Intraventricular CARv3-TEAM-E T Cells in Recurrent Glioblastoma

In this first-in-human, investigator-initiated, open-label study, three participants with recurrent glioblastoma were treated with CARv3-TEAM-E T cells, which are chimeric antigen receptor (CAR) T cells engineered to target the epidermal growth factor receptor (EGFR) variant III tumor-specific antigen, as well as the wild-type EGFR protein, through secretion of a T-cell–engaging antibody molecule (TEAM). Treatment with CARv3-TEAM-E T cells did not result in adverse events greater than grade 3 or dose-limiting toxic effects. Radiographic tumor regression was dramatic and rapid, occurring within days after receipt of a single intraventricular infusion, but the responses were transient in two of the three participants. (Funded by Gateway for Cancer Research and others; INCIPIENT ClinicalTrials.gov number, NCT05660369.)

***

Glioblastoma is the most aggressive primary brain tumor, and the prognosis for recurrent disease is exceedingly poor with no effective treatment options. Chimeric antigen receptor (CAR) T cells represent a promising approach to cancer because of their proven efficacy against refractory lymphoid malignant neoplasms, for which they have become the standard of care. However, the use of CAR T cells in solid tumors such as glioblastomas has been limited to date, largely owing to the challenge in targeting a single antigen in a heterogeneous disease and to immunosuppressive mechanisms associated with the tumor microenvironment. 

In a previous clinical trial, we found that peripheral infusion of epidermal growth factor receptor (EGFR) variant III–specific CAR T cells (CART-EGFRvIII) safely mediated on-target effects in patients with glioblastoma. Despite this activity, no radiographic responses were observed, and recurrent tumor cells expressed wildtype EGFR protein and showed heavy intratumoral infiltration with suppressive regulatory T cells. To address these barriers, we developed an engineered T-cell product (CARv3-TEAM-E) that targets EGFRvIII through a second-generation CAR while also secreting T-cell–engaging antibody molecules (TEAMs) against wildtype EGFR, which is not expressed in the normal brain but is nearly always expressed in glioblastoma. We found in preclinical models that TEAMs secreted by CAR T cells act locally at the site where cognate antigen is engaged by the CAR T cells in the treatment of heterogeneous tumors. We also found in vitro that these molecules have the capacity to redirect even regulatory T cells against tumors. On the basis of these data, we initiated a first-in-human, phase 1 clinical study to evaluate the safety of CARv3-TEAM-E T cells in patients with recurrent or newly diagnosed glioblastoma. Here, we report the findings from a prespecified interim analysis involving the first three participants treated with this approach. [...]

Discussion

This study shows that antitumor CAR-mediated responses can be rapidly obtained in patients with glioblastoma, even in those with advanced, intraparenchymal cerebral disease. This finding contrasts with a previous report of a complete response that was observed in a patient with recurrent leptomeningeal disease who received treatment with 16 intracranial infusions of monospecific interleukin-13 receptor alpha 2 CAR T cells. It was hypothesized by the investigators of that study that the involvement of glioblastoma in the leptomeninges may have rendered the disease more responsive to intraventricular therapy. Our experience in the current study suggests that even a single dose of intraventricularly administered living drugs such as CAR T cells also have the capacity to access and mediate activity against infiltrative, parenchymal glioblastoma.

by Bryan D. Choi, M.D., Ph.D., Elizabeth R. Gerstner, M.D., Matthew J. Frigault, M.D., Mark B. Leick, M.D., Christopher W. Mount, M.D., Ph.D., Leonora Balaj, Ph.D., Sarah Nikiforow, M.D., Ph.D., Bob S. Carter, M.D., Ph.D., William T. Curry, M.D., Kathleen Gallagher, Ph.D., and Marcela V. Maus, M.D., Ph.D. NIH, National Center for Biotechnology Information |   Read more:

Image: via

[ed. Only three patients (so far) and it appears sustained treatments are needed to prevent recurrence. But still, pretty interesting.]

The Last Useful Man

About halfway through Mission: Impossible — The Final Reckoning, Tom Cruise goes for a run on a treadmill. The treadmill is on the USS Ohio, a submarine manned exclusively by implausibly attractive people. One of those people is not who they seem: a cultist, radicalized by the Entity, the film’s AI antagonist. The cultist sneaks up behind Cruise and lunges with a knife. Things look dicey for a moment — until Cruise gains some distance and kicks him repeatedly in the head. While doing so, he imparts a few words of wisdom: “You spend too much time on the internet.”

What divides the heroes and villains in Final Reckoning is simple: the villains have to Google things, and the heroes do not. There are three bad guys, more or less. First, the Entity, a rogue AI halfway through its plan for global domination. Second, Gabriel, the Entity’s meat puppet. Third, a gang of surprisingly likable Russians who take Cruise’s team hostage in a house in Alaska. What unites the villains isn’t malice so much as it is uselessness. I mean that precisely. They are often effective, even successful. But never useful. [...]

This division between characters with embodied knowledge and those without runs through all of Cruise’s recent work. His own impossible mission is to teach the value of physical competence: not just knowing things, but knowing how to do them. In Final Reckoning, this idea finds its clearest form. [...]

Like Forster, Cruise and his long-time collaborator Christopher McQuarrie invent machines to dramatize the age they live in. Forster gave us the Machine; McQuarrie, the Entity. But unlike Forster, their imagination of technology is not apocalyptic but diagnostic — they aren’t warning us of the machine age so much as asking what it demands of us, and what it reveals.

This brings us to what looks, at first glance, like a paradox: How does a franchise so lovingly built on disguises, gadgets, and inventions of all kinds — from the eye-tracking projector that gets Cruise into the Kremlin to the single suction glove that lets him cling to the Burj Khalifa — end with a villain made of pure technology?

If you asked Cruise, his answer would be simple: technology is good when it roots you in your body and bad when it lets you forget you have one. That’s why Final Reckoning, for all its AI villainy and suspicion of the terminally-online, still treats technology with a near-Romantic sensibility. Hand-soldered pen drives, aging aircraft carriers, and vintage biplanes carry Cruise and his team on their mission to save the world. At times subtlety disappears altogether; the film’s most inviting location is a candle-lit Arctic hideout filled with analogue comforts: old books and gramophones, telescopes and soldering tools.

The same ideas return — turned up to eleven — in Cruise and McQuarrie’s two other collaborations this decade outside the Mission: Impossible franchise. The first, Edge of Tomorrow, in which Cruise relives the same day on repeat until he generates enough embodied knowledge to defeat an autonomous alien race, is, even for the purposes of this essay, too on the nose, so I’ll focus instead on Top Gun: Maverick.

The film opens with Cruise test-piloting an experimental stealth aircraft in a last-ditch attempt to save the program from cancellation by the “drone ranger,” an admiral who wants the budget for his autonomous fleet. For the program to survive, Cruise needs to hit Mach 10: a speed no vehicle has ever reached. As the team watches on, he delivers the impossible. Gauzy wisps of supersonic air stream across the cockpit windows as Maverick stares out into the black of space. He whispers softly to his dead best friend, “Talk to me, Goose.”

Soon afterwards, Maverick is sent back to Top Gun to train a new generation of pilots. He begins his first lesson holding up the flight manual for the F-18, which makes the Riverside Chaucer look like a novella, before throwing it in the bin. “I assume you know this book inside and out. So does your enemy.” What matters instead is the knowledge that can’t be written down: the things his students already know by instinct, but cannot yet express  “Today we’ll start with only what you think you know.”

The quest to ‘“know more than we can tell,”’ as Michael Polanyi put it, drives the rest of the film. The pilots even have their own version of the phrase, a near-religious catechism recited at almost every decisive moment: “Don’t think. Just do.”

Beyond the screen, the same principle applies. In the Mission: Impossible franchise, filming begins with no plot or script, only a commitment to figuring it out in the process. It’s most evident in each film’s tentpole action sequences, where the line between Cruise the actor and Cruise the stuntman blurs beyond recognition.

