherapy, he said. Researchers are studying a combination of ivermectin and an investigational cancer drug in people with breast cancer.

While some inaccurate social media posts claim that ivermectin can treat cancer because tumors themselves are parasitic, the promise of ivermectin for cancer has nothing to do with its anti-parasitic effect, Dr. Lee said. Rather, it seems that the drug may be able to modulate a signal involved with cancer growth.

But doctors still need larger, randomized clinical trials to better understand whether ivermectin could treat cancer. Just because a drug seems to work in animals doesn’t mean those results will translate into real-world outcomes, Dr. Johnson noted. There are “hundreds of medications that look to be promising in a preclinical setting” every year, he said, adding, “The vast majority of those will never be shown to be effective in humans.”

. . .

Doctors generally view ivermectin as safe at the doses prescribed to treat parasitic infections.

For the full story, see:

Dani Blum. “What Ivermectin Can and Can’t Do, and What the Dangers Are.” The New York Times (Tues., April 1, 2025): A21.

(Note: ellipses added.)

(Note: the online version has the date March 31, 2025, and has the title “What Ivermectin Can (and Can’t) Do.” In the first quoted sentence, the print version says “no evidence” and the online version says “not evidence.”)

The Blum article that I just quoted and cited, is a secondary companion article to a longer front-page article, also on ivermectin:

Richard Fausset. “No Evidence for Healing Powers, but ‘Tastes Like Dead Cancer’.” The New York Times (Tues., April 1, 2025): A1 & A21.

(Note: the online version has the date March 31, 2025, and has the title “Why the Right Still Embraces Ivermectin.”)

The paper cited below reviewed the published scientific literature as of 2020 on the mechanisms through which ivermectin could have anti-cancer effects, finding 24 articles documenting one or more mechanisms.

Tang, Mingyang, Xiaodong Hu, Yi Wang, Xin Yao, Wei Zhang, Chenying Yu, Fuying Cheng, Jiangyan Li, and Qiang Fang. “Ivermectin, a Potential Anticancer Drug Derived from an Antiparasitic Drug.” Pharmacological Research 163 (Jan. 2021): 105207.

Tang and co-authors are optimistic in their summary section quoted below. [In this quote IVM is “ivermectin” and MDR is “multidrug resistance”.]

. . ., the broad-spectrum antiparasitic drug IVM, which is widely used in the field of parasitic control, has many advantages that suggest that it is worth developing as a potential new anticancer drug. IVM selectively inhibits the proliferation of tumors at a dose that is not toxic to normal cells and can reverse the MDR of tumors. Importantly, IVM is an established drug used for the treatment of parasitic diseases such as river blindness and elephantiasis. It has been widely used in humans for many years, and its various pharmacological properties, including long- and short-term toxicological effects and drug metabolism characteristics are very clear. (Tang et al. Jan. 2021, pp. 7-8)

The paper cited below reviewed the published scientific literature as of 2019 on the effect of mebendazole on cancer, and found 26 in vitro studies showing anti-cancer biological effects, 14 in vivo studies showing anti-tumor effects, and six Phase 1 or Phase 2 clinical trials listed in ClinicalTrials.gov.

Guerini, Andrea Emanuele, Luca Triggiani, Marta Maddalo, Marco Lorenzo Bonù, Francesco Frassine, Anna Baiguini, Alessandro Alghisi, Davide Tomasini, Paolo Borghetti, Nadia Pasinetti, Roberto Bresciani, Stefano Maria Magrini, and Michela Buglione. “Mebendazole as a Candidate for Drug Repurposing in Oncology: An Extensive Review of Current Literature.” Cancers 11, no. 9 (Aug. 2019): article #1284.

Gary Taubes’s book, praised by Marty Makary and Siddhartha Mukherjee, and mentioned by me near the end of my commentary, is:

Taubes, Gary. Rethinking Diabetes: What Science Reveals About Diet, Insulin, and Successful Treatments. New York: Knopf, 2024.

[I thank Ivette Locay for sending me a link useful for my commentary.]

Mark Twain “Dared to State Things That Others Only Thought”

I have read three of Ron Chernow’s massive biographies, the ones on Rockefeller, Washington, and Hamilton. Because they are massive, reading them takes a long time, at least for a slow reader like me. But I learned a lot that is important or useful from them, especially the ones on Rockefeller and Hamilton. Because I am an admirer of both Chernow and Twain, I look forward to also reading Chernow’s biography of Twain.

