F.D.A. Chief Sets Low Bar for Cancer Progress–Three Months of Longer Life Is “A Major Therapeutic Advance”

F.D.A. regulations have slowed progress toward curing cancer. Rather than reduce regulations, the head of the F.D.A. redefines “progress” as occurring when a new drug increases average lifespan by a mere three months.

(p. D3) Was there a moment when you realized a new era had begun?

It was a gradual thing. I wish I could say I had an “a-ha” moment.

I remember though, one of our first approvals of a PD-1 drug (a drug that unleashes the immune system to fight cancer). A division director sent me an email with a survival curve for patients in a study. It was a Friday afternoon. I saw it and I nearly fell off my seat. It was such a positive study for these patients with squamous cell lung cancer. They lived an average of six months with standard chemotherapy. With the new drug they lived 9.2 months.

I called the division director and said, “What are we going to do to expedite this?”

We had to get a submission from the drug company and that can take several months. Sometimes it takes six months and sometimes up to a year because of the voluminous amount of material that must be provided.

We got the submission in a couple of months. Nivolumab was approved in March of 2015.

It was a major therapeutic advance. These were people who heretofore had few therapeutic options.

. . .

. . ., my regret? I won’t be here in 2049, my presumed 50th F.D.A. anniversary.

I would love to see what oncology looks like given the rapid changes in the past 25 years. Hang on tight. The velocity of innovation will only increase.

For the full review see:

Gina Kolata, interviewer. “F.D.A.’s Cancer Chief Is Forward Focused.” The New York Times (Tuesday, November 19, 2024): D3.

(Note: ellipses added.)

(Note: the online version of the review has the date Nov. 8, 2024, and has the title “He’s the F.D.A.’s Cancer Chief, Not a Fortune Teller.” The question is from the interviewer Gina Kolata.
The rest of the words are quoted from the answers of Dr. Richard Pazdur.)

Peppermint at One Time Required a Prescription, While Strychnine Was Sold Over-the-Counter

I suspect I would not much like the Remaking the American Patient book–it seems to blame capitalism for all of the ills of the healthcare system. But it does include one compelling example of the limitations of government regulation of drugs: allowing strychnine while restricting peppermint.

(p. D3) Medical historians who focus on the conquest of dire diseases serve up narratives of progress and triumph. Not Ms. Tomes, a professor of history at Stony Brook University, who has chosen to examine instead the health care experience of average healthy citizens, the great silent majority whose lives are punctuated by a variety of minor ills and only the occasional major calamity.

. . .

Are you perplexed by our regulatory chaos, with layer upon layer of well-meaning but persistently ineffective efforts to guarantee the safety of medical services? It turns out we come from a long tradition of such inadequacy: Patient safety has been the holy grail for everyone, long sought, never achieved.

Drug regulatory efforts have been inconsistent and confusing. (At one point in the 1940s, peppermint drops were available by prescription, while strychnine could be freely purchased by anyone).

For the full review see:

Abigail Zuger, M.D. “When Patients Became Purchasers.” The New York Times (Tuesday, January 26, 2016 [sic]): D3.

(Note: ellipsis added.)

(Note: the online version of the review has the date Jan. 23, 2016 [sic], and has the title “Review: ‘Remaking the American Patient’.”)

The book under review above is:

Tomes, Nancy. Remaking the American Patient: How Madison Avenue and Modern Medicine Turned Patients into Consumers, Studies in Social Medicine. Chapel Hill: The University of North Carolina Press, 2016.

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.”)

Some Mostly Useless Procedures “Enrich the Pockets of Medical Practitioners”

(p. D5) Many of the procedures people undergo to counter chronic knee pain in the hopes of avoiding a knee replacement have limited or no evidence to support them. Some enrich the pockets of medical practitioners while rarely benefiting patients for more than a few months.

I wish I had known that before I had succumbed to wishful thinking and tried them all.

. . .

Serious questions are now being raised about the benefits of the arthroscopic procedures that millions of people endure in hopes of delaying, if not avoiding, total knee replacements.

The latest challenge, published in May [2017] in BMJ by an expert panel that systematically reviewed 12 well-designed trials and 13 observational studies, concluded that arthroscopic surgery for degenerative knee arthritis and meniscal tears resulted in no lasting pain relief or improved function.

Three months after the procedure, fewer than 15 percent of patients experienced at best “a small or very small improvement in pain and function,” effects that disappeared completely within a year.

As with all invasive procedures, the surgery is not without risks, infection being the most common, though not the only, complication.

Furthermore, the panel added, “Most patients will experience an important improvement in pain and function without arthroscopy.”

For the full commentary see:

Jane E. Brody. “Personal Health; What I Wish I’d Known About My Knees.” The New York Times (Tuesday, July 4, 2017 [sic]): D5.

