Category: Entrepreneurship

The Number of Alzheimer’s Patients Is Too Few to Populate the Many Promising Clinical Trials

When the F.D.A. mandates randomized double-blind clinical trials (RCTs) be successfully performed before allowing the use of a new drug, it also mandates that diverse promising drugs will never be tested. Some of those drugs might help or even cure Alzheimer’s. The reason that some diverse promising drugs will never be tested, as explained by Gina Kolata in the passage quoted below, is that there are too few diagnosed and willing Alzheimer’s patients to conduct the number and kind of RCTs that the government mandates, for all the promising drugs under development. What is the alternative to mandated RCTs? Allow physicians to prescribe drugs that have a promising rationale. If their patients benefit the physicians will continue to prescribe the drug and they will tell their colleagues.

(p. D1) The task facing Eli Lilly, the giant pharmaceutical company, sounds simple enough: Find 375 people with early Alzheimer’s disease for a bold new clinical trial aiming to slow or stop memory loss.

There are 5.4 million Alzheimer’s patients in the United States. You’d think it would be easy to find that many participants for a trial like this one.

But it’s not. And the problem has enormous implications for treatment of a disease that terrifies older Americans and has strained families in numbers too great to count.

The Global Alzheimer’s Platform Foundation, which is helping recruit participants for the Lilly trial, estimates that to begin finding participants, it will have to inform 15,000 to 18,000 people in the right age groups about the effort.

Of these, nearly 2,000 must pass the initial screening to be selected for further tests to see if they qualify.

Just 20 percent will meet the criteria to enroll in Lilly’s trial: They must be aged 60 to 89, have mild but progressive memory loss for at least six months, and have two types of brain scans showing Alzheimer’s is underway.

Yet an 80 percent screening failure rate is typical for Alzheimer’s trials, said John Dwyer, president of the foundation. There is just no good way to quickly diagnose the disease.

The onerous process of locating just 375 patients illustrates a grim truth: finding patients on whom to test new Alzheimer’s treatments is becoming an insurmountable obstacle — no matter how promising the trial.

With brain scans, lab tests and memory tests, the cost per diagnosis alone is daunting — as much as $100,000 for each person who ends up enrolled in a trial, Mr. Dwyer said — even before they begin the experimental treatment.

Complicating the problem, the number of trials has exploded in recent years. There (p. D4) are more than 100 Alzheimer’s studies looking for a whopping 25,000 participants, Mr. Dwyer said.

To begin filling them all, 37.5 million patients in the right age group would first have to be informed. Ten percent would be referred to a trial site for screening.

Just 4 percent will move forward with an evaluation, and of these, just over 17 percent will drop out, given the current rate, leaving roughly 125,000 to be screened. And with an 80 percent screening failure rate, that leaves 25,000 participants of the 37.5 million who were first informed.

The numbers make it clear: There’s no way scientists are going to find 25,000 participants for all of the Alzheimer’s trials that have been approved.

“The irony is that the science has never been more promising,” Mr. Dwyer said. “How many promising drugs will be abandoned or their evaluation seriously delayed? Some good science is going to be left on cutting-room floor.”

For the full story see:

Gina Kolata. “Alzheimer’s Trials Hit a Roadblock.” The New York Times (Tuesday, July 24, 2018 [sic]): D1 & D4.

(Note: the online version of the story has the date July 23, 2018 [sic], and has the title “For Scientists Racing to Cure Alzheimer’s, the Math Is Getting Ugly.”)

Scientists Invest Much Money and Time to Develop Machines Able to Sniff as Well as a Dog

Seven years have passed since the article quoted below predicted that sniffing devices would be available to clinicians in three to five years. I believe the prediction was premature. In the meantime, we should be making more and better use of dog noses to sniff out disease.

(p. D5) But not every physician’s nose is a precision instrument, and dogs, while adept at sniffing out cancer, get distracted. So researchers have been trying for decades to figure out how to build an inexpensive odor sensor for quick, reliable and noninvasive diagnoses.

. . .

“You’re seeing a convergence of technology now, so we can actually run large-scale clinical studies to get the data to prove odor analysis has real utility,” said Billy Boyle, co-founder and president of operations at Owlstone, a manufacturer of chemical sensors in Cambridge, England.

