Socialist Mayor’s Environmental Bicycles Turn Paris Streets into Risky Chaos

(p. 4) PARIS — On a recent afternoon, the Rue de Rivoli looked like this: Cyclists blowing through red lights in two directions. Delivery bike riders fixating on their cellphones. Electric scooters careening across lanes. Jaywalkers and nervous pedestrians scrambling as if in a video game.

Sarah Famery, a 20-year resident of the Marais neighborhood, braced for the tumult. She looked left, then right, then left and right again before venturing into a crosswalk, only to break into a rant-laden sprint as two cyclists came within inches of grazing her.

“It’s chaos!” exclaimed Ms. Famery, shaking a fist at the swarm of bikes that have displaced cars on the Rue de Rivoli ever since it was remade into a multilane highway for cyclists last year. “Politicians want to make Paris a cycling city, but no one is following any rules,” she said. “It’s becoming risky just to cross the street!”

The mayhem on Rue de Rivoli — a major traffic artery stretching from the Bastille past the Louvre to the Place de la Concorde — is playing out on streets across Paris as the authorities pursue an ambitious goal of making the city a European cycling capital by 2024.

Mayor Anne Hidalgo, who is campaigning for the French presidency, has been burnishing her credentials as an ecologically minded Socialist candidate. She has earned admirers and enemies alike with a bold program to transform greater Paris into the world’s leading environmentally sustainable metropolis, reclaiming vast swaths of the city from cars for parks, pedestrians and a Copenhagen-style cycling revolution.

For the full story, see:

Liz Alderman. “PARIS DISPATCH; Europe’s New Cycling Capital, or a Pedestrian’s Nightmare?” The New York Times, First Section (Sunday, Oct. 3, 2021): 4.

(Note: the online version of the story was updated Oct. 4, 2021, and has the title “PARIS DISPATCH; As Bikers Throng the Streets, ‘It’s Like Paris Is in Anarchy’.”)

COVID-19 Vaccines Were Built on “Decades-Long Efforts to Create Other Vaccines”

Gregory Zuckerman’s The Frackers was a great deep dive into the lives of important non-Silicon Valley entrepreneurs. So far I am also enjoying Zuckerman’s new book, reviewed in the brief passages quoted below.

(p. 26) Zuckerman answers a question still circulating among both vaccine fans and skeptics: How could scientists develop the Covid-19 vaccines so quickly?

The answer is that they didn’t. The Covid-19 vaccines were built on the backs of decades-long efforts to create other vaccines, like one for the Zika virus and, in particular, several failures to develop a useful H.I.V. vaccine.

For the full, but short, review, see:

Eve Fairbanks. “THE SHORTLIST; Covid.” The New York Times Book Review (Sunday, January 9, 2022): 26.

(Note: the online version of the review has the date Dec. 29, 2021, and has the title “THE SHORTLIST; New Books Explore the Many Ways Covid Has Altered Our Lives.”)

The book under review is:

Zuckerman, Gregory. A Shot to Save the World: The inside Story of the Life-or-Death Race for a Covid-19. New York: Portfolio/Penguin, 2021.

Testing for Rare DNA Microdeletion Birth Defects Can Result in More False Positives Than True Positives

(p. 12) Between 2011 and 2013, a small California-based biotech company, Sequenom, tripled in size. The key to its success: MaterniT21, a new prenatal screening test that did remarkably well at detecting Down syndrome.

Older screening tests took months and required multiple blood tests. This new one generated fewer false positives with a single blood draw.

The test could also determine the sex of a fetus. It quickly became a hit. “You had people walking in saying, ‘I want this sex test,’” recalled Dr. Anjali Kaimal, a maternal-fetal medicine specialist at Massachusetts General Hospital.

Competitors began launching their own tests. Today, analyst estimates of the market’s size range from $600 million into the billions, and the number of women taking these tests is expected to double by 2025.

As companies began looking for ways to differentiate their products, many decided to start screening for more and rarer disorders. All the screenings could run on the same blood draw, and doctors already order many tests during short prenatal care visits, meaning some probably thought little of tacking on a few more.

For the testing company, however, adding microdeletions can double what an insurer pays — from an average of $695 for the basic tests to $1,349 for the expanded panel, according to the health data company Concert Genetics. (Patients whose insurance didn’t fully cover the tests describe being billed wildly different figures, ranging from a few hundred to thousands of dollars.)

But these conditions were so rare that there were few instances for the tests to find.

Take Natera, which ran 400,000 tests in 2020 for DiGeorge syndrome, a disorder associated with heart defects and intellectual disability.

