When Hospitals Compete Less, Prices Rise More

(p. B10) If the fries at your local burger joint are soggy or if you’re suddenly charged $25 for ketchup, you’ll probably eat somewhere else next time. That’s the beauty of competition.

Healthcare doesn’t quite work that way. For starters, you don’t always get to choose your medical provider—your insurer often does by contracting with them. And even the insurer can’t easily walk away, either: Giant hospital systems are swallowing up big chunks of the country’s healthcare system through vertical and horizontal integration. That leaves fewer parties with which to negotiate.

If McDonald’s bought Burger King and then Wendy’s, you could always cook at home instead, but nearly everyone needs to go to the doctor or the hospital at some point. Patients also aren’t nearly as cost sensitive as they would be with other purchases because employers and insurers pick up much of the tab. They often don’t even know the price ahead of time.

Hospital executives argue that mergers lead to improved efficiency and better outcomes for patients. But, after years of rampant consolidation between hospitals, most regions in the U.S. are now dominated by a few large players. That has led to higher prices and no significant improvements in patient care.

Rising costs don’t just lead to alarmingly high medical bills—they also make all of us worse off by increasing premiums, the bulk of which are paid by the nation’s employers. That affects even people who rarely visit a doctor. As those premiums soar and employers look to offset the cost, they indirectly eat into people’s paychecks.

Over the past two decades, there have been more than 1,000 mergers among the country’s approximately 5,000 hospitals, according to a forthcoming paper in American Economic Review: Insights.

For the full commentary see:

David Wainer. “As Hospitals Grow, So Does Your Bill.” The Wall Street Journal (Friday, June 7, 2024): B10.

(Note: the online version of the commentary has the date June 6, 2024, and has the same title as the print version.)

The paper in American Economic Review: Insights, mentioned above, is:

Brot-Goldberg, Zarek, Zack Cooper, Stuart Craig, and Lev Klarnet. “Is There Too Little Antitrust Enforcement in the U.S. Hospital Sector?” American Economic Review: Insights (forthcoming).

Gates’s TerraPower Breaks Ground on Small Nuclear Reactor

(p. A16) Outside a small coal town in southwest Wyoming, a multibillion-dollar effort to build the first in a new generation of American nuclear power plants is underway.

Workers began construction on Tuesday on a novel type of nuclear reactor meant to be smaller and cheaper than the hulking reactors of old and designed to produce electricity without the carbon dioxide that is rapidly heating the planet.

The reactor being built by TerraPower, a start-up, won’t be finished until 2030 at the earliest and faces daunting obstacles. The Nuclear Regulatory Commission hasn’t yet approved the design, and the company will have to overcome the inevitable delays and cost overruns that have doomed countless nuclear projects before.

What TerraPower does have, however, is an influential and deep-pocketed founder. Bill Gates, currently ranked as the seventh-richest person in the world, has poured more than $1 billion of his fortune into TerraPower, an amount that he expects to increase.

“If you care about climate, there are many, many locations around the world where nuclear has got to work,” Mr. Gates said during an interview near the project site on Monday. “I’m not involved in TerraPower to make more money. I’m involved in TerraPower because we need to build a lot of these reactors.”

Mr. Gates, the former head of Microsoft, said he believed the best way to solve climate change was through innovations that make clean energy competitive with fossil fuels, a philosophy he described in his 2021 book, “How to Avoid a Climate Disaster.”

Nationwide, nuclear power is seeing a resurgence of interest, with several start-ups jockeying to build a wave of smaller reactors and the Biden administration offering hefty tax credits for new plants.

. . .

In March [2024], TerraPower submitted a 3,300-page application to the Nuclear Regulatory Commission for a permit to build the reactor, but that will take at least two years to review. The company has to persuade regulators that its sodium-cooled reactor doesn’t need many of the costly safeguards required for traditional light-water reactors.

“That’s going to be challenging,” said Adam Stein, director of nuclear innovation at the Breakthrough Institute, a pro-nuclear research organization.

TerraPower’s plant is designed so that major components, like the steam turbines that generate electricity and the molten salt battery, are physically separate from the reactor, where fission occurs. The company says those parts don’t require regulatory approval and can begin construction sooner.

For the full story see:

Brad Plumer and Benjamin Rasmussen. “Climate-Minded Billionaire Makes a Bet on Nuclear Power.” The New York Times (Thursday, June 13, 2024): A16.

