A Pill-Free Antidepressant

<p>
 As Rachel Force bobs around her classroom at Elon University in North Carolina, she sports a blue headband and fanny pack, two accessories that are actually part of a device that delivers a low-level electric current to specific locations on her forehead. Force is an assistant professor of behavioral neuroscience, and she’s also the subject of her own neuroscience experiment with transcranial direct current stimulation, or tDCS. From her few sessions with the device, Force has seen “profound” changes.
</p>
<p>
 “I just felt generally less anxious,” she says.
</p>
<p>
 Force felt more spontaneous and extroverted in social situations that, prior to tDCS, she might have shied away from. She also takes an antidepressant that helps reduce the symptoms of her anxiety, but the tDCS “actually changed my behavior patterns.”
</p>
<figure class="richtext-image full-width">
<img alt="" class="richtext-image full-width" src="https://www.pbs.org/wgbh/nova/media/images/force-tdcs.width-990_W32T4or.jpg"/>
<figcaption>Rachel Force occasionally teaches while wearing a tDCS device.
        
    </figcaption>
</figure>
<p>
 The device releases a small amount of current, so small that most people don’t even feel it. The electrodes stimulate certain sections of the brain, but not enough to actually cause a neuron to fire. Rather “they change the cell properties” says Abhishek Datta, chief scientific officer for tDCS device-maker Soterix.
</p>
<div class="related"></div>
<p>
 The current will cause a cell membrane to polarize—either bump up or decrease the negative charge within—in a way that will affect the neuron’s potential to fire a signal. Just changing that potential is enough to make an impact, Datta says. Some studies have shown that tDCS can alleviate symptoms of depression, enhance cognition, aid in stroke rehabilitation, and reduce chronic pain. The technique has already been approved in Europe and Canada for treating pain and depression.
</p>
<p>
 In the United States, tDCS hasn’t been approved by the FDA for clinical use, though similar devices can be purchased as long as the company selling them makes no medical claims. And while researchers have found brain stimulation can treat depression, pain, speech, and motor problems, they don’t yet know exactly how it works or how to make the best use of it.
</p>
<p>
 But if they settle those questions, the payoff—for patients and companies—could be substantial.
</p>
<h2>
 Possible Advantages Over Pills
</h2>
<p>
 If tDCS is approved, it could treat people who don’t respond to medication or simply can’t take it. Take Force, for example. While nursing her children, she needed to switch antidepressants to one that doesn’t cross over into breast milk. She found one that worked for her, but some women may not have that option, especially when facing depression during pregnancy, which affects approximately 12% of pregnant women. These same women may not want to stay on or take antidepressants because experts don’t know how this type of medication may affect a developing brain. But at the same time, they can’t necessarily go untreated since depression can harm both the woman and the fetus.
</p>
<p>
 If those patients could instead switch to tDCS, they’d be able to use a depression treatment that is localized to their own brain and wouldn’t impact a developing a fetus. Or at least, that’s the theory.
</p>
<p>
 “People are more and more recognizing the potential advantages of something that is not a pill,” says Simone Vigod, a psychiatric researcher at the University of Toronto.
</p>
<div class="pullquote">
<p>
 As many as half of all depressed patients fail to respond to the current roster of antidepressants.
</p>
</div>
<p>
 Vigod is running a small pilot randomized controlled trial of tDCS on depressed pregnant women who don’t want to take antidepressants. For three weeks, participants will either get 15 sessions of tDCS (each lasting a half hour) or a sham procedure that serves as a control.
</p>
<p>
 The 18 participants in the trial come into an obstetric clinic five days a week to monitor the fetus while in their tDCS session. Not only do the nurses gather data for the study, the fact that they’re monitoring the fetus during the procedure has been reassuring for the women.
</p>
<p>
 “We really want to show how focal tDCS is,” says Vigod, who hopes to publish the data from the study next year. “If we showed that it was effective and also that it’s safe, this is something that women could use at home,” she adds.
</p>
<p>
 It’s not just depressed pregnant women who could benefit from tDCS. As many as half of all depressed patients fail to respond to the current roster of antidepressants.
</p>
<p>
 “The issue of non-response to antidepressants is a big, big problem,” says Daniel Blumberger, the co-director for Temerty Centre for Therapeutic Brain Intervention at the University of Toronto.
</p>
<div class="ad"></div>
<h2>
 Take-Home Kit for Depression
</h2>
<p>
 Blumberger studies the gamut of brain stimulation, which include tDCS, electroconvulsive therapy (ECT), and repetitive transcranial magnetic stimulation (rTMS). All these techniques have different advantages and disadvantages. Both ECT and rTMS have been approved for depression treatments in the United States, unlike tDCS.
</p>
<p>
 The downside of ECT, says Blumberger, is it’s fairly invasive: patients need muscle relaxant and a sedative since the procedure induces seizure. Plus, people are still scared of it because of its old reputation as “shock therapy.”
</p>
<p>
 The other, rTMS, uses a magnetic field to induce an electrical field and is less invasive but cumbersome and expensive, requiring a trained technician.
</p>
<p>
 Blumberger has studied use of rTMS and tDCS on older adults, who may avoid taking antidepressants because of the sheer number of other medications they need.
</p>
<p>
 “When it does work, people are very grateful, because these are people who have not responded or who have not been able to take other treatments,” Blumberger says.
</p>
<p>
 Though rTMS has a good track record, it’s hard to say if tDCS will offer the same results.
</p>
<p>
 “It’s working a slightly different mechanism of action than rTMS,” says Blumberger of tDCS. Still, he adds, “it can be an effective treatment for depression.”
</p>
<p>
 While some studies have found significant improvements when using tDCS over a placebo, one of Blumberger’s studies found no significant difference in results.
</p>
<p>
 The question of tDCS’s effectiveness could be settled with large clinical trials involving hundreds of patients, but scientists and device manufacturers haven’t wanted to fund those trials until they know the precise optimal dose and environment for using tDCS.
</p>
<p>
 Though they don’t know exactly how it works, one theory is that, in depressed people, an area of the brain at the left dorsolateral prefontal cortex—a region through to be involved in working memory, decision making, and social behavior—is less activated than in non-depressed individuals.
</p>
<p>
 When placing a positive electrode or anodal electrode on that region of the scalp, that region of the brain becomes more excitable and could alleviate the depression, says Datta, the Soterix CSO.
</p>
<p>
 “We’re targeting the right brain regions,” he says. “So right now it’s about maximizing the beneficial effects we’ve seen on smaller populations.”
</p>
<p>
 Ideally, tDCS will be another tool kit available for treating depression or other disorders. “You may come across patients who do not respond to drugs, who do not respond to rTMS, and tDCS presents them with yet another option to try out,” Datta says.
</p>
<p>
 Currently in the United States, if depressed patients fail to respond to one of four different drug treatments, the doctor may use rTMS to relieve the symptoms. But with rTMS, the patient has to go to a clinic. Soterix is also hoping to create a tDCS device that could potentially be used at home by patients.
</p>
<h2>
 A Warning
</h2>
<p>
 A number of companies—including Soterix—provide tDCS equipment to researchers studying the technology. Normally, such restricted use would continue until the FDA approved the devices for use outside the lab, but consumers haven’t been waiting around. So long as a company makes no medical claims, manufacturers can sell brain stimulation devices direct to consumers, marketing them with claims that they will enhance skills or athletic performance.
</p>
<p>
 Some people have taken to creating their own devices to improve their memories or learn new skills more quickly. However, the evidence supporting tDCS for cognitive enhancement is mixed. Such uses of brain stimulation have been hyped to the extent that neuroscience researchers recently put out a warning letter in the
 <i>
  Annals of Neurology
 </i>
 against do-it-yourself experiments.
</p>
<figure class="richtext-image full-width">
<img alt="" class="richtext-image full-width" src="https://www.pbs.org/wgbh/nova/media/images/halo-neuroscience-plank-side.width-990_LtkiApN.jpg"/>
<figcaption>One device available to consumers is mounted on the connecting band of a pair of headphones. Sold by Halo Neuroscience, it targets athletes.
        
