Science – Page 2 – artdiamondblog.com

Director of the N.I.H. Was “Subject to Censorship by the Actions of the Biden Administration”

During the Covid-19 pandemic, I had an invited essay cancelled by the OECD in which I argued for freedom of speech in science, and especially for toleration of a diversity of views during the pandemic. So I have sympathy for the attacks Dr. Bhattacharya suffered during the pandemic and wish him well as the Director of the National Institutes of Health.

(p. B1) Dr. [Jay] Bhattacharya, who has a medical degree and is a professor of medicine but never practiced, burst into the spotlight in October 2020, when he co-wrote an anti-lockdown treatise, the Great Barrington Declaration. It argued for “focused protection” — a strategy to protect the elderly and vulnerable while letting the virus spread among younger, healthier people.

Many scientists countered that walling off at-risk populations from the rest of society was a pipe dream.

The nation’s medical leadership, including Dr. Francis S. Collins, who retired last week, and Dr. Anthony S. Fauci, then director of the National Institute of Allergy and Infectious Diseases, denounced the plan. Referring to Dr. Bhattacharya and his co-authors as “fringe epidemiologists,” Dr. Collins wrote in an email that “there needs to be a quick and devastating takedown of its premises.”

Dr. Bhattacharya told senators on Wednesday [March 5, 2025] that he had been “subject to censorship by the actions of the Biden administration.” Past N.I.H. officials, he said, “oversaw a culture of cover-up, obfuscation and a lack of tolerance for ideas that differ from theirs.”

For the full story see:

Benjamin Mueller and Sheryl Gay Stolberg. “Guarded Nominee for N.I.H. Faces Sharp Questions on Vaccines and Research Cuts.” The New York Times (Thursday, March 6, 2025): A18.

(Note: bracketed date added.)

(Note: the online version of the story has the date March 5, 2025, and has the title “Guarded N.I.H. Nominee Faces Sharp Questions on Vaccines and Research Cuts.”)

George Church Is Optimistic About A.I., but in 2019 Also Was Optimistic He Would Reverse Aging in Dogs by 2022

Steve Lohr had an article in the NYT promoting the possibility that generative intelligence from A.I. will bring us scientific breakthroughs quicker. A new startup called “Lila” is trying to achieve this. George Church of Harvard is onboard.

Back on Sun., Dec. 8, 2019, 60 Minutes on ran a very optimistic segment in which Church says that through his lab’s work on gene editing, age reversal for dogs “might be a couple years away and then that takes another ten years to get through the human clinical trials” (Church as quoted in Pelley 2019).

In Lohr’s recent article, Church is quoted as saying “I think science is a really good topic for A.I.” (Church as quoted in Lohr, p. B5). The article describes science as basically a mechanical process of trial and error. Some science is like that, like when Gerhard Domagk had his lab crank through hundreds of chemicals to find one (Prontosil) that was a broad spectrum antibiotic. Maybe A.I. could more efficiently crank through a large set of possibilities. The only example of medical advance through A.I. in the article is that “Lila’s A.I. has generated novel antibodies to fight disease” (Lohr, p. B5).

A.I. can combine what is known in novel ways and produce text that is new, but is not necessarily sensible, correct, or useful, let alone a profound leap.

So it is not clear to me how well A.I. could help define and prioritize the possibilities. Lila scientists are feeding their A.I. program scientific literature, presumably weighting differing views by some bibliometric measures, like citations or journal rankings. But often a leap or breakthrough is at first rejected by the top journals, and not heavily cited by the establishment.

I do not see how A.I. could identify those early breakthroughs, much less be the source of them. And making and identifying such breakthroughs are key steps in scientific progress.

I was was pumped when I heard Church’s optimism in 2019 for longevity breakthroughs. But now it is more than five years later, and I have not seen claims of age reversal for dogs, let alone for humans. Maybe Covid delayed progress. Or maybe Church is not a good judge of what is required for scientific breakthroughs. This latter possibility seems more likely given Church’s hyper-enthusiasm for generative A.I.

Steve Lohr’s article is:

Lohr, Steve. “A.I. May Hasten Leaps in Science.” The New York Times (Thurs., March 13, 2025): B1 & B5.

