Category: Entrepreneurship

Innovative Entrepreneur Alfred Beach Privately Built and Operated America’s First Subway

Even classical liberals, strong supporters of free markets, often believe that utilities and mass transit need to be built and operated by governments. So I was delighted to learn from the book review quoted below that the first subway in the United States was privately built by a spirited innovative entrepreneur. That spirit still lives today, if we let it. (Ponder Travis Kalanick.)

(p. C9) In November 1869, the New York inventor Alfred Beach pushed the “move fast and break laws” principle to the limit in developing America’s first underground passenger railway. Without city approval—officials thought he was building a small system to improve mail delivery—he carved out a tunnel 8 feet wide, 300 feet long and right under Broadway.

. . .

Beach (1826-96) . . . was a remarkable character, a precocious innovator who channeled the forces—mass media and technological change—that were making the world modern. His father owned the New York Sun, the country’s most popular paper, and co-founded the Associated Press. Beach went to work for the Sun as a teenager; by 22 he was running it with his brother, and by 25 he sold his share to concentrate on his real passion: Scientific American, which he had bought a few years earlier. He and his partner made the publication a success and built a complementary business filing patents for the inventors who read it. When his client Thomas Edison “perfected the phonograph in 1877,” Mr. Algeo notes, he gave Beach the first demonstration, recording himself singing “Mary Had a Little Lamb.”

In 1849, when he was 23, Beach outlined in the magazine’s pages his vision of a railroad beneath Broadway, with two tracks, gas lights and stops on every corner. “The proposal was radical—the world’s first subway wouldn’t open in London for another fourteen years—and the technological hurdles were immense,” Mr. Algeo writes. The projected route involved a tunnel 20 times as long as the longest extant.

. . .

Beach . . . struggled to get approval for his plan, stymied by the interlocking corruption of Tammany bosses and real-estate interests. Elevated railways and other mass-transit rivals threatened in the meantime to crowd him out. When his railway finally did open, it lasted a mere three years, doomed by the financial crisis of 1873.

For the full review see:

Timothy Farrington. “Bookshelf; One Man’s Tunnel Vision.” The Wall Street Journal (Sat., Sept. 27, 2025): C9.

(Note: ellipses added.)

(Note: the online version of the review has the date September 25, 2025, and has the title “Bookshelf; ‘New York’s Secret Subway’: Tunnel Visions.”)

The book under review is:

Algeo, Matthew. New York’s Secret Subway: The Underground Genius of Alfred Beach and the Origins of Mass Transit. Washington, DC: Island Press, 2025.

Substrate Startup Develops Less Complex and Cheaper Way to Etch Computer Chips

To prepare for a workshop next week I have been reading a lot about Stuart Kauffman and Roger Koppl’s theory of the adjacent possible (TAP), as it is applied to the growth of technology. One of the implications of TAP is the that new technology gets progressively more complex, in the sense of using an ever larger number of components. I think that is often true but I can think of a couple of counter-examples. So I was interested to read yesterday that the production of computer chips may provide another counter-example.

(p. B1) In March [2025], James Proud, an unassuming British-born American without a college degree, sat in Vice President JD Vance’s office and explained how his Silicon Valley start-up, Substrate, had developed an alternative manufacturing process for semiconductors, one of the most fundamental and difficult challenges in tech.

For the past decade, semiconductors have been manufactured by a school-bus-size machine that uses light to etch patterns onto silicon wafers inside sterile, $25 billion factories. The machine, from the Dutch company ASML, is so critical to the chips in smartphones, A.I. systems and weaponry that Washington has effectively blocked sales of it to China.

But Mr. Proud said his company, which has received more than $100 million from investors, had developed a solution that would cut the manufacturing cost in half by channeling light from a giant instrument known as a particle accelerator through a tool the size of a car. The technique had allowed Substrate to print a high-resolution microchip layer comparable to images produced by the world’s leading semiconductor plants.

. . .

(p. B4) Mr. Proud moved to San Francisco from London in 2011 as a member of the first Thiel Fellowship class, a college alternative for aspiring founders created by Peter Thiel, the venture capitalist.

. . .

