Category: Entrepreneurship

Welcome Immigrant Innovators

Empirical research by reputable economists at some top schools concludes that although “immigrants represent 16 percent of all US inventors . . . immigrants are responsible for 36% of aggregate innovation, two-thirds of which is due to their innovation externalities on their native-born collaborators” (Bernstein et al. 2022, p. 1). (I have not yet looked carefully at this research, but have looked at other papers by Rebecca Diamond (no relation), finding them important and well-done.)

We should make it easier for innovators to enter the United States and harder for murderers and thieves to enter. And whatever immigration rules we adopt, we should enforce. We are unfair to those who follow our immigration rules if we allow others to enter the United States without following our rules.

Beyond that, I think our rules can be fairly generous, even letting in many non-innovative immigrants, if at the same time we adopt policies that give a probable path forward to current Americans who are among the least well-off. In a working paper that I hope to return to soon, I argue that we can create this path forward by unbinding entrepreneurs so that they can create more and better jobs for the least well-off.

(I thank my former student and current friend Aaron Brown for alerting me to the article on immigration.)

The empirical research on immigrant innovators mentioned above is:

Bernstein, Shai, Rebecca Diamond, Abhisit Jiranaphawiboon, Timothy McQuade, and Beatriz Pousada. “The Contribution of High-Skilled Immigrants to Innovation in the United States.” National Bureau of Economic Research Working Paper #30797, December 2022.

My working paper mentioned above is:

Diamond, Arthur M., Jr. “Robustly Redundant Labor Markets.” Working Paper. 2021.

Innovative Medical Project Entrepreneur Karikó Long Persevered to Develop mRNA Technology Behind Covid-19 Vaccines

The basic science and technology behind mRNA did not come easy and did not come quick. If the skeptics of Covid-19 vaccines knew this they might be less skeptical because one of the reasons they sometimes give for their skepticism is the speed with which the vaccines were developed. (Other reasons for skepticism I think are more defensible, such as the worry that the authorities downplayed the real side-effects that some vaccine recipients suffered from the vaccines. But on balance I still think the vaccines were a great achievement.) One of the heroes of the long slog is Katalin Karikó. Part of her story is sketched in the passages quoted below. She is a good example of an innovative medical project entrepreneur. When she was named a winner of the Nobel Prize she identified part of what it takes to succeed: “we persevere, we are resilient” (Karikó as quoted in Mosbergen, Loftus, and Zuckerman 2023, p. A2).

(p. A2) The University of Pennsylvania is basking in the glow of two researchers who this week were awarded the Nobel Prize in medicine for their pioneering work on messenger RNA.

Until recently, the school and its faculty largely disdained one of those scientists.

Penn demoted Katalin Karikó, shunting her to a lab on the outskirts of campus while cutting her pay. Karikó’s colleagues denigrated her mRNA research and some wouldn’t work with her, according to her and people at the school. Eventually, Karikó persuaded another Penn researcher, Drew Weissman, to work with her on modifying mRNA for vaccines and drugs, though most others at the school remained skeptical, pushing other approaches.

. . .

. . . on Monday [Oct. 2, 2023], when Karikó and Weissman were awarded the Nobel, on top of prestigious science prizes in recent years, the school expressed a different perspective on their work.

The reversal offers a glimpse of the clubby, hothouse world of academia and science, where winning financial funding is a constant burden, securing publication is a frustrating challenge and those with unconventional or ambitious approaches can struggle to gain support and acceptance.

“It’s a flawed system,” said David Langer, who is chair of neurosurgery at Lenox Hill Hospital, spent 18 years studying and working at Penn and was Karikó’s student and collaborator.

. . .

Penn wasn’t the only institution to doubt Karikó’s belief in mRNA when many other scientists pursued a different gene-based technology. In a reflection of how radical her ideas were at the time, she had difficulty publishing her research and obtaining big grants—prerequisites for those hoping to get ahead in science and gain academic promotions.

Another reason her relationship with the school frayed: Karikó could antagonize colleagues. In presentations, she often was the first to point out mistakes in their work. Karikó didn’t intend to offend, she just felt the need to call out mistakes, she later said.

For the full story see:

Gregory Zuckerman. “Penn Toasts Winning Scientist After Shunning Her for Years.” The Wall Street Journal (Thursday, Oct. 5, 2023 [sic]): A2.

