Smartphone psychiatry? How NIMH director Tom Insel turned from brain scanners to social tech

Thomas Insel, photo courtesy of The Atlantic.

Around this time, Insel told me recently, he’d just finished a talk describing the wonderful things the NIMH was discovering about the brain when a man in the audience said, “You don’t get it.”

“Excuse me?,” Insel said. “I don’t get what?”

“Our house is on fire,” the man said, “and you’re telling us about the chemistry of the paint. We need someone to focus on the fire.”

“I heard that,” Insel told me. “I went home and thought, There’s truth to that. It’s not just that we don’t know enough. The gap between what we know and what we do is unacceptable.”

This is the story of how NIMH director Tom Insel, the most powerful psychiatrist in the world, decided to try closing that gap with smartphones — not as treatment, but as a way to assess mood, and then marshal the social and clinical support to intervene when need be.

The Smartphone Psychiatrist, at The Atlantic, July/August 2017

Did the gene-drug revolution just arrive?

Did the genomic revolution arrive last week, or was that just the snowstorm?

The answer depends on whom you listened to and what they thought of a study published on March 17 that showed a gene-based drug called Repatha reduced cardiovascular risk by 15%. Some called the study a triumph because it showed a drug developed through gene discovery could directly control a faulty gene’s output to therapeutic effect.

Others offered that the 15% reduction of cardiovascular risk was rather modest, being lower than the 20–25% predicted and not impressive next to existing drugs; opined that the drug is “an ingenious solution for a problem that’s mostly already solved; and noted that the the death rate itself didn’t change.”

It’s messy. My own quick take is that it’s a bit early to say Repatha settles the growing debate over whether we’re placing outsized bets on gene-based drug development. I’ve too many other commitments at present to get into this in any detail. Fortunately, Derek Lowe did get into it, three times. Amid the gush about the study’s results, his multiple examinations of this question remind us of how fraught and difficult these questions are.

Here are three snips from three his posts. I highly recommend reading all three in toto.

His quick first take, on March 17

This morning we have three-year data from Amgen and their drug Repatha (evolocumab), an announcement that has been eagerly awaited. And it’s honestly not all that impressive. There’s a 15% relative reduction in cardiovascular risk (heart attack, stroke, etc.) relative to placebo, but investors were looking for something more over 20%. Insurance companies were probably looking for that, too, and given the price they’d have been happier to see something more like 25%. Amgen is defending the data (as quotes in this Adam Feuerstein piece show), but I don’t think that’s going to do the job. The numbers shouldn’t have to be interpreted and spun; in a three-year study with over 13,000 patients in each arm, the numbers should be able to speak for themselves, and they don’t.

His March 20 post provides a thorough explanation — and then some perspective-taking:

The Amgen study, while successful, was not all that compelling. Yes, the relative risk for the composite cardiovascular endpoints used in the study went down, but not by as much as observers were hoping for (15% reduction versus 20 or 25%). And when you get down to overall mortality, there was no change at all, which has to be a disappointment. Amgen has been arguing that this was a relatively short study, and that the first measurements were also taken at a relatively early point in the treatment, and that the overall trend is for better numbers as the treatment goes on (which may well continue). But while these points may be valid, it’s a little rich for Amgen to be making them, because they designed this trial themselves, presumably to generate the most compelling results in the shortest amount of time. The fact that they’re having to make such arguments at all is a sign that the trial definitely did not come out the way that they’d hoped – you can be sure that the plan was not to have to say “Well, gosh, it’s really not bad if you look closely”.

and

What does this tell us, then, about genomics-based drug discovery? PCSK9 is about as compelling a story as we’re likely to see in this space, and if it has indeed come up a bit short, that’s food for thought. To be fair to Amgen, they may well be right about the continued improvements over longer-term therapy, in which case this story may have a better ending. But the slam-dunk game-winning ending is already gone. That may be the main lesson we can draw for now – here’s a terrific case, and it still didn’t blow everyone away when it finally got to multiyear human therapy. Everyone who’s following genetic-based clues to human therapy (a big crowd indeed) should keep this in mind.

In that second, longest post, he gives a hat-tip to the observer who called the study a triumph, saying that “PCSK9 is indeed the real thing, and just what people were expecting” back around 2000 when we sequenced the genome and thought it’d cure everything. It’s a conciliatory post. And yet…

So there’s a case to be made that this target really is the dawn of the era that we all thought was dawning years ago. I can appreciate the celebratory tone of Plenge’s post, but at the same time, if you’d told people back in 1999 how things had worked out, they would likely have been (at some level) horrified that (a) it took until the mid–2010s for something like this to happen and (b) that this is the main example that we can point to, and that the landscape is not littered with similar stories. That brave new world is not the one we live in, though, and for the one we’re in, this is a good result and we should make the most of it.

