Tuesday, December 3, 2013
Grade Inflation at Harvard
[ed. If you spend your life sparing people’s feelings and feeding their vanity, you get so you can’t distinguish what should be respected in them.. F. Scott Fitzgerald.]
The median grade at Harvard College is an A-, and the most frequently awarded mark is an A, Dean of Undergraduate Education Jay M. Harris said on Tuesday afternoon, supporting suspicions that the College employs a softer grading standard than many of its peer institutions.
Harris delivered the information in response to a question from government professor Harvey C. Mansfield ’53 at the monthly meeting of the Faculty of Arts and Sciences.
“A little bird has told me that the most frequently given grade at Harvard College right now is an A-,” Mansfield said during the meeting’s question period. “If this is true or nearly true, it represents a failure on the part of this faculty and its leadership to maintain our academic standards.”
Harris then stood and looked towards FAS Dean Michael D. Smith in hesitation.
“I can answer the question, if you want me to.” Harris said. “The median grade in Harvard College is indeed an A-. The most frequently awarded grade in Harvard College is actually a straight A.”
by Mattew Q. Clarida and Nicholas P. Fandos, Harvard Crimson | Read more:
The median grade at Harvard College is an A-, and the most frequently awarded mark is an A, Dean of Undergraduate Education Jay M. Harris said on Tuesday afternoon, supporting suspicions that the College employs a softer grading standard than many of its peer institutions.Harris delivered the information in response to a question from government professor Harvey C. Mansfield ’53 at the monthly meeting of the Faculty of Arts and Sciences.
“A little bird has told me that the most frequently given grade at Harvard College right now is an A-,” Mansfield said during the meeting’s question period. “If this is true or nearly true, it represents a failure on the part of this faculty and its leadership to maintain our academic standards.”
Harris then stood and looked towards FAS Dean Michael D. Smith in hesitation.
“I can answer the question, if you want me to.” Harris said. “The median grade in Harvard College is indeed an A-. The most frequently awarded grade in Harvard College is actually a straight A.”
by Mattew Q. Clarida and Nicholas P. Fandos, Harvard Crimson | Read more:
Image: Wikipedia
The Secret Life of Grief
Eulogies ought to begin with a laugh, I decided, so this is how my eulogy began: with the story of how I learned that parents grow up, too.
My mom died on July 18, 2013, of pancreatic cancer, a subtle blade that slips into the host so imperceptibly that by the time a presence is felt, it is almost always too late. Living about 16 months after her diagnosis, she was "lucky," at least by the new standards of the parallel universe of cancer world. We were all lucky and unlucky in this way. Having time to watch a loved one die is a gift that takes more than it gives.
Psychologists call this drawn out period "anticipatory grief." Anticipating a loved one's death is considered normal and healthy, but realistically, the only way to prepare for a death is to imagine it. I could not stop imagining it. I spent a year and a half writing my mother a goodbye letter in my head, where, in the private theater of my thoughts, she died a hundred times. In buses and movie theaters, on Connecticut Avenue and 5th Avenue, on crosswalks and sidewalks, on the DC metro and New York subway, I lost her, again and again. To suffer a loved one's long death is not to experience a single traumatic blow, but to suffer a thousand little deaths, tiny pinpricks, each a shot of grief you hope will inoculate against the real thing.
A boundless black terror is how I imagined life without my mom. The history of grief, or what we know of it, is written by its greatest sufferers and ransacked with horror stories, lugubrious poetry, and downward-spiraling memoirs plunged in sadness. For some people, the death of a loved one is truly life-stopping, and I worried it would stop mine.For many of us, grief is something else: Resilience.
Then, in the weeks after she died, something strange happened. I did not plunge. Life did not stop. Instead, I felt something so unspeakably strange, so blasphemous, that I wondered if I could talk or write about it, at all. I felt okay.
Even stranger, I discovered, is that I wasn't strange, at all. Despite the warnings that grief would drag me through the prescribed five stages and discard me in a darker place, bereavement researchers have recently learned that we've been wrong about loss for centuries. For some, grief is a dull and unrelenting ache that fades—or doesn't. But for many of us, grief is something else. Grief is resilience.
If George Bonanno's office were discovered underground by a group of archaeologists, they would think they'd found a tomb. Volumes about death and mourning fill the wall-sized bookcase. Terra cotta figurines, excavated from Chinese burial sites, line the shelves, facing inward. At the center of the room, there is a full-size standing skeleton.
One afternoon in October, I visited Bonanno, perhaps the most renowned grief researcher in the United States, at Teachers College, Columbia University, to talk about his research. His lab might be trailblazing, but the mission is classically conservative. By studying grief like any other psychological condition, he has exposed the history of bereavement research to be a thread of fables."The more people engaged in their most intense emotions, the longer they would grieve. Laughter and smiling led to quicker recovering."
