“Advances in Gene Sequencing” Have Not “Unlocked the Key to Cures for Cancer”

(p. 10) In his new book, “The Song of the Cell,” Siddhartha Mukherjee has taken on a subject that is enormous and minuscule at once. Even though cells are typically so tiny that you need a microscope to see them, they also happen to be implicated in almost anything to do with medicine — and therefore almost anything to do with life.

. . .

If Mukherjee were another kind of storyteller — tidier, if less honest — he could have showcased a more linear narrative, emphasizing how developments in cell research have yielded some truly amazing possibilities. He himself has been collaborating on a project to engineer certain cells in the immune system so that they eat tumors without stirring up an indiscriminate inflammatory response.

But as a practicing physician, he has seen too much suffering and death to succumb to an easy triumphalism. He recalls the “exuberance” of the mid-2000s, when spectacular advances in gene sequencing had made it appear as if “we had unlocked the key to cures for cancer.” Such exuberance turned out to be fleeting; the data from clinical trials were “sobering.”

Many medical mysteries remain unsolved. If the book’s protagonist — our understanding of cell biology — seemed to be riding high again on new advances in immunology, such “self-assuredness” was laid low by the Covid-19 pandemic. Mukherjee presents a string of questions that are still unsettled. “The monotony of answers is humbling, maddening,” he writes. “We don’t know. We don’t know. We don’t know.”

For the full review, see:

Jennifer Szalai. “Building Blocks.” The New York Times Book Review (Sunday, November 13, 2022): 10.

(Note: ellipsis added.)

(Note: the online version of the review was updated Nov. 2, 2022, and has the title “Siddhartha Mukherjee Finds Medical Mystery — and Metaphor — in the Tiny Cell.”)

The book under review is:

Mukherjee, Siddhartha. The Song of the Cell: An Exploration of Medicine and the New Human. New York: Scribner, 2022..

Through Evolution, Body Parts Are Inelegantly Repurposed into Workaround Kluges

If the body itself is an amalgam of workaround kluges, then maybe our regulators should be more tolerant of medical MacGyvers who attempt to keep the body working through medical workaround kluges.

(p. A15) Mr. Pievani is a professor of biology at the University of Padua. His brief and thoughtful book (translated from the Italian by Michael Gerard Kenyon) isn’t just a description of imperfection, but a paean to it. There’s plenty of description and discussion, too, as “Imperfection” takes the reader on a convincing whirlwind tour of the dangers as well as the impossibility of perfection, how imperfection is built into the nature of the universe, and into all living things—including ourselves.

. . .

Readers wanting to get up to speed on imperfection would do well to attend to two little-known words with large consequences. The first is “palimpsest,” which in archaeology refers to any object that has been written upon, then erased, then written over again (sometimes many times), but with traces of the earlier writings still faintly visible. Every living thing is an evolutionary palimpsest, with adaptations necessarily limited because they’re built upon previous structures.

Consider, for example, childbirth. As smart critters, we’ve been selected (naturally) to have big heads. But in becoming bipedal, we had to rotate our pelvises, which set limits on the size of the birth canal. As a result, an unborn baby’s head is perilously close to being too big to get out. Usually, they manage it, but not without much painful laboring and sometimes, if this cephalopelvic disproportion is too great, or if the baby is malpositioned, by means of a cesarean delivery. In such cases, obstetricians take the newborn out the obvious way: through that large, unobstructed abdominal space between pelvis and lower ribs. Things would have been much easier and safer for mother and baby if the birth canal were positioned there, too, but our palimpsest nature precludes such a straightforward arrangement.

Which brings us to our second unusual word: “kluge,” something—assembled from diverse components—that shouldn’t work, but does. A kluge is a workaround: often clumsy, inelegant, inefficient, but that does its job nonetheless. Because we and all other living things are living palimpsests, we are kluges as well.

For the full review, see:

David P. Barash. “BOOKSHELF; Unintelligent Design.” The Wall Street Journal (Wednesday, October 26, 2022): A15.

(Note: ellipsis added.)

(Note: the online version of the review has the date October 25, 2022, and has the title “BOOKSHELF; ‘Imperfection’ Review: Unintelligent Design.”)

