Ever since Karen Straub had her thyroid removed because of cancer in 1999, she has struggled with her weight. She became diabetic and suffered from terrible acid reflux. So when her boss, California State Controller John Chiang, started a worksite wellness program for his staff, Straub decided to give it a try. She joined new Weight Watchers at Work meetings during lunch on Thursdays. She beams activity data from her accelerometer to the Healthrageous website, which allows her to track her activity and interact with her co-workers through a social media platform. She and her colleagues now compete to see who will be the top walker each week. She walks during her work breaks and for 15 minutes at lunch on most days. Since starting the program, Straub has lost 27 pounds. She doesn't have to take pills for her diabetes anymore. Her acid reflux has disappeared.

A common request has been for flexibility around the scheduling and length of lunch and work breaks to allow employees to attend onsite exercises at lunch or simply walk outside.

Chiang's job is to make sure California's tax dollars are well spent -- to root out waste, fraud, and abuse of public funds. Recognizing that the healthcare costs of state employees and retirees were among several threats to the state's fiscal health, Chiang commissioned a study to determine the proportion of costs that were due to modifiable factors such as diet, exercise and smoking. "We all understand that healthcare costs are spiraling out of control," Chiang said.

The California Public Employee's Retirement System health program covers nearly 1.3 million active and retired government employees and their families. Of $1.6 billion spent on healthcare for state employees in 2008, 22 percent was on high blood pressure, heart disease, stroke and kidney disease -- much of which could have been prevented through diet and exercise. The Urban Institute, which conducted the study, estimated that if changes in diet and exercise could reduce the prevalence of these diseases by 5 percent to 15 percent, it would save the state $18 to $54 million per year.

Unlike other worksite wellness programs -- CVS Caremark's, for example, has been lambasted in the media for fining employees $600 if they don't undergo an annual wellness review -- Chiang's program has been very popular among his staff, in part because he seems truly committed to improving their health and morale. Chiang is now working with Service Employees International Union (SEIU) local 1000 -- California's largest state employee union representing 95,000 members -- and others to pilot a worksite wellness program at the California Department of Public Health and the department of Health Care Services.

According to Sarah Zimmerman, deputy chief of staff for SEIU local 1000, "It's not Big Brother because they're designing something that is meaningful to them." The union's involvement has helped identify important obstacles to worksite wellness. A common request has been for flexibility around the scheduling and length of lunch and work breaks to allow employees to attend onsite exercises at lunch or simply walk outside. "A lot of times, managers don't know what is allowed or encouraged," said Zimmerman. "Sometimes it is simply clarifying what the policy is."

Blue Shield of California, which partnered with Chiang in developing the wellness program for his office, has also been experimenting with Wellvolution, a worksite wellness program for its own employees. According to Bryce Williams, Vice President for Wellbeing at Blue Shield CA, "the mantra of going to the gym for 20 to 30 minutes a day, 5 days a week, and changing your diet such that it is low salt and low sugar and low fat and fun free -- that model hasn't worked." His strategy has been to "make the environment such that the healthy choice is an easy choice." Making healthy choices easy choices has included thought to food placement in cafeterias: placing salad bars in the flow of traffic, healthy items at the cash register, soft drinks behind glass at the back, etc. Food is also labeled with Weight Watchers points to help those enrolled in the program.

Now she sleeps well and feels "like a human in the morning."

Lisa Krieger, an employee of Blue Shield of CA, joined Weight Watchers at Work through the Wellvolution program. Krieger, like most working moms, finds it hard to make time for herself. At least at work she can count on breaks and her lunch hour; there are no such breaks at home with the family. After starting Weight Watchers at Work "the weight just started falling off," said Krieger. And once she'd made some inroads through her diet, she had the energy to start exercising. Krieger used to weigh 100 pounds more, the equivalent of strapping three toddlers the size of Krieger's daughter to her frame. She used to get hot and sweaty with the slightest exertion; now she spends her evenings playing with her kids in the backyard. She used to snore and wake up in the middle of the night; now she sleeps well and feels "like a human in the morning."

"I recently got promoted at Blue Shield. I think the confidence and self esteem [that came with the weight loss] had a lot to do with me getting that promotion," said Krieger.

One common refrain I've heard is that losing weight initially through diet made it possible to exercise and lose even more. Linsey Webb, another Blue Shield of CA employee, felt great after losing 47 pounds through the Weight Watchers at Work program, and then wanted to do something more. She started with one boot camp class at work and then signed up for more. Like Krieger, Webb now sleeps better and finds it easier to keep up with her kids at home. "I had a lot of back pain when I was heavier," said Webb. "My back is perfectly fine now." Healthy habits have the potential to ripple through the rest of the family too. "We all go on walks. We try to make healthy choices when we shop or eat out. We go for hikes or find active things to do together," said Webb.

In addition to providing employees with a gym that has cardio equipment and weights as well as various exercise classes at no charge, Blue Shield of CA is bringing exercise into the office itself with treadmill desks, which max out at 2 mph, and stand-up workstations. Employees of Blue Shield of CA can sign up for up to three one hour shifts at the treadmill desk per week. According to Webb, who processes claims while on the treadmill, "at first it was kind of weird," but the treadmill desk has proved popular and is now constantly booked for use. As these new desks and workstations catch on, Blue Shield of CA is partnering with researchers at Stanford University to study their impact and how best to offer them to their employees.

Four out of five Blue Shield of CA employees have participated in at least one aspect of the Wellvolution program, including biometric screening, Weight Watchers at Work, fitness classes and events and quit smoking classes. Between 2008 and 2012 smoking rates dropped by 48 percent, regular physical activity increased by 32 percent, and rates of high blood pressure declined by 66 percent. Williams is now marketing the Wellvolution program to other businesses.

About two-thirds of employers offer worksite wellness programs, and with the Affordable Care Act authorizing grants to small businesses to set up such programs, that proportion is likely to increase over the next couple years. But not all worksite wellness programs have been successful in making their employees healthier or reigning in healthcare costs. The success of Safeway's much touted wellness program in reducing healthcare costs -- which inspired worksite wellness provisions in the Affordable Care Act -- turned out to be false. Safeway, too, offered employees onsite gyms with classes and subsidized cafeterias with healthier foods. Safeway's health care costs dropped by 12.5 percent after the company overhauled its benefits plans in 2006, three years before its Healthy Measures program started, but then resumed climbing. Only 11,000 of Safeway's 200,000 employees participated in Healthy Measures. The produce managers, deli counter workers and cashiers that make up the majority of Safeway's workforce didn't have access to the gym, cafeterias and other amenities at company headquarters.

My family's experience with worksite wellness programs is typical of many. We were given a small incentive to complete an online baseline health risk assessment, and then given recommendations on how we could be healthier. We each got calls from a nurse to discuss these recommendations, but neither of us had the time for that in the midst of our busy workdays. Worksite wellness programs won't save employers money -- and may in fact further drive up costs -- if they aren't designed to help employees actually change their habits.

A research engineer at the Laboratory for Tissue Engineering and Organ Fabrication at Massachusetts General Hospital, displays a titanium frame designed for the reconstruction of a human ear, as well as a plastic ear model. (Steven Senne / AP)

Media broadcasts stories of children with facial anomalies being "saved" from bullying via plastic surgery. Cases range from port wine stains and scars from cleft lip repairs to things even more noticeable, like a very misshapen nose. Although the surgical-repair approach seems to many like a no-brainer, medical professionals who care for children with facial anomalies see these cases as much more complicated. I asked Cassandra Aspinall, a senior social worker in the Craniofacial Center at Seattle Children's Hospital, to explain. Aspinall has worked at Seattle Children's for 27 years. Our discussion is lightly edited for clarity.

AD: If a child is being bullied over some facial anomaly, why shouldn't we see plastic surgery as the easy fix?

CA: Making decisions about surgically "fixing" someone's appearance is much more complicated than making a decision to medically manage asthma or diabetes. Some surgeries done on facial anomalies are meant to manage human interaction by changing appearance, and human interaction is always complex. When I work with these families, I try to find out what has been done to stop other people's reactions to the child's facial difference. I can't think of any situation where a person who is being singled out because of racial or ethnic differences would be told that that they should just change their race or religion to avoid someone else's prejudice.

What risks do you bring up when families are considering reconstructive surgeries?

Of course the physical risks that come with any surgery, but also the risks of changing one's appearance. A child and family may unexpectedly face stress after surgery from having "given in to the bullies," from feeling not strong enough to cope.

The trend in the pediatric care of children with socially-challenging anatomies seems to be toward team care -- social workers and psychologists as well as medical and surgical specialists.

It is. We're trying to do more to immediately support the patient, but also improve long-term outcomes. We may provide the most expert surgical treatment to a patient, but if the patient does not experience the change as positive, or if the change is short-lived because environmental issues are not addressed, then harm can ensue. The "problem being treated" has to be assessed rather than assumed. Other factors will also affect how an individual fares: how other people react, whether or not the family suffers financially from treatments. A multidisciplinary team can also work to reduce the trauma sometimes caused by medical interventions, an under-recognized concern.

When a child is born with a noticeable birth anomaly, parents often worry that that child will never be lovable. (Actually, all parents probably worry about this for all children.) What's the best way to address that worry?

The most important thing to do is to explicitly address it. The reactions of others can be a problem, but those reactions--or fears that those reactions will occur--must not be our only focus. We try to help families and young children by supporting identity formation that puts the medical condition in the background while staying focused on what a given child enjoys or finds interesting in the world, and helping others to do the same. All children can learn to be with those who support them and move away from those who do not. They can learn that one can choose to change oneself (including one's body) to satisfy the views of a few or one can align with those who share common interests and worldviews.

You were born with a cleft lip and your third child also turned out to have a cleft lip. What insight did these experiences give you?

My personal and professional experiences have reinforced for me the limits of modern medicine. My life experience has also taught me to be very careful about guarding my privacy while also being vocal about how others need to do the same. Other team members may advertise my life experiences as something I can share with patients and families as a way to provide guidance about their own evolving journey, but what they often miss is the importance of helping parents to focus on the differences in our experiences rather than trying to imagine that there is a "recipe" to make it work. I cannot confuse my life experience with any other person's, especially my own child's.

The face is particularly important to so many aspects of life. Does this mean we should be quicker to offer cosmetic plastic surgery for facial anomalies than other socially-challenging anomalies?

It is because the face is so important that we should take extra time in considering surgical treatments that change facial appearance. The risks are great. I worry that we often do not take the time to uncouple the offering of surgery from the process of making the decision to actually perform a surgery. I encourage parents to let children be part of decision-making, as much as possible. Parents often worry that delaying surgery may hurt their children or cause the parents to be seen as irresponsible. But waiting until their child can participate in a surgical decision can lead to important psychological benefits that maybe they haven't considered.

Because surgery is especially risky on newborns, surgeons do not perform primary cleft lip repair until children are several months old. That means parents have taken their babies home and gotten to know them with the cleft for months. Do they sometimes find the "repaired" face disorienting?

This is a very common -- almost universal -- reaction. The emotional work that parents go through is quite intense. Providing a clinical venue for honest conversation is critical. Parents do not want anyone to interpret their decision to move forward with a surgery to mean that they do not love and accept their children. At the same time, they are anxious about "meeting" their babies after surgery, as they are acutely aware the face will change. I talk with parents about how their brains have mapped out who their child is based on the face, and encourage them to understand their love will do the remapping necessary after surgery. But it can be hard.

What fears and hopes do children typically express about cosmetic facial surgeries?

Children worry about pain, waking up during surgery, and missing school and their friends. They worry that, by agreeing to an operation, they are giving in to the bullies or sending the message that they don't accept themselves, when really what they want is to just look a little bit less different. They want to be noticed for who they really are, not because their lip or nose is crooked or because their speech sounds different. At the same time, they have accepted who they are and for the most part accept these differences. So children facing surgery worry they may not recognize themselves afterwards.

Felix Baumgartner in 1999 preparing to base-jump from the arm of the Christ the Redeemer statue atop Corcovado mountain, overlooking Rio de Janeiro. Baumgartner camped out overnight at the site and used a high-tech crossbow to shoot over the arm of statue to climb up. (Reuters)

PROBLEM: When our bodies are in stressful situations, our adrenal glands release a hormone called cortisol. We can measure that cortisol to quantify physical (not mental) stress. Research has shown that for social stressors like public speaking, cortisol responses get smaller as people get more used to doing the stressful thing. Does your body ever really get used to things that can genuinely physically injure or kill you, though? Like, a lion attack, or falling from the sky?

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• Meditation Improves Attention, Memory
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METHODOLOGY: Researchers sent 40 people into the jungle. They then released a bunch of lions to attack them. Ha, no, they did the experiment with skydiving. Researchers at Northumbria University in Newcastle Upon Tyne, England, led by Dr. Michael Smith, measured cortisol levels in 24 skydivers right before and after they jumped. Some were veteran skydivers, some were new. The researchers also asked the skydivers how anxious they felt.

RESULTS: Veteran skydivers reported that they felt less anxious than the beginners. Cortisol levels, though, were equally high in both groups.

IMPLICATIONS: Skydiving seems to terrify the British body even after it stops terrifying the British mind. What else stopped stressing your mind but is still terrifying your body? Yogurt? Everything?

Frenchie is the heart and soul of his gym in Williamsburg, Brooklyn. The 72-year-old bodybuilder has been running the place for 36 years, with loads of weathered snapshots on the wall to prove it -- Speedos, oily muscles, the whole deal. "Wow! This place is old!" is a typical comment for a new visitor, Frenchie says. "Some people today, they want to go to [a] fancy place. There's plenty of places around, but -- people like the way it is. It got character!" Frenchie's Gym isn't 24 Hour Fitness, that's for sure. "The neighborhood keeps changing," the filmmakers write on Vimeo, "but Frenchie's not going anywhere." 

This Must Be the Place is a documentary series about home, belonging, and loving what you do. Combining intimate interviews with lovely cinematography, David Usui and Ben Wu of Lost & Found Films craft unique portraits of individuals and the places that mean the most to them. The directors talk about the project in an interview with the Atlantic Video channel here, and don't miss the rest of the series here. 

For more from Lost & Found Films, visit http://www.lostfoundfilms.com/.

The latest "virtual therapist" -- charged with helping diagnose depression -- comes from psychologist Albert Rizzo and computer scientist Louis-Philippe Morency at the University of Southern California. Their system of cameras and microphones analyzes a person's gestures, facial expressions, body habitus, and vocalization -- taking in 30 data points per second -- then compares them to those of typical depressed and non-depressed people. 