After the Trump administration persuaded TSMC to build a plant in Arizona, Mr. Proud decided to build his own company. He and his brother Oliver, 25, started reading books and academic papers on semiconductor lithography. They questioned why the process had become so complex and expensive.

One of the major costs in modern lithography machines, which have more than 100,000 parts, is how they use high-powered lasers to turn droplets of molten tin into a burst of extreme ultraviolet light. The machines use the light to etch a wafer of silicon in a process known as EUV lithography.

. . .

The team spent much of 2023 building a custom lithography tool. It featured thousands of parts and was small enough to fit in the back of a U-Haul. They tested it in computer simulations.

In early 2024, Substrate reserved a Bay Area particle accelerator for a make-or-break test. The company ran into problems when vibrations near the particle accelerator caused the tool to gyrate and blur the image, Mr. Proud said.

A frantic, daylong search found that the air-conditioning system was causing the vibration. Substrate adjusted the fan speed until the process printed “very beautiful and tiny things repeatedly” on a silicon wafer, Mr. Proud said.

For the full story see:

Tripp Mickle and Mike Kai Chen. “A Less Costly Route To Computer Chips?” The New York Times (Weds., Oct. 29, 2025): B1 & B4.

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

(Note: the online version of the story has the date Oct. 28, 2025, and has the title “Can a Start-Up Make Computer Chips Cheaper Than the Industry’s Giants?”)

We Need to “Tolerate Heterodox Smart People” if We Want to Achieve Big Things

Peter Thiel is often quoted as having said many years ago that “We wanted flying cars, instead we got 140 characters” (as quoted in Lewis-Kraus 2024), a reference to the original limit to the length of a tweet on Twitter. The quotations below are all from the more recent Peter Thiel, who was having a conversation with NYT columnist Ross Douthat. He still believes that we are not boldly pursuing big goals, the only exception being A.I. Is the constraint that big goals are impossible to achieve, or do we lack people smart enough or motivated enough to pursue them, or do we regulate motivated smart people into discouraged despair?

(p. 9) One question we can frame is: Just how big a thing do I think A.I. is? And my stupid answer is: It’s more than a nothing burger, and it’s less than the total transformation of our society. My place holder is that it’s roughly on the scale of the internet in the late ’90s. I’m not sure it’s enough to really end the stagnation. It might be enough to create some great companies. And the internet added maybe a few percentage points to the G.D.P., maybe 1 percent to G.D.P. growth every year for 10, 15 years. It added some to productivity. So that’s roughly my place holder for A.I.

It’s the only thing we have. It’s a little bit unhealthy that it’s so unbalanced. This is the only thing we have. I’d like to have more multidimensional progress. I’d like us to be going to Mars. I’d like us to be having cures for dementia. If all we have is A.I., I will take it.

. . .

And so maybe the problems are unsolvable, which is the pessimistic view. Maybe there is no cure for dementia at all, and it’s a deeply unsolvable problem. There’s no cure for mortality. Maybe it’s an unsolvable problem.

Or maybe it’s these cultural things. So it’s not the individually smart person, but it’s how this fits into our society. Do we tolerate heterodox smart people? Maybe you need heterodox smart people to do crazy experiments.

. . .

I had a conversation with Elon a few weeks ago about this. He said we’re going to have a billion humanoid robots in the U.S. in 10 years. And I said: Well, if that’s true, you don’t need to worry about the budget deficits because we’re going to have so much growth, the growth will take care of this. And then — well, he’s still worried about the budget deficits. This doesn’t prove that he doesn’t believe in the billion robots, but it suggests that maybe he hasn’t thought it through or that he doesn’t think it’s going to be as transformative economically, or that there are big error bars around it. But yeah, there’s some way in which these things are not quite thought through.

For the full interview, see:

Douthat, Ross. “Are We Dreaming Big Enough?” The New York Times, SundayOpinion Section (Sunday, June 29, 2025): 9.

(Note: ellipses added.)

(Note: the online version of the interview has the date June 26, 2025, and has the title “Peter Thiel and the Antichrist.”)

Peter Thiel’s yearning many years ago for flying cars was quoted more recently in:

Lewis-Kraus, Gideon. “Flight of Fancy.” The New Yorker, April 22, 2024, 28-39.