That number of tests would be expected to identify about 200 cases of the disorder according to a Times analysis of the company’s studies. It would also generate at least an equal number of false positive results.

That is a best-case scenario based on Natera’s recent claim to have improved its algorithm. In clinical trials, its test (p. 13) generated three times as many false positives as true ones. The company’s four other microdeletion screenings, which it said were run at least 24,000 times in 2020, would be expected to find about eight true postitves and bewen 17 and 134 fase ones, according to the analysis.

For the full story, see:

Sarah Kliff and Aatish Bhatia. “Prenatal Tests for Rare Defects Often Produce False Positives.” The New York Times, First Section (Sunday, January 2, 2022): 1 & 12-13.

(Note: the online version of the story has the date Jan. 1, 2022, and has the title “When They Warn of Rare Disorders, These Prenatal Tests Are Usually Wrong.” The last three paragraphs above appear in the online version, but not in this form in the print version. In the print version, the information in the last three paragraphs quoted above, appears mostly as part of an extended graphic.)

After Escaping Communism, Karikó Achieved “Critical Breakthrough” on Covid-19 Vaccine

(p. C8) “Infectious” is a chronicle of the “ongoing arms race between host and infection,” as Mr. Tregoning puts it, as well as the astounding medical progress in the past 100 years that has tipped this struggle in favor of humanity.

. . .

Before the pandemic, many doubted that vaccines based on messenger RNA would work at all, as the technique had a reputation for being finicky and unstable. That these new technologies have thus far outperformed traditional vaccines is an upset akin to Buster Douglas’s 1990 knockout of Mike Tyson. According to Mr. Tregoning, a large share of the credit belongs to the biochemist Katalin Karikó, who had a critical breakthrough that “massively improved the potency of the vaccine.” Ms. Karikó, “who fled Communist Hungary in 1985 with $1,200 hidden in a teddy bear,” was able to stabilize messenger RNA by studding it with methyl groups. This enabled the RNA to survive in the body just long enough to produce viral proteins for the immune system to target.

For the full review, see:

John J. Ross. “The Battle Inside Your Body.” The Wall Street Journal (Saturday, Dec. 11, 2021): C8.

(Note: ellipsis added.)

(Note: the online version of the review has the date December 10, 2021, and has the title “The Defenders: Three Books on the Science of Immunity.”)

The book under review in the passages quoted above is:

Tregoning, John S. Infectious. London, UK: Oneworld, 2021.

Passion, Dedication, and Caffeine Led to Muscular Dystrophy Progress, After Mutating Millions of Viruses to Find One That Works

Trial and error still matters in science and medicine.

(p. D1) CAMBRIDGE, Mass. — When Sharif Tabebordbar was born in 1986, his father, Jafar, was 32 and already had symptoms of a muscle wasting disease. The mysterious illness would come to define Sharif’s life.

Jafar Tabebordbar could walk when he was in his 30s but stumbled and often lost his balance. Then he lost his ability to drive. When he was 50, he could use his hands. Now he has to support one hand with another.

No one could answer the question plaguing Sharif and his younger brother, Shayan: What was this disease? And would they develop it the way their father had?

As he grew up and watched his father gradually decline, Sharif vowed to solve the mystery and find a cure. His quest led him to a doctorate in developmental and regenerative biology, the most competitive ranks of academic medical research, and a discovery, published in September in the journal Cell, that could transform gene therapy — medicine that corrects genetic defects — for nearly all muscle wasting diseases. That includes muscular dystrophies that affect about 100,000 people in the United States, according to the Muscular Dystrophy Association.

Scientists often use a disabled virus called an adeno-associated virus, or AAV, to deliver gene therapy to cells. But damaged muscle cells like the ones that afflict Dr. Tabebordbar’s father are difficult to treat. Forty percent of the body is made of muscle. To get the virus to those muscle cells, researchers must deliver enormous doses of medication. Most of the viruses end up in the liver, damaging it and sometimes killing patients. Trials have been halted, researchers stymied.

Dr. Tabebordbar managed to develop viruses that go directly to muscles — very few end up in the liver. His discovery could allow treatment with a fraction of the dosage, and without the disabling side effects.

. . .

(p. D4) There, fueled by caffeine, he works typically 14 hours a day, except on the days when he plays soccer with a group at M.I.T.

“He is incredibly productive and incredibly effective,” said Amy Wagers, who was Dr. Tabebordbar’s Ph.D. adviser and is a professor and co-chair of the department of stem cell and regenerative biology at Harvard. “He works all the time and has this incredible passion and incredible dedication. And it’s infectious. It spreads to everyone around him. That is a real skill — his ability to take a bigger vision and communicate it.”

. . .

