Whenever a recipe calls for flour or bread crumbs, substitute, almond flour.

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Leading the Sustainability Charge

By Adam Aston

The word “sustainability” may evoke fuzzy stereotypes of do-gooders putting ideals ahead of profits. But for today’s global corporations, it’s an essential modus operandi. The idea is to build mutually beneficial relationships with customers, employees, and investors for many years — not just this quarter. A classic example is Unilever’s program to provide free medical care in developing markets. This creates immediate goodwill and helps build a future generation of healthier, wealthier consumers with a soft spot for Unilever brands.

Sustainability is the best way forward in a world where new sales will increasingly come from developing markets and where key resources are likely to be in short supply. Innovest Strategic Value Advisors, a financial consultancy, has codified this thinking into an analytical model that rates companies according to dozens of sustainability measures

Beyond The Green Corporation

Imagine a world in which eco-friendly and socially responsible practices actually help a company’s bottom line. It’s closer than you think

Under conventional notions of how to run a conglomerate like Unilever, CEO Patrick Cescau should wake up each morning with a laserlike focus: how to sell more soap and shampoo than Procter & Gamble Co. (PG ) But ask Cescau about the $52 billion Dutch-British giant’s biggest strategic challenges for the 21st century, and the conversation roams from water-deprived villages in Africa to the planet’s warming climate.

The world is Unilever’s laboratory. In Brazil, the company operates a free community laundry in a São Paulo slum, provides financing to help tomato growers convert to eco-friendly “drip” irrigation, and recycles 17 tons of waste annually at a toothpaste factory. Unilever funds a floating hospital that offers free medical care in Bangladesh, a nation with just 20 doctors for every 10,000 people. In Ghana, it teaches palm oil producers to reuse plant waste while providing potable water to deprived communities. In India, Unilever staff help thousands of women in remote villages start micro-enterprises. And responding to green activists, the company discloses how much carbon dioxide and hazardous waste its factories spew out around the world.

As Cescau sees it, helping such nations wrestle with poverty, water scarcity, and the effects of climate change is vital to staying competitive in coming decades. Some 40% of the company’s sales and most of its growth now take place in developing nations. Unilever food products account for roughly 10% of the world’s crops of tea and 30% of all spinach. It is also one of the world’s biggest buyers of fish. As environmental regulations grow tighter around the world, Unilever must invest in green technologies or its leadership in packaged foods, soaps, and other goods could be imperiled. “You can’t ignore the impact your company has on the community and environment,” Cescau says. CEOs used to frame thoughts like these in the context of moral responsibility, he adds. But now, “it’s also about growth and innovation. In the future, it will be the only way to do business.”

A remarkable number of CEOs have begun to commit themselves to the same kind of sustainability goals Cescau has pinpointed, even in profit- obsessed America. For years, the term “sustainability” has carried a lot of baggage. Put simply, it’s about meeting humanity’s needs without harming future generations. It was a favorite cause among economic development experts, human rights activists, and conservationists. But to many U.S. business leaders, sustainability just meant higher costs and smacked of earnest U.N. corporate- responsibility conferences and the utopian idealism of Western Europe. Now, sustainability is “right at the top of the agendas” of more U.S. CEOs, especially young ones, says McKinsey Global Institute Chairman Lenny Mendonca.

MORE THAN PR
You can tell something is up just wading through the voluminous sustainability reports most big corporations post on their Web sites. These lay out efforts to cut toxic emissions, create eco-friendly products, help the poor, and cooperate with nonprofit groups. As recently as five years ago, such reports—if they appeared at all—were usually transparent efforts to polish the corporate image. Now there’s a more sophisticated understanding that environmental and social practices can yield strategic advantages in an interconnected world of shifting customer loyalties and regulatory regimes.

Embracing sustainability can help avert costly setbacks from environmental disasters, political protests, and human rights or workplace abuses—the kinds of debacles suffered by Royal Dutch Shell PLC (RDS ) in Nigeria and Unocal in Burma. “Nobody has an idea when such events can hit a balance sheet, so companies must stay ahead of the curve,” says Matthew J. Kiernan, CEO of Innovest Strategic Value Advisors. Innovest is an international research and advisory firm whose clients include large institutional investors. It supplied the data for this BusinessWeek Special Report and prepared a list of the world’s 100 most sustainable corporations, to be presented at the Jan. 24-28 World Economic Forum in Davos, Switzerland.

The roster of advocates includes Jeffrey Immelt, CEO of General Electric Co. (GE ), who is betting billions to position GE as a leading innovator in everything from wind power to hybrid engines. Wal-Mart Stores Inc. (WMT ), long assailed for its labor and global sourcing practices, has made a series of high-profile promises to slash energy use overall, from its stores to its vast trucking fleets, and purchase more electricity derived from renewable sources. GlaxoSmithKline (GSK ) discovered that, by investing to develop drugs for poor nations, it can work more effectively with those governments to make sure its patents are protected. Dow Chemical Co. (DOW ) is increasing R&D in products such as roof tiles that deliver solar power to buildings and water treatment technologies for regions short of clean water. “There is 100% overlap between our business drivers and social and environmental interests,” says Dow CEO Andrew N. Liveris.

Striking that balance is not easy. Many noble efforts fail because they are poorly executed or never made sense to begin with. “If there’s no connection to a company’s business, it doesn’t have much leverage to make an impact,” says Harvard University business guru Michael Porter. Sustainability can be a hard proposition for investors, too. Decades of experience show that it’s risky to pick stocks based mainly on a company’s long-term environmental or social-responsibility targets.

Nevertheless, new sets of metrics, which Innovest and others designed to measure sustainability efforts, have helped convince CEOs and boards that they pay off. Few Wall Street analysts, for example, have tried to assess how much damage Wal-Mart’s reputation for poor labor and environmental practices did to the stock price. But New York’s Communications Consulting Worldwide (CCW), which studies issues such as reputation, puts it in stark dollars and cents. CCW calculates that if Wal-Mart had a reputation like that of rival Target Corp. (TGT ), its stock would be worth 8.4% more, adding $16 billion in market capitalization.

