Entrepreneurship – Page 6 – artdiamondblog.com

Using the Blood of the Young to Rejuvenate the Organs of the Old

The strange longevity therapy described in the passages quoted below, are hard to test, especially if started at a time in life early enough to do the most good.

Phase 3 clinical trials to establish the efficacy of a therapy are in general very expensive, and they are especially very expensive for therapies aimed at extending lifespan. To know the efficacy of such therapies you have to run the trial for many years, before you can learn the lifespans of all of those in the trial.

This may be one reason why pharma firms instead invest in incremental improvements in health tested for those predicted to be near the end of their lives.

Azra Raza claims that the most promising therapies for cancer would be those applied early in the disease. But it is precisely these candidate therapies that would be most expensive to test through a hyper-expensive Phase 3 clinical trial. The result? Unnecessarily slow progress in curing cancer.

(p. B3) Several years ago, scientists studying aging at the Harvard Stem Cell Institute used a somewhat Frankensteinian technique known as parabiosis — surgically joining a young mouse and an old mouse so that they share blood — to see what would happen to the heart and skeletal muscle tissue. They knew from previous research that putting young blood in old mice caused them to grow biologically younger, and that young mice exposed to old blood aged faster.

The Harvard researchers, Amy Wagers and Dr. Richard Lee, found that the old mouse’s heart tissue had been repaired and rejuvenated, becoming young again. In fact, the size of the old mouse’s heart had reduced to that of a young heart.

“We all wondered, what’s the magic stuff in the blood?” said Lee Rubin, a professor of stem cell and regenerative medicine at Harvard and the co-director of the neuroscience program at the Stem Cell Institute. The “magic” they identified was a protein, GDF11, one of tens of thousands produced in the human body. . . . The scientists’ discoveries were published in the journals Cell and Science in 2013 and 2014.

. . .

“We’re interested in proteins like GDF11 that are excreted into the bloodstream because those can cause changes throughout the body,” said Dr. Mark Allen, the chief executive of Elevian. “And those are the kind of changes we want.”

. . .

The initial research into the rejuvenating properties of GDF11 has gotten some pushback from the scientific community. In 2015, after Dr. Wagers and Dr. Lee had published their results, a group of researchers led by David Glass, the executive director of the Novartis Institutes for Biomedical Research in Cambridge, Mass., at the time, challenged the accuracy of their findings in an article in the journal Cell Metabolism. The Harvard researchers subsequently countered the Novartis team’s findings in another paper published later that year in the journal Circulation Research, in which the Harvard researchers cited a problem with the Novartis team’s findings.

Dr. Glass, who is now at the biotechnology company Regeneron, said in a recent email that he stands by his original work, which showed that GDF11 inhibits, rather than helps, muscle regeneration. But, he added, “our work still leaves open the possibility that there could be positive effects of GDF11 in particular settings.”

Dr. Allen said that since the original controversy, Elevian’s research team has reproduced and extended its original findings in multiple studies, but none have yet been published in peer-reviewed journals. However, institutions unrelated to Elevian have conducted and published many preclinical studies demonstrating the therapeutic efficacy of rGDF11 (the form of GDF11 developed in a lab) in treating age-related diseases.

. . .

A significant challenge lies ahead for all of these companies: Commercializing a drug for aging is nearly impossible because the F.D.A. doesn’t recognize aging as a disease to be treated. And even if it were considered a disease, the clinical studies required to prove that a treatment for it worked would take many years.

“It is likely that clinical studies to see if some drug slows aging — and thereby delays the many consequences of aging — would take a long time,” Dr. Miller said.

. . .

The next big hurdle for Elevian is scaling its manufacturing, which requires specialized equipment and conditions. So much research is being conducted in biotech that contract manufacturers are “full up,” Dr. Allen said. “They are busy with Covid-related work, and there has been a lot of funding in biotech generally,” he added. “So it’s a challenge finding the space that meets our specifications.”

. . .

“By targeting fundamental mechanisms of aging, we have the opportunity to treat or prevent multiple aging-related diseases and extend the health span,” he said. “We want to make 100 the new 50.”

