F.D.A. Gives Early Approval to Leukemia Drug Iclusig

First there was Gleevec, the wonder cancer drug. Then came the sons of Gleevec. Now there is the grandson of Gleevec.

The Food and Drug Administration on Friday approved another Gleevec-like drug for the treatment of chronic myeloid leukemia, or C.M.L., adding to a crowded field vying to treat this rare cancer of white blood cells.

The new drug, Iclusig from Ariad Pharmaceuticals, works in some patients not helped by Gleevec or some of its imitators.

“The approval of Iclusig is important because it provides a treatment option to patients with C.M.L. who are not responding to other drugs,” Dr. Richard Pazdur, director of the agency’s office of cancer drugs, said in a statement.

Iclusig, known generically as ponatinib, is the first product to reach the market for Ariad, a biotechnology company in Cambridge, Mass., that was founded in 1991.

A tablet taken once a day, Iclusig (pronounced eye-CLUE-sig) will have a wholesale price of about $115,000 a year, the latest cancer drug to pierce the $100,000-a-year level. Ariad said the price was about 15 percent higher than the drug’s competitors’.

While the approval was expected, it came three months before the federal agency’s deadline of March 27, and the drug’s label allows broader use of the drug than some analysts expected. However, the label also contains a boxed warning about the side effects of blood clots and liver toxicity, something analysts did not expect.

Ariad’s shares, which have roughly doubled in the last year, sank 21 percent to $18.93 on Friday.

Chronic myeloid leukemia would seem at first glance to be an unattractive target for pharmaceutical companies. Not only is it rare — with about 5,000 new cases a year in the United States and 600 deaths — it is also one of the more effectively treated of cancers.

But it is also a well-understood cancer. Drug companies know how to attack it, so they do — something akin to looking for lost keys under the lamppost because that is where the light is. Iclusig is the third drug for chronic myeloid leukemia approved by the agency this year, after Pfizer’s Bosulif and Teva’s Synribo.

The disease occurs when pieces of two separate chromosomes come together to form what is known as the Philadelphia chromosome. A fusion of genes creates an aberrant protein, known as BCR-ABL, which fuels uncontrolled cell growth.

Gleevec, developed by Novartis and approved in 2001, inhibits the action of that errant protein. It turned chronic myeloid leukemia from a death sentence into a chronic disease for many patients and is still considered the paragon of molecularly targeted drugs. Global sales were $4.7 billion in 2011.

But about 20 to 30 percent of patients have cancers that do not respond to Gleevec or that develop resistance to it.

So companies developed other drugs — Tasigna from Novartis and Sprycel from Bristol-Myers Squibb — that also inhibit the aberrant protein but work in many of the cases that are resistant to Gleevec. But some cases do not respond to those drugs, either.

Iclusig was designed by chemists and computers at Ariad to work against cancer cells with a mutation — known as T315I — that makes them resistant to Gleevec, Tasigna and Sprycel.

However, Iclusig was approved not only for patients with that mutation but for any patient who has tried one of the other three drugs without success. Ariad estimates that each year about 2,500 patients with the disease switch therapies, making them candidates for Iclusig.

That can still be a lucrative market, given the high price of the drugs and the fact that patients must take them for the rest of their lives, which is usually many years. Dr. Harvey J. Berger, chief executive of Ariad since the company’s inception, said he expected annual sales to reach $600 million to $800 million in a few years.

The F.D.A. approved the drug based on a trial with 449 patients, all of whom received Iclusig. The patients had already tried treatment with one, two or three of the other drugs.

About 54 percent of patients in the early stage of the disease had a major cytogenic response, meaning a reduction in cells with the Philadelphia chromosome.

Iclusig was also approved Friday as a treatment for an even rarer cancer, acute lymphoblastic leukemia characterized by presence of the Philadelphia chromosome.

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F.D.A. Gives Early Approval to Leukemia Drug Iclusig

First there was Gleevec, the wonder cancer drug. Then came the sons of Gleevec. Now there is the grandson of Gleevec.

The Food and Drug Administration on Friday approved another Gleevec-like drug for the treatment of chronic myeloid leukemia, or C.M.L., adding to a crowded field vying to treat this rare cancer of white blood cells.

The new drug, Iclusig from Ariad Pharmaceuticals, works in some patients not helped by Gleevec or some of its imitators.

“The approval of Iclusig is important because it provides a treatment option to patients with C.M.L. who are not responding to other drugs,” Dr. Richard Pazdur, director of the agency’s office of cancer drugs, said in a statement.

Iclusig, known generically as ponatinib, is the first product to reach the market for Ariad, a biotechnology company in Cambridge, Mass., that was founded in 1991.

A tablet taken once a day, Iclusig (pronounced eye-CLUE-sig) will have a wholesale price of about $115,000 a year, the latest cancer drug to pierce the $100,000-a-year level. Ariad said the price was about 15 percent higher than the drug’s competitors’.

