Category: Methodology

Regulations Slow the Creation and Adoption of Healthcare Breakthroughs

CPR is “cardiopulmonary resuscitation.” ECPR is “extracorporeal CPR.” The ATTEST randomized double-blind clinical trial (RCT) provided dramatic evidence of the efficacy of ECPR. But the INCEPTION RCT seemed to provide equally strong evidence of a lack of efficacy. The key difference is the high level of experience and dedication of those implementing the ATTEST RCT, and the lack of experience, and likely lower dedication of those in the INCEPTION RCT. Dr. Demetris Yannopoulos has improved his techniques through trial and error, probably in some ways that he can articulate and in other ways that are harder to articulate. Gary Klein with his naturalistic decision-making research, writes that experience gives emergency workers a quick “recognition” of what needs to be done in different situations.

At what point in the development of a therapy do you perform the canonical RCT? In the case of Emil Freireich’s four drug chemo-cocktail for curing childhood leukemia, he continually improved the ingredients and doses of the cocktail. If an RCT had been performed too early in that process, the result would have been a lack of efficacy, and a therapy would have been abandoned that had the potential to be developed into a useful efficacious therapy. Ditto for Vince DeVita’s development of his chemo-cocktail for curing Hodgkin’s Lymphoma. Ditto also for the development of the drug that eventually proved efficacious in the For Blood and Money book, where Stanford cancer doctor and Pharmacyclics co-founder acquired and developed cancer therapy Imbruvica, but abandoned it after an RCT of it failed. But Miller was ousted by major Pharmacyclics stock-holder, and entrepreneurial non-scientist, Bob Duggan, who did not want to give up on Imbruvica. Duggan persevered, overseeing its further development, until a later RCT was performed that proved efficacy.

In an earlier entry, I documented a much simpler and cheaper CPR innovation that also promises to improve heart failure therapy, called “neuroprotective CPR” (NCPR). Which one, if either, of ECPR or NCPR should we endorse? Ideally, in a fully function medical marketplace, we could comfortably say: “let the market decide.” Entrepreneurial scientists and physicians could develop the therapies and see how many willing patients would be willing to pay for each. Maybe the more expensive ECPR therapy would initially only be bought by the better-off. But as Yannopoulos improves it, as he is already working to do, making it simpler and cheaper, it would eventually be appealing to a broader customers. In Openness, I claim that this is the common path of a great many breakthrough innovations in areas outside of medicine.

Notice that the ECPR was heavily funded by the Helmsley Trust, a private foundation. This is consistent with my claim that medical innovation benefits from a diversity of funding sources, especially of private funding sources that are more likely to fund a diversity of methods and to take chances with heterodox ideas, partly motivated by private funders’ greater mission-orientation due to having more ‘skin-in-the-game.’

Notice also that Yannopoulos’s implementation of ECPR was constrained by a scarcity of trained personnel. Yannopoulos could not act as a nimble entrepreneur because massive regulations limit nimble entrepreneurship in healthcare. This is especially try on labor market issues where massive labor market regulations pile on top of massive healthcare regulations. Breakthrough innovations are usually implemented by small nimble start-ups. To create Disneyland, Walt Disney created WED Enterprises, instead of try to created it with the large incumbent The Walt Disney Company. Jonathan Bush tried nimble labor market innovation in healthcare, but was stymied by regulations. So in the ECPR case, Yannopoulos had the beds to care for more cardiac arrest patients, but could not fill those rooms because of a lack of trained healthcare workers. He could not simply offer higher pay. He was part of a larger organization where he had limited decision-rights that reduced his nimble control. (On the importance of decision-rights, see Koch 2007.)

(p. 27) In reality, by the time a patient without a pulse arrives in the E.R., we know what the outcome is going to be. We continue CPR and shock the patient if we can. We insert a breathing tube and connect it to a ventilator. We inject medications: adrenaline, heart-rhythm drugs. But these treatments almost always fail.

. . .

Demetris Yannopoulos, an interventional cardiologist and professor at the University of Minnesota Medical School who created its Center for Resuscitation Medicine, refused to accept that this was the best doctors could do. In 2014, he began performing ECPR, a treatment that was starting to catch on in a few places, mostly in Asia and Europe. To his surprise, patients he didn’t expect to survive ended up doing well.  . . .

When a patient in cardiac arrest is placed on an extracorporeal membrane oxygenation (ECMO) machine, as Sauer was, the treatment is called ECPR. The type of ECMO intervention used in ECPR provides full life support, which means it does the work of both lungs and heart. (Another type of ECMO, used on Covid-19 patients, helps just with breathing.) ECMO evolved from the heart-lung machines that started being used during heart surgery in the 1950s.

. . .

ECPR by itself doesn’t actually cure anything. But by providing fresh blood flow to the brain and other organs, it lets the body rest and gives doctors time to fix the underlying problem, if it’s fixable.  . . .  After patients are hooked up to ECMO, angiograms of their hearts are typically performed to determine whether they have clogged arteries — as about 85 percent do. In Sauer’s case, Yannopoulos found a blockage in his largest heart vessel, the left anterior descending artery, also known as “the widow maker.” He inserted a stent to open it back up.

