M.I.T. Lab Hatches Ideas, and Companies, by the Dozens

HOW do you take particles in a test tube, or components in a tiny chip, and turn them into a $100 million company?

Dr. Robert Langer, 64, knows how. Since the 1980s, his Langer Lab at the Massachusetts Institute of Technology has spun out companies whose products treat cancer, diabetes, heart disease and schizophrenia, among other diseases, and even thicken hair.

The Langer Lab is on the front lines of turning discoveries made in the lab into a range of drugs and drug delivery systems. Without this kind of technology transfer, the thinking goes, scientific discoveries might well sit on the shelf, stifling innovation.

A chemical engineer by training, Dr. Langer has helped start 25 companies and has 811 patents, issued or pending, to his name. That’s not too far behind Thomas Edison, who had 1,093. More than 250 companies have licensed or sublicensed Langer Lab patents.

Polaris Venture Partners, a Boston venture capital firm, has invested $220 million in 18 Langer Lab-inspired businesses. Combined, these businesses have improved the health of many millions of people, says Terry McGuire, co-founder of Polaris.

Along the way, Dr. Langer and his lab, including about 60 postdoctoral and graduate students at a time, have found a way to navigate some slippery territory: the intersection of academic research and the commercial market.

Over the last 30 years, many universities — including M.I.T. — have set up licensing offices that oversee the transfer of scientific discoveries to companies. These offices have become a major pathway for universities seeking to put their research to practical use, not to mention add to their revenue streams.

In the sciences in particular, technology transfer has become a key way to bring drugs and other treatments to market. “The model of biomedical innovation relies on research coming out of universities, often funded by public money,” says Josephine Johnston, director of research at the Hastings Center, a bioethics research organization based in Garrison, N.Y.

Just a few of the products that have emerged from the Langer Lab are a small wafer that delivers a dose of chemotherapy used to treat brain cancer; sugar-sequencing tools that can be used to create new drugs like safer and more effective blood thinners; and a miniaturized chip (a form of nanotechnology) that can test for diseases.

The chemotherapy wafer, called the Gliadel, is licensed by Eisai Inc. The company behind the sugar-sequencing tools, Momenta Pharmaceuticals, raised $28.4 million in an initial public offering in 2004. The miniaturized chip is made by T2Biosystems,  which completed a $23 million round of financing in the summer of 2011.

“It’s inconvenient to have to send things to a lab,” so the company is trying to develop more sophisticated methods, says Dr. Ralph Weissleder, a co-founder, with Dr. Langer and others, of T2Biosystems and a professor at Harvard Medical School.

FOR Dr. Langer, starting a company is not the same as it was, say, for Mark Zuckerberg with Facebook. “Bob is not consumed with any one company,” says H. Kent Bowen, an emeritus professor of business administration at Harvard Business School who wrote a case study on the Langer Lab. “His mission is to create the idea.”

Dr. Bowen observes that there are many other academic laboratories, including highly productive ones, but that the Langer Lab’s combination of people, spun-out companies and publications sets it apart. He says Dr. Langer “walks into the great unknown and then makes these discoveries.”

Dr. Langer is well known for his mentoring abilities. He is “notorious for replying to e-mail in two minutes, whether it’s a lowly graduate school student or the president of the United States,” says Paulina Hill, who worked in his lab from 2009 to 2011 and is now a senior associate at Polaris Venture Partners. (According to Dr. Langer, he has corresponded directly with President Obama about stem cell research and federal funds for the sciences.)

Dr. Langer says he looks at his students “as an extended family,” adding that “I really want them to do well.”

And they have, whether in business or in academia, or a combination of the two. One former student, Ram Sasisekharan, helped found Momenta and now runs his own lab at M.I.T. Ganesh Venkataraman Kaundinya is Momenta’s chief scientific officer and senior vice president for research.

Hongming Chen is vice president of research at Kala Pharmaceuticals. Howard Bernstein is chief scientific officer at Seventh Sense Biosystems, a blood-testing company. Still others have taken jobs in the law or in government.