While the approval was expected, it came three months before the federal agency’s deadline of March 27, and the drug’s label allows broader use of the drug than some analysts expected. However, the label also contains a boxed warning about the side effects of blood clots and liver toxicity, something analysts did not expect.

Ariad’s shares, which have roughly doubled in the last year, sank 21 percent to $18.93 on Friday.

Chronic myeloid leukemia would seem at first glance to be an unattractive target for pharmaceutical companies. Not only is it rare — with about 5,000 new cases a year in the United States and 600 deaths — it is also one of the more effectively treated of cancers.

But it is also a well-understood cancer. Drug companies know how to attack it, so they do — something akin to looking for lost keys under the lamppost because that is where the light is. Iclusig is the third drug for chronic myeloid leukemia approved by the agency this year, after Pfizer’s Bosulif and Teva’s Synribo.

The disease occurs when pieces of two separate chromosomes come together to form what is known as the Philadelphia chromosome. A fusion of genes creates an aberrant protein, known as BCR-ABL, which fuels uncontrolled cell growth.

Gleevec, developed by Novartis and approved in 2001, inhibits the action of that errant protein. It turned chronic myeloid leukemia from a death sentence into a chronic disease for many patients and is still considered the paragon of molecularly targeted drugs. Global sales were $4.7 billion in 2011.

But about 20 to 30 percent of patients have cancers that do not respond to Gleevec or that develop resistance to it.

So companies developed other drugs — Tasigna from Novartis and Sprycel from Bristol-Myers Squibb — that also inhibit the aberrant protein but work in many of the cases that are resistant to Gleevec. But some cases do not respond to those drugs, either.

Iclusig was designed by chemists and computers at Ariad to work against cancer cells with a mutation — known as T315I — that makes them resistant to Gleevec, Tasigna and Sprycel.

However, Iclusig was approved not only for patients with that mutation but for any patient who has tried one of the other three drugs without success. Ariad estimates that each year about 2,500 patients with the disease switch therapies, making them candidates for Iclusig.

That can still be a lucrative market, given the high price of the drugs and the fact that patients must take them for the rest of their lives, which is usually many years. Dr. Harvey J. Berger, chief executive of Ariad since the company’s inception, said he expected annual sales to reach $600 million to $800 million in a few years.

The F.D.A. approved the drug based on a trial with 449 patients, all of whom received Iclusig. The patients had already tried treatment with one, two or three of the other drugs.

About 54 percent of patients in the early stage of the disease had a major cytogenic response, meaning a reduction in cells with the Philadelphia chromosome.

Iclusig was also approved Friday as a treatment for an even rarer cancer, acute lymphoblastic leukemia characterized by presence of the Philadelphia chromosome.

Read More..

Microsoft Battles Google by Hiring Political Brawler Mark Penn

SEATTLE — Mark Penn made a name for himself in Washington by bulldozing enemies of the Clintons. Now he spends his days trying to do the same to Google, on behalf of its archrival Microsoft.

Since Mr. Penn was put in charge of “strategic and special projects” at Microsoft in August, much of his job has involved efforts to trip up Google, which Microsoft has failed to dislodge from its perch atop the lucrative Internet search market.

Drawing on his background in polling, data crunching and campaigning, Mr. Penn created a holiday commercial that has been running during Monday Night Football and other shows, in which Microsoft criticizes Google for polluting the quality of its shopping search results with advertisements. “Don’t get scroogled,” it warns. His other projects include a blind taste test, Coke-versus-Pepsi style, of search results from Google and Microsoft’s Bing.

The campaigns by Mr. Penn, 58, a longtime political operative known for his brusque personality and scorched-earth tactics, are part of a broader effort at Microsoft to give its marketing the nimbleness of a political campaign, where a candidate can turn an opponent’s gaffe into a damaging commercial within hours. They are also a sign of the company’s mounting frustration with Google after losing billions of dollars a year on its search efforts, while losing ground to Google in the browser and smartphones markets and other areas.

Microsoft has long attacked Google from the shadows, whispering to regulators, journalists and anyone else who would listen that Google was a privacy-violating, anticompetitive bully. The fruits of its recent work in this area could come next week, when the Federal Trade Commission is expected to announce the results of its antitrust investigation of Google, a case that echoes Microsoft’s own antitrust suit in the 1990s. A similar investigation by the European Union is also wrapping up. A bad outcome for Google in either one would be a victory for Microsoft.

But Microsoft, based in Redmond, Wash., has realized that it cannot rely only on regulators to scrutinize Google — which is where Mr. Penn comes in. He is increasing the urgency of Microsoft’s efforts and focusing on their more public side.

In an interview, Mr. Penn said companies underestimated the importance of policy issues like privacy to consumers, as opposed to politicians and regulators. “It’s not about whether they can get them through Washington,” he said. “It’s whether they can get them through Main Street.”

Jill Hazelbaker, a Google spokeswoman, declined to comment on Microsoft’s actions specifically, but said that while Google also employed lobbyists and marketers, “our focus is on Google and the positive impact our industry has on society, not the competition.”

