Jessa Gamble | The Atlantic 2022 by The Atlantic Monthly Group. All Rights,2016:50-506390<p>In a time when college graduates return to live under their parents’ roofs and top careers require years of internships and graduate degrees, the age of adulthood is receding, practically into the 30s. Adolescence, loosely defined as the period between puberty and financial independence, now lasts about 15 years, twice as long as it did in the 1950s.</p><p>Part of this is due to the declining age of puberty in both males and females, but most of that extension appears in the 20s, when an increasing number of young people are still dependent on their parents. There is some concern that all of this dependence could lead to a lasting immaturity and failure to take on responsibility.</p><p>But according to developmental researchers, there is one lasting gift that extended adolescence can bestow, and it resides in the brain. “Neurobiological capital” is built through a protracted period of learning capacity in the brain, and it is a privilege that comes to those lucky enough to enjoy intellectually stimulating environments in late adolescence. Far from a contributor to emotional immaturity, the trend toward an adolescence that extends into the mid-20s is an opportunity to create a lifelong brain-based advantage.</p><p>Choirmasters’ records show that whereas choristers’ voices broke around age 18 in the mid-1700s, that age declined to 13 in 1960, and voices now break on average at age 10-and-a-half. Meanwhile, the age of first menstruation in girls has been declining by more than three months per decade. Much of that change comes down to improved nutrition, but in recent years the age drop <a href="">has become a health concern</a>. Marriage and financial security, on the other side of adolescence, now arrive close to age 30, in contrast to the early-20s marriages of the 1950s. In combination, those changes make for a more dominant life stage between childhood and adulthood.</p><p>Biologically, adolescence serves to prepare the brain for independence, and it represents the last surge of plasticity, when the brain is far more open to change than it was in middle childhood. The child-development expert Stuart Shanker says this pushes the teenager out of the house, replacing the overly comfortable embrace of the parent with the riskier world of peers and autonomy.</p><p>“Here, nature has spent eight or nine years getting the brain into a stable state in terms of higher functions, and then it’s all suddenly thrown back into chaos,” says Shanker. “We see changes in their reward system, which drives them into peer activities.”</p><p>The central task of adolescence is to develop the ability to self-regulate—to manage stress so that it does not interfere with the ability to follow through on plans and delay gratification. In particular, connectivity develops between the prefrontal cortex, crucial for executive functions like attention and decision-making, and the limbic system that drives emotion and reward.</p><p>Adults vary widely in the degree of success they achieve with this type of impulse control, and it has a large bearing on their life outcomes in work and relationships. Depression, obesity, and substance abuse are all exacerbated by self-regulation deficiencies, and adolescents who miss the opportunity to develop these capacities disproportionately run afoul of the law. For a teenager, potential rewards are almost irresistibly appealing, and the attendant risks seem worth it. The tendency to bet on a low-probability outcome is highest at age 16, and <a href="">arrests peak at 18</a>.</p><p>It’s not a matter of logic. In fact, a 15-year-old can reason and problem-solve as well as an adult in many areas of calculation, and they can <a href="">accurately identify</a> the risks of drug taking, unsafe sex, and crime. It’s when incentives, fatigue, social pressures, or stress come into play that an adolescent becomes more susceptible to irrational thinking. Last to develop are the circuits that deal with navigating other people’s needs and emotions, pushing past failure without losing determination, and connecting immediate actions to long-term consequences. With a longer adolescence, some people have an extra chance to strengthen these human capacities.</p><p>“There is reason to believe that continued exposure to novelty keeps the brain plastic for longer,” says Laurence Steinberg, a psychologist at Temple University whom many consider the leading <a href="">expert on adolescence</a>. Some of this evidence comes from brain studies of those who have had access to higher education.</p><p>The window for developing self-regulation closes when adult life settles into a routine, and the brain begins to exchange growth for efficiency. But if an adolescent continues to be stimulated intellectually—through higher education or travel, for example—their brain remains in its formative stage into the mid-20s, and even primes itself for future learning in adulthood. Dubbed “<a href="http://">metaplasticity</a>,” changing brain circuits through learning during adolescence can make subsequent modifications easier in those areas.</p><p>For parents, there are ways to encourage the brain to achieve better impulse control and stress management while the window of plasticity is open. Adolescents who develop exceptional self-regulation tend to have the benefit of parents who are neither too permissive nor too authoritarian. A warm, supportive, and firm hand lends teens the confidence to challenge themselves while steering them away from risky activities.</p><p>Steinberg likens the distinction between the brain’s adult state and its adolescent development mode to the difference between reading a new book and learning to read in the first place. For an adult to learn, she must pay attention and place information in the context of what she already knows. In contrast, an adolescent brain remembers things even through passive exposure. After that sensitive period has closed, the brain begins to focus on stabilizing the connections it has already made, through the process of myelination. It becomes exponentially more difficult to shape decision-making and higher cognitive functions. Those final pre-adult years may be the last, best chance to put a person on a healthy path.</p><p>While exciting as a prospect, the lifelong advantages of an extended adolescence can be economically exclusive. Protracted brain plasticity often depends on access to a stimulating environment—and the money that entails. Instead of falling into the rote tasks of an entry-level position after college, a debt-free graduate might volunteer overseas for a year and learn a new language and culture. In the world of enriching experiences and brain plasticity, as everywhere else, time is money. Parents who expect their children to make their way in the world after college, as they themselves did in the 70s and 80s, may be surprised to find they are not quite as obsolete as they had planned to be.</p><p>“Parents should prepare themselves for the timetable being different,” says Steinberg. “I never anticipated that my son would depend on us after college. Had I known that, we might have saved extra.”</p><p>To maximize neurobiological capital, it soon may not be enough for parents to sock away money in college savings accounts. Some may need to budget for a Neurobiological Runway Fund to cover the post-college years, too.</p>Jessa Gamble Segar / ReutersWorkers ride a 19th-century swing in New York.The Cognitive Benefits of Being a Man-Child2016-11-03T13:37:00-04:002016-11-03T17:55:19-04:00For men and women, extending adolescence has the potential to make the brain more capable in,2016:50-496547<p>In the vast arboretum near my home, ducks clamor on pond shores as shrieking children throw bread. The bike path bustles with university students, and, in winter, the adjacent canal teems with skaters. But for me, any health benefits that accrue from a brisk walk in the park are—I’m convinced—counteracted by the stress of encountering an off-leash dog.</p><aside class="callout-placeholder" data-source="special-report"></aside><p>My profound discomfort with canines may not rise to the level of phobia, but it is usually enough to turn a pleasant experience into a trial. When I see a dog, I may abruptly take a wide detour, or turn around altogether. Nevertheless, while easy, this approach probably isn’t helping me overcome my fear. According to science, the best solution to my dog problem is more dogs.</p><p>Exposure therapy, a form of cognitive behavioral therapy, involves subjecting patients to increasing amounts of things they fear, or otherwise hope to avoid. It is one of the great success stories of mental health, and it’s not just for phobias. Research on cases of intense fear and even traumatic brain injury shows that for a number of problems, the only way out is through.</p><p>After a concussion, for instance, many people find themselves unable to work. Reading for any length of time kicks off bouts of dizziness and a bright light could bring on crashing headaches. Even thinking for any length of time is exhausting. Anything but sitting still and sheltering the mind feels like a dangerous activity. That aversion to pain is perfectly natural, but it can lead to a stalled-out recovery.</p><p>Though the vast majority of concussion sufferers are fully recovered within three months or so, a “<a href="">miserable minority</a>”—5 percent or so—have persistent, debilitating symptoms. Long-term follow up shows no improvement, and even deterioration years down the road. Until recently there was no proven treatment for this seemingly permanent damage to quality of life.