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

(Note: the online version of the story has the date June 11, 2024, and has the title “Nuclear Power Is Hard. A Climate-Minded Billionaire Wants to Make It Easier.”)

Gates’s 2021 book, mentioned above, is:

Gates, Bill. How to Avoid a Climate Disaster: The Solutions We Have and the Breakthroughs We Need. New York: Knopf, 2021.

Starlink Gives Remote Tribes Voice, Information, and Fast Help in Emergencies

(p. 12) . . . Starlink, . . . has quickly dominated the satellite-internet market worldwide by providing service once unthinkable in . . . remote areas. SpaceX has done so by launching 6,000 low-orbiting Starlink satellites — roughly 60 percent of all active spacecraft — to deliver speeds faster than many home internet connections to just about anywhere on Earth, including the Sahara, the Mongolian grasslands and tiny Pacific islands.

Business is soaring. Mr. Musk recently announced that Starlink had surpassed three million customers across 99 countries. Analysts estimate that annual sales are up roughly 80 percent from last year, to about $6.6 billion.

. . .

. . . perhaps Starlink’s most transformative effect is in areas once largely out of the internet’s reach, like the Amazon. There are now 66,000 active contracts in the Brazilian Amazon, touching 93 percent of the region’s legal municipalities. That has opened new job and education opportunities for those who live in the forest. It has also given illegal loggers and miners in the Amazon a new tool to communicate and evade authorities.

One Marubo leader, Enoque Marubo (all Marubo use the same surname), 40, said he immediately saw Starlink’s potential. After spending years outside the forest, he said he believed the internet could give his people new autonomy. With it, they could communicate better, inform themselves and tell their own stories.

Last year, he and a Brazilian activist recorded a 50-second video seeking help getting Starlink from potential benefactors. He wore his traditional Marubo headdress and sat in the maloca. A toddler wearing a necklace of animal teeth sat nearby.

They sent it off. Days later, they heard back from a woman in Oklahoma.

. . .

Allyson Reneau’s LinkedIn page describes her as a space consultant, keynote speaker, author, pilot, equestrian, humanitarian, chief executive, board director and mother of 11 biological children. In person, she says she makes most of her money coaching gymnastics and renting houses near Norman, Okla.

. . .

Enoque was asking for 20 Starlink antennas, which would cost roughly $15,000, to transform life for his tribe.

. . .

[Allyson Reneau said] “One tool would change everything in their life. Health care, education, communication, protection of the forest.”

Ms. Reneau said she bought the antennas with her own money and donations from her children.

. . .

The internet was an immediate sensation.

. . .

They spend lots of time on WhatsApp. There, leaders coordinate between villages and alert the authorities to health issues and environmental destruction. Marubo teachers share lessons with students in different villages. And everyone is in much closer contact with faraway family and friends.

To Enoque, the biggest benefit has been in emergencies. A venomous snake bite can require swift rescue by helicopter. Before the internet, the Marubo used amateur radio, relaying a message between several villages to reach the authorities. The internet made such calls instantaneous. “It’s already saved lives,” he said.

For the full story see:

Jack Nicas and Victor Moriyama. “The Internet’s Final Frontier: Remote Amazon Tribes of Brazil.” The New York Times, First Section (Sunday, June 2, 2024): 1 & 12-13.

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

(Note: the online version of the story was updated June 21 [sic], 2024, and has the title “The Internet’s Final Frontier: Remote Amazon Tribes.”)

With Metformin Patent Expired, No Firm Has Incentive to Fund $50 Million Randomized Clinical Trial to Show It Aids Longevity

The article quoted below was published eight years ago. Dr. Barzilai and his team are still, even now, trying to raise the (probably higher) funds to conduct the metformin clinical trial. Firms have no incentive to conduct the clinical trial. Since the patent for metformin (originally issued for its efficacy against diabetes) expired in the year 2000, even if the clinical trial succeeded, no firm would be able to recover in revenue the $50 cost of conducting the clinical trial. Clinical trials are so hugely expensive largely due to the large and long Phase 3 component, intended to prove efficacy. That is why I salute Milton Friedman’s suggestion that a step in the right direction would be for the FDA to only mandate the smaller and quicker Phase 1 and Phase 2 components, mainly intended to prove safety. If the total cost of the clinical trial was much lower, it might be easier to find non-profit or academic funding. (It’s hard to raise $50 million on a GoFundMe page!)