    </figcaption>
</figure>
<p>
 One of the letter’s co-authors, University of Pennsylvania researcher Rachel Wurzman, emphasizes that scientists don’t know the potential harms that could come from tDCS. The most robust positive clinical trial results have been in depression and pain, she says, but even positive outcomes in tDCS trials are not enough to predict how an individual might respond to the treatment. Researchers have seen tremendous variability in cognitive measures and outcomes, Wurzman says.
</p>
<p>
 When using tDCS for cognitive enhancement, for example, about one-third of participants respond how researchers predict, one-third may respond in the opposite way, and another third may respond in a mixed fashion or not at all, Wurzman says.
</p>
<div class="newsletter"></div>
<p>
 Depression studies with tDCS have a better record, but there are still many unknowns. Datta explains that a number of factors can dictate the effectiveness of brain stimulation devices. There’s the placement of the electrodes, called the montage, which determines what section of the brain will be stimulated. There’s the dose, which can include the amplitude of current used and the amount of time a tDCS session runs. Finally, there’s the issue of what the person is doing while they receive treatment. Is the patient relaxed or excited? Amused or angry? What about active or sleepy? All could affect the outcome of tDCS treatments. Certain medications can also change people’s responses. Even hormonal cycles can affect the outcomes, Wurzman adds.
</p>
<p>
 Even if researchers see improvements for a particular function, it’s hard to tell if the same treatment is impairing a different one. In some cases, increased activity from one part of the brain will down-regulate transmission in another part of the brain, Wurzman says.
</p>
<p>
 “The brain tends to adapt in various ways,” she says. It could cause beneficial results, she adds, “but we need the research to measure the effects at that level.”
</p>
<p>
 Subtle changes in treatment can have an outsize impact, which is why researchers are so concerned with people playing with the technology. In some cases, merely changing the amplitude from 1 milliamp to 1.5 milliamps, researchers can see a response that’s opposite what they had wanted. Even head shape can affect the outcome by introducing variation in current flow.
</p>
<p>
 “There is no guarantee that the current flow in your brain is like the current flow on someone else on a reddit board’s brain, much less like the current flow in the 14 people that may have been tried in the depression study,” Wurzman says.
</p>
<h2>
 Potentially Life Changing
</h2>
<p>
 Despite the unknowns, Wurzman and other researchers are excited about the potential for tDCS to improve people’s lives.
</p>
<p>
 For pregnant women, depression during pregnancy is the biggest risk factor to developing postpartum depression. Both those disorders are linked to poor outcomes for a child, such as delayed motor development, Vigod says.
</p>
<p>
 “If we can treat women while they’re pregnant, that may be preventing a whole host of intergenerational problems,” she says.
</p>
<p>
 While Wurzman is encouraged by the clinical response to tDCS, particularly for ailments like depression and pain, she and her colleagues first need to understand just who will respond to this treatment best and what the circumstances of their treatment should be.
</p>
<p>
 “We don’t know what the optimal activity would be for different purposes, whether that’s cognitive enhancement or depression.”
</p>
<p>
 Force, the Elon University professor, suspects her classroom tDCS sessions have contributed to her new extroversion—after all, that part of her was on display as she taught. It could be possible that the tDCS treatment gave the part of the brain responsible for outgoing behavior a further boost, Force says.
</p>
<p>
 However it works, even after just a few sessions, Force noticed a powerful effect.
</p>
<p>
 “It really did change my life.”
</p>
<p>
 Photo credits: Rachel Force, NOVA/WGBH Educational Foundation, Halo Neuroscience
</p>

<p>Brain stimulation devices could greatly expand the options for treating depression and more.</p>

Taking the Pain Out of Addiction

<p>
</p>
<p>
 In his St. Louis clinic, psychiatrist Dr. Arturo Taca sees many well-heeled patients trying to detox from heroin: doctors, lawyers, nurses. “Normal people with normal values getting addicted to heroin,” he says.
</p>
<p>
 One thing they all have in common is that they have to fight the pain that comes with the symptoms of withdrawal from opioid addiction.
</p>
<p>
 Brian Comer was one of those patients. In college, Comer was introduced to using prescription painkillers, like oxycodone or Vicodin, as party drugs. “It’s such an easy way in,” Comer says. “There’s no easy way out.”
</p>
<figure class="richtext-image full-width">
<img alt="" class="richtext-image full-width" src="https://www.pbs.org/wgbh/nova/media/images/vicodin-pills.width-990_Cys8rab.jpg"/>
<figcaption>Pills of hydrocodone and acetaminophen, also known as Vicodin, are among those commonly abused to get high.
        
