Category: Entrepreneurship

Hackman Was the Inspiring Hero of The Poseidon Adventure

I was surprised to see a commentary on Gene Hackman by Ben Stiller, so I started reading. He wrote that one Hackman film had mattered to him a lot.
I doubted that we liked the same film, but I read on, feeling a bit of hope and suspense. I admit I felt a tingle of triumph when I read that we both liked the same film–The Poseidon Adventure.

Stiller said that at age 7 he watched it in the theatre about 10 times. I don’t remember if I ever saw it in the theatre, but I have watched it more than once and I think about it fairly often. What I think about is what the passengers do when the ship is flipped over by a mammoth wave. Almost all of the surviving passengers start hobbling toward the top deck of the ship, hoping for rescue. But the small band of misfits who had been sitting at Reverend Gene Hackman’s table, plus the cruise singer, are convinced by Hackman that the only hope for rescue is to go in the opposite direction, because the hull is now the highest point of the ship.

He convinces them and he leads them in the right direction. At a key moment he acts to save them. The movie had hope in the face of disaster, perseverance paying off, courage when almost everyone else is going in the wrong direction.

Stiller says that the movie, and Hackman’s character in it, inspired him to want to be an actor. When Stiller acted as Hackman’s son in The Royal Tenenbaums, he finally worked up the courage to tell Hackman how much Hackman’s performance in The Poseidon Adventure had meant to him. Hackman smiled at him and simply said “money job.” Then Hackman got up when they called for them to shoot their last scene together. Stiller stayed sitting for several seconds, seeming stunned. In their scene Stiller tells Hackman that he has gone through a lot recently. Hackman looks at him with great empathy, puts a hand reassuringly on his neck and says “I know.” He says it was the same sincerity that he saw in Hackman’s performance in The Poseidon Adventure, and he doesn’t think it was a money job.

Just now I watched a YouTube interview of Hackman by Johnny Carson on the filming of The Poseidon Adventure. Hackman has a modesty to him, and a sense of humor. He talks about the filming being fun, but also talks of being disappointed that they cut a scene in which he did a difficult stunt. He could have just let the stuntman do it, but he chose to do it. When he was doing the movie he took it seriously.
My take is that as a modest man, when he said “money job” he might have been deflating the awkward intensity of what Stiller had told him, and it might not have been the whole truth.

For Stiller’s full commentary see:

Ben Stiller. “Gene Hackman’s Simple Truth.” The New York Times (Sat., March 1, 2025): A19.

(Note: the online version of the commentary has the date Feb. 28, 2025, and has the title “Ben Stiller on Gene Hackman’s Simple Truth.”)

Global Warming Allows German Wine Entrepreneurs to Grow a “Superb” Chardonnay

In my Openness book, I argue that the costs of global warming have been exaggerated, partly because environmentalists forget that entrepreneurs can adapt, either lessening the costs, or sometimes even creating benefits. A case of creating benefits is apparently now the growing of “superb” chardonnay wine in Germany:

(p. D4) What accounts for the arrival of . . . German chardonnays? Certain wine regions like Rheinhessen, the Pfalz and the Obermosel have limestone soils, which chardonnay has a special affinity for, but the warming climate has made it possible to ripen chardonnay sufficiently to make superb wines.

Climate change influenced decisions to plant chardonnay in other ways as well.

“Climate change for us does not just mean it’s getting warmer and warmer, it means everything is getting more extreme — frost risk, weeks without rain, hailstorms,” said Klaus Peter Keller, . . . . “Therefore, we must spread the risk a bit more than we would 30 or 40 years ago. Rather than 100 percent riesling we have now 70 percent riesling, 15 percent pinot noir, 10 percent chardonnay and 4 percent others, and we think that will be the structure for the coming 30 or 40 years.”

Mr. Keller said he had wanted to plant pinot blanc rather than chardonnay but that their son Felix had pushed for chardonnay.

“Felix was right,” he said. “Chardonnay is much better adapted to climate change, with thicker skins, and it transmits the soil much better than pinot blanc.”

