Category: Health

Medical Research Focuses More on Antibiotics Than on Phages Partly Because Antibiotics Are Easier to Patent

(p. 13) While recent events have provided a painful reminder of the very bad viruses that prey on us, Tom Ireland’s “The Good Virus” is a colorful redemption story for the oft-neglected yet incredibly abundant phage, and its potential for quelling the existential threat of antibiotic resistance, which scientists estimate might cause up to 10 million deaths per year by 2050. Ireland, an award-winning science journalist, approaches the subject of his first book with curiosity and passion, delivering a deft narrative that is rich and approachable.

In the hands of d’Herelle and others, the phage became a potent tool in the fight against cholera. But, in the 1940s, when the discovery of the methods to produce penicillin at an industrial scale led to the “antibiotic era,” phage therapy came to be seen as quackery in Europe and America, in part, Ireland suggests, because antibiotics, unlike phages, fit the mold of capitalist society.

Capitalists love patents. A funny quirk of the patent system is that you cannot patent entire natural things, but you can sometimes patent the way you extract their byproducts. The first antibiotics, being the secretions of fungi, were easier to patent in the United States than phages, which were whole viruses.

For the full review, see:

Alex Johnson. “Going Viral.” The New York Times Book Review (Sunday, September 17, 2023): 13.

(Note: the online version of the review has the date Aug. 15, 2023, and has the title “A Reason to Cheer for Cells and the Viruses That Feed on Them.”)

The book under review is:

Ireland, Tom. The Good Virus: The Amazing Story and Forgotten Promise of the Phage. New York: W. W. Norton & Company, 2023.

Insulin Makers Said High Prices Mainly Went to Pay Higher Rebates to Pharmacy Benefit Manager (PBM) Firms

(p. A3) Novo Nordisk A/S is set to cut the U.S. list prices for several insulin drugs by up to 75%, the latest big drugmaker to make steep price reductions amid pressure to curb diabetes-treatment costs.

. . .

Novo’s price cuts follow Eli Lilly & Co.’s decision earlier this month to reduce list prices for its most commonly prescribed insulin products by 70%, effective in the fourth quarter of 2023.

. . .

Lilly, Novo and Sanofi SA are the leading sellers of insulins in the U.S. and worldwide. They had substantially raised the prices for their insulin products in the U.S. during the 2010s. The companies have said they didn’t make much from the higher list prices, because they had to pay larger rebates to the companies that manage drug benefits.

For the full story, see:

Peter Loftus. “Insulin Maker Plans Sharp Price Cut.” The Wall Street Journal (Wednesday, March 15, 2023): A3.

(Note: ellipses added.)

(Note: the online version of the story was updated March 14, 2023, and has the title “Novo Nordisk to Slash Insulin Prices by Up to 75%.”)

Okinawans Think Ikigai (a Reason for Living) Is Important for Long Life

(p. A11) Ask most people if they want to live to be 100 and the response is likely to be “Sure!” followed by “Wait a sec . . .” Questions suddenly abound: Am I going to be healthy? Am I going to be lonely? Will I be financially stable? Will I have outlived everyone I knew and loved? What author-researcher Dan Buettner set out to demonstrate in “Live to 100: Secrets of the Blue Zones” is that the solutions to those concerns are also the keys to longevity itself.

. . .

What is clear early on is that what Mr. Buettner “discovers” during his visits to Sardinia; Singapore; Okinawa, Japan; Ikaria, Greece; and even Loma Linda, Calif., is largely what we would expect: that much of what helps people live longer isn’t necessarily the purple Japanese sweet potatoes, or going to church every day, or having the limited stress load of a Greek shepherd. It is an Okinawan diet rich in nutrients and fiber, the walking uphill to the Sardinian church, and the community to which one belongs in Loma Linda when one is, for instance, a Seventh Day Adventist who plays pickleball.

. . .

There are many correlating clues to a longer life across the locations in “Live to 100.” Okinawans emphasize the importance of having an ikigai, or reason for living; in Costa Rica the same thing is called one’s plan de vida.