    </figcaption>
</figure>
<p>
 After a year or so of abusing pills, Comer realized he had become dependent on them. When opioid dependence sets in, people can only feel normal when they maintain a certain level of the drug in their system. If they don’t keep taking the drug, they’ll experience withdrawal. For opioids, that includes tremors, anxiety, cramps, and diarrhea. These symptoms make it incredibly difficult for people to break the grip of opioid addiction.
</p>
<p>
 Taca suspected that if he could make withdrawal easier and shorter for his patients, detox might be easier for them. The “aha” moment arrived when he was speaking to a friend, another doctor, who mentioned a small electronic device used to treat pain. If this device helps with pain, Taca thought, perhaps it can help patients manage the pain of detox. In his first tests with patients, he was amazed at the results. The device was able to alleviate most symptoms of withdrawal in 30 minutes. He called his friend back and said, “I think I just witnessed medical history.”
</p>
<p>
 Comer was one of those patients. He had spent more than five years trying to ditch opioids to no avail. But with just one session with the device, called the Bridge, his withdrawal symptoms practically vanished. He’s been clean for more than a year since.
</p>
<h2>
 A Start
</h2>
<p>
 The Bridge looks like an oversized hearing aid festooned with wires. It releases a small electrical signal that targets the amygdala, a part of the brain that’s rich in opioid receptors and which regulates fear. The amygdala also has been shown to play a role in reward-seeking behavior, a key component of addiction. When opioid-dependent patients stop taking the drugs, their amygdalas becomes saturated with a stress-stimulating hormone.
</p>
<p>
 During the dependency phase of addiction to prescription painkillers, the brain has to produce more and more noradrenaline to maintain normal levels of wakefulness. When those opioids are cut off, the same excessive levels of noradrenaline are pumped out for at least a week, which causes the symptoms of withdrawal. Taca says withdrawal is like the worst flu you’ve ever experienced, but worse. Along with feeling sick, people in withdrawal experience an intense fear or preoccupation with dying, he adds. “It’s harder for them to keep sober because they think they’re going to die.”
</p>
<p>
 The Bridge device was released only two years ago, though similar devices have been on the market for the past decade. The FDA has approved the Bridge to be marketed and used in the same manner as similarly approved pain relief devices. For now, it is classified for use in “electro-acupuncture,” but Innovative Health Solutions, the Indiana-based medical device company that makes the Bridge, is in the process of applying for approval to use it in detox treatments, which would make it eligible for coverage under many people’s insurance plans. So far,
 <a href="http://dx.doi.org/10.1080/00952990.2017.1295459">
  the only peer-reviewed article
 </a>
 to be published on use of the device in a detox setting was co-authored by Taca. It was a retrospective, uncontrolled study that looked at the results of people who had already received the treatment, not a pre-planned, double-blind study that is preferred by scientists when determining a treatment’s efficacy.
</p>
<p>
 For many in that study, a one-hour session with the Bridge was enough to greatly reduce withdrawal symptoms. Within the first ten minutes of using the device, Comer says he could feel a difference. For one, he had stopped hyperventilating. “I was able to actually sit.” And within the first hour of wearing the Bridge, “I noticed almost no symptoms of any withdrawal,” he says.
</p>
<p>
 That’s not to say the Bridge is a miracle device. Rather, it’s a start. What it does is open up some desperately-needed new options for breaking the cycle of addiction. After that, patients still have a long road to recovery.
</p>
<p>
</p>
<div class="ad"></div>
<h2>
 Breaking Dependence
</h2>
<p>
 During his dependency days, Comer eventually spent more than $100 a day on pain pills just to feel normal. His experience is fairly typical. Regular opioid users who still want to get a high have to take more and more of the drug. Many graduate to heroin or the dangerous painkiller fentanyl, a synthetic opioid that is 50 to 100 times more potent than morphine and has been driving an uptick in overdoses.
</p>
<p>
 Fortunately for Comer, he never reached that level of addiction. After dropping out of school and losing his job, he moved home with his parents at age 23, determined to get clean. He started with an addiction treatment medication called Suboxone, which is a combination of buprenorphine and naloxone, a drug also known as Narcan that’s commonly used to reverse overdoses.
</p>
<div class="pullquote">
<p>
 Withdrawal symptoms for treatment drugs can last even longer than those for addictive opioids.
</p>
</div>
<p>
 Buprenorphine is one of only three medications approved to treat opioid addiction, the other two being methadone and naltrexone (also known by its brand name, Vivitrol). Naltrexone is the only one that isn’t an opioid. Both methadone and buprenorphine are themselves long-acting opioids, though they don’t deliver the high found in heroin or pain pills. In theory, these treatments, along with therapy, allow people to quit deadlier opioids and gradually wean themselves off drugs all together. But between 40–60% of patients relapse after treatment.
</p>
<p>
 Comer was one of them. He could not quite shake his opioid dependence and ended up using Suboxone for four years, far longer than his time abusing painkillers. Though the Suboxone allowed Comer to feel more normal, every time he tried to wean off of it, withdrawal would upend his life. The problem was the treatment drugs—their withdrawal symptoms can last even longer than those for addictive opioids.
</p>
<p>
 Comer, who has bipolar disorder, had already been seeing Taca, who offered a new option to kick the Suboxone. It wasn’t a simple process. Comer still would have to endure withdrawals for a week before visiting the clinic to use the Bridge for an hour. But the payoff, Taca promised, would be worth it: after that hour, the pain of withdrawal would be greatly diminished.
</p>
<h2>
 Nationwide Epidemic
</h2>
<p>
 Comer’s story of opioid dependence is increasingly common. Nowadays, he more frequently hears about other people from his middle-class St. Louis suburb overdosing on heroin.
</p>
<p>
 His experience—and that of his community—isn’t unusual. According to the Centers for Disease Control and Prevention, more than 15,000 people died from overdoses involving prescription opioids in 2015, quadruple the number from 1999. Two million Americans have abused or were dependent on prescription opioids in 2015.
</p>
<p>
</p>
<div class="newsletter"></div>
<p>
 Opioid addiction is often treated more as a moral failing than a health problem, and that appears to have skewed treatment options. Though the general consensus from the medical community is that medication-assisted therapy is more effective at keeping people off opioids than counseling alone, only a minority of treatment programs use it.
</p>
<p>
 Only 13% of the more than 14,000 treatment facilities in the U.S. provided any of the medications approved for addiction treatment, according to a 2013 report by the U.S. Substance Abuse and Mental Health Services Administration. Methadone remains the most popular of the substitutes. Among patients at facilities offering medication-assisted treatment, some 330,000 received methadone. Only 48,000 received buprenorphine, and less than 4,000 were given naltrexone.
</p>
<h2>
 Getting Clean
</h2>
<p>
 Taca uses the Bridge to transition addicts to naltrexone, which blocks opioid receptors, leaving people unable to experience the highs of the drug should they relapse. It’s available as a once-a month injection.
</p>
<p>
 One of the reasons naltrexone is not commonly used is because its injectable form is relatively new, and it’s more expensive than methadone and buprenorphine. Another big hurdle is that patients can’t have opioids their system if they use it, so they have to detox first. That can be a daunting task.
</p>
<p>
 Comer experienced “constant uneasiness” when he was going through detox. His body become highly sensitive. During one withdrawal process, he couldn’t sleep for days—no position felt comfortable. The pain and misery were so intense, he says, that it can feel like “there really is no end in sight.”
</p>
<div class="pullquote">
<p>
 If you can get people on medications and into counseling, they seem to do better than with counseling alone.
</p>
</div>
<p>
 The challenge of detox is why many patients choose to use methadone or buprenorphine even though their withdrawal symptoms can be worse than for the original opioids they were addicted to. Still, either can help someone kick heroin as quickly as possible, which could save their life.
</p>
<p>
 With the Bridge, Taca hopes to take away the pain of withdrawal and make naltrexone a much more accessible treatment for addiction. And according to a recent study, naltrexone appears to be as effective as methadone and buprenorphine in keeping addicts from relapsing but doesn’t have the same risk of withdrawal.
</p>
<p>
 Still, there hasn’t a been a comprehensive study comparing all three medications, but the consensus is that they’re better than the alternative of continued addiction to pain killers. If you can get a group of 100 people on any of these medications and into counseling, says Dr. Joshua Lee, an addiction researcher at New York University School of Medicine, they all seem to do better over time than people in counseling alone.
</p>
<p>
 Lee tested naltrexone in a study among more than 300 parolees at five different sites. It was not a blinded study, so participants knew if they were getting naltrexone or just counseling. (The gold standard is a double-blind study, where neither patients nor doctors know who is getting which treatment.) The patients were seen every two weeks for a six month period. During that time, Lee and his colleagues found that those in the naltrexone group were much less likely to relapse. Approximately 60% had not relapsed at the six month mark, while about 60% in the counseling-only group had relapsed at that time.
</p>
<p>
 But those positive results waned when doctors stopped administering naltrexone after six months. “Once the naltrexone was gone, then it resumed the usual trajectory of steady relapse,” Lee says. The researchers followed up with participants six months after halting naltrexone treatments and found that 50% of both groups tested positive for opioids. That suggested to him that six months might not be long enough.
</p>
<p>
 Lee’s next study will tackle the question that many addiction researchers have—how do the three medications compare? He hopes to have results from that study by the end of the year.
</p>
<h2>
 Looking for Help
</h2>
<p>
 Ultimately, it seems that the best medication depends on a person’s circumstances. For those who have already detoxed—for instance, people getting out of jail—“your best option might be a shot of naltrexone the local sheriff is offering,” Lee says. One pilot program in Indiana, for instance, transitions parolees—most of whom have detoxed in jail—from the Bridge to naltrexone when they are released.
</p>
<p>
 Making the treatments widely available solves only part of the problem, though. Even if patients can find a treatment facility or a program that offers medication, insurance companies may not pay for it. In Comer’s case, his insurance didn’t pay for naltrexone, so aside from one dose he was given for free, he went without.
</p>
<p>
 It’s a challenge many patients face, from issues of access to lack of coverage to denied claims. “It is still really difficult to access behavioral health in general,” Lee adds. Seven years after the passage of the Affordable Care Act, two-thirds of plans violate at least one of the requirements for coverage of addiction treatments under the law, according to a recent report from the National Center on Addiction and Substance Abuse. “The most frequently excluded or not explicitly covered benefits were residential treatment and methadone maintenance therapy,” the authors wrote.
</p>
<p>
 Nearly every state lags in offering enough medication-assisted treatments programs for their opioid dependent populations. Indiana is one of them. It has one of the highest rates of opioid abuse in the country while also having one of the lowest capacities for treatment. State Senator Jim Merritt says Indiana is just starting to address its treatments gaps. The state has some pilot programs that offer the Bridge to patients in detox, and Merritt has some 15 pieces of legislation in play that address a variety of opioid addiction treatment gaps.
</p>
<p>
 “We need to continually talk about this being a struggle, this being about healthcare, not law enforcement,” Merritt says. “It’s an illness, not a character flaw.”
</p>
<p>
 Comer echoes that sentiment, urging people who are addicted to opioids to ask for help. He had initially tried to hide his addiction from his family and friends. “I could have been done one or two years sooner if there wasn’t such a massive stigma.” But now, with the help of the Bridge and therapy sessions, he’s getting back on track. “There’s nothing now that’s holding me back from having a life.”
</p>
<p>
 Photo credits:
 <a href="https://www.flickr.com/photos/kajeyomama/4263377132/">
  Kaje/Flickr (CC BY-NC)
 </a>
 , Innovative Health Solutions
</p>