John Berger and Susan Sontag’s delicious shoptalk and big hair

What a fabulous conversation this is, between two giants we’ve lost. You see here, in this quiet, quietly intense, intensely curious conversation — in which (a true rarity) the act of listening is every bit as concentrated as the wonderful talk — why these two have long been touchstones for so many people who came of intellectual age in ‘70s or ‘80s. This is just delicious. Drop in anywhere and you find yummy.

I’d never seen this before, didn’t know it existed, and am so grateful to @muhus, who curates one of my favorite Tumblrs, for pointing it out.

 

How Trump’s lies are like Putin’s, and how the press should deal

Donald Trump, photo by Gage Skidmore via Wikimedia Commons

Masha Gessen shows again why she’s invaluable right now.

Lying is the message. It’s not just that both Putin and Trump lie, it is that they lie in the same way and for the same purpose: blatantly, to assert power over truth itself. Take, for example, Putin’s statements on Ukraine. In March 2014 he claimed that there were no Russian troops in newly annexed Crimea; a month later he affirmed that Russians troops had been on the ground. Throughout 2014 and 2015, he repeatedly denied that Russian troops were fighting in eastern Ukraine; in 2016 he easily acknowledged that they were there. In each case, Putin insisted on lying in the face of clear and convincing evidence to the contrary, and in each case his subsequent shift to truthful statements were not admissions given under duress: they were proud, even boastful affirmatives made at his convenience. Together, they communicated a single message: Putin’s power lies in being able to say what he wants, when he wants, regardless of the facts. He is president of his country and king of reality

Trump has exhibited similar behavior, apparently for the same reason: when he claims that he didn’t make statements that he is on record as making, or when he claims that millions of people voting illegally cost him the popular vote, he is not making easily disprovable factual claims: he is claiming control over reality itself. Those puzzled by Trump’s election-fraud tweets, because they seem like sore-loser behavior on the part of the winner, or by his dismissing out of hand the CIA’s findings about Russian interference—against the views of many leading Republicans—are missing the point: Trump was demonstrating his ability to say whatever he wanted about the election, precisely because he had won it

….

After the election, the media’s ability to do its job has been undermined even further. The standard model of reporting requires journalists to give the president-elect say in any news story about him. Thus we now have a series of stories in which reported facts are juxtaposed with a quoted Tweet that dismisses or contradicts the facts themselves. Even a factual narrative can no longer be aired without an immediate challenge contained within the news story itself—and without demonstrating that Trump has once again asserted his power to say what he wants, facts be damned, when he wants, convention be damned, and how he wants, logic and the English language be damned.

It is time to raise the stakes from fact to truth. With a president who lies in order to demonstrate power, fact-checking is indeed useless if it’s the entire story. The media have to find a way to tell the bigger story—the story about the lies rather than the story of the lies; and the story about power that the lies obscure. For mainstream media with long institutional histories, this is even harder than it sounds. The objective style in American journalism often means that nothing can be asserted unless someone in a position of authority utters it. Take Ukraine again: American newspapers have been reluctant to call a war a war because the US administration was not calling it a war. Words like “military adventurism” and “insurgency” had to stand in for the truth. But unless we are willing to live in a world that is not only post-fact but also post-truth, journalists will have to stand up to the soon-to-be president by exposing not only his lies but also other people’s truths.

Get the rest at The Putin Paradigm, @NYRB, by Masha Gessen.

How anger creates a false feeling of power – and thus Trump

How was Trump able to harness so much anger, even though he had proposed no solutions and offered no way to build anything new? Martha Nussbaum offers that he could do this because anger, and the desire to damage the object of  your anger, gives a false feeling of strength and agency. The anger feels like strength; the destruction like a plan. But in the end it can get you nothing, or worse.

From Emma Green‘s Q&A with Martha Nussbaum at The Atlantic, where they’re just killing it lately:

Green: When you look at this year’s campaign—something like a Trump rally, for example—do you see a kind of collective anger?

Nussbaum: Oh, absolutely. Often, we feel helpless in lots of situations in our lives. The way anger gets a grip on us is it seems to be a way to extricate ourselves from helplessness. People—and I think this is particularly true of Americans—don’t like to be passive. They like to seize control. I think what Trump has found, and very cleverly so, is that there’s a lot of helplessness out there in the middle of America: People who feel they’re not doing as well as they want; people who aren’t doing as well as their parents did. Jobs are going to China; jobs are going to other countries. He makes them feel that if they turn their helplessness into rage, they will accomplish something.

Of course, they won’t.

The Anger of the American People

On Ending Blindness

Christian Guardino, sighted and singing. Photo by Brent Stirton, National Geographic, all rights reserved.

