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Sunday 29 January 2012

The Price For Sexy Legs

We already knew that wearing high heels is bad for you. Now, some proper science has been done to verify this.



A Scientific Look at the Dangers of High Heels


Not long ago, Neil J. Cronin, a postdoctoral researcher, and two of his colleagues at the Musculoskeletal Research Program at Griffith University in Queensland, Australia, were having coffee on the university’s campus when they noticed a young woman tottering past in high heels. “She looked quite uncomfortable and unstable,” Dr. Cronin says.

Some observers, particularly women, might have winced in sympathy or, alternatively, wondered where she’d bought stilettos. But the three researchers, men who study the biomechanics of walking, were struck instead by the scientific implications of her passage. “We began to consider what might be happening at the muscle and tendon level” in women who wear heels, Dr. Cronin says.

How shoes affect human gait is a controversial topic these days. The popularity of barefoot running, for instance, has grown in large part because of the belief, still unproven, that wearing modern, well-cushioned running shoes decreases foot strength and proprioception, the sense of how the body is positioned in space, and contributes to running-related injuries.

Whether high heels might likewise affect the wearer’s biomechanics and injury risk has received scant scientific attention, however, even though millions of women wear heels almost every day. So, in one of the first studies of its kind, the Australian scientists recruited nine young women who had worn high heels for at least 40 hours a week for a minimum of two years. The scientists also recruited 10 young women who rarely, if ever, wore heels to serve as controls. The women were in their late teens, 20s or early 30s.

The scientists asked the heel-wearing women to bring their favorite pair of high-heeled shoes to the lab. There, both groups of women were equipped with electrodes to track leg-muscle activity, as well as motion-capture reflective markers. Ultrasound probes measured the length of muscle fibers in their legs.
All of the women strode multiple times along a 26-foot-long walkway that contained a plate to gauge the forces generated as they walked. The control group covered the walkway 10 times while barefoot. The other women walked barefoot 10 times and in their chosen heels 10 times.

It was obvious, as the scientists had suspected watching the woman during their coffee break, that the women habituated to high heels walked differently from those who usually wore flats, even when the heel wearers went barefoot. But the nature and extent of the differences were surprising. In results published last week in The Journal of Applied Physiology, the scientists found that heel wearers moved with shorter, more forceful strides than the control group, their feet perpetually in a flexed, toes-pointed position. This movement pattern continued even when the women kicked off their heels and walked barefoot. As a result, the fibers in their calf muscles had shortened and they put much greater mechanical strain on their calf muscles than the control group did.

In that control group, the women who rarely wore heels, walking primarily involved stretching and stressing their tendons, especially the Achilles tendon. But in the heel wearers, the walking mostly engaged their muscles.

That biomechanical distinction is important, says Dr. Cronin, who is now a researcher at the University of Jyvaskyla in Finland. “Several studies have shown that optimal muscle-tendon efficiency” while walking “occurs when the muscle stays approximately the same length while the tendon lengthens. When the tendon lengthens, it stores elastic energy and later returns it when the foot pushes off the ground. Tendons are more effective springs than muscles,” he continues. So by stretching and straining their already shortened calf muscles, the heel wearers walk less efficiently with or without heels, he says, requiring more energy to cover the same amount of ground as people in flats and probably causing muscle fatigue.
The obvious question raised by the findings, though, is so what? Does it fundamentally matter if a woman’s calf muscle fibers shorten and she neglects her tendons while walking, especially if she loves the looks of her Louboutins?
That question is difficult for a biomechanist to answer, Dr. Cronin admits.

Aesthetics are outside the realm of his branch of science. But the risk of injury is not. “We think that the large muscle strains that occur when walking in heels may ultimately increase the likelihood of strain injuries,” he says. (This risk is separate from the chances that a woman, if unfamiliar with heels, may topple sideways and twist an ankle or bruise her self-image, which is an acute injury and happened to me only the one time.)

The risks extend to workouts, when heel wearers abruptly switch to sneakers or other flat shoes. “In a person who wears heels most of her working week,” Dr. Cronin says, the foot and leg positioning in heels “becomes the new default position for the joints and the structures within. Any change to this default setting,” he says, like pulling on Keds or Crocs, constitutes “a novel environment, which could increase injury risk.”

It should be noted, he adds, that in his study, the volunteers “were quite young, average age 25, suggesting that it is not necessary to wear heels for a long time, meaning decades, before adaptations start to occur.”

So, if you do wear heels and are at all concerned about muscle and joint strains, his advice is simple. Try, if possible, to ease back a bit on the towering footwear, he says. Wear high heels maybe “once or twice a week,” he says. And if that’s not practical or desirable, “try to remove the heels whenever possible, such as when you’re sitting at your desk.” The shoes can remain alluring, even nestled beside your feet.
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With research on the dangers of wearing heels getting headlines all over the world, will ladies cut down on the wearing of heels? Well, not till we change the image of what a pair of sexy legs should look like. Which of the following is sexier?



Monday 16 January 2012

Commercializing science

Stem-cell research: Never say die

Robert Lanza has been a public face for Advanced Cell Technology’s many ups and downs.
Sam Ogden
“Oh crap, this really puts us in the spotlight!” thought Robert Lanza when he first heard the news. Advanced Cell Technology (ACT), the biotechnology company in Marlborough, Massachusetts, of which Lanza is chief scientific officer, had for more than a year been operating in the shadow of Geron, a rival company in Menlo Park, California. Geron was bigger and better funded than ACT, and it was the first company to be approved by the US Food and Drug Administration (FDA) to test a therapy in humans based on embryonic stem (ES) cells. ACT was second. But in November, Geron announced that it was halting its trial to focus instead on cancer drugs. And with the announcement, Lanza says, he felt the weight of the ES-cell field fall on his shoulders.