Felix Keller said by email that his grandfather had tried planting chardonnay in 1988, but that the timing had been wrong.

“Back then, it didn’t ripen every year,” he said. “It took us until 2018 to try again. We believe chardonnay has a bright future in Germany because we now have the climate that used to be in Burgundy in the early ’90s.”

For the full commentary see:

Eric Asimov. “The Pour; A Surprise From Germany: Chardonnay.” The New York Times (Weds., March 5, 2025): D1 & D4.

(Note: ellipses added.)

(Note: the online version of the commentary was updated March 4, 2025, and has the same title as the print version.)

My book mentioned in my initial comments is:

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

Ramaswamy Avowed That the F.D.A. “Erects Unnecessary Barriers to Innovation”

The New York Times article quoted below worried that if Vivek Ramaswamy succeeded in “slashing regulation” of drugs, his own drug development firm would have benefitted. Maybe so, but that misses the main point–all the rest of us also would have benefitted by medical entrepreneurs being allowed to create more and quicker cures. Presumably The New York Times was relieved when Ramaswamy resigned from DOGE, but I was discouraged.

I was in favor of Elon Musk’s push to reduce the number of federal employees. But I was even more in favor of Vivek Ramaswamy’s push to deregulate innovative entrepreneurs.

[By the way, isn’t it predictable that The New York Times delights in highlighting Roivant’s one failure, but gives only passing scant mention to its six successes?]

(p. A10) Vivek Ramaswamy is the less famous and less wealthy half of the duo of billionaires that President-elect Donald J. Trump has designated to slash government costs.

. . .

At 39, he is one of the world’s youngest billionaires, having made his fortune in the pharmaceutical industry.  . . .

Mr. Ramaswamy, who owns a stake currently valued at nearly $600 million in a biotechnology company he started, has called for changes at the Food and Drug Administration that would speed up drug approvals.

. . .

Since being named to jointly lead DOGE, Mr. Ramaswamy had until recently been posting on Mr. Musk’s social media site X, hinting about where he may look to make changes in the government.

He called for slashing regulation, not just cutting government spending. He pointed to federal workers focused on diversity as potential targets for “mass firings.”

And he has been taking aim at the F.D.A. “My #1 issue with FDA is that it erects unnecessary barriers to innovation,” he wrote on X. He criticized the agency’s general requirement that drugmakers conduct two successful major studies to win approval rather than one.

Mr. Ramaswamy founded his biotechnology company, Roivant Sciences, in 2014, betting that he could find hidden gems whose potential had been overlooked by large drugmakers. The idea was to hunt for experimental medications languishing within large pharmaceutical companies, buy them for cheap and spin out a web of subsidiaries to bring them to market.

The venture is best known for a spectacular failure.

In 2015, Mr. Ramaswamy whipped up hype and investment around one of his finds, a potential treatment for Alzheimer’s disease being developed by one of his subsidiaries, Axovant. Two years later, a clinical trial showed that it did not work, erasing more than $1.3 billion in Axovant’s stock value in a single day.

Mr. Ramaswamy personally lost money on paper on the failure, but thanks to the savvy way he had structured his web of companies he and Roivant weathered the storm. Six products have won F.D.A. approval, and today Roivant has a market valuation of $8 billion.

Mr. Ramaswamy sold some of his Roivant stock to take a large payout in 2020, reporting nearly $175 million in capital gains on his tax return that year. But he is still one of the company’s largest shareholders.

If Mr. Ramaswamy recommends changes that speed up drug approvals through DOGE, that could be good news for Roivant, which is developing drugs that might come up for approval during Mr. Trump’s second term. The faster it can get medicines onto the market, the more valuable the company — and Mr. Ramaswamy’s stake in it — stands to become.

For the full story see:

Rebecca Robbins, Maureen Farrell and Jonathan Weisman. “From Ramaswamy’s High-Profile Perch, a Web of Potential Conflicts.” The New York Times (Thursday, January 16, 2025): A10.

(Note: ellipses added.)

(Note: the online version of the story has the date Jan. 15, 2025, and has the title “Ramaswamy Has a High-Profile Perch and a Raft of Potential Conflicts.”)