The therapist persona was crafted carefully. "Everything has been thought of," Morency told NPR's Alix Spiegel on today's Morning Edition. "We have recorded more than 200 'uh-huhs' ... a simple 'uh-huh' and a silence -- if they are done the right way -- can be extremely powerful. So we spent a lot of time on these little details." 

Those details, though, are rendered with an eerie ethereality. 

SimSensei's poise seems to be constantly set at 100, "uh-huh" registering as "I'm flawless, and I am judging you." Maybe they should've given her a wandering eye or something. Still, the idea is promising. Morency says they look at the tool like a physician might look at a blood test; part of the big picture that shapes a diagnosis. 

Surrounding this month's release of the Diagnostic and Statistical Manual (DSM), psychiatry is hearing a lot of blowback. People want harder science, more data behind the shifting diagnoses -- people including director of the National Institute of Mental Health Dr. Thomas Insel, whom I got to interview at an Atlantic Live event earlier this month. It was on C-SPAN, remember? In case you missed it: "A diagnostic approach based on the biology as well as the symptoms must not be constrained by the current DSM categories." While focusing on understanding the fundamental biology behind psychiatric illness, Insel and others believe that quantifiable data is crucial to the advancement of psychiatry -- data, maybe, like how a person at-east a person appears while interacting with a utopian humanoid whom they knew to be scrutinizing their every microgesture.

Actually this setup could catch people at their most expressive, because we're more comfortable looking at computers than we are at real people. Ha, no, we aren't. Ha.

Here's the video of people talking to the virtual therapist:

Spiegel's full interview with the program's creators is here.

However, in polio-affected areas of India, the faces of the campaign are much more local. In a single immunization round, 2.5 million vaccinators will work hard to make sure that 170 million children under the age of five are vaccinated. Nearly 700,000 booths are set up nationwide. It is a massive effort. These images are of the faces behind the polio effort in Aligarh, one of the many affected towns in Uttar Pradesh, India.

Public health is as much about medicine as it is about culture, GPEI has learned. So, local elders, and sometimes members of the local clergy, are given the title of "influencer." They accompany vaccinators or station themselves at vaccination booths. Their task is to convince parents that the vaccine is safe for the child to consume.

In-transit vaccinators are stationed, naturally, in areas of transit. They're at railway stations, at bus depots, in the middle of chaotic markets, and at cross points in the city. This lady had a keen eye for a unmarked pinky -- the sign of an unvaccinated child. She will be stationed at her post throughout the immunization round.

In the heart of Aligarh, in an area called Upper Kot, which is largely occupied by the Muslim community, a bazaar takes place daily. Stationed at the base of the main mosque, it's a busy area of activity. This health worker will be roaming the area from 8 a.m. to 5 p.m., trying to spot unvaccinated children. Her yellow vest tells the shoppers that she's a polio vaccinator.

Another influencer, who has been with the campaign for over five years. His motivation for working the polio booths? "I want children to be able to run around happily and freely," he told me in Hindi. He's been stationed with UNICEF health workers for the day. During the door-to-door activity, he will join the vaccinators as they navigate the maze-like communities.

Many of the health workers in the polio campaign are quite young. For them, the daily wages (that can amount to anything around $1 to $2) are an allure. For some of the older health workers, such as this woman, the polio campaign has become a rooted part of life. She's been working polio booths for the past 15 years.

This young vaccinator has been assigned to a polio booth in a predominantly Muslim section of the city. Given the mix of communities in northern India, GPEI accounts for Muslim populations by providing female vaccinators, signs written in Urdu, and members of the local ulema (clergy) who validate the vaccine.

The polio "booth" is a rather generalized term. A booth can consist of a rickety table on a street corner or the patio of a clinic, as seen here. The sign is the telling point. These three health workers are reporting to Mr. Khan, the polio district coordinator, of the day's activities.

Umar Muhammad Khan is an employee of the polio campaign. Overseeing the efforts in Aligarh for the past decade, Khan has been hired by the Polio Plus Committee in India to make sure that each National Immunization Day (and sub-NID) goes off without a hitch in his district.

Older children play a big role in the campaign. As a marketing tool, they place on masks, run around the neighborhoods, and play in the streets, spreading the message: It's time to get your children vaccinated for polio.

Two UNICEF health workers approach a Muslim household in the door-to-door campaign. The woman on the right, Khalida Sherwani, says that her job gives her an identity, and a feeling of importance in the community. Otherwise, she would just be sitting at home.

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PROBLEM: Public health officials spend a lot of time trying to figure out to how to be against obesity, as a disease, without being against obese people. (Or at least, most of them do.) It's probably safe to say that most of this complexity is lost on children, who pick up on societal cues as to what is socially acceptable and what is not.

METHODOLOGY: Andrew Hill and colleagues at the University of Leeds designed three versions of a simple story book about two friends, Alfie and Thomas, whose cat gets stuck in a tree. In one version, both Alfie and Thomas were "normal." In the two others, Thomas remained the same but Alfie was presented as either overweight or disabled. The books were read to 126 schoolchildren, ranging in age from 4 to 6 years old, who were then asked to rate Alfie and Thomas on a number of attributes. The procedure was repeated with female characters -- Alfina and Holly -- for another group of 150 children.

Normal Alfie, wheelchair Alfie, fat Alfie, and Thomas.

RESULTS: The children overwhelmingly decided that fat Alfie and wheelchair Alfie would be less likely to win in a race against Thomas (which is not entirely unreasonable). However, they also assumed that fat Alfie was less likely to do well in school, to be happy with the way he looks, or to get invited to parties. They rated him as more likely to be naughty and as having fewer friends than Thomas to play with. Their "rejection" of the fat character was consistent for his female counterpart, and was not influenced by the children's gender. One lone child, out of 43 who saw the version of the book in which Alfie was fat, said he'd chose him as a friend over Thomas, and only two out of the thirty students shown fat Alfina said they wanted to be her friend.

Things were better, if not great, for wheelchair Alfie. Aside from being perceived as physically slow, he was also assumed to be less likely than Thomas to do good school work or to get invited to parties.

IMPLICATIONS: Kids are cruel and quick to reject those who are different from them, but we usually say that's because they don't know any better. That's why so much of elementary school is spend learning to love and accept all kinds of people. But that they were much harsher critics of the fat character than the one with another -- and less common -- physical difference suggests that at their young age, they've already absorbed an upsetting message: that fat is a negative indicator of a person's character, and that overweight people are undesirable as friends and as people.

My fiancé and I are getting married, but we have no money. We like the idea of a small wedding, I'm crafty so I am down to do some handmade things, but time and time again I've seen this look tacky and/or cheap. One time I went to a backyard wedding that had a wonton buffet and it made me so sad. I see how handmade weddings can turn into Etsy nightmares, which now are my nightmares. Do you have any tips for making an ULTRA low budget wedding still classy without looking like something that ended up on the Bridezilla's cutting room floor?

Congrats on marrying your fiancé, number one. Two, ignore my dumb joke. Marriage! Congrats! What a weird thing that you're doing: being adults, starting a life together, etc.

I feel you on the tragedy of that wonton wedding. When I was nineteen I went to a friend's wedding that took place in a small backyard where they served spaghetti and garlic bread from a local restaurant. We both worked at a small hardware store making eight dollars an hour. BUT here's the kicker: The food they served was from the restaurant that they had their first date and the backyard comfortably fit everyone and they're still married and seem really in love. So who cares?

I think about how I would like to get married, or if that will even be a thing in 40 years, and I imagine a five-minute ceremony where a sassy elderly gay man will ask us, "So do you love each other or not?" and then we'll kiss and then we'll eat burritos and maybe go to a ballgame. That's it, dream day for me. I know that would be a sad nightmare for most people, but it's my hypothetical day so leave me alone.

As for YOUR wedding stuff: It sounds like you know what you think is bad, so I guess just don't do that? You are an adult human with objectivity, opinions and the give of reason; so if you make a place setting (or whatever wedding stuff you need to have a wedding, I don't know) and you hate it, then I would suggest not using it. The important thing is that you're happy and love your wedding. Oh, and don't be shitty to your friends and family beforehand. They are your biggest asset in saving money. For example: buy all of your booze from Costco and have a friend bartend, and if you have a photographer friend, have them take your photos. People really only care about the candid shots where people are looking at each other lovingly, anyway.

If you do end up with some sort of ugly aspect of your wedding; weird looking floral display, ugly cake, funny looking bridesmaid dresses, just say it's made from green materials. People will forgive appearance if they think it's good for the environment, just look at the Prius.

My friends complain a lot about relationships ending in the other person just fading away. As in, they just stop calling and become apathetic, instead of an actual definitive breakup. I hate when women do it to me, but I also find myself doing it sometimes. At what point do you owe someone a confrontational "This isn't working out" talk? And it has to be a talk (as in, not text or Gchat)?

I love this question so much. It's funny, I wonder how many relationships fail because of the uncertainty social media provides. I can't count how many times I've been party to conversations where a friend is stressing about their significant other not liking their status update, profile picture, blog post. Oh lord, he's starring another girl's tweets? I think it's over. It's a gross and weird world we're living in, where constant public validation seems to be a requirement.

I do have to say, social media has helped me maybe more than it has hurt. I can't tell you how many times friending a person I met at a party has gotten me laid (once).

But I feel like your question has much more to do with the timeless pang of rejection. Sure, it's fine when you fade out of a relationship or casual dating situation, but it sucks when someone does it to you because you're great and everyone should see that. No one wants to be left hanging, you know?

mhauri/flickr

It's tough when you first start dating someone to know when you have to let someone know that you don't want it to continue. I have this idea that I'm going to eventually sit someone down and give them this long beautiful speech about how wonderful they are but that we are different creatures and I'm a bird or something? I haven't figured it out completely yet, but I imagine finishing this soliloquy only to be met with a perplexed look and a "I know, we we're just hanging out." My advice is always to err on the side of human decency: If you're at six weeks you should at least call, especially if there were solid or tentative plans in the future, but I will accept email or text with the open invitation for a phone call. Anything longer than that and you've gotta just suck it up and do it in person. Ending things with someone is the worst, but I promise if you do it in a classy way with a clear, definitive end, you'll feel better and make her feel better.

I'm 29, and I've been dating this guy who's younger than me by quite a bit. I'm nervous about having sex with him because I can't stop thinking about how he grew up with high speed Internet and probably has seen more porn on a Tuesday than I have in my whole life. I've always been confident in bed, but for the first time in my life I'm starting to feel self-conscious. I read somewhere because of such early exposure to porn, kids are doing really extreme things early on. Should I just stick to guys who grew up with Sega Genesis?

Okay, so. There are several pieces of information that I don't have. You say he's significantly younger, but you don't say by how much. Legally, it can't be more than eleven years and if you're dating an 18-year-old, there's no way it's for the conversation. And without being argumentative, even an 18-year-old would remember the days of dial up. MY guess is we're talking about five years, tops. And who cares? He certainly doesn't.

The sex thing is another area where I wish I had more detail. Is he an asshole? If he's an asshole, then yeah, he might try to do things that you are uncomfortable with sexually without asking you first. You shouldn't date that guy. Watching porn, even an exorbitant amount of it, does not make a person a sexual deviant. Speaking as a mild-mannered porn over-watcher, there is a very clear line between reality and fake auditions.

Most likely he's just a regular dude, because most people are just regular dudes. Which means that the first time you two have sex he's not going to do anything other than be slightly disappointing. You say that you are usually confident in bed, which is great, all women should be. I'm looking forward to an era where we don't expect a gold star for asking for the things we need, sexually. But embrace that self-assuredness in all aspects of your life, don't balk just because this kid might not get your TaleSpin references.

Also, are you even into this guy? Or is he just available? I feel like I just reached the point where I can no longer just have sex with someone out of apathy. Kind of an important milestone, really. When I hear people already searching for fault in the person they're dating so early on, I have trouble understanding why they would want to continue. Don't get me wrong-- I've done this a million times: boring guy, weird laugher, funny smeller, sure why not? It's fine until it's not and if you're already trying to find an excuse as to why it's not going to work, then I don't understand investing time or energy.

Please believe me when I tell you that I totally get the age discomfort thing. I've dated men who were younger than me and it never quite fit. So for me, I would just casually say, "This will never work long term, you're too young for me." Which is neither constructive nor a jumping off point for like, a casual conversation but a GREAT way to destroy a relationship.

If age is a sticking point for you and you don't think it's something you will ever be comfortable with, then this is not relationship that you should pursue further. Although I do have to tell that since the original Sega console - which was great, sure - they have made huge leaps and jumps forward: better graphics, immersive gameplay and hey, the ability to save your game. You should check 'em out.

If you have questions about relationship etiquette, please send them to askalison@theatlantic.com.

Shaun Thompson leads an Insanity workout.

Insanity came by airmail, bound like a prized first edition. The first time I tried it, it didn't seem too bad. A little sore in the thighs maybe, a little weak in the hip flexors, but nothing insurmountable. The second week, too, stayed within the limits of my psychological health. Then at the end of the third week, there was a pure cardio workout that culminated in what were called level two drills: four regular pushups, four tricep pushups, eight high jumps. I was on my fifth set when I realized that I had forgotten to inhale. Or exhale. My sweat was pooling on the floor, sliding in rivulets down the tip of my nose.

No discipline? The program could fix that. Romantic troubles? Insanity would make my boyfriend rue the day he ever looked at another girl.

Afterward, I spread it all out, these instruments of my torture: 10 DVDs , a calendar, a pin-up poster, alluringly illustrated, and a diet booklet espousing the benefits of salmon and kale. Together they comprised the 60-day Insanity fitness regimen, of which I was currently on day 22. Billed as the hardest workout ever put on DVD, Insanity purportedly used max-interval training (an inversion of the usual short anaerobic exercises followed by less intense recovery periods) to get fast, durable results. These exercises included burpies, mummy kicks, and Spiderman push-ups, served up by a cast of leggy fitness instructors whose very muscled-but-not-too-muscled-ness spat in the face of Just the Way You Are. And why not? The premise of Insanity, after all, was that soon I'd be leaving my old body behind, and with it, my old mindset, my old bad habits. No discipline? The program could fix that. Romantic troubles? Insanity would make my boyfriend rue the day he ever looked at another girl.

