Archive for January 26th, 2023
Antidepressants help bacteria resist antibiotics
— Credit: Steve Gschmeissner/Science Photo Library
Liam Drew writes in Nature:
The emergence of disease-causing bacteria that are resistant to antibiotics is often attributed to the overuse of antibiotics in people and livestock. But researchers have homed in on another potential driver of resistance: antidepressants. By studying bacteria grown in the laboratory, a team has now tracked how antidepressants can trigger drug resistance1.
“Even after a few days exposure, bacteria develop drug resistance, not only against one but multiple antibiotics,” says senior author Jianhua Guo, who works at the Australian Centre for Water and Environmental Biotechnology at the University of Queensland in Brisbane. This is both interesting and scary, he says.
Globally, antibiotic resistance is a significant public-health threat. An estimated 1.2 million people died as a direct result of it in 20192, and that number is predicted to climb.
Early clues
Guo became interested in the possible contributions of non-antibiotic drugs to antibiotic resistance in 2014, after work by his lab found more antibiotic-resistance genes circulating in domestic wastewater samples than in samples of wastewater from hospitals, where antibiotic use is higher.
Guo’s group and other teams also observed that antidepressants — which are among the most widely prescribed medicines in the world — killed or stunted the growth of certain bacteria. They provoke “an SOS response”, Guo explains, triggering cellular defence mechanisms that, in turn, make the bacteria better able to survive subsequent antibiotic treatment.
In a 2018 paper, the group reported that Escherichia coli became resistant to multiple antibiotics after being exposed to fluoxetine3, which is commonly sold as Prozac. The latest study examined 5 other antidepressants and 13 antibiotics from 6 classes of such drugs and investigated how resistance in E. coli developed.
In bacteria grown in well-oxygenated laboratory conditions, the antidepressants caused the cells to generate reactive oxygen species: toxic molecules that activated the microbe’s defence mechanisms. Most prominently, this activated the bacteria’s efflux pump systems, a general expulsion system that many bacteria use to eliminate various molecules, including antibiotics. This probably explains how the bacteria could withstand the antibiotics without having specific resistance genes.
But exposure of E. coli to antidepressants also led to an increase in . . .
The Cause of Depression Is Probably Not What You Think
Joanna Thompson writes in Quanta:
People often think they know what causes chronic depression. Surveys indicate that more than 80% of the public blames a “chemical imbalance” in the brain. That idea is widespread in pop psychology and cited in research papers and medical textbooks. Listening to Prozac, a book that describes the life-changing value of treating depression with medications that aim to correct this imbalance, spent months on the New York Times bestseller list.
The unbalanced brain chemical in question is serotonin, an important neurotransmitter with fabled “feel-good” effects. Serotonin helps regulate systems in the brain that control everything from body temperature and sleep to sex drive and hunger. For decades, it has also been touted as the pharmaceutical MVP for fighting depression. Widely prescribed medications like Prozac (fluoxetine) are designed to treat chronic depression by raising serotonin levels.
Yet the causes of depression go far beyond serotonin deficiency. Clinical studies have repeatedly concluded that the role of serotonin in depression has been overstated. Indeed, the entire premise of the chemical-imbalance theory may be wrong, despite the relief that Prozac seems to bring to many patients.
A literature review that appeared in Molecular Psychiatry in July was the latest and perhaps loudest death knell for the serotonin hypothesis, at least in its simplest form. An international team of scientists led by Joanna Moncrieff of University College London screened 361 papers from six areas of research and carefully evaluated 17 of them. They found no convincing evidence that lower levels of serotonin caused or were even associated with depression. People with depression didn’t reliably seem to have less serotonin activity than people without the disorder. Experiments in which researchers artificially lowered the serotonin levels of volunteers didn’t consistently cause depression. Genetic studies also seemed to rule out any connection between genes affecting serotonin levels and depression, even when the researchers tried to consider stress as a possible cofactor.
“If you were still of the opinion that it was simply a chemical imbalance of serotonin, then yeah, it’s pretty damning,” said Taylor Braund, a clinical neuroscientist and postdoctoral research fellow at the Black Dog Institute in Australia who was not involved in the new study. (“The black dog” was Winston Churchill’s term for his own dark moods, which some historians speculate were depression.)
The realization that serotonin deficits by themselves probably don’t cause depression has left scientists wondering what does. The evidence suggests that there may not be a simple answer. In fact, it’s leading neuropsychiatric researchers to rethink what depression might be.