(Note: the online version of the Steve Lohr article has the date March 10, 2025, and has the title “The Quest for A.I. ‘Scientific Superintelligence’.”)

A transcript of the 60 Minutes segment on Church is:

Pelley, Scott. “A Harvard Geneticist’s Goal: To Protect Humans from Viruses, Genetic Diseases, and Aging.” In 60 Minutes. CBS News, (Sun., Dec. 8, 2019).

Tim Friede’s “Daredevilry” in Taking 650 Venom Injections and 200 Poisonous Snake Bites to Help Create a Universal Antivenom “for Humanity”

Back during Covid, over 38,000 adults volunteered to participate in a “challenge” clinical trial of the new vaccines, but such trials were not allowed. In a challenge trial each participant receives the vaccine and then is exposed to the disease. Phase 3 trials for efficacy can be completed much more quickly, with many fewer participants, and at much lower costs, if the trials are “challenge” trials.

We allow people the freedom to dangerous actions for fun or excitement, or to help humanity, like Tim Friede (below) injecting snake venom and letting snakes bite him. Why then did we not allow challenge trials with the Covid vaccine?

Note on another issue, that the researchers are planning in their next step to test their antivenom on dogs who are bitten by snakes. This is a good example of my ideal use of dogs in medical research–where the trial aims at benefits for both the humans AND the dogs.

(p. A1) Over nearly 18 years, the man, Tim Friede, 57, injected himself with more than 650 carefully calibrated, escalating doses of venom to build his immunity to 16 deadly snake species. He also allowed the snakes — mostly one at a time, but sometimes two, . . . — to sink their sharp fangs into him about 200 times.

This bit of daredevilry (one name for it) may now help to solve a dire global health problem. More than 600 species of venomous snakes roam the earth, biting as many as 2.7 million people, killing about 120,000 people and maiming 400,000 others — numbers thought to be vast underestimates.

In Mr. Friede’s blood, scientists say they have identified antibodies that are capable of neutralizing the venom of multiple snake (p. A19) species, a step toward creating a universal antivenom, they reported on Friday [May 2, 2025] in the journal Cell.

“I’m really proud that I can do something in life for humanity, to make a difference for people that are 8,000 miles away, that I’m never going to meet, never going to talk to, never going to see, probably,” said Mr. Friede, who lives in Two Rivers, Wis., where venomous snakes are not much of a threat.

. . .

“This is a bigger problem than the first world realizes,” said Jacob Glanville, founder and chief executive of Centivax, a company that aims to produce broad-spectrum vaccines, and lead author on the study.

Dr. Glanville and his colleagues found that two powerful antibodies from Mr. Freide’s blood, when combined with a drug that blocks neurotoxins, protected mice from the venom of 19 deadly snake species of a large family found in different geographical regions.

This is an extraordinary feat, according to experts not involved in the work. Most antivenoms can counter the venom from just one or a few related snake species from one region.

The study suggests that cocktails of antitoxins may successfully prevent deaths and injuries from all snake families, said Nicholas Casewell, a researcher at the Liverpool School of Tropical Medicine in England.

. . .

There were other mishaps — accidental bites, anaphylactic shocks, hives, blackouts. Mr. Friede describes himself as a nondegree scientist, but “there’s no college in the world that can teach you how to do it,” he said. “I was doing it on my own as best I could.”

Two teams of scientists sampled Mr. Friede’s blood over the years, but neither project led anywhere. By the time he met Dr. Glanville, in 2017, he was nearly ready to give up.

Dr. Glanville had been pursuing what scientists call broadly acting antibodies as the basis for universal vaccines against viruses. He grew up in a Maya village in the Guatemala highlands, and became intrigued by the possibility of using the same approach for universal antivenom.

. . .

The researchers next plan to test the treatment in Australia in any dogs that are brought into veterinary clinics for snakebites. They are also hoping to identify another component, perhaps also from Mr. Friede’s blood, that would extend full protection to all 19 snake species that were subjects of the research.

Mr. Friede himself is done now, however. His last bite was in November 2018, from a water cobra. He was divorced — his wife and children had moved out. “Well, that’s it, enough is enough,” he recalled thinking.

He misses the snakes, he said, but not the painful bites. “I’ll probably get back into it in the future,” he said. “But for right now, I’m happy where things are at.”