The first group consisted of what I call the easy sells -- cookie diets, tone-as-you-walk shoes, vibrating machines that claimed to shake your fat off -- products sold at corner stalls in strip malls and in banner ads squashed between the bad variety shows and soft-core porn that characterize certain stretches of the internet. They were most often ineffective, but people bought them on the off chance that they weren't.

By 2011, Americans were spending $1.2 billion a year on liposuction, $6 billion on yoga studios, $24 billion on gym memberships.

Hard sells, contrastingly, embraced the workout. They demanded the workout. They not only acknowledged how many glazed fritters the customer was going to have to give up, they made it a veritable mantra. Dig Deeper. Push Harder. Get Fit or Get Out. The hard sell was perhaps best embodied by NBC's The Biggest Loser, a sixty-minute prime time blitzkrieg of sweat, tears, and drill-sergeant-esque instructors. Contestants came on at 300 pounds, left at 150; weighed in at 250, weighed out at 120. Meanwhile, its host, Jillian Michaels, parlayed the show's success into a media empire as sprawling as Martha Stewart's.

The genius of the hard sell, of course, was that it wasn't a sell at all. As Beachbody executive Laura Ross put it, "We were just trying to be honest. If you wanted to get results, you would have to work your ass off." And therein lay the savvy of it: in an era of quick fixes, Insanity made logical sense. It asked for sixty days, every day. It asked you to sweat like it's monsoon season. And in return it promised a body as tight as rubber and as hard as sin.

***

To distinguish Insanity from P90x, Beachbody picked to star in its videos a relative unknown named Shaun Thompson. He had been teaching classes at the local Equinox in Santa Monica when he met Ross, who invited him to submit demo videos for another Beachbody program called Hip Hop Abs. They ended up being so good that he was signed not only for that series, but also for Insanity.

"It was obvious from the get-go that Shaun was extremely talented," Ross said. "Sometimes in fitness videos because of space constraints we end up doing movements that seem super contrived, super restrictive. But Shaun used to run track, he used to dance, and you can really see that in his posture, how he holds himself. He brought a natural athleticism to the exercises."

Insanity was nearly a year in development. In a way that would have been inconceivable to the likes of Jane Fonda, the modern fitness video is a meticulously choreographed beast, the product of concept meetings, design docs, A/B testing. Thompson spent hours working through single movements at the gym. Versions were edited, then re-edited. His last name became the snappy, monosyllabic T. The final version was tested on a focus group of 60, whose physical transformations were then sliced into a twenty-minute infomercial that would form the lion's share of Insanity's publicity plan.

"From the beginning, we knew that Insanity would be marketed primarily on television," Ross said. "We just had no clue that it would be so successful. And so every year, we've reshot the video. We send out a call, people mail in their before and after photos, their testimonials, and we feature those right alongside the professional stuff."

The result was a surprisingly seductive grassroots production -- people who started out looking like you and I, gradually doing things that you and I couldn't do with two more legs and a sledgehammer. In one segment, a forty-year-old mother of three whipped out a set of pull-ups, nary a love handle in sight. In another, Daikeler himself appeared shirtless, mugging for the camera. "Why didn't I have this body in high school?" he asked breezily. "Do you know how much more fun it would have been?"

The emphasis in the infomercials, as on the BeachBody.com forums, and in the myriad YouTube testimonials posted by ecstatic users, is partly on the results but mostly on the process. Finishing the program seems to inspire unique pride and satisfaction. You conquer Insanity. Can you ever really say that about StairMaster?

***

As for my own experience with the program, well, so far it's left me in awe of what a body can accomplish when faced with a HD screen and a buff man screaming, "Jack it off!" I've always been naturally thin, but I've never been strong. Insanity changed that. A couple weeks ago I went rock climbing with friends, and for the first time I felt that I was in control of my movements. I could trust my arms and legs to go where I wanted them to go.

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Of course, the price for strength is consistency. You'll find hundreds of accounts about Insanity online that all begin with "I never missed a day," and it's true: the program works best when you do the workouts on schedule. It also works best when you follow their diet plan, when you drink their recovery formula, when you sacrifice your first born to the God of Good Abs. What's less publicized is how effective it can be even when you slip up a little. Sometimes I'll miss a workout and that's okay. I'll gorge myself on my roommate's chocolate chip cookies just to rub it in and tomorrow pick up where I left off.

Maybe next time, I'll try Beachbody's new Focus T25, a ten-week series of 25-minute workouts for self-proclaimed busy people. I like the idea of working out during my lunch break -- and eating lunch, too.

PROBLEM: The pre-societal, animal model of conflict resolution is simple, brutal, and effective. Leaving aside political gambles, moral considerations, and the like, the strong are more willing to fight for their self-interest, while the weak find it more advantageous not to assert themselves. Extrapolated to a fairly simple conflict of interest -- wealth redistribution -- do modern humans operate under the same logic?

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METHODOLOGY: Researchers at Aarhus University in Denmark and UC Santa Barbara collected from several hundred men and women in Argentina, the U.S., and Denmark. They categorized the subjects by socioeconomic class, their upper-body strength, or "fighting ability" (as measured by the "circumference of the flexed bicep of the dominant arm"), and their responses to a questionnaire gauging their support for economic redistribution.

RESULTS: Rich men, who would benefit least from redistribution, were more likely to be opposed to it -- but only when they also had large biceps. There was a negative correlation between the two, so that rich men with less muscle strength were more open to redistribution. In men of lower socioeconomic status, the correlation was reversed: stronger men were more in favor of redistribution, while men with smaller muscles were less likely to support it.

These associations remained significant even once the researchers controlled for political party. No relationship between strength and ideology, however, was seen in women.

IMPLICATIONS: Evolutionarily speaking, write the authors, "it is a fitness error for weaker contestants to attempt to seize resources when they cannot prevail and for stronger ones to cede what they can cost-effectively defend," at least in men. For women (again, in terms of evolution), physical conflict is rarely worth it. Regardless of the high-minded ideas we may have about how our ideologies are formed, their findings suggest, whether we argue in favor of the common good or our own self-interest is to some degree influenced by who would win should it come down to an arm wrestle.

Oakland-based 23-year-old rapper Kreayshawn, of "Gucci Gucci" fame (now at 42 million YouTube views), wrote via Tumblr this morning to tell the world that she is with child.

Yeah, I'm pregnant! It sucks. If your [sic] not pregnant don't get pregnant for a while because there's all these symptoms that make you feel weird and hurt and are uncomfortable and 9 months is really really long especially towards the end. You have to pack away all your slutty crop tops and high waisted shorts. Your [sic] stressed all the time and in pain and bored on top of that because, at the end of the day if your friends cant smoke with you or even around you they will find something better to do. And when you do ge[t] to go out with some friends your feet and back usually hurt within an hour. ...

The ME, ME, ME GENERATION has done it again. (From last week's Time cover article: "Here's the cold, hard data: The incidence of narcissistic personality disorder is nearly three times as high for people in their 20s as for the generation that's now 65 or older.")

What is ... everything? Kreayshawn's Tumblr looks like a MySpace page. She lists her favorite book as "Tumblr." Put all your money in gold, everyone. Or, no, don't even.

As Elspeth Reeve pointed out last week, the cover story for The Altantic Monthly's September 1907 issue was "Why American Marriages Fail." Civilized society crumbling under each keystroke, it warned that "the rock upon which most of the flower-bedecked marriage barges go to pieces is the latter-day cult of individualism; the worship of the brazen calf of the Self." The article did not mention Kreayshawn by name.

When I first meet Morton Satin, he's seated in an office chair on a Tuesday morning, shaking his head at his computer screen. He glances over, sighing, and motions toward the monitor. Displayed is a press release from Science Daily claiming that salt depletes the body's calcium stores. "Every morning brings a new headline," he says sadly before launching into a diatribe about the supposedly shoddy science used in the article. "Sometimes, you feel like you're spinning your wheels, not moving forward but trying to prevent misinformation."

"More people die when they are on a low-sodium diet than when they are on a regular-salt diet," he proclaims.

The misinformation he's worried about concerns one of the most ubiquitous substances in our daily lives: salt. This week, experts convened by the Institute of Medicine concluded that "the evidence on direct health outcomes does not support recommendations to lower sodium intake ... to or even below 1,500 mg per day." The current recommendation is not to exceed 2,300 mg per day, though most Americans do. This slight paradigm shift -- to an idea that less salt is not always better, which is already disputed and will be slow to be accepted -- comes after years of advocacy from people like Satin.

Morton Satin

Satin, a molecular biologist, has begrudgingly accepted the nickname "The Salt Guru," after coming out of retirement to be the Vice President of Science and Research at The Salt Institute, a non-profit trade association based in Alexandria, Virginia. Before that, Satin spent sixteen years as the Director of the United Nations Food and Agriculture Organization's Agribusiness Program. It was there he achieved two of his most important successes: a patent for coconut water and one for the creation of gluten-free bread.

His office is more that of a man who writes coffee table books on coffee (which he recently did, to warm reception by The New Yorker) than of a molecular biologist who thinks the public institutes of health are spouting untruths. But, he does think that. He says the 2,300 mg line is too low, and he's not the only one. 

Science writer Gary Taubes, a salt defender and author of Good Calories, Bad Calories and Why We Get Fat, has written columns for The New York Times in which he defends salt's health properties. The problem with Satin as the loudest salt advocate, though, is that even while a close look at data does seem to lend credence to his claims, he works for the Salt Institute -- which salt companies help support. Credibility goes out the window, Taubes says, and it doesn't matter how loud you are, no one will listen.

Satin has a propensity for ambling off into his life's stories, eyes racing around the room as he wanders lazily into these arbitrary yarns. When telling these stories, he seems calm, at peace. And he stays that way until he speaks about salt's reception. At that point, his eyes narrow and mouth pinches, his voice rises, and his anger is prominent, ardent. "More people die when they are on a low-sodium diet than when they are on a regular-salt diet," he proclaims. "You have to look this thing with a truly open mind, and it's difficult because we really don't like to think of public institutions fooling us and screwing us ... [But] nothing justifies lying. Nothing justifies exaggerating. Nothing justifies misleading the public."

And that's exactly what he thinks most public health institutions, such as the United States Department of Agriculture and the Centers for Disease Control, are doing. The American Heart Association (AHA) has argued that 2,300 mg is too high. The argument is that high sodium intake increases blood pressure and leads to cardiovascular disease, strokes, and kidney disease. Consuming 2,300 mg at most helps keep this in check, according to the AHA. 

Satin readily admits, though, while disagreeing with these guidelines, that he doesn't know what the right amount is. His bible is the Dietary Reference Intake, which is an Institute of Medicine study supported by the National Academy of Sciences, The National Heart, Lung, and Blood Institute of the National Institutes of Health and the U.S. Department of Health and Human Services' Office of Disease Prevention and Health Promotion, among others.

The six-page letter refutes the Times piece, concluding that it could lead to "more hypertension, heart disease, deaths, misery, and medical costs down the road" if taken seriously.

The book offers an estimated average requirement (EAR) of various elements and minerals. Satin eagerly points at the top of page 270, which reads, "Because of insufficient data from dose-response trials, an EAR could not be established, and thus a Recommended Dietary Allowance could not be derived. Hence, an Adequate Intake is provided."

In plain language: It was impossible to determine how much salt we should be consuming, leaving Satin further incensed that someone would claim to know how much we shouldn't be eating. "You can guarantee if they had the evidence, it'd be there," he says. His view of the 2,300 mg line is that it was invented out of thin air. "It was a lie," he says. "I know scientists, and I know how they think: if there is no evidence, they made it up."

This, of course, raises the question: why would someone launch a national campaign against salt? Satin thinks it's a mixture of laziness, convenience, and the easy path to scientific popularity. It's easy to launch a campaign against something, and it becomes easier as more people think it's detrimental to their health

Satin cites Michael Jacobson, PhD, cofounder of the D.C.-based Center for Science in the Public Interest, as one of the leaders of the anti-salt movement. The website for his foundation states, "Salt, at the levels present in the diets of most people around the world, is probably the single most harmful substance in the food supply," and he's written an incendiary article titled "Salt: The Forgotten Killer and FDA's Failure to Protect the Public's Health."

"I admire him for all the wrong reasons," Satin says of Jacobson. "I don't think he's done a lick of homework since he left school. You have such a problem with people who want to do good but don't take the time to do the homework."

timsimpson1/flickr

Jacobson, though, says the science is there, in black and white. Lowering salt intake leads to longer life. "The key thing with salt or with sodium," he told me, "is that it promotes high blood pressure, and high blood pressure promotes heart attacks and strokes, which isn't conducive to long life," he says. "That's the elephant in the room."

Salt defenders, of course, disagree. Taubes has written, "The result [of eating salt] can be a temporary increase in blood pressure ... The scientific question is whether this temporary phenomenon translates to chronic problems."

Taubes, like Satin, doesn't think so. In fact, he also goes so far to say, "the possibility has been raised that if we were to eat as little salt as the USDA and CDC recommend, we'd be harming rather than helping ourselves." He too cites Jacobson as a leader in the anti-salt movement, well-intentioned but ultimately misguided.

"It's a kind of interesting phenomenon," Taubes says. "The people who care have always cared. The anti-salt people are convinced that salt is bad, and they convince themselves that they have to change the world. [But] the medical research community really doesn't know how to do science properly." Instead, he postulates that people believe salt is bad simply because that seems logical, even if it isn't. "The gist of it is that we jumped on salt early as a potential cause of hypertension because it seemed like an obvious cause," Taubes says. "The effort alone becomes reason to believe it. There's so much smoke, there must be fire."

If there's so little science actually supporting the fact that salt is detrimental to our collective health, it stands to reason that more people would be pointing this out. After all, almost everyone seems to be attempting to curb his sodium intake (or at least, pretending to attempt to curb it). But Taubes points out, "There's not a lot of pleasure to be taken by spending a majority of your life trying to prove that someone else's science is bad."

Even so, after Taubes' piece in the Times, Jacobson sent a letter to the editors on behalf of himself and seven medical doctors including Dr. Steve Havas, an adjunct professor at Northwestern University's medical school and a former American Medical Association vice president. The six-page letter refutes the Times piece, concluding that it could lead to "more hypertension, heart disease, deaths, misery, and medical costs down the road" if taken seriously.

