“A.I.s Are Overly Complicated, Patched-Together Rube Goldberg Machines Full of Ad-Hoc Solutions”

A.I. can be a useful tool for searching and summarizing the current state of consensus knowledge. But I am highly dubious that it will ever be able to make the breakthrough leaps that some humans are sometimes able to make. And I am somewhat dubious that it will ever be able to make the resilient pivots that all of us must sometimes make in the face of new and unexpected challenges.

(p. B2) In a series of recent essays, [Melanie] Mitchell argued that a growing body of work shows that it seems possible models develop gigantic “bags of heuristics,” rather than create more efficient mental models of situations and then reasoning through the tasks at hand. (“Heuristic” is a fancy word for a problem-solving shortcut.)

When Keyon Vafa, an AI researcher at Harvard University, first heard the “bag of heuristics” theory, “I feel like it unlocked something for me,” he says. “This is exactly the thing that we’re trying to describe.”

Vafa’s own research was an effort to see what kind of mental map an AI builds when it’s trained on millions of turn-by-turn directions like what you would see on Google Maps. Vafa and his colleagues used as source material Manhattan’s dense network of streets and avenues.

The result did not look anything like a street map of Manhattan. Close inspection revealed the AI had inferred all kinds of impossible maneuvers—routes that leapt over Central Park, or traveled diagonally for many blocks. Yet the resulting model managed to give usable turn-by-turn directions between any two points in the borough with 99% accuracy.

Even though its topsy-turvy map would drive any motorist mad, the model had essentially learned separate rules for navigating in a multitude of situations, from every possible starting point, Vafa says.

The vast “brains” of AIs, paired with unprecedented processing power, allow them to learn how to solve problems in a messy way which would be impossible for a person.

. . .

. . ., today’s AIs are overly complicated, patched-together Rube Goldberg machines full of ad-hoc solutions for answering our prompts. Understanding that these systems are long lists of cobbled-together rules of thumb could go a long way to explaining why they struggle when they’re asked to do things even a little bit outside their training, says Vafa. When his team blocked just 1% of the virtual Manhattan’s roads, forcing the AI to navigate around detours, its performance plummeted.

This illustrates a big difference between today’s AIs and people, he adds. A person might not be able to recite turn-by-turn directions around New York City with 99% accuracy, but they’d be mentally flexible enough to avoid a bit of roadwork.

For the full commentary see:

Christopher Mims. “We Now Know How AI ‘Thinks.’ It Isn’t Thinking at All.” The Wall Street Journal (Saturday, April 26, 2025): B2.

(Note: ellipses added.)

(Note: the online version of the commentary has the date April 25, 2025, and has the title “We Now Know How AI ‘Thinks’—and It’s Barely Thinking at All.”)

A conference draft of the paper that Vafa co-authored on A.I.’s mental map of Manhattan is:

Vafa, Keyon, Justin Y. Chen, Ashesh Rambachan, Jon Kleinberg, and Sendhil Mullainathan. “Evaluating the World Model Implicit in a Generative Model.” In 38th Conference on Neural Information Processing Systems (NeurIPS). Vancouver, BC, Canada, Dec. 2024.

Muriel Bristol Was Allowed to Act on What She Knew but Was Unable to Prove or Explain

Muriel Bristol knew that tea tasted better when the milk was poured in first, than when it was poured in after the tea. She knew it but couldn’t prove it and didn’t know why it was true. The world is better when more of us, more often, can act on what we know, but what we can neither prove nor explain. Too often regulations restrict the actions of entrepreneurs to what they can prove and explain, e.g., in the firing of employees.

This slows and reduces efficiency and innovation (not to mention freedom).

(p. C8) [Adam] Kucharski, a mathematically trained epidemiologist, says that the rigor and purity of mathematics has imbued it with extraordinary rhetorical power. “In an uncertain world, it is reassuring to think there is at least one field that can provide definitive answers,” he writes. Yet he adds that certainty can sometimes be an illusion. “Even mathematical notions of proof” are “not always as robust and politics-free as they might seem.”

. . .

