Category: Health

Finding a Disease Mechanism, and a Drug to Block It, Does Not Always Work

Many medical researchers think that the only route to progress is through basic research, and even then, progress may only consist of incrementally longer life or modest reductions in side-effects. For instance Dr. Paul Marks, who was influential in Nixon’s war on cancer, believed Nixon should only fund basic science, by which he meant cell genetics, and that such research would probably not cure cancer, but only help us to better manage it. Some medical researchers (e.g. Prasad and Cifu 2015; Raza 2019) have criticized this approach as “reductionism.” Others (e.g., Devita and Devita-Raeburn 2015; Prasad and Cifu 2015; Raza 2019) support a pluralistic approach–any method that yields major advances, especially cures, is okay.

Those who advocate basic science seek mechanisms of disease, and when they think they have found one, they seek a chemical that will interfere or block that mechanism. The article quoted below tells the illuminating story of scientists who identified inflammation as a major mechanism of atherosclerosis and found a drug (ziltivekimab) that interferes with that mechanism. They then tested it using the “gold standard”: a large-scale, double-blind randomized controlled trial (RCT). But to their “shock” they found that cardiovascular death rates were not lower for those taking the drug than for those taking a placebo.

The ultimate goal is cures. Finding a mechanism, and a chemical that blocks it, can be one path to a cure. But that path sometimes leads to a dead end. So we should allow researchers to follow other paths as well.

(p. D4) Novo Nordisk stunned the cardiology world last week when it announced that a large study it was running on an experimental drug for heart disease had failed. The drug, widely expected to be a blockbuster, was no better than a placebo.

The drug, ziltivekimab, reduces inflammation, which is generally thought to be a cause of atherosclerosis. Stopping that inflammation was hoped to be a way to save lives.

Now the drug’s failure is raising a troubling question. Is inflammation really a cause or is it just a marker of atherosclerosis, the way gray hair is a marker of aging?

Cardiologists had mixed reactions to the news. Dr. Sanjay Kaul, a cardiologist at Cedars Sinai, quoted Thomas Huxley on X: “The great tragedy of science — the slaying of a beautiful hypothesis by an ugly fact.”

Dr. David Maron of Stanford, who is president of the American Society for Preventive Cardiology, said the result “comes as a surprise and a big disappointment.”

But he added, something could have been wrong with the study: Perhaps it just wasn’t the right drug to target heart disease inflammation, or maybe patients in the trial were too sick to be helped by anti-inflammatory medications. There is too much evidence, he said, from pathology studies of plaques in arteries, animal studies, epidemiology and other clinical trials, to toss out the inflammation hypothesis.

“Inflammation is more than a marker of disease, it is a cause of the disease,” Dr. Maron said.

The Novo Nordisk study, called Zeus, involved more than 6,300 patients with heart disease or advanced kidney disease. They also had high levels in their blood of a marker of inflammation known as C reactive protein, or CRP. And they had high levels of interleukin-6, or il-6, a chemical that causes inflammation.

The drug did what it was supposed to do. It made il-6 levels plunge. CRP levels fell in concert.

With those signals indicating that inflammation was controlled, it seemed only logical that heart disease complications and cardiovascular death rates would drop, too. But that didn’t happen.

“I think we’re all in a state of shock,” said Dr. Martha Gulati of Houston Methodist, past president of the American Society for Preventive Cardiology.

For the full story, see:

Kolata, Gina. “Heart Drug Falters, Toppling a Theory.” The New York Times (Tues., August 11, 2026): D4.

(Note: the online version of the article has the date Aug. 6, 2026, and has the title “A Promising Heart Drug Fails, Challenging a Long-Held Theory of Disease.”)

When U.S. Firms Do the Hard Discovery of Disease Mechanisms, Chinese Firms Cash in With Quick Development of “Fast Followers”

The most binding constraint in drug development is identifying a mechanism by which the disease works, and targeting a weak point through which the mechanism can be slowed or shut down. Since this is the hardest, scarcest part of drug development, firms that achieve it should be rewarded. If they are, then we would find more resources going into searches for mechanisms of disease, and ultimately achieve more effective therapies and even cures. But Chinese firms are increasingly alert to U.S. firms’ advances in mechanism discovery. “After Novo Nordisk published landmark results in February 2021 showing strong results for its weight-loss drug semaglutide, at least 16 Chinese programs targeting the same mechanism filed for clinical-trial approval or dosed patients in China within 18 months, according to the biopharma market-intelligence firm Sleuth, and at least 62 such Chinese programs have launched through June 2026” (Martinez 2026, p. A10).

