Crispr Gene-Editing Tried Against Cancer

(p. D4) Doctors have for the first time in the United States tested a powerful gene-editing technique in people with cancer.

The test, meant to assess only safety, was a step toward the ultimate goal of editing genes to help a patient’s own immune system to attack cancer. The editing was done by the DNA-snipping tool Crispr.

The procedure was feasible and safe, early results indicate, but whether it is fighting the disease is unclear. Only three patients have been treated so far, and the longest follow-up is nine months. All three patients are in their 60s, with very advanced cancers that had progressed despite standard treatments like surgery, radiation and chemotherapy.

“The good news is that all of them are alive,” said Dr. Edward A. Stadtmauer, the section chief of hematologic malignancies at the University of Pennsylvania Abramson Cancer Center. He added, “The best response we’ve seen so far is stabilization of their disease.”

For the full story, see:

Denise Grady. “Editing Genes in Bid to Fight Cancer.” The New York Times (Tuesday, November 12, 2019): D4.

(Note: the online version of the story was updated Oct. 7, 2020 [sic], and has the title “Crispr Takes Its First Steps in Editing Genes to Fight Cancer.”)

Art Diamond Discusses “Policy Hurdles in the Fight Against Aging” on Caleb Brown’s Cato Daily Podcast

Caleb Brown, of the Cato Institute, posted an interview with me yesterday (May 27, 2022) on his “Cato Daily Podcast.” The topic, “Policy Hurdles in the Fight against Aging,” is related to a chapter in my book-in-progress on medical entrepreneurship that is to be entitled Less Costs, More Cures: Unbinding Medical Entrepreneurs.

Bennet Chose Pig’s Heart Since “It Was Either Die or Do This Transplant”

(p. A3) A man who had the first transplant to replace his human heart with a genetically-modified pig’s heart without immediate rejection died Tuesday afternoon at the University of Maryland Medical Center in Baltimore, two months after the groundbreaking surgery.

. . .

While Mr. Bennett only lived with the pig heart for a couple of months, Dr. Parsia Vagefi, UT Southwestern Medical Center’s chief of the division of surgical transplantation, said people shouldn’t view the transplant as a failure and that he hopes it serves as a “new beginning” for xenotransplantation.

“I think what this shows is just the enormous amount of progress that’s been made and hopefully it’s just the beginning that we continue to grow on,” he said.

Mr. Bennett wasn’t eligible for a more typical heart transplant because he didn’t comply with doctors’ orders or attend follow-up visits. Several transplant centers—including the Maryland one—declined to list him for the chance to get a human heart, according to David Bennett Jr. , Mr. Bennett’s son. He also didn’t regularly take his medication, the younger Mr. Bennett previously said.

The U.S. Food and Drug Administration had granted Mr. Bennett’s operation emergency authorization on New Year’s Eve. “It was either die or do this transplant,” he said the day before his surgery, according to the University of Maryland Medicine. The handyman and father of two called the transplant his “last choice.”

For the full story, see:

Allison Prang. “Pig-Heart Recipient Dies 2 Months Later.” The Wall Street Journal (Thursday, March 10, 2022): A3.

(Note: ellipsis added.)

(Note: the online version of the story was updated March 9, 2022, and has the title “The Patient Who Received a Pig Heart Dies Two Months After Transplant.” The first two sentences after the ellipsis appear in the online, but not the print, version.)

Imposing Permanent Daylight Savings Time Is Like Imposing Permanent Jet Lag

(p. A19) . . . when the U.S. Senate recently passed a bill to make daylight-saving time permanent, sleep experts became more alarmed.

Legislators picked the wrong time, they say.

Our internal clocks are connected to the sun, which aligns more closely with permanent standard time, says Muhammad Adeel Rishi, a pulmonologist and sleep physician at Indiana University. When the clocks spring forward, our internal clocks don’t change but are forced to follow society’s clock rather than the sun. DST is like permanent social jet lag.

Dr. Rishi is one of the authors of a 2020 position statement from the American Academy of Sleep Medicine, a professional society, supporting making standard time—not daylight-saving time—permanent.

. . .

One of the big problems with permanent DST, objectors note, is that in the winter the sun will rise later and many schoolchildren will be walking to school in the dark.

On the western edge of the eastern time zone in Indiana, for instance, the sun won’t rise in the winter until about 9 a.m., notes Dr. Rishi. “You’re basically putting these kids two hours off from their circadian biology,” he says.

For the full commentary, see:

Sumathi Reddy. “YOUR HEALTH; Body Clock Needs Sun In Morning.” The Wall Street Journal (Thursday, March 24, 2022): A19.

