Category: Books

Large Medical Databases Would Allow Discovery and Testing of Causal Patterns of Diseases

After considerable effort, as of the writing of the article quoted below, Dr. Wagle has only been able to gather data on 375 of the roughly 155,000 metastatic breast cancer patients in the U.S. Many have long complained about the difficulty in obtaining and consolidating medical records. Exploring the reasons would take a longer article than the one quoted below. Part of the story is the Health Insurance Portability and Accountability Act of 1996 (HIPAA). It was passed to protect patient privacy, but it served as cover for medical institutions to stonewall patients, policy makers, and other medical institutions from obtaining information. The institutions make the process of obtaining medical information as slow, opaque, and onerous as possible. Partly this is a result of the general inefficiency of medical bureaucracy. Regulations limit competition among medical institutions and limit entrepreneurship, allowing inefficiencies to persist. To those who are mission-oriented within the bureaucracy, providing records may seem a lower priority than issues affecting current medical care. But also, restricting information may increase patient lock-in. Ceteris paribus, a patient may choose to stay at an institution that has long health records for the patient. Also, providing less information to third parties may make the institution less vulnerable to criticism and law suits.

Ideally, Dr. Wagle’s database would serve as a modern day version of the dusty hospital archives that Dr. William Coley pursued to find a pattern among the patients who had been spontaneously cured of their cancer in the late 1800s.

From personal experience I can say that getting patient information is easier now than it was 30 years ago, at least for the patient to obtain their own information.

An important side point is Dr. Wagle’s emphasis on the value of obtaining patient narratives, in addition to coded data. Narratives allow the discovery of additional causes or effects, beyond what the initial coders include in the coded data. Gary Klein makes this point in defending the value of what he calls “stories” (Klein 2017).

(p. D4) Dr. Nikhil Wagle thought he had a brilliant idea to advance research and patient care.

Dr. Wagle, an oncologist at the Dana Farber Cancer Institute in Boston, and his colleagues would build a huge database that linked cancer patients’ medical records, treatments and outcomes with their genetic backgrounds and the genetics of their tumors.

The database would also include patients’ own experiences. How ill did they feel with the treatments? What was their quality of life? The database would find patterns that would tell doctors what treatment was best for each patient and what patients might expect.

The holdup, he thought, would be finding patients. Instead, the real impediment turned out to be gathering their medical records.

. . .

Dr. Wagle is making data from medical records and patients’ experiences public as he gets them. After 2 1/2 years, though, he is disappointed by how little there is to share.

The patient who inspired his project had a lethal form of thyroid cancer. She was expected to die in a few months. In desperation, doctors gave her a drug that by all accounts should not have helped.

To everyone’s surprise, her tumors shrank to almost nothing, and she survived. She was an “extraordinary responder.”

Why? It turned out that her tumor had an unusual mutation that made it vulnerable to the drug.

And that got Dr. Wagle thinking. What if researchers had a database that would allow them to find these lucky patients, examine their tumors, and discover genetic mutations that predict which drugs will work?

. . .

Dr. Wagle decided to build a database, starting with metastatic breast cancer, his specialty. There are about 155,000 metastatic breast cancer patients in the United States. He would use social media, online forums and advocacy groups to reach out to patients for their records.

. . .

Startlingly, faxing “is the standard,” Ms. McGillicuddy said, for medical records requests.

The process can be frustrating. Fax numbers can be out of date. Some medical centers will not accept electronic patient signatures on the permission forms.

Sometimes, the medical centers just ignore the request — and the second request. In the end, Ms. McGillicuddy said, the project gets fewer than half the records it requests.

Then comes the laborious task of extracting medical information from the records and entering it into the database. A faxed medical record may be 100 or 200 pages long.

So far, the breast cancer project has received 450 records for 375 patients. (Each patient tends to have more than one record, because the women typically are seen at more than one medical center.)

For the full story see:

Gina Kolata. “Concealing New Cancer Treatments.” The New York Times (Tuesday, May 22, 2018 [sic]): D4.

(Note: ellipses added.)

(Note: the online version of the story has the date May 21, 2018 [sic], and has the title “New Cancer Treatments Lie Hidden Under Mountains of Paperwork.” Where the wording of the versions differs, the passages quoted above follow the online version.)

Gary Klein’s main book that I praise in my initial comments is:

Klein, Gary A. Sources of Power: How People Make Decisions. 20th Anniversary ed. Cambridge, MA: The MIT Press, 2017.

