#Francis Crick Institute

[thepastisalreadywritten]

4 June 2024

[theroyalsandi]

STATE VISIT BY THE EMPEROR AND EMPRESS OF JAPAN Tuesday 25th - Thursday 27th June 2024

Their Majesties The Emperor and Empress of Japan will pay a State Visit to the United Kingdom as guests of His Majesty The King from Tuesday 25th to Thursday 27th June 2024.

Their Majesties The King and Queen will host the State Visit at Buckingham Palace.

STATE VISIT PROGRAMME:

SATURDAY 22nd JUNE • The Emperor and Empress of Japan will arrive privately in the United Kingdom on the afternoon of Saturday 22nd June at Stansted Airport. • Their Majesties will be greeted by His Excellency Mr Hajime Hayashi, Ambassador of Japan. The Viscount Brookeborough KG, Lord-in-Waiting, will greet Their Majesties on behalf of The King.

SUNDAY 23rd JUNE AND MONDAY 24TH JUNE • Before the State Visit formally commences, the Emperor will conduct a private programme of engagements, including a visit to Japan House and the Thames Barrier.

TUESDAY 25th JUNE • His Royal Highness The Prince of Wales will greet the Emperor and Empress of Japan, at their hotel, on behalf of The King on Tuesday morning. • His Royal Highness will travel with the Emperor and Empress to Horse Guards Parade, where Their Majesties will receive a Ceremonial Welcome. • The King and Queen will formally welcome the Emperor and Empress at the Royal Pavilion on Horse Guards Parade. Presentations will be made, the Guard of Honour will give a Royal Salute and the Japanese National Anthem will be played. • The King and Queen will formally welcome the Emperor and Empress at the Royal Pavilion on Horse Guards Parade. Presentations will be made, the Guard of Honour will give a Royal Salute and the Japanese National Anthem will be played. • The Emperor, accompanied by The King, will then inspect the Guard of Honour, formed of the 1st Battalion Welsh Guards with the Band of the Welsh Guards. Afterwards, the Emperor and Empress will join The King and Queen, and The Prince of Wales, in a carriage procession along The Mall to Buckingham Palace, where they will be met by a second Guard of Honour formed of the 1st Battalion Welsh Guards. • Following a lunch at Buckingham Palace, given by The King, His Majesty will invite the Emperor and Empress to view a special exhibition in the Picture Gallery of items from the Royal Collection relating to Japan. • In the afternoon, the Emperor and Empress will visit Westminster Abbey, where the Emperor will lay a wreath at the Grave of the Unknown Warrior. Their Majesties will take a tour of the Abbey, accompanied by the Dean of Westminster. • In the evening, The King, accompanied by The Queen and Members of the Royal Family, will give a State Banquet at Buckingham Palace for The Emperor and Empress of Japan. Speeches will be made by The King and the Emperor at the beginning of the banquet.

WEDNESDAY 26th JUNE • The Emperor will visit The Francis Crick Institute, the UK's flagship biomedical research centre. The Institute supports an innovative UK-Japan research partnership which covers a range of public health issues, including cancer, vaccines, and the role of genetics in infectious diseases. • That evening, The Emperor of Japan, joined by Their Royal Highnesses The Duke and Duchess of Edinburgh, will attend a Banquet at the Guildhall given by the Lord Mayor and City of London Corporation. The Lord Mayor and The Emperor will both make speeches at the end of the banquet.

THURSDAY 27th JUNE • The Emperor and Empress of Japan will formally bid farewell to The King and Queen at Buckingham Palace on the morning of the final day of the official State Visit programme. • The Emperor and Empress will travel to Young V&A, part of the V&A family of museums dedicated to the power of creativity around the world, where the museum's Japan: Myths to Manga exhibition is currently on display. • The Emperor will privately visit St. George's Chapel, Windsor Castle, to lay a wreath on the tomb of Queen Elizabeth II, in the King George VI Chapel. The Garter Banners of the current members of the Order of the Garter, including the banner belonging to • His Majesty's father, Emperor Emeritus Akihito, are displayed in the Quire of St. George's Chapel. • Later that afternoon, His Majesty the Emperor will tour the historic Temperate House at the Royal Botanic Gardens, Kew. The Millennium Seed Bank, coordinated by Kew is the world's largest collection of over 2.4 billion wild plant seeds spanning 97 countries, preserving Japanese and international biodiversity. Bronze Bonsai sculptures by artist Marc Quinn are currently displayed in the Temperate House, surrounded by a display of Bonsai trees from Kew's collection.

FRIDAY 28th JUNE • On their final day in the UK, The Emperor and Empress of Japan will visit Oxford for a private programme of engagements including a visit to the colleges where Their Majesties studied. • At the conclusion of the visit, The Lord Chamberlain will bid farewell to the Emperor and Empress on behalf of The King, before they depart from RAF Brize Norton.

[reasonsforhope]

"Scientists have created mice with two biological fathers by generating eggs from male cells, a development that opens up radical new possibilities for reproduction.

The advance could ultimately pave the way for treatments for severe forms of infertility, as well as raising the tantalising prospect of same-sex couples being able to have a biological child together in the future.

“This is the first case of making robust mammal oocytes [a.k.a. egg cells] from male cells,” said Katsuhiko Hayashi, who led the work at Kyushu University in Japan and is internationally renowned as a pioneer in the field of lab-grown eggs and sperm.

Hayashi, who presented the development at the Third International Summit on Human Genome Editing at the Francis Crick Institute in London on Wednesday, predicts that it will be technically possible to create a viable human egg from a male skin cell within a decade. Others suggested this timeline was optimistic given that scientists are yet to create viable lab-grown human eggs from female cells.

Previously scientists have created mice that technically had two biological fathers through a chain of elaborate steps, including genetic engineering. However, this is the first time viable eggs have been cultivated from male cells and marks a significant advance. Hayashi’s team is now attempting to replicate this achievement with human cells, although there would be significant hurdles for the use of lab-grown eggs for clinical purposes, including establishing their safety.

“Purely in terms of technology, it will be possible [in humans] even in 10 years,” he said, adding that he personally would be in favour of the technology being used clinically to allow two men to have a baby if it were shown to be safe.

“I don’t know whether they’ll be available for reproduction,” he said. “That is not a question just for the scientific programme, but also for [society].”

The technique could also be applied to treat severe forms of infertility, including women with Turner’s syndrome, in whom one copy of the X chromosome is missing or partly missing, and Hayashi said this application was the primary motivation for the research.

Others suggested that it could prove challenging to translate the technique to human cells. Human cells require much longer periods of cultivation to produce a mature egg, which can increase the risk of cells acquiring unwanted genetic changes.

Prof George Daley, the dean of Harvard Medical School, described the work as “fascinating”, but added that other research had indicated that creating lab-grown gametes from human cells was more challenging than for mouse cells. “We still don’t understand enough of the unique biology of human gametogenesis to reproduce Hayashi’s provocative work in mice,” he said.

Study Methods

The study, which has been submitted for publication in a leading journal, relied on a sequence of intricate steps to transform a skin cell, carrying the male XY chromosome combination, into an egg, with the female XX version.

