January 2025 – Page 3 – artdiamondblog.com

Drugs for Dog Longevity May Also Aid Human Longevity

Dogs have long contributed to advances in human medicine. For instance C. Walton Lillehei experimented on dogs to develop his path-breaking human open-heart operations (see the book King of Hearts). What pains me about those dog contributions is that the dogs themselves died in the experiments. In the more recent dog contributions to human medicine, as discussed in the passages quoted below, the dogs themselves have a good chance to benefit as they contribute to human health. I like that a lot better.

(p. A11) In the quest to help people live longer, scientists and companies are turning to dogs.

. . .

Behind the growing enthusiasm is a mix of scientists and entrepreneurs—building on the surging interest from people aiming to live longer. These groups say insights into dog longevity could provide lessons and perhaps eventually treatments that could help people, too.

. . .

On Tuesday [Nov. 28, 2023], a biotech startup that’s hoping to have the first FDA-approved treatment to extend healthy lifespan in dogs, took a step toward that goal. In a letter viewed by The Wall Street Journal, the Food and Drug Administration affirmed that its drug had demonstrated “reasonable expectation of effectiveness.”

The company, called Loyal, still has to complete several more steps before it can market the drug, and it’s only aimed at canines.

. . .

Celine Halioua, chief executive of Loyal, the biotech startup working toward conditional approval of its lifespan drug, says there is a larger aim in addition to helping dogs live healthier for longer. The company has set a possible precedent for other drugs to be approved for lifespan extension, potentially opening a door for other animal—or human—drug companies to follow.

“I think we can both take the opportunity to build better medicines for our dogs and also to better understand these really complex diseases,” says Halioua, whose own 85-pound Rottweiler mix, Della, is nearing the end of her projected lifespan.

The firm’s drug is an injectable that is designed to reduce levels of IGF-1, a hormone that drives cell growth, in large dogs. High blood levels of IGF-1 have been associated with shorter lifespans in some animal and human studies.

The company’s research has indicated that the drug can reduce those hormone levels, but it would still need a large clinical trial demonstrating it can extend dog lifespans in order to achieve full FDA approval. It also needs the agency’s signoff on the drug’s safety and proper manufacturing before getting conditional approval and beginning to sell it, which Loyal hopes to do in 2026.

Still, the FDA nod this week is a promising next step for the field, dog aging researchers say, and will likely drive more interest from biotech and pharmaceutical companies.

“If it is proven that the drug is effective in dogs then there is a higher chance that it will work in the case of humans, too,” says Eniko Kubinyi, a biologist studying dog behavior and cognition with the Budapest-based Family Dog Project.

For the full story see:

Alex Janin. “Secrets of Anti-Aging, Gleaned From Dogs.” The Wall Street Journal (Thursday, Nov. 30, 2023 [sic]): A11.

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

(Note: the online version of the story has the date November 29, 2023 [sic], and has the title “The Clues to Longer Life That Are Coming From Dogs.” The last four paragraphs quoted above appeared in the more detailed online version, but not the print version, of the article. Some of the earlier quoted sentences are quoted in the longer form that appeared in the online version.)

The biography of Lillehei mentioned in my opening comments above is:

Miller, G. Wayne. King of Hearts: The True Story of the Maverick Who Pioneered Open Heart Surgery. New York: Crown, 2000.

Innovative Medical Project Entrepreneur Alan Scott “Coaxed” the F.D.A. to Approve Botox

Even though Alan Scott may have been a “lousy businessman,” he appears nonetheless to still have been an important innovative medical project entrepreneur. (I have not yet read the book discussed in the passages quoted below, but I hope to read it soon. Besides my admiration for innovative project entrepreneurs, an added reason that I am interested in the book is that I have always suffered from esophoria, which is one form of the strabismus that Alan Scott was trying to treat.)

(p. C9) Today botulinum toxin—purified, diluted and known as Botox—nets annual sales in the billions. It is used to treat everything from wrinkles to migraines, yet the pioneer largely responsible for fulfilling Kerner’s prophecy and bringing botulinum into medicine is virtually unknown. He was, it turns out, a laconic Bay Area ophthalmologist named Alan Scott, a self-described “lousy businessman” who barely recouped his own expenses as he coaxed the product to FDA approval.

