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.

Non-Drug Treatments Are Under-Studied Because They Are Hard to Patent, and Hard to Test in Randomized Clinical Trials

(p. C3) In particular, decades of research show that mental, physical and social stimulation is one of the potential ways to ward off Alzheimer’s disease.

. . .

All of these findings come from observational studies that look at people’s existing lifestyle and cognitive health, as opposed to providing them with a “lifestyle treatment” and then assessing cognitive outcomes. The gold standard in modern medicine is randomized, blind, placebo-controlled trials, which are more quantifiable and objective, and there have been few such trials of lifestyle treatments for dementia and Alzheimer’s.

Those that exist have shown disparate results. For example, a study published in the journal Applied Neuropsychology in 2003 found that while mental drills could train people to do better on specific tasks like recalling words from a list, the effect didn’t translate into overall cognitive improvement. Clinical trials on social engagement are currently lacking.

One reason why the cognitive benefits of lifestyle enrichment haven’t been sufficiently studied is that nonpharmacological treatments such as physical exercise can’t be easily patented, so pharmaceutical companies aren’t interested in investing. It’s also difficult to use placebos. In drug trials, a look-alike sugar pill and a test drug are randomly assigned to participants, but there’s no equivalent of a sugar pill for enrichment activities. Instead, the control group either receives no intervention, a fact that can’t be easily hidden to avoid bias, or they receive some other interventions that may have effects of their own and muddle trial results.

For the full essay, see:

Han Yu. “An Active Lifestyle Can Help To Ward Off Alzheimer’s.” The Wall Street Journal (Saturday, Feb. 27, 2021 [sic]): C3.

(Note: ellipsis added.)

(Note: the online version of the essay has the date February 25, 2021 [sic], and has the title “Can an Active Lifestyle Help Ward Off Alzheimer’s?”)

The essay quoted above is adapted from Yu’s book is:

Yu, Han. Mind Thief: The Story of Alzheimer’s. New York: Columbia University Press, 2021.

The Dubious Result of a Randomized Controlled Trial (RCT)

Randomized controlled trials are widely viewed as the “gold standard” of medical evidence. But RCTs can be flawed in a variety of ways. They can have too few participants, they can be improperly randomized for a variety of reasons (not all relevant variables may have been identified or the protocol may not have been properly implemented). Forgive me, but the results of the RCT described below seem highly implausible. I believe that something about the RCT was flawed. Who can believe the result that those who engage in moderate exercise live shorter lives than those who only engage in very modest exercise. Common sense and many observational studies say the opposite, and such evidence should not be cavalierly dismissed.

(p. D6) Scientists have known for some time, . . ., that active people tend also to be long-lived people. According to multiple past studies, regular exercise is strongly associated with greater longevity, even if the exercise amounts to only a few minutes a week.

But almost all of these studies have been observational, meaning they looked at people’s lives at a moment in time, determined how much they moved at that point, and later checked to see whether and when they passed away. Such studies can pinpoint associations between exercise and life spans, but they cannot prove that moving actually causes people to live longer, only that activity and longevity are linked.

To find out if exercise directly affects life spans, researchers would have to enroll volunteers in long-term, randomized controlled trials, with some people exercising, while others work out differently or not at all. The researchers then would have to follow all of these people for years, until a sufficiently large number died to allow for statistical comparisons of the groups.

Such studies, however, are dauntingly complicated and expensive, one reason they are rarely done. They may also be limited, since over the course of a typical experiment, few adults may die. This is providential for those who enroll in the study but problematic for the scientists hoping to study mortality; with scant deaths, they cannot tell if exercise is having a meaningful impact on life spans.

Those obstacles did not deter a group of exercise scientists at the Norwegian University of Science and Technology in Trondheim, Norway, however. With colleagues from other institutions, they had been studying the impacts of various types of exercise on heart disease and fitness and felt the obvious next step was to look at longevity. So, almost 10 years ago, they began planning the study that would be published in October [2020] in The BMJ.

. . .

The scientists tested everyone’s current aerobic fitness as well as their subjective feelings about the quality of their lives and then randomly assigned them to one of three groups. The first, as a control, agreed to follow standard activity guidelines and walk or otherwise remain in motion for half an hour most days. (The scientists did not feel they could ethically ask their control group to be sedentary for five years.)

Another group began exercising moderately for longer sessions of 50 minutes twice a week. And the third group started a program of twice-weekly high-intensity interval training, or H.I.I.T., during which they cycled or jogged at a strenuous pace for four minutes, followed by four minutes of rest, with that sequence repeated four times.

. . .

