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Both Homocysteine and Cholesterol Are Actionable Causes of Atherosclerosis

Alan Donagan taught a thought-provoking graduate course on Action Theory when I was a philosophy student at the University of Chicago in the mid to late 1970s. Some of the course related to how we think about causes in the social sciences and in policy debates.

Often we seek THE cause of what we want (or what we want to avoid). But most results have multiple causes. Which cause is most important, and so to some appears to be THE cause, depends largely on which cause is most easily actionable, which can change based on our knowledge or our constraints.

The obituary passages quoted below tell the sad story of how Kilmer McCully found that an amino acid called homocysteine was one cause of atherosclerosis, a cause that was actionable (could be countered) by eating foods containing various of the B vitamins. Kilmer’s career was canceled by powerful academics committed to the dominant view that cholesterol was THE cause of atherosclerosis.

McCully’s Harvard lab was moved to the basement, and eventually he was pressured out of Harvard.

Later studies, including the large, influential, and continuing Framingham study, eventually vindicated McCully’s claim.

We know the wrongly-cancelled pay a price for deviating from the dominant view. But how often do the cancellers pay a price for wrongly cancelling?

(p. B6) Kilmer S. McCully, a pathologist at Harvard Medical School in the 1960s and ’70s whose colleagues banished him to the basement for insisting — correctly, it turned out — that homocysteine, an amino acid, was being overlooked as a possible risk factor for heart disease, died on Feb. 21 [2025] at his home in Winchester, Mass. He was 91.

. . .

Dr. McCully didn’t think cholesterol should be ignored, but he thought it was malpractice to disregard the significance of homocysteine. His bosses at Harvard disagreed. First, they moved his lab below ground; then they told him to leave. He struggled to find work for years.

. . .

Presenting the case of homocystinuria in a 9-year-old girl, doctors mentioned that her uncle had died from a stroke in the 1930s, when he was 8 and had the same disease. “How could an eight-year-old have died the way old people do?” Dr. McCully wrote, with his daughter, in “The Heart Revolution” (1999).

When Dr. McCully tracked down the autopsy report and tissue samples, he was astounded: The boy had hardened arteries, but there was no cholesterol or fat in the plaque buildup. A few months later, he learned about a baby boy with homocystinuria who had recently died. He also had hardened arteries.

“I barely slept for two weeks,” he wrote.

In 1969, Dr. McCully published a paper about the cases in The American Journal of Pathology. The next year, in the same journal, he described what happened after he injected rabbits with high doses of homocysteine. “The aortas of all 13 of the animals injected with homocysteine were moderately thickened,” he wrote, “compared to the controls.”

. . .

The medical profession responded with “stony silence,” Dr. McCully told The Times. . . .

. . .

“I felt for him, and I admired him,” J. David Spence, a professor emeritus at the University of Western Ontario who studies homocysteine, said in an interview. “He was neglected more than he ought to have been. It was sad.”

That began to change in the early 1990s, when large-scale, long-term studies of the risks for heart disease revealed that Dr. McCully had, in fact, been heading down the right path when Harvard relegated him to the basement.

. . .

As a teenager, Kilmer was enthralled by “Microbe Hunters,” Paul de Kruif’s 1926 book about Pasteur, Walter Reed, Robert Koch and others who investigated infectious diseases. He knew almost immediately that he wanted to become a scientist.

. . .

At a medical school reunion in 1999, his classmates presented him with a silver platter.

It was inscribed, “To Kim McCully, who saw the truth before the rest of us, indeed before the rest of medicine, and who would not be turned aside.”

For the full obituary see:

Michael S. Rosenwald. “Kilmer S. McCully Is Dead at 91; Fueled Debate on Heart Disease.” The New York Times (Monday, March 24, 2025): B6.

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

(Note: the online version of the obituary has the date March 21, 2025, and has the title “Kilmer McCully, 91, Dies; Pathologist Vindicated on Heart Disease Theory.”)

The book by McCully and his daughter, mentioned above, is:

McCully, Kilmer, and Martha McCully. Heart Revolution: The Vitamin B Breakthrough That Lowers Homocysteine Levels, Cuts Your Risk of Heart Disease, and Protects Your Health. New York: HarperCollins Publishers, 1999.