For the full story see:

Eilene Zimmerman. “Biotech Start-Up Invests in Anti-Aging Therapy.” The New York Times (Monday, August 1, 2022 [sic]): B3.

(Note: the online version of the story has the date July 19, 2022 [sic], and has the title “Can a ‘Magic’ Protein Slow the Aging Process?”)

The published academic articles supporting the promising effects of GDF11 are:

Katsimpardi, Lida, Nadia K. Litterman, Pamela A. Schein, Christine M. Miller, Francesco S. Loffredo, Gregory R. Wojtkiewicz, John W. Chen, Richard T. Lee, Amy J. Wagers, and Lee L. Rubin. “Vascular and Neurogenic Rejuvenation of the Aging Mouse Brain by Young Systemic Factors.” Science 344, no. 6184 (May 9, 2014): 630-34.

Loffredo, Francesco S., Matthew L. Steinhauser, Steven M. Jay, Joseph Gannon, James R. Pancoast, Pratyusha Yalamanchi, Manisha Sinha, Claudia Dall’Osso, Danika Khong, Jennifer L. Shadrach, Christine M. Miller, Britta S. Singer, Alex Stewart, Nikolaos Psychogios, Robert E. Gerszten, Adam J. Hartigan, Mi-Jeong Kim, Thomas Serwold, Amy J. Wagers, and Richard T. Lee. “Growth Differentiation Factor 11 Is a Circulating Factor That Reverses Age-Related Cardiac Hypertrophy.” Cell 153, no. 4 (May 9, 2013): 828-39.

Poggioli, Tommaso, Ana Vujic, Peiguo Yang, Claudio Macias-Trevino, Aysu Uygur, Francesco S. Loffredo, James R. Pancoast, Miook Cho, Jill Goldstein, Rachel M. Tandias, Emilia Gonzalez, Ryan G. Walker, Thomas B. Thompson, Amy J. Wagers, Yick W. Fong, and Richard T. Lee. “Circulating Growth Differentiation Factor 11/8 Levels Decline with Age.” Circulation Research 118, no. 1 (Jan. 2016): 29-37.

Sinha, Manisha, Young C. Jang, Juhyun Oh, Danika Khong, Elizabeth Y. Wu, Rohan Manohar, Christine Miller, Samuel G. Regalado, Francesco S. Loffredo, James R. Pancoast, Michael F. Hirshman, Jessica Lebowitz, Jennifer L. Shadrach, Massimiliano Cerletti, Mi-Jeong Kim, Thomas Serwold, Laurie J. Goodyear, Bernard Rosner, Richard T. Lee, and Amy J. Wagers. “Restoring Systemic Gdf11 Levels Reverses Age-Related Dysfunction in Mouse Skeletal Muscle.” Science 344, no. 6184 (May 9, 2014): 649-52.

The book by Asra Raza that I praise in my introductory comments is:

Raza, Azra. The First Cell: And the Human Costs of Pursuing Cancer to the Last. New York: Basic Books, 2019.

Healthcare Innovations Can Be Effective AND Cheap

Many are resigned to accept our current mess of a healthcare system because they fear that if the system was changed into a fully free market system they would not be able to afford anything approaching their current level of healthcare. But they do not understand what would change. If patients paid for their own healthcare there would be competition to provide cheaper healthcare services to the many. Henry Ford got rich finding ways to make cars better and cheaper. Bill Gates got rich mainly by making adequate operating systems cheaper.

If we made healthcare a free market, then healthcare would find its Henry Ford and Bill Gates. If patients directly paid for healthcare, then healtcare services would be more consumer oriented–for instance the value of patients’ time would be respected. Medical entrepreneurs would compete to bring us more cures and cheaper cures.

The problem is not that we are “fixated on profits” as is suggested in the last paragraph quoted below. The problem is that our non-market healthcare system creates perverse incentives and perverse regulatory constraints, so that simple frugal innovations are not rewarded.

[Below I first quote a few passages from The New York Times obituary of Cash, and then from The Wall Street Journal obituary of Cash.]

(p. A21) Richard A. Cash, who as a young public-health researcher in South Asia in the late 1960s showed that a simple cocktail of salt, sugar and clean water could check the ravages of cholera and other diarrhea-inducing diseases, an innovation that has saved an estimated 50 million lives, died on Oct. 22 at his home in Cambridge, Mass. He was 83.

