Home Invasions

At four in the morning I heard a scratching that sounded like someone was trying to break into our new home. J. and I were not yet fluent in the house’s natural yawning and moaning—the way it sighed when stretching its pilings and beams, or grunted against a pummeling Florida gale, or shuddered when thunder clapped—and I often startled at sounds, trying to discern which ones required attention. And I’d recently been diagnosed with partial hearing loss in my right ear, which meant I couldn’t make out certain sounds but also imagined noises that weren’t there.

In the predawn dark it was hard to tell if my tenuous hearing was playing tricks on me. Then I felt a paw press my calf. Arrow was awake. The dog had heard it too.

I got up to ensure the windows were locked. Outside, a gentle wind stirred the mango tree’s canopy. A distant streetlight flickered on and off like a lighthouse beacon.

J. groaned and rolled over. “What is it?”

“I heard something.”

Arrow growled, jumped off the bed, and began sniffing along the baseboards, moving the length of the room. When he galloped down the stairs, J. and I dutifully followed.

Arrow stood by the back door, ears up, eyes on us. Everything was just as we’d left it. Everything was silent—until it wasn’t. A scraping so violent it made my fingernails ache issued from a corner of the dining room. Afraid of scaring whatever it was away, J. eased open the back door, and the two of us stepped outside.

Frogs chirruped. Something—a bird, a fish, a single, lonesome alligator—shattered the glassy black surface of the pond. J. ran a flashlight over the siding, the eaves, the roof. Nothing.

“It’s already inside,” he said.

“Squirrels?”

“Maybe.” He sounded unconvinced.

“Not squirrels,” said the pest-control specialist who came later that morning, after J. had left for work. Squirrels are daytime animals, he explained. They sleep at night.

I hoped he would say opossum. I hoped he would say, even, raccoon. Either would have been inconvenient and unpleasant but more easily remedied—a Havahart trap, a relocation to a nearby nature preserve, a single hole to fill. Instead he said exactly what I didn’t want to hear.

In the Chinese zodiac, people born in the Year of the Rat are shrewd, fickle, creative, thrifty, and wise. They are a litter of cowardly, hot-tempered, picky musicians, entrepreneurs, lawyers, and writers. They may be plagued by a weak constitution and prone to head colds and other viruses. I was born in the Year of the Rat and, coincidentally or not, possess many of these characteristics. Though I’ve always considered myself hardy, my partial hearing loss—the cause of which doctors were yet unable to explain—suggested otherwise.

Each year of the Chinese zodiac has a corresponding element. Mine is water, which makes me a water rat. Water is an element of hiding and suggests an inability to choose something and stick to it. At times I’ve been true to my watery nature, having been accused of being unable to commit to a job, a person, a responsibility. My initial ambivalence about moving to Florida supported such accusations, and buying a house with J. was my attempt to act against type.

Still, I hadn’t counted on real, live rats. “I’m surprised you hadn’t heard them before,” said Rat Guy #1, as he came to be known. “From the looks of it they’ve been here a while.” He wore a utility belt below a belly like unproofed bread dough. As he walked, his belt jangled with keys, flashlight, laser pointer, measuring tape, Swiss Army knife. He sweated beyond what was socially acceptable, even by Florida standards.

I hadn’t heard them before, but it turned out other people had. J. confessed to noting some rustling when he’d been up late a few weeks earlier. And my brother said he’d heard something when he and my sister-in-law had stayed overnight. Earlier in my life I might have been surprised, angry even, to learn they’d withheld the truth, but by then I’d come to believe it was human nature to look away, to plead ignorance. That was precisely what I’d done for months when my ear had begun to alert me, persistently, that there was a problem.

“I’ll close up the entry points,” said Rat Guy #1. “Set traps, fog the attic.” The fogging, he assured me, was safe for humans and canines—so safe, in fact, that it wouldn’t even kill the rats. Instead it left behind a perfume they found intolerable, driving them away.

This was my introduction to the pest-control business, and over the next several months I discovered that exterminators each have their own predilections, their preferred baits and traps, their brands of flashlights and trash bags in which to dispose of their prey. I also learned that, along with sound machines promising to transmit high-frequency pitches detected only by vermin, fogging is a scam.

Criminal or immoral tricksters are called “dirty rats” or “rat finks,” but Rat Guy #1 didn’t strike me as either of these. For one of what would be many visits, he arrived with his octogenarian mother who had been “bored outta my gourd” and “wanted a look-about.” Our generally discriminating dog loved him. When his truck appeared in the driveway, Arrow wailed at the front door, anxious to be let outside to spastically run circles around the man with an excitement he rarely demonstrated for anyone else, including J. or me. This was the most persuasive argument in favor of trusting Rat Guy #1.

by Lenore Myka, The Sun |  Read more:

Image: © Doug McMains
[ed. I had a rat problem in my last house, and the constant rustling in the walls drove me crazy, day and night. After setting traps in the attic, I'd remove on average one, sometimes two dead ones every other day. When I finally found their entry point it was the size of a quarter. I'd skipped it before because it just didn't look like something a rat could squeeze through. But, that was it, and I eventually got them under control after barricading their front door. My friend Jerry in Texas had an even bigger problem. I forget if it was a warning light that was constantly on, or a hose leak or whatever, but the problems kept escalating until he finally took it into the shop to have it checked out. That's when they discovered that a rat family had built a nest up inside the car frame, just behind the gas tank. Apparently they'd been there a long time, as evidenced by all the chewed wires, hoses, and other debris they found. The funny thing is that during the previous month or two after he'd started noticing these problems he'd driven over 700 miles between various states, many on bumpy, dusty backroads. Hard to imagine what that must have felt like for those little guys, up there burrowed in the undercarriage. Tough, scrappy little animals.]

June 23, 1988: James Hansen Testified to Senate About Climate Change

Coal is the single greatest threat to civilization and all life on our planet. . . . the dirtiest trick that governments play on their citizens is that they are working for ‘clean coal.’ . . .The trains carrying coal to power plants are death trains. Coal-fired power plants are factories of death. — James Hansen

On June 23, 1988, NASA scientist James Hansen testified to the U.S. Senate stating the greenhouse effect had been detected, indicating that the climate was in fact changing.

Hansen was also arrested on this day in 2009 during a protest against mountaintop removal mining at Massey Energy Company.

Hansen has stated,

Several times in Earth’s long history rapid global warming of several degrees occurred. . . In each case more than half of plant and animal species went extinct. New species came into being over tens and hundreds of thousands of years. But these are time scales and generations that we cannot imagine. If we drive our fellow species to extinction we will leave a far more desolate planet for our descendants than the world that we inherited from our elders.

by Zinn Education Project |  Read more:

Image: uncredited
[ed.  "According to science historian Spencer R. Weart, Hansen's testimony increased public awareness of climate change. According to Richard Besel of California Polytechnic State University, Hansen's testimony "was an important turning point in the history of global climate change." According to Timothy M. O'Donnell of the University of Mary Washington, Hansen's testimony was "pivotal," "ignited public discussion of global warming and moved the controversy from a largely scientific discussion to a full blown science policy debate," and marked "the official beginning of the global warming policy debate." According to Roger A. Pielke of the National Center for Atmospheric Research, Hansen's "call to action" "elevated the subject of global warming and the specter of associated impacts such as more hurricanes, floods, and heat waves, to unprecedented levels of attention from the public, media, and policy makers." - Wikipedia.]