Serious money is lining up behind the sustainability agenda. Assets of mutual funds that are designed to invest in companies meeting social responsibility criteria have swelled from $12 billion in 1995 to $178 billion in 2005, estimates trade association Social Investment Forum. Boston’s State Street Global Advisors alone handles $77 billion in such funds. And institutions with $4 trillion in assets, including charitable trusts and government pension funds in Europe and states such as California, pledge to weigh sustainability factors in investment decisions.

Why the sudden urgency? The growing clout of watchdog groups making savvy use of the Internet is one factor. New environmental regulations also play a powerful role. Electronics manufacturers slow to wean their factories and products off toxic materials, for example, could be at a serious disadvantage as Europe adopts additional, stringent restrictions. American energy and utility companies that don’t cut fossil fuel reliance could lose if Washington joins the rest of the industrialized world in ordering curbs on greenhouse gas emissions. Such developments help explain why Exxon Mobil Corp. (XOM ), long opposed to linking government policies with global warming theories, is now taking part in meetings to figure out what the U.S. should do to cut emissions.

Investors who think about these issues obviously have long time horizons. But they encounter knotty problems when trying to peer beyond the next quarter’s results to a future years down the road. Corporations disclose the value of physical assets and investments in equipment and property. But U.S. regulators don’t require them to quantify environmental, social, or labor practices. Accountants call such squishy factors “intangibles.” These items aren’t found on a corporate balance sheet, yet can be powerful indicators of future performance.

If a company is at the leading edge of understanding and preparing for megatrends taking shape in key markets, this could constitute a valuable intangible asset. By being the first fast-food chain to stop using unhealthy trans fats, Wendy’s International Inc. (WEN ) may have a competitive edge now that New York City has banned the additives in restaurants. McDonald’s Corp. (MCD ), which failed to do so, could have a future problem.

Rising investor demand for information on sustainability has spurred a flood of new research. Goldman Sachs, Deutsche Bank Securities (DB ), ubs (UBS ), Citigroup (C ), Morgan Stanley, and other brokerages have formed dedicated teams assessing how companies are affected by everything from climate change and social pressures in emerging markets to governance records. “The difference in interest between three years ago and now is extraordinary,” says former Goldman Sachs (GS ) Asset Management CEO David Blood, who heads the Enhanced Analytics Initiative, a research effort on intangibles by 22 brokerages. He also leads Generation Investment Management, co-founded in 2004 with former Vice-President Al Gore, which uses sustainability as an investment criterion.

Perhaps the most ambitious effort is by Innovest, founded in 1995 by Kiernan, a former KPMG senior partner. Besides conventional financial performance metrics, Innovest studies 120 different factors, such as energy use, health and safety records, litigation, employee practices, regulatory history, and management systems for dealing with supplier problems. It uses these measures to assign grades ranging from AAA to CCC, much like a bond rating, to 2,200 listed companies. Companies on the Global 100 list on BusinessWeek’s Web site include Nokia Corp. (NOK ) and Ericsson (ERICY ), which excel at tailoring products for developing nations, and banks such as hsbc Holdings (HBC ) and abn-Amro (ABN ) that study the environmental impact of projects they help finance.

Some of Innovest’s conclusions are counterintuitive. Hewlett-Packard (HPQ ) and Dell (DELL ) both rate AAA, for example; market darling Apple (AAPL ) gets a middling BBB on the grounds of weaker oversight of offshore factories and lack of a “clear environmental business strategy.” An Apple spokesman contests that it is a laggard, citing the company’s leadership in energy-efficient products and in cutting toxic substances. Then there’s Sony Corp. (SNE ) vs. Nintendo. Wall Street loves the latter for a host of reasons, not least that its Wii video game system, the first to let users simulate actions such as swinging a sword or tennis racket, was a Christmas blockbuster. Sony, meanwhile, has a famously dysfunctional home electronics arm, and was embarrassed by exploding laptop batteries and long delays in bringing out its PlayStation 3 game console. Nintendo’s stock has more than tripled in three years; Sony’s has languished.

WEIGHING THE EFFORTS
Viewed through the lens of sustainability, however, Sony looks like the better bet. It is an industry leader in developing energy-efficient appliances. It also learned from a 2001 fiasco, when illegal cadmium was found in PlayStation cables bought from outside suppliers. That cost Sony $85 million, says Hidemi Tomita, Sony’s corporate responsibility general manager. Now, Sony has a whole corporate infrastructure for controlling its vast supplier network, helping it avert or quickly fix problems. Nintendo, a smaller Kyoto-based company focused on games, shows less evidence of the global management systems needed to cope with sudden regulatory shifts or supplier problems, says Innovest. A Nintendo spokesman says it meets all environmental rules and is “always reviewing and considering” the merits of new global sustainability guidelines.

BP seems to disprove the sustainability thesis altogether. CEO John Browne has preached environmentalism for a decade, and BP consistently ranked atop most sustainability indexes. Yet in the past two years it has been hit with a refinery explosion that killed 15 in Texas, a fine for safety violations at a refinery in Ohio, a major oil pipeline leak in Alaska, and a U.S. Justice Dept. probe into suspected manipulation of oil prices.Browne has recently announced his retirement. BP’s shares have slid 10% since late April. Exxon’s are up around 12%.

Innovest still rates BP a solid AA, while labeling Exxon a riskier BB. And PetroChina? Innovest gives it a CCC. Here’s why: BP wins points for plowing $8 billion into alternative energies to diversify away from oil and engages community and environmental groups. Exxon has done less to curb greenhouse gas emissions and promote renewables and has big projects in trouble spots like Chad. “I would still say Exxon is a bigger long-term risk,” says Innovest’s Kiernan. Petro- China is easier to justify. Begin with its safety record: A gas well explosion killed 243 people in 2003; another fatal explosion in 2005 spewed toxic benzene into a river, leaving millions temporarily without water. PetroChina has been slow to invest in alternative energy, Innovest says, and its parent company has big bets in the Sudan.

Do Innovest’s metrics make a reliable guide for picking stocks? Dozens of studies have looked for direct relationships between a company’s social and environmental practices and its financial performance. So far the results are mixed, and Kiernan admits Innovest can’t prove a causal link. That’s little help to portfolio managers who must post good numbers by yearend. “The crux of the problem is that we are looking at things from the long term, but we’re still under short-term review from our clients,” says William H. Page, who oversees socially responsible investing for State Street Global Advisors.