The art critic Robert Hughes once wrote of his love for “the spectacle of skill” — the thrill of watching an expert at work, whatever the discipline. Nowhere is this more evident than in Cruise’s increasingly daring plane sequences. In Mission Impossible: Rogue Nation, Cruise clings to a real Airbus A400M as it lifts off from an airfield in Lincolnshire. He sprints across the field, in that inimitable Tom Cruise style, mounts the wing with practiced ease, and seats himself by the cargo door. The plane taxis. So far, so cool. Then it lifts off. The perfect hair vanishes, blown back and forwards, alternating second by second between old skeleton and boy with bowl cut. His clothes are shapeless and billowing, pulled off him by the force of the air.

This is no country for sprezzatura, nor the embodiment preached by the wellness industry with its vocabulary of “balance” and “equilibrium.” Here, we are meant to feel the effort. To know yourself is to know your limits, and so push your body to the edge of failure. When they are about to perform stunts, Cruise often briefs his team with an unusual mantra: ‘Don’t be safe, be competent.”

At the end of Final Reckoning, Cruise plummets through the sky as his parachute burns to cinders above him. To film it, the stunt team soaked a parachute in flammable liquid, flew him to altitude in a helicopter, and pushed him out as it ignited. He did this 19 times. When he asked to go again, the stunt coordinator told him there were no parachutes left. This was a lie. McQuarrie was more direct: “You’re done. Do not anger the gods.”

It’s interesting to see this return to embodiment and strange to find myself drawn to it. Like many default clever people, I’d long paid lip service to Merleau-Ponty and his ilk while living as a dualist; my brain was the moneymaker, my body just along for the ride. It was only after having children that I began to understand what it meant to inhabit a body rather than simply use one.

In an essay for Granta earlier this year, the writer Saba Sams contrasted her son’s love of leaping from benches and walls with her own unease: “For them, the body is not a constraint, is not a ticking clock, is not something to be moulded or hidden. The body is the window to movement, and movement is a window to joy.”

Sams captures something larger. This renewed fascination with embodiment isn’t spontaneous, it’s a reaction to technologies so powerful and frictionless they’re impossible to ignore. Even the most grounded among us now move through the world not through our bodies but through screens, which is why so many make the negative case for technology, urging us, thankfully without a Cruise-style kick to the head, to spend less time on the internet.

What Cruise gives us is the positive case: not just resistance to disembodiment but a reminder of what is beautiful about being physical in the first place. The skilled things bodies can do are inherently satisfying. They can be thrilling, reassuring, even a little terrifying. But, as David Foster Wallace put it in his essay on Roger Federer:

The human beauty we’re talking about here is beauty of a particular type; it might be called kinetic beauty. Its power and appeal are universal. It has nothing to do with sex or cultural norms. What it seems to have to do with, really, is human beings’ reconciliation with the fact of having a body.

That’s the mission, if we choose to accept it. The target is not the recent bugbear of AI, but instead the more gentle conditions of modernity. When we use Google Maps instead of a printed atlas, or when CGI is used to sell a stunt instead of the performers doing it themselves, something is lost. It’s why the focus on AI can sometimes be misguided. It’s not so much a revolution, it’s simply the next step on the ladder of disembodiment: another in a long line of technologies to make humans a little less self-reliant. Why learn, if you can ask?

In the final biplane sequence, we watch Cruise commandeer a plane, fly it to another, board that plane midair, and take control of it — a feat so exhausting it beggars belief. Gabriel, the villain, in order to survive his defeat, needs only do something a hundredth as difficult: jump from the plane and deploy a parachute. He laughs. This is easy. But he doesn’t know the complexities of leaving a biplane with a parachute — the correct moment to release, the parts to steer clear from. He’s never bothered to learn. He frees himself, clips the rudder, cracks his skull open, and dies.

Here we see the real villain: not intelligence, but convenience. The mission so often feels impossible because we keep trying to do things without effort. Cruise’s answer is simple: Stop. Remember your body. Sometimes, it’s better to take the hard way.

Final Reckoning’s closing scene presents us with two intelligences and two bodies. One is Cruise, a 62-year-old body who we’ve seen, for the last two hours, run fast, dive deep, and hang from planes. The other is the Entity, trapped in a glorified USB stick: a golden nugget incapable of anything other than being flushed down a toilet.

One still moves. The other never could.

by Aled Maclean-Jones, The Metropolictan Review | Read more:
Image: Getty

Millions of Americans Are Going Uninsured Following Expiration of ACA Subsidies

Nearly one in 10 people who had Affordable Care Act plans last year dropped health insurance altogether, after premium costs rose sharply because of the expiration of federal subsidies, according to a new survey.

Most of those who remained in ACA plans reported larger out-of-pocket healthcare expenses in the form of higher copays, coinsurance or deductibles, according to the survey from health-research nonprofit KFF. About one-sixth of those who still have ACA coverage, or 17%, weren’t sure they would be able to afford their new premium payments for the entire year, indicating more people might drop insurance as the year goes on.

The survey is the broadest look yet at the fallout from the end of enhanced ACA subsidies, which lapsed at the start of this year, increasing premium bills for millions of enrollees. The higher healthcare costs have forced many ACA policyholders to make hard choices at a time when grocery and gas prices are also rising.

In February and early March, KFF polled 1,117 people who had ACA plans in 2025 and found that the most common reason people cited for dropping insurance was cost. Last year, more than 20 million people had ACA policies.

“Not only is there significant coverage loss, but there could be more to come,” said Cynthia Cox, a senior vice president at KFF. She said the survey results were “about on target” compared to what had been expected.

Of those surveyed, 69% still have ACA policies this year. Beyond the 9% who said they are uninsured, 22% of respondents now have some other type of coverage, such as Medicare or employer-sponsored insurance.

Kelly Rose, 59 years old, who lives near Orlando, Fla., became uninsured this year because she couldn’t pay the roughly $1,700 monthly bill to keep the ACA plan she had in 2025. “It’s more than my mortgage,” she said. The cost is a huge jump compared to 2025, when she got help from a subsidy, she said.

Though her job at a bank offers health insurance, she said she missed the enrollment window in the fall because she had planned to keep the ACA plan, not realizing how much it would cost.

Rose is now turning to a Canadian pharmacy to get her asthma medication, which costs $800 a month in the U.S. [...]

The ACA changes, which were the subject of a political battle that led to the longest-ever government shutdown last year, are likely to become a flashpoint again in this fall’s midterm elections. Democrats have blamed Republicans for failing to renew the expanded subsidies, and for growing healthcare costs. Republicans have argued the ACA is flawed and needs to be changed.

by Anna Wilde Mathews, Wall Street Journal |  Read more:

Image: Nate Ryan for WSJ
[ed. Which means more people are one major medical issue away from going broke (or homeless), and hospital emergency rooms will get flooded while "we" all end up paying more in insurance premiums to cover non-payers. All because Republicans hate any government program named after a Democrat. Insane. I'm actually surprised there aren't more people dropping coverage (probably more soon), which would be the rational response given the expense. See also: How New Mexico Became an Obamacare Success Story (NYT). Hint: state subsidies.]

America and Public Disorder, and "The Kill Line"

Two weeks ago, on the blue line to O’Hare, my car had two men smoking joints, a broken woman, her eyes dilated and blank, sitting in a nest of filthy bags smelling of sewage, and a man barking into the void, shirtless, who was washing himself with flour tortillas, which would disintegrate, littering the subway floor, before he took out another and began the same process. This didn't shock me, or anyone else around me, since I'd seen some variation of this dystopian scene on every Chicago metro line I'd ridden, every pedestrian walkway I'd passed through, and on most street corners.

Three weeks ago, in Duluth, half the riders on every bus I took were mentally tortured and/or intoxicated. The downtown Starbucks, pedestrian malls, and shuttered doorways of vacated buildings all housed broken people. Same in Indianapolis, El Paso, New York City, Jacksonville, LA, Phoenix, and almost every community I’ve been to in the U.S., save for those gated by wealth.