In Washington, Mr. Penn is a lightning rod. He developed a relationship with the Clintons as a pollster during President Bill Clinton’s 1996 re-election campaign, when he helped identify the value of “soccer moms” and other niche voter groups.

As chief strategist for Hillary Clinton’s unsuccessful 2008 campaign for president, he conceived the “3 a.m.” commercial that raised doubts about whether Barack Obama, then a senator, was ready for the Oval Office. Mr. Penn argued in an essay he wrote for Time magazine in May that “negative ads are, by and large, good for our democracy.”

But his approach has ended up souring many of his professional relationships. He left Mrs. Clinton’s campaign after an uproar about his consulting work for the government of Colombia, which was seeking the passage of a trade treaty with the United States that Mrs. Clinton, then a senator, opposed.

“Google should be prepared for everything but the kitchen sink thrown at them,” said a former colleague who worked closely with Mr. Penn in politics and spoke on condition of anonymity. “Actually, they should be prepared for the kitchen sink to be thrown at them, too.”

Hiring Mr. Penn demonstrates how seriously Microsoft is taking this fight, said Michael A. Cusumano, a business professor at M.I.T. who co-wrote a book about Microsoft’s browser war.

“They’re pulling out all the stops to do whatever they can to halt Google’s advance, just as their competition did to them,” Professor Cusumano said. “I suppose that if Microsoft can actually put a doubt in people’s mind that Google isn’t unbiased and has become some kind of evil empire, they might very well get results.”

Nick Wingfield reported from Seattle and Claire Cain Miller from San Francisco.

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Maurice Herzog, 93, Dies; Led Historic Himalaya Climb

Maurice Herzog, a French alpinist who was hailed as a hero in his country in 1950 when he and a fellow climber became the first men to conquer a peak of more than 26,000 feet, that of Annapurna I in the Himalayas, died on Thursday in Neuilly-sur-Seine, near Paris. He was 93.

His death was confirmed by Christian Brincourt, a longtime friend and former climbing partner. In a tribute, President François Hollande of France said Mr. Herzog’s climb was “engraved enduringly in our collective memory.”

Before Mr. Herzog led a team up Annapurna in the spring of 1950, men had in fact climbed higher — close to 28,000 feet on Mount Everest and K-2, the two tallest mountains in the world. But those climbers had not reached the summits, and it would be three years before Edmund Hillary and Tenzing Norgay did so on Everest.

Mr. Herzog and Louis Lachenal reached the summit of Annapurna — the world’s 10th-highest peak, at 26,545 feet — on June 3 in brutal conditions; Mr. Herzog suffered frostbite that cost him most of his fingers and toes.

His star rose higher after he wrote an account of the journey that became what some call the most popular mountaineering book ever written. Titled “Annapurna: The First Conquest of an 8,000-Meter Peak,” the book is a harrowing tale of courage, camaraderie and nearly catastrophic struggle.

“The whole of this book has been dictated at the American Hospital at Neuilly, where I am still having rather a difficult time,” he wrote in the introduction, a year after the journey. The book concluded with a famous inspirational line: “There are other Annapurnas in the lives of men.”

The book is said to have sold more than 11 million copies by 2000; National Geographic Adventure magazine called it “the most influential mountaineering book of all time”; Sports Illustrated ranked it 77th in its list of the top 100 sports books ever written. In recent years, however, Mr. Herzog was accused of suppressing competing versions of the climb for his own self-aggrandizement.

In the 2000 book “True Summit: What Really Happened on the Legendary Ascent of Annapurna,” the alpinist and writer David Roberts depicted Mr. Herzog as something of a glory hog. By Mr. Roberts’s account, Mr. Herzog used his prominence to obscure the achievement of Mr. Lachenal, whose diary often conflicted with Mr. Herzog’s book, telling of infighting among the climbers. (Mr. Lachenal also lost digits in the climb.)

Mr. Herzog’s daughter, Felicité, wrote a book in which she portrayed her father as a megalomaniac who “rewrote history, betrayed and neglected his entourage without ever having the sense of hurting anyone because society judged him to be so good.”

But he remained admired in France. Last year he was decorated with the Grand Cross of the Legion of Honor, France’s highest civilian honor.

Mr. Herzog was born on Jan. 15, 1919. He fought in the French resistance during the German occupation of France in World War II. After his famous climb, he served in several government posts, including as secretary of state for sports when Charles de Gaulle was prime minister and as mayor of the resort town of Chamonix in the French Alps. He was a member of the International Olympic Committee for 25 years and helped bring the 1992 winter games to Albertville, France.

He is survived by his daughter, from his first marriage, as well as his second wife, Elisabeth, and two sons, Mathias and Sébastien.

In 1953, Mr. Herzog wrote an essay for The New York Times in which he described the first time he went climbing in the Alps as a student, finding himself isolated, vulnerable, in peril — and thrilled.