</p><p>The <a href="">best </a>treatment for overcoming concussions is a type of cognitive-behavioral therapy that includes going back to work for a longer workday each week, and exercising with progressively greater intensity, even if one’s symptoms come roaring back with a vengeance. Only by pushing through the misery, it seems, can the brain get back to its normal activities.</p><p>Exposure therapy is also a highly effective tool for overcoming post-traumatic stress. Reliving the battlefield from the safety of a peacetime environment has been shown to <a href="">gradually remove</a> the expectation of harm from the memory.</p><p>Ethically, for both concussions and PTSD, however, a treatment that consists of suffering is a tough sell for doctors, who have taken an oath not to do harm. The approach is one of the most underutilized treatments for PTSD, because psychologists <a href="">are deeply uncomfortable</a> with re-traumatizing their patients. And exposure therapy also holds little appeal in the short run for patients. For a concussion-sufferer, seeking out more pain feels like exactly the wrong thing to do.</p><p>Of course, many other medical treatments are also painful, and the long-term benefits are considered worth the trade-off. But in the case of exposure therapy, there is no palliative option—no anesthetic or painkiller—because the discomfort is not a side effect, it’s the main event.</p><p>Recently, a more palatable route has been introduced with virtual reality. The Virtual Reality Medical Center in San Diego, for example, offers VR therapy for all manner of fears. Heights, driving, needles and blood, spiders, enclosed spaces—you name it, they treat it. First steps in traditional phobia treatment sometimes involve imagining fearful scenarios, but a patient’s mind is naturally resistant to those thoughts and will go to some lengths to avoid fleshing out terrifying visions. Virtual reality scenarios have proved useful in social phobias, wherein patients have a debilitating fear of interacting with other people.</p><p>For social phobias, exposure therapy in the real world is hard to control, because social interactions are so complex and unpredictable. A course of virtual-reality therapy will lead the patient through a number of exercises. First they might have to <a href=";script=sci_arttext">approach someone on the street</a> or walk into a party where people turn to look at them. Finally, they might have to greet guests and—one of the most common of all fears—give a speech.</p><p>The practical drawback of virtual-reality therapy is that immersive environments are expensive to create and phobias come in many varieties. If someone has a paralyzing fear of paperclips, they are unlikely to find an off-the-shelf exposure program to treat them. That’s why others are turning to augmented reality, where the real, physical world is supplemented by input—either visual or audio—from a computer.</p><p>A head-up display screen that a patient looks through, for instance, can simply overlay a real-world environment with progressively closer-moving images of that patient’s feared object. Children who fear cockroaches can build up their courage until those insects appear to be walking all over their hands. Augmented reality treatment seems to be <a href="">as effective</a> long term for small animal phobias as actual exposure to those animals.</p><p>Only<a href=";aid=1046424&amp;fileId=S0033291707000086"> 8 percent</a> of phobia sufferers seek professional help for it, and fear of the treatment itself may be part of that. I am unlikely to subject myself to any more dogs than I already encounter in a given day, though a computerized dog sounds just about manageable. If some newer treatments are more humane, others still turn to that old maxim: No pain, no gain.</p>Jessa Gamble Moraes / ReutersInteracting with dogs in virtual or augmented reality could help someone get over a crippling fear of them.When Pain Is the Best Therapy2016-08-19T08:00:00-04:002016-08-19T08:00:25-04:00Exposing people to what they fear—even in virtual reality—is an effective way to overcome,2016:50-496106<p>It has been 30 years since the first findings that heart attacks are most common in the early morning. Since then, research has revealed that those first three hours after waking are also when a cardiac event is most damaging. In fact, the whole cardiovascular system is controlled by circadian rhythms that influence the likelihood of stroke, kidney failure, and heart attacks.</p><aside class="callout-placeholder" data-source="special-report"></aside><p>If this new knowledge about circadian rhythms has taught us anything, it is the value of time as a dimension in medicine. Many physiological changes are tied to 24-hour body rhythms, and these changes have been revealed, in part, through continuous monitoring of the same individuals through time. Other forms of vigilant patient-tracking—sometimes over decades for a single person—have demonstrated  that to understand how diseases develop, there is no substitute for watching someone’s health change in real time.</p><p>“Aging studies are based on age cohorts. They look at trends in the likelihood of having diseases as a function of age,” says Germaine Cornelissen, the director of the Halberg Chronobiology Center at the University of Minnesota. “Longitudinal monitoring can look at trends as a function of age in the same person, starting with presumably healthy subjects.”</p><p>There is an inherent story-telling appeal to the longitudinal study. <em>The Up Series</em>, a British documentary that revisits the same children every seven years of their lives, demonstrates the entrenched nature of the class system in England. Unfolding before the audience’s eyes, each child’s life follows a course seemingly predestined by his or her circumstances of birth.</p><p>The longitudinal study’s main limitation is that it is not an experiment, where one factor is intentionally manipulated by a scientist. To draw more solid conclusions, babies in the documentary series would have been randomly assigned to families along the socio-economic spectrum. In recognition of basic ethical standards and to be true to life, studies like these are based on observation.</p><p>The 75-year <a href="">Study of Adult Development</a> at Harvard Medical School followed hundreds of American men who came of age during the Second World War. For this generation, alcoholism was the largest cause of divorce, and smoking was the greatest contributor to early death. Even levers of life happiness—overwhelmingly determined by warm relationships—could be teased out from this study.</p><p>The longitudinal study has great power because it can compare later values with the same person’s baseline state. Many of the established baselines in medicine have been much better studied in men than in women, who tend to have lower blood pressure and higher heart rates, among other differences. What is average for the general population may represent an alarming shift for any given person.</p><p>The trouble is, long-term observation is only possible if it is as unobtrusive as possible. The moment monitoring becomes burdensome for subjects, the results may not be representative of normal life—and subjects may start disappearing from a study.</p><p>Take blood pressure, which is particularly hard to observe in real time over the course of months in a healthy person. “A major hurdle to the kind of longitudinal monitoring we would like to do is reluctance to use the monitor,” says Cornelissen. “We are looking for a non-invasive way to monitor continuously for a week or longer that does not use uncomfortable cuffs.”</p><p>One potential avenue would be a flexible electronic circuit like the one John Rogers, a materials scientist at Northwestern University, has developed. Dubbed “<a href="">epidermal electronics</a>,” the device sticks like a temporary tattoo over a vein or artery on the forearm. It delivers continuous heat, and based on the rate of cooling, infers the amount of blood flow carrying that heat away.</p><p>The contemporary craze for health-monitoring smart-phone apps has prepared a wide segment of society for tracking their medical data through time. Cornelissen is hopeful that a long-term crowd-sourcing approach to blood pressure measurement could contribute much more to our understanding than one-off studies.</p><p>Blood pressure and heart rate rise during the day and fall at night. The changes are under control of the brain’s master clock, the suprachiasmatic nucleus, which orchestrates the body’s circadian rhythms. Some diagnosed cases of high blood pressure are accompanied by large swings; a daytime measure of high blood pressure may actually become low blood pressure at night, and there are some indications that this change may be a bigger concern than blood pressure itself.</p><p>New research suggests that these vascular variability disorders—or circadian overswing—may be masquerading as high blood pressure when it is measured only at mid-day doctor’s appointments. Some patients even suffer a shift in the timing of their rhythm, experiencing peak blood pressure at night and lowest blood pressure in the day, out of sync with the rest of their physiology.