The book under review is:

Pievani, Telmo. Imperfection: A Natural History. Translated by Michael Gerard Kenyon. Cambridge, MA: The MIT Press, 2022.

Medical Entrepreneurs “Muster the Courage and Determination to Forge Brazenly Ahead”

(p. C7) The accidental birth and stuttering development of cell biology is the focus of Siddhartha Mukherjee’s “The Song of the Cell.” It is an audacious, often mesmerizing, frequently dizzying, occasionally exhausting and reliably engaging tour of cell biology and scientific inquiry. Dr. Mukherjee, an oncologist at Columbia University and the author of “Emperor of All Maladies: A Biography of Cancer” (2010), enthusiastically instructs and, much of the time, delights—all the while hustling us across a preposterously vast and intricate landscape.

. . .

In the course of describing the evolution of cell biology, Dr. Mukherjee reminds us of the critical role of technological innovation, like the microscopes used by Leeuwenhoek and Hooke, which first revealed the existence of the cellular world. Similarly, it was the invention of the electron microscope, and its deliberate application to biology by pioneering Rockefeller University scientist George Palade, that afforded researchers the resolution needed to examine the components of an individual cell.

. . .

Dr. Mukherjee’s dual roles as clinical oncologist and cell biologist find a common voice as he grapples with the complexity of cancer, “cell biology visualized in a pathological mirror.” He notes the heterogeneity of tumors, observing that while “two ‘breast cancers’ may look identical under the pathologist’s microscope,” the cancers may differ genetically and require different treatments. Even a single breast tumor, he writes, “is actually a collage of mutant cells—an assembly of non-identical diseases.” Because of the maddening similarity between cancer cells and normal cells, targeting cancer can be challenging: A promising therapy may fail, as it did for one of his friends, because it also attacks healthy cells.

Ultimately, Dr. Mukherjee seems to decide, we must accept, rather than rationalize away, the baffling idiosyncrasies that we observe in cell biology and see reflected in the behavior of cancers. Why did his friend’s cancer spread to some organs but spare others? Why did the treatment his friend received eliminate tumors in the skin but not the lungs? “There are mysteries beyond mysteries,” he writes, and he cautions us against succumbing to reductionist explanations. Cells, by themselves, are “incomplete explanations for organismal complexities.” We must understand the context in which a cell exists, he emphasizes, its local environment. Even then, he admits, we often “don’t even know what we don’t know.”

Dr. Mukherjee’s hard-won lessons contain a message for us all: We should resist simple, universal explanations in life science—cell biology, in particular, is rarely that cooperative. The journey he relates also reminds us to appreciate the researchers who, despite the unforgiving and rarely predictable terrain before them, muster the courage and determination to forge brazenly ahead.

For the full review, see:

David A. Shaywitz. “Fantastic Voyage Within.” The Wall Street Journal (Saturday, October 29, 2022): C7.

(Note: ellipses added.)

(Note: the online version of the review has the date October 28, 2022, and has the title “‘The Song of the Cell’ Review: Fantastic Voyage Within.”)

The book under review is:

Mukherjee, Siddhartha. The Song of the Cell: An Exploration of Medicine and the New Human. New York: Scribner, 2022.

With Both Covid and Monkeypox, C.D.C. Wrongly “Tried to Maintain Control Over Testing”

(p. A14) Too often in a crisis, government officials look for easy solutions, with dramatic and immediate impact. But there are none for managing pandemics.

“A pandemic is by definition a problem from hell. You’re vanishingly unlikely to be able to remove all of its negative consequences,” said Bill Hanage, an epidemiologist at the Harvard T.H. Chan School of Public Health.

Instead, he added, officials should bet on combinations of imperfect strategies, with an emphasis on speed over accuracy.

In both the coronavirus pandemic and the monkeypox outbreak, for example, the C.D.C. at first tried to maintain control over testing, instead of disseminating the responsibility as widely as possible. The move led to limited testing, and left health officials blind to the spread of the viruses.

The Food and Drug Administration was slow to help academic labs develop alternatives for testing, and encouraged the highest quality of diagnosis. It may be reasonable for officials to ask which test is faster or which one produces the least errors, Dr. Hanage said, but “all of them are better than not doing anything.”

For the full commentary, see:

Apoorva Mandavilli. “Unprepared for Covid and Monkeypox. And the Next Outbreak, Too.” The New York Times (Saturday, October 1, 2022): A14.