“I believe what I felt that day closely resembles what we call happiness,” he wrote. “I also believe that if I felt such happiness in such rigorous circumstances it is because the planned, organized, predigested happiness that the modern world offers is not complete. It leaves certain sides of man’s nature unsatisfied.”

Scott Sayare contributed reporting from Paris.

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Advertising: Sean Avery Is Not the Average Ad Executive

IT is not surprising that someone who works in advertising once interned at Vogue and has the fashion sense, and looks, to model occasionally. Similarly, it is not unusual to find ex-athletes at agencies. Nor is it out of the ordinary that someone in the industry is also an owner of a bar. Or active in causes like marriage equality and helping the victims of Hurricane Sandy. Or turns up, from time to time, in the gossip columns.

When all that biographical information is on one résumé, however, the result is, to paraphrase a familiar slogan, not your father’s Madison Avenue.

The résumé belongs to Sean Avery, who spent 12 years playing for National Hockey League teams that included the New York Rangers. Not long after finishing his hockey career in March, Mr. Avery began working with David Lipman, the longtime advertising executive, whose business interests include the Lipman agency in New York.

For a time, the signers at the end of Mr. Avery’s e-mails described him as the chief strategy officer at Lipman. More recently, he has become “kind of an editor at large,” he said, handling a range of assignments for the agency and its parent, Revolate Holdings. Revolate also has investments in companies in apparel (Genetic Denim, Nic & Zoe), media (Archetypes, Tauntr) and sports (ProCamps, Spartan Race).

Along with working with Mr. Lipman, who is the chairman and chief creative officer at Lipman and chief creative officer at Revolate, Mr. Avery spends time with Michael Mendenhall, partner and president at Revolate, and Andrew Spellman, chief executive at Revolate.

Mr. Avery, who is 32, does not shy from discussing the sheer unexpectedness of what he calls “this transition I’ve gone through.”

When he replies to a question at a meeting or after-work event like, “Oh, so what brings you here?” Mr. Avery said, “You always see this shift in a person’s face, half confusion, half interest.”

But advertising is not so far afield, he added, because when he was playing hockey, “I was always marketing myself.”

In addition, Mr. Avery is keenly interested in technology and social media. And, as a former professional athlete, “I had the cash,” he said, to be “a consumer since I was 19, a high-end, luxury-brand consumer.”

The transition has not been seamless, Mr. Avery acknowledged.

“Sometimes I don’t do it the right way,” he said of his interactions at Lipman. “It’s not a locker room; you can’t challenge people the same way: ‘Let’s go. We need you.’ ”

When that impulse comes over him now, “I go for a walk,” he added, laughing.

“The hardest thing is the long days,” Mr. Avery said, referring to employees at the agency “who are in 10, 12 hours every day.”

“For 15 years I had the same day,” he recalled. “I would wake up, eat, practice, work out, eat and sleep, then I would go and play. So now, an eight- or nine-hour day in the office, I can’t do it.”

Still, “I love going in there,” Mr. Avery said, meaning the Lipman headquarters, in the meatpacking district, where he works from the top-floor office of Mr. Lipman.

A client who works with Mr. Avery is effusive in her praise.

“As a professional athlete, you have love of the game and passion, and Sean is certainly bringing that to Lipman,” said Susan Duffy, chief marketing officer at Stuart Weitzman, a shoe marketer, which just re-signed with the agency for a second year.

She ticked off attributes like “his love of business, his love of the luxury market, his love of fashion,” adding: “He wasn’t classically trained, with an M.B.A. or college. He has an M.B.A. degree in social networking. He’s a connector.”

Mr. Avery is involved in the campaign for the Stuart Weitzman line for spring and summer 2013, which will bring in the supermodel Kate Moss as the brand’s new face, to be photographed by Mario Testino. In a meeting last week at Lipman, Mr. Avery beamed as he offered a preview of ads featuring Ms. Moss in knee-high gladiator sandals.

“It was so odd how it all happened,” Mr. Lipman said of Mr. Avery’s arrival, “but it’s beautiful.”

Mr. Lipman and Mr. Avery met in May 2011, after a client suggested that Mr. Avery appear in a campaign for Hickey Freeman men’s suits. Mr. Lipman, familiar with Mr. Avery’s reputation as an outspoken agitator on (and sometimes off) the ice, demurred. Days later, Mr. Lipman read an article about Mr. Avery’s becoming the first pro athlete to speak out for legalizing same-sex marriage in New York State by appearing in a video for New Yorkers for Marriage Equality.

“I’m flabbergasted. It floored me,” Mr. Lipman said. Now, Mr. Avery is “integral to my thought processes; he challenges me, he supports me, he has in each meeting at least one idea.”

“That doesn’t mean there aren’t growing pains,” Mr. Lipman added, laughing, citing how, at 3 p.m., Mr. Avery, recalling his hockey life, will sometimes ask, “Isn’t it time for a nap?”