I spent much of last winter working on a story about what it might take to end global blindness. I’m tickled to see the result now on and inside the cover of September’s National Geographic. The four-section story is about determination in the face of tough odds. Here’s a snip from the first section, about gene therapy fashioned by a group led by Penn’s Jean Bennett, and one from the last section, about the extraordinary Namibian cataract surgeon Helena Ndume, who is possibly the most amazing person I’ve ever met.

Christian, the doctor told Elizabeth, had a retinal disease called Leber congenital amaurosis (LCA). His vision, already bad, would never significantly improve. Nothing could be done. The boy would see little of the world and would always walk, once he learned how, with a cane.

Christian did need a cane, and his mother’s guiding hand, when in 2012, at age 12, he first visited a clinic run by the University of Pennsylvania’s Scheie Eye Institute. Yet this January he walked through the institute’s main building cane free and seemingly fearless. Joking and chatting, the teen led a klatch of Ph.D.’s, M.D.’s, lab techs, and me through the airy lobby. He marveled at the towering atrium, the shiny balconies where people sat having coffee.

“Whoa!” he said as we neared the building’s exit—for before us an enormous revolving door turned its huge blades. His mother was some distance behind; he was on his own. Christian neither stopped nor paused. He walked calmly through the opening of the spinning wedge of steel and glass and held his pace as one glass wall closed behind him and another smoothly swung out of his way. He stepped into the sunlight.

Christian Guardino could see. Everything that had posed an obstacle before—light and dark, steel and glass, the mobile and the immovable—now brought him pleasure. The world had opened before him.

Helena Ndume dancing with one of the 30,000 patients she has given sight to. Photo Brent Stirton, National Geographic, all rights reserved.

Helena Ndume dancing with one of the 30,000 patients she has given sight to. Photo Brent Stirton, National Geographic, all rights reserved.

Cataracts, a disease of poverty, cause half of all blindness on Earth. In the developed world, people with cataracts routinely get treated as soon as they have trouble seeing the TV. In the developing world, people with cataracts routinely go blind. The treatment everywhere is simple: Get clinician and patient in the same room, prep the latter, spend 15 to 20 minutes replacing the cloudy natural lens with a clear artificial lens, do a post-op checkup. In developing countries, treatment usually costs $15 to $100. Yet it reaches few who need it.

Working with Namibia and other African governments and the nonprofit SEE International, Ndume is trying to fix this by running “cataract camps.” At these gatherings in underserved areas, Ndume and other surgeons operate on up to 500 people a week. The United Nations last year recognized Ndume’s “service to humanity” with its inaugural Nelson Rolihlahla Mandela Prize.

It’s a fitting honor for someone who 41 years ago, as a girl of 15, left a different kind of darkness when she fled the apartheid that the South African government had imposed on Namibia. With three friends she made her way to a camp in Angola run by the Namibian resistance movement SWAPO; survived a machine gun attack soon after she arrived; braved hippo-infested rivers and hostile helicopter patrols to find safety in Zambia; told SWAPO she’d like to go to fashion school but was sent instead to medical school in Leipzig, Germany; and there married a countryman who soon after was killed in Angola. She bore their baby alone, finished her ophthalmology training, rejoiced when Namibia won its independence in 1990, and returned for good in 1996 with her child, her education, and a determination to help those who could not see.

The rest is here:Why There’s New Hope for Ending Blindness

Many thanks to editors Jamie Shreeve and Patty Edmonds and to the enormously talented photographer Brent Stirton, whose gorgeous photos grace the story, and whose partnership on this story was a huge blessing. Most of all, all my heart to the many people who shared their lives and work with me for this story — the researchers, patients, family members, and others, many who do not appear in this brief treatment, who helped me understand it. It’s hard to overstate my admiration for their generosity, courage, determination, humility, and good humor. Meeting such people, and hearing their stories and thoughts in person, is by far the most wonderful part of this splendid but difficult job.

If you like the story, consider subscribing to the Geographic. It’s wonderfully affordable, gorgeous, and your money will support the sort of extended reporting that a story like this requires.

The most terrifying childhood condition you’ve never heard of | Spectrum

Bernardo and Gina Pace

I’m honored to have written this story of a rare, severely debilitating disorder; the researchers trying to crack it; and the uncommon love between a father and his 24-year-old daughter.

You should read it here. For those who like teasers:

The first sign, at least in retrospect, was a reticence, he recalls in the memoir, that Gina hadn’t been displaying as she blossomed through her second and into her third year: “a little less eye contact … a little less chatter, a little more pointing.” In the stroller, rolling around Rome, she sometimes sat quietly upright, not relaxed, her eyes fixed forward.