Lanza and his company have had plenty of experience in the spotlight, but the attention has not always been flattering. Since the late 1990s, ACT has gained a reputation as a renegade company, accused of overhyping results to raise attention and money. Critics say that the company has damaged the field more than once with its high-profile, controversial announcements, such as one describing the company's attempts to clone a human embryo1 in 2001. ACT's actions — and the highly politicized nature of stem-cell research — scared off investors, leaving the company teetering on the verge of bankruptcy for most of the past decade.
But the scrappy biotech refused to die, in part because of Lanza's doggedness. ACT is now performing early-phase clinical trials testing the safety of implanting retinal cells derived from human ES cells into the eye to treat certain types of blindness.
Lanza says that this time, he aims to do things right: direct good science focused on treating disease, publish in reputable journals with rigorous peer-review processes and work with high-quality collaborators and clinical centres for its trials. “We're a different company now,” says Lanza.
Not everyone is convinced. Even if positive results emerge from these trials, ACT will still face major challenges in getting an ES-cell-based therapy approved for wider use. And some in the field are sceptical about ACT's reformation. “Can you really trust a company that has a spotty record?” says Arthur Caplan, a bioethicist at the University of Pennsylvania in Philadelphia.
It's not just Lanza who has a stake in the answer. With Geron out of the game, ACT's success or failure will be important for a field looking to prove itself worthy of further research funding. “If the trials are positive, that would fundamentally transform the debate,” says Christopher Thomas Scott, director of the Program on Stem Cells and Society at Stanford University in California.

Problem child

ACT began in the mid-1990s as an animal-cloning outfit owned by Avian Farms, a Maine-based poultry genetics company. ACT quickly shifted focus when Michael West — who founded Geron — became its chief executive in 1998. Human ES cells had just been isolated for the first time, and researchers were excited about their potential use in regenerative medicine.
But many were concerned that patients' immune systems would reject cells derived from unrelated embryos. To solve this, West proposed 'therapeutic cloning' — taking the nucleus out of a patient's cell, transferring it into an egg cell to create a cloned embryo, then using that embryo to derive patient-matched stem-cell lines.
In 1999, using money he had made at Geron, West bought ACT. Lanza, a physician who had spent the past 20 years working in academic research and biotech on organ and cell transplantation, was one of West's first recruits. The team moved quickly to try to make therapeutic cloning a reality.
If the American public had not yet heard of human cloning or ACT by the fall of 2001, it could hardly have missed the hype that began on 25 November that year. West appeared on Meet the Press, a nationally televised US political talk show, to discuss a paper, published that day, in which ACT scientists described the first cloning of a human embryo. “We've taken the first halting steps toward what we think is going to be a new area of medicine,” West said.
West appeared on several other news shows in the following days. CNN and US News and World Report heralded the work as a breakthrough, and West and his team hailed the “dawn of a new age in medicine” in a report for Scientific American (now owned by Nature Publishing Group).
In the paper1, published in the now-defunct online journal e-biomed, West, Lanza and their colleagues showed that they could pull a nucleus from a human egg cell, replace it with a whole adult ovarian cell and generate an embryo that divided into six cells. It then stopped growing, far short of the 100-cell blastocyst stage from which stem cells can be derived.
The work pressed a political hot button. That summer, President George W. Bush had approved federal funding for human ES-cell research, but only for a small number of cell lines that had already been created. He also voiced staunch opposition to human cloning of any kind, and a bill to ban it had been advancing through the US Congress, much to the chagrin of researchers who saw promise in therapeutic cloning.
ACT's announcement stoked fears that scientists were trying to clone humans for reproductive purposes — and conflated reproductive cloning and human-embryonic-stem-cell research in many people's minds. “It gave critics plenty of ammunition to insist that if stem-cell research was funded, human reproductive cloning would be funded too,” says Caplan. “It had a huge deleterious impact for years.”
Scientists, meanwhile, dismissed the finding. The ACT team hadn't gained new insight into the human developmental process, says George Daley, a stem-cell researcher at Children's Hospital Boston in Massachusetts. “I was not in a position to defend the cloning that they were doing because it was ineffective in what they were trying to do,” he says. “It was more for publicity than for science.”
Jose Cibelli, who was first author on the paper and left ACT in 2002 for a faculty position at Michigan State University in East Lansing, says that in an ideal world he would have waited until the team could grow the embryos to the blastocyst stage before publishing the work. But he had heard rumours that other groups were pursuing the same goal, and he was worried about getting scooped. (A successful derivation of stem cells from a cloned human embryo was not reported until October 2011, and these stem cells had three sets of chromosomes rather than two2.)
West says that he pushed ahead with publication in the interest of transparency. “It was our policy not to hide what we were doing and why,” he says. “We wanted to be honest, accurate and open.”
The announcement ended up hurting the company, however. ACT was trying to raise a needed round of venture-capital financing when the cloning news broke. The negative attention combined with the political uncertainty around stem-cell funding killed the deal, says Greg Bonfiglio, who was with Anthem Venture Partners of Santa Monica, California, at the time, and would have been the lead investor on that round.