After Mr. Avery previewed the Stuart Weitzman ads, Mr. Lipman previewed a print and video campaign for another client, 7 for All Mankind jeans, that is to be introduced in February. Mr. Avery will appear in the campaign, sporting in some ads, through makeup, the kinds of black eye and cut lip emblematic of his previous career.

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Life Expectancy Rises Around World, Study Finds

A sharp decline in deaths from malnutrition and infectious diseases like measles and tuberculosis has caused a shift in global mortality patterns over the past 20 years, according to a report published on Thursday, with far more of the world’s population now living into old age and dying from diseases mostly associated with rich countries, like cancer and heart disease.

Tony Karumba/Agence France-Presse — Getty Images

Children in Nairobi, Kenya. Sub-Saharan Africa lagged in mortality gains, compared with Latin America, Asia and North Africa.

The shift reflects improvements in sanitation, medical services and access to food throughout the developing world, as well as the success of broad public health efforts like vaccine programs. The results are striking: infant mortality declined by more than half from 1990 to 2010, and malnutrition, the No. 1 risk factor for death and years of life lost in 1990, has fallen to No. 8.

At the same time, chronic diseases like cancer now account for about two out of every three deaths worldwide, up from just over half in 1990. Eight million people died of cancer in 2010, 38 percent more than in 1990. Diabetes claimed 1.3 million lives in 2010, double the number in 1990.

“The growth of these rich-country diseases, like heart disease, stroke, cancer and diabetes, is in a strange way good news,” said Ezekiel Emanuel, chairman of the department of medical ethics and health policy at the University of Pennsylvania. “It shows that many parts of the globe have largely overcome infectious and communicable diseases as a pervasive threat, and that people on average are living longer.”

In 2010, 43 percent of deaths in the world occurred at age 70 and older, compared with 33 percent of deaths in 1990, the report said. And fewer child deaths have brought up the mean age of death, which in Brazil and Paraguay jumped to 63 in 2010, up from 30 in 1970, the report said. The measure, an average of all deaths in a given year, is different from life expectancy, and is lower when large numbers of children die.

But while developing countries made big strides the United States stagnated. American women registered the smallest gains in life expectancy of all high-income countries’ female populations between 1990 and 2010. American women gained just under two years of life, compared with women in Cyprus, who lived 2.3 years longer and Canadian women who gained 2.4 years. The slow increase caused American women to fall to 36th place in the report’s global ranking of life expectancy, down from 22nd in 1990. Life expectancy for American women was 80.5 in 2010, up from 78.6 in 1990.

“It’s alarming just how little progress there has been for women in the United States,” said Christopher Murray, director of the Institute for Health Metrics and Evaluation, a health research organization financed by the Bill and Melinda Gates Foundation at the University of Washington that coordinated the report. Rising rates of obesity among American women and the legacy of smoking, a habit women formed later than men, are among the factors contributing to the stagnation, he said. American men gained in life expectancy, to 75.9 years from 71.7 in 1990.

Health experts from more than 300 institutions contributed to the report, which provided estimates of disease and mortality for populations in more than 180 countries. It was published in The Lancet, a British medical journal.

The World Health Organization issued a statement on Thursday saying that some of the estimates in the report differed substantially from those done by United Nations agencies, though others were similar. All comprehensive estimates of global mortality rely heavily on statistical modeling because only 34 countries — representing about 15 percent of the world’s population — produce quality cause-of-death data.

Sub-Saharan Africa was an exception to the trend. Infectious diseases, childhood illnesses and maternity-related causes of death still account for about 70 percent of the region’s disease burden, a measure of years of life lost due to premature death and to time lived in less than full health. In contrast, they account for just one-third in South Asia, and less than a fifth in all other regions. Sub-Saharan Africa also lagged in mortality gains, with the average age of death rising by fewer than 10 years from 1970 to 2010, compared with a more than 25-year increase in Latin America, Asia and North Africa.

Globally, AIDS was an exception to the shift of deaths from infectious to noncommunicable diseases. The epidemic is believed to have peaked, but still results in 1.5 million deaths each year.

Over all, the change means people are living longer, but it also raises troubling questions. Behavior affects people’s risks of developing cancer, heart disease and diabetes, and public health experts say it is far harder to get people to change their ways than to administer a vaccine that protects children from an infectious disease like measles.

“Adult mortality is a much harder task for the public health systems in the world,” said Colin Mathers, a senior scientist at the World Health Organization.

Tobacco use is a rising threat, especially in developing countries, and is responsible for almost six million deaths a year globally. Illnesses like diabetes are also spreading fast.

Donald G. McNeil Jr. contributed reporting.

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Life Expectancy Rises Around World, Study Finds

A sharp decline in deaths from malnutrition and infectious diseases like measles and tuberculosis has caused a shift in global mortality patterns over the past 20 years, according to a report published on Thursday, with far more of the world’s population now living into old age and dying from diseases mostly associated with rich countries, like cancer and heart disease.

Tony Karumba/Agence France-Presse — Getty Images

Children in Nairobi, Kenya. Sub-Saharan Africa lagged in mortality gains, compared with Latin America, Asia and North Africa.