. . ., proving what is “obvious and simple” isn’t always easy. Kucharski offers the delightful example of Muriel Bristol, a scientist who always put the milk in her cup before pouring her tea, because she insisted it tasted better. In the 1920s, a skeptical statistician designed a blind taste test to see if Bristol could distinguish between cups of milk-then-tea and cups of tea-then-milk. Bristol got all of them right. In 2008, the Royal Society of Chemistry reported that when milk is poured into hot tea, “individual drops separate from the bulk of the milk” and allow “significant denaturation to occur.” The result is a burnt flavor. Eighty years after Bristol was statistically vindicated, she was chemically vindicated too.

For the full review see:

Jennifer Szalai. “Proving It Doesn’t Necessarily Make It True.” The New York Times (Saturday, May 3, 2025): C8.

(Note: ellipses, and bracketed name, added.)

(Note: the online version of the review has the date April 30, 2025, and has the title “Just Because You Can Prove It Doesn’t Make It True.”)

The book under review is:

Kucharski, Adam. Proof: The Art and Science of Certainty. New York: Basic Books, 2025.

“Effort Means That You Care About Something”

In my Openness book, I argue that we should allow each other the freedom to choose intensity over work-life balance. David Brooks is sometimes thought-provoking and eloquent, for instance in the passages quoted below where he defends intensity.

One question that Brooks discusses elsewhere in his essay is: how do you find your “passion,” your “misery,” your “vocation”? He tries but after reading his answers, I think the mystery mostly remains. The best answer to this question that I have found is in a book by John Chisholm called Unleash Your Inner Company. Chishom suggests that you should apply yourself to something worth doing, and work to do it better. If you do that, he suggests, you are likely to eventually find you increasingly care about what you are doing.

(p. 9) My own chosen form of misery is writing. Of course, this is now how I make a living, so I’m earning extrinsic rewards by writing. But I wrote before money was involved, and I’m sure I’ll write after, and the money itself isn’t sufficient motivation.

Every morning, seven days a week, I wake up and trudge immediately to my office and churn out my 1,200 words — the same daily routine for over 40 years. I don’t enjoy writing. It’s hard and anxiety-filled most of the time. Just figuring out the right structure for a piece is incredibly difficult and gets no easier with experience.

I don’t like to write but I want to write. Getting up and trudging into that office is just what I do. It’s the daily activity that gives structure and meaning to life. I don’t enjoy it, but I care about it.

We sometimes think humans operate by a hedonic or utilitarian logic. We seek out pleasure and avoid pain. We seek activities with low costs and high rewards. Effort is hard, so we try to reduce the amount of effort we have to put into things — including, often enough, the effort of thinking things through.

And I think we do operate by that kind of logic a lot of the time — just not when it comes to the most important things in our lives. When it comes to the things we really care about — vocation, family, identity, whatever gives our lives purpose — we are operating by a different logic, which is the logic of passionate desire and often painful effort.

. . .

. . . I have found that paradoxically life goes more smoothly when you take on difficulties rather than try to avoid them. People are more tranquil when they are heading somewhere, when they have brought their lives to a point, going in one direction toward an important goal. Humans were made to go on quests, and amid quests more stress often leads to more satisfaction, at least until you get to the highest levels. The psychologist Carol Dweck once wrote: “Effort is one of the things that gives meaning to life. Effort means that you care about something.”

All this toil is not really about a marathon or a newspaper article or a well-stocked shelf at the grocery store. It’s about slowly molding yourself into the strong person you want to be. It’s to expand yourself through challenge, steel yourself through discipline and grow in understanding, capacity and grace. The greatest achievement is the person you become via the ardor of the journey.

. . .

So, sure, on a shallow level we lead our lives on the axis of pleasure and pain. But at the deeper level, we live on the axis between intensity and drift. Evolution or God or both have instilled in us a primal urge to explore, build and improve. But life is at its highest when passion takes us far beyond what evolution requires, when we’re committed to something beyond any utilitarian logic.

For the full commentary see:

David Brooks. “A Surprising Route to the Best Life Possible.” The New York Times, SundayOpinion Section (Sun., March 30, 2025): 9.

(Note: ellipses added.)

(Note: the online version of the commentary has the date March 27, 2025, and has the same title as the print version. The first couple of paragraphs quoted above appear in the longer online version, but not in the shorter print version, of the commentary. In the third quoted paragraph, the words “like” and “want” are italicized.)

