Author: Art Diamond

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Administration is set to recommend on Tuesday [June 28, 2022] whether to update existing Covid-19 vaccines to target a newer version of the coronavirus in a booster shot that Americans could get in the fall.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 But the virus is evolving so quickly that new vaccine formulations are out of date before such trials are even finished.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.”)

Rickets Is Now Rare Because Vitamin D Is Easy to Get

(p. A15) Rickets is one of those diseases that seem incredibly old-fashioned. It’s difficult to comprehend, now, how widespread this bone ailment once was: In some cities less than a century ago, 90% of children showed symptoms of rickets during wintertime. But ubiquity has its benefits. In “Starved for Light,” Christian Warren convincingly argues that modern medicine would be unrecognizable without the many advances in treatment that trace their roots to this once-widespread disease.

Rickets results from a lack of vitamin D, which we need to help shuttle calcium and phosphorus into our bones. Our bodies manufacture vitamin D whenever ultraviolet sunlight hits our skin; we can also get it through food. A deficiency in vitamin D causes the softening and bending of bones characteristic of rickets; victims are often left bowlegged or knock-kneed, or with curved spines or misshapen pelvises. The worst cases leave babies unable to crawl or even sit up straight.

. . .

Given how disgusting cod-liver oil tastes, some countries began combating rickets by adding vitamin D to milk in the 1930s—an odd choice, since milk contains no vitamin D naturally. (Amusingly, Mr. Warren calls the practice an “in uddero” health intervention.) The choice seems even odder, the author wryly notes, when there’s a much simpler solution to preventing rickets: going outside for a few minutes. Instead, we’ve effectively turned “a dairy product into a drug-delivery device,” severing the ancient interplay between “sun, skin, and bone.”

For the full review see:

Sam Kean. “Bookshelf; A Disease Of Deficiency.” The Wall Street Journal (Monday, Dec. 9, 2024): A15.

(Note: ellipsis added.)

(Note: the online version of the review has the date December 8, 2024, and has the title “Bookshelf; ‘Starved for Light’: A Disease of Deficiency.”)

The book under review is:

Warren, Christian. Starved for Light: The Long Shadow of Rickets and Vitamin D Deficiency. Chicago: University of Chicago Press, 2024.

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.

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.

W.H.O. Ignored Those Who Knew Covid Was Airborne

The article quoted below provides more evidence that the World Health Organization (W.H.O.) failed to protect world health during the Covid pandemic. Its funding and decision-making processes made failure highly likely.

In the absence of W.H.O, how can we learn quickly of potential pandemic threats from around the world? The Covid book co-authored by Ridley documents quick and effective Twitter (now X) networks that spread and evaluated Covid information. Maybe a proof of concept?

(p. D3) In early February 2020, China locked down more than 50 million people, hoping to hinder the spread of a new coronavirus. No one knew at the time exactly how it was spreading, but Lidia Morawska, an expert on air quality at Queensland University of Technology in Australia, did not like the clues she managed to find.

It looked to her as if the coronavirus was spreading through the air, ferried by wafting droplets exhaled by the infected. If that were true, then standard measures such as disinfecting surfaces and staying a few feet away from people with symptoms would not be enough to avoid infection.

Dr. Morawska and her colleague, Junji Cao at the Chinese Academy of Sciences in Beijing, drafted a dire warning. Ignoring the airborne spread of the virus, they wrote, would lead to many more infections. But when the scientists sent their commentary to medical journals, they were rejected over and over again.

“No one would listen,” Dr. Morawska said.

It took more than two years for the World Health Organization to officially acknowledge that Covid spread through the air.

For the full story see:

Carl Zimmer. “Covid Proved Airborne. Could Bird Flu Be, Too?” The New York Times (Tuesday, February 4, 2025): D3.

(Note: the online version of the story has the date February 3, 2025, and has the title “Could the Bird Flu Become Airborne?”)

The book co-authored by Ridley that I praise in my initial comments is:

Chan, Alina, and Matt Ridley. Viral: The Search for the Origin of Covid-19. New York: Harper, 2021.

S.B.A. “Forgives” Most Covid “Loans” Even Though at Least 17% Were Issued to Fraudsters

We used to handle suffering during crises by mutual aid societies or by giving philanthropy to those we know best–our friends and neighbors. The potential fraudster is less likely to defraud their brother or neighbor, than some unknown taxpayer in a distant state. And the local philanthropist is more likely to be able to judge which relative or neighbor will benefit from aid. Giving billions to fraudsters fueled the future inflation that ordinary decent citizens would latter struggle with.

If the federal government wanted to reduce the pain from the pandemic, the best way would have been to reduce the number, and shorten the length, of mandates. Handing so much money to fraudsters, with so little due diligence, is outrageous.

[Admission: I was the victim of identity theft when the S.B.A. gave a fraudster, using my name, tens of thousands of dollars for a potato farm supposedly run by me. Then the S.B.A. had the audacity to start sending me threatening letters about my alleged failure to pay back the loans they had given to the fraudster.]

