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

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

. . .

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

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

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

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

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

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

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

For the full obituary, see:

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

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

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

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

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

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

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

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

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

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

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

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

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

For the full story, see:

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

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

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

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

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

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

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

. . .

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

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

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

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

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

For the full story, see:

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

(Note: ellipses added.)

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

The international consensus mentioned above was published as:

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

Excessive Hygiene from Masking, Distancing, and Deep-Cleaning, Can Increase Allergies and Auto-Immune Diseases

(p. A17) The idea that exposure to some infectious agents is protective against immune-related disorders isn’t new and comes with significant scientific heft. The so-called hygiene hypothesis is constructed from epidemiologic evidence, laboratory studies and clinical trials that, put together, support the notion that an excessive emphasis on antisepsis is implicated in misalignments of the immune system that risk disease.

Allergic and autoimmune diseases are far less common in communities with less hygiene, and autoimmune disorders increase in children who migrate from areas with less emphasis on hygiene to areas with more emphasis. They are less common in agricultural communities, where exposure to dirt and animals is common, compared with neighboring communities with shared genetics but little farming. Children who attend daycare early in life—runny noses, colds and all—have less asthma and fewer allergies. Animal studies, laboratory experiments and small trials in humans all point in a similar direction: Avoiding exposure to some microbes prevents the immune system from training well and predisposes to autoimmune diseases.

. . .

This isn’t a paean to infections and poor hygiene but a reminder of the importance of balance. When I prescribe antibiotics, they have to be strong enough to treat my patient’s infection. But if I overtreat, I run the risk of giving the patient colitis (inflammation of the colon) without additional benefits. Current hygiene policies and practices need rebalancing.

. . .

The extreme concern for hygiene at the onset of Covid-19 was intuitive and understandable. The virus was spreading fast, information on routes of transmission was limited, and we as a society tried to protect one another from infection. But policies that were easy to support two years ago need re-evaluation. Distancing, deep-cleaning and masking aren’t “more is better” kinds of goods.

On the other side of the balance, health risks from extended intensive hygiene are credible. As Omicron recedes and we internalize the paucity of Covid-19 benefits from some hygiene practices, we should balance those against the benefits we lose by shielding our immune systems from normal exposures—and the ones we withhold from children by preventing the exchange of microbes through play and smiles.

For the full commentary, see:

Eran Bendavid. “Covid and the ‘Hygiene Hypothesis’.” The Wall Street Journal (Wednesday, February 2, 2022): A17.

(Note: ellipses added.)

(Note: the online version of the commentary has the date February 1, 2022, and has the same title as the print version.)

The Elite Experts Who Have Failed, Tend to Censor the Heterodox Outsiders Who They Fear

(p. 8) When you have a chronic illness and struggle to get better, you try to maintain a certain equilibrium by distinguishing yourself from all those other sick people, the ones who are trying truly crazy things while you are proceeding sensibly and moderately along the path to health.

. . .

These exotic treatments, from acupuncture to IV vitamin C to magnet therapy and more, weren’t the core of what helped me eventually gain ground and improve — strong and various doses of antibiotics played the central role. But they were the most educational part of my slow, still-continuing recovery, in the sense of what they revealed about the complexity and strangeness of the world.

The strangest of them all was the Rife machine.

. . .

Naturally, it worked.

What does “worked” mean, you may reasonably ask? Just this: By this point in my treatment, there was a familiar feeling whenever I was symptomatic and took a strong dose of antibiotics — a temporary flare of pain and discomfort, a desire to move or rub the symptomatic areas of my body, a sweating or itching feeling, followed by a wave of exhaustion and then a mild relief. I didn’t get this kind of reaction with every alternative treatment I tried. But with the Rife machine I got it instantly: It was like having a high dose of antibiotics hit the body all at once.

Of course, this was obviously insane, so to the extent that I was able I conducted experiments, trying frequencies for random illnesses to see if they elicited the same effect (they did not), setting up blind experiments where I ran frequencies without knowing if they were for Lyme disease or not (I could always tell).

. . .