Treating the Wrong Disease
The focus on serotonin in depression began with a tuberculosis drug. In the 1950s, doctors started prescribing iproniazid, a compound developed to target lung-dwelling Mycobacterium tuberculosis bacteria. The drug wasn’t particularly good for treating tuberculosis infections — but it did bless some patients with an unexpected and pleasant side effect. “Their lung function and everything wasn’t getting much better, but their mood tended to improve,” said Gerard Sanacora, a clinical psychiatrist and the director of the depression research program at Yale University.
Perplexed by this outcome, researchers began studying how iproniazid and related drugs worked in the brains of rats and rabbits. They discovered that . . .
Barr Pressed Durham to Find Flaws in the Russia Investigation. It Didn’t Go Well.
Charlie Savage, Adam Goldman and Katie Benner report in the NY Times (gift link, no paywall):
WASHINGTON — It became a regular litany of grievances from President Donald J. Trump and his supporters: The investigation into his 2016 campaign’s ties to Russia was a witch hunt, they maintained, that had been opened without any solid basis, went on too long and found no proof of collusion.
Egged on by Mr. Trump, Attorney General William P. Barr set out in 2019 to dig into their shared theory that the Russia investigation likely stemmed from a conspiracy by intelligence or law enforcement agencies. To lead the inquiry, Mr. Barr turned to a hard-nosed prosecutor named John H. Durham, and later granted him special counsel status to carry on after Mr. Trump left office.
But after almost four years — far longer than the Russia investigation itself — Mr. Durham’s work is coming to an end without uncovering anything like the deep state plot alleged by Mr. Trump and suspected by Mr. Barr.
Moreover, a monthslong review by The New York Times found that the main thrust of the Durham inquiry was marked by some of the very same flaws — including a strained justification for opening it and its role in fueling partisan conspiracy theories that would never be charged in court — that Trump allies claim characterized the Russia investigation.
Interviews by The Times with more than a dozen current and former officials have revealed an array of previously unreported episodes that show how the Durham inquiry became roiled by internal dissent and ethical disputes as it went unsuccessfully down one path after another even as Mr. Trump and Mr. Barr promoted a misleading narrative of its progress.
Mr. Barr and Mr. Durham never disclosed that their inquiry expanded in the fall of 2019, based on a tip from Italian officials, to include a criminal investigation into suspicious financial dealings related to Mr. Trump. The specifics of the tip and how they handled the investigation remain unclear, but Mr. Durham brought no charges over it.
Mr. Durham used Russian intelligence memos — suspected by other U.S. officials of containing disinformation — to gain access to emails of an aide to George Soros, the financier and philanthropist who is a favorite target of the American right and Russian state media. Mr. Durham used grand jury powers to keep pursuing the emails even after a judge twice rejected his request for access to them. The emails yielded no evidence that Mr. Durham has cited in any case he pursued.
There were deeper internal fractures on the Durham team than previously known. The publicly unexplained resignation in 2020 of his No. 2 and longtime aide, Nora R. Dannehy, was the culmination of a series of disputes between them over prosecutorial ethics. A year later, two more prosecutors strongly objected to plans to indict a lawyer with ties to Hillary Clinton’s 2016 campaign based on evidence they warned was too flimsy, and one left the team in protest of Mr. Durham’s decision to proceed anyway. (A jury swiftly acquitted the lawyer.)
Now, as Mr. Durham works on a final report, the interviews by The Times provide new details of how he and Mr. Barr sought to recast the scrutiny of the 2016 Trump campaign’s myriad if murky links to Russia as unjustified and itself a crime.
Mr. Barr, Mr. Durham and Ms. Dannehy declined to comment. The current and former officials who discussed the investigation all spoke on the condition of anonymity because of the legal, political and intelligence sensitivities surrounding the topic.
A year into the Durham inquiry, Mr. Barr declared that the attempt “to get to the bottom of what happened” in 2016 “cannot be, and it will not be, a tit-for-tat exercise. We are not going to lower the standards just to achieve a result.”
But Robert Luskin, a criminal defense lawyer and former Justice Department prosecutor who represented two witnesses Mr. Durham interviewed, said that he had a hard time squaring Mr. Durham’s prior reputation as an independent-minded straight shooter with his end-of-career conduct as Mr. Barr’s special counsel.
“This stuff has my head spinning,” Mr. Luskin said. “When did these guys drink the Kool-Aid, and who served it to them?”
An Odd Couple
A month after Mr. Barr was confirmed as attorney general in February 2019, the special counsel Robert S. Mueller III ended the Russia investigation and turned in his report without charging any Trump associates with engaging in a criminal conspiracy with Moscow over its covert operation to help Mr. Trump win the 2016 election.