(p. A1) When J. Bryan Quesenberry first learned that the federal government was sending out hundreds of billions of dollars to help businesses survive during the Covid-19 pandemic, he thought: “There’s going to be fraud here. There just has to be.”

A few months later, Mr. Quesenberry started sifting through a list of businesses that received Paycheck Protection Program loans, which were intended to help small businesses ravaged by the pandemic continue paying their employees. The Oregon lawyer said he knew businesses were not allowed to receive more than one loan during a single round, so he searched for “double dippers.”

He soon found dozens of businesses across the country that appeared to improperly obtain P.P.P. loans. During the summer of 2020, Mr. Quesenberry started suing those firms to try to help the government recover funds.

“It just blows my mind,” Mr. Quesenberry said. “That’s tax money that comes out of your pocket and that comes out of my pocket.”

As federal officials try to retrieve billions in stolen pandemic relief funds, private citizens are scouring public data, company websites and social media pages to help identify potential cases. Those who have filed suits say they are motivated by the desire to root out wrongdoers and expose corporate fraud.

But there is also a strong financial incentive. Under the False Claims Act, private citizens can file lawsuits on behalf of the federal government against those who may have defrauded the United States. If the government recovers funds, those citizens can typically earn between 15 and 30 percent of that amount.

. . .

(p. A15) The armchair sleuthing highlights how widespread pandemic fraud was and how federal investigators have struggled to keep up with it. In its haste to stave off an economic crisis and provide immediate aid to Americans, Washington distributed billions of dollars with few strings and little oversight. The Small Business Administration’s inspector general has estimated that more than $200 billion — or at least 17 percent of the pandemic loans the agency distributed — was awarded to “potentially fraudulent actors.” The majority of P.P.P. loans have been forgiven by the federal government.

While federal investigators have gone after some of the biggest perpetrators of fraud, limited resources have hindered their ability to go after the estimated thousands of people who improperly took government money.

. . .

Some private citizens said that it often took hours to investigate leads, and that they were unearthing cases that might otherwise slip through the cracks. Although Mr. Quesenberry said he relied primarily on information available on the internet to build cases, he said it was a time-intensive process that often required combing through government websites, Yelp pages, news articles and LinkedIn profiles. He said he thought he added value because he was pulling together evidence to “paint the picture of fraud.”

Mr. Quesenberry has earned more than $400,000 from 10 cases that have helped the federal government recover more than $3 million, according to a review of documents from U.S. attorney’s offices. Mr. Quesenberry said he had been investigating pandemic fraud for about four and a half years and was now working on his cases full time.

. . .

Hadar Susskind, the president and chief executive of Americans for Peace Now, said officials thought they had qualified for the loan because they did not consider the nonprofit to be a political organization. He said they had settled because it could have been costlier to go to court.

Mr. Susskind said he had never met Mr. Abrams, but he believed the complaint was “very much ideologically motivated” because of the nonprofit’s work to promote Israeli-Palestinian peace.

In an email, Mr. Abrams said: “In America these anti-Israel organizations have the right to spin, distort or even outright lie about Israel. However, they do not have the right to subsidize their activities with government monies for which they were not eligible.”

Mr. Abrams said he had long done other activist work, including recently representing a Jewish high school student who was the victim of antisemitic bullying. He said that he did not charge fees in those matters, and that the “whistle-blower cases do generate significant revenue so things more or less balance out.”

For the full story see:

Madeleine Ngo. “Fraud Hunters Earn Windfalls Tied to Covid.” The New York Times (Monday, November 25, 2024): A1 & A15.

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

(Note: the online version of the story has the date Nov. 23, 2024, and has the title “They Investigated Pandemic Fraud, Then Earned Thousands.”)

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.

Dying Cells in a Tumor May Be a Cause of Metastasis

I have read that most cancer deaths occur due to metastasis. Cancer that remains limited to an original tumor can often be managed as a long-term chronic condition. If Cheung (below) is right that dying cells in a tumor are an important cause of metastasis, then does that suggest that senolytic drugs that kill senescent cells, may be useful in delaying or stopping metastasis?

(p. D7) Much about how tumors metastasize — spread and take up residence in faraway sites — still remains a mystery, said Dr. Kevin Cheung, an associate professor of hematology and oncology at the Fred Hutch Cancer Center in Seattle, Washington. His research recently showed that dead and dying cells within a tumor might create an environment that makes it easier for living tumor cells to get out and spread.

For the full story see:

Nina Agrawal. “Exploring Some Big Questions About Cancer.” The New York Times (Tuesday, February 4, 2025): D7.

(Note: the online version of the story has the date Jan. 29, 2025, and has the title “7 Big Questions About Cancer, Answered.”)

The academic article co-authored by Cheung and mentioned above is:

Yamamoto, Ami, Yin Huang, Brad A. Krajina, Margaux McBirney, Andrea E. Doak, Sixuan Qu, Carolyn L. Wang, Michael C. Haffner, and Kevin J. Cheung. “Metastasis from the Tumor Interior and Necrotic Core Formation Are Regulated by Breast Cancer-Derived Angiopoietin-Like 7.” Proceedings of the National Academy of Sciences 120, no. 10 (2023): e2214888120.