When I set out to write about the entire chronic-illness experience, I hesitated over whether to tell this kind of story. After all, if you’re trying to convince skeptical readers to take chronic sickness seriously, and to make the case for the medical-outsider view of how to treat Lyme disease, reporting that you’ve been dabbling in pseudoscience and that it works is a good way to confirm every stereotype about chronic ailments and their treatment: It’s psychosomatic … it’s all the power of suggestion … it’s a classic placebo effect … poor Ross, taken in by the quacks … he’ll be ‘doing his own research’ on vaccination next

    .

    But there are two good reasons to share this sort of story. The first is that it’s true, it really happened, and any testimony about what it’s like to fight for your health for years would be dishonest if it left the weird stuff out.

    The second is that this kind of experience — not the Rife machine specifically, but the experience of falling through the solid floor of establishment consensus and discovering something bizarre and surprising underneath — is extremely commonplace. And the interaction between the beliefs instilled by these experiences and the skepticism they generate (understandably) from people who haven’t had them, for whom the floor has been solid all their lives, is crucial to understanding cultural polarization in our time.

    On both sides of our national divides, insider and outsider, establishment and populist, something in human psychology makes us seek coherence and simplicity in our understanding of the world. So people who have a terrible experience with official consensus, and discover that some weird idea that the establishment derides actually seems to work, tend to embrace a new rule to replace the old one: that official knowledge is always wrong, that outsiders are always more trustworthy than insiders, that if Dr. Anthony Fauci or the Food and Drug Administration get some critical things wrong, you can’t trust them to get anything right.

    This impulse explains why fringe theories tend to cluster together, the world of outsider knowledge creating its own form of consensus and self-reinforcement. But it also explains the groupthink that the establishment often embraces in response, its fear that pure craziness automatically abounds wherever official knowledge fails, and its commitment to its own authority as the only thing standing between society and the abyss.

    This is a key dynamic in political as well as biomedical debates. The conspicuous elite failures in the last 20 years have driven many voters to outsider narratives, which blend plausible critiques of the system with outlandish paranoia. But the insiders only see the paranoia, the QAnon shaman and his allies at the gates. So instead of reckoning with their own failures, they pull up the epistemic drawbridge and assign fact checkers to patrol the walls. Which in turn confirms for outsiders their belief that the establishment has essentially blinded itself and only they have eyes to see.

    What we need, I’m convinced, are more people and institutions that sustain a position somewhere in between.

For the full commentary, see:

Ross Douthat. “How I Became Extremely Open-Minded.” The New York Times, SundayReview Section (Sunday, November 7, 2021): 8.

(Note: ellipses added.)

(Note: the online version of the commentary has the date November 6, 2021, and has the same title as the print version. The passages that are underlined above, were in italics in the original. In the underlined passages I use a hyphen were the original had ellipses.)

The passages quoted above are from a commentary adapted from Douthat’s book:

Douthat, Ross. The Deep Places: A Memoir of Illness and Discovery. New York: Convergent Books, 2021.

Best New Climate Models Fail at Accurately “Hind-Casting” Past Temperatures

(p. A1) BOULDER, Colo.—For almost five years, an international consortium of scientists was chasing clouds, determined to solve a problem that bedeviled climate-change forecasts for a generation: How do these wisps of water vapor affect global warming?

They reworked 2.1 million lines of supercomputer code used to explore the future of climate change, adding more-intricate equations for clouds and hundreds of other improvements. They tested the equations, debugged them and tested again.

The scientists would find that even the best tools at hand can’t model climates with the sureness the world needs as rising temperatures impact almost every region.

When they ran the updated simulation in 2018, the conclusion jolted them: Earth’s atmosphere was much more sensitive to greenhouse gases than decades of previous models had predicted, and future temperatures could be much higher than feared—perhaps even beyond hope of practical remedy.

(p. A9) “We thought this was really strange,” said Gokhan Danabasoglu, chief scientist for the climate-model project at the Mesa Laboratory in Boulder at the National Center for Atmospheric Research, or NCAR.

. . .

As world leaders consider how to limit greenhouse gases, they depend heavily on what computer climate models predict. But as algorithms and the computer they run on become more powerful—able to crunch far more data and do better simulations—that very complexity has left climate scientists grappling with mismatches among competing computer models.

