Category: Health

Johan Hultin Self-Funded Trip to Find 1918 Flu Virus in the Permafrost

(p. B9) Dr. Hultin’s quest to find victims of the 1918 flu was sparked in 1950 by an offhand remark over lunch with a University of Iowa microbiologist, William Hale. Dr. Hale mentioned that there was just one way to figure out what caused the 1918 pandemic: finding victims buried in permafrost and isolating the virus from lungs that might be still frozen and preserved.

Dr. Hultin, a medical student in Sweden who was spending six months at the university, immediately realized that he was uniquely positioned to do just that. The previous summer, he and his first wife, Gunvor, spent weeks assisting a German paleontologist, Otto Geist, on a dig in Alaska. Dr. Geist could help him find villages in areas of permafrost that also had good records of deaths from the 1918 flu.

After persuading the university to provide him with a $10,000 stipend, Dr. Hultin set off for Alaska. It was early June 1951.

. . .

He removed still-frozen lung tissue from the victims, closed the grave and took the tissue back to Iowa, keeping it frozen on dry ice in the passenger compartment of a small plane.

Back in the lab, Dr. Hultin tried to grow the virus by injecting the lung tissue into fertilized chicken eggs — the standard way to grow flu viruses. He was caught up in the excitement of his experiment, he said, and had not thought about the possible danger of introducing a deadly virus into the world.

“I remember the sleepless nights,” he said. “I couldn’t wait for morning to come to charge into my lab and look at the eggs.”

But the virus was not growing.

He tried squirting lung tissue into the nostrils of guinea pigs, white mice and ferrets, but again he failed to revive the virus.

“The virus was dead,” he said.

Dr. Hultin never published his results but bided his time, working as a pathologist in private practice in San Francisco and hoping for another opportunity to resurrect that virus.

His chance came in 1997, when, sitting by a pool on vacation with his wife in Costa Rica, he noticed a paper published in Science by Dr. Jeffery K. Taubenberger, now chief of the viral pathogenesis and evolution section at the National Institute of Allergy and Infectious Diseases.

It reported a remarkable discovery. Dr. Taubenberger had searched a federal repository of pathology samples dating to the 1860s and found fragments of the 1918 virus in snippets of lung tissue from two soldiers who had died in that pandemic. The tissue had been removed at autopsy, wrapped in paraffin and stored in the warehouse.

Dr. Hultin immediately wrote to Dr. Taubenberger, telling him about his trip to Alaska. He offered to return to Brevig to see if he could find more flu victims.

“I remember getting that letter and thinking: ‘Gosh. This is really incredible. This is amazing,’” Dr. Taubenberger said in an interview this week. He thought the next step would be to apply for a grant for Dr. Hultin to return to Brevig. If all went well, Dr. Hultin might go back in a year or two.

Dr. Hultin had a different idea.

“I can’t go this week, but maybe I can go next week,” he told Dr. Taubenberger.

He added that he would go alone and pay for the trip himself so that there would be no objections from funding agencies, no delays, no ethics committees and no publicity.

. . .

Using the tissue Dr. Hultin provided, Dr. Taubenberger’s group published a paper that provided the genetic sequence of a crucial gene, hemagglutinin, which the virus had used to enter cells. The group subsequently used that tissue to determine the complete sequence of all eight of the virus’s genes.

. . .

Before results from the study of the Brevig woman’s virus were published, Dr. Hultin asked the villagers if they wanted the village to be identified in a news release and a journal article. They might be besieged by media. “Maybe you won’t like that,” he warned them.

The Brevig residents came to a consensus: Publish the paper and identify the village. Dr. Hultin was listed as a co-author.

For the full obituary, see:

Gina Kolata. “Dr. Johan Hultin, 97, Whose Work Helped Map 1918 Pandemic, Dies.” The New York Times (Friday, January 28, 2022): B9.

(Note: ellipses added.)

(Note: the online version of the obituary was updated January 28, 2022, and has the title “Johan Hultin, Who Found Frozen Clues to 1918 Virus, Dies at 97.”)

Gina Kolata devotes a chapter to Hultin’s search for the 1918 flu virus in her book:

Kolata, Gina. Flu: The Story of the Great Influenza Pandemic of 1918 and the Search for the Virus That Caused It. New York: Farrar, Straus & Giroux, Inc., 1999.

IBM Sells Failed Watson Artificial Intelligence Health Unit

(p. B3) International Business Machines Corp. agreed to sell the data and analytics assets from its Watson Health business to investment firm Francisco Partners, the companies said Friday [January 21, 2022].

. . .

The Watson Health business uses artificial intelligence to analyze diagnostic tests and other health data and to manage care.

IBM had big aspirations for its Watson artificial intelligence to help in medical research and improve patient outcomes, but the technology’s impact has fallen short of early hopes. Partners and clients have moved away from projects that were built around Watson technology in recent years, although IBM had spent billions of dollars making acquisitions to bolster the business.

“IBM took a risk of becoming a disrupter in the complex health care industry but was only able to garner limited success,” UBS analyst David Vogt said in a note Friday.

For the full story, see:

Matt Grossman. “IBM Sells Its Watson Health Assets To Investment Firm as It Refocuses.” The Wall Street Journal (Saturday, January 22, 2022): B3.

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

(Note: the online version of the story was updated Jan. 21, 2022, and has the title “IBM Sells Watson Health Assets to Investment Firm.”)

Instead of Centralizing With C.D.C., the Need for Speed Requires “Clinical and Commercial Labs to Create and Deploy Tests”

(p. A22) The faulty coronavirus testing kits developed by the Centers for Disease Control and Prevention in the early weeks of the pandemic were not only contaminated but had a basic design flaw, according to an internal review by the agency.