When Chinese pharma firms learn of the discovery of a new mechanism they are quickly developing, and running trials on, “fast follower” drugs that make use of the same mechanism, but affect the mechanism with a slightly different chemical entity. They can run the trials more quickly, partly because their government and scientific institutions tolerate, and even encourage, them to cut corners in a variety of ways (Ritchie 2020, p. 70). They can then gain fast approval of their fast follower drugs, receiving a larger part of the rewards from the therapy than the firms that achieved the hardest part by discovering and proving the mechanism.

As long as this system continues, it creates a perverse incentive for firms to be fast followers, rather than discoverers of fundamental mechanisms. It also creates a perverse incentive for firms discovering new mechanisms to practice secrecy rather than transparency.

Small mission-oriented startups are the most likely source of the discovery of new mechanisms. But they are also the most resource-constrained, and the least able to conduct large trials. Secrecy will make it harder for them to raise funds, making it harder for them to survive, let alone thrive. The situation for the small firms is all the worse because the FDA requires large Phase 3 double-blind randomized clinical trials, which are especially hard for small firms to fund and execute.

My musings above were informed and stimulated partly by the article:

Xavier Martinez. “U.S. Biotechs Step Up Secrecy To Beat Chinese Drug Copycats.” The Wall Street Journal (Fri., July 10, 2026): A1 & A5.

(Note: the online version of this article has the date July 9, 2026, and has the title “U.S. Biotechs Are Keeping More Secrets to Beat Copycats in China.”)

The book I reference above on Chinese RCTs is:

Ritchie, Stuart. 2020. Science Fictions: How Fraud, Bias, Negligence, and Hype Undermine the Search for Truth. Metropolitan Books.

The Burdens of Prior Approval Still Bedevil Our Over-Regulated Semi-Socialist Healthcare System

In June 2025 many healthcare insurance companies promised to reduce the burden of requirements for prior authorization for treatments. Prior authorization delays treatment, increases uncertainty, and burdens patients and healthcare providers with substantial costs in time and effort to fill out paperwork. As of May 2026, surveys of doctors, administrators, and patients still found prior authorization requirements to be a burden, many not detecting a noticeable change.

This is consistent with what Dr. Ben Goldacre has observed about big pharma firms. When patients or policy makers complain about some practices, such as lack of transparency in reporting clinical trials that fail to support a new drug, the firms promise to take action, and policy makers move on to other issues, thinking that the complaint has been resolved. But often the firms do not deliver on their promises, which amount to “fake fixes” (Goldacre 2013, pp. 47, 54, 299, 333, and 343). Letting our guard down based on the “false reassurance” (Goldacre 2013, pp. 47 and 54) of their promises, no one holds them responsible.

What is true of big pharma firms may also be true of healthcare insurance firms.

The problem is not that the firms are led by evil people, but that perverse incentives lead good people to do bad things. The perverse incentives are an unintended consequence of a baroque system built largely with good intentions.

For the article documenting the continuing burden of prior authorization rules, see:

Reed Abelson. “Insurance Still Stalling Approvals.” The New York Times (Mon., May 18, 2026): B1 & B3.

(Note: the online version of the article has the same date as the print version, and has the title “Medical Care Delays for Approval Persist, Despite Insurers’ Promises.”)

Goldacre’s book, that I praise above, is:

Goldacre, Ben. 2013. Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients. New York: Farrar, Straus and Giroux.

