Category: Books

Otherwise “Savvy Consumers,” Mistakenly Trusting the F.D.A., Let Down Their Guard on Drug Quality

(p. 6) In the fall of 2012, a young consumer safety officer at the Food and Drug Administration volunteered for a job that few of his colleagues wanted: inspecting the Indian manufacturing plants that make many of America’s low-cost generic drugs.

In a world of drab auditors, Peter Baker stood apart.

. . .

America needs generic drugs. They make up 90 percent of the American drug supply. Without them, every large-scale government health program — the Affordable Care Act, Medicare Part D, the Veterans Health Administration, charitable programs for the developing world — would be unaffordable.

. . . what Mr. Baker uncovered in six years of doing foreign inspections exposed the dangerous compromises behind the production of generic drugs, and the F.D.A.’s limits as a global regulatory agency.

. . .

. . ., first in India and then in China, he uncovered fraud or deceptive practices in almost four-fifths of the drug plants he inspected. Some of the plants used hidden laboratories, secretly repeated tests and altered results to produce fake data that fundamentally misrepresented drug quality, then submitted that data to regulators.

. . .

The F.D.A. declares that “Americans can be confident in the quality of the products the F.D.A. approves.” Because of that reassurance, even savvy consumers — the sorts of people who are well versed in the quality distinctions between Velveeta and artisanal Cheddar — don’t think about how and where their drugs are made when they head to a pharmacy. Their only question usually is: Can they afford, or will their insurance cover, the drug being dispensed?

The F.D.A., which approved more than 1,000 new generic drug products last year, faces a vast challenge in safeguarding these medications. Nearly forty percent of all our generic drugs are made in India. Eighty percent of active ingredients for both our brand and generic drugs come from abroad, the majority from India and China. America makes almost none of its own antibiotics anymore.

. . .

In the United States, F.D.A. investigators typically show up unannounced to inspect plants. But overseas, the F.D.A. has opted to announce the vast majority of its foreign inspections in advance. Overseas plants even “invite” the F.D.A. to inspect; the investigators then become the company’s guests and agree on an inspection date in advance. Plant officials have served as hosts and helped to arrange local travel.

The F.D.A. has defended this system as the best way to ease the complex logistics of getting visas and ensuring access to the plants. But the resulting inspections are largely “staged,” say a number of F.D.A. staff members. With advance notice and low-cost labor, the plants can make anything look like anything. “You give them a weekend, they’ll put up a building,” as one F.D.A. investigator put it.

. . .

And there was an additional negative consequence to the F.D.A.’s system of advanced notice. With the companies serving as travel agents, F.D.A. investigators spoke of inappropriate perks: hotel upgrades, for which the investigators would never see a bill; golf outings, massages, and trips to the Taj Mahal. The result was what some F.D.A. employees referred to as “regulatory tourism.” The F.D.A. said in response that “any allegations of improper conduct by F.D.A. personnel are investigated.”

A new head of the F.D.A.’s India office, Altaf Lal, arrived in mid-2013. To tame the twin problems of company fraud and compromised investigators, Mr. Lal made a novel pitch to agency officials. He proposed a pilot program to make all inspections in India either on short notice or unannounced. By December 2013, he had a green light. The results were instantaneous.

In January 2014, the F.D.A. was planning an unannounced inspection at a plant in northern India on a Monday. Fearing that plant officials had heard they were coming, Mr. Baker and his colleague went a day early, unannounced. They proceeded to the quality control laboratory, expecting it to be quiet on Sunday morning. Instead, they were stunned to see a hive of activity. Dozens of workers hunched over documents, backdating them. On one desk, Mr. Baker found a notebook listing the documents the workers needed to fabricate in anticipation of the inspectors’ arrival. There were Post-it notes stuck to some surfaces, noting what data to change.

In large swaths of India’s generic drug industry, the pilot program uncovered a long-running machinery dedicated not to producing perfect drugs but to producing perfect data. At one plant, Mr. Baker went straight to the microbiology laboratory and found the paperwork for testing the sterility of the plant in perfect order: microbial limits testing, biological indicators, all the samples with perfect results. Yet most of the samples didn’t exist. The plant was testing almost nothing. The laboratory was a fake.