(p. C7) More than a century after his death, Mark Twain remains one of the most recognizable voices in American literature—the author of “The Adventures of Tom Sawyer” (1876), “Life on the Mississippi” (1883) and “Adventures of Huckleberry Finn” (1884), the latter among the most consequential novels ever written in English and possibly (if you believe Ernest Hemingway) the source of American literature itself.

. . .

In his biography of the famed satirist, Ron Chernow tracks, with patience and care, Twain’s journey over nearly eight tumultuous decades. Mr. Chernow’s tale is enlivened by blazing quotes from Twain’s prodigious interviews, diaries and letters.  . . .  The quotes tend to burn a hole in the page, and it’s difficult for a biographer to recover. Mr. Chernow, whose lives of George Washington, Alexander Hamilton and Ulysses S. Grant are revered for their sound scholarship, clear writing and strong narrative drive, weaves Twain’s sizzling remarks almost seamlessly into his own narrative.

We watch as Twain lunges from coast to coast, rolling up and down the Mississippi (as a riverboat pilot in his early days), moving from country to country, writing books and articles, investing large sums in various hair-brained schemes.

. . .

This was, in Twain’s own phrase, the Gilded Age. He admired, even idealized, those who made huge sums of money through their entrepreneurial energy and acumen. He had the same energy, but he didn’t have the right vehicles for speculation nor the business sense to make his investments pay off. As Mr. Chernow observes, Twain could well have enjoyed an easy life of writing and giving lectures, having married a wealthy woman and published several bestsellers. “Instead, he had started a publishing house and financed a typesetter”—the Paige Compositor, which was supposed to replace manual typesetting but failed spectacularly because of engineering flaws—“before he had the expertise or requisite fortune to bring them to completion.” His expenses soon dwarfed his income and he was forced to abandon his Hartford mansion, never to return.

. . .

Twain was “a man who professed to be chronically lazy,” says Mr. Chernow, yet he left behind him a vast portfolio of writings that included 30 books, several thousand magazine articles and some 12,000 letters. “Mark Twain had not only moved people to laughter and tears with his books,” Mr. Chernow writes, “but had challenged them with unorthodox views as he ventured out from his safe cubbyhole as the avuncular humorist. He had dared to state things that others only thought.” It’s because of this bravery, and his peerless gift for expression, that we still value him and will never stop reading his books, which never grow old.

For the full review see:

Jay Parini. “A Most American Writer.” The Wall Street Journal (Saturday, May 10, 2025): C7.

(Note: ellipses added.)

(Note: the online version of the review has the date May 9, 2025, and has the title “‘Mark Twain’: The Most American Writer.”)

The book under review is:

Chernow, Ron. Mark Twain. New York: The Penguin Press, 2025.

Vinyl LP Records Have Been Mostly Replaced, but in Kansas Not Completely Destroyed

In my Openness book, I argue that Schumpeter’s phrase “creative destruction” misleads by overemphasizing the extent of destruction in the process of breakthrough innovation, so I prefer to call the process “innovative dynamism.” A new innovation is often better than the old in many, but not all, traits. A minority of people who put heavy weight on the traits where the old product is better, will still prefer the old product. If the minority is large enough, and willing to pay enough for their preference, then there will be enough demand for the old product to remain in production, rather than be fully replaced (i.e., destroyed).

Illustrating my point, The New York Times ran two full pages on Chad Kassem, a Kansas entrepreneur who is working hard, with some success, at making higher quality vinyl LP records. He has 114 employees and annual revenue of over $1 million.

He is even introducing incremental innovations to the old product: (p. 6) “Kassem hired veterans of the record-making business and indulged their ideas for modernizing a process that (p. 7) had barely changed since the 1970s. Among other innovations, they introduced computerized controls and found ways to regulate the fluctuating temperature of vinyl in the presses.”

The New York Times article is:

Ben Sisario. “In a Digital World, Pursuing an Ideal Of Perfect Vinyl.” The New York Times, Arts&Leisure Section (Sun., March 9, 2025): 6-7.

(Note: the online version of The New York Times article on the resilience of vinyl was updated March 7, 2025, and has the title “The Wizard of Vinyl Is in Kansas.”)

My book mentioned in my initial comments is:

Diamond, Arthur M., Jr. Openness to Creative Destruction: Sustaining Innovative Dynamism. New York: Oxford University Press, 2019.

Tim Friede’s “Daredevilry” in Taking 650 Venom Injections and 200 Poisonous Snake Bites to Help Create a Universal Antivenom “for Humanity”

Back during Covid, over 38,000 adults volunteered to participate in a “challenge” clinical trial of the new vaccines, but such trials were not allowed. In a challenge trial each participant receives the vaccine and then is exposed to the disease. Phase 3 trials for efficacy can be completed much more quickly, with many fewer participants, and at much lower costs, if the trials are “challenge” trials.

