Even before his CIA connections came out, West’s experiments got him in plenty of trouble

Saturday, June 14th, 2025

Chaos by Tom O’NeillDespite the furtive nature of “Jolly” West’s research, Tom O’Neill explains (in Chaos: Charles Manson, the CIA, and the Secret History of the Sixties), he could be surprisingly garrulous

Among the press clippings in his file were two items from Portland, Oregon, newspapers, both dated October 1963—the murky period between his Oklahoma hypnosis studies and the Haight-Ashbury Project. West had given an address to the Mental Health Association of Oregon, letting it slip that he was inducing insanity in the lab. He framed these studies as positive developments: they might someday cure mental illness.

“We are at the dawning of a new era,” West told the crowd, “learning for the first time to produce temporary mental derangement in the laboratory.” The Oregon Journal noted that West “listed the new hallucination drug LSD, along with other drugs, hypnosis, and sleep deprivation as some of the things that [he was] using to produce temporary mental illness effects in normal people.” Reporting that West had done “extensive work” with LSD, the Journal continued: “The most important contribution of the drug so far is in producing model mental illnesses.”

Almost fifteen years later, besieged by reporters after the New York Times alleged that he’d taken part in MKULTRA’s secret LSD experimentation program, West insisted that all of his LSD work “had been confined to animals,” denying any CIA affiliation. When reporters pointed out that he’d received an awful lot of money from the agency, he retorted that he’d had no idea that the Geschickter Fund and other sources were CIA fronts. Legally, the CIA was obligated to tell the University of Oklahoma that one of its faculty had been on the agency payroll. Oklahoma revealed a heavily redacted memo saying that an unnamed professor—West, I confirmed through financial records—had been investigating “a number of dissociative phenomena” on humans “in the lab,” including an exceptionally rare clinical disorder known as “latah,” “a neurotic condition marked by automatic obedience.”

None of the allegations harmed West’s reputation. By then he’d left Oklahoma for UCLA, where he offered a steady stream of denials and continued to thrive through his retirement in 1988. Irascible and arrogant, he was quick to threaten lawsuits when anyone brought up the charges. Sometimes he threw in diversionary tactics: in a 1991 rebuttal, he claimed, “My secret connection to Washington, D.C. is not as a spook, but rather as a confidential advisor to Presidents… From Eisenhower to Bush, Democrat and Republican Presidents alike have freely sought and received my counsel.” In a 1993 letter to the editor of the UCLA Bruin, he had the temerity to compare his accusers to Nazi propagandists “in Goebbels’ tradition of the Big Lie.” West added, “I have never taken part in ‘mind-control’ experiments funded by the CIA or anybody else”: a statement belied by his own files.

Even before his CIA connections came out, West’s experiments got him in plenty of trouble. In 1972, he announced plans to build a lab in an abandoned Nike Missile base in the Santa Monica Mountains. He would call it “The Center for the Study and Reduction of Violence,” or the Violence Center, for short. There, in perfect isolation, he could study the origins and control of human violence by experimenting on prisoners. Governor Ronald Reagan gave the Violence Center a full-throated endorsement.

But West’s proposal for grant money landed him in hot water. He planned to test radical forms of behavior modification, implanting electrodes and “remote monitoring devices” in prisoners’ brains. A federal investigation concluded that the program involved “coercive methods” that threatened “privacy and self-determination.”

The committee’s disclosures stymied the Violence Center before it got past the planning stages. The California legislature vetoed the project; UCLA’s student body rose up in protest of West. And this, to reiterate, was before anyone had a clue about his CIA work.

His friends called him “Jolly”

Saturday, June 7th, 2025

Chaos by Tom O’NeillThrough his research on the Haight-Ashbury Free Medical Clinic, Tom O’Neill learned that yet another shadowy researcher kept an office there — as he explains in Chaos: Charles Manson, the CIA, and the Secret History of the Sixties — and this researcher’s work with LSD had clearer, more nefarious ties to the CIA than any of the others:

At least his name wasn’t Smith this time: he was Dr. Louis Jolyon West. His friends called him “Jolly,” for his middle name, his impressive girth, and his oversized personality.

[…]

Born in Brooklyn in 1924, West had enlisted in the army air force during World War II, eventually rising to the rank of colonel. He came to my interest when I learned that he’d accepted an office at the Haight-Ashbury clinic from David Smith himself to recruit subjects for LSD research.

Earlier in his career, West researched methods of controlling human behavior at Cornell University. During the Korean War, he helped to “deprogram” returning prisoners of war who’d allegedly been brainwashed. His success earned him national attention. Around the same time, he achieved still more fame when he joined civil rights activists like his friend the actor Charlton Heston, as well as Dr. Martin Luther King Jr., in marches demanding equal rights for African Americans. Ironically, while he was fighting for the rights of some, he was suspected of infringing on those of others. His detractors alleged that through the fifties and early sixties, at air force bases in Texas and Oklahoma, he performed experiments on unwitting subjects using LSD and hypnosis.

After John F. Kennedy was assassinated in November 1963, West psychiatrically examined Jack Ruby, who’d murdered Kennedy’s assassin, Lee Harvey Oswald. Not long before Ruby was due to testify for the Warren Commission, West examined him alone in his jail cell. He emerged to report that Ruby had suffered an “acute psychotic break.” Sure enough, Ruby’s testimony before the commission succeeded only in making him sound unhinged. He could never fully explain why he’d decided to kill Oswald.

Through the seventies, journalists linked West to the CIA’s mind-control research program, MKULTRA. He denied all involvement, vigorously attacking anyone who suggested otherwise. He kept up those attacks until his death in 1999. Then seventy-four, he’d been diagnosed with metastatic cancer, and he prevailed on his son to help him commit suicide with a cocktail of pills.

[…]

West had spent the last decades of his career at UCLA, where he’d become something of an institution, heading the psychiatry department’s renowned neuroscience center; the university had named an auditorium in his honor. When I called the school, I learned that he’d donated his papers to them, but since no one had asked to see them, they’d never been processed. No one had so much as opened the first box. I would be the first reporter to look at them.

[…]

Late in the fall of 1966, Jolly West arrived in San Francisco to study hippies and LSD. The Bay Area had seen an unprecedented migration of middle-class youth and an explosion of recreational drug use. West felt he had to witness it firsthand. He secured a government grant and took a yearlong sabbatical from his professorship at the University of Oklahoma, nominally to pursue a fellowship at Stanford, although that school had no record of his participation in a program there.

West was a square—tall, broad, and crew cut, with an all-American look in keeping with his military past. If he wanted a good glimpse of the hippies, he’d have to blend in. He started cobbling together a new wardrobe and skipping haircuts.

At least he had a solid knowledge base. The summer of love had yet to come, and the Tate–LaBianca murders were still years away, but West would effectively predict them both. In a 1967 psychiatry textbook, he’d contributed a chapter called “Hallucinogens,” warning students of a “remarkable substance” percolating through college campuses and into cities across the United States. It was LSD, known to leave users “unusually susceptible and emotionally labile” as it caused a “loosening of ego structure.” That language was reminiscent of the “reprogramming” spiel that Charles Manson would soon develop, urging his acid-tripping followers to “negate their egos.”

When West cautioned against the “LSD cults” springing up in America’s “bohemian” quarters, he described exactly the kind of disenchanted wanderers who’d flock to a personality like Manson’s in the years to come. West had a hunch that alienated kids “with a pathological desire to withdraw from reality” would crave “shared forbidden activity in a group setting to provide a sense of belonging.”

Another paper by West, 1965’ s “Dangers of Hypnosis,” foresaw the rise of dangerous groups led by “crackpots” who hypnotized their followers into violent criminality. Contrary to the prevailing science at the time, West asserted that hypnosis could make people so pliable that they’d violate their moral codes. Scarier still, they’d have no memory of it afterward. Just because such outcomes were rare, he argued, didn’t mean they were impossible.

West cited two cases to back up his argument: a double murder in Copenhagen committed by a hypno-programmed man, and a “military offense” induced experimentally at an undisclosed U.S. Army base. He “personally knew” of two other instances, and he’d “heard on excellent authority” of three more, but he didn’t elaborate. Later, I’d get a sense of what, or who, he might have had in mind.

When he arrived in Haight-Ashbury, then, West was the only scientist in the world who’d predicted the emergence of potentially violent “LSD cults.” How had he learned so much about acid? You’d never know from his published writing that he’d conducted innumerable experiments with it. In San Francisco, he hoped to conduct more still.

In the Haight, West found a group of kindred spirits at David Smith’s new clinic, where plenty of shrinks from the “straight world” were basking in hippiedom. Getting his bearings at the HAFMC, he arranged for the use of a crumbling Victorian house on nearby Frederick Street, where he opened what he described as a “laboratory” disguised as a “hippie crash pad.” This would serve as a “semi-permanent observation post,” granting him an up-close-and-personal look at the youth. He installed six graduate students in the “pad,” telling them to “dress like hippies” and “lure” itinerant kids into the apartment. Passersby were welcome to do as they pleased and stay as long as they liked, as long as they didn’t mind grad students taking copious notes on their behavior.

The “pad” opened in June 1967, at the dawn of the summer of love. West took pains to ensure that it felt realistic, decorating it “with posters, flowers and paint.” Thus was born the Haight-Ashbury Project, as he called it, or “HAP,” for short. For the next six months, he undertook “an ongoing program of intensive interdisciplinary study into the life and times of the hippies.”