This is the exact sort of statement Taubes thinks the salt industry needs to defend itself against. After all, it's not as if this is the first time the scientific community has found itself split over a particular foodstuff. In the 1970s, sugar was the major culprit. So the sugar industry attempted to shift the blame. "One of other offenses that the sugar industry threw up in the 70s ... was to hire anti-fat people to prove sugar was innocent," Taubes says. "When your livelihood is on the line, you do whatever is necessary."

In this case, The Salt Institute has hired Morton Satin and has reached out to Taubes. It has launched a series of videos featuring Satin as "The Salt Guru." In them, he fights against "misinformation" by offering litanies of facts about salt. The Institute has launched media campaigns defending salt, and Taubes has defended the polemical element in his articles.

"The salt industry has to protect itself," Taubes says. "They were getting hammered by bad science." In the next breath he follows with, "If [The Salt Institute] offered me money to do something, I would turn them down." He's worried about his credibility and, though he denies this, Satin claims he won't answer the Institute's calls. "[Taubes] doesn't want to be connected with our shit," Satin says over lunch. "It's discouraging. [I] end up feeling like I'm the candy man, and he doesn't want anything to do with us."

He lifts a piece of bread, which is appropriately crusted with large crystals of salt. "You're not supposed to put your credibility in the Institute or in a person," Satin says. "You're supposed to put your credibility in the evidence."

But the Institute comes with a reputation, even if it's given and not earned. Havas, the doctor at Northwestern, compares American salt intake's health detriments to a jumbo jet crashing every single day, says "[The interest of] The Salt Institute, you have to recognize, [is] in having salt sales be higher. It's like believing stuff coming out of the cigarette companies. They've got a commercial interest."

When I present this idea, Satin shakes his head as if it pains him. "It's not in our interest for anyone to get sick," Satin says. "The industry takes care of itself." In fact, "Food salt is only about 15 percent of the salt in the salt industry." There's also animal salt, road salt, industrial salt, and medical salt. Satin and Taubes have the same motto: they're not fighting for salt to profit. They're fighting because if salt isn't what's leading so many people to early graves -- something else is. Keeping an eye on salt means keeping an eye off whatever the true culprit might be.

"I would like to see it resolved, even if they say salt is bad for you," Satin says tiredly. "I'd like to just see it resolved."

At 16 months-old, a foster child in South Carolina known as M.C. underwent genital cosmetic surgery. The goal was to refashion M.C.'s "ambiguous" genitals to look feminine, in order to match the child's female gender assignment. M.C., now eight years old, though, identifies as a boy.

His adoptive parents, Mark and Pam Crawford, believe the state was wrong to allow the surgery and that doctors were wrong not to inform those making the decision that the surgery was not medically necessary. A recently-filed lawsuit, brought on behalf of M.C., alleges that doctors "robbed M.C. not only of his healthy genital tissue but also of the opportunity to decide what should happen to his own body."

Doctors have believed for many years, based on little to no evidence, that children require male-typical or female-typical genitals in order to grow up psychologically healthy.

This case is as groundbreaking as claimed by the two groups representing the plaintiff, Advocates for Informed Choice (an intersex legal rights group) and the Southern Poverty Law Center. Never before in U.S. litigation has a child's right to genital integrity been asserted in this fashion, and so the case is likely to cause quite a stir among pediatric groups treating these kinds of children. Unfortunately the case is also causing a host of misunderstandings.

First off, contrary to some news reports and commentaries, M.C. was not born "with both sets of genitals," male and female. As I've explained elsewhere, the only way you could be born with "both sets of genitals" is if you had two bottoms. The clitoris and the penis are homologues -- they are the same organ developmentally -- so you get one or the other, or one in-between organ. Similarly, the labia majora and the scrotum are homologues -- so you get either a set of labia majora, a scrotum, or something in between. But you can't have all the female parts (clitoris, labia majora, etc.) and all the male parts (penis, scrotum, etc.) on one person; even if there were room enough, sexual physiology wouldn't allow it.

What people mean when they say a person "was born with both sets of genitals" is that a child may be born with a phallus that looks a lot like a penis plus a vagina (the tubular organ that goes from the outside of the body towards the uterus, if there is a uterus). This can happen because of hormones, in conditions like congenital adrenal hyperplasia and partial androgen insensitivity syndrome. But to say that gives you "both sets of genitals" is to pretend that somehow all that matters to males is their penises and all that matters to females in their vaginas. In fact, many of us women also care about our clitorises. (For that matter, many men care about their scrotums.)

This then leads to another misunderstanding with M.C.'s case: some folks seem to be commenting as if, had M.C. come to see himself as the female gender he was originally assigned, we would not care that surgeons had removed most of M.C.'s phallus. In other words, we are supposed only to care about the removal of phallic tissue in this case because M.C. is a boy. But in fact, we should very much care about phallic tissue even when it comes in (or off) a female. When Mr. Rogers sang, "Boys are fancy on the outside, girls are fancy on the inside," he was prepping his audience to need Dr. Ruth. All girls are entitled to be fancy --sometimes super fancy -- on the outside, too. Many intersex women who had their clitorises surgically shortened in infancy are legitimately angry about having had tissue (and thus sensation) taken from them.

Because M.C. has rejected the gender assignment given to him, this case is also causing some people to confuse intersex (sex anatomy that is read as being not typical to males or females) with transgender (rejection of the gender assignment given to a person at birth). M.C. is a relatively rare case in involving both intersex and transgender. Far more often, the concerns of intersex and transgender people represent opposite sides of the same coin: intersex people get surgeries they don't want, and transgender people can't get the surgeries they do want. M.C. should certainly be supported in his self-identification as a boy, but one would hope that the courts might understand his rights to have been violated even if he had grown to be a girl.

In that sense, it will be interesting to see whether the courts agree with the plaintiff's lawyers that the 14th Amendment is at play here, and whether they will limit that Amendment's scope to cases where "a boy lost his penis." If, in fact, they understand the case as being an unfair situation in which "a child lost healthy genital tissue for no legitimate medical reason without fully informed consent," then the implications will be much broader, perhaps touching even on routine neonatal male circumcision.

Of course, whether there was a legitimate medical reason will be one issue with which the courts will wrestle. Doctors have believed for many years, based on little to no evidence (and in some cases, faked evidence), that children require male-typical or female-typical genitals, matched to their gender assignments, in order to grow up psychologically healthy. Although the Southern Poverty Law Center's involvement might lead some to believe this case represents a sort of surgical hate crime, in fact, surgeons have performed these types of surgery in the belief they do so in the patients' best interests. They really care about these children.

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But recently -- since M.C. was born -- major medical consensuses have moved away from the assumption that genital-normalizing surgery is required in all cases of intersex. This case is likely to drive surgeons to be even more hesitant to remove healthy genital tissue and healthy gonads from children like M.C. Ideally, the case will also lead more parents like Mark and Pam Crawford to understand that parenting sometimes involves forms of unpredictability that cannot, and even should not, be made to disappear.

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PROBLEM: Making a conscious effort to be happy, according to researchers, is responsible for as much as 40 percent of the variation in how good people actually feel. But trying too hard can backfire: a 2003 study found that when people "try to feel happier" while listening to classical music, they end up feeling worse than if they had just sat and listened.

METHODOLOGY: Researchers at the University of Missouri recruited 167 "generally well-functioning" students and attempted to manipulate their moods. About half of the participants were told to "really focus on trying to feel happier" while listening to music. Some were played the piece used in the 2003 study: Igor Stravinsky's "Rite of Spring," which is characterized as "complex and discordant," and thus kind of a downer. Others were played Aaron Copland's "Rodeo," a more upbeat and generally positive piece. The other half were instructed to "just relax and be yourself" while listening to the music, and explicitly told not to try to improve their mood.

After 12 minutes of listening, the participants were asked to rate their mood on a sliding scale from "very negative" to "very positive," and to indicate, on a scale from one to 15, how much they agreed with positive mood descriptions like "happy," "joyful," and "satisfied."

RESULTS: Participants who listened to the Copland tune while trying their hardest to feel happy finished out the study in a significantly more positive mood. Everyone who listened to Stravinsky, on the other hand, ended up at about the same level, which was also more or less equivalent to the mood of people who listened to Copland without making an effort to feel happy.

IMPLICATIONS: The researchers went into this study with the assumption (based on past experiments) that it is indeed possibly to talk yourself into being happy. Here they showed that context matters in making self-pep-talks effective. For those who don't want life to always feel like a high-energy, major-key Copland tune, however, it's yet to be determined if discordant music can help us become more emotionally complex.

NBC, the number-five television network in the United States, has The Michael J. Fox Show buried in a 9:30 slot this fall, so there's nowhere to go but up. As Richard Lawson pointed out, Fox's newsman role gives the network opportunities to crossover with other NBC properties like the spiraling Today show. Other crossover aspects are clearly biographical. The show stands to do good for a commonly misconceived medical condition, and potentially well.

For almost a decade, the United States has been standing in the way of an idea that could lead to cures for some of the world's most devastating illnesses. The class of maladies is known as neglected diseases, and they almost exclusively affect those in the developing world. The same idea, if realized, might also be used in more affluent nations to goad the pharmaceutical industry into producing critical innovations that the free market has yet to produce - things like new antibiotics, which are likely to be used judiciously, and are unlikely to be wildly profitable.

But the idea, which advocates have outlined as a treaty, and which will have its fate decided next week at the World Health Organization (WHO) where it has languished for years amid bureaucratic tumult, is "good enough to be dangerous," in the words of one person close to the negotiations. It has thus drawn the fierce opposition of those who benefit most from the status quo, the pharmaceutical giants and the nations that claim them.

"It's a precedent. It's a competing paradigm," Jamie Love, 63, the director of Knowledge Ecology International, a progressive group agitating in favor of the idea, told me. "And the Obama administration, instead of wrapping its arms around it and trying to breathe some life into the future so we don't have $200,000 drugs, is killing it."

James Love in Alaska, 1974, and at KEI's D.C. ofifces in 2010 [Dashiell Love]

When I met Love in February at his office in Washington, D.C., he had just returned from Geneva, where the WHO is based, and he planned to be on a return flight shortly. Coach class, he assured me. Love has a boyish face with pale blue eyes and an inscrutable energy about him. The energy, according to those who know him, is nothing new. As a young man, he dropped out of college in Washington and moved to Alaska, where he became a longshoreman and cannery worker and opened two small NGOs. The work drew the attention and support of Ralph Nader, and, in 1980, Love moved to Boston on a fellowship to Harvard's Kennedy School. He added a second Master's degree from Princeton, where he studied with Joseph Stiglitz.

"Part of the problem is that nobody understands what we're talking about," Love told me in his office, a small loft beneath a gabled roof on Connecticut Avenue. "There's really only twenty or thirty of us who understand what we're trying to do with this."

Bill Gates, speaking to the Royal Academy of Engineers in London last March, managed to capture the problem that Love's idea would be leveled against: "Our priorities are tilted by marketplace imperatives," Gates said. "The malaria vaccine, in humanist terms, is the biggest need, but it gets virtually no funding. If you are working on male baldness or the other things you get an order of magnitude more researching funding because of the voice in the marketplace."

This fact -- that research-based pharmaceutical companies focus on the most lucrative products, rather than the most needed -- is particularly damning for the global poor, whose diseases will never be profitable enough to attract the industry. The WHO has recognized 17 such diseases, known as either type III or neglected tropical diseases (NTDs). Almost all of them edge on biblical in both scope and horror.

"The needs are pervasive because these diseases have been so understudied," said Peter Hotez, the founding dean of the National School of Tropical Medicine at Baylor University. "Look at a disease like hook worm infection. Well we now know that single dose mebemindizole doesn't work against Nacator americanus, which is the major hookworm. Why is that? We really don't know," Hotez said. "The WHO I think did us a disservice a few years back when they coined the term 'tool ready' versus 'tool deficient' diseases. All neglected tropical diseases are tool ready, and those same diseases are tool deficient," Hotez said, meaning drugs exist to fight all of the conditions, but many are met by severe resistance and others are poorly adapted for low-resource settings.

The WHO list of NTDs includes Chagas disease, which has a burden of disease five times that of malaria in Latin America, and Dengue fever, which 40 percent of the world's population remains at risk of acquiring. It also includes river blindness, which affects 20 million people in sub-Saharan Africa and leads to infections that itch so severely -- as worms die in the flesh -- that sufferers turn to nails, scalding water, and other violent means to numb the sensation. The existing drug for the disease, Ivermectin, requires six doses over three years to be effective, a regiment that would be difficult to deliver in affluent countries with robust health systems, and is nearly impossible to accomplish in rural Africa.

Neglected diseases, even when coupled with type II diseases, things like malaria and tuberculosis that primarily affect the global poor, receive less than two percent of the $160 billion spent on medical research and development (R&D) each year.

The idea, which has gained the support of a range of academics and economists from around the world, as well as Doctors Without Borders/Médecins Sans Frontières (MSF), Oxfam, Health Action International (HAI), and DNDi, aims to develop new cures for those diseases, and to manufacture the drugs and vaccines at prices affordable to the global poor.

It hinges on the incredible discrepancy between the cost of developing a drug or vaccine -- an expensive and risky enterprise -- and the actual cost of manufacturing a drug, which is often astoundingly cheap.

"Once you sort of turn that corner and you realize that intellectual property rights are really man made policies ... then it just opens your mind up."

"So there is the idea that there are gaps in research," Love told me in February, "and the second idea is that linking the cost of R&D to the price of the drug through the grant of a monopoly is inherently problematic, and the problems are diverse." The existing system relies on the promise of drug sales under patent to incentivize innovation -- an effective monopoly on production, typically lasting more than a decade. That system leads drug makers to set prices at whatever level they think the market can bear, regardless of the cost of manufacture or even the cost of development. The point was driven home last year, when Memorial Sloan-Kettering Cancer Center, in New York, refused a new colorectal cancer drug priced at over $130,000 per year. The drug maker, Sanofi, promptly cut the price in half.

The point is also particularly egregious in the case of lifesaving antiretroviral drugs (ARVs) for those suffering from HIV/AIDS. The fight to make those medications accessible to the global poor was another battle in which Jamie Love was intimately involved.

"If you're looking for sort of the intellectual driver for the idea, it's undoubtedly Jamie," said Robert Weissman, who now runs the storied advocacy group Public Citizen. Weissman was alongside Love in 2001 when Love made the most important play of his career: He asked Yusef Hamied, a chemist and the director of the Indian pharmaceutical manufacturer Cipla, for a rock-bottom price to produce a cocktail of ARVs. At the time, the pill regiments were selling for over $10,000 per year under patent-protected prices. Hamied said that Cipla could produce the drugs for a dollar a day per person.