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

(Note: the online version of the story has the date October 4, 2023 [sic], and has the title “After Shunning Scientist, University of Pennsylvania Celebrates Her Nobel Prize.”)

The source of the Karikó quote in my opening comments is:

Dominique Mosbergen, Peter Loftus and Gregory Zuckerman. “Pair Met With Doubts, Now Win Nobel Prize.” The Wall Street Journal (Tuesday, Oct. 3, 2023 [sic]): A1-A2.

(Note: the online version of the story was updated October 2, 2023 [sic], and has the title “Pioneers of mRNA Find Redemption in Nobel Prize.”)

For more detailed accounts of Karikó’s life, struggles, and research see:

Karikó, Katalin. Breaking Through: My Life in Science. New York: Crown, 2023.

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.

A.I. May Create More and Better Jobs

In my Openness book, I made good use of The New Division of Labor book by Levy and Murnane that gave plentiful evidence that the innovative dynamism exemplified by the computer revolution on balance resulted in more and better jobs. The Levy/Murnane book is now over 20 years old, so the skeptical might question whether what was true about computers is also still true about artificial intelligence (A.I.). Now one of the book co-authors, Frank Levy, has co-authored a new working paper in which he answers “yes.” The working paper has recently been summarized by Steve Lohr.

Steve Lohr’s article is:

Steve Lohr. “A.I. Is Poised to Put Midsize Cities on the Map.” The New York Times (Mon., December 30, 2024): B1-B2.

(Note: the online version of the Steve Lohr article has the date Dec. 26, 2024, and has the title “How A.I. Could Reshape the Economic Geography of America.”)

The academic working paper co-authored by Frank Levy, that Lohr summarized in The New York Times article mentioned and cited above is:

Abrahams, Scott, and Frank S. Levy. “Could Savannah Be the Next San Jose? The Downstream Effects of Large Language Models.” In SSRN, June 23, 2024.

The book co-authored by Frank Levy and mentioned in my initial comments is:

Levy, Frank, and Richard J. Murnane. The New Division of Labor: How Computers Are Creating the Next Job Market. Princeton, NJ: Princeton University Press, 2004.

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.

Drugs for Dog Longevity May Also Aid Human Longevity

Dogs have long contributed to advances in human medicine. For instance C. Walton Lillehei experimented on dogs to develop his path-breaking human open-heart operations (see the book King of Hearts). What pains me about those dog contributions is that the dogs themselves died in the experiments. In the more recent dog contributions to human medicine, as discussed in the passages quoted below, the dogs themselves have a good chance to benefit as they contribute to human health. I like that a lot better.

(p. A11) In the quest to help people live longer, scientists and companies are turning to dogs.

. . .

Behind the growing enthusiasm is a mix of scientists and entrepreneurs—building on the surging interest from people aiming to live longer. These groups say insights into dog longevity could provide lessons and perhaps eventually treatments that could help people, too.

. . .

On Tuesday [Nov. 28, 2023], a biotech startup that’s hoping to have the first FDA-approved treatment to extend healthy lifespan in dogs, took a step toward that goal. In a letter viewed by The Wall Street Journal, the Food and Drug Administration affirmed that its drug had demonstrated “reasonable expectation of effectiveness.”

The company, called Loyal, still has to complete several more steps before it can market the drug, and it’s only aimed at canines.

. . .

Celine Halioua, chief executive of Loyal, the biotech startup working toward conditional approval of its lifespan drug, says there is a larger aim in addition to helping dogs live healthier for longer. The company has set a possible precedent for other drugs to be approved for lifespan extension, potentially opening a door for other animal—or human—drug companies to follow.

“I think we can both take the opportunity to build better medicines for our dogs and also to better understand these really complex diseases,” says Halioua, whose own 85-pound Rottweiler mix, Della, is nearing the end of her projected lifespan.

The firm’s drug is an injectable that is designed to reduce levels of IGF-1, a hormone that drives cell growth, in large dogs. High blood levels of IGF-1 have been associated with shorter lifespans in some animal and human studies.

The company’s research has indicated that the drug can reduce those hormone levels, but it would still need a large clinical trial demonstrating it can extend dog lifespans in order to achieve full FDA approval. It also needs the agency’s signoff on the drug’s safety and proper manufacturing before getting conditional approval and beginning to sell it, which Loyal hopes to do in 2026.