The Ubiquitous Claim That the “Gold Standard” for Testing the Safety and Efficacy of a Treatment Is a Randomized Controlled Trial

I am working on revising a paper that currently has the title “FDA-Mandated “Gold Standard” RCTs Hike Costs and Block Cures.” In the paper I state that a ubiquitous assertion is that “the gold standard” method for learning the safety and efficacy of a medical treatment is a randomized controlled trial (RCT). I have accumulated many examples to support my statement, but to save space in the paper, I am going to list the examples in this blog entry. As time permits, I will update this list as I encounter added examples.

This matters because I believe that calling RCTs “the gold standard,” functions to shut down any discussion of whether any other methods, such as well-done observational studies, might be cheaper, more ethical, or even more sound, than RCTs. (Calling RCTs “the gold standard” serves to locate such a discussion outside the Overton window of politely acceptable discourse.) Arguments and evidence are thus ignored that deserve to be heard and pondered.

Here are a few quotations supporting my claim that RCTs are ubiquitously viewed as the “gold standard” of medical research.

“Generations of medical students have been taught, quite rightly, that the double-blind, randomized [sic], placebo-controlled trial is the gold standard of evidence for new treatments” (Ritchie 2020, 110).

“The purists of evidence-based medicine demand data from randomized controlled trials (RCTs) before doing anything. Those trials are the gold standard of medical evidence, . . .” (Attia 2023, 50; italics in original).

“. . . the results of preliminary clinical trials, the gold standard in medicine, are compelling, despite the small sample sizes” (Whiteman 2023, 167).

“. . . a randomised [sic] clinical trial – medicine’s gold standard for sorting genuine treatments from quackery” (Yong 2016, 231).

“It was the only randomized controlled trial, the gold standard test of efficacy in medicine, ever done in iMCD” (Fajgenbaum 2019, 189).

“Some of these papers are randomized controlled trials (RCTs), which are considered “the gold standard” because they randomly separate people into a test and a control group. If the test group gets the effect and the control group doesn’t, it suggests a cause because the test food is the only difference” (Williams 2021, 204).

“The randomized controlled trial is the gold standard for evidence in clinical medicine” (Prasad and Cifu 2015, 119).

“First devised in the late 1940s (in a study of tuberculosis treatments), the RCT is arguably the most important medical technology of the 20th century. When large and well designed, it is the most powerful way to elucidate the truth in all of medical science. And though it cannot tell you about the mechanism of how a treatment works biologically, it can show conclusively whether a given intervention accomplishes a given goal. In medicine, it is the gold standard for proving a claim” (Prasad and Cifu, 2015, 124).

Without providing you the passages, here are some additional sources that support the ubiquity of the claim that RCTs are the “gold standard” of medical research: Bothwell et al. (2016); Concato and Horwitz (2018); Cook (2018); Hariton and Locascio (2018); Jones and Steel (2018); Mowat et al. (2018).

The full citations for the publications briefly cited above are:

Attia, P. 2023. Outlive: The Science and Art of Longevity. Harmony.

Bothwell, L. E., J. A. Greene, S. H. Podolsky, and D. S. Jones. 2016. “Assessing the Gold Standard — Lessons from the History of RCTs.” New England Journal of Medicine 374, no. 22 (June 2): 2175–81.

Concato, J., and R. I. Horwitz. 2018. “Randomized Trials and Evidence in Medicine: A Commentary on Deaton and Cartwright.” Social Science & Medicine 210 (Aug.): 32–36.

Cook, T. D. 2018. “Twenty-Six Assumptions That Have to Be Met If Single Random Assignment Experiments Are to Warrant “Gold Standard” Status: A Commentary on Deaton and Cartwright.” Social Science & Medicine 210 (Aug.): 37–40.

Fajgenbaum, D. 2019. Chasing My Cure: A Doctor’s Race to Turn Hope into Action; A Memoir. Ballantine Books.

Hariton, Eduardo, and Joseph J. Locascio. 2018. “Randomised Controlled Trials – the Gold Standard for Effectiveness Research: Study Design: Randomised Controlled Trials.” BJOG: an international journal of obstetrics and gynaecology 125, no. 13 (Dec.): 1716–16.

Jones, A., and D. Steel. 2018. “A Combined Theoretical and Empirical Approach to Evidence Quality Evaluation: A Commentary on Deaton and Cartwright.” Social Science & Medicine 210 (Aug.): 74–76.