The Academic “Herd Mindset” May Be the Cause of What Elon Musk Calls the “Woke Mind Virus”

(p. B3) “I listen to podcasts about the fall of civilizations to go to sleep,” Musk said this past week during an appearance at the Milken Institute conference. “So perhaps that might be part of the problem.”

One provocateur, in particular, has caught his attention of late: Gad Saad, a marketing professor at Concordia University in Montreal, and author of the book “The Parasitic Mind: How Infectious Ideas Are Killing Common Sense.”

. . .

Saad wrote that “The Parasitic Mind” was inspired, in part, by his experience in academia, where he described a herd mindset that chastised innovative thinkers. He described pushback he encountered, including his ideas being labeled as “sexist nonsense” and his efforts to use “biologically-based theorizing” to explain consumer behavior being dismissed as too reductionistic.

“The West is currently suffering from such a devastating pandemic, a collective malady that destroys people’s capacity to think rationally,” the 59-year-old Saad wrote at the beginning of his book. “Unlike other pandemics where biological pathogens are to blame, the current culprit is composed of a collection of bad ideas, spawned on university campuses, that chip away at our edifices of reason, freedom, and individual dignity.”

. . .

Another inspiration for his book, Saad writes, was his experience as a boy fleeing with other Jews from his home in Lebanon during that country’s civil war. In the book, he detailed some of the horrors he experienced, including the kidnapping of his parents.

. . .

Musk has said his concerns about Woke Mind Virus, his way of labeling progressive liberal beliefs that he says are overly politically correct and stifling to public debate and free speech, helped fuel his desire to acquire the social-media company Twitter turned X in late 2022.

For the full commentary see:

Tim Higgins. “His Musings Fuel Musk’s Nightmares.” The Wall Street Journal (Monday, May 13, 2024): B3.

(Note: ellipses added.)

(Note: the online version of the commentary has the date May 11, 2024, and has the title “The Man Whose Musings Fuel Elon Musk’s Nightmares.” The last two ellipses above indicate where I omit sentences that appeared in the longer online version, but not in the print version.)

The Saad book that has influenced Elon Musk is:

Saad, Gad. Parasitic Mind: How Infectious Ideas Are Killing Common Sense. New York: Regnery Publishing, 2020.

The Patterns in Unexpected Cancer Cures Can Yield Actionable Insight

The method for fighting cancer discussed by Gina Kolata in the passages quoted below, is similar to the method that led William Coley to first develop immunotherapy in the late 1800s. Coley searched the archives of his hospital, seeking any cases in which cancer seemed to have been spontaneously cured. When he had a few cases he looked for a common feature that might explain the cures. He found that in each case the patient had a severe viral or bacterial infection. When the patient’s immune system cured them of the infection, it also, as a desirable side-effect, cured them of the cancer. In the case of the rare ovarian discussed below, Dr. Levine hypothesizes that the common feature of the rare single-mutation cancers that can be cured by immunotherapy drugs, is that there is a mutated master gene that turns on and off other genes–creating an abnormal variation that somehow alerts the immune system of the presence of tumor cells that should be attacked. (The article quoted below is now over six years old–I wonder if in those six years Dr. Levine has found evidence to support, modify, or reject his hypothesis?) [My memory is foggy on this, but I think Steven Rosenberg may also have applied a similar method after he encountered a case of spontaneous cancer cure when he was working in a veteran’s hospital early in his career–see Rosenberg and Barry, 1992.]

Notice that the four patients only were cured because they had the courage and boldness to ask their oncologist to try a therapy that the standard protocol said would fail. And notice that the four patients only were cured because they had oncologists who had the courage and boldness to violate accepted protocols. Or maybe something besides courage and boldness explains the oncologists’ actions. Maybe the oncologists were practicing medicine in countries were hospitals, regulatory agencies, and health insurance companies did not exert as much pressure to follow the protocol as is exerted in the United States? (I wonder if there is enough information publicly available to check this possibility.)

Notice that instead of searching a dusty archive, Levine joined a patient ovarian cancer Yahoo discussion group. Patients were trying to be in control of their cancers, and unlike some doctors, Levine had the humility to think he could learn from what these activist patients reported. Citizen science is a resource to be used, not a distraction to be tamped down or ridiculed. [Amy Dockser Marcus defends citizen science, and gives an extended example, in her We the Scientists.]

Finally note that the method pursued by Coley and Levine can yield genuine actionable knowledge. Randomized double-blind clinical trials are not the only sources of knowledge.

Gina Kolata has written many thought-provoking articles. I hope to follow-up on this one sometime.

