Category: Books

Rickets Is Now Rare Because Vitamin D Is Easy to Get

(p. A15) Rickets is one of those diseases that seem incredibly old-fashioned. It’s difficult to comprehend, now, how widespread this bone ailment once was: In some cities less than a century ago, 90% of children showed symptoms of rickets during wintertime. But ubiquity has its benefits. In “Starved for Light,” Christian Warren convincingly argues that modern medicine would be unrecognizable without the many advances in treatment that trace their roots to this once-widespread disease.

Rickets results from a lack of vitamin D, which we need to help shuttle calcium and phosphorus into our bones. Our bodies manufacture vitamin D whenever ultraviolet sunlight hits our skin; we can also get it through food. A deficiency in vitamin D causes the softening and bending of bones characteristic of rickets; victims are often left bowlegged or knock-kneed, or with curved spines or misshapen pelvises. The worst cases leave babies unable to crawl or even sit up straight.

. . .

Given how disgusting cod-liver oil tastes, some countries began combating rickets by adding vitamin D to milk in the 1930s—an odd choice, since milk contains no vitamin D naturally. (Amusingly, Mr. Warren calls the practice an “in uddero” health intervention.) The choice seems even odder, the author wryly notes, when there’s a much simpler solution to preventing rickets: going outside for a few minutes. Instead, we’ve effectively turned “a dairy product into a drug-delivery device,” severing the ancient interplay between “sun, skin, and bone.”

For the full review see:

Sam Kean. “Bookshelf; A Disease Of Deficiency.” The Wall Street Journal (Monday, Dec. 9, 2024): A15.

(Note: ellipsis added.)

(Note: the online version of the review has the date December 8, 2024, and has the title “Bookshelf; ‘Starved for Light’: A Disease of Deficiency.”)

The book under review is:

Warren, Christian. Starved for Light: The Long Shadow of Rickets and Vitamin D Deficiency. Chicago: University of Chicago Press, 2024.

Using the Blood of the Young to Rejuvenate the Organs of the Old

Phase 3 clinical trials to establish the efficacy of a therapy are in general very expensive, and they are especially very expensive for therapies aimed at extending lifespan. To know the efficacy of such therapies you have to run the trial for many years, before you can learn the lifespans of all of those in the trial.

This may be one reason why pharma firms instead invest in incremental improvements in health tested for those predicted to be near the end of their lives.

Azra Raza claims that the most promising therapies for cancer would be those applied early in the disease. But it is precisely these candidate therapies that would be most expensive to test through a hyper-expensive Phase 3 clinical trial. The result? Unnecessarily slow progress in curing cancer.

(p. B3) Several years ago, scientists studying aging at the Harvard Stem Cell Institute used a somewhat Frankensteinian technique known as parabiosis — surgically joining a young mouse and an old mouse so that they share blood — to see what would happen to the heart and skeletal muscle tissue. They knew from previous research that putting young blood in old mice caused them to grow biologically younger, and that young mice exposed to old blood aged faster.

The Harvard researchers, Amy Wagers and Dr. Richard Lee, found that the old mouse’s heart tissue had been repaired and rejuvenated, becoming young again. In fact, the size of the old mouse’s heart had reduced to that of a young heart.

“We all wondered, what’s the magic stuff in the blood?” said Lee Rubin, a professor of stem cell and regenerative medicine at Harvard and the co-director of the neuroscience program at the Stem Cell Institute. The “magic” they identified was a protein, GDF11, one of tens of thousands produced in the human body.  . . .  The scientists’ discoveries were published in the journals Cell and Science in 2013 and 2014.

. . .

“We’re interested in proteins like GDF11 that are excreted into the bloodstream because those can cause changes throughout the body,” said Dr. Mark Allen, the chief executive of Elevian. “And those are the kind of changes we want.”

. . .

The initial research into the rejuvenating properties of GDF11 has gotten some pushback from the scientific community. In 2015, after Dr. Wagers and Dr. Lee had published their results, a group of researchers led by David Glass, the executive director of the Novartis Institutes for Biomedical Research in Cambridge, Mass., at the time, challenged the accuracy of their findings in an article in the journal Cell Metabolism. The Harvard researchers subsequently countered the Novartis team’s findings in another paper published later that year in the journal Circulation Research, in which the Harvard researchers cited a problem with the Novartis team’s findings.