My book mentioned in my initial comments is:

Diamond, Arthur M., Jr. Openness to Creative Destruction: Sustaining Innovative Dynamism. New York: Oxford University Press, 2019.

The book by Chisholm that I praise in my initial comments is:

Chisholm, John. Unleash Your Inner Company: Use Passion and Perseverance to Build Your Ideal Business. Austin, TX: Greenleaf Book Group Press, 2015.

The Hurdles to Getting Paxlovid Reduce Its Use

Requiring prescriptions for most drugs is defended as a way to protect patients. But getting a quick physician appointment, making the appointment, and then getting the prescription filled, can all take nontrivial amounts of time and effort, especially burdensome for the poor or for those with work or family duties. Many drugs, such as Paxlovid for Covid, only work if taken in the early days of the disease. As a result, few people end up taking Paxlovid.

How does that protect patients?

If we respected the right of adult patients to make their own decisions, as soon as they had symptoms of Covid, they could go to a pharmacy and purchase Paxlovid.
Showing respect would both be moral, and would be more effective against the disease.

(p. A19) . . . Paxlovid seems to reduce the chance of hospitalization and death from Covid by more than 85 percent, . . .

. . .

But having drugs, especially highly effective ones like Paxlovid, is critical. And for these medications to succeed they must be taken correctly. People need to start them within five days of an infection, and because of the deficiencies of our testing system and other problems in health care, beginning treatment that quickly is difficult.

. . .

If you test positive, you can’t go straight to a pharmacy for the drug therapy like you did for the test. You need a prescription for the medication, which often requires a doctor’s visit. That presupposes that you have a doctor (many people don’t), and that there’s an appointment available. Before the pandemic, fewer than half of people in the United States could get a same-day or next-day appointment with their provider when they were sick.

If you’re lucky enough to traverse this gantlet successfully, though, you now need to get your prescription filled. Most insurance will restrict where you can get your medications paid for, and it’s hit or miss whether that pharmacy will have pills in stock. If not, hopefully they’ll be in a few days later, but those are precious days.

Too few people understand that much of the U.S. health care system is set up to make it harder for people to get care — an attempt to drive down overall health care spending. That’s why your insurance likely has higher deductibles than it used to, and more visits come with co-pays or coinsurance. But poorer people have a harder time covering these costs, so this worsens disparities and makes it harder for those who need help the most to get it.

We see this play out with Covid-19 treatments. A recent study looked at how efficiently and effectively Medicare beneficiaries (all of whom were elderly) received monoclonal antibody therapy from 2020 to 2021 for Covid. It found that those at highest risk were the least likely to be treated, in large part because it was difficult to navigate these hurdles within the 10 days from infection that treatment requires.

It doesn’t need to be this way.  . . .  Pharmacists could be more empowered to talk to patients about whether the pills are safe for them and distribute pill packs without a prescription if patients qualify.

For the full commentary, see:

Aaron E. Carroll. “Covid Drugs Might Work Well, but Our Health System Doesn’t.” The New York Times (Monday, February 14, 2022 [sic]): A19.

(Note: ellipses added.)

(Note: the online version of the commentary has the date Feb. 13, 2022 [sic], and has the title “Covid Drugs May Work Well, but Our Health System Doesn’t.”)

The Last Lonely Night Watchman Blows His Horn, “Signaling That All Is Well”

When I was a graduate student in philosophy and economics the exciting new read for the liberty-inclined was Robert Nozick’s Anarchy, State, and Utopia. I was at first rejected from the philosophy graduate program at the University of Chicago because I had the audacity to praise Ayn Rand in my application essay. The rejection decision was eventually reversed. But imagine my reaction when then-young Harvard philosophy professor Robert Nozick had the guts to write a paper evaluating the philosophy of Ayn Rand. My memory is that he did not praise all that is Rand. But that is not the point; the point is that Nozick took Rand seriously. Regardless of the contents of his main book, Nozick was my hero.

The book is pretty good too. I still ponder much that Nozick pondered. Should we eat animals that think and feel? Should a libertarian society approve of people who voluntarily join an authoritarian community? If we could plug ourselves into a machine that would give us the false illusion that all is well, should we?