</p><p>A study at Tokyo Women’s Medical University tracked blood pressure over a 48-hour period to separate straightforward hypertension from high blood pressure with vascular variability problems—either in the size of the change or in its timing. Over the next six years, fewer than 10 percent of the hypertensive subjects had a cardiovascular “morbid event” such as heart attack or stroke. Of those with a vascular variability problem, however, that number rose to 29 percent, and even higher for subjects with multiple rhythm problems.</p><p>With every increase in blood pressure, the risk factor for cardiovascular problems goes up, but the daily change in blood pressure is healthy until it crosses a threshold. Above that threshold, stroke or kidney failure in the next six years becomes much more likely.</p><p>Longitudinal studies are the opposite of today’s quick-and-dirty experiments that yield publishable results before the current round of Ph.D. students turns over. Often researchers who start them have long retired or died before a longitudinal study comes to fruition. But that’s exactly the sort of commitment needed. The word “monitoring” is rarely sexy, but it represents the sort of slow receptivity that has built a solid case around the climate crisis, and other steadily evolving conditions. To understand how people change, one must watch them changing.</p>Jessa Gamble Nicholson / ReutersResearchers may soon have much more advanced devices for tracking blood pressure than the one pictured here, at a medical clinic in Los Angeles.Modern Medicine Is Too Reliant on Short-Term Studies2016-08-17T09:00:00-04:002016-08-17T09:24:33-04:00Vigilant, long-term monitoring of patients is the,2016:50-494414<p>Eight hours of uninterrupted sleep per night—it’s so widely recommended it approaches an axiom. The strange thing is, there’s nothing natural about it. In a landmark <a href=";jsessionid=99CF0E1CE0E8FF9B77485BA3BA9CA245.f01t04">1992 study</a>, Thomas Wehr demonstrated that humans, like many other animals, are naturally inclined to sleep in bouts, separated by periods of activity. Given 10 hours per day of light, instead of the modern sixteen hours of artificial lights-on time, subjects sleep in two symmetrical blocks of several hours each. In the middle of the night, they wake up fully for up to three hours.</p><aside class="callout-placeholder" data-source="special-report"></aside><p>In 2010, I gave a <a href="">talk at TEDGlobal</a> in which I described this alternative sleeping pattern as a candidate for our ancestral sleep schedule. Pre-industrial literature from <i>Canterbury Tales</i> to <i>Wuthering Heights </i><a href="">describes</a> a “first sleep” (sometimes called “beauty sleep” or “dead sleep”) and a “second sleep” in early modern English society. And ever since that talk was translated into 39 languages and approached the two-million-view mark, I have been receiving emails from polyphasic sleepers—people who sleep in spurts around the clock.</p><p>There is a seemingly inexhaustible supply of people who want to experiment with their own sleep. With the rise of productivity culture, time is money, both in the literal sense and in a broader kind of experiential currency. Many resent the third of their lives lost to unconsciousness and wish to be present for more of it. Some of those people—overwhelmingly male, in late adolescence—try sleeping polyphasically, in bits. If naps can be refreshing, the logic goes, perhaps that’s all we really need.</p><p>Buckminster Fuller, who prefigured our current crop of MIT-dropout geniuses in twice being expelled from Harvard, was in some ways a lifelong adolescent male. He spent a couple of years following a “Dymaxion sleep schedule” in which he would work for several hours, nap briefly, then work again, around the clock. He marveled at his productivity within a 22-hour daily waking life.</p><p>Though Fuller’s rhythm was dictated by his fatigue levels, and so entailed flexibility, a movement struck up around polyphasic sleeping on rigid schedules. The unfortunately named “Uberman schedule” involves twenty-minute naps every four hours, while the “Everyman schedule” at least recognizes the need for a core sleep—albeit usually less than three hours, with naps in between. There is little interest among this crew in the two-phase sleep of our ancestors, presumably because it does not result in more time spent awake and, one senses, manically typing lines of code into a laptop.</p><p>Scientists have attempted to study the effects of such a schedule, but it is very difficult when the vast majority of one’s test subjects drop out within a few days from the sheer misery of life. If round-the-clock napping is healthy, it sure doesn’t feel like it. A word of warning to those adolescent males who haven’t finished growing: One robust finding is that the release of growth hormone is strongly suppressed during polyphasic sleep, and its timing goes haywire.</p><p>Diehard polyphasic sleepers reassure neophytes on internet message boards that after the first month or so, the body adjusts to the new schedule. Keep suffering through and you will enter the promised land, they say. Any grogginess after that is blamed on inevitable slip-ups, like collapsing into your morning oatmeal and blowing the whole schedule.</p><p>On the one hand, there is no such thing as full adjustment to sleeping out of sync with one’s circadian rhythms, the 24-hour cycle of bodily functioning that humans share with almost all life on a rotating planet. Lab rats die early if you put them on similar schedules. On the other hand, there is some twisted truth to polyphasic sleep being more efficient.</p><p>Severe sleep deprivation activates a “recovery sleep” whenever a person finally gets shuteye. In this state, the power of the slowest brainwaves is much stronger. In other words, exhaustion brings on deeper sleep, which is why catching up on a lost night of sleep does not require an hour-for-hour reckoning. Polyphasic sleep, then, becomes more efficient as exhaustion increases. During naps, the body makes a valiant effort to survive.</p><p>But most of the perceived adjustment to wacky sleep schedules—including the long waking hours of trainee doctors or truck drivers—consists of a dangerous lack of conscious access to our own cognitive functioning. Sleep is the most powerful cognitive enhancer we know of, and without it people are much more impaired than they realize. Just as a drinker emerging from the bar is not the best judge of his ability to drive, many of society’s four-hour sleepers should not be operating heavy machinery.</p><p>That’s not to say that sleeping in blocks is unhealthy. Following the biphasic (two-block) pattern of our ancestors is a fine idea if one can fit a day’s aspirations into ten daytime hours and a midnight anti-nap. Likewise, a siesta in the early afternoon fits with a natural dip in our body’s arousal levels. As long as there are long stretches where sleep cycles can proceed undisturbed, the brain will awaken ready to learn again.</p><p>Many of us don’t have that luxury. Just a couple of weeks ago, Elon Musk tweeted that after working on the latest model of the Tesla car, he was “aiming to pull an all-nighter and complete the master product plan.” If your life looks like that, naps can play an important role. They commonly serve as catch-up sessions after a short night’s sleep, but they are actually much more effective if used prophylactically; that is, rather than conking out the morning after, try napping before an expected late night. The extra minutes will more than pay for themselves in added stamina.</p><p>Sleep fulfills important biological functions, particularly in the brain but also elsewhere in the body. With further research, we may one day curtail the need for sleep, condensing it so that people who would like to sleep less could still be fully refreshed. Our waking lifespan could be extended dramatically. But as in so many issues of biology, this cannot be achieved by willpower alone. The need for shuteye cannot be overcome by refusing to sleep.</p>Jessa Gamble Munoz / ReutersNap time!Why Napping Can't Replace a Good Night's Rest2016-08-04T11:06:00-04:002016-08-15T12:11:43-04:00Sleeping in spurts has the appeal of productivity, but inevitably you’ll collapse in your morning,2016:50-494081<p>In February 2012, a dozen members of the Food and Drug Administration’s Neurological Device Panel spent a Friday on the stage of a Hilton ballroom hearing about cranial electrotherapy stimulation (CES) devices. Tracey Kirsch was in the audience while the panel was warned by FDA personnel no fewer than 25 times that CES—a weak, pulsed electrical current delivered across the head—causes seizures. Kirsch runs a company that produces AlphaStim, one such device that attaches to the ear lobes and may treat anxiety, depression, and insomnia by briefly inhibiting activity in the brain’s cortex.</p><aside class="callout-placeholder" data-source="special-report"></aside><p>The hearing in Washington would determine whether CES devices would be reclassified from a Class III device (meant for life-sustaining products like heart valves) to a Class II device (alongside powered wheelchairs and pregnancy tests). Having used her allotted 45 minutes in the morning to argue for reclassification, Kirsch could not rise to object that not a single seizure had been caused in the 30-year marketing history of the product. Despite their largest customer being Veteran’s Affairs, many of whose patients are routinely offered CES treatment in VA facilities, there seems to be a mistrust of the technology at the FDA, expressed through sometimes-arbitrary criteria that discard the majority of supporting evidence. Eventually a witness clarified that the one documented seizure had happened during a clinical trial’s five-day drug washout period, before the electrotherapy had even begun. Unlike CES, benzodiazepine withdrawal frequently causes seizures.