The system is set up so that cheap (off-patent) drugs like metformin do not get tested, and so do not get FDA approval for off-label uses. So the system is set up to reduce the use of low cost, but possibly effective, medicines.

(p. D5) “Aging is by far the best predictor of whether people will develop a chronic disease like atherosclerotic heart disease, stroke, cancer, dementia or osteoarthritis,” Dr. James L. Kirkland, director of the Kogod Center on Aging at the Mayo Clinic, said in an interview. “Aging way outstrips all other risk factors.”

He and fellow researchers, who call themselves “geroscientists,” are hardly hucksters hawking magic elixirs to extend life. Rather, they are university scientists joined together by the American Federation for Aging Research to promote a new approach to healthier aging, which may — or may not — be accompanied by a longer life. They plan to test one or more substances that have already been studied in animals, and which show initial promise in people, in hopes of finding one that will keep more of us healthier longer.

As Dr. Kirkland wrote in . . ., “Aging: The Longevity Dividend”: “By targeting fundamental aging processes, it may be possible to delay, prevent, alleviate or treat the major age-related chronic disorders as a group instead of one at a time.”

. . .

The team, which includes Dr. Nir Barzilai, director of the Institute for Aging Research at Albert Einstein College of Medicine in The Bronx, and Steven N. Austad, who heads the biology department at the University of Alabama at Birmingham, plans to study one promising compound, a generic drug called metformin already widely used in people with Type 2 diabetes. They will test the drug in a placebo-controlled trial involving 3,000 elderly people to see if it will delay the development or progression of a variety of age-related ailments, including heart disease, cancer and dementia. Their job now is to raise the $50 million or so needed to conduct the study for the five years they expect it will take to determine whether the concept has merit.

. . .

Several studies have . . . found that individuals with exceptional longevity experience a compression of morbidity and spend a smaller percentage of their life being ill, Dr. Barzilai and his colleague Dr. Sofiya Milman wrote in the “Aging” book.

For the full commentary see:

Jane E. Brody. “Pursuing the Dream of Healthy Aging.” The New York Times (Tuesday, February 2, 2016 [sic]): D5.

(Note: ellipses added.)

(Note: the online version of the commentary has the date February 1, 2016 [sic], and has the title “Finding a Drug for Healthy Aging.”)

Dr. Kirkland’s co-edited book mentioned above is:

Olshansky, S. Jay, George M. Martin, and James L. Kirkland, eds. Aging: The Longevity Dividend, A Subject Collection from Cold Spring Harbor Perspectives in Medicine. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, 2015.

One study that documents that those who live 107 or more years do not have more years of illness and morbidity (the “compression of morbidity hypothesis”) is:

Sebastiani, Paola, and Thomas T. Perls. “The Genetics of Extreme Longevity: Lessons from the New England Centenarian Study.” Frontiers in Genetics 3 (Nov. 30, 2012).

“Extended School Closures Did Not Significantly Stop the Spread of Covid, While the Academic Harms for Children Have Been Large and Long-Lasting”

(p. A13) Four years ago this month, schools nationwide began to shut down, igniting one of the most polarizing and partisan debates of the pandemic.

Some schools, often in Republican-led states and rural areas, reopened by fall 2020. Others, typically in large cities and states led by Democrats, would not fully reopen for another year.

A variety of data — about children’s academic outcomes and about the spread of Covid-19 — has accumulated in the time since. Today, there is broad acknowledgment among many public health and education experts that extended school closures did not significantly stop the spread of Covid, while the academic harms for children have been large and long-lasting.

For the full story see:

Sarah Mervosh, Claire Cain Miller and Francesca Paris. “Pandemic School Closures Came at a Steep Cost to Students, Data Shows.” The New York Times (Friday, March 29, 2024): A13.

(Note: the online version of the story was updated March 19, 2024, and has the title “What the Data Says About Pandemic School Closures, Four Years Later.”)

Physicians Are Reluctant to Assign Their Patients to a Clinical Trial of a New Therapy That Might Replace the Therapy They Know and Practice

(p. D1) After learning he had early stage prostate cancer, Paul Kolnik knew he wanted that cancer destroyed immediately and with as little disruption as possible to his busy life as the New York City Ballet’s photographer.