Not everyone I admired totally admired Nozick’s book. I remember reading (or hearing) Milton Friedman say that it was good but “too Talmudic.” (I assume that Friedman meant that there was too much back and forth nit-picking on minor issues, and too little dispositive empirical evidence on big issues.)

The main constructive section of Nozick’s book defends the libertarian’s minimal state, what Nozick memorably calls “the night-watchman state”–the fundamental justifiable function of government is to act as a conscientious night watchman. (Today many who call themselves “libertarians” are anarchists which is why I now sometimes call myself a “classical liberal.”) (For fans of The Lord of the Ring: I think of the Rangers, the unappreciated protectors of the Hobbits, as kin to night watchmen.)

Nozick solidified the heroic image of the night watchman going about his job.

(p. A11) Mr. Stein, a journalist and editor for BBC Travel, has globetrotting in his veins, but this book is much more than a travelogue.  . . .  . . . under the drizzle of a wet November, he climbs 14 stories to the belfry of a Swedish church with Scandinavia’s last night watchman and listens to the watchman’s call, on a 4-foot-long copper horn, signaling that all is well.

. . .

In reading about the night watchman, alone in the dark tower above Ystad, along Sweden’s southern coast, I felt the wind and rain, I awed at the sacrifice, I understood the power of tradition. Those who listen to his horn night after night, even cracking open their windows in subzero temperatures for the comfort of its lonely bellow, know that the world would be different without it. It would be poorer, less a home to mankind.

. . .

Mr. Stein’s great gift—his sensitivity and his dedication to capturing joy and hope, however fleeting—is worth giving to others.

For the full review see:

Brandy Schillace. “Bookshelf; The Great Chain Of Humanity.” The Wall Street Journal (Friday, Jan. 3, 2025): A11.

(Note: ellipses added.)

(Note: the online version of the review has the date January 2, 2025, and has the title “Bookshelf; ‘Custodians of Wonder’: The Great Chain of Humanity.”)

The book under review is:

Stein, Eliot. Custodians of Wonder: Ancient Customs, Profound Traditions, and the Last People Keeping Them Alive. New York: St. Martin’s Press, 2024.

Nozick’s book, mentioned in my introductory comments, is:

Nozick, Robert. Anarchy, State, and Utopia. New York: Basic Books, Inc., 1974.

Regulators Wanted to Renege on Promise to Clinical Trial Volunteers Who Got the Placebo

Everyone agrees that those who receive the placebo in a randomized double-blind controlled trial (RCT) are losers in the clinical lottery. The question is whether the epistemic gain from RCTs justifies the pain for the losers? I am not a fan of Fauci, but his proposed solution to the dilemma in the case discussed below seems plausible, if we assume (as I do not) that RCTs are a necessary condition for all actionable medical knowledge and yet we still attempt to treat clinical trial volunteers ethically. My even better solution is to allow all willing volunteers to take the experimental drug, with no-one receiving a placebo. Then use some Bayesian updating technique to gather information from the comparison of results for study participants who volunteered to take the drug, with results for study participants who did not volunteer to take the drug. The study would not be blind, but useful information could be obtained, for instance if no one who takes the drug suffers from the disease, but many who do not take the drug, do suffer from the disease. In that case we have evidence that the drug is effective.

(p. A7) In October [2020], Judith Munz and her husband, Scott Petersen, volunteered for a coronavirus vaccine trial. At a clinic near their home in Phoenix, each got a jab in the arm.

Dr. Petersen, a retired physician, became a little fatigued after his shot, and developed redness and swelling on his arm. But Ms. Munz, a social worker, didn’t notice any change. “As much as I wanted it, I couldn’t find a darned thing,” she said. “It was a nothing burger.”

She knew there was a 50-50 chance that she would get the vaccine, developed by Johnson & Johnson. Judging from her lack of symptoms, she guessed she had received the placebo.

At the time, Ms. Munz thought that anyone who had received the placebo would get the real vaccine as soon as the trial showed it was safe and effective. She looked forward to the peace of mind it would bring. But last month, she was asked to sign a modified consent form indicating that people who got the placebo might have to wait up to two years to get the vaccine, if they got one at all.