Scraping by

The disappearance of the venture funding sent ACT on a financial downward slide from which it would take nearly ten years to recover, says Bonfiglio, who has dealt with the company on several more occasions. Researchers at Geron, meanwhile, had successfully derived neurons from human embryonic stem cells3 and were pursuing research that would eventually look to repair the damage caused by spinal-cord injuries, a possible use for embryonic stem cells that was much touted at the time. ACT was largely dismissed as a sideshow.
Lanza is now the longest-serving employee of the company. He says that a “tough childhood” in Stoughton, a town south of Boston, Massachusetts, helped him to develop a thick skin.
Unlike many Boston-area academics, Lanza has the 'R'-dropping accent of the region, most noticeable when he talks about one of his main preoccupations: Stargardt's disease. “Stahgahdt's” — as he says it — is one of the two types of degenerative blindness his company is targeting in its clinical trials. The other, the 'dry' form of age-related macular degeneration, is the most common cause of age-related blindness. Both diseases result from the death of retinal cells, a process that Lanza suspects can be slowed or even halted using stem-cell-derived replacements.
“It was our policy not to hide what we were doing and why. We wanted to be honest, accurate and open.”
After the venture funding fell through, West sold ACT's animal-cloning division to generate revenue. By 2004, however, money had again started to run low. But Lanza and West had recently hired Irina Klimanskaya, who, as a researcher at Harvard University in Cambridge, Massachusetts, had helped to derive many of the institution's first human ES-cell lines and who had a knack for working with scant resources. At ACT, she began optimizing a protocol for transforming ES cells (derived from embryos donated through fertility clinics) into retinal pigmented epithelial (RPE) cells. These are lost in both Stargardt's and dry age-related macular degeneration4.
Stopping vision loss didn't quite have the dramatic appeal of Geron's goal of reversing paralysis. But focusing on the eye may have been a wise decision, say experts.
“The eye is an ideal place to begin this type of experimental work,” says Michael Young, an ophthalmology researcher at the Schepens Eye Research Institute in Boston. Surgeons already have protocols for injecting cells directly into the eye, and they can measure changes in the retina just by peering into it. The eye is relatively sealed off from the immune system compared with other parts of the body, which may reduce the risk of cell rejection.
Moreover, transplanted RPEs do not need to form synapses, or connections, with neurons, unlike other retinal cell types. “If cell-based therapy in the eye is going work, it's got to work with the RPEs,” says Thomas Reh, a neurobiologist at the University of Washington in Seattle.
By 2004, Lanza and his team were ready to start testing the RPE cells in animals — but they were paralysed by a lack of money. The cells sat in a freezer for almost a year. Meanwhile, the company's phone service was turned off, purchases of basic lab supplies grew harder to justify and the skeleton crew of remaining scientists wondered week to week whether they would get paid.
Some left, but Klimanskaya opted to stay on. “I believe in the company, in the cells, in the technology and in my own skills,” she says. “Why should I quit?”
Out of desperation, West agreed at the end of 2004 to take the company public to gain access to a new source of funding. But the legal, accounting and marketing costs of going public through an initial public offering (IPO) were far beyond the company's reach. Instead, in early 2005, ACT merged with Two Moons Kachinas, an obscure, Utah-based outfit that sold Native American dolls. Two Moons was essentially a 'shell' company, allowing ACT to take it over and become a publicly traded firm. This 'reverse merger' was much cheaper than an IPO, but the US$8 million it raised had more strings attached.
As part of the deal, investors required the company to name a new chief executive. “The issue with ACT at that time was never about the quality of the science team,” says Bonfiglio, who led the deal. “The business skills were not resident on that team.” The new chief executive, William Caldwell, had more than 30 years of experience in banking, transportation and telecommunications, but none in biotech.

Out of the ashes

With the infusion of cash, ACT went on a hiring spree. West, who became the company's president and chief scientific officer, moved to California and recruited several researchers in hope of starting a lab that could tap into funding from the San Francisco-based California Institute for Regenerative Medicine (CIRM), a $3-billion, state-backed fund for stem-cell research.
Meanwhile, Lanza built up his team in Massachusetts and forged ahead with the RPE transplantation studies in rats. In 2006, positive results began to materialize5 and ACT opened its new headquarters, a 1,400-square-metre research facility in Alameda, California, which included a lab capable of growing cells according to the strict standards required for human trials.
Just as optimism was running high, the company made another very public stumble. In August 2006, Lanza and his co-authors published a paper6 in Nature showing that a single cell could be plucked from an 8–10-cell human embryo and grown into stem cells. Lanza wanted to show that it was possible to derive stem cells without destroying the embryo, to sidestep ethical concerns.
In fact, the embryos were destroyed in the experiments, but that had not been made clear in the original version of the paper, the press releases about it or in some of Lanza's press interviews. Nature issued two clarifications after its original press release, but many news organizations had already reported that the embryos were unharmed. When the truth became clear, critics pounced.
Opponents of ES-cell research saw the debacle as an attempt to mislead the public, and scientists criticized the method as impractical and still ethically problematic. Biopsying embryos puts them at risk, says Daley, so some will be lost.
Lanza says that the Nature paper was only meant to be a proof of principle and that the company soon perfected the technique so that embryos survived. But the episode reinforced perceptions that the company hyped its results, this time to boost its stock value. If that was the intent, the effect was short-lived. The increase in share price on the day of the announcement — from $0.42 to $1.83 — would be reversed in the weeks and months that followed.
Unable to raise enough money from conventional sources, Caldwell turned to last-resort financing. ACT borrowed cash from investors and then repaid them in shares on a monthly basis, using the lowest share price of the previous month. As that price dropped, ACT had to issue more and more shares, forcing the price down even further. Caldwell completed several rounds of this 'death-spiral financing' between 2005 and 2010 to keep Lanza's RPE research going, and the company sank further into debt.
By 2007, West says, he was not getting along with Caldwell and left ACT to head another company to develop products for ES-cell research. In 2008, ACT closed its Alameda facility — the CIRM funding never materialized — but Caldwell stayed in Los Angeles. By the time the markets crashed later that year, ACT's stock price had dwindled to pennies. Caldwell lost all of his executives, and the entire RPE development team left.
Still, Lanza was convinced that RPE therapy held the key to the company's survival. He was, moreover, impressed with Caldwell's dedication to the project. “He got all excited [about the science], and that was important,” Lanza says. “He was really my partner.” The two worked tirelessly throughout 2009 to rebuild the company. Caldwell eked out funding so that Lanza and his team could do the studies needed for FDA approval of the clinical trials. “We knew we had one chance,” says Lanza.
In November 2010, when a fax arrived saying that the trial had been approved, a cheer went through the office. “We came out of the ashes,” says Lanza. “It was a long time coming.”
There was little time for celebration, however. The team still needed approval from the clinical centres conducting the trials before they could start treating patients.
Lanza usually began each morning by answering a slew of e-mails from Caldwell, who often worked later hours in Los Angeles. So he was concerned when, on the morning of 14 December, his inbox was empty. The call came later that afternoon from Caldwell's wife. The man who had kept ACT afloat for the past six years had died unexpectedly, aged 63. Describing the loss now, Lanza becomes quite emotional and almost can't continue. “It was like I lost a father,” he says.
The company faced yet another bleak period. But Gary Rabin, an investment banker who had been on ACT's board since 2007, stepped in as interim leader. Within two weeks, he had secured $25 million in financing from two firms that Caldwell had been courting. Rabin, who is now ACT's chairman and chief executive, says that the funding is enough to pay for the company's two ongoing trials and should last through 2012.