. . .

Dr. Cash, the son of a doctor, arrived in East Pakistan, today Bangladesh, in 1967 as part of a project through the U.S. Public Health Service. There he worked with another young American doctor, David Nalin, to respond to a cholera outbreak outside the capital, Dhaka.

The two had already been researching a simple oral rehydration therapy and knew of other, previous efforts, all of which had failed. But they believed that the therapy held promise, especially in the face of mounting deaths.

They realized that a main problem was volume: Past efforts had resulted in too little or too much hydration. Dr. Cash and Dr. Nalin conceived a trial in which they carefully measured the amount of liquid lost and replaced it with the same amount, mixed with salt and sugar to facilitate absorption.

They divided 29 patients into three groups, with one group receiving an IV drip, another an oral treatment through a tube, and the third an oral treatment by drinking from a cup.

Other doctors and nurses found their experiment bizarre and tried to stop them. But Dr. Cash and Dr. Nalin persisted, splitting the work between them in two 12-hour shifts, to ensure the integrity of the trial.

The results were definitive: Only three of the tubed patients — and only two who drank the solution — needed additional IV treatment.

. . .

“We’re enamored by high technology,” he said at the Council on Foreign Relations. “And we’re not in love with low-tech. Low-tech is always seen in our eyes as second-class. Why would you do this, when you could do that? And I would argue just the opposite.”

For the full obituary from The New York Times that is quoted above, see:

Clay Risen. “Richard A. Cash, 83, Who Saved Millions From Dehydration, Dies.” The New York Times (Monday, November 4, 2024): A21.

(Note: ellipses added.)

(Note: the online version of the obituary has the date Nov. 2, 2024, and has the title “Richard A. Cash, Who Saved Millions From Dehydration, Dies at 83.”)

(p. C6) Half a liter of water, plus a pinch of salt and a fistful of sugar. As scientific insights go, it can’t compare to the intricate equations developed to split the atom or map the planets’ paths. But its simplicity was crucial to its monumental impact.

That simple solution—the cornerstone of Oral Rehydration Therapy, or ORT—has proved extraordinary in staving off and reversing the devastating consequences of dehydration caused by cholera and other diarrheal diseases, saving tens of millions of lives since its development nearly six decades ago. In 1978, an editorial in the Lancet called ORT “potentially the most important medical advance of the century.”

. . .

Cash saw this ethos of simplicity and accessibility as instructive for a western medical system that’s infatuated with high-tech solutions, dismissive of low-tech ones and fixated on profits—and where, consequently, an overnight stay in the hospital for dehydration can result in a four-figure bill. “A solution that can’t be applied,” he told Harvard Magazine, “is really no solution at all.”

For the full obituary from The Wall Street Journal that is quoted immediately above, see:

Jon Mooallem. “A Doctor Whose Simple Treatment Prevented Millions Of Cholera Deaths.” The Wall Street Journal (Saturday, Nov. 9, 2024): C6.

(Note: ellipsis added.)

(Note: the online version of the obituary has the date November 7, 2024, and has the title “Richard Cash, Whose Rehydration Therapy Saved Millions of Lives, Dies at 83.”)

Regulators Do Not Understand the Sense of Urgency of Some Who Are Dying

Many know that the first gift of Prometheus to humanity was fire. Fewer know that his second gift was blind hope. International value surveyor Ronald Inglehart concluded that happiness depends less on current status than on hope for the future.

Many who are facing death without any standard therapy to save them, are anxious to try a Hail Mary experiment–a potential therapy with many risks, but with a possible path forward, with hope.

A libertarian or classical liberal says that they have the right to choose hope.

In the concluding passages quoted below it is easy to sense the hope that the pig kidney transplant gave Tawana Looney.

(p. A18) A 53-year-old Alabama woman with kidney failure who waited eight years for an organ transplant has received a kidney harvested from a genetically modified pig, NYU Langone Health surgeons announced on Tuesday [Dec. 17, 2024].

The patient, Towana Looney, went into surgery just before Thanksgiving. She was in better health than others who have received porcine organs to date and left the hospital 11 days after the procedure.