TALKING A GOOD FIGHT
Yet Kiernan and many other experts maintain sustainability factors are good proxies of management quality. “They show that companies tend to be more strategic, nimble, and better equipped to compete in the complex, high-velocity global environment,” Kiernan explains. That also is the logic behind Goldman Sachs’s intangibles research. In its thick annual assessments of global energy and mining companies, for example, it ranks companies on the basis of sustainability factors, financial returns, and access to new resource reserves. Top-ranking companies, such as British Gas, Shell, and Brazil’s Petrobras (PBR ), are leaders in all three categories. For the past two years, the stocks of elite companies on its list bested their industry peers by more than 5%—while laggards underperformed, Goldman says.

Still, BP’s (BP ) woeful performance highlights a serious caveat to the corporate responsibility crusade. Companies that talk the most about sustainability aren’t always the best at executing. Ford Motor Co. (F ) is another case in point. Former CEO William C. Ford Jr. has championed green causes for years. He famously spent $2 billion overhauling the sprawling River Rouge (Mich.) complex, putting on a 10-acre grass roof to capture rainwater. Ford also donated $25 million to Conservation International for an environmental center.

But Ford was flat-footed in the area most important to its business: It kept churning out gas-guzzling SUVs and pickups. “Having a green factory was not Ford’s core issue. It was fuel economy,” says Andrew S. Winston, director of a Yale University corporate environmental strategy project and co-author of the book Green to Gold.

The corporate responsibility field is littered with lofty intentions that don’t pay off. As a result, many CEOs are unsure what to do exactly. In a recent McKinsey & Co. study of 1,144 top global executives, 79% predicted at least some responsibility for dealing with future social and political issues would fall on corporations. Three of four said such issues should be addressed by the CEO. But only 3% said they do a good job dealing with social pressures. “This is uncomfortable territory because most CEOs have not been trained to sense or react to the broader landscape,” says McKinsey’s Mendonca. “For the first time, they are expected to be statesmen as much as they are functional business leaders.” Adding to the complexity, says Harvard’s Porter, each company must custom-design initiatives that fit its own objectives.

Dow Chemical is looking at the big picture. It sees a market in the need for low-cost housing and is developing technologies such as eco-friendly Styrofoam used for walls. CEO Liveris also cites global water scarcity as a field in which Dow can “marry planetary issues with market opportunity.” The U.N. figures 1.2 billion people lack access to clean water. Dow says financial solutions could help 300 million of them. That could translate into up to $3 billion in sales for Dow, which has a portfolio of cutting-edge systems for filtering minute contaminants from water. To reach the poor, Dow is working with foundations and the U.N. to raise funds for projects.

Philips Electronics (PHG ) also is building strategies around global megatrends. By 2050, the U.N. predicts, 85% of people will live in developing nations. But shortages of health care are acute. Among Philips’ many projects are medical vans that reach remote villages, allowing urban doctors to diagnose and treat patients via satellite. Philips has also developed low-cost water-purification technology and a smokeless wood-burning stove that could reduce the 1.6 million deaths annually worldwide from pulmonary diseases linked to cooking smoke. “For us, sustainability is a business imperative,” says Philips Chief Procurement Officer Barbara Kux, who chairs a sustainability board that includes managers from all business units.

Such laudable efforts, even if successful, may not help managers make their numbers next quarter. But amid turbulent global challenges, they could help investors sort long-term survivors from the dinosaurs.

Take a look at the World Clock that shows the current status of major global health, environmental and social statistics, updated in real time. You can see the rate of population growth, new cases of disease, injury, death, biodiversity loss, marriage and divorce…. It’s like a (rather depressing) impact dashboard for the Planet! This kind of ‘impact context’ should be a touchstone for any impact analysis– if focused down to the region where a company or organization does its work, it makes a great starting point for what the “addressable market” is in terms of any of these social or environmental issues.

World Clock’s makers compiled it from highly credible sources of statistical datasets, but they have not verified any of it and it may be spotty in parts, so it would be worth verifying if you plan to use it.

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HEALTH CARE
Fresenius Medical Care, IMS Health, Quest Diagnostics

Germany’s Fresenius and New Jersey’s Quest Diagnostics both stand out for promoting wellness. The two have managed to help improve their products by focusing on sustainable design and business practices. In Fresenius dialysis systems, for example, the company tracks the cost per treatment in terms of energy, water use, and waste generated. Each year, it tries to trim these measures, while at the same time improving the dialysis system’s performance and the company’s profits. As a provider of sales management and the company’s profits. As a provider of sales management and market research services, IMS Health in Fairfield, Conn., doesn’t have a big environmental footprint, yet has made sustainability a central value.

When Jean-Pierre Garnier took over as CEO of GlaxoSmithKline (GSK ) seven years ago, the company’s reputation on corporate social responsibility was at its nadir. As part of a coalition of 39 pharmaceutical companies, the drugmaker was suing Nelson Mandela’s South African government for voiding patents on prescription drugs. Mandela’s top priority was giving desperately sick patients access to HIV treatments, and GSK—the world’s largest supplier—was standing in the way. “It was a public relations disaster,” Garnier concedes.

The experience convinced Garnier that GSK should lead the crusade to improve access to medicine. In 2001, GSK became the first major drugmaker to sell its AIDS medicines at cost in 100 countries worldwide. And it has granted eight licenses to local companies to produce generic versions of these medicines.

In fact, GSK sells 90% of its vaccines, in volume terms, at not-for-profit prices to customers in the developing world. In 2005, it set a new paradigm in the vaccine industry. It chose Mexico over other, wealthier nations as the launch pad for Rotarix, a new vaccine against gastrointestinal rotavirus. “We wanted to get the vaccine to the children who needed it most,” Garnier explains.

Creating medicines for the Third World while still posting a profit required fancy financial footwork. GSK has formed 14 different partnerships with the World Health Organization and other nongovernmental bodies, and with philanthropies such as the Bill & Melinda Gates Foundation. These programs provided funding for research on two different HIV vaccines, new treatments for tuberculosis, and a pediatric vaccine against malaria. In the latter case, a collaboration with the Gates Foundation and a group called the Malaria Vaccine Initiative led to a vaccine that provides a minimum of 18 months of protection against malaria. It could be on the market within four years. “The commitment [of GSK] to developing a malaria vaccine is outstanding,” says Dr. Tore Godal, the former head of the Global Alliance for Vaccines & Immunization (GAVI).

