Category: Methodology

Knowledge from Self-Experimentation Should Be Publishable

(p. D4) When Bob Hariri developed a product he thought could be useful as a human-skin replacement for burn victims, he had no trouble finding a subject willing to test it–himself.
An entrepreneur and a neurosurgeon with both a medical degree and a doctorate, Dr. Hariri is one of a number of scientists who have experimented on themselves with new or yet-to-be approved medical products or technologies, and who say such practice can be indispensable in the development of innovative biomedical treatments.
Some scientists are pushing for self-experimentation data to be reported publicly and more systematically to aid scientific progress. Alex Zhavoronkov, chief executive of an aging-research company called InSilico Medicine Inc., and others hope to start a peer-reviewed journal on self-experimentation, where scientists and other qualified individuals would publish high-quality case studies of tests performed on themselves. He plans to launch a crowdfunding operation in the next few months to fund it.
The idea is “to unlock the knowledge [of self-experimentation] that resides there anyway,” says Dr. Zhavrononkov, who takes an old diabetes drug called metformin that is supposed to have antiaging properties, even though it hasn’t been approved for that purpose.
. . .
Advocates say self-experimentation can yield information that is hard to get from a clinical trial. The experimenter feels what it’s like to be the patient and gets insight into how to improve testing procedures. Also, a number of individual reports, when cobbled together, can start to yield a picture of whether a new treatment is likely to work or not, though one wouldn’t rely on those reports alone to conclude safety or effectiveness.

For the full story, see:
Wang, Shirley S. “Why Medical Researchers Experiment on Themselves.”The Wall Street Journal (Tues., January 26, 2016): D4.
(Note: ellipsis added.)
(Note: the online version of the story has the date Jan. 25, 2016, and has the title “IN THE LAB; More Medical Researchers Engage In Self-Experimentation.”)

Innovation Benefits from Constructive Arguments

(p. 7) When Wilbur and Orville Wright finished their flight at Kitty Hawk, Americans celebrated the brotherly bond. The brothers had grown up playing together, they had been in the newspaper business together, they had built an airplane together. They even said they “thought together.”
These are our images of creativity: filled with harmony. Innovation, we think, is something magical that happens when people find synchrony together. The melodies of Rodgers blend with the lyrics of Hammerstein. It’s why one of the cardinal rules of brainstorming is “withhold criticism.” You want people to build on one another’s ideas, not shoot them down. But that’s not how creativity really happens.
When the Wright brothers said they thought together, what they really meant is that they argued together. One of their pivotal decisions was the design of a propeller for their plane. They squabbled for weeks, often shouting back and forth for hours. “After long arguments we often found ourselves in the ludicrous position of each having been converted to the other’s side,” Orville reflected, “with no more agreement than when the discussion began.” Only after thoroughly decimating each other’s arguments did it dawn on them that they were both wrong. They needed not one but two propellers, which could be spun in opposite directions to create a kind of rotating wing. “I don’t think they really got mad,” their mechanic marveled, “but they sure got awfully hot.”
. . .
Wilbur and Orville Wright came from a wobbly family. Their father, a preacher, never met a moral fight he wasn’t willing to pick. They watched him clash with school authorities who weren’t fond of his decision to let his kids miss a half-day of school from time to time to learn on their own. Their father believed so much in embracing arguments that despite being a bishop in the local church, he had multiple books by atheists in his library — and encouraged his children to read them.
. . .
The Wright brothers weren’t alone. The Beatles fought over instruments and lyrics and melodies. Elizabeth Cady Stanton and Susan B. Anthony clashed over the right way to win the right to vote. Steve Jobs and Steve Wozniak argued incessantly while designing the first Apple computer. None of these people succeeded in spite of the drama — they flourished because of it. Brainstorming groups generate 16 percent more ideas when the members are encouraged to criticize one another. The most creative ideas in Chinese technology companies and the best decisions in American hospitals come from teams that have real disagreements early on. Breakthrough labs in microbiology aren’t full of enthusiastic collaborators cheering one another on but of skeptical scientists challenging one another’s interpretations.
If no one ever argues, you’re not likely to give up on old ways of doing things, let alone try new ones. Disagreement is the antidote to groupthink. We’re at our most imaginative when we’re out of sync. There’s no better time than childhood to learn how to dish it out — and to take it.