For the full story see:

Apoorva Mandavilli. “Man of 200 Snake Bites May Be the Antivenom.” The New York Times (Saturday, May 3, 2025): A1 & A19.

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

(Note: the online version of the story has the date May 2, 2025, and has the title “Universal Antivenom May Grow Out of Man Who Let Snakes Bite Him 200 Times.”)

The academic article in the journal Cell mentioned above is:

Glanville, Jacob, Mark Bellin, Sergei Pletnev, Baoshan Zhang, Joel Christian Andrade, Sangil Kim, David Tsao, Raffaello Verardi, Rishi Bedi, Sindy Liao, Raymond Newland, Nicholas L. Bayless, Sawsan Youssef, Ena S. Tully, Tatsiana Bylund, Sujeong Kim, Hannah Hirou, Tracy Liu, and Peter D. Kwong. “Snake Venom Protection by a Cocktail of Varespladib and Broadly Neutralizing Human Antibodies.” Cell 188 (2025): 1-18.

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.

Pasteur Saw That “Germs Were Everywhere in the Air”

The passages quoted below show how Pasteur respected his audience by finding a clear and compelling way to communicate that “germs” float in the air. The essay quoted below is adapted from Zimmer’s recently released Air-Borne book.

In other parts of Air-Borne, Zimmer discusses how the W.H.O. and the C.D.C. ignored the implications of the findings of Pasteur and others, relevant to the air-borne (aerosol) spread of diseases such as Covid-19.

(p. D8) On the evening of April 7, 1864, in an amphitheater filled with Parisian elites, Pasteur stood surrounded by lab equipment and a lamp to project images on a screen. He told the audience it would not leave the soiree without recognizing that the air was rife with invisible germs. “We can’t see them now, for the same reason that, in broad daylight, we can’t see the stars,” he said.

At Pasteur’s command, the lights went out, save for a cone of light that revealed floating motes of dust. Pasteur asked the audience to picture a rain of dust falling on every surface in the amphitheater. That dust, he said, was alive.

Pasteur then used a pump to drive air through a sterile piece of cotton. After soaking the cotton in water, he put a drop under a microscope. He projected its image on a screen for the audience to see. Alongside soot and bits of plaster, they could make out squirming corpuscles. “These, gentlemen, are the germs of microscopic beings,” Pasteur said.

Germs were everywhere in the air, he said — kicked up in dust, taking flights of unknown distances and then settling back to the ground, where they worked their magic of fermentation. Germs broke down “everything on the surface of this globe which once had life, in the general economy of creation,” Pasteur said.

“This role is immense, marvelous, positively moving,” he added.

The lecture ended with a standing ovation. Pasteur’s hunt for floating germs elevated him to the highest ranks of French science.

For the full essay see:

Zimmer, Carl. “He Showed That Germs Floated in Air.” The New York Times (Tuesday, February 18, 2025): D8.

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

(Note: the online version of the essay was updated Feb. 18, 2025, and has the title “Louis Pasteur’s Relentless Hunt for Germs Floating in the Air.”)

Zimmer’s essay, quoted above, is adapted from his book:

Zimmer, Carl. Air-Borne: The Hidden History of the Life We Breathe. New York: Dutton, 2025.

90% of Biomedical Articles Are “Either Misleading, Wrong or Completely Fabricated”

The right to health freedom is primarily an ethical issue. But the uncertainty and unreliability of much medical “knowledge” (as argued in the book reviewed in the passages quoted below) seems to strengthen the case for patient self-determination.

(p. A15) The largest repositories of biomedical research in the U.S. and Europe, PubMed and Europe PMC, contain 84 million articles between them, and add a million more each year. According to recent estimates, up to 90% of those papers—75 million total—contain information that’s either misleading, wrong or completely fabricated.

Over the past 20 years, certain branches of science have endured a so-called reproducibility crisis, in which countless papers have been exposed as shoddy if not bogus. Sometimes these revelations are merely embarrassing, but in biomedical research, incorrect publications can cost lives as doctors and drugmakers rely on them to treat patients.

In “Unreliable: Bias, Fraud, and the Reproducibility Crisis in Biomedical Research,” Csaba Szabo—a physician with doctorates in physiology and pharmacology—dissects the ways he’s seen research go wrong in his 30 years in academia and industry: data manipulation, poor experimental design, statistical errors and more.