He got a position in the lab of Pardis Sabeti at the Broad Institute and set to work. His plan was to mutate millions of viruses and isolate those that went almost exclusively to muscles.

The result was what he’d hoped — viruses that homed in on muscle, in mice and also in monkeys, which makes it much more likely they will work in people.

As scientists know, most experiments fail before anything succeeds and this work has barely begun.

“I will do 100 experiments and 95 will not work,” Dr. Tabebordbar said.

But he said this is the personality that is required of a scientist.

“The mind-set I have is, ‘this is not going to work.’ It makes you very patient.”

. . .

Now Dr. Tabebordbar has moved on to his next step. His life, other than his brief stint in biotech, has been in academia, but he decided that he wants to develop drugs. About a year ago, he co-founded a drug company, called Kate Therapeutics, that will focus on gene therapy for muscle diseases and will move there for the next phase of his career.

For the full story, see:

Gina Kolata. “Determined Yet Patient, He Looks for a Cure.” The New York Times (Tuesday, November 9, 2021): D1 & D4.

(Note: ellipses bracketed date added.)

(Note: the online version of the story has the date Nov. 4, 2021, and has the title “He Can’t Cure His Dad. But a Scientist’s Research May Help Everyone Else.”)

Entrepreneurial Bystander Identifies Stranger’s Cancerous Mole and Saves His Life

(p. B9) Nadia Popovici kept shifting her eyes from the hockey game to the back of Brian Hamilton’s neck.

Mr. Hamilton, an assistant equipment manager for the Vancouver Canucks, had a small mole there. It measured about two centimeters and was irregularly shaped and red-brown in color — possible characteristics of a cancerous mole, signs that Ms. Popovici had learned to spot while volunteering at hospitals as a nursing assistant.

Maybe he already knew? But if so, why was the mole still there? She concluded that Mr. Hamilton did not know.

“I need to tell him,” Ms. Popovici, 22, told her parents at the Oct. 23 [2021] N.H.L. game between the Canucks and the Seattle Kraken at the Climate Pledge Arena in Seattle.

Ms. Popovici typed a message on her phone and waited for the game to end. After waving several times, she finally drew Mr. Hamilton’s attention, and placed her phone against the plexiglass.

“The mole on the back of your neck is possibly cancerous. Please go see a doctor!” the message read, with the words “mole,” “cancer” and “doctor” colored bright red.

Mr. Hamilton said he looked at the message, rubbed the back of his neck and kept walking, thinking, “Well, that’s weird.”

. . .

Indeed, Ms. Popovici was correct, and she had just saved his life.

. . .

Specifically, doctors later told him, it was type-2 malignant melanoma, a type of skin cancer that, because it was detected early, could be easily removed and treated.

For the full story, see:

Eduardo Medina. “Discovering Cancerous Mole From Stands, She Saves a Life.” The New York Times (Tuesday, January 4, 2022): B9.

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

(Note: the online version of the story was updated Jan. 4, 2022, and has the title “Hockey Fan Spots Cancerous Mole at Game and Delivers a Lifesaving Note.”)

Pharmaceutical Entrepreneur Solomon Got Rich by Finding a Drug to Help His Son

(p. A19) Howard Solomon was building the pharmaceutical company Forest Laboratories, not by manufacturing drugs but by licensing them. In his search for deals in the United States and Europe, he learned about citalopram, a Danish antidepressant. He did not license it, though, believing the U.S. market was saturated with drugs to treat depression.

Then, in 1994, a family crisis intervened: His older son, the writer Andrew Solomon, had fallen into a deep depression. Mr. Solomon moved Andrew into his apartment on the Upper East Side of Manhattan and took weeks off from work to take care of him; . . . .

. . .

After two types of antidepressants were unable to help Andrew, a third did. His experience persuaded his father to make the deal a few years later for citalopram, which, under the name Celexa, became a billion-dollar drug for Forest Labs in the class of selective serotonin reuptake inhibitors, along with Prozac, Zoloft and Paxil.

. . .

Forest Labs was transformed by licensing Celexa from H. Lundbeck, the Danish company that developed it. But Lundbeck’s chief executive, Erik Sprunk-Jansen, was initially reluctant to speak to Mr. Solomon because licensing deals with some other U.S. companies had unraveled.

“Howard flew to Denmark to meet with him,” Phil Satow, a former executive vice president of Forest Labs, said in a phone interview. “Both were lovers of ballet, which became the common chord between them, and they developed a strong relationship.”

Celexa’s sales grew quickly, peaking at nearly $1.5 billion in 2003. Forest Labs then licensed Lexapro, an upgraded version of Celexa, which first reached $2 billion in sales in 2007.