While vital to calculating ways to survive a warming world, climate models are hitting a wall. They are running up against the complexity of the physics involved; the limits of scientific computing; uncertainties around the nuances of climate behavior; and the challenge of keeping pace with rising levels of carbon dioxide, methane and other greenhouse gases. Despite significant improvements, the new models are still too imprecise to be taken at face value, which means climate-change projections still require judgment calls.

“We have a situation where the models are behaving strangely,” said Gavin Schmidt, director of the National Aeronautics and Space Administration’s Goddard Institute for Space Sciences, a leading center for climate modeling. “We have a conundrum.”

. . .

In its guidance to governments last year, the U.N. climate-change panel for the first time played down the most extreme forecasts.

Before making new climate predictions for policy makers, an independent group of scientists used a technique called “hind-casting,” testing how well the models reproduced changes that occurred during the 20th century and earlier. Only models that re-created past climate behavior accurately were deemed acceptable.

In the process, the NCAR-consortium scientists checked whether the advanced models could reproduce the climate during the last Ice Age, 21,000 years ago, when carbon-dioxide levels and temperatures were much lower than today. CESM2 and other new models projected temperatures much colder than the geologic evidence indicated. University of Michigan scientists then tested the new models against the climate 50 million years ago when greenhouse-gas levels and temperatures were much higher than today. The new models projected higher temperatures than evidence suggested.

For the full story, see:

Robert Lee Hotz. “Climate Scientists Encounter Computer Models’ Limits.” The Wall Street Journal (Monday, February 7, 2022): A1 & A9.

(Note: ellipses added.)

(Note: the online version of the story has the date February 6, 2022, and has the title “Climate Scientists Encounter Limits of Computer Models, Bedeviling Policy.”)

“People Are Now Coming to Their Own Conclusions About Covid”

(p. 3) Lauren Terry, 23, thought she would know what to do if she contracted Covid-19. After all, she manages a lab in Tucson that processes Covid tests.

But when she developed symptoms on Christmas Eve, she quickly realized she had no inside information.

“I first tried to take whatever rapid tests I could get my hands on,” Ms. Terry said. “I bought some over the counter. I got a free kit from my county library. A friend gave me a box. I think I tried five different brands.” When they all turned up negative, she took a P.C.R. test, but that too, was negative.

With clear symptoms, she didn’t believe the results. So she turned to Twitter. “I was searching for the Omicron rapid test efficacy and trying to figure out what brand works on this variant and what doesn’t and how long they take to produce results,” she said. (The Food and Drug Administration has said that rapid antigen tests may be less sensitive to the Omicron variant but has not identified any specific tests that outright fail to detect it.) “I started seeing people on Twitter say they were having symptoms and only testing positive days later. I decided not to see anybody for the holidays when I read that.”

She kept testing, and a few days after Christmas she received the result she had expected all along.

Though it’s been almost two years since the onset of the pandemic, this phase can feel more confusing than its start, in March 2020. Even P.C.R. tests, the gold standard, don’t always detect every case, especially early in the course of infection, and there is some doubt among scientists about whether rapid antigen tests perform as well with Omicron. And, the need for a 10-day isolation period was thrown into question after the Centers for Disease Control and Prevention announced that some people could leave their homes after only five days.

“The information is more confusing because the threat itself is more confusing,” said David Abramson, who directs the Center for Public Health Disaster Science at the N.Y.U. School of Global Public Health. “We used to know there was a hurricane coming at us from 50 miles away. Now we have this storm that is not well defined that could maybe create flood or some wind damage, but there are so many uncertainties, and we just aren’t sure.”

Many people are now coming to their own conclusions about Covid and how they should behave. After not contracting the virus after multiple exposures, they may conclude they can take more risks. Or if they have Covid they may choose to stay in isolation longer than the C.D.C. recommends.

And they aren’t necessarily embracing conspiracy theories. People are forming opinions after reading mainstream news articles and tweets from epidemiologists; they are looking at real-life experiences of people in their networks.

For the full story, see:

Alyson Krueger. “Covid Experts, the Self-Made Kind.” The New York Times, SundayStyles Section (Sunday, January 23, 2022): 3.