For the full television review, see:

John Anderson. “Netflix’s Lessons in Longevity.” The Wall Street Journal (Wednesday, Aug. 30, 2023): A11.

(Note: ellipses added.)

(Note: the online version of the television review has the date August 29, 2023, and has the title “‘Live to 100: Secrets of the Blue Zones’ Review: Lessons in Longevity.” In the original the word ikigai and the phrase plan de vida are in italics.)

Buettner’s latest book on blue zones is:

Buettner, Dan. The Blue Zones Secrets for Living Longer: Lessons from the Healthiest Places on Earth. Washington, D.C.: National Geographic, 2023.

Weight Loss Drugs Discovered Through “Tedious Trial and Error”

The first sentence quoted below implies that weight loss drugs are an exception in being discovered through trial and error rather than “through a logical process.” But I believe that drug discoveries in recent decades for cancer, heart disease, and Alzheimer’s also owe a lot to trial and error processes.

(p. A1) While other drugs discovered in recent decades for diseases like cancer, heart disease and Alzheimer’s were found through a logical process that led to clear targets for drug designers, the path that led to the obesity drugs was not like that. In fact, much about the drugs remains shrouded in mystery. Researchers discovered by accident that exposing the brain to a natural hormone at levels never seen in nature elicited weight loss. They really don’t know why, or if the drugs may have any long-term side effects.

“Everyone would like to say there must be some logical explanation or order in this that would allow predictions about what will work,” said Dr. David D’Alessio, chief of endocrinology at Duke, who consults for Eli Lilly among others. “So far there is not.”

. . .

(p. A16) . . . results from a clinical trial reported last week indicate that Wegovy can do more than help people lose weight — it also can protect against cardiac complications, like heart attacks and strokes.

But why that happens remains poorly understood.

“Companies don’t like the term trial and error,” said Dr. Daniel Drucker, who studies diabetes and obesity at the Lunenfeld-Tanenbaum Research Institute in Toronto and who consults for Novo Nordisk and other companies. “They like to say, ‘We were extremely clever in the way we designed the molecule,” Dr. Drucker said.

But, he said, “They did get lucky.”

. . .

After tedious trial and error, Novo Nordisk produced liraglutide, a GLP-1 drug that lasted long enough for daily injections. They named it Victoza, and the F.D.A. approved it as a treatment for diabetes in 2010.

It had an unexpected side effect: slight weight loss.

. . .

Finally, after liraglutide was approved in 2010 for diabetes, Dr. Knudsen’s proposal to study the drug for weight loss moved forward. After clinical trials, the F.D.A. approved it as Saxenda for obesity in 2014. The dose was about twice the diabetes dose. Patients lost about 5 percent of their weight, a modest amount.

. . .

Despite the progress on weight loss, Novo Nordisk continued to focus on diabetes, trying to find ways to make a longer-lasting GLP-1 so patients would not have to inject themselves every day.

The result was a different GLP-1 drug, semaglutide, that lasted long enough that patients had to inject themselves only once a week. It was approved in 2017 and is now marketed as Ozempic.

It also caused weight loss — 15 percent, which is three times the loss with Saxenda, the once-a-day drug, although there was no obvious reason for that. Suddenly, the company had what looked like a revolutionary treatment for obesity.

. . .

Researchers continue to marvel at these biochemical mysteries. But doctors and patients have their own takeaway: The drugs work. People lose weight.

For the full story, see:

Gina Kolata. “Medical Mystery Shrouds Drugs for Weight Loss.” The New York Times (Friday, August 18, 2023): A1 & A16.

(Note: ellipses added.)

(Note: the online version of the story has the date Aug. 17, 2023, and has the title “We Know Where New Weight Loss Drugs Came From, but Not Why They Work.”)

Paper Makers Lobby to Retain Mandate for Costly and Useless Long Pamphlets with Prescription Drugs

(p. B5) Doctors and pharmacists receive lengthy pamphlets for all prescription drugs that can stretch as long as a dining-room table. Efforts to go digital in this heavily regulated industry are finally making headway, offering drugmakers the chance to provide up-to-date information while also saving money, trees and greenhouse-gas emissions.