The shift reflects improvements in sanitation, medical services and access to food throughout the developing world, as well as the success of broad public health efforts like vaccine programs. The results are striking: infant mortality declined by more than half from 1990 to 2010, and malnutrition, the No. 1 risk factor for death and years of life lost in 1990, has fallen to No. 8.

At the same time, chronic diseases like cancer now account for about two out of every three deaths worldwide, up from just over half in 1990. Eight million people died of cancer in 2010, 38 percent more than in 1990. Diabetes claimed 1.3 million lives in 2010, double the number in 1990.

“The growth of these rich-country diseases, like heart disease, stroke, cancer and diabetes, is in a strange way good news,” said Ezekiel Emanuel, chairman of the department of medical ethics and health policy at the University of Pennsylvania. “It shows that many parts of the globe have largely overcome infectious and communicable diseases as a pervasive threat, and that people on average are living longer.”

In 2010, 43 percent of deaths in the world occurred at age 70 and older, compared with 33 percent of deaths in 1990, the report said. And fewer child deaths have brought up the mean age of death, which in Brazil and Paraguay jumped to 63 in 2010, up from 30 in 1970, the report said. The measure, an average of all deaths in a given year, is different from life expectancy, and is lower when large numbers of children die.

But while developing countries made big strides the United States stagnated. American women registered the smallest gains in life expectancy of all high-income countries’ female populations between 1990 and 2010. American women gained just under two years of life, compared with women in Cyprus, who lived 2.3 years longer and Canadian women who gained 2.4 years. The slow increase caused American women to fall to 36th place in the report’s global ranking of life expectancy, down from 22nd in 1990. Life expectancy for American women was 80.5 in 2010, up from 78.6 in 1990.

“It’s alarming just how little progress there has been for women in the United States,” said Christopher Murray, director of the Institute for Health Metrics and Evaluation, a health research organization financed by the Bill and Melinda Gates Foundation at the University of Washington that coordinated the report. Rising rates of obesity among American women and the legacy of smoking, a habit women formed later than men, are among the factors contributing to the stagnation, he said. American men gained in life expectancy, to 75.9 years from 71.7 in 1990.

Health experts from more than 300 institutions contributed to the report, which provided estimates of disease and mortality for populations in more than 180 countries. It was published in The Lancet, a British medical journal.

The World Health Organization issued a statement on Thursday saying that some of the estimates in the report differed substantially from those done by United Nations agencies, though others were similar. All comprehensive estimates of global mortality rely heavily on statistical modeling because only 34 countries — representing about 15 percent of the world’s population — produce quality cause-of-death data.

Sub-Saharan Africa was an exception to the trend. Infectious diseases, childhood illnesses and maternity-related causes of death still account for about 70 percent of the region’s disease burden, a measure of years of life lost due to premature death and to time lived in less than full health. In contrast, they account for just one-third in South Asia, and less than a fifth in all other regions. Sub-Saharan Africa also lagged in mortality gains, with the average age of death rising by fewer than 10 years from 1970 to 2010, compared with a more than 25-year increase in Latin America, Asia and North Africa.

Globally, AIDS was an exception to the shift of deaths from infectious to noncommunicable diseases. The epidemic is believed to have peaked, but still results in 1.5 million deaths each year.

Over all, the change means people are living longer, but it also raises troubling questions. Behavior affects people’s risks of developing cancer, heart disease and diabetes, and public health experts say it is far harder to get people to change their ways than to administer a vaccine that protects children from an infectious disease like measles.

“Adult mortality is a much harder task for the public health systems in the world,” said Colin Mathers, a senior scientist at the World Health Organization.

Tobacco use is a rising threat, especially in developing countries, and is responsible for almost six million deaths a year globally. Illnesses like diabetes are also spreading fast.

Donald G. McNeil Jr. contributed reporting.

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Companies See High-Tech Factories as Fonts of Ideas

Heather Ainsworth for The New York Times

Workers at a G.E. battery plant in upstate New York. G.E. has researchers nearby, which allows for more collaboration.

SCHENECTADY, N.Y. — The Obama administration has long heralded the potential of American factories to offer good, stable middle-class jobs in an economy that desperately needs them. But experts say there might be another advantage to expanding manufacturing in the United States: a more innovative economy.

A growing chorus of economists, engineers and business leaders are warning that the evisceration of the manufacturing work force over the last 30 years might not have scarred just Detroit and the Rust Belt. It might have dimmed the country’s capacity to innovate and stunted the prospects for long-term growth.

“In sector after sector, we’ve lost our innovation edge because we don’t produce goods here anymore,” said Mitzi Montoya, dean of the college of technology and innovation at Arizona State University.

These experts say that in industries that produce complex, high-technology products — things like bioengineered tissues, not light bulbs — companies that keep their research and manufacturing employees close together might be more innovative than businesses that develop a schematic and send it overseas for low-wage workers to make. Moreover, clusters of manufacturers, where workers and ideas can naturally flow between companies, might prove more productive and innovative than the same businesses if they were spread across the country.