Ms. Munz found the form vague, confusing and, most of all, unfair. “You put yourself out there with that risk,” she said. “I am owed that vaccine.”

. . .

But on Wednesday [Dec. 2, 2020], 18 leading vaccine experts — including a top regulator at the Food and Drug Administration — argued that vaccinating placebo groups early would be disastrous for the integrity of the trials. If all of the volunteers who received placebo shots were to suddenly get vaccinated, scientists would no longer be able to compare the health of those who were vaccinated with those who were not.

“If you’re going to prioritize people to get vaccinated, the last people you should vaccinate are those who were in a placebo group in a trial,” said Richard Peto, a medical statistician at the University of Oxford. Mr. Peto and his colleagues laid out their concerns in a new commentary in The New England Journal of Medicine.

. . .

Yet the prospect of giving people something useless in the face of a life-threatening disease has always been fraught. Even Jonas Salk balked at the idea of giving people placebos when researchers designed a trial to test his new polio vaccine in 1953.

“I would feel that every child who is injected with a placebo and becomes paralyzed will do so at my hands,” he complained. The study, Dr. Salk declared, “would make Hippocrates turn over in his grave.”

. . .

Dr. Fauci sketched out one possible way to balance the obligation owed to people who took the placebo against the need for more data from the trials. Vaccine makers could give everyone who got the placebo the vaccine — while also giving everyone who got the vaccine the placebo. None of the trial participants would know which order they got the doses. The trial could therefore continue to be blinded.

. . .

After learning that it may take two years before Johnson & Johnson will provide her with the real vaccine, Ms. Munz, who is 68, is considering trying to get Pfizer or Moderna’s version as soon as she’s eligible thanks to her age.

“I’ll drop out, which I can do, and I’ll get the vaccine,” she said.

Holly Janes, a biostatistician at the Fred Hutchinson Cancer Research Center in Seattle, and her colleagues are preparing for this kind of erosion. She and her colleagues are now working on statistical methods to squeeze the most insight out of the trials no matter what their fate.

“It won’t be ideal from a purely scientific vantage point, because we lose the direct comparison between vaccine and placebo,” she said. “But we’re trying to strike a balance between doing what some would argue is right for the participants, and maximizing the public health value that comes out of these trials.”

For the full story see:

Carl Zimmer and Noah Weiland. “Should Volunteers Who Got Placebo Be First to Get the Real Thing?” The New York Times (Thursday, December 3, 2020): A7.

(Note: ellipses, and bracketed year and date, added.)

(Note: the online version of the story was updated Dec. 18, 2020 [sic], and has the title “Many Trial Volunteers Got Placebo Vaccines. Do They Now Deserve the Real Ones?”)

When Free People Do Not Volunteer for Clinical Trials, Should Researchers Recruit Prisoners?

On the issue of how to ethically motivate prisoners to volunteer for clinical trails on the efficacy of salt-restricted diets, why not offer wages to the prisoners? Prisoners are already sometimes paid small amounts for other activities, like making license plates. Better yet, take my suggestion with a grain of salt, and settle the dispute with well-done observational studies.

(p. D3) Suppose you wanted to do a study of diet and nutrition, with thousands of participants randomly assigned to follow one meal plan or another for years as their health was monitored?

In the real world, studies like these are nearly impossible. That’s why there remain so many unanswered questions about what’s best for people to eat. And one of the biggest of those mysteries concerns salt and its relationship to health.

But now a group of eminent researchers, including the former head of the Food and Drug Administration, has suggested a way to resolve science’s so-called salt wars. They want to conduct an immense trial of salt intake with incarcerated inmates, whose diets could be tightly controlled.

The researchers, who recently proposed the idea in the journal Hypertension, say they are not only completely serious — they are optimistic it will happen.

. . .

Dr. Daniel W. Jones, a professor of medicine and physiology at the University of Mississippi School of Medicine and former president of the American Heart Association, was alarmed by the bitter arguments and increasingly personal disputes between researchers who disagree about salt.

So he invited senior medical scientists on both sides of the debate to meet in Jackson, Miss., to figure out how to settle their differences.

. . .

So suppose you do the study in prisons, said Dr. Jones. Is the research supposed to benefit the prisoners or just the population in general? If the prisoners would not benefit, the study would be unethical.