Eugene Helveston seeks to rescue Scott from oblivion in “Death to Beauty,” a pandemic passion project and labor of love. As an ophthalmologist “of the same era,” Dr. Helveston knew Scott professionally and participated as a researcher in the original clinical trial of botulinum in the mid-1980s. Recognizing that only a few people were still around who could “tell the story firsthand,” Dr. Helveston resolved to document this medical history and corresponded with Scott from June 2021 until Scott’s death six months later, at age 89. The result is an absorbing insider’s account of an exceptional journey.

. . .

Scott was especially interested in strabismus, a disorder characterized by misaligned eyes. The condition was usually treated with surgery, with often disappointing results. Scott began to wonder if strabismus could be treated without surgery by injecting a substance that would weaken a specific eye muscle and thus help restore alignment. It was this line of research that led him to contemplate botulinum, which he requested and received from Schantz in 1972, delivered by the Postal Service in a sealed metal container. Fatefully, he reported promising results in animal models the next year without first filing a patent, which meant that his valuable intellectual property went unprotected.

To enable human testing, Scott submitted an application to the FDA in 1974; the document “lay on some FDA desk for almost four years,” he told Dr. Halversten, before a nudge from a colleague re-engaged the agency. Scott received testing authorization in 1978 and injected the first human subject with a low test dose to evaluate safety. There were no complications, and the trial proceeded.

. . .

Though Botox never gained much traction for the treatment of strabismus, the drug’s other uses lifted it to blockbuster status. Scott received only modest compensation for his foundational work, yet by all accounts he had no regrets. Allergan may have “got all the money,” he said, but “we had all the fun.”

For the full review see:

David A. Shaywitz. “Toning Up With a Toxin.” The Wall Street Journal (Saturday, Dec. 17, 2024): C9.

(Note: ellipses added.)

(Note: the online version of the review has the date February 9, 2024, and has the title “‘Death to Beauty’ Review: The Birth of Botox.”)

The book under review is:

Helveston, Eugene M. Death to Beauty: The Transformative History of Botox. Bloomington, IN: Indiana University Press, 2024.

Price Controls on Drugs Reduce Drug Innovation

Price controls on drugs may reduce some short-term healthcare costs for consumers, but will also reduce the innovation that brings us more cures, less pain, and fewer side effects. If we want to both reduce costs for consumers and increase innovation, we should end government mandates for the Phase 3 clinical trials–the phase of clinical trials that make up most of the cost of gaining regulatory approval.

(p. A19) The Biden White House has proposed requiring Medicare to “negotiate” drug prices.

. . .

Unfortunately, the debate is being informed by erroneous Congressional Budget Office analysis. CBO says . . . the supply of new drugs will only be reduced by 5% from 2021 to 2039, a loss of only two drugs a year.

The CBO minimizes the harmful effects on innovation, but the entire supply chain that funds medical R&D relies on rate-of-return assessments driven by future earnings. An analysis I released this week finds 10 times the effect on R&D, a loss of up to some 340 drugs over the same period.

The White House also claims that price controls won’t hamstring innovation because they only govern top-selling drugs. But the occasional blockbuster funds the roughly 90% of pipeline drugs that never pass Food and Drug Administration review. CBO even acknowledges that only the top 7% of Medicare drugs drive U.S. profits. Targeting financially successful drugs could make large segments of the development portfolio unprofitable, even if such drugs aren’t affected by price controls.

For the full commentary see:

Tomas J. Philipson. “Biden’s Price Controls Will Make Good Health More Expensive.” The Wall Street Journal (Thursday, Sept. 16, 2021 [sic]): A19.

(Note: ellipses added.)

(Note: the online version of the commentary has the date September 15, 2021 [sic], and has the same title as the print version.)

The research brief co-authored by Philipson and mentioned above is:

Philipson, Tomas J., and Troy Durie. “The Evidence Base on the Impact of Price Controls on Medical Innovation.” Issue Brief. Becker Friedman Institute, University of Chicago, Sept. 14, 2021.