We allow people the freedom to dangerous actions for fun or excitement, or to help humanity, like Tim Friede (below) injecting snake venom and letting snakes bite him. Why then did we not allow challenge trials with the Covid vaccine?

Note on another issue, that the researchers are planning in their next step to test their antivenom on dogs who are bitten by snakes. This is a good example of my ideal use of dogs in medical research–where the trial aims at benefits for both the humans AND the dogs.

(p. A1) Over nearly 18 years, the man, Tim Friede, 57, injected himself with more than 650 carefully calibrated, escalating doses of venom to build his immunity to 16 deadly snake species. He also allowed the snakes — mostly one at a time, but sometimes two, . . . — to sink their sharp fangs into him about 200 times.

This bit of daredevilry (one name for it) may now help to solve a dire global health problem. More than 600 species of venomous snakes roam the earth, biting as many as 2.7 million people, killing about 120,000 people and maiming 400,000 others — numbers thought to be vast underestimates.

In Mr. Friede’s blood, scientists say they have identified antibodies that are capable of neutralizing the venom of multiple snake (p. A19) species, a step toward creating a universal antivenom, they reported on Friday [May 2, 2025] in the journal Cell.

“I’m really proud that I can do something in life for humanity, to make a difference for people that are 8,000 miles away, that I’m never going to meet, never going to talk to, never going to see, probably,” said Mr. Friede, who lives in Two Rivers, Wis., where venomous snakes are not much of a threat.

. . .

“This is a bigger problem than the first world realizes,” said Jacob Glanville, founder and chief executive of Centivax, a company that aims to produce broad-spectrum vaccines, and lead author on the study.

Dr. Glanville and his colleagues found that two powerful antibodies from Mr. Freide’s blood, when combined with a drug that blocks neurotoxins, protected mice from the venom of 19 deadly snake species of a large family found in different geographical regions.

This is an extraordinary feat, according to experts not involved in the work. Most antivenoms can counter the venom from just one or a few related snake species from one region.

The study suggests that cocktails of antitoxins may successfully prevent deaths and injuries from all snake families, said Nicholas Casewell, a researcher at the Liverpool School of Tropical Medicine in England.

. . .

There were other mishaps — accidental bites, anaphylactic shocks, hives, blackouts. Mr. Friede describes himself as a nondegree scientist, but “there’s no college in the world that can teach you how to do it,” he said. “I was doing it on my own as best I could.”

Two teams of scientists sampled Mr. Friede’s blood over the years, but neither project led anywhere. By the time he met Dr. Glanville, in 2017, he was nearly ready to give up.

Dr. Glanville had been pursuing what scientists call broadly acting antibodies as the basis for universal vaccines against viruses. He grew up in a Maya village in the Guatemala highlands, and became intrigued by the possibility of using the same approach for universal antivenom.

. . .

The researchers next plan to test the treatment in Australia in any dogs that are brought into veterinary clinics for snakebites. They are also hoping to identify another component, perhaps also from Mr. Friede’s blood, that would extend full protection to all 19 snake species that were subjects of the research.

Mr. Friede himself is done now, however. His last bite was in November 2018, from a water cobra. He was divorced — his wife and children had moved out. “Well, that’s it, enough is enough,” he recalled thinking.

He misses the snakes, he said, but not the painful bites. “I’ll probably get back into it in the future,” he said. “But for right now, I’m happy where things are at.”

For the full story see:

Apoorva Mandavilli. “Man of 200 Snake Bites May Be the Antivenom.” The New York Times (Saturday, May 3, 2025): A1 & A19.

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

(Note: the online version of the story has the date May 2, 2025, and has the title “Universal Antivenom May Grow Out of Man Who Let Snakes Bite Him 200 Times.”)

The academic article in the journal Cell mentioned above is:

Glanville, Jacob, Mark Bellin, Sergei Pletnev, Baoshan Zhang, Joel Christian Andrade, Sangil Kim, David Tsao, Raffaello Verardi, Rishi Bedi, Sindy Liao, Raymond Newland, Nicholas L. Bayless, Sawsan Youssef, Ena S. Tully, Tatsiana Bylund, Sujeong Kim, Hannah Hirou, Tracy Liu, and Peter D. Kwong. “Snake Venom Protection by a Cocktail of Varespladib and Broadly Neutralizing Human Antibodies.” Cell 188 (2025): 1-18.

Democratic Donor Warren Buffett Praises DOGE

(p. A1) . . . at the end of Saturday’s Berkshire Hathaway annual meeting, the Oracle of Omaha dropped a bonbshell before a gathering of some 17,000 shareholders: that he’s set to step aside as Berkshire CEO, with vice chairman Abel taking his place.