Garnier says efforts such as these give the company several advantages over its rivals. Top scientists are drawn to GSK because they want their research to make a difference. Doing good, and being admired for it, also boosts general morale at the company, he says. “This creates a more aligned and engaged workforce, which helps us outperform our competitors.”

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PHARMACEUTICALS
Roche, Novo Nordisk, GlaxoSmithKline

Balancing contrary goals — earning healthy profits while making drugs affordable to the poor — is one of Big Pharma’s most daunting global challenges. All three of the drugmakers here score well by tackling this problem head on. Switzerland’s Roche has committed to setting up local factories in sub-Saharan Africa and other impoverished regions to produce generic HIV/AIDS medicines. GSK, based in London, is the sole company with a team of scientists researching tuberculosis, malaria, and HIV/AIDS, all three priority-diseases as identified by the U.N.’s World Health Organization. Novo Nordisk is working to make its diabetes products available worldwide. The Danish company has also developed a sustainable diabetes-care model for developing countries that aims to slow or reverse the onset of diabetes, rather than merely sell drugs to treat the disease.

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UTILITIES
FPL Group, Iberdrola, Scottish & Southern Energy

In just a few years, FPL Group, the parent of Florida Power & Light, has emerged from its home market to develop solar and wind energy projects that span 24 states — more than any other big energy player in the U.S. The Jupiter (Fla.) utility is also regarded as a leader in communicating such efforts to its shareholders. Across the Atlantic, Scottish & Southern Energy, based in Britain, sets a high standard for clean energy, as well: Renewable assets represent 17% of its total capacity. At Spain’s Iberdrola, one of Europe’s fastest-growing diversified utilities, renewable energy is a top growth goal too. Already one of the Continent’s largest wind developers, the Bilbao-based utility is pursuing wave power and is developing some of the world’s largest offshore wind farms.

Red Wine

By Sally Squires, April 22, 2008, Washington Post – There’s mounting evidence that drinking wine and other alcoholic beverages increases the risk of breast cancer.

That’s not the image that many people have about sipping wine, beer or other alcoholic beverages in moderation. A recent Harvard study of 878 people found that nearly two-thirds of drinkers and about a third of teetotalers considered such imbibing to be safe and healthful. So healthful that about 30 percent of those surveyed said the purported health benefits of alcohol are one reason they drink.

The link between alcohol and breast cancer is something that “almost nobody in the study had heard about,” says the survey’s lead author, Kenneth Mukamal, an internist at Beth Israel Deaconess Hospital in Boston. Only 10 percent correctly identified breast cancer as a possible risk of moderate drinking, the researchers reported in the journal Family Medicine.

Since the survey ended, Mukamal continues to informally poll people at cocktail parties. “I’ve spoken with other colleagues and friends who I would have considered to be fairly sophisticated consumers,” he says. “And most have no idea about this, either.”

Yet just this month, Danish researchers added to a substantial base of evidence linking alcohol consumption to an increased risk of breast cancer in women. These results offer a cautionary note for younger women and underscore that it’s never too early to go easy on alcohol. The researchers tracked nearly 10,000 women for 27 years. They found that the amount of alcohol the women consumed when the study began, rather than after menopause, correlated best with their breast cancer risk nearly three decades later.

If women do drink, there’s widespread agreement that they should avoid having more than one drink per day. (A drink is 5 ounces of wine, 12 ounces of beer or 1.5 ounces of distilled spirits such as whiskey, tequila or vodka.) Just that amount of alcohol translates to “about a 10 percent increased risk of breast cancer,” says Eric Rimm, an associate professor of epidemiology and nutrition at the Harvard School of Public Health.

More alcohol equals more risk. How much more? “Some studies suggest that two or more drinks per day are associated with about a 30 to 40 percent increase in the risk of breast cancer,” says JoAnn E. Manson, chief of preventive medicine at Harvard’s Brigham and Women’s Hospital and a professor of medicine at Harvard Medical School. For women who have other risk factors — a mother or sister with breast cancer, for example — “that can be a substantial risk,” Manson notes.

Just how alcohol raises breast cancer risk is something that researchers are still trying to understand. Alcohol is known to boost estrogen and other hormones, which are linked to breast cancer. In animals, alcohol has also produced some abnormalities of the mammary gland.

Mixing alcohol with hormone replacement therapy can be particularly risky, since alcohol and estrogen seem to augment each other. “That combination is something to avoid,” Manson says.

But there may be ways to help cut the risk from drinking alcohol. One nutrient under investigation is the B vitamin, folic acid. Also known as folate, this vitamin gets its name from the Latin word for leaf, because it occurs in green, leafy vegetables, such as spinach, turnip greens and Swiss chard. Citrus fruits and dried beans are also rich in folate. Research suggests that women who eat a lot of fruit and vegetables have a lower risk of breast cancer.

Since 1998, the Food and Drug Administration has mandated folate fortification in grain products, such as bread and pasta, to help prevent spina bifida and other neural-tube birth defects. Folate is also a common ingredient of multivitamins and of prenatal vitamins.

Alcohol blocks folate absorption from food. So researchers have wondered whether diets high in folate might offer protection against breast cancer among women who drink. A 1998 study published in the Journal of the American Medical Association studied nearly 3,500 women with breast cancer and found no link between folate intake and overall breast cancer risk. But when researchers looked at women who had at least one drink of alcohol per day, they found that breast cancer risk was greatest among those with the lowest folate intake. “Our findings suggest that the excess risk of breast cancer associated with alcohol consumption may be reduced by adequate folate intake,” the team reported.

In March, Manson and her colleagues published a report of a 10-year study of multivitamin use and breast cancer risk in nearly 40,000 women. Taking a multivitamin did not protect against breast cancer, except in women who consumed at least one drink daily. Those results “suggest that multivitamin use might help to counteract the elevated risk of breast cancer for women consuming alcohol,” Manson says.

But experts say that doesn’t mean that it’s okay to imbibe and then pop a multivitamin or eat a lot of spinach to compensate. “There’s no conclusive evidence that any vitamin or nutrient can cancel out the adverse effects of alcohol on breast cancer,” Manson says. “Studies to date have been inconsistent.”