. . .

His desire to work into his 80s was, he said, inspired by the example of Giuseppe Verdi.

“Growing up, he’d talk about Verdi writing ‘Falstaff’ in his 80s,” Andrew Solomon said. “‘Imagine that,’ he’d say, ‘in his 80s, he wrote some of the greatest music ever written.’ That was the path he hoped to follow.”

For the full obituary, see:

Richard Sandomir. “Howard Solomon, 94, Whose Business Feats Were Personal, Is Dead.” The New York Times (Wednesday, January 19, 2022): A19.

(Note: ellipses added.)

(Note: the online version of the obituary was updated Jan. 18, 2022, and has the title “Howard Solomon, 94, Dies; His Business Success Had a Personal Connection.”)

Research on Robust Bacteria Immune System, Serendipitously Led to CRSPR Gene-Editing

(p. C8) The author of “The Secret Body,” Daniel M. Davis, is another immunologist by trade.

. . .

Mr. Davis tells us how advances in microscopy have revealed unexpected structures inside human cells, and describes how efforts to map every cell type in the body have turned up a previously unknown tracheal cell that may be pivotal in understanding cystic fibrosis. The daunting structural complexity of the human brain, however, has thus far frustrated attempts to map out even minuscule portions of it.

A recurring theme in “The Secret Body” is “how a discovery of great medical significance [may begin] with relatively obscure research.” Recently, researchers found that bacteria boast a surprisingly robust immune system, which resists viral infection by attacking an intruding virus’s genes. Part of this system, the CRISPR complex, can be used to edit the genomes of human cells, even to tinker with the genetic makeup of embryos.

For the full review, see:

John J. Ross. “The Battle Inside Your Body.” The Wall Street Journal (Saturday, Dec. 11, 2021): C8.

(Note: ellipsis added.)

(Note: the online version of the review has the date December 10, 2021, and has the title “The Defenders: Three Books on the Science of Immunity.”)

The book under review in the passages quoted above is:

Davis, Daniel M. The Secret Body: How the New Science of the Human Body Is Changing the Way We Live. Princeton, NJ: Princeton University Press, 2021.

Larry King “Wanted to Stay Alive Forever”

(p. 23) King spent his life dodging death, resistant but haunted by its specter.

. . .

King took four human growth hormone pills every day, hoping they would buy him more time; . . . .

. . .

He deplored the idea of exiting the party while it was still going on, knowing he could never get back in. “Larry wanted to stay alive forever,” his best friend, Herb Cohen, told me. “He didn’t want to leave. He wouldn’t know who won the World Series.”

For the full obituary, see:

Jazmine Hughes. “Larry King.” The New York Times Magazine (Sunday, December 26, 2021): 22-23.

(Note: ellipses added.)

(Note: the online version of the obituary has the date Dec. 22, 2021, and has the title “Did Larry King’s Obsession With Death Fuel His ‘Indomitable’ Will to Live?”)

Biden’s Science Advisors Do Not Agree on What “Science” Says to Do Against Covid-19

(p. A1) WASHINGTON — On the day President Biden was inaugurated, the advisory board of health experts who counseled him during his transition officially ceased to exist. But its members have quietly continued to meet regularly over Zoom, their conversations often turning to frustration with Mr. Biden’s coronavirus response.

Now, six of these former advisers have gone public with an extraordinary, albeit polite, critique — and a plea to be heard. In three opinion articles published on Thursday [Jan. 6, 2022] in The Journal of the American Medical Association, they called for Mr. Biden to adopt an entirely new domestic pandemic strategy geared to the “new normal” of living with the virus indefinitely, not to wiping it out.

. . .

(p. A11) Like any White House, Mr. Biden’s prizes loyalty and prefers to keep its differences in house; in that regard, the articles are an unusual step. The authors say they wrote them partly because they have not made headway talking directly to White House officials.

. . .

The authors shared the articles with White House officials before they were published, but it was unclear whether the administration would adopt any of their suggestions. Dr. Anthony S. Fauci, Mr. Biden’s top medical adviser for the pandemic, declined to comment on the articles.

The White House press secretary, Jen Psaki, told reporters she had not read the articles, and dismissed a question about whether the president “is coming around to accepting” that Covid-19 is here to stay, even though several recent media accounts suggested that the administration was beginning to operate under that assumption.

. . .

The most surprising thing about the articles is that they were written at all. Several of the authors said in interviews they were dismayed that the administration seemed caught off guard by the Delta and Omicron variants. Dr. Bright, who helped write two of the pieces, recalled the warning he issued when the advisory board had its last meeting on Jan. 20, 2021.