For centuries, grief has lived a secret life, hiding in plain view, even from our experts. Sigmund Freud coined the phrase "the work of grief," and ever since, there has lingered an idea that mourning is homework to do before we move on. The first systemic study of grief in the United States, by the Harvard psychiatrist Erich Lindemann, in 1942, described a horror show, marked by restlessness, hostility, hallucinations, and an overwhelming preoccupation with the dead. Lindemann had gathered a group of bereaved people—many of whom had lost friends in a recent night-club fire—and recorded his observations, motivated by the conviction that traumatic loss was a medical problem. Grievers who seemed normal in the weeks after, he claimed, were victims of dangerous repression.
Twenty years later, in the 1960s, Elisabeth Kubler-Ross' five stages of loss would tattoo themselves onto the collective conscious of Americans. Kubler-Ross, a Swiss-born psychiatrist, interviewed patients at a Chicago hospital about the experience of dying. She devised a theory of five periods, from anger to acceptance, with each stage serving an essential part in the mourning process. Her book, On Death and Dying, became a national bestseller, but it wasn't just a mess of shoddy science. It was shoddy science based on people who were dying, not people who were grieving.
Bonanno's work, which has redefined the science of grief research, revealed that Freud was wrong about work, Lindemann was wrong about repression, and Kubler-Ross was wrong about everything. The deepest grief is powerful, but sometimes short-lived, and most of us are wired to compartmentalize our most heart-breaking tragedies, even if it makes us feel ashamed to feel all right in the face of expectations that we feel terrible.
We are, both tragically and indispensably, born to grieve.
My mom died on July 18, 2013, of pancreatic cancer, a subtle blade that slips into the host so imperceptibly that by the time a presence is felt, it is almost always too late. Living about 16 months after her diagnosis, she was "lucky," at least by the new standards of the parallel universe of cancer world. We were all lucky and unlucky in this way. Having time to watch a loved one die is a gift that takes more than it gives.Psychologists call this drawn out period "anticipatory grief." Anticipating a loved one's death is considered normal and healthy, but realistically, the only way to prepare for a death is to imagine it. I could not stop imagining it. I spent a year and a half writing my mother a goodbye letter in my head, where, in the private theater of my thoughts, she died a hundred times. In buses and movie theaters, on Connecticut Avenue and 5th Avenue, on crosswalks and sidewalks, on the DC metro and New York subway, I lost her, again and again. To suffer a loved one's long death is not to experience a single traumatic blow, but to suffer a thousand little deaths, tiny pinpricks, each a shot of grief you hope will inoculate against the real thing.
A boundless black terror is how I imagined life without my mom. The history of grief, or what we know of it, is written by its greatest sufferers and ransacked with horror stories, lugubrious poetry, and downward-spiraling memoirs plunged in sadness. For some people, the death of a loved one is truly life-stopping, and I worried it would stop mine.For many of us, grief is something else: Resilience.
Then, in the weeks after she died, something strange happened. I did not plunge. Life did not stop. Instead, I felt something so unspeakably strange, so blasphemous, that I wondered if I could talk or write about it, at all. I felt okay.
Even stranger, I discovered, is that I wasn't strange, at all. Despite the warnings that grief would drag me through the prescribed five stages and discard me in a darker place, bereavement researchers have recently learned that we've been wrong about loss for centuries. For some, grief is a dull and unrelenting ache that fades—or doesn't. But for many of us, grief is something else. Grief is resilience.
If George Bonanno's office were discovered underground by a group of archaeologists, they would think they'd found a tomb. Volumes about death and mourning fill the wall-sized bookcase. Terra cotta figurines, excavated from Chinese burial sites, line the shelves, facing inward. At the center of the room, there is a full-size standing skeleton.
One afternoon in October, I visited Bonanno, perhaps the most renowned grief researcher in the United States, at Teachers College, Columbia University, to talk about his research. His lab might be trailblazing, but the mission is classically conservative. By studying grief like any other psychological condition, he has exposed the history of bereavement research to be a thread of fables."The more people engaged in their most intense emotions, the longer they would grieve. Laughter and smiling led to quicker recovering."
For centuries, grief has lived a secret life, hiding in plain view, even from our experts. Sigmund Freud coined the phrase "the work of grief," and ever since, there has lingered an idea that mourning is homework to do before we move on. The first systemic study of grief in the United States, by the Harvard psychiatrist Erich Lindemann, in 1942, described a horror show, marked by restlessness, hostility, hallucinations, and an overwhelming preoccupation with the dead. Lindemann had gathered a group of bereaved people—many of whom had lost friends in a recent night-club fire—and recorded his observations, motivated by the conviction that traumatic loss was a medical problem. Grievers who seemed normal in the weeks after, he claimed, were victims of dangerous repression.