. . .

(p. 28) Several years after the program started, Yannopoulos, Bartos and their team conducted the first randomized, controlled trial of ECPR. The results were published in The Lancet in 2020 as the ARREST trial.  . . .

After enrolling just 30 patients, the ARREST trial was stopped early by an N.I.H. board because the patients who got ECPR did so much better than the control-group subjects who received standard resuscitation, and it would have been unethical to continue the study. After six months, 43 percent of the 14 patients who got ECPR were alive with good brain function, compared with zero in the control group.

. . .

The Helmsley Trust gave Yannopoulos grants totaling $19.4 million, which enabled him to add this “hub and spoke” mobile component to his program: The university hospital would be the hub, and a truck and some local hospitals would be the spokes. “It was a real big bet,” Panzirer told me.

To reach patients in areas that were more suburban and rural, Yannopoulos first had to team up with surrounding health systems. Competition is more often the norm among health systems, rather than collaboration, but he persuaded his chief executive, James Hereford, to gather his counterparts from other institutions. Eventually, they were willing to work together. But they had to sort out a lot more than simply agreeing to collaborate. How would insurers pay for what they were doing? Would the initial hospital get the money, or would the university hospital? Would malpractice coverage protect doctors outside their own institutions? What about transport?

Every question could be turned into a reason for hospital administrators and lawyers to say no.

. . .

(p. 29) The economics of ECPR are in line with those of other established lifesaving interventions, like dialysis and heart transplants. And if patients don’t survive, ECPR may perfuse their bodies with enough oxygen to keep their organs eligible for donation. The program in Minnesota costs about $3.2 million a year to operate, which is covered by its revenue. This doesn’t include the start-up funding from the Helmsley Trust, however, or the significant groundwork Yannopoulos laid before that — or his personal sacrifices. “When I started, I had hair and my beard was black,” says Yannopoulos, who is mostly bald and gray. For seven years, he was not paid for his ECPR work; some years, he was on call every day. Today, he still spends about 6,500 hours on call annually. “It’s the force of his will more than anything,” Hereford says when explaining why the program has succeeded.

. . .

Yannopoulos has invited physicians from all over to visit his program; afterward, he often hears from them that replicating his work at their home institutions — getting health and E.M.S. systems to collaborate, finding institutional support and start-up funding, coordinating 24/7 staffing — seems too daunting. For these reasons, Yannopoulos regards his ECPR program as “an administrative and political achievement, rather than a scientific or technological one.”

. . .

(p. 30) The trial, called INCEPTION, compared ECPR with standard care across 10 medical centers in the Netherlands. It was the first randomized, controlled trial to look at ECPR across multiple facilities, and unlike the ARREST trial, it found that ECPR resulted in similar survival as standard treatments.  . . .

Yet there are reasons to interpret the study as saying more about the real-world challenges of developing and implementing ECPR programs than it does about the treatment itself. In the INCEPTION trial, it took roughly a half-hour longer for patients to get on an ECMO machine once they arrived at the hospital than it did in the ARREST study. Of the patients who got ECPR, 12 percent were not successfully connected to the machines, compared with zero in ARREST. Several Dutch hospitals handled only a couple of ECPR cases a year, which means they hadn’t yet acquired the right skills. “I think they were destined for failure because of that rollout, with no experience up front,” Bartos says.

Experience matters profoundly: According to a 2022 paper based on data from the Extracorporeal Life Support Organization, an international nonprofit that Robert Bartlett founded, patients treated at centers that perform fewer than 10 ECPR procedures yearly have 64 percent lower odds of survival; for every 10-case increase, the odds go up 11 percent. (The Minnesota program treats about 150 every year.)

Not only does the procedure itself require mastery, but so, too, does the care in the I.C.U. afterward — an ineffable art as much as a precise science.

. . .

(p. 45) . . . it’s not much of a surprise to hear Yannopoulos ask, “What does INCEPTION have to do with what we’re doing?” His program was carefully developed, with deep expertise, over years, to achieve the best outcomes; INCEPTION studied what would happen if a lot of hospitals started doing ECPR tomorrow.

Engineering the ideal ECPR program can feel like a maddening calculus involving experience, availability and distance — all to beat time. To treat patients faster, maybe doctors should go directly to the scene. For more than a decade, doctors in France have been doing just that, performing ECPR on the streets of Paris, in Métro stations, even on the oak parquet floors of the Louvre. Early on, Lionel Lamhaut, the head of Paris’s ECMO team, was told that he was “a cowboy to try to do something outside the hospital.” But as he and his colleagues persisted, they “started a new way of thinking.”

. . .