Male skin cells were reprogrammed into a stem cell-like state to create so-called induced pluripotent stem (iPS) cells. The Y-chromosome of these cells was then deleted and replaced by an X chromosome “borrowed” from another cell to produce iPS cells with two identical X chromosomes.

“The trick of this, the biggest trick, is the duplication of the X chromosome,” said Hayashi. “We really tried to establish a system to duplicate the X chromosome.”

Finally, the cells were cultivated in an ovary organoid, a culture system designed to replicate the conditions inside a mouse ovary. When the eggs were fertilised with normal sperm, the scientists obtained about 600 embryos, which were implanted into surrogate mice, resulting in the birth of seven mouse pups. The efficiency of about 1% was lower [although not THAT much lower] than the efficiency achieved with normal female-derived eggs, where about 5% of embryos went on to produce a live birth.

The baby mice appeared healthy, had a normal lifespan, and went on to have offspring as adults. “They look OK, they look to be growing normally, they become fathers,” said Hayashi.

Going Further

He and colleagues are now attempting to replicate the creation of lab-grown eggs using human cells.

Prof Amander Clark, who works on lab-grown gametes at the University of California Los Angeles, said that translating the work into human cells would be a “huge leap”, because scientists are yet to create lab-grown human eggs from female cells.

Scientists have created the precursors of human eggs, but until now the cells have stopped developing before the point of meiosis, a critical step of cell division that is required in the development of mature eggs and sperm. “We’re poised at this bottleneck at the moment,” she said. “The next steps are an engineering challenge. But getting through that could be 10 years or 20 years.”

-via The Guardian (US), 3/8/23

[religion-is-a-mental-illness]

By: James B. Meigs

Published: Spring 2024

Michael Shermer got his first clue that things were changing at Scientific American in late 2018. The author had been writing his “Skeptic” column for the magazine since 2001. His monthly essays, aimed at an audience of both scientists and laymen, championed the scientific method, defended the need for evidence-based debate, and explored how cognitive and ideological biases can derail the search for truth. Shermer’s role models included two twentieth-century thinkers who, like him, relished explaining science to the public: Carl Sagan, the ebullient astronomer and TV commentator; and evolutionary biologist Stephen Jay Gould, who wrote a popular monthly column in Natural History magazine for 25 years. Shermer hoped someday to match Gould’s record of producing 300 consecutive columns. That goal would elude him.

In continuous publication since 1845, Scientific American is the country’s leading mainstream science magazine. Authors published in its pages have included Albert Einstein, Francis Crick, Jonas Salk, and J. Robert Oppenheimer—some 200 Nobel Prize winners in all. SciAm, as many readers call it, had long encouraged its authors to challenge established viewpoints. In the mid-twentieth century, for example, the magazine published a series of articles building the case for the then-radical concept of plate tectonics. In the twenty-first century, however, American scientific media, including Scientific American, began to slip into lockstep with progressive beliefs. Suddenly, certain orthodoxies—especially concerning race, gender, or climate—couldn’t be questioned.

“I started to see the writing on the wall toward the end of my run there,” Shermer told me. “I saw I was being slowly nudged away from certain topics.” One month, he submitted a column about the “fallacy of excluded exceptions,” a common logical error in which people perceive a pattern of causal links between factors but ignore counterexamples that don’t fit the pattern. In the story, Shermer debunked the myth of the “horror-film curse,” which asserts that bad luck tends to haunt actors who appear in scary movies. (The actors in most horror films survive unscathed, he noted, while bad luck sometimes strikes the casts of non-scary movies as well.) Shermer also wanted to include a serious example: the common belief that sexually abused children grow up to become abusers in turn. He cited evidence that “most sexually abused children do not grow up to abuse their own children” and that “most abusive parents were not abused as children.” And he observed how damaging this stereotype could be to abuse survivors; statistical clarity is all the more vital in such delicate cases, he argued. But Shermer’s editor at the magazine wasn’t having it. To the editor, Shermer’s effort to correct a common misconception might be read as downplaying the seriousness of abuse. Even raising the topic might be too traumatic for victims.

The following month, Shermer submitted a column discussing ways that discrimination against racial minorities, gays, and other groups has diminished (while acknowledging the need for continued progress). Here, Shermer ran into the same wall that Better Angels of Our Nature author Steven Pinker and other scientific optimists have faced. For progressives, admitting that any problem—racism, pollution, poverty—has improved means surrendering the rhetorical high ground. “They are committed to the idea that there is no cumulative progress,” Shermer says, and they angrily resist efforts to track the true prevalence, or the “base rate,” of a problem. Saying that “everything is wonderful and everyone should stop whining doesn’t really work,” his editor objected.

Shermer dug his grave deeper by quoting Manhattan Institute fellow Heather Mac Donald and The Coddling of the American Mind authors Greg Lukianoff and Jonathan Haidt, who argue that the rise of identity-group politics undermines the goal of equal rights for all. Shermer wrote that intersectional theory, which lumps individuals into aggregate identity groups based on race, sex, and other immutable characteristics, “is a perverse inversion” of Martin Luther King’s dream of a color-blind society. For Shermer’s editors, apparently, this was the last straw. The column was killed and Shermer’s contract terminated. Apparently, SciAm no longer had the ideological bandwidth to publish such a heterodox thinker.

American journalism has never been very good at covering science. In fact, the mainstream press is generally a cheap date when it comes to stories about alternative medicine, UFO sightings, pop psychology, or various forms of junk science. For many years, that was one factor that made Scientific American’s rigorous reporting so vital. The New York Times, National Geographic, Smithsonian, and a few other mainstream publications also produced top-notch science coverage. Peer-reviewed academic journals aimed at specialists met a higher standard still. But over the past decade or so, the quality of science journalism—even at the top publications—has declined in a new and alarming way. Today’s journalistic failings don’t owe simply to lazy reporting or a weakness for sensationalism but to a sweeping and increasingly pervasive worldview.

It is hard to put a single name on this sprawling ideology. It has its roots both in radical 1960s critiques of capitalism and in the late-twentieth-century postmodern movement that sought to “problematize” notions of objective truth. Critical race theory, which sees structural racism as the grand organizing principle of our society, is one branch. Queer studies, which seeks to “deconstruct” traditional norms of family, sex, and gender, is another. Critics of this worldview sometimes call it “identity politics”; supporters prefer the term “intersectionality.” In managerial settings, the doctrine lives under the label of diversity, equity, and inclusion, or DEI: a set of policies that sound anodyne—but in practice, are anything but.

This dogma sees Western values, and the United States in particular, as uniquely pernicious forces in world history. And, as exemplified by the anticapitalist tirades of climate activist Greta Thunberg, the movement features a deep eco-pessimism buoyed only by the distant hope of a collectivist green utopia.