So Mr. Kolnik, 65, chose a type of radiation treatment that is raising some eyebrows in the prostate cancer field. It is more intense than standard radiation and takes much less time — five sessions over two weeks instead of 40 sessions over about two months or 28 sessions over five to six weeks.

. . .

The National Cancer Institute has just agreed to fund a clinical trial that researchers hope will settle which treatment is better. It will randomly assign 538 men to have either a short course of five intense radiation sessions over two weeks or 28 treatments over five and a half weeks, comparing outcomes for quality of life as well as disease-free survival.

But it will be at least eight years before the answers are in. In the meantime, men and their doctors are left with uncertainty.

“Ideally, we want to show five treatments (p. D4) is better,” said Dr. Rodney J. Ellis, a radiation oncologist at Case Comprehensive Cancer Center in Cleveland and the principal investigator for the trial.

One reason for the dearth of data is that prostate cancer usually grows slowly, if at all, so it can take many years to see if a treatment saved lives. It is expensive and difficult to follow patients for such a long time, and the treatments given to the men often change over a decade, making doctors wonder if the results are relevant.

Also, researchers who have tried to conduct studies comparing treatments often failed because specialists were already convinced that the method they used was best and were reluctant to assign men to other treatments. Dr. Ian Thompson of the University of Texas Health Science Center in San Antonio, said he was involved with several clinical trials that withered for that reason.

. . .

The researchers on the new study think recruitment will not be a major problem because they are comparing different courses of radiation, rather than entirely different approaches — for example, surgical removal of the prostate versus implantation of radioactive seeds in the prostate. A study to investigate those two approaches closed because investigators were able to enroll only 20 patients, Dr. Thompson said.

. . .

A few years ago, Dr. Yu and his colleagues looked at Medicare data and reported that men who had more intense radiation therapy were more likely to have urinary problems after two years than those who had the longer-course therapy.

Dr. Yu noted that his study was not a randomized trial, the gold standard, but he said the results were not reassuring. Now, though, he is not so sure the intense therapy is worse.

“In my own experience, these men have done really well,” he said. “That tells us that techniques improved, or the medical claims we evaluated were not indicative of major toxicity, or the way we and others at high-volume centers deliver radiotherapy is different.”

The lack of solid data bothers Dr. Daniel W. Lin, chief of urologic oncology at the University of Washington. When men ask him about the shorter radiation course, he tells them, “It probably can work but it doesn’t have long-term results and it hasn’t been tested against standard radiation.”

At centers like Sloan Kettering, doctors are relying on their own experience.

Dr. Michael J. Zelefsky, a radiation oncologist who treated Mr. Kolnik there, said that several years ago, 90 percent of his patients had the standard course of treatment. Now 90 percent choose the shorter course. On the basis of Sloan Kettering’s experience with several hundred men who had the intense radiation therapy over the past three years, the treatment, he said, “is emerging as a very exciting form of therapy.”

For the full story see:

Gina Kolata. “Unproven Therapy Gains Ground.” The New York Times (Tuesday, March 21, 2017 [sic]): D1 & D4.

(Note: ellipses added.)

(Note: the online version of the story has the date March 20, 2017 [sic], and has the title “Popular Prostate Cancer Therapy Is Short, Intense and Unproven.”)

Monarch Butterflies Thrive on Poisonous Milkweed

(p. D5) The caterpillar of the monarch butterfly eats only milkweed, a poisonous plant that should kill it. The caterpillars thrive on the plant, even storing its toxins in their bodies as a defense against hungry birds.

For decades, scientists have marveled at this adaptation. On Thursday [Oct. 3, 2019 [sic]), a team of researchers announced they had pinpointed the key evolutionary steps that led to it.

Only three genetic mutations were necessary to turn the butterflies from vulnerable to resistant, the researchers reported in the journal Nature. They were able to introduce these mutations into fruit flies, and suddenly they were able to eat milkweed, too.

Biologists hailed it as a tour-de-force that harnessed gene-editing technology to unscramble a series of mutations evolving in some species and then test them in yet another.

“The gold standard is to directly test mutations in the organism,” said Joseph W. Thornton, an evolutionary biologist at the University of Chicago. The new study “finally elevates our standards.”

For the full story see:

Carl Zimmer. “MATTER; How Monarch Butterflies Evolved to Eat Poison.” The New York Times (Tuesday, October 8, 2019 [sic]): D5.

(Note: bracketed date added.)