Supporting Philipson’s argument is a 2024 working paper showing that Medicare-mandated price cuts in medical equipment has resulted in less innovation in medical equipment:

Ji, Yunan, and Parker Rogers. “The Long-Run Impacts of Regulated Price Cuts: Evidence from Medicare.” NBER Working Paper #33083, Oct. 2024.

When Ronald Reagan Needed the Owls of Hogwarts

One of my favorite scenes in the first Harry Potter movie is when an owl tries to deliver to Harry Potter an acceptance letter to Hogwarts. Ever since Voldemort murdered Harry’s parents when he was a baby, Harry has lived under a staircase with the Dursleys (Mrs. Dursley was the sister of Harry’s mother). Mr. Dursley, and the other Dursleys too, do not like Harry, hence his living under a staircase. Mr. Dursley sees the letter to Harry, opens it, and when he realizes the contents tears it up. Then a few other copies arrive and Dursley burns them. It would appear that Harry’s hope of escape is dashed.

But then something wonderful. Countless owls fly toward the Dursley house, each carrying copies of the letter. Acceptance letters start pouring through the front door mail slot, down the chimney, and through every opening in the house. Soon the inside of the Dursley house is buried in acceptance letters. Dursley cannot stop Harry from knowing.

I thought of this scene when I was reading the Wikipedia entry for “Human Events.” Human Events was a smallish weekly readers-digest-type newspaper that my father subscribed to for many years (in the 1960s and 1970s?). Copies of Human Events would always be piled up next to his chair in the living room. Human Events was a contrarian publication presenting conservative/libertarian commentaries on the issues of the day.

The Wikipedia article says that starting in 1961, Ronald Reagan is an avid reader of Human Events. In the 1970s he writes articles that appear in Human Events. When he is president, Reagan’s top aides Baker, Darman, and Deaver do not like what is in Human Events, and try to keep copies of it away from him. When Reagan realizes that his aides are blocking Human Events, he “arranged for multiple copies to be sent to the White House residence every weekend” (Edwards 2011, as quoted in Wikipedia entry on “Human Events“).

Unfortunately for Reagan he does not have a flock of wise owls providing redundant information. But Reagan is his own owl.

Harry could not fire Dursley; I wonder why Reagan did not fire Baker, Darman, and Deaver?

Wikipedia gives the source of the Edwards quote as:

Edwards, Lee. “Reagan’s Newspaper.” URL: http://www.humanevents.com/article.php?id=41609

Britain’s Socialized Medicine Can Take Many Hours to Transport Emergency Patients

(p. A1) WREXHAM, Wales — Rachel Parry and Wayne Jones, two paramedics with the Wrexham Ambulance Service, pulled up to a hospital in northern Wales with a patient just after 10 a.m. one early December [2022] morning.

That’s when their wait began.

It would be 4:30 p.m. before their patient, a 47-year-old woman with agonizing back pain and numbness in both of her legs, would be handed over to the emergency room of Wrexham Maelor Hospital. It was more than 12 hours since she had first called 999, the British equivalent of 911.

The delays have grown so bad — and so common — the two paramedics said, that their first interaction with patients is no longer an introduction.

“We start with an apology now,” Ms. Parry said. “Every job is, like, they open the front door, ‘Hi, we are so sorry we are late.’ That has become the norm.”

The sight of ambulances lined up for hours outside hospitals has become distressingly familiar in Wales, which last month recorded its worst wait times ever for life-threatening emergency calls. But the problem is far from isolated. Ambulances services in England, Scotland and Northern Ireland are also experiencing record-high waits.

It’s a near-crisis situation that experts say signals a breakdown of the compact between Britons and their revered National Health Service: that the government will provide responsible, efficient health care services, mostly free, across all income levels.

. . .

(p. A7) While Ms. Parry and Mr. Jones waited at the hospital with their second patient, there were at least 21 calls in their response area that they and other paramedics also stuck at the hospital could not be deployed to. During their 12-hour shift, they picked up only three patients.