(Note: the online version of the commentary was updated Sept. 30, 2022, and has the title “New Infectious Threats Are Coming. The U.S. Probably Won’t Contain Them.”)

M.R.I. Inventor and Entrepreneur Earned Patent, But Was Denied Nobel Prize

(p. B10) Dr. Raymond Damadian, who built the first magnetic resonance imaging scanner, which revolutionized doctors’ ability to diagnose cancer and other illnesses — but who, to his dismay, saw the Nobel Prize for the science behind it go to two others — died on Aug. 3 [2022] at his home in Woodbury, N.Y.

. . .

The vision of scanning the human body without radiation came to Dr. Damadian in the late 1960s, he said, when he was working on nuclear magnetic resonance spectroscopy — which, until then, had been used to identify the chemical makeup of the contents of a test tube — at Downstate Medical Center (now SUNY Downstate Health Sciences University) in Brooklyn.

Working with rats, he discovered that when tissues were placed in a magnetic field and hit with a pulse of radio waves, cancerous ones emitted distinctly different radio signals than healthy ones.

He published his findings in 1971 in the journal Science and was granted a patent three years later for an “apparatus and method for detecting cancer in tissue.” It took 18 months to build the first M.R.I., originally known as a nuclear magnetic resonance scanner, or N.M.R. Its first scan, on July 3, 1977, was of Lawrence Minkoff, one of Dr. Damadian’s assistants — a vivid and colorful image of his heart, lungs, aorta, cardiac chamber and chest wall.

“Having birthed the original idea of the N.M.R. body scanner, we were intent on being the first to accomplish it,” Dr. Damadian said in the book “Gifted Mind: The Dr. Raymond Damadian Story, Inventor of the M.R.I.,” published in 2015, which he wrote with Jeff Kinley. “Failing to do so meant we might be denied the recognition for the original idea.”

But the technology behind the M.R.I. had several fathers.

Acknowledging that he was inspired by Dr. Damadian’s work, Paul C. Lauterbur of the State University of New York at Stony Brook had figured out how to translate the radio signals bounced off tissue into images. And Peter Mansfield of the University of Nottingham in England had developed mathematical techniques for analyzing the data, making the process more practical.

Employing the techniques he pioneered, Dr. Damadian’s company, Fonar, based in Melville, N.Y., produced the first commercial scanner in 1980.

. . .

While working at Downstate and later at Fonar, Dr. Damadian was aware of Dr. Lauterbur, a chemist who was also working on M.R.I. imaging and with whom he shared the National Medal of Technology.

In “Gifted Mind,” Dr. Damadian acknowledged that Dr. Lauterbur “realized that the N.M.R. signal differences in diseased and normal tissues I discovered could be used to construct a picture (image).”

But in 2003, when Dr. Lauterbur and Dr. Mansfield won the Nobel Prize in Medicine for their contributions to the science of magnetic resonance imaging, Dr. Damadian was enraged.

. . .

A year later, Dr. Damadian received one of the two annual Bower Awards given by the Franklin Institute, a science museum in Philadelphia. He was cited for his business leadership.

“There is no controversy in this,” said Dr. Bradford A. Jameson, a professor of biochemistry at Drexel University who was the chairman of the committee that chose the winners. “If you look at the patents in this field, they’re his.”

. . .

Dr. Damadian continued to innovate. He created open M.R.I. machines, which alleviate the claustrophobia patients can experience during scans when they are moved slowly through a tight tunnel, as well as mobile and stand-up scanners.

In recent years, he was focused on research that included imaging cerebral spinal fluid as it flowed to the brain.

For the full obituary, see:

Richard Sandomir. “Raymond Damadian, 86, Is Dead; Creator of the First M.R.I. Scanner.” The New York Times (Thursday, August 18, 2022): B10.

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

(Note: the online version of the obituary was updated Aug. 19, 2022, and has the title “Raymond Damadian, Creator of the First M.R.I. Scanner, Dies at 86.” Where there is a minor difference between the online and print versions, the passages quoted above follow the online version.)

Damadian’s biography mentioned above is:

Kinley, Jeff, and Raymond Damadian. Gifted Mind: The Dr. Raymond Damadian Story, Inventor of the MRI. Green Forest, AZ: Master Books, 2015.