Dr. Langer says he spends about eight hours a week working on companies that come out of his lab. Of the 25 that he helped start, he serves on the boards of 12 and is an informal adviser to 4. All of his entrepreneurial activity, which includes some equity stakes, has made him a millionaire. But he says he is mainly motivated by a desire to improve people’s health.

Operating from the sixth floor of the David H. Koch Institute for Integrative Cancer Research on the M.I.T. campus in Cambridge, Mass., Dr. Langer’s lab has a research budget of more than $10 million for 2012, coming mostly from federal sources.

The research in labs like Dr. Langer’s is eyed closely by pharmaceutical companies. While drug companies employ huge research and development teams, they may not be as freewheeling and nimble, Dr. Langer says. The basis for many long-range discoveries has “come out of academia, including gene therapy, gene sequencing and tissue engineering,” he says.

He has served as a consultant to pharmaceutical companies. Their large size, he says, can end up being an impediment.

“Very often when you are going for real innovation,” he says, “you have to go against prevailing wisdom, and it’s hard to go against prevailing wisdom when there are people who have been there for a long time and you have some vice president who says, ‘No, that doesn’t make sense.’ ”

Pharmaceutical companies are eager to tap into the talent at leading research universities. In 2008, for example, Washington University in St. Louis announced a $25 million pact with Pfizer to collaborate more closely on biomedical research.

But in some situations, the close — critics might say cozy — ties between business and academia have the potential to create conflicts of interest.

There was a controversy earlier this year when it was revealed that the president of the University of Texas M.D. Anderson Cancer Center owned stock in Aveo Oncology, which had announced earlier that the university would be leading clinical trials of one of its cancer drugs.  Last month, the University of Texas announced that he would be allowed to keep his ties with three pharmaceutical companies, including Aveo Oncology; his holdings will be placed in a blind trust.

Read More..

M.I.T. Lab Hatches Ideas, and Companies, by the Dozens

HOW do you take particles in a test tube, or components in a tiny chip, and turn them into a $100 million company?

Dr. Robert Langer, 64, knows how. Since the 1980s, his Langer Lab at the Massachusetts Institute of Technology has spun out companies whose products treat cancer, diabetes, heart disease and schizophrenia, among other diseases, and even thicken hair.

The Langer Lab is on the front lines of turning discoveries made in the lab into a range of drugs and drug delivery systems. Without this kind of technology transfer, the thinking goes, scientific discoveries might well sit on the shelf, stifling innovation.

A chemical engineer by training, Dr. Langer has helped start 25 companies and has 811 patents, issued or pending, to his name. That’s not too far behind Thomas Edison, who had 1,093. More than 250 companies have licensed or sublicensed Langer Lab patents.

Polaris Venture Partners, a Boston venture capital firm, has invested $220 million in 18 Langer Lab-inspired businesses. Combined, these businesses have improved the health of many millions of people, says Terry McGuire, co-founder of Polaris.

Along the way, Dr. Langer and his lab, including about 60 postdoctoral and graduate students at a time, have found a way to navigate some slippery territory: the intersection of academic research and the commercial market.

Over the last 30 years, many universities — including M.I.T. — have set up licensing offices that oversee the transfer of scientific discoveries to companies. These offices have become a major pathway for universities seeking to put their research to practical use, not to mention add to their revenue streams.

In the sciences in particular, technology transfer has become a key way to bring drugs and other treatments to market. “The model of biomedical innovation relies on research coming out of universities, often funded by public money,” says Josephine Johnston, director of research at the Hastings Center, a bioethics research organization based in Garrison, N.Y.

Just a few of the products that have emerged from the Langer Lab are a small wafer that delivers a dose of chemotherapy used to treat brain cancer; sugar-sequencing tools that can be used to create new drugs like safer and more effective blood thinners; and a miniaturized chip (a form of nanotechnology) that can test for diseases.