For a time, these changes seemed explainable by their move to Italy. Her older sister was in school full-time, while Gina went to preschool just two or three days a week. It didn’t seem odd that Gina had few friends over and tended to play quietly alongside them.“She just needs time is the truce I offer the situation,” writes Bernardo about that year, “as if it were mine to offer. Piano, piano, the Italians say: little by little.”

Yet by October 1995, when Gina was 3, both her parents were shocked but not exactly surprised when a teacher said she thought Gina might have autism.

Six months later, after the family moved back to the United States, a specialist in New York agreed — “she was emphatic about it,” says Bernardo — and suggested they see Yale’s Fred Volkmar, a leading expert, then and now, in obscure developmental disorders, including CDD. Gina, now 4, was far behind where she’d been a year before. Volkmar told them she had CDD.

Today, Bernardo recognizes that Gina is lucky, as these things go, and significantly more capable than many people with CDD. Yet getting the diagnosis then “was devastating,” he says, and part of him initially refused to accept it. Much would fall away in the months and years to come, including his marriage to Gina’s mother. At first, though, there was grief. “There were a lot of tears there. There still are sometimes,” he says. “You have this idea of what’s possible in your child’s life. It’s a really hard thing to let go of.”

The most terrifying childhood condition you’ve never heard of, at Spectrum.

“He Thinks He’s Untouchable”. Buzzfeed outs another serial harasser. 

Accountability journalism ain’t quite dead yet. Azeen Ghorayshi with another great scoop on horrid behavior.

One of the employees was an administrator whom Katze had hired, at an unusually high salary, on the implicit condition that she submit to his sexual demands. He personally rewarded this woman, known as Mary Roe in some court documents, with “thousands or even tens of thousands” of dollars a year in cash and gifts, the investigation found.

The university found that Katze also sexually harassed another administrative employee, known as Jane Doe in court documents. According to the investigations, Katze asked her to clean his apartment, purchase marijuana and Percocet for him, email escorts and place personal ads for him, and “schedule his manicures, pedicures, haircuts, and hair lightening appointments.” Meanwhile, he joked about having sex with her, made sexual comments about her appearance, sent her sexually suggestive emails, and, on two occasions, tried while drunk to kiss or touch her.

The university had received at least seven previous complaints about Katze’s behavior, including claims that he was frequently intoxicated in the lab, watched porn on his university computer, belittled his employees, and retaliated against lab members who challenged him. A UW spokesperson said the school dealt with allegations against Katze, over the years, with “letters to him, admonishments, etcetera.” But his employment was never suspended or terminated.

“He Thinks He’s Untouchable.”

My Four Months as a Private Prison Guard: A Mother Jones Investigation | Mother Jones

A MoJo reporter gets a job as a prison guard at a private prison. The orientation was a bit disorienting.

The human resources director comes in and scolds Reynolds for napping. He perks up when she tells us that if we recruit a friend to work here, we’ll get 500 bucks. She gives us an assortment of other tips: Don’t eat the food given to inmates; don’t have sex with them or you could be fined $10,000 or get 10 years at hard labor; try not to get sick because we don’t get paid sick time. If we have friends or relatives incarcerated here, we need to report it. She hands out fridge magnets with the number of a hotline to use if we feel suicidal or start fighting with our families. We get three counseling sessions for free.

This is one crazy story. Epic reporting. My Four Months as a Private Prison Guard, by Shane Bauer, at MoJo.

Andre Fenton, comeback memory player of the year

06/13/2016 WOODS HOLE, MA Dr. Andre Fenton (cq) poses for a photo at the Marine Biological Laboratories in Woods Hole. (Aram Boghosian for The Boston Globe)

06/13/2016 WOODS HOLE, MA Dr. Andre Fenton (cq) poses for a photo at the Marine Biological Laboratories in Woods Hole. (Aram Boghosian for The Boston Globe)

Carl Zimmer on memory researcher Andre Fenton, comeback researcher of the year.

In an age when we get a lot of our medical news in click-baity headlines and hasty tweets, it’s easy to believe that scientific research is constantly barreling forward like a jet. The saga of PKMzeta shows just how contorted the true path of science can be. Fenton and Sacktor have worked together with what some of their colleagues consider a near-obsession for 14 years on PKMzeta. And after all that work, and years of setbacks, they feel like only now are they just able to start figuring out what this molecule does to let us form memories.

“Now we know it’s important,” Fenton said in a recent interview. “But what is it actually doing? I can tell you it’s crucial biochemically, but you shouldn’t feel satisfied that you understand memory any better. Because you don’t. We still don’t know what it means for memory.”

Get the rest at Stat: Memory researchers were rebuffed by science, and came roaring back, by Carl Zimmer.