Nimble Wine Entrepreneurs Adapt Grapes, and Wine-Making Method, to Warmer Temperatures and Changing Tastes

I have argued briefly in my Openness book, and at greater length in my “Innovative Dynamism Improves the Environment” article, that we tend to overestimate the harm from global warming in part because we tend to underestimate the nimble adaptability of entrepreneurs. The essay quoted below describes how wine entrepreneurs in Spain are returning to old grape varieties and old technologies for aging the wine, varieties and technologies that both are better adapted to warmer temperatures and are better at making the lighter and less alcoholic wines that are currently in higher demand.

(p. C3) In the rolling hills of Valencia in Spain, winemaker Pablo Calatayud has joined forces with scientists and archaeologists to mount a small viticultural revolution—one that reaches back to pre-Roman times to recreate what have become known as ancestral wines.

At his Celler del Roure, Calatayud is using large, egg-shaped clay amphorae to make wine pressed from grapes native to the region. The process is reconstructed from old texts and drawings carved into archaeological finds across the Mediterranean, including an ancient Iberian settlement that overlooks his own vineyard.

This sort of winemaking is not just a stunt, and Calatayud is hardly alone. Rising temperatures in most European wine regions are changing the taste and potency of red wine. Warmer weather means that grapes ripen more quickly and more intensely, with more sugar and thus more alcohol. In Spain, the alcohol level in notable wines aged in oak barrels now routinely exceeds 15%. But many consumers are turning away from such dark, heavy, tannin-rich wines, demanding instead reds that are lighter, more refreshing and lower in alcohol.

The grape varieties used to make ancestral wines are better suited to warmer climes than such stars of modern winemaking as Cabernet Sauvignon, Merlot and Tempranillo. The ancient varieties tend to ripen later, some even in late October, with lower sugar levels, and some have thinner skins, which makes them less tannic.

And in contrast to the oak barrels favored for aging modern red wines, which can add heavy, smoky flavors, amphorae don’t affect a wine’s taste. The clay allows for gentle micro-oxygenation—exposure to outside air—helping to preserve acidity and aromatic freshness.

As a result, the new amphora wines are breezy, light-colored and fruity on the nose—but never sweet nor exceeding 13% alcohol.

The results have pleased both critics and consumers. Wines by Celler del Roure now receive ratings as high as 96 points from top reviewers like Robert Parker Wine Advocate and are exported globally, including to the U.S.

For the full essay, see:

Bojan Pancevski. “The Growing Buzz Around Ancestral Wines.” The Wall Street Journal (Sat., July 19, 2025): C3.

(Note: the online version of the essay has the date July 17, 2025, and has the same title as the print version.)

Norma Swenson Defended Health Freedom for Women

A recurring question raised by my libertarian and classical liberal friends is: how can we persuade others of the value of freedom? One answer is to especially seek conversation with those who strongly object to losing their freedom in some part of their life that they value. As I read the obituary of Norma Swenson, co-author of the book Our Bodies, Ourselves, I thought I recognized her as a libertarian fellow-traveler. She passionately sought for herself and other women to have greater freedom in making their own medical decisions.

Today, born out of outrage over the government’s over-reaching Covid controls, a “health freedom” movement has grown and organized, seeking more broadly (though not always consistently) for all adults to be able to make their own medical decisions.

Libertarians and classical liberals should let those seeking health freedom know that we are with them, in principle and in practice. Many of my own blog entries defend health freedom, for instance here and here.

(p. B11) Norma Swenson was working to educate women about childbirth, championing their right to have a say about how they delivered their babies, when she met the members of the collective that had put out the first rough version of what would become the feminist health classic “Our Bodies, Ourselves.”

. . .

She . . . [knew] quite a bit about the medical establishment, the paternalistic and condescending behavior of male doctors (only 6 percent of incoming medical students were women in 1960) and the harmful effect such behavior had on women’s health. She had lived it, during the birth of her daughter in 1958.

. . .

She would go on to help make “Our Bodies, Ourselves” a global best seller.

. . .

The author Barbara Ehrenreich called it a manifesto of medical populism.

. . .