Still, the FDA nod this week is a promising next step for the field, dog aging researchers say, and will likely drive more interest from biotech and pharmaceutical companies.

“If it is proven that the drug is effective in dogs then there is a higher chance that it will work in the case of humans, too,” says Eniko Kubinyi, a biologist studying dog behavior and cognition with the Budapest-based Family Dog Project.

For the full story see:

Alex Janin. “Secrets of Anti-Aging, Gleaned From Dogs.” The Wall Street Journal (Thursday, Nov. 30, 2023 [sic]): A11.

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

(Note: the online version of the story has the date November 29, 2023 [sic], and has the title “The Clues to Longer Life That Are Coming From Dogs.” The last four paragraphs quoted above appeared in the more detailed online version, but not the print version, of the article. Some of the earlier quoted sentences are quoted in the longer form that appeared in the online version.)

The biography of Lillehei mentioned in my opening comments above is:

Miller, G. Wayne. King of Hearts: The True Story of the Maverick Who Pioneered Open Heart Surgery. New York: Crown, 2000.

Innovative Medical Project Entrepreneur Alan Scott “Coaxed” the F.D.A. to Approve Botox

Even though Alan Scott may have been a “lousy businessman,” he appears nonetheless to still have been an important innovative medical project entrepreneur. (I have not yet read the book discussed in the passages quoted below, but I hope to read it soon. Besides my admiration for innovative project entrepreneurs, an added reason that I am interested in the book is that I have always suffered from esophoria, which is one form of the strabismus that Alan Scott was trying to treat.)

(p. C9) Today botulinum toxin—purified, diluted and known as Botox—nets annual sales in the billions. It is used to treat everything from wrinkles to migraines, yet the pioneer largely responsible for fulfilling Kerner’s prophecy and bringing botulinum into medicine is virtually unknown. He was, it turns out, a laconic Bay Area ophthalmologist named Alan Scott, a self-described “lousy businessman” who barely recouped his own expenses as he coaxed the product to FDA approval.

Eugene Helveston seeks to rescue Scott from oblivion in “Death to Beauty,” a pandemic passion project and labor of love. As an ophthalmologist “of the same era,” Dr. Helveston knew Scott professionally and participated as a researcher in the original clinical trial of botulinum in the mid-1980s. Recognizing that only a few people were still around who could “tell the story firsthand,” Dr. Helveston resolved to document this medical history and corresponded with Scott from June 2021 until Scott’s death six months later, at age 89. The result is an absorbing insider’s account of an exceptional journey.

. . .

Scott was especially interested in strabismus, a disorder characterized by misaligned eyes. The condition was usually treated with surgery, with often disappointing results. Scott began to wonder if strabismus could be treated without surgery by injecting a substance that would weaken a specific eye muscle and thus help restore alignment. It was this line of research that led him to contemplate botulinum, which he requested and received from Schantz in 1972, delivered by the Postal Service in a sealed metal container. Fatefully, he reported promising results in animal models the next year without first filing a patent, which meant that his valuable intellectual property went unprotected.

To enable human testing, Scott submitted an application to the FDA in 1974; the document “lay on some FDA desk for almost four years,” he told Dr. Halversten, before a nudge from a colleague re-engaged the agency. Scott received testing authorization in 1978 and injected the first human subject with a low test dose to evaluate safety. There were no complications, and the trial proceeded.

. . .

Though Botox never gained much traction for the treatment of strabismus, the drug’s other uses lifted it to blockbuster status. Scott received only modest compensation for his foundational work, yet by all accounts he had no regrets. Allergan may have “got all the money,” he said, but “we had all the fun.”

For the full review see:

David A. Shaywitz. “Toning Up With a Toxin.” The Wall Street Journal (Saturday, Dec. 17, 2024): C9.

(Note: ellipses added.)

(Note: the online version of the review has the date February 9, 2024, and has the title “‘Death to Beauty’ Review: The Birth of Botox.”)

The book under review is:

Helveston, Eugene M. Death to Beauty: The Transformative History of Botox. Bloomington, IN: Indiana University Press, 2024.

Price Controls on Drugs Reduce Drug Innovation

Price controls on drugs may reduce some short-term healthcare costs for consumers, but will also reduce the innovation that brings us more cures, less pain, and fewer side effects. If we want to both reduce costs for consumers and increase innovation, we should end government mandates for the Phase 3 clinical trials–the phase of clinical trials that make up most of the cost of gaining regulatory approval.