The men and women in the high-intensity-intervals group were about 2 percent less likely to have died than those in the control group, and 3 percent less likely to die than anyone in the longer, moderate-exercise group. People in the moderate group were, in fact, more likely to have passed away than people in the control group.

For the full story see:

Gretchen Reynolds. “Working Out With Intensity.” The New York Times (Tuesday, December 29, 2020 [sic]): D6.

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

(Note: the online version of the story was updated Nov. 10, 2021 [sic–yes 2021], and has the title “The Secret to Longevity? 4-Minute Bursts of Intense Exercise May Help.” Where the wording of the versions slightly differs, the passages quoted above follow the online version.)

The study published in The British Medical Journal (BMJ), and mentioned above, is:

Stensvold, Dorthe, Hallgeir Viken, Sigurd L. Steinshamn, Håvard Dalen, Asbjørn Støylen, Jan P. Loennechen, Line S. Reitlo, Nina Zisko, Fredrik H. Bækkerud, Atefe R. Tari, Silvana B. Sandbakk, Trude Carlsen, Jan E. Ingebrigtsen, Stian Lydersen, Erney Mattsson, Sigmund A. Anderssen, Maria A. Fiatarone Singh, Jeff S. Coombes, Eirik Skogvoll, Lars J. Vatten, Jorunn L. Helbostad, Øivind Rognmo, and Ulrik Wisløff. “Effect of Exercise Training for Five Years on All Cause Mortality in Older Adults—the Generation 100 Study: Randomised Controlled Trial.” BMJ 371 (2020): m3485.

Egyptians May Have Tried Surgery on Brain Cancer 4,600 Years Ago

(p. D2) Scientists led by Edgard Camarós, a paleopathologist at the University of Santiago de Compostela in Spain, were studying an approximately 4,600-year-old Egyptian skull when they found signs of brain cancer and its treatment.

. . .

Using a microscope, he and Tatiana Tondini of the University of Tübingen in Germany and Albert Isidro of the University Hospital Sagrat Cor in Spain, the study’s other authors, found cut marks around the skull’s edges surrounding dozens of lesions that earlier researchers had linked to metastasized brain cancer. The shape of the cuts indicated that they had been made with a metal tool. This discovery, reported in a study published Wednesday [May 29, 2024] in the journal Frontiers in Medicine, suggests that ancient Egyptians studied brain cancer using surgery. If the cuts were made while the person was alive, they may have even attempted to treat it.

. . .

The new discovery not only expands scientific knowledge of Egyptian medicine, it may also push back the timeline of humanity’s documented attempts to treat cancer by up to 1,000 years.

For the full story see:

Jordan Pearson. “An Ongoing Search: In an Ancient Egyptian Skull, Evidence of a Cancer Treatment.” The New York Times (Tuesday, June 4, 2024): D2.

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

(Note: the online version of the story has the date May 29, 2024, and has the title “Ancient Skull With Brain Cancer Preserves Clues to Egyptian Medicine.” 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.

To Reduce the Huge Costs of Randomized Clinical Trials, Groups Are Excluded for Whom the Trials Matter Most

(p. D5) Geriatricians have complained for years that figuring out treatments for their patients becomes dramatically more difficult when older people are excluded from clinical trials and other research.

For an 83-year-old, what are the risks and benefits of a surgical procedure, drug or medical device tested primarily on those in their 50s? When a drug trial excludes those who have several diseases and take other drugs, how do the results pertain to older adults — most of whom have several diseases and take other drugs?

. . .

Critics of age exclusion had reason to celebrate in December, when the National Institutes of Health issued new policy guidelines for the research it funds.

Starting next January, grant applicants will have to explain how they intend to include people of all ages, providing acceptable justifications for any group they leave out. The agency will monitor investigators to make sure they comply.

“It’s the right starting point,” said Dr. Florence Bourgeois, a pediatrician at Harvard Medical School. (Children also wind up taking drugs tested only in adults.)

. . .

How often are old people left out of important medical research? In 2011, it looked like progress when Dr. Donna Zulman and her colleagues at the University of Michigan reviewed 109 clinical trials published in leading journals and found that just 20 percent set upper age limits for participation.

An earlier review of trials published from 1994 to 2006 had found that 39 percent shut out people over age 65.

But, as the University of Michigan team also pointed out, even without age limits, studies may bar participants who have multiple disorders or disabilities, or those with limited life expectancy or cognitive impairment. Some researchers won’t enroll nursing home residents.

Those restrictions, too, effectively push older people out of clinical trials and other studies.

Maddeningly, exclusion rates remain high even for studies of diseases particularly common at older ages. Dr. Bourgeois and her colleagues looked at clinical trials for heart disease medications, for instance — primarily blood thinners, cholesterol and blood pressure drugs.