(Note: ellipses added.)

(Note: the online version of the commentary has the date March 23, 2022, and has the title “YOUR HEALTH; Why Permanent Daylight-Saving Time Is Seen as Bad for Your Health.”)

Discoverer of Catalyst Role of mRNA Had Trouble “Getting His Work Published”

(p. B12) Sidney Altman, a molecular biologist who was awarded the Nobel Prize for Chemistry for sharing in the discovery that ribonucleic acid, or RNA, was not just a carrier of genetic information but could also be a catalyst for chemical reactions in cells — a breakthrough that paved the way for new gene therapies and treatments for viral infections — died on April 5 [2022] in Rockleigh, N.J.

. . .

HAs seems to happen so often in science, Dr. Altman stumbled upon his discovery. “I wasn’t looking for what I found,” he said in a 2010 interview with Harry Kreisler at the Institute for International Studies at the University of California, Berkeley.

He had studied how a small RNA molecule, called transfer RNA, carries genetic code to make new proteins. Some of the code is not necessary, so an enzyme cuts it out before it is used.

Then, in 1978, Dr. Altman began studying an RNA-cutting enzyme from E. coli bacteria that was composed of an RNA molecule and a protein. He managed to separate the two pieces and test them to see how they reacted in the enzyme process. Much to his surprise, he discovered that the protein did not perform as an enzyme without the RNA molecule. He later discovered that the RNA molecule could be the catalyst, even without the protein.

The finding ran completely contrary to what at the time was established theory, which held that it was the proteins that were the catalysts in enzymes.

The discovery of what are now known as ribozymes was so radical that Dr. Altman had trouble getting it accepted.

Joel Rosenbaum, a professor of cell biology at Yale and a colleague of Dr. Altman’s, told Chemistry World magazine that when Dr. Altman first tried to get other scientists to accept his research, “the community of molecular biologists, including several at Yale working on RNA, did not want to believe the work.”

“He had a hard time obtaining invitations to speak at scientific meetings and, indeed, getting his work published,” Dr. Rosenbaum said.

For the full obituary, see:

Dylan Loeb McClain. “Sidney Altman, Who Stumbled on a Breakthrough in Genetics, Dies at 82.” The New York Times (Saturday, April 16, 2022): B12.

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

(Note: the online version of the obituary was updated April 18, 2022, and has the same title as the print version.)

Gary Becker Foresaw a Cure for Obesity that Daniel Kahneman Wrote Was “Implausible”

I have found much of value in Daniel Kahneman’s Thinking, Fast and Slow. But the following passage is not included in what I value.

A famous example of the Chicago approach is titled A Theory of Rational Addiction; it explains how a rational agent with a strong preference for intense and immediate gratification may make the rational decision to accept future addiction as a consequence. I once heard Gary Becker, one of the authors of that article, who is also a Nobel laureate of the Chicago school, argue in a lighter vein, but not entirely as a joke, that we should consider the possibility of explaining the so-called obesity epidemic by people’s belief that a cure for diabetes will soon become available. He was making a valuable point: when we observe people acting in ways that seem odd, we should first examine the possibility that they have a good reason to do what they do. Psychological interpretations should only be invoked when the reasons become implausible—which Becker’s explanation of obesity probably is.

Source: Kahneman, Daniel. Thinking, Fast and Slow. New York: Farrar, Straus and Giroux, 2011, p. 412.

Gary Becker is vindicated again:

(p. A16) An experimental drug has enabled people with obesity or who are overweight to lose about 22.5 percent of their body weight, about 52 pounds on average, in a large trial, the drug’s maker announced on Thursday.

The company, Eli Lilly, has not yet submitted the data for publication in a peer-reviewed medical journal or presented them in a public setting. But the claims nonetheless amazed medical experts.

“Wow (and a double Wow!)” Dr. Sekar Kathiresan, chief executive of Verve Therapeutics, a company focusing on heart disease drugs, wrote in a tweet. Drugs like Eli Lilly’s, he added, are “truly going to revolutionize the treatment of obesity!!!”

Dr. Kathiresan has no ties to Eli Lilly or to the drug.

. . .

The Eli Lilly study lasted 72 weeks and involved 2,539 participants. Many qualified as obese, while others were overweight but also had such risk factors as high blood pressure, high cholesterol levels, cardiovascular disease or obstructive sleep apnea.

They were divided into four groups. All received diet counseling to reduce their calorie intake by about 500 a day.

One group was randomly assigned to take a placebo, while the other three received doses of tirzepatide ranging from 5 milligrams to 15 milligrams. Patients injected themselves with the drug once a week.