The book that inspired a teenage McCully to become a scientist is:

Kruif, Paul de. Microbe Hunters. New York: Harcourt, Brace and Company, 1926.

Extinct Homo Erectus Could Adapt to Global Warming and “Thrived in a Harsh Desert Landscape”

In my Openness book I argue that environmentalists often exaggerate the harm from global warming because they fail to consider the extent of human adaptability. Recent evidence (see below) suggests that even our extinct ancestor, Homo erectus, was already more adaptable to climate change than other advanced primates such as chimpanzees and orangutans.

(p. D3) Chimpanzees live only in African rainforests and woodlands. Orangutans live only in the jungles of Indonesia. But humans live pretty much everywhere. Our species has spread across frozen tundras, settled on mountaintops and called other extreme environments home.

Scientists have historically seen this adaptability as one of the hallmarks of modern humans and a sign of how much our brains had evolved. But a new study hints that maybe we aren’t so special.

A million years ago, researchers have found, an extinct species of human relatives known as Homo erectus thrived in a harsh desert landscape once considered off limits before Homo sapiens came along.

“It’s a significant shift in the narrative of adaptability, expanding it beyond Homo sapiens to include their earlier relatives,” said Julio Mercader, an archaeologist at the University of Calgary and an author of the study, which was published Thursday [Jan. 2?, 2025] in the journal Communications Earth and Environment.

. . .

For hundreds of thousands of years, the researchers determined, Engaji Nanyori had been a comfortable open woodland. But around a million years ago, the climate dried up and the trees vanished. The landscape turned to a Mojave-like desert shrub land — an extremely arid place that seemed inhospitable for early hominins.

“The data led us to a pivotal question: How did Homo erectus manage to survive and even thrive under such challenging conditions?” Dr. Mercader said.

Instead of fleeing, the hominins figured out how survive in their changing home. “Their greatest asset was their adaptability,” Dr. Mercader said.

They changed the way they searched for animal carcasses to scavenge, for example. The hominins found the ponds and streams that sprang into existence after storms. They didn’t just drink at these fleeting watering holes. They hunted the animals that also showed up there, butchering their carcasses by the thousands.

The hominins also adapted by upgrading their tools. They took more care when chipping flakes from stones to give them a sharper edge. Rather than just pick up rocks wherever they were, they preferred material from particular places. And once they made a tool, they carried it with them.

For the full story see:

Carl Zimmer. “Early Human Relatives Thrived in Harsh Desert.” The New York Times (Tuesday, January 28, 2025): D3.

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

(Note: the online version of the story was updated Jan. 20, 2025, and has the title “Extinct Human Species Lived in a Brutal Desert, Study Finds.”)

The academic paper in Communications Earth and Environment, mentioned above, is:

Mercader, Julio, Pamela Akuku, Nicole Boivin, Alfredo Camacho, Tristan Carter, Siobhán Clarke, Arturo Cueva Temprana, Julien Favreau, Jennifer Galloway, Raquel Hernando, Haiping Huang, Stephen Hubbard, Jed O. Kaplan, Steve Larter, Stephen Magohe, Abdallah Mohamed, Aloyce Mwambwiga, Ayoola Oladele, Michael Petraglia, Patrick Roberts, Palmira Saladié, Abel Shikoni, Renzo Silva, María Soto, Dominica Stricklin, Degsew Z. Mekonnen, Wenran Zhao, and Paul Durkin. “Homo Erectus Adapted to Steppe-Desert Climate Extremes One Million Years Ago.” Communications Earth & Environment 6, no. 1 (2025): 1-13.

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.

Ed Leamer Doubted the Robustness of Many Econometric Studies

Ed Leamer showed that a lot of econometric studies in economics amounted to economists searching among the plethora of plausible specifications of variables and functional forms, until they found one that yielded the sign and statistical significance of the variable they cared about. So, for example, an economist who thought capital punishment deterred murder, could produce that result, and an economist who thought capital punishment did strong>not deter murder, could also produce that result.

Leamer suggested that economists should show whether their results varied under a variety of specifications, in order to show the robustness of the claimed main result.

(p. C6) One day in elementary school, Edward Leamer noticed that his teacher had written the wrong answer to a math problem on the blackboard, so he stood up and told her so. His teacher took another look and assured him that it was correct. Again he protested, so she asked him to take his seat.