The DEI worldview took over our institutions slowly, then all at once. Many on the left, especially journalists, saw Donald Trump’s election in 2016 as an existential threat that necessitated dropping the guardrails of balance and objectivity. Then, in early 2020, Covid lockdowns put American society under unbearable pressure. Finally, in May 2020, George Floyd’s death under the knee of a Minneapolis police officer provided the spark. Protesters exploded onto the streets. Every institution, from coffeehouses to Fortune 500 companies, felt compelled to demonstrate its commitment to the new “antiracist” ethos. In an already polarized environment, most media outlets lunged further left. Centrists—including New York Times opinion editor James Bennet and science writer Donald G. McNeil, Jr.—were forced out, while radical progressive voices were elevated.

This was the national climate when Laura Helmuth took the helm of Scientific American in April 2020. Helmuth boasted a sterling résumé: a Ph.D. in cognitive neuroscience from the University of California–Berkeley and a string of impressive editorial jobs at outlets including Science, National Geographic, and the Washington Post. Taking over a large print and online media operation during the early weeks of the Covid pandemic couldn’t have been easy. On the other hand, those difficult times represented a once-in-a-lifetime opportunity for an ambitious science editor. Rarely in the magazine’s history had so many Americans urgently needed timely, sensible science reporting: Where did Covid come from? How is it transmitted? Was shutting down schools and businesses scientifically justified? What do we know about vaccines?

Scientific American did examine Covid from various angles, including an informative July 2020 cover story diagramming how the SARS-CoV-2 virus “sneaks inside human cells.” But the publication didn’t break much new ground in covering the pandemic. When it came to assessing growing evidence that Covid might have escaped from a laboratory, for example, SciAm got scooped by New York and Vanity Fair, publications known more for their coverage of politics and entertainment than of science.

At the same time, SciAm dramatically ramped up its social-justice coverage. The magazine would soon publish a flurry of articles with titles such as “Modern Mathematics Confronts Its White, Patriarchal Past” and “The Racist Roots of Fighting Obesity.” The death of the twentieth century’s most acclaimed biologist was the hook for “The Complicated Legacy of E. O. Wilson,” an opinion piece arguing that Wilson’s work was “based on racist ideas,” without quoting a single line from his large published canon. At least those pieces had some connection to scientific topics, though. In 2021, SciAm published an opinion essay, “Why the Term ‘JEDI’ Is Problematic for Describing Programs That Promote Justice, Equity, Diversity, and Inclusion.” The article’s five authors took issue with the effort by some social-justice advocates to create a cute new label while expanding the DEI acronym to include “Justice.” The Jedi knights of the Star Wars movies are “inappropriate mascots for social justice,” the authors argued, because they are “prone to (white) saviorism and toxically masculine approaches to conflict resolution (violent duels with phallic light sabers, gaslighting by means of ‘Jedi mind tricks,’ etc.).” What all this had to do with science was anyone’s guess.

Several prominent scientists took note of SciAm’s shift. “Scientific American is changing from a popular-science magazine into a social-justice-in-science magazine,” Jerry Coyne, a University of Chicago emeritus professor of ecology and evolution, wrote on his popular blog, “Why Evolution Is True.” He asked why the magazine had “changed its mission from publishing decent science pieces to flawed bits of ideology.”

“The old Scientific American that I subscribed to in college was all about the science,” University of New Mexico evolutionary psychologist Geoffrey Miller told me. “It was factual reporting on new ideas and findings from physics to psychology, with a clear writing style, excellent illustrations, and no obvious political agenda.” Miller says that he noticed a gradual change about 15 years ago, and then a “woke political bias that got more flagrant and irrational” over recent years. The leading U.S. science journals, Nature and Science, and the U.K.-based New Scientist made a similar pivot, he says. By the time Trump was elected in 2016, he says, “the Scientific American editors seem to have decided that fighting conservatives was more important than reporting on science.”

Scientific American’s increasing engagement in politics drew national attention in late 2020, when the magazine, for the first time in its 175-year history, endorsed a presidential candidate. “The evidence and the science show that Donald Trump has badly damaged the U.S. and its people,” the editors wrote. “That is why we urge you to vote for Joe Biden.” In an e-mail exchange, Scientific American editor-in-chief Helmuth said that the decision to endorse Biden was made unanimously by the magazine’s staff. “Overall, the response was very positive,” she said. Helmuth also pushed back on the idea that getting involved in political battles represented a new direction for SciAm. “We have a long and proud history of covering the social and political angles of science,” she said, noting that the magazine “has advocated for teaching evolution and not creationism since we covered the Scopes Monkey Trial.”

Scientific American wasn’t alone in endorsing a presidential candidate in 2020. Nature also endorsed Biden in that election cycle. The New England Journal of Medicine indirectly did the same, writing that “our current leaders have demonstrated that they are dangerously incompetent” and should not “keep their jobs.” Vinay Prasad, the prominent oncologist and public-health expert, recently lampooned the endorsement trend on his Substack, asking whether science journals will tell him who to vote for again in 2024. “Here is an idea! Call it crazy,” he wrote: “Why don’t scientists focus on science, and let politics decide the election?” When scientists insert themselves into politics, he added, “the only result is we are forfeiting our credibility.”

But what does it mean to “focus on science”? Many of us learned the standard model of the scientific method in high school. We understand that science attempts—not always perfectly—to shield the search for truth from political interference, religious dogmas, or personal emotions and biases. But that model of science has been under attack for half a century. The French theorist Michel Foucault argued that scientific objectivity is an illusion produced and shaped by society’s “systems of power.” Today’s woke activists challenge the legitimacy of science on various grounds: the predominance of white males in its history, the racist attitudes held by some of its pioneers, its inferiority to indigenous “ways of knowing,” and so on. Ironically, as Christopher Rufo points out in his book America’s Cultural Revolution, this postmodern ideology—which began as a critique of oppressive power structures—today empowers the most illiberal, repressive voices within academic and other institutions.

Shermer believes that the new style of science journalism “is being defined by this postmodern worldview, the idea that all facts are relative or culturally determined.” Of course, if scientific facts are just products of a particular cultural milieu, he says, “then everything is a narrative that has to reflect some political side.” Without an agreed-upon framework to separate valid from invalid claims—without science, in other words—people fall back on their hunches and in-group biases, the “my-side bias.”

Traditionally, science reporting was mostly descriptive—writers strove to explain new discoveries in a particular field. The new style of science journalism takes the form of advocacy—writers seek to nudge readers toward a politically approved opinion.

“Lately journalists have been behaving more like lawyers,” Shermer says, “marshaling evidence in favor of their own view and ignoring anything that doesn’t help their argument.” This isn’t just the case in science journalism, of course. Even before the Trump era, the mainstream press boosted stories that support left-leaning viewpoints and carefully avoided topics that might offer ammunition to the Right. Most readers understand, of course, that stories about politics are likely to be shaped by a media outlet’s ideological slant. But science is theoretically supposed to be insulated from political influence. Sadly, the new woke style of science journalism reframes factual scientific debates as ideological battles, with one side presumed to be morally superior. Not surprisingly, the crisis in science journalism is most obvious in the fields where public opinion is most polarized.