Twenty years later, in the 1960s, Elisabeth Kubler-Ross' five stages of loss would tattoo themselves onto the collective conscious of Americans. Kubler-Ross, a Swiss-born psychiatrist, interviewed patients at a Chicago hospital about the experience of dying. She devised a theory of five periods, from anger to acceptance, with each stage serving an essential part in the mourning process. Her book, On Death and Dying, became a national bestseller, but it wasn't just a mess of shoddy science. It was shoddy science based on people who were dying, not people who were grieving.
Bonanno's work, which has redefined the science of grief research, revealed that Freud was wrong about work, Lindemann was wrong about repression, and Kubler-Ross was wrong about everything. The deepest grief is powerful, but sometimes short-lived, and most of us are wired to compartmentalize our most heart-breaking tragedies, even if it makes us feel ashamed to feel all right in the face of expectations that we feel terrible.
We are, both tragically and indispensably, born to grieve.
by Derek Thompson, The Atlantic | Read more:
Image: Arkadiusz Benedykt/flickr
The Period is Pissed
Say you find yourself limping to the finish of a wearing workday. You text your girlfriend: “I know we made a reservation for your bday tonight but wouldn’t it be more romantic if we ate in instead?” If she replies,
we could do thatThen you can ring up Papa John’s and order something special. But if she replies,
we could do that.Then you should probably drink a cup of coffee: You’re either going out or you’re eating Papa John’s alone.
This is an unlikely heel turn in linguistics. In most written language, the period is a neutral way to mark a pause or complete a thought; but digital communications are turning it into something more aggressive. “Not long ago, my 17-year-old son noted that many of my texts to him seemed excessively assertive or even harsh, because I routinely used a period at the end,” Mark Liberman, a professor of linguistics at the University of Pennsylvania, told me by email. How and why did the period get so pissed off?
It might be feeling rejected. On text and instant message, punctuation marks have largely been replaced by the line break. I am much more likely to type two separate messages without punctuation:
sorry about last nightThan I am to send a single punctuated message:
next time we can order little caesars
I’m sorry about last night. Next time we can order Little Caesars.And, because it seems begrudging, I would never type:
sorry about last night.“The unpunctuated, un-ended sentence is incredibly addicting,” said Choire Sicha, editor of the Awl. “I feel liberated to make statements without that emphasis, and like I'm continuing the conversation, even when I'm definitely not.”
next time we can order little caesars.
Other people probably just find line breaks more efficient. An American University study of college students’ texting and instant messaging habits found they only used sentence-final punctuation 39 percent of the time in texts and 45 percent of the time in online chats. The percentages were even lower for “transmission-final punctuation”: 29 percent for texts and 35 percent for IMs. The same is likely true of Twitter, where the 140-character limit has made most punctuation seem dispensable.
“In the world of texting and IMing … the default is to end just by stopping, with no punctuation mark at all,” Liberman wrote me. “In that situation, choosing to add a period also adds meaning because the reader(s) need to figure out why you did it. And what they infer, plausibly enough, is something like ‘This is final, this is the end of the discussion or at least the end of what I have to contribute to it.’”
by Ben Crair, TNR | Read more:
Image: uncredited
#Oz
The Tin Woodman, raising his ax, ran toward the little man and cried, “Who are you?” The little man trembled, “I am Oz, the Great and Terrible!” Our friends looked at each other in surprise and dismay. “I thought Oz was a Great Wizard,” said Dorothy.
“I did, too,” said the Scarecrow.
“How did you do it?” asked the Lion.
“How are you Oz, the Great and Terrible?” asked the Tin Woodman.
“Two words,” said the little man. “Personal branding.”
Dorothy glanced at the Tin Woodman in confusion. At last she addressed the man quietly. “Are you not a Great Wizard, then?”
The little man laughed. “Why, I’m the Great Wizard.”
He added, “Good branding makes your target market see you as the only choice, not just the best choice. I’ve spent years researching and developing my distinctive yet authentic ‘Wizard’ brand.”
There was a long pause. “I think you are a very bad man,” said Dorothy, finally. “Well, I’m trending, so it really doesn’t matter what you think,” said Oz.
The Scarecrow wiped a tear from his eyes. “But how shall I ever get my brains?”
“Your brains are the least of your problems,” said Oz, “for your personal brand is as fresh as the hay in your coat sleeves! You need a major overhaul—I can’t tell if you’re going for faux-hipster ironic Brooklynite or ‘young conservative’ urban farmer-chic.”
The Scarecrow tugged self-consciously at his coat sleeves.
“Forget about the brains and focus on the wardrobe, the style, the message. Personally, I see you in a dirty wife-beater and Ray-Bans— playfully self-aware about your country roots, but with a sense of cool detachment.”