Mowat, Ryan, S. V. Subramanian, and Ichiro Kawachi. 2018. “Randomized Controlled Trials and Evidence-Based Policy: A Multidisciplinary Dialogue.” Social Science & Medicine 210 (Aug.): 1.

Prasad, V. K., and A. S. Cifu. 2015. Ending Medical Reversal: Improving Outcomes, Saving Lives. Johns Hopkins University Press.

Ritchie, S. 2020. Science Fictions: How Fraud, Bias, Negligence, and Hype Undermine the Search for Truth. Metropolitan Books.

Whiteman, N. 2023. Most Delicious Poison: The Story of Nature’s Toxins—from Spices to Vices. Little, Brown Spark.

Williams, R. A. 2021. Fixing Food: An FDA Insider Unravels the Myths and the Solutions. Post Hill Press.

Yong, E. 2016. I Contain Multitudes: The Microbes within Us and a Grander View of Life. Ecco.

Aspire to Achieve the Hebrew Birthday Blessing

Peter Thiel and I praise the pursuit of what Jim Collins and Jerry Porras called “BHAGs” (big, hairy, audacious goals). One such BHAG would be to make lives of 120 years common.

“The Hebrew blessing on a birthday is that you should live to 120 (Moses’ age when he died in good shape with all of his marbles)” (Weiss 2026, A13). Jeanne Calment lived to 122, providing proof-of-concept that a life of 120 years is possible.

Longer lives would allow us to pursue more ambitious projects, and would give us more second and third chances when our first projects fail. The pursuit of ambitious goals is one path to a meaningful, fulfilling life. One such goal is to add many years to each of our lives.

The source of the Weiss quote is:

Lou Weiss. “When Your Friends All Turn 70.” The Wall Street Journal (Fri., July 10, 2026): A13.

(Note: the online version of the Weiss commentary has the date July 9, 2026, and has the same title as the print version.”)

The publications that I refer to in my first sentence are:

Collins, James C., and Jerry I. Porras. 1994. Built to Last: Successful Habits of Visionary Companies. HarperBusiness.

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

Thiel, Peter, and Blake Masters. 2014. Zero to One: Notes on Startups, or How to Build the Future. Crown Business.

Regulatory Healthcare Price Caps Create Perverse Incentives With Unintended Consequences

Lorens Helmchen and Tony LaSasso’s op-ed in The New York Times argues that when regulators enforce price caps on medical treatments, they create perverse incentives for healthcare providers. For fragile patients with complicated maladies, the cost of treatment may exceed the price cap the regulators allow the healthcare provider to charge. In that case the healthcare provider has a perverse incentive either to deny the patient care, or to give the patient a lower, ineffective, level of care.

I argue elsewhere that there are better ways to reduce the too-high costs of healthcare, e.g., increase competition by repealing certificate of need requirements before opening new healthcare facilities, reduce practice restrictions on nurse practitioners, and eliminate the mandated Phase 3 RCTs required for FDA drug approval.

The Helmchen and LaSasso op-ed is:

Lorens Helmchen and Tony LoSasso. “Capping the Cost of Health Care Is a Mistake.” The New York Times (Tues., July 20, 2026): A23.

(Note: the online version of the op-ed has the date July 20, 2026, and has the title “This Is Not the Answer to Soaring Health Care Costs.”)

With Skin-in-the-Game Urgency, Wexler Sought Cure and Was Enrolled in RCT in Spite of Age

I argue that a person who has a disease, or has a relative who has a disease, sometimes has a skin-in-the-game sense of urgency in seeking a cure for the disease. The urgency sometimes energizes them to ignore perverse incentives, and to overcome obstacles and constraints, that slow or block the efforts of academics, pharma firms, or government regulators, to fight the disease. The passages quoted below suggest that Nancy Wexler has a skin-in-the-game urgency to cure Huntington’s disease.

An important side-note to her story is that investigators conducting an RCT to test a possible drug to fight Huntington’s disease, decided to enroll Wexler in their RCT, despite her being older than the upper limit set in their RCT protocol. This illustrates my claim that in the actual messy real-world there are many ways that RCTs, as implemented, deviate from the ideal “gold standard” RCTs that are discussed in the theoretical literature.