People who are not incarcerated can choose how much sodium they consume, but prisoners cannot — they eat whatever the facility provides. If there is uncertainty about the ideal amount of sodium, the experts concluded, prisoners would benefit from a study that settled the matter.

. . .

Dr. Macklin, in a telephone interview, also said many prisoners would be happy to jump in. She has taught in a maximum security facility and has studied the ethics of doing research in prisons.

“They would say they want to give back to society,” Dr. Macklin said.

. . .

Prison administrators have told Dr. Jones they would be willing to consider a proposal for a randomized trial of salt.

For the full story see:

Gina Kolata. “Looking to Prison for a Health Study.” The New York Times (Tuesday, June 5, 2018 [sic]): D3.

(Note: ellipses added.)

(Note: the online version of the story has the date June 4, 2018 [sic], and has the title “The Ideal Subjects for a Salt Study? Maybe Prisoners.”)

The academic article co-authored by Dr. Jones that proposes a randomized double-blind clinical trial (RCT) in prisons is:

Jones, Daniel W., Friedrich C. Luft, Paul K. Whelton, Michael H. Alderman, John E. Hall, Eric D. Peterson, Robert M. Califf, and David A. McCarron. “Can We End the Salt Wars with a Randomized Clinical Trial in a Controlled Environment?” Hypertension 72, no. 1 (July 2018): 10-11.

When the Highly Restrictive Enrollment Criteria for Clinical Trials Steal Hope from the Innocently Desperate, It “Just Feels Unjust”

Muscular dystrophy is sometimes called “Duchenne.” The full name of the disease is “Duchenne muscular dystrophy.” When I was a student at Monroe elementary school a classmate named Frank Goldsberry played on the basketball team. In high school he was in a wheel chair with muscular dystrophy. When the high school principle, Howard Crouch, proposed to do away with the academic honor of valedictorian on the ground that there was some arbitrariness in who received it, I argued that to do would be to diminish the honor given to academic achievement. Crouch relented. It turned out that our valedictorian was Frank Goldsberry. He died a few years later in his early 20s. Frank’s father told my mother that Frank was grateful to me for speaking up. Howard Crouch had a point, but I am glad that after working hard under dire circumstances, Frank received the award.

The F.D.A. should stop mandating randomized double-blind clinical trials (RCTs) so that those who have muscular dystrophy can seek any therapy that they, their parents, and their physicians believe has promise. Not everyone will be cured, but we will learn what works through a Bayesian process of trial and error. More parents and boys will be allowed to hold on to hope.

(p. D1) Lucas was 5 before his parents, Bill and Marci Barton of Grand Haven, Mich., finally got an explanation for his difficulties standing up or climbing stairs. The diagnosis: muscular dystrophy.

Mr. Barton turned to Google.

“The first thing I read was, ‘no cure, in a wheelchair in their teens, pass in their 20s,” Mr. Barton said. “I stopped. I couldn’t read any more. I couldn’t handle it.”

Then he found a reason to hope. For the first time ever, there are clinical trials — nearly two dozen — testing treatments that might actually stop the disease.

The problem, as Mr. Barton soon discovered, is that the enrollment criteria are so restrictive that very few children qualify. As a result, families like the Bartons often are turned away.

. . .

Ryan and Brooke Saalman know how hard it can be to know what to do. “We did a lot of praying,” said Ms. Saalman, mother of two boys with Duchenne in Columbus, Ga.

They decided to enroll their oldest son, Jacob, 6, in a trial of a highly experimental drug.

. . .

. . . they discovered that gene therapy may be irreversible. And if it didn’t work, Ja-(p. D3)cob would be ineligible for an even more promising approach in the future: gene editing, to snip out the deadly mutation that causes Duchenne, an effort now in preclinical development.

. . .

The Bartons found out about a gene-therapy trial at Nationwide Children’s Hospital in Columbus, Ohio, testing a treatment by Sarepta Therapeutics.

They watched a miraculous video of a little boy struggling to walk up a flight of stairs before treatment — and then doing it easily afterward.

“This was what we were hoping for,” Mr. Barton said.

Lucas was the right age, and he seemed to qualify. But testing showed that he carries antibodies to the virus used to deliver the treatment. It would not work for him.