The challenges ahead

Now, the company's future hinges on the outcome of the trials. Final results won't be out until 2013, and they will show mainly whether the cell transplants are safe. The patients enrolled in the trial are in the late stages of vision loss, so the chances of dramatic improvement are remote, experts say.
Still, Rabin and Lanza are optimistic. If the treatment is safe and even moderately effective, they say they would consider partnering with a pharmaceutical company to help take the programme forward — although they are still working out their plan. Scott, with Stanford's Program on Stem Cells and Society, says that positive results could fire up patient advocacy groups, which can be powerful in building support. And a good outcome could encourage investment in other stem-cell therapy companies, says Bonfiglio, who is now managing partner at Proteus Venture Partners in Palo Alto, California.
But even if the trial results are positive, ACT will face enormous challenges in commercializing the technology. The company will have to show the FDA that its RPE cells can slow vision loss in bigger and more expensive clinical trials.
And even if the treatment works, storing and distributing the cells, which often have short shelf-lives, is expensive and logistically difficult, says Chris Mason, head of the Stem Cell and Regenerative Medicine Bioprocess Group at University College London.
These challenges were thrown into stark relief when Geron halted its stem-cell trial in November, having decided that the hurdles to commercializing the therapy were too great. Now, it is up to ACT to face them. “The departure of Geron from the field will ultimately place a greater burden on ACT in terms of educating the FDA and establishing standards for safety and efficacy,” Bonfiglio says.
ACT is not entirely alone: other stem-cell-based therapies are moving towards the clinic. For example, a consortium of research groups called the London Project to Cure Blindness aims to test RPE transplants from embryonic stem cells in patients with macular degeneration this year. A group in Japan hopes to test a similar approach in humans using stem cells from reprogrammed adult cells within the next three years.
Still, some who have tracked ACT's trajectory say that the company might have what it takes to succeed. “What has kept ACT going is persistence, tenacity and vision,” says Ronald Green, ACT's long-time ethics adviser and a professor of religion and ethics at Dartmouth College in Hanover, New Hampshire.
Lanza says that at times he considered giving up and working on something less controversial. “If I wasn't a stubborn Italian,” he says, “I would have thrown up my hands at least 25 times.”

Nature Volume: 481,Pages: 130–133

Wednesday 11 January 2012

Are you doomed to be fat?

An article from the New York Times..

The Fat Trap

By TARA PARKER-POPE

For 15 years, Joseph Proietto has been helping people lose weight. When these obese patients arrive at his weight-loss clinic in Australia, they are determined to slim down. And most of the time, he says, they do just that, sticking to the clinic’s program and dropping excess pounds. But then, almost without exception, the weight begins to creep back. In a matter of months or years, the entire effort has come undone, and the patient is fat again. “It has always seemed strange to me,” says Proietto, who is a physician at the University of Melbourne. “These are people who are very motivated to lose weight, who achieve weight loss most of the time without too much trouble and yet, inevitably, gradually, they regain the weight.”

Anyone who has ever dieted knows that lost pounds often return, and most of us assume the reason is a lack of discipline or a failure of willpower. But Proietto suspected that there was more to it, and he decided to take a closer look at the biological state of the body after weight loss.

Beginning in 2009, he and his team recruited 50 obese men and women. The men weighed an average of 233 pounds; the women weighed about 200 pounds. Although some people dropped out of the study, most of the patients stuck with the extreme low-calorie diet, which consisted of special shakes called Optifast and two cups of low-starch vegetables, totaling just 500 to 550 calories a day for eight weeks. Ten weeks in, the dieters lost an average of 30 pounds.

At that point, the 34 patients who remained stopped dieting and began working to maintain the new lower weight. Nutritionists counseled them in person and by phone, promoting regular exercise and urging them to eat more vegetables and less fat. But despite the effort, they slowly began to put on weight. After a year, the patients already had regained an average of 11 of the pounds they struggled so hard to lose. They also reported feeling far more hungry and preoccupied with food than before they lost the weight.

While researchers have known for decades that the body undergoes various metabolic and hormonal changes while it’s losing weight, the Australian team detected something new. A full year after significant weight loss, these men and women remained in what could be described as a biologically altered state. Their still-plump bodies were acting as if they were starving and were working overtime to regain the pounds they lost. For instance, a gastric hormone called ghrelin, often dubbed the “hunger hormone,” was about 20 percent higher than at the start of the study. Another hormone associated with suppressing hunger, peptide YY, was also abnormally low. Levels of leptin, a hormone that suppresses hunger and increases metabolism, also remained lower than expected. A cocktail of other hormones associated with hunger and metabolism all remained significantly changed compared to pre-dieting levels. It was almost as if weight loss had put their bodies into a unique metabolic state, a sort of post-dieting syndrome that set them apart from people who hadn’t tried to lose weight in the first place.