Deregulation of Hearing Aids Will Lower Costs and Increase Innovation

(p. A1) The Food and Drug Administration decided on Tuesday to allow hearing aids to be sold over the counter without a prescription to adults, a long-sought wish of consumers frustrated by expensive exams and devices.

The high cost of hearing aids, which are not covered by basic Medicare, has discouraged millions of Americans from buying the devices. Health experts say that untreated hearing loss can contribute to cognitive decline and depression in older people.

Under the F.D.A.’s new rule, people with mild to moderate hearing loss should be able to buy hearing aids online and in retail stores as soon as October, without being required to see a doctor for an exam to get a prescription.

. . .

“This could fundamentally change technology,” said Nicholas Reed, an audiologist at the Department of Epidemiology at Johns Hopkins Bloomberg School of Public Health. “We don’t know what these companies might come up with. We may literally see new ways hearing aids work, how they look.”

. . .

The change has been percolating for years. In 2016, a proposal for the F.D.A. to approve over-the-counter hearing aids for adults with mild to moderate hearing was released in a report by the National Academies of Science, Engineering and Medicine. The following year, Senators Chuck Grassley, a Republican of Iowa, and Elizabeth Warren, a Democrat of Massachusetts, introduced a bill enabling the agency to make the change. Congress approved the legislation and President Trump signed it into law.

Finalizing regulations has moved slowly since then, with some conflict over details, like how the federal rule would interact with state laws on hearing aid returns or warranty policies and how much the devices should amplify sound.

Mr. Biden issued an executive order last July calling for greater competition in the economy, which urged the F.D.A. to take action “to promote the wide availability of low-cost hearing aids.”

For the full story, see:

Christina Jewett. “F.D.A. Decides to Allow Over-the-Counter Sales of Hearing Aids.” The New York Times (Wednesday, August 17, 2022): A1 & A23.

(Note: ellipses added.)

(Note: the online version of the story was updated Aug. 23, 2022, and has the title “F.D.A. Clears Path for Hearing Aids to Be Sold Over the Counter.”)

Since Adderall Is “Highly Regulated” Pharmacies and Patients Can’t “Quickly Pivot” in Response to Scarcity

(p. A13) The Food and Drug Administration has declared a nationwide shortage of Adderall, a medication used to treat A.D.H.D. that has had surging demand in recent years.

. . .

Adderall, which contains the stimulant amphetamine, is a controlled substance and highly regulated, so it is difficult for pharmacies to quickly pivot and carry new brands, analysts said.

. . .

While a number of companies make Adderall and generic versions, pharmacies may find it difficult to pivot to other suppliers because of amphetamine’s status as a controlled substance that typically includes restrictions on its use and monitoring of prescription orders. Any given pharmacy might risk raising red flags with the Drug Enforcement Administration by doubling its supply, said Erin Fox, an expert on drug shortages at the University of Utah.

“With a controlled substance, it’s harder for patients to call around and find a pharmacy that has product for them,” Ms. Fox said.

For the full story, see:

Christina Jewett. “F.D.A. Confirms Widespread Shortages of Adderall.” The New York Times (Friday, October 14, 2022): A13.

(Note: ellipses added.)

(Note: the online version of the story has the date Oct. 13, 2022, and has the title “F.D.A. Confirms Wide Shortage of Adderall.”)

Periodic Fasting May Reduce Inflammation That Causes Multiple Maladies

(p. A15) Mr. Hendricks sees fasting as a way of combating a range of ailments. (“Surgery without a scalpel” was how some doctors once described the practice.) He cites studies showing fasting to be effective against arthritis, hypertension and fibromyalgia, among other afflictions. The medical logic in these cases is that fasting reduces inflammation—the source of multiple maladies—while promoting insulin sensitivity, stimulating DNA repair and generating antioxidants that neutralize a harmful molecule known as reactive oxygen species. Mr. Hendricks argues that fasting leads to better outcomes from chemotherapy, too—by causing healthy cells to go dormant and avoid the treatment’s toxic chemicals.

And, yes, fasting triggers weight loss. The fasting Mr. Hendricks has in mind is periodic, its frequency and duration varying from person to person.