To drum up hippie business, West stopped by the HAFMC, where David Smith could furnish willing subjects. Smith even gave him an office. Having a nationally recognized researcher like West working out of the HAFMC would attract sorely needed government funding.

“We helped him with research,” Smith told me. He was sympathetic to West’s project, even though he admitted that he never bothered to find out what it was, or what its objectives were. He assumed that West, like himself, was diagnosing “psychedelic patterns in the counterculture,” trends that others had dismissed as boorish fads.

“They came over and interviewed kids that came into our clinic,” Smith said of West and his students. “He wanted to know, ‘What is a hippie?’” Smith reminded me that “this was a very new population… the fact that large numbers of white middle-class kids would use illicit drugs was a total mindblower.”

Who was paying for all this? According to records in West’s files, his “crash pad” was funded by the Foundations Fund for Research in Psychiatry, Inc., which had bankrolled a number of his other projects, too, across decades and institutions. For reasons soon to be clear, I concluded that the Foundations Fund was a front for the CIA.

This wouldn’t have been the agency’s first “disguised laboratory” in San Francisco. A few years earlier, the evocatively titled Operation Midnight Climax had seen CIA operatives open at least three Bay Area safe houses disguised as upscale bordellos, kitted out with one-way mirrors and kinky photographs. A spy named George Hunter White and his colleagues hired prostitutes to entice prospective johns to the homes, where the men were served cocktails laced with acid. White scrupulously observed the ensuing activities, whatever they were. The goal was to see if LSD, paired with sex, could be used to coax sensitive information from the men—something of a psychedelic honeypot experiment. White so enjoyed the proceedings that he had a portable toilet and a mini-fridge installed on his side of the mirror, so he could watch the action and swill martinis without taking a bathroom break. He later wrote to his CIA handler, “I was a very minor missionary, actually a heretic, but I toiled wholeheartedly in the vineyards because it was fun, fun, fun. Where else could a red-blooded American boy lie, kill and cheat, steal, deceive, rape and pillage with the sanction and blessing of the All-Highest? Pretty Good Stuff, Brudder!”

West knew better than to commit such sentiments to paper, but by 1967 he’d “toiled wholeheartedly in the vineyards,” too. Before he moved to the Haight, he’d supervised a similar study in Oklahoma City, hiring informants to infiltrate teenage gangs and engender “a fundamental change” in “basic moral, religious or political matters.” The title of the project was Mass Conversion. As I was soon to see, its funds came from Sidney J. Gottlieb, the head of the CIA’s MKULTRA program.

[…]

Bob Conrich, a cofounder of the HAFMC, saw through the ruse right away. West “walked into the clinic one day and my first reaction was that he’d read too many Tim Leary interviews,” Conrich wrote to me. West was a careerist in hippies’ clothing. “What I remember is his enthusiasm for the whole ‘summer of love’ thing, which seemed exaggerated and insincere.”

[…]

He soon concluded that the constellation of sex, drugs, and communalism shining over the Haight that summer was “doomed to fail”: “The very chemicals they use will inevitably enervate them as individuals and bleed the energies of the hippie movement to its death.” He called this an “ineffable tragedy,” but it’s hard to imagine he saw it that way. For West, the failure of sixties idealism was the most desirable outcome—one that he was quite possibly working toward. A copy of his résumé from this period hints at the thrust of his research. He was at work on a book called Experimental Psychopathology: The Induction of Abnormal States. But he never published it. Nor, on the surface, would “the induction of abnormal states” dovetail with the stated goals of his HAP. By the early seventies he removed the title from his résumé and never mentioned it again.

Stephen Pittel, the forensic psychologist, worked briefly with West in 1968 and referred to him as “the only benevolent psychopath I ever met.” The man could “charm the pants off of anyone, and manipulate people into doing all sorts of things they didn’t want to do.”

[…]

The grad students hired to man West’s “crash pad” laboratory were assigned to keep diaries of their work. In unguarded moments, nearly all these students admitted that something didn’t add up. They weren’t sure what they were supposed to be doing, or why West was there. And often he wasn’t there.

[…]

When West made one of his rare appearances, he was “dressed funny,” like a hippie; sometimes he would have friends in tow, costumed just as poorly. Collins wrote, “The rest of us tended to look to them in trying to understand what we were supposed to do or what Jolly wanted. Their general reply was that this was a good opportunity to have fun. I gather that they did. They spent a good deal of the time stoned.”

[…]

Pressed for specific guidelines, West exuded “phoniness and dishonesty,” suggesting that the students answer sweeping, high-flown questions about the Haight, such as “Is this an asphalt Sherwood Forest?” She “got the impression that this question had already been answered.”

[…]

Albert Hofmann, the Swiss scientist who’d discovered its hallucinogenic qualities in 1943, described it as a “sacred drug” that gestured toward “the mystical experience of a deeper, comprehensive reality.” The actor Cary Grant, on the advice of his shrink, took some one hundred LSD trips during their weekly meetings in the late fifties, experiencing a “rebirth” and picturing himself “as a giant penis launching off from Earth like a spaceship.”

Charles Fischer, a drug researcher who worked with David Smith, described to me the early perceptions of acid, when “trips” were planned like literal journeys. “Very few people took LSD without having somebody being a ‘trip leader,’” Fischer said. The suggestibility from LSD was akin to hypnosis—and Jolly West, of course, had known well enough to study the two in tandem. “You can tell somebody to hurt somebody, but you call it something else,” Fischer explained. “Hammer the nail into the wood, and the wood, perhaps, is a human being… [It] could result in some violent activity, even though LSD was considered a love drug.”

[…]

Full-fledged U.S. research into LSD began soon after the end of World War II, when American intelligence learned that the USSR was developing a program to influence human behavior through drugs and hypnosis. The United States believed that the Soviets could extract information from people without their knowledge, program them to make false confessions, and perhaps persuade them to kill on command.

The CIA, then in its infancy, saw mind control as a natural extension of communism, spreading like fire where the forces of unreason prevailed. In 1949 it launched Operation Bluebird, a mind-control program whose chipper name belied its brutal ambitions and its propensity for trampling on human rights. In its yen to best the Soviets, the CIA tested drugs on American citizens—most in federal penitentiaries or on military bases—who didn’t even know about, let alone consent to, the battery of procedures they underwent.

Their abuse found further justification in 1952, when, in Korea, captured American pilots admitted on national radio that they’d sprayed the Korean countryside with illegal biological weapons. It was a confession so beyond the pale that the CIA blamed Communists: the POWs must have been “brainwashed.” The word, a literal translation of the Chinese xi nao, didn’t appear in English before 1950.

[…]

Once the Korean War was over and the American POWs returned, the army brought in a team of scientists to “deprogram” them. Among those scientists was a young psychiatrist from Cornell, Dr. Louis J. West. He would later claim to have studied eighty-three prisoners of war, fifty-six of whom had been forced to make false confessions. West interviewed them at length, undoing the treacheries of the “thought reform” they’d undergone in enemy hands. He and his colleagues were credited with reintegrating the POWs into Western society and, maybe more important, getting them to renounce their claims about having used biological weapons.

West’s success with the POWs gained him entrée to the upper echelons of the intelligence community. As the Cold War bred paranoia, the CIA accelerated its mind-control efforts, and West, I learned, carved out a niche he’d occupy for decades to come. Initially, the agency wanted only to prevent further brainwashing by the Soviets. But the extraordinary power of psychotropic drugs, particularly LSD, was hard to ignore. Thus a defensive program became an offensive one. Operation Bluebird morphed into Operation Artichoke, a search for an all-purpose truth serum.

Dr. Sidney Gottlieb, a poisons expert who headed the chemical division of the CIA’s Technical Services Staff, had convinced the agency’s director, Allen Dulles, that mind-control ops were the future. Gottlieb, whose aptitude and amorality had earned him the nickname the “Black Sorcerer,” developed gadgetry straight out of schlocky sci-fi: high-potency stink bombs, swizzle sticks laced with drugs, exploding seashells, poisoned toothpaste, poisoned handkerchiefs, poisoned cigars, poisoned anything. Mind control became Gottlieb’s pet project. Dulles, convinced that the American dream was at stake, ensured that Gottlieb was well funded. In a speech at Princeton University, Dulles warned that Communist spies could turn the American mind into “a phonograph playing a disc put on its spindle by an outside genius over which it has no control.” Just days after those remarks, on April 13, 1953, he officially set Project MKULTRA into motion.

The project’s broadest goal was “to influence human behavior.” Under its umbrella were 149 subprojects, many involving research that used unwitting participants. Having persuaded an Indianapolis pharmaceutical company to replicate the Swiss formula for LSD, the CIA had a limitless domestic supply of its favorite new drug. The agency hoped to produce couriers who could embed hidden messages in their brains, to implant false memories and remove true ones in people without their awareness, to convert groups to opposing ideologies, and more. The loftiest objective was the creation of hypno-programmed assassins.

In their defense, CIA spooks weren’t above experimenting on themselves. The same substance that held the promise of controlling minds and quashing communism was used in churlish office pranks, with agents quietly slipping LSD into their colleagues’ drinks to achieve much needed “firsthand knowledge.” A plan to spike the punch bowl at the CIA Christmas party was quashed when higher-ups reminded the office that it could cause insanity.