. . . as much money as the Helmsley Trust has given, it is not enough to overcome some of the structural limitations in the American health care system. The organization funded a multimillion-dollar expansion of the cardiovascular I.C.U. at Yannopoulos’s hospital to add 12 more spacious rooms specifically designed to accommodate patients on ECMO. But on a weekend in January when I visited, the I.C.U. was closed to new ECPR patients: Not enough nurses were available to work, so four beds in the unit were kept empty.

Even as Yannopoulos and his team hit administrative roadblocks like these, they are still trying to redefine what is medically possible. Recently, a 74-year-old man collapsed on the streets of St. Paul and went into cardiac arrest. Forty-two minutes after the first 911 call, the man was already on ECMO and had regained his pulse. Yannopoulos was optimistic about the case, given how quickly ECMO was started, even though the patient had not been shocked with a defibrillator — which meant he technically fell outside the protocol and should not have received ECPR at all. (After a week in the I.C.U., the man died when his family decided to stop all treatment.)

The man’s heart was almost certainly in pulseless electrical activity (P.E.A.), which many experts think should not be treated with ECPR. Of the three published ECPR randomized, controlled trials, only one did not limit the intervention to people with shockable rhythms. That ambitious trial, in Prague, included patients whose hearts were in the same P.E.A. pattern as the St. Paul man’s. The study was stopped early when it appeared that ECPR wasn’t saving significantly more people than standard care was. These enigmatic cases that lack shockable rhythms are vexing: When the Prague data was reanalyzed without these patients, the findings were favorable for ECPR.

Yannopoulos is undeterred by the Prague results. “You have to decide what’s more important: your survival rate” — what is often used in studies and by institutions to justify support for a program — “or the number of patients you actually save.” Because its program is now well established, Yannopoulos’s team is starting to treat patients with less promising rhythms, even though that may drive down its overall survival rate.  . . .

Yannopoulos wonders if, in a decade or perhaps less, ECPR science will still require the same specially trained teams using the same high-tech equipment — at least before patients get to the hospital. Instead, he imagines small cannulas that will be easy to place in the patient’s neck and attached to compact, simple machines that provide some blood flow to the brain. In his vision, which he is currently working to realize, medics could be trained to start people on this, and then doctors could transition them to regular ECMO once they reach the hospital. If the brain is protected, the rest of the body can eventually recover.

. . .

“There is this idea that people in cardiac arrest, you cannot harm them,” Yannopoulos says. For some doctors, that means cycling relentlessly through chest compressions and medications, so they feel as if they did everything they could. For others, it means briefly going through the motions, so they feel as if they did something. And for still others, it has always seemed kindest to do nothing at all, to let their patients die peacefully. Because almost none of them lived — no matter what the doctors did. “But now we know what is possible,” Yannopoulos says. “So if you’re not achieving that, then you are harming them in a way, right?”

For the full story see:

Helen Ouyang. “Reinventing CPR.” The New York Times Magazine (Sunday, March 31, 2024): 22-31 & 45.

(Note: ellipses added.)

(Note: the online version of the story was updated June [sic] 19, 2024, and has the title “The Race to Reinvent CPR.”)

Some references relevant to my discussion at the start of this entry are:

Bush, Jonathan, and Stephen Baker. Where Does It Hurt?: An Entrepreneur’s Guide to Fixing Health Care. New York: Portfolio, 2014.

DeVita, Vincent T., and Elizabeth DeVita-Raeburn. The Death of Cancer: After Fifty Years on the Front Lines of Medicine, a Pioneering Oncologist Reveals Why the War on Cancer Is Winnable–and How We Can Get There. New York: Sarah Crichton Books, 2015.

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

Klein, Gary A. Seeing What Others Don’t: The Remarkable Ways We Gain Insights. Philadelphia, PA: PublicAffairs, 2013.

Klein, Gary A. Sources of Power: How People Make Decisions. 20th Anniversary ed. Cambridge, MA: The MIT Press, 2017.

Klein, Gary A. Streetlights and Shadows: Searching for the Keys to Adaptive Decision Making. Cambridge, MA: The MIT Press, 2009.

Koch, Charles G. The Science of Success: How Market-Based Management Built the World’s Largest Private Company. Hoboken, NJ: Wiley & Sons, Inc., 2007.

Silberner, Joanne. “How a Plunger Improved CPR.” The New York Times (Tues., June 27, 2023): D5.

Taleb, Nassim Nicholas. Skin in the Game: Hidden Asymmetries in Daily Life. New York: Random House, 2018.

Vardi, Nathan. For Blood and Money: Billionaires, Biotech, and the Quest for a Blockbuster Drug. New York: W. W. Norton & Company, 2023.

The “Innovative Approach” of the Dog Aging Project May Have Hurt Its Odds for Renewed Funding

Veterinary medicine is less regulated than human medicine, and so trial and error experiments may allow faster innovation that would benefit both dogs and humans.

(p. D3) In late 2019, scientists began searching for 10,000 Americans willing to enroll their pets in an ambitious new study of health and longevity in dogs. The researchers planned to track the dogs over the course of their lives, collecting detailed information about their bodies, lifestyles and home environments. Over time, the scientists hoped to identify the biological and environmental factors that kept some dogs healthy in their golden years — and uncover insights about aging that could help both dogs and humans lead longer, healthier lives.