Health officials had already acknowledged that the test kits were contaminated, but the internal report, whose findings were published in PLOS ONE on Wednesday, also documented a design error that caused false positives.

. . .

The C.D.C.’s test was designed to detect three distinct regions, or target sequences, of the virus’s genetic material. The test kits contain a set of what are known as primers, which bind to and make copies of the target sequences, and probes, which produce a fluorescent signal when these copies are made, indicating that genetic material from the virus is present.

The primers and probes need to be carefully designed so that they bind to the target sequences and not to each other. In this case, that did not happen. One of the probes in the kit sometimes bound to one of the primers, producing the fluorescent signal and generating a false positive.

“It’s something that should have been caught in the design phase,” said Susan Butler-Wu, a clinical microbiologist at the Keck School of Medicine of the University of Southern California. “That’s one thing that you check for.”

. . .

The bigger lesson, Dr. Butler-Wu said, is that the responsibility for developing diagnostic tests should be distributed more widely during a public health emergency. Rather than relying on the C.D.C. to be the sole test developer, officials could also enlist clinical and commercial labs to create and deploy tests.

“It’s great that there’s all these additional checks in place, but what are you going to do when there’s a new emerging pathogen and we need to respond quickly?” she said. “I don’t think that’s a viable model for responding to a pandemic.”

For the full story, see:

Emily Anthes. “C.D.C. Finds Design Error In Testing Kits It Distributed.” The New York Times Thursday, December 16, 2021): A22.

(Note: ellipses added.)

(Note: the online version of the story has the date Dec. 15, 2021, and has the title “C.D.C. Virus Tests Were Contaminated and Poorly Designed, Agency Says.”)

The PLOS ONE article mentioned above is:

Lee, Justin S., Jason M. Goldstein, Jonathan L. Moon, Owen Herzegh, Dennis A. Bagarozzi, Jr., M. Steven Oberste, Heather Hughes, Kanwar Bedi, Dorothie Gerard, Brenique Cameron, Christopher Benton, Asiya Chida, Ausaf Ahmad, David J. Petway, Jr., Xiaoling Tang, Nicky Sulaiman, Dawit Teklu, Dhwani Batra, Dakota Howard, Mili Sheth, Wendi Kuhnert, Stephanie R. Bialek, Christina L. Hutson, Jan Pohl, and Darin S. Carroll. “Analysis of the Initial Lot of the CDC 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel.” PLOS ONE 16, no. 12 (Dec. 15, 2021). DOI: 10.1371/journal.pone.0260487.

FDA Only Approves Drugs That Fight Diseases and FDA Does Not See Aging as a Disease

(p. R2) Will people eventually routinely live—and live healthily—longer? That’s the vision of the burgeoning field of aging research, where scientists are trying to extrapolate tantalizing life-prolonging findings from animal experiments into medicines that slow, prevent or even reverse the aging process for humans.

Leading candidates for stanching aging include two familiar drugs—metformin, a front-line diabetes treatment, and rapamycin, long used to prevent transplant patients from rejecting donated organs. Both have been shown to increase longevity in animal studies and both target molecular processes linked to the aging of cells.

Another approach is a new class of drugs called senolytics, which clear the body of so-called senescent cells, old cells that stop dividing but don’t die. They accumulate in tissues throughout the body and secrete factors that damage other cells. They are linked to such aging conditions as frailty, cognitive impairment and lack of physical resilience.

Also in the mix is a strategy called cellular reprogramming in which scientists are seeking to turn back the clock on aging cells, restoring functions characteristic of younger cells.

. . .

. . ., the Food and Drug Administration doesn’t recognize aging as a disease to be treated, meaning there isn’t a clear path to approval for a drug that targets the biology of aging. Researchers instead have to design trials that can quantify whether a drug improves health or extends survival in a specific age-related disease. A pill that a large and generally healthy population would take, perhaps for decades, would have to clear a high safety bar.

. . .

Researchers are working to develop biomarkers in blood or other bodily sources that can quantify the aging process and serve as drug targets or as proxies to indicate a drug is working or not. Without validated biomarkers, it could take 20 or 30 years in some cases to run a randomized trial to prove whether a drug safely extended life.

For the full story, see:

Ron Winslow. “A Pill to Turn Back the Clock.” The Wall Street Journal (Thursday, Jan. 13, 2022): R2.

(Note: ellipses added.)

(Note: the online version of the story has the date January 11, 2022, and has the title “Can You Fight Aging? Scientists Are Testing Drugs to Help.”)

Diamond to Give “How to Cure Cancer” Talk at Gustavus Adolphus College

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!

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:

Daniel Halperin. “Omicron Is Spreading. Resistance Is Futile.” The Wall Street Journal (Tuesday, January 25, 2022): A17.

(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:

Abaluck, Jason, Laura H. Kwong, Ashley Styczynski, Ashraful Haque, Md. Alamgir Kabir, Ellen Bates-Jefferys, Emily Crawford, Jade Benjamin-Chung, Shabib Raihan, Shadman Rahman, Salim Benhachmi, Neeti Zaman Bintee, Peter J. Winch, Maqsud Hossain, Hasan Mahmud Reza, Abdullah All Jaber, Shawkee Gulshan Momen, Aura Rahman, Faika Laz Banti, Tahrima Saiha Huq, Stephen P. Luby, and Ahmed Mushfiq Mobarak. “Impact of Community Masking on Covid-19: A Cluster-Randomized Trial in Bangladesh.” Science 375, no. 6577 (Jan. 14, 2022). DOI: 10.1126/science.abi9069.

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:

Penelope Green. “Alan Scott, 89, Eye Doctor Behind Medical Use of Botox.” The New York Times (Tuesday, January 18, 2022): B11.

(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:

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.