. . .

The medications are among a new class of drugs called incretins, which are naturally occurring hormones that slow stomach emptying, regulate insulin and decrease appetite. The side effects include nausea, vomiting and diarrhea. But most patients tolerate or are not bothered by these effects.

For the full story, see:

Gina Kolata. “Experimental Obesity Drug Produces 20% Weight Loss.” The New York Times (Friday, April 29, 2022): A16.

(Note: ellipses added.)

(Note: the online version of the story was updated May 1, 2022, and has the title “Patients Taking Experimental Obesity Drug Lost More Than 50 Pounds, Maker Claims.” Where there is a slight difference in wording between the online and the print versions, the passages quoted above follow the online version.)

Kahneman’s book is:

Kahneman, Daniel. Thinking, Fast and Slow. New York: Farrar, Straus and Giroux, 2011.

CAR T Therapy Is a Durable “Cure” for Some Leukemia Cancers

(p. A17) Doug Olson was feeling kind of tired in 1996. When a doctor examined him she frowned. “I don’t like the feel of those lymph nodes,” she said, poking his neck. She ordered a biopsy. The result was terrifying. He had chronic lymphocytic leukemia, a blood cancer that mostly strikes older people and accounts for about a quarter of new cases of leukemia.

“Oh Lordy,” Mr. Olson said. “I thought I was done for.” He was only 49 and, he said, had always been healthy.

Six years went by without the cancer progressing. Then it started to grow. He had four rounds of chemotherapy but the cancer kept coming back. He had reached pretty much the end of the line when his oncologist, Dr. David Porter at the University of Pennsylvania, offered him a chance to be among the very first patients to try something unprecedented, known as CAR T cell therapy.

In 2010, he became the second of three patients to get the new treatment.

At the time, the idea for this sort of therapy “was way out there,” said Dr. Carl June, the principal investigator for the trial at Penn, and he had tempered his own expectations that the cells he was providing to Mr. Olson as therapy would survive.

“We thought they would be gone in a month or two,” Dr. June said.

Now, a decade later, he reports that his expectations were completely confounded. In a paper published Wednesday in Nature, Dr. June and his colleagues, Dr. J. Joseph Melenhorst and Dr. Porter, report that the CAR T treatment made the cancer vanish in two out of the three patients in that early trial. All had chronic lymphocytic leukemia. The big surprise, though, was that even though the cancer seemed to be long gone, the CAR T cells remained in the patients’ bloodstreams, circulating as sentinels.

“Now we can finally say the word ‘cure’ with CAR T cells,” Dr. June said.

Although most patients will not do as well, the results hold out hope that, for some, their cancer will be vanquished.

For the full story, see:

Gina Kolata. “Potential Leukemia Cure Leads to New Mysteries.” The New York Times (Thursday, February 3, 2022): A17.

(Note: the online version of the story has the date Feb. 2, 2022, and has the title “A Cancer Treatment Makes Leukemia Vanish, but Creates More Mysteries.”)

Stereotyping Older Adults May Shorten Their Lives

(p. D3) Dr. Robert N. Butler, a psychiatrist, gerontologist and founding director of the National Institute on Aging, coined the term “ageism” a half-century ago. It echoes “sexism” and “racism,” describing the stereotyping of and discrimination against older adults.

Among the mementos in Dr. Levy’s small office at Yale is a treasured photo of her and Dr. Butler, who died in 2010. One could argue that she is his heir.

A psychologist and epidemiologist, Dr. Levy has demonstrated — in more than 140 published articles over 30 years and in a new book, “Breaking the Age Code” — that ageism results in more than hurt feelings or even discriminatory behavior. It affects physical and cognitive health and well-being in measurable ways and can take years off one’s life.

. . .

Another memento in Dr. Levy’s office is a card on her bulletin board that reads, “Ask Me About 7.5.” The souvenir came from a Wisconsin anti-ageism campaign and refers to her 2002 longevity study, which for two decades followed hundreds of residents older than 50 in a small Ohio town. The study found that median survival was seven and a half years longer for those with the most positive beliefs about aging, compared with those having the most negative attitudes.

. . .

We absorb these stereotypes from an early age, through disparaging media portrayals and fairy tales about wicked old witches. But institutions — employers, health care organizations, housing policies — express a similar prejudice, enforcing what is called “structural ageism,” Dr. Levy said. Reversing that will require sweeping changes — an “age liberation movement,” she added.