. . .

A theme running through “The Oldest Cure in the World” is the author’s exasperation with the American approach to practicing medicine. Few physicians, he notes, are knowledgeable about fasting, despite the benefits it provides. He favorably profiles two researchers—Valter Longo and Satchin Panda, at the University of Southern California and the Salk Institute, respectively—who have conducted ground-breaking studies on the value of restrictive food consumption.

The book’s most compelling story features an infant who in 1993 started having daily seizures after his first birthday. Neither medications nor brain surgery provided significant relief. Pediatric neurologists told the parents that their son, Charlie, faced a life of mental and physical retardation.

Charlie’s father discovered an obscure clinic at Johns Hopkins University that offered a treatment that involved brief fasting followed by a high-fat, ketogenic diet. The family’s neurologist dismissed the treatment as unworkable, but the family tried it anyway. On the second day of Charlie’s fast, the seizures stopped. Over time, his physical and mental development returned to normal, and he has grown up to be as healthy as his siblings. Later research has shown that fasting and a high-fat diet is a potent method for reducing seizures in epileptic children.

For the full review, see:

Matthew Rees. “BOOKSHELF; No First Helpings.” The Wall Street Journal (Friday, October 7, 2022): A15.

(Note: ellipsis added.)

(Note: the online version of the review has the date October 6, 2022, and has the title “BOOKSHELF; ‘The Oldest Cure in the World’ Review: No First Helpings.”)

The book under review is:

Hendricks, Steve. The Oldest Cure in the World: Adventures in the Art and Science of Fasting. New York: Harry N. Abrams, 2022.

Covid-19 Health Effects Will Keep Reducing Labor Force

(p. A1) As the United States emerges from the pandemic, employers have been desperate to hire. But while demand for goods and services has rebounded, the supply of labor has fallen short, holding back the economy.

. . .

(p. A20) Morning Consult found in August [2022] that prime-age adults who aren’t working cited a variety of often overlapping reasons for not wanting jobs. In a monthly poll of 2,200 people, 40 percent said they believed that they wouldn’t be able to find a job with enough flexibility, while 38 percent were limited by family situations and personal obligations. But the biggest category, at 43 percent, was medical conditions.

Other data suggest some of that is due to long-term complications from Covid-19, although estimates of how many people have been knocked out of the work force by Covid range tremendously.

Katie Bach, a Brookings Institution fellow, put the impact at two million to four million full-time workers, based on her interpretation of the Census Bureau’s Household Pulse Survey and other research. (The total affected may be larger, with many who suffer from long Covid reducing their hours rather than stopping work.) A Federal Reserve economist didn’t specify a number, but observed that even as Covid-related hospitalizations and deaths receded, the share of people saying they were not able to work because of illness or disability had remained elevated in Labor Department data after spiking in early 2021.

Another analysis, in a paper published by the National Bureau of Economic Research, found that people who’d taken a week off for health-related reasons in 2020 and 2021 were 7 percent less likely to be in the labor force a year later — which equates to about 500,000 workers.

Whatever the magnitude, the effects are likely to be significant and long-lasting. Vaccines provide imperfect protection against getting long Covid, studies suggest, and other post-viral diseases have proven difficult to recover from. “I certainly don’t think the worst is behind us,” Ms. Bach said.

For the full story, see:

Lydia DePillis. “Pool of Labor In U.S. Stays Bafflingly Low.” The New York Times (Saturday, September 13, 2022): A1 & A20.

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

(Note: the online version has the date Sept. 12, 2022, and has the title “Who Are America’s Missing Workers?”)

The NBER paper mentioned above is:

Goda, Gopi Shah, and Evan J. Soltas. “The Impacts of Covid-19 Illnesses on Workers.” National Bureau of Economic Research Working Paper No. 30435, Sept. 2022.

Proposed 20 Years Ago, Heart Polypill Is Safe, Effective, and Easier to Take, but Is Not Allowed by FDA

(p. A7) Heart disease kills more people than any other condition, but despite advances in treatment and prevention, patients often do not stick to their medication regimens. Now researchers may have found a solution: a so-called polypill that combines three drugs needed to prevent cardiovascular trouble.