Mr. Trump would repeatedly portray the Mueller report as having found “no collusion with Russia.” The reality was more complex. In fact, the report detailed “numerous links between the Russian government and the Trump campaign,” and it established both how Moscow had worked to help Mr. Trump win and how his campaign had expected to benefit from the foreign interference.
That spring, Mr. Barr assigned Mr. Durham to scour the origins of the Russia investigation for wrongdoing, telling Fox News that he wanted to know if “officials abused their power and put their thumb on the scale” in deciding to pursue the investigation. “A lot of the answers have been inadequate, and some of the explanations I’ve gotten don’t hang together,” he added.
While attorneys general overseeing politically sensitive inquiries tend to keep their distance from the investigators, Mr. Durham visited Mr. Barr in his office for at times weekly updates and consultations about his day-to-day work. They also sometimes dined and sipped Scotch together, people familiar with their work said.
In some ways, they were an odd match. . .
Continue reading. (gift link, no paywall)
The backstory of the Half Moon Bay mass shooting in California
Half Moon Bay is up the coast from where I live — back in the day and perhaps still, it had a terrific little cafe right next to the ocean that served superb seafood — so the shooting there caught my eye.
The LA Times has a report by Alexandra E. Petri and Salvador Hernandez that sheds some light on the situation. They write:
HALF MOON BAY, Calif. — The man charged with killing seven co-workers in a pair of mass shootings at farms in Half Moon Bay admitted to his role in the deadly shootings in a jailhouse interview Thursday.
Chunli Zhao, 66, spoke to NBC Bay Area’s Janelle Wang, telling the reporter he had experienced “years of bullying” and working long hours at the farm before he took a semiautomatic handgun and opened fire on his co-workers Monday.
“He admitted that he did do it,” Wang said in the report.
San Mateo County Dist. Atty. Stephen M. Wagstaffe told The Times in an interview that although he could not go into details in the case, Zhao’s comments to the TV station were “consistent with what he told law enforcement.”
In the 15-minute interview, Zhao also said he had been suffering from “some sort of mental illness” and was “not in his right mind” at the time of the shooting.
Zhao said he planned to turn himself in to law enforcement when he drove to the San Mateo County Sheriff’s Office and was writing a note in his car before he was taken into custody.
Wang said Zhao also told her that he regretted the deadly incident.
Zhao’s comments also come as state officials say they have opened investigations into labor and workplace practices at the two sites of Monday’s fatal shootings and cast a spotlight on the lives of California’s farmworkers who often live and work in dangerous conditions.
The investigation comes after Gov. Gavin Newsom on Tuesday visited the beachside community, where he spoke with the victims’ families and co-workers about the deadly shooting and their workplace environments.
Without naming specifics, Newsom said some farmworkers were “living in shipping containers” and working for $9 an hour, well below the state minimum wage of $15.50.
“No healthcare, no support, no services, but [they’re] taking care of our health, providing a service to us each and every day,” he said at the news conference.
A spokesperson for Newsom called the workers’ conditions “simply deplorable” in a statement.
“Our country relies on their back-breaking work, yet Congress cannot even provide them the stability of raising their families and working in this country without fear of deportation, which contributes to their vulnerability in the workplace,” Daniel Villaseñor, deputy press secretary for Newsom’s office, said in the statement. “California is investigating the farms involved in the Half Moon Bay shooting to ensure workers are treated fairly and with the compassion they deserve.”
<>News of the investigation was
The Abortion Pill’s Secret Money Men
Hannah Levintova writes in Mother Jones:
In 1993, a group of activists rented a warehouse in suburban Westchester County, New York. It was smaller than they’d hoped and had limited ventilation, but the two other locations they’d tried to rent belonged to universities and required jumping through too many bureaucratic hoops—the exact sort of paper trail this group was trying to avoid.
Led by renowned pro-choice activist Lawrence Lader, their goal was to replicate RU-486, the revolutionary abortion pill developed in the 1980s by French manufacturer Roussel-Uclaf—which was unwilling to navigate American abortion politics to bring the pill stateside. Lader’s group, code-named ARM Research Council, set up shop just months after Dr. David Gunn was shot and killed outside his Florida clinic, the first US physician to be murdered by an anti-abortion activist. Perhaps unsurprisingly, no US manufacturer wanted to wade into the increasingly fraught abortion debate to bring the medication to American women, either. So with the help of lawyers and activists, Lader had smuggled RU-486 into the United States, and his group was going to try to reproduce it.
