Double-Blind Clinical Trials Are NOT the Only Source of Good Evidence

(p. 16) Back in her office, . . . [rheumatologist Jennifer Frankovich] found that the scientific literature had no studies on patients like this to guide her. So she did something unusual: She searched a database of all the lupus patients the hospital had seen over the previous five years, singling out those whose symptoms matched her patient’s, and ran an analysis to see whether they had developed blood clots. “I did some very simple statistics and brought the data to everybody that I had met with that morning,” she says. The change in attitude was striking. “It was very clear, based on the database, that she could be at an increased risk for a clot.”
The girl was given the drug, and she did not develop a clot. “At the end of the day, we don’t know whether it was the right decision,” says Chris Longhurst, a pediatrician and the chief medical information officer at Stanford Children’s Health, who is a colleague of Frankovich’s. But they felt that it was the best they could do with the limited information they had.
A large, costly and time-consuming clinical trial with proper controls might someday prove Frankovich’s hypothesis correct. But large, costly and time-consuming clinical trials are rarely carried out for uncommon complications of this sort. In the absence of such focused research, doctors and scientists are increasingly dipping into enormous troves of data that already exist — namely the aggregated medical records of thousands or even millions of patients to uncover patterns that might help steer care.
. . .
(p. 17) . . . , developing a “learning health system” — one that can incorporate lessons from its own activities in real time — remains tantalizing to researchers. Stefan Thurner, a professor of complexity studies at the Medical University of Vienna, and his researcher, Peter Klimek, are working with a database of millions of people’s health-insurance claims, building networks of relationships among diseases. As they fill in the network with known connections and new ones mined from the data, Thurner and Klimek hope to be able to predict the health of individuals or of a population over time. On the clinical side, Longhurst has been advocating for a button in electronic medical-record software that would allow doctors to run automated searches for patients like theirs when no other sources of information are available.
With time, and with some crucial refinements, this kind of medicine may eventually become mainstream. Frankovich recalls a conversation with an older colleague. “She told me, ‘Research this decade benefits the next decade,’ ” Frankovich says. “That was how it was. But I feel like it doesn’t have to be that way anymore.”

For the full story, see:
VERONIQUE GREENWOOD. “Eureka; Dr. DATA; Can Statistical Analysis Tell Us What Clinical Trials Cannot?” The New York Times Magazine (Sun., OCT. 5, 2014): 16-17.
(Note: ellipses, and bracketed name, added.)
(Note: the online version of the story has the date OCT. 3, 2014, and has the title “Eureka; Can Big Data Tell Us What Clinical Trials Don’t?”)

26 Different Drugs Lengthen Healthy Life Span in Mice

(p. F5) For thousands of years, people have sought to escape or outrun their mortality with potions, pills and elixirs, often blended with heavy doses of hope and will.
In the “Epic of Gilgamesh,” a Mesopotamian king searched for the secret of immortality after the death of his best friend. At least three Chinese emperors in the Tang dynasty died after consuming treatments containing lead and mercury that they hoped would make them immortal. In the late 19th century, a French-American physiologist seemed to have found the elixir of life by injecting the elderly and himself with extracts from animal testicles.
. . .
“By targeting fundamental aging processes, we might be able to delay the major age-related chronic diseases instead of picking them off one at time,” said Dr. James Kirkland, a professor of aging research and head of the Robert and Arlene Kogod Center on Aging at the Mayo Clinic. “For example, we don’t want to have situation where we, say, cure cancer and then people die six months later of Alzheimer’s disease or a stroke. It would be better to delay all of these things together.”
This is where the field known as the biology of aging is moving — to develop drugs that will increase life span and what researchers refer to as health span, the period of life when people are able to live independently and free from disease.
Dr. Kirkland said that at least six drugs had been written up in peer-reviewed journals and that he knew of about 20 others that appear to affect life span or health span in mice. The goal is to see if those benefits can be translated into humans to increase their longevity, “to find interventions that we can use in people that might, say, make a person who’s 90 feel like they’re 60 or a person who’s 70 feel like they’re 40 or 50.”
Other researchers are studying centenarians, seeking to understand whether certain genes have carried them past 100 years old and kept them in good health.

For the full story, see:
TRACEY SAMUELSON. “Science (and Quacks) vs. the Aging Process.” The New York Times (Weds., Nov. 19, 2014): F5.
(Note: ellipsis added.)
(Note: the online version of the story has the date NOV. 18, 2014.)

