Category: Methodology

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.”)

“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.

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.

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.

After a Century an Important Serendipitous Health Hunch Is Pursued

All of us (you, me, dogs, and physicians) observe patterns all the time. Some of the patterns, if pursued, could make the world much better. When a physician observes a pattern, even one they cannot articulately describe or justify, they could change their practices, curing more patients, saving more lives. But they are constrained from deviating from mainstream protocols by government regulations, insurance company rules, hospital administrators, and potential lawsuits. How many serendipitous discoveries that would help us flourish are delayed a century, or even totally snuffed out?

(p. C2) . . . my eye was drawn to a new study in the New England Journal of Medicine finding that hysterosalpingography cured some cases of infertility. Hystero refers to the uterus. Salpingo, I knew, relates to the fallopian tubes that funnel eggs to the uterus. Ography relates to imaging—but how could taking a picture of reproductive organs cure anything?

Doctors use hysterosalpingography to see if there are blockages that could be causing fertility problems.

. . .

To look at blockages, technicians have to introduce a teaspoon or two of a dye that’s opaque to X-rays. How that material is introduced, it turns out, is the key to the procedure’s effect on childlessness.

. . .

Smaller studies had given the scientists an idea of what to do next. They randomly chose half of the women to get the X-ray-opaque dye dissolved in oil, while the other half got the dye in water.

. . .

In an average of three months, whether treated or not, about 40% of the women receiving the oil-based dye material became pregnant, while only 29% of the women who got the water-based dye material conceived.

Hysterosalpingography is exactly a century old this year. Luckily, some astute doctors guessed that the method of taking a picture was having an unintended fertility effect, and now research has backed this up. Such serendipity in medical progress is neatly captured by a saying of the great French biologist Louis Pasteur about the need to be ready to see the unexpected: “In the fields of observation, chance only favors the prepared mind.”

The realization that supposedly inert oil could help to fulfill some couples’ dreams has built slowly. No one knows exactly how it works.

For the full commentary see:

Melvin Konner. “Mind & Matter; Can Just Taking a Picture Help to Treat Infertility?” The Wall Street Journal (Saturday, July 29, 2017 [sic]): C2.

(Note: ellipses added.)

(Note: the online version of the commentary has the date July 26, 2017 [sic], and has the same title as the print version. The Latin words in the first quoted sentence appear in italics in the original version.)

The New England Journal of Medicine article discussed in the passages above is:

Dreyer, Kim, Joukje van Rijswijk, Velja Mijatovic, Mariëtte Goddijn, Harold R. Verhoeve, Ilse A.J. van Rooij, Annemieke Hoek, Petra Bourdrez, Annemiek W. Nap, Henrike G.M. Rijnsaardt-Lukassen, Catharina C.M. Timmerman, Mesrure Kaplan, Angelo B. Hooker, Anna P. Gijsen, Ron van Golde, Cathelijne F. van Heteren, Alexander V. Sluijmer, Jan-Peter de Bruin, Jesper M.J. Smeenk, Jacoba A.M. de Boer, Eduard Scheenjes, Annette E.J. Duijn, Alexander Mozes, Marie J. Pelinck, Maaike A.F. Traas, Machiel H.A. van Hooff, Gijsbertus A. van Unnik, Cornelia H. de Koning, Nan van Geloven, Jos W.R. Twisk, Peter G.A. Hompes, and Ben W.J. Mol. “Oil-Based or Water-Based Contrast for Hysterosalpingography in Infertile Women.” New England Journal of Medicine 376, no. 21 (May 25, 2017): 2043-52.

Dogs Pass a Smell Test–Locating Ancient Buried Human Remains

(p. D1) On a sunny summer day in Croatia several years ago, an archaeologist and two dog handlers watched as two dogs, one after another, slowly worked their way across the rocky top of a wind-scoured ridge overlooking the Adriatic Sea.

. . .

Panda, a Belgian Malinois with a “sensitive nose,” according to her handler, Andrea Pintar, had begun exploring the circular leftovers of a tomb when she suddenly froze, her nose pointed toward a stone burial chest. This was her signal that she had located the scent of human remains.

Ms. Pintar said the hair on her arms rose. “I was skeptical, and I was like, ‘She is kidding me,’” she recalled thinking about her dog that day.