(Note: the online version of the story was updated Oct. 3, 2019 [sic], and has the title “MATTER; These Butterflies Evolved to Eat Poison. How Could That Have Happened?”)

The article in Nature mentioned above is:

Karageorgi, Marianthi, Simon C. Groen, Fidan Sumbul, Julianne N. Pelaez, Kirsten I. Verster, Jessica M. Aguilar, Amy P. Hastings, Susan L. Bernstein, Teruyuki Matsunaga, Michael Astourian, Geno Guerra, Felix Rico, Susanne Dobler, Anurag A. Agrawal, and Noah K. Whiteman. “Genome Editing Retraces the Evolution of Toxin Resistance in the Monarch Butterfly.” Nature 574, no. 7778 (Oct. 2019): 409–12.

The “corresponding author” (often considered the primary author) of the article is Noah K. Whiteman, who has published a book that extensively discusses cases such as the monarch butterfly, where a creature has evolved the ability to consume or make use of chemicals that are poisonous to other creatures:

Whiteman, Noah. Most Delicious Poison: The Story of Nature’s Toxins―from Spices to Vices. New York: Little, Brown Spark, 2023.

Archeologist Claims Ancient Egyptians Had Advanced Medical Knowledge

(p. A17) Ancient Egyptian doctors were the first to explore and treat cancer, according to scientists who examined two skulls with tumors and found evidence they had been operated on.

. . .

It might never be possible to know whether these two ancient Egyptians were treated for cancer while they were alive, Camarós said. But given the civilization’s advanced medical knowledge—historical and archaeological records show they built prostheses, put in dental fillings and treated traumatic injuries—he is convinced their physicians were attempting surgical interventions.

“They even had a word for tumor,” he said. “And they knew it was something people were dying from.”

For the full story, see:

Aylin Woodward. “Ancient Egyptians Were First To Treat Cancer.” The Wall Street Journal (Thursday, May 30, 2024): A16.

(Note: ellipsis added.)

(Note: the online version of the story has the date May 29, 2024, and has the title “Ancient Egyptians Were First to Treat Cancer. Skulls Show Evidence of Surgery.”)

The study co-authored by Camarós and summarized above is:

Tondini, Tatiana, Albert Isidro, and Edgard Camarós. “Case Report: Boundaries of Oncological and Traumatological Medical Care in Ancient Egypt: New Palaeopathological Insights from Two Human Skulls.” Frontiers in Medicine 11 (2024).

The Joy of the Smell Test

If actionable knowledge can come for several sources, but we forbid action based on some of those sources, we will limit our effective action. In the case of health, unnecessary suffering and death will result. In previous entries I highlighted cases where dogs’ advanced ability to smell can diagnose and warn of human maladies more accurately, quicker, and cheaper than other methods. Dog-detectable maladies include Covid, epileptic seizures, and cancer. But the medical establishment underuses this source of knowledge because it is not viewed as scientifically respectable. (And perhaps also because those who practice scientifically respectable ways of knowing, benefit from limiting competition?) The passages quoted below sketch the story of a “hyperosmic” nurse who can smell a distinct odor that identifies those who have and who will have Parkinson’s. Note that follow-up research on this outside-the-box diagnostic method was not funded by governments or universities but by a private foundation founded and funded by Parkinson’s patients and their families and friends. Having a terrible disease sometimes leads to despair, sometimes to a sense of urgency.

(p. 30) As a boy, Les Milne carried an air of triumph about him, and an air of sorrow.  . . .  “We were very, very much in love,” Joy, now a flaxen-haired 72-year-old grandmother, told me recently. In a somewhat less conventional way, she also adored the way Les smelled, and this aroma of salt and musk, accented with a suggestion of leather from the carbolic soap he used at the pool, formed for her a lasting sense of who he was. “It was just him,” Joy said, a steadfast marker of his identity, no less distinctive than his face, his voice, his particular quality of mind.

Joy’s had always been an unusually sensitive nose, the inheritance, she believes, of her maternal line. Her grandmother was a “hyperosmic,” and she encouraged Joy, as a child, to make the most of her abilities, quizzing her on different varieties of rose, teaching her to distinguish the scent of the petals from the scent of the leaves from the scent of the pistils and stamens. Still, her grandmother did not think odor of any kind to be a polite topic of conversation, and however rich and enjoyable and dense with information the olfactory world might be, she urged her granddaughter to keep her experience of it to herself.