The chemotherapy wafer, called the Gliadel, is licensed by Eisai Inc. The company behind the sugar-sequencing tools, Momenta Pharmaceuticals, raised $28.4 million in an initial public offering in 2004. The miniaturized chip is made by T2Biosystems,  which completed a $23 million round of financing in the summer of 2011.

“It’s inconvenient to have to send things to a lab,” so the company is trying to develop more sophisticated methods, says Dr. Ralph Weissleder, a co-founder, with Dr. Langer and others, of T2Biosystems and a professor at Harvard Medical School.

FOR Dr. Langer, starting a company is not the same as it was, say, for Mark Zuckerberg with Facebook. “Bob is not consumed with any one company,” says H. Kent Bowen, an emeritus professor of business administration at Harvard Business School who wrote a case study on the Langer Lab. “His mission is to create the idea.”

Dr. Bowen observes that there are many other academic laboratories, including highly productive ones, but that the Langer Lab’s combination of people, spun-out companies and publications sets it apart. He says Dr. Langer “walks into the great unknown and then makes these discoveries.”

Dr. Langer is well known for his mentoring abilities. He is “notorious for replying to e-mail in two minutes, whether it’s a lowly graduate school student or the president of the United States,” says Paulina Hill, who worked in his lab from 2009 to 2011 and is now a senior associate at Polaris Venture Partners. (According to Dr. Langer, he has corresponded directly with President Obama about stem cell research and federal funds for the sciences.)

Dr. Langer says he looks at his students “as an extended family,” adding that “I really want them to do well.”

And they have, whether in business or in academia, or a combination of the two. One former student, Ram Sasisekharan, helped found Momenta and now runs his own lab at M.I.T. Ganesh Venkataraman Kaundinya is Momenta’s chief scientific officer and senior vice president for research.

Hongming Chen is vice president of research at Kala Pharmaceuticals. Howard Bernstein is chief scientific officer at Seventh Sense Biosystems, a blood-testing company. Still others have taken jobs in the law or in government.

Dr. Langer says he spends about eight hours a week working on companies that come out of his lab. Of the 25 that he helped start, he serves on the boards of 12 and is an informal adviser to 4. All of his entrepreneurial activity, which includes some equity stakes, has made him a millionaire. But he says he is mainly motivated by a desire to improve people’s health.

Operating from the sixth floor of the David H. Koch Institute for Integrative Cancer Research on the M.I.T. campus in Cambridge, Mass., Dr. Langer’s lab has a research budget of more than $10 million for 2012, coming mostly from federal sources.

The research in labs like Dr. Langer’s is eyed closely by pharmaceutical companies. While drug companies employ huge research and development teams, they may not be as freewheeling and nimble, Dr. Langer says. The basis for many long-range discoveries has “come out of academia, including gene therapy, gene sequencing and tissue engineering,” he says.

He has served as a consultant to pharmaceutical companies. Their large size, he says, can end up being an impediment.

“Very often when you are going for real innovation,” he says, “you have to go against prevailing wisdom, and it’s hard to go against prevailing wisdom when there are people who have been there for a long time and you have some vice president who says, ‘No, that doesn’t make sense.’ ”

Pharmaceutical companies are eager to tap into the talent at leading research universities. In 2008, for example, Washington University in St. Louis announced a $25 million pact with Pfizer to collaborate more closely on biomedical research.

But in some situations, the close — critics might say cozy — ties between business and academia have the potential to create conflicts of interest.

There was a controversy earlier this year when it was revealed that the president of the University of Texas M.D. Anderson Cancer Center owned stock in Aveo Oncology, which had announced earlier that the university would be leading clinical trials of one of its cancer drugs.  Last month, the University of Texas announced that he would be allowed to keep his ties with three pharmaceutical companies, including Aveo Oncology; his holdings will be placed in a blind trust.

Read More..

M.I.T. Lab Hatches Ideas, and Companies, by the Dozens

HOW do you take particles in a test tube, or components in a tiny chip, and turn them into a $100 million company?