<p>A new device can help opioid patients detox by getting them over a significant hurdle—the painful withdrawal symptoms.</p>

Bringing Change to the Food System with Blockchain

<div class="related"></div>
<p>
</p>
<p>
 This past holiday season, I met the farmer who raised my Thanksgiving turkey. I didn’t go to his farm, though, nor did I run into him at a farmers’ market. Rather, I tracked him down using a blockchain, the same technology that underpins bitcoin and other so-called cryptocurrencies.
</p>
<p>
 Mike Neal was just as delighted to talk to me as I was to find him. “I’m just thrilled that you would buy a turkey that came off my farm,” he told me over the phone. When I mentioned that I purchased his turkey near St. Louis, Missouri, he was even more surprised. “I was just under the assumption that almost all of my turkeys were all sold in Texas.”
</p>
<figure class="richtext-image full-width">
<img alt="Mike Neal" class="richtext-image full-width" src="https://www.pbs.org/wgbh/nova/media/images/mike-neal.width-990_IDrmD7B.jpg"/>
<figcaption>Mike Neal on his farm outside Crawford, Texas.
        
    </figcaption>
</figure>
<p>
 Under the current agricultural system, it’s the norm for both the farmer and consumer to be disconnected. Neal raises flocks of 50,000 turkeys a couple times a year on his farm, outside of Crawford, Texas. The turkeys are owned and hatched by Cargill, and up until recently, there wouldn’t have been an easy way for the consumer or farmer to follow that vast food chain. The blockchain changes that.
</p>
<p>
 Last year, when a flock of newborn turkeys made the journey to Neal’s farm, the occasion was marked in a digital file or block of information. The baby turkeys, called poults, spent just over 90 days on the farm roaming their turkey house to drink and eat and growing to about 15 pounds without the aid of growth hormones or growth-inducing antibiotics.
</p>
<p>
 Then the flock was sent to the processor, and once again, a new block was created marking the processor’s name, its location, and the turkey’s arrival. This new block was linked to the previous one in such a way that the information was, for all intents and purposes, immutable. Finally, my turkey became one of the many birds filling store freezers last Thanksgiving.
</p>
<p>
 While blockchains were first created to underpin the bitcoin cryptocurrency, the technology is spreading to the far corners of our economy. Banks like Goldman Sachs and UBS are exploring blockchain technology and how it might apply to existing financial markets, and companies like IBM and GE are looking to apply it to diverse industries including healthcare and electricity. Blockchains have the potential to find their way into just about any transaction that requires verification, which represents a significant portion of the world’s economy.
</p>
<h2>
 Behind the Blockchain
</h2>
<p>
 Supply chains, like those that raised, processed, and sold my turkey, are well-suited to blockchains because, at heart, they consist of a series of transactions. Trust in those transactions is part of what makes a supply chain valuable, just like with currencies like bitcoin.
</p>
<p>
 On some level, blockchains and the trust they inspire are what gives bitcoin and other cryptocurrencies their value. In a blockchain, transactions are recorded to an open ledger that everyone can see. Once entries have been made to the ledger, it’s extraordinarily difficult to change them—practically impossible given today’s computing power.
</p>
<p>
 The immutable nature of blockchain relies on the fact that each transaction has its own digital signature that’s then cryptographically crunched into what’s known as a hash. Each transaction or block is represented by one of these hashes, and each subsequent block contains the hash of the previous one. If someone were to try to alter the blockchain—say, to steal bitcoin or falsify information about the way turkey was raised—they would have to alter that block and all of the blocks that came after it to ensure that the hash record lines up. The amount of work required to do that is substantial enough to make a blockchain essentially impervious.
</p>
<p>
 Blockchains can also be transparent in the same way old library cards were: In those cards, people could see a list of the previous patrons who checked out the book. In a blockchain transaction, as each party passes the product and data down the chain, they are confirming a certain truth about what happened with that item.
</p>
<div class="ad"></div>
<h2>
 Transparent Transactions
</h2>
<p>
 For increasingly savvy consumers, blockchains offer a chance to shed light on otherwise opaque systems like agriculture.
</p>
<p>
 The labels on a package of ground beef—“grass-fed,” “all-natural,” or “antibiotic-free”—can be surprisingly difficult to trace. Even the small number of large corporations that control most of the meat industry can have a hard time tracking down all of that information, says Cody Hopkins, the general manager of Grass Roots Cooperative, a farmer-owned co-op based in Arkansas.
</p>
<figure class="richtext-image full-width">
<img alt="" class="richtext-image full-width" src="https://www.pbs.org/wgbh/nova/media/images/baby_turkey_in_fl.width-990_jWA2lUt.jpg"/>
<figcaption>A turkey poult
        