. . .

Les spent long hours in the surgical theater, which in Macclesfield had little in the way of ventilation, and Joy typically found that he came home smelling of anesthetics, antiseptics and blood. But he returned one August evening in 1982, shortly after his 32nd birthday, smelling of something new and distinctly unsavory, of some thick must. From then on, the odor never ceased, though neither Les nor almost anyone but his wife could detect it.  . . .

Les had lately begun to change in other ways, however, and soon the smell came to seem almost trivial. It was as if his personality had shifted. Les had rather suddenly become detached, ill-tempered, apathetic. He ceased helping out with many household chores; he snapped at his boys.

. . .

When he began referring to “the other person,” a shadow off to his side, she suspected a brain tumor. Eventually she prevailed upon him to see his doctor, who referred him to a neurologist in Manchester.

Parkinson’s disease is typically classed as a movement disorder, and its most familiar symptoms — tremor, rigidity, a slowing known as bradykinesia — are indeed motoric. But the disease’s autonomic, psychological and cognitive symptoms are no less terrible and commonly begin during the so-called prodrome, years before any changes in movement.

. . .

(p. 31) Feeling desperate, Joy eventually persuaded Les to go with her to a meeting of local Parkinson’s patients and their caregivers.

The room was half full by the time they arrived. Near the coat stand, Joy squeezed behind a man just as he was taking off his jacket and suddenly felt a twitch in her neck, as if some fight-or-flight instinct had been activated, and she raised her nostrils instinctively to the air. She often had this reaction to strong, unexpected scents. In this case, bizarrely, it was the disagreeable odor that had hung about her husband for the past 25 years. The man smelled just like him, Joy realized. So too did all the other patients. The implications struck her immediately.

For nearly all the recorded history of medicine and until only quite recently, smell was a central preoccupation. The “miasma” theory of disease, predominant until the end of the 19th century, held that illnesses of all kinds were spread by noxious odors. By a similar token, particular scents were understood to be curative or prophylactic. More than anything, however, odor was a tool of diagnosis.

The ancients of Greece and China confirmed tuberculosis by tossing a patient’s sputum onto hot coals and smelling the fumes. Typhoid fever has long been known to smell of baking bread; yellow fever smells of raw meat. The metabolic disorder phenylketonuria was discovered by way of the musty smell it leaves in urine, while fish-odor syndrome, or trimethylaminuria, is named for its scent.

. . .

(p. 33) Most diseases can be identified by methods more precise and ostensibly scientific than aroma, however, and we tend to treat odor in general as a sort of taboo. “A venerable intellectual tradition has associated olfaction with the primitive and the childish,” writes Mark Jenner, a professor of history at the University of York. Modern doctors are trained to diagnose by inspection, palpation, percussion and auscultation; “inhalation” is not on the list, and social norms would discourage it if it were.

During her time as a nurse, Joy had done it anyway, reflexively, and learned to detect the acetone breath that signaled an impending diabetic episode, the wet brown cardboard aroma of tuberculosis — “not wet white cardboard, because wet white cardboard smells completely different,” she explained — or the rancidness of leukemia. The notion that Parkinson’s might have a distinctive scent of its own had not occurred to her then, but when it did occur to her years later, it was hardly exotic.

She and Les worried that the normosmics of the world, unfamiliar with medical smells and disinclined to talk about odor in general, might not take her discovery very seriously. They searched for an open-minded scientist and after several weeks settled on Kunath, the Parkinson’s researcher at the University of Edinburgh. In 2012, Joy attended a public talk he gave. During the question-and-answer session, she stood to ask, “Do people with Parkinson’s smell different?” Kunath recalls. “I said, ‘Do you mean, Do people with Parkinson’s lose their sense of smell?’” (Smell loss is in fact a common early symptom of the disease.) “And she said: ‘No, no, no. I mean, Do they smell different?’ And I was just like, ‘Uh, no.’” Joy went home. Kunath returned to his usual work.

Six months later, however, at the urging of a colleague who had once been impressed by cancer-sniffing dogs, Kunath found Joy’s name and called her. She told him the story of Les’s new smell. “I think if she’d told me that, as he got Parkinson’s, he had a change in smell, or if it came afterwards, I probably wouldn’t have followed up any more,” Kunath told me. “But it’s this idea that it was years before.”