For the full commentary, see:
Grant, Adam. “Kids, Would You Please Start Fighting?” The New York Times, SundayReview Section (Sun., NOV. 5, 2017): 7.
(Note: ellipses added.)
(Note: the online version of the commentary has the date NOV. 4, 2017.)

“Not Prepared to Compromise, in Ill-Considered Conversation, the Greater Truths”

(p. B15) Mr. Pomerance was a somewhat out-of-the-mainstream playwright living in London in 1977 when Foco Novo, a theater company he had founded with Roland Rees and David Aukin, began thinking about staging “The Elephant Man,” based on the true story of Joseph Merrick, a man with severe physical deformities who became a celebrity in Victorian England in the 1880s.
. . .
The resulting play invited theatergoers to contemplate, among many other themes, what is normal and what isn’t.
. . .
Mr. Pomerance was not a talkative sort. “The final impression he gives,” a Times reporter wrote in 1979, “is of a man of considerable intellectual integrity who is not prepared to compromise, in ill-considered conversation, the greater truths he seeks to express on stage.”

For the full obituary, see:
NEIL GENZLINGER. “Bernard Pomerance, 76; Wrote ‘Elephant Man’.” The New York Times (Weds., AUG. 30, 2017): B15.
(Note: ellipses added.)
(Note: the online version of the obituary has the date AUG. 29, 2017, and has the title “Bernard Pomerance, Who Wrote ‘The Elephant Man,’ Dies at 76.”)

Rate of Inflation Is Still a “Mystery” to Economists

(p. A2) CLEVELAND–Federal Reserve Chairwoman Janet Yellen on Tuesday [Sept. 26, 2017] defended the central bank’s projection for a gradual path of rate increases over the next few years despite the past few months of unexpectedly low inflation.
. . .
Inflation, under the Fed’s preferred measure, has undershot the central bank’s 2% target for much of the past five years. Although Ms. Yellen said she expects inflation to gradually move up to the target, she acknowledged the uncertainty surrounding that prediction.
. . .
“How should policy be formulated in the face of such significant uncertainties? In my view, it strengthens the case for a gradual pace of adjustments,” Ms. Yellen told a National Association for Business Economics conference in Cleveland.
. . .
Still, the Fed’s understanding of inflation is “imperfect,” she said, calling the shortfall in inflation “a mystery.” “We recognize that something more persistent may be responsible for the current undershooting.”

For the full story, see:
David Harrison. “Yellen Firm on Rates; Inflation a ‘Mystery’.” The Wall Street Journal (Weds., Sept. 27, 2017): A2.
(Note: ellipses, and bracketed date, added.)
(Note: the online version of the story has the date Sept. 26, 2017, and has the title “Yellen Defends Fed Rate-Rise Plan Despite ‘Mystery’ of Low Inflation.”)

More Cures If Local Physicians Can Conduct Clinical Trials

(p. A17) The good news is that technology innovations are moving us toward modern clinical trial designs. Electronic health records, now common in U.S. medical practices, allow physicians to collect timely and detailed data that could be used for exploring ways of bringing clinical research directly to patients. Those records are becoming the technological building blocks of a new research model based on real-world evidence, which aims to provide insights regarding the usage and potential benefits or risks of a drug by analyzing patient data collected as part of routine delivery of care.
Real-world evidence captures the experience of real-world patients, who are generally more diverse than the selective cohorts enrolled in clinical trials. Additionally, real-world data from electronic health records may be used after a drug’s approval to answer important questions about its use. Researchers can, for example, search through anonymized data from patients taking a specific cancer drug to see whether those with a certain tumor mutation respond better or worse than other patients. Such information could help doctors personalize therapies based on the patient’s genomic makeup.
Moving clinical research to a doctor’s office, the point of routine care, may also address the difficulties patients and doctors face with off-label drugs. If local physicians can participate in conducting real-world randomized clinical trials in their own practices, new uses of approved drugs could be carefully studied, potentially generating evidence supporting approval of a new use. Real-world clinical trials could also limit disruptions to patients’ lives by reducing the need for long-distance travel.