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

(Note: the online version of the commentary has the date July 3, 2017 [sic], and has the same title as the print version.)

The May 2017 BMJ academic review article mentioned above, is:

Siemieniuk, Reed A. C., Ian A. Harris, Thomas Agoritsas, Rudolf W. Poolman, Romina Brignardello-Petersen, Stijn Van de Velde, Rachelle Buchbinder, Martin Englund, Lyubov Lytvyn, Casey Quinlan, Lise Helsingen, Gunnar Knutsen, Nina Rydland Olsen, Helen Macdonald, Louise Hailey, Hazel M. Wilson, Anne Lydiatt, and Annette Kristiansen. “Arthroscopic Surgery for Degenerative Knee Arthritis and Meniscal Tears: A Clinical Practice Guideline.” BMJ 357 (May 10, 2017).

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.”)

“Most Published Research Findings Are False”

(p. 10) 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.

Even With Quick Cheap Malaria Lab Tests, Dog Noses Can Still “Be Very Useful”

(p. D4) A small pilot study has shown that dogs can accurately identify socks worn overnight by children infected with malaria parasites — even when the children had cases so mild that they were not feverish.

The study, a collaboration between British and Gambian scientists and the British charity Medical Detection Dogs, was released last week at the annual convention of the American Society of Tropical Medicine and Hygiene.

. . .

The new study, its authors said, does not mean that dogs will replace laboratories. Inexpensive rapid tests for malaria have been available for over a decade; more than 200 million people in dozens of countries are infected each year.

But for sorting through crowds, malaria-sniffing dogs could potentially be very useful.

Some countries and regions that have eliminated the disease share heavily trafficked borders with others that have not. For example, South Africa, Sri Lanka and the island of Zanzibar have no cases but get streams of visitors from Mozambique, India and mainland Tanzania.

And when a region is close to eliminating malaria, dogs could sweep through villages, nosing out silent carriers — people who are not ill but have parasites in their blood that mosquitoes could pass on to others.

. . .

If just one chemical indicated cancer or malaria, “we’d have discovered it by now,” said Claire Guest, who founded Medical Detection Dogs in 2008 and oversaw dog training in the study. “It’s more like a tune of many notes, and the dogs can pick it up.”

For the full commentary see:

Donald G. McNeil Jr. “Global Health; Sniffing Out Malaria in Its Tracks.” The New York Times (Tuesday, November 6, 2018 [sic]): D4.

(Note: ellipses added.)

(Note: the online version of the commentary has the date Nov. 5, 2018 [sic], and has the title “Global Health; Dogs Can Detect Malaria. How Useful Is That?”)

A later-published version of the initial “small pilot study” discussed above is:

Guest, Claire, Margaret Pinder, Mark Doggett, Chelci Squires, Muna Affara, Balla Kandeh, Sarah Dewhirst, Steven V. Morant, Umberto D’Alessandro, James G. Logan, and Steve W. Lindsay. “Trained Dogs Identify People with Malaria Parasites by Their Odour.” The Lancet Infectious Diseases 19, no. 6 (June 2019): 578-80.

Democratic New York Department of Environmental Conservation Raids Home, Seizing and Killing P’Nut, Internet-Famous Orphan Pet Squirrel

(p. A15) . . . P’Nut was an internet-famous squirrel who was seized and euthanized by New York State wildlife agents last week . . .

. . .

. . . Elon Musk lionized the rodent as a Jedi martyr — more powerful in death than in life.

“RIP Peanut,” read a post on a Trump campaign’s official TikTok account on Sunday [Nov. 3, 2024]. “Needlessly murdered by Democrat bureaucrats in New York.”

. . .

P’Nut’s journey from cowboy-hat-wearing Instagram cutie to conservative lightning rod began on Oct. 30 [2024]. That was when New York State Department of Environmental Conservation officers, responding to what the agency said were anonymous complaints, arrived at the home of his owner, Mark Longo, in Pine City in Chemung County. In New York State, it is illegal to house animals considered wildlife without a special permit; Mr. Longo has said he was in the process of applying for one.

D.E.C. agents seized the squirrel, which Mr. Longo had cared for ever since its mother was hit by a car seven years ago. Agents also apprehended Fred the raccoon. At some point, the squirrel bit a person involved with the investigation, according to a statement put out by the agency, leading its officers to swiftly euthanize both animals to test for rabies.

In tearful online posts, Mr. Longo and his wife, Daniela, railed against tax dollars being spent to kill the animals they considered pets.

. . .

In Macon, Ga., Marjorie Taylor Greene, the Georgia congresswoman, spoke at a Trump rally and compared Peanut’s fate to that of Laken Riley, a local woman who was killed by a Venezuelan man who had once lived in New York. She blamed Democrats in New York City, which is 200 miles from Pine City, for euthanizing P’Nut.