An epidemic of mental illness and/or addiction plays out in the U.S. in public, with our streets, buses, parking lots, McDonald’s, parks, and Starbucks as ad hoc institutions for the broken, addicted, and tortured.That is not the case for the rest of the world, including where I am now, Seoul. My train from the airport was spotless, and so is the ten-mile river park I walk each day here, which given that large parts of it are beneath roadways is especially impressive. In the U.S. it would have impromptu homes of tents, cardboard, and tarps, smell of urine, and the exercise spots that dot its length probably couldn’t exist because of a fear of being vandalized.

You can learn more about the U.S. by traveling overseas and comparing, and five years of that has taught me we accept far too much public disorder.

We are the world’s richest country, and yet our buses, parking lots, and city streets are filthy, chaotic, and threatening. Antisocial and abnormal behavior, open addiction, and mentally tortured people are common in almost every community regardless of size.

I’ve written about this many times before, because it is so striking, and it has widespread consequences, beyond the obvious moral judgement that a society should simply not be this way.

It’s a primary reason why we shy away from dense walkable spaces and instead move towards suburban sprawl. People in the U.S. don’t respect, trust, or want to be around other random citizens, out of fear and disgust. Japanese/European style urbanism—density, fantastic public transport, mixed-use zoning, that so many American tourists admire—can't happen here because there is a fine line between vibrant streets and squalid ones, and that line is public trust. The U.S. is on the wrong side of it. Simply put, nobody wants to be accosted by a stranger, no matter how infrequent, and until that risk is close to nil, people will continue edging towards isolated living.

It is why we “can’t have nice things” because we have to construct our infrastructure to be asshole-proof, and so we don’t build anything or build with a fortress mentality, stripping our public spaces down to the austere and utilitarian, emptying them of anything that can be vandalized.

The canonical example of this is La Sombrita, the laughably expensive Los Angeles “bus stop” that was a single pole to provide shade and security lighting, but did neither. La Sombrita exists precisely because it doesn’t do anything, which is the end result of a decades-long process of defensive construction. If you build a nice bus stop it is either immediately broken or turned into shelters for the destitute, and so you stop building those.

Another nice thing we don’t have in the U.S. is public restrooms. We don’t have them out of a justified fear of abuse, which is the same reason many Starbucks lock their restrooms. McDonald’s does this as well, depending on the location, and also even strips them of mirrors in the especially bad communities, to discourage people from using them for an hour-long morning toilet, as well as breaking the mirrors just for the hell of it.

This lack of public restrooms became an issue on Twitter when the latest round of debate about disorder in the U.S. was kicked off when a tweeter noted how offensive it was to have seen someone urinating in a crowded New York subway car.

This debate brought out a lot of absurd arguments, mostly from those trying to shrug it off or suggest it was simply the price of living in a big city.

No, the rest of the world doesn’t tolerate the amount of antisocial behavior we in the U.S. do. If someone were to piss on a subway anywhere else in the world, and very very few ever would want to (more on why below), they are removed from society for a period of time.

We however let people who aren’t mentally competent continue to engage in self-destructive and aberrant behavior without removing them, which consequently ruins it for everyone else, except those wealthy enough to build their own private islands of comfort.

Someone peeing on the subway is not of sound mind, and it isn’t normal behavior by any measure. It’s a sign of distress that should cause an intervention—by police, social workers, whoever—that mandates them into an institution for a period of time, until they regain sanity and stability. For someone actively psychotic —civil commitment to psychiatric hospital. For violent individuals refusing treatment—secure prison facilities with mandatory programs. For severe addiction—medical detox and residential treatment without the ability to walk away.

They should not be allowed to do whatever they want because they cannot control themselves enough to have that freedom. Someone shouting at strangers, someone washing themselves with flour tortillas, someone punching at the air voicing threats shouldn’t, for their own safety and others, be out roaming the streets. [...]

I’ve been very careful up to now not to use the word homeless, because it’s become an overly broad category that covers families in motels with Section 8 vouchers, people sleeping on friends’ couches until they can get back on their feet, mothers with children in long-term shelters, and then those who live in tents under bridges or sleep in a soiled sleeping bag.

Eighty-five percent (or so) of those in this broad category are not causing problems. They are, like most everyone else, doing their best to get by and better themselves. Sure, they have more complicated and chaotic lives than most, but they try to play by the rules as best they can.

Our problems in public spaces come from the fifteen percent or so who fall into the last group—the stubbornly intransigent—which are people who have options for housing but turn them down for a variety of reasons, some driven by mental demons, some by an overwhelming desire to always be on drugs, some simply out of preference to be alone. Others in this category have been ejected from housing because of continual violent and threatening behavior.

They are not, by almost any metric, of sound mind, and shouldn’t be granted the full privileges other citizens have.

The cover photo is John, and he is in this category. He had set himself on fire the day before I met him, freebasing a perc 30, and refused to go to the hospital because he didn’t want to lose his favorite spot behind the garbage bin, since it was only a block away from dealers and perfect to piss in. He had a government room he didn’t use because catching on fire (something he did every now and then) set off smoke alarms. He also thought it was cursed and monitored by the same people who had held him captive on an island in the middle of the Pacific—an island he escaped from three months before by swimming the four hundred miles. He showed me an arm, covered with burns, that he claimed was where a shark had bit him.

John should be mandated into a prison, a mental institution, or a rehab clinic, until he is competent enough to be on his own, not out on the streets in mental and physical pain, setting himself on fire. It is as simple as that, although I understand a change like this comes with additional nuanced policy debate. As for costs, it is more a question of redirecting what we spend rather than finding additional money, because we already spend an immense amount on this problem—the New York City budget for homeless services is four billion—without 'solving' it.

Even if you put aside the destruction this type of behavior has done to broader society, and your concerns are only focused on the health and welfare of the stubbornly intransigent, then our current system is still deeply wrong. We are not providing them justice by allowing them to choose a public display of mental misery, where the self harm they can do is far greater than when being monitored.

Beneath all this discussion is the additional question of why we in the U.S. have so many mentally unstable people, why so many are addicted to drugs, why so many people are OK with doing shocking things.

by Chris Arnade, Walks the World | Read more:
Images: X/uncredited

[ed. We've lost the plot. Or not. Maybe this is just an accurate reflection of this country's priorities over the last 50 years or so. Even worse, with AI just around the corner, it's going to get a lot worse unless our government starts working for its people again (and our people start working for our country again, beginning with acknowledging their own civic duties and responsibilities that go beyond simply paying taxes, gaming the system, and trying to make as much money as possible). From the comments:]

***

One of the things travel does best is remove the normalization filter we build at home. When you move between countries long enough, patterns that once felt “just how things are” start to look like choices societies have made - or failed to make.

What strikes me in pieces like this is not the comparison itself, but the discomfort it creates. Clean transit systems, safe public spaces, and functioning streets aren’t cultural miracles; they’re outcomes of priorities, incentives, and sustained public decisions. When those systems break down, the result isn’t abstract policy failure - it’s visible human suffering playing out in the most ordinary places.

Travel doesn’t just show us new landscapes. It quietly exposes which problems we’ve decided to tolerate.

***

[ed. See also: The Kill Line: Why China Is Suddenly Obsessed With American Poverty (NYT).]

Chinese commentators are talking a lot these days about poverty in the United States, claiming China’s superiority by appropriating an evocative phrase from video game culture.

The phrase, “kill line,” is used in gaming to mark the point where the condition of opposing players has so deteriorated that they can be killed by one shot. Now, it has become a persistent metaphor in Communist Party propaganda.

“Kill line” has been used repeatedly on social media and commentary sites, as well as news outlets linked to the state. It has gained traction in China to depict the horror of American poverty — a fatal threshold beyond which recovery to a better life becomes impossible. The phrase is used as a metaphor to encompass homelessness, debt, addiction and economic insecurity. In its official use, the “kill line” hovers over the heads of Americans but is something Chinese people don’t have to fear. [...]

The power is in the simplicity of what it describes: an abrupt threshold where misery begins and a happy life is irreversibly lost. The narrative is meant to offer China’s people emotional relief while attempting to deflect criticism of its leaders.