“Wife-beater, Ray-Bans,” repeated the Scarecrow to himself. He felt an oddly intuitive understanding, for not having a brain put him at a great advantage in the world of branding.
by Ethan Kuperberg, New Yorker | Read more:
Image: Metro-Goldwyn-Mayer/Getty
Amazon Drones Could Face Some Grief from FAA
Say what you will about Amazon CEO Jeff Bezos, he does have an ability to think outside the proverbial box: his company is prepping to deliver packages to customers via airborne drone.
If the FAA approves Amazon’s airborne delivery (something the latter anticipates won’t take place until 2015 at the earliest), the company will use the drones to place items on residential doorsteps within 30 minutes. As detailed in a video posted on Amazon’s Website, workers at Amazon Fulfillment Centers (a corporate synonym for “warehouses”) will load each new item into a hard case, which the drone will lock to its undercarriage before flying off; once it lands at the target address, it will leave the case with the item inside. Amazon’s calling the service “Amazon Prime Air,” which suggests it’ll be a perk for Amazon Prime members willing to pay a premium.
“The FAA is actively working on rules and an approach for unmanned aerial vehicles that will prioritize public safety,” read an accompanying note on Amazon’s Website. “Safety will be our top priority, and our vehicles will be built with multiple redundancies and designed to commercial aviation standards.”
Despite those assurances, several questions remain. For starters, it’s extremely likely that the FAA will require a human pilot or supervisor for each drone flight. If that’s the case, Amazon will need to hire hundreds of new employees to guide the aircraft, in addition to building new systems capable of monitoring variables such as local weather and air traffic—for liability’s sake alone, it’s virtually certain the drones won’t fly unless conditions are ideal. (...)
Domestic drones also come with physical dangers, as well. In October, a small helicopter drone tumbled out of the sky over midtown Manhattan, crashing to the sidewalk near Grand Central Station; on the way down it almost hit a businessman, who plucked out the video card from the wreckage and handed it over toa local television-news station. In the video, the drone (a Phantom Quadcopter) buzzes some skyscapers before the pilot—clearly inexperienced—crashes it against the side of a building. Drone enthusiasts and engineers blamed the Quadcopter’s poor performance on the pilot’s possible reliance on GPS mode in an area with tall buildings, which block GPS signals, potentially leading vehicles disastrously off-target.
by Nick Kolakowski, Slashdot | Read more:
Image: Amazon
Russell Wilson, Makes Case For MVP
[ed. I'm probably biased but Russell Wilson is one of the most exciting and talented quarterbacks I've seen in a long, long time.]
It's OK. We all were, really. Even the Seahawks passed on the Wisconsin quarterback twice before taking him off the board with the No. 75 overall pick in the third round of the 2012 draft.
It's a shame, too. Wilson's only crime as a prospect was his height. No quarterback could stand at 5'11 and compete with the best quarterbacks in the NFL. We didn't care about his compact throwing motion, rocket arm or uncanny ability to sense and avoid pressure in the pocket while keeping his eyes downfield. What does any of that matter? He's short, remember?
If we only knew then what we know now, maybe we wouldn't have been so shallow. Maybe we would have looked beyond the measuring stick and realized that a future star was sitting right in front of us. It's not like he was hiding. Wilson played for Wisconsin, albeit for only a season after transferring from N.C. State, where Mike Glennon took over for Wilson while he was pondering a professional baseball career. Wilson was in the spotlight.
Not only were his obvious passing tools on display in one of college football's biggest conferences, but so to was his charismatic personality and leadership qualities. His relentless attitude on the field was there, too. He attacked every area of the field with his arm and made defenses pay with his legs.
But when it came time to evaluate Wilson as an NFL prospect, he was too short. He didn't fit the mold of traditional pocket passer. That was the end of the story. Drew Brees, after all, was the only short quarterback to reach the coveted "elite status" in the NFL. Nobody considered that Wilson could succeed at a similar level. Nobody considered that in just his second season, Wilson would be better than Brees. (...)
Just face it, you were wrong about him. You didn't think a 5'11 quarterback would ever be considered one of the best in the NFL. You didn't think he would enter the league and help the Seahawks win 10 games by more than 15 points, a number only bested by Manning and the Broncos. And you certainly didn't think, out of all the talented quarterbacks in the 2013 class, that Wilson would be the one making a case to be the NFL's Most Valuable Player in just his second season.
by Matthew Fairburn, SBNation | Read more:
Image: Kirby Lee-USA TODAY Sports
Monday, December 2, 2013
Coding Kids
The doorbell rings, and Katie Wenger, 13, leaps up from the family dinner table and throws open the front door. On the stoop of her family’s building in Chelsea stands a 26-year-old Yale graduate named Allison Kaptur. Formerly a financial analyst, Kaptur quit to teach herself how to program and now works as a facilitator at Hacker School, a “writers’ retreat for programmers,” with a sideline as a coding tutor. The two descend the stairs to a basement study, and Katie shuts the door. “I’ve got exciting news,” she says. “I’m going to launch a start-up! It’s called Let Us.”“What will it do?”