</p><p>“There were 50 people from the FDA at the front, facing the panel, and they were high-fiving, texting each other, breaking into the panel discussions,” says Kirsch. “They were out to win.”</p><p>In the face of frustration from disenchanted business owners like Kirsch, the FDA has the unenviable task of protecting Americans from medical dangers and duds. It must marshal all of the data on safety and effectiveness of new interventions, from cough syrup to spinal implants. Balancing those twin factors can be a haphazard and subjective affair, and it does not stop when a license to bring a product to market is issued. As a result, each person who relies on a given medicine is a data point in the society-wide assessment of that medicine’s healing powers. In coming years, Americans will all have a role to play in the ongoing research on drugs we take every day.</p><p>Working incognito in Chicago’s stockyards, Upton Sinclair couldn’t have known what an upheaval his 1905 novelization would cause. <em>The Jungle</em> documented exploitation of meat packers, as well as unsanitary handling of meat. It would provoke an uproar that led to a series of laws, including the 1906 Pure Food and Drugs Act that minted the FDA as a protection agency.</p><p>In its current incarnation, the FDA oversees a vast array of products, including food, pharmaceuticals, and medical devices. Drugs may be advertised and companies may vie for market share, but FDA regulation attempts to ensure that companies cannot compete with one another by cutting corners that put the safety of their customers at risk. All potential side effects must be out in the open and deemed worth the risk. Neither can those companies profit from selling a substandard product that does not achieve the effects they claim it does.</p><p>Already historically a sluggish process, licensing seems to have slowed to a crawl in recent years. Take for example some hypothetical new device that is similar in form and function to one that is already established on the market. In 1976, the FDA <a href="">would have taken 38 days</a> to process the completed application for classification. By 2015, the average time was 172 days, on top of years of clinical research.</p><p>“Obtaining clinical data takes time, typically three or more years for even a small pilot study,” says Kelly Roman, of Fisher-Wallace Laboratories, another CES company.</p><p>Medical-device companies—unlike drug conglomerates—are predominantly small businesses, and the process of bringing their inventions to market can be prohibitively expensive. After a device is finally cleared, its design may become obsolete within a couple of years.</p><p>For drug licensing, part of the time burden comes from the FDA’s dueling mandates of safety and efficacy, each of which requires different kinds of tests and controls. Each stage of research emphasizes the two factors to different extents, and these priorities are reflected in the experimental design. The weighting of safety and efficacy priorities remains a subject of debate.</p><p>For example, a new vaccine introduces risk to a broad section of an otherwise healthy population, while making them less vulnerable to a specific disease. In this case, any side effects will weigh heavily in the benefit-to-risk ratio, because the benefit of immunity is small when spread across millions of people, most of whom likely would not have contracted the disease anyway.</p><p>“I think the FDA needs to get out of the efficacy business,” says Daniel Kirsch, Tracey’s husband and business partner. “They should just focus on safety.”</p><p>The psychiatrist Jason Worchel agrees: “This is almost an insult to those of us who are physicians. Of course we monitor our patients, and if it’s ineffective we would change [the prescription].”</p><p>In practice, the earliest efficacy studies are not even contemplated until safety studies have been done, first using animals and then human subjects. Mary Foulkes, the former director of the FDA’s Office of Biostatistics and Epidemiology, informally describes the process: “We try it on one human being. Well, that didn’t seem to kill them. Then we try it on another.”</p><p>The next step is a dose evaluation, to find the maximum tolerated dose. Sometimes, safety is the limit set by a subject saying, “Please, no more. I can’t take it.”</p><p>Kirsch’s idea is that if the efficacy question is set aside, American citizens’ right to safety might be more easily guarded, even as the regulation process is streamlined. Efficacy then could be sorted out in the medical journals and the market. But on closer inspection, this doesn’t hold up, because safety and efficacy are inextricably entwined. Not just a mitigating factor against safety fears, efficacy is in fact a component of safety, which is defined as “a judgment of the acceptability of risk in a specified situation.” In other words, a product is deemed safe if its risks are more than compensated by its effectiveness at combatting the health problem, especially if that health problem is severe. Still, there is a good argument to be made that safety is not sufficiently weighted against efficacy.</p><p>Foulkes likens the data-set on the effects of any given drug to Swiss cheese. As much as researchers try to shrink those holes in the excel sheet where data is missing, they must ultimately make assumptions about what would fill those holes if the data was there. When it comes to efficacy data, the rules for filling in those holes are well spelled out. In analyzing safety outcomes, though, late-stage clinical trials often take a less-methodical approach. The current system is particularly bad at measuring adverse reactions that emerge over the course of a trial, as opposed to anticipated reactions for which experimenters are on the lookout.</p><p>“With a new class of drug, the safety issues are largely unknown,” says Foulkes. “If we take the case of Ebola, we were flying blind.”</p><p>As a statistician, Foulkes would like to see more rigor all the way through the drug-approval process. “There are a lot of patient testimonials presented to the FDA advisory boards,” she says. “Those are just anecdotes, and they provide very little information compared with confirmatory randomized controlled trials.”</p><p>Drugs are necessarily licensed before long-term hazards come to light, so post-licensing surveillance continues indefinitely. Efficacy, too, is a continuously shifting and nuanced concept, and some drugs become less effective over time as people’s pathogens adjust to them. Without monitoring in the population long after licensing, we might never know it.</p><p>In the future, Foulkes is hopeful that electronic medical records will capture far more of the problems with drugs once they’re released into the world than FDA’s current reporting mechanism. The FDA’s MedWatch program receives thousands of reports of adverse reactions every day, but this only captures an estimated 30 percent of the serious events. There are no obligations for physicians to report symptoms, because unlike trial subjects, patients don’t agree to share information when they take a drug. The whole of society then becomes a Swiss cheese of data, with no guarantee that the patients in the holes are happy with their treatment.</p><p>Which brings us to civic duty. The bioethicist Ezekiel Emanuel argues that people are morally obligated to participate in clinical trials, in just the same way that people are obligated to donate blood if healthy and able. Perhaps that obligation to future generations goes further. In an interconnected world, citizens would do well to view their own health in the context of their nation’s health and, indeed, the globe’s.</p><p>As the world faces a crisis in antibiotics resistance as well as increasing danger of spillover diseases from other species, it will take everyone to uphold effective healthcare. Given the size and complexity of the shared health community, reporting symptoms is the only way forward.</p><p>Meanwhile, setting aside the human foibles that plague all of our systems, clinical research continues to advance our wellbeing. “If I were on my deathbed and the doctor said I might be eligible as a subject for a new treatment, I know enough about clinical trials—I would jump at that,” says Foulkes.</p><p>In turn-of-the-century America, that’s a lot more than Upton Sinclair could have said.</p>Jessa Gamble Reed / ReutersThe FDA's Dueling Priorities2016-08-03T09:56:00-04:002016-08-03T10:08:07-04:00The organization’s challenge is balancing drugs’ safety and,2016:50-493661<p>In 1981, Ian Gregson popped into the prosthetics shop in a Vancouver hospital to buy a new leg. The shopkeeper took various measurements, then made a plaster cast of the amputee’s residual limb to craft an attachment.</p><aside class="callout-placeholder" data-source="special-report"></aside><p>“The leg was just trash. It was two inches short, with a suction socket, and no padding,” says Gregson. “It was very painful. I tried and tried, but it didn’t work.”</p><p>Prosthetic limbs, particularly the sockets that hold them on, must be carefully fitted to an amputee. Now a stunt man in the film industry and a two-time competitor at the Paralympic Games, for shot put and discus throw, Gregson describes his current socket-maker as an artist, a master who passes his skills on to a few select protégés.