It was her daughter’s birth that had made Ms. Swenson an activist. She wanted to deliver the baby naturally, without medication. Her decision was such an anomaly that residents at the Boston Lying-In Hospital gathered to watch her labor. It went swimmingly.

But Ms. Swenson, who was in a 12-bed ward, was surrounded by women who were suffering. They were giving birth according to the practices of the era: with a dose of scopolamine, a drug that induced so-called twilight sleep and hallucinations, followed by a shot of Demerol, an opioid.

She remembered the women screaming, trying to climb out of their beds, calling for their mothers and cursing their husbands before being knocked out by the Demerol, their babies delivered by forceps.

It was barbaric, she thought. “These women weren’t being helped,” she said in 2018, “they were being controlled.”

For the full obituary, see:

Penelope Green. “Norma Swenson, 93, an Author Of ‘Our Bodies, Ourselves.” The New York Times (Friday, June 20, 2025): B11.

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

(Note: the online version of the obituary was updated June 16, 2025, and has the title “Norma Swenson, an Author of ‘Our Bodies, Ourselves,’ Dies at 93.”)

The most recent edition of the book co-authored by Norma Swenson is:

Boston Women’s Health Book Collective. Our Bodies, Ourselves. New York: Atria Books, 2011.

F.D.A. Approves Vertex’s Nonaddictive Drug to Block Pain

Ann Case and Angus Deaton’s Deaths of Despair is a depressing but important book. I have read parts of it but plan to read it from cover to cover soon. They document and analyze a substantial group of Americans, mostly whites without college degrees, who die from alcohol, narcotics, or suicide. Starting in the 1990s their numbers grew. Part of the problem for some of the despairing is having jobs that give them hope for a better future, jobs that at least allow them to securely start and raise a family.

The growth in narcotics use is thoughtfully described in an earlier book, Dreamland by Sam Quinones. In some of the book Quinones writes about the same non-degree despairing whites as Case and Deaton, but he also in other parts of the book, discusses rising narcotics use among the better-off. His is a thoughtful complex narrative, involving diverse victims and diverse causes.

One component is that, from desire for euphoria, or to end pain, people start using narcotics that are addictive. Then they must fight, or succumb to, the addiction for the rest of their lives. For those drawn in by a desire to end pain, the news in the passages quoted below is important–the approval of suzetrigine, a drug that blocks some kinds of pain without being addictive. Quinones in his 2015 book reports his conversation with an expert who was pessimistic that such a drug would ever be possible (pp. 311-312).

A second reason suzetrigine is of interest is that it is being brought to market by Vertex, a firm that I have discussed in earlier blog entries, most recently here. Vertex was a once-small innovative mission-oriented start-up that got big. The continuing question is whether the big Vertex can sustain its earlier innovative culture.

(p. A11) The Food and Drug Administration approved a new medication Thursday [Jan. 30, 2025] to treat pain from an injury or surgery. It is expensive, with a list price of $15.50 per pill. But unlike opioid pain medicines, it cannot become addictive.

That is because the drug, suzetrigine, made by Vertex Pharmaceuticals and to be sold as Journavx, works only on nerves outside the brain, blocking pain signals. It cannot get into the brain.

Researchers say they expect it to be the first of a new generation of more powerful nonaddictive drugs to relieve pain.

To test the drug, Vertex, which is based in Boston, conducted two large clinical trials, each with approximately 1,000 patients who had pain from surgery. They were randomly assigned to get a placebo; to get the opioid sold as Vicodin, a widely used combination pain medicine of acetaminophen (Tylenol) and hydrocodone; or to get suzetrigine.

. . .

Suzetrigine eased pain as much as the combination opioid. Both were better than the placebo at relieving pain.

For the full story see:

Gina Kolata. “F.D.A. Approves a Non-Addictive Opioid.” The New York Times (Sat., February 1, 2025): A11.

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

(Note: the online version of the story has the date Jan. 30, 2025, and has the title “F.D.A. Approves Drug to Treat Pain Without Opioid Effects.”)

The Case and Deaton book, cited in my introductory comments, is:

Case, Anne, and Angus Deaton. Deaths of Despair and the Future of Capitalism. Princeton, N.J.: Princeton University Press, 2020. Reprint, pb 2021 (with new preface).