Mr. Boyle, an electronics engineer, formed the company with two friends in 2004 to develop sensors to detect chemical weapons and explosives for customers, including the United States government. But when Mr. Boyle’s girlfriend and eventual wife, Kate Gross, was diagnosed with colon cancer in 2012, his focus shifted to medical sensors, with an emphasis on cancer detection.

Ms. Gross died at the end of 2014. That she might still be alive if her cancer had been detected earlier, Mr. Boyle said, continues to be a “big motivator.”

. . .

A similar diagnostic technology is being developed by an Israeli chemical engineer, Hossam Haick, who was also touched by cancer.

“My college roommate had leukemia, and it made me want to see whether a sensor could be used for treatment,” said Mr. Haick, a professor at Technion-Israel Institute of Technology in Haifa. “But then I realized early diagnosis could be as important as treatment itself.”

. . .

In the United States, a team of researchers from the Monell Chemical Senses Center and the University of Pennsylvania received an $815,000 grant in February [2017] from the Kleberg Foundation to advance work on a prototype odor sensor that detects ovarian cancer in samples of blood plasma.

. . .

“We are trying to make the device work the way we understand mammalian olfaction works,” said Charlie Johnson, director of the Nano/Bio Interface Center at the University of Pennsylvania, who is leading the fabrication effort. “DNA gives unique characteristics for this process.”

In addition to these groups, teams in Austria, Switzerland and Japan also are developing odor sensors to diagnose disease.

“I think the fact that you’re seeing so much activity both in commercial and academic settings shows that we’re getting a lot closer,” said Cristina Davis, a biomedical engineer and professor at the University of California, Davis, who also is helping to develop an odor sensor to diagnose disease.

“My estimate is it’s a three- to five-year time frame” before such tools are available to clinicians, she added.

For the full story see:

Kate Murphy. “The Race to Sniff Out Disease.” The New York Times (Tuesday, May 2, 2017 [sic]): D5.

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

(Note: the online version of the story has the date May 1, 2017 [sic], and has the title “One Day, a Machine Will Smell Whether You’re Sick.”)

Ozempic Profits Poured into Massive Supercomputer Meant to Power AI for Future Drug Development

I think AI is currently being oversold. But I am very ignorant and could be wrong, so I favor a diversity of privately-funded bets on what will work to bring us future breakthrough innovations.

(p. B2) Two of the world’s most important companies are now in a partnership born from the success of their most revolutionary products. The supercomputer was built with technology from Nvidia—and money from the Novo Nordisk Foundation. The charitable organization has become supremely wealthy as the largest shareholder in Novo Nordisk, which means this project was made possible by the breakthrough drugs that have sent the Danish company’s stock price soaring.

To put it another way, it’s the first AI supercomputer funded by Ozempic.

It was named Gefion after the goddess of Norse mythology who turned her sons into oxen so they could plow the land that would become Denmark’s largest island.

. . .

Whatever you call it, Gefion is a beast. It is bigger than a basketball court. It weighs more than 30 tons. It took six months to manufacture and install. It also required an investment of $100 million.

. . .

When it’s fully operational, the AI supercomputer will be available to entrepreneurs, academics and scientists inside companies like Novo Nordisk, which stands to benefit from its help with drug discovery, protein design and digital biology.

For the full commentary see:

Ben Cohen. “It’s a Giant New Supercomputer That Might Transform an Entire Country.” The Wall Street Journal (Saturday, Nov. 2, 2024): B2.

(Note: ellipses added.)

(Note: the online version of the commentary has the date November 1, 2024, and has the title “Science of Success; The Giant Supercomputer Built to Transform an Entire Country—and Paid For by Ozempic.”)

Neuroscience Evidence that Our Brains Store Tacit Knowledge Separately from Articulate Formal Knowledge

(p. 10) On Aug. 25, 1953, a Connecticut neurosurgeon named William Beecher Scoville drilled two silver-dollar-size holes into the skull of Henry Molaison, a 27-year-old man with epilepsy so severe he had been prohibited from walking across stage to receive his high school diploma. Scoville then used a suction catheter to slurp up Molaison’s medial temporal lobes, the portion of the brain that contains both the hippocampus and the amygdala. The surgeon had no idea if the procedure would work, but Molaison was desperate for help: His seizures had become so frequent that it wasn’t clear if he would be able to hold down a job.