In their warehouse, they got to work building an underground drug laboratory, complete with a huge, customized ventilation hood, fire prevention devices, and specially designed sinks. The whole project “had the trappings of a CIA operation,” Lader would later write. They figured out a system for replenishing their near-constant need for dry ice from a supplier 15 miles away, and crafted a strategy to avoid detection by anti-abortion groups, the garbage collector, and their landlord. If anyone asked what they were up to, the group—which included a doctor who lived 1,000 miles away and asked to go by Dr. X; a Columbia University chemist working for free; and two assistants—agreed on a cover story: They were working on a new treatment for cancer.
Meanwhile, Roussel-Uclaf and its parent company were in a drawn-out negotiation with a Manhattan-based reproductive health nonprofit, called the Population Council, over the official patent for RU-486. The same month that the French company finally agreed to give the Council the patent, Lader’s secret lab announced that it had successfully developed its own copy of the drug, whose scientific name is mifepristone. The two groups knew of each other’s work, and Lader had even reached out to the Population Council about collaborating, but the Council had demurred.
Lader’s group knew American women could not wait the many years it would take for the Council to arrange an official manufacturing operation with full approval from the Food and Drug Administration. So, it got its own permission from the FDA to conduct limited testing, which would allow it to start distributing small batches of the drug to a network of 10 clinics. There, patients could get both mifepristone and misoprostol, a common ulcer drug, which, when taken in tandem, can cause a medication abortion. For the few who were able to try it, it was an emotional and physical relief: It meant they could have an abortion privately and without a vacuum aspiration machine, whose suction “feels like you’re getting the life sucked out of you,” as one early mifepristone recipient described it to the Boston Globe.
All the while, the Council was working to find a manufacturer willing to make the drug, win full FDA authorization, and sell it across America.
When the FDA finally approved mifepristone seven years later, the Council’s distribution venture, which came to be called Danco Labs, was ready to go. Within two months, . . .
Continue reading. Capitalism will always seek and often find a way to grow profits.
How the White Cube Came to Dominate the Art World
Abigail Cain writes at Artsy.net:
In 1976, artist and critic Brian O’Doherty set the art world abuzz with a three-part essay published in Artforum. Titled “Inside the White Cube,” it gave a catchy new name to a mode of display that had long ago achieved dominance in museums and commercial galleries. As the story goes, copies of the magazine flew off the shelves. O’Doherty himself has said that the level of response shocked him: “It was a huge wave, and I said, ‘What is this?’… It struck a nerve, to the point where several people came up to me and said, ‘You know, I was about to write that.’”
More recently, in a 2012 paper, the writer Whitney Birkett traced the history of the “white cube”—looking at its origins before O’Doherty’s 1976 essay. In Birkett’s paper, she also analyzes the ways in which the white cube’s dominance, which was once revolutionary, has come to feel static as well as potentially off-putting to modern audiences. In Birkett’s words, the white cube, “now elevates art above its earthly origins, alienating uninitiated visitors and supporting traditional power relationships.”
As Birkett’s paper points out, while O’Doherty deserves credit for coining the phrase white cube (a label that has since become a staple of the art-world lexicon), the actual display strategy was invented decades earlier. Today, New York’s Museum of Modern Art is widely credited with institutionalizing the approach in the 1930s. But the evolution of the white cube goes back much further, with MoMA representing the culmination of a long stretch of experimentation and debate by museum directors and curators spanning continents and centuries.
Major public museums began to spring up in the 18th century, most notably the British Museum in 1759 and the Louvre in 1793. These institutions had largely grown out of private collections, in which artworks were displayed in dense, symmetrical arrangements that connoisseurs believed allowed for a better comparison of styles and movements. They were also influenced by the Paris salons, where paintings jostled for space on walls hung floor to ceiling with art. Artists were captivated by these new public spaces, and museum galleries were a frequent subject of early 19th-century painting.
It wasn’t just artists who were fascinated by these institutions. Attendance swelled throughout the 19th century, with London’s South Kensington Museum (now the Victoria & Albert Museum) reporting 456,000 annual visitors in 1857, compared to over a million in 1870. Collections also grew over time, and soon the museums of the Victorian era were dealing with issues of overcrowding in terms of both people and paintings.
“Even in the middle of the 19th century, it was generally recognized that museums should isolate works of art on walls to avoid overcrowding and to accentuate quality for visitors,” Andrew McClellan, a professor of art history at Tufts University, told me. “It was recognized that crowded walls hampered proper appreciation of individual works of art.” As English economist William Stanley Jevons put it in an 1881–82 essay, “the general mental state produced by such vast displays is one of perplexity and vagueness, together with some impression of sore feet and aching heads.”