“It’ll be like Chatroulette, but connected to Facebook.” Katie describes her concept for an online environment in which strangers can randomly meet and either just chat or interact educationally as student and teacher. Kaptur nods. “Okay,” she says. “A little later, we can talk about the pieces we would need to make that work.”
For most people, software programming’s social cachet falls somewhere between that of tax preparation and autism. But it’s catching fire among forward-thinking New York parents like Katie’s, who see it as endowing their children both with a strategically valuable skill and a habit for IQ-multiplying intellectual rigor. According to WyzAnt, an online tutoring marketplace, demand for computer-science tutors in New York City has doubled each of the past two years. And if one Silicon Alley–backed initiative pans out, within a decade every public-school kid in the city will have access to coding, up from a couple of thousand.
Down in the Wengers’ study, Kaptur flips open a MacBook Air. “For now, let’s work on a hangman game.” Lines of Python code fill the screen. On a piece of paper the two begin sketching out a stick figure and a flow diagram to figure out how the program will render it. Katie breathes a sigh. “This is more complicated than I thought it would be,” she says. “This is going to take more than an hour.” Sure enough, by the time Kaptur packs up to go, they haven’t yet gotten around to rendering the stickman’s arms, let alone plotted out the next billion-dollar app.
Back upstairs, the parents are lingering over a long dinner. Katie’s mother, Susan Danziger, runs a web-video start-up; her father, Albert Wenger, is a managing partner in the VC firm Union Square Ventures, an early investor in Twitter, Tumblr, Foursquare, Zynga, and Kickstarter. The couple started Katie and her two brothers on programming when they were 7 or 8. “The goal isn’t necessarily for everyone to become a computer-science engineer, just as when you teach people how to write English, the goal isn’t for everybody to become an author,” says Wenger. “The point is that it’s a very important way of analyzing the world, thinking about the world, interacting with the world, and manipulating the world. It is a fundamental enabling skill that is applicable across the widest imaginable set of domains.”
by Jeff Wise, NY Magazine | Read more:
Image: Brian Finke
The Big Sleep
One evening in late May, four senior employees of Merck, the pharmaceutical company, sat in the bar of a Hilton Hotel in Rockville, Maryland, wearing metal lapel pins stamped with the word “team.” They were in a state of exhausted overpreparedness. The next morning, they were to drive a few miles to the headquarters of the Food and Drug Administration and attend a meeting that would decide the future of suvorexant, a new sleeping pill that the company had been developing for a decade. Merck’s team hoped to persuade a committee of seventeen, composed largely of neurologists, that suvorexant was safe and effective. The committee, which would also hear the views of F.D.A. scientists, would deliver a recommendation to the agency. If the government approved suvorexant—whose mechanism, inspired partly by research into narcoleptic dogs, is unlike anything on the market—it would be launched within a year. Some industry analysts had described it as a possible blockbuster, a term usually reserved for drugs with annual earnings of a billion dollars. Merck had not created a blockbuster since 2007, when it launched Januvia, a diabetes drug. The company was impatient. A factory in Las Piedras, Puerto Rico, was ready to start production.
David Michelson, who runs Merck’s clinical research in neuroscience, said of suvorexant, “It’s huge. It’s a major product.” He was sitting perfectly still in his chair; his hair flopped a little over his forehead. He looked as if he were waiting in an airport for a very late flight.
For months, in rooms across Merck’s archipelago of mismatched buildings north of Philadelphia, Michelson had taken part in role-playing rehearsals for the F.D.A. meeting. The focus had been on readying Joe Herring, another Merck neuroscientist; he would be the primary speaker, having run the later clinical trials of suvorexant. Herring, a straight-backed, athletic-looking man in his fifties, had just gone up to his room, for an early night. “Joe had to find a way to be authentic,” Michelson recalled. “He had to find a way to engage with the audience without becoming too informal.” During the meeting, Herring would have access to a library of twenty-one hundred and seventy PowerPoint slides.
The Merck team was frustrated. The F.D.A. had just shown them the draft of a presentation, titled “Suvorexant Safety,” that would be delivered by Ronald Farkas, an F.D.A. neuroscientist who had reviewed thousands of pages of Merck data. In a relentless PowerPoint sequence, Farkas made suvorexant sound disquieting, almost gothic. He noted suicidal thoughts among trial participants, and the risk of next-day sleepiness. He quoted from Merck’s patient notes: “Shortly after sleep onset, the patient had a dream that something dark approached her. The patient woke up several times and felt unable to move her arms and legs and unable to speak. Several hours later, she found herself standing at the window without knowing how she got there.” A woman of sixty-eight lay down to sleep “and had a feeling as if shocked, then felt paralyzed and heard vivid sounds of people coming up the stairs, with a sense of violent intent.” A middle-aged man had a “feeling of shadow falling over his body, hunted by enemies, hearing extremely loud screams.”