At the vast majority of the unannounced inspections, the investigators found things the plants no longer had time to fix: Infestations of birds and insects. A pile of critical manufacturing records, tossed in a trash bin. An employee bathroom near a sterile manufacturing area in one plant lacked drainage piping, so urine puddled directly onto the floor.

(p 7) Under the pilot program, the rate of inspections resulting in the F.D.A.’s most serious finding, “official action indicated,” increased by almost 60 percent, according to my own analysis of F.D.A. records. Before long, drugs from numerous plants in India had been banned from the United States market. Given these results, it seemed logical for the F.D.A. to make unannounced inspections or short notice the norm around the world. But in July 2015, F.D.A. officials decided to terminate the program and return to largely pre-announced inspections in India. When asked why, the agency declined to explain its reasoning and stated that “after evaluation of the pilot a decision was made to discontinue the pilot.”

For the full essay see:

Katherine Eban. “Can You Trust Generic Drugs?” The New York Times Sunday Opinion Section (Sunday, May 12, 2019 [sic]): 6-7.

(Note: ellipses added.)

(Note: the online version of the essay has the date May 11, 2019 [sic], and has the title “Americans Need Generic Drugs. But Can They Trust Them?” In the original of both print and online versions, the word “anything” is in italics both times it appears. In the quotes above where the online and print versions differ, the quotes follow the somewhat more detailed online version.)

The essay quoted above is adapted by Eban from her book:

Eban, Katherine. Bottle of Lies: The inside Story of the Generic Drug Boom. New York: Ecco, 2019.

Tainted Sulfa Drugs Led Feds to Mandate Drug Safety Tests

Note that the impetus for the creation of mandated drug licensing was an episode of tainted sulfa drugs. The motive of the mandate was to assure safety. The later impetus for the strengthening of mandated drug licensing was the thalidomide episode. Again the motive was to assure safety.

Economists annoyingly emphasize trade-offs. If we stuck to regulation for safety, we could vastly reduce the costs of drug development, allowing more and faster drug innovation.

A case can even be made for doing away with safety regulation. Firms have incentives to produce safe drugs, and private certifying organizations provide information, for instance Consumer Reports. And there are many examples of F.D.A.-approved drugs that turned out to be unsafe (e.g., Vioxx). Mandated safety regulations reduce consumer freedom to choose, and slow the amount and speed of new cures. Mandated efficacy regulations reduce them even more.

(p. C6) Between the late 1930s and the late 1940s, every major class of antibiotics was developed, as William Rosen meticulously recounts in “Miracle Cure: The Creation of Antibiotics and the Birth of Modern Medicine.” Rosen’s highly informed retelling captures the drama of scientists’ quest, against long odds, to find and produce bacteria-killing drugs—and the egos, ambitions, brilliance and resolve that drove them.

. . .

It is a strength of “Miracle Cure” that Rosen places its many tales of discovery in their larger contexts, explaining for instance the near-complete lack of drug-safety regulation that prevailed when the Tennessee-based S.E. Massengill Co. began selling Elixir Sulfanilamide in October 1937. To make the drug more palatable, the company’s chief chemist had dissolved it, along with raspberry flavoring, in a toxic chemical also used in brake fluid. At least 73 people died. The Federal Food Drug and Cosmetic Act became law the following year. Companies would no longer be able to market new drugs without government licensing. And the government would have to ensure that they were safe.

This book is not for the casual reader. At some points Rosen gets into weeds so thick that only aficionados will find a way through. Still, it’s an important contribution to a still-germane yet fast-receding history. And it’s all the more impressive that Rosen, formerly a book editor and publisher, wrote it as he was battling his own intractable disease. An aggressive cancer took his life in April 2016. He left behind a history worth reading.

For the full review see:

Meredith Wadman. “Medicine’s Age of Wonders.” The Wall Street Journal (Saturday, May 20, 2017 [sic]): C6.