The most sensitive work was conducted far from Langley—farmed out to scientists at colleges, hospitals, prisons, and military bases all over the United States and Canada. The CIA gave these scientists aliases, funneled money to them, and instructed them on how to conceal their research from prying eyes, including those of their unknowing subjects. Feeling that it was their patriotic duty, the scientists accepted their secret missions in defiance of the Hippocratic oath: “First, do no harm.”

In 1949, at the Nuremberg trials that adjudicated the crimes of World War II, the United States adopted the International Code for Human Experimentation: “A person must give full and informed consent before being used as a subject.” MKULTRA scientists flouted this code constantly, remorselessly—and in ways that stupefy the imagination. Their work encompassed everything from electronic brain stimulation to sensory deprivation to “induced pain” and “psychosis.” They sought ways to cause heart attacks, severe twitching, and intense cluster headaches.

[…]

Operated on a strict need-to-know basis, MKULTRA was so highly classified that when John McCone succeeded Dulles as CIA director late in 1961 he was not informed of its existence. Fewer than half a dozen agency brass were aware of MKULTRA at any period during its twenty-year history. When Gottlieb retired, in 1972 or ’73, the project retired with him.

[…]

Director Richard Helms ordered Gottlieb to destroy all MKULTRA files. In January 1973, the Technical Services Staff shredded countless documents describing the use of hallucinogens, including every known copy of a manual called “LSD: Some Un-Psychedelic Implications.”

[…]

In their haste to purge their misdeeds, the agents forgot about a cache of some sixteen thousand additional papers in an off-site warehouse. Even internally, those files would remain undiscovered for several years, but it was only a matter of time until the story broke; MKULTRA had become fodder for rumors around Washington.

In December 1974, the project finally came to light in a terrific flash of headlines and intrigue. Seymour Hersh reported it on the front page of the New York Times: “Huge C.I.A. Operation Reported in U.S. Against Antiwar Forces.”

[…]

First came the Church Committee and the Rockefeller Commission, each mentioned earlier regarding CHAOS and COINTELPRO. The Church Committee’s final report unveiled a 1957 internal evaluation of MKULTRA by the CIA’s inspector general. “Precautions must be taken,” the document warned, “to conceal these activities from the American public in general. The knowledge that the agency is engaging in unethical and illicit activities would have serious repercussions.” A 1963 review from the inspector general put it even more gravely: “A final phase of the testing of MKULTRA products places the rights and interests of U.S. citizens in jeopardy.”

In fact, as the Church Committee’s report went on, MKULTRA had caused the deaths of at least two American citizens. One was a psychiatric patient who’d been injected with a synthetic mescaline derivative. The other was Frank Olson, a CIA-contracted scientist who’d been unwittingly dosed with LSD at a small agency gathering in the backwoods of Maryland presided over by Gottlieb himself. Olson fell into an irreparable depression afterward, which led him to hurl himself out the window of a New York City hotel where agents had brought him for “treatment.” (Continued investigation by Olson’s son, Eric, strongly suggests that the CIA arranged for the agents to fake his suicide; they threw him out of the window themselves out of fear that he would blow the whistle on MKULTRA and the military’s use of biological weapons in the Korean War.)

[…]

Senators Ted Kennedy and Daniel Inouye subpoenaed a number of CIA spooks. Among them was Gottlieb, rousted from his retirement in California and forced to defend his actions before the Senate. Or rather, before some of the Senate. Gottlieb claimed that his heart condition precluded the possibility of his addressing the whole chamber; instead, he was installed in an anteroom, where he answered questions from a select group while the masses listened over a public address system.

As the New York Times pointed out, Gottlieb “managed to elude the lights and microphones and the crush of reporters waiting for him in the Senate hearing room.” He was spared the sight of the incredulity that spread over their faces as he admitted that he had destroyed MKULTRA’s files not to cover up “illegal activity,” but “because this material was sensitive and capable of being misunderstood.” He resented the harm done to his reputation, and he was loath to provide specifics about MKULTRA experiments, saying that he’d never witnessed any himself.

Gottlieb’s destruction of the MKULTRA files was a federal crime. It was investigated by the Justice Department in 1976, but, according to the Times, “quietly dropped.” His brutal courses of experimentation broke any number of laws, and his perjury that day did, too. But he was never prosecuted. He’d testified before the Senate only under the condition that he receive total criminal immunity.

[…]

Surviving records named eighty institutions, including forty-four universities and colleges, and 185 researchers, among them Louis J. West. The New York Times identified him, in a front-page lead story, no less, as one of seven suspected scientists who’d secretly participated in MKULTRA under academic cover. And yet not one researcher was ever federally investigated, and only two victims were ever notified. The Times had called MKULTRA “a secret twenty-five year, twenty-five million dollar effort by the CIA to learn how to control the human mind.” It looked like no one would suffer any consequences for it.

Griffin Bell, the Attorney General at the time of the revelations, told me the files never arrived at the Justice Department, despite Stansfield Turner’s sworn claim to the contrary. Bell said they must’ve just “fall[ en] through the cracks.” As for Turner himself, he told me he could no longer remember having testified that the CIA sent the files. “I’m just drawing a total blank here,” he said. I read his remarks back to him. “I guess I did testify about this,” he said. “Somebody fed me the stuff and I played it back.”

The New York Times ran twenty-seven stories on MKULTRA, eight on the front page. But no one in the press corps, and none of the senators involved, followed up to see that the promised investigations took place.

[…]

West’s archive comprised two hundred boxes, most of them full of ephemera. There were tons of press clippings. West had tracked the media’s coverage of assassinations, the CIA, aggression in cats, psychosurgery, capital punishment, alcoholism among Native Americans, behavior modification, and the civil rights movement, among other subjects. I was intrigued to see many clippings on the Manson murders, and papers by Roger Smith, David Smith, and Alan Rose.

[…]

On August 25, among a batch of research papers on hypnosis, I found them: letters between West and his CIA handler, “Sherman Grifford.”

I didn’t recognize the name, so as soon as I got home, I began tearing through every book I had that mentioned MKULTRA, hoping that it would jump out at me. In the first and most definitive of the bunch, John Marks’s The Search for the Manchurian Candidate, there it was, buried in a footnote: “CIA operators and agents all had cover names,” it said, “even in classified documents. Gottlieb was ‘Sherman R. Grifford.’”

So West really had lied all those years. Not only was he a part of MKULTRA, he’d corresponded with the “Black Sorcerer” of MKULTRA himself. Preserved in his files, the letters picked up midstream, with no prologue or preliminaries. The first one was dated June 11, 1953, a mere two months after MKULTRA started. West was then chief of psychiatric service at the airbase at Lackland, Texas.

Addressing Gottlieb as “S.G.,” he outlined the experiments he proposed to perform using a combination of psychotropic drugs and hypnosis. Enumerating short-and long-term goals, he offered a nine-point list, beginning with a plan to discover “the degree to which information can be extracted from presumably unwilling subjects (through hypnosis alone or in combination with certain drugs), possibly with subsequent amnesia for the interrogation and/ or alteration of the subject’s recollection of the information he formerly knew.” Another item proposed honing “techniques for implanting false information into particular subjects… or for inducing in them specific mental disorders.” West wanted to reverse someone’s belief system without his knowledge, and make it stick. He hoped to create “couriers” who would carry “a long and complex message” embedded secretly in their minds, and to study “the induction of trance-states by drugs.” All of these were the goals of MKULTRA, and they bore a striking resemblance to Manson’s accomplishments with his followers more than a decade later.

“Needless to say,” West added, the experiments “must eventually be put to test in practical trials in the field.”

West’s colleagues wouldn’t approve of his activities. He yearned to “cut down considerably the number of people who can properly call me to account.” Because he’d be using drugs that were “not on the Air Force list of standard preparations,” he wanted to secure “some sort of carte blanche.” (He would go on to suggest a number of security measures in his letters, including disguised funding, double envelopes, and false names.)

Next West addressed a sensitive matter: who would the guinea pigs be? He listed four groups—basic airmen, volunteers, patients, and “others, possibly including prisoners in the local stockade.” Only the volunteers would be paid. The others could be unwilling, and, though it wasn’t spelled out, unwitting. It’d be easier to preserve his secrecy if he was “inducing specific mental disorders” in people who already exhibited them. “Certain patients requiring hypnosis in therapy, or suffering from dissociative disorders (trances, fugues, amnesias, etc.) might lend themselves to our experiments.”

As if to prove his thoroughness, he affixed two addenda to his four-page letter, begging Gottlieb to get one of his superiors, a Major Robert Williams, “transferred to another base.” Williams was “an uncomfortably close scrutinizer of all my activities” who believed that hypnosis was “tampering with the soul,” West complained.

Gottlieb’s reply came on letterhead from “Chemrophyl Associates,” a front company he used to correspond with MKULTRA subcontractors. “My Good Friend,” he wrote, “I had been wondering whether your apparent rapid and comprehensive grasp of our problems could possibly be real… you have indeed developed an admirably accurate picture of exactly what we are after. For this I am deeply grateful.” He would arrange top-secret clearances for anyone who might become ensnared in their work, giving West “a separate sum” for the purchase of materials.

Gottlieb saluted his new recruit: “We have developed quite an asset in the relationship we are developing with you.”