</p><p>Gregson’s favored quad socket has a rounded rectangular opening with a silicone liner. After a test socket confirms the fit, the real thing is cast, followed by sandpaper and a heat gun for adjustments. Gregson insists that the personal touch is what really makes the difference, and there will always be something that needs tucking in or letting out. Even the way someone stands during a measurement—if his hips aren’t completely level—can throw off the fit.</p><p>Expert prosthetics makers are rare animals, however, and cannot be mass-produced, unlike technology. While an exact fit via traditional methods calls for almost virtuosic expertise, the emergence of 3-D printing may allow for much more precise appliances—ones that could be made right at home. Bespoke 3-D printouts could even disrupt orthodontics and other common correctives.</p><p>The human leg has a more complex structure than any external cast can discern, and it changes with every motion and flex. David Sengeh of the biomechatronics group at MIT Media Lab, is working to convert the iterative process of prosthetics-building into a one-time procedure by focusing on amputees’ internal anatomy. He begins by mapping a remaining limb using Magnetic Resonance Imaging (MRI), which reveals the shape and consistency of its underlying tissue. <a href="">More accurate</a> than traditional caliper- or laser-scanning techniques, the MRI distinguishes among bone, muscle, and articular cartilage and avoids the alignment problems that come from an external scan.</p><p>Using the tibia as a reference point, computer-aided design is combined with an engineering technique called finite element analysis to predict which internal pressure points on the residual limb could most comfortably bear the load of the body’s weight. An algorithm designs a socket that is flexible in some areas and rigid in others, using a variety of materials.</p><p>“We’ve been able to make the [world’s] first socket entirely from quantitative methods,” says Sengeh. “No human hands were involved in defining the shape, including the cut lines and material properties of the socket.”</p><p>Throughout the 1990s, Sengeh’s home country of Sierra Leone suffered a civil war, where around 8,000 people had one or more limbs violently amputated. Many of those amputees had access to prosthetics but abandoned them because of the discomfort of a bad fit. In contrast, Gregson was run over by a train in a part of England that didn’t often see that type of traumatic injury. The surgeon had done his best, but Gregson’s residual limb was left boney, without the fleshy parts that can make a socket more comfortable.</p><p>Sengeh’s idea is that a good-enough algorithm can eventually reproduce the expertise of a human prosthetist. Anywhere in the world, an amputee can send Sengeh a minimal set of data, and he can mail back a comfortable prosthetic socket. Alternatively, a 3-D printer in the amputee’s town could produce the socket on the same day the measurements were taken.</p><p>The next step would be to scale up the project, but until then, amputees will continue to fit their prosthetics to purpose. “Even I, with access to first-class health care, use duct tape on it all the time. I’d be in the shop every week if I went in to fix every little squeak,” says Gregson. “The biggest issue comes if I gain or loose weight. Then the socket becomes too tight or too loose.”</p><p>“People always have their own solutions—experimenting with themselves and hacking their own prosthetics,” agrees Sengeh.</p><p>Perhaps the greatest promise lies in combining those two approaches: the high-tech equipment and the human ingenuity that people bring to their own problems. For example, Amos Dudley, a college student studying digital design, recently fixed his own protruding and overlapping incisors at about 1 percent of the cost of orthodontic treatment.</p><p>As an undergraduate, Dudley had very little spare cash but one significant asset: access to New Jersey Institute of Technology’s fabrication labs, which included a high-resolution 3D printer, computer-assisted design software, and a vacuum forming machine. After taking a cast of his own teeth and plotting a route for each one, Dudley created 12 clear aligners to bring his teeth incrementally closer to a perfect smile. He bought retainer plastic on e-Bay, and his total outlay was only $60.</p><p>“They’re much more comfortable than braces, and fit my teeth quite well,” Dudley <a href="">writes on his personal blog</a>. “I was pleased to find, when I put the first one on, that it only seemed to put any noticeable pressure on the teeth that I planned to move.”</p><p>After 16 weeks, the misalignment was fixed, but Dudley continues to wear the final aligner at night to guard his teeth against the damage of grinding. It provides the perfect fit as a whitening tray. (Dentists caution that the aligners can only solve for rotation and tilt problems in simple cases.)</p><p>Assuming that 3-D printers follow the pricing pattern of new technologies—cheaper with time—the cost difference between professional and amateur manufacturing will only grow in the coming years. In the future, distance from a specialist or lack of resources may be no barrier to comfort.</p>Jessa Gamble Ermochenko / Reuters3-D Printing a Better Prosthetic2016-07-29T13:11:00-04:002016-07-29T13:21:39-04:00Algorithms can be used to design cheap, perfect-fitting limbs, orthodontics, and other,2016:50-493265<p dir="ltr">In the high-ceilinged basement lab, the ear lies flat, encapsulated in a dish on a sheet-metal cabinet. It’s actually a piece of apple carved to look like an ear, yet it’s not really an apple either; the cellulose has been washed of its apple cells and populated instead with human ones. They are HeLa cells, the <a href="">infamously ubiquitous</a> cultured offspring of a long-ago cervical cancer. I am looking at an ear made of cervix, held together by apple.</p><aside class="callout-placeholder" data-source="special-report"></aside><p dir="ltr">“Biohacking is the new gardening,” says Andrew Pelling, who leads the Pelling Laboratory for Biophysical Manipulation at the University of Ottawa. Pelling eschews the current vogue for genetic and chemical biological manipulation, investigating instead the ways in which cells behave when their physical surroundings change.</p><p dir="ltr">The apple ear was created as an artistic statement, referring to a famous case of a human ear that was grafted onto a mouse’s back, and its choice of HeLa cells was intentionally provocative. But the fusion of plant and animal it represents holds promise for regenerative medicine, in which defective body parts may be replaced by engineered alternatives.</p><p dir="ltr">Biomaterials engineers, who create stand-ins for our own body tissues, historically focus on animal species, like pigs, with organs similar to ours. Until now, the plant kingdom has been largely neglected, but it offers a vast variety of architectures, many of which can serve the needs of human physiology. It also offers an escape route from expensive, proprietary biomaterials: an open-source approach.</p><p dir="ltr">A central challenge in organ creation is the development of materials that can host the new cells within the body, holding the organ’s shape and organization. In a synthetic approach, a molded polymer scaffold can hold the shape of an organ, then biodegrade as new cells gradually replace it. Alternatively, real donor organs can be washed of all the donors’ cells until they are white “ghost organs”—collagen structures that are then colonized with a patient’s own cells. In either case, the man-made and organic biomaterials are commercially produced or harvested and processed, at great cost.</p><p dir="ltr">Billions of dollars change hands in the biomaterials sector each year, replacing skin, cartilage, bone, and whole organs. The industry attracts talented researchers ready to profit from their intellectual property, but it also prices out most of the world. For example, few people can spend $800 per cubic centimeter of human decellularized dermal allograft tissue to reconstruct a badly torn rotator cuff in the shoulder, but at less than 1 cent, the same amount of apple is well within reach.</p><p dir="ltr">Take a McIntosh red apple from the grocery store (or a home garden), slice it and wash it with soap, then sterilize it with boiling water, <a href="">like so</a>, and you have a cellulose mesh ready for human cells. Implanted under skin, the scaffolding quickly fills with cells from the surrounding tissue, and blood vessels soon follow. After eight weeks it is still compatible with the body, with no attempt by the immune system to reject it. The plant segment is brought to life as part of an animal.   </p><p dir="ltr">Though some of Pelling’s work involves genetic manipulation, his enthusiasm lies more in the physical manipulation of cells—prodding them with tiny needles, stretching them with lasers, or putting them into containers of various shapes to see how they organize themselves. This last approach has potential applications in some of the thorniest problems in medicine, such as paraplegia.</p><p dir="ltr">The tiny capillaries in asparagus stalks happen to be the right size and shape for spinal cord repairs. Pelling and a local neuroscientist have shown that nerve cells from mice grow nicely into those channels, and while spinal cord implants tend to break down in the body, plant cellulose does not. “At the same time, it’s really inert—it’s akin to titanium,” says Pelling. Similarly, rose petals can form the scaffolding for skin grafts.