(Note: the online version of the story has the date January 21, 2022, and has the title “So You Think You’re a Covid Expert (but Are You?).”)

Expert Medical Advice Often Flip-Flops

(p. D6) A History of Medical Flip-Flops

Shifting medical advice is surprisingly common, and it tends to fall into three categories: emerging guidance, replacement advice and reversals.

Emerging guidance comes during times of crisis — like pandemics — and is destined to change quickly. In the past several months, guidance about the best way to treat Covid patients, masks to prevent transmission and the limits of vaccine protection have all shifted as knowledge of the coronavirus and its variants has evolved.

Sometimes it’s hard to tell the difference between replacement advice, which is issued when research improves on advice that came before it, and a full reversal, which comes about because a common medical practice got ahead of the science and never actually worked or even caused harm. Here are some examples of true medical flip-flops in recent years.

MENOPAUSE HORMONES TO PROTECT THE HEART: In 2002, decades of advice about the heart benefits of menopause hormones seemed to change overnight when a major study called the Women’s Health Initiative was halted after researchers detected more heart attacks in the women taking hormones. In hindsight, doctors had misinterpreted data from observational research. The current advice: Hormones can relieve menopause symptoms but shouldn’t be used for chronic disease prevention.

VIOXX AS A LOWER-RISK ARTHRITIS TREATMENT: In 1999, the Food and Drug Administration approved Vioxx as a breakthrough pain reliever because it lowered the risk of gastrointestinal problems. But by 2004, Merck had withdrawn the drug because studies showed it significantly raised the risk of heart attack.

ARTHROSCOPIC SURGERY ON AGING KNEES: For years, the partial removal of torn meniscus tissue was the most common orthopedic procedure in the United States, with about 700,000 performed a year. In 2013, a researcher in Finland compared the operation to a “sham” procedure and found there was no benefit. Most doctors now recommend physical therapy instead.

VITAMIN MEGADOSES TO LOWER CANCER AND HEART RISK: For years, doctors believed various vitamins could lower risk for cancer and heart disease, but a number of studies showed just the opposite. A study of beta carotene and vitamin A found that the supplements actually increased the risk of lung cancer in male smokers. A study of vitamin E and selenium, thought to protect against prostate cancer, increased risk for the disease.

STENTS FOR STABLE HEART DISEASE: Doctors used to insert stents — tiny wire mesh tubes that prop open arteries — in millions of otherwise stable patients with heart disease. A study found that the surgical procedure was no better than drug therapy for preventing heart attacks.

Dr. Vinay Prasad, associate professor at the University of California San Francisco, and Dr. Adam S. Cifu, a professor of medicine at the University of Chicago Department of Medicine, coined the term “medical reversal” and concluded that about 40 percent of common medical practices that they reviewed turned out to be useless or harmful. In their book, “Ending Medical Reversal: Improving Outcomes, Saving Lives,” they noted that most of these failed treatments were initially embraced because they were based on logical reasoning.

“The thing that’s often behind reversal: All of these things have a good story, they have good pathophysiological rationale,” Dr. Cifu said. “They should work. But things only work if they’ve been shown in people to work, and people are so complicated.”

For the full story, see:

Tara Parker-Pope. “Shifting Medical Advice Is a Feature, Not a Bug.” The New York Times (Tuesday, November 2, 2021): D6.

(Note: the online version of the story was updated Oct. 24, 2021, and has the title “Is the New Aspirin Advice a Medical Flip-Flop, or Just Science?” The paragraphs on menopause hormones to protect the heart and on vitamin megadoses to lower cancer and heart risk appear in the online version, but not in the print version.)

The book co-authored by Prasad and mentioned above is:

Prasad, Vinayak K., and Adam S. Cifu. Ending Medical Reversal: Improving Outcomes, Saving Lives. Baltimore: Johns Hopkins University Press, 2015.

The “Gold Standard” of Randomized Clinical Trials “Has Its Own Issues”

(p. R2) . . ., closely held Epic Systems Corp., maker of one of the most widely used electronic health record systems, searched a segment of its database in the spring of 2020 to find that routine breast, colon and cervical cancer screenings in the U.S. had each dropped by more than 85% during the first weeks of the Covid-19 pandemic. The report helped spur efforts to persuade people to make up for missed screenings.