“You Don’t Reach Serendip by Plotting a Course for It”

(p. 320) As John Barth wrote in The Last Voyage of Somebody the Sailor, “You don’t reach Serendip by plotting a course for it. You have to set out in good faith for elsewhere and lose your bearings serendipitously.”28 The challenge for educational institutions, government policy, research centers, funding agencies, and, by extension, all modern medicine, will be how to encourage scientists to lose their bearings creatively. What they discover may just save our lives!

Source:
Meyers, Morton A. Happy Accidents: Serendipity in Modern Medical Breakthroughs. New York: Arcade Publishing, 2007.
(Note: italics in original.)

“It Is the Individual Who Is the Agent of the Action”

(p. C6) Mr. Mischel begins by describing how, in the late 1960s, he and his colleagues devised a straightforward experiment to measure self-control at the Bing Nursery School at Stanford University. In its simplest form, children between the ages of 4 and 6 were given a choice between one marshmallow now or two marshmallows if they waited 15 minutes. Some kids ate the marshmallow right away, but most would engage in unintentionally hilarious attempts to overcome temptation.
. . . About a third of the original subjects, the researchers reported, deferred gratification long enough to get the second treat.
. . . in 2006, . . . Mr. Mischel published a new paper in the prestigious journal Psychological Science. The researchers had done a follow-up study with the students they had tested 40 years before, examining the sort of adults they had grown into. They found that the children who were able to delay gratification had higher SAT scores entering college, higher grade-point averages at the end of college and made more money after college. Perhaps not surprisingly, they also tended to have a lower body-mass index.
. . .
In his commencement address, Adm. McRaven explained his final life lesson with an anecdote: “In SEAL training there is a bell,” he explained. “A brass bell that hangs in the center of the compound for all the students to see. All you have to do to quit–is ring the bell. Ring the bell and you no longer have to wake up at 5 o’clock. Ring the bell and you no longer have to do the freezing cold swims. Ring the bell and you no longer have to do the runs, the obstacle course, the PT–and you no longer have to endure the hardships of training. Just ring the bell.” To ring the bell is to give up.
Interestingly, one of Mr. Mischel’s lesser-known marshmallow experiments had a similar setup, with a bell that the children could ring to call back the experimenter and save them from themselves. For the children, though, ringing the bell was not giving up but calling in the cavalry. His book is an encouraging reminder that, despite all the factors that urge us to indulge, “at the end of that causal chain, it is the individual who is the agent of the action and decides when to ring the bell.” You are ultimately in control of your self.

For the full review, see:
MICHAEL SHERMER. “Willpower and Won’t Power; To resist the tempting treat, kids looked away, squirmed, sang or simply pretended to take a bite.” The Wall Street Journal (Sat., Sept. 20, 2014): C6.
(Note: ellipses added.)
(Note: the online version of the review has the date Sept. 19, 2014, and has the title “Book Review: ‘The Marshmallow Test’ by Walter Mischel; To resist the tempting treat, kids looked away, squirmed, sang or simply pretended to take a bite.”)

The book under review is:
Mischel, Walter. The Marshmallow Test: Mastering Self-Control. New York: Little, Brown and Company, 2014.