He called Perdita Barran, an analytical chemist, to ask what she made of Joy’s claims. Barran suspected Joy was simply smelling the usual odor of the elderly and infirm and misattributing it to Parkinson’s. “I knew, because we all know, that old people are more smelly than young people,” says Barran, who is now a professor of mass spectrometry at the University of Manchester. Still, Barran was personally acquainted with the oddities of olfaction. Following a bike accident, she had for several years experienced various bizarre distortions to her own sense of smell. The idea that Joy might be capable of experiencing odors that no one else could did not strike her as entirely outlandish.

She and Kunath ran a small pilot study in Edinburgh. Through Parkinson’s UK, they recruited 12 participants: six local Parkinson’s patients and six healthy controls. Each participant was asked to wear a freshly laundered T-shirt for 24 hours. The worn shirts were then cut in half down the center, and each half was placed in its own sealed plastic bag. Kunath oversaw the testing. Joy smelled the T-shirt halves at random and rated the intensity of their Parkinsonian odor. “She would find a positive one, and would say, ‘There — it’s right there. Can you not smell it?’” Kunath recalled. Neither he nor the graduate student assisting him could smell a thing.

Kunath unblinded the results at the end of the day. “We were on a little bit of a high,” he recalled. Not only had Joy correctly identified each sample belonging to a Parkinson’s patient, but she was also able, by smell, to match each sample half to its partner. Barran’s skepticism evaporated. Still, Joy’s record was not perfect. She had incorrectly identified one of the controls as a Parkinson’s patient. The researchers wondered if the sample had been contaminated, or if Joy’s nose had simply gotten tired. By Barran’s recollection, Kunath’s response was: “It’s fine! It’s one false positive!” Barran herself was slightly more cautious: Joy had mislabeled both halves of the man’s T-shirt.

Of more immediate interest, though, was the question of what was causing the smell in the first place. The odor seemed to be concentrated not in the armpits, as the researchers had anticipated, but at the neckline. It took them several weeks to realize that it perhaps came from sebum, the lipid-rich substance secreted by the skin. Sebum is among the least studied biological substances. “It is actually another waste disposal for our system,” Barran says. “But no one had ever thought that this was a bodily fluid we could use to find out about disease.”

Barran set out to analyze the sebum of Parkinson’s patients, hoping to identify the particular molecules responsible for the smell Joy detected: a chemical signature of the disease, one that could be detected by machine and could thus form the basis of a universal diagnostic test, a test that ultimately would not depend on Joy’s or anyone else’s nose. No one seemed to be interested in funding the work, though. There were no established protocols for working with sebum, and grant reviewers were unimpressed by the tiny pilot study. They also appeared to find the notion of studying a grandmother’s unusual olfactory abilities to be faintly ridiculous. The response was effectively, “Oh, this isn’t science — science is about measuring things in the blood,” Barran says.

Barran turned to other projects. After nearly a year, however, at a Parkinson’s event in Edinburgh, a familiar-looking man approached Kunath. He had served as one of the healthy controls in the pilot study. “You’re going to have to put me in the other category,” he said, according to Kunath. The man had recently been diagnosed with Parkinson’s. Kunath was stunned. Joy’s “misidentification” had not been an error, but rather an act of clairvoyance. She had diagnosed the man before medicine could do so.

Funding for a full study of Joy, the smell and its chemical components now came through. “We saw something in the news, and we thought, Wow, we’ve got to act on that!” says Samantha Hutten, the director of translational research at the Michael J. Fox Foundation. “The N.I.H. is not going to fund that. Who’s going to fund it if not us?”

. . .

(p. 51) Joy has enjoyed her fame, but the smell work also radicalized her, in its way, and she has a reputation for being a bit intransigent in her advocacy. The initial scientific skepticism toward her was of a piece, she thought, with what she already held to be the medical corps’s hopeless wrongheadedness about Parkinson’s disease. For Joy, as for many caregivers, the psychological aspects of the illness were by far the most difficult to manage, much less accept, and these happened to be precisely the symptoms neurologists seemed least interested in acknowledging, let alone addressing.  . . .

To Joy’s mind, still more proof of this medical obstinacy came from the discovery that she was not alone in her ability to smell Parkinson’s disease. When the research first began to attract attention in the media, Barran and Kunath received messages from around the world from people reporting that they, too, had noticed a change in the smell of their loved ones with Parkinson’s.
  . . .  But for the smell taboo, Joy thought, someone somewhere might have taken these people seriously, and the importance of the odor might have been realized decades sooner.