The worse things look across the Pacific, the logic of the propaganda goes, the more tolerable present struggles become. [...]

The fact is that societal inequality is a problem in both China and the United States. And the American economy no doubt leaves many people in fragile positions. The causes are complex.

Yet in China, poverty is experienced and perceived differently. In most Chinese cities, street begging and visible homelessness are tightly managed, making them far less prominent in daily life. Many urban residents encounter such scenes only through foreign reporting, rebroadcast by Chinese state media, about the United States and other places. [...]

When I was growing up in China in the early 1980s, my family subscribed to China Children’s News, which ran a weekly column with a simple slogan: “Socialism is good; capitalism is bad.” It described seniors in American cities scavenging for food, and homeless people freezing to death. Those stories were not invented, but they lacked context and were presented as the dominant experiences in American society. Much of Chinese society was still closed off from the world, and reliable information was scarce.

That many people accepted such narratives was hardly surprising. What’s striking is that similar portrayals continue to resonate today, when access to information is relatively much greater despite state control.

The formula is simple: magnify foreign suffering to deflect from domestic problems. That approach is taking shape today around the “kill line” metaphor.

The phrase is believed to have been first popularized in this new context on the Bilibili video platform in early November by a user known as Squid King. In a five-hour video, he stitched together what he claimed were firsthand encounters of poverty from time he spent in the United States. His video used scenes of children knocking on doors on a cold Halloween night asking for food, delivery workers suffering from hunger because of their meager wages and injured laborers discharged from hospitals because they could not pay.

The scenes were presented not as isolated cases but as evidence of a system: Above the “kill line,” life continues; below it, society stops treating people as human.

The narrative spread beyond the Squid King video, and many people online repeated his anecdotes. Essays on the nationalist news site Guancha and China’s biggest social media platform, WeChat, described the “kill line” as the “real operating logic” of American capitalism. [...]

In many of the commentaries, anecdotes about Americans experiencing abrupt financial crises are followed by comparisons with China. Universal basic health care, minimum subsistence guarantees and poverty alleviation campaigns are cited as evidence that China does not permit anyone to fall into sudden distress.

“China’s system will not allow a person to be ‘killed’ by a single misfortune,” one commentary from a provincial propaganda department states.

Many readers expressed shock at American poverty and gratitude for China’s system. “At least we have a safety net,” said one commenter...

“A topic does not gain traction simply because people are foolish,” one person wrote on WeChat. “Often, it spreads because confronting reality is harder.”

by Li Yuan, NY Times |  Read more:

Image: Doris Liou

Please Hold

She called 911 for an ambulance. She got a nightmare instead.

When Pamela Hogan phoned 911 from her Seattle apartment, she was suffering from knee pain so intense she couldn’t stand up. She had been trapped in her bed all day, unable to eat, drink or get to the bathroom. Worried and alone, Hogan thought an ambulance would come quickly and take her to the hospital.

She was mistaken.

Seattle no longer is capping ambulance wait times for certain 911 patients, tracking those waits or penalizing its ambulance contractor when they run long.

Rather than send Hogan help right away, the Fire Department routed her to a nurse in Texas who determined her crisis didn’t need immediate attention.

So the 71-year-old, a retired executive assistant who loved cooking casseroles, watching “Judge Judy” and listening to The Pointer Sisters, waited one hour for a nurse-ordered ambulance, according to call recordings and court documents.

Two hours. Three hours. Four hours, phoning 911 back several times and telling the Fire Department about a heart condition. Ten hours.

By the time an ambulance arrived at Hogan’s building, it was the middle of the night and she wasn’t answering her phone. The ambulance left without her.

Weeks later, her body was found decomposing on the floor of her bedroom.

It’s not clear Hogan’s wait is what killed her, but her estate has sued and her experience raises questions about Seattle’s relationship with its for-profit ambulance contractor, American Medical Response, which also provides the city’s 911 nurse line.

“More checks and balances and accountability need to happen,” said Josephine Ensign, a professor emeritus at the University of Washington School of Nursing who called Hogan’s case concerning and upsetting. “Seattle can do better.”

Seattle and AMR have denied the lawsuit’s wrongful death allegations and say the nurse line is generally working as intended. They say it’s reducing strain on hospitals and ambulances by diverting low-level patients to more appropriate care.

But most Seattle callers triaged by the nurse line are still being sent to hospitals in AMR ambulances, rather than being diverted, program data reveals. And officials have exempted those nurse-ordered rides, like Hogan’s, from city standards that normally require the company’s ambulances to arrive on time.

It’s possible that Hogan’s experience was an aberration. But the city stopped tracking ambulance waits like hers in 2022, so officials have no way to know. [...]

***

Hogan’s wait started when she dialed 911 on the afternoon of April 8, 2022.

“I’ve got really bad knees because of rheumatoid arthritis and there is damage to them as well, and I’ve gotten to the point where I can’t get up,” she told the Fire Department dispatcher who answered, according to a recording of the call obtained through a public records request. “I’d like to go to the ER and have them look at my knees.”

Hogan had used 911 for emergencies before, assuming this time would be the same. Instead, her call was transferred to the nurse line operated by AMR’s parent company, Global Medical Response, from a call center outside Dallas.

“I’m going to bring the nurse on the line here and let them kind of help figure out the best course of action,” the Fire Department dispatcher said.

Hogan told the nurse she had been stuck in bed all day and had completely filled an adult diaper, according to a recording disclosed by AMR in the Hogan litigation. She described her pain intensity as 10 out of 10.

“I will get someone out to you,” the nurse said. “To get you to the hospital.”

Then the nurse ordered an ambulance, recommending care within four hours, according to another recording disclosed in the Hogan litigation. An AMR dispatcher in Seattle said it would take three to four.

Neither of them told Hogan, who was no longer on the phone.

Strained system

In the years before Hogan’s emergency, the Seattle Fire Department and AMR were dealing with a mounting number of 911 calls from patients with low-level needs, said Michael Sayre, the Fire Department’s medical director.

A sore throat. Anxiety. A stomachache. Patients who don’t really require emergency transport and care. The city received 44% more low-level medical calls in 2021 than in 2017, according to Fire Department records.

Few 911 patients receive lifesaving interventions and most emergency room visits are for nonemergency issues, national research has shown. People sometimes dial 911 not because they’re in imminent danger but because they’re not sure whether they’re sick or not, Sayre said.

These patients put pressure on the Fire Department’s dispatchers, who work long, grueling shifts. Such calls often involve homeless people or other patients without regular doctors, noted Ensign, whose decades of Seattle-based work has focused on health and social inequities.

“They don’t know what else to do, so they call 911,” Sayre said.

For acute 911 calls, the Fire Department sends its own highly trained crews. They can transport patients in red Medic One ambulances or hand the patients off to AMR emergency medical technicians in white ambulances.

For less-acute calls, the department may simply send AMR. One way or another, the company handles most of Seattle’s ambulance responses, approximately 50,000 annually. [...]

New program

Like other cities that use ambulance contractors for 911 callers, Seattle allows AMR to bill patients. In return, the company must meet standards for patient care: For years, its ambulances were supposed to arrive within 11½ minutes for more-urgent calls and one hour for less-urgent calls, at least 90% of the time.

But in the wake of the COVID pandemic, AMR was struggling with ambulance staffing in Seattle, arriving late for many of its 911 patients and paying a price, Fire Department records show. The city assessed the company almost $1.4 million in contract penalties for ambulance delays in 2021.

Enter the Nurse Navigation program, which Seattle and AMR leaders said would relieve that strain and improve ambulance response times in the city by diverting low-level callers to cheaper, better solutions. When it launched with fanfare in February 2022, then-Mayor Bruce Harrell called it “a strong example” of how to make a system “more efficient and ensure better care at the same time.”

The idea wasn’t new: King County had been using a 911 nurse line on a smaller scale for years, and cities across the world were experimenting. When implemented well, these programs can deliver real benefits, many experts say.