“He refused to sit down,” his brother, the author Laurence Leamer, said in a gathering on Zoom to celebrate his brother last month. “His whole life, he’s refused to sit down.”

Leamer, an economist who died Feb. 25 at the age of 80 from complications stemming from ALS (or Lou Gehrig’s disease), was best known for standing up and telling economists that they were doing it wrong. In influential papers like 1983’s “Let’s Take the Con Out of Econometrics” and his seminal book, “Specification Searches” (1978), Leamer warned economists that the methods they were using to analyze data produced weak findings that couldn’t hold up to scrutiny. He said economists often had a bias toward the results they wanted or that were the kinds of firm conclusions that led to press coverage, funding and policy positions they supported.

What’s more, Leamer warned economists that they weren’t being honest about the strength of their conclusions or transparent about the fact that they had run other tests that showed different results.

For the full obituary, see:

Chris Kornelis. “The Economist Who Called Out Other Economists.” The Wall Street Journal (Saturday, March 15, 2025): C6.

(Note: the online version of the obituary has the date March 14, 2025, and has the title “Edward Leamer, Economist Who Said Economists Were Doing It Wrong, Dies at 80 [sic].” Where the wording is different between the versions, the last three sentences quoted above follow the online version.)

Leamer’s wonderful paper, mentioned above, is:

Leamer, Edward E. “Let’s Take the Con Out of Econometrics.” American Economic Review 73, no. 1 (March 1983): 31-43.

Leamer’s book, mentioned above, is:

Leamer, Edward E. Specification Searches: Ad Hoc Inference with Nonexperimental Data, Wiley Series in Probability and Mathematical Statistics. New York: John Wiley & Sons, Inc., 1978.

Public Health “Experts” Rebuffed Renegades Who Saw Covid Spread in Aerosols

Steven Johnson’s The Ghost Map shows how rigid adherence to the miasma theory of disease shut out alternatives. And an alternative was indeed needed to explain the spread of cholera. But the defeat of the miasma theory for cholera may have been too complete, prejudicing scientists to oppose theories of disease-spread through the air, which turn out to be important for some diseases, such as Covid-19.

(p. C9) In early 2020, as word spread of a frightening new respiratory outbreak in China, the World Health Organization and the Centers for Disease Control and Prevention were pressed for advice. Both initially counseled social distancing, guided by the assumption that the disease was spread by large, boggy droplets that fell rapidly to the ground after being expelled by coughing or sneezing.

By avoiding such projectiles and keeping surfaces clean, the reasoning went, infection could be avoided. Yet this advice ignored—with tragic consequences—nearly a century of science suggesting that many respiratory diseases can spread via microdrops that are exhaled during normal breathing and can remain suspended in the air for hours.

In “Air-Borne,” the New York Times science writer Carl Zimmer seeks to explain how public-health officials could have overlooked such an important mechanism of the Covid-19 contagion. He begins his meticulous history with the ancient Greek physician Hippocrates, who taught that illness could be caused by “an invisible corruption of the air,” which he termed a “miasma.”

. . .

While the field of aerobiology may have entered the new millennium stuck on a “stagnant plateau,” as one journal article lamented, hope was starting to emerge. Advances in technology led to a more complete characterization of the aerobiome. A range of scientists from around the world, meanwhile, re-examined the possibility of airborne transmission and discovered the evidence against it wanting.

Following the emergence of Covid-19, many of these researchers were appalled by the seemingly reflexive—“mind-boggling,” in the words of one scientist—rejection of airborne transmission by public-health agencies. At first, these renegades individually struggled to have their work published but were largely rebuffed.

After an early Covid-19 outbreak among a choir in Washington state was initially attributed to large-droplet spread, a more detailed analysis by a unified group of skeptical researchers suggested that airborne transmission was far more likely. On Dec. 23, 2021—nearly 21 months after tweeting “FACT: #COVID19 is NOT airborne”—the WHO “finally issued a clear public statement that the virus was airborne,” Mr. Zimmer writes. A triumph for persistent scientists, perhaps, but also a pointed reminder of the complexity, fragility and deeply human dependencies of evolving science.

For the full review see:

David A. Shaywitz. “Microbes in the Mist.” The Wall Street Journal (Saturday, March 15, 2025): C9.

(Note: ellipsis added.)