[ed. Which was all it took for climate change skeptics to spring into action, and here we are...]

AI in Biology

If you wind your way through a quiet, wooded suburb outside of The City, you’ll reach a harbor. Situated on a hill overlooking the water, there is a Temple of Science. This Temple is centered around a task of the utmost importance: preserving a magical thread that connects the past, present, and future of the life sciences.

On one end, there is a gentle tug from the ghosts of Barbara McClintock, Martha Chase, and Alfred Hershey, reminding you of their elegant experiments that became part of the canon of genetics. Farther along, figures like Jim Watson grip the thread more fervently as they advocate for the centrality of their discoveries in the birth of molecular biology. If you put one hand in front of the other and continue to follow where it takes you, you’ll pass through the rise of genomics and end up on the frontier of biology.

Of course, I’m talking about Cold Spring Harbor Laboratory. For over one hundred years, this little research institute in Long Island, New York has punched well above its weight. CSHL played a critical role in multiple paradigm shifts in biology—including genetics, molecular biology, and genomics—as evidenced by the eight Nobel Prizes awarded to researchers from “The Lab” over the years. When normalizing for size, the Nature Index ranked CSHL as the most prolific biomedical research institution in the world.

I’ll never forget my first visit to The Lab. In February of 2020, I flew from Seattle to interview for the CSHL graduate school program. Famously (among researchers on the grad school interview circuit), they would arrange for each recruit to be picked up in a black car from the airport.

The campus itself, which is a direct physical representation of the magical thread that The Lab preserves, is equally memorable. A cluster of pristinely maintained colonial buildings, each painted white, borders the water. Above them is the Upper Campus, consisting of darker, modern renditions of the same pattern. Scientific art installations—like the Waltz of the Polypeptides or a gazebo with a phage structure on the tip—can be found along the walking trails.

Over the course of three days, I hurried around The Lab for a wide range of activities, including eleven interviews with faculty—two to three times the number that most other graduate school programs typically scheduled. It was wonderful and intense.

Ultimately, I was persuaded to go west for graduate school. Thankfully, there are many reasons to continue coming back to CSHL, which has been described as “the crossroads of biology.” Each year, they host dozens of conferences and courses that draw top researchers from around the world.

But one particular conference stands out in importance. Since 1933, CSHL has hosted an annual Symposium on Quantitative Biology. Reginald Harris, who conceived of the conference, wrote that the “primary motive of the conference symposia is to consider a given biological problem from its chemical, physical and mathematical, as well as from its biological aspects.” In retrospect, this was visionary.

Over the next several decades, chemists and physicists would revolutionize the life sciences. In 1944, Erwin Schrödinger, a leading physicist, wrote What is Life?, a book exploring open questions in biology through a new lens. It inspired many researchers and students, including a young James Watson, to pursue biological research. In 1953, at the 20th annual CSHL Symposium, Watson presented the structure of DNA for the first time in public.

For obvious reasons, this gave the CSHL Symposia a sort of “mythic quality” moving forward. This reputation compounded quickly. Over the next 15 years, the pioneers of molecular genetics would travel each year to present their most important discoveries—such as the central dogma and the genetic code—at CSHL.

The tradition continues to this day. Each year, the Symposium is organized around a topic considered to represent the frontier of life sciences research.

Which brings us to the topic of the 90th Cold Spring Harbor Laboratory Symposium on Quantitative Biology: AI in Biology.

Readers of this newsletter are not strangers to the fact that AI is reshaping biology. The tools derived from breakthroughs such as AlphaFold have been adopted by seemingly all biologists at this point. But it was stunning to see these advances celebrated so prominently in this venue. It felt historical.

As Bruce Stillman, CSHL’s current President, pointed out in his opening remarks, this topic connects back to the very origin of the Symposia—as the name suggests. Harris had spotted the emergence of a new quantitative paradigm in biology. Between then and now, molecular genetics did in fact transform biology into an information science.

It’s becoming more clear each day that the next chapter of this story is AI. Sydney Brenner, one of the most central figures of molecular biology, gave one of the most incisive criticisms of the field in his Nobel Prize lecture: “We’re drowning in a sea of data and starving for knowledge.” AI is starting to change that equation.

For five days, top researchers in the field shared updates on their efforts to use machine learning to decipher the mechanisms of DNA, RNA, proteins, cells, tissues, organs (especially the brain), and how information flows between these different biological scales. And there were examples of how AI agents might be able to autonomously carry out some of this research—which was met with a combination of excitement and anxiety from attendees.

It was one of the most compelling conferences I’ve ever attended, so I want to share some of what I saw. Before jumping in, this requires a few quick notes on the format of the event.

First, attending a Symposium feels like drinking from a scientific firehose—by design. CSHL is truly a Temple, or maybe even a monastery. Most attendees stay on campus and don’t leave for the duration of the conference. Talks are back-to-back all day in the main auditorium, followed by communal meals and poster sessions that run throughout the evening. It’s non-stop. My goal isn’t to give an exhaustive blow-by-blow, but to highlight some of the themes and topics I found most exciting.

Second, following in the tradition of Watson, many researchers share more new and unpublished data than is typical at other conferences. To respect this tradition, I’m going to focus on the data shared that has already been published, with more high-level descriptions of new research directions and results.

With all that said, let’s get into it! [...]

Agents, Agents, Agents

Maybe I’m in a bubble in San Francisco, but it’s hard not to constantly hear about AI agents in the year 2026. It’s strange to think, but it’s been three and a half years since ChatGPT was first released. That’s long enough for many humans to feel frustrated by the shortcomings of what was once magic. Now, we want these models to do work for us, and to carry out longer, more complex projects that require reasoning.

There are now many efforts to develop systems for “agentic science,” where AI models are able to autonomously develop new hypotheses, design experiments, and analyze results. This concept was another recurring theme at the symposium.

Pushmeet Kohli hit on this the first evening. The last third of his talk focused on DeepMind’s efforts to build an AI Co-Scientist, which they published a new paper on last month. Given a research goal by a human scientist, this system develops a research plan and then kicks off a “tournament” of agents competing to develop new hypotheses. Agents within this system have different tasks. Some are designed to “reflect” on the ideas being generated. Others are tasked with “evolving” them.

While the goal is hypothesis generation, the AI Co-Scientist itself is no longer just a hypothetical. DeepMind has already given early access to academic researchers working in a wide variety of biomedical domains. Kohli highlighted a high profile example where the Co-Scientist was able to predict a new mechanism of bacterial gene transfer before the result was published in the literature.

by Elliot Hershberg, The Century of Biology | Read more:
Image: uncredited/CSHL

[ed. See also: What’s new in biology: June 2026 (Works in Progress).]

The Last Great Wilderness

Ping-pong sponges, ‘black smokers’ and floating somethings: the secrets of the deep sea.

If you want to follow in the footsteps of the great explorers, forget the moon and Mars: the ocean floor is where the real action is. The deep ocean, the part that’s deeper than 200 metres, covers about 66% of the Earth’s surface. Most of it has never been surveyed in detail. Even less has been seen up close. If the current rate of observation continues, a complete visual survey of the ocean floor will take about 5m years. [...]