Dr. Robert Langer, 64, knows how. Since the 1980s, his Langer Lab at the Massachusetts Institute of Technology has spun out companies whose products treat cancer, diabetes, heart disease and schizophrenia, among other diseases, and even thicken hair.

The Langer Lab is on the front lines of turning discoveries made in the lab into a range of drugs and drug delivery systems. Without this kind of technology transfer, the thinking goes, scientific discoveries might well sit on the shelf, stifling innovation.

A chemical engineer by training, Dr. Langer has helped start 25 companies and has 811 patents, issued or pending, to his name. That’s not too far behind Thomas Edison, who had 1,093. More than 250 companies have licensed or sublicensed Langer Lab patents.

Polaris Venture Partners, a Boston venture capital firm, has invested $220 million in 18 Langer Lab-inspired businesses. Combined, these businesses have improved the health of many millions of people, says Terry McGuire, co-founder of Polaris.

Along the way, Dr. Langer and his lab, including about 60 postdoctoral and graduate students at a time, have found a way to navigate some slippery territory: the intersection of academic research and the commercial market.

Over the last 30 years, many universities — including M.I.T. — have set up licensing offices that oversee the transfer of scientific discoveries to companies. These offices have become a major pathway for universities seeking to put their research to practical use, not to mention add to their revenue streams.

In the sciences in particular, technology transfer has become a key way to bring drugs and other treatments to market. “The model of biomedical innovation relies on research coming out of universities, often funded by public money,” says Josephine Johnston, director of research at the Hastings Center, a bioethics research organization based in Garrison, N.Y.

Just a few of the products that have emerged from the Langer Lab are a small wafer that delivers a dose of chemotherapy used to treat brain cancer; sugar-sequencing tools that can be used to create new drugs like safer and more effective blood thinners; and a miniaturized chip (a form of nanotechnology) that can test for diseases.

The chemotherapy wafer, called the Gliadel, is licensed by Eisai Inc. The company behind the sugar-sequencing tools, Momenta Pharmaceuticals, raised $28.4 million in an initial public offering in 2004. The miniaturized chip is made by T2Biosystems,  which completed a $23 million round of financing in the summer of 2011.

“It’s inconvenient to have to send things to a lab,” so the company is trying to develop more sophisticated methods, says Dr. Ralph Weissleder, a co-founder, with Dr. Langer and others, of T2Biosystems and a professor at Harvard Medical School.

FOR Dr. Langer, starting a company is not the same as it was, say, for Mark Zuckerberg with Facebook. “Bob is not consumed with any one company,” says H. Kent Bowen, an emeritus professor of business administration at Harvard Business School who wrote a case study on the Langer Lab. “His mission is to create the idea.”

Dr. Bowen observes that there are many other academic laboratories, including highly productive ones, but that the Langer Lab’s combination of people, spun-out companies and publications sets it apart. He says Dr. Langer “walks into the great unknown and then makes these discoveries.”

Dr. Langer is well known for his mentoring abilities. He is “notorious for replying to e-mail in two minutes, whether it’s a lowly graduate school student or the president of the United States,” says Paulina Hill, who worked in his lab from 2009 to 2011 and is now a senior associate at Polaris Venture Partners. (According to Dr. Langer, he has corresponded directly with President Obama about stem cell research and federal funds for the sciences.)

Dr. Langer says he looks at his students “as an extended family,” adding that “I really want them to do well.”

And they have, whether in business or in academia, or a combination of the two. One former student, Ram Sasisekharan, helped found Momenta and now runs his own lab at M.I.T. Ganesh Venkataraman Kaundinya is Momenta’s chief scientific officer and senior vice president for research.

Hongming Chen is vice president of research at Kala Pharmaceuticals. Howard Bernstein is chief scientific officer at Seventh Sense Biosystems, a blood-testing company. Still others have taken jobs in the law or in government.

Dr. Langer says he spends about eight hours a week working on companies that come out of his lab. Of the 25 that he helped start, he serves on the boards of 12 and is an informal adviser to 4. All of his entrepreneurial activity, which includes some equity stakes, has made him a millionaire. But he says he is mainly motivated by a desire to improve people’s health.