More than half of the trials had upper age limits, usually 75 or 80, and only about 12 percent of participants were aged 75 or older. Yet nearly 40 percent of people hospitalized with heart attacks are over age 75.

For the full story see:

Paula Span. “The Clinical Trial Is Open. Older People Need Not Apply.” The New York Times (Tuesday, April 17, 2018 [sic]): D5.

(Note: ellipses added.)

(Note: the online version of the story has the date April 13, 2018 [sic], and has the title “The Clinical Trial Is Open. The Elderly Need Not Apply.”)

Some published academic articles supporting the points made in the passages quoted above are:

Bourgeois, Florence T., Liat Orenstein, Sarita Ballakur, Kenneth D. Mandl, and John P. A. Ioannidis. “Exclusion of Elderly People from Randomized Clinical Trials of Drugs for Ischemic Heart Disease.” Journal of the American Geriatrics Society 65, no. 11 (Nov. 2017): 2354-61.

Bourgeois, Florence T., Srinivas Murthy, Catia Pinto, Karen L. Olson, John P.A. Ioannidis, and Kenneth D. Mandl. “Pediatric Versus Adult Drug Trials for Conditions with High Pediatric Disease Burden.” Pediatrics 130, no. 2 (Aug. 2012): 285-92.

Cruz-Jentoft, Alfonso J., Marina Carpena-Ruiz, Beatriz Montero-Errasquín, Carmen Sánchez-Castellano, and Elisabet Sánchez-García. “Exclusion of Older Adults from Ongoing Clinical Trials About Type 2 Diabetes Mellitus.” Journal of the American Geriatrics Society 61, no. 5 (May 2013): 734-38.

Lewis, Joy H., Meredith L. Kilgore, Dana P. Goldman, Edward L. Trimble, Richard Kaplan, Michael J. Montello, Michael G. Housman, and José J. Escarce. “Participation of Patients 65 Years of Age or Older in Cancer Clinical Trials.” Journal of Clinical Oncology 21, no. 7 (April 2003): 1383-89.

McGarvey, Caoimhe, Tara Coughlan, and Desmond O’Neill. “Ageism in Studies on the Management of Osteoporosis.” Journal of the American Geriatrics Society 65, no. 7 (July 2017): 1566-68.

Zulman, Donna M., Jeremy B. Sussman, Xisui Chen, Christine T. Cigolle, Caroline S. Blaum, and Rodney A. Hayward. “Examining the Evidence: A Systematic Review of the Inclusion and Analysis of Older Adults in Randomized Controlled Trials.” Journal of General Internal Medicine 26, no. 7 (July 2011): 783-90.

After Safe Drinking Water, Vaccines Were the Second “Most Successful Medical Interventions of the 20th Century”

(p. B11) Dr. Paul D. Parkman, whose research was instrumental in identifying the virus that causes rubella and developing a vaccine that has prevented an epidemic of the disease in the United States for more than 50 years, died on May 7 [2024] at his home in Auburn, N.Y., in the Finger Lakes region. He was 91.

. . .

In 1966, Dr. Parkman, Dr. Harry M. Meyer Jr. and their collaborators at the National Institutes of Health, including Maurice R. Hilleman, disclosed that they had perfected a vaccine to prevent rubella. Dr. Parkman and Dr. Meyer assigned their patents to the N.I.H. so that the vaccines could be manufactured, distributed and administered promptly.

“I never made a nickel from those patents because we wanted them to be freely available to everybody,” he said in an oral history interview for the N.I.H. in 2005.

President Lyndon B. Johnson thanked the researchers, noting that they were among the few who could “number themselves among those who directly and measurably advance human welfare, save precious lives, and bring new hope to the world.”

Still, after Dr. Parkman retired from the government in 1990, as director of the Food and Drug Administration’s Center for Biologics Evaluation and Research, he expressed concern about what he called the unfounded skepticism that persisted about the value of vaccines.

“With the exception of safe drinking water, vaccines have been the most successful medical interventions of the 20th century,” he wrote in 2002 in Food and Drug Administration Consumer, an agency journal.

For the full obituary see:

Sam Roberts. “Paul D. Parkman, 91, Researcher Whose Work Helped to Eliminate Rubella.” The New York Times (Friday, May 24, 2024): B11.

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

(Note: the online version of the obituary has the date May 21, 2024, and has the title “Dr. Paul Parkman, Who Helped to Eliminate Rubella, Dies at 91.”)

The 2002 article by Parkman mentioned above is:

Parkman, Paul D. “We Can’t Forget the Value of Vaccines.” Food and Drug Administration Consumer 36, no. 4 (July-Aug. 2002): 40.