In what is apparently the largest and longest randomized controlled trial of this approach, patients who were prescribed a polypill within six months of a heart attack were more likely to keep taking their drugs and had significantly fewer cardiovascular events, compared with those receiving the usual assortment of pills.

The participants also experienced one-third fewer cardiovascular deaths, although their overall risk of death from all causes was not significantly changed.

The study of more than two thousand heart patients, who were followed for three years, was published Friday morning in The New England Journal of Medicine, as the findings were presented at the European Society of Cardiology Congress in Barcelona.

. . .

The polypill combines a blood-pressure medication, a cholesterol-lowering drug and aspirin, which helps prevent blood clots. The idea was first floated two decades ago in a more radical form: Advocates proposed giving a daily polypill to everyone once they turned 55, saying it would slash cardiovascular events globally by 80 percent.

. . .

The polypill used in the study has not been approved by the Food and Drug Administration and is not available to patients in the United States right now. Dr. Fuster said the results of the new trial would be submitted to the agency shortly in an effort to obtain approval.

He called the results of the new study “striking,” and said the benefit of the polypill for prevention rivaled that of low-dose aspirin, which is now routinely prescribed to people who have already had a heart attack or other cardiovascular event.

And since participants became even more likely to keep taking the polypill over time, he said, “The potential results could be even better with more follow-up.” Several studies have shown that only about half of patients, or even less, take all their medications as instructed.

The new study, a randomized controlled clinical trial, enrolled just under 2,500 patients at 113 sites in Spain, Italy, France, Germany, Poland, the Czech Republic and Hungary.

. . .

Over three years, 12.7 percent of the patients taking an assortment of pills experienced another heart attack or stroke, or died of a cardiac event or needed urgent treatment to open a blocked artery, compared with 9.5 percent of patients taking a polypill, for a relative reduction in risk of 24 percent.

There was no difference between the two groups in overall mortality, however, as the reduction in cardiovascular deaths in the polypill group was offset by deaths from other causes.

For the full story, see:

Roni Caryn Rabin. “Heart Disease Patients Are More Likely to Stick to a One-Pill Daily Regimen, Researchers Say.” The New York Times (Saturday, August 27, 2022): A7.

(Note: ellipses added.)

(Note: the online version of the story has the date Aug. 26, 2022, and has the title “How to Get Heart Patients to Take Their Pills? Give Them Just One”)

Stimulating Brain with Electrical Currents Can Improve Long-Term Memory for Older Adults

(p. A5) Zapping the brain with weak electrical currents that mimic normal neural activity can boost memory in healthy older adults, at least over the short term, researchers said in a study published Monday [Aug. 22, 2022] in the journal Nature Neuroscience.

. . .

The researchers found that repeated delivery of low-frequency currents to a brain region known as the parietal cortex—located in the upper back portion of the organ—improved recall of words toward the end of the 20-word lists. When the researchers targeted the prefrontal cortex at the front of the brain with high-frequency currents, the study participants saw improvements in their ability to remember words from the beginning of the lists.

. . .

The electrical stimulation improved both short- and longer-term memory lasting minutes by about 50 to 65 percent over four days of treatment, Dr. Reinhart said. The improvements persisted one month after the treatment sessions. Short-term, or working, memory involves storing information over a period of seconds like remembering a phone number someone just gave you. Long-term memory involves storing and then retrieving information over minutes, days, months or years.

. . .

Though the apparatus used in the experiments is lightweight and easy to use, Dr. Reinhart said, it hasn’t been cleared for clinical use by the U.S. Food and Drug Administration and for now is available only in research settings.

For the full story see:

Aylin Woodward and Daniela Hernandez. “Electrical Brain Stimulation Is Shown to Boost Memory.” The Wall Street Journal (Tuesday, Aug. 23, 2022): A5.

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

(Note: the online version of the story has the date August 22, 2022, and has the title “Improve Memory by Zapping Your Brain? Study Says It’s Possible.”)

The academic article summarized in the passages quoted above is:

Grover, Shrey, Wen Wen, Vighnesh Viswanathan, Christopher T. Gill, and Robert M. G. Reinhart. “Long-Lasting, Dissociable Improvements in Working Memory and Long-Term Memory in Older Adults with Repetitive Neuromodulation.” Nature Neuroscience 25, no. 9 (Sept. 2022): 1237-46.