“What we see here is a coordinated defense mechanism with multiple components all directed toward making us put on weight,” Proietto says. “This, I think, explains the high failure rate in obesity treatment.”
While the findings from Proietto and colleagues, published this fall in The New England Journal of Medicine, are not conclusive — the study was small and the findings need to be replicated — the research has nonetheless caused a stir in the weight-loss community, adding to a growing body of evidence that challenges conventional thinking about obesity, weight loss and willpower. For years, the advice to the overweight and obese has been that we simply need to eat less and exercise more. While there is truth to this guidance, it fails to take into account that the human body continues to fight against weight loss long after dieting has stopped. This translates into a sobering reality: once we become fat, most of us, despite our best efforts, will probably stay fat.

I have always felt perplexed about my inability to keep weight off. I know the medical benefits of weight loss, and I don’t drink sugary sodas or eat fast food. I exercise regularly — a few years ago, I even completed a marathon. Yet during the 23 years since graduating from college, I’ve lost 10 or 20 pounds at a time, maintained it for a little while and then gained it all back and more, to the point where I am now easily 60 pounds overweight.

I wasn’t overweight as a child, but I can’t remember a time when my mother, whose weight probably fluctuated between 150 and 250 pounds, wasn’t either on a diet or, in her words, cheating on her diet. Sometimes we ate healthful, balanced meals; on other days dinner consisted of a bucket of Kentucky Fried Chicken. As a high-school cross-country runner, I never worried about weight, but in college, when my regular training runs were squeezed out by studying and socializing, the numbers on the scale slowly began to move up. As adults, my three sisters and I all struggle with weight, as do many members of my extended family. My mother died of esophageal cancer six years ago. It was her great regret that in the days before she died, the closest medical school turned down her offer to donate her body because she was obese.
It’s possible that the biological cards were stacked against me from the start. Researchers know that obesity tends to run in families, and recent science suggests that even the desire to eat higher-calorie foods may be influenced by heredity. But untangling how much is genetic and how much is learned through family eating habits is difficult. What is clear is that some people appear to be prone to accumulating extra fat while others seem to be protected against it.

In a seminal series of experiments published in the 1990s, the Canadian researchers Claude Bouchard and Angelo Tremblay studied 31 pairs of male twins ranging in age from 17 to 29, who were sometimes overfed and sometimes put on diets. (None of the twin pairs were at risk for obesity based on their body mass or their family history.) In one study, 12 sets of the twins were put under 24-hour supervision in a college dormitory. Six days a week they ate 1,000 extra calories a day, and one day they were allowed to eat normally. They could read, play video games, play cards and watch television, but exercise was limited to one 30-minute daily walk. Over the course of the 120-day study, the twins consumed 84,000 extra calories beyond their basic needs.

That experimental binge should have translated into a weight gain of roughly 24 pounds (based on 3,500 calories to a pound). But some gained less than 10 pounds, while others gained as much as 29 pounds. The amount of weight gained and how the fat was distributed around the body closely matched among brothers, but varied considerably among the different sets of twins. Some brothers gained three times as much fat around their abdomens as others, for instance. When the researchers conducted similar exercise studies with the twins, they saw the patterns in reverse, with some twin sets losing more pounds than others on the same exercise regimen. The findings, the researchers wrote, suggest a form of “biological determinism” that can make a person susceptible to weight gain or loss.

But while there is widespread agreement that at least some risk for obesity is inherited, identifying a specific genetic cause has been a challenge. In October 2010, the journal Nature Genetics reported that researchers have so far confirmed 32 distinct genetic variations associated with obesity or body-mass index. One of the most common of these variations was identified in April 2007 by a British team studying the genetics of Type 2 diabetes. According to Timothy Frayling at the Institute of Biomedical and Clinical Science at the University of Exeter, people who carried a variant known as FTO faced a much higher risk of obesity — 30 percent higher if they had one copy of the variant; 60 percent if they had two.

This FTO variant is surprisingly common; about 65 percent of people of European or African descent and an estimated 27 to 44 percent of Asians are believed to carry at least one copy of it. Scientists don’t understand how the FTO variation influences weight gain, but studies in children suggest the trait plays a role in eating habits. In one 2008 study led by Colin Palmer of the University of Dundee in Scotland, Scottish schoolchildren were given snacks of orange drinks and muffins and then allowed to graze on a buffet of grapes, celery, potato chips and chocolate buttons. All the food was carefully monitored so the researchers knew exactly what was consumed. Although all the children ate about the same amount of food, as weighed in grams, children with the FTO variant were more likely to eat foods with higher fat and calorie content. They weren’t gorging themselves, but they consumed, on average, about 100 calories more than children who didn’t carry the gene. Those who had the gene variant had about four pounds more body fat than noncarriers.
I have been tempted to send in my own saliva sample for a DNA test to find out if my family carries a genetic predisposition for obesity. But even if the test came back negative, it would only mean that my family doesn’t carry a known, testable genetic risk for obesity. Recently the British television show “Embarrassing Fat Bodies” asked Frayling’s lab to test for fat-promoting genes, and the results showed one very overweight family had a lower-than-average risk for obesity.

A positive result, telling people they are genetically inclined to stay fat, might be self-fulfilling. In February, The New England Journal of Medicine published a report on how genetic testing for a variety of diseases affected a person’s mood and health habits. Over all, the researchers found no effect from disease-risk testing, but there was a suggestion, though it didn’t reach statistical significance, that after testing positive for fat-promoting genes, some people were more likely to eat fatty foods, presumably because they thought being fat was their genetic destiny and saw no sense in fighting it.