Operating from the sixth floor of the David H. Koch Institute for Integrative Cancer Research on the M.I.T. campus in Cambridge, Mass., Dr. Langer’s lab has a research budget of more than $10 million for 2012, coming mostly from federal sources.

The research in labs like Dr. Langer’s is eyed closely by pharmaceutical companies. While drug companies employ huge research and development teams, they may not be as freewheeling and nimble, Dr. Langer says. The basis for many long-range discoveries has “come out of academia, including gene therapy, gene sequencing and tissue engineering,” he says.

He has served as a consultant to pharmaceutical companies. Their large size, he says, can end up being an impediment.

“Very often when you are going for real innovation,” he says, “you have to go against prevailing wisdom, and it’s hard to go against prevailing wisdom when there are people who have been there for a long time and you have some vice president who says, ‘No, that doesn’t make sense.’ ”

Pharmaceutical companies are eager to tap into the talent at leading research universities. In 2008, for example, Washington University in St. Louis announced a $25 million pact with Pfizer to collaborate more closely on biomedical research.

But in some situations, the close — critics might say cozy — ties between business and academia have the potential to create conflicts of interest.

There was a controversy earlier this year when it was revealed that the president of the University of Texas M.D. Anderson Cancer Center owned stock in Aveo Oncology, which had announced earlier that the university would be leading clinical trials of one of its cancer drugs.  Last month, the University of Texas announced that he would be allowed to keep his ties with three pharmaceutical companies, including Aveo Oncology; his holdings will be placed in a blind trust.

Read More..

Morsi Urged to Retract Edict to Bypass Judges in Egypt

Tara Todras-Whitehill for The New York Times

A demonstrator takes a breather during protests in downtown Cairo on Saturday. More Photos »

CAIRO — The association of judges here called Saturday for courts across Egypt to suspend all but their most vital activities to protest an edict by President Mohamed Morsi granting himself unchecked power by setting his decrees above judicial review until the ratification of a new constitution.

The judges’ strike, which drew the support of the leader of the national lawyers’ association, would be the steepest escalation yet in a political struggle between the country’s new Islamist leaders and the institutions of the authoritarian government that was overthrown last year. As it spills into the courts and the streets, the dispute also increasingly threatens to undermine the credibility of Egypt’s political transition as well.

A council that oversees the judiciary denounced Mr. Morsi’s decree, which was issued Thursday, as “an unprecedented attack on judicial independence,” and urged the president to retract parts of the decree eliminating judicial oversight.

State news media reported that judges and prosecutors had already walked out in Alexandria, and there were other news reports of walkouts in Qulubiya and Beheira, but those could not be confirmed.

Outside Egypt’s high court in Cairo, the police fired tear gas at protesters who were denouncing Mr. Morsi and trying to force their way into the building, the second day in a row that protesters took to the streets over the presidential decree, which critics have decried as a return to autocracy.

Abdel Meguid Mahmoud, a prosecutor appointed by Mr. Morsi’s predecessor, Hosni Mubarak, declared to a crowd of cheering judges that the presidential decree was “null and void.” He denounced what he described as “the systematic campaign against the country’s institutions in general and the judiciary in particular.”

A coalition of disparate opposition leaders including the liberal former United Nations diplomat Mohamed ElBaradei, the leftist-nationalist Hamdeen Sabahy, and the former Mubarak-government foreign minister Amr Moussa formed a self-proclaimed National Salvation Front to oppose the decree. In addition to demanding the dissolution of the constitutional assembly, the group declared that it would not speak with Mr. Morsi until he withdrew his decree.

“We will not enter into a dialogue about anything while this constitutional declaration remains intact and in force,” Mr. Moussa said. “We demand that it be withdrawn and then we can talk.”

As the judges group called for a suspension of the courts, a growing number of lawyers filed claims demanding that the courts seek to overturn Mr. Morsi’s decree, joining the battle between the executive and judicial powers.