Today, the Dog Aging Project has enrolled 47,000 canines and counting, and the data are starting to stream in. The scientists say that they are just getting started.

“We think of the Dog Aging Project as a forever project, so recruitment is ongoing,” said Daniel Promislow, a biogerontologist at the University of Washington and a co-director of the project. “There will always be new questions to ask. We want to always have dogs of all ages participating.”

But Dr. Promislow and his colleagues are now facing the prospect that the Dog Aging Project might have its own life cut short. About 90 percent of the study’s funding comes from the National Institute on Aging, a part of the National Institutes of Health, which has provided more than $28 million since 2018. But that money will run out in June, and the institute does not seem likely to approve the researchers’ recent application for a five-year grant renewal, the scientists say.

“We have been told informally that the grant is not going to be funded,” said Matt Kaeberlein, the other director of the Dog Aging Project and a former biogerontology researcher at the University of Washington. (Dr. Kaeberlein is now the chief executive of Optispan, a health technology company.)

. . .

Steven Austad, a biogerontologist at the University of Alabama at Birmingham who is not part of the research team, said he was surprised that the researchers’ grant might not be renewed. “The importance of the things they publish and the depth of detail will increase over time, but I thought they got off to a really good start,” he said. “A large study like this really deserves a chance to mature.”

Dr. Austad’s miniature dachshund, Emmylou, is enrolled in the Dog Aging Project. But at 2 years old, he noted, Emmylou is “not going to teach them a lot about aging for a long time yet.”

The project’s innovative approach might have worked against it, Dr. Austad added. Reviewers accustomed to evaluating short-term research on lab mice and long-term studies of humans may not have known what to make of an enormous epidemiological study of pet dogs.

Whatever the reason, the refusal to commit to more funding is “wrong,” Dr. Kaeberlein said. “It’s just really, really difficult to justify this decision, if you look at the productivity and the impact of the project.”

That impact extends beyond the findings themselves, he added. “This project has engaged almost 50,000 Americans in biomedical scientific research.”

Over the last few years, Shelley Carpenter, of Gulfport, Miss., has provided the researchers with regular updates on and medical records for her Pembroke Welsh corgi, Murfee. (She also collected a cheek swab for genomic sequencing.) Ms. Carpenter, whose previous corgi died from a neurodegenerative disease similar to A.L.S., hoped that the project might produce new medical knowledge that could help both dogs and people.

For the full story see:

Emily Anthes. “Scientists Scramble to Keep Dog Aging Project Alive.” The New York Times (Tuesday, January 16, 2024): D3.

(Note: ellipses added.)

(Note: the online version of the story has the date Jan. 11, 2024, and has the same title as the print version.)

Patient-Reported Health Information Deserves Respect

Patients may have more accurate knowledge of their health than the information found in doctors’ blood tests, as reported in the study summarized below. The credibility of patient self-knowledge provides an added reason, besides respect for freedom, why government should not mandate an individual’s food and drug decisions.

(p. D4) . . . a . . . study . . . suggests that how patients say they feel may be a better predictor of health than objective measures like a blood test. The study, published in Psychoneuroendocrinology, used data from 1,500 people who took part in the Texas City Stress and Health Study, which tracked the stress and health levels of people living near Houston.

. . .

The study found that when people said they felt poorly, they had high virus and inflammation levels. People who reported feeling well had low virus and inflammation levels.

“I think the take-home message is that self-reported health matters,” said Christopher P. Fagundes, an assistant psychology professor at Rice University and a co-author of the study. “Physicians should pay close to attention to their patients. There are likely biological mechanisms underlying why they feel their health is poor.”

For the full story see:

Tara Parker-Pope. “Doctors, Listen to Patients.” The New York Times (Tuesday, July 19, 2016 [sic]): D4.

(Note: ellipses added.)

(Note: the online version of the story has the date July 15, 2016 [sic], and has the title “Doctors Should Listen to Patient Instincts.”)

The academic paper co-authored by Fagundes and mentioned above is:

Murdock, Kyle W., Christopher P. Fagundes, M. Kristen Peek, Vansh Vohra, and Raymond P. Stowe. “The Effect of Self-Reported Health on Latent Herpesvirus Reactivation and Inflammation in an Ethnically Diverse Sample.” Psychoneuroendocrinology 72 (Oct. 2016): 113-18.

Following Salt Consumption Guidelines Increases Risk of Death

Official experts often turn out to be wrong, as in the salt consumption guidelines discussed below. The fallibility of expert knowledge provides an added reason, besides respect for freedom, why government should not mandate an individual’s food and drug decisions.

(p. D4) People with high blood pressure are often told to eat a low-sodium diet. But a diet that’s too low in sodium may actually increase the risk for cardiovascular disease, a review of studies has found.