As it happened, Scoville’s operation did lessen Molaison’s seizures. Unfortunately, it also left him with anterograde amnesia: From that day forth, Molaison was unable to form new memories. Over the course of the next half-century, Patient H.M., as Molaison was referred to in the scientific literature, was the subject of hundreds of studies that collectively revolutionized our understanding of how memory, and the human brain, works. Before H.M., scientists thought that memories originated and resided in the brain as a whole rather than in any one discrete area. H.M. proved that to be false. Before H.M., all memories were thought of in more or less the same way. H.M.’s ability to perform dexterous tasks with increasing proficiency, despite having no recollection of having performed the tasks before, showed that learning new facts and learning to do new things happened in different places in the brain.

. . .

Several well-received books have already been written about Molaison, including one published in 2013 by Suzanne Corkin, the M.I.T. neuroscientist who controlled all access to and oversaw all research on ­Molaison for the last 31 years of his life.

What else, you might wonder, is there to say? According to the National Magazine Award-winning journalist Luke Dittrich, plenty. Dittrich arrived at Molaison’s story with a distinctly personal perspective — he is Scoville’s grandson, and his mother was Corkin’s best friend growing up — and his work reveals a sordid saga that differs markedly from the relatively anodyne one that has become accepted wisdom.

. . .

(p. 11) In her book, Corkin described Molaison as carefree and easygoing, a sort of accidental Zen master who couldn’t help living in the moment. In one of her papers, which makes reference to but does not quote from a depression questionnaire Molaison filled out in 1982, Corkin wrote that Molaison had “no evidence of anxiety, major depression or psychosis.” Dittrich located Molaison’s actual responses to that questionnaire, which had not been included in Corkin’s paper. Among the statements Molaison circled to describe his mental state were “I feel that the future is hopeless and that things cannot improve” and “I feel that I am a complete failure as a person.”

. . .

Molaison has long been portrayed as the victim of a surgeon’s hubris. Dittrich’s book, and the reaction to it, highlight why the lessons learned from his life cannot be limited to those stemming from a single act in the distant past. It’s easy to criticize the arrogance of researchers after they’re dead — and after we’ve already enjoyed the fruits of their work. With most of the principals in the tragedy of “Patient H.M.” now gone, the question at the core of Dittrich’s story — did the pursuit of knowledge conflict with the duty of care for a human being? — remains, in every interaction between scientist and vulnerable subject.

For the full review see:

Seth Mnookin. “Man Without a Past.” The New York Times Book Review (Sunday, September 4, 2016 [sic]): 10.

(Note: ellipses added.)

(Note: the online version of the review has the date Aug. 29, 2016 [sic], and has the title “A Book Examines the Curious Case of a Man Whose Memory Was Removed.”)

The book under review above is:

Dittrich, Luke. Patient H.M.: A Story of Memory, Madness, and Family Secrets. New York: Random House, 2016.

The earlier book by Corkin mentioned above is:

Corkin, Suzanne. Permanent Present Tense: The Unforgettable Life of the Amnesic Patient, H. M. New York: Basic Books, 2013.

The Ingenuity of Scientists and Entrepreneurs Can Find New Uses for the Previously Useless or Underutilitized

(p. D2) It may be unpleasant to contemplate the ultimate fate of all the material from your own body that you flush down the pipes. But it’s time we talk about biosolids — the disinfected leftovers from the water treatment process.

This sandy material contains nutrient-rich organic content that’s good for agriculture. But it also makes nice bricks, according to Abbas Mohajerani, a civil engineer at Royal Melbourne Institute of Technology University in Australia. He’s talking about the kind we use for building.

“Biosolids bricks look the same, smell the same and have similar physical and mechanical properties as normal fired clay bricks,” he said.

For the full story see:

JoAnna Klein. “Ultimate Recycling: When You Flushed The Toilet, They Made A Few Bricks.” The New York Times (Tuesday, February 5, 2019 [sic]): D2.

(Note: the online version of the story has the date Jan. 31, 2019 [sic], and has the title “You Flushed the Toilet. They Made Some Bricks.” Where the versions differ, the passages quoted above are from the more detailed online version.)

Mohajerani’s co-authored academic article proposing that human manure can usefully be turned into bricks for buildings is:

Mohajerani, Abbas, Aruna Ukwatta, Tristan Jeffrey-Bailey, Michael Swaney, Mohtashim Ahmed, Glen Rodwell, Simon Bartolo, Nicky Eshtiaghi, and Sujeeva Setunge. “A Proposal for Recycling the World’s Unused Stockpiles of Treated Wastewater Sludge (Biosolids) in Fired-Clay Bricks.” Buildings 9, no. 1 (2019): article #14.