A General Electric facility in upstate New York provides a test case. In a custom-built facility the size of four football fields, workers are casting into thin tubes a kind of ceramic that G.E. invented. Those tubes get filled with a secret chemical “brownie mix,” packaged into batteries and shipped across the world.

The plant sits just a few miles down the road from the research campus where G.E. scientists developed the technology. That allows them to work out kinks on the assembly line, and test prototypes of and uses for the battery, the company’s scientists said.

“We’re not thinking about just one generation,” said Glen Merfeld of G.E.’s chemical energy systems laboratory, showing off a test battery his employees had run into exhaustion. “We’re working on the second, the third, the fourth, the fifth.”

The idea is to knit together manufacturing, design, prototyping and production, said Michael Idelchik, vice president for advanced technologies, who holds a dozen patents himself. “We believe that rather than a sequential process where you look at product design and then how to manufacture it, there is a simultaneous process,” Mr. Idelchik said. “We think it is key for sustaining our long-term competitive advantage.”

Economists and policy experts are now researching whether such strategies offer the same benefits for other businesses — and examining how those benefits might show up in national data on innovation, productivity and growth.

At the Massachusetts Institute of Technology, Suzanne Berger has helped to start the Production in the Innovation Economy project to study the subject. “It is something that’s very difficult to establish systematically,” said Professor Berger. “You really have to be willing to look at case-by-case evidence, qualitative evidence. That’s what we’re trying to do.”

Thus far, she said, the anecdotal evidence from about 200 companies has proved striking, with company after company detailing the advantages of keeping makers and thinkers together. That does not mean every business, she stressed. Companies with products early in their life cycle seemed to benefit more than ones with products on the market for years. So did companies making especially complicated or advanced goods, from new medicines to new machines.

“It’s the companies where the challenge of producing on a commercial scale requires levels of scientific activity that are just as complex as the original challenge of developing the technology,” Professor Berger said.

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In Cairo Crisis, Unheard Voice From the Poor

Tara Todras-Whitehill for The New York Times

In Boulaq, so long neglected that houses regularly collapse, there had been little expectation that leaders would provide. But the disregard of the new president has been harder to take. More Photos »

CAIRO — A faded poster of Hosni Mubarak hangs on a wall in a crumbling neighborhood here, reminding residents of an empty pledge to find jobs for young people. Down the street, a campaign banner for his successor, Mohamed Morsi, hangs across the road, a reminder of more recent promises unkept.

In the neighborhood, called Boulaq, so long neglected that houses regularly collapse, there was little expectation that Mr. Mubarak would provide. But Mr. Morsi’s disregard has been much harder to take.

“We had high hopes in God, that things would improve,” Fathi Hussein said as he built a desk of dark wood for one of his clients, who are dwindling. “I elected a president to be good for the country. I did not elect him to impose his opinions on me.”

Away from the protests and violence that have marked the painful struggle over Egypt’s identity in the run-up to a referendum on Saturday on a constitution, residents of Boulaq have their own reasons to be consumed with the crisis. The chants of the protesters, for bread and freedom, resonate in Boulaq’s alleyways. In many of its industrial workshops, passed from struggling fathers to penniless sons, disappointment with the president, his Muslim Brotherhood supporters as well as the leaders of the opposition grows daily.

There is a sense in Boulaq that the raging arguments would be better resolved in places like this, where most Egyptians live, carrying the burdens of poverty with no help from an indifferent state, and where the revolution’s promise of dignity is long overdue.

When he took office five months ago, Mr. Morsi seemed to understand. “He talked about the conditions of the poor, the people in the slums,” said Amr Abdul Hafiz, a barber. “He talked about the street vendors and the tuk-tuk drivers. We thought he felt for us.”

The barber and many of his neighbors were convinced that Mr. Morsi and the Brotherhood had earned their chance to rule. People remembered the Brotherhood’s charity after the earthquake in 1992, and its decades of struggle as an outlaw movement. In stages, though, doubts grew as the Brotherhood broke its promises and Mr. Morsi seized power, culminating in his decision to ram through his constitution. Boulaq’s residents, including the president’s supporters, bristled at the thought of being treated as subjects again.

“He became occupied with other issues,” Mr. Abdul Hafiz said. “They want power, to make up for all the injustice they suffered, as if we were the ones who inflicted the injustice on them.”

At night, the arguments rage at a storied cafe on Abu Talib Street, with an intensity that no one here recalls seeing before. By day, the arguments simmer, in a neighborhood whose former grandeur still peeks out from underneath the rot.

Everywhere, people tell stories about the government’s failures, suggesting that the new leaders had turned out no better than the old ones.

In the shadow of a fallen dwelling, one of many that make Boulaq look as if it suffered a war, a widow stood over workmen she had hired to fix a ruptured sewer pipe. The ministry assigned to handle such matters had ignored her calls for three months, so she and her neighbors collected the money to pay for the repairs themselves.