As with Airplanes, Lives Must Be Risked to Achieve Routine Safety in Spaceships

(p. A21) SEATTLE — ONE clear winter day in 1909, in Hampshire, England, a young man named Geoffrey de Havilland took off in a twin-propeller motorized flying machine of his own design, built of wood, piano wire and stiff linen hand-stitched by his wife. The launch was flawless, and soon he had an exhilarating sensation of climbing almost straight upward toward the brilliant blue sky. But he soon realized he was in terrible trouble.
The angle of ascent was unsustainable, and moments later de Havilland’s experimental plane crashed, breaking apart into a tangled mass of shards, splinters and torn fabric, lethal detritus that could easily have killed him even if the impact of smashing into the ground did not. Somehow, he survived and Sir Geoffrey — he was ultimately knighted as one of the world’s great aviation pioneers — went on to build an astonishing array of military and civilian aircraft, including the world’s first jet airliner, the de Havilland Comet.
I thought immediately of de Havilland on Friday when I heard that Virgin Galactic’s SpaceShipTwo, a rocket-powered vehicle designed to take well-heeled tourists to the edge of space, had crashed on a flight over the Mojave Desert, killing one test pilot and seriously injuring the other.
. . .
Certainly the Wright brothers and others like de Havilland were involved in what we now view as an epic quest, but many experts of the day were certain that flight, however interesting, was destined to be not much more than a rich man’s hobby with no practical value.
“The public has greatly over-estimated the possibilities of the aeroplane, imagining that in another generation they will be able to fly over to London in a day,” said a Harvard expert in 1908. “This is manifestly impossible.” Two other professors patiently explained that while laymen might think that “because a machine will carry two people another may be constructed that will carry a dozen,” in fact “those who make this contention do not understand the theory of weight sustentation in the air.”
. . .
There will be tragedies like the crash of SpaceShipTwo and nonlethal setbacks such as the fiery explosion, also last week, of a remote-controlled rocket intended for a resupply mission to the International Space Station. There will be debates about how to improve regulation without stifling innovation. Some will say private industry can’t do the job — though it’s not as if the NASA-sponsored Apollo or space shuttle missions went off without a hitch (far from it, sadly).
But at the heart of the enterprise there will always be obsessives like Sir Geoffrey, who forged ahead with his life’s work of building airplanes despite his own crash and, incredibly, the deaths of two of his three sons while piloting de Havilland aircraft, one in an attempt to break the sound barrier. Getting to routine safety aloft claimed many lives along the way, and a hundred years from now people will agree that in that regard, at least, spaceships are no different from airplanes.

For the full commentary, see:
SAM HOWE VERHOVEK. “Not a Flight of Fancy.” The New York Times (Tues., NOV. 4, 2014): A21.
(Note: ellipses added.)
(Note: the online version of the commentary has the date NOV. 3, 2014.)

Obamacare Advisor Says Obscure Law Passed Due to “Stupidity of the American Voter”

(p. A4) Jonathan Gruber, the economist at the heart of a fresh debate about the Affordable Care Act, has had more than a dozen appointments to visit the White House since Democrats began drafting the health law in 2009, records show.
The visits included at least one group meeting with President Barack Obama , as well as appointments with senior administration officials who helped shape the 2010 law that expanded health insurance to millions of Americans.
The White House in recent days has tried to distance itself from Mr. Gruber, a 49-year-old Massachusetts Institute of Technology economist, since a 2013 video surfaced last week in which he said the law passed because of the “huge political advantage” of the legislation’s lacking transparency. He also referred to the “stupidity of the American voter.”
Republicans have seized on the comments as evidence that supporters of the law purposely misled the public about its costs.
“It is amusing to watch Washington liberals discount Mr. Gruber’s truth-telling as a gaffe and disown” his involvement in the law, said Sen. Orrin Hatch (R., Utah).

For the full story, see:
STEPHANIE ARMOUR and COLLEEN MCCAIN NELSON. “Health Adviser Gruber Logged Regular White House Visits.” The Wall Street Journal (Tues., Nov. 18, 2014): A4.
(Note: the online version of the story has the date Nov. 17, 2014.)

Outsiders Persevere to Pursue Breakthroughs

(p. 315) Despite all the examples given, mainstream medical research stubbornly continues to assume that new drugs and other advances will follow exclusively from a predetermined research path. Many, in fact, will. Others, if history is any indication, will not. They will come not from a committee or a research team but from an individual, a maverick who views a problem with fresh eyes. Serendipity will strike and be seized upon by a well-trained scientist or clinician who also dares to rely upon intuition, imagination, and creativity. Unbound by traditional theory, willing to suspend the usual set of beliefs, unconstrained by the requirement to obtain approval or funding for his or her pursuits, this outsider will persevere and lead the way to a dazzling breakthrough. Eventually, once the breakthrough becomes part of accepted medical wisdom, the insiders will pretend that the outsider was one of them all along.

Source:
Meyers, Morton A. Happy Accidents: Serendipity in Modern Medical Breakthroughs. New York: Arcade Publishing, 2007.

Leading Computability Expert Says Humans Can Do What Computers Cannot

(p. B4) What does Turing’s research tell us?
“There is some scientific basis for the view that humans are doing something that a machine isn’t doing–and that we don’t even want our machine to do,” says S. Barry Cooper, a mathematician at Leeds and the foremost scholar of Turing’s work.
The math behind this is deep, but here’s the short version: Humans seem to be able to decide the validity of statements that should stump us, were we strictly computers as Turing described them. And since all modern computers are of the sort Turing described, well, it seems that we’ve won the race against the machines before it’s even begun.
. . .
The future of technology isn’t about replacing humans with machines, says Prof. Cooper–it’s about figuring out the most productive way for the two to collaborate. In a real and inescapable way, our machines need us just as much as we need them.