. . .

The biggest problem, however, lies with scientists who strive to do good work but feel pressured to cut corners. Scientists cannot work without grant money, but of the 70,000 applications the National Institutes of Health receive each year, only 20% get funded. Leading journals reject up to 99% of papers submitted, and only one in 200 doctoral graduates ever becomes a full professor. Even with tenure, professors can suffer salary cuts or have their labs handed to higher-performing colleagues if they don’t keep pulling in cash. Some sadistic research professors even pit their graduate students against each other in “dogfights”—they run the same experiment, but only the first to get results publishes. No wonder researchers massage data or fudge images: Forget “publish or perish.” It’s “fib or forgo your career.”

. . .

Given this tsunami of mistakes, the author points out that cynical types have suggested we treat all biomedical research as fraudulent unless proved otherwise. The cost is staggering: The U.S. wastes tens of billions of dollars annually on useless research, shortening or even costing patient lives. Most scientists can’t even reproduce their own data half the time, and the number of papers retracted rose to 10,000 in 2023 from 500 in 2010.

. . .

Most importantly, Dr. Szabo calls for systematic changes in how science gets done.

. . .

Above all, he despises the broken status quo, where “everybody acts politely . . . keeps their mouths shut, and acts like the whole process is functioning perfectly well.”

For the full review see:

Sam Kean. “Bookshelf; Reaching For Results.” The Wall Street Journal (Tuesday, March 24, 2025): A15.

(Note: ellipses between paragraphs added; ellipsis internal to paragraph, in original.)

(Note: the online version of the review was updated March 24, 2025, and has the title “Bookshelf; ‘Unreliable’: Reaching for Results.”)

The book under review is:

Szabo, Csaba. Unreliable: Bias, Fraud, and the Reproducibility Crisis in Biomedical Research. New York: Columbia University Press, 2025.

Vindication is Sweet, Even 60 Years Too Late

When I was a child my mother would stick an oral thermometer in my mouth. When she returned she would always be annoyed with me, saying that I didn’t have it in right, because my temperature was too low. She would say with irritation: ‘Now this time do it right!’ So I would feel discouraged and would give the thermometer a hard jab into my mouth until it hurt. But my temperature would still be too low.

The story below suggests, decades too late for me, that maybe it wasn’t my fault. Maybe the official mandated “normal” temperature of 98.6 was wrong!

(p. D6) We seem to be getting cooler. Since 1851, when the standard was set at 37 degrees centigrade, or 98.6 Fahrenheit, the average human body temperature has steadily declined.

. . . . The analysis is in eLife.

. . .

. . . improvements in sanitation and improved dental and medical care have reduced chronic inflammation, and the constant temperatures maintained by modern heating and air conditioning have helped lower resting metabolic rates. Today, a temperature of 97.5 may be closer to “normal” than the traditional 98.6.

For the full story see:

Nicholas Bakalar. “Is 98.6 No Longer ‘Normal’?” The New York Times (Tuesday, January 21, 2020): D6.

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

(Note: the online version of the story was updated Jan. 21, 2020 [sic], and has the title “Body Temperature 2.0: Do We Need to Rethink What’s Normal?”)

The academic paper in eLife, mentioned above, is:

Protsiv, Myroslava, Catherine Ley, Joanna Lankester, Trevor Hastie, and Julie Parsonnet. “Decreasing Human Body Temperature in the United States since the Industrial Revolution.” eLife 9 (2020): e49555.

A Nimble Evolving Virus Can Outpace Sluggish Vaccine Clinical Trials

The long time that Phase 3 clinical trials take is a major cost. This is especially true for the poor souls whose dire disease will kill them soon. It is also true, as was the case for the rapidly evolving Covid virus discussed below, where the disease is evolving so fast that it is a moving target.

We should calibrate relative risks. What is the risk from delay? What is the risk from less certainty about efficacy?

When the risks from delay are huge, it makes sense to use quicker, allegedly less certain, sources of knowledge, rather than wait for the allegedly certain results of Phase 3 clinical trials.

(p. A13) WASHINGTON — A panel of independent experts advising the Food and Drug Administration is set to recommend on Tuesday [June 28, 2022] whether to update existing Covid-19 vaccines to target a newer version of the coronavirus in a booster shot that Americans could get in the fall.