The Covid pandemic was a crisis not just for public health but for the public’s trust in our leading institutions. From Anthony Fauci on down, key public-health officials issued unsupported policy prescriptions, fudged facts, and suppressed awkward questions about the origin of the virus. A skeptical, vigorous science press could have done a lot to keep these officials honest—and the public informed. Instead, even elite science publications mostly ran cover for the establishment consensus. For example, when Stanford’s Jay Bhattacharya and two other public-health experts proposed an alternative to lockdowns in their Great Barrington Declaration, media outlets joined in Fauci’s effort to discredit and silence them.

Richard Ebright, professor of chemical biology at Rutgers University, is a longtime critic of gain-of-function research, which can make naturally occurring viruses deadlier. From the early weeks of the pandemic, he suspected that the virus had leaked from China’s Wuhan Institute of Virology. Evidence increasingly suggests that he was correct. I asked Ebright how he thought that the media had handled the lab-leak debate. He responded:

Science writers at most major news outlets and science news outlets have spent the last four years obfuscating and misrepresenting facts about the origin of the pandemic. They have done this to protect the scientists, science administrators, and the field of science—gain-of-function research on potential pandemic pathogens—that likely caused the pandemic. They have done this in part because those scientists and science administrators are their sources, . . . in part because they believe that public trust in science would be damaged by reporting the facts, and in part because the origin of the pandemic acquired a partisan political valance after early public statements by Tom Cotton, Mike Pompeo, and Donald Trump.

During the first two years of the pandemic, most mainstream media outlets barely mentioned the lab-leak debate. And when they did, they generally savaged both the idea and anyone who took it seriously. In March 2021, long after credible evidence emerged hinting at a laboratory origin for the virus, Scientific American published an article, “Lab-Leak Hypothesis Made It Harder for Scientists to Seek the Truth.” The piece compared the theory to the KGB’s disinformation campaign about the origin of HIV/AIDS and blamed lab-leak advocates for creating a poisonous climate around the issue: “The proliferation of xenophobic rhetoric has been linked to a striking increase in anti-Asian hate crimes. It has also led to a vilification of the [Wuhan Institute of Virology] and some of its Western collaborators, as well as partisan attempts to defund certain types of research (such as ‘gain of function’ research).” Today we know that the poisonous atmosphere around the lab-leak question was deliberately created by Anthony Fauci and a handful of scientists involved in dangerous research at the Wuhan lab. And the case for banning gain-of-function research has never been stronger.

One of the few science journalists who did take the lab-leak question seriously was Donald McNeil, Jr., the veteran New York Times reporter forced out of the paper in an absurd DEI panic. After leaving the Times—and like several other writers pursuing the lab-leak question—McNeil published his reporting on his own Medium blog. It is telling that, at a time when leading science publications were averse to exploring the greatest scientific mystery of our time, some of the most honest reporting on the topic was published in independent, reader-funded outlets. It’s also instructive to note that the journalist who replaced McNeil on the Covid beat at the Times, Apoorva Mandavilli, showed open hostility to investigating Covid’s origins. In 2021, she famously tweeted: “Someday we will stop talking about the lab leak theory and maybe even admit its racist roots. But alas, that day is not yet here.” It would be hard to compose a better epitaph to the credibility of mainstream science journalism.

As Shermer observed, many science journalists see their role not as neutral reporters but as advocates for noble causes. This is especially true in reporting about the climate. Many publications now have reporters on a permanent “climate beat,” and several nonprofit organizations offer grants to help fund climate coverage. Climate science is an important field, worthy of thoughtful, balanced coverage. Unfortunately, too many climate reporters seem especially prone to common fallacies, including base-rate neglect, and to hyping tenuous data.

The mainstream science press never misses an opportunity to ratchet up climate angst. No hurricane passes without articles warning of “climate disasters.” And every major wildfire seemingly generates a “climate apocalypse” headline. For example, when a cluster of Quebec wildfires smothered the eastern U.S. in smoke last summer, the New York Times called it “a season of climate extremes.” It’s likely that a warming planet will result in more wildfires and stronger hurricanes. But eager to convince the public that climate-linked disasters are rapidly trending upward, journalists tend to neglect the base rate. In the case of Quebec wildfires, for example, 2023 was a fluky outlier. During the previous eight years, Quebec wildfires burned fewer acres than average; then, there was no upward trend—and no articles discussing the paucity of fires. By the same token, according to the U.S. National Hurricane Center, a lower-than-average number of major hurricanes struck the U.S. between 2011 and 2020. But there were no headlines suggesting, say, “Calm Hurricane Seasons Cast Doubt on Climate Predictions.”

Most climate journalists wouldn’t dream of drawing attention to data that challenge the climate consensus. They see their role as alerting the public to an urgent problem that will be solved only through political change.

Similar logic applies to social issues. The social-justice paradigm rests on the notion that racism, sexism, transphobia, and other biases are so deeply embedded in our society that they can be eradicated only through constant focus on the problem. Any people or institutions that don’t participate in this process need to be singled out for criticism. In such an atmosphere, it takes a particularly brave journalist to note exceptions to the reigning orthodoxy.

This dynamic is especially intense in the debates over transgender medicine. The last decade has seen a huge surge in children claiming dissatisfaction with their gender. According to one survey, the number of children aged six to 17 diagnosed with gender dysphoria surged from roughly 15,000 to 42,000 in the years between 2017 and 2021 alone. The number of kids prescribed hormones to block puberty more than doubled. Puberty blockers and other treatments for gender dysphoria have enormous potential lifelong consequences, including sterility, sexual dysfunction, and interference with brain development. Families facing treatment decisions for youth gender dysphoria desperately need clear, objective guidance. They’re not getting it.

Instead, medical organizations and media outlets typically describe experimental hormone treatments and surgeries as routine, and even “lifesaving,” when, in fact, their benefits remain contested, while their risks are enormous. In a series of articles, the Manhattan Institute’s Leor Sapir has documented how trans advocates enforce this appearance of consensus among U.S. scientists, medical experts, and many journalists. Through social-media campaigns and other tools, these activists have forced conferences to drop leading scientists, gotten journals to withdraw scientific papers after publication, and interfered with the distribution of Abigail Shrier’s 2020 book Irreversible Damage, which challenges the wisdom of “gender-affirming care” for adolescent girls. While skeptics are cowed into silence, Sapir concludes, those who advocate fast-tracking children for radical gender therapy “will go down in history as responsible for one of the worst medical scandals in U.S. history.”

In such an overheated environment, it would be helpful to have a journalistic outlet advocating a sober, evidence-based approach. In an earlier era, Scientific American might have been that voice. Unfortunately, SciAm today downplays messy debates about gender therapies, while offering sunny platitudes about the “safety and efficacy” of hormone treatments for prepubescent patients. For example, in a 2023 article, “What Are Puberty Blockers, and How Do They Work?,” the magazine repeats the unsubstantiated claim that such treatments are crucial to preventing suicide among gender-dysphoric children. “These medications are well studied and have been used safely since the late 1980s to pause puberty in adolescents with gender dysphoria,” SciAm states.