Current guidelines recommend a daily maximum of 2.3 grams of sodium a day — the amount found in a teaspoon of salt — for most people, and less for the elderly or people with hypertension.

Researchers reviewed four observational studies that included 133,118 people who were followed for an average of four years. The scientists took blood pressure readings, and estimated sodium consumption by urinalysis. The review is in The Lancet.

Among 69,559 people without hypertension, consuming more than seven grams of sodium daily did not increase the risk for disease or death, but those who ate less than three grams had a 26 percent increased risk for death or for cardiovascular events like heart disease and stroke, compared with those who consumed four to five grams a day.

In people with high blood pressure, consuming more than seven grams a day increased the risk by 23 percent, but consuming less than three grams increased the risk by 34 percent, compared with those who ate four to five grams a day.

For the full story see:

Nicholas Bakalar. “Low-Salt Diet as a Heart Risk.” The New York Times (Tuesday, Oct. 11, 2016 [sic]): D4.

(Note: ellipses added.)

(Note: the online version of the story has the date May 25, 2016 [sic], and has the title “A Low-Salt Diet May Be Bad for the Heart.”)

The academic paper reporting the results summarized above is:

Mente, Andrew, Martin O’Donnell, Sumathy Rangarajan, Gilles Dagenais, Scott Lear, Matthew McQueen, Rafael Diaz, Alvaro Avezum, Patricio Lopez-Jaramillo, Fernando Lanas, Wei Li, Yin Lu, Sun Yi, Lei Rensheng, Romaina Iqbal, Prem Mony, Rita Yusuf, Khalid Yusoff, Andrzej Szuba, Aytekin Oguz, Annika Rosengren, Ahmad Bahonar, Afzalhussein Yusufali, Aletta Elisabeth Schutte, Jephat Chifamba, Johannes F. E. Mann, Sonia S. Anand, Koon Teo, and S. Yusuf. “Associations of Urinary Sodium Excretion with Cardiovascular Events in Individuals with and without Hypertension: A Pooled Analysis of Data from Four Studies.” The Lancet 388, no. 10043 (2016): 465-75.

Techno-Optimist Claims AI Tools “Will Help Scientists Design Therapies Faster and Better”

(p. A13) It is said that triumphant Roman generals, to ensure that the rapture of victory didn’t go to their heads, would require a companion to whisper in their ear: “Remember, you are only a man.” Jamie Metzl worries that we may have learned all too well such lessons in humility. Given remarkable recent advances in technology—and the promise of more to come—we need to lean into our emerging godlike powers, he believes, and embrace the opportunity to shape the world into a better place. In “Superconvergence,” he sets out to show us how, after first helping us overcome our hesitations.

. . .

. . . the big advances will be in medicine—and indeed are already in evidence. Mr. Metzl points to the blisteringly fast development of the Covid-19 mRNA vaccine, from digital file to widespread immunization in less than a year; and to gene-editing technologies like Crispr. He cites the experience of Victoria Gray, a young woman from Mississippi who was suffering from sickle-cell disease until, in 2019, researchers in Nashville, Tenn., reinfused her with her own cells, which had been Crispr-edited; the treatment worked, liberating her from the disease’s tormenting pain and crippling fatigue. For Mr. Metzl, these are just the first intimations of a revolution to come. AI tools like DeepMind’s Alphafold, he says, will help scientists design therapies faster and better.

To get smarter about human health, though, AI will need more information, and here Mr. Metzl’s ebullience edges toward the willful suspension of disbelief. His imagined future of healthcare will require “collecting huge amounts of genetic and systems biology data in massive and searchable databases.” The details will include not only medical records and the results of laboratory tests but data from the sensors he anticipates will be everywhere—“bathrooms, bedrooms, and offices”—as information is hoovered up from “toilets, mirrors, computers, phones and other devices without the people even noticing.” While acknowledging that such a scenario sounds like “an authoritarian’s dream and a free person’s nightmare,” he suggests that the chance to catch disease early may offset the risks. This trade-off promises to be a tough sell.

More than many techno-optimists, Mr. Metzl seems to grasp the intricacy of biological systems; he notes that they are beyond our full understanding right now. Even so, a time will come when “the sophistication of our tools and understanding meets and then exceeds the complexity of biology.”

For the full review, see:

David A. Shaywitz. “Getting Better, Faster.” The Wall Street Journal (Thursday, July 11, 2024): A13.

(Note: the online version of the review has the date July 10, 2024, and has the title “‘Superconvergence’ Review: Getting Better, Faster.”)

The book under review is:

Metzl, Jamie. Superconvergence: How the Genetics, Biotech, and AI Revolutions Will Transform Our Lives, Work, and World. New York: Timber Press, 2024.

Kahneman’s “Adversarial Collaboration” Might Bring Us More Joy and Better Science

(p. A19) Professor Kahneman, who died . . . at the age of 90, is best known for his pathbreaking explorations of human judgment and decision making and of how people deviate from perfect rationality. He should also be remembered for a living and working philosophy that has never been more relevant: his enthusiasm for collaborating with his intellectual adversaries. This enthusiasm was deeply personal. He experienced real joy working with others to discover the truth, even if he learned that he was wrong (something that often delighted him).