. . .

Advocates arguing such prescription information should go fully digital say the instructions are only for medical professionals, who often already consult up-to-date electronic versions and leave the papers unread and discarded. Proponents of keeping paper say the printed instructions are consulted frequently enough to help ensure medicine is used safely.

. . .

“It’s like a dream come true looking in the facility and seeing the packs coming off the manufacturing lines without these paper leaflets,” said Pam Cheng, operations and sustainability chief at pharmaceutical company AstraZeneca. “This is like win, win, win.”

AstraZeneca spends $30 million a year on the papers globally and is pushing to digitize prescribing information as part of its goal to cut 50% of emissions across its value chain by 2030, Cheng said. The company aims to have a plan by 2025 for all its medical information to go electronic by the end of the decade. Many other pharma companies also want to go digital.

. . .

The U.S. Food and Drug Administration in 2014 proposed to replace the paper information with a digital source, saying it would ensure information is up-to-date and bring environmental and cost benefits. However, an obscure clause in the FDA’s Congressional spending bill has blocked the move, with intense lobbying from two dedicated groups: the Alliance to Modernize Prescribing Information, representing drugmakers such as AstraZeneca, Eli Lilly and Pfizer, and the Pharmaceutical Printed Literature Association, backed by paper producers such as Avery Dennison, JP Gould and WestRock.

. . .

Other countries have digitized drug information, with Japan leading the way. In 2021, the country required drug inserts to go digital by August 2023, both those for patients and medical professionals.

For the full story, see:

Dieter Holger. “Bill Would Let Drugmakers Stop Printing Long Pamphlets.” The Wall Street Journal (Friday, June 16, 2023): B5.

(Note: ellipses added.)

(Note: the online version of the story has the date June 15, 2023, and has the title “One Change Could Help U.S. Drugmakers Save 11 Million Trees a Year.”)

Michael Milken Applies “Entrepreneurial Zeal” to Quest to Live Forever

(p. B3) Michael Milken wants to live forever.

. . .

Milken in April [2023] published “Faster Cures,” a book that is part memoir, part a recounting of his efforts to bring the results of medical research to patients more quickly.

. . .

Shortly after his release from prison in 1993, he received a diagnosis of terminal prostate cancer and was told he had 12 to 18 months to live. He survived thanks to a relentless pursuit of the latest treatments and a dramatic change in diet. Longevity is one focus of the Milken Institute.

. . .

While at Berkeley, Milken read a book called “Corporate Bond Quality and Investor Experience” that examined, among other things, yield charts and default rates for bonds issued by railroads, utilities and industrial companies between 1900 and 1943.

The data revealed something surprising, he recounted in “Faster Cures:” While risk and return had always been presumed to be directly correlated, the reality was that the market had historically overestimated the risk of higher-yielding investments. Investors actually got lower returns on a portfolio of high-grade bonds than they did on a portfolio of low-grade ones over time because the higher yields more than made up for the higher level of defaults.

Milken continued his work on high-yield bonds while pursuing an M.B.A. from the University of Pennsylvania’s Wharton School. When he graduated in 1970, he joined the staff of Drexel, where he had previously worked as a consultant.

Bonds issued by Drexel were the primary source of financing for the likes of cable-industry titan Ted Turner, cellular pioneer Craig McCaw, fiber-optic entrepreneur William McGowan and casino magnate Steve Wynn.

“There was an entrepreneurial zeal in that firm that I haven’t seen since,” said Ted Virtue, a Drexel alumnus who now runs private-equity firm MidOcean Partners.

. . .

Milken’s work on prostate cancer has also made him an influential figure in medical research, where he has developed a reputation for being data-driven and impatient with bureaucracy. Every year he hosts a summit for scientists working on prostate cancer.

“Mike looked at the problem of cancer like a business problem to be solved,” said Dr. Karen Knudsen, CEO of the American Cancer Society. “He wasn’t focused on the flashy. He really focused on what is going to make a difference.”