(Note: ellipsis added.)

(Note: the online version of the review has the date May 19, 2017 [sic], and has the same title as the print version.)

The book under review is:

Rosen, William. Miracle Cure: The Creation of Antibiotics and the Birth of Modern Medicine. New York: Penguin Books, 2018.

Mainstream Approach to Alzheimer’s Is Built on Doctored Data

Widespread fraud among highly credentialled, and richly financed, medical researchers results in fewer and slower cures. Many millions of dollars are required to bring a major drug to market, much of it due to the hyper-costly and mandated Phase 3 randomized double-blind clinical trials. There are more good ideas than can receive such financing. The intense competition creates a temptation to cut various corners, as the book review quoted below emphasizes.

Aaron Rothstein, the reviewer of Piller’s Doctored book, emphasizes the sad revelation of widespread fraud. But in an earlier entry on this blog, I quoted an essay of Piller’s that suggests that Piller also has something substantive to say about how to cure Alzheimer’s. The current system is broken, vastly reducing the diversity of approaches to curing important diseases like Alzheimer’s. Piller suggests that the ruling clique among Alzheimer’s researchers may in effect be silencing other approaches that could bring us a better faster cure.

Rothstein downplays this substantive aspect of Piller’s book. (It probably reflects too much cynicism on my part to wonder how close Rothstein himself is to the ruling clique?)

I look forward to reading Piller’s book, both for what it has to say about widespread fraud and for what it has to say about Alzheimer’s. Doctored is scheduled for release in a few days, on February 4, 2025.

(p. C9) In 2023 my colleagues and I were preparing to enroll patients in a clinical trial of a new drug that promised to mitigate brain damage in stroke victims. The National Institutes of Health, a governmental organization that funds billions of dollars of research every year, had committed $30 million to the trial. The drug was, in part, the brainchild of Berislav Zlokovic, a neuroscientist at the University of Southern California.

Then, suddenly, the NIH paused the trial. Charles Piller, an investigative journalist for Science magazine, had published an article alleging that multiple papers from Dr. Zlokovic, including many supporting the new drug, contained seemingly altered data. Though Dr. Zlokovic disputed some of the concerns, this news stunned us. We might have put patients at risk, while offering groundless hope. A fraud of the sort Mr. Piller described would violate the basic ethics of clinical trials and overturn the presumption of trust on which the practice of medicine relies.

I thought of this episode often as I read Mr. Piller’s “Doctored,” which brings together his long-form journalism about neuroscience-research malfeasance, including that alleged of Dr. Zlokovic. Though the book sometimes attempts to do too much—diving into scientific theories about the causes of Alzheimer’s, for example—its strength lies in Mr. Piller’s dramatic and damning investigation of scientific transgression. The author’s reporting is largely based on the research of Matthew Schrag, a Vanderbilt neurologist who uses technical expertise to identify episodes of misconduct.

. . .

Mr. Piller thoroughly double checks Dr. Schrag’s work. He asks researchers and image analysts to confirm Dr. Schrag’s findings, and they concur.

. . .

“Doctored” demonstrates how some of the most accomplished and elite scientific gatekeepers may have lied, cheated, squandered trust and endangered lives. How did this happen? The temptations of ego and fame perennially entice humans, but our system of peer review, grant funding and administrative oversight is meant to check these temptations.

The scientific publication process does not contain all the safeguards one might expect. Peer reviewers do not always see the original data from authors. Thus they trust that numbers or images in a manuscript accurately reflect the experiment. And determining whether an image is fraudulent requires skilled image analysis that peer reviewers may not possess. Furthermore, digging for such mistakes is costly: It takes time away from other research, from teaching, from seeing patients and from home life.

What can be done about this? Making raw data available to peer reviewers and giving them time to review articles could help. Mr. Piller suggests a less professionally incestuous relationship between researchers, the Food and Drug Administration, the NIH and pharmaceutical companies could reduce favoritism in funding. A major overhaul of the finances and administrative swell of our system would help, as well.