(p. A19) The Biden White House has proposed requiring Medicare to “negotiate” drug prices.

. . .

Unfortunately, the debate is being informed by erroneous Congressional Budget Office analysis. CBO says . . . the supply of new drugs will only be reduced by 5% from 2021 to 2039, a loss of only two drugs a year.

The CBO minimizes the harmful effects on innovation, but the entire supply chain that funds medical R&D relies on rate-of-return assessments driven by future earnings. An analysis I released this week finds 10 times the effect on R&D, a loss of up to some 340 drugs over the same period.

The White House also claims that price controls won’t hamstring innovation because they only govern top-selling drugs. But the occasional blockbuster funds the roughly 90% of pipeline drugs that never pass Food and Drug Administration review. CBO even acknowledges that only the top 7% of Medicare drugs drive U.S. profits. Targeting financially successful drugs could make large segments of the development portfolio unprofitable, even if such drugs aren’t affected by price controls.

For the full commentary see:

Tomas J. Philipson. “Biden’s Price Controls Will Make Good Health More Expensive.” The Wall Street Journal (Thursday, Sept. 16, 2021 [sic]): A19.

(Note: ellipses added.)

(Note: the online version of the commentary has the date September 15, 2021 [sic], and has the same title as the print version.)

The research brief co-authored by Philipson and mentioned above is:

Philipson, Tomas J., and Troy Durie. “The Evidence Base on the Impact of Price Controls on Medical Innovation.” Issue Brief. Becker Friedman Institute, University of Chicago, Sept. 14, 2021.

Supporting Philipson’s argument is a 2024 working paper showing that Medicare-mandated price cuts in medical equipment has resulted in less innovation in medical equipment:

Ji, Yunan, and Parker Rogers. “The Long-Run Impacts of Regulated Price Cuts: Evidence from Medicare.” NBER Working Paper #33083, Oct. 2024.

The Lovable, Frustrating, Vulnerable “Big Easy”

Our daughter is a loyal Notre Dame graduate, so we went to New Orleans for the Sugar Bowl game, scheduled for January 1, but ultimately played on January 2. The day before the scheduled game, we were in Jackson Square on New Year’s Eve for the countdown to 2025. For us a little partying goes a long way, so we headed back to the Marriott about 12:30. About two and a half hours later, a couple of blocks from where we had been, the terrorist plowed his truck through the crowd, killing 14, and seriously injuring many more.

They call New Orleans “the Big Easy.” I appreciate its joy, its spontaneity, its libertarian tolerance. But I can only visit New Orleans, I cannot live there.

When I arrive in a hotel I want a glass of ice water. In our two most recent visits to Marriott hotels in New Orleans, the ice machines on our floor did not at first work. It never worked during our stay at the first hotel and worked only occasionally at the second hotel. When I complained at the first hotel, I got a joyful grin and a shrug–the ice machine had been that way for several days and who knows when or if it would be fixed? It’s “easy” to celebrate; it’s hard to fix ice machines and keep them running.

There were barriers on Bourbon Street that could have kept the terrorist from killing 14. But it has come out that they were not working and it was not “easy” to fix them. (There were also supposed to be levies that could have reduced the damage from Hurricane Katrina, but it was not “easy” to fix them either.)

I like visiting New Orleans. I like its joyful spontaneity. But what makes New Orleans “the Big Easy” also makes it “the Big Frustrating” and “the Big Vulnerable.” I like visiting New Orleans but I want to live in a city where type-A personalities do what is hard: build, fix, and protect.

Regulations Discourage Search for Magic Bullet Cures

The so-called “Inflation Reduction Act” mandates that several of the biggest blockbuster drugs must have prices negotiated between Medicare and Pharma firms. As the commentary quoted below suggests, this creates an incentive for Pharma firms to develop many middling drugs rather than a couple of blockbuster drugs. Paul Ehrlich’s “magic bullet” may be impossible, but we will never know if no-one is trying to discover it.creates an

(p. B10) A true home run in the drug industry is when a company develops a mega-blockbuster that transforms its finances for years.

But with Medicare trying to bring costs down by targeting the industry’s most expensive drugs, a portfolio of medium-size moneymakers that can keep your name off the U.S. government’s naughty list can be a wise strategy.