For the full commentary, see:
Amy Abernethy and Sean Khozin. “Clinical Drug Trials May Be Coming to Your Doctor’s Office; Electronic medical records make possible a new research model based on real-world evidence.” The Wall Street Journal (Weds., Sept. 13, 2017): A17.
(Note: the online version of the commentary has the date Sept. 12, 2017.)

Amateur Archaeologists Uncover Most Important Roman Site in Half Century

(p. A6) BOXFORD, England — Their ages range from 9 to about 80. They include a butcher and a builder. Some devoted vacation days to laboring on their hands and knees in an open field.
The group of amateur archaeologists — 55 in all, though only two dozen toiled on a typical day — were part of an excavation project near the village of Boxford, in southern England. They had to contend not just with days of backbreaking work, but also with a daunting, two-week deadline to complete the challenging dig.
Their commitment was handsomely repaid, though, in a few magical moments one Saturday last month. As a layer of soil was carefully scooped away, small, muddy pieces of red-colored tiling glinted in the sunlight, probably for the first time in more than one and a half millenniums.
The mosaic that slowly emerged from the earth is part of a Roman villa, thought to date from 380 A.D., toward the end of the period of Roman domination of England. The find is being described as the most important of its type in Britain in more than half a century, and in this picturesque, riverside village of thatched cottages, the scale of the discovery is still sinking in.
. . .
“It was down to the volunteers, it really was. I get quite emotional about it; it was something to see their drive,” added Mr. Nichol, project officer for Cotswold Archaeology, a company whose normal work includes helping real estate developers preserve archaeological finds.
. . .
So for the organizers, it was a relief, rather than a disappointment, when the earth was pushed back to conceal their discovery.
The night before that was done, Mr. Nichol decided to keep watch over the site from his S.U.V. with a supply of food, a sleeping bag and a bottle of red wine, all donated by volunteers.
The Roman owner of the villa would have invited guests to eat and drink on this spot, using the mosaic as a talking point, so a mildly bacchanalian vigil did not seem out of place.
“I was on my own in the field; it was incredible,” Mr. Nichol said. He described how, in the solitude, he felt drawn back across the centuries to experience a unique connection to the more-than-1,600-year-old archaeological site, and to the mythological images of its extraordinary, colorful mosaic.
“The wine did help,” he added.

For the full story, see:
STEPHEN CASTLE. “BOXFORD JOURNAL; A Link to Roman Era Is Unearthed in the English Countryside.” The New York Times (Tues., SEPT. 19, 2017): A6.
(Note: ellipses added.)
(Note: the online version of the story has the date SEPT. 18, 2017, and has the title “BOXFORD JOURNAL; Amateur U.K. Archaeologists Stumble on a Roman Masterpiece.”)

Amateur Inventors Are Crowdsourced to Solve Scientific Problems

(p. A3) At his laboratory console, Rhiju Das is making a game of a pressing public-health problem. He is recruiting thousands of videogamers to develop a better test for tuberculosis, which infects about one-third of the world’s population.
All they have to do is design a single molecule that can diagnose the disease in a patient’s bloodstream quickly, easily and cheaply–a task that so far has eluded public-health experts. To muster a crowd of amateurs to attempt it, Dr. Das, a biochemist at the Stanford University School of Medicine, and his colleagues this week launched the OpenTB challenge on a Web-based videogame called Eterna.
“The players themselves are going to be the inventors,” said Dr. Das. “Any molecule that a top player can make in the game, we will test it in the laboratory.”
. . .
In a game called Phylo, developed at McGill University, 300,000 players have been cross-indexing disease-related DNA sequences from dozens of species. And in Quantum Moves, conceived at Aarhus University in Denmark, 10,000 players are applying the bizarre laws of quantum mechanics to improve computer design.
“The number of projects has exploded,” said McGill computer scientist Jerome Waldispuhl, who co-founded the Phylo project.
Despite initial misgivings about the accuracy of crowdsourced research, players have produced reliable results and a dozen or so peer-reviewed research papers.
Typically, the players drawn to the science games have no special scientific expertise. They usually are intrigued by the chance to make a useful contribution to research in their spare time.
. . .
By harnessing human intuition and visual perception, these crowdsourcing games highlight differences between human and machine intelligence, several game designers said. “All of these citizen-science projects are like a snapshot of what is uniquely human at the moment,” said physicist Jacob Sherson at Aarhus University who helped to design Quantum Moves.