While knowing my genetic risk might satisfy my curiosity, I also know that heredity, at best, would explain only part of why I became overweight. I’m much more interested in figuring out what I can do about it now.
The National Weight Control Registry tracks 10,000 people who have lost weight and have kept it off. “We set it up in response to comments that nobody ever succeeds at weight loss,” says Rena Wing, a professor of psychiatry and human behavior at Brown University’s Alpert Medical School, who helped create the registry with James O. Hill, director of the Center for Human Nutrition at the University of Colorado at Denver. “We had two goals: to prove there were people who did, and to try to learn from them about what they do to achieve this long-term weight loss.” Anyone who has lost 30 pounds and kept it off for at least a year is eligible to join the study, though the average member has lost 70 pounds and remained at that weight for six years.

Wing says that she agrees that physiological changes probably do occur that make permanent weight loss difficult, but she says the larger problem is environmental, and that people struggle to keep weight off because they are surrounded by food, inundated with food messages and constantly presented with opportunities to eat. “We live in an environment with food cues all the time,” Wing says. “We’ve taught ourselves over the years that one of the ways to reward yourself is with food. It’s hard to change the environment and the behavior.”

There is no consistent pattern to how people in the registry lost weight — some did it on Weight Watchers, others with Jenny Craig, some by cutting carbs on the Atkins diet and a very small number lost weight through surgery. But their eating and exercise habits appear to reflect what researchers find in the lab: to lose weight and keep it off, a person must eat fewer calories and exercise far more than a person who maintains the same weight naturally. Registry members exercise about an hour or more each day — the average weight-loser puts in the equivalent of a four-mile daily walk, seven days a week. They get on a scale every day in order to keep their weight within a narrow range. They eat breakfast regularly. Most watch less than half as much television as the overall population. They eat the same foods and in the same patterns consistently each day and don’t “cheat” on weekends or holidays. They also appear to eat less than most people, with estimates ranging from 50 to 300 fewer daily calories.

Kelly Brownell, director of the Rudd Center for Food Policy and Obesity at Yale University, says that while the 10,000 people tracked in the registry are a useful resource, they also represent a tiny percentage of the tens of millions of people who have tried unsuccessfully to lose weight. “All it means is that there are rare individuals who do manage to keep it off,” Brownell says. “You find these people are incredibly vigilant about maintaining their weight. Years later they are paying attention to every calorie, spending an hour a day on exercise. They never don’t think about their weight.”

Janice Bridge, a registry member who has successfully maintained a 135-pound weight loss for about five years, is a perfect example. “It’s one of the hardest things there is,” she says. “It’s something that has to be focused on every minute. I’m not always thinking about food, but I am always aware of food.”
Bridge, who is 66 and lives in Davis, Calif., was overweight as a child and remembers going on her first diet of 1,400 calories a day at 14. At the time, her slow pace of weight loss prompted her doctor to accuse her of cheating. Friends told her she must not be paying attention to what she was eating. “No one would believe me that I was doing everything I was told,” she says. “You can imagine how tremendously depressing it was and what a feeling of rebellion and anger was building up.”

After peaking at 330 pounds in 2004, she tried again to lose weight. She managed to drop 30 pounds, but then her weight loss stalled. In 2006, at age 60, she joined a medically supervised weight-loss program with her husband, Adam, who weighed 310 pounds. After nine months on an 800-calorie diet, she slimmed down to 165 pounds. Adam lost about 110 pounds and now weighs about 200.

During the first years after her weight loss, Bridge tried to test the limits of how much she could eat. She used exercise to justify eating more. The death of her mother in 2009 consumed her attention; she lost focus and slowly regained 30 pounds. She has decided to try to maintain this higher weight of 195, which is still 135 pounds fewer than her heaviest weight.

“It doesn’t take a lot of variance from my current maintenance for me to pop on another two or three pounds,” she says. “It’s been a real struggle to stay at this weight, but it’s worth it, it’s good for me, it makes me feel better. But my body would put on weight almost instantaneously if I ever let up.”

So she never lets up. Since October 2006 she has weighed herself every morning and recorded the result in a weight diary. She even carries a scale with her when she travels. In the past six years, she made only one exception to this routine: a two-week, no-weigh vacation in Hawaii.

She also weighs everything in the kitchen. She knows that lettuce is about 5 calories a cup, while flour is about 400. If she goes out to dinner, she conducts a Web search first to look at the menu and calculate calories to help her decide what to order. She avoids anything with sugar or white flour, which she calls her “gateway drugs” for cravings and overeating. She has also found that drinking copious amounts of water seems to help; she carries a 20-ounce water bottle and fills it five times a day. She writes down everything she eats. At night, she transfers all the information to an electronic record. Adam also keeps track but prefers to keep his record with pencil and paper.

“That transfer process is really important; it’s my accountability,” she says. “It comes up with the total number of calories I’ve eaten today and the amount of protein. I do a little bit of self-analysis every night.”
Bridge and her husband each sought the help of therapists, and in her sessions, Janice learned that she had a tendency to eat when she was bored or stressed. “We are very much aware of how our culture taught us to use food for all kinds of reasons that aren’t related to its nutritive value,” Bridge says.

Bridge supports her careful diet with an equally rigorous regimen of physical activity. She exercises from 100 to 120 minutes a day, six or seven days a week, often by riding her bicycle to the gym, where she takes a water-aerobics class. She also works out on an elliptical trainer at home and uses a recumbent bike to “walk” the dog, who loves to run alongside the low, three-wheeled machine. She enjoys gardening as a hobby but allows herself to count it as exercise on only those occasions when she needs to “garden vigorously.” Adam is also a committed exerciser, riding his bike at least two hours a day, five days a week.

Janice Bridge has used years of her exercise and diet data to calculate her own personal fuel efficiency. She knows that her body burns about three calories a minute during gardening, about four calories a minute on the recumbent bike and during water aerobics and about five a minute when she zips around town on her regular bike.