"Jamie got that it had to be a dollar a day, that it wasn't $400 a year, that the price of a dollar a day would move the whole debate," Weissman said.

Hamied's offer made headlines around the world. It set a floor in the market and lead the prices for name brand drugs to fall precipitously.

"Before all this, we had a meeting with the U.S. Trade Representative and we were talking about how keeping these prices and patents in place was costing millions and millions of lives in Africa," Weissman recalled, referring to Love and himself. "And the Trade Rep. said to us -- I'll never forget this -- 'I don't work for millions of people in Africa.'"

The $10,000 that pharmaceutical companies were willing to charge for ARVs -- and that their US government was willing to defend as reasonable at the WTO -- was egregious in part because the drugs can be produced so cheaply, as Cipla proved. But the prices were also impossible to justify because the development cost for the first generation of ARVs was close to nothing for private industry. The drugs, known as dideoxynucleotides, were almost all developed in the 1960s at Wayne State University under National Institutes for Health (NIH) grants to research cancer therapies. And, in the 1980s, it was again NIH researchers who thought to test the compounds against the AIDS virus.

Love traces the genesis of the idea to a similar situation, this one involving cancer drugs. In the early 1990's, Love began investigating Taxol for Senator Ron Wyden of Oregon. The drug is used to treat breast and ovarian cancer, and was developed by the NIH and produced for less than a dollar per milligram for clinical trials. Bristol-Meyers Squibb, once effectively given the patent, sold the drug for $4.87 per milligram, roughly moving the price from $100 per dose to $850 per dose.

"I do a lot of historical research on the things I do. I like to go back and look at earlier disputes and case studies on particular drugs or legislation or just try to figure out how we got where we are," Love said. One of the cases Love climbed into involved Cisplatin, the drug that saved Lance Armstrong's life. The drug was also developed within NIH and effectively handed to Bristol-Meyers.

"In the old days, the government would grant five year monopolies on government-funded inventions that were done by NIH or universities or something, but if you wanted more than five years, you could ask the government to extend the monopoly," Love said.

In the Cisplatin case, when Bristol-Meyers wanted to extend the patent, the government negotiated a 30 percent drop in the drug's price, and for Bristol-Meyers to contribute $40 million in grants to research of the NIH's choosing.

The case fundamentally changed how Love thought about intellectual property.

"Once you sort of turn that corner and you realize that intellectual property rights are really man made policies and they're designed to do something, and there's other ways to induce that same thing that can compete those ideas, then it just opens your mind up."

Love's idea suggests the use of cash prizes -- rather than patents -- to incentivize research; say, $2 billion for an effective therapeutic drug for Chagas disease. A cure, once developed, proven, and awarded a prize, would then exist as open-access intellectual property, with manufacturers around the world competing to produce the drug in the most cost effective manner. Implementing the idea, Love said, "is effectively leveraging the power of the free market twice, once to produce the thing you want and then again to manufacture it as economically as possible." The concept is known as delinking.

The prospect also has interesting second-order effects. "The numbers have to be big enough," Love said. "You can't replace monopolies that involve billions of dollars with prizes that involve thousands of dollars, but it's financially easy to do that because the savings from delinking are so big." Because drug makers are no longer dependent on sales, delinking would relieve huge strains on budgets beyond research and development; the industry only spends about 16 cents on the dollar for R&D. Massive ad campaigns, for instance, would become obsolete in such a system, because the innovator's profits are no longer tethered to sales, the same for gifts and meals to woo physicians.

Love's concept of delinking is outlined in a proposal for an R&D treaty, which remains in limbo at the WHO in Geneva. It will have its fate decided in late May, at the annual World Health Assembly (WHA), the democratic forum of members states that governs the WHO.

The proposal adds a second, equally powerful idea to Love's, one inspired by open-source software models.

A post-doctoral student in Edinburgh, Scotland, who had been tracking the project's open lab books online, produced a compound that Todd's own lab couldn't figure out how to synthesize.

Historically, basic research and drug innovation has been done in silos, with little communication across companies and labs. That isolation guarantees that researchers repeat failures that have already occurred elsewhere, a problem that becomes glaring in the case of neglected diseases, where the total research investment is a fraction of what it is for profitable diseases. The lack of information sharing also guarantees that some labs remain stymied by problems that researchers in other places may know how to solve.

"The existing funding structures are competitive, national grant based," said John Wilbanks, who works at the non-profit Sage Bionetworks and is a fellow at the Kauffman Foundation. "So, for most people, the rational economic decision is not to share, not to collaborate, in order to obtain additional taxpayer grants to continue the research and to keep employment."

Wilbanks's background is largely in tech, and the group he works for is building a platform for computational biology akin to GitHub, a system that lets computer programmers track their contributions to open-source code.

"The fear is that by spending my time working on your project, for which I don't have a system to get credit that the existing system recognizes, I will be less competitive over time than someone who participates in the traditional system of information hoarding and publication," Wilbanks said. "We're trying to fix that problem through openness, similar to the R&D treaty."

To combat the problem, the R&D treaty would create an observatory, an open platform for researchers in disparate corners of the globe to pool data and coordinate their work. Grants given to fund their studies would come with provisions requiring that the research exist on that public, cloud-based observatory.

Such an open system also means that help can come from unexpected places. Mathew Todd, a chemistry professor and researcher in Sydney, is currently running an open-source malaria project. He explained how a post-doctoral student in Edinburgh, Scotland, who had been tracking the project's open lab books online, produced a compound that his own lab couldn't figure out how to synthesize.

"The chemistry wasn't working out, and we were being open with this," Todd said. "And he looked at it and said, 'Well I can make that.' And so he went off and made it, and we were interacting with him by Twitter, sort of following his progress and he was posting his experimental data to our lab books online, and he made it."

"It's that kind of example where you think, 'Well if everything's open and it's clear what needs to be done and anybody can chip in, then that means you're going to attract the expertise you need without actually knowing who those people are," Todd said.

Todd told me he's put forward a proposal to host a panel focused on the future of intellectual property and drug development at the February meeting of the American Association for the Advancements of the Sciences. "I think the time is right to have that discussion about whether the patents are working, and whether they're necessary for drug discovery," Todd said. "I want to hear from people on both sides. I think we just have to have that conversation."

***

Last November, the Obama administration made its most strident effort to date to stall the idea. Because successive U.S. administrations have stonewalled the process so effectively, negotiations on actual language for an R&D treaty have never begun. That hasn't prevented the intellectual scaffolding beneath the idea from developing, though.

To fund the system -- research grants and an observatory to produce and coordinate the foundational science, and prizes to incentivize the pharmaceutical industry to spring off of that basic research -- the treaty would commit member states to spending 0.01 percent of GDP on neglected diseases each year. The U.S. already spends at that level, and would have no further financial obligations. No other country comes close.

Nonetheless, the idea of binding financial commitments by way of treaty has been a centerpiece of US opposition.

"They are using a process argument, saying we are against the form, but in fact what they are opposing is the content of the negotiations," said Judit Rius, the U.S. manager of Doctors Without Borders/Médecins Sans Frontières Essential Medicines Campaign. "When governments get serious about an issue, they agree to binding global norms and they agree to be held accountable. And that's what we want," Rius said. "What the U.S. is really opposing is a conversation about the how this funding should be spent. They are protecting the current business model, the status quo innovation models."

At the November meeting, the U.S. hammered through a resolution effectively neutering the idea in a late night vote. It was held four hours after simultaneous translation of the debate ceased, with only 25 of the original 194 member state representatives remaining in the negotiating hall.

"At least with the Bush guys you could have a conversation with them about this kind of stuff."

"I've never seen something like that happen in an international negotiation," Carlos Correa, the representative from Argentina, told me. "The meeting should have been terminated, because clearly some of the delegations were not able to follow the debate. In these cases, the governments generally say, 'Well this is not possible to go on, so we'll finish and inform the assembly there was no conclusion.'"

According to delegates present at the meeting, which took place behind closed doors, it was clear from the outset that the U.S. had no intention of negotiating in good faith. "The U.S. was delaying the issue and opposing it totally," one negotiator said. "Very little real negotiation, they were very radical. They were even insisting on some ideas that were not totally correct."

The resolution that emerged from the November session will be taken up in late May, at the annual meeting of the World Health Assembly. If the measure is adopted, further consideration of the idea will be pushed until at least 2016. The resolution also includes the unusual provision of being sealed, barring any further discussion at the WHA.

The document also suggests the creation of a pilot program and an observatory to monitor research, but does so without allocating funds, and with such vague language as to render the resolution moot.

The U.S. has promised to bury the resolution altogether if other countries try to reopen negotiations in May.

"We saw in January that the U.S. negotiator said publically what we had been told he was saying in November behind closed doors, which is that, 'If you change even one comma, we'll kill it altogether," Rius said.

Early in the November meeting, the U.S. moved to quiet a Colombian negotiator. Nils Daulaire, the lead U.S. representative in Geneva, has made a habit of using backchannels to sideline other delegates voicing positions he does not share.

The negotiator in question declined several requests for comment for this piece.

"She was very well prepared, and she was taking the floor several times during the first day," another delegate told me. "And I saw that the U.S. delegation was a little bit nervous, because usually Colombia -- in the last years -- they never take the floor on these issues and they always support the U.S. position. Around four o'clock on the afternoon of the first day, she was called outside the room, and one hour after she came back to the room and she never took the floor again in the next two and a half days. She stayed until two o'clock in the morning the last day, but she never took the floor again."

Nils Daulaire [Wikimedia Commons]

In March, when I spoke with Daulaire, an assistant secretary for global affairs at the Department of Health and Human Services (HHS), I asked what had provoked his complaint. His response took the kind of emphatic tone that conveys both displeasure and the desire to say a great deal more: "I'm not familiar with any formal diplomatic complaint against the Colombian representative," he said. "I don't know where that comes from." Daulaire struck the same tone later in our conversation, when I asked at what level within the Obama administration the U.S. position had been crafted. "I do not discuss internal administration processes," he said.

Daulaire has a round nose and soft chestnut hair with a beard and glasses, lending the overall affect of a college dean. He is -- according to his official biography -- the speaker of seven languages, and a graduate of both Harvard College and Harvard Medical School. He is known as exceedingly ambitious, and is rumored to have put himself forward to replace Eric Goosby as U.S. AIDS Coordinator. The position is one of the most vaulted in the field of global health.

"He is very trenchant in his views, and I'm not sure whether that is because he's hearing that from the industry or whether he's hearing that from the administration, but he's looking at where the political wind is going," one source with intimate knowledge of the debate said.

Daulaire's efforts to derail the November meeting started more than a month before he and his staff arrived in Geneva. His office sent representatives to a WHO regional meeting in Angola to discourage support for the treaty amongst African states, and Daulaire himself made bilateral calls to number of negotiators and ministers of health. On the calls, he asked whether the officials were prepared, at the November meeting, to commit their governments to financing the treaty. None of the officials Daulaire called have the power to make such a commitment, nor does Daulaire himself. Moreover, the treaty he asked them to commit to financing has not yet been written, largely because of Daulaire's own intransigence.

"Nils says, 'The U.S. is the biggest funder of R&D, and we don't think anyone else is going to put up the money,'" one civil society member said. "But the bizarre thing about that is when developing countries said, 'We will put some money up, whether we will reach sort of figure that the experts came up with, we might not but we're prepared to do it incrementally,' he just said, 'No I don't believe you, let's just take the whole thing off the table.' It's very strange to me that the U.S., being the largest funder, is actively undermining putting pressure on other countries to step up to the plate."

"I was sort of looking forward to working with the guy," Jamie Love said of Daulaire. "Everybody knew that he was close to the industry, but that's not necessarily a bad thing. But he really changed when he got the job [at HHS]. At least with the Bush guys you could have a conversation with them about this kind of stuff."

Daulaire's deputy at HHS, Holly Wong, previously worked for the drug industry's main lobby group, PhRMA, and as director of public affairs at Schering-Plough Pharmaceuticals. The company was acquired by Merck in 2009.

Before his appointment to HHS, Daulaire ran a nonprofit called the Global Health Council (GHC) for close to a decade. The group was based in White River Junction, Vermont, where Daulaire lived. The organization had an annual budget of close to $7 million, although it didn't actually provide any health services. After Daulaire left, the organization was handed off to Jeff Sturchio, a former Vice President at Merck. Sturchio drove the group into the ground in less than three years. "It was really a lobby group," one observer said, speaking of the GHC. "At the World Health Assembly meetings they would rent huge halls in the Intercontinental with very expensive food and drinks," another recalled.

The GHC's main function appears to have been providing briefings for incoming members of Congress and new presidential administrations. "I don't think anyone has filled that role," Jonathan Quick, who is trying to revive the GHC, told me. Quick spent eight years working at the WHO as the Director of Essential Drugs and Medicines Policy.

Quick and several others in the global health space pushed back against questions about GHC's lobbying, arguing that the organization served as a kind of hub for advocates of greater U.S. involvement in global health. I asked Quick about his thoughts on the U.S. opposition to the R&D treaty, and whether he, having worked at the WHO, had misgivings about U.S. negotiators having such strong ties to the pharmaceutical industry.

"The U.S. is interesting, having seen it from the WHO side," Quick said. "Most countries when they come to the World Health Assembly lead with their health policies. And they bring to the WHA the values and policies they have at home. There are a few countries where that's difficult, because there are such strong commercial interests that there's a tension. That's always been a very difficult challenge for people representing the U.S. in the international health sphere."

The battle for the idea has peaked at a time when the pharmaceutical industry finds itself under extraordinary duress. Despite significant advances in drug development technology, the number of new drugs per billion dollars spent on R&D has halved every decade since 1950. And the industry, over the course of the current decade, is watching many of its most profitable drugs come off of patent. In November 2011, Pfizer lost exclusivity on the most lucrative drug ever made, Lipitor. The statin grossed more than $130 billion for the company. The patent on GlaxSmithKline's Advair also went dry in 2011. The drug made $7.8 billion in 2009 alone. Eli Lilly, which has been hit hardest by the patent cliff, lost its patent on Zyprexa in 2011. The antipsychotic made them close to $5 billion per year. The firm is projected to lose half of its total sales across the decade.