The Quinones book, cited in my introductory comments, is:

Quinones, Sam. Dreamland: The True Tale of America’s Opiate Epidemic. New York: Bloomsbury Press, 2015.

“One Man’s Poison Is Another Man’s Cure”*

*The title “One Man’s Poison Is Another Man’s Cure” is a proverb that is widely attributed to the poet Lucretius. (I have not found a documented source.)

My commentary was posted on the Foundation for Economic Education (FEE) web site on Mon., Aug. 18, 2025.

Below are notes on sources supporting claims I make in the commentary.

https://www.1daysooner.org/ [website of group defending human challenge trials]

Attia, Peter. Outlive: The Science and Art of Longevity. New York: Harmony, 2023, pp. 78 & 84-86. [source of Attia’s views of rapamycin]

Bailey, Clifford J., and Caroline Day. “Metformin: Its Botanical Background.” Practical Diabetes International 21, no. 3 (April 2004): 115-17. [source on metformin]

Freeberg, Ernest. The Age of Edison: Electric Light and the Invention of Modern America, Penguin History American Life. New York: The Penguin Press, 2013, pp. 87 & 200-201. [source on electrification of New York faster than London]

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. https://www.cell.com/cell/abstract/S0092-8674(25)00402-7

Harrison, David E., Randy Strong, Zelton Dave Sharp, James F. Nelson, Clinton M. Astle, Kevin Flurkey, Nancy L. Nadon, J. Erby Wilkinson, Krystyna Frenkel, Christy S. Carter, Marco Pahor, Martin A. Javors, Elizabeth Fernandez, and Richard A. Miller. “Rapamycin Fed Late in Life Extends Lifespan in Genetically Heterogeneous Mice.” Nature 460, no. 7253 (July 16, 2009): 392-95. https://www.nature.com/articles/nature08221

Ineichen, Benjamin V., Eva Furrer, Servan L. Grüninger, Wolfgang E. Zürrer, and Malcolm R. Macleod. “Analysis of Animal-to-Human Translation Shows That Only 5% of Animal-Tested Therapeutic Interventions Obtain Regulatory Approval for Human Applications.” PLOS Biology 22, no. 6 (2024): e3002667. [The title is misleading because the main message of the article is that “Notably, our meta-analysis showed an 86% concordance between positive results in animal and clinical studies.” The authors further explain: “We conclude that, contrary to widespread assertions, the rate of successful animal-to-human translation may be higher than previously reported. Nonetheless, the low rate of final approval indicates potential deficiencies in the design of both animal studies and early clinical trials.” (The quotations are both from the Abstract on p. 1) (See also: “How can we make sense of the fact that animal studies and early clinical trials seem to show promise, yet there is very limited official approval for these therapies? There are 2 possible explanations: One scenario is that the strict requirements of RCTs and regulatory approval are causing many potentially valuable treatments to be left behind. The other scenario is that both animal studies and early clinical trials may have limitations in their design, such as a lack of proper randomization and blinding, which affects their internal validity [45].” p. 12 https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3002667)]

Jewett, Christina. “Charlatans’ No Reason to Curb Untested Drugs, Kennedy Says.” The New York Times (Fri., June 6, 2025): A1 & A11. https://www.nytimes.com/2025/06/05/health/kennedy-stem-cells-experimental-treatments.html?searchResultPosition=1

Kinch, Michael. Between Hope and Fear: A History of Vaccines and Human Immunity. New York: Pegasus Books, 2018, pp. 33-34. [one source on Jesty]

Mandavilli, Apoorva. “Man of 200 Snake Bites May Be the Antivenom.” The New York Times (Sat., May 3, 2025): A1 & A19. https://www.nytimes.com/2025/05/02/health/snakes-universal-antivenom-tim-friede.html?searchResultPosition=1