Advisers to Mr. Morsi, a former leader of the Muslim Brotherhood and Egypt’s first democratically elected president, defended his action, saying he was trying to prevent the courts from disbanding the Islamist-dominated constitutional assembly, which is writing a new constitution. The nation’s top courts had already dissolved the Islamist-led parliament and an earlier Islamist-led constituent assembly.

The advisers said a court decision on the new constitutional assembly had been expected as soon as next Sunday.

The judges’ group, as well as the newly unified secular opposition, have demanded that Mr. Morsi withdraw his decree, and that he disband and replace the current constitutional assembly. Many of the assembly’s non-Islamist members, including secularists and representatives of the Coptic Church, had already quit the body to protest the Islamists’ domination.

The increasingly vocal criticism of the assembly threatens to undermine the legitimacy of the ultimate charter, and has only increased the likelihood that the Islamist leaders may seek to pass and ratify it on their own, over the opposition of other groups, further damaging its credibility.

The opposition to the decree has also reinforced the fears of Islamists that judges appointed by former President Hosni Mubarak and the secular opposition were deliberately seeking to derail the process rather than accept their defeats at the polls.

Nevine Ramzy and Mai Ayyad contributed reporting.

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Gadgetwise Blog: Having a Beer With a Smartphone

Drinking beer used to be simple. But the exploding popularity of craft beer over the past several years has changed that, giving beer drinkers a new world of possibilities — and a range of hard decisions.

Predictably, the ever-expanding roster of oatmeal stouts and vanilla porters has been accompanied by the creation of dozens of beer-related apps. These include local guides to the best pints, inane games, beery social networks and recommendation engines that determine which beers you might like based on what you have enjoyed in the past.

An app released this month, Craft Beer New York, gives local connoisseurs an excellent guide to the city’s bars, breweries and bottle shops ($1.99 for iPhones and other iOS devices; you must be 17 years old to download this and the other Apple beer apps). Its developer, Blue Crow Media, also makes attractive apps focused on coffee. The content for this app comes from Joshua M. Bernstein, a beer writer living in Prospect Heights, Brooklyn, and the author of Brewed Awakening, a book about the craft beer movement.

The app rates 122 bars, 34 shops and 22 breweries. I first tested it out in Astoria, Queens, where I live, and it seemed to get things right without just picking the most obvious places to drink. There were short entries on half a dozen establishments, including specific recommendations on which beers to order.

It is worth noting that this app is different from a guide to bars. Good spots will not show up if they have pedestrian beer selections. At the same time, bars do not automatically get good ratings for having lots of choices. Mr. Bernstein acknowledges that the Beer Authority, a 70-tap bar that recently opened on a stretch of Eighth Avenue in Midtown Manhattan, is “a life preserver for folks working around the Port Authority.” But the app still sticks it with a 2 out of 5 rating because of its unimaginative décor, high prices and a tendency to play lame music.

Mr. Bernstein updates the app with newly opened establishments, and it also has a news tab that includes bulletins on things like how to ensure that an I.P.A. is fresh, or how to help out beer-related businesses affected by Hurricane Sandy. An Android version is due out in early 2013.

One of the more popular beer apps is Untappd, a location-based social-networking app for beer drinkers (free and available for Android and iOS). The app is designed to get people to share their impressions of beers, keeping track of what they liked while also guiding friends and strangers to good bars and brews. The app has an active community, but like any crowdsourced project there is a lot to sift through to find anything useful.

Another way to find new beers to try is to tell an algorithm what you drink and have it determine what else you might like. BrewGene is a nice version of this idea (free and available for Android, iOS or on the Web). It has a truly extensive database. I recently ordered a Goose Island I.P.A. from a bar, but when I went to enter it into the app found that there were five different beers with that name. I rated a few beers from the app’s top 100 list, and it began generating credible suggestions for me. The app’s ability to point me toward an establishment that would serve me these beers is lacking, however. Its “Places” function pulled in a seemingly random selection of nearby bars, bodegas and restaurants. There’s supposed to be a beer menu for each establishment, but all the ones I got were blank.