The deep ocean is the largest ecosystem on Earth. It is also in many ways the most extreme, home to crushing pressures, extremes of heat and cold, and a near total absence of sunlight. Animals inhabiting this midnight world tend to be equally extreme. It is a menagerie that abounds in superlatives: the largest, the oldest, the blackest, the most luminous. But those are only the ones we know about. Most of the animals dwelling in the benthos, the true deep, remain unknown to science. Virtually every scientific expedition to reach this zone of darkness returns with new species in tow. In the past year, scientists have discovered more than 1,100 new marine species. Among them are a ghost shark (not really a shark), a ping-pong ball sponge (which does look like a cluster of ping-pong balls), a number of luridly coloured worms and a floating something that resembles a tiny jet plane made out of pale pink jelly, and which scientists have not yet been able fit into any of the primary categories of animal life. [...]

For over 50 years, would-be industrialists and entrepreneurs have floated the idea of mining the ocean floor, but without much happening in practice. But in our search for new sources of metals needed for batteries and microchips, we may now be on the cusp of destroying the world’s largest – and strangest – ecosystem before we get a chance to understand it.

by Jacob Mikanowski, The Guardian | Read more:

Images: Jim Maragos/AP; Nekton Ocean Census/Schmidt Ocean Institute

In Support of Mandatory Nucleic Acid Synthesis Screening and Recordkeeping

As life sciences researchers, builders of AI and biotechnology, and experts with a wide range of views on how to approach AI policy, we call on legislators to make screening of orders for synthetic nucleic acids — and the equipment needed to make them — mandatory.

The ability to order synthetic DNA online has accelerated vaccine development, powered basic research, and made it possible for small teams to access capabilities that used to be confined to major institutions. Since the publication of protocols to reconstruct viruses from strands of DNA more than two decades ago, it has also been recognized as a point in the biotechnology supply chain where a bad actor could cause outsized harm. Recognizing the vulnerability, synthesis companies formed the International Gene Synthesis Consortium in 2009 to develop and implement voluntary safeguards against misuse.

While the issue is not new, the pace of progress in artificial intelligence is. AI systems now outperform PhD-level virologists on questions about highly technical laboratory procedures in their own domains of expertise. The evidence about what this means for present-day biosecurity threats is genuinely mixed, but the trend is hard to dispute. AI systems are improving rapidly, and alongside incredible benefits to science and medicine, there is a real possibility that the knowledge barriers which have historically prevented bad actors from obtaining biological weapons will meaningfully erode.

Support for screening does not depend on any particular view of AI; the biosecurity case has been recognized by scientists and governments for decades. Screening is also one of the best understood and least disruptive biosecurity measures available. It asks providers of synthesized DNA and manufacturers of synthesis machines to check synthesis requests for sequences of concern and to verify customer legitimacy before shipping orders. Providers should also record synthesis orders and sequence data to support legitimate biosecurity investigations, so that any threat that might evade initial screening can be traced back to its source — including when individual sequences would not raise concern in isolation. Awareness of traceability itself deters misuse.

Many of the largest and most responsible providers in the industry already screen and record orders voluntarily because it is well understood that they have an important role to play in maintaining public trust in and mitigating potential misuse of this important technology.

For these reasons, the undersigned support mandatory nucleic acid synthesis screening, including recordkeeping, in the United States.

Given the pace at which the underlying technology is changing, we believe the need is urgent. Congress should act this session, and we applaud the legislative efforts currently underway. To ensure a consistent national standard rather than a patchwork of conflicting laws, states should also consider implementing requirements based on existing federal and industry guidelines.

This is a rare moment of agreement across stakeholders that are often at odds. We hope policymakers will meet it with decisive action.

Sincerely,
Signatories: — *Everybody*

[ed. No brainer, right? You don't just leave potential life-threatening bio-warfare components laying around with no oversight. Right?]

***

Amrith Ramkumar (WSJ): Top artificial-intelligence executives are joining security experts in calling for Congress to protect against biological threats posed by AI, adding to growing pressure on lawmakers to address the technology’s risks.

Three major chief executive officers—OpenAI’s Sam Altman, Anthropic’s Dario Amodei and Demis Hassabis of Google’s DeepMind AI lab—are among the signatories of a letter urging Congress to require safeguards when companies order synthetic DNA and RNA, a key step in developing certain vaccines and biotech breakthroughs.

… It was organized by two tech-focused think tanks that said the topic is a rare source of agreement among libertarians, progressives, researchers and rival executives.

Dean W. Ball: I am honored to have signed on to this letter. This is an urgent priority for near-term action by Congress. Biotech is advancing rapidly on its own, and I—and many others—believe the “Mythos moment” in AI/bio is coming soon. It is time for action.

revisions to existing nucleic acid screening requirements were mandated by an EO POTUS signed a year ago; I worked on them while in govt. I genuinely don’t know what happened to that work after I left but it is nine months behind schedule. Congress acting is better anyway.

Joshua Teperowski Monrad: People are so astounded when I tell them this isn't already law

Alec Stapp: it really is insane [...]

Other signatories include Patrick Collison, Paul Graham, Mustafa Suleyman, Alexandr Wang and a lot more where that came from.

We need such letters, despite this having ~100% support among those who understand any side of this, this is such a slam dunk that we should be doing this even before considerations of AI making malicious action vastly easier.

Why? Because political awareness is basically still near zero:

Will Poff-Webster: When I was a Senate staffer and occasionally got the chance to bring up biosecurity risks from AI, the response was often, “What? AI might be able to do that?”

This letter shows how easy it’d be for Congress to act on this

via:

Dognosis

At a former pomegranate farm on the outskirts of Bengaluru, a team of specially trained dogs is doing something that some of the world's most sophisticated medical machines cannot — detecting multiple types of cancer from a single breath, at early stages, for two dollars a test.

Dognosis, the Indian startup behind this system, published the results last week of its Phase 2 clinical trial in the Journal of Clinical Oncology — the world's most influential cancer journal — making it the largest study of its kind ever conducted and placing canine-based diagnostics firmly into the mainstream of medical science.

What Dognosis Does

The company was co-founded by Akash Kulgod, who built on his Honours thesis at Berkeley, and Itamar Bitan, who brings a decade of Special Ops K9 training experience from Israel. What the two founders realised was that the solution to early cancer detection had been living in our homes the whole time — the dog's nose, a product of fifteen millennia of co-evolution with humans, can detect the faint chemical trace of cancer in breath at a resolution that machines, algorithms, and laboratory tests have never come close to matching.

Therefore, Dognosis is building an ultra-affordable, non-invasive breath-based multi-cancer early detection test that combines trained dogs' exceptional olfactory abilities with brain-computer interfaces and machine learning to create quantitative signatures of disease.

How the Test Works

The test is straightforward: a person breathes normally into a cotton face mask for 10 minutes. The mask is sealed, stored, and later evaluated by trained detection dogs at a central laboratory. Each sample is assessed independently by at least three dogs and their assessments are combined using an advanced Bayesian statistical model that weighs each dog's track record and the participant's background information. No blood is drawn, no scan is needed, and no fasting is required.

 
The Science: What the Dogs Are Smelling

The dogs are detecting changes in volatile organic compounds — substances produced by the body when diseases like cancer are present. These VOCs create a unique odour signature or volatilome that trained dogs can identify, just as they are trained to detect explosives and drugs.