(Note: the online version of the review has the date March 14, 2025, and has the title “‘Air-Borne’: The Microbes in the Mist.”)

The book under review is:

Zimmer, Carl. Air-Borne: The Hidden History of the Life We Breathe. New York: Dutton, 2025.

Global Warming Allows German Wine Entrepreneurs to Grow a “Superb” Chardonnay

In my Openness book, I argue that the costs of global warming have been exaggerated, partly because environmentalists forget that entrepreneurs can adapt, either lessening the costs, or sometimes even creating benefits. A case of creating benefits is apparently now the growing of “superb” chardonnay wine in Germany:

(p. D4) What accounts for the arrival of . . . German chardonnays? Certain wine regions like Rheinhessen, the Pfalz and the Obermosel have limestone soils, which chardonnay has a special affinity for, but the warming climate has made it possible to ripen chardonnay sufficiently to make superb wines.

Climate change influenced decisions to plant chardonnay in other ways as well.

“Climate change for us does not just mean it’s getting warmer and warmer, it means everything is getting more extreme — frost risk, weeks without rain, hailstorms,” said Klaus Peter Keller, . . . . “Therefore, we must spread the risk a bit more than we would 30 or 40 years ago. Rather than 100 percent riesling we have now 70 percent riesling, 15 percent pinot noir, 10 percent chardonnay and 4 percent others, and we think that will be the structure for the coming 30 or 40 years.”

Mr. Keller said he had wanted to plant pinot blanc rather than chardonnay but that their son Felix had pushed for chardonnay.

“Felix was right,” he said. “Chardonnay is much better adapted to climate change, with thicker skins, and it transmits the soil much better than pinot blanc.”

Felix Keller said by email that his grandfather had tried planting chardonnay in 1988, but that the timing had been wrong.

“Back then, it didn’t ripen every year,” he said. “It took us until 2018 to try again. We believe chardonnay has a bright future in Germany because we now have the climate that used to be in Burgundy in the early ’90s.”

For the full commentary see:

Eric Asimov. “The Pour; A Surprise From Germany: Chardonnay.” The New York Times (Weds., March 5, 2025): D1 & D4.

(Note: ellipses added.)

(Note: the online version of the commentary was updated March 4, 2025, and has the same title as the print version.)

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 Entrepreneur Bill Gates Believes He Is “on the Autism Spectrum”

In my “Openness” book I argue and present some evidence that toleration for those who think different, including those on the Autism spectrum, will allow more innovative entrepreneurs to flourish, bringing benefits to us all. In the first volume of his autobiography, innovative entrepreneur Bill Gates speculates that he is on the Autism spectrum.

(p. A17) Mr. Gates was, he says, a “happy boy,” according to family lore. He had a wide grin, excess energy and a tendency to rock his body when he was deep in thought. Mr. Gates speculates that today he “probably would be diagnosed on the autism spectrum.”

For the full review see:

David A. Shaywitz. “Bookshelf; A Life of DOS And Don’ts.” The Wall Street Journal (Tuesday, Feb. 4, 2025): A17.

(Note: the online version of the review has the date February 3, 2025, and has the title “Bookshelf; ‘Source Code’: A Life of DOS and Don’ts.”)

The first volume of Bill Gates’s autobiography is:

Gates, Bill. Source Code: My Beginnings. New York: Alfred A. Knopf, 2025.

My book, that I mention in my opening comments, is:

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

Songbirds Adapt to Global Warming by Shrinking in Size

In my Openness book I argue that global warming is not as much of a threat as many claim. One part of my argument is that humans, and non-human life too, is much more adaptable than the environmentalists realize. Songbirds discussed below exemplify the point.

(p. A3) North American songbirds have been shrinking steadily in size over the past 40 years, according to scientists who measured tens of thousands of the feathered creatures from dozens of different species and attributed the changes to rising temperatures.

As the birds’ bodies got smaller, their wings gradually got longer, the scientists said in a paper published Wednesday [Dec. 4, 2019] in the journal Ecology Letters. The longer wings, the researchers said, may help offset the loss of body mass so the birds can fly efficiently on their long migrations.

. . .

Warm-blooded animals are generally larger in cold climates and smaller in warm climates because more compact creatures usually release heat more quickly, according to biologists and ecologists.