For the full review see:

Aaron Rothstein. “Medical Promise Betrayed.” The Wall Street Journal (Saturday, Jan. 25, 2025): C9.

(Note: the online version of the review has the date January 24, 2025, and has the title “‘Doctored’ Review: Medical Promise Betrayed.”)

The book under review is:

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

The Last Lonely Night Watchman Blows His Horn, “Signaling That All Is Well”

When I was a graduate student in philosophy and economics the exciting new read for the liberty-inclined was Robert Nozick’s Anarchy, State, and Utopia. I was at first rejected from the philosophy graduate program at the University of Chicago because I had the audacity to praise Ayn Rand in my application essay. The rejection decision was eventually reversed. But imagine my reaction when then-young Harvard philosophy professor Robert Nozick had the guts to write a paper evaluating the philosophy of Ayn Rand. My memory is that he did not praise all that is Rand. But that is not the point; the point is that Nozick took Rand seriously. Regardless of the contents of his main book, Nozick was my hero.

The book is pretty good too. I still ponder much that Nozick pondered. Should we eat animals that think and feel? Should a libertarian society approve of people who voluntarily join an authoritarian community? If we could plug ourselves into a machine that would give us the false illusion that all is well, should we?

Not everyone I admired totally admired Nozick’s book. I remember reading (or hearing) Milton Friedman say that it was good but “too Talmudic.” (I assume that Friedman meant that there was too much back and forth nit-picking on minor issues, and too little dispositive empirical evidence on big issues.)

The main constructive section of Nozick’s book defends the libertarian’s minimal state, what Nozick memorably calls “the night-watchman state”–the fundamental justifiable function of government is to act as a conscientious night watchman. (Today many who call themselves “libertarians” are anarchists which is why I now sometimes call myself a “classical liberal.”) (For fans of The Lord of the Ring: I think of the Rangers, the unappreciated protectors of the Hobbits, as kin to night watchmen.)

Nozick solidified the heroic image of the night watchman going about his job.

(p. A11) Mr. Stein, a journalist and editor for BBC Travel, has globetrotting in his veins, but this book is much more than a travelogue.  . . .  . . . under the drizzle of a wet November, he climbs 14 stories to the belfry of a Swedish church with Scandinavia’s last night watchman and listens to the watchman’s call, on a 4-foot-long copper horn, signaling that all is well.

. . .

In reading about the night watchman, alone in the dark tower above Ystad, along Sweden’s southern coast, I felt the wind and rain, I awed at the sacrifice, I understood the power of tradition. Those who listen to his horn night after night, even cracking open their windows in subzero temperatures for the comfort of its lonely bellow, know that the world would be different without it. It would be poorer, less a home to mankind.

. . .

Mr. Stein’s great gift—his sensitivity and his dedication to capturing joy and hope, however fleeting—is worth giving to others.

For the full review see:

Brandy Schillace. “Bookshelf; The Great Chain Of Humanity.” The Wall Street Journal (Friday, Jan. 3, 2025): A11.

(Note: ellipses added.)

(Note: the online version of the review has the date January 2, 2025, and has the title “Bookshelf; ‘Custodians of Wonder’: The Great Chain of Humanity.”)

The book under review is:

Stein, Eliot. Custodians of Wonder: Ancient Customs, Profound Traditions, and the Last People Keeping Them Alive. New York: St. Martin’s Press, 2024.

Nozick’s book, mentioned in my introductory comments, is:

Nozick, Robert. Anarchy, State, and Utopia. New York: Basic Books, Inc., 1974.

Amar Bhidé on Uncertainty

I have not read the latest book by Amar Bhidé, briefly discussed in the passages quoted below, but I have assigned a couple of his earlier books in my Economics of Entrepreneurship and Economics of Technology seminars. Bhidé asks important questions and I like his empirically rich and methodologically pluralist approach to answering them.