According to Dognosis, over 40 double-blind trials published in peer-reviewed journals have demonstrated that dogs can detect various diseases, including different types of cancer, with high accuracy, and this ability is now well-established in scientific literature spanning journals including Nature and The Lancet.

The Phase 2 Trial: What It Found

According to the paper published in the Journal of Clinical Oncology, the study was conducted across six hospitals in Karnataka — three each in Hubballi and Bengaluru — in an assessor-masked, multi-centre case-control format. A total of 3,275 participants were enrolled, with 1,773 used for training and 1,502 for testing. The test cohort included 283 treatment-naïve, biopsy-confirmed cancer cases spanning seven major cancer groups and 1,219 controls including healthy volunteers.

The Phase 2 data showed 91% accuracy in detecting cancer-associated VOC breath signals across seven cancer groups, with accuracy stable across cancer types as well as in early stages — when detecting cancer early matters the most. The study was conducted in collaboration with Medical Detection Dogs, a UK-based charity and world leader in canine bio-detection research. 

"We've known for over two decades that dogs are capable of detecting multiple types of cancers with high accuracy," said Akash Kulgod, chief executive officer of Dognosis. "The challenge has always been building a system around canine olfaction that is reproducible, scalable, and aimed at a clinical problem worth solving."

"Multi-cancer risk stratification from a single breath sample in countries like India is that problem, and this study shows that it can be done," Kulgod said.

 
Why It Matters

The rise of multi-cancer early detection tests and AI-powered imaging has created an acute need for effective first-tier screening, which breath-based testing is uniquely positioned to fulfil — particularly in low- and middle-income countries where expensive imaging infrastructure remains out of reach for the majority of patients.

At $2 per test, Dognosis's system costs a fraction of existing screening tools, many of which also fail to detect cancer at its earliest and most treatable stages.

by NDTV Profit News |  Read more:

Image: uncredited via

Evolutionary Quandaries

xkcd via: here/here

Ben Sasse's Warning

When Ben Sasse walked onto the Senate floor in November 2015 to deliver his first speech as a member of the upper chamber, he did something unusual: He had waited a full year to speak. It’s part of a Senate tradition known as the “maiden speech.” A historian by training and a management consulting associate by early vocation, he had spent his first year in the chamber interviewing colleagues, studying how the institution functioned, and developing a diagnosis before offering it publicly. When he finally spoke, the speech landed with enough force that Sen. Mitch McConnell (R-KY) distributed the text to every Republican senator, a gesture the Senate GOP leader at the time rarely made.

“No one in this body thinks the Senate is laser-focused on the most pressing issues facing the nation,” Sasse told his colleagues. “No one.”

The indictment was bipartisan, surgical, and delivered with the calm of a man who had considered it carefully before speaking. The Senate, he argued, had surrendered its institutional identity to the rhythms of the 24-hour news cycle, to the demand for sound bites, and to the incentive to grandstand for a narrow base and raise money rather than legislate for a country. “The people despise us all,” he said. “And why is this? Because we’re not doing our job.”

It served as a warning that went unheeded, and 11 years later, we’re watching more dysfunction in government than ever before. Sasse, now dying of Stage 4 pancreatic cancer at 54, is still saying the same thing. The diagnosis has not changed the message. It has sharpened it.

Whether Sasse was a “good” or “effective” senator is debatable. Whether Washington currently has enough senators like him is not a close question.

The criticism that followed him throughout his eight-year tenure is almost entirely subjective. His critics on the Left saw a man willing to deplore Trumpism in public while voting with President Donald Trump‘s agenda in practice. His critics on the Right, particularly as the party realigned, saw a posturing institutionalist more interested in making points and serving as a pundit than in getting on board fully with the president’s policies. The most durable version of this critique runs something like: He gave great speeches and passed no significant legislation.

Yuval Levin, founding editor of National Affairs and director of Social, Cultural, and Constitutional Studies at the American Enterprise Institute, largely rejects both sets of criticisms. On the Trump question specifically, Levin is direct: “The notion that there was much more he could have done to hold Trump to account is misdirected and mistaken. He took on Trump when he disagreed with him, and when he thought Trump had exceeded his authority or violated his oath. And unlike most Senate Republican critics of Trump, he ran for reelection and won after doing that.”

The objection to the lack of signature legislation mistakes the Senate’s function for a body it was never designed to be. In the framework Sasse spent years articulating, the Senate is not primarily a factory for producing legislation. It is a deliberative institution meant to apply friction to democratic impulses in the House of Representatives, to slow things down when people want to move too fast, and to force the executive and judiciary to operate within appropriate constitutional limits. By that standard, which is closer to the Founders’ intent than the one applied by Sasse’s critics, he understood and performed his role better than most of his colleagues.

The “pundit” critique oversimplifies his actual record. Sasse served on the Senate Intelligence Committee throughout his tenure, and his work on China there was substantive and largely ahead of the political mainstream. When it was still unfashionable for a Republican to identify Beijing as a generational geopolitical threat rather than an irritating trade partner, Sasse was making that case in the committee rooms that mattered. He had genuine expertise in China’s intelligence operations and, accordingly, used his position, spending considerable time in secure facilities at times when most of his colleagues were busier developing a social media strategy.

Sen. Mark Warner (D-VA), who worked alongside him on the intelligence committee, offered perhaps the most precise characterization of what made Sasse different, telling Scott Pelley on 60 Minutes in April that Sasse “never really thought about things as conservative, liberal. He thought much more about issues, such as the future and the past.” Senate Majority Leader John Thune (R-SD) said Sasse had a “concern not just for today, but for tomorrow and the future” and that he “wasn’t distracted by all the noise that goes around us on a daily basis.” [...]

Levin, who watched Sasse’s tenure closely, offers a candid accounting of his legislative limitations. “It’s true that Ben was not an active legislator, advancing proposals, sponsoring and co-sponsoring legislation, and building coalitions,” he said. “He was active in some key committees, especially the Intelligence Committee, where it seemed to him that active engagement could make a difference. But I think he concluded this was not the case in some of his other committees and that he might be more useful as a critic and observer of the institution. No individual senator gets a lot done right now, and of course, that’s part of the frustration he had.”

But the moments that defined Sasse as a senator were the ones that did not produce legislation, and those are the moments worth examining without the usual condescension.

On the first day of Justice Brett Kavanaugh‘s Supreme Court confirmation hearings in September 2018, the chamber descended almost immediately into the theater that had by then become customary. Protesters disrupted proceedings from the gallery. Democratic senators jockeyed for camera time. The atmosphere was more performance than inquiry. Into this circus, Sasse delivered a 12-minute statement that went viral because it said plainly what almost no one in that room was willing to say: The hysteria around confirmation hearings is a symptom, not the disease. Congress had spent decades delegating its legislative authority to executive agencies and now blamed the courts for filling the vacuum.

“It is predictable now that every confirmation hearing is going to be an overblown, politicized circus,” he said. “And it’s because we’ve accepted a bad new theory about how our three branches of government should work.” The corrective he offered was simple: Congress should pass laws and stand before voters. The executive should enforce those laws. Judges should apply them, not write them. Naturally, no one disagreed out loud.