Dr. Glass, who is now at the biotechnology company Regeneron, said in a recent email that he stands by his original work, which showed that GDF11 inhibits, rather than helps, muscle regeneration. But, he added, “our work still leaves open the possibility that there could be positive effects of GDF11 in particular settings.”

Dr. Allen said that since the original controversy, Elevian’s research team has reproduced and extended its original findings in multiple studies, but none have yet been published in peer-reviewed journals. However, institutions unrelated to Elevian have conducted and published many preclinical studies demonstrating the therapeutic efficacy of rGDF11 (the form of GDF11 developed in a lab) in treating age-related diseases.

. . .

A significant challenge lies ahead for all of these companies: Commercializing a drug for aging is nearly impossible because the F.D.A. doesn’t recognize aging as a disease to be treated. And even if it were considered a disease, the clinical studies required to prove that a treatment for it worked would take many years.

“It is likely that clinical studies to see if some drug slows aging — and thereby delays the many consequences of aging — would take a long time,” Dr. Miller said.

. . .

The next big hurdle for Elevian is scaling its manufacturing, which requires specialized equipment and conditions. So much research is being conducted in biotech that contract manufacturers are “full up,” Dr. Allen said. “They are busy with Covid-related work, and there has been a lot of funding in biotech generally,” he added. “So it’s a challenge finding the space that meets our specifications.”

. . .

“By targeting fundamental mechanisms of aging, we have the opportunity to treat or prevent multiple aging-related diseases and extend the health span,” he said. “We want to make 100 the new 50.”

For the full story see:

Eilene Zimmerman. “Biotech Start-Up Invests in Anti-Aging Therapy.” The New York Times (Monday, August 1, 2022 [sic]): B3.

(Note: the online version of the story has the date July 19, 2022 [sic], and has the title “Can a ‘Magic’ Protein Slow the Aging Process?”)

The published academic articles supporting the promising effects of GDF11 are:

Katsimpardi, Lida, Nadia K. Litterman, Pamela A. Schein, Christine M. Miller, Francesco S. Loffredo, Gregory R. Wojtkiewicz, John W. Chen, Richard T. Lee, Amy J. Wagers, and Lee L. Rubin. “Vascular and Neurogenic Rejuvenation of the Aging Mouse Brain by Young Systemic Factors.” Science 344, no. 6184 (May 9, 2014): 630-34.

Loffredo, Francesco S., Matthew L. Steinhauser, Steven M. Jay, Joseph Gannon, James R. Pancoast, Pratyusha Yalamanchi, Manisha Sinha, Claudia Dall’Osso, Danika Khong, Jennifer L. Shadrach, Christine M. Miller, Britta S. Singer, Alex Stewart, Nikolaos Psychogios, Robert E. Gerszten, Adam J. Hartigan, Mi-Jeong Kim, Thomas Serwold, Amy J. Wagers, and Richard T. Lee. “Growth Differentiation Factor 11 Is a Circulating Factor That Reverses Age-Related Cardiac Hypertrophy.” Cell 153, no. 4 (May 9, 2013): 828-39.

Poggioli, Tommaso, Ana Vujic, Peiguo Yang, Claudio Macias-Trevino, Aysu Uygur, Francesco S. Loffredo, James R. Pancoast, Miook Cho, Jill Goldstein, Rachel M. Tandias, Emilia Gonzalez, Ryan G. Walker, Thomas B. Thompson, Amy J. Wagers, Yick W. Fong, and Richard T. Lee. “Circulating Growth Differentiation Factor 11/8 Levels Decline with Age.” Circulation Research 118, no. 1 (Jan. 2016): 29-37.