When the Prostate Cancer Foundation lacked the resources to fund a major study Knudsen needed to conduct to advance her research, she said, Milken introduced her to executives from a pharmaceutical company who he thought would be interested in the science. The company ended up funding the study.

For the full story, see:

Miriam Gottfried. “Bond King, Felon, Billionaire Philanthropist.” The Wall Street Journal (Saturday, July 15, 2023): B3.

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

(Note: the online version of the story was updated July 14, 2023, and has the title “Bond King, Felon, Billionaire Philanthropist: The Nine Lives of Michael Milken.”)

Milken’s book on how to cure more diseases faster is:

Milken, Michael. Faster Cures: Accelerating the Future of Health. New York: William Morrow, 2023.

“Persistent Plucky Outsiders” Innovate a Better Way to Stop Bleeding

(p. 20) Charles Barber’s “In the Blood” treats a consequential topic, and contains moments of real insight, drama and humor.

. . .

Though hemorrhage is a leading cause of death in both war and peacetime, we learn, the techniques for stopping it haven’t improved significantly for millenniums. Barber explores the mysteries of the “coagulation cascade” — during which diverse proteins activate in intricately choreographed sequence to facilitate clotting — as well as the “lethal triad” of hypothermia, acidosis and coagulopathy (impaired clotting) that can send the body into shock.

We watch a surgeon at a Navy hospital in Bethesda slit the femoral arteries of a herd of 700-pound pigs, then apply different hemostatic agents to the spurting wounds, to see which substance stops the bleeding best. Most products, backed by biotech and medical companies, fail: The poor beasts bleed out. But zeolite, a simple mineral with hitherto unknown hemostatic properties, saves their bacon every time.

Barber’s earlier books feature persistent, plucky outsiders who strive to change the world, and he finds two more likely subjects in the men who brought zeolite’s lifesaving properties to light. Frank Hursey is the brilliant, nerdy engineer who discovers that this cheap, highly porous mineral, used by industry to absorb radiation, chemicals and bad odors, also happens to accelerate clotting, by mopping up water in the blood and thereby concentrating its coagulation agents. (Later Hursey finds that another inexpensive mineral, kaolin, works even better.)

Barely anyone pays attention to Hursey’s discovery until he partners with Bart Gullong, a down-on-his-luck salesman who rebrands Hursey’s invention “QuikClot” and persuades a military scientist to try it out on people. Hursey and Gullong are soon befriended by iconoclasts within the armed forces medical establishment, more of Barber’s appealing, quirky, determined Davids, who together take on two of the biggest Goliaths around: the military-industrial complex and Big Pharma.

For the full review, see:

Tom Mueller. “The Home Front.” The New York Times (Sunday, Aug. 20, 2023): 20.

(Note: ellipsis added.)

(Note: the online version of the review has the date July 26, 2023, and has the title “A Fight to Save Soldiers, From the Lab to the Battlefield.”)

The book under review is:

Barber, Charles. In the Blood: How Two Outsiders Solved a Centuries-Old Medical Mystery and Took on the Us Army. New York: Grand Central Publishing, 2023.

Heat Wave in India Causes Rise in Mortality

(p. A11) An unusually intense heat wave has swept across northern India in the last four days, with some hospitals in the state of Uttar Pradesh recording a higher-than-usual number of deaths. Doctors there are convinced there’s a link between the punishing temperatures and the deaths of their patients, but officials are investigating what role the dangerous combination of heat and humidity played in the rise in mortality.

For the full story, see:

Alex Travelli and Hari Kumar. “Northern India Endures a Heat Wave, and a Wave of Deaths, as a Possible Link Is Pondered.” The New York Times (Monday, June 19, 2023): A11.

(Note: the online version of the story has the date June 18, 2023, and has the title “Northern India Endures a Heat Wave, and a Wave of Deaths.”)