“It’s frustrating,” Mr. Jones said. “These people are out in the community and they are desperate.”

Good Samaritans sometimes step in and drive people in distress to the hospitals themselves. While Ms. Parry and Mr. Jones were waiting with their patients, two cars pulled into the ambulance drop-off point with patients. In both cases — one in which an elderly woman fell and broke her wrists and another in which a woman collapsed in a supermarket — the driver had called the emergency services only to be told it would be hours before an ambulance could come.

“Bystanders are doing more jobs than me today,” Ms. Parry said in frustration, after helping both arrivals into the hospital.

. . .

Families also find the long waits excruciating as they watch their loved ones suffer. Frank Taylor waited three hours with his wife Ann Taylor, 79, for an ambulance, saying it was hard for him to see her in so much pain.

When the paramedics arrived, he was relieved to see them swiftly hook her up to oxygen before gently carrying her, wrapped in a blue knit blanket, down the stairs to the ambulance.

But when they reached the hospital, it was another two-hour wait before Ms. Taylor was finally taken inside.

Around 8:30 p.m., Ms. Taylor was transferred from the emergency room to the intensive care unit, the final stop after a long day of uncertainty.

Last year, Ms. Taylor was moved to a nursing home after her health declined — she has end-stage lung disease — and Mr. Taylor visits her daily. It was there that the ambulance picked her up.

. . .

While he praised the care of the paramedics, Mr. Taylor said the wait time was frustrating. He worried about his wife’s dignity during this final stage of her life.

For the full story, see:

Megan Specia. “A Day With a U.K. Ambulance: Painful Waits, Crowded Hospitals.” The New York Times (Wednesday, December 21, 2022 [sic]): A1 & A7.

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

(Note: the online version of the story was updated Dec. 22, 2022 [sic], and has the title “One Day With an Ambulance in Britain: Long Waits, Rising Frustration.”)

The Lovable, Frustrating, Vulnerable “Big Easy”

Our daughter is a loyal Notre Dame graduate, so we went to New Orleans for the Sugar Bowl game, scheduled for January 1, but ultimately played on January 2. The day before the scheduled game, we were in Jackson Square on New Year’s Eve for the countdown to 2025. For us a little partying goes a long way, so we headed back to the Marriott about 12:30. About two and a half hours later, a couple of blocks from where we had been, the terrorist plowed his truck through the crowd, killing 14, and seriously injuring many more.

They call New Orleans “the Big Easy.” I appreciate its joy, its spontaneity, its libertarian tolerance. But I can only visit New Orleans, I cannot live there.

When I arrive in a hotel I want a glass of ice water. In our two most recent visits to Marriott hotels in New Orleans, the ice machines on our floor did not at first work. It never worked during our stay at the first hotel and worked only occasionally at the second hotel. When I complained at the first hotel, I got a joyful grin and a shrug–the ice machine had been that way for several days and who knows when or if it would be fixed? It’s “easy” to celebrate; it’s hard to fix ice machines and keep them running.

There were barriers on Bourbon Street that could have kept the terrorist from killing 14. But it has come out that they were not working and it was not “easy” to fix them. (There were also supposed to be levies that could have reduced the damage from Hurricane Katrina, but it was not “easy” to fix them either.)

I like visiting New Orleans. I like its joyful spontaneity. But what makes New Orleans “the Big Easy” also makes it “the Big Frustrating” and “the Big Vulnerable.” I like visiting New Orleans but I want to live in a city where type-A personalities do what is hard: build, fix, and protect.

The Second Arthur Mansfield Diamond Would Be 100 Today

Happy Birthday Dad! He was the second Arthur Mansfield Diamond and would be 100 today.

I think if we adopt the right policies, many of us could live to 100. Too late for Dad, and almost certainly for me.

The first Arthur Mansfield Diamond died in 1933, I think. I was told he played the piano by ear and I saw an article saying that when he was a young man he briefly was a book-keeper for the family vaudeville activities. He looked dapper in a straw hat and knew Knute Rockne of Notre Dame. My Dad was eight when cancer took the first Arthur Mansfield Diamond. My Grandma, with no college degree, raised four children during the Great Depression. Cabbage was nutritious and cheap, so Grandma served a lot of sauerkraut. As an adult Dad hated sauerkraut.