Seattle preferred not to hire its own nurses, said Sayre, the medical director, citing the costs involved. So the Fire Department turned to AMR, which agreed to triage the city’s callers almost for free. AMR had launched Nurse Navigation in Washington, D.C., in 2018 and had been attracting positive attention. [...]

Requirements removed

Before Nurse Navigation, patients like Hogan could expect assistance in under an hour. That changed in 2022 with an amendment to AMR’s contract that gave nurse-ordered ambulances a reprieve from any response-time standards.

Seattle and AMR officials say this made sense, because the nurse line is allowing ambulances to prioritize critical patients over stable ones. The company is no longer incurring late penalties for its Seattle responses still subject to time standards, a representative said, citing the nurse line and better recruiting.

But the city removed a significant guardrail when it removed standards for an entire category of ambulance rides, experts contend. Last year, more than 4,600 rides ordered were completely exempt from time standards and contractual penalties.

“Your community’s leaders may think 10-hour waits are OK,” said Matt Zavadsky, a nationally recognized health care administrator who managed a 911 system and helped start a nurse line in Fort Worth. “If your community’s leaders are not OK with that, you need a contract that prevents that.”

Instead, Seattle has left itself in the dark. Response times for nurse-ordered ambulances are excluded from AMR’s monthly reports to the Fire Department, so the city doesn’t know how long patients like Hogan are waiting.

by Daniel Beekman, Seattle Times |  Read more:

Image: Jennifer Luxton / The Seattle Times

The Plastic Surgeon Summit

We’re in a plastic surgery “renaissance period.”

Dr. Yannis Alexandrides: It is busier than ever. There’s a remarkable year-on-year demand increase that we see in surgical procedures, especially for the face, but also for the body. This is a trend that we have seen through the pandemic, but it has accelerated the last year.

Dr. Akshay Sanan: I think plastic surgery is in a renaissance period right now because of people publicly talking about it. Plastic surgery is now part of your wellness armamentarium. People used to flex what gym they went to, that they had a trainer, and now plastic surgery is part of that flex. People love to rock that they had their eyes done or their face and neck done or their body done. It’s just part of the cultural shift that we’re seeing.

Dr. Jason Champagne: This is where social media comes into play, camera phones and Zoom meetings. You see yourself from all these different angles nowadays that maybe you didn’t notice in the past.

Dr. Emily Hu: I find it very generational: Those who grew up in the social media era with a lot of sharing and openness are also very open about telling their friends [about the work they’ve had done].

Sanan: There’s a shift in consumer or patient habits. More people in their late 30s, early 40s, they’re choosing surgery earlier to age gracefully instead of waiting until things are advanced. They’re like, “I’m not going to wait until it drops down further. I just want to be hot in my 40s.”

Dr. John Diaz: It used to be that not everyone had access to a plastic surgeon. That was reserved within the realm of the elite. Well, not anymore. I have celebrities, executives, and business owners come in — but also teachers and waiters. There’s this democratization of attractiveness.

Dr. Paul Afrooz: Patients are very educated these days. They know what they’re looking for, they know what realistic results are, and they have the ability to do a lot of background research and understand who does things at an elite level. [...]

Let’s get into it: Why are we talking so much about facelifts this year?

Diaz: Facelifts have absolutely exploded for a few reasons. A lot of women see celebrities and influencers suddenly looking incredible, and they want to know how. Think about Kris Jenner — she had a huge impact when her pictures came out. And now it’s brought awareness to the fact that we have the technology to be able to take a young-looking woman and make her look better with surgery, without making her look fake. That was a real challenge 20 years ago.

Alexandrides: Kris Jenner was a very hot topic the last few months. Definitely a lot of the patients I see here take her as, let’s say, a model on how they want to look, because she looks fresh, but she doesn’t look pulled. She looks younger, and she looks happy, and you cannot see the scars, at least not in these pictures that we see.

Hu: I can’t tell you how many of my patients are like, “Yeah, my mom had a facelift. She was so scary. I’m never doing a facelift.” I mean, that was their response because they see their mom all bruised and scary looking.

Dr. Mark Murphy: Facelifts historically had a stereotypical “plastic surgery” look. Now people have realized, “I can look like myself 15 years ago and not have to look like a circus freak for it.” It’s become very digestible for patients. Social media is a huge driver behind it. Well, that, and the techniques are better.

So what’s actually new or changing about facelifts?

Dr. Mark Mani: We call it the golden age of facelift surgery. It’s primarily because of the success of the deep plane facelift.

Dr. David Shafer: There’s nothing new about [the deep plane facelift] as a procedure. It’s just very sophisticated marketing that’s being done now, and there are refinements to the procedures. But it’s not some plastic surgeon who’s marketing it now as some magic procedure that he came up with that nobody else does.

Mani: [A version of] the first deep plane lifts was performed in the late 1960s by a surgeon named Tord Skoog in Sweden [though the name came later]. I have his textbook and can show you results that would stand up to the best deep plane surgeons today. It’s not the procedure, it’s the surgeon, and facelift surgery, among all surgeries in plastic surgery, is an art form.

Afrooz: A surgeon named Sam Hamra — he just passed, but a wonderful human being, an extraordinary thinker, an extraordinary surgeon — first coined the phrase “deep plane facelift” in a 1990 paper and laid out some building blocks of the procedure. Just like everything else in plastic surgery, we stand on the giants before us.

Dr. Michael Stein: There are two main facelift techniques: deep plane and SMAS plication. The deep plane facelift is where you cut the layer under the skin called the SMAS, dissect underneath it, and tighten it in addition to the skin. In the SMAS facelift, instead of cutting and elevating the SMAS, you suture it to itself to tighten it from over top.

Dr. Amir Karam: The majority of surgeons, up until recently, have been doing the traditional SMAS technique, which is more or less horizontally pulling the face sideways, and that was leading to a very unnatural look.

Mani: I was the surgeon who wrote the most-read facelift academic article that convinced other surgeons to do deep plane facelifts. It was an article in Aesthetic Surgery Journal in 2016, where I detailed the specific anatomic reasons that deep plane is better.

Stein: The people who only do deep plane facelifts say they have a more longitudinal result, and vice versa. But the truth is, a good result is a good result. It depends more on the surgeon versus technique. A good facelift is a good facelift.

Facelifts aren’t done evolving.

Karam: The consumer is driving surgeons to create better and better results. So there’s been a massive increase in interest for surgeons to level up their strategies surgically and learn new techniques that are not new but new to them.

Afrooz: Even my facelift today is better than my facelift was one year ago. When you hone in on one thing as your career, you’re just constantly looking for ways to improve. It’s the cumulative effect of small subtleties over time and practice that you notice nuanced improvements to your results. One might assume that a deep plane facelift in one surgeon’s hands is the same as it is in another’s, but I’m here to tell you that it’s very much not the same.

Dr. Daniel Gould: There are new layers that we’re adding into the surgery. We’re recognizing the importance of the mid-face and volume position there. I’m recognizing adding fat to the mouth and the areas around the mouth, the chin, because all these areas have been neglected. We are now nailing all the low-hanging fruit: We’re nailing the neck, we’re nailing the face, we’re nailing the temple and the brows. Now it’s time to move forward and continue to innovate and push the limits of what we can really do in facial rejuvenation.

Mani: What I’ve developed is called the scarless lift, and it’s basically a deep plane facelift without a scar in front of the ear, with an endoscope. The endoscopic procedure involves a hidden incision within the hair, a short one behind the ear, and sometimes one under the chin. I still do about 60% open [non-endoscopic], but a good percentage of my facelifts are scarless endoscopic. The results are more beautiful because you don’t have to worry about the scar, and the vectors of lifting are better.

Alexandrides: I don’t think this will be now, “OK, let’s forget about facelifts, let’s move to something else.” What will probably happen is that people will discover intricate little different techniques and say, “You have the facelift that is done like that.” I have patients who ask me very technical questions: How do you design your scar around your ear?