Taking note of these criticisms, the National Gallery in London began to experiment with picture placement in the mid-1800s. . .
NY Times invents a Biden scandal — and the public’s reaction
Jamison Foser writes at Finding Gravity:
When New York Times chief White House correspondent Peter Baker tweeted yesterday that the discovery of classified documents at Joe Biden’s personal office and home, though “markedly different” from Donald Trump’s mishandling of classified documents, would nevertheless inoculate Trump from criticism, it wasn’t hard to spot the flaw in Baker’s reasoning. NYU journalism professor Jay Rosen responded to Baker:
Rosen’s critique of the “savvy style,” is spot on — as far as it goes. But here it’s missing an essential element. Baker isn’t just telling us perception matters more than truth — he is actively shaping perception, not merely observing or predicting it.
Look back at Baker’s tweet: “Democrats will now have a hard time using Trump’s mishandling of classified papers against him, even though the particulars of the two cases are markedly different.” Stop and think about that for a second. Why would this be true? If the two cases are “markedly different,” why would Democrats “have a hard time using Trump’s mishandling of classified papers against him”? The only way that makes sense is if the public wrongly perceives the two cases to be similar, rather than markedly different. And how does the public learn about the two cases? Well, in large part from journalists like Peter Baker. So if journalists like Peter Baker treat the cases as markedly different (as Peter Baker knows they are), the public will perceive them as markedly different, and Democrats won’t have any trouble using Trump’s mishandling of classified papers against him. But of course Baker isn’t treating them like they’re markedly different. He’s treating the Biden discovery as a huge problem for Biden, and a reprieve for Trump. And by doing that, he might indeed help cause the public to wrongly perceive the two cases to be similar. Baker is, in effect, both predicting the consequences of Baker’s own bad journalism (though he of course omits his role and treats the consequences as things that will just inevitably happen all on their own) and helping bring them about.
It isn’t just Peter Baker, of course. Baker’s tweet reflects the core thesis that has driven the New York Times’ coverage of the Biden documents from the very beginning. From January 9 to January 24, the Times’ news side has generated 19 articles plus four videos, a podcast, and a slideshow
about the discovery of classified documents at Biden’s home and foundation office. More than an article per day for two weeks — a volume of coverage that itself misleads the public about how important this is. I reviewed each one of those articles this morning, and two things immediately jumped out:
- From the very beginning — literally from the first article to the most recent, and nearly every piece in between — the Times has grudgingly acknowledged that the Trump and Biden document situations are very different. Because they are.
- From the very beginning — literally from the first article to the most recent, and nearly every piece in between — the Times has asserted that the Biden document discovery, although entirely different from the Trump document scandal, will be politically damaging to Biden and inoculate Trump from criticism.
Rather than . . .
BBS for a BBS result, and Hairy Crab Oolong for the tea
Today’s shaving soap, Extro 17 Stormo, has an interesting fragrance: “Woody, aromatic fragrance … with top notes of black pepper and with hints of heliotropes, resins, and coffee and with a background of incense, oud, amber, musk, and red pepper.” The soap is relatively soft and gray in color, and it makes an extremely nice lather, helped today by my Simpson Emperor 3 Super.
The container is a heavy (i.e., quite thick) glass jar, a format I like and that one sees also in The Dead Sea shaving soap by RazoRock and in the Meißner Tremonia line. Barrister & Mann also used glass jars (and may still use them) — I have two Reserve shaving soaps in squat glass jars — but these jars are not nearly so thick or heavy as the others mentioned. I was at first taken aback by the heft of the sturdy, thick glass, but not I like it a lot. The Extro soaps provide another option for those who favor glass over plastic for their shaving soaps. (It may be a coincidence, but all the shaving soaps I’ve tried that come in glass jars are superior shaving soaps.)
The razor today is RazoRock’s redoubtable stainless-steel BBS, a remarkably good razor, both comfortable and efficient, that easily produce a totally smooth outcome after three enjoyable passes.
Irisch Moos was the aftershave, and the fragrance seemed especially vivid and pleasant this morning. I applied a good splash with a couple of squirts of Grooming Dept’s Aion Hydrating Gel.
The tea this morning is Murchie’s Hairy Crab Oolong, a tea that has a remarkable sweetness: ” this semi-fermented Oolong tea has a lovely ripe peach overtone and a fragrance comparable to that of Jasmine.”
Later On 