For the full commentary, see:
Mims, Christopher. “KEYWORDS; Why Humans Needn’t Fear the Machines All Around Us; Turing’s Heirs Realize a Basic Truth: The Machines We Create Are Not, Indeed Cannot Be, Replacements for Humans.” The Wall Street Journal (Tues., DEC. 1, 2014): B4.
(Note: ellipsis added.)
(Note: the online version of the commentary has the date Nov. 30, 2014, and has the title “KEYWORDS; Why We Needn’t Fear the Machines; A Basic Truth: Computers Can’t Be Replacements for Humans.”)

One of the major books by the Turing and computability expert quoted in the passages above, is:
Cooper, S. Barry. Computability Theory, Chapman Hall/CRC Mathematics Series. Boca Raton, Florida: Chapman and Hall/CRC Mathematics, 2003.

Oldest Outlines of Human Hands Found in Indonesia

(p. A17) A team of researchers reported in the journal Nature on Wednesday [October 8, 2014] that paintings of hands and animals in seven limestone caves on the Indonesian island of Sulawesi may be as old as the earliest European cave art.
. . .
The researchers said the earliest images, with a minimum age of 39,900 years, are the oldest known stenciled outlines of human hands in the world. Blowing or spraying pigment around a hand pressed against rock surfaces would become a common practice among cave artists down through the ages — . . .

For the full story, see:
JOHN NOBLE WILFORD. “Paintings in Indonesia May Predate Oldest Known Cave Art.” The New York Times (Thurs., OCT. 9, 2014): A17.
(Note: ellipses, and bracketed date, added.)
(Note: the online version of the story has the date OCT. 8, 2014, and has the title “Cave Paintings in Indonesia May Be Among the Oldest Known.”)

Greenpeace Desecrates Fragile, Ancient Hummingbird Etching in Peru

(p. A7) CARACAS, Venezuela — An expression of concern by the environmental group Greenpeace about the carbon footprint was marred this week by real footprints — in a fragile, and restricted, landscape near the Nazca lines, ancient man-made designs etched in the Peruvian desert.
The Peruvian authorities said activists from the group damaged a patch of desert when they placed a large sign that promoted renewable energy near a set of lines that form the shape of a giant hummingbird.
. . .
. . . the Peruvian authorities were seething over the episode, which they said had scarred one of the country’s most treasured national symbols.
. . .
“The hummingbird was in a pristine area, untouched,” Mr. Castillo said. “Perhaps it was the best figure.”
Mr. Castillo said that the culture ministry had sent out a team with drone aircraft equipped with cameras so that they could evaluate the damage without entering the delicate area.
He said that the harm was both physical and symbolic.
“This stupidity has co-opted part of the identity of our heritage that will now be forever associated with the scandal of Greenpeace,” he said.

For the full story, see:
WILLIAM NEUMAN. “Peru Is Indignant After Greenpeace Makes Its Mark on Ancient Site.” The New York Times (Sat., DEC. 13, 2014): A7.
(Note: ellipses added.)
(Note: the online version of the story has the date DEC. 12, 2014.)

Successful Discoverers “Follow the Evidence Wherever It Leads”

(p. 314) Why are particular people able to seize on such opportunities and say, “I’ve stumbled upon a solution. What’s the problem?” Typically, such people are not constrained by an overly focused or dogmatic mindset. In contrast, those with a firmly held set of preconceptions are less likely to be distracted by an unexpected or contradictory observation, and yet it is exactly such things that lead to the blessing of serendipitous discovery.
Serendipitous discoverers have certain traits in common. They have a passionate intensity. They insist on trying to see beyond their own and others’ expectations and resist any pressure that would close off investigation. Successful medical discoverers let nothing stand in their way. They break through, sidestep, or ignore any obstacle or objection to their chosen course, which is simply to follow the evidence wherever it leads. They have no patience with dogma of any kind.
The only things successful discoverers do not dismiss out of hand are contradictory–and perhaps serendipitously valuable–facts. They painstakingly examine every aspect of uncomfortable facts until they understand how they fit with other facts. Far from being cavalier about method, serendipitous discoverers subject their evidence and suppositions to the most rigorous methods they can find. They do not run from uncertainty, but see it as the raw material from which new scientific and medical certainties can be wrought.

Source:
Meyers, Morton A. Happy Accidents: Serendipity in Modern Medical Breakthroughs. New York: Arcade Publishing, 2007.