    </figcaption>
</figure>
<p>
 In our modern food chain, there are many steps from farm to table, he says. “There is maybe one entity in that whole chain that might have the whole story of where that product started and what happened to it along the way before it gets on the supermarket shelf,” Hopkins says.
</p>
<p>
 A large meat producer might know the whole story of that food chain, he added, although it does take them quite a while to piece together because different food distributors use different accounting systems—everything from paper receipts to tracker chips and bar codes.
</p>
<p>
 “Each of these steps along the way often operate in silos,” Hopkins says.
</p>
<p>
 Grass Roots turned to blockchains to offer a way around those silos. Grass Roots started using a blockchain this August for all the chicken products, then added pork and turkey in the fall. Their farmers and processors use an app from a startup named Provenance, which applies blockchains to food systems. In 2016, for example, Provenance worked with tuna fishermen in Indonesia to record their catches and begin a blockchain that proves they receive fair wages and the seafood was sustainably fished. The fishermen all have phones, and they register a catch by sending a simple text.
</p>
<div class="pullquote">
<p>
 More transparency could help consumers learn the costs of each step involved in meat production
</p>
</div>
<p>
 Like the fishermen, at Grass Roots, each entity along the way—the farmer, processors, etc.—have access to the platform. When farmer receives a batch of chickens, they register it on a blockchain. When the farmer sends it to processor, they transfer that asset to the processor, but it doesn’t show up on the blockchain until the processor is notified, receives the chickens, and confirms this unique transaction. That continues until the processed chickens are mailed directly to consumers, who can then review each step via the blockchain.
</p>
<p>
 Hopkins says that Grass Roots hopes to add price transparency information to the block chain, such as the cost of grain and labor, so consumers could see how much a farmer or processor nets in each transaction. This would be a huge change for the agriculture industry. As it stands, consumers and most farmers under contract to meat producers have no idea what causes the price fluctuations in their market. “Farmers don’t know if they’re getting a fair shake from these companies,” Hopkins says.
</p>
<p>
 With more transparency, consumers and farmers can learn the costs of each step involved in meat production. It could also reveal weak links in the chain. “That transparency has a lot of benefits including food safety,” Hopkins adds. “It takes the mystery out of the meat system, really.”
</p>
<h2>
 Food Safety
</h2>
<p>
 For those involved in the food system, safety improvements are the main draw of blockchain. And from the perspective of food safety experts, that could be a very beneficial change. The patchwork system of global food distribution not only makes it hard to track labor and environmental concerns, but slows the detective work of finding the source of an outbreak of food-borne illness. “The trace back of trying to find the source of the contaminant is still difficult,” says Amy Kircher, director of the Food Protection and Defense Institute. “We don’t have an incredibly transparent food safety system.”
</p>
<p>
 As it stands now, if local officials identify a foodborne illness outbreak, they can load that information to a central database overseen by the CDC. The database allows health officials to find patterns in illness outbreaks that could help them determine the source and extent of the problem. The challenge is that “you have to have a large amount of cases before any outbreak is even identified,” Kircher says. And even then, finding the original source is a “laborious process,” she adds.
</p>
<div class="newsletter"></div>
<p>
 To see how the blockchain could streamline recalls, imagine you unknowingly bought a contaminated chicken pot pie at the store. Every ingredient came from different suppliers, different processors, and different farms. Some of those entities may use sophisticated databases to track transactions, while others may still operate using paper receipts. Finding the infectious culprit would mean chasing down those receipts, calling processors, retailers, all of which takes time.
</p>
<p>
 But with a blockchain, every time an ingredient was processed or delivered, someone has to log its progress. Should an outbreak occur, investigators would only have to look at the blockchain to trace the source. It would be the central, canonical source of information about where each ingredient traveled from farm to table. Such a central repository would also speed recalls, saving lives. Kircher and her colleagues at the Food Protection and Defense Institute could also use a blockchain to anticipate possible targets for food fraud or vulnerabilities in a distribution system.
</p>
<p>
 “That really helps, from a food safety perspective,” Kircher says.
</p>
<h2>
 Blockchain Everywhere?
</h2>
<p>
 For blockchain to have an impact, more people and companies will have to be connected. More major corporations are going to have sync up their distribution systems, and more small farms need to participate. That’s beginning to happen. Retailers such as Walmart and Kroger along with their suppliers, including Dole and Tyson Foods, are partnering with IBM to create a pilot project using blockchain.
</p>
<p>
 Both big producers and small farms are seeing blockchain as an opportunity. For large corporations, use of the technology can garner more trust from consumers. And for smaller operations, the addition of a transparent supply chain enables farmers and consumers to get a “fair shake,” as Hopkins says.
</p>
<p>
 The world of cryptography seems to be about as far as you can get from the work of raising birds, but farmer Mike Neal is not intimidated by it. “As far as I’m concerned, what Cargill is doing is just a refined process of connecting, me, a grower, with you, a consumer,” he says. “It enables you to actually say, ‘It’s a real person out here growing these turkeys.’ ”
</p>
<p>
 Photo credits: Honeysuckle White,
 <a href="https://www.flickr.com/photos/kristieg/490287213/">
  Kristie's NaturesPortraits/Wikimedia Commons (CC BY)
 </a>
 , luvhotpepper/iStockphoto
</p>

<p>The technology behind the bitcoin cryptocurrency could make the trip from farm to table more transparent.</p>

How Sleep Can Heal Our Brains

<p>
 “The thing about sleep that is maddening is we don’t know what it’s for,” Paul Shaw says with a hint of frustration. Rather than truly grasping the role sleep plays in our complicated biology, the neuroscientist has been stuck merely describing it. He’s not alone.
</p>
<p>
 But Shaw doesn’t just want to understand sleep for sleep’s sake. He wants to uncover the mysteries of sleep because he thinks it not only has the potential to keep us healthy, but to fix what’s broken.
</p>
<p>
 His main tool can be found in neatly packed rows of test tubes at his lab at Washington University in St. Louis, which contain generation upon generation of well-rested fruit flies. These flies are created with genetic deficiencies that mimic human disorders, such as Alzheimer’s disease. Shaw fixes these ailing flies, not with genetic modification or drugs, but by putting them to slee
</p>
<figure class="richtext-image full-width">
<img alt="" class="richtext-image full-width" src="https://www.pbs.org/wgbh/nova/media/images/fruitflytesttubes.width-990_vAtp1ls.jpg"/>
<figcaption>Rows of test tubes filled with fruit flies form the test population for Paul Shaw's research into sleep.
        
    </figcaption>
</figure>
<p>
 “We make them sleep, and they become normal,” says Shaw. “Sleep is letting the brain solve the problem in the best way possible.”
</p>
<p>
 This is not just about reminding people to get their beauty rest. If what Shaw has found with fruit flies applies to humans, we could potentially use devices or drugs to enhance sleep, and those same techniques could be used to treat or even prevent debilitating diseases like Alzheimer’s.
</p>
<div class="related"></div>
<p>
 The trick, Shaw says, is in letting the brain do what it’s good at. “Whatever a neuron can do, sleep can make it better.”
</p>
<h2>
 Insomniac Flies
</h2>
<p>
 To start understanding the benefits of enhanced sleep, Shaw has become the sandman for fruit fries, an animal he can use to test sleep against a variety of disorders, including memory deficits. Yes, even flies can learn and form memories.
</p>
<p>
 Shaw uses two methods to test memory in fruit flies: First he offers the flies a choice to go either to a lit tube or a dark tube, with the lit side coated in quinine, which makes it bitter. Flies favor the light, but eventually they learn that the light side is bitter and instead go for the dark tube. In another test, Shaw puts male flies next to a female who has already mated. After failed attempts to mate, the male flies eventually stop trying even when Shaw puts in an virgin female.
</p>
<figure class="richtext-image full-width">
<img alt="" class="richtext-image full-width" src="https://www.pbs.org/wgbh/nova/media/images/fruitflymatingcells.width-990_QdpK5R2.jpg"/>
<figcaption>If a male fruit fly unable to mate with the female in a cell, a normal fruit fly will remember and stop attempting to mate. If the fly has a mutation meant to replicate a neurological disorder, it will keep attempting to mate.
        