West returned the camaraderie. “It makes me very happy to realize that you consider me ‘an asset,’” he replied. “Surely there is no more vital undertaking conceivable in these times.”

With that, the record of their correspondence ceased for nearly nine months. When it resumed, in April 1954, West had begun arrangements to relocate to the University of Oklahoma School of Medicine, which wanted him to head its psychiatry department. He would be a civilian again. Gottlieb commended his “new look,” noting, “it appears at the moment to be a move which would in the long run be beneficial for us.” He signed off intimately, “Give my regards to your family.”

West had lied to his prospective employer, writing, “My present job is purely clinical and I have been doing no research, classified or otherwise.” The university took him at his word. Now performing his duties for Gottlieb at both the university and the air force base, West asked the judge advocate at Lackland for permission to accept money from the Geschickter Fund for Medical Research, which he called “a non-profit private research foundation.” In fact, as the CIA later acknowledged, Geschickter was another of Gottlieb’s fictions, enabling him to keep West and other researchers properly paid.

[…]

In a paper titled “The Psychophysiological Studies of Hypnosis and Suggestibility,” he claimed to have achieved the impossible: he knew how to replace “true memories” with “false ones” in human beings without their knowledge. In case the CIA didn’t grasp the significance of this, he put it in layman’s terms: “It has been found to be feasible to take the memory of a definite event in the life of an individual and, through hypnotic suggestion, bring about the subsequent conscious recall to the effect that this event never actually took place, but that a different (fictional) event actually did occur.”

The document, marked “classified,” was right there in West’s files; I had to assume that the CIA had destroyed any copies. They’ve never publicly acknowledged West’s groundbreaking deed. He’d done it, he claimed, by administering “new drugs” effective in “speeding the induction of the hypnotic state and in deepening the trance that can be produced in given subjects.”

As in his initial experiments, West performed most of these psychiatric feats on mental health patients. “The necessity to obtain most of the subject material from a population of psychiatry patients made standardized observations very difficult,” he groused. In the report, which doubled as a request for continued funding—a successful request; West received government backing through 1965 at the least—he enthusiastically described a high-tech laboratory he planned to construct at Oklahoma. It would include “a special chamber [where] various hypnotic, pharmacologic, and sensory-environmental variables will be manipulated.”

West had hypnotized mental patients and “normal subjects” and exposed them to a host of drugs, including chlorpromazine, reserpine, amphetamines, and LSD—the same ones that David Smith would inject in his confined rodents about a decade later. Of course, at least two of these, LSD especially, would prove instrumental in the Manson Family’s group psychology.

[…]

Acid, he wrote, made people more difficult to hypnotize; it was better to pair hypnosis with long bouts of isolation and sleep deprivation. Using hypnotic suggestion, he claimed, “a person can be told that it is now a year later and during the course of this year many changes have taken place… so that it is now acceptable for him to discuss matters that he previously felt he should not discuss… An individual who insists he desires to do one thing will reveal that secretly he wishes just the opposite.”

Since West’s paper was light on specifics, it’s hard to know if it was only a ploy for more funding.

[…]

At the National Security Archives in D.C., I found the version of “The Psychophysiological Studies of Hypnosis and Suggestibility” that the CIA had turned over to the Senate. West’s name and affiliation were redacted, as expected. But what shocked me was that the Senate’s version didn’t include West’s nine-page attachment, but rather an unsigned summary. There was no mention of West’s triumphant accomplishment, the replacement of “the memory of a definite event in the life of an individual” with a “fictional event.”

In sworn testimony, the CIA said that everything it shared with Congress was intact except for the redactions of researchers’ and institutions’ names. Now it turned out they hadn’t just censored West’s report; they’d completely misrepresented its contents.

Where your sugar comes from matters just as much as how much you consume

Friday, June 6th, 2025

New research from Brigham Young University suggests that where your sugar comes from matters just as much as how much you consume:

In the most extensive analysis of its kind, researchers from BYU and institutions in Germany examined data from over 500,000 people across multiple continents. Their discovery? Sugars from drinks like soda and even fruit juice were consistently linked to a higher risk of developing type 2 diabetes (T2D). Surprisingly, sugars from other sources did not show this same risk. In fact, some were even linked to a lower risk.

[…]

With each additional 12-oz serving of sugar-sweetened beverages (i.e., soft drinks, energy drinks, and sports drinks) per day, the risk for developing T2D increased by 25%. This strong relationship showed that the increased risk began from the very first daily serving with no minimum threshold below which intake appeared to be safe.

With each additional 8-oz serving of fruit juice per day (i.e., 100% fruit juice, nectars and juice drinks), the risk for developing T2D increased by 5%.

The above risks are relative not absolute. For example, if the average person’s baseline risk of developing T2D is about 10%, four sodas a day could raise that to roughly 20%, not 100%.

Comparatively, 20 g/day intakes of total sucrose (table sugar) and total sugar (the sum of all naturally occurring and added sugars in the diet) showed an inverse association with T2D, hinting at a surprising protective association.

[…]

Sugar-sweetened beverages and fruit juice supply isolated sugars, leading to a greater glycemic impact that would overwhelm and disrupt liver metabolism, thereby increasing liver fat and insulin resistance.

On the other hand, dietary sugars consumed in or added to nutrient-dense foods, such as whole fruits, dairy products, or whole grains, do not cause metabolic overload in the liver. These embedded sugars elicit slower blood glucose responses due to accompanying fiber, fats, proteins, and other beneficial nutrients.

The VR game was designed to give the eye muscles a workout

Monday, June 2nd, 2025

Researchers at Kwansei Gakuin University in Japan developed a VR game that aims to improve players’ eyesight:

It’s a relatively simple target shooting game developed in Unity for Meta Quest 2. The game features three lanes, each with a circular target on a stick. Pressing down the trigger button on the controller activates a virtual laser beam. Pointing this laser towards a lane highlights the lane and target and puts the player into “aim” mode. But to successfully hit the target, players have to move the controller’s stick in the direction indicated by the small Landolt C (a black ring shape with a gap used in Japanese eye tests) in the middle of the target.

VR Vision Training Game

The VR game was designed to give the eye muscles a workout, as players alternate between switching their gaze between targets at different distances and focusing on the Landolt C to see where the gap is. At the end of the game, players were treated to an arcade-style results screen, showing how many hits, misses and combos they got, as well as whether they broke a new record (apparently, some participants got very competitive about high scores).

The results showed that the game was effective in improving the vision of all the participants over the six week study period. For the severely myopic participants in particular, it was found that the more often they played the game, the more their sight improved.

The Landolt C was developed by the Swiss-born ophthalmologist Edmund Landolt:

The Landolt C consists of a ring that has a gap, thus looking similar to the letter C. The gap can be at various positions (usually left, right, bottom, top and the 45° positions in between) and the task of the tested person is to decide on which side the gap is. The size of the C and its gap are reduced until the subject makes a specified rate of errors. The minimum perceivable angle of the gap is taken as measure of the visual acuity. It is generally practised in the laboratory.

The stroke width is 1?5 of the diameter, and the gap width is the same. This is identical to the letter C from a Snellen chart. The Landolt C is the standard optotype for acuity measurement in most European countries. It was standardized, together with measurement procedures, by the German DIN, as DIN 58220 (now EN ISO 8596).

His research started with sixteen albino mice

Saturday, May 31st, 2025

Chaos by Tom O’NeillWhen he launched the Haight-Ashbury Free Medical Clinic, David Smith left a loose end dangling in his past, Tom O’Neill explains (in Chaos: Charles Manson, the CIA, and the Secret History of the Sixties) — he’d never actually received his PhD in pharmacology:

He’d completed a two-year research project on amphetamines and their effects on groups of confined mice, but he never finished his dissertation. Although he shrugged off the lapse—he’d already completed medical school, after all, and he’d taken quickly to his new life in the Haight—it surprised many of his closest friends, and in our interviews, he was reluctant to admit it. It wasn’t like him to leave something undone.

[…]

His research started with sixteen albino mice. With the assistance of other researchers, he separated these into two groups of eight in “aggregate” settings—small, closely confined communities intended to simulate crowding. Then he injected the mice with amphetamines. Over the next twenty-four hours, they transformed from docile animals into frantic combatants, fighting one another until they died either from injuries, self-inflicted wounds from overgrooming, or simple exhaustion. The violence was unremitting; Smith described “frenzied attacks of unrelenting rage.” Afterward, all that remained in the blood-spattered cages were scattered, dismembered body parts. Simply by confining the animals in close quarters, he’d increased the toxicity of the amphetamines more than four times.

In another attempt, some of the mice were dosed with other chemicals—mescaline, chlorpromazine, or reserpine—before they received amphetamine injections. The extra drugs sometimes had a sorting effect, segregating the mice that would kill from the mice that wouldn’t. Or they had a soothing effect, all but eliminating the violent tendencies.

Smith told me he’d started his research having foreseen an influx of amphetamine abusers in San Francisco. He didn’t say how he’d predicted that influx, but he was right. In the summer of ’67, as he opened his clinic, amphetamines exploded in popularity in the Haight.

“When the speed scene hit, it was a total shock to everybody,” he told me. “Suddenly, what I’d learned in pharmacology relative to amphetamines was applicable [to people].”