“Democrats in New York City went in and raided a home to kill a squirrel,” Ms. Greene said. “Yet it was the same State of New York that let the criminal illegal alien go that came to Georgia that murdered our very own Laken Riley.”

. . .

. . . the animals’ owner, Mr. Longo, 34, considers himself apolitical. He is not registered with any political party and said he has never voted in his life.

. . .

He has spent the past days grieving, he said, and when he found a stray almond that Peanut had sneaked into his pocket, he burst into tears. He was just grateful, he said, “that somebody is giving P’Nut a voice.”

“I don’t care if it was the blue side or the red side,” he added. “Somebody on this planet is fighting for my animals.”

For the full story see:

Sarah Maslin Nir. “Death of a Pet Squirrel Is a G.O.P. Rallying Cry.” The New York Times (Wednesday, November 6, 2024): A15.

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

(Note: the online version of the story has the date Nov. 4, 2024, and has the title “How the Death of a Celebrity Squirrel Became a Republican Rallying Cry.”)

240 Million Year Old Case of Cancer in Amniotes (“Group That Includes Reptiles, Birds and Mammals”)

Paleontologists have discovered a femur bone with cancer that belonged to a 240 million-year-old ancestor of turtles. The case is the oldest (so far) case of cancer in amniotes, which is the “group that includes reptiles, birds and mammals.” In the past some have suggested that cancer is a side effect of human economic development. Yara Hariday, a current paleontologist and former medical student says: “What makes this really cool is that now we understand that cancer is basically a deeply rooted switch that can be turned on or off, . . . . It’s not something that happened recently in our evolution. It’s not something that happened early in human history, or even in mammal history” (p. D6).

For the full story see:

Asher Elbein. “A Diagnosis 240 Million Years Too Late.” The New York Times (Tuesday, February 12, 2019 [sic]): D6.

(Note: ellipsis added.)

(Note: the online version of the story has the date Feb. 7, 2019 [sic], and has the title “The Patient Had Bone Cancer. The Diagnosis Arrived 240 Million Years Too Late.”)

The academic study co-authored by Hariday on the ancient cancer is:

Haridy, Yara, Florian Witzmann, Patrick Asbach, Rainer R. Schoch, Nadia Fröbisch, and Bruce M. Rothschild. “Triassic Cancer—Osteosarcoma in a 240-Million-Year-Old Stem-Turtle.” JAMA Oncology 5, no. 3 (March 2019): 425-26.

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.

Universally Applicable Egg Guidelines Are Impossible Because Some Are Hypo-Responders and Others Are Hyper-Responders to Dietary Cholesterol

(p. D5) “Intervention studies have shown that moderate egg consumption doesn’t appreciably raise cholesterol levels,” Dr. Hu [chairman of nutrition and epidemiology at the Harvard T.H. Chan School of Public Health] said. “Low to moderate consumption of three or four eggs a week doesn’t appear to have a major effect on blood cholesterol unless the person has high cholesterol or Type 2 diabetes.”

He added, “In most previous studies of healthy people, moderate egg consumption was not associated with a significant increase in cardiovascular risk.” However, among 21,275 participants in the Physicians’ Health Study who were followed for more than 20 years, those who ate one or more eggs a day were more likely to develop heart failure than those who ate eggs infrequently.

“Contradictory findings among different studies are not unusual — it’s part of the scientific process,” Dr. Hu said. “In forming guidelines, you have to look at the totality of evidence rather than overreact to a single new study.”

Zachary S. Clayton, author of a comprehensive review of research on egg consumption and heart health published in Nutrition in 2017, said in an interview that giving two eggs a day for 12 weeks to healthy people didn’t raise any of their cardiovascular risk factors and “actually decreased their triglyceride levels.”

But, Dr. Clayton, a postdoctoral fellow in nutrition at the University of Colorado, Boulder, said, “It’s important to distinguish between hypo-responders and hyper-responders to dietary cholesterol. If someone is a hyper-responder, eating two eggs a day would increase the risk of cardiovascular disease.”

For the full commentary see:

Jane E. Brody. “Cracking the Code on Eggs and Your Diet.” The New York Times (Tuesday, April 23, 2019 [sic]): D5.

(Note: bracketed words quoted from earlier in the commentary.)

(Note: the online version of the commentary has the date April 22, 2019 [sic], and has the title “Should You Be Eating Eggs?”)

Clayton’s co-authored academic review article on the effects of egg consumption, mentioned above, is:

Clayton, Zachary S., Elizabeth Fusco, and Mark Kern. “Egg Consumption and Heart Health: A Review.” Nutrition 37 (May 2017): 79-85.