That is at least one reason why big pharma is investing heavily in biotech companies developing antibody-drug conjugates. Known as ADCs, these treatments work like a guided missile by pairing antibodies with toxic agents to fight cancer. In short, they enable a more targeted form of chemotherapy that goes straight into the cancer cells while minimizing harm to healthy cells.

. . .

One reason most ADCs aren’t likely to become mega-blockbusters like Keytruda, a cancer immunotherapy that has earned 35 approvals across 16 types of cancer, is that they aren’t one-size-fits-all drugs. Instead, they are designed to target a specific protein that is expressed on the surface of a cancer cell. That means that each drug is made with an antibody targeting a subset of cancer. There are more than 100 ADCs being tested in humans by pharma and biotech companies.

For the full commentary see:

David Wainer. “Heard on the Street; Drug Industry’s Secret Weapon: ‘Guided Missiles’.” The Wall Street Journal (Friday, Oct. 27, 2023 [sic]): B10.

(Note: ellipsis added.)

(Note: the online version of the commentary has the date October 26, 2023 [sic], and has the title “Heard on the Street; ‘Guided Missile Drugs’ Could Be Big Pharma’s Secret Weapon.”)

Dislodging Entrenched Special Interests Requires the Courage to Be the Target of Ill-Will

Many years ago, for reasons I forget, I listened to an interview posted online with Charlie Munger, who for decades was Warren Buffett’s sidekick at Berkshire Hathaway. One portion of Munger’s comments struck me as particularly insightful, so insightful, that I replayed that portion several times so I could write down a rough transcript of the comments. I am posting that rough transcript a few paragraphs below.

A lot of progress in healthcare, and in the world more broadly, depends on individual heroes who have the courage to be the target of ill-will in order to champion truth and virtue, against the powerful special interests that benefit from falsehood and corruption. Those who speak out are often cancelled and have their careers ruined. We remember a few of the names of those who eventually were vindicated. For example Ignaz Semmelweis was cancelled by the medical establishment for arguing that doctors should wash their hands before delivering babies. He eventually was vindicated and remembered, though long after he died of a beating in an insane asylum. Several much-more-recent examples can be found in Marty Makary’s thought-provoking Blind Spots. (Makary has been named by President-Elect Trump to head the Food and Drug Administration.)

Those like Semmelweis who suffered but were vindicated, are painful to ponder. How much more painful to ponder are those who fought the good fight but were never vindicated, and so are utterly forgotten? We justly honor the unknown soldier. We should find a way to also justly honor the unknown speaker of truth to power.

I cringe at Donald Trump’s occasional rudeness and bullying, but I hope that his courage to be the target of ill-will, allow him to succeed in unbinding the entrepreneurs who create breakthrough innovations.

Below is my transcript of a small portion of Charlie Munger’s comments at the University of Michigan in 2010. My memory is that Munger made his comments in answers to expansive questions from Becky Quick as part of a celebration to honor Munger’s donations to the University of Michigan. Munger’s story below is from health care, but the moral from the story applies much more broadly. (Munger’s interest in health care led him to chair the board of trustees of Good Samaritan Hospital in Los Angeles for over 30 years.)

And so there’s a lot of abuse in health care. And one of the ways you fix it is to, is for the people who have the power, they exercise it to prevent the abuse.

In a lot of places you have live and let live, in the hospitals it’s live and let live, because nobody wants to criticize anybody. That’s a huge mistake, a huge mistake.

In our leading academic hospitals (I’m sure this isn’t happening in Michigan); [1:41:03 of recording] but I have a friend whose daughter is head of infectious diseases and something at a medical school hospital, a great hospital.

And of course the doctors there are fishing the patients out of nursing homes, and bringing them in so they can walk by the beds, and bill them. And they are bringing in these terrible infections. And that takes a lot of treatment, and a lot of walks by the bed, and so on, and so on.

Of course the parents of this particular doctor recognize that she is sort of risking her life going through medical school because of the abuse of the system by some of the doctors in a hospital where nobody is stopping the abuse.

It’s like Burke said, for evil to triumph in the world, all that is necessary is that good men do nothing. And all over America some people are intervening to stop some of these abuses. And, and you have to identify them; you have to rationalize them; you have to be willing to take the ill-will.

I have a friend, this is another wonderful story on human nature, chief of the medical staff, southern California hospital.