(p. R2) “Uncertainty and Enterprise: Venturing Beyond the Known” is a must-read for anyone seeking a roadmap to the bewildering array of new technologies exploding today. Written with considerable charm by the distinguished economist and scholar Amar Bhidé— . . . —the book makes a compelling case that hard facts alone cannot prove or predict whether a new political movement, business idea, technology or TV series will succeed. The author offers a fascinating array of stories, examples and ideas of great thinkers— . . . —rather than relying solely on math or statistics. This book provides a new way of looking not only at risk but, more importantly, at uncertainty in an unpredictable world.

For the full review, see:

Elaine Chao. “12 Months of Reading: Elaine Chao.” The Wall Street Journal (Saturday, December 7, 2024): R2.

(Note: ellipses added.)

(Note: the online version of the review was updated Dec. 6, 2024, and has the title “Who Read What in 2024: Political Voices: Elaine Chao.”)

The book praised by Chao is:

Bhidé, Amar. Uncertainty and Enterprise: Venturing Beyond the Known. New York: Oxford University Press, 2024.

Reductio ad Absurdum: When a Functional MRI Showed Activity in a Dead Salmon’s Brain

I have long thought that most college students would benefit from a course in practical reasoning. One topic in such a course would be to define and illustrate the Reductio ad Absurdum argument. The argument starts with a proposition, and then infers an absurdity from the proposition, thereby refuting the original proposition. The review quoted below mentions such an argument that implicitly starts with the proposition that fMRI scans are reliable guides to human thought. The absurdity is that fMRI scans sometimes light up in the presence of a dead Atlantic salmon, which would seem to suggest that the salmon is thinking. The conclusion: be careful what you infer from fMRI scans.

My favorite reductio ad absurdum argument starts with the proposition that all actionable knowledge must derive from randomized double-blind clinical trials (RCTs). The argument then shows that no RCTs have been performed to show the efficacy of parachutes. The absurdity is that before anyone uses a parachute when exiting a flying airplane, he must first find an RCT to prove the efficacy of parachutes. The conclusion: when you volunteer for the first such RCT, hope that you are not assigned to the control group!

(p. A15) In 2009 a group of researchers placed a dead salmon in a functional magnetic resonance imaging (fMRI) scanner and showed the fish some photos of people in social situations. Their results, presented under the title “Neural Correlates of Interspecies Perspective Taking in the Post-Mortem Atlantic Salmon,” were surprising. The scans revealed a red spot of activity centered in the salmon’s brain.

The authors of the study weren’t trying to pull a fast one on the scientific community. Nor did they believe in zombie fish. They were showing that statistics, used incorrectly, can demonstrate almost anything. Specifically, a certain type of data analysis, often used on fMRI scans, can find signal where there should be only noise.

Russell Poldrack, a psychologist at Stanford University, mentions the stunt in “The New Mind Readers: What Neuroimaging Can and Cannot Reveal About Our Thoughts.” His book, ostensibly about fMRI and its use in studying how the brain functions (hence “functional”), serves as a lesson in how the science works—or should work. Through blunders and baloney, innovation and self-correction, the young field of cognitive neuroscience is quickly evolving.

For the full review see:

Matthew Hutson. “Bookshelf; Scanning For Thoughts.” The Wall Street Journal (Wednesday, November 28, 2018 [sic]): A15.

(Note: the online version of the review has the date November 27, 2018 [sic], and has the title “Bookshelf; ‘The New Mind Readers’ Review: Scanning for Thoughts.”)

The book under review is:

Poldrack, Russell. The New Mind Readers: What Neuroimaging Can and Cannot Reveal About Our Thoughts. Princeton, NJ: Princeton University Press, 2018.

The parachute reductio argument is in:

Smith, Gordon C. S., and Jill P. Pell. “Parachute Use to Prevent Death and Major Trauma Related to Gravitational Challenge: Systematic Review of Randomised Controlled Trials.” BMJ 327, no. 7429 (Dec. 18, 2003): 1459-61.

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.

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.