Bioprospecting Tweaks Venom to Cure Diseases

(p. C3) One of the earliest treatments for ailments from gout to baldness was apitherapy, the medical application of bee venom, which was used in ancient Greece, China and Egypt. The ancient Greeks associated snakes and their venoms with medicine through the god Asclepius, whose followers prescribed venoms as cures and whose staff had a snake wrapped around it—the inspiration for the well-known symbol of medicine today.

Even so, scientists have only recently started to intensively explore the healing powers of venom. “In the 1980s and ’90s, people weren’t saying, ‘We should use venoms as a drug source,’ ” says Glenn King, a biologist at the University of Queensland in Brisbane, Australia. That changed at the beginning of this century: Scientists started to look at venoms as “complex molecular libraries,” he says. The bodily mechanisms that venoms derail often turn out to be the same ones that we need to manipulate to cure deadly diseases.

. . .

Chemical engineers have taken to mining living organisms, fine-tuning their chemicals to be more potent and precise. This process, known as bioprospecting, has had increasing appeal for scientists eager to tackle incurable diseases. Bioprospecting involves selecting a species with a type of venom known to have a specific effect on the human body—say, a snake with venom that causes a steep drop in blood pressure. The scientists will adjust the level of the toxin or tweak it biochemically so that it becomes not harmful but therapeutic.

. . .

Cancer is a natural target, and treatments may be lurking not just in scorpion venom but in the venoms of bees, snakes, snails, and even mammals. A compound derived from venomous shrews concluded a Phase I trial last year. This innovative peptide blocks a calcium channel called TRPV6, which is abundant in cancer cells, starving them of an essential element needed to grow and divide.

. . .

Each venomous animal is an artisanal mixologist, crafting chemical cocktails that can contain thousands of ingredients. The wealth of potential in venoms—each with its unique recipe—is hard to overstate.

For the full commentary see:

Christie Wilcox. “The Healing Powers of Venom.” The Wall Street Journal (Saturday, July 23, 2016 [sic]): C3.

(Note: ellipses added.)

(Note: the online version of the commentary was updated July 25, 2016 [sic], and has the title “The Healing Power of Venom.”)

The commentary quoted above is related to the author’s book:

Wilcox, Christie. Venomous: How Earth’s Deadliest Creatures Mastered Biochemistry. New York: Scientific American/Farrar, Straus and Giroux, 2016.

In Middle Ages the Less Credentialed Offered “Daily Care,” While “Experts” Theorized

(p. 12) A new book about medieval views on medicine helps explain the Oby nuns’ contentment with the cheapness of their lives. In “Medieval Bodies: Life and Death in the Middle Ages,” the British art historian Jack Hartnell tackles a difficult phenomenon: the medieval embrace of medical “theories that have since been totally disproven to the point of absurdity but which nevertheless could not have seemed more vivid or logical in the Middle Ages.”

The doctors of Europe and the Mediterranean were not practical specialists but rather scholars of Greek and Roman natural philosophy, which taught a theory of nature composed of four basic elements (fire, water, earth, air). Each was associated with differing levels of moisture and heat. The human body contained four viscous liquids or “humors”: phlegm, blood, yellow bile and black bile. A doctor’s job was to correct an uneven humoral balance, drying up perceived wetness with spices or relieving an excess of heat with cooling herbs.

While experts promulgated theory, daily care was mostly administered by midwives, apothecaries, dentists and the odd entrepreneurial carpenter. A local barber might puncture your neck to drain three pints of blood if you complained of a headache.

For the full review see:

Josephine Livingstone. “Death by a Thousand Cuts.” The New York Times Book Review (Sunday, January 5, 2020 [sic]): 12.

(Note: the online version of the review has the date Nov. 19, 2019 [sic], and has the title “Bad Bishops, Bloodletting and a Plague of Caterpillars.”)

The book under review is:

Hartnell, Jack. Medieval Bodies: Life and Death in the Middle Ages. New York: W. W. Norton & Company, 2019.

Formal and Tacit Knowledge Are Located in Different Parts of the Brain

Brenda Milner turned 106 on July 15, 2024.