Mannick, Joan B., Giuseppe Del Giudice, Maria Lattanzi, Nicholas M. Valiante, Jens Praestgaard, Baisong Huang, Michael A. Lonetto, Holden T. Maecker, John Kovarik, Simon Carson, David J. Glass, and Lloyd B. Klickstein. “mTOR Inhibition Improves Immune Function in the Elderly.” Science Translational Medicine 6, no. 268 (2014): doi:10.1126/scitranslmed.3009892. https://www.science.org/doi/abs/10.1126/scitranslmed.3009892?__hsfp=1773666937&__hstc=12316075.81f04695664b9dc054b5f524eb53b5a4.1525132803174.1525132803175.1525132803176.1&__hssc=12316075.1.1525132803177

Morgan, Kate. “Vaccine Protesters Find Winning Slogan: ‘Health Freedom.” The New York Times (Weds., Jan. 1, 2025): A11. https://www.nytimes.com/2024/12/28/well/health-freedom-medical-freedom-covid.html?searchResultPosition=1

Smith, Dana G. “Is the Secret to a Longer Life Hidden in a Transplant Drug?” The New York Times (Weds., Sept. 25, 2024): A1 & ?. https://www.nytimes.com/2024/09/24/well/live/rapamycin-aging-longevity-benefits-risks.html

Subbaraman, Nidhi. “A Universal Antivenom, from a Man Bitten by Snakes 200 Times.” The Wall Street Journal (Sat., June 14, 2025): C5. https://www.wsj.com/science/biology/snake-bite-blood-universal-antivenom-6de30fda?mod=Searchresults_pos1&page=1

Whiteman, Noah. Online notes to accompany Most Delicious Poison: The Story of Nature’s Toxins―from Spices to Vices. New York: Little, Brown Spark, 2023. [source of claim that 40% of drugs come from traditional medicine]

Zuckerman, Gregory. A Shot to Save the World: The inside Story of the Life-or-Death Race for a Covid-19 Vaccine. New York: Portfolio/Penguin, 2021, pp. 5-6. [one source on Jesty]

Brigham and Epstein Have the Guts to Nudge the Overton Window

The Overton Window is the range of “officially acceptable” or “politically correct” policy views. The left has been successful at shifting the window in their direction, for instance, in cancelling those who question any aspect of the global warming ideology for being outside polite discourse. In the face of cancel culture it takes courage to challenge the current Overton Window. Brigham and Epstein (see below) have that courage. Their views should be considered.

(p. B12) Exxon Mobil, Occidental Petroleum and other oil giants are expected to receive billions of dollars of incentives to collect and bury carbon emissions. Texas oil billionaire Ben “Bud” Brigham and pro-fossil-fuels activist Alex Epstein want to turn off the tap.

Brigham, a serial entrepreneur and libertarian from Austin, is urging President Trump and the Republicans who are considering slashing a host of energy incentives to go further and nix tax credits for carbon capture.

. . .

Brigham says he doubts carbon capture can be profitable without public funding and that it is a distraction from firms’ core mission of finding oil and gas. He says that the subsidies distort markets and encourage cronyism.

A geophysicist by training, Brigham made his fortune building and selling two oil companies for a total of about $7 billion. He is an Ayn Rand fan who has produced two movies based on the philosopher’s work. He was also a major backer of what is now the Civitas Institute, a conservative center that launched in 2022 at the University of Texas at Austin.

Brigham first met Epstein, another Rand fan, about a decade ago. The two men bonded over a common belief in the importance of free markets and fossil fuels. Epstein is the author of “The Moral Case for Fossil Fuels,” a book saying that the imperative to fuel societies flourishing with oil and gas outweighs climate-change risks. It has given Republicans ammunition to counter the left’s climate push, oil lobbyists say.

For the full story, see:

Benoît Morenne. “Oil Tycoon, Philosopher Fight Carbon-Capture Goals.” The Wall Street Journal (Tues., July 1, 2025): B12.

(Note: ellipsis added.)

(Note: the online version of the story has the date June 28, 2025, and has the title “The Oil Tycoon and the Philosopher Threatening Big Oil’s Bet on Carbon Capture.”)

Epstein’s book, mentioned above, is:

Epstein, Alex. The Moral Case for Fossil Fuels. New York: Portfolio, 2014.