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.

Nvidia Entrepreneur’s Work-Life Imbalance: Ferocious Hard Work

(p. A15) Mr. Kim’s book is nothing like Walter Isaacson’s portraits of tech geniuses Steve Jobs or Elon Musk. It is more prosaic, focusing on the technical and human ground war of building a company. Even so, there is drama in Nvidia’s remarkable rise, and Mr. Kim’s reporting offers plenty of incident and portraiture.

. . .

As a teenager, we are told, Mr. Huang was a formidable table-tennis player and earned money by cleaning tables and bathrooms at a local Denny’s, a toughening experience that prepared him for life as a tech CEO. As a business sage, Mr. Huang says that work is simply perseverance in the face of difficult odds and that character is the source of greatness. Asked how to be successful, he will respond: “I wish upon you ample doses of pain and suffering.”

. . .

By . . . -the late 1990s—Mr. Huang had figured out a particular way of building and managing his company. The bedrock precept was ferociously hard work. New employees were told that the culture was “ultra-aggressive.” Mr. Huang demanded that they work at the “speed of light,” constrained (as Mr. Kim puts it) “only by the laws of physics—not by internal politics or financial concerns.”

. . .

Does all of this success make Mr. Huang happy? Apparently not. After one especially successful quarter, he began a review meeting by saying: “I look in the mirror every morning and say, ‘you suck.’ ” He still enjoys publicly dressing down employees, saying that humiliation is a small price to pay for group learning. He believes that he can “torture” his people “into greatness.” When employees begin to ramble in his presence, he will start to murmur “LUA,” a warning to the speaker. The abbreviation means: “Listen to the question. Understand the question. Answer the Question.”

For the full review see:

Philip Delves Broughton. “Bookshelf; The Hard Work Of Tech Mastery.” The Wall Street Journal (Monday, Dec. 16, 2024): A15.

(Note: ellipses added.)

(Note: the online version of the review has the date December 15, 2024, and has the title “Bookshelf; The Nvidia Way’: The Hard Work of Tech Mastery.”)

The book under review is:

Kim, Tae. The Nvidia Way: Jensen Huang and the Making of a Tech Giant. New York: W. W. Norton & Company, 2024.

Idaho Cut or Simplified 95% of Regulations by a “Sunset” Review

In my Openness book, I argue that government regulations bind entrepreneurs and reduce innovation. As part of an antidote, I suggest that “sunset laws,” where regulations automatically expire, if not renewed. Later, at a small conference on Adam Thierer’s latest book, I was discouraged to hear a couple of participants grant the plausibility of the “antidote,” but report that in actual practice it does not work because almost all old regulations get renewed. Some hope returned when I read a report from James Broughel of a successful sunset review process:

Idaho has proved deregulation is possible. The state repealed and revised its administrative rules code through a sunset review process in 2019. The results were dramatic. Since then, 95% of state regulations have been eliminated or simplified. The sky didn’t fall. Most regulations, when subject to genuine scrutiny, fail to justify their existence.

I will keep my eyes open on this issue, looking for more evidence.

James Broughel’s commentary is:

James Broughel. “Recipe for a Regulatory Spring Cleaning.” The Wall Street Journal (Tues., Nov. 26, 2024): A13.

(Note: the online version of the commentary has the date November 25, 2024, and has the same title as the print version.)

My book mentioned above is:

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

Adam Thierer’s book mentioned above is:

Thierer, Adam. Evasive Entrepreneurs and the Future of Governance: How Innovation Improves Economies and Governments. Washington, D.C.: Cato Institute, 2020.

Off-Label Drug Use Shows F.D.A. Phase 3 Trials Could Be Dropped, Adding New Cures and Lowering Costs

The F.D.A. allows physicians to prescribe drugs for “off-label” use. These drugs were originally approved for a different “on-label” use. For that approval the drugs had to pass through Phase 1 and Phase 2 clinical trials, mainly to show safety, and massively expensive Phase 3 clinical trials to show efficacy for the on-label use.