. . .

Dr. Robert Montgomery, director of the NYU Langone Transplant Institute, co-led the surgery with Dr. Jayme Locke, a transplant surgeon who applied two years ago for approval from the Food and Drug Administration to perform the operation for Ms. Looney.

. . .

The experimental procedure was approved by the Food and Drug Administration under its expanded access or compassionate use program, which allows unapproved products to be used when patients have life threatening conditions.

. . .

About two years ago, Dr. Locke contacted Ms. Looney. Dr. Locke was intent on finding better solutions for patients with kidney failure, which is rampant in Alabama and disproportionately affects the state’s Black residents.

It was the beginning of a conversation that spanned nearly two years while the physician sought special F.D.A. permission to do the xenotransplant on Ms. Looney, who was eager to get started.

“I said, ‘OK, where do I sign?’” Ms. Looney recalled.

“But she said, ‘This is new territory. This is new ground. I don’t know what might happen, and a lot of things could go wrong here.’ I said, ‘OK, when are we going to do it?’ And she went through all the if’s and and’s and what might happen again.”

The dialogue continued on and off for months. “We talked every day, and every day we talked she said, ‘Are you sure?’ And I said, ‘I’m positive. My mind is made up,’” Ms. Looney said.

Last month, while Ms. Looney was sitting in her dialysis chair during her morning treatment, her phone rang. It was Dr. Locke, who asked, “How do you feel about flying up to New York?”

Dr. Locke explained that she would do the surgery with Dr. Montgomery, the mentor who trained her.

“I said, ‘But what about Christmas? What about Thanksgiving?’ ” Ms. Looney said.

“She said, ‘It is going to be the best Christmas present you ever got.’ I said, ‘Yes, ma’am, it is.’”

For the full story see:

Roni Caryn Rabin. “Alabama Woman Gets Nation’s 3rd Pig Kidney Transplant.” The New York Times (Wednesday, December 18, 2024): A18.

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

(Note: the online version of the story has the date Dec. 17, 2024, and has the title “Alabama Woman Receives Nation’s Third Pig Kidney Transplant.”)

Chinese Communist Regulators Will Want to Deep-Six DeepSeek

Many policy experts have worried than China’s economy will surpass the economy of the United States. If we lived in a world of totally free trade, I would not care if this happened. Economics is not a competitive sport where one team can win only if another team loses. A free economy is not a zero-sum game. If you are OK with me mixing metaphors: a rising tide really does lift all boats. (Amar Bhidé (quoting Paul Krugman, if memory serves) does a good job of making this point in The Venturesome Economy.)

But even though it wouldn’t bother me, China’s economy will not surpass that of the United States if China continues to oppressively regulate its economy and we continue to exuberantly unregulate our economy. An economy thrives when entrepreneurs thrive and entrepreneurs thrive when unregulated.

Consider the recent hand-wringing over the recently announced DeepSeek Chinese A.I. program. The Chinese Communists will be especially energetic in regulating entrepreneurs in the A.I. sector because the Communists cannot afford to have Chinese A.I. programs giving true answers to questions in any way related to the Chinese economy, or to the corruption and authoritarianism of the Chinese Communist regime. A.I. policy expert Barath Harithas understates the situation when he says: “Overregulation and the need to adhere to ‘core socialist values’ could risk neutering A.I.’s potential” (as quoted in Pierson and Wang 2025, p. A4).

Barath Haritas’s statement on overregulation of A.I. in China can be found in:

David Pierson and Berry Wang. “Success of DeepSeek Lifts China, but Party May Halt Its Progress.” The New York Times (Tues., February 4, 2025): A4.

(Note: the online version of the article has the date February 2, 2025, and has the title “DeepSeek Is a Win for China in the A.I. Race. Will the Party Stifle It?”)

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

Bhidé, Amar. The Venturesome Economy: How Innovation Sustains Prosperity in a More Connected World. Princeton, NJ: Princeton University Press, 2008.