The federal government is hoping to improve the vaccine to better boost people’s immunity before a likely resurgence of the virus this winter. But to move that quickly, it may need to abandon the lengthy human trials that have been used to test coronavirus vaccines over the past two years in favor of a faster process that relies more on laboratory tests and animal trials.

The most recent trials with human volunteers have taken five months, even using relatively small groups. But the virus is evolving so quickly that new vaccine formulations are out of date before such trials are even finished.

For the full story see:

Sharon LaFraniere. “Chasing Fast-Evolving Virus, F.D.A. May Move to Update Covid Vaccine.” The New York Times (Tuesday, June 28, 2022 [sic]): A13.

(Note: bracketed date and bolded words, added.)

(Note: the online version of the story has the date June 27, 2022 [sic], and has the title “F.D.A. May Move Toward Updating Vaccines.”)

Trial-and-Error Exploration of Venoms Can Yield Useful Drugs

Several decades ago the fastest path to medical advance was claimed to be theoretical science. That approach has not paid off as richly as predicted.
But it may still. (When Pets.com failed, some said we should have known you cannot make money selling pet supplies online. But now Chewy.com succeeds.) Nonetheless the contempt the theoreticians heaped upon empirical trial-and-error research was not justified. Much is still left to be learned by that method, as exemplified in the passages quoted below.

(p. D1) Efforts to tease apart the vast swarm of proteins in venom — a field called venomics — have burgeoned in recent years, and the growing catalog of compounds has led to a number of drug discoveries. As the components of these natural toxins continue to be assayed by evolving technologies, the number of promising molecules is also growing.

“A century ago we thought venom had three or four components, and now we know just one type of venom can have thousands,” said Leslie V. Boyer, a professor emeritus of pathology at the University of Arizona. “Things are accelerating because a small number of very good laboratories have been pumping out information that everyone else can now use to make discoveries.”

She added, “There’s a pharmacopoeia out there waiting to be explored.”

. . .

(p. D8) The techniques used to process venom compounds have become so powerful that they are creating new opportunities. “We can do assays nowadays using only a couple of micrograms of venom that 10 or 15 years ago would have required hundreds of micrograms,” or more, Dr. Fry said. “What this has done is open up all the other venomous lineages out there that produce tiny amounts of material.”

There is an enormous natural library to sort through. Hundreds of thousands of species of reptile, insect, spider, snail and jellyfish, among other creatures, have mastered the art of chemical warfare with venom. Moreover, the makeup of venom varies from animal to animal. There is a kind of toxic terroir: Venom differs in quantity, potency and proportion and types of toxin, according to habitat and diet, and even by changing temperatures due to climate change.

Venom is made of a complex mix of toxins, which are composed of proteins with unique characteristics. They are so deadly because evolution has honed their effectiveness for so long — some 54 million years for snakes and 600 million for jellyfish.

. . .

Numerous venom-derived drugs are on the market. Captopril, the first, was created in the 1970s from the venom of a Brazilian jararaca pit viper to treat high blood pressure. It has been successful commercially. Another drug, exenatide, is derived from Gila monster venom and is prescribed for Type 2 diabetes. Draculin is an anticoagulant from vampire bat venom and is used to treat stroke and heart attack.

The venom of the Israeli deathstalker scorpion is the source of a compound in clinical trials that finds and illuminates breast and colon tumors.

Some proteins have been flagged as potential candidates for new drugs, but they have to journey through the long process of manufacture and clinical trials, which can take many years and cost millions of dollars. In March [2022], researchers at the University of Utah announced that they had discovered a fast-acting molecule in cone snails. Cone snails fire their venom into fish, which causes the victims’ glucose levels to drop so rapidly it kills them. It holds promise as a drug for diabetes. Bee venom appears to work with a wide range of pathologies and has recently been found to kill aggressive breast cancer cells.

For the full story see:

Jim Robbins. “Venoms May Cure What Ails You.” The New York Times (Tuesday, May 3, 2022 [sic]): D1 & D5.

(Note: the online version of the story was updated May 6, 2022 [sic], and has the title “Deadly Venom From Spiders and Snakes May Also Cure What Ails You.”)

