Month: August 2026

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.)

Scientists Find “64,000 Square Miles of Climate Resilient Ocean” Where “Corals Are More Likely to Survive”

When environmentalists want to highlight the harm from global warming they frequently present the dire plight of the world’s coral reefs as a prime example. Now, in The New York Times Science section, Katharine Houreld reports that a new scientific study documents that the plight is far less dire than environmentalists had previously thought:

(p. D2) As spiking ocean temperatures are devastating reefs around the world, a handful of scientists have found a reason for cautious optimism. They’ve used artificial intelligence to detect sheltered pockets where cool currents, reduced exposure to sunlight and locations outside cyclone paths mean corals are more likely to survive.

The study, led by the Wildlife Conservation Society and presented at the Our Ocean Conference in Mombasa, Kenya, is currently undergoing peer review for publication in the journal Environmental Research Letters.

Five scientists identified 42 factors that create the conditions for the coral havens, called refugia, and then ran those through a program with nearly 38,000 human observations of coral cover and composition gathered over 65 years. The program identified more than 64,000 square miles of climate-resilient ocean in 72 countries.

The work found three times as many refugia as a landmark 2018 assessment known as the 50 Reefs Study, the first paper to systematically identify areas around the globe where coral might still be saved.

Houreld’s article is:

Katharine Houreld. “Cooler Currents: Down in the Reefs, Uplifting News About Global Warming.” The New York Times (Tues., June 30, 2026): D2.

(Note: the online version of the Houreld article was updated June 29, 2026, and has the title “Climate: There’s a Bit of Good News for Coral Reefs.” Where there is a slight difference in wording, the quotations above follow the print version.)

The academic preprint summarized in Houreld’s article is:

Zawada, Kyle J. A., Emily S. Darling, Stacy D. Jupiter, Timothy R. McClanahan, and Joseph M. Maina. 2026. Machine-Learning and Prioritization Models Reveal Climate Refugia for Coral Reefs into 2050. EcoEvoRxiv (May 20).