    </figcaption>
</figure>
<p>
 In his recent experiment, published
 <a href="http://www.cell.com/current-biology/abstract/S0960-9822%2815%2900342-5">
  last year
 </a>
 in
 <i>
  Current Biology
 </i>
 , Shaw created different types of mutant flies that could not form memories. These flies would not remember to avoid the females or the light vial. Among this flawed population, Shaw used three different methods to put them to sleep, by giving them one of two different drugs or adjusting a gene that promotes sleep. In all cases, these “broken” but rested flies passed their memory test, demonstrating that sleep alone—rather than the way it is induced—is the critical factor in improving the flies’ memory.
</p>
<p>
 None of the treatments fixed the underlying genetic deficiency that caused the memory problems, Shaw says. He doesn’t yet know how, but sleep is somehow allowing the brain either to use a different circuit or use different molecules within the same circuit to allow the brain to resume forming memories. In essence, sleep was restoring some of their mental abilities.
</p>
<p>
 While Shaw’s work doesn’t translate directly into humans, just across the street, one of his colleagues at Washington University has found a link between Alzheimer’s disease and sleep.
</p>
<h2>
 Broken Memories
</h2>
<p>
 In 2009, Washington University neurologist David Holtzman
 <a href="http://www.sciencemag.org/content/326/5955/1005.abstract?keytype=ref&amp;siteid=sci&amp;ijkey=yhagR2oLYK3W6">
  showed
 </a>
 that if animals are deprived of sleep over time, they accumulate a protein waste product called beta-amyloid. In Holzman’s experiments, if sleep is improved with a drug, the accumulation of this protein decreases.
</p>
<p>
 “In Alzheimer’s disease, beta-amyloid can build up because you’re unfortunate enough to have a genetic mutation that causes you to make too much of it, or, in the later onset form of the disease, you probably clear too little of it” he says. Once beta-amyloid starts building up in the brain, it forms an insoluble protein that can’t be cleared away and is thought to lead to Alzheimer’s.
</p>
<p>
 Holtzman has been following up with his experiment to see whether sleep or something associated with sleep affects amyloid buildup. “So far, most of our evidence is suggesting that it really is the sleep itself that is protective,” he says.
</p>
<div class="pullquote">
<p>
 “Those people who had the least amount of deep non-REM sleep showed the greatest amount of forgetting across that night.”
</p>
</div>
<p>
 Brain activity leads to the production of beta-amyloid, but during sleep, synaptic activity is almost 40% lower than while awake, Holtzman says, so people simply make less of the protein when they sleep.
</p>
<p>
 It’s possible that sleep also helps clear the protein out, and other researchers like Mathew Walker, a professor of cognitive neuroscientist at the University of California, Berkeley, are tackling that question. Walker is among the researchers who think of sleep as a “power cleanse” for the brain. He’s seen it at work.
</p>
<div class="ad"></div>
<p>
 Sleep, beta-amyloid, and Alzheimer’s disease are wrapped together in a terrible cycle, according to Walker’s research,
 <a href="http://www.nature.com/neuro/journal/v18/n7/abs/nn.4035.html">
  published
 </a>
 last summer in
 <i>
  Nature Neuroscience
 </i>
 . “The more of that bad protein that builds up, the less deep sleep you have,” he says. “The less deep sleep you have, the less you’re able to remove that protein.”
</p>
<p>
 Walker tested whether beta-amyloid buildup predicted a person’s ability to remember facts. He and his colleagues scanned the brains of cognitively healthy older adults, who had a range of beta-amyloid within their brain. The team focused on the medial prefontal cortex, a section of brain just above and between the eyes where we generate the deep sleep called slow-wave sleep. It’s also the region that gathers the sticky beta-amyloid proteins that can kickstart Alzheimer’s.
</p>
<p>
 He and his colleagues found that the people with the largest amount of beta-amyloid in that part of the brain showed the greatest loss of their slow-wave sleep. They also didn’t remember facts studied the night before as well as people without as much protein buildup. “Those people who had the least amount of deep non-REM sleep showed the greatest amount of forgetting across that night,” Walker says.
</p>
<p>
 “We’ve been missing a middleman here in the puzzle of Alzheimer’s disease, and that missing middleman is sleep degeneration.” It sounds depressing, Walker concedes, but there is a sunny side. Unlike other puzzles in treating neurological disorders, sleep is something we can improve.
</p>
<h2>
 Sleep Well
</h2>
<p>
 There are a variety of ways to improve sleep, from physical exercise to relaxation techniques. But in certain cases of insomnia, the only thing that seems to work is medication. The current crop of sleep aids mostly includes benzodiapenes, such as Xanax, and hypnotics, such as Ambien. They reliably knock people out, but one problem with hypnotics is that they sedate, and sedation does not mimic the brain activity we experience during real sleep, the kind of activity that allows for memory formation.
</p>
<p>
 “The electrical signature of sleep that you get when you take these medications is not really a signature that you could argue reflects naturalistic sleep,” Walker says.
</p>
<p>
 Shaw has some hope that a new class of sleep aids, called orexin receptor antagonists, will provide a good alternative. These drugs work by blocking the signaling of orexin, a chemical in the brain that causes wakefulness. By targeting orexin, the drug is affecting a much more localized section of the brain than other sleep aids, meaning that it has the potential for fewer side effects. Studies have also
 <a href="http://stm.sciencemag.org/content/5/179/179ra44">
  shown
 </a>
 orexin antagonists do not disrupt memory formation compared to other sleep aids.
</p>
<p>
 Once we are asleep, there are different ways to possibly further enhance memory formation. Trans-cranial direct current brain stimulation, or TDCS, amplifies the quality of deep brain waves in ways that improve the consolidation of memories during sleep. It works by transmiting an electric signal to the brain so small you don’t feel it. By improving slow wave sleep, such a device could potentially help keep out the toxic proteins that cause Alzheimer’s.
</p>
<div class="newsletter"></div>
<p>
 Other treatments have the potential to help reinforce memory formation. People consolidate memories by replaying them in their brain at night when they sleep, says Ken Paller, a professor of psychology at Northwestern University. Paller has done experiments in which playing a sound can reactivate a memory in subjects. In one of those experiments, people were asked to study a picture with a cat in it and were asked to remember the location of the picture the next day. Paller played cat sounds while the subjects slept, essentially reactivating that memory during slow wave sleep. Those who heard the cat noise remembered information about the picture location better than those who did not receive the auditory reminder.
</p>
<p>
 Researchers have also used auditory or olfactory cues during sleep to reactivate certain memories, Paller says. In experiments of the latter, subjects take a memory test while a certain smell is in the air. Exposure to that smell later in sleep kick-starts the memory. Paller says such a technique may potentially allow individuals to select the memories they want to retain, such as names of grandchildren.
</p>
<h2>
 The Dream
</h2>
<p>
 If all the potential for sleep sounds too good to be true, Shaw says he’s gotten similar push back from reviewers who were skeptical about his research showing that sleep improved memory problems.
</p>
<p>
 At first, Shaw wanted to see just how useful sleep could be, but now he’s got to go back and understand the how. The next step is to focus on one or two memory problems in different parts of the brain and determine just how sleep is fixing each problem, Shaw says. “We’re really trying to figure out how and where.”
</p>
<figure class="richtext-image full-width">
<img alt="" class="richtext-image full-width" src="https://www.pbs.org/wgbh/nova/media/images/paulshaw.width-990_mqMeood.jpg"/>
<figcaption>Neurobiologist Paul Shaw discusses talks with a researcher in his lab.
        
