Methodology – artdiamondblog.com

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.

If Risks Are Low and Alternatives Few, Let Patients Try Therapies That Lack Proof of Efficacy

I like Dr. Shirvalkar’s decision process quoted below. He says that a patient should be allowed to take a therapy without proof of efficacy, if the costs and risks are low.

This decision process is consistent with my suggestion that the F.D.A. should stop mandating efficacy, and limit itself to only mandating safety, thus greatly reducing the costs of drug development.

(p. D7) Acetaminophen. Acupuncture. Massage. Muscle relaxants. Cannabinoids. Opioids. The list of available treatments for low back pain goes on and on. But there’s not good evidence that these treatments actually reduce the pain, according to a new study that summarized the results of hundreds of randomized trials.

. . .

Aidan Cashin, the paper’s first author and deputy director of the research group Center for Pain IMPACT at Neuroscience Research Australia, said the aim of the study was to identify which first-line treatments for low back pain had any specific effects beyond a placebo, which might merit further study and which may not be worth pursuing.

. . .

One limitation of the type of analysis that Dr. Cashin conducted was that it aggregated data from different studies and different populations in order to emulate one large trial. But in the process, a strong signal from one study that a treatment worked could be diluted amid noise from other studies that may not have been designed as well, he said.

. . .

The evidence for something like heat might be inconclusive, doctors said, but they would still recommend that patients try it. “It’s cheap, it’s accessible, it almost causes no harm,” Dr. Shirvalkar said.

For the full story see:

Nina Agrawal. “Low Back Pain Relief Is Stubbornly Elusive.” The New York Times (Tuesday, March 25, 2025): D7.

(Note: ellipses added.)

(Note: the online version of the story was updated March 24, 2025, and has the title “What Works for Low Back Pain? Not Much, a New Study Says.” Where the versions differ, in the passages quoted above, I follow the online version.)

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.

Animals Consume Effective Medicines Without Spending Billions on Phase 3 Clinical Trials

Animals are free to self-medicate and apparently often do so effectively. Isn’t it ironic that our government F.D.A. restricts the freedom of humans to self-medicate?

(p. A13) . . . as Jaap de Roode reveals in “Doctors by Nature: How Ants, Apes, and Other Animals Heal Themselves,” many animals seek out substances to relieve illnesses or battle parasites that drag their health down: . . .

Mr. de Roode, a biology professor at Emory University, chronicles animal self-medication in everything from caterpillars and bees to pigs and dolphins. The drugs take the form of minerals, fungi and especially plants. Often, the drug is ingested for therapeutic reasons, as when chimps eat Velcro-like leaves to scour parasitic worms from their intestines. Many creatures also take drugs prophylactically, to prevent disease. The feline love of catnip, Mr. de Roode suggests, is probably an evolutionary adaptation: The plant deters disease-carrying mosquitoes, so cats with a taste for it ended up more equipped for survival.

. . .

Many plants produce chemicals called alkaloids that taste foul and cause other unpleasant sensations, but can also fight off parasites. After noticing that woolly bear caterpillars infested with fly maggots tend to seek out alkaloid-rich plants, scientists documented—by threading tiny wires into the caterpillars’ mouths—that the infected critters’ taste buds fired far more often when eating these plants than did the taste buds of the uninfected. The bugs’ sensory perception changed to make drugs more attractive. If the consumption of some irregular substance leads to a drop in infection load and alleviates negative symptoms, then, Mr. de Roode convincingly argues, animals are indeed using medicine. Caterpillar, heal thyself.

. . .

Humans can benefit from studying animal medicine, too. Most of our drugs are either plant compounds or derived from plant compounds. But researchers have systematically studied only a few hundred of the earth’s estimated tens of thousands of plant species. To guide researchers’ studies, scientists could note which ones animals consume and concentrate on those. Let Mother Nature do the research and development for us.

For the full review see:

Sam Kean. “Bookshelf; Medicinal Kingdom.” The Wall Street Journal (Friday, March 28, 2025): A13.

(Note: ellipses added.)