The independent journalist Jesse Singal, a longtime critic of slipshod science reporting, demolishes these misleading claims in a Substack post. In fact, the use of puberty blockers to treat gender dysphoria is a new and barely researched phenomenon, he notes: “[W]e have close to zero studies that have tracked gender dysphoric kids who went on blockers over significant lengths of time to see how they have fared.” Singal finds it especially alarming to see a leading science magazine obscure the uncertainty surrounding these treatments. “I believe that this will go down as a major journalistic blunder that will be looked back upon with embarrassment and regret,” he writes.

Fortunately, glimmers of light are shining through on the gender-care controversy. The New York Times has lately begun publishing more balanced articles on the matter, much to the anger of activists. And various European countries have started reassessing and limiting youth hormone treatments. England’s National Health Service recently commissioned the respected pediatrician Hilary Cass to conduct a sweeping review of the evidence supporting youth gender medicine. Her nearly 400-page report is a bombshell, finding that evidence supporting hormone interventions for children is “weak,” while the long-term risks of such treatments have been inadequately studied. “For most young people,” the report concludes, “a medical pathway will not be the best way to manage their gender-related distress.” In April, the NHS announced that it will no longer routinely prescribe puberty blocking drugs to children.

Scientific American has yet to offer an even-handed review of the new scientific skepticism toward aggressive gender medicine. Instead, in February, the magazine published an opinion column, “Pseudoscience Has Long Been Used to Oppress Transgender People.” Shockingly, it argues for even less medical caution in dispensing radical treatments. The authors approvingly note that “many trans activists today call for diminishing the role of medical authority altogether in gatekeeping access to trans health care,” arguing that patients should have “access to hormones and surgery on demand.” And, in an implicit warning to anyone who might question these claims and goals, the article compares today’s skeptics of aggressive gender medicine to Nazi eugenicists and book burners. Shortly after the Cass report’s release, SciAm published an interview with two activists who argue that scientists questioning trans orthodoxy are conducting “epistemological violence.”

There’s nothing wrong with vigorous debate over scientific questions. In fact, in both science and journalism, adversarial argumentation is a vital tool in testing claims and getting to the truth. “A bad idea can hover in the ether of a culture if there is no norm for speaking out,” Shermer says. Where some trans activists cross the line is in trying to derail debate by shaming and excluding anyone who challenges the activists’ manufactured consensus.

Such intimidation has helped enforce other scientific taboos. Anthony Fauci called the scientists behind the Great Barrington Declaration “fringe epidemiologists” and successfully lobbied to censor their arguments on social media. Climate scientists who diverge from the mainstream consensus struggle to get their research funded or published. The claim that implicit racial bias unconsciously influences our minds has been debunked time and again—but leading science magazines keep asserting it.

Scientists and journalists aren’t known for being shrinking violets. What makes them tolerate this enforced conformity? The intimidation described above is one factor. Academia and journalism are both notoriously insecure fields; a single accusation of racism or anti-trans bias can be a career ender. In many organizations, this gives the youngest, most radical members of the community disproportionate power to set ideological agendas.

“Scientists, science publishers, and science journalists simply haven’t learned how to say no to emotionally unhinged activists,” evolutionary psychologist Miller says. “They’re prone to emotional blackmail, and they tend to be very naive about the political goals of activists who claim that scientific finding X or Y will ‘impose harm’ on some group.”

But scientists may also have what they perceive to be positive motives to self-censor. A fascinating recent paper concludes: “Prosocial motives underlie scientific censorship by scientists.” The authors include a who’s who of heterodox thinkers, including Miller, Manhattan Institute fellow Glenn Loury, Pamela Paresky, John McWhorter, Steven Pinker, and Wilfred Reilly. “Our analysis suggests that scientific censorship is often driven by scientists, who are primarily motivated by self-protection, benevolence toward peer scholars, and prosocial concerns for the well-being of human social groups,” they write.

Whether motivated by good intentions, conformity, or fear of ostracization, scientific censorship undermines both the scientific process and public trust. The authors of the “prosocial motives” paper point to “at least one obvious cost of scientific censorship: the suppression of accurate information.” When scientists claim to represent a consensus about ideas that remain in dispute—or avoid certain topics entirely—those decisions filter down through the journalistic food chain. Findings that support the social-justice worldview get amplified in the media, while disapproved topics are excoriated as disinformation. Not only do scientists lose the opportunity to form a clearer picture of the world; the public does, too. At the same time, the public notices when claims made by health officials and other experts prove to be based more on politics than on science. A new Pew Research poll finds that the percentage of Americans who say that they have a “great deal” of trust in scientists has fallen from 39 percent in 2020 to 23 percent today.

“Whenever research can help inform policy decisions, it’s important for scientists and science publications to share what we know and how we know it,” Scientific American editor Helmuth says. “This is especially true as misinformation and disinformation are spreading so widely.” That would be an excellent mission statement for a serious science publication. We live in an era when scientific claims underpin huge swaths of public policy, from Covid to climate to health care for vulnerable youths. It has never been more vital to subject those claims to rigorous debate.

Unfortunately, progressive activists today begin with their preferred policy outcomes or ideological conclusions and then try to force scientists and journalists to fall in line. Their worldview insists that, rather than challenging the progressive orthodoxy, science must serve as its handmaiden. This pre-Enlightenment style of thinking used to hold sway only in radical political subcultures and arcane corners of academia. Today it is reflected even in our leading institutions and science publications. Without a return to the core principles of science—and the broader tradition of fact-based discourse and debate—our society risks drifting onto the rocks of irrationality.

[ Via: https://archive.today/j03w3 ]

==

Scientific American now embodies the worst of far-left anti-science nonsense.

[usa-journal]

Breakthrough in Fly Brain Research Paves Way for Understanding Human Cognition

Scientists have achieved a monumental breakthrough by mapping the fly brain, revealing the position, shape, and connections of all its 130,000 cells and 50 million intricate connections. This research represents the most detailed analysis of an adult animal's brain to date and is being hailed as a "huge leap" in understanding human cognition.

The fly's brain, though tiny, supports a range of complex behaviors, including walking, hovering, and even producing mating songs. Dr. Gregory Jefferis, a leader in the research from the Medical Research Council's Laboratory of Molecular Biology in Cambridge, emphasizes that this mapping could illuminate the mechanisms behind thought processes in humans. He noted the lack of understanding about how brain cell networks facilitate our interactions with the world.

Despite humans having a million times more neurons than the fruit fly, the new wiring diagram, or connectome, will aid scientists in deciphering cognitive functions. Published in the journal Nature, the imagery showcases a stunningly complex structure that reveals how a small organ can perform powerful computational tasks.

Dr. Mala Murthy, co-leader of the project from Princeton University, stated that this connectome will be transformative for neuroscientists, allowing for a better understanding of healthy brain function and the potential to compare it with malfunctioning brains.

Dr. Lucia Prieto Godino from the Francis Crick Institute supports this view, highlighting that while simpler organisms like worms and maggots have had their connectomes mapped, the fly’s intricate wiring is a significant achievement. This success paves the way for mapping larger brains, potentially leading to a human connectome in the future.