(p. D1) At age 80, Nancy Wexler has Huntington’s disease, a dreaded brain disease that destroys a person’s ability to control movements. There is no treatment. There is no cure.

. . .

Nancy is not just any Huntington’s disease patient. For decades, she led a research effort in a remote area of Venezuela that found the gene responsible for Huntington’s. That work yielded a blood test that enable at-risk people to find out if they are destined to get the disease.

. . .

(p. D5) After graduating from Radcliffe College, she was in Europe on Fulbright fellowship when she was called home to learn her mother had the disease.

. . .

When his wife’s slide into the disease could no longer be denied, Milton called both sisters home and sat them down in his bedroom. The 50-50 chance now hung over both of them, too. He gave them some advice they never forgot: Don’t waste your life.

Alice decided to ignore Huntington’s and her own risk. “I didn’t want to have anything to do with it,” she told me. She became a historian.

Nancy had a different reaction. She would make Huntington’s the focus of her life, getting a Ph.D. in clinical psychology from the University of Michigan. Her thesis subject: the experiences of people with Huntington’s, and of those at risk for getting it. She thought of that choice as a way of coping with her situation. She wrote that it was a version of something the American Psychiatric Association called implosion theory — “a technique used in behavior therapy where the client is flooded with experiences believed to be relevant to the client’s fear.”

“I could talk about Huntington’s without seeming selfish and whiny,” she explained. “I could talk about how people felt in the context of helping them.”

. . .

On frequent trips to California, Nancy was also helping her father lead the Huntington Disease Foundation. The group’s gatherings couldn’t be further from the staid scientific meetings that are the main staple of academic life. There were no traditional talks, no slides. Instead, Nancy and her father invited creative scientists — who may or may not have ever thought about Huntington’s before — to brainstorm about ways to find the gene, scrawling their ideas on a whiteboard. The meetings always included a Huntington’s patient, or the family member of a patient, so the scientists could understand what was a stake.

. . .

The search for the gene began in earnest in 1980, focusing on three communities around Lake Maracaibo, Venezuela, that had the greatest prevalence of Huntington’s disease in the world.

. . .

Nancy led the research team, returning to Venezuela regularly for 22 years and collecting more than 4,000 blood samples from Venezuelans. She cared deeply for them, and even helped establish a nursing home for Huntington’s patients.

For the full article, see:

Gina Kolata. “Carrying On After Choosing Uncertainty.” The New York Times (Tues., June 23, 2026): D1 & D5.

(Note: ellipses added. In the original article, the phrase Don’t waste your life is italicized for emphasis.)

(Note: the online version of the article has the date June 11, 2026, and has the title “The Researcher Who Didn’t Want to Know.”)

In the Actual Messy Real-World, RCTs Can Be a Fool’s Gold Standard

George Stigler used to emphasize that when we compare markets to the government we often make an unfair comparison. We compare the ideal theoretical government, with the actual messy real-world market. We do the same thing in comparing methods of reaching medical truth. In this analogy the role of the government is played by double-blind randomized clinical trials (RCTs). In ideal theory, RCTs are the “gold standard.” The story quoted from below, shows that a lot can go wrong when RCTs are conducted in the actual messy real-world.

Note that the flaws in the RCT were NOT caught in the peer-review process, but were caught by “online sleuths and physicians,” practitioners with a sense of urgency and mission.

(p. D2) Early this year, a medical journal article caught the attention of cancer patients and doctors worldwide because of its extraordinary conclusion. Simply changing the time of day that immunotherapy was administered appeared to produce a stunning benefit for lung cancer patients.

Those who received IV infusions in the morning had their cancer kept at bay for twice as long as those who got it in the afternoon, according to the results from a clinical trial in China and published in the journal Nature Medicine in February [2026]. The study also reported that the patients lived nearly twice as long.

. . .

But on Wednesday [June 24, 2026], Nature Medicine retracted the study, citing a list of inconsistencies and irregularities in the trial’s design and results.

. . .