Sinha, Manisha, Young C. Jang, Juhyun Oh, Danika Khong, Elizabeth Y. Wu, Rohan Manohar, Christine Miller, Samuel G. Regalado, Francesco S. Loffredo, James R. Pancoast, Michael F. Hirshman, Jessica Lebowitz, Jennifer L. Shadrach, Massimiliano Cerletti, Mi-Jeong Kim, Thomas Serwold, Laurie J. Goodyear, Bernard Rosner, Richard T. Lee, and Amy J. Wagers. “Restoring Systemic Gdf11 Levels Reverses Age-Related Dysfunction in Mouse Skeletal Muscle.” Science 344, no. 6184 (May 9, 2014): 649-52.

The book by Asra Raza that I praise in my introductory comments is:

Raza, Azra. The First Cell: And the Human Costs of Pursuing Cancer to the Last. New York: Basic Books, 2019.

W.H.O. Ignored Those Who Knew Covid Was Airborne

The article quoted below provides more evidence that the World Health Organization (W.H.O.) failed to protect world health during the Covid pandemic. Its funding and decision-making processes made failure highly likely.

In the absence of W.H.O, how can we learn quickly of potential pandemic threats from around the world? The Covid book co-authored by Ridley documents quick and effective Twitter (now X) networks that spread and evaluated Covid information. Maybe a proof of concept?

(p. D3) In early February 2020, China locked down more than 50 million people, hoping to hinder the spread of a new coronavirus. No one knew at the time exactly how it was spreading, but Lidia Morawska, an expert on air quality at Queensland University of Technology in Australia, did not like the clues she managed to find.

It looked to her as if the coronavirus was spreading through the air, ferried by wafting droplets exhaled by the infected. If that were true, then standard measures such as disinfecting surfaces and staying a few feet away from people with symptoms would not be enough to avoid infection.

Dr. Morawska and her colleague, Junji Cao at the Chinese Academy of Sciences in Beijing, drafted a dire warning. Ignoring the airborne spread of the virus, they wrote, would lead to many more infections. But when the scientists sent their commentary to medical journals, they were rejected over and over again.

“No one would listen,” Dr. Morawska said.

It took more than two years for the World Health Organization to officially acknowledge that Covid spread through the air.

For the full story see:

Carl Zimmer. “Covid Proved Airborne. Could Bird Flu Be, Too?” The New York Times (Tuesday, February 4, 2025): D3.

(Note: the online version of the story has the date February 3, 2025, and has the title “Could the Bird Flu Become Airborne?”)

The book co-authored by Ridley that I praise in my initial comments is:

Chan, Alina, and Matt Ridley. Viral: The Search for the Origin of Covid-19. New York: Harper, 2021.

Chinese Communist Regulators Will Want to Deep-Six DeepSeek

Many policy experts have worried than China’s economy will surpass the economy of the United States. If we lived in a world of totally free trade, I would not care if this happened. Economics is not a competitive sport where one team can win only if another team loses. A free economy is not a zero-sum game. If you are OK with me mixing metaphors: a rising tide really does lift all boats. (Amar Bhidé (quoting Paul Krugman, if memory serves) does a good job of making this point in The Venturesome Economy.)

But even though it wouldn’t bother me, China’s economy will not surpass that of the United States if China continues to oppressively regulate its economy and we continue to exuberantly unregulate our economy. An economy thrives when entrepreneurs thrive and entrepreneurs thrive when unregulated.

Consider the recent hand-wringing over the recently announced DeepSeek Chinese A.I. program. The Chinese Communists will be especially energetic in regulating entrepreneurs in the A.I. sector because the Communists cannot afford to have Chinese A.I. programs giving true answers to questions in any way related to the Chinese economy, or to the corruption and authoritarianism of the Chinese Communist regime. A.I. policy expert Barath Harithas understates the situation when he says: “Overregulation and the need to adhere to ‘core socialist values’ could risk neutering A.I.’s potential” (as quoted in Pierson and Wang 2025, p. A4).

Barath Haritas’s statement on overregulation of A.I. in China can be found in:

David Pierson and Berry Wang. “Success of DeepSeek Lifts China, but Party May Halt Its Progress.” The New York Times (Tues., February 4, 2025): A4.