He delivered a version of the same argument at Justice Amy Coney Barrett‘s hearing in 2020. Neither speech moved the institution. Both captured something true and important about why the institution was failing, and both were widely shared by people who had largely stopped expecting a sitting senator to say anything worth sharing. The Kavanaugh statement was described in this publication at the time as the civics lesson Washington desperately needed. That it needed to be given by a freshman senator to the full Senate Judiciary Committee was Sasse’s real point.

He also understood, more clearly than most of his colleagues, that the Senate’s dysfunction was not incidental but structural. The cameras, he argued, were a bad incentive. The constant travel and time spent fundraising corroded the relationships that make effective governing possible. Most tellingly, he believed that senators had come to treat their office as the purpose of their lives rather than a temporary form of service to something larger. When Pelley noted on 60 Minutes that many senators he knew “would not be able to breathe without that job,” Sasse replied that he feared that was true and that it represented “a much, much deeper problem.” The best title a person could hold, he said, was dad, mom, neighbor, friend. Senator was “a great way to serve. It should be your 11th calling or maybe sixth, but never top.”

When he resigned from the Senate in January 2023 with four years remaining in his term to become president of the University of Florida, many observers treated it as confirmation of the pundit critique: He could not stay the course. The more honest reading is that he had concluded the institution was, as he told Pelley, “very, very unproductive” and that there were better things for him to do. “We didn’t do real things,” he said. “And it felt like the opportunity cost was really high.” He moved to Florida, then stepped down from that post roughly a year and a half later when his wife, Melissa, was diagnosed with epilepsy and required full-time care. The man who had argued that being a senator should rank no higher than sixth on a person’s list of priorities was living accordingly.

Then, on Dec. 23, 2025, he posted the news to X. “Last week I was diagnosed with metastasized, stage-four pancreatic cancer, and am gonna die.” He was 53. Doctors at MD Anderson Cancer Center had cataloged the full spread: lymphoma, vascular cancer, lung cancer, liver cancer, and pancreatic cancer, the point of origin. He had been given three to four months to live. He called it what it was: “Advanced pancreatic is nasty stuff; it’s a death sentence.”

What followed was unexpected, at least to anyone who had expected Sasse to retreat from public life. He launched a podcast called Not Dead Yet. He sat down for a conversation with New York Times columnist Ross Douthat on the latter’s Interesting Times podcast in April, which was released just days after the interview aired and subsequently circulated widely. He appeared on 60 Minutes with Pelley on April 26, his face visibly marked by his medication, a drug called daraxonrasib from Revolution Medicines that had shrunk his tumors by 76% and extended his life by months that were not supposed to exist. He credited the extra time to “providence, prayer, and a miracle drug.”

The Douthat interview was the more intimate of the two conversations and the more remarkable. Douthat asked Sasse at the close whether he felt ready to die. Sasse said he did not feel ready but that he had hope, grounded in his Reformed Christian faith, that he would be with God. The response moved Douthat visibly to tears, something Sasse responded to with his characteristic dry humor. Earlier in the conversation, Sasse reflected on what the disease had given him alongside what it had taken. “I hate pancreatic cancer,” he told Douthat. “I would never wish it on anyone, but I would never want to go back to a time in my life where I didn’t know the prayer of pancreatic cancer. I can’t keep the planets in orbit. I can’t even grow skin on my face.”

The “prayer of pancreatic cancer,” as Sasse uses the phrase, is something like the acknowledgment of dependence that most people spend their healthiest years avoiding. He is not unusual among the terminally ill in arriving at that acknowledgment. He is unusual in the way he has extended it outward, into public argument, into the same institutional critique he was making in November 2015. On 60 Minutes, he was asked what Congress was missing, and he named the artificial intelligence revolution, the future of work, and the complete absence of 2030 or 2050 thinking in either party. Then, without prompting, he returned to the frame he had always used. “The Senate needs to be less like Instagram. The Senate needs to be more deliberative, and that means less smack-down nonsense,” he told Pelley, adding, “The Senate should be plodding, and steady, and boring, and trustworthy.”

by Jay Caruso, Washington Examiner |  Read more:

Image: uncredited via

[ed. I knew very little about Ben Sasse before reading an article about daraxonrasib, the new breakthrough drug given to him in his treatment for aggressive pancreatic cancer. It goes without saying that Congress would be an entirely different place if there were more people like him. See also: Pancreatic cancer just met its match (Works in Progress):]

***

"For most of the last half-century, a diagnosis of metastatic pancreatic cancer was a death sentence. In December 2025, former Nebraska Senator Ben Sasse announced he had been diagnosed with stage four pancreatic cancer that had spread to his lungs, liver and other organs, and was given three to four months to live from the time of diagnosis. With little to lose, he enrolled in a clinical trial for an experimental drug. Four months later, he reported a 76 percent reduction in tumor volume, describing the drug, daraxonrasib, as a ‘miracle’. His face, ravaged by a severe skin rash from the treatment, told a more complicated story. Yet he was alive and grateful to be able to talk to his family.

A few days after Sasse’s interview, in April 2026, Revolution Medicines announced Phase 3 trial results for daraxonrasib showing the drug had roughly doubled survival in patients with metastatic pancreatic cancer compared to standard chemotherapy. For a disease where median survival has long been measured in months and where little had changed for decades, that result represents a genuine turning point.

But the significance extends beyond pancreatic cancer. Daraxonrasib is among the first drugs in an emerging generation designed to target RAS, a protein implicated in roughly a quarter of all human cancers and long considered beyond reach, in all its mutant forms. And it belongs to a broader class of medicines, molecular glues, that are beginning to show what becomes possible when drugs no longer depend on finding a ready-made pocket in their target. Several compounds in this class are now in clinical development, each probing a different protein that previous generations of drugs could not touch."

Monk Seals Under Attack

The response was swift.

A week after a bystander’s cellphone video appeared to show a tourist heaving a coconut-sized rock at a Hawaiian monk seal swimming in calm waters off Lahaina, barely missing its head, federal authorities charged the Seattle resident with harassing the endangered animal.

On Wednesday, they arrested the person believed to be in the video: Igor Mykhaylovych Lytvynchuk, 38. He’s expected to appear in court in Honolulu on May 27.

Those decisive moves followed near-universal outrage as images of the startled male monk seal and a defiant Lytvynchuk went viral in Hawaiʻi and beyond, prompting calls for action.

 

Outside of high-profile incidents such as that, authorities struggle to prosecute those who harass or even intentionally kill Hawaiʻi’s monk seals — one of the world’s most endangered species and a culturally important animal in the islands.

Protecting the mammals from human harm, advocates say, remains a complex and uphill battle.

Most incidents don’t get caught on camera. Federal enforcement is stretched awfully thin across the Pacific region. Misinformation about the seals competing with fishermen for food, seal advocates say, continues to spread through local communities and spur attacks. [...]

On Maui, Mayor Richard Bissen vowed to personally see that Lytvynchuk, who was vacationing there, would be prosecuted to the fullest extent of the law. If convicted, Lytvynchuk faces up to one year in prison for each charge plus fines of up to $50,000 under the Endangered Species Act and up to $20,000 under the Marine Mammal Protection Act.

Initially, authorities believed the seal nearly hit was a female named Lani but later determined it was a different, male seal, Bissen said in an Instagram post Thursday. [...]

