Category: Entrepreneurship

Some Medical Researchers Seek Patient Input on Execution of Studies

In the story quoted below some medical researchers are seeking patient involvement in studies, but I was disappointed to realize that the involvement is mostly superficial with the aim of getting patient agreement to be part of the study. The researchers in the story still see a big divide between patients and doctors. Doctors see patterns and create hypotheses to be tested. Patients, if they want, can stand by posters, and make minor suggestions on the execution of study design.

I suggest, more ambitiously, that patients sometimes, if allowed, can see patterns and create hypotheses. They have the incentive, the skin in the game. And sometimes they have direct experience on what works and what does not work.

(p. R6) Joel Nowak, a 66-year-old Brooklyn, N.Y., resident with metastatic prostate cancer, knows a lot about cancer research. Over the years, he has contributed blood, saliva and medical information to studies in hopes of helping investigators battle the disease.

But something has nagged at him. Almost always, Mr. Nowak says, investigators want data, “but you never hear from them again.”

Then he was asked to join a new endeavor that is trying to change that—by making participants into partners.

The Metastatic Prostate Cancer Project, launched by the Broad Institute of MIT and Harvard and the Dana-Farber Cancer Institute in Boston, is trying to give participants a bigger stake in studies by asking them for input, inviting them to events and keeping them updated on progress.

. . .

Patients are . . . invited for a tour of the Broad Institute to see its gene-sequencing machines or to meet and share ideas with researchers, says Nikhil Wagle, director of the umbrella initiative.

Dr. Wagle thinks the approach has led to unusually fast and large enrollment. More than 4,000 people enrolled in the breast-cancer project and over 290 in the angiosarcoma initiative. In just a few weeks, more than 200 signed up for the prostate-cancer study.

. . .

Keeping participants up-to-date is another concern for researchers. It is an issue close to home for Corrie Painter, principal investigator of the angiosarcoma project at the Broad and one of the creators of all three of the institute’s cancer initiatives.

Dr. Painter draws on her experiences as a cancer survivor and research participant in shaping interactions with patients. She was diagnosed with angiosarcoma nearly eight years ago. Dr. Painter says that after her diagnosis, like many patients, she felt frustrated at being treated more “as passive recipients of care rather than part of the process of discovery.”

. . .

Meanwhile, some patients are taking the opportunity to play a larger role in shaping studies. Mr. Nowak, for one, joined a patient advisory council of the prostate-cancer project. Members communicate on videoconferences, email exchanges and in person. During a meeting at the Broad, researchers showed a prototype for the saliva kits that were going to be mailed to patients to collect samples.

The advocates told researchers to take “Metastatic Prostate Cancer Project” off the box. “There are a lot of men who don’t want other people to know they have cancer,” says Mr. Nowak.

For the full story see:

Amy Dockser Marcus. “Researchers Look to Enlist Patients as Partners.” The Wall Street Journal (Monday, Feb. 25, 2018 [sic]): R6.

(Note: ellipses added.)

(Note: the online version of the story has the date Feb. 25, 2018 [sic], and has the title “Medical Researchers Look to Enlist Patients as Partners.” The last two ellipses above indicate where I omit sentences that appeared in the longer online version, but not in the print version.)

Marcus’s story is related to her book:

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.

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.

If Immortality Does Not Violate the Laws of Physics, Entrepreneurs Can Achieve It

The late Nobel-Prize-winning physicist and idiosyncratic Richard Feynman also said something similar to the quote attributed to Arram Sabeti below.

I do not believe that Feynman was explicitly named, or had any lines, in the movie “Opennheimer,” but you can see his character in the background of one scene playing the bongo drums. Perhaps he was eccentric, but I liked his views on methodology and his unpretentious, optimistic, and straightforward spirit.

(p. 9) As the longevity entrepreneur Arram Sabeti told The New Yorker: “The proposition that we can live forever is obvious. It doesn’t violate the laws of physics, so we can achieve it.”

For the full commentary see:

Dara Horn. “The Men Who Want to Live Forever.” The New York Times, SundayReview Section (Sunday, January 28, 2018 [sic]): 9.