An F.D.A. presentation that focusses on individual “adverse events”—and draws attention to patients feeling “hunted by enemies”—is discouraging to a drug’s sponsor. Michelson called the presentation “somewhat unusual,” and emitted a dry laugh.
Darryle Schoepp, the head of Merck’s neuroscience division, was at the other end of the table. During the human trials of suvorexant, he noted, it had been taken two hundred and seventy thousand times, and “every time you take a drug it’s an opportunity for something to happen that the user can report.” He added, “Go back to the early days of Ambien. I wonder how many patient days of data they had with Ambien.”
Ambien, which is now available generically as zolpidem, is one of America’s most popular drugs, and it played a role—silent or spoken—in many conversations that I had heard on visits to the Merck offices. Zolpidem was the cheap drug that suvorexant had to take on, if not unseat, in order to succeed in the sleep-medication market. In addition, rising public worry about risks associated with taking Ambien—ranging from amnesiac devouring of Pop-Tarts to premature death—had reduced the F.D.A.’s tolerance for side effects in sleep medications.
John Renger was also at the bar. A forty-four-year-old neuroscientist, he has a round face, cropped hair, and a neat goatee. He helped lead the company to the suvorexant molecule, and ran the first tests on rats, mice, dogs, and rhesus monkeys. He, too, was politely indignant about the F.D.A. “They’ve taken the emphasis off efficacy,” he said, adding, “They’re saying any residual effects are bad. But they’re not looking at the balance—‘What is the improvement in this mechanism?’ ”
The central nervous system is in an ever-adjusting balance between inhibition and excitation. Ambien, like alcohol or an anesthetic, triggers the brain’s main inhibitory system, which depends on binding between gaba—gamma-aminobutyric acid, a neurotransmitter—and gaba receptors on the surface of billions of neurons. gabareceptors can be found throughout the brain, and when they’re activated the brain slows. Ambien encourages the process by sticking to the receptors, holding open the door to the neurotransmitter. Suvorexant, which Merck describes as “rationally designed”—rather than stumbled upon, like most drugs—influences a more precise set of neurotransmitters and receptors. Orexin neurotransmitters, first identified fifteen years ago, promote wakefulness. When suvorexant is in the brain, orexin is less likely to reach orexin receptors. Instead of promoting general, stupefying brain inactivity, suvorexant aims at standing in the way of a keep-awake signal. This difference may or may not come to mean a lot to insomniacs, but Merck’s marketing is likely to encourage the perception that suvorexant ends the dance by turning off the music, whereas a drug like Ambien knocks the dancer senseless.
If the Merck scientists succeeded at the F.D.A., they would be the first to bring an orexin-related drug to market. “It’s an amazing achievement,” Richard Hargreaves, the fourth colleague at the Hilton, said. “Everyone should be really proud.” But, he added, “my worry is that a new mechanism is being evaluated on the science of an old mechanism.”
“With Ambien, you’ve got a drug that’s got basically only onset,” Renger said, dismissively. That is, it sends you to sleep but might not keep you asleep. “Suvorexant has the onset, but it has the great maintenance, especially in the last third of the night, where other drugs fail.” And even though suvorexant keeps working longer than Ambien, suvorexant patients don’t feel groggier afterward, as you might expect. Impassioned, Renger imagined himself addressing the F.D.A.: “Why aren’t you giving this a chance?”
“Drugs usually have some side effects,” Schoepp said. “It’s all benefit-risk.” He added, “There is some dose where suvorexant will be ultimately safe—because nothing will happen. If you go low enough, it becomes homeopathic.”
They stood to go to their rooms. Schoepp murmured, “I’d love to take it right now.”
David Michelson, who runs Merck’s clinical research in neuroscience, said of suvorexant, “It’s huge. It’s a major product.” He was sitting perfectly still in his chair; his hair flopped a little over his forehead. He looked as if he were waiting in an airport for a very late flight.For months, in rooms across Merck’s archipelago of mismatched buildings north of Philadelphia, Michelson had taken part in role-playing rehearsals for the F.D.A. meeting. The focus had been on readying Joe Herring, another Merck neuroscientist; he would be the primary speaker, having run the later clinical trials of suvorexant. Herring, a straight-backed, athletic-looking man in his fifties, had just gone up to his room, for an early night. “Joe had to find a way to be authentic,” Michelson recalled. “He had to find a way to engage with the audience without becoming too informal.” During the meeting, Herring would have access to a library of twenty-one hundred and seventy PowerPoint slides.