Nor is there any evidence that one type of alcohol is better — or worse — than any other in terms of breast cancer risk. Red wine is often touted for health benefits. But there’s “no clear evidence that beer or liquor is more or less likely to increase breast cancer risk than wine,” Manson says.

What counts is how much you drink. Simply put, the more alcohol a woman drinks, the greater her risk of breast cancer. Or to put it another way, everything in moderation.

A new study in mice indicates that overeating, rather than the 1) ___ it causes, is the trigger for developing metabolic syndrome, a collection of heath risk factors that increases an individual’s chances of developing insulin resistance, fatty liver, heart disease and type 2 diabetes. How and where the body stores excess, unused 2) ___ appears to matter most when determining a person’s risk of developing metabolic syndrome, researchers at UT Southwestern Medical Center suggest. Most people today think that obesity itself causes metabolic syndrome. We’re ingrained to think that obesity is the cause of all health problems, when in fact it is the spillover of fat into organs other than fat cells that damages these organs, such as the heart and the liver. Depositing fatty 3) ___ in fat cells where they belong, actually delays that harmful spillover. The study, is to be published in a future issue of the Proceedings of the National Academy of Sciences. It is among the first to suggest that weight gain is an early symptom of pre-metabolic syndrome, rather than a direct 4) ___. Obesity delays the onset of metabolic syndrome, but it doesn’t prevent it. People who are obese or overweight are on the road to developing metabolic syndrome unless they stop overeating. Sooner or later, it will happen. Currently about 50 million Americans suffer from metabolic syndrome. The exact cause of metabolic syndrome is 5) ___, but obesity and lack of exercise have been considered to be the primary underlying contributors to its development. Several studies in Dallas have shown that overweight patients with metabolic syndrome have increased fat levels in their liver, heart and pancreas. Individuals with congenital generalized lipodystrophy — a genetic condition in which people are born with no fat cells in which to store fat — develop metabolic syndrome at an earlier age than people who are obese. They also develop more severe cases of 6) ___ syndrome earlier than their obese counterparts. The goal of this study was to determine whether an individual’s capacity to store fat in fat cells plays a role in whether they develop metabolic syndrome and type 2 diabetes and at what point that occurs. For the study, the researchers compared mice genetically altered to prevent their fat cells from expanding when overfed to mice with no such protections against becoming obese. The normal mice got fat when overfed, but didn’t develop signs of metabolic syndrome until about 7 weeks into the experiment, at about 12 weeks of age. The mice engineered to remain slim, however, enjoyed no such pre-diabetic honeymoon period. Some became seriously ill at 4 to 5 weeks of age and displayed evidence of severe heart problems and marked hyperglycemia by 10 weeks of age, a full 8 weeks before the normal mice displayed even minimal heart problems. The genetically altered mice also suffered devastating damage to heart cells and to the insulin-secreting cells in their pancreas. Mice engineered to stay slim got sick quicker because the extra calories were not stored in the 7) ___ cells, the one place in the body equipped to store fat. Instead, fat was stored in other tissues, mimicking what happens in people with congenital generalized lipodystrophy. Recognition of this should encourage physicians and obese patients to pursue more aggressive interventions before they develop metabolic 8) ___, rather than after the onset of disease, as is customary. Mice genetically engineered to be obese are at no more risk of developing metabolic syndrome than normal mice. It’s not the amount of body fat, but where it is stored in the body that appears to matter most to health. It’s better to put surplus calories in fat cells than in the rest of the body because fat cells are designed specifically for fat storage. You won’t be as trim, but you’ll be 9) ___.The study results also imply that any gene that impairs the ability to store fat in the fat cells likely predisposes an individual to metabolic syndrome and type 2 diabetes.

ANSWERS: 1) obesity; 2) calories; 3) molecules; 4) cause; 5) unknown; 6) metabolic; 7) fat; 8) syndrome; 9) healthier

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Photograph by Ralf-Finn Hestoft

Neil Shubin and Tiktaalik

By Nell Porter Brown, Harvard University Magazine – In 2005, parents and school officials in Dover, Pennsylvania, were locked in a courtroom debate over a school-board mandate that intelligent design be presented as an alternative to evolution in ninth-grade science classes. The judge in the case ultimately ruled in the parents’ favor, deciding that the requirement was unconstitutional. Throughout the trial, paleontologist Neil Shubin, Ph.D. ’87, Bensley professor in the department of organismal biology and anatomy at the University of Chicago, struggled to remain quiet in his office: on his desk lay the bones of a strange flat-headed, fish-cum-crocodile-like creature-with-a-neck that he and colleagues had found the year before while scraping away at ancient rocks in the Canadian Arctic.

Roughly 375 million years old, from the Late Devonian period, the fossilized creature was a genus of the extinct sarcopterygian (lobe-finned) fish that shares several key features with tetrapods (early four-legged animals). In addition to the neck and non-conical head, Tiktaalik roseae, as it was named, boasted expanded ribs and parts of a shoulder, along with webbed fins—inside which were also primitive bones corresponding to an upper arm, forearm, and pieces of a wrist. All are explicitly non-fish features. Shubin and other scientists say Tiktaalik helps bridge the gap in our understanding of what changes occurred as sea animals crept ashore, and plays a critical role in understanding—and proving—human origins.

“During the Dover trial, I couldn’t tell anyone apart from colleagues about our find,” Shubin says now, with a smile: the news was an exclusive, scheduled to be announced in Nature’s April 2006 cover story. Most of the nation’s news media, major publications, and science magazines followed up with articles about Tiktaalik (the word means “large, freshwater fish” in the Inuktitut dialect of Inuit).

Hailed as “the fish that crawled out of the water” and “the missing link,” Tiktaalik is by far the most important discovery of Shubin’s career, which has centered on the evolution of limbed beings. “I’ve devoted my life to this evolutionary biology stuff—I love it,” he exclaims. “I enjoy going to work because it’s fun working with worms, fish, and salamanders. I think it’s beautiful that remedies for the problems we suffer from will be found by seeing pieces of us nestled in the most primitive and humble creatures that live on the earth.”