Dow Chemical CEO Oreffice Candidly Called Environmentalists “Professional Merchants of Doom”

I have the impression that few C.E.O.s today display the open candor that Ralph Nader admired in Paul Oreffice. Is that because cancel culture has been efficient at weeding out any rising executives who might be tempted to be candid? Or do I have a mistaken impression due to the press not reporting as often on the candid comments still being made by some C.E.O.s?

[I was happy to see that Oreffice had learned public speaking in a Toastmasters Club. I heard a lot about Toastmasters as a child–my father was very active in Toastmasters and was eventually elected President of the whole international self-help organization.]

(p. C6) In a 1977 speech at Central Michigan University, Jane Fonda accused Dow Chemical of exposing workers to dangerous substances and not paying its fair share of taxes. Paul Oreffice, who was then president of Dow’s U.S. operations, sent a letter to the university denouncing Fonda as “an avowed communist sympathizer” who was spreading “venom against free enterprise.”

He also cut off Dow’s donations to the university.

. . .

Addressing a business conference in 1979, Oreffice described environmentalists as “professional merchants of doom” and enemies who were destroying free enterprise, according to a Washington Post report.

. . .

Ralph Nader, the consumer-protection crusader, often was at odds with Oreffice but saw merit in his candor. “He is comparatively open to interviews, to questions from audiences, to debates,” Nader wrote in “The Big Boys,” a 1986 book written with William Taylor. “Despite his position as chief executive of a major corporation embroiled in ongoing controversies, he chooses not to hide behind company spokesmen and other bureaucratic shields.”

. . .

Oreffice resisted organization charts because he believed they “put people in boxes.”

. . .

. . ., Oreffice . . . learned public speaking at a Toastmasters club, . . .

As a CEO, he reduced costs and bureaucracy through attrition rather than mass layoffs. “How can you expect allegiance from your employees when you don’t show them any yourself?” he wrote in his memoir.

For the full obituary see:

James R. Hagerty. “An Outspoken Former CEO Of Dow Chemical.” The Wall Street Journal (Saturday, February 1, 2025): C6.

(Note: ellipses added.)

(Note: the online version of the obituary has the date January 29, 2025, and has the title “Paul Oreffice, Outspoken Former CEO of Dow Chemical, Dies at 97.” Where the wording is different between the two versions, the passages quoted above follow the online version.)

Oreffice’s memoir mentioned above is:

Oreffice, Paul. Only in America: From Immigrant to CEO. Macon, GA: Stroud & Hall Publishers, 2006.

Curing Cellular Senescence Could Extend Healthy Lifespan

Senolytics are chemicals that kill senescent cells, cells that do function properly but do not die. The cells are believed to cause aging and eventual death. They also are believed to cause illnesses such as coronary artery disease and Alzheimer’s. If senescent cells can be expelled, then we can hope to extend, not just lifespan, but what really matters–healthy lifespan.

(p. A10) The same underlying factors that contribute to aging also play a role in the development of diseases, says Richard Faragher, a professor of biogerontology at the University of Brighton and board member of the American Federation for Aging Research. He cites the example of a biological process called cellular senescence, which is when cells that stop dividing but don’t die build up as people age. The process is linked to various age-related diseases.

“Can we do anything to impact the fundamental biology of human aging? I think the answer is an emphatic yes,” says Faragher.

Longevity drugs, if proven to work, could slow or prevent the onset of age-related conditions rather than treating them after they develop, and eventually save millions on chronic disease spending in later life, advocates say. In 2021, the costliest 1% of traditional Medicare beneficiaries accounted for 19% of spending, according to the nonpartisan watchdog agency the Medicare Payment Advisory Commission. Beneficiaries in their last year of life tend to generate more spending than others.

For the full story see:

Alex Janin. “The Scientific Fight Over Whether Aging Is a Disease.” The Wall Street Journal (Wednesday, Feb. 5, 2025): A10.

(Note: the online version of the story has the date January 27, 2025, and has the same title as the print version.)

Land Use Regulations Slow Home Building

Productivity in manufacturing in the U.S. between 1930 and 2020 has increased, with stagnation for the last 10 years. In contrast, residential construction productivity increased, with more variability, from 1930 until the 1970s, and then stagnated or decreased. Starting in the 1970s an increase in land use and environmental regulations caused the stagnation.