Given the well-established link, many scientists had predicted in recent years that global warming would affect the size of many animals. Yet until recently, there wasn’t much evidence of the effect at work during modern warming trends.

The new findings are the latest in a series of technical reports this year that link changes in body size among birds to warmer temperatures around the world.

Last month, researchers in Australia who studied physical changes in 82 songbird species, including honeyeaters, fairy-wrens and thornbills, reported in the Royal Society B journal that birds there have grown smaller due to warming over the last half-century, as the annual mean temperature increased regionally by about 0.012 degrees Celsius. They based their conclusions on an analysis of 12,000 museum specimens.

In March [2019], researchers at the University of Cape Town in South Africa who tracked the weight of a long-tailed songbird common across Africa called the mountain wagtail found the species gradually became lighter between 1976 and 1999, as regional temperatures increased by 0.18 degrees Celsius. They published their findings in the journal Oecologia.

For the full story see:

Robert Lee Hotz. “Songbirds Shrink in Size, Study Finds.” The Wall Street Journal (Thursday, December 5, 2019 [sic]): A3.

(Note: bracketed date and year added.)

(Note: the online version of the story has the date December 4, 2019 [sic], and has the title “Songbirds Are Shrinking in Size, Study Finds.”)

My book mentioned above is:

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

The academic paper in Ecology Letters, mentioned above, is:

Weeks, Brian C., David E. Willard, Marketa Zimova, Aspen A. Ellis, Max L. Witynski, Mary Hennen, and Benjamin M. Winger. “Shared Morphological Consequences of Global Warming in North American Migratory Birds.” Ecology Letters (2019).

The academic paper in the Royal Society B journal, mentioned above, is:

Gardner, Janet L., Tatsuya Amano, Anne Peters, William J. Sutherland, Brendan Mackey, Leo Joseph, John Stein, Karen Ikin, Roellen Little, Jesse Smith, and Matthew R. E. Symonds. “Australian Songbird Body Size Tracks Climate Variation.” Proceedings of the Royal Society B 286, no. 1916 (2019).

The academic paper in the Oecologia journal, mentioned above, is:

Prokosch, Jorinde, Zephne Bernitz, Herman Bernitz, Birgit Erni, and Res Altwegg. “Are Animals Shrinking Due to Climate Change? Temperature-Mediated Selection on Body Mass in Mountain Wagtails.” Oecologia 189, no. 3 (2019): 841-49.

Nvidia Entrepreneur’s Work-Life Imbalance: Ferocious Hard Work

(p. A15) Mr. Kim’s book is nothing like Walter Isaacson’s portraits of tech geniuses Steve Jobs or Elon Musk. It is more prosaic, focusing on the technical and human ground war of building a company. Even so, there is drama in Nvidia’s remarkable rise, and Mr. Kim’s reporting offers plenty of incident and portraiture.

. . .

As a teenager, we are told, Mr. Huang was a formidable table-tennis player and earned money by cleaning tables and bathrooms at a local Denny’s, a toughening experience that prepared him for life as a tech CEO. As a business sage, Mr. Huang says that work is simply perseverance in the face of difficult odds and that character is the source of greatness. Asked how to be successful, he will respond: “I wish upon you ample doses of pain and suffering.”

. . .

By . . . -the late 1990s—Mr. Huang had figured out a particular way of building and managing his company. The bedrock precept was ferociously hard work. New employees were told that the culture was “ultra-aggressive.” Mr. Huang demanded that they work at the “speed of light,” constrained (as Mr. Kim puts it) “only by the laws of physics—not by internal politics or financial concerns.”

. . .

Does all of this success make Mr. Huang happy? Apparently not. After one especially successful quarter, he began a review meeting by saying: “I look in the mirror every morning and say, ‘you suck.’ ” He still enjoys publicly dressing down employees, saying that humiliation is a small price to pay for group learning. He believes that he can “torture” his people “into greatness.” When employees begin to ramble in his presence, he will start to murmur “LUA,” a warning to the speaker. The abbreviation means: “Listen to the question. Understand the question. Answer the Question.”

For the full review see:

Philip Delves Broughton. “Bookshelf; The Hard Work Of Tech Mastery.” The Wall Street Journal (Monday, Dec. 16, 2024): A15.

(Note: ellipses added.)