</p><p dir="ltr">“This kind of exploratory work is important, because it expands the toolkit,” says Jeffery Karp, a biomaterials expert at Harvard Medical School. “Basic discoveries provide more options for those of us in translational medicine.”</p><p dir="ltr">Pelling Lab is in Canada, where it benefits from a permissive regulatory environment. Unlike Europe, where there has been strong resistance to genetically modified organisms (GMOs), or the United States, with its history of controversy around early human development, Canada encourages its nascent biohacking movement as an adjunct to the health research community. In 2011, Canada’s national public health department even sponsored a symposium about “<a href="">Our Post-Human Future</a>,” whose parting discussions debated “Can Technology Be Governed?”</p><p dir="ltr">To be applied in medicine, open-source biomaterials—like the recipe above for decellularized apple—still must run the gauntlet of trial phases for approval by regulatory bodies. With no profit at the end of that process, the clinical testing may have to be funded outside of the private sector. Globally available, locally producible, and inexpensive biomaterials could be a goal picked up by philanthropists.</p><p dir="ltr">While some biological research requires certified lab facilities of various safety levels, many do not. Pelling’s lab is developing the methods to allow the general public to Tweet suggested experiments to the lab or directly control a microscope, and to replicate the results at home using do-it-yourself, home biohacking equipment and widely available materials.</p><p dir="ltr">“Imagine people set up cell cultures the same way they donate computer power to SETI”—the search for extraterrestrial intelligence—says Pelling. “Everybody would be looking at a piece of the puzzle, and we could assay hundreds of conditions.”</p><p dir="ltr">Exploratory spaces like Pelling’s lab—and his storefront makerspace in development, where members of the public will be able to muck around with biohacking—promise to bring cell manipulation to the streets, for better or worse. And with plant-based, open-source biomaterials and do-it-yourself cell-culture incubators, distributed health research could be on the way.</p>Jessa Gamble Dunham / AP Compared to synthetic models like this polymer ear, plants could provide cheaper, more accessible scaffolding for growing organs in labs.Growing Organs on Apples2016-07-27T14:52:00-04:002016-07-29T13:15:03-04:00The future of regenerative medicine may be,2016:50-492872<p>At a shamanic ceremony in Mexico, an initiate is deep in his psychedelic visions. Some sort of wreath is placed on his head and the incessant rattling of indigenous instruments strengthens the trance. Candlelight flickers over a puke bucket as the drugged vision-seeker loses muscular control and sinks to the mattress, feeling a profound connectedness to the universe.</p><p>It’s a familiar scene to those who have been following the ayahuasca craze, in which Americans have flocked to South America for traditional knowledge-flavored encounters with Amazonian hallucinogenic plants. But this particular ritual is appropriated from Gabon, and it is marketed to heroin addicts. Like many other hallucinogens, ibogaine—the psychoactive compound derived from the roots of the iboga tree—induces several hours of awe, insight, and self-reflection. Unlike the others, however, ibogaine also removes all trace of heroin withdrawal. Users come to with no craving for a hit.</p><aside class="callout-placeholder" data-source="special-report"></aside><p>Drug recovery begins, so the story goes, with a crucial insight when an addict hits “rock bottom” and finally becomes ready to change. Given the notorious savagery of heroin withdrawal—along with the perceived importance of insight —ibogaine sounds like a panacea. The trouble is, the problem with heroin addiction is not withdrawal.</p><p>“I would never relapse when I was actively sick with withdrawal. The horribleness is exaggerated—certainly not as bad as a serious illness,” says addictions expert Maia Szalavitz, who is also a former heroin and cocaine addict. “It’s more like giving up the love of your life. You feel you will never have safety and comfort again.”</p><p>Howard Lotsof, who first discovered and popularized ibogaine’s application to addictions in the 1960s, later found there was more to the problem. Having had an intense trip and kicking his own withdrawal, he gave it to a couple of friends. They marveled at how their withdrawal symptoms had disappeared, then decided to go and buy some more heroin.</p><p>Physical dependence is only part of addiction, and not even part of its definition. Above all, it is a psychiatric problem. Cocaine, for instance, is powerfully addictive without dependence. Drug addiction is defined as the compulsive use of drugs despite negative consequences. That’s why tough love approaches don’t work; resistance to punishment is an intrinsic part of the condition.</p><p>After an ibogaine trip, users tend to describe experiences with a powerful other who describes to them how the world works, including the steps they must take to align themselves to their true paths. Those profound insights may figure prominently in recovery stories, but as Szalavitz argues in <em>Unbroken Brain: A Revolutionary New Way of Understanding Addiction</em>, about 10 percent of addicts are basically ready to quit at any given time and will respond to whatever they try.</p><p>“In my experience, I had an insight and went into recovery the next day,” she says. “But those people relapse a lot.”</p><p>Szalavitz frames addiction as a developmental disorder. Fewer than 10 percent of addicts develop their habits after their early 20s, when the cortex finishes developing and introduces an adult aversion to risk. Additionally, addicts are usually dealing with some other mental health problem or trauma that makes them vulnerable, and contrary to popular belief, most opiate addictions are not lifelong. They are resolved within five years—a little longer for heroin. The real task is mostly a matter of keeping addicts alive and otherwise healthy (Hepatitis C- and HIV-negative) until they can age out of addiction, preferably without a criminal record.</p><p>The best way to do that is well established. Methadone and other long-term maintenance treatments cut mortality in half. They create physical dependence but not addiction, and they form a foundation for a stable life.</p><p>Ibogaine was briefly picked up for testing by the pharmaceutical industry, in the early 1990s, but dropped after some cardiac problems emerged. Available on a gray market in Canada and Mexico, it is a Schedule 1 controlled substance in the United States, a list that includes LSD, pot, and, yes, heroin. Perhaps this contributes to its appeal among drug users, who often gravitate to underground culture anyway.</p><p>There are other reasons an addict might shy away from mainstream programs, though. Eighty percent of treatment programs, including court-ordered treatments, are based on the Alcoholics Anonymous 12-step process, which requires surrendering to a higher power. The only reason this blending of church and state has not reached the U.S. Supreme Court is that wherever such treatment orders have been appealed, the appeal courts have agreed that it violates the constitutional right to freedom of religion.</p><p>“The official policy is that [addiction]’s a ‘biopsychosocial-spiritual’ disorder,” says Szalavitz. “How are they going to convince people it’s a health problem when you throw ‘spiritual’ into it? They would never use the word ‘spiritual’ for something like depression.”</p><p>A disease with prayer as an answer is a contradiction that is somehow no longer seen as a paradox in the troubled-teen industry. Still, other problems arise when a college student with a mild drinking problem is told his first step is to admit that he’s a full-blown, life-long alcoholic. It’s no wonder addicts are turning to other sorts of unearthly experiences that are less infantilizing.</p><p>History shows that for the most part, adults don’t want to be addicted to things. At the turn of the century, heroin was an ingredient in many over-the-counter products. When FDA labeling came into effect, consumption of those products plummeted. The issue, then, is that small percentage of the population that is prone to developing a destructive habit.</p><p>If ibogaine is the only treatment someone will accept, it may be a useful option to keep on the table, says Szalavitz, but maintenance treatments are by far the better and safer course. For the rest of us, she suggests a revolutionary new approach to our fellow humans who are traumatized and struggling with addiction: “Be nice to them.”</p>Jessa Gamble Luis Gonzalez / ReutersA Psychedelic Can Cure Heroin Withdrawal2016-07-25T12:43:00-04:002016-07-25T16:43:28-04:00But it can’t cure,2016:50-492641<p dir="ltr">Get to the site of a problem, pack a big punch at the right time, and leave everywhere else alone. That’s what drugs of the future will have to do. Now, a Jello-like substance is giving patients a peek at that approach.  </p><p dir="ltr">Researchers have created a gel that can attach to inflammation sites and slowly deliver drugs to combat a wide variety of ailments—ulcerative colitis, arthritis and mucositis, to name a few. Inflammation is part of the body’s immune response, bringing extra blood to an injured area, but in cases of chronic inflammation, the heat, pain, and swelling become a problem. Developed at the Laboratory for Accelerated Medical Innovation at the Brigham and Women’s Hospital, the hydrogel—a solid material with high water content—can carry a combination of drugs, and matches its drug release to the level of inflammation around it.