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Photograph courtesy of Neil Shubin

Remains, and a reconstruction of what researchers believe Tiktaalik roseae looked like as it roamed its corner of the earth millions of years ago

His new book, Your Inner Fish, is an infectious exploration of the 3.5-billion-year history of the human body. It traces our organs back to fossils and prehistoric DNA—how our arm and hand bones came from fins; how our teeth first formed as spiky structures in the mouths of tiny, ancient, jawless lamprey-like fish known as conodonts; and how major aspects of our genome are similar to those of worms. Our ability to talk, for example, depends on the larynx, which is composed primarily of cartilage akin to the gill bars in a fish or shark. Even hiccups—a nerve spasm and inhalation, followed almost immediately (35 milliseconds, Shubin writes) by the “hic” sound—are the product of our shared history with fish and tadpoles, respectively. And the process through which teeth first formed in fish—at base, from the interaction between two layers of tissue—is the same process involved in the subsequent development of scales, hairs, feathers, and sweat glands.

Shubin says he wrote the book to explain his work to his father, Seymour Shubin, who still writes crime novels and thrillers for a living at 87. “I gave him the first draft and he said, ‘I don’t understand it,’” Shubin said at a winter reading at Harvard Book Store in Cambridge. “He told me, ‘Neil, nobody ever lost money writing a page turner.’ I said, ‘Dad, I’m a scientist. We don’t write page turners.’ But I wrote it over again. And this time he liked it.”

Your Inner Fish, in fact, is something of an adventure tale. It pulls in the reader even though the Tiktaalik discovery took six years and four often frustrating, error-filled trips into deep wilderness to complete. “For starters, there were polar bears,” says Shubin, a city boy from Philadelphia. “And polar bears eat people.” On the group’s first expedition to the Canadian Arctic, in 1999—which Shubin calls a “colossal bad choice” all around—they took rifles and motion detectors, which they set up in their tents before going to sleep. Not long after, the detectors went off and everyone jumped up, cocked their guns, and raced outside. Nothing was there. This scenario played out at least four times before someone realized that it was not lurking man-eaters setting the detectors off, but ferocious winds. “These detectors were made for suburban New Jersey, not the Arctic,” Shubin jokes. “You’ve just got to learn in fieldwork that you never get it just right.”

That wasn’t the first field trip to leave a strong impression on him. As a child, he loved going to museums, especially the Academy of Natural Sciences in Philadelphia and the Natural History Museum in New York City. In high school, he worked on an urban archaeological site and “loved ancient Egypt and Tutankhamen and seeing the past inside the dirt,” he explains. “Paleontology pulled me into the immediacy of discoveries. If you know where to look, and crack inside the rocks, and find a physical piece of evidence that can change the way we look at our past—this struck me as very powerful.” At Columbia, he majored in biology and anthropology, which led to paleontology and then doctoral work at Harvard.

In the 1980s, academic research in anatomy and development focused on the relationships between living creatures and fossils on the cellular level, using embryos. “Only a handful of people were doing it, and few as well as those at Harvard,” Shubin points out. (This was before new technological tools enabled scientists to work on the molecular level.) His first Harvard-affiliated expedition came in 1983, on the field team of professor of biology and curator of vertebrate paleontology Farish A. Jenkins Jr., who was working in the American West, looking for new sites and early mammals that could help explain how humans developed the ability to chew. Shubin writes that the mammalian method for chewing first emerged in fossil records dating from 225 million to 195 million years ago, in big-headed reptiles that walked on all fours and had bony jaws with teeth that fell out and re-grew throughout their lives.

Having finally learned how to spot bones in the dust, mud, and dirt, Shubin grew eager to lead his own trip. He explored 200-million-year-old Connecticut rocks a half-day’s trip away from Cambridge before expanding to Nova Scotia; ultimately, he found enough bones to fill a few shoeboxes among the sandstone cliffs in the Bay of Fundy. Among them was a significant find: a piece of an early mouse-like mammal with a tiny jaw and a few teeth best seen under a microscope. The remains of this tritheledont, previously linked only to South Africa, showed it had a human way of chewing food. “I had an idea for field research and Harvard had the resources to support this independent research,” he says. “If that hadn’t existed, I wouldn’t be here talking about all of this today.”

By now, his main academic interest was the morphology of the tetrapod limb. Working with the embryos of salamanders, frogs, and fish, Shubin wrote his dissertation on developmental biology and the similarities between fins and limbs. He spent the next two years doing postdoctoral work at the University of California, Berkeley, where he also met and married geologist Michele Seidl ’85 (now director of planning for biological sciences at the University of Chicago). An 11-year stint at the University of Pennsylvania followed.

At Penn, and still searching for the origins of limbed creatures, Shubin focused his sights on the already well-studied Catskill Formation of Pennsylvania. In the Late Devonian age, when Shubin and others say some animals were making the switch from sea to land, this region was akin to today’s Amazon River delta, he notes, with many streams draining into a large sea where Pittsburgh now stands. In 1993, he and one of his graduate students, Ted Daeschler, began visiting rock zones recently blasted out by the state transportation department to prepare for more roadways. To their surprise, Shubin relates in Your Inner Fish, Daeschler one day found “a marvelous shoulder bone” that they named Hynerpeton, Greek for “little creeping animal from Hyner,” Pennsylvania.

The two men formed a dynamic partnership—Shubin always pushing on to the next target; Daeschler patiently working to examine a given spot thoroughly. In 1998 they were in Shubin’s office, having an academic argument about the next most plausible search sites, when one of them pulled out a geology textbook to prove a point and found a diagram that stopped them short. It showed three places on earth with known Late Devonian freshwater rocks: eastern North America—home of Hynerpeton; the east coast of Greenland (where the earliest known tetrapods had already been found); and well-exposed rocks in the Canadian Arctic that, the duo realized, were unexplored. No paleontological field guides existed for that area, but Shubin knew one man who had led previous trips to Greenland and was experienced enough to help them: Farish Jenkins. (Later that day, Shubin adds, he and Daeschler went to a Chinese restaurant where Shubin’s fortune cookie held this gem: “Soon you will be at the top of the world.” This slip of paper was taped to his office door for years.)

That first outing, in 1999—the time of the motion-detector debacle, when terrible weather kept the researchers inside tents for three weeks rereading every book they’d brought—was on Melville Island in the western part of the Canadian Arctic. They found plenty of fish fossils, but all appeared to be deep-water dwellers, not the shallows skimmers that ultimately crept on shore.