The Merck team was frustrated. The F.D.A. had just shown them the draft of a presentation, titled “Suvorexant Safety,” that would be delivered by Ronald Farkas, an F.D.A. neuroscientist who had reviewed thousands of pages of Merck data. In a relentless PowerPoint sequence, Farkas made suvorexant sound disquieting, almost gothic. He noted suicidal thoughts among trial participants, and the risk of next-day sleepiness. He quoted from Merck’s patient notes: “Shortly after sleep onset, the patient had a dream that something dark approached her. The patient woke up several times and felt unable to move her arms and legs and unable to speak. Several hours later, she found herself standing at the window without knowing how she got there.” A woman of sixty-eight lay down to sleep “and had a feeling as if shocked, then felt paralyzed and heard vivid sounds of people coming up the stairs, with a sense of violent intent.” A middle-aged man had a “feeling of shadow falling over his body, hunted by enemies, hearing extremely loud screams.”
An F.D.A. presentation that focusses on individual “adverse events”—and draws attention to patients feeling “hunted by enemies”—is discouraging to a drug’s sponsor. Michelson called the presentation “somewhat unusual,” and emitted a dry laugh.
Darryle Schoepp, the head of Merck’s neuroscience division, was at the other end of the table. During the human trials of suvorexant, he noted, it had been taken two hundred and seventy thousand times, and “every time you take a drug it’s an opportunity for something to happen that the user can report.” He added, “Go back to the early days of Ambien. I wonder how many patient days of data they had with Ambien.”
Ambien, which is now available generically as zolpidem, is one of America’s most popular drugs, and it played a role—silent or spoken—in many conversations that I had heard on visits to the Merck offices. Zolpidem was the cheap drug that suvorexant had to take on, if not unseat, in order to succeed in the sleep-medication market. In addition, rising public worry about risks associated with taking Ambien—ranging from amnesiac devouring of Pop-Tarts to premature death—had reduced the F.D.A.’s tolerance for side effects in sleep medications.
John Renger was also at the bar. A forty-four-year-old neuroscientist, he has a round face, cropped hair, and a neat goatee. He helped lead the company to the suvorexant molecule, and ran the first tests on rats, mice, dogs, and rhesus monkeys. He, too, was politely indignant about the F.D.A. “They’ve taken the emphasis off efficacy,” he said, adding, “They’re saying any residual effects are bad. But they’re not looking at the balance—‘What is the improvement in this mechanism?’ ”
The central nervous system is in an ever-adjusting balance between inhibition and excitation. Ambien, like alcohol or an anesthetic, triggers the brain’s main inhibitory system, which depends on binding between gaba—gamma-aminobutyric acid, a neurotransmitter—and gaba receptors on the surface of billions of neurons. gabareceptors can be found throughout the brain, and when they’re activated the brain slows. Ambien encourages the process by sticking to the receptors, holding open the door to the neurotransmitter. Suvorexant, which Merck describes as “rationally designed”—rather than stumbled upon, like most drugs—influences a more precise set of neurotransmitters and receptors. Orexin neurotransmitters, first identified fifteen years ago, promote wakefulness. When suvorexant is in the brain, orexin is less likely to reach orexin receptors. Instead of promoting general, stupefying brain inactivity, suvorexant aims at standing in the way of a keep-awake signal. This difference may or may not come to mean a lot to insomniacs, but Merck’s marketing is likely to encourage the perception that suvorexant ends the dance by turning off the music, whereas a drug like Ambien knocks the dancer senseless.
If the Merck scientists succeeded at the F.D.A., they would be the first to bring an orexin-related drug to market. “It’s an amazing achievement,” Richard Hargreaves, the fourth colleague at the Hilton, said. “Everyone should be really proud.” But, he added, “my worry is that a new mechanism is being evaluated on the science of an old mechanism.”
“With Ambien, you’ve got a drug that’s got basically only onset,” Renger said, dismissively. That is, it sends you to sleep but might not keep you asleep. “Suvorexant has the onset, but it has the great maintenance, especially in the last third of the night, where other drugs fail.” And even though suvorexant keeps working longer than Ambien, suvorexant patients don’t feel groggier afterward, as you might expect. Impassioned, Renger imagined himself addressing the F.D.A.: “Why aren’t you giving this a chance?”
“Drugs usually have some side effects,” Schoepp said. “It’s all benefit-risk.” He added, “There is some dose where suvorexant will be ultimately safe—because nothing will happen. If you go low enough, it becomes homeopathic.”
They stood to go to their rooms. Schoepp murmured, “I’d love to take it right now.”
by Ian Parker, New Yorker | Read more:
Image: Kenji Aoki
Sunday, December 1, 2013
Far From My Tree
[ed. The flipside to Holding Them Closer.]My eldest son is 20 years old, lives in a house crammed with seven scrabbly roommates, works part time in a restaurant kitchen, doesn’t drive, is a vegetarian, and has homemade tattoos etched into his thighs.
He’s firmly a musician – a drummer in a loud punk band, and he loves nothing more than to tour across North America, playing gigs in sketchy houses in Oakland, Calif., and south Chicago.