So if we want more and better and cheaper housing, the key is less government regulation.

The study I summarize above is:

D’Amico, Leonardo, Edward L. Glaeser, Joseph Gyourko, William R. Kerr, and Giacomo A.M. Ponzetto. “Why Has Construction Productivity Stagnated? The Role of Land-Use Regulation.” National Bureau of Economic Research Working Paper No. 33188, Nov. 2024.

Davos Worries Innovative European Firms Will Relocate to U.S. for Fewer Regs and “Kinder” Trump

Many of those with the passion to persevere in overcoming the necessary and unnecessary (regulatory) obstacles to medical innovation, do so because they have a sense of urgency due to skin in the game–they or a relative is directly affected by the disease they are passionate to cure. Dr. Edward Scolnick whose story I quote below, is a great example. In the story, we find another example, Ted Stanley, who donated $100 million to Scolnick because Stanley’s son is also suffering mental illness. And perhaps an indirect example? Rienhoff does not directly have skin in the game, but he is playing a key role because of Scolnick’s passion, and Scolnick’s passion is due to his skin in the game.

If we want more cures we will reduce the unnecessary (regulatory) obstacles so that those with less skin in the game (and so less passion to persevere) will also innovate.

[“Skin in the game” has been emphasized by Taleb in his book with that title.]

(p. A2) The U.S. was outperforming much of the world before Trump was elected.

His agenda could extend that outperformance by making the U.S. the preferred destination for foreign investment via lower taxes and regulation and even cheaper energy, while his promised tariffs hurt others’ exports.

. . .

Many at Davos blamed Europe’s dismal outlook on the failures of its own leaders, not on Trump.

European scientists are making progress on technologies that use genetically engineered microbes to solve any number of problems, said Kasim Kutay, the chief executive of Novo Holdings, which manages the assets and wealth of the foundation that controls Danish pharmaceutical company Novo Nordisk.

It takes seven to eight years, however, to get such a product approved by European regulators, compared with two to three in the U.S., he said: “A lot of that innovation is happening in Europe, but the companies ultimately seek funding in the U.S.”

One particular source of anxiety in Europe is that its top companies will move to the U.S. in search of higher stock valuations, less regulation and kinder treatment by Trump.

Rich Nuzum, global chief investment strategist for investment consultants Mercer, said Trump’s deregulatory drive might jolt Europe into action.

“If the U.S. economy continues to power ahead, if every company wants to be headquartered in the U.S. and traded in the U.S. because of a lighter regulatory burden…European C-suites will say to European policymakers, ‘Do something, or we’re going to move overseas.’”

The U.S. accounted for 44% of Swedish telecom equipment giant Ericsson’s net sales in the third quarter of 2024, up from 31% a year earlier. Chief Executive Börje Ekholm has criticized excessive regulation for discouraging the upgrading of Europe’s networks. Asked if Ericsson would move its head office to the U.S., Ekholm said: “We are Swedish based. But I think every company in Europe will need to think about this going forward.”

Like Europe, China faces headwinds; tariffs would be just one more.

China’s problem “is not Trump,” said Keyu Jin, a British-based economist specializing in the Chinese economy. “It’s the unemployment numbers. So many companies going under. So much debt the government owes to the private sector. The problems with young people. The ‘lying flat’ problem.”

For the full story see:

Greg Ip. “Davos Dissects Risks, Rewards of Trump.” The Wall Street Journal (Thursday, Jan. 23, 2025): A2.

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

(Note: the online version of the story has the date January 22, 2025, and has the title “Trump’s Arrival Brightens U.S. Outlook, Darkens Everyone Else’s.”)

Musk’s Defense of Free Speech Leads an E.V. Hater to Become a Tesla Cybertruck Lover

I admire Elon Musk’s energy, his ability to focus his mind in spite of distractions, and his ambitious entrepreneurship. The kid in me who got up early to watch Apollo space launches admires his ambition to take us to Mars. But what I admire most is his willingness to put that ambition at risk by spending $44 billion to buy Twitter (now X) in order to defend free speech. Too often entrepreneurs will put their dream above everything else. Musk put free speech above his dream.