Dad was always reading. He is the only person I ever met who read all three volumes of Solzhenitsyn’s Gulag Archipelago. And he read a conservative reader’s digest weekly (or monthly?) newspaper called Human Events. He was a Republican lawyer in an overwhelmingly Democratic county.

When my brothers and I were young he read aloud to us most of the Oz books, and other books including Atlas Shrugged. Thank you Dad, especially for that.

I wish I had finished my book before he died–he would have read it, argued with me about parts of it, but I think mostly liked it.

Dad was active in Toastmasters, a self-help organization for those who want to improve their public speaking. He rose to become the International President. Their headquarters is near Disneyland. When Dad first joined the Toastmasters board, he spent some time in the park. When he returned from that first trip, I remember his excitement at the then-new attraction, the Tiki Room–seeing what was possible in audio animatronics. Mom and Dad took us to Disneyland and on road trips to most of the U.S.

I remember Dad telling me in his last year that one of his regrets is that he won’t know how things turn out.

Dad was not perfect; neither am I. But I miss him and wish I could still talk with him, and thank him for his wit, his curiosity, and his courage in holding unpopular views when he thought they were right.

To End Drug Shortages Make Healthcare a Free Market

Drug shortages are sometimes blamed on the free market. A bum rap. In a free market when supply declines or demand increases, prices rise, and the increase in price incentivizes a greater quantity supplied, eventually ending a short-run period where quantity demanded at the going price exceeds quantity supplied at the going price (in other words, a shortage). But healthcare in America is far from a free market. Every aspect is highly regulated. Prices are negotiated, often by middlemen called (Pharmacy Benefit Managers, aka PBMs), entry is not free, and the demanders (patients) often do not know (or care) about the prices, since they are paid by a third party (insurers, employers, or the government). Perverse incentives abound.

(p. A26) There’s been a bombardment of bad news for drug supplies. The American Society of Health-System Pharmacists found this summer that nearly all of the members it surveyed were experiencing drug shortages, which generally affect half a million Americans. Cancer patients have scrambled as supplies of chemotherapy drugs dwindle. Other shortages include antibiotics for treatable diseases, such as the only drug recommended for use during pregnancy to prevent congenital syphilis (a disease that is 11 times more common today than a decade ago), and A.D.H.D. medications, without which people struggle to function in their day-to-day lives. The toll on Americans is heavy.

Over half of the shortages documented this summer by health consulting firm IQVIA had persisted for more than two years. But even though drug shortages affect millions of Americans, policymakers and industry leaders have provided little to no long-term relief for people in need.

Shortages have occurred regularly since at least the early 2000s, when national tracking began. Hundreds of drugs, in every major therapeutic category, have been unavailable for some period. The average drug shortage lasts about 1.5 years. Even when substitute medications are available, they may be suboptimal (for example, deaths by septic shock rose by 10 percent during a 2011 shortage of the first-line medication, norepinephrine) or have spillover effects (such as possibly increasing the risk of antimicrobial resistance). In addition to harming patients, shortages have cost health systems billions of dollars in increased labor and substitute medications.

. . .

Large hospital chains can readily monitor shortage risks and preemptively place large orders. This panic buying can wipe out inventory, and leave hospitals with fewer resources strapped since they may get notice of a drug shortage only when it’s too late. There is little penalty for over-ordering because unused drugs can often be returned.

. . .

Addressing the underlying fragility of our essential drug supply will take structural change and investments. While all industries must grapple with how to build resilient supply chains, the pharmaceutical industry is unique. The people who are most affected by supply chain vulnerabilities — patients — are also those with least say in the choice to buy from reliable manufacturers. When people buy cars, they may pay more based on company reputation, ratings by outside testers and reviews from other customers. In contrast, patients bear the harm of drug shortages, yet they cannot choose the manufacturers of their essential drugs nor evaluate their reliability.

For the full commentary see:

Emily Tucker. “We’re Stuck in a Constant Cycle of Drug Shortages.” The New York Times (Thursday, December 7, 2023 [sic]): A26.