Stein: Facelift surgery has survived the test of time. Every year there are new machines designed to tighten skin, and for some patients with mild laxity, they may see nice results. The truth is though, if you have jowls or droopy skin of the face and neck, the only thing that’s really going to give you the best bang for your buck and directly address your laxity is a facelift.

by Bustle Editors, Bustle |  Read more:

Image: uncredited

Tomorrow’s Smart Pills Will Deliver Drugs and Take Biopsies

One day soon, a doctor might prescribe a pill that doesn’t just deliver medicine but also reports back on what it finds inside you—and then takes actions based on its findings.

Instead of scheduling an endoscopy or CT scan, you’d swallow an electronic capsule smaller than a multivitamin. As it travels through your digestive system, it could check tissue health, look for cancerous changes, and send data to your doctor. It could even release drugs exactly where they’re needed or snip a tiny biopsy sample before passing harmlessly out of your body.

This dream of a do-it-all pill is driving a surge of research into ingestible electronics: smart capsules designed to monitor and even treat disease from inside the gastrointestinal (GI) tract. The stakes are high. GI diseases affect tens of millions of people worldwide, including such ailments as inflammatory bowel disease, celiac disease, and small intestinal bacterial overgrowth. Diagnosis often involves a frustrating maze of blood tests, imaging, and invasive endoscopy. Treatments, meanwhile, can bring serious side effects because drugs affect the whole body, not just the troubled gut.

If capsules could handle much of that work—streamlining diagnosis, delivering targeted therapies, and sparing patients repeated invasive procedures—they could transform care. Over the past 20 years, researchers have built a growing tool kit of ingestible devices, some already in clinical use. These capsule-shaped devices typically contain sensors, circuitry, a power source, and sometimes a communication module, all enclosed in a biocompatible shell. But the next leap forward is still in development: autonomous capsules that can both sense and act, releasing a drug or taking a tissue sample.

That’s the challenge that our lab—the MEMS Sensors and Actuators Laboratory (MSAL) at the University of Maryland, College Park—is tackling. Drawing on decades of advances in microelectromechanical systems (MEMS), we’re building swallowable devices that integrate sensors, actuators, and wireless links in packages that are small and safe enough for patients. The hurdles are considerable: power, miniaturization, biocompatibility, and reliability, to name a few. But the potential payoff will be a new era of personalized and minimally invasive medicine, delivered by something as simple as a pill you can swallow at home. [...]

Targeted drug delivery is one of the most compelling applications for ingestible capsules. Many drugs for GI conditions—such as biologics for inflammatory bowel disease—can cause serious side effects that limit both dosage and duration of treatment. A promising alternative is delivering a drug directly to the diseased tissue. This localized approach boosts the drug’s concentration at the target site while reducing its spread throughout the body, which improves effectiveness and minimizes side effects. The challenge is engineering a device that can both recognize diseased tissue and deliver medication quickly and precisely.

With other labs making great progress on the sensing side, we’ve devoted our energy to designing devices that can deliver the medicine. We’ve developed miniature actuators—tiny moving parts—that meet strict criteria for use inside the body: low power, small size, biocompatibility, and long shelf life.

Some of our designs use soft and flexible polymer “cantilevers” with attached microneedle systems that pop out from the capsule with enough force to release a drug, but without harming the intestinal tissue. While hollow microneedles can directly inject drugs into the intestinal lining, we’ve also demonstrated prototypes that use the microneedles for anchoring drug payloads, allowing the capsule to release a larger dose of medication that dissolves at an exact location over time.

In other experimental designs, we had the microneedles themselves dissolve after injecting a drug. In still others, we used microscale 3D printing to tailor the structure of the microneedles and control how quickly a drug is released—providing either a slow and sustained dose or a fast delivery. With this 3D printing, we created rigid microneedles that penetrate the mucosal lining and gradually diffuse the drug into the tissue, and soft microneedles that compress when the cantilever pushes them against the tissue, forcing the drug out all at once.

by Reza Ghodssi, Justin Stine, Luke Beardslee, IEEE Spectrum |  Read more:

Image: Maximilian Franz/Engineering at Maryland Magazine

Embryo Selection Company Herasight Goes All In On Eugenics

Multiple commercial companies are now offering polygenic embryo selection on a wide range of traits, including genetic predictors of behavior and IQ. I’ve previously written about the methodological unknowns around this technology but I haven’t commented on the ethics. I think having a child is a very personal decision and it’s not my place to tell people how to do it. But the new embryo selection company, Herasight, has started advocating for eugenic societal norms that I find disturbing and worth raising alarm over. Because this is a fraught topic, I’ll start with some basic definitions.

What is eugenics?

Eugenics is an ideology that advocates for conditioning reproductive rights on the perceived genetic quality of the parents. Francis Galton, the father of eugenics, declared that eugenics’ “first object is to check the birth-rate of the Unfit, instead of allowing them to come into being”. This goal was to be achieved through social stigma and, if necessary, by force. The Eugenics Education Society, for instance, advocated for education, segregation, and — “perhaps” — compulsory sterilization to prevent the “unfit and degenerate” from reproducing:

A core component of defining “the unfit” was heredity. Eugenicists are not just interested in improving people’s phenotypes — a goal that is widely shared by modern society — but the future genotypic distribution. The genetic stock. This is why eugenic policies historically focus on sterilization, including the sterilization of unaffected relatives who harbor genotype but not phenotype. If someone commits a crime, they face time in prison for their actions, but under eugenic reasoning their law-abiding sibling or child is also suspect and should be stigmatized (or forcefully prevented) from passing on deficient genetic material.

A simple two-part test for eugenics is then: (1) Is it concerned with the future genetic stock? (2) Is it advocating for restricted reproduction, either through stigma or force, for those deemed genetically inferior?

Is embryo selection eugenics?

I have publicly resisted applying the “eugenics” label to embryo selection writ large and I continue to do so. Embryo selection is a tool and its use is morally complex. A couple can choose to have embryo screening for a variety of reasons ranging from frivolous (“we want to have a blue eyed baby”) to widely supported (“we carry a recessive mutation that would be fatal in our baby”), none of which have eugenic intent. Embryo selection can even be an anti-eugenic tool, as in the case of high-risk couples who have already decided against having children. If embryo selection technology allows them to lower the risk to a comfortable level and have a child they would otherwise have avoided, then the outcome is literally the opposite of eugenic selection: “unfit” individuals (at least as they see themselves) now have an incentive to produce more offspring than they would have. In practice, IVF remains a physically and emotionally demanding procedure, and my guess is that individual eugenic intentions — the desire to select out unfit embryos with the specific motivation of improving the “genetic stock” of the population — are exceedingly rare.

Is Herasight advocating for eugenics?

While I do not think embryo selection is eugenic in itself, like any reproductive technology, it can be wielded for eugenic purposes. The new embryo selection company Herasight, in my opinion, is advocating for exactly that. To understand why, it is useful to first understand the theories put forth by Herasight’s director of scientific research and communication Jonathan Anomaly (in case you’re wondering, that is a chosen last name). Anomaly is a self-proclaimed eugenicist [Update: Anomaly has clarified that this description was not provided by him and he requested that it be removed]:

Prior to joining Herasight, Anomaly wrote extensively on the ethics of embryo selection, notably in a 2018 article titled “Defending eugenics”. How does Anomaly defend eugenics? First, he reiterates the classic position that eugenics is a resistance to the uncontrolled reproduction of the “unfit” (emphasis mine, throughout):

Darwin argued that social welfare programs for the poor and sick are a natural expression of our sympathy, but also a danger to future populations if they encourage people with serious congenital diseases and heritable traits like low levels of impulse control, intelligence, or empathy to reproduce at higher rates than other people in the population. Darwin feared that in developed nations “the reckless, degraded, and often vicious members of society, tend to increase at a quicker rate than the provident and generally virtuous members”

Anomaly goes on to sympathize with Darwin’s position and that of the classic eugenicists, arguing that “While Darwin’s language is shocking to contemporary readers, we should take him seriously”, later that “there is increasingly good evidence that Darwin was right to worry about demographic trends in developed countries”, and that we should “stop allowing [the Holocaust] to silence any discussion of the merits of eugenic thinking”.