</p><aside class="callout-placeholder" data-source="special-report"></aside><p dir="ltr">When the gel is injected into the joint of an arthritis patient, for example, it will only release its anti-inflammatory payload when the patient is experiencing a flare, a spike in pain and swelling. When it encounters healthy tissue, it stays intact and does not release its payload.</p><p dir="ltr">“There are lots of enzymes present in inflammation that can degrade the gel,” explains Jeff Karp, the principal investigator. That breakdown of the gel releases the drug it carries.</p><p dir="ltr">The gel could be used in radiation therapy for head and neck cancers, by working to soothe the painful mouth ulcers called mucositis that often develop from exposure to the high-energy radiation.</p><p dir="ltr">“Mucositis is the biggest complaint from patients, and it often leads to a lowered dose of the therapy,” says Karp.</p><p dir="ltr">If the side effects were alleviated, more patients might safely complete their scheduled course of therapy at the higher dose, and we would expect increased survival rates.</p><p dir="ltr">Not only is the drug delivery targeted, but the gel also attaches more easily to the site of inflammation than to the healthy tissues around it.</p><p dir="ltr">“Ulcers have more of a positive charge than the other tissues, so the materials we use are more negatively charged,” says Karp.</p><p dir="ltr">Targeted release reduces, to one-fifth or less, the extent to which the drug can be absorbed into whole-body systems, keeping the action at the local site where it is needed. Systemic absorption is often the origin of side effects. Doses can be spaced at longer intervals, and the drug is generally more effective and less toxic. For a patient with inflammatory bowel disease, this could mean replacing a daily enema to a once-per-week regimen that targets the positively-charged surface of an inflamed colon.</p><p dir="ltr">Inflammation-activated gels can be used to carry and release drugs other than anti-inflammatories. The latest application for Karp’s innovation is in limb transplantation. A hind limb from a black rat transplanted to a white rat is usually rejected around 11 days later. With regular immune suppressant therapy that time is extended to 33 days. But with an injection of hydrogel loaded with the same immune suppressant drug, the leg is maintained up to 150 days later. Working with the US Army, a group in Pittsburg is taking this research further, into the pig model. Pigs are often used to test such medical procedures, because their response closely mimics the human response.  </p><p dir="ltr">Inflammation, though widespread in human ailments, is just one possible catalyst of drug release. In a future where a medical problem can activate its own solution, our diseases may all but order their drugs for delivery.</p>Jessa Gamble Burton / APThe transplanted arms of American soldier Brendan M. Marrocco, who lost both limbs in Iraq. The Gel That's Revolutionizing Pain Treatment2016-07-22T14:06:00-04:002016-07-25T10:41:10-04:00An injectable, jello-like substance reduces chronic inflammation, and may aid limb,2016:50-491777<p dir="ltr">After a songbird loses its hearing due to physical trauma or loud noise, the sensory hair cells in its inner ear regenerate naturally. The healed bird can use its restored hearing to decode complex songs from other birds. In fact, this ear repair is almost universal in vertebrates. Fish and frogs share it. Only for mammals is hair cell death irreparable.</p><aside class="callout-placeholder" data-source="special-report"></aside><p dir="ltr">More than a third of seniors suffer from at least moderate hearing loss, and while hearing aids have improved over the years, no drug currently exists on the market to recover their lost hearing. In the lower vertebrates like fish and birds, those new hair cells arise from the supporting cells of the cochlea’s lining. Now, for the first time, scientists are developing methods that could do the same for humans.</p><p dir="ltr">We owe our hearing to a tiny field of swaying cilia deep in the skull. Four rows of hair cells sprout in the snail-shaped cochlea of the inner ear, which is filled with fluid. Sound vibrations cause them to bend, opening pores that activate electrical signals bound for the brain. We are born with 15,000 hair cells in each ear, but unlike skin or other cell types, they do not turn over or replenish themselves. Loss of these hair cells over time accounts for much of the age-related hearing loss around the world, as well as that caused by too much loud noise. A loud sound can permanently bend or physically prune a fragile hair cell, rendering it ineffective.</p><p>Dr. Albert Edge showed in 2013 that a “notch inhibitor” class molecule gives rise to new hair cells in a culture. Each hair cell responds best to a particular frequency of sound—they are arranged in order of frequency along the cochlea—so scientists can pinpoint the effect of these new cells on hearing. When regenerated hair cells were then grown in the cochlea of mice, the pitches corresponding to their placement were better detected by the animals.</p><p>Edge and his team first noticed the drug’s potential in a serendipitous report of its side effects in dementia treatment.</p><p dir="ltr">“We thought, ‘These side effects in an Alzheimer’s patient are exactly what we’re looking for in treating deafness’,” says Edge. “So we decided to try that idea out in these mice.”</p><p dir="ltr">Dutch company Audion Therapeutics, of which Edge is a part, is working on a proof of concept for regeneration of human-ear hair cells. They are using compounds developed by pharmaceutical giant Eli Lilly and applying them locally to the inner ear. With funding from the European Union’s Horizon 2020 fund, which provides extra stimulus to promising but risky investments, animal tests are well under way as part of Project REGAIN. Audion is now planning its first small, human clinical trials.</p><p dir="ltr">“Primarily we aim to show that it is safe and well tolerated,” says Rolf Jan Rutten, Audion’s CEO, “And also we will look for an efficacy signal.”</p><p dir="ltr">Meanwhile, this year in Farmington, Connecticut, start-up Frequency Therapeutics’ patent filings indicate they have been developing ways to induce supporting cells to multiply, then become hair cells, using a notch inhibitor. The procedure would involve releasing the drug locally, perhaps as a foam or using a tube in the tympanic membrane to send doses into the middle ear.</p><p dir="ltr">Unlike drug trials for long-treated ailments like rheumatoid arthritis, there is no development trajectory for something as new and different as hair cell regeneration. It is anyone’s guess how many years or, indeed, decades it will be before hearing-loss patients can benefit from these discoveries. Still, this challenge of bringing a product to market has the atmosphere of a race. Frequency Therapeutics declined an interview on the subject on the basis that they are in “stealth mode” pending a big research announcement.</p><p dir="ltr">“It is a competitive field, but everybody has their own approach,” says Ruttan. “Obviously there will be one of us that will be successful first, but it may be that our different approaches are complementary.”</p><p dir="ltr">In an organ as complex as the ear, he says, there is a place in the ecosystem for everyone. Perhaps that ecosystem even has room for a mammal that can regenerate its hearing like a songbird.</p>Jessa Gamble Wojazer / Reuters Human Hearing Loss Could Be Reversible2016-07-19T11:12:41-04:002016-07-20T12:15:31-04:00Many animals regenerate the tiny hair cells that enable hearing—and there are promising signs that people can be made to do the,2016:50-491039<p dir="ltr">You were up late drinking with clients. Your head is pounding, and all you want to do is to take an Advil and go back to bed. But you’re on a deadline. If you’re a believer in modern-day elixirs, it’s time to press the “whoops button” and get your day back with IV vitamins.</p><aside class="callout-placeholder" data-source="special-report"></aside><p dir="ltr">Celebrities have been touting them for years, citing vague life affirming and energy-boosting effects. “We got nuffffin but love &amp; vittys in our veinzzzz #vitaminpush,” reads Miley Cyrus’s Instagram caption for a photo of the cringing singer with tubes taped to her tattooed arm. Now registered nurses from boutique clinics will show up at your office, home, or hotel room and hook you up to an IV bag full of fluids and nutrients for around $500. In a number of cities, IV vitamin clinic buses trawl the streets for clients.</p><p dir="ltr">The trouble is, there’s no evidence it works.</p><p dir="ltr">With names like The Hangover Club, VitaSquad, and The Drip Room, dozens of IV vitamin providers fall into the high-end alternative medicine sector, with no support from peer-reviewed studies. They all use Lactated Ringer’s Injection, a solution for fluid and electrolyte recovery, and various cocktails containing trace elements and an alphabet of vitamins.</p><p dir="ltr">Some even include the local anesthetic lidocaine, which can provoke life-threatening reactions, as well as the anti-oxidant glutathione, which has not been approved by the FDA as an IV product. Treatments last anywhere between 30 minutes and two hours depending on the volume of the cocktail and the size of your veins.