He appears to have only one pair of pants – dirty, black cutoff jeans, and his shirts are also of the ripped-off-arms variety. I’m not sure who has been ripping up all his clothes. Maybe there’s a wild dog living in his house.
I’m both proud of and horrified for my boy. His jaw is squarely set, and he’s acutely committed to what he wants to do. And that is to tour with his band in their black-panel van, crisscrossing borders, dodging death in dubious neighborhoods, sleeping on strangers’ couches, and eating vegetarian burritos.
As my children traveled through their teenage years, I emphasized to them: Find your passion and follow it. What I really meant was: Find your passion, but do it in the way I did it. That is, go to college first, get a liberal arts degree, meander through your 20s, and then supplement your undergraduate degree with graduate studies. All while wearing clean, intact clothing.
But what if, as Andrew Solomon so eloquently addresses in his masterpiece, “Far From the Tree,” your child ends up so very different from you? I read “Far From the Tree” because it speaks of children with disabilities (and my youngest son has Down syndrome), but I gained a deeper knowledge of all children who stray from their parents. If we face reality squarely, and give our children the space to be who they want to be, every single child should be different from his parents, and should be allowed and even encouraged to fall far from our trees.
My oldest boy does not show up to family events in his collared shirt and pressed pants. In fact, he rarely shows up at all. He doesn’t respond to calls from grandparents, although he will send thank you texts for birthday gifts, so he still has a sliver of decorum. He’s proudly anti-establishment, and my current lifestyle with my husband (and his stepfather) – living in the suburbs and driving a BMW – clearly disgusts him.
I watch my friends’ children embarking on their second year of college, most of them still living at home with their parents. They are clean-cut, unfailingly polite, sit quietly at dinner parties and patiently dole out answers to questions from adults. Inevitably, someone asks me, “What’s your son doing?” and then I feel a strange mix of pride and apology. “He’s living his life,” I say. “But what graduate program? What path is he taking?” “He’s not in a program,” I say. “He’s working and playing in a band.” They take a deep gulp of wine and look down at their expensive shoes.
by Sue Robins, NY Times | Read more:
Image: uncredited
All Is Fair in Love and Twitter
In Silicon Valley, ideas are not in short supply. At every coffee shop, beer garden and technology conference, there are legions of start-up founders, like screenwriters clutching their scripts, desperate to show off an app or site that they believe will be the next big thing. Yet around 75 percent of start-ups fail. Usually it’s not simply because the ideas are bad (although some certainly are), but because of a multitude of other problems. They are either ahead of their time or too late. Some have too much money and collapse under their own weight; others have trouble raising the capital they need to survive. Still others implode because of the poor management and infighting of founders who have no experience actually running companies.
For the ones that make it, success often comes down to a lot of luck. YouTube was one of dozens of video-sharing sites in existence when it was purchased for $1.7 billion by Google. Instagram wasn’t the first app on iTunes to share photos, yet Facebook still paid $1 billion for it. Twitter wasn’t the first place to share a status online; it was certainly the luckiest. Celebrities joined the service, then a queen, presidents, news organizations and, of course, Justin Bieber. Seven years after it was founded, the company with a catchy name had more than 2,000 employees, more than 200 million active users and a market value estimated at $16 billion. When it makes its initial public offering, many of Twitter’s co-founders, employees and investors are going to become very, very rich. Evan Williams, a co-founder who financed the company out of his pocket during its first year, is expected to make more than $1 billion. Dorsey, the company’s executive chairman and putative mastermind, will make hundreds of millions.
But in Silicon Valley, luck can be a euphemism for something more sinister. Twitter wasn’t exactly conceived in a South Park playground, and it certainly wasn’t solely Dorsey’s idea. In fact, Dorsey forced out the man who was arguably Twitter’s most influential co-founder before the site took off, only to be quietly pushed out of the company himself later. (At which point, he secretly considered joining his biggest competitor.) But, as luck would have it, Dorsey was able to weave a story about Twitter that was so convincing that he could put himself back in power just as it was ready to become a mature company. And, perhaps luckiest of all, until now only a handful of people knew what really turned Twitter from a vague idea into a multibillion-dollar business.
Genesis stories tend to take on an outsize significance in Silicon Valley. Steve Jobs dropped out of Reed College, traveled the world, dated Joan Baez and helped create a revolutionary computing company. Mark Zuckerberg wrote the initial code for Facebook while ranking the attractiveness of girls in his Harvard dorm room. In the Valley, these tales are called “the Creation Myth” because, while based on a true story, they exclude all the turmoil and occasional back stabbing that comes with founding a tech company. And while all origin stories contain some exaggerations, Twitter’s is cobbled together from an uncommon number of them.
by Nick Bilton, NY Times | Read more:
Image: Paul Sahre
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