The published academic article on the use of cone snail venom to derive a new insulin for diabetes is:

Xiong, Xiaochun, Alan Blakely, Jin Hwan Kim, John G. Menting, Ingmar B. Schäfer, Heidi L. Schubert, Rahul Agrawal, Theresia Gutmann, Carlie Delaine, Yi Wolf Zhang, Gizem Olay Artik, Allanah Merriman, Debbie Eckert, Michael C. Lawrence, Ünal Coskun, Simon J. Fisher, Briony E. Forbes, Helena Safavi-Hemami, Christopher P. Hill, and Danny Hung-Chieh Chou. “Symmetric and Asymmetric Receptor Conformation Continuum Induced by a New Insulin.” Nature Chemical Biology 18, no. 5 (2022): 511-19.

The published academic article on the use of honeybee venom against breast cancer is:

Duffy, Ciara, Anabel Sorolla, Edina Wang, Emily Golden, Eleanor Woodward, Kathleen Davern, Diwei Ho, Elizabeth Johnstone, Kevin Pfleger, Andrew Redfern, K. Swaminathan Iyer, Boris Baer, and Pilar Blancafort. “Honeybee Venom and Melittin Suppress Growth Factor Receptor Activation in Her2-Enriched and Triple-Negative Breast Cancer.” npj Precision Oncology 4, no. 1 (2020): 24.

A recent book persuasively argued for the medical promise of drugs derived from “poison”:

Whiteman, Noah. Most Delicious Poison: The Story of Nature’s Toxins―from Spices to Vices. New York: Little, Brown Spark, 2023.

For the Last 30 Years, a Cure for Type 1 Diabetes “Is Just Five Years Away”

The article quoted below describes the “despair” of many with chronic diseases, and there willingness to “become human guinea pigs,” taking new therapies that may have risks, but also have some unknown change of a cure.

We should allow adults to make this choice. First because we respect their right to freedom. Second because we do not want to take away their hope, which is a key component of well-being. Third because allowing volunteers to try bold uncertain therapies, we will progress further and faster to cures.

Note that substantial funding for bold experiments is from a foundation headed by a doctor who himself has Type 1 diabetes. He has skin in the game, a sense of urgency.

Note also that a small pharma firm made progress, and convinced sufferers of the disease that the firm sincerely was mission-oriented. But ViaCyte was also severely financially constrained, given the huge costs of Phase 3 clinical trials. They were bought by Vertex, a company that started out small with the same mission-oriented passion (see Worth 1994) but seemed to lose some of that passion as they grew, due to the need to hire those who were good at raising money and dealing with regulators (see Worth 2014). Is it meaningful that an early success of Vertex was the drug Kalydeco for the relatively rare cystic fibrosis disease and that much of their financing was from a foundation of parents of children with cystic fibrosis, parents who felt plenty of urgency.

The odds are against Vertex curing Type 1 diabetes, but I hope they beat the odds.

If we want to better the odds for a cure, we should make drug development an order of magnitude cheaper by ending the mandate for Phase 3 clinical trials (in other words, we regulate only for safety, no longer for efficacy). Then small, passionate, entrepreneurial firms like ViaCyte can survive, thrive, and bring cures to market. Otherwise the financial hurdles will cause small firms like ViaCyte to sell out to large less entrepreneurial firms like Vertex.

(p. D5) In the three decades since she was first diagnosed with Type 1 diabetes, Lisa Hepner has clung to a vague promise she often heard from doctors convinced medical science was on the cusp of making her body whole again. “Stay strong,” they would say. “A cure is just five years away.”

. . .

“‘The cure is five years away’ has become a joke in the diabetes community,” Ms. Hepner said. “If it’s so close, then what’s taking so long? And in the meantime, millions of us have died.”

. . .

Therapies developed from human embryonic stem cells, many experts say, offer the best hope for a lasting cure. “The Human Trial” offers a rare glimpse into the complexities and challenges of developing new therapies — both for the patients who volunteer for the grueling clinical trials required by the Food and Drug Administration, and for the ViaCyte executives constantly scrambling to raise the money needed to bring a new drug to market. These days, the average cost, including the many failed trials along the way, is a billion dollars.