A bunch of non-board-certified anesthesiologists, who came out of, I forget the sub-branch of medicine; but it’s not, it’s not chiropractic, but it’s . . . anyway they got in control of the anesthesia department of the hospital.

[1:42 of recording]

And he could see that they had created three totally unnecessary deaths and had covered up every single one. And he knew that this was just gonna to ruin his life. So he got rid of them all. Changed the whole system. He ruined families, he ruined incomes, he cleaned house. And he told me the story 20 years later, and I said what happened. And he said, to this day none of the people I cleaned out and none of their friends has ever spoken to me. He was willing to take all that ill will to do the Lord’s work, and do it right.

And you can say, why did he wait for the third death? Maybe he felt he needed that much horror to accomplish the fix.

But all over America, there are stories like that. That’s a GOOD story about human nature. That’s a story about wisdom and virtue triumphing; and of course they don’t always win.

Even in a bull fight, the bull sometimes wins.

[1:44 of recording– relevant segment over]

The interview with Munger is:

Quick, Rebecca (interviewer). “A Conversation with Charlie Munger.” University of Michigan Ross School of Business, Sept. 14, 2010.

(Note: at three places in the recording I roughly indicate in brackets the time into the posted recording, in case anyone wants to watch the video and check the accuracy of my rough transcript. Let me know if you find an error.)

The Marty Makary book that I praise in my initial comments is:

Makary, Marty. Blind Spots: When Medicine Gets It Wrong, and What It Means for Our Health. New York: Bloomsbury Publishing, 2024.

“Epiphany” on a New Approach to Cure “Half of All Cancers”

Many health experts view immunotherapy as the most promising broad approach for curing cancers. Within the broad immunotherapy approach there are many sub-approaches–distinct approaches on how to activate the immune system against cancer. The article quoted below discusses a new sub-approach.

(p. D4) Within every cancer are molecules that spur deadly, uncontrollable growth. What if scientists could hook those molecules to others that make cells self-destruct? Could the very drivers of a cancer’s survival instead activate the program for its destruction?

That idea came as an epiphany to Dr. Gerald Crabtree, a developmental biologist at Stanford, some years ago during a walk through the redwoods near his home in the Santa Cruz mountains.

“I ran home,” he said, excited by the idea and planning ways to make it work.

Now, in a paper published Wednesday [July 26, 2023] in the journal Nature, Dr. Crabtree, a founder of Shenandoah Therapeutics, which is developing cancer drugs, along with Nathanael S. Gray, a professor of chemical and systems biology at Stanford, and their colleagues report that they have done what he imagined on that walk. While the concept is a long way from a drug that could be given to cancer patients, it could be a target for drug developers in the future.

. . .

In laboratory experiments with cells from a blood cancer, diffuse large B-cell lymphoma, the researchers designed and built molecules that hooked together two proteins: BCL6, a mutated protein that the cancer relies on to aggressively grow and survive, and a normal cell protein that switches on any genes it gets near.

. . .

BCL6, at one end of the dumbbell, guides the molecule toward cell-death genes that are part of every cell’s DNA and are used to get rid of cells that are no longer needed.

. . .

When the dumbbell, guided by BCL6, gets near the cell-death genes, the normal protein on the end of the dumbbell arms those death genes. Unlike other processes in the cell that can be reversed, turning on cell-death genes is irreversible.

. . .

The concept could potentially work for half of all cancers, which have known mutations that result in proteins that drive growth, Dr. Crabtree said. And because the treatment relies on the mutated proteins produced by the cancer cells, it could be extremely specific, sparing healthy cells.

For the full story see:

Gina Kolata. “A Key to Making Cancers Self-Destruct.” The New York Times (Tuesday, August 8, 2023 [sic]): D4.

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

(Note: the online version of the story was updated July 31, 2023 [sic], and has the title “Flipping a Switch and Making Cancers Self-Destruct.” Where the wording of the versions differs, the passages quoted above follow the online version.)

The academic article co-authored by Crabtree in Nature (published in July with an “issue date” of Aug. 10) and mentioned above is:

Gourisankar, Sai, Andrey Krokhotin, Wenzhi Ji, Xiaofan Liu, Chiung-Ying Chang, Samuel H. Kim, Zhengnian Li, Wendy Wenderski, Juste M. Simanauskaite, Haopeng Yang, Hannes Vogel, Tinghu Zhang, Michael R. Green, Nathanael S. Gray, and Gerald R. Crabtree. “Rewiring Cancer Drivers to Activate Apoptosis.” Nature 620, no. 7973 (Aug. 10, 2023): 417-25.