(Note: the online version of the review has the date December 15, 2024, and has the title “Bookshelf; The Nvidia Way’: The Hard Work of Tech Mastery.”)

The book under review is:

Kim, Tae. The Nvidia Way: Jensen Huang and the Making of a Tech Giant. New York: W. W. Norton & Company, 2024.

Idaho Cut or Simplified 95% of Regulations by a “Sunset” Review

In my Openness book, I argue that government regulations bind entrepreneurs and reduce innovation. As part of an antidote, I suggest that “sunset laws,” where regulations automatically expire, if not renewed. Later, at a small conference on Adam Thierer’s latest book, I was discouraged to hear a couple of participants grant the plausibility of the “antidote,” but report that in actual practice it does not work because almost all old regulations get renewed. Some hope returned when I read a report from James Broughel of a successful sunset review process:

Idaho has proved deregulation is possible. The state repealed and revised its administrative rules code through a sunset review process in 2019. The results were dramatic. Since then, 95% of state regulations have been eliminated or simplified. The sky didn’t fall. Most regulations, when subject to genuine scrutiny, fail to justify their existence.

I will keep my eyes open on this issue, looking for more evidence.

James Broughel’s commentary is:

James Broughel. “Recipe for a Regulatory Spring Cleaning.” The Wall Street Journal (Tues., Nov. 26, 2024): A13.

(Note: the online version of the commentary has the date November 25, 2024, and has the same title as the print version.)

My book mentioned above is:

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

Adam Thierer’s book mentioned above is:

Thierer, Adam. Evasive Entrepreneurs and the Future of Governance: How Innovation Improves Economies and Governments. Washington, D.C.: Cato Institute, 2020.

Off-Label Drug Use Shows F.D.A. Phase 3 Trials Could Be Dropped, Adding New Cures and Lowering Costs

The F.D.A. allows physicians to prescribe drugs for “off-label” use. These drugs were originally approved for a different “on-label” use. For that approval the drugs had to pass through Phase 1 and Phase 2 clinical trials, mainly to show safety, and massively expensive Phase 3 clinical trials to show efficacy for the on-label use.

When off-label use is allowed, that shows that the F.D.A. is accepting drugs for a use where efficacy has NOT been shown.

This is a proof of concept for my suggestion (that I originally heard from Nobel-Prize-winner Milton Friedman) that F.D.A. regulation should be pared back to just Phase 1 and Phase 2, for safety. Since the Phase 3 trials are usually far more expensive than the Phase 1 and Phase 2 combined, this would allow far more new drugs to be developed.

If the development of new drugs was cheaper, Fajgenbaum and others would not need to spend N.I.H.’s 48 millions of taxpayer dollars to comb through already-approved drugs to see if one can be jury-rigged as a therapy for a different disease.

(p. A6) [Dr. David Fajgenbaum, an immunologist at the University of Pennsylvania and . . . Castleman patient who studies the disease] . . . has matched rare-disease patients with drugs that are already in pharmacies for other conditions for over 10 years, starting with himself.

. . .

Every Cure, a nonprofit Fajgenbaum helped found in 2022, received funding on Wednesday [Feb. 28, 2024] that could surpass $48 million from the federal Advanced Research Projects Agency for Health. Fajgenbaum and his team will spend the money to build a drug-repurposing database and algorithms that patients, doctors and researchers can use to find drugs for untreated diseases.

There are over 10,000 known rare diseases and most don’t have a drug approved to treat them. The FDA said it has approved over 19,000 prescription drugs.

The notion of finding new uses for existing drugs has been around for a long time. Once the FDA approves a drug, doctors can prescribe it off-label to patients with other conditions they think it will help. Ozempic, originally approved for people with Type 2 diabetes, is now used by millions of people without the disease for weight loss.

The National Institutes of Health and research institutions have invested over the years in drug repurposing, hoping it would be faster and less costly to find new uses for drugs that have already made it to market, a process that can take more than a decade and cost $2 billion. But systematically matching approved treatments to unmet needs has been hard.

. . .

“Our end goal is not FDA approval. Our end goal is giving patients maximum access to medications,” said Tracey Sikora, co-founder of Every Cure.

For the full story see:

Amy Dockser Marcus. “Repurposed Drugs Give People With Rare Diseases New Hope.” The Wall Street Journal (Thursday, Feb. 29, 2024 [sic]): A6.