When Ronald Reagan Needed the Owls of Hogwarts

One of my favorite scenes in the first Harry Potter movie is when an owl tries to deliver to Harry Potter an acceptance letter to Hogwarts. Ever since Voldemort murdered Harry’s parents when he was a baby, Harry has lived under a staircase with the Dursleys (Mrs. Dursley was the sister of Harry’s mother). Mr. Dursley, and the other Dursleys too, do not like Harry, hence his living under a staircase. Mr. Dursley sees the letter to Harry, opens it, and when he realizes the contents tears it up. Then a few other copies arrive and Dursley burns them. It would appear that Harry’s hope of escape is dashed.

But then something wonderful. Countless owls fly toward the Dursley house, each carrying copies of the letter. Acceptance letters start pouring through the front door mail slot, down the chimney, and through every opening in the house. Soon the inside of the Dursley house is buried in acceptance letters. Dursley cannot stop Harry from knowing.

I thought of this scene when I was reading the Wikipedia entry for “Human Events.” Human Events was a smallish weekly readers-digest-type newspaper that my father subscribed to for many years (in the 1960s and 1970s?). Copies of Human Events would always be piled up next to his chair in the living room. Human Events was a contrarian publication presenting conservative/libertarian commentaries on the issues of the day.

The Wikipedia article says that starting in 1961, Ronald Reagan is an avid reader of Human Events. In the 1970s he writes articles that appear in Human Events. When he is president, Reagan’s top aides Baker, Darman, and Deaver do not like what is in Human Events, and try to keep copies of it away from him. When Reagan realizes that his aides are blocking Human Events, he “arranged for multiple copies to be sent to the White House residence every weekend” (Edwards 2011, as quoted in Wikipedia entry on “Human Events“).

Unfortunately for Reagan he does not have a flock of wise owls providing redundant information. But Reagan is his own owl.

Harry could not fire Dursley; I wonder why Reagan did not fire Baker, Darman, and Deaver?

Wikipedia gives the source of the Edwards quote as:

Edwards, Lee. “Reagan’s Newspaper.” URL: http://www.humanevents.com/article.php?id=41609

The Second Arthur Mansfield Diamond Would Be 100 Today

Dad holding me as a baby in 1953.
Dad holding me as a baby in 1953.

Happy Birthday Dad! He was the second Arthur Mansfield Diamond and would be 100 today.

I think if we adopt the right policies, many of us could live to 100. Too late for Dad, and almost certainly for me.

The first Arthur Mansfield Diamond died in 1933, I think. I was told he played the piano by ear and I saw an article saying that when he was a young man he briefly was a book-keeper for the family vaudeville activities. He looked dapper in a straw hat and knew Knute Rockne of Notre Dame. My Dad was eight when cancer took the first Arthur Mansfield Diamond. My Grandma, with no college degree, raised four children during the Great Depression. Cabbage was nutritious and cheap, so Grandma served a lot of sauerkraut. As an adult Dad hated sauerkraut.

Dad was always reading. He is the only person I ever met who read all three volumes of Solzhenitsyn’s Gulag Archipelago. And he read a conservative reader’s digest weekly (or monthly?) newspaper called Human Events. He was a Republican lawyer in an overwhelmingly Democratic county.

When my brothers and I were young he read aloud to us most of the Oz books, and other books including Atlas Shrugged. Thank you Dad, especially for that.

I wish I had finished my book before he died–he would have read it, argued with me about parts of it, but I think mostly liked it.

Dad was active in Toastmasters, a self-help organization for those who want to improve their public speaking. He rose to become the International President. Their headquarters is near Disneyland. When Dad first joined the Toastmasters board, he spent some time in the park. When he returned from that first trip, I remember his excitement at the then-new attraction, the Tiki Room–seeing what was possible in audio animatronics. Mom and Dad took us to Disneyland and on road trips to most of the U.S.

I remember Dad telling me in his last year that one of his regrets is that he won’t know how things turn out.

Dad was not perfect; neither am I. But I miss him and wish I could still talk with him, and thank him for his wit, his curiosity, and his courage in holding unpopular views when he thought they were right.