Father Spends 20 Years Researching to Cure His Children’s Type 1 Diabetes

The development of a new drug to cure Type 1 diabetes is big news, a triumph of medicine. The process of developing the medicine and bringing it to market interests me for several reasons. One is that Doug Melton spent 20 years of effort on it. His passion was due to having skin in the game: he has two children with the disease. Another is that it took so many years “of painstaking, repetitive, frustrating work.” I emphasize the common importance of trial-and-error in many major medical discoveries. Another is that the trial-and-error was to develop a “chemical cocktail to turn stem cells into islet cells.” Several major medical advances have required nimble and persistent trial-and-error to adjust drug cocktails, in terms of components and doses. Examples include HIV, Hodgkin’s lymphoma, and childhood leukemia.

A final reason I am interested in the case is that Melton selected the Vertex company to bring the drug to market. Vertex is an interesting case of a large firm struggling to keep the innovative culture of its startup roots. I read a book about its struggles called The Antidote. I intend to read an earlier book about its early years called The Billion Dollar Molecule.

(p. 17) A single infusion of a stem cell-based treatment may have cured 10 out of 12 people with the most severe form of type 1 diabetes. One year later, these 10 patients no longer need insulin. The other two patients need much lower doses.

The experimental treatment, called zimislecel and made by Vertex Pharmaceuticals of Boston, involves stem cells that scientists prodded to turn into pancreatic islet cells, which regulate blood glucose levels. The new islet cells were infused and reached the liver, where they took up residence.

The study was presented Friday evening [June 20, 2025] at the annual meeting of the American Diabetes Association and published online by The New England Journal of Medicine.

“It’s trailblazing work,” said Dr. Mark Anderson, professor and director of the diabetes center at the University of California in San Francisco. “Being free of insulin is life changing,” added Dr. Anderson, who was not involved in the study.

. . .

The treatment is the culmination of work that began more than 25 years ago when a Harvard researcher, Doug Melton, vowed to find a cure for type 1 diabetes. His 6-month-old baby boy developed the disease and, then, so did his adolescent daughter. His passion was to find a way to help them and other patients.

He began, he said, with an “unwavering belief that science can solve the most difficult problems.”

It took 20 years of painstaking, repetitive, frustrating work by Dr. Melton and a team of about 15 people to find the right chemical cocktail to turn stem cells into islet cells. He estimated that Harvard and others spent $50 million on the research.

Dr. Peter Butler, a professor of medicine at the University of California, Los Angeles and a consultant to Vertex, said he was awed by the achievement of the Harvard team.

“The fact that it worked at all is just freaking amazing to me,” he said. “I can guarantee there were a thousand negative experiments for every positive one.”

When Dr. Melton finally succeeded, he needed a company to take the discovery into the clinic. He joined Vertex, which took up the challenge.

For the full story see:

Gina Kolata. “People With Severe Diabetes May Have Been Cured in a Small Trial of a New Drug.” The New York Times, First Section (Sun., June 22, 2025): 17.

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

(Note: the online version of the story was updated June 21, 2025, and has the title “People With Severe Diabetes Are Cured in Small Trial of New Drug.” The online version says that the article appeared on page 24 of the New York edition of the print version. But the article appeared on page 17 of my National edition.)

The NEJM academic article co-authored by Melton and mentioned above is:

Reichman, Trevor W., James F. Markmann, Jon Odorico, Piotr Witkowski, John J. Fung, Martin Wijkstrom, Fouad Kandeel, Eelco J.P. de Koning, Anne L. Peters, Chantal Mathieu, Leslie S. Kean, Bote G. Bruinsma, Chenkun Wang, Molly Mascia, Bastiano Sanna, Gautham Marigowda, Felicia Pagliuca, Doug Melton, Camillo Ricordi, and Michael R. Rickels. “Stem Cell–Derived, Fully Differentiated Islets for Type 1 Diabetes.” The New England Journal of Medicine (published online on June 20, 2025), DOI: 10.1056/NEJMoa2506549.

The books that I mentioned about Vertex are:

Werth, Barry. The Antidote: Inside the World of New Pharma. New York: Simon & Schuster, 2014.

Werth, Barry. The Billion-Dollar Molecule: One Company’s Quest for the Perfect Drug. New York: Simon & Schuster, 1994.