(Note: ellipses added.)

(Note: the online version of the commentary has the date Dec. 6, 2023 [sic], and has the title “America Is Having Yet Another Drug Shortage. Here’s Why It Keeps Happening.”)

F.D.A. Should Allow Physicians and Parents the Freedom to Give Preterm Infants Probiotics

Substantial observational evidence shows that the status of a person’s microbiome can have a large effect on the person’s health. We still have a lot to learn about which bacteria are helpful and the details of how they help. But patients must act under uncertainty, or in the case of the preterm infants discussed in the passages quoted below, physicians and parents must act under uncertainty. Given the current evidence and the uncertainty, the F.D.A. is arrogantly wrong to ban probiotics.

(p. A5) For years, hospitals around the world have tried to protect prematurely born babies from life-threatening gut disease by giving them probiotics. Then . . . [in Oct. 2023], American hospitals stopped.

The Food and Drug Administration had linked an infant’s recent death to one of the products. It warned doctors about using them in preterm infants without getting agency permission first, and pushed Abbott Laboratories and another major manufacturer, Infinant Health, to stop selling them.

. . .

Neonatologists in the U.S. and other developed countries have learned to help smaller and smaller babies stay alive. As they treat tinier babies, the medical challenges mount, including a swift-onset disease known as necrotizing enterocolitis, or NEC.

. . .

To help prevent NEC, nearly all neonatal units in Australia and New Zealand give probiotics, as do a majority in several European countries. About 40% in the U.S. did before the FDA’s actions, according to recent surveys and neonatologists’ estimates.

Nearly all of the products consist of live bacteria intended to help create a healthy community of microbes in the gut. Scientists don’t know exactly how they work, but suspect they prevent harmful bacteria from overwhelming the bowels.

. . .

Neonatal units across the U.S. halted use of the probiotics because popular versions were no longer available and the FDA warned doctors against using probiotics for preterm babies outside of clinical trials.

“I was stunned,” said Jennifer Canvasser, who started a NEC patient advocacy group after her infant son died 10 years ago, weakened by the disease. “To think about families having one potential less way to prevent this devastating disease is just concerning.”

Probiotics supporters say the FDA disregarded the evidence favoring probiotics for preterm babies, saying that they likely save hundreds of infants for every one probiotic-caused infection, which can be treated with antibiotics.

An analysis of more than 100 studies involving more than 25,000 premature infants, published . . . [in Oct. 2023] in the journal JAMA Pediatrics, found that probiotics containing multiple strains of bacteria were associated with reduced deaths and NEC.

For the full story see:

Liz Essley Whyte. “Discord Arises Over Treating Preemie Babies.” The Wall Street Journal (Saturday, Nov. 17, 2023 [sic]): A5.

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

(Note: the online version of the story was updated Nov. 16, 2023 [sic], and has the title “Doctors, FDA Fight Over Giving Probiotics to Premature Babies.” The passages quoted above omit the subheadings that appear in the print, but not the online, version of the story.)

The analysis published in JAMA Pediatrics and mentioned above is:

Wang, Yuting, Ivan D. Florez, Rebecca L. Morgan, Farid Foroutan, Yaping Chang, Holly N. Crandon, Dena Zeraatkar, Malgorzata M. Bala, Randi Q. Mao, Brendan Tao, Shaneela Shahid, Xiaoqin Wang, Joseph Beyene, Martin Offringa, Philip M. Sherman, Enas El Gouhary, Gordon H. Guyatt, and Behnam Sadeghirad. “Probiotics, Prebiotics, Lactoferrin, and Combination Products for Prevention of Mortality and Morbidity in Preterm Infants: A Systematic Review and Network Meta-Analysis.” JAMA Pediatrics 177, no. 11 (2023): 1158-67.

For a useful discussion of how current medical protocols, especially the over-prescription of antibiotics, harm the microbiome, see chapter 3 of:

Makary, Marty. Blind Spots: When Medicine Gets It Wrong, and What It Means for Our Health. New York: Bloomsbury Publishing, 2024.