Among the issues that the journal cited in its retraction notice: Records that were supposed to be locked before the study started were changed midway through. There were discrepancies between the Chinese version of the study’s plan and the translated version. Every patient remained treated and tracked in the study’s first year, and no one dropped out because of side effects — highly unusual in an oncology study. And unusual patterns were found in the timing of follow-up scans.

“Due to the amount and nature of the problems identified, the editors no longer have confidence in the integrity of the results,” the journal said.

. . .

China’s critics often question the reliability of its biomedical research. Experts said that, similar to studies in the United States, China’s research output spans a wide range in quality: Some Chinese scientists run their studies at the most meticulous standards. Others were said to cut corners.

. . .

The study had enrolled 210 patients with advanced lung cancer at Hunan Cancer Hospital in Changsha, a city in south-central China. Patients were randomly assigned to receive infusions of an immunotherapy — Merck’s blockbuster drug Keytruda or Tyvyt, which is not approved in the United States — either before or after 3 p.m.

The study reported that tumors did not progress for 11 months in patients who received the earlier infusions, compared with six months for those given the later infusions. Patients receiving the earlier infusions lived for 28 months, compared with 17 months for those infused later in the day.

. . .

Dr. Anil Makam, an epidemiologist and health services researcher at the University of California, San Francisco, said such a drastic benefit, if real, would have prompted infusion clinics to overhaul staffing and scheduling to shift appointments to earlier in the day.

“If we believed the effects, it would be malpractice not to,” he said.

But within days after the study’s publication in Nature Medicine, online sleuths and physicians like Dr. Makam began raising concerns on social media and in blog posts. Less than three weeks after the study was published, the journal published an editor’s note saying it was investigating the issues.

In a statement on Thursday [June 25, 2026], Dr. João Monteiro, chief editor of Nature Medicine, which is published by Springer Nature, said, “We are grateful to the research community for bringing these concerns to our attention.”

For the full article, see:

Rebecca Robbins. “‘Too Good to Be True’: Chinese Study on Cancer Therapy Is Retracted.” The New York Times (Tues., June 30, 2026): B3.

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

(Note: the online version of the Houreld article was updated June 25, 2026, and has the title “‘Too Good to Be True’: A Chinese Study on Timing Cancer Therapy Is Retracted.” Where there is a slight difference in wording, the quotations above follow the print version.)

Elders Can Catalyze Progress

Max Planck is oft-quoted as saying that new theories do not triumph by convincing their opponents but by their opponents dying off and a new generation taking over. The claim is plausible but some evidence suggests it is false (Hull et al. 1978; Diamond 1980).

Our elders may sometimes be obstacles to progress, but they also may sometimes instead be catalysts of progress.

Those who deviate from mainstream views often suffer in terms of job security and career advancement. So most tone down their deviations and swim with the current.

But when you retire, your money and your time are your own. The penalties of deviation are fewer. And some, when they retire, want to take advantage of a last chance to make the world better. So to pursue their ikigai they swim toward progress, not toward prudence.

Take Ira Long who died recently. She had been an organic chemist. When she retired she wanted to take more direct action to do good. The AIDs epidemic was in full swing, so she contributed her expertise to the AIDs activists who stood up against the FDA to save lives by making new therapies available sooner.

Those involved with both sides of the conflict, say that Iris Long made a difference:

(p. 30) Iris Long, a chemist whose knowledge of the intricacies of pharmaceutical clinical trials and the Food and Drug Administration’s approval process made her a transformational figure in ACT UP, the militant political action group dedicated to ending the AIDS crisis, died on April 4 [2026] in Astoria, Queens.

. . .

By 1987, when Dr. Long first attended a meeting of ACT UP, the AIDS Coalition to Unleash Power, she had retired from her work as an organic chemist. She was looking to help people directly, rather than in a laboratory. She was not politically active, didn’t know anyone with AIDS and wasn’t even sure she had ever met anyone who was gay.

“God, the epidemic was getting so bad, and she thought she could help,” Jim Eigo, a writer and leading ACT UP member who worked closely with Dr. Long, said in an interview.

. . .