Phage Therapy Renaissance-“Once Derided as an Idea for Cranks and Commies”

(p. C7) As engaging as it is expansive, “The Good Virus” describes the distinctive biology and murky history of bacteriophage (generally shortened to “phage”), a form of life that is remarkably abundant yet obscure enough to have been termed the “dark matter of biology.”

. . .

In a South London research institute in the early 1910s, the meticulous English bacteriologist Frederick Twort set out to grow the smallpox virus in petri dishes, hoping it could be “observed and studied like bacteria.” He succeeded in growing only contaminating bacteria, but within these colonies he noticed the occasional small clearing, as if something invisible was killing the bacteria. With the outbreak of World War I, Twort lost funding, closed his lab and published his results in 1915, cautiously suggesting that a virus could be the cause of the observed phenomenon. Few took notice.

Twort’s unlikely competitor would be Felix d’Herelle, a free-spirited Frenchman . . .

. . .

He found the same glassy spots that Twort had observed and (with noticeably less restraint) announced in 1917 that he had discovered a new form of life, which he called “bacteriophage.” D’Herelle went on to use phage to treat five sick boys successfully. But his “wild and abrasive style” (in Mr. Ireland’s words) antagonized his peers, who conspired to undermine him.

D’Herelle’s discoveries inspired many, including George Eliava, a microbiologist from the Soviet Union’s republic of Georgia. In 1936, he would establish the first institute (and still one of the few) devoted to bacteriophage research. Unfortunately for Eliava, he soon ran afoul of the Soviet secret police, who disappeared him in 1937. The institute continued to pursue the development of phage therapy and scored many victories—phage helped treat soldiers suffering from gangrene, for example. But there were also frustrating failures, in part because the phage weren’t adequately purified and often because they weren’t appropriately matched to the specific strain of infecting bacteria.

. . .

. . ., the “dubious and unreliable nature of commercial American phage products” in the 1930s, we learn, meant that “whether they worked for a particular patient was a complete lottery.”

During World War II, the West turned decisively to newly discovered penicillin, sharing the formula for it with the Soviets but not the methods of mass production. Thus the Soviets continued to rely on phage as the therapy of choice for bacterial infections. When a Soviet researcher tried to obtain production rights to penicillin in 1949, he was arrested by government authorities and died under interrogation, all for the crime of nizkopoklonstvo—adulation of the West.

. . .

Once “derided as an idea for cranks and commies,” Mr. Ireland writes, phage therapy seems to be enjoying a renaissance. Having been sustained for years by an idiosyncratic global community of true believers, phage-based medicines have now attracted the attention of high-powered biotechnologists and investors.

For the full review, see:

David A. Shaywitz. “The Enemy of My Enemy.” The Wall Street Journal (Saturday, Aug. 5, 2023): C7.

(Note: ellipses added. In the original, the Russian word nizkopoklonstvo is in italics.)

(Note: the online version of the review has the date August 4, 2023, and has the title “‘The Good Virus’ Review: An Unlikely Healer.”)

The book under review is:

Ireland, Tom. The Good Virus: The Amazing Story and Forgotten Promise of the Phage. New York: W. W. Norton & Company, 2023.

Fish Would Remember More if Hot Water Could Be Air Conditioned

(p. A4) . . ., a new study suggests for the first time that high water temperatures can cause memory loss in reef fish, and even render them unable to learn at all.

. . .

The researchers designed a maze with a reward in one hallway. For about two weeks before maze training began, three groups of fish were gradually exposed to different temperatures: 28to 28.5 degrees Celsius for the control group, 30to 30.5 Celsius for the second, and 31.5 to32 Celsius for the third.

. . .

The researchers spent five days training the fish to navigate the maze and to associate a blue tag with their reward. Five days after training ended, they tested the fish to see which groups could remember how to find the tag, and their reward, in the maze.

The control group did well, quickly remembering how to reach the reward in the maze. But fish in even the moderately hot group didn’t fare as well. Although they learned to navigate the maze quickly during training, five days later, all evidence of their experience had vanished. In earlier experiments, Dr. Luchiari found that damselfish could remember experiences for at least 15 days, so an inability to remember the maze after only five was striking.