When off-label use is allowed, that shows that the F.D.A. is accepting drugs for a use where efficacy has NOT been shown.

This is a proof of concept for my suggestion (that I originally heard from Nobel-Prize-winner Milton Friedman) that F.D.A. regulation should be pared back to just Phase 1 and Phase 2, for safety. Since the Phase 3 trials are usually far more expensive than the Phase 1 and Phase 2 combined, this would allow far more new drugs to be developed.

If the development of new drugs was cheaper, Fajgenbaum and others would not need to spend N.I.H.’s 48 millions of taxpayer dollars to comb through already-approved drugs to see if one can be jury-rigged as a therapy for a different disease.

(p. A6) [Dr. David Fajgenbaum, an immunologist at the University of Pennsylvania and . . . Castleman patient who studies the disease] . . . has matched rare-disease patients with drugs that are already in pharmacies for other conditions for over 10 years, starting with himself.

. . .

Every Cure, a nonprofit Fajgenbaum helped found in 2022, received funding on Wednesday [Feb. 28, 2024] that could surpass $48 million from the federal Advanced Research Projects Agency for Health. Fajgenbaum and his team will spend the money to build a drug-repurposing database and algorithms that patients, doctors and researchers can use to find drugs for untreated diseases.

There are over 10,000 known rare diseases and most don’t have a drug approved to treat them. The FDA said it has approved over 19,000 prescription drugs.

The notion of finding new uses for existing drugs has been around for a long time. Once the FDA approves a drug, doctors can prescribe it off-label to patients with other conditions they think it will help. Ozempic, originally approved for people with Type 2 diabetes, is now used by millions of people without the disease for weight loss.

The National Institutes of Health and research institutions have invested over the years in drug repurposing, hoping it would be faster and less costly to find new uses for drugs that have already made it to market, a process that can take more than a decade and cost $2 billion. But systematically matching approved treatments to unmet needs has been hard.

. . .

“Our end goal is not FDA approval. Our end goal is giving patients maximum access to medications,” said Tracey Sikora, co-founder of Every Cure.

For the full story see:

Amy Dockser Marcus. “Repurposed Drugs Give People With Rare Diseases New Hope.” The Wall Street Journal (Thursday, Feb. 29, 2024 [sic]): A6.

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

(Note: the online version of the story has the date February 28, 2024 [sic], and has the title “This Doctor Found His Own Miracle Drug. Now He Wants to Do It for Others.”)

For more on Fajgenbaum’s story, read his autobiographical account:

Fajgenbaum, David. Chasing My Cure: A Doctor’s Race to Turn Hope into Action; a Memoir. New York: Ballantine Books, 2019.

F.D.A.’s Project Optimus Adds to Complexity and Length of Mandated Clinical Trials, Further Burdening Innovative Startups

One of Joseph Schumpeter’s profound subtle points in the key chapter 7 of Capitalism, Socialism and Democracy is that the kind of thinking and rules that aim for optimization, restrict the kind of creative, inspired thinking or improvisational pivoting that results in the greatest and fastest progress and flourishing. (My interpretation of Schumpeter.)

Great leaps forward have tended to originate from small startups. But increasing the size, length, and costs of mandated clinical trials, as the F.D.A. is doing with “Project Optimus,” will make it harder for small startups to survive, let alone flourish.

(p. B2) For years, Food and Drug Administration officials have expressed concern that cancer drug doses are often too high, leading to unnecessary side effects. An FDA program launched in 2021, Project Optimus, requires companies to re-examine how they set doses of cancer treatments.

This typically involves larger clinical trials to test doses to find those that optimally balance safety and efficacy. Entrepreneurs support the aim, but some fear the initiative will add time and cost to drug development, putting startups at a further disadvantage to larger competitors.

“I don’t think anybody disagrees with the idea that we’re trying to find the best thing for the patient,” said David Bearss, chief executive of biotechnology startup Halia Therapeutics. “I hope it doesn’t have unintended consequences of actually suppressing innovation.”

. . .