(Note: the online version of the commentary has the date Jan. 25, 2018 [sic], and has the same title as the print version.)

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.

Bacteria Can Be Genetically Reprogrammed to Cure Cancer Tumors in Mice

Reprograming bacteria to cure cancer tumors is a novel and plausible approach, but there are many other novel and plausible approaches. Cancer is a complicated and diverse disease; maybe we will eventually see “cancer” as many different diseases. We have too much uncertainty to mandate one centrally planned approach. Plus citizens have the right to keep the money they earn and to choose how to spend that money. We should keep taxation and regulations low so that diverse funders can follow their judgements to fund diverse approaches.

(p. D3) Scientists have used genetically reprogrammed bacteria to destroy tumors in mice. The innovative method one day may lead to cancer therapies that treat the disease more precisely, without the side effects of conventional drugs.

The researchers already are scrambling to develop a commercial treatment, but success in mice does not guarantee that this strategy will work in people. Still, the new study, published on Wednesday in the journal Nature Medicine, is a harbinger of things to come, said Dr. Michael Dougan, an immunologist at Massachusetts General Hospital in Boston.

. . .

Our immune cells can sometimes recognize and destroy cancer cells without assistance. But tumors may hide from the immune system by taking advantage of a gene called CD47.

Normally, the gene makes a protein that studs the surface of red blood cells, a kind of sign that reads, “Don’t Eat Me.” Immune cells see it, and pass by healthy red blood cells.

. . .

In recent years, scientists have been developing antibodies that can attach to CD47 proteins on cancer cells, masking the “Don’t Eat Me” sign. Then the body’s immune cells learn to recognize the cancer cells as dangerous and attack.

. . .

Nicholas Arpaia, an immunologist at Columbia University in New York, and Tal Danino, a synthetic biologist, wondered if they could use bacteria to turn the immune system against cancer cells — but from within tumors, rather than from outside.

. . .

The researchers inserted the nanobody gene into the bacteria, turning them into nanobody factories. Then the team injected five million of the altered microbes into mouse tumors.

The bacteria were also programmed to commit mass suicide. After they established themselves and multiplied, 90 percent of the bacteria ripped themselves apart, spilling out nanobodies. The nanobodies attached to CD47 proteins on the cancer cells, robbing them of their camouflage.

. . .

Dr. Danino co-founded a company, GenCirq, that is exploring using these reprogrammed bacteria to treat cancer. Dr. Arpaia is on the leadership board.

Their goal is to treat some forms of metastatic cancer with a pill of programmed bacteria. In earlier research, Dr. Danino and colleagues showed that bacteria swallowed by mice can reach the liver and invade tumors there.

For the full commentary see:

Carl Zimmer. “Matter; Bacteria, Altered to Destroy Cancer.” The New York Times (Tuesday, July 9, 2019 [sic]): D3.

(Note: ellipses added.)

(Note: the online version of the commentary has the date July 3, 2019 [sic], and has the title “Matter; New Weapons Against Cancer: Millions of Bacteria Programmed to Kill.”)

The paper in PLOS Biology co-authored by Thomas Stoeger and mentioned above is:

Chowdhury, Sreyan, Samuel Castro, Courtney Coker, Taylor E. Hinchliffe, Nicholas Arpaia, and Tal Danino. “Programmable Bacteria Induce Durable Tumor Regression and Systemic Antitumor Immunity.” Nature Medicine 25, no. 7 (July 2019): 1057-63.

Potential Malaria Breakthrough Drug Forgotten and Now Ignored Due to Its Chemical Relative and Its Venue of Invention

Progress in science, like progress everywhere, is not inevitable. Progress often requires champions or entrepreneurs to persist in overcoming obstacles. In the case of DFDT, the obstacles arise due to the drug’s association with the chemical DDT and with Nazi Germany, the first of which is unjustly reviled and the second of which is justly reviled. But DFDT should not be judged by either its relatives or its venue of origins It should be judged by its efficacy against malaria, and by its effects, if any, on the environment.