Enforcement Challenges

Out of at least 16 incidents of confirmed, intentional monk seal killings by humans in the past 17 years that remain unsolved, federal officials have only managed to prosecute one case. That incident, on Kauaʻi, dates back to 2009.

NOAA’s Office of Law Enforcement, which is charged with protecting the seals under endangered species rules, did not respond this week to requests for comment.

Maria Sagapolu, assistant director of the office’s Pacific Islands Division, said in 2024 that there were fewer than 12 people to cover enforcement of the entire U.S. Pacific region, including Hawai‘i, Guam and other U.S. territories.

The Pacific represents the smallest of the OLE’s five divisions but has to cover the largest area, according to Sagapolu, representing some 1.7 million square miles. [...]

Among the $7.5 million in green fee tourism outreach funding cut by the Legislature was a $700,000 proposal to work with the tourism industry on better visitor outreach and more “culturally grounded messaging that promotes safe wildlife interactions,” according to a statement from the Department of Land and Natural Resources on Thursday.

Those dollars also would have funded a pilot marine protected species reporting app, the agency said, for the community to help report a host of threats related to Hawaiʻi’s wildlife, including monk seals. The project was recommended by Gov. Josh Green’s volunteer Green Fee Advisory Council, but the Senate removed its funding last month.

by Marcel Honoré, Honolulu Civil Beat | Read more:
Images: Hawaiʻi District Court document/2026; The Marine Mammal Center, NOAA Permit #24359/2023
[ed. The human capacity for stupidity and cruelty can never be underestimated (which appears to have infected Molokai as well). When a witness confronted the man, he said “he did not care and was ‘rich’ enough to pay any fines,”. Video here (Hawaii News Now).]

Why Consciousness Researchers Have Failed (So Far)

Oh god, I barely made it through.

Experienced sensations while reading: frustration, dread, restless legs, and overwhelming waves of weariness. At one point I felt physically nauseous.

I’ve been trying to figure out why, since (a) Michael Pollan is a great writer who has proven his chops over countless other topics, and (b) this is objectively quite a good book about the science of consciousness. Indeed, I should be happy! Consciousness is clearly having “a moment” right now—a science book about consciousness has been on The New York Times bestseller list for nine weeks, and meanwhile, the online world is abuzz with debates about AI consciousness.

And yet… I hated Pollan’s book.

I felt that every next chapter or section could have been predicted by some statistical machine for producing books about consciousness (“Okay, here’s the part about David Chalmers coming up”). And yes, I have the advantage of being a researcher in the same subject and have even worked with some of the figures Pollan writes about, which is why in my own The World Behind the World (we all seem to gravitate to the same titles, huh) I broadly told much the same story. But you can even go back to science journalist John Horgan’s The Undiscovered Mind, published in 1999, to get similar progress beats and quite familiar names. It’s been 27 years, during which the discussion has (as many fields of science do) centered around major figures like neuroscientists Christof Koch or Giulio Tononi or Antonio Damasio or philosophers like David Chalmers. There’s always the part where Alison Gopnik makes an appearance. Karl Friston pops his head in. And all these people are intellectual titans. Truly. But honestly, this stage of consciousness research feels played out.

Like you have Christof Koch, one of the highest-profile figures, who broke open the field in the 1990s with Francis Crick (co-discoverer of DNA’s structure) and gave one of the first proposals for a neural correlate of consciousness: gamma oscillations in the ~40Hz range in the cortex.

Koch, who is soon to turn seventy, was for a while after the death of Francis Crick a staunch supporter of Integrated Information Theory (I was part of the team that worked on developing that theory after Giulio Tononi proposed it, and even once did a conference submission with Koch himself). But now Koch has apparently moved on to other approaches to consciousness, mentioning his attendance of an ayahuasca ceremony and his accessing of a “universal mind.”

Here’s Pollan talking to Koch at the end of the book:

When I confessed to Koch my fear—that after my five-year journey into the nature and workings of consciousness, I somehow knew less than I did when I started—he simply smiled.

“But that’s good,” he said. “That’s progress.”

No, it isn’t!

Consciousness is not here for our personal therapy. It’s not tied to our life journeys. And I’m guilty of all that artsy and personal stuff too! But it’s no longer about how the grand mystery makes us feel, or the friends we made along the way.

It’s all changed.

HOW WE FAILED

Right now, there’s some college student falling in love with a chatbot instead of the young woman who sits next to him in class, all because science literally cannot tell him that the chatbot is lying about experiencing love. On the other hand, if somehow AIs are conscious, either right now (to some degree), or near-future ones will become so, then they deserve rights and protections, and the entire legal and social apparatus of our civilization must expand rapidly to include radically different types of minds (or we must choose to restrict what kinds of minds we create). There are immediate practical matters here. Long term, we also need to protect against extremely bad futures where only non-conscious intelligences remain—the worst of all possible worlds is that our civilization acts like a reverse metamorphosis, where something weaker but more beautiful, organic consciousness, gets shed in the birth of some horrible star-devouring insect made of matrix multiplication. And then it turns out there is nothing it is like to be two matrices multiplying.

While it’s my opinion that modern LLMs operate more like tools right now, or at best like a lesser statistical approximation of what a good human output would be (with their main advantage being search, not insight), this is all just the beginning of the technology. The door is open and will never be closed again.

Of course, consciousness matters far beyond just AI. Table stakes for actual scientific progress on consciousness include shifting neuroscience and psychiatry from pre-paradigmatic to post-paradigmatic sciences (and all the pile-on effects from that). This was always true. But my point here is that LLMs act like a forcing function. Before everything changed, consciousness research was an unhurried subfield of neuroscience that was always a little weird and niche; therefore academics are guilty of treating consciousness like an academic exercise. [...]

Due to the rise of behaviorism and logical positivism, “consciousness” became a dirty word in science for half a century or more—precisely when the rest of the sciences rocketed ahead! The consciousness winter only really ended in the 1990s because of the collective weight of several Nobel Prize winners (like Francis Crick and Gerald Edelman) determined to make it acceptable again.

The two major scientific conferences (which are how scientists organize) devoted to consciousness also only started in the mid-90s. That’s just 30 years ago! Modern science is incredibly powerful, maybe the most powerful force in existence, but in the grand scheme of things, 30 years is not long at all. That’s just one generation of scientists and thinkers. Kudos to them. Pretty much all of the big names (including definitely Koch) deserve their laurels, and contra Pollan, I do think consciousness actually has made progress over the last 30 years, in that our conceptions are a lot cleaner, the definitional problem is pretty much solved, a lot of the space of initial possible theories is mapped, the problems and difficulties are much better known and clearly outlined, and there is organizational and behind-the-scenes structure that exists in the form of established conferences and labs and minor amounts of funding, etc.

And that’s another thing: no one has tried throwing money at the consciousness problem, at all—and for many problems, from AI to cancer cures, a necessary component often ends up being finance and scale and concentrating talent.

Humanity spends something like a billion dollars a year on CERN. To compare, let’s look at the biggest scientific funder in the United States, the NIH. Out of 103,280 grants awarded to scientists during the 2007-2017 decade, want to guess how many were about directly studying the contents of consciousness?

Five.