“Practically anyone will tell you someone biking is going to burn 11 calories a minute,” she says. “That’s not my body. I know it because of the statistics I’ve kept.”

Based on metabolism data she collected from the weight-loss clinic and her own calculations, she has discovered that to keep her current weight of 195 pounds, she can eat 2,000 calories a day as long as she burns 500 calories in exercise. She avoids junk food, bread and pasta and many dairy products and tries to make sure nearly a third of her calories come from protein. The Bridges will occasionally share a dessert, or eat an individual portion of Ben and Jerry’s ice cream, so they know exactly how many calories they are ingesting. Because she knows errors can creep in, either because a rainy day cuts exercise short or a mismeasured snack portion adds hidden calories, she allows herself only 1,800 daily calories of food. (The average estimate for a similarly active woman of her age and size is about 2,300 calories.)

Just talking to Bridge about the effort required to maintain her weight is exhausting. I find her story inspiring, but it also makes me wonder whether I have what it takes to be thin. I have tried on several occasions (and as recently as a couple weeks ago) to keep a daily diary of my eating and exercise habits, but it’s easy to let it slide. I can’t quite imagine how I would ever make time to weigh and measure food when some days it’s all I can do to get dinner on the table between finishing my work and carting my daughter to dance class or volleyball practice. And while I enjoy exercising for 30- or 40-minute stretches, I also learned from six months of marathon training that devoting one to two hours a day to exercise takes an impossible toll on my family life.

Bridge concedes that having grown children and being retired make it easier to focus on her weight. “I don’t know if I could have done this when I had three kids living at home,” she says. “We know how unusual we are. It’s pretty easy to get angry with the amount of work and dedication it takes to keep this weight off. But the alternative is to not keep the weight off. ”

“I think many people who are anxious to lose weight don’t fully understand what the consequences are going to be, nor does the medical community fully explain this to people,” Rudolph Leibel, an obesity researcher at Columbia University in New York, says. “We don’t want to make them feel hopeless, but we do want to make them understand that they are trying to buck a biological system that is going to try to make it hard for them.”

Leibel and his colleague Michael Rosenbaum have pioneered much of what we know about the body’s response to weight loss. For 25 years, they have meticulously tracked about 130 individuals for six months or longer at a stretch. The subjects reside at their research clinic where every aspect of their bodies is measured. Body fat is determined by bone-scan machines. A special hood monitors oxygen consumption and carbon-dioxide output to precisely measure metabolism. Calories burned during digestion are tracked. Exercise tests measure maximum heart rate, while blood tests measure hormones and brain chemicals. Muscle biopsies are taken to analyze their metabolic efficiency. (Early in the research, even stool samples were collected and tested to make sure no calories went unaccounted for.) For their trouble, participants are paid $5,000 to $8,000.

Eventually, the Columbia subjects are placed on liquid diets of 800 calories a day until they lose 10 percent of their body weight. Once they reach the goal, they are subjected to another round of intensive testing as they try to maintain the new weight. The data generated by these experiments suggest that once a person loses about 10 percent of body weight, he or she is metabolically different than a similar-size person who is naturally the same weight.

The research shows that the changes that occur after weight loss translate to a huge caloric disadvantage of about 250 to 400 calories. For instance, one woman who entered the Columbia studies at 230 pounds was eating about 3,000 calories to maintain that weight. Once she dropped to 190 pounds, losing 17 percent of her body weight, metabolic studies determined that she needed about 2,300 daily calories to maintain the new lower weight. That may sound like plenty, but the typical 30-year-old 190-pound woman can consume about 2,600 calories to maintain her weight — 300 more calories than the woman who dieted to get there.
Scientists are still learning why a weight-reduced body behaves so differently from a similar-size body that has not dieted. Muscle biopsies taken before, during and after weight loss show that once a person drops weight, their muscle fibers undergo a transformation, making them more like highly efficient “slow twitch” muscle fibers. A result is that after losing weight, your muscles burn 20 to 25 percent fewer calories during everyday activity and moderate aerobic exercise than those of a person who is naturally at the same weight. That means a dieter who thinks she is burning 200 calories during a brisk half-hour walk is probably using closer to 150 to 160 calories.

Another way that the body seems to fight weight loss is by altering the way the brain responds to food. Rosenbaum and his colleague Joy Hirsch, a neuroscientist also at Columbia, used functional magnetic resonance imaging to track the brain patterns of people before and after weight loss while they looked at objects like grapes, Gummi Bears, chocolate, broccoli, cellphones and yo-yos. After weight loss, when the dieter looked at food, the scans showed a bigger response in the parts of the brain associated with reward and a lower response in the areas associated with control. This suggests that the body, in order to get back to its pre-diet weight, induces cravings by making the person feel more excited about food and giving him or her less willpower to resist a high-calorie treat.

“After you’ve lost weight, your brain has a greater emotional response to food,” Rosenbaum says. “You want it more, but the areas of the brain involved in restraint are less active.” Combine that with a body that is now burning fewer calories than expected, he says, “and you’ve created the perfect storm for weight regain.” How long this state lasts isn’t known, but preliminary research at Columbia suggests that for as many as six years after weight loss, the body continues to defend the old, higher weight by burning off far fewer calories than would be expected. The problem could persist indefinitely. (The same phenomenon occurs when a thin person tries to drop about 10 percent of his or her body weight — the body defends the higher weight.) This doesn’t mean it’s impossible to lose weight and keep it off; it just means it’s really, really difficult.