“The last thing I said,” he recalled, “is that our vaccines are going to get weaker and eventually fail. We must now prepare for variants; we have to put a plan in place to continually update our vaccines, our diagnostics and our genomics so we can catch this early. Because the variants will come, and we should never be surprised and we should never underestimate this virus.”

. . .

The president recently released a new winter strategy, just as the Omicron variant began spreading in the United States.

. . .

He has insisted there will be no lockdowns, and has repeatedly pleaded with Americans to get vaccinated.

“I honest to God believe it’s your patriotic duty,” Mr. Biden said recently.

But Dr. Bright said such language was turning off Americans, including many Trump voters, who are resistant to vaccines.

“The message continues to berate unvaccinated people and almost bully unvaccinated people,” said Dr. Bright, who led a federal biomedical agency during the Trump administration but quit the government after being demoted for complaining about political interference in science. “There are so many reasons people are unvaccinated; it’s not just because they follow Trump.”

The authors say the administration needs to look past Omicron and acknowledge that it may not mark the end of the pandemic — and to plan for a future that they concede is unknowable.

For the full story, see:

Sheryl Gay Stolberg. “Ex-Aides Urge U.S. to Remake Covid Strategy.” The New York Times (Friday, January 7, 2022): A1 & A11.

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

(Note: the online version of the story has the date Jan. 6, 2022, and has the title “Former Biden Advisers Urge a Pandemic Strategy for the ‘New Normal’.”)

The three JAMA articles mentioned above are:

Emanuel, Ezekiel J., Michael Osterholm, and Celine R. Gounder. “A National Strategy for the “New Normal” of Life with Covid.” JAMA (Jan. 6, 2022). DOI: 10.1001/jama.2021.24282.

Michaels, David, Ezekiel J. Emanuel, and Rick A. Bright. “A National Strategy for Covid-19: Testing, Surveillance, and Mitigation Strategies.” JAMA (Jan. 6, 2022).
DOI:10.1001/jama.2021.24168.

Borio, Luciana L., Rick A. Bright, and Ezekiel J. Emanuel. “A National Strategy for Covid-19 Medical Countermeasures: Vaccines and Therapeutics.” JAMA (Jan. 6, 2022). DOI: 10.1001/jama.2021.24165.

Is Ignorance Bliss, When Knowledge Is Not Actionable?

(p. C1) . . . even in today’s pandemic world, cancer holds a special place in the anxious imagination. Its advance is often stealthy, its prognosis potentially frightening and its treatments damaging and life-altering. Once its shadow falls on us, we fear it will never go away—that there will always be another relapse and a return to harsh therapies that subsume our lives.

. . .

(p. C2) The borders of “Cancerland”—a term the oncologist David Scadden coined with the title of his 2018 memoir—begin to feel all-encompassing. In the past, entry was reserved for those with a diagnosis of cancer. Today everyone, in one way or another, slowly becomes a citizen.

. . .

The promise of detecting cancer in its earliest stages, together with that of identifying those at genetic risk for future cancer, is powerfully alluring. And yet the prospect of farther-reaching surveillance for this elusive long-term illness also warrants caution. In the 1950s, the sociologist Erving Goffman coined the term “total institution” for a community in which “a great number of similarly situated people, cut off from the wider community for a considerable time, together lead an enclosed, formally administered round of life.”

Total institutions, such as mental hospitals, prisons and even boarding schools, have rituals of entry and exit. They inculcate belonging. They invent their own vocabulary and codes of behavior; they have an internal logic, impenetrable to others. They encourage surveillance and create anxiety: Members are united by a common sense of purpose, by the feeling of being chosen or marked. Those who are expelled may feel a sense of betrayal, while those who remain can be consumed by the guilt of survivorship.

In this new era of cancer treatment, I wonder whether we unwittingly, but insidiously, intensify the totality of the “cancer institution” for patients. When I once asked a woman with a rare sarcoma about her life outside the hospital, she observed, “I am in the hospital even when I am outside the hospital.”

For the full commentary, see:

Siddhartha Mukherjee. “Will We All Soon Live in Cancerland?” The Wall Street Journal (Saturday, Dec. 18, 2021): C1-C2.

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

(Note: the online version of the commentary was updated Dec. 17, 2021, and has the same title as the print version.)

Muckherjee’s commentary is adapted from his chapter in The New Deal for Cancer book:

Mukherjee, Siddhartha. “The New Borders of Cancerland.” In A New Deal for Cancer: Lessons from a 50 Year War, edited by Abbe R. Gluck and Charles S. Fuchs. New York: PublicAffairs, 2021, pp. 27-42.