The Bartons were drained, devastated. And for now, there is no other trial that Lucas qualifies for.

“I had my put my hopes into this,” Mr. Barton said. “It was the miracle.”

Dr. Jeffrey Bigelow, a neurologist, and his wife, Alexis Bigelow, of Millcreek, Utah, hoped against hope that their son Henri, 8, would qualify for the only gene therapy trial that will accept boys his age.

Then the Bigelows found out that enrollees of Henri’s age have to be able to lie down and then stand up with their hands at their sides in less than 10 seconds.

It took Henri 10 seconds to do that last spring, when he was evaluated for another trial. Now it would probably take him 20 seconds, his father said.

“It feels like Henri is being punished for losing the ability to stand up from the ground too soon,” Dr. Bigelow said.

He also worries about older boys with Duchenne who are lucky enough to still walk. They are shut out from the trial because they are not yet in wheelchairs. And other trials won’t accept boys that old.

“These are boys who, like Henri, desperately need the treatment, and if they don’t get it in the next one to two years, likely will be confined to a wheelchair, to never walk again,” Dr. Bigelow said.

“This just feels unjust.”

For the full story see:

Gina Kolata. “One Shot To Qualify For Hope.” The New York Times (Tuesday, March 26, 2019 [sic]): D1 & D3.

(Note: ellipses added.)

(Note: the online version of the story has the date March 25, 2019 [sic], and has the title “For Many Boys With Duchenne Muscular Dystrophy, Bright Hope Lies Just Beyond Reach.”)

Neuroscience Evidence that Our Brains Store Tacit Knowledge Separately from Articulate Formal Knowledge

(p. 10) On Aug. 25, 1953, a Connecticut neurosurgeon named William Beecher Scoville drilled two silver-dollar-size holes into the skull of Henry Molaison, a 27-year-old man with epilepsy so severe he had been prohibited from walking across stage to receive his high school diploma. Scoville then used a suction catheter to slurp up Molaison’s medial temporal lobes, the portion of the brain that contains both the hippocampus and the amygdala. The surgeon had no idea if the procedure would work, but Molaison was desperate for help: His seizures had become so frequent that it wasn’t clear if he would be able to hold down a job.

As it happened, Scoville’s operation did lessen Molaison’s seizures. Unfortunately, it also left him with anterograde amnesia: From that day forth, Molaison was unable to form new memories. Over the course of the next half-century, Patient H.M., as Molaison was referred to in the scientific literature, was the subject of hundreds of studies that collectively revolutionized our understanding of how memory, and the human brain, works. Before H.M., scientists thought that memories originated and resided in the brain as a whole rather than in any one discrete area. H.M. proved that to be false. Before H.M., all memories were thought of in more or less the same way. H.M.’s ability to perform dexterous tasks with increasing proficiency, despite having no recollection of having performed the tasks before, showed that learning new facts and learning to do new things happened in different places in the brain.

. . .

Several well-received books have already been written about Molaison, including one published in 2013 by Suzanne Corkin, the M.I.T. neuroscientist who controlled all access to and oversaw all research on ­Molaison for the last 31 years of his life.

What else, you might wonder, is there to say? According to the National Magazine Award-winning journalist Luke Dittrich, plenty. Dittrich arrived at Molaison’s story with a distinctly personal perspective — he is Scoville’s grandson, and his mother was Corkin’s best friend growing up — and his work reveals a sordid saga that differs markedly from the relatively anodyne one that has become accepted wisdom.

. . .

(p. 11) In her book, Corkin described Molaison as carefree and easygoing, a sort of accidental Zen master who couldn’t help living in the moment. In one of her papers, which makes reference to but does not quote from a depression questionnaire Molaison filled out in 1982, Corkin wrote that Molaison had “no evidence of anxiety, major depression or psychosis.” Dittrich located Molaison’s actual responses to that questionnaire, which had not been included in Corkin’s paper. Among the statements Molaison circled to describe his mental state were “I feel that the future is hopeless and that things cannot improve” and “I feel that I am a complete failure as a person.”

. . .