Archaeologists had found fragments of human bone and teeth in the chest, but these had been removed months earlier for analysis and radiocarbon dating. All that was left was a bit of dirt, the stone slabs of the tomb and the cracked limestone of the ridge.

. . .

(p. D6) . . . the experiment in Croatia marked the start of one of the most careful inquiries yet carried out of an unusual archaeological method. If such dogs could successfully locate the burial sites of mass executions, dating from World War II through the conflicts in the Balkans in the 1990s, might they be effective in helping archaeologists find truly ancient burials?

. . .

That “test run” was the beginning of a careful study on whether human-remains detection dogs could be an asset to archaeologists. Setting up a controlled study was difficult. Dr. Glavaš had to learn the scientific literature, such as scent theory, far outside the standard confines of archaeology; the same was true for Ms. Pintar and the field of archaeology.

. . .

“I think dogs are really capable of this, but I think it’s a logistical challenge,” said Adee Schoon, a scent-detection-animal expert from the Netherlands who was not involved in the study. “It’s not something you can replicate again and again. It’s hard to train.”

And, as Dr. Schoon noted, dogs are “great anomaly detectors.” Something as subtle as recently disturbed soil can elicit a false alert from a dog that is not rigorously trained.

Nonetheless, the team returned to the necropolis for the first controlled tests in September 2015, and again a full year later. Both times, they used all four of Ms. Pintar and Mr. Nikolić’s cadaver dogs: Panda, Mali, a third Belgian Malinois and a German shepherd. They worked them on both known and double-blind searches, in areas where nobody knew if tombs were located.

The dogs located four tombs new to the archaeologists. Dr. Glavaš had suspected that a fifth site might hold a burial chest, and the dogs’ alerts, combined with excavation, proved her suspicion correct.

In September 2019, the Journal of Archaeological Method and Theory published the results of their study: “This research has demonstrated that HRD dogs are able to detect very small amounts of specific human decomposition odor as well as to indicate to considerably older burials than previously assumed,” Dr. Glavaš and Ms. Pintar wrote.

Dr. Schoon, who researches and helps create protocols to train scent-detection animals worldwide, said the Iron Age necropolis study was nicely designed and “really controlled.”

. . .

Cadaver dogs are also helping archaeologists at some especially challenging sites. Mike Russo and Jeff Shanks, archaeologists with the National Park Service’s Southeast Archeological Center, had created at least 14 test holes near a promising site in northwest Florida that had been flattened during an earlier era of less diligent archaeology. They found nothing.

“We knew where it should be, but when we went there, there was absolutely no mound,” Mr. Russo said.

They then asked Suzi Goodhope, a longtime cadaver-dog handler in Florida, to bring her experienced detection dog, Shiraz, a Belgian Malinois, to the site in 2013. Shiraz and Ms. Goodhope worked the flat, brushy area for a long time. Then, Shiraz sat. Once.

“I was pretty skeptical,” Mr. Shanks said.

Nonetheless, the archaeologists dug. And dug. They went down nearly three feet — and there they found a human toe bone more than 1,300 years old.

Passing sniff tests

What is the future of using human-remains detection dogs as a noninvasive tool in archaeology?

Some archaeologists, forensic anthropologists, geologists, scientists — and even H.R.D. dog handlers who know how challenging the work is — say they have great potential. But challenges abound.

Although researchers are learning ever more about the canine olfactory system, they are still trying to pinpoint what volatile organic compounds in human remains are significant to trained dogs.

. . .

Detection dogs also must be trained for archaeology with more consistency. Often humans are the limiting factor. Sometimes, Dr. Schoon said, she can almost see a dog thinking, “Is that all you want me to do? I can do much more!”

For the full story see:

Cat Warren. “Sniffing Out New (Old) Digs.” The New York Times (Tuesday, May 19, 2020 [sic]): D1 & D6.

(Note: ellipses added.)

(Note: the online version of the story was updated May 25, 2020 [sic], and has the title “When Cadaver Dogs Pick Up a Scent, Archaeologists Find Where to Dig.”)

The academic article documenting that dogs are able use their hypercapable noses to smell ancient human remains is:

Glavaš, Vedrana, and Andrea Pintar. “Human Remains Detection Dogs as a New Prospecting Method in Archaeology.” Journal of Archaeological Method and Theory 26, no. 3 (Sept. 2019): 1106-24.