The research team has successfully identified separate circuits for various functions, illustrating how movement-related circuits are positioned at the base of the brain, while those responsible for vision are located on the sides. The study not only identifies these circuits but also explains their connections, enhancing our understanding of neural processing.

Interestingly, researchers are already applying these circuit diagrams to understand why flies are so hard to catch. The wiring related to vision quickly processes incoming threats, sending signals to the fly's legs to jump away faster than conscious thought.

To create the wiring diagram, researchers used a technique involving slicing the fly brain into 7,000 incredibly thin pieces, photographing each slice, and digitally reconstructing the whole. They employed artificial intelligence to analyze neuron shapes and connections, correcting over three million errors manually.

Dr. Philipp Schlegel from the Medical Research Council highlights that this data serves as a comprehensive map of brain connectivity, akin to a detailed Google Maps for the neural networks. This combined information will facilitate countless discoveries in neuroscience in the coming years.

While a human connectome remains elusive due to the complexity of the human brain, researchers believe that advancements in technology may allow for such mapping in about three decades. The fly brain research marks a significant step toward unlocking the mysteries of human cognition and understanding our own minds better.

The study was conducted by the FlyWire Consortium, an international collaboration of scientists dedicated to advancing neuroscience.

[aimeedaisies]

STATE VISIT BY THE EMPEROR AND EMPRESS OF JAPAN

Tuesday 25th - Thursday 27th June 2024

Their Majesties The Emperor and Empress of Japan will pay a State Visit to the United Kingdom as guests of His Majesty The King from Tuesday 25th to Thursday 27th June 2024.

SATURDAY 22nd JUNE

The Emperor and Empress of Japan will arrive privately in the United Kingdom on the afternoon of Saturday 22nd June at Stansted Airport.

Their Majesties will be greeted by His Excellency Mr Hajime Hayashi, Ambassador of Japan. The Viscount Brookeborough KG, Lord-in-Waiting, will greet Their Majesties on behalf of The King.

SUNDAY 23rd JUNE AND MONDAY 24th JUNE

Before the State Visit formally commences, the Emperor will conduct a private programme of engagements, including a visit to Japan House and the Thames Barrier.

TUESDAY 25th JUNE

His Royal Highness The Prince of Wales will greet the Emperor and Empress of Japan, at their hotel, on behalf of The King on Tuesday morning.

His Royal Highness will travel with the Emperor and Empress to Horse Guards Parade, where Their Majesties will receive a Ceremonial Welcome.

The King and Queen will formally welcome the Emperor and Empress at the Royal Pavilion on Horse Guards Parade. Presentations will be made, the Guard of Honour will give a Royal Salute and the Japanese National Anthem will be played.

The Emperor, accompanied by The King, will then inspect the Guard of Honour, formed of the 1st Battalion Welsh Guards with the Band of the Welsh Guards. Afterwards, the Emperor and Empress will join The King and Queen, and The Prince of Wales, in a carriage procession along The Mall to Buckingham Palace, where they will be met by a second Guard of Honour formed of the 1st Battalion Welsh Guards.

Following a lunch at Buckingham Palace, given by The King, His Majesty will invite the Emperor and Empress to view a special exhibition in the Picture Gallery of items from the Royal Collection relating to Japan.

In the afternoon, the Emperor and Empress will visit Westminster Abbey, where the Emperor will lay a wreath at the Grave of the Unknown Warrior. Their Majesties will take a tour of the Abbey, accompanied by the Dean of Westminster.

In the evening, The King, accompanied by The Queen and Members of the Royal Family, will give a State Banquet at Buckingham Palace for The Emperor and Empress of Japan. Speeches will be made by The King and the Emperor at the beginning of the banquet.

WEDNESDAY 26th JUNE

The Emperor will visit The Francis Crick Institute, the UK's flagship biomedical research centre.

The Institute supports an innovative UK-Japan research partnership which covers a range of public health issues, including cancer, vaccines, and the role of genetics in infectious diseases.

That evening, The Emperor of Japan, joined by Their Royal Highnesses The Duke and Duchess of Edinburgh, will attend a Banquet at the Guildhall given by the Lord Mayor and City of London Corporation. The Lord Mayor and The Emperor will both make speeches at the end of the banquet.

THURSDAY 27th JUNE

The Emperor and Empress of Japan will formally bid farewell to The King and Queen at Buckingham Palace on the morning of the final day of the official State Visit programme.

The Emperor and Empress will travel to Young V&A, part of the V&A family of museums dedicated to the power of creativity around the world, where the museum's Japan: Myths to Manga exhibition is currently on display.

The Emperor will privately visit St. George's Chapel, Windsor Castle, to lay a wreath on the tomb of Queen Elizabeth Il, in the King George VI Chapel. The Garter Banners of the current members of the Order of the Garter, including the banner belonging to His Majesty's father, Emperor Emeritus Akihito, are displayed in the Quire of St. George's Chapel.

Later that afternoon, His Majesty the Emperor will tour the historic Temperate House at the Royal Botanic Gardens, Kew. The Millennium Seed Bank, coordinated by Kew is the world's largest collection of over 2.4 billion wild plant seeds spanning 97 countries, preserving Japanese and international biodiversity. Bronze Bonsai sculptures by artist Marc Quinn are currently displayed in the Temperate House, surrounded by a display of Bonsai trees from Kew's collection.

FRIDAY 28th JUNE

On their final day in the UK, The Emperor and Empress of Japan will visit Oxford for a private programme of engagements including a visit to the colleges where Their Majesties studied.

At the conclusion of the visit, The Lord Chamberlain will bid farewell to the Emperor and Empress on behalf of The King, before they depart from RAF Brize Norton.

[mckitterick]

Scientists create synthetic human embryos

from the exclusive Guardian story:

Using stem cells, scientists have created synthetic human embryos in a groundbreaking advance that sidesteps the need for eggs or sperm.

Scientists say these model embryos, which resemble those in the earliest stages of human development, could provide a crucial window on the impact of genetic disorders and the biological causes of recurrent miscarriage.

The work also raises serious ethical and legal issues, as the lab-grown entities fall outside current legislation in most countries.

Prof Magdalena Żernicka-Goetz, of the U of Cambridge and the California Institute of Technology, described the work in a plenary address at the International Society for Stem Cell Research’s annual meeting in Boston.

“We can create human embryo-like models by the reprogramming of embryonic stem cells,” she told the meeting.

There is no near-term prospect of the synthetic embryos being used clinically. It would be illegal to implant them into a patient’s womb, and it is not yet clear whether these structures have the potential to continue maturing beyond the earliest stages of development.

Previously, Żernicka-Goetz’s team and a rival group at the Weizmann Institute in Israel showed that stem cells from mice could be encouraged to self-assemble into early embryonic structures with an intestinal tract, the beginnings of a brain, and a beating heart. Since then, a race has been under way to translate this work into human models, and several teams have been able to replicate the very earliest stages of development.