(Note: the online version of the article has the date February 2, 2025, and has the title “DeepSeek Is a Win for China in the A.I. Race. Will the Party Stifle It?”)

The book by Amar Bhidé that I praise in my initial comments is:

Bhidé, Amar. The Venturesome Economy: How Innovation Sustains Prosperity in a More Connected World. Princeton, NJ: Princeton University Press, 2008.

Dow Chemical CEO Oreffice Candidly Called Environmentalists “Professional Merchants of Doom”

I have the impression that few C.E.O.s today display the open candor that Ralph Nader admired in Paul Oreffice. Is that because cancel culture has been efficient at weeding out any rising executives who might be tempted to be candid? Or do I have a mistaken impression due to the press not reporting as often on the candid comments still being made by some C.E.O.s?

[I was happy to see that Oreffice had learned public speaking in a Toastmasters Club. I heard a lot about Toastmasters as a child–my father was very active in Toastmasters and was eventually elected President of the whole international self-help organization.]

(p. C6) In a 1977 speech at Central Michigan University, Jane Fonda accused Dow Chemical of exposing workers to dangerous substances and not paying its fair share of taxes. Paul Oreffice, who was then president of Dow’s U.S. operations, sent a letter to the university denouncing Fonda as “an avowed communist sympathizer” who was spreading “venom against free enterprise.”

He also cut off Dow’s donations to the university.

. . .

Addressing a business conference in 1979, Oreffice described environmentalists as “professional merchants of doom” and enemies who were destroying free enterprise, according to a Washington Post report.

. . .

Ralph Nader, the consumer-protection crusader, often was at odds with Oreffice but saw merit in his candor. “He is comparatively open to interviews, to questions from audiences, to debates,” Nader wrote in “The Big Boys,” a 1986 book written with William Taylor. “Despite his position as chief executive of a major corporation embroiled in ongoing controversies, he chooses not to hide behind company spokesmen and other bureaucratic shields.”

. . .

Oreffice resisted organization charts because he believed they “put people in boxes.”

. . .

. . ., Oreffice . . . learned public speaking at a Toastmasters club, . . .

As a CEO, he reduced costs and bureaucracy through attrition rather than mass layoffs. “How can you expect allegiance from your employees when you don’t show them any yourself?” he wrote in his memoir.

For the full obituary see:

James R. Hagerty. “An Outspoken Former CEO Of Dow Chemical.” The Wall Street Journal (Saturday, February 1, 2025): C6.

(Note: ellipses added.)

(Note: the online version of the obituary has the date January 29, 2025, and has the title “Paul Oreffice, Outspoken Former CEO of Dow Chemical, Dies at 97.” Where the wording is different between the two versions, the passages quoted above follow the online version.)

Oreffice’s memoir mentioned above is:

Oreffice, Paul. Only in America: From Immigrant to CEO. Macon, GA: Stroud & Hall Publishers, 2006.

Libertarians Salute Trump for Keeping His Promise to Pardon Free Trade Innovator Ross Ulbricht

Libertarians believe that governments should stay out of voluntary exchanges between consenting adults. So when Ross Urlbricht set up Silk Road as a platform for exchange that excluded governments, he became a libertarian hero. (For an extensive account see Bilton 2017.) When Ulbricht was given a disproportionately severe sentence, he became a martyred libertarian hero.

Libertarians are conflicted about Donald Trump. They like his courage and perseverance, but don’t like his name-calling and bullying. They like his deregulation and downsized bureaucracies, but don’t like his tariffs and industrial policy.

Trump promised that if elected, he would pardon Ross Ulbricht. On the first full day of his second term, The Donald kept his promise. Libertarians like that–a lot!

Michael Milken was an entrepreneurial finance innovator whose RICO conviction, instigated by Rudy Giuliani in his New York City prosecutor days, was a travesty of justice. (See: Kornbluth 1992; (an aside in) Milken 2023, and Sandler 2023.) The second Bush could and should have pardoned Milken, but did not. Trump late in his first term did, putting justice ahead of political correctness.

Not many people care about Ulbricht and Milken, but those who do care, care–inclining them to keep open minds on Donald Trump.