(p. D1) In postwar Allied intelligence reports examined by Dr. Ward and his colleagues, German scientists claimed their insecticide, now called DFDT, was more effective than DDT. Allied officials dismissed those assertions as fanciful, especially given the deplorable behavior of Hoechst, the German chemical manufacturer that developed the insecticide, during the war. The company had forced residents of countries occupied by Germany to work in its factories, and it tested drugs on concentration camp prisoners.

The insecticide was forgotten for decades.

Now, work by Dr. Ward and his colleagues, reported this month [Oct. 2019] in an article in the Journal of the American Chemical Society, appears to corroborate the German claims. The forgotten compound killed mosquitoes in as little as one-fourth the time as DDT.

. . .

(p. D4) Conceivably the more lethal DFDT could be used in even smaller, possibly safer doses. A new option could allow public health officials to rotate insecticides and thwart the resistance to DDT in many mosquitoes today.

“It’s exciting and desperately needed,” said Duane J. Gubler, an emeritus professor in the emerging infectious diseases program at Duke University and the National University of Singapore Graduate Medical School. He was not involved in the study.

But will anyone today risk the time and money needed to determine whether DFDT could be a safe and effective tool against malaria as well as other mosquito-borne diseases like Zika, dengue and yellow fever?

“Donors, governments, they just don’t want the backlash, even if it’s not wholly justified,” said Bart Kahr, Dr. Ward’s colleague at N.Y.U. and an author of the paper.

. . .

The N.Y.U. chemists started the research with no interest in insecticides whatsoever.

They were studying materials that crystallize in a twisted helical pattern. One of the ways to identify such molecules is to scan the internet for images of crystals made by hobbyists. DDT, they found, exhibited the characteristic pinwheel gradients of a helical crystal when illuminated with polarized light.

Jingxiang Yang, a postdoctoral researcher at N.Y.U., started growing DDT crystals and found not only the expected crystals but also more jumbled, chaotic patterns.

“There was some organized and some crazy,” Dr. Kahr said. “We didn’t expect the other stuff, and that other stuff turned out to be a different arrangement of molecules in the crystal. That form wasn’t known to science.”

That led to the next set of experiments. “Since we have two forms,” Dr. Kahr said, “it was natural to ask, which of these forms was the historical killer of insects?”

It turned out that the chaotic form of DDT is deadlier.

As they were going through early scientific data on DDT, the N.Y.U. chemists found mentions of DFDT.

The compound, difluoro-diphenyl-trichloro-ethane is the same molecule as DDT, except with fluorine atoms replacing two of the chlorines.

The Germans developed DFDT at least in part to avoid paying the licensing fees for DDT to the Swiss. It is also possible that the chemical ingredients for DFDT, although considerably more expensive at the time than those for DDT, may have been more readily available in wartime Germany.

. . .

Dr. Kahr wonders: If DFDT had displaced DDT, would the 1955 push have succeeded in bringing malaria under control before resistance set in? “What if this compound wasn’t forgotten,” he said. “What would the world be like? Science doesn’t go as linearly as the general public thinks it does.”

For the full story see:

Kenneth Chang. “Old Mix To Fight Malaria?” The New York Times (Tuesday, October 22, 2019 [sic]): D1 & D4.

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

(Note: the online version of the story was updated Oct. 22, 2019 [sic], and has the title “A Nazi Version of DDT Was Forgotten. Could It Help Fight Malaria?” Where the more detailed online version differs from the print version, the passages quoted above follow the print [sic] version.)

The academic article co-authored by Ward, Kahr, and others, and mentioned above, is:

Zhu, Xiaolong, Chunhua T. Hu, Jingxiang Yang, Leo A. Joyce, Mengdi Qiu, Michael D. Ward, and Bart Kahr. “Manipulating Solid Forms of Contact Insecticides for Infectious Disease Prevention.” Journal of the American Chemical Society 141, no. 42 (2019): 16858-64.