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

(Note: the online version of the story has the date February 28, 2024 [sic], and has the title “This Doctor Found His Own Miracle Drug. Now He Wants to Do It for Others.”)

For more on Fajgenbaum’s story, read his autobiographical account:

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

Covid Citizen Scientists Provided Quick and Useful Knowledge

The essay quoted below claims that patients can provide useful knowledge about the symptoms of the diseases that afflict them. I agree, but would go even further. One source of knowledge that all humans have, and even non-humans to some extent, is the observation of patterns. Patients can observe which behaviors, medicines, circumstances make their disease better and which make their disease worse. Of course sometimes patients can be biased, can fool themselves. That can be a reason that patients disagree about what works. But another reason that patients can disagree is that patients have different bodies so that what works for one patient may not work for another. Researchers and clinicians are increasingly recognizing this when they advocate and practice “personalized” (aka “precision”) medicine.

And the academic and popular literatures have exaggerated the extent to which biases undermine our observation of patterns. The exaggeration is partly because bias is bad news, and bad news sells. The usual reliability of observed patterns has been persuasively defended in Gary Klein’s The Sources of Power.

Note another point in the passages quoted below. Patients have a sense of “urgency” that scientists often lack. Sometimes quick imperfect conclusions are actionable, while slow peer-reviewed conclusions are too late to be actionable. And sometimes peer-reviewed conclusions give us conclusions that are both slow and imperfect. Ioannides argues that “most published research findings are false” (2005). I am currently reading Piller’s Doctored that discusses highly-cited papers from the Alzheimer’s literature that illustrate Ioannides’s claim.

(p. C3) A month after her Covid-19 diagnosis last March [2020], Lisa McCorkell wanted to know why she was still struggling with a cough, shortness of breath and other debilitating symptoms. Her doctors didn’t have answers, so she and a group of other Covid patients took matters into their own hands. They formed a research group on a Slack channel and launched their own study.

“I was looking for validation, that my experience was reflected in the others,” said Ms. McCorkell, 28, of Oakland, Calif., who was finishing her graduate studies in public policy when she was diagnosed.

. . .

Covid citizen scientists generated information about symptoms, such as neurological issues, that didn’t garner a lot of attention at the start of the pandemic. They highlighted the overlooked challenges faced by people whose symptoms last longer than 28 days. The studies were limited by drawing largely from patients who joined online support groups, but they gained the kind of recognition by professional scientists that citizen science doesn’t always get. . . .

The pandemic has created an opening for citizen scientists, because even now clinicians don’t fully understand the virus. Early clinical trial data comes mainly from studies involving hospitalized patients, whose experiences may not apply to those who are suffering but don’t end up in the emergency room.

. . .

Patients who want to lead Covid research projects often must navigate tension between their sense of urgency and the traditional scientific process, which typically requires a long peer review process before publication in a journal, said Emily Sirotich, a Ph.D. student at McMaster University in Canada. On March 12, the day the WHO declared Covid a pandemic, Ms. Sirotich joined a Twitter conversation between rheumatology patients and doctors, who were on equal footing when it came to Covid: No one understood the disease. “Everyone was worried,” she said.

. . .

Patients wanted to share the survey data right away, but the researchers argued that the scientific community wouldn’t use the information to inform patient care without the validation of going through peer review. “It has to be accurate,” said Ms. Sirotich.

The two groups tried to strike a balance, Ms. Sirotich said. Patients created overview summaries of the raw data that they immediately disseminated to support groups for use in personal decision making. The physicians and patients also co-wrote and submitted articles with more detailed data analysis to peer-reviewed journals and conferences.

“Covid gave us the opportunity to show that patients can produce valid data and reliable information about what they are experiencing,” Ms. Sirotich said.

In December [2020], the Patient-Led Research for Covid-19 group posted a paper based on analyzing data from over 3,700 patients to the MedRxiv public server, which professional scientists have used throughout the pandemic to quickly make results available to the wider community before peer review. The group also plans to submit the paper to a scientific journal.

Eric Topol, director of the Scripps Research Translational Institute in La Jolla, Calif., and a proponent of patients tracking their own health, tweeted the results. “There is a dearth of information about Covid,” Dr. Topol later said. As a professional scientist, he added, “The paper provided invaluable new insights to me.”