Jarvik’s Father’s Heart Disease Drove Him to Persist in Developing First Permanent Artificial Heart

Robert Jarvik had skin in the game, had a sense of urgency, with his father suffering from severe heart disease. And he understood that the usual path toward an eventual breakthrough, is to keep “working it through so it can be better.”

(p. B10) Dr. Robert K. Jarvik, the principal designer of the first permanent artificial heart implanted in a human — a procedure that became a subject of great public fascination and fierce debate about medical ethics — died on Monday [May 26, 2025] at his home in Manhattan. He was 79.

. . .

In a 1989 interview with Syracuse University Magazine, Dr. Jarvik admitted that his belief that the Jarvik-7 was advanced enough to be used widely on a permanent basis was “probably the biggest mistake I have ever made.”

Still, he defended his work. Of the five recipients of the permanent Jarvik-7, he told the magazine, “These were people who I view as having had their lives prolonged,” adding that they survived nine months on average when some had been expected to live “no more than a week.”

“I don’t think that kind of thing makes a person in medicine want to stop,” he said. “It just makes you all the more interested in working it through so it can be better.”

. . .

From an early age, Robert was a tinkerer. As a teenager, he made his own hockey mask and began developing a surgical stapler. He attended Syracuse University from 1964 until 1968, intending to study architecture, but his interest turned to medicine after his father survived an aortic aneurysm, and he received a degree in zoology. Dr. Norman Jarvik died in 1976 after a second aneurysm.

“I knew that my father was going to die of heart disease, and I was trying to make a heart for him,” Robert Jarvik once said. “I was too late.”

. . .

According to a 2023 study of the artificial heart market, a descendant of the original Jarvik-7, now owned by another company, is called the SynCardia Total Artificial Heart. It is designed primarily for temporary use in patients who face imminent death while awaiting transplants. The study found that the device had been implanted in more than 1,700 patients worldwide.

For the full obituary, see:

Jeré Longman. “Robert Jarvik, a Designer of the First Artificial Heart, Is Dead at 79.” The New York Times (Friday, May 30, 2025): B10.

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

(Note: the online version of the obituary has the date May 29, 2025, and has the title “Robert Jarvik, 79, Dies; a Designer of the First Permanent Artificial Heart.”)

Electricity May Be a Pellet in the “Magic Buckshot” Against Cancer

In a recent entry I claimed that the cure for many diseases may not be Paul Ehrlich’s one “magic bullet” but may instead be “magic buckshot.” A recent article in The Wall Street Journal suggests that one pellet in the magic buckshot against cancer is electricity. As proof of concept, the article claims that after surgery, radiation, and chemotherapy for a glioblastoma brain cancer, adding electrodes to the skull that deliver low-intensity electricity to the brain, will add a median of 4.9 months to the patient’s lifespan.

The Wall Street Journal article mentioned above is:

Brianna Abbott. “Next Hope in Treating Cancer: Electricity.” The Wall Street Journal (Tues., May 20, 2025): A10.

(Note: the online version of the article has the date May 16, 2025, and has the title “The Next Frontier to Treat Cancer: Electricity.”)

The Wall Street Journal article links to the following article in JAMA:

Stupp, Roger, Sophie Taillibert, Andrew Kanner, William Read, David M. Steinberg, Benoit Lhermitte, Steven Toms, Ahmed Idbaih, Manmeet S. Ahluwalia, Karen Fink, Francesco Di Meco, Frank Lieberman, Jay-Jiguang Zhu, Giuseppe Stragliotto, David D. Tran, Steven Brem, Andreas F. Hottinger, Eilon D. Kirson, Gitit Lavy-Shahaf, Uri Weinberg, Chae-Yong Kim, Sun-Ha Paek, Garth Nicholas, Jordi Bruna, Hal Hirte, Michael Weller, Yoram Palti, Monika E. Hegi, and Zvi Ram. “Effect of Tumor-Treating Fields Plus Maintenance Temozolomide Vs Maintenance Temozolomide Alone on Survival in Patients with Glioblastoma: A Randomized Clinical Trial.” JAMA 318, no. 23 (Dec. 19, 2017): 2306-16.