</p><p dir="ltr">The moment a nutrient like magnesium or Vitamin C is formulated for injection, it becomes a prescription drug, because of all the ways it could go wrong. Done incorrectly the IV can cause a severe bloodstream infection, and any undissolved crystals can clog up capillaries in the lungs.</p><p dir="ltr">If these were the only drawbacks to vitamin IVs, it might be worth letting individuals make their own decisions about whether to use them. But these treatments have another cost. Some people with damaged intestines and preterm babies—whose digestive systems are not yet developed—receive all of their nutrition from intravenous drips.</p><p dir="ltr">"It's not a free ride. We see lots of infections, but people have been kept alive for decades that way," says Dr. David Seres, director of medical nutrition at Columbia University Medical Center’s Institute of Human Nutrition.</p><p dir="ltr">Unfortunately the United States suffers from a shortage of the very IV drugs and nutrients sold in vitamin therapy clinics. Since 2011, 90% of American hospitals have reported shortages in these products, and nutrients like calcium, fat, and vitamins have often been omitted from nutrition products for intravenously fed patients.</p><p dir="ltr">In that time, there has not been a single period when every nutritional component was readily available at once. In 2014, the FDA even temporarily allowed the import of saline from Europe to alleviate the constricted supply.</p><p dir="ltr">Unless you have some sort of intestinal problem that prevents you from absorbing nutrients, all of this water and all of these vitamins are just as easily taken up as part of your diet. And even then, the balance of evidence suggests taking vitamin supplements is a bad idea.  </p><p dir="ltr">“I don’t think there’s a single vitamin that doesn’t have some toxicity associated with too much,” says Seres. “Just because something is a nutrient—a vitamin or an antioxidant—doesn’t mean that more is better.”</p><p dir="ltr">Indeed, randomized controlled studies show the wrong kind of correlation between vitamin supplements and some diseases, such as Beta-Carotene and lung cancer, calcium and heart disease, or vitamin E and prostate cancer. The “goldilocks rule” applies to most aspects of nutrition, and the recommended doses are a happy medium for healthy people.</p><p dir="ltr">It may come as a disappointment to fans of radical intervention, but the best cure for hangovers is temperance and the best source of vitamins is food.</p>Jessa Gamble Allegri / Reuters Mainlining Vitamins Is Silly and Harmful 2016-07-13T11:22:18-04:002016-07-13T11:22:18-04:00The high-priced hangover treatment takes life-saving nutrients from those who need them,2016:50-489830<p dir="ltr">Food tastes better than Soylent. On that, there is universal agreement. Bland in flavor but audacious in concept, everything else about the beige food replacement is fiercely contested. Foodies decry the decline of experiential eating, cultural critics bemoan the loss of communal mealtimes, and others warn of techno-hubris. There have also been questions about Soylent’s nutritional content, and yet, the company’s proprietary mix is almost certainly an improvement on the average North American diet.</p><aside class="callout-placeholder" data-source="special-report"></aside><p dir="ltr">Last summer, a ready-to-drink “magical milkshake” called Soylent 2.0—developed by Los Angeles startup Rosa Labs in consultation with a Columbia University medical school professor—promised to provide all the elements of a healthy diet.</p><p dir="ltr">The original project aimed to eliminate the need for food, turning eating into an optional, recreational activity, but those claims have been dialed back. “While not intended to replace every meal, Soylent can replace any meal,” reads the promotional material. Despite these warnings, many of the Soylent staff are reputed not to eat much. Soylent proponents argue that even the healthiest selection of fruits and vegetables at a local farmer’s market represents a wasteful culture. With almost seven-and-a-half billion people to feed on the planet, we may no longer be entitled to consume the products of agriculture full time.</p><p dir="ltr">Large-scale agriculture is implicated in antibiotics resistance, environmental destruction, greenhouse-gas release, and other pollution. Animal husbandry’s ecological footprint is of particular concern. Each of us eats 200 pounds of meat each year (a historical high) and 30 pounds of cheese. For these reasons, Soylent drinkers are willing to bet the future is mostly vegan and dirt-cheap.</p><p dir="ltr">This is not the first time the full complement of nutrients has been attempted in a single drink. At intensive care units around the world, for example, up to 40% of patients are malnourished, which leads to weakened breathing and immune function. Patients incapable of feeding themselves are tube fed with polymeric enteral formulas. A standard formula is enriched with nutrients specific to the patient’s needs—fish oils for respiratory distress, glutamine for severe burns, motility agents, and immune-enhancing additives.</p><p dir="ltr">Soylent is promoted on a platform of personal responsibility. The idea is that the gluttonous variety of the grocery store is not only destroying us health-wise, it also represents the decadence of a society in decline. The fact that more than 70% of American adults are overweight is just a symptom of our broader overconsumption of resources.</p><p dir="ltr">But creating a full, healthy long-term diet for an active person is a larger challenge. Soylent’s attempt at reinventing this particular wheel produced quite a different model. While hospital tube feeding products often resemble old-school baby formula—milk powder, sugar, some form of oil—Soylent is all vegan. The liquid version is based on tapioca-derived starch, soy protein, algal oil, and beet sugar.</p><p dir="ltr">There are exactly 25% of recommended nutrients like vitamin A and chromium in each of the four daily meals. This suggests that instead of being assessed by nutritional testing, the recipe itself was <em>designed</em> according to the test criteria. In criticism of this approach, numerous nutritionists have decried the arrogance of reducing the needs of humans to the list of currently understood nutrients. Since the first ship captain loaded up a ship’s cargo with biscuits and then wondered why his crew came down with scurvy, diets have mostly been a trial and error experiment—physiological understanding is improving all the time.</p><p dir="ltr">What those nutritionists don’t mention is that they wouldn’t touch today’s standard diet with a ten-foot pole either.</p><p dir="ltr">North Americans are simultaneously overweight and malnourished, and a diet like Soylent, for all of its flaws, provides less of the problem ingredients like sugar and cholesterol and more of the nutrients. With clinical studies still pending, no responsible nutritionist could or would approve Soylent more strongly than the recommended food group guidelines. But a review of the ingredients reveals that the liquid concoction conforms to Michael Pollan’s health advice: “Eat food, not too much, mostly plants.” That is, if you can call it food.</p><p>For someone who eats the average amount of added sugars as part of their diet—more than three times that recommended by the USDA—it stands to reason they would see a reduction of their fasting glucose levels. Likewise, triglycerides and LDL cholesterol should respond, when Soylent’s vegan algal profile is compared with a greasy American diet.</p><p dir="ltr">Eating the recommended volume-per-day would also be expected to lead to weight loss, given that the average American caloric intake is just under 2,700 per day. The mean weight for a man is now more than 195 pounds and his height is less than 5’10.’</p><p dir="ltr">From a nutritional perspective, it is hard to imagine how the same diet day in, day out, could possibly provide the variety of nutrients needed. But again, the average North American diet is hardly diverse. A number of surveys show that fewer than ten meals, in regular rotation, form the entirety of many diets.</p><p dir="ltr">Unsurprisingly, the monotony of a single, unvarying meal is a common theme among Soylent’s critics, though some Soylent-drinkers do spice up the flavor with additives. On the other hand, a joyless existence without flavor might be offset by the reduction in misery from the health consequences of crappy eating.</p><p dir="ltr">It’s also cheaper. Much cheaper—just over $200 for a month’s-worth, even at the current small scale of production, whereas the average American spends about $600 per month on food.</p><p dir="ltr">So Soylent is more healthy than junk food. Does that mean we should all replace our meals with “meal replacements”? Of course not. That Soylent is healthier is more of an indictment of our broken lifestyles than it is a reason to slurp sludge, day after day. “Better than junk food” is a low bar to set, but no lower than our standards for anything else we put in our mouths.</p><p dir="ltr">If food as we know it is a luxury, will it be mostly algae for us from now on? One thing is certain: Whether or not this start-up has hit on the magic formula for perfect nutrition, it’s a sure bet that society at large hasn’t.</p>Jessa Gamble / Stringer / Getty Soylent Is Healthier Than the Average North American Diet2016-07-11T11:07:48-04:002016-07-12T17:15:51-04:00And that’s embarrassing.