“She was their scientific North Star,” Dr. Anthony S. Fauci, the former director of the National Institute of Allergy and Infectious Diseases, said in an interview. “She told them that if you’re going to interact with the scientific community, you’re going to have to understand the science.”

. . .

Her guidance, Mr. Eigo said, empowered key ACT UP members, including Mark Harrington, to communicate with researchers and officials at the F.D.A. and other government agencies on a more equal, and therefore less confrontational, footing.

“They became so expert,” said Peter Staley, a prominent member of ACT UP, “that I witnessed some shocking conversations between Mark Harrington and Fauci talking about his lab work, and Fauci would just look stunned by Mark’s questions.”

. . .

Dr. Long, Mr. Eigo and Garry Kleinman, another ACT UP member, made a presentation to New York University doctors who were conducting clinical trials for AIDS drugs. The meeting soon led the F.D.A. to adopt parallel drug trials — with the result that patients who had exhausted azidothymidine, or AZT, the first drug approved to treat AIDS, could now take another drug (initially ganciclovir) that had passed the agency’s safety trials even while it was still being tested for effectiveness.

. . .

. . . Dr. Long knew that her background could be useful to the group. Her research had focused on a class of antiretroviral drugs called nucleoside analogues — altered sugar molecules trained to lure diseased cells away from healthy cells — of which AZT was one.

“She fully recognized that this would be one of the biggest epidemics in the history of mankind, and that not enough people were stepping up,” Mr. Staley said.

At an early meeting, Dr. Long was speaking to a large group that was growing restless with her presentation. She was not a gifted speaker — although she was better in small groups — but the activist Vito Russo rose to her defense.

“Shut up and listen!” he shouted, according to Mr. France’s book. “Listen! I don’t think any of you paid Iris Long the respect you should. There is no one doing any work in ACT UP that has a greater chance of doing real good for people with AIDS.”

. . .

“I was always a laboratory person, and now, interacting with people, it was completely different and something I had never done before,” she told the ACT UP Oral History Project in 2003. “I was not a joiner before, at all. But I was a fighter-type person that would fight for somebody’s rights.”

The AIDs activist rebellion is an important proof-of-concept. The concept is that the FDA should allow patients more choice of what medicines they consume. (Or another way to say it is that the power of the FDA to restrict free choice should be limited.) This is one of the rare cases where those with urgent ‘skin-in-the-game’ succeeded in speeding up or unbinding the regulatory process, in order to save lives (see Bhidé 2017).

While waiting for more libertarian policies, those with limited longevity may infer from the AIDs example that guerilla activist tactics can be justified and effective (see Thierer 2020, Tusk 2018).

Other cases where those who quit their jobs, or retired from them, swam toward progress can be found in in Richard Harris’s Rigor Mortis exposé. Contaminated cell lines are apparently endemic in medical research, undermining the reproducibility and clinical usefulness of much research. Scientists using the cell lines do not have the time or incentive to investigate this. If they discovered that their cell lines were contaminated, their past research and future careers could be jeopardized.

So to identify the contamination it takes the rare mission-oriented persons who are free of (or who have freed themselves from) perverse incentives.

Roland Nardone, at the age of 77, “was asked what he intended to do with the rest of his life” (Harris 2017, p. 96). He embarked on a “ten-year quest to straighten out . . . [the] glaring problem” of “bogus cell lines” (Harris 2017, pp. 96-97).

Amanda Capes-Davis “quit her job” at an institute in Sydney, Australia “to devote her full attention” to identifying contaminated cell lines (Harris 2017, pp. 97-98).

Christopher Korch “retired from academic, spends his energy, . . . , trying to untangle decades of bungled science surrounding cell cultures” (Harris 2017, p. 102).

Those with their own resources are less constrained to conform, and so pay a lower price when they choose to catalyze progress. This group includes the retired, as well as self-made entrepreneurs, the inheritors of wealth, or the occupiers of sinecures. PalmPilot founder and neuroscientist Jeff Hawkins (2021) is an example, as are some of the Victorian gentlemen scientists (see Champlin 1994; Harris 2017, pp. 169-170; Knell 2000; Maddox 2017; Repcheck 2004; Rudwick 1985).