That’s probably, at most, a couple million dollars in funding over a decade. Total. So if you’re a consciousness researcher, what can you do, cheaply? What can you do, for free? You can pontificate. You can propose your own theory of consciousness! That requires no funding whatsoever. And so for 30 years the meta in consciousness research has been to create your own theory of consciousness. We’ve let a thousand flowers bloom. The problem is that, if any flower is at all true or promising, you can’t identify it, as its sweet subjectivity-solving scent is completely masked by the bunches of corpse flowers around it. We have too many flowers, and one more just isn’t meaningful anymore. As is sometimes said at the end of fairy tales: “Snip, snap, snout. This tale’s told out.”

What we need are efforts at field-clearing, and methods that can actually make progress on consciousness in ways not tied to just promoting or trying to find evidence for some pre-chosen pet theory—which means finding ways to select over theories, to test theories en masse, so you don’t reinvent the wheel each time, and, perhaps most importantly, you have to do all this while scaling institutions with funding to specifically get a bunch of smart people in a room working together on this.

ME GETTING OFF MY ASS

If the 2020s were all about intelligence, then necessarily the 2030s will be all about consciousness. Intelligence is about function, while consciousness is about being, and forays and progress into understanding (and shaping) function will in turn force our attention toward a better understanding of being. And if the answer to “Why has consciousness not been solved?” is secretly “Material and historical conditions made it hard for anyone to actually try!” then the answer is to actually try.

I refuse to live in a civilization where we consciousness researchers have so obviously failed. I refuse to live in a civilization where we cannot tell consciousness from non-consciousness. Where we can offer no guidance for the future. Where we cannot explain the difference between actually experiencing things vs just processing them. In the short term, this is destabilizing and harmful. In the long term, it may be literally existentially dangerous.

by Erik Hoel, Intrinsic Perspective |  Read more:

Image: Michael Pollan/Penguin Random House

[ed. I thought consciousness research was going great guns since it's central to determining AGI (artificial general intelligence). Huh. See also: His ‘Machine’ Could Uncover the Origin of Human Consciousness—And if It Truly Connects to the Whole Universe (Popular Mechanics)]

Hantavirus Update

A working timeline: 

• Mid-March: Dutch couple possibly contract virus on bird watching landfill excursion.
• April 1: MV Hondius departs southern Argentina.
• April 6: Dutch man falls ill.
• April 11: He dies.
• April 24: St. Helena. Man’s body is taken off ship and wife flies with it to South Africa. The Dutch woman is already sick before boarding flight to South Africa.
• April 26: The Dutch woman dies in SA at a hospital.
• April 27: A British man who is sick is flown from Ascension Island to South Africa.
• May 2: A German woman dies on the MV Hondius.

Meanwhile, we have people leaving the ship and flying all over the world:

Some Hantavirus Cruise Passengers Are Back in the U.S. MedPage Today

Two British people self isolating at home after leaving cruise ship in St Helena BBC. “The UKHSA also said British people currently on the ship would be flown home on a charter flight, probably from the Canary Islands, as long as they didn’t have symptoms.”

Patient with a hantavirus infection being treated in hospital Switzerland Federal Office of Public Health (press release)

Passenger with hantavirus was briefly on board a KLM aircraft in Johannesburg KLM (press release)

Spanish passenger on the ‘Hondius’: ‘There are 23 people who got off on Saint Helena and have been wandering around’ El Pais

by Conor Gallagher, Naked Capitalism | Read more:

[ed. Time to pull that old "definition of insanity" cliche' out again. Even if this does eventually burn out, it appears we've learned very little in the last few years.]

Super Bird

Before it took off, the bird ate parts of its own liver, kidneys, and gut. That was the only way to be light enough to fly. Then it flew 8,425 miles from Alaska to Australia, in 11 days, without eating, drinking, or landing once. 

The bird is called B6. It's a bar-tailed godwit, four months old, weighing about as much as a can of beans. In October 2022, scientists at the US Geological Survey tracked its flight from Alaska all the way to Tasmania. The trip took 11 days and 1 hour. It is still the longest non-stop flight of any animal on Earth. 

For two weeks before takeoff, godwits eat until they almost double in weight. Fat ends up being 55% of their body, more than any bird ever measured. Then they shrink their own insides. About a quarter of their liver, kidneys, stomach, and intestines gets broken down and reused for fuel, making room for the extra fat and cutting weight. Their heart and wing muscles grow bigger at the same time. 

They never drink along the way. The water they need comes out of burning fat, the same reaction their muscles use for energy. They also never really sleep. B6 flapped its wings for 264 straight hours, cruising around 35 miles per hour with help from storm tailwinds. By the time it landed, it had lost almost half its body weight. The shrunken organs grew back over the following weeks. Scientists still cannot explain the navigation. B6 had never made this flight before. Adult godwits leave Alaska weeks earlier, so young birds fly alone with nobody to follow. How a four-month-old bird finds its way across 8,425 miles of open ocean to a place it has never seen is still an open question. About 100,000 bar-tailed godwits leave Alaska every fall. Most of them land in New Zealand or Australia 10 or 11 days later, having eaten parts of themselves to get there.

by Anish Moonka, X |  Read more: 

Image: All Day Astronomy

Why Your Job’s Complexity Level May Affect Your Risk of Dementia

Getting an education is important for a lot of reasons, but there might be one reason you haven’t heard — it could lower your risk of dementia later in life. Decades of research have supported this claim, with one study showing that each additional year of formal education lowers the risk of Alzheimer’s disease or other types of dementia by 7 percent.

Now, a growing body of evidence suggests that the jobs we hold throughout our lives may matter just as much or more than years of education. Having a job that involves high levels of decision-making or creativity, rather than repetitive or manual tasks, could help keep the mind sharp and active.

“Many studies suggest that, if people are working in complex jobs during their lifetime, they have a lower likelihood of developing dementia in later life,” said Jinshil Hyun, assistant professor of neurology at Albert Einstein College of Medicine.

Roles like managers, teachers, lawyers and doctors are considered high complexity jobs, while clerical, transportation and assembly line work have lower complexity. The findings are consistent with the idea that taking part in mentally stimulating activities throughout the lifespan can help preserve late-life brain health and boost cognitive reserve — the brain’s ability to cope with age- or disease-related changes.

But don’t worry if your job doesn’t meet the criteria — there are other things that you can do to improve your cognitive reserve, such as reading, socializing and volunteering.

Why work might be linked to dementia risk

“We spend most of our day in work, at least eight hours a day. So that’s like, a third of our time engaged in work, sometimes more,” said Naaheed Mukadam, professor of psychiatry at University College London. “That’s a large part of what our brain is engaged in and therefore will have a large contributory effect on cognitive reserve development.”

In a recent study, Mukadam and her colleagues investigated which factors could be influencing education’s protective effect against dementia. Their analysis included 384,284 participants and took note of health behaviors like drinking, smoking and exercise; medical conditions like hypertension and diabetes; occupational complexity; and income. The results uncovered that occupational complexity is actually the biggest reason more education tends to lower your risk of dementia, accounting for more than 70 percent of that link.

“We found that occupational complexity explained the biggest proportion of that relationship between education and dementia,” she said. “People who have more education tend to get into better paid, more complex jobs. Then, the benefits for their physical and cognitive health compound in that way.”

Multiple studies have found that those with higher income have a lower risk of dementia, and the researchers speculate that job complexity likely plays a major role in that relationship as well.