. . .

Professor Kahneman saw . . . “angry science,” which he described as a “nasty world of critiques, replies and rejoinders” and “as a contest, where the aim is to embarrass.” As Professor Kahneman put it, those who live in that nasty world offer “a summary caricature of the target position, refute the weakest argument in that caricature and declare the total destruction of the adversary’s position.” In his account, angry science is “a demeaning experience.”

. . .

Professor Kahneman meant both to encourage better science and to strengthen the better angels of our nature.

For the full commentary see:

Cass R. Sunstein. “The Value of Collaborating With Adversaries.” The New York Times (Wednesday, April 3, 2024): A19.

(Note: ellipses added.)

(Note: the online version of the commentary has the date April 1, 2024, and has the title “The Nobel Winner Who Liked to Collaborate With His Adversaries.”)

Since Wood Tools Are Rarely Preserved, “Preservation Bias Distorts Our View of Antiquity”

(p. D3) In 1836, Christian Jürgensen Thomsen, a Danish antiquarian, brought the first semblance of order to prehistory, suggesting that the early hominids of Europe had gone through three stages of technological development that were reflected in the production of tools. The basic chronology — Stone Age to Bronze Age to Iron Age — now underpins the archaeology of most of the Old World (and cartoons like “The Flintstones” and “The Croods”).

Thomsen could well have substituted Wood Age for Stone Age, according to Thomas Terberger, an archaeologist and head of research at the Department of Cultural Heritage of Lower Saxony, in Germany.

“We can probably assume that wooden tools have been around just as long as stone ones, that is, two and a half or three million years,“ he said. “But since wood deteriorates and rarely survives, preservation bias distorts our view of antiquity.” Primitive stone implements have traditionally characterized the Lower Paleolithic period, which lasted from about 2.7 million years ago to 200,000 years ago. Of the thousands of archaeological sites that can be traced to the era, wood has been recovered from fewer than 10.

Dr. Terberger was team leader of a study published last month in the Proceedings of the National Academy of Sciences that provided the first comprehensive report on the wooden objects excavated from 1994 to 2008 in the peat of an open-pit coal mine near Schöningen, in northern Germany. The rich haul included two dozen complete or fragmented spears (each about as tall as an N.B.A. center) and double-pointed throwing sticks (half the length of a pool cue) but no hominid bones. The objects date from the end of a warm interglacial period 300,000 years ago, about when early Neanderthals were supplanting Homo heidelbergensis, their immediate predecessors in Europe. The projectiles unearthed at the Schöningen site, known as Spear Horizon, are considered the oldest preserved hunting weapons.

For the full story see:

Franz Lidz. “In the Stone Age, Wood Was Pivotal, a Study Says.” The New York Times (Tuesday, May 7, 2024): D3.

(Note: the online version of the story was updated May 6, 2024, and has the title “Was the Stone Age Actually the Wood Age?”)

Terberger’s co-authored academic paper mentioned above is:

Leder, Dirk, Jens Lehmann, Annemieke Milks, Tim Koddenberg, Michael Sietz, Matthias Vogel, Utz Böhner, and Thomas Terberger. “The Wooden Artifacts from Schöningen’s Spear Horizon and Their Place in Human Evolution.” Proceedings of the National Academy of Sciences 121, no. 15 (2024): e2320484121.

The Absence of a Randomized Double-Blind Clinical Trial Is Used as an Excuse to Ignore an Emergency Procedure That Saves Lives

In an urgent emergency the son and wife of a man with a stopped heart, improvised the use of a toilet plunger to get his heart to start pumping again. In his wonderful account of the sources of insight, Gary Klein told a different example of urgent emergency improvisation: “Wag” Dodge saved himself from a massive wildfire racing toward him by lighting a match to the grass at his feet to pre-burn a patch he could lie down in. When the wildfire reached him, it passed on both sides, avoiding the patch that now had no fuel. Neither the son-and-mother, nor Wag Dodge, got their insight from collaboration or a randomized double-blind controlled trial.

(p. D5) In 1988, a 65-year-old man’s heart stopped at home. His wife and son didn’t know CPR, so in desperation they grabbed a toilet plunger to get his heart going until an ambulance showed up.

Later, after the man recovered at San Francisco General Hospital, his son gave the doctors there some advice: Put toilet plungers next to all of the beds in the coronary unit.

The hospital didn’t do that, but the idea got the doctors thinking about better ways to do CPR, or cardiopulmonary resuscitation, the conventional method for chest compressions after cardiac arrest. More than three decades later, at a meeting of emergency medical services directors this week in Hollywood, Fla., researchers presented data showing that using a plunger-like setup leads to remarkably better outcomes for reviving patients.

. . .