Lynn Haraldson, a 48-year-old woman who lives in Pittsburgh, reached 300 pounds in 2000. She joined Weight Watchers and managed to take her 5-foot-5 body down to 125 pounds for a brief time. Today, she’s a member of the National Weight Control Registry and maintains about 140 pounds by devoting her life to weight maintenance. She became a vegetarian, writes down what she eats every day, exercises at least five days a week and blogs about the challenges of weight maintenance. A former journalist and antiques dealer, she returned to school for a two-year program on nutrition and health; she plans to become a dietary counselor. She has also come to accept that she can never stop being “hypervigilant” about what she eats. “Everything has to change,” she says. “I’ve been up and down the scale so many times, always thinking I can go back to ‘normal,’ but I had to establish a new normal. People don’t like hearing that it’s not easy.”
What’s not clear from the research is whether there is a window during which we can gain weight and then lose it without creating biological backlash. Many people experience transient weight gain, putting on a few extra pounds during the holidays or gaining 10 or 20 pounds during the first years of college that they lose again. The actor Robert De Niro lost weight after bulking up for his performance in “Raging Bull.” The filmmaker Morgan Spurlock also lost the weight he gained during the making of “Super Size Me.” Leibel says that whether these temporary pounds became permanent probably depends on a person’s genetic risk for obesity and, perhaps, the length of time a person carried the extra weight before trying to lose it. But researchers don’t know how long it takes for the body to reset itself permanently to a higher weight. The good news is that it doesn’t seem to happen overnight.

“For a mouse, I know the time period is somewhere around eight months,” Leibel says. “Before that time, a fat mouse can come back to being a skinny mouse again without too much adjustment. For a human we don’t know, but I’m pretty sure it’s not measured in months, but in years.”

Nobody wants to be fat. In most modern cultures, even if you are healthy — in my case, my cholesterol and blood pressure are low and I have an extraordinarily healthy heart — to be fat is to be perceived as weak-willed and lazy. It’s also just embarrassing. Once, at a party, I met a well-respected writer who knew my work as a health writer. “You’re not at all what I expected,” she said, eyes widening. The man I was dating, perhaps trying to help, finished the thought. “You thought she’d be thinner, right?” he said. I wanted to disappear, but the woman was gracious. “No,” she said, casting a glare at the man and reaching to warmly shake my hand. “I thought you’d be older.”

If anything, the emerging science of weight loss teaches us that perhaps we should rethink our biases about people who are overweight. It is true that people who are overweight, including myself, get that way because they eat too many calories relative to what their bodies need. But a number of biological and genetic factors can play a role in determining exactly how much food is too much for any given individual. Clearly, weight loss is an intense struggle, one in which we are not fighting simply hunger or cravings for sweets, but our own bodies.

While the public discussion about weight loss tends to come down to which diet works best (Atkins? Jenny Craig? Plant-based? Mediterranean?), those who have tried and failed at all of these diets know there is no simple answer. Fat, sugar and carbohydrates in processed foods may very well be culprits in the nation’s obesity problem. But there is tremendous variation in an individual’s response.

The view of obesity as primarily a biological, rather than psychological, disease could also lead to changes in the way we approach its treatment. Scientists at Columbia have conducted several small studies looking at whether injecting people with leptin, the hormone made by body fat, can override the body’s resistance to weight loss and help maintain a lower weight. In a few small studies, leptin injections appear to trick the body into thinking it’s still fat. After leptin replacement, study subjects burned more calories during activity. And in brain-scan studies, leptin injections appeared to change how the brain responded to food, making it seem less enticing. But such treatments are still years away from commercial development. For now, those of us who want to lose weight and keep it off are on our own.

One question many researchers think about is whether losing weight more slowly would make it more sustainable than the fast weight loss often used in scientific studies. Leibel says the pace of weight loss is unlikely to make a difference, because the body’s warning system is based solely on how much fat a person loses, not how quickly he or she loses it. Even so, Proietto is now conducting a study using a slower weight-loss method and following dieters for three years instead of one.

Given how hard it is to lose weight, it’s clear, from a public-health standpoint, that resources would best be focused on preventing weight gain. The research underscores the urgency of national efforts to get children to exercise and eat healthful foods.

But with a third of the U.S. adult population classified as obese, nobody is saying people who already are very overweight should give up on weight loss. Instead, the solution may be to preach a more realistic goal. Studies suggest that even a 5 percent weight loss can lower a person’s risk for diabetes, heart disease and other health problems associated with obesity. There is also speculation that the body is more willing to accept small amounts of weight loss.

But an obese person who loses just 5 percent of her body weight will still very likely be obese. For a 250-pound woman, a 5 percent weight loss of about 12 pounds probably won’t even change her clothing size. Losing a few pounds may be good for the body, but it does very little for the spirit and is unlikely to change how fat people feel about themselves or how others perceive them.

So where does that leave a person who wants to lose a sizable amount of weight? Weight-loss scientists say they believe that once more people understand the genetic and biological challenges of keeping weight off, doctors and patients will approach weight loss more realistically and more compassionately. At the very least, the science may compel people who are already overweight to work harder to make sure they don’t put on additional pounds. Some people, upon learning how hard permanent weight loss can be, may give up entirely and return to overeating. Others may decide to accept themselves at their current weight and try to boost their fitness and overall health rather than changing the number on the scale.

For me, understanding the science of weight loss has helped make sense of my own struggles to lose weight, as well as my mother’s endless cycle of dieting, weight gain and despair. I wish she were still here so I could persuade her to finally forgive herself for her dieting failures. While I do, ultimately, blame myself for allowing my weight to get out of control, it has been somewhat liberating to learn that there are factors other than my character at work when it comes to gaining and losing weight. And even though all the evidence suggests that it’s going to be very, very difficult for me to reduce my weight permanently, I’m surprisingly optimistic. I may not be ready to fight this battle this month or even this year. But at least I know what I’m up against.

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I don't know of anyone who is OBSCENELY fat. I do know of people who used to be "meaty" and have manged to keep it off for a long time. Don't give up if you are trying to lose weight... but do it wisely. Either way, enjoy life, enjoy food, and lead a healthy lifestyle! Regardless of your weight, size and shape.. HAPPY NEW YEAR!