Similarly, Hyun and her colleagues found in a 2021 study that occupational complexity is predictive of later-life dementia, independent of education. They looked at the effects on dementia-free survival time, or how many years a person lived before being diagnosed with dementia, in 10,195 participants from six countries. As expected, high school graduates had a 26 percent increase in dementia-free survival time compared to people who only completed middle school or less.

After controlling for education, high occupational complexity, compared to low occupational complexity, was associated with a 19 percent increase in dementia-free survival time. Hyun speculates that the greater mental stimulation of a complex job builds cognitive reserve, which helps people resist cognitive decline and stay mentally sharp for longer, even in the presence of harmful plaques seen in Alzheimer’s-affected brains.

“The cognitive reserve hypothesis suggests that, if people are doing cognitively enriching activities, then their brain has a more efficient network,” Hyun said.

by Meeri Kim, The Washington Post/Seattle Times |  Read more:

Image: iStock

[ed. Or just develop a life long love of learning. Eric Hoffer would be a good example (longshoreman/philosopher). What'll happen when more people offload their thinking to an AI assistant?]

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.]

Carving Up Big Bend

 

A massive border wall expansion is underway (Washington Post/Archive Today)

TERLINGUA, Texas — The Trump administration is building hundreds of miles of border wall through iconic national parks, public lands and ecologically sensitive wilderness, empowered by provisions in the One Big Beautiful Bill that provided $46.5 billion in funding and a 2005 law that waived dozens of environmental rules for border security projects. [...]

The aggressive pace — three new miles of wall a week — has alarmed advocates and national parks staff who say the construction will destroy pristine country, threaten endangered species, and cut off access to sacred Indigenous and archaeological sites. And it has sparked an unusual degree of bipartisan pushback, with sheriffs, conservative county judges, environmentalists and Texas state lawmakers lobbying Trump officials to change course. [...]

The Department of Homeland Security has issued waivers under the 2005 REAL ID Act, allowing the department to disregard the wall’s impact on plants and animals normally protected by the Endangered Species Act. The project is exempted from the National Environmental Policy Act — a sweeping law that mandates an extensive review of a federal action’s potential impacts and public consultation that can take years...

Sorting through complicated legal and property ownership issues slowed down border wall construction in Texas during the first Trump administration. But the federal government is now skipping meetings with local officials and landowners and awarding contracts to out-of-state firms. Last month, the Army Corps of Engineers sent packets to Texas landowners along the wall’s path containing maps showing the land they planned to take. The proposed construction could include anything from ground sensors and infrared cameras to 30-foot steel bollards affixed with floodlights and gravel roads for Border Patrol vehicles — and often all of the above.

Big Bend National Park has emerged as a political flash point in the new expansion, with many landowners and conservationists describing a border wall as an unnecessary encroachment from big government seizing one of the last vestiges of unspoiled freedom and frontier.

by Arelis R. Hernández, Jake Spring, John Muyskens and Thomas Simonetti, Washington Post | Read more:
Images: YouTube/WaPo

[ed. Of all the national parks in the lower 48 Big Bend is the one I'd most like to visit. Beautiful and rugged, and not overly ruined by tourism (yet) or walls (yet). More great pictures in the article. If you've seen the movie Fandango (with Kevin Costner) you know the area. Then there's Marfa (a small nearby arts community) and Terlingua (ref: Jerry Jeff Walker's Viva Terlingua). And, a night sky that's been documented as the darkest in the country (floodlights will do wonders for that). I guess it's ok to just ignore every law on the books and outright take people's property against their will in this administration.]

Vertical Farming

via:
[ed. Impressive.]

***

"While most vertical farms are limited to lettuces, Plenty spent the past decade designing a patent-pending, modular growing system flexible enough to support a wide variety of crops – including strawberries. Growing on vertical towers enables uniform delivery of nutrients, superior airflow and more intense lighting, delivering increased yield with consistent quality.

Every element of the Plenty Richmond Farm–including temperature, light and humidity–is precisely controlled through proprietary software to create the perfect environment for the strawberry plants to thrive. The farm uses AI to analyze more than 10 million data points each day across its 12 grow rooms, adapting each grow room’s environment to the evolving needs of the plants – creating the perfect environment for Driscoll’s proprietary plants to thrive and optimizing the strawberries’ flavor, texture and size. Even pollination has been engineered by Plenty, using a patent-pending method that evenly distributes controlled airflow across the strawberry flowers for more efficient and effective pollination than using bees, supporting more uniform strawberry size and shape."  ~ Greater Richmond Partnership

Teshekpuk Lake

Arctic Alaska oil and gas lease sale draws record bidding, despite legal clouds (AK Beacon)

The first lease sale in the National Petroleum Reserve in Alaska since 2019 generated $163 million in high bids, but some bids were for protected land

***

A controversial oil and gas federal lease sale in the National Petroleum Reserve in Alaska generated a new bidding record, according to results released on Wednesday. It was the first auction held in that Arctic Alaska territory since 2019.

The lease sale produced $163 million in high bids, beating the $104 million mark set during the first competitive oil and gas lease sale in the Indiana-sized reserve, which was held in 1999 during the Clinton administration.

Eleven companies submitted bids for more than 1.3 million acres of the nearly 5.5 million acres offered in the auction.

Kevin Pendergast, Alaska state director for the U.S. Bureau of Land Management, called the results “historic.”

“This is the strongest sale we have ever had in the National Petroleum Reserve in Alaska by nearly every measure. It makes clear that for the NPR-A, despite all the successes to date, the best days are still ahead,” Pendergast said at the conclusion of the bid opening, which lasted about two hours.

In statements issued after the bid reading, federal and state officials hailed the results. [...]

The lease sale was one of five mandated in the reserve over the next 10 years by the sweeping budget and tax bill called the “One Big Beautiful Bill Act.” That mandate calls for lease sales to be conducted under a Trump administration management plan that opened 82% of the reserve to oil development. Previously, the Obama administration held annual lease sales in the petroleum reserve, but that administration’s management plan protected about half of the land through the designation of “special areas” considered important to wildlife and to Native cultural practices.

Federal officials auctioned tracts of protected land

Much of the bidding in Wednesday’s sale was for territory that was previously off-limits to oil development under protections that date as far back as the Reagan administration. [ed. guess who helped write and fight for those protections.]

The inclusion of long-protected land in the sale, predominantly the area around ecologically sensitive Teshekpuk Lake, made the lease sale contentious. It is the subject of two lawsuits filed by Native and environmental groups.

Bids were accepted even for tracts within an area encircling Teshekpuk Lake, the North Slope’s largest lake, despite a federal court order issued Monday that reinstated development prohibitions there.

by Yareth Rosen, Alaska Beacon |  Read more:

Image: YouTube

[ed. Nice video, you should watch it. $163 million is not nothing, but it's not a lot. Prudhoe Bay - before there was any infrastructure or pipeline - garnered $900 million, and it was a much smaller area. When I was overseeing oil and gas leasing in the arctic in the 80s there was very little interest in NPR-A - except for Teshekpuk Lake, one of the most ecologically important areas on the North Slope (along with ANWR). We used to joke that if you wanted to find oil just look for the most environmentally sensitive area you could find in a lease sale and bid there. Not a joke anymore.]