I appreciate Marta Podemska-Mikluch’s perseverance over the long pandemic in arranging my conversations with Gustavus Adolphus College students on some of my current research on medical entrepreneurship. I am looking forward to my visit!
Category: Health
Surgical Masks Provide Wearer Modest Protection Against Infection from Covid-19
(p. A17) The first large randomized community-level study, published last month in Science, found that while generic surgical masks provided a modest (about 10%) reduction in the risk of infection from Delta, cloth masks didn’t significantly reduce risk. Masks may be even less protective against an extremely contagious variant like Omicron.
For the full commentary, see:
(Note: the online version of the commentary has the date Jan. 24, 2022, and has the same title as the print version.)
The article in Science mentioned above is:
Alan Scott’s Use of Botulism to Fix Eye Muscles Led to Serendipitous Discovery of Botox to Smooth Wrinkles
(p. B11) It is a neurotoxin 100 times more deadly than cyanide and the cause of the food-borne illness known as botulism. During World War II and for some years after, the Department of Defense hoped to develop it as a chemical weapon. But it wasn’t until the 1970s that Alan Scott, an ophthalmologist, turned the botulinum toxin into a pharmaceutical, when he began to investigate it as a medical treatment for serious eye impairments.
. . .
When, in 1978, Dr. Scott first injected the powerful paralytic into the eye muscles of a patient who had undergone retinal detachment surgery that had left his eye pulled to one side, he didn’t know who was more nervous, himself or the patient, he told Scientific American magazine in 2016.
But the procedure succeeded, and Dr. Scott would go on to refine one of the world’s deadliest poisons into a life-altering treatment — he called it Oculinum — for those who suffered from conditions like strabismus, a misalignment of the eyes.
Doctors also began using it to treat migraines and jaw-clenching, among other ailments, and as they did so many of their delighted patients noticed a curious byproduct: The toxin’s ability to paralyze targeted facial muscles smoothed the lines around them, though its effects wore off after a few months.
For the full obituary, see:
(Note: ellipsis added.)
(Note: the online version of the obituary was updated Jan. 20, 2022, and has the title “Alan Scott, Doctor Behind the Medical Use of Botox, Dies at 89.”)
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:
(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:
(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:
(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:
(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:
(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.