On Abu Talib Street, Mr. Abdul Hafiz fretted over the dangers facing his pregnant wife, whose belly was swelling with excessive amniotic fluid. An appointment to see a doctor at a private hospital, which would cost $80, was too expensive. The administrators at a public hospital told her she could see a doctor a month after she was supposed to give birth.

Security guards threw Mr. Abdul Hafiz out of the hospital when he pointed out how ridiculous that was.

He wanted a change from Mr. Mubarak, who had coverings placed over the houses in Boulaq during the public opening of a nearby building “to hide insects like us.” It was part of a pattern of neglect that stretched back for decades, when the land under the residents was sold to investors in shady deals that no one has untangled.

Mai Ayyad contributed reporting.

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Another Look at a Drink Ingredient, Brominated Vegetable Oil

James Edward Bates for The New York Times

Sarah Kavanagh, 15, of Hattiesburg, Miss., started an online petition asking PepsiCo to change Gatorade’s formula.

Sarah Kavanagh and her little brother were looking forward to the bottles of Gatorade they had put in the refrigerator after playing outdoors one hot, humid afternoon last month in Hattiesburg, Miss.

But before she took a sip, Sarah, a dedicated vegetarian, did what she often does and checked the label to make sure no animal products were in the drink. One ingredient, brominated vegetable oil, caught her eye.

“I knew it probably wasn’t from an animal because it had vegetable in the name, but I still wanted to know what it was, so I Googled it,” Ms. Kavanagh said. “A page popped up with a long list of possible side effects, including neurological disorders and altered thyroid hormones. I didn’t expect that.”

She threw the product away and started a petition on Change.org, a nonprofit Web site, that has almost 200,000 signatures. Ms. Kavanagh, 15, hopes her campaign will persuade PepsiCo, Gatorade’s maker, to consider changing the drink’s formulation.

Jeff Dahncke, a spokesman for PepsiCo, noted that brominated vegetable oil had been deemed safe for consumption by federal regulators. “As standard practice, we constantly evaluate our formulas and ingredients to ensure they comply with federal regulations and meet the high quality standards our consumers and athletes expect — from functionality to great taste,” he said in an e-mail.

In fact, about 10 percent of drinks sold in the United States contain brominated vegetable oil, including Mountain Dew, also made by PepsiCo; Powerade, Fanta Orange and Fresca from Coca-Cola; and Squirt and Sunkist Peach Soda, made by the Dr Pepper Snapple Group.

The ingredient is added often to citrus drinks to help keep the fruit flavoring evenly distributed; without it, the flavoring would separate.

Use of the substance in the United States has been debated for more than three decades, so Ms. Kavanagh’s campaign most likely is quixotic. But the European Union has long banned the substance from foods, requiring use of other ingredients. Japan recently moved to do the same.

“B.V.O. is banned other places in the world, so these companies already have a replacement for it,” Ms. Kavanagh said. “I don’t see why they don’t just make the switch.” To that, companies say the switch would be too costly.

The renewed debate, which has brought attention to the arcane world of additive regulation, comes as consumers show increasing interest in food ingredients and have new tools to learn about them. Walmart’s app, for instance, allows access to lists of ingredients in foods in its stores.

Brominated vegetable oil contains bromine, the element found in brominated flame retardants, used in things like upholstered furniture and children’s products. Research has found brominate flame retardants building up in the body and breast milk, and animal and some human studies have linked them to neurological impairment, reduced fertility, changes in thyroid hormones and puberty at an earlier age.

Limited studies of the effects of brominated vegetable oil in animals and in humans found buildups of bromine in fatty tissues. Rats that ingested large quantities of the substance in their diets developed heart lesions.

Its use in foods dates to the 1930s, well before Congress amended the Food, Drug and Cosmetic Act to add regulation of new food additives to the responsibilities of the Food and Drug Administration. But Congress exempted two groups of additives, those already sanctioned by the F.D.A. or the Department of Agriculture, or those experts deemed “generally recognized as safe.”

The second exemption created what Tom Neltner, director of the Pew Charitable Trusts’ food additives project, a three-year investigation into how food additives are regulated, calls “the loophole that swallowed the law.” A company can create a new additive, publish safety data about it on its Web site and pay a law firm or consulting firm to vet it to establish it as “generally recognized as safe” — without ever notifying the F.D.A., Mr. Neltner said.

About 10,000 chemicals are allowed to be added to foods, about 3,000 of which have never been reviewed for safety by the F.D.A., according to Pew’s research. Of those, about 1,000 never come before the F.D.A. unless someone has a problem with them; they are declared safe by a company and its handpicked advisers.

“I worked on the industrial and consumer products side of things in the past, and if you take a new chemical and put it into, say, a tennis racket, you have to notify the E.P.A. before you put it in,” Mr. Neltner said, referring to the Environmental Protection Agency. “But if you put it into food and can document it as recognized as safe by someone expert, you don’t have to tell the F.D.A.”

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