(Note: the online version of the review has the date March 27, 2025, and has the title “Bookshelf; ‘Doctors by Nature’: Medicinal Kingdom.”)

The book under review is:

Roode, Jaap de. Doctors by Nature: How Ants, Apes, and Other Animals Heal Themselves. Princeton, NJ: Princeton University Press, 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.

Ed Leamer Doubted the Robustness of Many Econometric Studies

Ed Leamer showed that a lot of econometric studies in economics amounted to economists searching among the plethora of plausible specifications of variables and functional forms, until they found one that yielded the sign and statistical significance of the variable they cared about. So, for example, an economist who thought capital punishment deterred murder, could produce that result, and an economist who thought capital punishment did strong>not deter murder, could also produce that result.

Leamer suggested that economists should show whether their results varied under a variety of specifications, in order to show the robustness of the claimed main result.

(p. C6) One day in elementary school, Edward Leamer noticed that his teacher had written the wrong answer to a math problem on the blackboard, so he stood up and told her so. His teacher took another look and assured him that it was correct. Again he protested, so she asked him to take his seat.

“He refused to sit down,” his brother, the author Laurence Leamer, said in a gathering on Zoom to celebrate his brother last month. “His whole life, he’s refused to sit down.”

Leamer, an economist who died Feb. 25 at the age of 80 from complications stemming from ALS (or Lou Gehrig’s disease), was best known for standing up and telling economists that they were doing it wrong. In influential papers like 1983’s “Let’s Take the Con Out of Econometrics” and his seminal book, “Specification Searches” (1978), Leamer warned economists that the methods they were using to analyze data produced weak findings that couldn’t hold up to scrutiny. He said economists often had a bias toward the results they wanted or that were the kinds of firm conclusions that led to press coverage, funding and policy positions they supported.

What’s more, Leamer warned economists that they weren’t being honest about the strength of their conclusions or transparent about the fact that they had run other tests that showed different results.

For the full obituary, see:

Chris Kornelis. “The Economist Who Called Out Other Economists.” The Wall Street Journal (Saturday, March 15, 2025): C6.

(Note: the online version of the obituary has the date March 14, 2025, and has the title “Edward Leamer, Economist Who Said Economists Were Doing It Wrong, Dies at 80 [sic].” Where the wording is different between the versions, the last three sentences quoted above follow the online version.)

Leamer’s wonderful paper, mentioned above, is:

Leamer, Edward E. “Let’s Take the Con Out of Econometrics.” American Economic Review 73, no. 1 (March 1983): 31-43.

Leamer’s book, mentioned above, is:

Leamer, Edward E. Specification Searches: Ad Hoc Inference with Nonexperimental Data, Wiley Series in Probability and Mathematical Statistics. New York: John Wiley & Sons, Inc., 1978.

Innovative Entrepreneur Bill Gates Believes He Is “on the Autism Spectrum”

In my “Openness” book I argue and present some evidence that toleration for those who think different, including those on the Autism spectrum, will allow more innovative entrepreneurs to flourish, bringing benefits to us all. In the first volume of his autobiography, innovative entrepreneur Bill Gates speculates that he is on the Autism spectrum.

(p. A17) Mr. Gates was, he says, a “happy boy,” according to family lore. He had a wide grin, excess energy and a tendency to rock his body when he was deep in thought. Mr. Gates speculates that today he “probably would be diagnosed on the autism spectrum.”

For the full review see:

David A. Shaywitz. “Bookshelf; A Life of DOS And Don’ts.” The Wall Street Journal (Tuesday, Feb. 4, 2025): A17.

(Note: the online version of the review has the date February 3, 2025, and has the title “Bookshelf; ‘Source Code’: A Life of DOS and Don’ts.”)

The first volume of Bill Gates’s autobiography is:

Gates, Bill. Source Code: My Beginnings. New York: Alfred A. Knopf, 2025.

My book, that I mention in my opening comments, is:

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

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.

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.

. . .

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: . . .

. . .

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.”

. . .

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.

. . .

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.”