But she has found reason for optimism: Damaging ideas about age can change. Using the same subliminal techniques that measure stereotypical attitudes, her team has been able to enhance a sense of competence and value among older people. Researchers in many other countries have replicated their results.

For the full commentary, see:

Paula Span. “How Ageism Can Take Years Off Seniors’ Lives.” The New York Times (Tuesday, April 26, 2022): D3.

(Note: ellipses added.)

(Note: the online version of the commentary was updated April 28, 2022, and has the title “Exploring the Health Effects of Ageism.” Where there is a slight difference in wording between versions, the passages quoted above are from the online version.)

Levy’s book mentioned in the commentary above is:

Levy, Becca. Breaking the Age Code: How Your Beliefs About Aging Determine How Long and Well You Live. New York: William Morrow, 2022.

BioNTech Is Running Clinical Trials for mRNA Cancer Vaccines

(p. C2) Scientists are . . . advancing mRNA vaccines and therapies to treat cancer, which poses a particular challenge because tumor cells arise from the body’s own cells and can easily deceive the immune system into thinking they are normal. Cancer patients today receive varying types of treatments, but they involve therapies manufactured outside the body. The mRNA researchers believe that the body’s own immune system can be used against cancer if it’s given the right tools.

BioNTech, now a household name for its Covid-19 vaccine with Pfizer, was founded in 2008 to pursue mRNA cancer treatments. The German company says that even at a low dose, a strong enough mRNA treatment can be developed to prompt immune cells to make certain proteins and to train the rest of the immune system to recognize and target tumor cells that express these same proteins. “It needs to be louder and more aggressive for cancer because the immune system needs stronger persuasion to attack something that appears to resemble a normal cell which it should respect and not attack,” said Özlem Türeci, BioNTech’s chief medical officer.

The company’s pipeline includes at least 10 cancer vaccines in human clinical trials using mRNA for skin, pancreatic, ovarian and other tumors. Two of its most advanced programs in mid-stage clinical studies, one for melanoma and the other for head and neck cancer, harness mRNA to make specific proteins seen with these cancers that will prompt a vigorous response from the patient’s immune system. Research from BioNTech published in 2020 in the journal Nature showed that the treatment caused the lesions of melanoma patients to shrink.

Some of BioNTech’s other cancer treatments are tailored to individual patients. A tumor is removed surgically and then shipped to the company’s laboratories, where researchers sequence the DNA and search for proteins, using machine learning to decide which ones are needed for that individual’s therapy. To address how quickly cancer can spread in the body, BioNTech designs and develops these clinical-trial treatments in just four to six weeks—a potentially lifesaving turnaround time for more pressing cases.

For the full essay, see:

Jared S. Hopkins and Felicia Schwartz. “Can the Technology Behind Covid Vaccines Cure Other Diseases?” The Wall Street Journal (Saturday, February 5, 2022): C1-C2.

(Note: ellipsis added.)

(Note: the online version of the essay has the date February 4, 2022, and has the same title as the print version.)

Modern Medical Consensus Supports Thousands of Years of Indian Ayurvedic Tradition of Nasal Rinsing

(p. D6) To the uninitiated, the neti pot may seem like yet another wellness trend. After all, the teapot-like vessel was popularized in the United States by the celebrity surgeon Dr. Mehmet Oz, who called it a “nose bidet” on “The Oprah Winfrey Show” and has been criticized for promoting unproven supplements and health products.

Rinsing warm saltwater through your nose — in one nostril and out the other — as an antidote for a variety of woes like sinus inflammation, congestion and allergies may seem strange and possibly scary;  . . .

But according to ear, nose and throat doctors, nasal rinsing, which traces back thousands of years to the Ayurvedic medical traditions of India, is an unusual example of a practice that is at once ancient, trendy and evidence-based. And, it’s safe and inexpensive to boot.

It has a “very, very high level of evidence, randomized controlled trial evidence, that shows that it does work and it does help,” said Dr. Zara Patel, an associate professor of otolaryngology at the Stanford University School of Medicine. Here’s what we know.

. . .

In 2021, an international team of experts published a consensus on how best to manage common sinus issues, like chronic inflammation of the nasal and sinus passages that can cause runny nose, congestion, impaired sense of smell and facial pressure or pain. They concluded, based on the best yet limited evidence, that regular rinsing with saltwater was one of the treatments most proven to be effective.

Other small studies have suggested that saltwater rinses can help with seasonal or environmental allergy symptoms like congestion, runny nose, itching and sneezing.