When the Highly Restrictive Enrollment Criteria for Clinical Trials Steal Hope from the Innocently Desperate, It “Just Feels Unjust”

Muscular dystrophy is sometimes called “Duchenne.” The full name of the disease is “Duchenne muscular dystrophy.” When I was a student at Monroe elementary school a classmate named Frank Goldsberry played on the basketball team. In high school he was in a wheel chair with muscular dystrophy. When the high school principle, Howard Crouch, proposed to do away with the academic honor of valedictorian on the ground that there was some arbitrariness in who received it, I argued that to do would be to diminish the honor given to academic achievement. Crouch relented. It turned out that our valedictorian was Frank Goldsberry. He died a few years later in his early 20s. Frank’s father told my mother that Frank was grateful to me for speaking up. Howard Crouch had a point, but I am glad that after working hard under dire circumstances, Frank received the award.

The F.D.A. should stop mandating randomized double-blind clinical trials (RCTs) so that those who have muscular dystrophy can seek any therapy that they, their parents, and their physicians believe has promise. Not everyone will be cured, but we will learn what works through a Bayesian process of trial and error. More parents and boys will be allowed to hold on to hope.

(p. D1) Lucas was 5 before his parents, Bill and Marci Barton of Grand Haven, Mich., finally got an explanation for his difficulties standing up or climbing stairs. The diagnosis: muscular dystrophy.

Mr. Barton turned to Google.

“The first thing I read was, ‘no cure, in a wheelchair in their teens, pass in their 20s,” Mr. Barton said. “I stopped. I couldn’t read any more. I couldn’t handle it.”

Then he found a reason to hope. For the first time ever, there are clinical trials — nearly two dozen — testing treatments that might actually stop the disease.

The problem, as Mr. Barton soon discovered, is that the enrollment criteria are so restrictive that very few children qualify. As a result, families like the Bartons often are turned away.

. . .

Ryan and Brooke Saalman know how hard it can be to know what to do. “We did a lot of praying,” said Ms. Saalman, mother of two boys with Duchenne in Columbus, Ga.

They decided to enroll their oldest son, Jacob, 6, in a trial of a highly experimental drug.

. . .

. . . they discovered that gene therapy may be irreversible. And if it didn’t work, Ja-(p. D3)cob would be ineligible for an even more promising approach in the future: gene editing, to snip out the deadly mutation that causes Duchenne, an effort now in preclinical development.

. . .

The Bartons found out about a gene-therapy trial at Nationwide Children’s Hospital in Columbus, Ohio, testing a treatment by Sarepta Therapeutics.

They watched a miraculous video of a little boy struggling to walk up a flight of stairs before treatment — and then doing it easily afterward.

“This was what we were hoping for,” Mr. Barton said.

Lucas was the right age, and he seemed to qualify. But testing showed that he carries antibodies to the virus used to deliver the treatment. It would not work for him.

The Bartons were drained, devastated. And for now, there is no other trial that Lucas qualifies for.

“I had my put my hopes into this,” Mr. Barton said. “It was the miracle.”

Dr. Jeffrey Bigelow, a neurologist, and his wife, Alexis Bigelow, of Millcreek, Utah, hoped against hope that their son Henri, 8, would qualify for the only gene therapy trial that will accept boys his age.

Then the Bigelows found out that enrollees of Henri’s age have to be able to lie down and then stand up with their hands at their sides in less than 10 seconds.

It took Henri 10 seconds to do that last spring, when he was evaluated for another trial. Now it would probably take him 20 seconds, his father said.

“It feels like Henri is being punished for losing the ability to stand up from the ground too soon,” Dr. Bigelow said.

He also worries about older boys with Duchenne who are lucky enough to still walk. They are shut out from the trial because they are not yet in wheelchairs. And other trials won’t accept boys that old.

“These are boys who, like Henri, desperately need the treatment, and if they don’t get it in the next one to two years, likely will be confined to a wheelchair, to never walk again,” Dr. Bigelow said.

“This just feels unjust.”

For the full story see:

Gina Kolata. “One Shot To Qualify For Hope.” The New York Times (Tuesday, March 26, 2019 [sic]): D1 & D3.

(Note: ellipses added.)

(Note: the online version of the story has the date March 25, 2019 [sic], and has the title “For Many Boys With Duchenne Muscular Dystrophy, Bright Hope Lies Just Beyond Reach.”)

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.