Have a favorite New York City app? Send tips via e-mail to appcity@nytimes.com or via Twitter to @joshuabrustein.

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Nintendo’s Wii U Takes Aim at a Changed Video Game World

REDMOND, Wash.

TUCKED in the woods here, west of State Route 520, is a little piece of the Mario Kingdom.

Behind the unassuming doors is the business built by Mario, the pudgy plumber, and Luigi, his lanky brother, as well as characters like Link, wielder of the mystical Master Sword, and Princess Zelda, of the royal family of Hyrule. All of them, and more, are the pixelated children of Shigeru Miyamoto, the Walt Disney of video games and creative genius of the Nintendo Company of Japan.

But while Mr. Miyamoto is dreaming his dreams across the Pacific, an army of marketing types is at work here in Redmond, inside the shiny new headquarters of Nintendo of America. This palace of play is quiet, but there’s trouble brewing in the world around it: three decades after the mustachioed Mario burst into arcades via Donkey Kong, plucking countless quarters from people’s pockets, the kingdom is under siege.

Nintendo’s enemies have arrived by battalions. Angry Birds, Fruit Ninja and other inexpensive, downloadable games, particularly for cellphones and tablets, have invaded its turf. Changing tastes and technology have called into question the economics of traditional game consoles, whether from Nintendo or Microsoft, maker of the Xbox. Nintendo recently posted the first loss in its era as a video games company, a prospect that would have been unimaginable only a few years ago. And while game consoles aren’t going away, analysts are skeptical that the business will regain its former stature soon.

All of which makes Nintendo’s next move, and what is happening here, so crucial. Nintendo counterattacked on Nov. 18, when a new version of its Wii game console arrived in stores nationwide.

The original Wii, the first wireless, motion-capturing console, was nothing less than revolutionary. The simplicity of its controller, which Mr. Miyamoto helped design, attracted new audiences like women and older people. Customers lined up in stores for it — and then it simply faded. Now, the new console, the Wii U, may be Nintendo’s last, best hope for regaining its former glory. Executives are hoping for a holiday hit, and perhaps even another runaway success.

Initial demand appears high. GameStop, the video game retailer, opened 3,000 stores at midnight on Thursday for Black Friday sales, and before long almost all its Wii Us were sold out, according to Tony Bartel, GameStop’s president. “I think people are starving for innovation, and Wii U is giving them that innovation," Mr. Bartel says. 

THE Wii U is a recognition that the living room is no longer the province of a single screen. More people, particularly the young, now watch TV with a smartphone or tablet in hand, the better to tweet a touchdown or update their Facebook status during a commercial. The Wii U looks like a mash-up of an iPad and a traditional console, with a touch screen embedded in the middle. It’s no mere festival of joysticks, buttons and triggers.

But will it be the blowout that Nintendo needs? Many industry veterans and game reviewers are skeptical. They question whether the Wii U can be as successful as the original, now that many gamers have moved on to more abundant, cheaper and more convenient mobile games.

“I actually am baffled by it,” Nolan K. Bushnell, the founder of Atari and the godfather of the games business, says of the Wii U. “I don’t think it’s going to be a big success.”

The bigger question is what the future holds for any of the major game systems, including new ones that Sony and Microsoft are expected to release next year. Echoing other industry veterans, Mr. Bushnell says that consoles are already delivering remarkable graphics and that few but the most hard-core players will be willing to pay hundreds of dollars for a new game box.

“These things will continue to sputter along, but I really don’t think they’ll be of major import ever again,” he says. “It feels like the end of an era to me.”

Nintendo is unbowed. Mr. Miyamoto was involved in developing the original Wii, and had a role in the Wii U as well. He rarely gives interviews, and was unavailable for comment for this article.