"We're public companies, and sometimes the CEOs are kind of stuck," said Derek Lowe, a chemist who has worked in the industry since 1989. "Every one of our drugs is a wasting asset, they're all wasting away in front of you." Lowe also runs a blog about the industry, called In the Pipeline. The site manages to couple reverence for the complexity of drug development with sharp critiques of the industry. Last year, for instance, when it became clear that the industry's largest players had put unprecedented sums into buybacks of their own stock in 2011 -- a total of $76 billion across the largest 15 companies, which is $14 billion more than the entire NIH budget -- Lowe wrote a long post. "It gets me because companies are in effect saying, 'you know what? We are better off spending this money to make the shareholders happy than spending it doing what we are allegedly supposed to be doing, which is discovering drugs,'" Lowe said.

Bill Gates at the 2005 World Health Assembly [Anja Niedringhaus/AP]

I asked Lowe about the state of the industry. "It's tough right now because the drug industry is at this adolescent stage, we're at that awkward stage. We've gone through a lot of the easy targets, and there's a lot of real big opportunities out there, but the reason they're big opportunities is because nobody's been able to do anything with them," Lowe said. "We keep spending tons of money on these things and missing."

Jack Scannell is one of the people trying to usher in a new era of drug discovery. "In very broad terms, I'm pretty pessimistic about the industry," Scannell said. "I don't think at a sort of aggregate, macro level classical R&D as it's been done for the last forty or fifty years has a particularly bright future." Scannell is British, and dropped out of medical school in favor of a PhD in computational neuroscience from Newcastle University. He met Malcolm Young there, and the pair worked a together on systems for analyzing networks, specifically for mapping neuronal activity.

Scannell worked as a consultant in the drug industry and then as an equity analyst, but quit last year to team up with Young once more at small biotech firm Scannell described as "heretical." The company is called e-Therapeutics, and its approaching drug design via the pair's background in networks. "Go back to how the drug industry says it discovers drugs. It looks for individual targets and then it optimizes drugs for high affinity binding on that target," Scannell said. The strategy, to Scannell's and Young's eyes, fails to take into account the complexity of biological systems.

"If you look at the structure of protein-protein interaction networks in cells, or the metabolic networks, these have been designed by evolution to be robust. You've got feedback loops, you've got parallel pathways, you've got redundancies. And what that says is, if you start your search process looking for an individual molecular component you want to perturb to influence a disease, probably evolution has designed your cell that, if you perturb that component, nothing is going to happen." Given the approach, Scannell said, "Maybe it shouldn't be surprising that 95 percent of drugs going into clinical trials fail."

"Historically, you can make a very strong case that the way drugs were discovered when it was cheap and easy -- you can't do all this now because of the regulators, but some of this you might be able to do -- was essentially through broad phenotypic screening, very often in man," Scannell said. "Drugs were regarded as potential tools that might do something useful, and then people essentially searched for uses for the tool. And today we do the exact opposite. Which is we say, we want something that cures Alzheimer's disease, let's design something that cures Alzheimer's disease, and frankly that just doesn't work."

I asked Derek Lowe, the chemist and blogger, for his thoughts on the principle of delinking R&D from the actual manufacture of drugs, and why he thought the industry, facing such a daunting outlook, would reject an idea that could turn fallow fields of research on neglected diseases into profitable ones. "I really think it could be viable," he said. "I would like to see it given a real trial, and neglected diseases might be the place to do it. As it is, we really already kind of have a prize model in the developed countries, market exclusivity. But, at the same time, you could look at it and it will say, 'You will only make this amount of money and not one penny more by curing this tropical disease.' Their fear probably is that if that model works great, then we'll move on to all the other diseases."

***

In January, at the final WHO meeting before the World Health Assembly in late May, a number of countries began agitating over the circumstances of the November meeting. China, in particularly, argued loudly for the democratic ideals of the WHO, and every state's right to be heard. The meeting grew so contentious that the Director-General, Margaret Chan, began to sing "Getting to Know You," from the musical The King and I to try to calm the negotiators.

The tactic failed, and Nils Daulaire made it clear that the U.S. would kill what remained of the idea if any country moved to reopen negotiations at the World Health Assembly.

The meeting grew so contentious that the Director-General, Margaret Chan, began to sing "Getting to Know You" to try to calm the negotiators.

I spoke with Daulaire in February, and asked him to clarify the U.S. position. "I'm not sure that I understand that the treaty is the sole way or the preferred way to get to the aim that we have, which is to make more products available at affordable or no cost to the people who need it most," Daulaire said. "I think the idea of the treaty is ill-considered, and is not going to lead us in the direction we want to go."

Daulaire argued that the process of drafting a treaty is long and expensive, and that it would be better to model something on the Global Fund to Fight AIDS, Tuberculosis and Malaria or the GAVI alliance. "If we had started that process [of designing GAVI ] in 2000 by proposing that we would have a binding international treaty with required contributions, etc. we would still be negotiating the terms of that treaty," Daulaire said. "I just consider the amount of time we're spending debating what is essentially a dead idea to be not very well spent. It's simply a dumb idea."

Ideas, though, are powerful things, and last September, as it became clear that the developing world planned to fight for the treaty at the November meeting, Daulaire's office put out a quiet call for competing ideas. The request came via email from the Institute of Medicine, a wing of the National Academy of Science. The message was leaked to the blog Don't Trade Our Lives Away .

"HHS was hoping that an independent body such as IOM could suggest alternative ideas for consideration at the WHO," the email reads. "Given that these ideas need to be developed before the WHO Executive Board meeting in January, there is insufficient time (and insufficient money) to employ the usual IOM consensus committee study process." It concludes, "The IOM is committed to being of service to the country and this is one of the times when we can pull together and make a special contribution."

Daulaire arrived at the November meeting in Geneva without a competing idea to put forward.

Daulaire's other suggestion has been criticized. "You cannot think that the R&D mess that we are currently in is going to be solved with the GAVI model," Judit Rius of MSF said. "GAVI is basically about taking vaccines that have been produced by Pfizer, GSK, and by other northern pharmaceutical companies, and giving those companies huge subsidies so that they will give time-limited price discounts and accelerate delivery to the developing world."

This R&D void was also acknowledged by John-Arne Røttingen, the Norwegian doctor who led the second expert working group for the WHO, known as the Consultative Expert Working Group (CEWG). The report of a first expert group was thrown out for issues of political malfeasance -- it became clear that proposals from developing countries were excluded from consideration, and that experts met with pharmaceutical industry representatives but not civil society members.

I spoke with Røttingen by phone, and asked if he thought the ideas within the R&D treaty could be implemented through some kind of global partnership. "To actually get agreement on something like this with wide member state involvement, you need some sort of platform to negotiate," he said, implying a treaty negotiation would provide such a forum. "GAVI and the Global Fund are first and foremost mechanisms for procurement for commodities that already exist. The R&D landscape is completely different. In addition to agreeing on financing and doing collective action here, you also need to agree on some principles and norms on how to structure the R&D system. That's a lot more complicated than just buying commodities in a market."

I first learned about the R&D treaty in December, in a speech Røttingen gave at conference at Mt. Sinai Medical School, in New York. In his talk, he specifically called on the Gates Foundation to take a position on the matter. The Foundation is the one of the WHO's largest funders, and its second largest funder of researcher for neglected diseases -- only the U.S. government contributes more each year.

"The Gates Foundation has unfortunately been very absent in the process," Røttingen said when we spoke. "They have not been willing to engage I would say, and have not come forward with any constructive ideas on how they could be a part of a more concerted action. They seem to be satisfied with the status quo where governments are in general not contributing their fair share to this area of R&D."

Their absence has been noted by others. "I think it's very interesting that Gates is not commentating on this," one longtime observer said. "He has been asked about it, and he either claims to not to know anything about it or says, 'Oh that might be interesting, we have to look into it.' But they are singularly failing to publicly engage in this despite Gates acknowledging the lack of funding. And I think that's a sign in itself."

The Foundation did not respond to multiple requests for comment for this piece.

I spoke with Jamie Love again in March as the WHA meeting approached. He was in Geneva once more, this time working to expand copyright exceptions for products that benefit the blind. I asked him for his thoughts on whether the idea could be brought to life through some agreement other than a treaty.

"You can argue about whether or not it should be through treaty or some other legal instrument, but that's a separate issue of whether the commitments should have a binding nature," Love said. "And if you look at what takes place at GAVI or these other PDPs or the Global fund, they've struggled to keep their funding levels up." He added by email: "It depends a lot on what you think you are doing -- creating a global system of finance, or just passing the hat for some odd donations."

I also asked Love about Gates's role in the process.

"Frankly, it's our perception that they're really, in their own channels, in opposition to it," Love said. "We'd like to be able to work with them once in a while, not always be the on the other side of the street," he added. "Nobody's really eager to make enemies of the biggest philanthropist there ever was, right? But we've kind of done it I guess, because you know sometimes you just gotta do what you gotta do. You can't ignore some issues, so we step up, which we often do when other people are looking for cover."

Love and others point to Gates's complicated history with Microsoft and his departure from Harvard as an undergraduate as coloring his view on the need for strong intellectual property law.

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"He slowly, as Foundation and as a philanthropist, is being drawn into more open-source policies," Love said. "If you look at the licensing he does on his own government-funded research, he has experienced a little bit of frustration when he doesn't get sufficient openness in the research he's funded himself, so he's begin to put things that much very much like open-source provisions in his own licenses," Love said. "That has been progress, and people have noticed that. It used to be that if you applied to the program to fund libraries -- I know somebody that did this -- she was told you had to eliminate the words 'open-source' because they couldn't fund anything that had even the words."

In the current debate, documents submitted to WHO working groups attacking the idea were largely authored by individuals and groups that receive support from Gates.

The Gates Foundation was also the largest funder of Nils Dualaire's Global Health Council. They donated more than $30 million.

On May 19th, Jamie Love will again fly to Geneva, this time for the 66th World Health Assembly. It remains unclear whether the developing world states will challenge Nils Daulaire and his promise to kill what remains of the R&D treaty.

PROBLEM: "Marijuana use is associated with an acute increase in caloric intake," goes the clinical jargon for popular lore. Still despite eating more while high (by some measures, over 600 extra calories per day), marijuana users' extra intake doesn't seem to be reflected in increased BMI. Indeed, studies have identified a reduced prevalence of obesity in the pot smoking community.

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METHODOLOGY: Researchers at the University of Nebraska, the Harvard School of Public Health, and Beth Israel Deaconess Medical Center analyzed data from a nationally representative sample of over 4,600 adults. About 12 percent of the participants self-identified as current marijuana users, and another 42 percent reported having used the drug in the past. The participants were tested for various measures of blood sugar control: their fasting insulin and glucose levels; insulin resistance; cholesterol levels; and waist circumference.

RESULTS: Current marijuana users had significantly smaller waist circumference than participants who had never used marijuana, even after adjusting for factors like age, sex, tobacco and alcohol use, and physical activity levels. They also had higher levels of HDL ("good cholesterol"). The most significant differences between those who smoked marijuana and those who never or no longer did was that current smokers' insulin levels were reduced by 16 percent and their insulin resistance (a condition in which the body has trouble absorbing glucose from the bloodstream) was reduced by 17 percent.

People who had previously used marijuana, but not in the past thirty days, tended to have similar outcomes, but to a much lesser degree. In addition, none of these measures were impacted by how much marijuana people reported smoking.

IMPLICATIONS: Although they're not sure exactly how it happens, write the authors, these findings suggest that marijuana somehow works to improve insulin control, regulating body weight and perhaps explaining why marijuana users have a lower incidence of diabetes. Adding to the big questions -- "can weed can treat obesity?" and "marijuana makes you skinny?!" -- is the possibility that marijuana might be useful in helping people to manage their blood sugar.

Here are the responses to that question graphed over the last 18 years:

I don't think there should be two green lines on one chart. I just, don't think that's the way charts are meant to be. 

Despite a majority of Americans in favor, gay marriage is still only legal in 12 states, Minnesota having become the twelfth yesterday. The same people surveyed drastically underestimated the national picture, though: they guessed that 30 percent of Americans, not 53, are in favor. 

With the Supreme Court poised to rule on the Defense of Marriage Act, lest they end up on the wrong green line of history, justices might do well to consider that another 18 years at this rate will see approval for same-sex marriage at 104 percent.

Most of us know what it's like to stay in a job or a relationship after it's stopped being satisfying, or to take on a project that's too big and be reluctant to admit it. CEOs have been known to allocate manpower and money to projects long after it becomes clear that they are failing. Think of JP Morgan's "London Whale" Bruno Iksil, who doubled down on a losing bet rather than admit his losses and ultimately cost the bank over six billion dollars. Similarly there was John Edwards, who couldn't bring himself to end his losing bid for the presidency even after his mistress became pregnant. 

The costs to a person who does not know when to quit can be enormous. In economics it's known as sunk cost fallacy, though the costs are more than financial. While we recognize the fallacy almost immediately in others, it's harder to see in ourselves. Why?

There are several powerful, largely unconscious psychological forces at work. We may throw good money after bad or waste time in a dead-end relationship because we haven't come up with an alternative; or because we don't want to admit to our friends and family, or to ourselves, that we were wrong. But the most likely culprit is this innate, overwhelming aversion to sunk costs.

Once you've realized that you probably won't succeed, or that you are unhappy with the results, it shouldn't matter how much time and effort you've already put into something.

Sunk costs are the investments that you've put into something that you can't get back out. They are the years you spent training for a profession you hate, or waiting for your commitment-phobic boyfriend to propose. They are the thousands of dollars you spent on redecorating your living room, only to find that you hate living in it. Once you've realized that you probably won't succeed, or that you are unhappy with the results, it shouldn't matter how much time and effort you've already put into something. If your job or your boyfriend have taken up some of the best years of your life, it doesn't make sense to let them use up the years you've got left. An ugly living room is an ugly living room, no matter how much money you spent making it so.

As studies by behavioral economists like Daniel Kahnemen and Dan Ariely show, people are generally loss-averse. Putting in a lot, only to end up with nothing to show for it, is just too awful for most of us to seriously consider. The problem is one of focus. We worry far too much about what we'll lose if we just move on, instead of focusing on the costs of not moving on: more wasted time and effort, more unhappiness, and more missed opportunities.