At a time when the soaring price of insulin and other life-sustaining drugs has tarnished public perceptions of the pharmaceutical industry, the film is also noteworthy for its admiring portrayal of a biotech company whose executives and employees appear genuinely committed to helping humanity. . . .

. . .

“The Human Trial,” which can also be viewed online, has become a rallying cry for Type 1 patients, many of whom believe only greater visibility can unleash the research dollars needed to find a cure.

Those who have seen the film have also been fortified by seeing their own struggles and dashed hopes reflected in the journeys of the film’s two main subjects, Greg Romero and Maren Badger, who became among the first patients to have the experimental cell pouches implanted under their skin.

The despair that drives them to become human guinea pigs can be hard to watch. Mr. Romero — whose father also had the disease, went blind before he was 30 and then died prematurely — confronts his own failing vision while grappling with the pain of diabetes-related nerve damage. “I hate insulin needles, I hate the smell of insulin. I just want this disease to go away,” Mr. Romero, 48, says numbly at one point in the film.

. . .

. . . there is more recent news that did not make it into the film. [In July 2022], ViaCyte was acquired by Vertex, the competing biotech company that has been developing its own stem-cell treatment. That treatment has shown early success, and last year the company announced that a retired postal worker who took part in clinical trials had been cured of Type 1 diabetes.

After almost a lifetime of hearing a cure was just around the corner, Dr. Aaron Kowalski, chief executive of the JDRF (Juvenile Diabetes Research Foundation), the world’s biggest funder of Type 1 research, counts himself as an optimist. A dozen more drug companies are pursuing a cure than a decade ago, he said, and the organization this year plans to spend $100 million on cure research. “It’s not a matter of if this will happen, it’s a matter of when,” said Dr. Kowalski, who is a scientist and has had the disease since childhood, as has a younger brother. “Our job is to make sure it happens faster.”

For the full review see:

Andrew Jacobs. “The Long, Long Wait for a Diabetes Cure.” The New York Time (Tuesday, Aug. 9, 2022 [sic]): D5.

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

(Note: the online version of the review was updated Aug. 10, 2022 [sic], and has the same title as the print version. Where the two versions have slightly different wording, the passages quoted above follow the online version.)

Werth’s account of the founding and early mission-orientation of Vertex is:

Werth, Barry. The Billion-Dollar Molecule: One Company’s Quest for the Perfect Drug. New York: Simon & Schuster, 1994.

Werth’s account the later growth and risk of loss of mission-orientation is:

Werth, Barry. The Antidote: Inside the World of New Pharma. New York: Simon & Schuster, 2014.

Innovative Research Is More Likely to Come from Small Teams

The incentives and constraints of doing research in medicine make the process very expensive, which leads it increasingly be a large group activity.
The article below suggests that large group research tends to be less innovative. We should reduce the costs by reducing regulations, including the mandate that no drug can be sold without an F.D.A.-approved Phase 3 clinical trial to prove efficacy.

(p. D3) In the largest analysis of the issue thus far, investigators have found that the smaller the research team working on a problem, the more likely it was to generate innovative solutions. . . .

The new research, published on Wednesday [Feb. 13, 2019] in the journal Nature, is the latest contribution from an emerging branch of work known as the science of science — the study of how, when and through whom knowledge advances.

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In the study, a trio of investigators led by James A. Evans, a sociologist at the University of Chicago, mined selections from three vast databases: . . .

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When the team correlated this disruption rating to the size of the group responsible for the project or paper, they found a clear pattern: smaller groups were more likely to produce novel findings than larger ones. Those novel contributions usually took a year or so to catch on, after which larger research teams did the work of consolidating the ideas and solidifying the evidence.

“You might ask what is large, and what is small,” said Dr. Evans. “Well, the answer is that this relationship holds no matter where you cut the number: between one person and two, between ten and twenty, between 25 and 26.”

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Psychologists have found that people working in larger groups tend to generate fewer ideas than when they work in smaller groups, or when working alone, and become less receptive to ideas from outside.

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The new study suggests that a different kind of funding approach may be needed, one that takes more risk and spends the time and money to support promising individuals and small groups, Dr. Evans said.

“Think of it like venture capitalists do,” he said. “They expect a 5 percent success rate, and they try to minimize the correlation between the business they fund. They have a portfolio, one that gives them a higher risk-tolerance level, and also higher payoffs.”