And it’s not just the $44 billion. Many of his actual and potential Tesla customers are left-wing environmentalists who criticize his purchase of Twitter, and later his leading D.O.G.E. If that dislike leads to lower sales and profits at Tesla, then Musk will have even fewer funds to take us to Mars.

But the outcome is not certain. Maybe a society with free speech is one that is more likely to allow Musk the freedom to take trial-and-error risks to get us to Mars. And there is a small chance that Tesla will sell more cars because of his principled stand.

Tesla owners who supported Harris for President are buying bumper stickers to slap on their Teslas that read “I Bought This Before We Knew Elon Was Crazy” (Peyser 2024, p. D4).

But consider Berkeley Professor Morgan Ames who bought a Tesla in 2013. Even though she did not like Elon Musk’s views she later bought a second Tesla “because she couldn’t find other electric cars that matched Tesla’s capabilities” (Peyser 2024, p. D4).

And there is Oklahoman Sean Ziese who said to his wife: “If Elon is going to start supporting conservatives and free speech, I’m going to start supporting Elon, even though I hate E.V.s” (Ziese as quoted in Peyser 2024, p. D4). Then Ziese went out and bought himself a Tesla Cybertruck.

Ziese now concludes that his driving a Tesla Cybertruck is “a really neat experience. It never would have happened if Elon never would have bought X, and, you know, got free speech going again” (Ziese as quoted in Peyser 2024, p. D4).

The source article quoted above is:

Eve Peyser. “Tesla Owners Don’t Drive Away Quietly.” The New York Times (Thurs., December 19, 2024): D4.

(Note: the online version of the Eve Peyser article has the date Dec. 11, 2024, and has the title “For Tesla Owners, a Referendum Through Bumper Stickers.”)

Once You Experience Entrepreneurship “Everything Else Is Boring”

(p. B12) C. Richard Kramlich, an early investor in Silicon Valley who co-founded the investment giant New Enterprise Associates, helping to fuel the booming tech industry, died on Saturday [Feb. 1, 2025] at his home in Oakville, Calif., in the Napa Valley. He was 89.

. . .

He co-founded his own firm, New Enterprise Associates, or NEA, building it from an initial $16 million fund in the 1970s to one that now oversees investments of nearly $26 billion.

But he stood out among Silicon Valley’s sea of swashbuckling financiers because of his grace and kindness, said Scott Sandell, the chief investment officer and executive chairman of NEA.

. . .

When he was 13, Dick followed in his father’s entrepreneurial footsteps, starting his own “little lightbulb company,” he said in a 2015 interview with the Computer History Museum. “My father encouraged me to do it if I used my own money, and so I bought half a train car worth of lightbulbs from Sylvania Corporation” and resold them from his bedroom.

He added: “I come from three generations of entrepreneurs, and once you get it in your DNA, everything else is boring.”

. . .

. . . Mr. Kramlich met a pair of entrepreneurs who were both named Steve (Jobs and Wozniak). Their company, Apple Computer, was not as good as two other personal computer companies in the market, Mr. Kramlich said in 2015. But their sense of design and entrepreneurial spark were impressive. “They had pizazz,” he said, “where the other two companies were more engineering oriented.”

. . .

Venture capital investing is designed to absorb many losses in pursuit of one home-run deal, leaving a graveyard of failed start-ups along the way. But Mr. Kramlich was known for sticking with struggling investments long after others had abandoned them.

“He used to say, ‘Never say die,’” Mr. Sandell said.

In the early 1980s, Forethought, the start-up behind PowerPoint software, was about to run out of money, and NEA’s partners refused to pony up more. So Mr. Kramlich convinced his wife that they should pause work on the house they were building on Stinson Beach and use the cash to keep the company alive instead. The gamble paid off: In 1987, Microsoft bought Forethought for $14 million, and PowerPoint went on to become one of the world’s best-known software programs.

For the full obituary see:

Erin Griffith. “Richard Kramlich, 89, A Silicon Valley Investor Revered for Humaneness.” The New York Times (Wednesday, February 8, 2025): B12.

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

(Note: the online version of the obituary has the date Feb. 6, 2025, and has the title “C. Richard Kramlich, Early Investor in Silicon Valley, Dies at 89.”)

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.”