(p. D1) No one expected the four young women to live much longer. They had an extremely rare, aggressive, and fatal form of ovarian cancer. There was no standard treatment.

The women, strangers to one another living in different countries, asked their doctors to try new immunotherapy drugs that had revolutionized treatment of cancer. At first, they were told the drugs were out of the question — they would not work against ovarian cancer.

Now it looks as if the doctors were wrong. The women managed to get immunotherapy, and their cancers went into remission. They returned to work; their lives returned to normalcy.

. . .

“We need to study the people who have a biology that goes against the conventional generalizations.”

Four women hardly constitutes a clinical trial. Still, “it is the exceptions that give you the best insights,” said Dr. Drew Pardoll, who directs the Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins Medicine in Baltimore.

The cancer that struck the young women was hypercalcemic small cell ovarian cancer, which typically occurs in a woman’s teens or 20s. It is so rare that most oncologists never see a single patient with it.

. . .

(p. D3) Women with this form of ovarian cancer were sharing news and tips online in a closed Yahoo group. Dr. Levine asked to become part of the group and began joining the discussions. There he discovered patients who had persuaded doctors to give them an immunotherapy drug, even though there was no reason to think it would work.

The women reported that their tumors shrank immediately.

. . .

Lung cancer, a genetic type of colorectal cancer and melanoma have huge numbers of mutations, and immunotherapy drugs often are successful in treating them. Cancers of the prostate, pancreas, breast, ovaries — and most other tumors — carry few mutations.

“These are the cancers that rarely respond,” Dr. Pardoll said.

The idea that the drugs might work against something like hypercalcemic ovarian cancer, which is fueled by just one genetic mutation, just made no sense.

“For the vast majority of cancers, there is an amazingly clean correlation between response to therapy and mean mutational load,” Dr. Pardoll said.

. . .

And then came a handful of women with a rare ovarian cancer. Oriana Sousa, 28, a psychologist in Marinha Grande, Portugal, was one of them.

She found out she had cancer in December 2011.

. . .

For the next four years, Ms. Sousa’s doctors tried to control the cancer, giving her rounds of chemotherapy, radiotherapy and surgery. But every time, new tumors emerged.

. . .

Things are different now. In 2015, she finally persuaded a doctor to give her an immunotherapy drug, nivolumab. Immediately, her tumors shrank and continued shrinking as she continued with the drug — so much that her doctors now say she has no evidence of disease. Life has returned to normal.

. . .

What saved her? Dr. Eliezer M. Van Allen, a cancer researcher at Dana-Farber Cancer Institute, has come across one clue.

He found that a gene mutated in kidney cancer was sort of a master regulator of other genes, controlling which were turned on and when. But the regulated genes were normal and did not produce proteins that the immune system might recognize as abnormal.

Nonetheless, patients responding to immunotherapy were the ones with the master gene mutation. “We saw this result and weren’t sure what to make of it,” he said.

Dr. Levine and his colleagues found the same phenomenon in patients with hypercalcemic ovarian cancers. One explanation, he and Dr. Van Allen said, is that the immune system may recognize that cells in which genes are erratically turning on and off are dangerous and should be destroyed.

“That is strictly hypothesis,” Dr. Levine cautioned.

For the full story see:

Gina Kolata. “Cured Unexpectedly.” The New York Times (Tuesday, February 20, 2018 [sic]): D1 & D3.

(Note: ellipses added.)

(Note: the online version of the story has the date Feb. 19, 2018 [sic], and has the title “Doctors Said Immunotherapy Would Not Cure Her Cancer. They Were Wrong.”)

The academic article co-authored by Dr. Levine that reports on the remission of a rare ovarian cancer in four women is:

Jelinic, Petar, Jacob Ricca, Elke Van Oudenhove, Narciso Olvera, Taha Merghoub, Douglas A. Levine, and Dmitriy Zamarin. “Immune-Active Microenvironment in Small Cell Carcinoma of the Ovary, Hypercalcemic Type: Rationale for Immune Checkpoint Blockade.” Journal of the National Cancer Institute 110, no. 7 (2018): 787-90.

The book by Marcus that I praise above is:

Marcus, Amy Dockser. We the Scientists: How a Daring Team of Parents and Doctors Forged a New Path for Medicine. New York: Riverhead Books, 2023.

Rosenberg’s encounter with a case of spontaneous cancer cure, that I mention above, can be found somewhere early in:

Rosenberg, Steven A., and John M. Barry. The Transformed Cell: Unlocking the Mysteries of Cancer. New York: G.P. Putnam’s Sons, 1992.