. . .

(p. A4) It was little surprise that the very first question from moderator Becky Quick of CNBC in the Saturday [May 3, 2025] Q&A had to do with tariffs.

. . .

While critical of Trump’s tariffs, Buffett had little bad to say about Trump’s budget and program-slashing Department of Government Efficiency.

He called the current 7% gap between the federal government’s revenues and expenditures unsustainable. Whether that’s two or 20 years “it’s something that cannot go on forever,” he said. And if it isn’t brought under control, he said, it risks rampant inflation.

“I think it’s a job I don’t want, but it’s a job I think should be done, and Congress doesn’t seem to be doing it,” Buffett said.

For the full story, see:

Cordes, Henry J. “Buffett to Step Down as CEO of Berkshire.” Omaha World-Herald (Sunday, May 4, 2025): A1 & A4.

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

(Note: the online version of the article has the title “Warren Buffett stepping down as Berkshire Hathaway CEO at end of year; shareholders react.”)

A Rare Antibody in James Harrison’s Blood Protected the Lives of 2.4 Million Australian Babies

I recently purchased from Amazon, but have not read, Good Blood, which describes the discovery of a cure, and the struggle for acceptance of the cure, for the RH disease sketched in the passages quoted below. The disease affected my family, but I am not sure I remember exactly how. I am Rh positive and I think my mother was Rh negative. I think with each child after me, there was increasing risk and worry of possible bad health effects.

According to the Amazon summary for Good Blood, the book also describes the devotion of master blood donor James Harrison, whose recent obituary is quoted below.

Starting at least in the 1960s medical experts were often optimistic that future medical advances would come from designer chemicals enabled by scientific advances in our knowledge of chemistry and biological processes. Taxpayer funding was devoted to that approach in Nixon’s War on Cancer. But fewer medical advances have come from that approach than hoped, and more advances than expected have continued to come from the evolved usable chemicals (sometimes poisons, sometimes antibodies) of plants, animals, and exceptional human beings like Mr. Harrison.

Mao is often misquoted as saying ‘Let a thousand flowers bloom,’ but someone should say it (at least if the cost of planting the flowers is not too high).

(p. A25) James Harrison did not much care for needles. Whenever he donated plasma, he would look away as the tip went into his arm.

But Mr. Harrison was one of the most prolific donors in history, extending his arm 1,173 times. He may have also been one of the most important: Scientists used a rare antibody in his plasma to make a medication that helped protect an estimated 2.4 million babies in Australia from possible disease or death, medical experts say.

“He just kept going and going and going,” his grandson Jarrod Mellowship said in an interview on Monday [March 3, 2025]. “He didn’t feel like he had to do it. He just wanted to do it.”

. . .

Mr. Harrison’s plasma contained the rare antibody anti-D. Scientists used it to make a medication for pregnant mothers whose immune systems could attack their fetuses’ red blood cells, according to Australian Red Cross Lifeblood.

Anti-D helps protect against problems that can occur when babies and mothers have different blood types, most often if the fetus is “positive” and the mother is “negative,” according to the Cleveland Clinic. (The positive and negative signs are called the Rhesus factor, or Rh factor.)

In such cases, a mother’s immune system might react to the fetus as if it were a foreign threat. That can lead babies to develop a dangerous and potentially fatal condition, hemolytic disease of the fetus and newborn, which can cause anemia and jaundice.

. . .

In Australia, scientists from the Walter and Eliza Hall Institute of Medical Research in Melbourne are working to create a synthetic version of the drug using what some have called “James in a Jar,” an antibody that can be made in a lab.

But for now, human donors are essential: The anti-D shots are made with donated plasma, and Mr. Harrison was one of about 200 donors among the 27 million people in Australia, Lifeblood said.

. . .

Mr. Harrison knew the importance of his work firsthand. At 14, he needed a lot of blood transfusions during a major lung surgery. The experience inspired him to donate and encourage others to donate, too.

For the full obituary, see:

Amelia Nierenberg. “James Harrison, Whose Rare Antibodies Helped Millions, Is Dead at 88.” The New York Times (Saturday, March 8, 2025): A25.

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

(Note: the online version of the obituary was updated March 7, 2025, and has the title “James Harrison, Whose Antibodies Helped Millions, Dies at 88.”)

The Good Blood book, mentioned above, is:

Guthrie, Julian. Good Blood: A Doctor, a Donor, and the Incredible Breakthrough That Saved Millions of Babies. New York: Harry N. Abrams Press, 2020.