    </figcaption>
</figure>
<p>
 After slogging through these experiments, the sleep experts I spoke with are sure to get their own proper rest. Once Holtzman and his team started finding their links to lack of sleep and Alzheimer’s, he altered his sleep habits. “I’m on my best behavior, better than I was before.”
</p>
<div class="pullquote">
<p>
 “The more your brain has to do, the more you’re going to need sleep for it to happen.”
</p>
</div>
<p>
 Walker and Shaw both talk about the need to rethink sleep in our culture. “We have to at some point simply abandon the notion that sleep is a luxury that we can choose or choose not to engage in,” Walker says. “Sleep is a biological imperative in every species we’ve studied to date.”
</p>
<p>
 It’s not uncommon for people to talk about being too busy for sleep, Shaw says, but he insists the opposite is true. “The more your brain has to do, the more you’re going to need sleep for it to happen.”
</p>
<p>
 Ultimately, Shaw says his hope would be for sleep to slow or reverse neurological diseases or augment other medicines patients may need.
</p>
<p>
 There are both genetic and environmental components to a disease like Alzheimer’s—it doesn’t seem possible one drug could fix all the causes of the disease, he says. But if sleep is good in general, it could be that one thing that could help, he adds.
</p>
<p>
 “That would be the dream. Even if it doesn’t cure it, it will help it.”
</p>
<p>
 Photo credits: Leah Shaffer,
 <a href="https://www.flickr.com/photos/khan/2600541287/">
  Muthahar Khan/Flickr (CC BY-ND)
 </a>
</p>

<p>Whatever our brains can do, neuroscientists are discovering that sleep can make them better.</p>

Vaping Is Far From Harmless

<p>
</p>
<p>
 Vicki Beckmann exhales a thick, sweet-smelling mist into the air of Vapor Worx, an e-cigarette shop in St. Charles, Missouri.
</p>
<p>
 “I like more of the fruity stuff,” she says of the e-cigarette flavorings that line the walls of the shop.
</p>
<p>
 Beckmann, an employee of Vapor Worx, began using an e-cigarette to quit regular cigarettes four years ago. She convinced her father to do the same. Her dad was warned smoking would kill him, she says. “I told him, just try it, and I’ll buy it for you.”
</p>
<p>
 Now, he’s been cigarette free for three years, she says. And Beckmann is slowly lowering the levels of nicotine in the “juice” that fills his e-cigarette device. “He doesn’t wake up in the morning coughing all the time anymore. He just generally feels better,” she says.
</p>
<div class="pullquote">
<p>
 E-cigarettes are now a $6 billion industry worldwide
</p>
</div>
<p>
 As e-cigarettes take off in popularity, Beckmann’s story is not unique. The devices, which contain no tobacco but instead use heat to vaporize a nicotine-laced liquid, can be seen as a less toxic alternative to traditional cigarettes.
</p>
<div class="related"></div>
<p>
 Just a few short years ago, e-cigarette shops like Vapor Worx didn’t even exist, and now they fill the strip malls of towns like St. Charles, with names like VaporWize, Vapology, or others playing on “vape,” the name given to the practice of inhaling the nicotine-laced fog.
</p>
<p>
 Where you find smokers, you’ll find demand for e-cigarettes or “vaping” products, and Missouri is no exception, with 21% of adults smoking tobacco, one of the higher rates in the country. E-cigarettes first emerged online in the mid-2000s, and the business has since grown to become $6 billion industry worldwide, eclipsing the total sales for all nicotine replacement therapy products. Today, it’s estimated that the industry is growing at an estimated rate of 42% per year, in part due to spending by big tobacco companies as they buff up their versions of e-cigs.
</p>
<p>
 There are now hundreds of different devices and thousands of different flavors for those devices. But the hazy, lazy days at the vape shop may be numbered. This may, the FDA ruled that e-cigarettes products will be subject to the same regulation applied to cigarettes. In addition to prohibiting the sale of e-cigarettes to those under 18, this means that manufacturers and retailers of vapor “juices” will have to register ingredients with the FDA, a process that could be onerous and expensive for small operators. After August 8, vapor retailers will have three years to comply with the rules by registering and labeling their product ingredients.
</p>
<p>
 For now, Vapor Worx owner Cliff Brown is waiting to see how it all plays out. “We have no idea of whose really going to be policing it,” he says.
</p>
<div class="ad"></div>
<h2>
 More Than One
</h2>
<p>
 The reason for the confusion among health researchers and retailers is that an e-cigarette is not just one single device or chemical, making it hard to track and regulate. E-cigarettes can work in a couple of different ways. The most common are pen-shaped rechargeable devices that have a refillable tank that holds a nicotine-laced liquid flavor compound. The liquid is then vaporized but not burned by a heating element to produce an aerosol that delivers nicotine to the user.
</p>
<p>
 Many people assume that e-cigarettes are less toxic than standard cigarettes, but there is little data to back that up.
</p>
<p>
 But if someone is trying to switch to e-cigarettes from cigarettes, are they ultimately doing themselves a favor? “The short answer, is no,” says Dr. Stanton Glantz, a professor of medicine at the University of California, San Francisco.
</p>
<p>
 Glantz analyzed a number of different studies that examined the use of e-cigarettes in quitting smoking. He found that use of e-cigarettes in fact lowered a person’s chance of successfully quitting cigarettes by 28%. This aligns with another recent study that found the most successful way to quit smoking is to go cold turkey instead of slowly weaning off cigarettes.
</p>
<p>
 “The evidence is quite consistent that, for most people, they make it harder to quit,” Glantz says. “That doesn’t mean that some people don’t use some to quit. They do, but that’s a small fraction.”
</p>
<p>
 Not everyone has come to the same conclusion, though. Muhannad Malas, a researcher at the University of Toronto, says that the lack of long-term randomized placebo-controlled studies has been problematic. In lieu of those, reviews of observational studies, like Glantz’s, are the next best thing. Malas’s own review of more 60 studies comparing e-cigs with smoking cessation aids found that they may be helpful for some smokers in quitting or reducing their cigarette smoking but, “the evidence was definitely inconclusive.”
</p>
<h2>
 More Than Just “Harmless” Vapor
</h2>
<p>
 The more scientists learn about e-cigarettes and their impact on human health, the more complicated the picture becomes. For one, no one knows exactly how toxic these products are because the use varies from person to person. And, contrary to what marketing materials may say, e-cigarettes produce a lot more than just “harmless” water vapor.
</p>
<p>
 E-cigarette juice contains a mix of propylene glycol, glycerin, nicotine, and flavoring agents approved by the FDA as “Generally Recognized As Safe” (GRAS) for consumption. When this mix is heated, a group of compounds known as carbonyls are produced. This includes compounds such formaldehyde and acrolein. While cigarettes generally produce a thousand times more carbonyls because of the combustion process, e-cigarettes produce a varying amount depending on the ratio of glycol to glycerin in the vaping fluid and how much of it is heated, says Daniel Conklin, an environmental cardiologist at the University of Louisville.
</p>
<p>
 Conklin has investigated how e-cigarettes might affect cardiovascular disease using a type of mouse bred with a disorder that mimics heart disease seen in humans. Acrolein is of particular concern because it is considered to be the main contributor to the increased risk of cardiovascular disease among cigarette smokers, he says.
</p>
<p>
 For 12 weeks, the animals were exposed to traditional cigarette smoke and an e-cigarette aerosol at two concentrations of nicotine, ten and 36 milligrams per milliliter, which spans the range of nicotine usually found electronic cigarette juices. The mice were also exposed to acrolein by itself at 0.5 and 1 parts per million (levels typically found in cigarette smoke). Lastly, a group of mice were exposed to just nicotine in water.
</p>
<div class="pullquote">
<p>
 One puff of an e-cigarette is likely less toxic than a traditional cigarette, but we don’t know how many puffs the typical e-cigarette user is taking.
</p>
</div>
<p>
 Unsurprisingly, standard cigarette smoke had greatest effect, increasing atherosclerosis risk about three times over the baseline. Oral nicotine doubled atherosclerosis risk, while acrolein “seemed to have a dose dependent increase” with risk doubling at higher levels. E-cigarettes seemed to also have a dose dependent result. At the higher concentration, 36 milligrams per milliliter of nicotine, the e-cigarette aerosol doubled the risk of atherosclerosis. Even nicotine alone appeared to induce atherosclerosis acceleration in mice, Conklin noted.
</p>
<p>
 Although he stresses the limitations of one experiment performed on mice, they are cause for concern. He also stresses that how these products are used changes rapidly. For example, some e-cigarettes can be tweaked to deliver more vapor. “There is some concern that we don’t really know how much aldehyde like acrolein is being generated by these modifiable electronic cigarettes.”
</p>
<p>
 How e-cigarettes are used also adds to the confusion. While there is decades worth of data on how a traditional cigarette is smoked, there is little consistency in how e-cigarettes deliver nicotine and flavor compounds. One study found that these products might deliver different levels of nicotine during each use and there were significant differences between “labeled and true levels” of nicotine in juices. One puff of an e-cigarette is likely less toxic than a traditional cigarette, but it’s not known how many puffs the typical e-cigarette user is taking.
</p>
<p>
 “We don’t really know what that frequency does to the health outcome,” Conklin says.
</p>
<h2>
 Thousands of Flavors
</h2>
<p>
 Back at Vapor Worx, Beckmann tells me that she used to smoke real cigarettes “for the calming effect more than anything,” she says. “I can’t really say that I enjoyed the flavor of it.”
</p>
<p>
 Just as there is no standard use pattern for e-cigarettes, it’s impossible to a pin down a single taste preference for vaping. There are thousands of different flavors, ranging from those that mimic a cigar to bubblegum or blueberry.
</p>
<p>
 When Beckmann was able to switch to e-cigarettes, she found the fruity flavors “more enjoyable,” she says. “For my dad it was the opposite. It just depends on each individual.”
</p>
<figure class="richtext-image full-width">
<img alt="" class="richtext-image full-width" src="https://www.pbs.org/wgbh/nova/media/images/e-cigarette-liquids.width-990_qaSSWQm.jpg"/>
<figcaption>E-cigarette fluids come in myriad flavors, which can produce potentially dangerous compounds when heated.
        