Government Gave “40 Years of Seriously Incorrect Advice” on Trans Fats

The government’s advice often turns out to be wrong. That is an added argument for not giving the government the power to enforce its advice through mandatory regulations. (“Added” to the fundamental argument based the right to free choice.)

[In May 2021 Nicholas Wade, the author of the review quoted below, showed enormous courage in being one of the first few to risk cancelation by presenting a cogent case that Covid leaked from a Wuhan lab.]

(p. C9) Rachel Carson rightly complained in “Silent Spring” that farmers were sloshing far too many harmful pesticides into the environment. But she took aim at the wrong one. DDT, a mild and enormously effective pesticide, helped rid the United States of malaria and its benefits, if more discriminately pursued, could have outweighed its costs.

The overstrict verdict against DDT is an instance of the harms that can ensue when scientific evidence is ignored. This and other cases described by Paul A. Offit in “Pandora’s Lab: Seven Stories of Science Gone Wrong” raise provocative questions about the reasons that science is misused in modern society.

. . .

Another case of medical advice based on insufficient data is that of dietary fat. As Dr. Offit tells the story, in the 1970s the government advised cutting down on fat consumption. In the 1980s the message changed. Unsaturated fats were good; only saturated fats were bad: Eat margarine, not butter. But then it turned out that unsaturated fats came in two forms, known to chemists as “cis” and “trans,” and that “trans fats” were appallingly active promoters of heart disease. Margarine and hydrogenated vegetable cooking oils, whose use had been encouraged, were rich in trans fats. After 40 years of seriously incorrect advice, trans fats were mostly eliminated from the American diet only in 2012.

. . .

Besides his overconfidence in the checking mechanisms of science, Dr. Offit goes too easy on the motives of those who abuse science. Environmentalists, for instance, are interested in achieving political results, not in distracting scientific caveats and uncertainties, which they do their best to suppress. It is their propensity to take everything to excess that leads to obscurantist positions, such as irrational fear of genetically modified crops.

For the full review see:

Nicholas Wade. “A Little Knowledge.” The Wall Street Journal (Saturday, April 8, 2017 [sic]): C9.

(Note: ellipses added.)

(Note: the online version of the review was updated April 7, 2017 [sic], and has the same title as the print version.)

The book under review is:

Offit, Paul A. Pandora’s Lab: Seven Stories of Science Gone Wrong. Washington, D.C.: National Geographic, 2017.

“Most Published Research Findings Are False”

(p. C1) How much of biomedical research is actually wrong? John Ioannidis, an epidemiologist and health-policy researcher at Stanford, was among the first to sound the alarm with a 2005 article in the journal PLOS Medicine. He showed that small sample sizes and bias in study design were chronic problems in the field and served to grossly overestimate positive results. His dramatic bottom line was that “most published research findings are false.”

The problem is especially acute in laboratory studies with animals, in which scientists often use just a few animals and fail to select them randomly. Such errors inevitably introduce bias. Large-scale human studies, of the sort used in drug testing, are less likely to be compromised in this way, but they have their own failings: It’s tempting for scientists (like everyone else) (p. C2) to see what they want to see in their findings, and data may be cherry-picked or massaged to arrive at a desired conclusion.

A paper published in February [2017] in the journal PLOS One by Estelle Dumas-Mallet and colleagues at the University of Bordeaux tracked 156 biomedical studies that had been the subject of stories in major English-language newspapers. Follow-up studies, they showed, overturned half of those initial positive results (though such disconfirmation rarely got follow-up news coverage). The studies dealt with a wide range of issues, including the biology of attention-deficit hyperactivity disorder, new breast-cancer susceptibility genes, a reported link between pesticide exposure and Parkinson’s disease, and the role of a virus in autism.

Reviews by pharmaceutical companies have delivered equally grim numbers. In 2011, scientists at Bayer published a paper in the journal Nature Reviews Drug Discovery showing that they could replicate only 25% of the findings of various studies. The following year, C. Glenn Begley, the head of cancer research at Amgen, reported in the journal Nature that he and his colleagues could reproduce only six of 53 seemingly promising studies, even after enlisting help from some of the original scientists.

With millions of dollars on the line, industry scientists overseeing clinical trials with human subjects have a stronger incentive to follow high standards. Such studies are often designed in cooperation with the U.S. Food and Drug Administration, which ultimately reviews the findings. Still, most clinical trials produce disappointing results, often because the lab studies on which they are based were themselves flawed.