Those Open to the Unexpected Can Benefit from Serendipity

Serendipitous discoveries often involve seeing something unexpected and imagining a use for it. I am currently reading Mary Makary’s Blind Spots. To explain the inertia of the medical establishment, he points out that seeing our expectations contradicted is painful for us; it causes what Leon Festinger called “cognitive dissonance.” Cognitive dissonance causes stress. Most of us minimize the stress by denying or papering over the experiences that contradict expectations. It takes effort, often painful effort, to keep the contradiction in mind. One of my heroes is Oswald Avery, who discovered that the genetic material is DNA. Before he focused on DNA, he worked hard to understand the behavior of the Pneumococcus bacteria that cause pneumonia. Then Fred Griffith showed that only encapsulated Pneumococcus bacteria could cause pneumonia since unencapsulated Pneumococcus can be eliminated by the immune system, and showed further that unencapsulated Pneumococcus could acquire capsules, and become infectious. This transformation of the Pneumococcus contradicted Avery’s expectations, likely causing the him the stress, and the Graves disease, that paralyzed his research for six months (Barry 2005, pp. 421-422). But Avery did not suppress the contradiction. Eventually he pivoted (or if it takes six months I should say ‘eventually he painfully changed direction’) to the research that led to DNA as the genetic material.

(p. A15) Horace Walpole, who coined the term “serendipity” in a 1754 letter, believed that “the best discoveries are made while one is searching for something else,” according to Mr. Pievani. But blind luck, although often important, is not sufficient in itself, as emphasized by Louis Pasteur when he observed that “chance favors the prepared mind.”

“Serendipity” provides a catalog of serendipitous discoveries.  . . .

Mr. Pievani offers a useful and informative survey but sometimes layers his material so elaborately as to be off-putting. Early on, for example, we learn that “in 1762, Venetian playwright Carlo Gozzi, the anti-Goldoni who in the same year published the Turandot, which would inspire Giacomo Puccini, brought to the theater a fairy tale, The Deer King, which in the midst of the rococo revived the novella by Khusrau and Armeno, in particular the theme of the transmigration of souls from human to animal.” Huh? Aside from showcasing Mr. Pievani’s extensive learning, such digressions mostly demonstrate his need for a ruthless editor.

“Serendipity,” translated from the Italian by Michael Gerard Kenyon, is most intriguing when it focuses on people with prepared minds who didn’t merely find something they weren’t looking for but were in fact searching for something else when they had a breakthrough.

. . .

In 1928 Fleming, a microbiologist, had been growing Staphylococcus aureus in petri dishes. One day, upon returning from vacation, he noticed that one of the cultures had been accidentally contaminated with a Penicillium mold, which had mysteriously killed the surrounding bacteria. As a military doctor in World War I, Fleming had seen many soldiers die of bacterial infections, and he surmised that maybe this mold would help cure comparable illness.

. . .

. . ., without a prepared mind à la Pasteur, many key discoveries would have been missed. Mr. Pievani makes clear that “if you do not have predictions and expectations in mind, you will never be able to see that an accidental observation is incongruent and therefore potentially a harbinger of serendipity.” The author seeks to encourage what he calls an “ecology of serendipity” that facilitates scientific discovery. He has some suggestions, notably that one should be a “xenophile: love all things strange, all things different, foreign and new, the exceptions, the deviations.”

For the full review see:

Barash, David P. “BOOKSHELF; Progress By Accident.” The Wall Street Journal (Tuesday, Dec. 17, 2024): A15.

(Note: ellipses added.)

(Note: the online version of the review has the date December 16, 2024, and has the title “BOOKSHELF; ‘Serendipity’: Progress by Accident.” In both versions of the article, the names of works of literature and species of bacteria or mold, are italicized.)

The book under review is:

Pievani, Telmo. Serendipity: The Unexpected in Science. Translated by Michael Gerard Kenyon. Cambridge, Mass.: The MIT Press, 2024.

The book by Barry that I reference in my initial comments is:

Barry, John M. The Great Influenza: The Story of the Deadliest Pandemic in History. Revised ed. New York: Penguin Books, 2005.