Throughout Love Needs Care, Smith draws parallels between the rodents he’d studied and the speed-addled hippies in the Haight. The mice on speed, he wrote, “become inordinately aggressive and assaultive… [turning] upon one another with unexpected savagery. Their violent behavior is probably intensified by confinement for it is strikingly similar to that observed in amphetamine abusers who consume the drugs in crowded atmospheres.”

In the Haight, Smith watched as people living cheek by jowl took huge doses of speed, inspiring paranoia and hallucinations. Once peaceful and well-adjusted, the “speed freaks” of San Francisco now “lashed out with murderous rage at any real or imagined intrusion,” assaulting, raping, or torturing to relieve the paranoid tension. “Cut off from the straight world, crammed together in inhuman conditions, and controlled by chemicals,” Smith concluded, “they behaved, quite naturally, like rats in a cage.”

[…]

In fact, according to Dr. Eugene Schoenfeld, who participated in a portion of Smith’s rat research in 1965, LSD was an integral component of the project. Smith and his colleagues would inject the rats with acid in hopes of making them more suggestible before he gave them amphetamines. Suggestibility was among the most prized effects of LSD from a clinical perspective. And yet Smith kept LSD out of the official documentation of his research. The article he published in the Journal of Psychedelic Drugs never mentioned acid.

I asked Smith if LSD was part of his protocol. He denied it—then, a moment later, without provocation, he reversed himself.

“Yeah, I stuck LSD in them,” he said.

But he couldn’t explain why. “I was sticking all different kinds of drugs in them,” he added. In his recollection, LSD “produced disorganized behavior, but not violent behavior.” The rats would just wander around in a daze.

If you’ve noticed that I’ve used “rats” and “mice” interchangeably, there’s a reason for that—Smith used them interchangeably, too, even though the two species have vastly different behavioral patterns, especially in groups. In his Journal of Psychedelic Drugs article, he calls them mice; in Love Needs Care and another book he published, they’re rats. Schoenfeld insisted that he’d worked with rats during his part of the research. But Smith was adamant that they were mice, and he couldn’t explain his confusion on the subject.

Like the San Francisco Project and Roger Smith’s Amphetamine Research Project (ARP), some of David Smith’s research, according to his academic papers, was funded by the National Institute of Mental Health (NIMH), which, as mentioned earlier, later acknowledged that the CIA used it as a front for LSD research. And though David never mentioned it in his writing, his work owed a clear debt to the landmark research of another NIMH psychologist, John B. Calhoun, who’d studied rat populations since 1946.

Calhoun reported that rats in confined groups—even without drugs—became uncharacteristically aggressive. They’d erupt in rape, murder, cannibalism, and infanticide. A dominant male rat emerged in the “behavioral sink”—Calhoun’s term for his aggregated rat cultures—subjugating other males into a tribe of cowering, enfeebled followers and organizing female rats into a “harem” of sex slaves. The strangest group to emerge was “the probers”: “hypersexualized” male rats that stalked and raped both males and females, and often cannibalized their young. The probers would commit “frenzied” and “berserk” attacks against rat families sleeping in their burrows, leaving the remains of half-eaten victims. Again, no drugs were involved here; the probers emerged simply as a result of their confinement. They deferred only to the dominant male rat, fleeing if he caught sight of them.

Calhoun’s study was a watershed. In the midsixties, amid growing concerns about population density, social scientists, politicians, and journalists cited him to explain the riots in America’s overcrowded ghettos. His term “behavioral sink”—defined as “the outcome of any behavioral process that collects animals together in unusually great numbers… aggravating all forms of pathology that can be found within [the] group”—entered the scientific lexicon almost right away. David Smith used it extensively in his writing and in interviews with me.

[…]

Plus, the more interesting subtleties of Calhoun’s research—the emergence of a dominant male, a harem of subservient females, and an underclass of “probers,” all of which, it had to be said, sounded a lot like the Family—had gone entirely unnoted in Smith’s project. I wondered if amphetamines, with or without LSD, had increased the dominant male’s grip on his followers.

Given how eerily Smith’s research prefigured the creation of the Family—under David’s nose, in the Haight, during the summer of ’67—I wondered if he had deliberately underreported it. I’ve never come close to proving that he did, but I haven’t been able to explain the holes in it, either. Why would he use LSD to induce suggestibility in rats before injecting them with amphetamines and making them berserk?

[…]

The reams of record keeping you’d expect from clinical experimentation simply weren’t there. Stephen Pittel, a forensic psychologist who’d worked with both Smiths at the HAFMC, volunteered a stunning bit of information that Roger and David had neglected to share with me.

“The only thing I remember about ARP was that it got burglarized one night and Roger lost all of his files,” Pittel told me. Their disappearance had been jarring, in part because Roger was “an unusually paranoid guy to begin with.”

[…]

The HAFMC’s original chief psychiatrist, Dr. Ernest Dernburg, remembered the theft of the ARP files, too. As he recalled, they’d gone missing right after the announcement of Manson’s arrest for the Tate–LaBianca murders and that “Roger, understandably, was pretty upset.” Nothing else was taken from the HAFMC, which led the staff to believe that the police or some federal agency might’ve removed the files. These were research papers, he reminded me: “It didn’t make sense for someone to steal these things when they didn’t inherently have any value to the average individual. It seemed to have a more nefarious purpose.”

The Smiths both denied that the theft had ever happened. “You’re dealing with aging memories,” David said. But Dernburg and Pittel—full-time doctors, and credible sources, I thought—stood by their stories. “They were absolutely stolen,” Pittel said. Dernburg, perturbed by David’s insinuation about his faculties, told me more that he remembered. “It was a considerable amount of research—the premier amphetamine research conducted at a street level. It would have been very important to the clinic… and it disappeared. Call David. Ask Roger if he has the files or knows where they are.”

[…]

David Smith had studied these same phenomena, formulating an idea that he called “the psychedelic syndrome,” first articulated in 1967 or early ’68. The gist was that acid, when taken by groups of like-minded people, led to a “chronic LSD state” that reinforced “the interpretation of psychedelic reality.” The more often the same group of “friends” dropped acid, the more they encouraged one another to adopt the worldview they’d discovered together on LSD, thus producing “dramatic psychological changes.”

Usually the psychedelic syndrome was harmless, but regular LSD use could cause “the emergence of a dramatic orientation to mysticism.” And in people with “prepsychotic personalities,” Smith wrote, LSD precipitated “a long-term psychological disorder, usually a depressive reaction or a schizophrenic process.”

Had Smith seen this “syndrome” in the Family? After Manson had been arrested for the murders, David wrote, “Charlie could probably be diagnosed as ambulatory schizophrenic.” He said the same thing when I asked about Manson: “I felt that he was schizo.” It was Roger Smith who’d had the better diagnosis, and the earlier one, David maintained: “Roger said that he knew from day one that Charlie was a psychopath.”

But Roger apparently never thought it was necessary to intervene—to send his parolee back to prison or to get him proper psychiatric care. Instead, he sent him to the Haight and watched him drop acid every day, accruing suggestible young followers as he went. Meanwhile, David was studying the exact psychological conditions that gave rise to the Manson Family while he treated them at his clinic.

The subterranean humanity was nonsense

Friday, May 30th, 2025

Invented to make beef last through a long voyage, Bovril became a famous British kitchen staple:

Less well-known is its link to an odd, pioneering science fiction novel.

A stout black jar of Bovril with a cheery red top lurks in many a British kitchen, next to tins of treacle and boxes of tea. The gooey substance, made of rendered-down beef, salt and other ingredients, can be spread on toast or made into a hot drink, but what many people don’t realise is that this old-fashioned comfort food has a surprising link to science fiction.

The “Bov” part of the name is easy enough to decipher — from “bovine”, meaning associated with cattle. But the “vril” bit? That’s a different story, literally.

In 1871, an anonymous novel was published about a race of super-humans living underground. The narrator of The Coming Race, who has fallen into their realm during a disastrous descent into a mine shaft, is shocked to learn that they are telepathic, thanks to the channeling of a mysterious energy called vril.

“Through vril conductors, they can exercise influence over minds, and bodies animal and vegetable, to an extent not surpassed in the romances of our mystics,” the narrator realises. Vril gives them strength, as well, rendering them capable of incredible feats. The people call themselves the Vril-Ya, and their society seems in many ways superior to that of the surface dwellers.

The Coming Race was a runaway bestseller. It eventually became clear that the anonymous author was Edward Bulwer-Lytton, the prominent politician and writer (and, to give you a sense of his prose, the first person to start a novel: “It was a dark and stormy night…”). It became such a cultural touchstone that 20 years later, the Royal Albert Hall in London played host to the Vril-Ya Bazaar and Fete, to raise money for a school of massage “and electricity”.

In 1895, a writer for The Guardian newspaper started a review of a new novel with this statement: “The influence of the author of The Coming Race is still powerful, and no year passes without the appearance of stories which describe the manners and customs of peoples in imaginary worlds, sometimes in the stars above, sometimes in the heart of unknown continents in Australia or at the Pole, and sometimes below the waters under the earth.” The work under review? The Time Machine, by H G Wells.

And so you can see how, in the 1870s, when John Johnston, Scottish meat entrepreneur, was coming up with a name for his bottled beef extract, “vril” was a tip-of-the-tongue reference.

[…]

Johnston and other makers of the substance were responding to a demand for beef products in Europe, where raising cattle was prohibitively expensive, and the growth of cattle ranches in South America, Australia and Canada.