For the full essay see:

Harris, Richard. “Dismal Science In the Search for Cures.” The Wall Street Journal (Saturday, April 8, 2017 [sic]): C1-C2.

(Note: bracketed year added.)

(Note: the online version of the essay was updated April 7, 2017 [sic], and has the title “The Breakdown in Biomedical Research.”)

The essay quoted above is adapted from Mr. Harris’s book:

Harris, Richard. Rigor Mortis: How Sloppy Science Creates Worthless Cures, Crushes Hope, and Wastes Billions. New York: Basic Books, 2017.

The 2005 paper by Ioannidis mentioned above is:

Ioannidis, John P. A. “Why Most Published Research Findings Are False.” PLoS Medicine 2, no. 8 (2005): 696-701.

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.

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.

“I’m Sick of It, I’m Leaving” Are First Words of Children in Primitive Village Routinely Eating Grubs and Starch Tasting Like “Gummy Mucous”

(p. C9) As she tended soldiers during the Crimean War, a British nurse found herself appalled by the wretched, vermin-infested conditions at the army’s hospital in Istanbul. She began collecting figures showing the devastating effects of the filth and the dramatic benefits of the sanitary improvements she implemented. Her presentation on the need for cleaner care facilities, published in 1858, led to reforms that ultimately saved millions of lives and increased life expectancy in the U.K. Florence Nightingale, it turns out, was a pioneering data scientist.

Data, when used to reveal the value of hospital hygiene or the harm of tobacco smoke, can be a vital force for good, as Tim Harford reminds us in “The Data Detective.”

. . .

Imprecise and inconsistent definitions are one source of confusion.  . . .  . . . “infant mortality,” a key data point for public health, varies depending on the specific time in fetal development when the line is drawn between a miscarriage and a tragically premature birth.

. . .

To learn from data, it’s essential to present it well. For her analysis after the Crimean War, Florence Nightingale created one of the first infographics, using shrewdly designed diagrams to tell a memorable story. From the outset, she regarded visually compelling data displays as indispensable to making her arguments.

. . .

An authentically open mind can make a difference, Mr. Harford says, noting that the top forecasters tend to be not experts but earnest learners who constantly take in new data while challenging and refining their hypotheses. Data, Mr. Harford concludes, can illuminate and inform as well as distract and deceive. It’s often maddeningly hard to know the difference, but it would be unforgivable not to try.

For the full review see:

Wade Davis. “To Hear a Dying Tongue.” The Wall Street Journal (Saturday, Aug. 10, 2019 [sic]): C9.

(Note: ellipses added.)

(Note: the online version of the review has the date Aug. 9, 2019 [sic], and has the title “‘A Death in the Rainforest’ Review: To Hear a Dying Tongue.”)

The book under review is:

Kulick, Don. A Death in the Rainforest: How a Language and a Way of Life Came to an End in Papua New Guinea. Chapel Hill, NC: Algonquin Books, 2019.

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.

Rationality-Defender Stigler Saw Voting as Irrational, but Did It Anyway

Nobel Prize winner George Stigler contributed to the Public Choice literature and was a staunch defender of rationality. One example would be his paper with Gary Becker, “De Gustibus Non Est Disputandum.” One popular, much discussed conclusion of some public choice theorists is that it is irrational to vote. The argument goes that the marginal effect of one vote is almost always miniscule, so the expected benefit to the voter is equally miniscule. On the other hand, the time and effort it takes to vote are always more than miniscule. So the expected costs of voting exceed the expected benefits. Ergo it is irrational to vote. When I was a graduate student, taking courses in philosophy and economics, and for a couple of years as a post-doctoral fellow, I frequently stopped by the office of the Journal of Political Economy where Stigler was an editor. I believe it was there that I heard Stigler, definitely on an election day, say “Here I go to do something irrational.”

Stigler is well-known for his humorous biting comments. These could be tough on others. But this story shows that they also could be directed at himself.

I do not know if anyone has fully solved the paradox of the irrationality of voting. I guess you would have to say something about how the effects of all good people ceasing to vote would be far from marginal and far from good.

I once mentioned to distinguished Public Choice theorist Dwight Lee that a positive result of the personal benefits of voting being miniscule to a voter, is that the voter was freed from voting their personal narrow self-interest, and could vote their conscience about what served the general good. (Maybe something like what Rawls hoped for behind his “veil of ignorance” in A Theory of Justice.) I believe that Dwight told me that he already published a paper that expressed this positive result, but I never took the time to look for that paper.