Recent research by Northwestern University psychologists Daniel Molden and Chin Ming Hui demonstrates an effective way to be sure you are making the best decisions when things go awry: focus on what you have to gain by moving on, rather than what you have to lose. When people think about goals in terms of potential gain, that's a "promotion focus," which makes them more comfortable making mistakes and accepting losses. When people adopt a "prevention focus," they think about goals in terms of what they could lose if they don't succeed, so they become more sensitive to sunk costs. This is the focus people usually adopt, if unconsciously, when deciding whether or not to walk away. It usually tells us not to walk away, even when we should.

In one of their studies, Molden and Hui put participants into either a promotion or prevention focus (by asking them to write about their goals in terms of either gains or losses, respectively). Next, each participant was told to imagine that he or she was CEO of an aviation company that had committed $10 million to developing a plane that can't be detected by radar. With the project near completion and $9 million already spent, a rival company announces the availability of their own radar-blank plane, which is both superior in performance and lower in cost. The question put to CEOs was simple: do you invest the remaining $1 million and finish your company's (inferior, more expensive, and of course less marketable) plane, or cut your losses and move on?

Molden and Hui found that participants with a prevention focus stayed the course and invested the remaining $1 million roughly 80 percent of the time. The odds of making that mistake were significantly reduced by adopting a promotion focus: Those people invested the remaining $1 million less than 60 percent of the time.

When we see our goals in terms of what we can gain, rather than what we might lose, we are more likely to see a doomed endeavor for what it is.

Suddenly, it seems, everyone is singing the praises of oocyte cryopreservation -- or what most of us call egg freezing -- as the latest cure for a woman's declining fertility. But egg freezing isn't quite the panacea the media would have you believe, and it turns out, all this coverage may be pushing an individualized solution to a deeper systemic problem.

Take Sarah Elizabeth Richard's recent Wall Street Journal article, "Why I Froze My Eggs (And You Should Too)." Never mind that Richards, author of a new book, Motherhood, Rescheduled, hasn't yet used any of the 70 eggs she's banked to try to have a biological baby. She still firmly believes that the greatest gender equalizer for women is the $50,000 she spent on freezing her eggs, for what she calls the psychological relief of having baby insurance -- not career conscious movements like "leaning in," or more family flexible policies like telecommuting and increased maternity leave.

Richards firmly believes that the greatest gender equalizer for women is the $50,000 she spent on freezing her eggs.

"There is no question that the media is hooked on social egg freezing," said Diane Tober, a medical anthropologist and associate director of the Center for Genetics and Society in Berkley. It makes a great story, explained Tober, because they're framing it through a "feminist lens": that egg freezing is going to be "the big game changer" for women who want to have it all and break through their biological barriers.

But the real game changer for professional women, according to Tober, is a level playing field in the workplace -- to become a society that supports flexible work environments and family leave policies, and provides better, quality childcare -- so women actually can have children in their peak fertility years. Unfortunately though, for the media, this lacks the appealing personal narrative of egg freezing. At a friend's baby shower for example (as Richards describes her own emotional journey), it's certainly more comforting to know that your eggs are "safely" frozen away so you can have your baby when you're ready, than to argue that American companies should institute longer maternity leaves and more flexible work arrangements.

"A lot of women, especially affluent women, are perpetuating the myth in the media and telling younger women, if you freeze your eggs, you won't have the pressure of finding the right partner," Tober said. But while they're framing the issue as an extension of choice, the truth is, at $7,000 to $10,000 a round, plus storage fees, only a fraction of adult women would ever have this choice (even if, one day, insurance companies or employers picked up part of the tab).

The rest of the female population, meanwhile, remains stuck in a work place that still doesn't adequately support families and mothers -- a public dialogue that can easily be lost when the media is telling women how easy it can be if we all just freeze our eggs. And then what's going to happen to these women at 45 when they try to continue their career and raise a newborn? Nothing, materially, will have changed since they were 36, unless they're all planning on a corner office with an adjacent nursery, like Marissa Meyer built, to accommodate their babies and nannies.

Calls for a society that supports flexible work environments and family leave policies lack the appealing personal narrative of egg freezing.

At the same time, there's also the potential for an odd, egg freezing dichotomy and wealth divide, between the women who can afford to freeze their eggs to pursue their careers, and the women in their twenties who may soon be able to sell their eggs for medical research. A new bill under consideration in the California legislature and sponsored by the American Society for Reproductive Medicine, AB 926, would allow researchers to pay women cash for their eggs, overturning the existing National Academy of Sciences guidelines. Proponents of AB 926 argue that the bill promotes social equality by offering "fair compensation" to women and "treat[ing] them equally to other research subjects."

Tober believes that the media is missing the other half of the egg freezing story -- that women who sell their eggs aren't like traditional subjects in clinical trials. Researchers aren't studying their reactions to experimental drugs or procedures. They're seeking a woman's raw material for scientific work, eggs that (unlike sperm donation) require high doses of hormone shots and a medical procedure that can result in health complications to harvest. So, while you have privileged, professional women electively freezing their eggs on one end of the spectrum, AB 926 creates a real risk -- that low-income women and college students under financial pressure will be enticed to sell their eggs for science -- on the other.

"Egg freezing is seen as this big revolution now, like the Pill was for reproductive rights, women's health, and family planning in the 1960s," said Dr. Frederick Licciardi, a fertility expert and OB/GYN at NYU, who says about 20 percent of his patients now request oocyte cryopreservation, in large part, he believes, because of all the positive press. But egg freezing, he reminds patients, isn't like the birth control pill yet (in terms of cost, relative ease, or outcome), and women need to understand that while it may feel empowering to freeze their eggs, it's far from a foolproof method to optimize career success and family planning.

"I think the media is fascinated with this," Licciardi explained, "because as many great steps as we have made in our society, this is first method of female empowerment that feels really big and new in a long time."

Success rates after age 37 are as low as 50 percent, and the cost per live birth is as high as $74,564 by age 40.

But a woman's egg is only one part of the fertility equation. Dr. Irene Su, a reproductive endocrinologist and clinical researcher the University of California, San Diego, works primarily with breast cancer survivors and patients interested in medical freezing. "No matter how old the woman, whether they've had cancer or not," said Dr. Su, "the chances of success of egg freezing and implementation and ultimately a viable pregnancy are about the overall health of the mother. It's a bigger picture than just when and if you froze your eggs." Regardless of the age of a woman's eggs, those who get pregnant later in life have a higher risk of high blood pressure, diabetes, pelvic inflammation, placenta previa, miscarriage, and early delivery because of preeclampsia.

The media is also ignoring the very real issue of how cost-effective egg freezing actually is for women in their mid to late thirties (assuming they want to thaw their eggs after age 40) -- and how much each year makes a difference, much like it does for natural fertility rates, where a woman's chances of becoming pregnant decrease by 15 percent annually after age 35.

Dr. Nicole Noyes, co-director of the NYU Fertility Center and professor at the NYU School of Medicine, studied 900 women, asking: is it more cost-effective to freeze your eggs before you're 40, than to arrive at a fertility clinic at 40 to freeze your eggs or try in vitro fertilization for the first time? Noyes and her research team constructed a model, presented as an abstract in the journal Fertility and Sterility, to determine whether egg freezing is a cost-effective method of treating age-related infertility, as measured by live birth success rates from previously observed clinical practice.

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Noyes found that for women younger than 39 who were delaying childbirth, egg freezing alone (with no other fertility measures) was a cost-effective means of increasing their likelihood of having a biological child. Freezing after 39, however, was not cost-effective compared to multiple rounds of IVF. Women who froze their eggs between 30 and 35 had a 61 to 72 percent chance of successfully having a baby, at a cost per live birth of $34,221 to $43,408. But egg freezing after 37 or 38 starts to look less compelling, according to Noyes's data, with success rates falling to as low as 42 percent, and the cost per live birth rising dramatically to as high as $74,564 by age 40.

"Of course for most women I see," Dr. Noyes said, "the issue isn't about money. It's about having a healthy baby -- and that's really all they care about." And those, it seems, are the only stories the media finds worth telling.

PROBLEM: When rooms are continually smoked in, they become "reservoirs of tobacco smoke toxicants that accumulate in carpets, dust, upholstery, mattresses, curtains and furniture, penetrate wallpaper and paint, and are even stored in drywall." It's what some experts refer to as "third-hand smoke," and no one's quite sure how to clean it up. And while it's easy enough to keep smokers confined to designated rooms, smoke itself is harder to contain.

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METHODOLOGY: Two non-smoking women were recruited by researchers at San Diego State University to spend their weekends at low to mid-budget local hotels. Overall, they sampled 30 non-smoking and 29 smoking rooms in hotels that allow smoking, and 10 rooms in hotels that ban it altogether. 

Before they arrived for each 12 to 14-hour stay, a research assistant would set up equipment to measure the air quality and presence of surface contaminants in the room. The women would then spend the night (they were allowed one pre-approved, non-smoking visitor), being sure to touch everything a typical hotel guest would touch, from the drapes to the TV remote, for at least 30 seconds. The women's fingers and urine were tested for traces of nicotine and other byproducts of cigarette smoke before and after their stay.

RESULTS: Non-smoking hotel rooms generally contained more third-hand smoke when they were part of hotels that allowed smoking in other, designated rooms. They had, on average, twice the amount of nicotine on surfaces and seven times as much 3EP (another cigarette byproduct) in the air. In smoking-permitted rooms, of course, the presence of these contaminants was much higher.

The women, after spending the night in a hotel that permitted smoking, even after requesting a non-smoking room, the next morning had significantly more nicotine on their fingers, and five to six times the amount of cotinine -- a biomarker of second-hand smoke exposure -- in their urine.

IMPLICATIONS: It's unclear exactly how cigarette byproducts ended up in places they didn't belong. It could, write the authors, be the result of smoke migration, or from other patrons ignoring the ban, or from hotels not being entirely upfront about honoring people's requests for non-smoking rooms. Research budgets didn't allow for a proper analysis of luxury hotels, but the same principle probably applies across the board: Like most things that may have happened in a hotel room before you got there, and that may or may not have left some residue, you're probably best not thinking too much about it. 

Around 10 percent of honey in the U.S. contains spores from the bacteria Clostridium botulinum. That's not really a problem for big humans because it's just the spores, not the botulinum toxin. In infants (humans less than 13 months old), though, those spores can turn into botulinum toxin in their intestines. Not the kind of toxin that throws off chakras or warrants a juice cleanse, but the sort that poisons nerve endings and paralyzes muscles. It is the same toxin that's commercially sold as BOTOX® to assuage muscle spasms and treat migraines and smile lines. In this case, the tiny humans can get a full-blown case of botulism. 

Infant botulism can mean anything from subtle changes in muscle tone to so-called "floppy baby syndrome" to "sudden, unexpected death." None of this is common, but it's been repeatedly documented and established that infant botulism from honey does happen. It's not common for kids to get eaten by alligators, either, but that doesn't mean you let your baby live with an alligator family. Unless you do.

Honey pacifier

A study last week in the journal Pediatrics found that of 397 parents of infants in the Houston area, 11 percent reported using honey-pacifiers with their infants. That means buying pacifiers that contain honey, which are still sold. Some actually contain corn syrup instead of honey -- even if they're still sold as "honey pacifiers" but that too can contain botulinum spores.

Most of the parents (81 percent) at the clinic where this study took place were Hispanic, most indigent and of Mexican descent. The parents said they use the honey pacifiers either out of tradition, because the infants seem to prefer them, and/or because they felt there were health benefits (e.g., "helps with constipation or colic").

The only research about botulism and honey-pacifiers specifically are case reports around dipping a pacifier in honey. Even though the honey-pacifiers in question don't drip honey, it does amount to putting a tenuous sack of honey in the infant's mouth. Even assuming it remains intact, this kind of promotes a suboptimal baby-loves-honey culture. That's potentially a gateway to, as the study's authors put it, "dipping the pacifier in honey, or adding it to other foods or drinks."

There are obviously cultural traditions and folk wisdom about the benefits of honey-pacifiers to consider, of the sort that would not likely persist if there were no truth to them. They deserves research, but, as a greater pacifier debate rages, spreading word about botulism and honey is important. About 80 percent of the parents in this study said they did not know that honey was potentially dangerous in any way, much less the thing about sudden unexpected death.

You might say Saccharomyces cerevisiae yeast are the house-cats of the microbial world. Although they've been domesticated at least since the Pharaohs ruled Egypt -- the earliest records show that people by then already were using the "sugar-loving" yeast to leaven bread and brew beer -- this fungus's less civilized cousins can really mess you up.

Yeast are found everywhere in the environment. The one-celled organisms -- called "yeast" from the Old English gist/gyst and Indo-European root word yes, meaning boil, foam or bubble -- don't need sunlight, do need oxygen, and are naturally drawn to sugar-rich hosts for the carbon they thrive on.

"There are people who will contend that civilization began so that humans could make beer."

Fruit and berry skins are among their favorite habitats, but the spaces between your toes, your skin, gut, genitals -- and even crude oil, which is 84 percent carbon -- suit them just fine, too. Basically if there is carbon to be had, one yeast or another will have adapted to having it.

Although some species of fungi have a single-cell yeast "phase," they aren't what we ordinarily think of as "yeast." Of the 1,500 identified species of yeast that live around, in, and on us, three in particular stand out. Foremost is S. cerevisiae. Besides its ancient and ever greater role in food, beverages, and nutritional supplements, modern biotechnology has harnessed the metabolic process of S. cerevisiae -- we know it as fermentation -- to manufacture lifesaving medicines, fuel our vehicles, and even clean up oil spills.

Harmless to healthy people and present in/on all of us, Candida albicans becomes a one-celled monster when it finds a weak immune system. It's notorious for afflicting three-quarters of all women at some time in their lives with the itching, irritation, burning sensation, and soreness associated with so-generically-called yeast infections. Candidiasis, the technical name for those infections, also shows up in the form of diaper rash on a baby, jock itch, or white milky-looking thrush on the tongue.

The far more sinister Cryptococcus neoformans this year will kill hundreds of thousands of people, as it does each year. Preying on those with suppressed immunity, it's found in soil all over the world -- especially where lots of birds, particularly pigeons, leave their droppings. We all inhale C. neoformans' microscopic, airborne fungal spores, mostly with no problems. But people whose immune systems are compromised -- because they have untreated HIV infection, take immunosuppressive drugs, receive an organ transplant, or are pregnant, for example -- are at risk for developing the pneumonia-type illness cryptococcosis or, if the infection spreads to the brain, the life-threatening cryptococcal meningitis.