There was no way to get fresh meat from these far-flung places to Europe. But rendering the meat down into a paste and sealing it in jars yielded a shelf-stable product that could make the long journeys involved. (Johnston was not the only player in the meat extract game — Justus von Liebig, one of the founders of organic chemistry, founded Leibig’s Extract of Meat Company to commercialise his process. The company later went on to produce Oxo bouillon cubes and Fray Bentos pies.)

How do you make a salty meat paste sound nourishing? By linking it to a fantastical substance with great powers. An excitable advert for Bovril in the program from the Vril-Ya Bazaar reads, “Bo-VRIL is the materialised ideal of the gifted author of ‘The Coming Race’… it will exert a marvellous influence on the system, exhilarating without subsequent depression, and increasing the mental and physical vitality without taxing the digestive organs. It is a tonic as well as a food, and forms the most Perfect Nourishment known to Science.”

[…]

Members of the theosophy movement, including the spiritualist medium Madame Blavatsky, claimed that vril was real. Willy Ley, a German rocket enthusiast writing about conspiracy theories in Germany during the rise of the Nazis in the magazine Astounding Science Fiction, said there was a society in Berlin that believed in vril: “They knew that the book was fiction, Bulwer-Lytton had used that device in order to be able to tell the truth about this ‘power’.

“The subterranean humanity was nonsense, Vril was not. Possibly it had enabled the British, who kept it as a State secret, to amass their colonial empire.”

I have discussed the pursuit of the almighty vril before.

That burning feeling is real

Monday, May 12th, 2025

The first scientist to draw the connection between exercise and lactic acid was Jöns Jacob Berzelius, Alex Hutchinson explains, the Swedish chemist who devised the modern system of chemical notation (H2O, etc.):

Sometime around 1807, he noticed that the chopped-up muscles of dead deer contained lactic acid, a substance that had only recently been discovered in soured milk. Crucially, the muscles of stags that had been hunted to death contained higher levels of lactic acid, while deer from a slaughterhouse who had their limbs immobilized in a splint before their death had lower levels, suggesting that the acid was generated by physical exertion.

A century later, physiologists at the University of Cambridge used electric stimulation to make frogs’ legs twitch until they reached exhaustion, and observed high lactic acid levels. The levels were even higher if they performed the experiment in a chamber without oxygen, and lower if they provided extra oxygen. That finding helped establish the prevailing twentieth-century view: your muscles need oxygen to generate energy aerobically; if they can’t get enough oxygen, they switch to generating energy anaerobically, which produces lactic acid as a toxic byproduct that eventually shuts your muscles down.

Athletes going lactic feel the burn and typically back off a bit:

In interviews with athletes who’ve begun using baking soda, a common theme is that they’re able to push harder for longer before feeling that burn in their legs, which in turn enables them to race faster.

One theory about the feeling of going lactic is that you’re literally starving your brain of oxygen. If you push hard enough, it’s not just your muscles that go more acidic; your whole bloodstream follows. Thanks to a phenomenon called the Bohr effect, rising acidity reduces the ability of your red blood cells to ferry oxygen from your lungs to the rest of your body, including your brain. In one study, all-out rowing caused oxygen saturation to drop from 97.5 to 89.0 percent, which is a big drop—big enough, perhaps, to slow you down and contribute to the out-of-body feeling at the end of hard races.

We also have nerve sensors that keep the brain informed about the metabolic status of the muscles. These group III/IV afferents, as they’re known, keep tabs on the real-time levels of molecules like lactate and hydrogen ions. If you block these nerves with spinal injections of fentanyl, exercise feels great—too great, in fact, because you’ll lose all sense of pacing, go out too hard, then hit the wall.

The most telling finding about the lactic burn, in my view, was a 2013 study where they injected various molecules into the thumbs of volunteers in an attempt to reproduce that familiar feeling. Injecting lactate didn’t do it. Neither did injecting hydrogen ions, or ATP, a fuel molecule whose levels are also elevated during hard exercise. Injecting them in pairs didn’t do it either. But injecting all three at the levels you’d experience during moderate exercise produced a sensation of fatigue in their thumbs, even though they weren’t moving them. And injecting higher levels turned fatigue into pain.

That’s a distinction I try to keep in mind in the late stages of hard workouts, and at the crux of races. That burning feeling is real, and it’s associated with lactate and acidity and muscular fuel levels. But it’s just a feeling.

Researchers flipped the position of just two atoms in LSD’s molecular structure

Monday, April 21st, 2025

University of California, Davis, researchers have developed a new, neuroplasticity-promoting drug closely related to LSD with reduced hallucinogenic potential:

To design the drug, dubbed JRT, researchers flipped the position of just two atoms in LSD’s molecular structure. The chemical flip reduced JRT’s hallucinogenic potential while maintaining its neurotherapeutic properties, including its ability to spur neuronal growth and repair damaged neuronal connections that are often observed in the brains of those with neuropsychiatric and neurodegenerative diseases.

[…]

JRT exhibited powerful neuroplastic effects and improved measures in mice relevant to the negative and cognitive symptoms of schizophrenia, without exacerbating behaviors and gene expression associated with psychosis.

[…]

Olson said that it took his team nearly five years to complete the 12-step synthesis process to produce JRT. The molecule was named after Jeremy R. Tuck, a former graduate student in Olson’s laboratory, who was the first to synthesize it and is a co-first author of the study along with Lee E. Dunlap, another former graduate student in Olson’s laboratory.

[…]

Key findings included:

  • JRT and LSD have the exact same molecular weight and overall shape, but distinct pharmacological properties.
  • JRT is very potent and highly selective for binding to serotonin receptors, specifically 5-HT2A receptors, the activation of which are key to promoting cortical neuron growth.
  • JRT promoted neuroplasticity, or growth between cellular connections in the brain, leading to a 46% increase in dendritic spine density and an 18% increase in synapse density in the prefrontal cortex.
  • JRT did not produce hallucinogenic-like behaviors that are typically seen when mice are dosed with LSD.
  • JRT did not promote gene expression associated with schizophrenia. Such gene expression is typically amplified with LSD use.
  • JRT produced robust anti-depressant effects, with it being around 100-fold more potent than ketamine, the state-of-the-art fast-acting anti-depressant.
  • JRT promoted cognitive flexibility, successfully addressing deficits in reversal learning that are associated with schizophrenia.

Joe Lonsdale presents a blueprint for FDA reform

Sunday, April 13th, 2025

The new FDA report from Joe Lonsdale and team is impressive, Alex Tabarrok says, as he shares a few of the recommendation which caught his eye:

In the U.S., anyone running a clinical trial must manufacture their product under full Good Manufacturing Practices (GMP) regardless of stage. This adds enormous cost (often $10M+) and more importantly, as much as a year’s delay to early-stage research. Beyond the cost and time, these requirements are outright irrational: for example, the FDA often requires three months of stability testing for a drug patients will receive after two weeks. Why do we care if it’s stable after we’ve already administered it? Or take AAV manufacturing—the FDA requires both a potency assay and an infectivity assay, even though potency necessarily reflects infectivity.

This change would not be unprecedented either. By contrast, countries like Australia and China permit Phase 1 trials with non-GMP drug with no evidence of increased patient harm.

[…]

With modern AI and digital infrastructure, trials should be designed for machine-readable outputs that flow directly to FDA systems, allowing regulators to review data as it accumulates without breaking blinding. No more waiting nine months for report writing or twelve months for post-trial review. The FDA should create standard data formats (akin to GAAP in finance) and waive documentation requirements for data it already ingests. In parallel, the agency should partner with a top AI company to train an LLM on historical submissions, triaging reviewer workload so human attention is focused only where the model flags concern. The goal is simple: get to “yes” or “no” within weeks, not years.

[…]

When negative results aren’t published, companies duplicate failed efforts, investors misallocate capital, and scientists miss opportunities to refine hypotheses. Publishing all trial outcomes — positive or negative—creates a shared base of knowledge that makes drug development faster, cheaper, and more rational. Silence benefits no one except underperforming sponsors; transparency accelerates innovation.

The FDA already has the authority to do so under section 801 of the FDAAA, but failed to adopt a more expansive rule in the past when it created clinicaltrials.gov. Every trial on clincaltrials.gov should have a publication associated with it that is accessible to the public, to benefit from the sacrifices inherent in a patient participating in a clinical trial.

[…]

We need multiple competing approval frameworks within HHS and/or FDA. Agencies like the VA, Medicare, Medicaid, or the Indian Health Service should be empowered to greenlight therapies for their unique populations. Just as the DoD uses elite Special Operations teams to pioneer new capabilities, HHS should create high-agency “SWAT teams” that experiment with novel approval models, monitor outcomes in real time using consumer tech like wearables and remote diagnostics, and publish findings transparently. Let the best frameworks rise through internal competition—not by decree, but by results.

The Return of the Dire Wolf?

Monday, April 7th, 2025

Time magazine announces the return of the dire wolf:

The dire wolf once roamed an American range that extended as far south as Venezuela and as far north as Canada, but not a single one has been seen in over 10,000 years, when the species went extinct. Plenty of dire wolf remains have been discovered across the Americas, however, and that presented an opportunity for a company named Colossal Biosciences.