The following year, better prepared for five weeks in the wild, Shubin, Daeschler, and their team set up camp on Ellesmere Island, with permission from the Inuit people of the Nunavut Territory. One evening, an undergraduate in the party, Jason Downs, failed to return to the base camp on time. “We were very worried, but then he came limping into the cook tent with a wild-eyed stare, like he’d been chased by polar bears,” Shubin recalls. “But we knew he hadn’t been, because his pockets were full of bones.” That same night, the team spent hours (in the Arctic summer, the sun never sets) documenting the site and gathering fragments.

Fast-forward to July 2004. With grant money running out, and the prognosis looking poor, Shubin and Daeschler opted for a fourth and final trip (their third to Ellesmere). Shubin describes cracking ice and rock in the bottom of a quarry one day when he saw a patch of fossilized scales and a jaw-like “blob” in ice unlike any fish mouth he’d ever seen. The next day, while foraging at the top of the same quarry, Shubin’s colleague and former fellow graduate student Stephen Gatesy, Ph.D. ’89 (now a biology professor at Brown), dug out a piece of rock and “we realized we saw a flat-headed something, something unknown,” Shubin reports. “It was a snout sticking straight out from the rock.”

The team spent the rest of the summer painstakingly chipping away at the rock around the creature so they could wrap up the boulder-cum-fossil and transport it thousands of miles to the lab where, for two months, preparers used dental tools to pick apart the specimen. What was revealed was a creature with eyes on top of its flat head, a neck, upper arm bones, a wrist, parts of a palm, and “an elbow joint that Tiktaalik would’ve used to push itself up off the substrate, as if it were doing push-ups,” Shubin explains. “And it had ribs—larger and more expandable ribs than you’d ever see on a fish.” In short, “Tiktaalik is not a random find,” he says. “It is a piece of the human story.”

To date, the core research team has found about 20 individuals—based on isolated fins, jaws, and other pieces—but only about four really good specimens. “We’re the only people working up there and we’re going back this summer, in July, in hopes of finding more bones,” Shubin says. “You never know what’s going to happen when you get there, because of the weather, but the goal is to go to the original site and work on new areas around it” to find slightly younger or slightly older rocks and see if any bones they contain shed light on further developmental changes. The group has found other water-based creatures—some “really bizarre-looking” armored fish, some eight- or nine-foot-long predatory fish, and some fish as tiny as a fingernail.

Shubin is excited that the Tiktaalik find has also inspired other scientists, who are looking at new, undisclosed geological locations for more Late Devonian specimens. “We are beginning to unlock the mechanisms that underlie evolutionary change, so we can ask what is the genetic and developmental recipe that built the human, and how is it different from fish?” he says. “We’re at a moment in scientific discovery where we can begin to see that that kind of understanding is possible within our lifetimes, that the basic tool kit and developmental processes are very ancient—that a version of same tool kit that builds a worm builds a human. It’s been a remarkable time for paleontology, a very powerful revolution on a lot of scientific fronts.”

After his talk at Harvard Book Store, the audience asked Shubin questions that ranged from specifics about Tiktaalik’s anatomy to his arctic experiences and plans for the future, to his views on intelligent design and creationism. Did he think his discovery would sway religious beliefs? What should teachers say about Tiktaalik—how is it a scientific tool for students? “No degree of evidence will shift the views of a creationist, ” Shubin responded, then added with a laugh, “but if, next to my Tiktaalik, I’d found a human skull, then that would be truly devastating” to evolutionists. What about intelligent design? “I don’t have time for it because it’s not testable, it’s not science,” Shubin explained. “I have a job to do and that’s making hypotheses and going out in the field and finding out if they are true. I became a scientist because I like looking at creatures and discovering new things that tell us about the history of life.”

By Jonathan Weisman, April 11, 2008, The Washington Post – Freshman Rep. Kevin McCarthy (R) is a stickler for rules, a plus of sorts when you are one of six lawmakers serving on that quaintest of House entities, the 18th-century-vintage Franking Commission, which decides whether lawmakers’ constituent communications pass ethical muster.

He is also a Californian, a believer in the latest communications technology, especially video links to his own House performances. So when he discovered that embedding YouTube videos on his official Web site violated his commission’s prohibition on links to commercial sites, he brought the issue to the commission’s chairman, Rep. Michael Capuano (D-Mass.).

Capuano’s response may have been a tad cavalier — “just go ahead and do it; everyone else does” — but it did set the antiquated Franking Commission on a technological journey. The result is that within a month, that most modern of institutions, YouTube, plans to create a government ghetto, free of advertising, where lawmakers can post the videos of their choice.

Nobody has ever accused Congress of being particularly hip. Sen. Ted Stevens (R-Alaska) became something of a Luddite legend when he called the Internet “a series of tubes.”

“I make no bones about it. I don’t know anything about this stuff,” Capuano said with a shrug.

But they’re cottoning on. More than 100 House members have multimedia pages and YouTube links on their Web sites — all in violation of House rules that date to when lawmakers communicated with voters through snail mail and newsletters.

The reason is simple enough: The Franking Commission frowns on official links to campaign-related Web sites, political parties, advocacy groups and “any site the primary purpose of which is the conduct of commerce.”

Rep. Mike Pence (R-Ind.) has marveled aloud at the democratic possibilities presented by YouTube. But type his name in the YouTube search, click on his visit to Haditha, Iraq, and up pop related videos on Pence’s floor speeches, a Rush Limbaugh interview — and “Avril Lavigne-Hot.”

House and Senate members can use in-house video technology, but it’s slow and cumbersome, and the more lawmakers use the Capitol’s computer servers, the worse it gets. Just try using McCarthy’s squeaky-clean video gallery page. (Members of the Senate don’t seem to have a problem with creaky video service, however, because there are fewer of them.)

At a Franking Commission meeting earlier this year, McCarthy suggested directly embedding YouTube videos on lawmakers’ Web sites. Constituents would not be thrown to a commercial site, and would not wait endlessly watching their hourglass cursors. But even that pesky YouTube label on the lower right-hand corner was an advertisement of sorts.