(p. D5) At 98, Dr. Milner is not letting up in a nearly 70-year career to clarify the function of many brain regions — frontal lobes, and temporal; vision centers and tactile; the left hemisphere and the right — usually by painstakingly testing people with brain lesions, often from surgery. Her prominence long ago transcended gender, and she is impatient with those who expect her to be a social activist. It’s science first with Dr. Milner, say close colleagues, in her lab and her life.

Perched recently on a chair in her small office, resplendent in a black satin dress and gold floral pin and banked by moldering towers of old files, she volleyed questions rather than answering them. “People think because I’m 98 years old I must be emerita,” she said. “Well, not at all. I’m still nosy, you know, curious.”

. . .

Dr. Milner changed the course of brain science for good as a newly minted Ph.D. in the 1950s by identifying the specific brain organ that is crucial to memory formation.

She did so by observing the behavior of a 29-year-old Connecticut man who had recently undergone an operation to relieve severe epileptic seizures. The operation was an experiment: On a hunch, the surgeon suctioned out two trenches of tissue from the man’s brain, one from each of his medial temporal lobes, located deep below the skull about level with the ears. The seizures subsided.

But the patient, an assembly line worker named Henry Molaison, was forever altered. He could no longer form new memories.

. . .

In a landmark 1957 paper Dr. Milner wrote with Mr. Molaison’s surgeon, she concluded that the medial temporal areas — including, importantly, an organ called the hippocampus — must be critical to memory formation. That finding, though slow to sink in, would upend the accepted teaching at the time, which held that no single area was critical to supporting memory.

Dr. Milner continued to work with Mr. Molaison and later showed that his motor memory was intact: He remembered how to perform certain physical drawing tests, even if he had no memory of learning them.

The finding, reported in 1962, demonstrated that there are at least two systems in the brain for processing memory: one that is explicit and handles names, faces and experiences; and another that is implicit and incorporates skills, like riding a bike or playing a guitar.

“I clearly remember to this day my excitement, sitting there with H. M. and watching this beautiful learning curve develop right there in front of me,” Dr. Milner said. “I knew very well I was witnessing something important.”

. . .

For Dr. Milner, after a lifetime exploring the brain, the motive for the work is personal as well as professional. “I live very close; it’s a 10-minute walk up the hill,” she said. “So it gives me a good reason to come in regularly.”

For the full story see:

Benedict Carey. “At 98, ‘Still Nosy’ About the Brain.” The New York Times (Tuesday, May 16, 2017 [sic]): D5.

(Note: ellipses added.)

(Note: the online version of the story has the date May 15, 2017 [sic], and has the title “Brenda Milner, Eminent Brain Scientist, Is ‘Still Nosy’ at 98.”)

The “landmark 1957 paper” mentioned above is:

Scoville, William Beecher, and Brenda Milner. “Loss of Recent Memory after Bilateral Hippocampal Lesions.” Journal of Neurology, Neurosurgery & Psychiatry 20, no. 1 (Feb. 1957): 11-21.

Allowing Entrepreneurial Physicians to Improvise Can Save Patient Lives, Especially for Rare Conditions

The article quoted below makes the case, by example, that drugs that would be rejected based on early randomized double-blind clinical trials, can be revived by clever trial-and-error adjustments. Such improvisations saved the life of Magglio Boscarino, whose body began to develop antibodies that attacked the medicine that had been successfully treating his rare Pompe disease. Emil Freireich used trial-and-error adjustments to develop the chemo cocktail that cured many of childhood leukemia. He mentored Vincent DeVita who used trial-and-error adjustments to develop the chemo cocktails that cured many of Hodgkin’s lymphoma. Another approach, advocated by Dr. Ridker in a passage below, is to learn which patients will be able to take the drug with developing resistance to it–a form of personalized medicine that does not seem easily compatible with the oft-claimed “gold standard” of randomized double blind clinical trials.

(p. D1) The miracle treatment that should have saved Becka Boscarino’s baby boy almost killed him.

Doctors diagnosed her newborn son, Magglio, with Pompe disease, a rare and deadly genetic disorder that leads to a buildup of glycogen in the body. Left untreated, the baby would probably die before his first birthday.

There is just one treatment: a series of infusions. But after the boy received his fifth dose, he turned blue, stopped breathing and slipped into anaphylactic shock.

The problem? Eventually doctors discovered that Magglio’s body was producing antibodies to the very drug saving his life.

. . .

In a paper published in March [2017] by The New England Journal of Medicine, Pfizer reported that in the final phase of testing a new drug to lower cholesterol, many of the 30,000 patients taking it had stopped re-(p. D6)sponding to it.