Relying on deft genetic engineering and ancient, preserved DNA, Colossal scientists deciphered the dire wolf genome, rewrote the genetic code of the common gray wolf to match it, and, using domestic dogs as surrogate mothers, brought Romulus, Remus, and their sister, 2-month-old Khaleesi, into the world during three separate births last fall and this winter—effectively for the first time de-extincting a line of beasts whose live gene pool long ago vanished. TIME met the males (Khaleesi was not present due to her young age) at a fenced field in a U.S. wildlife facility on March 24, on the condition that their location remain a secret to protect the animals from prying eyes.

The dire wolf isn’t the only animal that Colossal, which was founded in 2021 and currently employs 130 scientists, wants to bring back. Also on their de-extinction wish list is the woolly mammoth, the dodo, and the thylacine, or Tasmanian tiger. Already, in March, the company surprised the science community with the news that it had copied mammoth DNA to create a woolly mouse, a chimeric critter with the long, golden coat and the accelerated fat metabolism of the mammoth.

If all this seems to smack of a P.T. Barnum, the company has a reply. Colossal claims that the same techniques it uses to summon back species from the dead could prevent existing but endangered animals from slipping into extinction themselves.

[…]

It takes surprisingly few genetic changes to spell the difference between a living species and an extinct one. Like other canids, a wolf has about 19,000 genes. (Humans and mice have about 30,000.) Creating the dire wolves called for making just 20 edits in 14 genes in the common gray wolf, but those tweaks gave rise to a host of differences, including Romulus’ and Remus’ white coat, larger size, more powerful shoulders, wider head, larger teeth and jaws, more-muscular legs, and characteristic vocalizations, especially howling and whining.
The dire wolf genome analyzed to determine what those changes were was extracted from two ancient samples—one a 13,000-year-old tooth found in Sheridan Pit, Ohio, the other a 72,000-year-old ear bone unearthed in American Falls, Idaho.

[…]

Colossal’s dire wolf work took a less invasive approach, isolating cells not from a tissue sample of a donor gray wolf, but from its blood. The cells they selected are known as endothelial progenitor cells (EPCs), which form the lining of blood vessels. The scientists then rewrote the 14 key genes in the cell’s nucleus to match those of the dire wolf; no ancient dire wolf DNA was actually spliced into the gray wolf’s genome. The edited nucleus was then transferred into a denucleated ovum. The scientists produced 45 engineered ova, which were allowed to develop into embryos in the lab. Those embryos were inserted into the wombs of two surrogate hound mixes, chosen mostly for their overall health and, not insignificantly, their size, since they’d be giving birth to large pups. In each mother, one embryo took hold and proceeded to a full-term pregnancy. (No dogs experienced a miscarriage or stillbirth.) On Oct. 1, 2024, the surrogates birthed Romulus and Remus. A few months later, Colossal repeated the procedure with another clutch of embryos and another surrogate mother. On Jan. 30, 2025, that dog gave birth to Khaleesi.

[…]

“The idea that we could just take a vial of blood, isolate EPCs, culture them, and clone from them, and they have a pretty high cloning efficiency, we think it’s a game changer,” says George Church, Colossal co-founder, and professor of genetics at both Harvard University and the Massachusetts Institute of Technology. The less invasive cell-sampling process will make the procedure easier on animals, and the fact that Colossal’s methods worked on this early go-round boosts company confidence that they are on track for much broader de-extinction and rewilding.

Borrowing a name from Game of Thrones for a dire wolf makes perfect sense, but Khaleesi? The actual (fictional) dire wolves in the stories are:

Grey Wind, adopted by Robb Stark.
Lady, adopted by Sansa Stark.
Nymeria, adopted by Arya Stark.
Shaggydog, adopted by Rickon Stark.
Summer, adopted by Bran Stark.
Ghost, adopted by Jon Snow.

Scientific purists will note that the “dire wolves” created by Colossal are merely ordinary wolves with a few gene edits. Previous “dire wolves” have been dogs bred to look like wolves.

Artificial sweetener shows surprising power to overcome antibiotic resistance

Sunday, April 6th, 2025

Professor Ronan McCarthy, at Brunel University of London’s Antimicrobial Innovations Center, and his team have found that saccharin shows surprising power to overcome antibiotic resistance:

“Saccharin breaks the walls of bacterial pathogens, causing them to distort and eventually burst, killing the bacteria. Crucially, this damage lets antibiotics slip inside, overwhelming their resistance systems.”

[…]

The international team found that saccharin both stops bacterial growth and disrupts DNA replication and stops the bacteria from forming biofilms—sticky, protective layers that help them survive antibiotics.

They also created a saccharin-loaded hydrogel wound dressing that, in tests, outperformed market-leading silver-based antimicrobial dressings currently used in hospitals.

“This is very exciting,” Prof McCarthy added. “Normally it takes billions of dollars and decades to develop a new antibiotic. But here we have a compound that’s already widely used, and it not only kills drug-resistant bacteria but also makes existing antibiotics more effective.

“Artificial sweeteners are found in many diet and sugar-free foods. We discovered that the same sweeteners you have with your coffee or in a ‘sugar-free’ drink could make some of the world’s most dangerous bacteria easier to treat.”

What does saccharin do to benign bacteria?

Beginning in 1957, massive tunnel complexes were drilled into the volcanic rock and granite by hard-rock miners working twenty-four hours a day, seven days a week

Friday, March 21st, 2025

Area 51 by Annie JacobsenUnderground tunnels, called N-tunnels, P-tunnels, and T-tunnels, have been drilled next door to Area 51, Annie Jacobsen explains (in Area 51), for decades:

The 1,150-foot-long tunnel at Jackass Flats, drilled into the Calico Mountains, through which NERVA scientists and engineers like T. D. Barnes accessed their underground workstations is but one example of an underground tunnel at the Nevada Test Site. The NERVA complex in Area 25 has since been dismantled and “deactivated,” according to the Department of Energy, but elsewhere at the test site dozens of tunnel complexes exist. In the 1960s, one tunnel dug into the granite mountain of Rainer Mesa, in Area 12, reached down as far as 4,500 feet, nearly a mile underground. There are many such government tunnels and bunkers around America, but it was the revelation of the Greenbrier bunker by Washington Post reporter Ted Gup in 1992 that set off a firestorm of conspiracy theories related to postapocalypse hideouts for the U.S. government elite—and since 1992, these secret bunkers have been woven into conspiracy theories about things that go on at Area 51.

The Greenbrier bunker is located in the Allegheny Mountains, 250 miles southwest of the nation’s capital. Beginning in 1959, the Department of Defense spearheaded the construction of a 112,544-square-foot facility eight hundred feet below the West Virginia wing of the fashionable five-star Greenbrier resort. This secret bunker, completed in 1962, was to be the place where the president and certain members of Congress would live after a nuclear attack. The Greenbrier bunker had dormitories, a mess hall, decontamination chambers, and a hospital staffed with thirty-five doctors. “Secrecy, denying knowledge of the existence of the shelter from our potential enemies, was paramount to all matters of operation,” Paul Bugas, the former onsite superintendent at the Greenbrier bunker, told PBS when asked why the facility was kept secret from the public. Many citizens agree with the premise. Conspiracy theorists disagree. They don’t believe that the government keeps secrets to protect the people. Conspiracy theorists believe the leaders of government are only looking to protect themselves.

The underground tunnels and bunkers at the Nevada Test Site may be the most elaborate underground chambers ever constructed by the federal government in the continental United States. The great majority of them are in Area 12, which is located approximately sixteen miles due west of Area 51 in a mountain range called Rainier Mesa. Beginning in 1957, massive tunnel complexes were drilled into the volcanic rock and granite by hard-rock miners working twenty-four hours a day, seven days a week. To complete a single tunnel took, on average, twelve months. Most tunnels ran approximately 1,300 feet below the surface of the earth, but some reached a mile underground. Inside these giant cavities, which averaged one hundred feet wide, the Atomic Energy Commission and the Department of Defense have exploded at least sixty-seven nuclear bombs. There, the military has tested nuclear blast and radiation effects on everything from missile nose cones to military satellites. A series called the Piledriver experiments studied survivability of hardened underground bunkers in a nuclear attack. The Hardtack tests sought to learn how “to destroy enemy targets [such as] missile silos and command centers” using megaton bombs. Inside the T-tunnels, scientists created vacuum chambers to simulate outer space, expanding on those dangerous late-1950s upper atmospheric tests code-named Teak and Orange. And the Department of Defense even tested how a stockpile of nuclear weapons inside an underground bunker would hold up to a nuclear blast.

Richard Mingus has spent many years inside these underground tunnel complexes, guarding many of the nuclear bombs used in the tests before they were detonated. In Mingus’s five decades working at the test site, these were his least favorite assignments. “The tunnels were dirty, filthy, you had to wear heavy shoes because there was so much walking on all kinds of rock rubble,” Mingus explains. “The air was bad and everything was stuffy. There were so many people working so many different jobs. Carpenters, welders… There were forty-eight-inch cutting machines covering the ground.” Most of the equipment was hauled in on railroad tracks, which is at least partially responsible for inspiring conspiracy theories that include trains underneath Area 51—though the conspiracy theorists believe they’re able to ferry government elite back and forth between Nevada and the East Coast. In reality, according to Atomic Energy Commission records, the Defense Department built the train system in the tunnels to transport heavy military equipment in and out. If employees wanted to, men like Richard Mingus could ride the train cars down into the underground tunnel complexes, but Mingus preferred to walk.