The new procedure, known as neuroprotective CPR, has three components. First, a silicone plunger forces the chest up and down, not only pushing blood out to the body, but drawing it back in to refill the heart. A plastic valve fits over a face mask or breathing tube to control pressure in the lungs.

The third piece is a body-positioning device sold by AdvancedCPR Solutions, a firm in Edina, Minn., that was founded by Dr. Lurie. A hinged support slowly elevates a supine patient into a partial sitting position. This allows oxygen-starved blood in the brain to drain more effectively and to be replenished more quickly with oxygenated blood.

. . .

. . ., a study carried out in four states found . . . [p]atients who received neuroprotective CPR within 11 minutes of a 911 call were about three times as likely to survive with good brain function as those who received conventional CPR.

. . .

Dr. Karen Hirsch, a neurologist at Stanford University and a member of the CPR standards committee for the American Heart Association, said that the new approach was interesting and made physiological sense, but that the committee needed to see more research on patients before it could formally recommend it as a treatment option.

“We’re limited to the available data,” she said, adding that the committee would like to see a clinical trial in which people undergoing cardiac arrests are randomly assigned to conventional CPR or neuroprotective CPR. No such trials are happening in the United States.

Dr. Joe Holley, the medical director for the emergency medical service that serves Memphis and several surrounding communities, isn’t waiting for a larger trial. Two of his teams, he said, were getting neurologically intact survival rates of about 7 percent with conventional CPR. With neuroprotective CPR, the rates rose to around 23 percent.

His crews are coming back from emergency calls much happier these days, too, and patients are even showing up at fire stations to thank them for their help.

“That was a rare occurrence,” Dr. Holley said. “Now it’s almost a regular thing.”

For the full story see:

Joanne Silberner. “How a Plunger Improved CPR.” The New York Times (Tuesday, June 27, 2023 [sic]): D5.

(Note: ellipses added.)

(Note: the online version of the story has the date June 15, 2023 [sic], and has the title “How a Toilet Plunger Improved CPR.”)

The Gary Klein book that I praised above is:

Klein, Gary. Seeing What Others Don’t: The Remarkable Ways We Gain Insights. Philadelphia, PA: PublicAffairs, 2013.

The “study carried out in four states,” and mentioned above, is:

Moore, Johanna C., Paul E. Pepe, Kenneth A. Scheppke, Charles Lick, Sue Duval, Joseph Holley, Bayert Salverda, Michael Jacobs, Paul Nystrom, Ryan Quinn, Paul J. Adams, Mack Hutchison, Charles Mason, Eduardo Martinez, Steven Mason, Armando Clift, Peter M. Antevy, Charles Coyle, Eric Grizzard, Sebastian Garay, Remle P. Crowe, Keith G. Lurie, Guillaume P. Debaty, and José Labarère. “Head and Thorax Elevation During Cardiopulmonary Resuscitation Using Circulatory Adjuncts Is Associated with Improved Survival.” Resuscitation 179 (2022): 9-17.

Orangutan Effectively Self-Medicates to Heal Facial Wound

The Food and Drug Administration (FDA) is currently investigating whether Rakus the orangutan conducted a randomized double-blind clinical trial to prove the safety and efficacy of akar kuning before he applied it to his wound.

(p. D3) Scientists observed a wild male orangutan repeatedly rubbing chewed-up leaves of a medicinal plant on a facial wound in a forest reserve in Indonesia.

. . .

“Once I heard about it, I got extremely excited,” said Isabelle Laumer, a primatologist with the Max Planck Institute of Animal Behavior in Germany, in part because records of animals medicating themselves are rare — even more so when it comes to treating injuries. She and colleagues detailed the discovery in a study published Thursday [May 2, 2024] in the journal Scientific Reports.

The plant Rakus used, known as akar kuning or yellow root, is also used by people throughout Southeast Asia to treat malaria, diabetes and other conditions. Research shows it has anti-inflammatory and antibacterial properties.

. . .

Orangutans rarely eat the plant. But in this case, Rakus ingested a small amount and also coated the wound several times. Five days after the wound was noticed, it had closed, and less than a month later “healed without any signs of infection,” Dr. Laumer said.

Michael Huffman, a visiting professor at the Institute of Tropical Medicine at Nagasaki University in Japan, who wasn’t involved in the study, said, “This is to the best of my knowledge the first published study to demonstrate an animal using a plant with known biomedical properties for the treatment of a wound.”

Primates have been observed appearing to treat wounds in the past, but not with plants. A group of more than two dozen chimpanzees in Gabon in Central Africa have been seen chewing up and applying flying insects to their wounds, said Simone Pika, an expert on animal cognition at Osnabrück University in Germany who documented that observation.

For the full story see:

Douglas Main. “Primate Self-Medicates To Heal His Wound.” The New York Times (Tuesday, May 7, 2024): D3.

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

(Note: the online version of the story has the date May 2, 2024, and has the title “Orangutan, Heal Thyself.”)