In April, researchers in China created synthetic embryos from monkey cells and implanted them into the wombs of adult monkeys, a few of which showed initial signs of pregnancy but none of which developed beyond a few days. Scientists say it is not clear whether the barrier to more advanced development is merely technical or has a more fundamental biological cause.

“It’s going to be hard to tell whether there’s an intrinsic problem with them or whether it’s just technical,” said Robin Lovell-Badge, the head of stem cell biology and developmental genetics at the Francis Crick Institute. This unknown potential made the need for stronger legislation pressing, he said.

“Our human model is the first three-lineage human embryo model that specifies amnion and germ cells, precursor cells of egg and sperm,” Żernicka-Goetz told the Guardian before the talk. “It’s beautiful and created entirely from embryonic stem cells.”

so we're about to completely leap over the first steps of making test-tube babies - gathering eggs and sperm and having them get things rolling - and going straight to manufacturing embryos, huh

[ancientstuff]

This is fascinating. Although they can't tell what the lives were like of the people with these various syndromes, we can at least say (it seems to me) that they weren't ostracised or discarded, given that they did not have unusual burials.

[bpod-bpod]

Nurturing T cells

The organ in your chest called the thymus – where the immune system's T cells mature – is composed of a number of cell types, including epithelial cells, vital for T-cell development. This study characterises epithelial stem cells and reveals their capacity to self-renew and organise, providing insight for prolonging T-cell activity as it declines with ageing and for tackling thymic disorders

Read the published research paper here

Image from work by Roberta Ragazzini and colleagues

Epithelial Stem Cell Biology & Regenerative Medicine Laboratory, The Francis Crick Institute, London, UK

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in Developmental Cell, August 2023

You can also follow BPoD on Instagram, Twitter and Facebook

[pardon-my-scifi]

Well holy fucking shit. I have so many feelings about this. I've been thinking about TS in terms of the last 70 years or so. Now there is proof someone a couple thousand years ago had Turner Syndrome. Imma just be in the corner with my feels.

[catinfroghat]

I don't know if I would/could ever move to london but I should apply for this job at the francis crick institute because it's actually eerily similar to what I did during my master's degree

[mariacallous]

Antipsychotics come from a long line of accidents. In 1876, German chemists created a textile dye called methylene blue, which happened to also dye cells. It meandered into biology labs and, soon after, proved lethal against malaria parasites. Methylene blue became modern medicine’s first fully synthetic drug, lucking into gigs as an antiseptic and an antidote for carbon monoxide poisoning. Cue the spinoffs: A similar molecule, promethazine, became an antihistamine, sedative, and anesthetic. Other phenothiazines followed suit. Then, in 1952, came chlorpromazine.

After doctors sedated a manic patient for surgery, they noticed that chlorpromazine suppressed his mania. A series of clinical trials confirmed that the drug treated manic symptoms, as well as hallucinations and delusions common in psychoses like schizophrenia. The US Food and Drug Administration approved chlorpromazine in 1954. Forty different antipsychotics sprang up within 20 years. “They were discovered serendipitously,” says Jones Parker, a neuroscientist at Northwestern University. “So we don't know what they actually do to the brain.”

But Parker really wants to know. He has spent his career studying brains flooded with dopamine, the condition that underpins psychosis. And while he doesn’t pretend to fully understand antipsychotics either, he believes he’s got the right approach to the job: gazing directly into brains. With a combination of tiny lenses, microscopes, cameras, and fluorescent molecules, Parker’s lab can observe thousands of individual neurons in mice, in real time, as they experience different antipsychotic drugs. That’s now paying dividends. In results appearing in the August issue of Nature Neuroscience, Parker shows that an assumption about antipsychotics that’s almost as old as the drugs themselves is …. well, wrong.

Neuroscientists have long thought that antipsychotics dampen extreme dopamine transmission by sticking to receptors in a type of cell called spiny projection neurons, or SPNs. The drugs basically box out the dopamine at receptor proteins called D1 or D2 (where “D” stands for dopamine). Each of the spiny neurons sport either D1 or D2—they’re genetically distinct. Experiments on calf brain extracts in the 1970s showed that the most powerful antipsychotics are the ones that cling strongly to the D2 SPNs in particular, so decades worth of antipsychotics were designed and refined with D2 in mind.

But when Parker’s team probed how four antipsychotics affect D1, D2, and mouse behavior, they found that the most drug interaction is actually happening at D1 neurons. “It’s good to start with a logical prediction and then let the brain surprise you,” Parker says.

The notion that D1 receptors may be a more important target upends decades of research in a $15 billion market for drugs that are famously erratic. Antipsychotics don’t work for about 30 percent of people who try them. They’re plagued by side effects, from extreme lethargy to unwanted facial movements, and rarely address the cognitive symptoms of psychosis, like social withdrawal and poor working memory.

Assumptions about D2 ran deep, says Katharina Schmack, a psychiatrist and neuroscientist who was not involved in the work and studies psychosis at the Francis Crick Institute in the United Kingdom: “This was the textbook knowledge.”

“I was surprised, but kind of excited” by the new study’s conclusions, she continues. Now, she says, “We can start to understand the actual mechanism. And that is the first step to then really get to much better treatments.”

Psychosis flares up in the striatum, a small, curved tissue tucked deep in the brain that helps control how you move, feel, and make decisions. Densely packed neurons extend their spiny branches out of the striatum like ribbon cables. Dopamine prompts those neurons to send signals elsewhere in the brain. This interface is where a blaze of dopamine is thought to overwhelm the mind.

About 95 percent of the neurons connecting the striatum to the rest of the brain are SPNs, each sporting either a D1 or D2 receptor. When dopamine clings to D1, those neurons become more excitable; when it clings to D2, those get less so. The entire system interconnects, so it’s hard to pin down true causes and effects. But Parker believes that by monitoring individual cells, scientists can reverse engineer enough of the circuitry to learn how to deliver drugs to it in the most effective way possible.

The first step in his experiment was to mimic excess dopamine in mice by giving them amphetamines. “You inject them with amphetamine, and they run more. If you inject them with antipsychotics first, they run less. That’s the state of the art,” Parker says.

Then, to find out exactly which neurons the amphetamines were interacting with, his team implanted small endoscopes into each mouse’s brain and rigged tiny 2-gram microscopes to peer through the endoscopes. Parker learned this type of in vivo imaging during a postdoc as a Pfizer employee doing research at Stanford University with Mark Schnitzer, a biophysicist who pioneered the method to study neurons more generally. The endoscopes are invasive, but not so bothersome that they get in the way of experiments.

Since D1 and D2 neurons are genetically distinct, the scientists were able to study each individually. As a way to tell them apart, they had designed fluorescent molecules that tagged only the cells with a particular genetic sequence. They then recorded how the neurons reacted after amphetamine injections: D1 SPNs became more excitable, or responsive, and D2 became less so. This matched the textbook theory, Parker says, “but no one had actually shown that yet.”