Anomaly then proposes several potential eugenic interventions, one of which is a “parental licensing” scheme that prevents unfit parents from having children:

The typical response is for the state to step in and pay for all of these things, and in extreme cases to remove children from their parents and put them in foster care. But it would be more cost-effective to prevent unwanted pregnancies than treating their consequences, especially if we could achieve this goal by subsidizing the voluntary use of contraception. It may also be more desirable from the standpoint of future people.

The phrase “future people” figures repeatedly in Anomaly’s writing as a euphemism for the more conventional eugenic concept of genetic stock. This connection is made explicit when he explains the most compelling reason for supporting parental licensing:

The most compelling reason (though certainly not a decisive reason) for supporting parental licensing is that traits like impulse control, health, intelligence, and empathy have significant genetic components. What matters is not just that some parents are unwilling or unable to take care of their children; but that in many cases they are passing along an undesirable genetic endowment.

What are we really talking about here? Anomaly has proposed a technocratic rebranding of eugenic sterilization: instead of taking away your reproductive rights clinically, the state will take away your reproductive license and, if you still have children, impose “fines or other costs” (though Anomaly does not make the “other costs” explicit, eugenic sterilization is mentioned as an example in the very next sentence). How would the state decide who should lose their license? Anomaly explains:

For a parental licensing scheme to be fair, we would need to devise criteria that are effective at screening out only parents who impose significant risks of harm on their children or (through their children) on other people.

A fundamental normative principle of our society is that all members are created equal and endowed with unalienable rights. What Anomaly envisions instead is a society where the state can seize one of the most intimate of human freedoms — the right to become a parent — based on innate factors. How does the state determine whether a future child imposes significant risk on future people? By inspecting the biological makeup of the parents and identifying “undesirable genetic endowments” that will harm others “through their children”. This is a policy built explicitly on genetic desirability and undesirability, where those deemed genetically unfit are stripped of their rights to have children and/or fined for doing so — aka bog-standard coercive eugenics.

Today, Anomaly is the spokesperson for a company that screens parents for “undesirable genetic endowments” and, for a price, promises to boost their genetic desirability and their value to future people. It is easy to see how Herasight fits directly into the eugenic parental licensing scheme Anomaly proposed. Having an open eugenicist as the spokesperson for an embryo selection company seems, to me, akin to hiring Hannibal Lecter to do PR for a hospital, but perhaps Anomaly has radically changed his views since billing himself as a eugenicist in 2023?

Herasight (with Anomaly as first author) recently published a perspective white-paper on the ethics polygenic selection, from which we can glean their corporate position. The perspective outlines the potential benefits and harms of embryo selection. The very first positive benefit listed? The “benefits to future people”. While this section starts with a focus the welfare of individual children, it ends with the same societal motivations as classical eugenics: the social costs of the unfit on communities and the benefits of the fit to scientific innovation and the public good: [...]

When eugenics goes mainstream

Let’s review: eugenics has as a goal of limiting the birthrate of the “unfit” or “undesirable” for the benefit of the group. Anomaly describes himself as a eugenicist and explicitly echoes this goal through, among other policies, a parental licensing proposal. Anomaly now runs a genetic screening company. The company recently published a perspective paper advocating for the stigmatization of “unfit” parents who do not screen. Anomaly, as spokesperson, reiterates that their goal is indeed eugenics — “Yes, and it’s great!”. With any other person one could argue that they were clueless or trolling; but if anyone knows what eugenics means, it is a person who has spent the past decade defending it.

I have to say I am floored by how strange this all is. My personal take on embryo selection has been decidedly neutral. I think the expected gains are limited by the genetic architecture of the traits being scored and the companies are mostly fudging the numbers to look good. As noted above, I also think a common use of this technology will be to calm the nerves of parents who otherwise would have gone childless. So I have no actual concerns about changes to the genetic make-up of the population or genetic inequality or any of the other utopian/dystopian predictions. But I am concerned that the marketing around the technology revives and normalizes classic eugenic arguments: that society is divided into the genetically fit and the genetically unfit, and the latter need to be stigmatized away from parenthood for the benefit of the former. I am particularly disturbed by the giddiness with which Anomaly and Herasight have repeatedly courted eugenics-related controversy as part of their launch campaign.

Even stranger has been the response, or rather non-response, from the genetics community. Social science geneticists and organizations spent the past decade writing FAQs warning against the use of their methods and data for individual prediction and against genetic essentialism. Many conference presentations and seminars start with a section on the sordid history of eugenics and the sterilization programs in the US and Nazi Germany, vowing not to repeat the mistakes of the past. Now, a company is openly advocating for eugenics (in fact, a company with direct connections to these social science organizations) and these organizations are silent. It is hard not to conclude that the FAQs and warnings were just lip service. And if the experts aren’t raising alarms, why would the public be alarmed?

by Sasha Gusev, The Infinitesimal |  Read more:

Image: Anselm Kiefer, Die Ungeborenen (The Unborn), 2002

[ed. With neophyte Nazis seemingly everywhere these days, CRISPR advances, and technocrats who want to live forever, it's perhaps not surprising that eugenics would be making a comeback. Update: Jonathan Anomaly, director of scientific research and communication for Herasight and whose articles I criticize here, responds in a detailed comment. I recommend reading his response together with this post. Anomaly’s role in the company has also been clarified. See also: Have we leapt into commercial genetic testing without understanding it? (Ars Technica).]

Alcohol Death Rates in Europe

Source: Institute for Health Metrics and Evaluation (OWID)
via:
[ed. A few surprises.]

"Alcohol death rates in Europe. Apparently very low in cultures where drunkenness is frowned upon and where alcohol is only consumed in company of others and served alongside meals. Spain and Italy for example." via:

The Century of the Maxxer

Most people, being average, do not understand what maxxing really means. Look at me! they squeal. I’m sleepmaxxing! They mean that they’re trying to get eight hours a night. Or they’re proteinmaxxing, which means they’ve bought a big tub of whey powder. I’m such a houseplantmaxxer, they tell the fiddle-leaf fig they ordered online. It’s fun to play around with a new word. But sleepmaxxing does not mean getting a red light and taping your mouth shut; it means putting yourself in a medically induced coma. There is only one way of proteinmaxxing, which is to get one hundred percent of your daily calories from lean protein. Anything else would, by definition, be less than fully maxxed. Doctors will tell you that eating only protein causes something called ‘rabbit starvation,’ and if you keep at it you’ll experience vomiting, seizures, and death in fairly short order. They’re right, but the proteinmaxxer accepts his fate. Meanwhile the houseplantmaxxer has thick mats of algae sliming over every surface, the walls, the ceilings, swallowing the sofa, digesting the bookshelf and all its contents, blobbing and dribbling, wet in the middle of the bed, green on the windowpanes, covering everything except the UV lights and the massive pans of water left on a constant boil in every room, so the air stays oppressively, Cretaceously thick.

This is what it means to be a maxxer. We are a long way away from the optimisation of the self; to maxx is an intense form of asceticism. The maxxer is the person who willingly sacrifices every aspect of their lives except one, the maxximand, which is extended to infinity until it begins to develop the distance and vastness of a god.

Probably the world’s most prominent maxxer is a man called Braden Peters, who calls himself Clavicular. Clavicular is a looksmaxxer; his austerity is to make himself as beautiful as possible. If you’re good looking enough, you can ascend, break out of your genetic destiny and into a new order of being, where the subhumans will crawl after you with lolling tongues. Clavicular started looksmaxxing at the age of fourteen, injecting himself with testosterone. He also shoots anabolic steroids, human growth hormone, peptides, botox, and crystal meth. He’s had multiple plastic surgeries. His other secret is bonesmashing, which is exactly what it sounds like: he smashes his own cheekbones with a hammer so they grow back bigger. It’s impossible to know what he would have looked like if he hadn’t done all this, since his ‘before’ pictures all show a prepubescent child, but it’s hard not to conclude that he’s utterly ruined his body. He didn’t go through a normal puberty; his glands are completely incapable of producing testosterone by themselves, and if he ever stops taking the hormones he’ll rapidly decompose into a genderless lump. The various injections have also left him totally sterile; his balls are almost certainly fucked up in ways we can barely imagine. He is a meth addict. And while he really does have legions of lesser beings crawling after him with lolling tongues, they do all seem to be men.