Laumer’s co-authored academic paper mentioned above is:

Laumer, Isabelle B., Arif Rahman, Tri Rahmaeti, Ulil Azhari, Hermansyah, Sri Suci Utami Atmoko, and Caroline Schuppli. “Active Self-Treatment of a Facial Wound with a Biologically Active Plant by a Male Sumatran Orangutan.” Scientific Reports 14, no. 1 (2024): article #8932.

Seeds of Plant Mostly Used for Pain Relief in Roman Era, Found Stashed in Buried Bone in “Far-Flung” Province

A couple of thousand years ago some humans had figured out how to use a medicinal plant for effective pain relief. And they did so without having conducted randomized double-blind clinical trials. And no agency of the government blocked them from easing their pain.

(p. D2) . . ., Mr. van Haasteren was cleaning the mud from yet another bone when something unexpected happened: Hundreds of black specks the size of poppy seeds came pouring out from one end.

The specks turned out to be seeds of black henbane, a potently poisonous member of the nightshade family that can be medicinal or hallucinogenic depending on the dosage.  . . .

This “very special” discovery provides the first definitive evidence that Indigenous people living in such a far-flung Roman province had knowledge of black henbane’s powerful properties, said Maaike Groot, an archaeozoologist at the Free University of Berlin and a co-author of a paper published in the journal Antiquity last month describing the finding.

The plant was mostly used during Roman times as an ointment for pain relief, although some sources also reference smoking its seeds or adding its leaves to wine.

For the full story see:

Rachel Nuwer. “Psychedelic Stash: Ancient Seeds Courtesy of a Doctor, or a Doctor Feel Good.” The New York Times (Tuesday, April 9, 2024): D2.

(Note: ellipses added.)

(Note: the online version of the story has the date March 21, 2024, and has the title “Long Before Amsterdam’s Coffee Shops, There Were Hallucinogenic Seeds.”)

The academic paper co-authored by Groot and mentioned above is:

Groot, Maaike, Martijn van Haasteren, and Laura I. Kooistra. “Evidence of the Intentional Use of Black Henbane (Hyoscyamus niger) in the Roman Netherlands.” Antiquity 98, no. 398 (2024): 470-85.

Conservatives Are Better Than Liberals at “the Separation of Facts from Feelings”

(p. A13) I don’t know who’s going to win the presidential election, and neither do you. Neither, for that matter, does Nate Silver, notwithstanding his reputation as a political prognosticator. He is more accurately characterized as a forecaster, which is to say that he deals in probabilities, not outright predictions.

. . .

. . . since I first encountered his work in 2009, Mr. Silver has always struck me as an honest practitioner. Although he describes himself as a “center-left liberal,” he frequently provokes antagonism from fellow liberals when his data and analysis point in directions they’d rather not go.

. . .

Mr. Silver’s career as a political pundit is something of an accident. After earning a bachelor’s degree in economics at the University of Chicago in 2000, he went to work as a KPMG consultant. Bored with his job, he started playing online poker, at first for fun. He says he “eventually deposited money at a real-money site and ran it up from 25 bucks to 15,000 bucks.” He quit KPMG and got a part-time job writing about baseball statistics, but 80% of his income came from poker winnings.

Then in 2006 Congress passed the Unlawful Internet Gambling Enforcement Act, which effectively banned online poker by making it unlawful for the sites to accept payments. “That killed my livelihood,” Mr. Silver says. “I started following politics. I had more time on my hands. I also wanted to see the people behind the bill ousted from office, which they were.” Its primary sponsor, Rep. Jim Leach (R., Iowa), lost his bid for a 16th term.

Mr. Silver still plays poker semiprofessionally—in person—and has earned $855,800 in tournaments, according to the Hendon Mob database. He has a new book out next week, “On the Edge: The Art of Risking Everything,” in which he interviews professional gamblers, venture capitalists, adventurers and others known for their “mastery of risk” and develops a philosophical framework around their insights.

The book touches only lightly on politics, but some of its concepts have obvious application. One of them is “decoupling,” which means, roughly, thinking with analytical detachment, including the separation of facts from feelings. Journalists used to call it objectivity, an aspiration that has fallen out of fashion in recent decades, especially in the Trump era.

A failure to decouple explains the widespread denial of Mr. Biden’s decline in the months before his withdrawal. Clear evidence became mistakable when distorted through the lenses of partisanship, ideology and antipathy toward Mr. Trump. There is no reason to believe people on the left are intrinsically more prone to this sort of error, but Mr. Silver thinks that “liberal bubbles are bigger than conservative bubbles.” Domination of big cities and influential institutions makes it easier for those on the left simply to ignore opposing views.

For the full interview see:

James Taranto. “The Weekend Interview; President Kamala Harris? What Are the Odds?” The Wall Street Journal (Saturday, Aug 10, 2024): A13.

(Note: ellipses added.)

(Note: the online version of the interview has the date August 9, 2024, and has the same title as the print version.)

The “new book” by Silver mentioned above is:

Silver, Nate. On the Edge: The Art of Risking Everything. New York: The Penguin Press, 2024.