For the full story, see:
Robert Lee Hotz. “Videogamers Wanted: to Fight TB.” The Wall Street Journal (Weds., May 4, 2016): A3.
(Note: ellipses added.)
(Note: the online version of the story has the date May 3, 2016, and has the title “Videogamers Are Recruited to Fight Tuberculosis and Other Ills.” The sentence quoting Jerome Waldispuhl, appeared in the online, but not the print, version of the article.)

“Unfettered Science, If We Have the Courage to Let It Unfold”

(p. 26) “How to Tame a Fox” sets out to answer a simple-seeming question: What makes a dog a dog? Put another way, how did an animal that started out as a bloodthirsty predator become one that now wants nothing more than a nice belly rub and the chance to gaze adoringly at a member of another species? In the late 1950s, a Russian scientist named Dmitri Belyaev decided to address this puzzle by taking the unheard-of tack of replicating the domestication process in real time. He and his colleagues took silver foxes, widely bred in vast Siberian farms for their luxurious pelts, and made them into friendly house pets. It was a deceptively simple process: Take the puppies from only the friendliest foxes, breed them and repeat. Lyudmila Trut, the current lead researcher of the silver fox experiment, who began work as Belyaev’s intern, along with Lee Alan Dugatkin, an American scientist and writer at the University of Louisville, documents their monumental effort in this sparkling new book.
Belyaev died in 1985, but the experiment is still ongoing, with 56 generations of foxes bred to date — a far cry from the snarling creatures that used to snap at the hands of their caretakers when the research began. The new foxes run toward people, jump on the bed and nuzzle one another as well as their human caretakers. Such a behavioral transformation was to some degree expected, since they were bred from the tamest members of their groups. Perhaps more intriguing, they also look more doglike, with floppy ears, wagging tails and piebald fur.
. . .
The book, . . . , is not only about dogs, or foxes, or even science under siege from political interests. . . . It may serve — particularly now — as a parable of the lessons that can emerge from unfettered science, if we have the courage to let it unfold.

For the full review, see:
MARLENE ZUK. “Fox and Friends.” The New York Times Book Review (Sun., MAY 7, 2017): 26.
(Note: ellipses added.)
(Note: the online version of the review has the date MAY 5, 2017, and has the title “How Do You Make a Fox Your Friend? Fast-Forward Evolution.”)

The book under review, is:
Dugatkin, Lee Alan, and Lyudmila Trut. How to Tame a Fox (and Build a Dog): Visionary Scientists and a Siberian Tale of Jump-Started Evolution. Chicago: University of Chicago Press, 2017.

“The Data Run Counter to Your Anecdotes”

(p. A13) “Shattered,” by campaign reporters Jonathan Allen and Amie Parnes, narrates the petty bickering, foolish reasoning and sheer arrogance of a campaign that was never the sure thing that its leader and top staffers assumed. The authors, in a mostly successful attempt to get their sources to talk candidly, promised them that they wouldn’t be identified.
. . .
The juicy quotes would mean more if they were on the record, but mostly it works: You can’t pinpoint the identity of any one “top aide” or “close Hillary ally,” but the authors’ language leads you to believe they include the most senior Clinton advisers–Mr. Podesta, longtime Clinton confidante Huma Abedin, campaign manager Robby Mook, speechwriter Dan Schwerin, policy adviser Jake Sullivan –and probably the candidate herself.
. . .
Successful politicians must have a tacit sense of what voters want to hear and how they might be persuaded. Mrs. Clinton–in stark contrast to her husband–was never interested in that component of campaigning. You got the feeling she didn’t like people all that much.
Mr. Mook’s scientific “model” of how the campaign should run emphasized demographics, constituents’ voting histories, regional electoral patterns, and so on. When staffers objected to his directives, the authors record, the response was always the same: “The data,” as Mr. Mook at one point put it to former President Bill Clinton, “run counter to your anecdotes.”