So at a meeting this week, the commission hit on a compromise that could push House Web sites into the modern age of mass communications. Aides to House Speaker Nancy Pelosi (D-Calif.) put out a request for an easy-to-use video Web site that could establish a commercial-free zone devoid of Avril Lavigne footage or “Planet Unicorn” ring tones, another inexplicable byproduct of a search for Pence-related video.

Within a month, the one and only responder, YouTube, should have its commercial-free zone up and running, Capuano said. Republicans on the commission still fret that with only one such site, the House could be seen as picking winners and losers on the Web. Rep. Tom Price (R-Ga.), another commission member, said the panel’s Republicans want to keep the new rules fluid enough to use any future Web site that comes forward with a better plan.

“Technology moves fast. Congress moves slow,” he said.

But, hey, any video’s got to be better than the still-life photo gallery on Capuano’s admittedly old-school Web page.

“To me, the Web is a necessary evil,” he admitted, “like cellphones.”

Article From: http://runaholics.blogspot.com/

By Gina Kolata – The New York Times – THE runner’s high: Every athlete has heard of it, most seem to believe in it and many say they have experienced it. But for years scientists have reserved judgment because no rigorous test confirmed its existence.

Yes, some people reported that they felt so good when they exercised that it was as if they had taken mood-altering drugs. But was that feeling real or just a delusion? And even if it was real, what was the feeling supposed to be, and what caused it?

Some who said they had experienced a runner’s high said it was uncommon. They might feel relaxed or at peace after exercising, but only occasionally did they feel euphoric. Was the calmness itself a runner’s high?

Often, those who said they experienced an intense euphoria reported that it came after an endurance event.

My friend Marian Westley said her runner’s high came at the end of a marathon, and it was paired with such volatile emotions that the sight of a puppy had the power to make her weep.

Others said they experienced a high when pushing themselves almost to the point of collapse in a short, intense effort, such as running a five-kilometer race.

But then there are those like my friend Annie Hiniker, who says that when she finishes a 5-k race, the last thing she feels is euphoric. “I feel like I want to throw up,” she said.

The runner’s-high hypothesis proposed that there were real biochemical effects of exercise on the brain. Chemicals were released that could change an athlete’s mood, and those chemicals were endorphins, the brain’s naturally occurring opiates. Running was not the only way to get the feeling; it could also occur with most intense or endurance exercise.

The problem with the hypothesis was that it was not feasible to do a spinal tap before and after someone exercised to look for a flood of endorphins in the brain. Researchers could detect endorphins in people’s blood after a run, but those endorphins were part of the body’s stress response and could not travel from the blood to the brain. They were not responsible for elevating one’s mood. So for more than 30 years, the runner’s high remained an unproved hypothesis.

But now medical technology has caught up with exercise lore. Researchers in Germany, using advances in neuroscience, report in the current issue of the journal Cerebral Cortex that the folk belief is true: Running does elicit a flood of endorphins in the brain. The endorphins are associated with mood changes, and the more endorphins a runner’s body pumps out, the greater the effect.

Leading endorphin researchers not associated with the study said they accepted its findings.

“Impressive,” said Dr. Solomon Snyder, a neuroscience professor at Johns Hopkins and a discoverer of endorphins in the 1970’s.

“I like it,” said Huda Akil, a professor of neurosciences at the University of Michigan. “This is the first time someone took this head on. It wasn’t that the idea was not the right idea. It was that the evidence was not there.”

For athletes, the study offers a sort of vindication that runner’s high is not just a New Agey excuse for their claims of feeling good after a hard workout.

For athletes and nonathletes alike, the results are opening a new chapter in exercise science. They show that it is possible to define and measure the runner’s high and that it should be possible to figure out what brings it on. They even offer hope for those who do not enjoy exercise but do it anyway. These exercisers might learn techniques to elicit a feeling that makes working out positively addictive.

The lead researcher for the new study, Dr. Henning Boecker of the University of Bonn, said he got the idea of testing the endorphin hypothesis when he realized that methods he and others were using to study pain were directly applicable.

The idea was to use PET scans combined with recently available chemicals that reveal endorphins in the brain, to compare runners’ brains before and after a long run. If the scans showed that endorphins were being produced and were attaching themselves to areas of the brain involved with mood, that would be direct evidence for the endorphin hypothesis. And if the runners, who were not told what the study was looking for, also reported mood changes whose intensity correlated with the amount of endorphins produced, that would be another clincher for the argument.

Dr. Boecker and colleagues recruited 10 distance runners and told them they were studying opioid receptors in the brain. But the runners did not realize that the investigators were studying the release of endorphins and the runner’s high. The athletes had a PET scan before and after a two-hour run. They also took a standard psychological test that indicated their mood before and after running.

The data showed that, indeed, endorphins were produced during running and were attaching themselves to areas of the brain associated with emotions, in particular the limbic and prefrontal areas.

The limbic and prefrontal areas, Dr. Boecker said, are activated when people are involved in romantic love affairs or, he said, “when you hear music that gives you a chill of euphoria, like Rachmaninoff’s Piano Concerto No. 3.” The greater the euphoria the runners reported, the more endorphins in their brain.

“Some people have these really extreme experiences with very long or intensive training,” said Dr. Boecker, a casual runner and cyclist, who said he feels completely relaxed and his head is clearer after a run.

That was also what happened to the study subjects, he said: “You could really see the difference after two hours of running. You could see it in their faces.”

In a follow-up study, Dr. Boecker is investigating if running affects pain perception. “There are studies that showed enhanced pain tolerance in runners,” he said. “You have to give higher pain stimuli before they say, ‘O.K., this hurts.’ ”

And, he said, there are stories of runners who had stress fractures, even heart attacks, and kept on running.

Dr. Boecker and his colleagues have recruited 20 marathon runners and a similar number of nonathletes and are studying the perception of pain after a run, and whether there are related changes in brain scans. He is also having the subjects walk to see whether the effects, if any, are because of the intensity of the exercise.

The nonathletes can help investigators assess whether untrained people experience the same effects. Maybe one reason some people love intense exercise and others do not is that some respond with a runner’s high or changed pain perception.

Annie might question that. She loves to run, but wonders why. But her husband tells her that the look on her face when she is running is just blissful. So maybe even she gets a runner’s high.

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