Because Project Optimus is still relatively new it will take a while for its full impact to be known. But it will likely add six to 12 months to the drug-development process, said Tara Raghavan, a pharmaceutical patent lawyer and partner with law firm Benesch Friedlander Coplan & Aronoff.

For the full story, see:

Brian Gormley. “FDA Drug Initiative Vexes Startups.” The Wall Street Journal (Friday, Aug 30, 2024): B2.

(Note: ellipsis added.)

(Note: the online version of the story has the date August 29, 2024, and has the title “FDA Wants Safer Cancer Drugs, but Some Startups Fear Unintended Consequences.”)

In my comments I mention Schumpeter’s chapter 7 on creative destruction that can be found in his messy, inspired masterpiece:

Schumpeter, Joseph A. Capitalism, Socialism and Democracy. 3rd ed. New York: Harper and Row, 1950.

Harold Ridley’s Innovative Project Was to Replace a Cataract with a Plexiglass Lens

I am currently working on a book on medical entrepreneurship. Harold Ridley deserves inclusion.

Innovative entrepreneurs often observe anomalies and realize how the anomalies can be put to good use, where others would not notice the anomalies, or would notice them, shrug, and forget. (In Ridley’s case the anomalie was that the plastic fragments in Cleaver’s eyes “weren’t causing any inflammation or infection.”)

Pasteur famously said that ‘chance favors a prepared mind.’ If he had read Kirzner, he might have added ‘chance also favors an alert mind.’ (Kirzner’s account of entrepreneurship emphasizes the importance of entrepreneurial alertness.)

(p. A17) On Aug. 15, 1940, Royal Air Force pilot Gordon Cleaver scrambled into the cockpit of his Hawker Hurricane and lifted into the sky.  . . .  He was shot down over Winchester. Enemy bullets shattered his canopy, showering debris into his eyes. Flying blind and in excruciating pain, Cleaver managed to escape his doomed plane and parachute to the ground.

. . .

Cleaver’s damaged eyes were examined by a 34-year-old ophthalmologist, Harold Ridley. Shards of Plexiglas from his shattered canopy remained in the pilot’s eyes. This was a disaster. Foreign bodies in the eye such as lead or shrapnel usually caused inflammation or infection so severe that the eyes often had to be removed. But Ridley noticed something peculiar: The fragments of clear plastic weren’t causing any inflammation or infection. They sat quietly inside Cleaver’s eyes, glistening in the light of the ophthalmoscope. This was a shocking discovery.

Ridley examined Cleaver multiple times. The pilot’s sight was severely damaged, but the Plexiglas remained inert in his eyes, causing no inflammation. In 1948, while Ridley was removing a cataract—a clouding of the eye’s lens—for another patient, the memory of Cleaver’s case sparked an epiphany. A medical student observing the operation said, “It’s a pity you can’t replace the cataract with a clear lens.” Ridley recalled the well-tolerated Plexiglas in Cleaver’s eyes and realized that he could use the material to make an intraocular lens that the body wouldn’t reject.

. . .

His invention has saved the sight of millions. But instead of stirring professional acclaim, Ridley’s invention was a disaster for his career. The ophthalmology establishment labeled him a heretic.

Leaders in the field accused him of malpractice, ridiculed him at science conferences and poisoned colleagues against his ideas. They argued that the procedure was a “time bomb” and that “manufacturers should be prosecuted for supplying implants.” Ridley worked for decades to improve his operation and gain converts, but fell into a deep depression. When he retired in 1971, he considered his career a failure.

For the full commentary see:

Andrew Lam. “The Doctor and the Pilot Who Saved the Eyesight of Million.” The Wall Street Journal (Monday, Feb. 8, 2025): A17.

(Note: ellipses added.)

(Note: the online version of the commentary has the date February 7, 2025, and has the same title as the print version.)

Lam’s commentary is related to his book:

Lam, Andrew. Saving Sight. Bokeelia, FL: Irie Books, 2013.

For Kirzner on entrepreneurial alertness see:

Kirzner, Israel M. Competition and Entrepreneurship. Chicago: University of Chicago Press, 1973.

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.