And there is some evidence that rinsing can help soothe symptoms of acute upper respiratory infections, like those caused by common cold or flu viruses, though there is less research on this use. One of the largest studies to date, published in 2008, was conducted on about 400 children aged 6 to 10 with colds or flus in the Czech Republic. Among the children who used saltwater rinses several times per day, their symptoms resolved more quickly and they were less likely to use fever medications, decongestants or antibiotics, or to have to miss school, than the children who didn’t rinse.

Dr. Patel, who practices in California, said that rinsing can also help clear fine particles from wildfire smoke, which can be irritating.

Though the evidence that rinsing helps with these various nasal issues is of mixed quality, experts say there are few downsides to trying it. “The risk is so low and the potential benefit so high for rinsers” that it’s worth giving it a go, said Dr. Nyssa Farrell, an assistant professor of otolaryngology at Washington University School of Medicine in St. Louis.

For the full story, see:

Alice Callahan. “What to Know About Nasal Irrigation.” The New York Times (Tuesday, February 1, 2022): D6.

(Note: ellipses added.)

(Note: the online version of the story was updated January 31, 2022, and has the title “Do Neti Pots Really Work?”)

The international consensus mentioned above was published as:

Orlandi RR, Kingdom TT, Smith TL, Bleier B, DeConde A, Luong AU, Poetker DM, Soler Z, Welch KC, Wise SK, Adappa N, Alt JA, Anselmo-Lima WT, Bachert C, Baroody FM, Batra PS, Bernal-Sprekelsen M, Beswick D, Bhattacharyya N, Chandra RK, Chang EH, Chiu A, Chowdhury N, Citardi MJ, Cohen NA, Conley DB, DelGaudio J, Desrosiers M, Douglas R, Eloy JA, Fokkens WJ, Gray ST, Gudis DA, Hamilos DL, Han JK, Harvey R, Hellings P, Holbrook EH, Hopkins C, Hwang P, Javer AR, Jiang RS, Kennedy D, Kern R, Laidlaw T, Lal D, Lane A, Lee HM, Lee JT, Levy JM, Lin SY, Lund V, McMains KC, Metson R, Mullol J, Naclerio R, Oakley G, Otori N, Palmer JN, Parikh SR, Passali D, Patel Z, Peters A, Philpott C, Psaltis AJ, Ramakrishnan VR, Ramanathan M Jr, Roh HJ, Rudmik L, Sacks R, Schlosser RJ, Sedaghat AR, Senior BA, Sindwani R, Smith K, Snidvongs K, Stewart M, Suh JD, Tan BK, Turner JH, van Drunen CM, Voegels R, Wang Y, Woodworth BA, Wormald PJ, Wright ED, Yan C, Zhang L, Zhou B. “International Consensus Statement on Allergy and Rhinology: Rhinosinusitis 2021.” International Forum of Allergy & Rhinology. 11, no. 3 (March 2021): 213-739. doi: 10.1002/alr.22741. PMID: 33236525.

During Pandemic, Delayed Medical Procedures Rose from 4.6 to 6 Million in England’s Socialized Healthcare System

(p. A8) LONDON — Lara Wahab had been waiting for more than two years for a kidney and pancreas transplant, but months had passed without any word. So last month she called the hospital, and got crushing news.

There had been a good match for her in October [2021], the transplant coordinator told her, which the hospital normally would have accepted. But with Covid-19 patients filling beds, the transplant team could not find her a place in the intensive care unit for postoperative care. They had to decline the organs.

“I was just in shock. I knew that the N.H.S. was under a lot of strain, but you don’t really know until you’re waiting for something like that,” she said, referring to the National Health Service. “It was there, but it sort of slipped through my fingers,” she added of the transplant opportunity.

Ms. Wahab, 34, from North London, is part of an enormous and growing backlog of patients in Britain’s free health service who have seen planned care delayed or diverted, in part because of the pandemic — a largely unseen crisis within a crisis. The problems are likely to have profound consequences that will be felt for years.

The numbers are stark: In England, nearly 6 million procedures are currently delayed, a rise from the backlog of 4.6 million before the pandemic, according to the N.H.S. The current delays most likely impact more than five million people — a single patient can have multiple cases pending for different ailments — which represents almost one-tenth of the population. Hundreds of thousands more haven’t been referred yet for treatment, and many ailments have simply gone undiagnosed.

For the full story, see:

Megan Specia. “In Britain, an Ever-Growing Backlog of Non-Covid Care.” The New York Times (Thursday, January 27, 2022): A8.

(Note: bracketed year added.)

(Note: the online version of the story was updated January 27, 2022, and has the title “‘I Feel Really Hopeless’: In U.K., Millions See Non-Covid Health Care Delayed.”)