But researchers have a much more ambitious vision for this data: to help guide how doctors treat individual patients in real time.

“The evidence from real-world data is a different and exciting new path,” says Jackie Gerhart, a physician who works with the informatics team at Epic. “You can get a lot of outcomes information from medical records that can help change care for individual patients.”

. . .

To be sure, patient records are observational, and thus subject to confounders and other shortcomings that can undercut their reliability in pointing to treatment options.

But the gold standard has its own issues. Randomized clinical trials, which control for differences in patient health status and other variables, are the preferred evidence to inform patient care. Yet such trials generally exclude an especially common group of patients—those with multiple ailments. Moreover, the elderly, children, women, minority groups and people who live far from medical research centers have long been underrepresented in such studies.

As a result, the highest-quality evidence that medicine produces doesn’t apply to most patients doctors see in daily practice. “There are so many clinical situations where the evidence that is needed does not exist,” says Nigam Shah, professor of medicine and biomedical data science at Stanford University Medical School.

Researchers have believed for at least a half-century that data in patient medical records could help fill the gaps.

. . .

The struggles of International Business Machines Corp.’s Watson raises [a] . . . yellow flag. It had ambitions to develop a tool for cancer doctors that would mine patient health records and thousands of pages of research from the peer-reviewed medical literature for treatment advice. But it hit walls, including accuracy and the complexity of combining data from electronic health records, billing claims and published research to provide a cohesive product. Doctors who used the service rarely changed treatment plans. IBM says it discontinued Watson for Oncology at the end of 2020.

For the full story, see:

Ron Winslow. “Mining the Gold in Patient Records.” The Wall Street Journal (Thursday, December 9, 2021): R2.

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

(Note: the online version of the story has the date December 3, 2021, and has the title “Medical Records Data Offers Doctors Hope of Better Patient Care.” In a couple of passages there are a few extra words in the online version, which is the version quoted above.)

“Unprecedented” and “Huge” Serendipitous Discovery of 60 Million Icefish Nests

(p. D3) As soon as the remotely operated camera glimpsed the bottom of the Weddell Sea, more than a thousand feet below the icy ceiling at the surface, Lilian Boehringer, a student researcher at the Alfred Wegener Institute in Germany, saw the icefish nests. The sandy craters dimpled the seafloor, each the size of a hula hoop and less than a foot apart. Each crater held a single, stolid icefish, dark pectoral fins outspread like bat wings over a clutch of eggs.

Aptly named icefishes thrive in waters just above freezing with enormous hearts and blood that runs clear as vodka. . . .

The sighting occurred in February 2021 in the camera room aboard a research ship, the Polarstern, which had come to the Weddell Sea to study other things, not icefish. It was 3 a.m. near Antarctica, meaning the sun was out but most of the ship was asleep. To Ms. Boehringer’s surprise, the camera kept transmitting pictures as it moved with the ship, revealing an uninterrupted horizon of icefish nests every 20 seconds.

. . .

The nests persisted for the entire four-hour dive, with a total of 16,160 recorded on camera. After two more dives by the camera, the scientists estimated the colony of Neopagetopsis ionah icefish stretched across 92 square miles of the serene Antarctic sea, totaling 60 million active nests. The researchers described the site — the largest fish breeding colony ever discovered — in a paper published Thursday in the journal Current Biology.

“Holy cow,” said C.-H. Christina Cheng, an evolutionary biologist at the University of Illinois-Urbana-Champaign, who was not involved with the research. “This is really unprecedented,” she said. “It is crazy dense. It is a major discovery.”

. . .

“The seafloor is not just barren and boring,” Dr. Purser said. “Such huge discoveries are still there to be made, even today in the 21st century.”

For the full story, see:

Sabrina Imbler. “Deep in Frigid Waters, Icefish Colonies Thrive.” The New York Times (Tuesday, January 18, 2022): D3.

(Note: ellipses added.)

(Note: the online version of the story has the date January 13, 2022, and has the title “‘Major Discovery’ Beneath Antarctic Seas: A Giant Icefish Breeding Colony.”)

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.)