    </figcaption>
</figure>
<p>
 The profusion of flavors further complicates the public health picture. Though the different flavors are approved by the FDA as safe for consumption, the environment in the stomach is very different from the lungs.
</p>
<p>
 Take popcorn flavoring, for example. Back in 2000, eight workers from a microwave popcorn processing plant became sick with severe lung disorder, later dubbed “popcorn lung.” A subsequent investigation linked their sickness to airborne exposure to butter flavoring chemicals including diacetyl, which is used in a variety of food products. How diacetyl and similar compounds might damage lungs isn’t understood, but it one hypothesis suggests that these chemicals impair the function of immune cells in the respiratory system. Regardless, the chemical is now categorized under OSHA regulations as an “inhalation hazard.”
</p>
<div class="pullquote">
<p>
 Flavor compounds could suppress immune function more broadly than cigarettes.
</p>
</div>
<p>
 Beckmann is aware of the dangers of diacetyl, and she says that flavor makers are phasing it out, and if they’re not, they’ll have disclaimers. “We stay away from it.”
</p>
<p>
 Yet avoiding those compounds may be difficult. In a study published last year, scientists at Harvard School of Public Health detected diacetyl in 39 out of 51 e-cigarette flavors tested, including flavors one wouldn’t associate with popcorn, such as “menthol” and “tobacco.”
</p>
<div class="newsletter"></div>
<p>
 In one recent experiment, scientists examined the effect of cinnamon flavored e-cigs containing cinnamaldehyde on tissue cells from smokers’ nasal cavities. The cinnamaldehyde-containing e-liquids seemed to compromise the function of immune cells such as macrophages, natural killer cells, and neutrophils. The same researchers, led by toxicologist Ilona Jaspers at the University of North Carolina, also took tissue samples from non-smokers, cigarette smokers, and e-cig users to study the impact of smoke and vapor on immune gene function. As expected, smokers’ samples showed suppression of immune genes in the nasal mucosa. E-cig users not only had the same immune gene changes, but they also showed suppression of additional immune genes, suggesting that the flavor compounds could suppress immune function more broadly than cigarettes.
</p>
<p>
 For scientists it just adds the growing list of unknowns. There are over 7,000 flavors right now and several hundred e-cig products and probably hundreds more if you include modified versions, Conklin says. Combined with how frequently people are vaping, he adds, “it’s not clear at all how that influences that toxicity.”
</p>
<h2>
 Kicking the Habit
</h2>
<p>
 If vapor devices were just used to transition away from cigarettes, they might not cause as alarm among public health researchers. But the products are also quickly becoming popular with young people who don’t smoke at all. A recent survey from the CDC found that 32% of high schoolers reported trying cigarettes, while 45% have used electronic vapor products.
</p>
<p>
 The new regulation from the FDA should help keep vapor devices away from teenagers, but what’s less clear is if the laissez-faire vaping culture helps or hinders more people trying to quit cigarettes.
</p>
<p>
 Despite stories like Beckmann’s, “for most people, they inhibit quitting,” Glantz says.
</p>
<p>
 I found my way to Beckmann’s shop because, like her, I wanted to help my father kick his pack-a-day habit. But, then I wondered: if he succeeds in switching from a pack of cigarettes to hundreds of daily puffs of a cigar-flavored vapor, will that make a notable dent in his cardiovascular health?
</p>
<p>
 So far, it’s a moot point because he has yet to try the vapor products we bought him months ago. And therein lies the problem: everyone’s addiction and smoking preferences are different.
</p>
<p>
 Methods for quitting cigarettes can vary widely by the individual, but those who are using smoking cessation devices found more success when part of a counseling program, Glantz says. “It may be that informal use of nicotine replacement keeps people smoking, as opposed to when it’s consciously being used as part of a supportive smoking cessation effort.”
</p>
<p>
 Glantz might not be as concerned if the vaping trend only included local shops like Vapor Worx. But Big Tobacco companies are putting their muscle into marketing, putting vaping in front of a much broader audience. At that shop, clients and the employees are dubious of any Big Tobacco products. The shop even sources some of its juices and e-cigarette “boxes” locally. The FDA regulations will likely change that, though. The big companies may be all that’s left standing, since they can afford to register their ingredients with the agency.
</p>
<p>
 No matter who manufactures or sells e-cigarettes, the end result is the same. “You’re inhaling hot aerosol ultra-fine particles, aldehyde and nicotine,” Glantz says, “and that’s not so good.”
</p>
<p>
 “There’s a lot we don’t know about e-cigarettes,” he adds. “But I think we already know enough to know that they are less dangerous than a cigarette, but they’re not safe.”
</p>
<p>
 Photo credits: Maurio Grigollo/iStockphoto,
 <a href="https://www.flickr.com/photos/87735223@N02/11359260005/sizes/l">
  Lindsay Fox/Flickr (CC-BY)
 </a>
</p>

<p>While safer than smoking cigarettes, inhaling e-cigarettes’ nicotine-laced fog is anything but healthy.</p>

Leah Shaffer

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