They were speaking from a very motivated standpoint, trying to shut down something that they thought would hurt their interests

Sunday, March 16th, 2025

Viral by Alina Chan and Matt RidleyFive years ago, the SARS-CoV-2 virus shut down the world and changed it forever:

While initial reports suggested that the virus had jumped from wild animals to humans at a market in Wuhan, China, others pointed to the Wuhan Institute of Virology — the only lab actively experimenting with closely related viruses. Since these viruses have never been found naturally within 1,000 miles of Wuhan, a local outbreak made little sense — yet questioning this brought swift political and institutional backlash from scientists worried about risking their careers and their work. But while working at the Broad Institute in Cambridge, scientist Alina Chan kept publicly questioning the official story, despite attempts from influential scientists and the media to cast the hypothesis as a conspiracy theory.

[…]

So back in 2020 when I interviewed you for Boston, you were basically a postdoc with a Twitter account. Since then, you’ve published a book as well as influential opinion pieces in Science magazine and the New York Times, and have shifted to work on the challenges relating to research that can cause pandemics. How has your life changed?

My gosh, five years, that’s a lot to cover. I mean, almost everything has changed.

[…]

Has your confidence that the pandemic resulted from a lab incident changed since 2020?

Back then, I was pretty agnostic. I was about 50/50. To the rest of society, that seemed insane because all of the top scientists were saying that this was a racist, anti-scientific conspiracy theory.

Yes, and now we know, thanks to the Freedom of Information Act, that they were colluding to suppress discussion of the lab-leak theory and were secretly trying to get you disciplined or fired. How did that make you feel?

Scientists are people. They have a lot of different pressures in their lives. Pressures to keep their labs running, to publish, to advance in their career. These virologists were not speaking scientifically. They were speaking from a very motivated standpoint, trying to shut down something that they thought would hurt their interests. Even in a situation where millions of people were dying. That shocked me.

What finally convinced you that the Wuhan Institute of Virology was the likely cause of the pandemic?

For me, the thing that really shifted the balance of evidence was the discovery of a 2018 research proposal called Defuse that was submitted by the Wuhan Institute of Virology and their U.S. collaborators that specifically said, “We’re gonna look for novel SARS-like viruses in the wild, we’re gonna put in these novel furin cleavage sites and see what happens, and we’re gonna test these viruses in human cells to see how these features can impact their ability to replicate and cause disease.” And then, barely two years later, exactly such a virus causes an outbreak in their city, very far away from where these viruses are found naturally. To me, that extreme coincidence was too much to ignore.

They hiked inside several atomic craters

Friday, March 14th, 2025

Area 51 by Annie JacobsenA little-known fact, Annie Jacobsen explains (in Area 51), is that to prepare for what it would actually be like to walk around on the geology of the moon, the astronauts visited the Nevada Test Site:

There, they hiked inside several atomic craters, learning what kind of geology they might have to deal with on the lunar surface’s inhospitable terrain.

[…]

“I was with them in 1965, and again five years later when they came back,” Williams recalls. This time the astronauts arrived with a lunar roving vehicle to test what it might be like driving on the moon.

[…]

The lunar roving vehicle was not a fast-moving vehicle, and the astronauts took turns driving it. “NASA had built it and had driven it in a lot of flat places,” Williams explains. “But before it came to the test site and drove on the craters, the vehicle had no real experience on inhospitable terrain.

[…]

The craters Williams was talking about are subsidence craters—geologic by-products of underground bomb tests. When a nuclear bomb is placed in a deep vertical shaft, as hundreds were at the test site (not to be confused with tunnel tests), the explosion vaporizes the surrounding earth and liquefies the rock. Once that molten rock cools, it solidifies at the bottom of the cavity, and the earth above it collapses, creating the crater. The glass-coated rock, giant boulders, and loose rubble that remain resemble the craters found on the moon. So similar in geology were the atomic craters to moon craters that in voice transcripts sent back during the Apollo 16 and Apollo 17 missions, astronauts twice referred to the craters at the Nevada Test Site. During Apollo 16, John W. Young got specific. A quarter of a million miles away from Earth, while marveling at a lunar crater laden with rocks, Young asked fellow astronaut Charles M. Duke Jr., “Remember how it was up at that crater? At Schooner.” He was referring to the atomic crater Ernie Williams took the astronauts to in Area 20. During Apollo 17, while looking at the Haemus Mountains, Harrison H. Schmitt can be heard talking about the Buckboard Mesa craters in Area 19. For Ernie Williams, hearing this comparison was a beautiful moment. For lunar-landing conspiracy theorists, of which there are millions worldwide, the feeling was one of suspicion. For these naysayers, Schmitt’s telemetry tapes, the moon photographs, the moon rocks—everything having to do with the Apollo moon missions would become grist for a number of ever-growing conspiracies that have been tied to man’s journey to the moon.

The medieval house might have been built to specifications approved by a rodent council

Sunday, February 23rd, 2025

Dozens of rodents carry plague, Ed West notes, but it would only become deadly to humans when Yersinia pestis infected the flea of the black rat (Rattus rattus):

Black rats are sedentary homebodies and don’t like to move more than 200 metres from their nests; they especially like living near to humans, which is what makes them so much more dangerous than more adventurous rodents. Black rats have been our not-entirely-welcome companion for thousands of years, and were living near human settlements in the Near East from as far back as 3000 BC; the Romans and their roads helped them spread across the empire and brought them to Britain, the oldest rat remains here being found from the fourth century, underneath Fenchurch Street in London.

Black rats were especially comfortable in the typical medieval house, and while stone buildings became a feature of life in the 12th century, most were still made of wood and straw. In the words of historian Philip Ziegler, ‘The medieval house might have been built to specifications approved by a rodent council as eminently suitable for the rat’s enjoyment of a healthy and care-free life.’ This type of rat is also a very good climber, so could easily live in the thatched roofs which were common then.

Because of its preferred home, the black rat is also called the house rat or ship rat, while the brown rat prefers sewers. On top of this, the animals are fecund to a horrifying degree; one black rat couple can theoretically produce 329 million descendants in three years. So the typical medieval city had lots of rats, and with them came lots of fleas.

Fleas are nature’s great survivors. They can endure in all sorts of conditions, and some have developed the ability to live off bits of bread and only require blood for laying eggs. The black rat flea, called Xenopsylla cheopis, is also exceptionally hardy, able to survive between 6-12 months without a host, living in an abandoned nest or dung, although it is only active when the temperature is between 15-20 centigrade. As John Kelly wrote in The Great Mortality, the Oriental rat flea is ‘an extremely aggressive insect. It has been known to stick its mouth parts into the skin of a living caterpillar and suck out the caterpillar’s bodily fluids and innards’. What a world.

There are two types of flea: fur fleas and nest fleas, and only the former travels with its host rather than remaining in the nest. The rat flea is a fur flea, and while it prefers to stay on its animal of choice, they will jump on to other creatures if they’re nearby – unfortunately, in the 14th century that happened to be us. (In fact, they will attach themselves to most farmyard animals, and only the horse was left alone, because its odour repulses them, for some reason.)

As part of the great and disgusting chain of being, the rats inadvertently brought the plague to humans, but it wasn’t fun for the rats either, or the fleas for that matter. When the hungry flea bites the rat, the pestis triggers a mutation in the flea guts causing it to regurgitate the bacteria into the wound, so infecting the rat. (Yes, it is all a bit disgusting). Y. pestis can be transmitted by 31 different flea species, but only in a rodent does the quantity of bacillus become large enough to block the fleas’s stomach.

The flea therefore feeds more aggressively as it dies of starvation, and its frantic feeding makes the host mammal more overrun with the bacterium. The fleas also multiply as the plague-carrying rat gets sick, so that while a black rat will carry about seven fleas on average, a dying rat will have between 100 and 150. Rats were infected with the disease far more intensely than humans, so that ‘the blood of plague-infected rats contains 500-1,000 times more bacteria per unit of measurement than the blood of plague-infected humans.’

When the disease is endemic to rodents it’s called ‘sylvatic plague’, and when it jumps to humans it’s called ‘bubonic’ plague. For Y pestis to spread, there will ideally be two populations of rodents living side by side: one must be resistant to the disease so that it can play host, and the other non-resistant so the bacteria can feed on it. There needs to be a rat epidemic to cause a human epidemic because it provides a ‘reservoir’ for the disease to survive. Robert Gottfried wrote: ‘Y pestis is able to live in the dark, moist environment of rodent burrows even after the rodents have been killed by the epizootic, or epidemic. Thus as a new rodent community replaces the old one, the plague chain can be revived’. The rat colony will all be dead within two weeks of infection and then the fleas start attacking humans.

The first human cases would typically appear 16-23 days after the plague had arrived in a rat colony, with the first deaths taking place after about 20-28 days. It takes 3-5 days after infection for signs of the disease to appear in humans, and a similar time frame before the victim died. Somewhere between 20-40 per cent of infected people survived, and would thereafter mostly be immune.

What happened next would have been terrifying. ‘From the bite site, the contagion drains to a lymph node that consequently swells to form a painful bubo,’ or swelling lump, ‘most often in the groin, on the thigh, in an armpit or on the neck. Hence the name bubonic plague.’