Clavicular lives in a sort of nightmare clown world, where he is constantly being approached in ordinary shopping centres by small, strange, awkward men who say things like ‘I’m known in Orlando as the Asian Mogger. I would have the honour if you could verify me as the Orlando Asian Mogger.’ There are various misshapen freaks of nature, men with shoulders wider than they’re tall, sinister stalking giants on artificially lengthened legs, who travel across the country to stand next to him and compare physiques. Like a mythical gunslinger, the great mogger needs to constantly watch the horizon for whoever’s coming to mog him. Other men adore him in more nakedly eroticised ways. In one video, he’s live-streaming a fun casual hangout with Andrew Tate, Tristan Tate, Nick Fuentes, a bunch of other people sitting in silence looking at their phones, and menial staff vacuuming in the background. One of the men is berating a woman sat in Clavicular’s lap. ‘You are not an 8. You’re not an 8. You’re a thirsty 7, you’re asking for validation, and you’re sitting in a 10’s lap.’ ‘That’s kinda rude,’ she says. ‘That’s kinda rude,’ agrees Tristan Tate. ‘Clavicular’s at least an 11.’ Clavicular doesn’t say anything. What gives the scene its particularly haunting resonance is that throughout this exchange, he seems to be eating soup.

In all his interactions with women that aren’t directly supervised by a Tate brother, Clavicular is painfully passive and awkward. The women who like him are all of a type: hot but autistic beyond belief, brainrotted, barfing up a constant stream of overenthusiastic tryhard 4chan nazi jargon that he seems to find deeply embarrassing. Normal women treat him with undisguised contempt. He is constantly having his cortisol spiked by foids. It turns out that being maximally beautiful is not actually the same as maximising your chances of getting laid. Clavicular will never be a female sex symbol; that role goes to men like Slavoj Žižek and Danny DeVito. But maxxing is not optimisation. The maxxer is not trying to have an enjoyable life. He’s trying to reduce himself to a single principle.

Things get confused when the maxximand is also a generally upheld value like beauty. But every maxxer has his shadow, the person maxxing the opposite principle. Clavicular’s shadow is someone who calls himself The Crooked Man. The Crooked Man is a looksminimiser, which is another way of saying he’s an uglymaxxer. His strategy has been to spend a year working out only one side of his body, which has left him with an enormous bulging trap on one shoulder and nothing at all on the other. He looks like a cartoon monster. He stands around shirtless in his empty millennial-grey house, adrift in some suburb somewhere, grey walls, grey carpet, no decorations except cables snaking around on the floor, making video content. He is a kind of Platonic ideal of the maxxer, far more than Clavicular. The Crooked Man’s house appears to get zero natural light. All his gym equipment is at home; you can see him benching 225 on one side only in one of its many large and empty rooms. Plastic Venetian blinds. It’s night outside. It’s always night outside. The sun never shines on The Crooked Man. Incredible things are happening in America.

There’s a reason Clavicular has become the media’s go-to symbol for maxxing, even though The Crooked Man is a much better exemplar. He keeps things on a very comfortable terrain. Maxxing, the line goes, is an outgrowth of incel culture. It’s about men, the problem with men, the crisis of masculinity; it’s about how men are now facing the kind of toxic body politics that women have had to deal with forever, and how they’re developing their own hysterias in response; it’s about online extremism, it’s about the harmful narratives that seduce young men into various forms of misogyny; before long it’s about how we all need to put the kettle on and have a proper talk about our men’s mental health. They’re not entirely wrong; there really is a crisis of masculinity, it really is expressing itself through the mainstreaming of misogyny and the proliferation of a diseased relation to the self. It’s just that maxxing comes from something else entirely.

Despite what you might have heard, the word maxxing is not originally incel slang. Incels might have appropriated it, but it began with another kind of loser altogether, the tabletop role-playing gamer.

by Sam Kriss, Numb at the Lodge |  Read more:

Image: Cassidy Araiza for The New York Times
[ed. See also: Handsome at Any Cost (NYT); and, From “Mar-a-Lago face” to uncanny AI art: MAGA loves ugly in submission to Trump (Salon).]

I Regret to Inform You that the FDA is FDAing Again

I had high hopes and low expectations that the FDA under the new administration would be less paternalistic and more open to medical freedom. Instead, what we are getting is paternalism with different preferences. In particular, the FDA now appears to have a bizarre anti-vaccine fixation, particularly of the mRNA variety (disappointing but not surprising given the leadership of RFK Jr.).

The latest is that the FDA has issued a Refusal-to-File (RTF) letter to Moderna for their mRNA influenza vaccine, mRNA-1010. An RTF means the FDA has determined that the application is so deficient it doesn’t even warrant a review. RTF letters are not unheard of, but they’re rare—especially given that Moderna spent hundreds of millions of dollars running Phase 3 trials enrolling over 43,000 participants based on FDA guidance, and is now being told the (apparently) agreed-upon design was inadequate. [...]

In context, this looks like the regulatory rules of the game are being changed retroactively—a textbook example of regulatory uncertainty destroying option value. STAT News reports that Vinay Prasad personally handled the letter and overrode staff who were prepared to proceed with review. Moderna took the unusual step of publicly releasing Prasad’s letter—companies almost never do this, suggesting they’ve calculated the reputational risk of publicly fighting the FDA is lower than the cost of acquiescing.

Moreover, the comparator issue was discussed—and seemingly settled—beforehand. Moderna says the FDA agreed with the trial design in April 2024, and as recently as August 2025 suggested it would file the application and address comparator issues during the review process.

Finally, Moderna also provided immunogenicity and safety data from a separate Phase 3 study in adults 65+ comparing mRNA-1010 against a licensed high-dose flu vaccine, just as FDA had requested—yet the application was still refused.

What is most disturbing is not the specifics of this case but the arbitrariness and capriciousness of the process. The EU, Canada, and Australia have all accepted Moderna’s application for review. We may soon see an mRNA flu vaccine available across the developed world but not in the United States—not because it failed on safety or efficacy, but because FDA political leadership decided, after the fact, that the comparator choice they inherited was now unacceptable.

The irony is staggering. Moderna is an American company. Its mRNA platform was developed at record speed with billions in U.S. taxpayer support through Operation Warp Speed — the signature public health achievement of the first Trump administration. The same government that funded the creation of this technology is now dismantling it. In August, HHS canceled $500 million in BARDA contracts for mRNA vaccine development and terminated a separate $590 million contract with Moderna for an avian flu vaccine. Several states have introduced legislation to ban mRNA vaccines. Insanity.

The consequences are already visible. In January, Moderna’s CEO announced the company will no longer invest in new Phase 3 vaccine trials for infectious diseases: “You cannot make a return on investment if you don’t have access to the U.S. market.” Vaccines for Epstein-Barr virus, herpes, and shingles have been shelved. That’s what regulatory roulette buys you: a shrinking pipeline of medical innovation.

An administration that promised medical freedom is delivering medical nationalism: fewer options, less innovation, and a clear signal to every company considering pharmaceutical investment that the rules can change after the game is played. And this isn’t a one-product story. mRNA is a general-purpose platform with spillovers across infectious disease and vaccines for cancer; if the U.S. turns mRNA into a political third rail, the investment, talent, and manufacturing will migrate elsewhere. America built this capability, and we’re now choosing to export it—along with the health benefits.

by Alex Tabarrok, Marginal Revolution |  Read more:

Image: Brian Snyder/Reuters

[ed. See also: F.D.A. Refuses to Review Moderna Flu Vaccine (NYT); and, Trump official overruled FDA scientists to reject Moderna’s flu shot (Ars Technica).]