Their cholesterol levels, which had plunged when they began taking the drug, were rising again. As it turned out, the subjects had begun making antibodies to the drug.

Pfizer was forced to stop the trial and pull the drug after investing billions of dollars.

. . .

By the time Magglio was 6 months old, he was weak and lacked muscle tone. Then came the diagnosis of Pompe disease and the beginning of his treatments, infusions with an enzyme his body was failing to make.

At first, Magglio improved. Within a few months, he was learning to sit up and to use his arms. His enlarged heart was shrinking. But his fifth treatment was a disaster.

He fell into anaphylactic shock and stopped breathing.

. . .

Magglio was hardly alone: Most babies with Pompe disease who received the only available treatment soon produced antibodies that rendered it useless.

“We tried everything, but these babies did not make it,” said Dr. Priya Kishnani, a professor of pediatrics at Duke University.

Dr. Kishnani realized she had to find a way to trick the immune system so it would leave the infused protein alone. Her idea was to give the babies a chemotherapy drug, rituximab, that wipes out cells that develop into antibody producers.

Along with it, she tried giving the children methotrexate, which destroys many of the body’s white blood cells, and infusions of antibodies from pooled donors’ serum so the children would have a way to fight off infections.

And for babies like Magglio, who already were making antibodies that blocked the drug they need, she added another drug — bortezomib — to eliminate those antibody-producing cells.

As the children’s immune systems were brought under control, the treatments began to work again. “It was breathtaking,” Dr. Kishnani said. “We were able to rescue these babies.”

. . .

At Brigham and Women’s Hospital in Boston, cardiologist Dr. Paul Ridker, who directed the Pfizer study, is taking a different tack.

He wants to do a large genetic study to see if he can predict which patients will develop antibodies to the Pfizer drug and perhaps to other drugs that the immune system might see as foreign.

“We probably have the best opportunity ever afforded to understand the cause of these antibodies,” Dr. Ridker said. “That would be very valuable for the development of future drugs if you could say, ‘This one patient out of 20 should not take this drug.’”

It would mean, too, that drugs that might have been abandoned could be developed for the patients who can tolerate them.

For the full story see:

Gina Kolata. “When the Body Rejects the Treatment.” The New York Times (Tuesday, May 16, 2017 [sic]): D1 & D6.

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

(Note: the online version of the story has the date May 15, 2017 [sic], and has the title “When the Immune System Thwarts Lifesaving Drugs.”)

The 2017 paper reporting the failed Pfizer clinical trial and mentioned above is:

Ridker, Paul M, Jean-Claude Tardif, Pierre Amarenco, William Duggan, Robert J. Glynn, J. Wouter Jukema, John J.P. Kastelein, Albert M. Kim, Wolfgang Koenig, Steven Nissen, James Revkin, Lynda M. Rose, Raul D. Santos, Pamela F. Schwartz, Charles L. Shear, and Carla Yunis. “Lipid-Reduction Variability and Antidrug-Antibody Formation with Bococizumab.” New England Journal of Medicine 376, no. 16 (April 20, 2017): 1517-26.

Noncredentialled Intense Outsider Duggan Brings Two Blockbuster Cancer Drugs to Market

(p. B11) There is a myth that making money in biotechnology stocks requires an advanced degree. But Bob Duggan, an avid surfer who never graduated from college, has proven that notion wrong. Twice.

Duggan’s latest investment, Summit Therapeutics SMMT 9.25%increase; green up pointing triangle, has become one of the industry’s greatest bets in recent years. The stock is up more than 1,000% in the past 12 months thanks to data from a late-stage trial that showed that its drug, Ivonescimab, beat Merck’s blockbuster cancer drug Keytruda in patients with a form of lung cancer. Duggan, who was already a billionaire before the Summit investment, is now worth about $16 billion, according to Forbes data.

There is much still to be worked out with the drug, which Summit licensed from Chinese biotech Akeso in 2022. For starters, investors are eager to see how it performs in global trials outside of China. What is remarkable about Summit’s success so far, though, is that this isn’t even Duggan’s first time making billions in biotech.

About 20 years ago, Duggan, a member of the Church of Scientology, began acquiring shares in a little-known biotech company called Pharmacyclics. He was drawn to the company’s cancer drug Xcytrin because of a personal loss: his son’s death from brain cancer. Pharmacyclics ultimately dropped the development of Xcytrin after multiple setbacks but went on to develop leukemia blockbuster Imbruvica. In 2015, AbbVie paid $21 billion for the company.