For The New York Times‘s snidely dismissive view of the Ulbricht pardon see:

David Yaffe-Bellany and Ryan Mac. “Pardon Is Won By Leveraging Trump’s Needs.” The New York Times (Fri., January 24, 2025): A1 & A15.

(Note: the online version of the article has the date January 22, 2025, and has the title “How Trump Was Persuaded to Pardon an Online Drug Kingpin.”)

The best known account of Ulbricht’s Silk Road is:

Bilton, Nick. American Kingpin: The Epic Hunt for the Criminal Mastermind Behind the Silk Road. New York: Portfolio, 2017.

The books on Milken mentioned in my comments are:

Kornbluth, Jesse. Highly Confident: The Crime and Punishment of Michael Milken. New York: William Morrow & Co., 1992.

Milken, Michael. Faster Cures: Accelerating the Future of Health. New York: William Morrow, 2023.

Sandler, Richard V. Witness to a Prosecution: The Myth of Michael Milken. ForbesBooks: Charleston, South Carolina, 2023.

Medical Oversight Boards Jeopardize Patient Safety by Ignoring or Forgiving the “Egregious Misconduct” of Healthcare Providers

(p. C7) In her excellent book, “The Licensing Racket,” the Vanderbilt law professor Rebecca Haw Allensworth presents plenty of cases of hair braiders, barbers and interior decorators who have been prevented from working by license restrictions that inflate prices without improving safety or quality. But Ms. Allensworth has bigger targets in mind.

Most people will concede that licensing for hair braiders and interior decorators is excessive while licensing for doctors, nurses and lawyers is essential. Hair braiders pose little to no threat to public safety, but subpar doctors, nurses and lawyers can ruin lives. To Ms. Allensworth’s credit, she asks for evidence. Does occupational licensing protect consumers? The author focuses on the professional board, the forgotten institution of occupational licensing.

. . .

(p. C8) You might hope that boards that oversee nurses and doctors would prioritize patient safety, but Ms. Allensworth’s findings show otherwise. She documents a disturbing pattern of boards that have ignored or forgiven egregious misconduct, including nurses and physicians extorting sex for prescriptions, running pill mills, assaulting patients under anesthesia and operating while intoxicated.

In one horrifying case, a surgeon breaks the white-coat code and reports a fellow doctor for performing a surgery so catastrophically botched that he assumes the practitioner must be an imposter. Others also report “Dr. Death” to the board. But Ms. Allensworth notes, “at the time of the complaints to the medical board, [Dr. Death] was only one third of the way through the thirty-seven spinal surgeries he would perform, thirty-three of which left the patients maimed or dead.” The board system seems incapable of acting decisively and Dr. Death’s rampage is only ended definitively when he is indicted—the initial charges include “assault with a deadly weapon,” the scalpel—and eventually imprisoned.

No system is perfect, but Ms. Allensworth’s point is that the board system is not designed to protect patients or consumers. She has a lot of circumstantial evidence that signals the same conclusion. The National Practitioner Data Bank (NPDB), for example, collects data on physician misconduct and potential misconduct as evidenced by medical-malpractice lawsuits. But “when Congress tried to open the database to the public, the [American Medical Association] ‘crushed it like a bug.’”

One of the most infuriating aspects of the system is that the AMA and the boards limit the number of physicians with occupational licensing, artificially scarce residency slots and barriers preventing foreign physicians from practicing in the U.S. Yet when a physician is brought before a board for egregious misconduct, the AMA cites physician shortage as a reason for leniency. When it comes to disciplining bad actors, the mantra seems to be that “any physician is better than no physician,” but when it comes to allowing foreign-trained doctors to practice in the U.S., the claim suddenly becomes something like “patient safety requires American training.”

. . .

I agree that licensing boards have failed to effectively discipline their members, but I think we should eliminate restrictions on supply. The adage “any physician is better than no physician” should not be a shield for negligent doctors, but it underscores an essential truth. The real harm lies in the scarcity created by licensing.

. . .