For the full story see:

Scott Sayare. “The Smell Test.” The New York Times Magazine (Sunday, June 16, 2024): 28-33, 51 & 53.

(Note: ellipses added; bold in original.)

(Note: the online version of the story has the date June 3, 2024, and has the title “The Woman Who Could Smell Parkinson’s.”)

Endo Applied His Practical Knowledge of Molds to Search for First Statin

(p. 24) Akira Endo, a Japanese biochemist whose research on fungi helped to lay the groundwork for widely prescribed drugs that lower a type of cholesterol that contributes to heart disease, died on June 5 [2024]. He was 90.

. . .

Dr. Endo said his career was also inspired by a biography he read of Alexander Fleming, the Scottish biologist who discovered penicillin in the 1920s.

“For me Fleming was a hero,” he told Igaku-Shoin, a Japanese medical publisher, in 2014. “I dreamed of becoming a doctor as a child, but realized a new horizon as people who are not doctors can save people’s lives and contribute to society.”

After studying agriculture at Tohoku University, he joined Sankyo, a Japanese pharmaceutical company, in the late 1950s. His first assignment was manufacturing enzymes for fruit juices and wines at a factory in Tokyo.

He developed a more efficient way of cultivating mold by applying a method he had used as a child to make miso and pickled vegetables, he later told M3, a website for Japanese medical professionals.

. . .

. . ., he grew more than 6,000 fungi in the early 1970s as part of an effort to find a natural substance that could block a crucial enzyme involved in the production of cholesterol.

“I knew nothing but mold, so I decided to look for it in mold,” he said.

He eventually found what he was looking for: a strain of penicillium, or blue mold, that, in chickens, reduced levels of an enzyme that cells need to make LDL cholesterol.

For the full obituary see:

Hisako Ueno and Mike Ives. “Akira Endo, Scholar of Statins, Is Dead at 90.” The New York Times (Sunday, June 16, 2024): 24.

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

(Note: the online version of the obituary was updated June 15, 2024, and has the title “Akira Endo, Scholar of Statins That Reduce Heart Disease, Dies at 90.”)

Alert Children Make “Staggering Discovery” That “Advances Science”

(p. D2) In the summer of 2022, two boys hiking with their father and a 9-year-old cousin in the North Dakota badlands came across some large bones poking out of a rock. They had no idea what to make of them.

The father took some photos and sent them to a paleontologist friend. Later, the relatives learned they’d made a staggering discovery: They’d stumbled upon a rare juvenile skeleton of a Tyrannosaurus rex.

. . .

The friend of the father who identified the fossil, Tyler Lyson, who is the museum’s curator of paleontology, said in a statement that the boys had made an “incredible dinosaur discovery that advances science and deepens our understanding of the natural world.”

. . .

In a video, the brothers, Jessin and Liam Fisher, 9 and 12, and their cousin, Kaiden Madsen, now 11, said that they were busy hiking and exploring when they first came across the bones and had no inkling they could be so special. “I didn’t have a clue,” Jessin says in the video. At first, he added, Dr. Lyson believed they belonged to a duck-billed dinosaur.

For the full story see:

Livia Albeck-Ripka. “Family Discovery: Stumbling Upon a Tyrannosaurus Rex In the Badlands of North Dakota.” The New York Times (Tuesday, June 11, 2024): D2.

(Note: ellipses added.)

(Note: the online version of the story was updated June 10, 2024, and has the title “Family Discovers Rare T. Rex Fossil in North Dakota.” Where the wording of the versions differs, the passages quoted above follow the online version.)

The study co-authored by Camarós, and mentioned above, is:

Tondini, Tatiana, Albert Isidro, and Edgard Camarós. “Case Report: Boundaries of Oncological and Traumatological Medical Care in Ancient Egypt: New Palaeopathological Insights from Two Human Skulls.” Frontiers in Medicine 11 (2024) DOI: 10.3389/fmed.2024.1371645.

On the antiquity of cancer, see also:

Haridy, Yara, Florian Witzmann, Patrick Asbach, Rainer R. Schoch, Nadia Fröbisch, and Bruce M. Rothschild. “Triassic Cancer—Osteosarcoma in a 240-Million-Year-Old Stem-Turtle.” JAMA Oncology 5, no. 3 (March 2019): 425-26.