. . .

Nathan Vardi, author of “For Blood and Money,” which chronicles the development of Imbruvica and a competitor molecule, says that during his research he noticed that many people in biotech circles thought Duggan simply got lucky. While luck certainly plays a big role in the binary world of drug development, few would stick to that argument now.

So what is his secret? One thing Vardi points to is the ability to know when to retreat and when to go all in on an investment. “Duggan has a lifetime of experience making big bets with his own money on the line and figuring out when to hold or fold,” he wrote in an email. “Nobody gets these things completely right, but I think we have to admit he’s doing really well.”

Duggan, who built successful businesses in baking and robotics before jumping into biotechnology, suggests that the naivete of an outsider, combined with the intensity he brings to whatever he does, allowed him to try unconventional things. Nathan Vardi, author of “For Blood and Money,” which chronicles the development of Imbruvica and a competitor molecule, says that during his research he noticed that many people in biotech circles thought Duggan simply got lucky. While luck certainly plays a big role in the binary world of drug development, few would stick to that argument now.

So what is his secret? One thing Vardi points to is the ability to know when to retreat and when to go all in on an investment. “Duggan has a lifetime of experience making big bets with his own money on the line and figuring out when to hold or fold,” he wrote in an email. “Nobody gets these things completely right, but I think we have to admit he’s doing really well.”

Duggan, who built successful businesses in baking and robotics before jumping into biotechnology, suggests that the naivete of an outsider, combined with the intensity he brings to whatever he does, allowed him to try unconventional things.

For the full commentary see:

David Wainer. “Heard on the Street; An Outsider Crashes the Biotech Party.” The Wall Street Journal (Saturday, Sept. 24, 2024): B11.

(Note: ellipsis added.)

(Note: the online version of the commentary has the date September 23, 2024, and has the title “Heard on the Street; How a Surfer Who Never Finished College Became a Biotech Billionaire.” The sentence starting with “Léon Bottou” appears in the online, but not the print, version. Where there are small differences between the versions, the passages quoted above follow the online version.)

The book by Vardi mentioned above is:

Vardi, Nathan. For Blood and Money: Billionaires, Biotech, and the Quest for a Blockbuster Drug. New York: W. W. Norton & Company, 2023.

Refrigeration Preserves Three-Quarters of Food Americans Eat

(p. 10) Consider the improbable fact of the supermarket banana. In “Frostbite,” an exploration of the vast system known as the cold chain, the journalist Nicola Twilley follows the banana through a “seamless network of thermal control.” This series of refrigerated trucks, rail cars, shipping containers and warehouses ends in the ripening room, with its temperature gauges and gas immersion baths, all to meet our demand for ripe tropical fruit in all seasons. “Produce is a labor of love,” a warehouse owner tells her. “I tell people that working here is like a face tattoo — you’ve got to be really sure you want it.”

Twilley is a food and health reporter who has studied cold and refrigeration for many years.

. . .

The home refrigerator is barely a century old. Twilley is shown how simple it is to build one, and then tells us just why it took so long to figure out. Early efforts were bent toward making ice with giant and dangerous machinery; breakthroughs in the use of vacuum pumps and compressors “cut out the middleman” of the ice itself.

. . .

One story leads into another. A technology invented to dry photographic film at Eastman Kodak led first to the extraction of fish oil and, eventually, bagged salad.

. . .

. . .; I found this book hard to put down. The startling statistics — the cold chain preserves almost three-quarters of the food Americans eat; American households open the fridge door an average of 107 times a day — separate tales of unsung scientists. We meet the self-taught engineer Fred Jones, who invented the first mobile mechanical refrigeration unit, expanding the speed and size of the cold chain. Twilley also introduces the physicist Barbara Pratt, who perfected the refrigerated shipping container by traveling the world in one.

For the full review see:

Sallie Tisdale. “Freeze Frame.” The New York Times Book Review (Sunday, August 4, 2024): 9.

(Note: ellipses added.)

(Note: the online version of the review has the date June 24, 2024, and has the title “Have Refrigerators Spoiled Everything?”)

The book under review is:

Twilley, Nicola. Frostbite: How Refrigeration Changed Our Food, Our Planet, and Ourselves. New York: Penguin Press, 2024.