Voluntary certification can effectively replace many occupational licenses. Consider computer security, one of the most critical fields for consumer safety. Instead of requiring occupational licenses, professionals in this field rely on certifications such as the CISSP (Certified Information Systems Security Professional) to demonstrate expertise and competence.

. . .

The medical profession is unlikely to be delicensed, but as Ms. Allensworth’s book shows, we shouldn’t let the AMA dictate the terms of medical education. Many European countries offer combined undergraduate and medical degree programs that take only six years, compared to the eight or more years required in the U.S.

Advances in artificial intelligence, which Ms. Allensworth doesn’t explore, may also catalyze reform. AI is already transforming fields such as legal research and medical diagnostics, automating tasks once reserved for licensed professionals. As these technologies advance, they can reduce reliance on rigid licensing systems by ensuring quality and safety through innovative tools.

For the full review see:

Alex Tabarrok. “Permission To Join The Field.” The Wall Street Journal (Saturday, Feb. 8, 2025): C7-C8.

(Note: ellipses added.)

(Note: the online version of the review has the date February 7, 2025, and has the title “‘The Licensing Racket’: There’s a Board for That.”)

The book under review is:

Allensworth, Rebecca Haw. The Licensing Racket: How We Decide Who Is Allowed to Work, and Why It Goes Wrong. Cambridge, MA: Harvard University Press, 2025.

Those Who Criticize the Powerful “Are Seldom Seen Distinctly by the Age in Which They Live”

Founding Father Benjamin Rush was apparently willing to take the ill-will that comes to those who challenge the lazy, incompetent, or corrupt.

The importance of being willing to be the target of ill-will was well-described by Charlie Munger.

(p. C7) During the spring of 1813, former presidents John Adams and Thomas Jefferson were united in grief at the death of a mutual friend who had recently persuaded them to forget their bitter rivalries. Like the two celebrated statesmen, the eminent physician and social reformer Benjamin Rush had been a Founding Father, one of 56 men who signed the Declaration of Independence in 1776.

. . .

. . ., after George Washington’s beaten army was pushed back across the Delaware River and Philadelphia’s militia marched to his assistance, Rush volunteered his medical skills. He helped tend the wounded from the Second Battle of Trenton, on Jan. 2, 1777, and the next day witnessed the bloody aftermath of Washington’s victory at Princeton.

Months later, Rush was appointed surgeon-general of the Continental Army’s so-called Middle Department—a key geographical sector that included Pennsylvania. He had ambitious plans for reform and outlined them in a pamphlet titled “Directions for Preserving the Health of Soldiers.” In a statement true for future American wars, he observed: “A greater proportion of men have perished with sickness in our armies than have fallen by the sword.” To curb that toll, Rush urged radical changes in food, clothing and hygiene. In his improving zeal, he unleashed a barrage of unrestrained letters to his friends in Congress that swiftly kindled a feud with his superior, Dr. William Shippen.

Rush accused Shippen of neglect, incompetence and corruption but underestimated his antagonist’s political clout.

. . .

(p. C8) . . ., Rush himself had always suspected that his outspoken views would affect his reputation, observing: “The most acceptable men in practical society, have been those who have never shocked their contemporaries, by opposing popular or common opinions.” He added, with considerable prescience: “Men of opposite characters, like objects placed too near the eye, are seldom seen distinctly by the age in which they live.” Through the efforts of Mr. Fried and Mr. Unger, what Benjamin Rush characterized as “the distant and more enlightened generations” are now better placed to judge him.

For the full review see:

Stephen Brumwell. “American Hippocrates.” The Wall Street Journal (Saturday, May 20, 2017 [sic]): C7-C8.

(Note: ellipses added.)

(Note: the online version of the review has the date Sept. 20, 2018 [sic], and has the title “‘Rush’ and ‘Dr. Benjamin Rush’ Review: American Hippocrates.”)

The books under review are:

Fried, Stephen. Rush: Revolution, Madness, and Benjamin Rush, the Visionary Doctor Who Became a Founding Father. New York: Crown, 2018.

Unger, Harlow Giles. Dr. Benjamin Rush: The Founding Father Who Healed a Wounded Nation. New York: Da Capo Press, 2018.

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 received 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.