Molaison has long been portrayed as the victim of a surgeon’s hubris. Dittrich’s book, and the reaction to it, highlight why the lessons learned from his life cannot be limited to those stemming from a single act in the distant past. It’s easy to criticize the arrogance of researchers after they’re dead — and after we’ve already enjoyed the fruits of their work. With most of the principals in the tragedy of “Patient H.M.” now gone, the question at the core of Dittrich’s story — did the pursuit of knowledge conflict with the duty of care for a human being? — remains, in every interaction between scientist and vulnerable subject.

For the full review see:

Seth Mnookin. “Man Without a Past.” The New York Times Book Review (Sunday, September 4, 2016 [sic]): 10.

(Note: ellipses added.)

(Note: the online version of the review has the date Aug. 29, 2016 [sic], and has the title “A Book Examines the Curious Case of a Man Whose Memory Was Removed.”)

The book under review above is:

Dittrich, Luke. Patient H.M.: A Story of Memory, Madness, and Family Secrets. New York: Random House, 2016.

The earlier book by Corkin mentioned above is:

Corkin, Suzanne. Permanent Present Tense: The Unforgettable Life of the Amnesic Patient, H. M. New York: Basic Books, 2013.

Formal and Tacit Knowledge Are Located in Different Parts of the Brain

Brenda Milner turned 106 on July 15, 2024.

(p. D5) At 98, Dr. Milner is not letting up in a nearly 70-year career to clarify the function of many brain regions — frontal lobes, and temporal; vision centers and tactile; the left hemisphere and the right — usually by painstakingly testing people with brain lesions, often from surgery. Her prominence long ago transcended gender, and she is impatient with those who expect her to be a social activist. It’s science first with Dr. Milner, say close colleagues, in her lab and her life.

Perched recently on a chair in her small office, resplendent in a black satin dress and gold floral pin and banked by moldering towers of old files, she volleyed questions rather than answering them. “People think because I’m 98 years old I must be emerita,” she said. “Well, not at all. I’m still nosy, you know, curious.”

. . .

Dr. Milner changed the course of brain science for good as a newly minted Ph.D. in the 1950s by identifying the specific brain organ that is crucial to memory formation.

She did so by observing the behavior of a 29-year-old Connecticut man who had recently undergone an operation to relieve severe epileptic seizures. The operation was an experiment: On a hunch, the surgeon suctioned out two trenches of tissue from the man’s brain, one from each of his medial temporal lobes, located deep below the skull about level with the ears. The seizures subsided.

But the patient, an assembly line worker named Henry Molaison, was forever altered. He could no longer form new memories.

. . .

In a landmark 1957 paper Dr. Milner wrote with Mr. Molaison’s surgeon, she concluded that the medial temporal areas — including, importantly, an organ called the hippocampus — must be critical to memory formation. That finding, though slow to sink in, would upend the accepted teaching at the time, which held that no single area was critical to supporting memory.

Dr. Milner continued to work with Mr. Molaison and later showed that his motor memory was intact: He remembered how to perform certain physical drawing tests, even if he had no memory of learning them.

The finding, reported in 1962, demonstrated that there are at least two systems in the brain for processing memory: one that is explicit and handles names, faces and experiences; and another that is implicit and incorporates skills, like riding a bike or playing a guitar.

“I clearly remember to this day my excitement, sitting there with H. M. and watching this beautiful learning curve develop right there in front of me,” Dr. Milner said. “I knew very well I was witnessing something important.”

. . .

For Dr. Milner, after a lifetime exploring the brain, the motive for the work is personal as well as professional. “I live very close; it’s a 10-minute walk up the hill,” she said. “So it gives me a good reason to come in regularly.”

For the full story see:

Benedict Carey. “At 98, ‘Still Nosy’ About the Brain.” The New York Times (Tuesday, May 16, 2017 [sic]): D5.

(Note: ellipses added.)

(Note: the online version of the story has the date May 15, 2017 [sic], and has the title “Brenda Milner, Eminent Brain Scientist, Is ‘Still Nosy’ at 98.”)

The “landmark 1957 paper” mentioned above is:

Scoville, William Beecher, and Brenda Milner. “Loss of Recent Memory after Bilateral Hippocampal Lesions.” Journal of Neurology, Neurosurgery & Psychiatry 20, no. 1 (Feb. 1957): 11-21.