The Iris Long obituary quoted above is:

Richard Sandomir. “Iris Long, 92, Chemist, Virus Expert And Science Mentor to AIDS Activists.” The New York Times, First Section (Sun., April 19, 2026): 30.

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

(Note: the online version of the article has the date April 17, 2026, and has the title “Iris Long, Scientific Mentor to AIDS Activists, Dies at 92.”)

Bibliography of Other Articles and Books Mentioned above:

Bhidé, Amar. “Constraining Knowledge: Traditions and Rules That Limit Medical Innovation.” Critical Review 29, no. 1 (Jan. 2017): 1–33.

Champlin, Peggy. Raphael Pumpelly: Gentleman Geologist of the Gilded Age. Tuscaloosa, AL: University of Alabama Press, 1994.

Diamond, Arthur M., Jr. “Age and the Acceptance of Cliometrics.” Journal of Economic History 40, no. 4 (Dec. 1980): 838–41.

France, David. How to Survive a Plague: The Inside Story of How Citizens and Science Tamed Aids. New York: Knopf, 2016.

Harris, Richard. Rigor Mortis: How Sloppy Science Creates Worthless Cures, Crushes Hope, and Wastes Billions. New York: Basic Books, 2017.

Hawkins, Jeff. A Thousand Brains: A New Theory of Intelligence. New York: Basic Books, 2021.

Hull, David L., Peter D. Tessner, and Arthur M. Diamond, Jr. “Planck’s Principle: Do Younger Scientists Accept New Scientific Ideas with Greater Alacrity Than Older Scientists?” Science 202 (Nov. 17, 1978): 717–23.

Knell, Simon J. The Culture of English Geology, 1815-1851. Farnham, UK: Ashgate Publishing Ltd, 2000.

Maddox, Brenda. Reading the Rocks: How Victorian Geologists Discovered the Secret of Life. New York: Bloomsbury USA, 2017.

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Federal Government Should Respect Citizens by Being Honest About Vaccine Side-Effects

I believe that some vaccines are among the most effective medical interventions to save lives. But I also believe in free choice, and that the government should be transparent in admitting the side-effects that occur, to varying degrees, with all vaccines. So I was puzzled and annoyed by the article quoted below on a CDC panel vote to withdraw support for immediate vaccination of neonates against hepatitis B. One of those seeking withdrawal of support for the vaccine cited “vaccine-injury claims paid out by the National Vaccine Injury Compensation Program” as evidence of side-effects. Then we get to the part that puzzles and annoys me: “the federal government has said that such settlements shouldn’t be used to draw conclusions about vaccine safety.”

Why not? It’s not the only relevant evidence, but it is relevant evidence. Why should we exclude it? Because it goes against the federal government’s status quo mandate? If there is a better reason, the article does not mention it.

(p. A1) A key vaccine panel at the Centers for Disease Control and Prevention voted 8-3 to nix a recommendation that all newborns be given a first dose of hepatitis B vaccine.

. . .

(p. A4) The newly appointed acting director of the drugs division at the Food and Drug Administration, Dr. Tracy Beth Hoeg, suggested to the panel that hepatitis B vaccines shouldn’t be given to children at all. She pointed to other countries including Denmark that don’t recommend the hepatitis B vaccine for all newborns. CDC scientist Adam Langer said many of those other countries including Denmark have national health systems, in which it is easier to screen and track infected mothers.

[Mark Blaxill, a longtime antivaccine activist who now works at the CDC] argued that vaccine-injury claims paid out by the National Vaccine Injury Compensation Program showed that the hepatitis B vaccine causes harm. But the federal government has said that such settlements shouldn’t be used to draw conclusions about vaccine safety.

For the full story see:

Liz Essley Whyte and Sabrina Siddiqui. “Vaccine Panel Nixes Hepatitis B Guidance.” The Wall Street Journal (Sat., Dec. 6, 2025): A1 & A4.

(Note: ellipsis added; the words in brackets are from a couple of paragraphs earlier in the article.)

(Note: the online version of the story has the date December 5, 2025, and has the title “CDC Panel Remade by RFK Jr. Votes to Alter Hepatitis B Vaccine Guidance.”)