For the full review, see:
Barton Swaim. “BOOKSHELF; Hillary the Unready.” The Wall Street Journal (Tues., April 18, 2017): A13.
(Note: ellipses added.)
(Note: the online version of the review has the date April 17, 2017, and has the title “BOOKSHELF; How Hillary Lost the White House.”)

The book under review, is:
Allen, Jonathan, and Amie Parnes. Shattered: Inside Hillary Clinton’s Doomed Campaign. New York: Crown, 2017.

94-Year-Old Applies for Patent on Slow-Hunch Solid State Battery

(p. 7) In 1946, a 23-year-old Army veteran named John Goodenough headed to the University of Chicago with a dream of studying physics. When he arrived, a professor warned him that he was already too old to succeed in the field.
Recently, Dr. Goodenough recounted that story for me and then laughed uproariously. He ignored the professor’s advice and today, at 94, has just set the tech industry abuzz with his blazing creativity. He and his team at the University of Texas at Austin filed a patent application on a new kind of battery that, if it works as promised, would be so cheap, lightweight and safe that it would revolutionize electric cars and kill off petroleum-fueled vehicles. His announcement has caused a stir, in part, because Dr. Goodenough has done it before. In 1980, at age 57, he coinvented the lithium-ion battery that shrank power into a tiny package.
We tend to assume that creativity wanes with age. But Dr. Goodenough’s story suggests that some people actually become more creative as they grow older. Unfortunately, those late-blooming geniuses have to contend with powerful biases against them.
. . .
Years ago, he decided to create a solid battery that would be safer. Of course, in a perfect world, the “solid-state” battery would also be low-cost and lightweight. Then, two years ago, he discovered the work of Maria Helena Braga, a Portuguese physicist who, with the help of a colleague, had created a kind of glass that can replace liquid electrolytes inside batteries.
Dr. Goodenough persuaded Dr. Braga to move to Austin and join his lab. “We did some experiments to make sure the glass was dry. Then we were off to the races,” he said.
Some of his colleagues were dubious that he could pull it off. But Dr. Goodenough was not dissuaded. “I’m old enough to know you can’t close your mind to new ideas. You have to test out every possibility if you want something new.”
When I asked him about his late-life success, he said: “Some of us are turtles; we crawl and struggle along, and we haven’t maybe figured it out by the time we’re 30. But the turtles have to keep on walking.” This crawl through life can be advantageous, he pointed out, particularly if you meander around through different fields, picking up clues as you go along. Dr. Goodenough started in physics and hopped sideways into chemistry and materials science, while also keeping his eye on the social and political trends that could drive a green economy. “You have to draw on a fair amount of experience in order to be able to put ideas together,” he said.

For the full commentary, see:
Kennedy, Pagan. “To Be a Genius, Think Like a 94-Year-Old.” The New York Times, SundayReview Section (Sun., APRIL 9, 2017): 7.
(Note: ellipsis added.)
(Note: the online version of the commentary has the date APRIL 7, 2017.)

Since 1880 North America Is Warmer by One and a Half Degrees Fahrenheit

(p. A23) Anyone who has read the 2014 report of the Intergovernmental Panel on Climate Change knows that, while the modest (0.85 degrees Celsius, or about 1.5 degrees Fahrenheit) warming of the earth since 1880 is indisputable, as is the human influence on that warming, much else that passes as accepted fact is really a matter of probabilities. That’s especially true of the sophisticated but fallible models and simulations by which scientists attempt to peer into the climate future. To say this isn’t to deny science. It’s to acknowledge it honestly.

For the full commentary, see:
Stephens, Bret. “Climate of Complete Certainty.” The New York Times (Sat., APRIL 29, 2017): A23.
(Note: the online version of the commentary has the date APRIL 28, 2017.)