Then things got weird. Each of the mice had already been injected with one of four drugs: haloperidol, a first-generation drug from the 1950s known for motor side effects; olanzapine, a second-gen drug; clozapine, a powerful drug that’s administered when others don’t work; and MP-10, a drug candidate Pfizer had developed that looked effective in animals but failed during clinical trials in 2019 when it exacerbated psychosis in humans.

Most neuroscientists would wager that the three effective drugs should ignite some action in D2 SPNs, and might do nothing at D1. Indeed, haloperidol and olanzapine countered the amphetamine’s effect on D2, as expected. But clozapine didn’t. And the big surprise was that controlling D1 neurons seemed to be the factor that mattered most. All three effective drugs normalized the action at D1, and MP-10 didn’t. In fact, MP-10 had leveled out activity at D2 but actually made the abnormal D1 activity worse. “It exacerbated the hyperactivity,” Parker says. “That kind of sealed the deal.”

Next, Parker wondered how general this effect is. Most antipsychotics developed over the past 70 years stick to dopamine receptors, but a new generation binds to other sites, like acetylcholine receptors. Might these new drugs still be doing something to D1 neurons indirectly?

Parker’s team picked three promising new drugs—all in the final clinical trials needed for FDA approval—and repeated the first round of experiments. All three somehow normalized D1 activity too. “We were really surprised,” Parker says.

Schmack says it’s “fascinating” that this pattern holds for antipsychotics that target different receptors. “It seems to be a very consistent observation,” she says.

The behavior of the mice also told a consistent story. In both rounds of testing, all of the antipsychotics—except MP-10, which was already known to be ineffective—helped amphetamine-agitated mice slow down and move normally. And their neural activity told a consistent story about why. While the effects on D2 neurons varied, each of those six drugs normalized D1 neurons—suggesting D1 is the receptor that matters more.

To Schmack, these results suggest that drug companies should target D1 in testing—she thinks a drug candidate’s effect on that receptor could be a good proxy for its likelihood of success. “It’s something that we are always desperately in need of,” she says.

“It is extremely powerful, and a wonderful screening tool,” agrees Jessica Walsh, a neuropharmacologist at University of North Carolina at Chapel Hill who was not involved in the work. “With all the drugs that already exist, this really shows that with drugs that we thought selectively targeted one receptor—perhaps that’s not the entire story.”

Parker makes a convincing case for targeting D1, Walsh says, by running through the “whole gamut” of drugs: “It was a humongous effort.” Yet Walsh notes that the interconnections between neurons like D1 and D2 SPNs mean that D2 SPNs may still be important. It’s possible that some drugs level out D1 activity by sticking to D2 receptors.

“It is tricky to shift the role of D2 receptors as being crucial,” Robert McCutcheon, a psychosis researcher at the University of Oxford, England, wrote in an email to WIRED. He suggests testing other approved drugs with no supposed attraction to D1 receptors, like amisulpride.

The field still longs for a better grasp of which neural circuits respond most to antipsychotics. “This is the first step to actually disentangling the exact effects,” says Schmack. “We can develop new antipsychotic drugs that target new points in this way, and might have less side effects than the antipsychotic drugs that we have right now.”

Parker’s current plan is to test what happens when he blocks the D1 receptor just sometimes, with drugs called “partial agonists.” The drugs compensate for high dopamine and low dopamine. It’s a different approach than just blocking dopamine altogether, and Parker hopes his new results bode well for D1 partial agonists in particular. That’s because despite having more dopamine in their striatum, people with schizophrenia actually have lower dopamine levels in their cortex, a feature that neuroscientists think contributes to social withdrawal and forgetfulness. “Such a drug could be both antipsychotic and cognition-promoting,” Parker says. His lab has begun testing candidates.

The Nature Neuroscience study’s results open new inroads to treating psychosis, Parker says. “If we’re not constrained by this idea that they always need to bind this receptor or do this one thing to this type of neuron, we can begin to think about what might be possible in other ways.”

[grandmaster-anne]

23 November 2022 President Cyril Ramaphosa of South Africa, with the Earl of Wessex, during a visit to the Francis Crick Institute in London, as part of his state visit to the UK. 

[myfeeds]

Ancient genomes reveal immunity adaptation in early farmers

Researchers at the Ancient Genomics Laboratory at the Crick studied available genome-wide DNA from 677 individuals dating to Stone Age Europe, spanning the movement of Neolithic farmers from the Near East into Europe about 8000 years ago, where they mixed with Mesolithic hunter-gatherers already in Europe. They were interested in whether any particular genes might have coded for adaptations important to early farming groups, and looked for evidence of rapid evolution in these populations. Since about 20% of the ancestry of descendant late Stone Age people could be traced to the local European hunter-gatherers, the researchers also asked whether any particular genes showed evidence of more hunter-gatherer ancestry. They found that a large genetic region responsible for immune responses to diseases — the major histocompatibility complex (MHC) — showed both the strongest evidence of rapid evolution, and more Mesolithic hunter-gatherer ancestry than expected, suggesting that genetic variants in the MHC region already present in Europe were passed down preferentially. It has previously been thought that the transition to farming was associated with increased natural selection on immunity variants, as people started living closer to animals and eating more animal products. This research supports this view, but also shows that diversity in immune genes may be just as important as adaptation to lifestyle. The research team speculates that either the hunter-gatherers already had genetic adaptations against bacteria, viruses or other microorganisms in Europe, or that having many different forms of the genes was advantageous. Tom Davy, PhD student at the Francis Crick Institute and lead author, said: “It was really exciting to see for the first time that immunity is important for the transition to farming in a prehistoric population. The later Neolithic people had far more farmer ancestry in general, so we expected to see the same at the MHC region, especially as many diseases have been linked to Neolithic periods. But we saw about 50:50 ancestry from Neolithic farmers and Mesolithic hunter-gatherers here, showing that natural selection favoured genes from the hunter-gatherers already in Europe. “At the moment we’re not quite sure whythis happened, but a proposal is that the European hunter-gatherers had genetic variations which allowed them to fight Europe-specific diseases. Or picking up a variety of genes from both hunter-gatherers and farmers was beneficial because it resulted in lots of diversity at this major group of genes, allowing people to better fight off disease.” The team also confirmed results from previous studies, showing that genes coding for skin pigmentation showed the greatest representation for Neolithic farmer ancestry, with these variations coming into Europe from the Near East. This may be to maintain vitamin D levels when sources, such as diet and exposure to sunlight, change. Pontus Skoglund, Group Leader of the Ancient Genomics Laboratory at the Crick, said: “The shift to farming was an important transition all over the world, resulting in changing diets and exposure to infectious disease. “Previous research has suggested that adaptation in genetic regions relating to immunity, such as the MHC, has been important in recent time periods, and this research now provides similar evidence for adaptation in prehistory. By growing the ancient genomic record, we will be able to better understand the role of immunity in other periods of the human past.”

[zehub]

La pollution de l’air à l’origine de la démence ? Les scientifiques britanniques enquêtent

Des scientifiques britanniques lancent une étude novatrice pour élucider le lien entre pollution atmosphérique et démence. Cette recherche, menée par le prestigieux Francis Crick Institute, vis