***

Thinking past these unpleasantries, consider that 50 billion pints and 67 billion cans of beer are consumed in the United States each year, according to the Beer Institute. "He was a wise man who invented beer," said Plato.

In fact, said Jim Koch, founder and owner of the Boston Beer Company, brewers of Sam Adams, "There's some debate about which came first, beer or bread. It appears most likely it was beer."

Koch called yeast -- specifically the S. cerivisiae used in both beer and bread -- a "miracle organism." He explained, "There are people who will contend that civilization began so that humans could make beer. They figured out how to grow grain, but needed to figure out how to turn the grain into a source of nutrition and safe hydration."

The alcohol produced by yeast's fermentation -- breaking down carbon into carbon dioxide and ethanol (alcohol) -- is among the most powerful sterilizing agents available. This is why, Koch said, even the Pilgrims didn't pack the Mayflower with barrels of water that could carry all kinds of harmful organisms -- typhus, cholera, and hepatitis among them.

"Instead, they provisioned it with beer," he said, "almost a gallon a day for every man, woman, and child."

Boston Public Library/Flickr

It wasn't that the pleasure-phobic Puritans were closet lushes. "The reason was beer was a safe form of hydration," said Koch. The alcohol produced by yeast's fermentation kills every potentially harmful organism in the beer. "When God made the universe," said Koch, "he or she made nothing harmful to human beings that can grow in beer."

Gods have been invoked, thanked, and cursed since the Greeks credited Dionysus with creating wine and winemaking. But it was the Frenchman Louis Pasteur who revealed new knowledge that even the gods had never imparted. In 1857 Pasteur created the field of microbiology when he proved that alcoholic fermentation is conducted by living yeast rather than by either a chemical reaction or by magic. Viniculturists ever since have sought to capitalize on the new understanding about yeast that microbiology opened up for them.

One winemaker, noted for using "wild" yeast to make what many consider his magical zinfandels, is Joel Peterson. The owner of Sonoma, California-based Ravenswood Winery told me he prefers the indigenous yeast found on the grapes he uses because they have been used for millennia in the kind of traditional winemaking he practices. "I get more interesting characters out of the wild yeast fermentation than I do out of a monoclonal yeast fermentation," he said.

Because it takes longer -- and therefore costs more -- to let the wild yeast ferment at their natural pace, Peterson said most big commercial wineries "give an overwhelming dose of Saccharomyces" so it dominates the others, ferments faster, and is more likely to yield a predictably consistent flavor.

It wasn't coincidental that Peterson chose the less-traveled path with the less-predictable native yeast: His background as a microbiologist prepared him well. In his earlier line of work, Peterson worked closely with yeast -- though of the pathogenic sort. As a medical researcher, he studied chronic mucocutaneous candidiasis, an immune disorder in which a lack of resistance to Candida causes recurrent or persistent infections of the skin, mucous membranes, and nails, usually with Candida albicans.

Peterson said it's important to understand that each type of yeast thrives or dies according to its particular diet and environment. "The layman says 'yeast,' and that's all they get," he said. "I hope you'll make it really clear that these yeasts are very separate from one another. So Saccharomyces would never behave like Candida. It has a host and food it likes. If you put Candida albicans in grape slurry, it would die."

***

In the vagina, however, Candida not only live, but can really go wild if the mix of yeast and bacteria is off-kilter.

This happens when a woman is, for example, taking antibiotics, which decrease the amount of lactobacillus bacteria in her vagina, or her estrogen level is increased during pregnancy or from taking high-dose estrogen birth control pills or hormone therapy. It can also happen when diabetes isn't controlled or the immune system is impaired by HIV or another factor. Although it's not usually transmitted sexually, it can be.

"Yeasts are colonized in about 80 percent of women."

Jill Maura Rabin, MD, professor of obstetrics and gynecology and head of urogynecology at Hofstra North Shore-LIJ School of Medicine, in Hempstead, New York, explained that the vagina's normal pH is 3.8 to 4.2. "If you keep a normal vaginal acid, it's almost impossible to grow yeast or flora in the vagina," she said.

Nevertheless, "yeasts are colonized in about 80 percent of women," said Rabin, adding,"The importance of vaginal flora in terms of general health is as a mirror of what is going on the body."

Rabin said it's wise to weigh the risks and benefits of treating a yeast infection yourself versus seeing a doctor. "By yourself, the benefit is it saves money and time," she said. "But the risk of treating yourself is you may spend money on something you didn't need, masking what's there and making it more difficult to treat."

For women who have already "been there, done that," Rabin said it's fine to treat yourself if you are confident of what you're dealing with. She elaborated in a telephone interview, "For people who know themselves well and have classic symptoms, have had [yeast infections] in the past and have no other comorbidities, I don't believe there is a risk in going to the drugstore and treating it."

On the other hand, Rabin recommends seeing a doctor if you aren't prone to yeast infections or it's not clearing up with over-the-counter treatment.

To keep Candida in check, Rabin recommends regularly taking probiotics, ideally in yogurt. "I prefer people to get their supplements in food," she said. She also suggested Luvena, a vaginal "prebiotic" that stimulates the growth of healthy lactobacillus bacteria; vaginal acid jelly that can be used three times a week right after menstruation when the pH is up; or boric acid suppositories, particularly for pregnant women.

For women prone to repeat infections -- overweight women with high-carbohydrate diets tend to have repeats -- Rabin said wearing cotton underwear is a must. "Cotton is more absorptive, but also the fibers have air space where nylon doesn't," she explained. For women who have chronic yeast infections, Rabin offers simple advice for at least partly addressing the problem: "Go commando," she said.

***

You could wear a cotton mask over your face, but will still very likely inhale somewhere, at some time, the spores of Cryptococcus neoformans. Unless your immune system is severely compromised, however, you aren't likely ever to know this particular pathogen has taken up residence in your body.

Before antiretroviral therapy (ART) became available in the mid-1990s, five to ten percent of people with the advanced stage of untreated HIV infection known as AIDS were at great risk for developing the cough, fever, and shortness of breath associated with cryptococcosis in the lungs. Without the immune strength to restrain C. neoformans and its equally insidious relative Cryptococcus gattii, the fungus wreaks even greater havoc if it infects the central nervous system. Fever, headache, and a change in mental status are among the dreaded signs that cryptococcus is causing the inflammation of the brain and meninges known as cryptococcal meningitis.

Cryptococcosis is diagnosed by a microscopic exam, tissue or body fluid culture, or a rapid test performed on blood and/or cerebrospinal fluid. Treatment of an asymptomatic, mild, or moderate case involves at least six months of prescription antifungal medication, typically fluconazole or itraconazole.

An estimated 625,000 people will die from cryptococcal meningitis this year.

The Centers for Disease Control and Prevention estimate there are one million new cases of cryptococcal meningitis worldwide each year. With a mortality rate of 50 to 70 percent, an estimated 625,000 people will die from the disease -- most of them in sub-Saharan Africa, where it is one of the leading causes of death in HIV-positive people. In the U.S. today, there are only two to seven cases per 1,000 people, for a mortality rate of about 12 percent. Even if it doesn't kill you, the CDC says C. neoformans meningitis may lead to permanent neurologic damage.

"Fortunately more and more HIV-positive people are getting on treatment," said Kenneth H. Mayer, MD, medical research director at the Fenway Institute in Boston and professor of medicine at Harvard Medical School. Noting there are other populations still at risk -- including people on chemotherapy -- Mayer said that "rates of cryptococcosis in the U.S. have plummeted among people with HIV." He added, "If people with HIV start treatment and are adherent to their meds, their risks are exceedingly low."

***

Yeast has dramatically reduced the risk of contracting HIV -- as well as other deadly pathogens. Once again, Saccharomyces cerevisiae is providing for humanity's health and well-being -- not only in our bakeries, breweries, and wineries, but in our laboratories as well.

Thanks to modern biotechnology, Factor 8 -- the blood-clotting protein lacking in hemophiliacs -- is produced in genetically altered S. cerivisiae. Before the early 1990s advent of recombinant synthesized factor products, Factor 8 was made from donated human plasma. In the 1980s, tens of thousands of hemophiliacs who depended on "factor" to live were infected with HIV, and died from AIDS, as a result of contaminated Factor 8 products.

Besides its other admirable and useful qualities, you might call S. cerivisiae the host with the most. It's also called the most important organism in modern biotechnology.

It was in the lab of Gerald R. Fink, a biology professor at MIT's Whitehead Institute for Biomedical Research, that a process was discovered in 1977 which allows researchers to introduce a foreign piece of DNA into yeast cells and have it expressed in subsequent generations of the yeast.

Fink described in an interview how his discoveries have led scientists not only to manufacture Factor 8 in S. cerivisiae, but also Hepatitis B vaccine, Gardisil (for HPV), and numerous other human and animal biopharmaceutical products. Because yeast, like human cells, are eukaryotic -- possessing both a nucleus, membrane-bound organelles, and mitochondria -- biotechnological techniques have made yeast the hosts of choice for human genes.

"A lot of what people are having injected into them," said Fink, "are vaccines that are human protein made in yeast by putting the gene from humans into yeast."

Half the insulin used to manage the metabolic imbalances of the world's 366 million diabetics is produced in Saccharomyces. The rest is produced in a bacteria, Escherichia coli -- better known as E. coli, the culprit behind regular outbreaks of infection from contaminated food and water that lead to vomiting and diarrhea, and can lead to kidney failure.

Fink said that in biotech applications S. cerivisiae, ordinary bread yeast, is preferable to E. coli not only because it reproduces prolifically, but because it's safe. Even after using it to produce the viral antigens used in vaccines, "you can feed it to animals," he said. Because literally thousands of pounds of yeast can be produced from a small batch, Fink added, "You can get a pretty penny for Saccharomyces" by selling the excess that isn't needed.

"This becomes a bigger issue when you are dealing with biofuels," he explained, "because, in the end, as in any industrial process, you have a problem in that you've produced so much, what do you do with the stuff?" E. coli is used to manufacture many other biotherapeutics. But after you've got what you want from it, there's the problem of having a tremendous amount of a harmful organism. This is why, said Fink, "there are processes people use E. coli for, but if you have the choice, you do it in yeast."

As scientific knowledge increases, and yeast continues to expand in usefulness and value to a variety of industries, it's clear the potential of these microorganisms is far from exhausted.

Of course not everyone is enthusiastic about all of what biotechnology has made possible, as evidenced by the ever-growing movement against so-called GMOs (genetically modified organisms) in agriculture and food.

But while debates rage over whether or not GMOs in our foods have negative consequences, a bit of perspective seems called for. Dr. Fink said that National Research Council studies haven't showed evidence of untoward effects. Pointing to the tremendous benefits of the pharmaceutical products manufactured in genetically modified yeast, he added, "Why is it not okay to eat things, but it's okay to inject them in your veins?"

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In time even bigger questions may present themselves: Has Saccharomyces, the "house cat," been domesticated to the point we can anticipate its every action and reaction, even after we've manipulated the very blueprint of its life? Is it possible the anti-GMOers will one day shout, "We told you so!" when the human genome becomes mutated in some unforeseen harmful ways because of the "cat" that got out of the bag?

For the time being, such questions are probably best debated over a frosty brew or glass of fine wine. While we're quaffing our thirst, how about raising a toast to our old friend Saccharomyces cerivisiae.

PROBLEM: The properly cautious parent is advised to soak their baby's pacifier daily in equal parts white vinegar and water, and, each time it hits the floor, to wash it in hot, soapy water. The "hygiene hypothesis," on the other hand, posits that when kids are overly sterilized, they never learn how to fight off pathogens.  

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METHODOLOGY: Pregnant women in Sweden were invited to participate in a study lead by researchers at the University of Gothenburg. Specifically targeting families where allergic disease was prevalent, they interviewed the new parents of 184 infants every six months about their pacifier cleaning processes, and asked them to keep journals tracking their behavior. The researchers collected the infants' saliva in order to analyze their oral microbes, and the babies were tested for an array of allergies at 18 and 36 months.

RESULTS: When their parents "cleaned" their pacifiers by sucking on them, the infants at 18 months were 12 percent less likely to have asthma, 37 percent less likely to have eczema, and trended toward a lower likelihood of being sensitive to airborne and food allergens than the children whose parents rinsed or boiled their pacifiers. At just four months, the researchers were able to tell the difference between kids whose parents were mouth-cleaners and those who were not just by analyzing the bacterial DNA from their spit. 

When they tested the infants again at 36 months, they were no longer significantly less likely to have asthma or be sensitive to allergens. But they remained 51 percent less likely to have eczema. 

IMPLICATONS: The word "clean" is in quotes here for a reason. While the parents were removing physical signs of dirt, they were in fact making the pacifiers dirtier, imparting "a complex mixture of aerobic and anaerobic bacteria" to their infants. (Kissing, write the authors, would likely do the same thing.) Because those bacteria are basically harmless -- the kids whose parents used mouth-cleaning weren't any more likely to develop respiratory infections -- this was actually a good thing, affording them increased immunity, at least temporarily, from allergic diseases.

What happens to a gum that has as much caffeine as a half-cup of coffee but gets pulled off the market one week after its release because of "concern about the proliferation of caffeine in the nation's food supply"?

Does the issue of potential limits on caffeinating every person in every possible way dry up? Or fester like a sore -- feeling libertarian outrage at the questioning of the good sense of caffeinated oatmeal.

Wrigley released Alert Energy Gum on April 30. It contained 40 milligrams of caffeine per piece, which is half as much as a Red Bull, or a handful of caffeinated gummy bears. It's not the first energy gum. Jolt has one, and so does Mentos. Wrigley's might have been the last, though, because the day after its launch, the FDA announced it was looking into the safety of caffeine and "prepared to go through the regulatory process to establish clear boundaries and conditions on caffeine use." 

Wrigley "paused" production of the gum this week.

The FDA denied that the gum's launch inspired the announcement. Still, timing was not good for Wrigley and their sunshine-colored gum, especially as the FDA highlighted that "the American Academy of Pediatrics discourages the consumption of caffeine and other stimulants by children and adolescents."

The move could be something of a bellwether in energy-product public relations. What happens to the images of companies selling caffeinated socks, raisins, and whatnot from here out, until the FDA finishes its inquisition, quells concerns? Do they start to stink like rotten, caffeinated meat? Maybe they just sag under the heavy load of 20,000 energy-drink-related trips to the E.R. Or do they explode?