Fish in the hottest group failed to learn the maze at all, taking roughly the same amount of time to navigate it throughout the whole experiment.

For the full story, see:

Rebecca Dzombak. “Fish Get More Forgetful In Higher Temperatures.” The New York Times (Thursday, Aug. 24, 2023): A4.

(Note: ellipses added.)

(Note: the online version of the story has the date Aug. 23, 2023, and has the title “Damselfish in Distress: Warmer Seas Might Be Clouding Their Brains.”)

Caution in Interpreting Alternative Explanations of Ancient Artifacts

A few weeks ago, an article highlighted the finding of female bones in a burial along with a sword. It was interpreted that the sword belonged to a distinguished female warrior and was interpreted as evidence against patriarchal assumptions.

(p. D1) The epitaph on more than one Roman tombstone read: “A gang of doctors killed me.”

Medical remedies have improved since those times — no more smashed snails, salt-cured weasel flesh or ashes of cremated dogs’ heads — but surgical instruments have changed surprisingly little. Scalpels, needles, tweezers, probes, hooks, chisels and drills are as much part of today’s standard medical tool kit as they were during Rome’s imperial era.

Archaeologists in Hungary recently unearthed a rare and perplexing set of such appliances. The items were found in a necropolis near Jászberény, some 35 miles from Budapest, in two wooden chests and included a forceps, for pulling teeth; a curet, for mixing, measuring and applying medicaments, and three copper-alloy scalpels fitted with detachable steel blades and inlaid with silver in a Roman style. Alongside were the remains of a man presumed to have been a Roman citizen.

The site, seemingly undisturbed for 2,000 years, also yielded a pestle that, judging by the abrasion marks and drug residue, was probably used to grind medicinal herbs. Most unusual were a bone lever, for putting fractures back in place, and the handle of what appears to have been a drill, for trepanning the skull and extracting impacted weaponry from bone.

The instrumentarium, suitable for performing complex operations, provides a glimpse into the advanced medical prac-(p. D4)tices of first-century Romans and how far afield doctors may have journeyed to offer care. “In ancient times, these were comparatively sophisticated tools made of the finest materials,” said Tivadar Vida, director of the Institute of Archaeology at Eötvös Loránd University, or ELTE, in Budapest and leader of the excavation.

Two millenniums ago Jászberény and the county around it were part of the Barbaricum, a vast region that lay beyond the frontiers of the Empire and served as a buffer against possible outside threats. “How could such a well-equipped individual die so far from Rome, in the middle of the Barbaricum,” mused Leventu Samu, a research fellow at ELTE and a member of the team on the dig. “Was he there to heal a prestigious local figure, or was he perhaps accompanying a military movement of the Roman legions?”

. . .

The tool-laden grave was discovered last year at a site where relics from the Copper Age (4500 B.C. to 3500 B.C.) and the Avar period (560 to 790 A.D.) had been found on the surface. A subsequent survey with a magnetometer identified a necropolis of the Avars, a nomadic peoples who succeeded Attila’s Huns. Among the rows of tombs, the researchers uncovered the man’s grave, revealing a skull, leg bones and, at the foot of the body, the chests of metal instruments. “The fact that the deceased was buried with his equipment is perhaps a sign of respect,” Dr. Samu said.

That is not the only possibility. Dr. Baker said that she often cautioned her students about interpreting ancient artifacts, and asked them to consider alternative explanations. What if, she proposed, the medical tools were interred with the so-called physician because he was so bad at his practice that his family and friends wanted to get rid of everything associated with his poor medical skills? “This was a joke,” Dr. Baker said. “But it was intended to make students think about how we jump to quick conclusions about objects we find in burials.”

For the full story, see:

Franz Lidz. “Old Roman Medicine Wasn’t So Pleasant.” The New York Times (Tuesday, June 13, 2023): D1 & D4.

(Note: ellipsis added.)

(Note: the online version of the story also has the date June 13, 2023, and has the title “Scalpel, Forceps, Bone Drill: Modern Medicine in Ancient Rome.”)