But one recent evening in Redmond, Corey Olcsvary, a Nintendo product marketing specialist, was slashing his fingers across the touch screen on the GamePad, as the Wii U controller is called, casting “throwing stars” at a ninja gang that sprang from the corners of a giant TV screen. In another game, a group of players chased Mario — one of the most popular video game characters ever — around a maze shown on a TV while Mr. Olcsvary stared at a bird’s-eye view of the maze on his GamePad and tried to help Mario dodge his pursuers. The players shouted when they caught sight of Mario’s red overalls and cheered when they tackled him.

Starting in December, people will also be able to use the GamePad as a remote control to set recordings and change channels on their cable and satellite TV services.

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Protests Erupt After Egypt’s Leader Seizes New Power

CAIRO — Opponents of President Mohamed Morsi were reported to have set fire to his party’s offices in several Egyptian cities on Friday in a spasm of protest and clashes after he granted himself broad powers above any court declaring himself the guardian of Egypt‘s revolution, and used his new authority to order the retrial of Hosni Mubarak.

Maya Alleruzzo/Associated Press

Egyptian protesters chanted antigovernment slogans and waved a national flag in Tahrir Square on Friday.

In the Mediterranean city of Alexandria, the opponents of the Muslim Brotherhood’s Freedom and Justice Party clashed with followers of Mr. Morsi, an Islamist, who won Western and regional plaudits only days ago for brokering a cease-fire to halt eight days of lethal exchanges between Israeli forces and militants in the Gaza Strip.

Mr. Morsi, Egypt’s first democratically elected president, portrayed his decree assuming the new powers as an attempt to fulfill popular demands for justice and protect the transition to a constitutional democracy. He said it was necessary to overcome gridlock and competing interests. But the unexpected breadth of the powers he seized raised immediate fears that he might become a new strongman.

“We are, God willing, moving forward, and no one stands in our way,” Reuters quoted Mr. Morsi as saying on Friday said in a suburban mosque here after Friday prayers.

“I fulfill my duties to please God and the nation and I take decisions after consulting with everyone,” he said. “Victory does not come without a clear plan and this is what I have.”

He spoke as state television reported that his party’s offices in the Suez Canal cities of Suez, Port Said and Ismailia had been burned as his foes rampaged. Thousands of people protesting Mr. Morsi’s power grab gathered in Tahrir Square here — the focal point of protests that, last year, swept away Mr. Mubarak. Elsewhere in the capital, the president’s supporters massed in even larger numbers outside the presidential palace where Mr. Morsi said his aim was “to achieve political, social and economic stability.”

“I am for all Egyptians. I will not be biased against any son of Egypt,” he said on a stage outside the presidential palace, Reuters, reported, adding he was working for social and economic stability. “Opposition in Egypt does not worry me, but it has to be real and strong,” he said.

Sounding defensive at times and employing some of the language favored by his autocratic predecessor, Mr. Morsi justified his power grab as necessary to move Egypt’s revolution forward.

“The people wanted me to be the guardian of these steps in this phase,” he said, reminding his audience that he was freely elected after a contest “that the whole world has witnessed.”

“I don’t like, and don’t want — and there is no need — to use exceptional measures,” he said. “But those who are trying to gnaw the bones of the nation,” he added, “must be held accountable.”

News reports said clashes spread from Alexandria to the southern city of Assyut. But the severity of the clashes was not immediately clear.

Mr. Morsi’s new powers prompted one prominent adversary, Mohamed ElBaradei, to say on Twitter: “Morsi today usurped all state powers & appointed himself Egypt’s new pharaoh.”

“An absolute presidential tyranny,” Amr Hamzawy, a liberal member of the dissolved Parliament and prominent political scientist, wrote in an online commentary. “Egypt is facing a horrifying coup against legitimacy and the rule of law and a complete assassination of the democratic transition.”

Mr. Morsi issued the decree on Thursday at a high point in his five-month-old presidency, when he was basking in praise from the White House and around the world for his central role in negotiating a cease-fire that the previous night had stopped the fighting in the Gaza Strip.

But his political opponents immediately called for demonstrations on Friday to protest his new powers. “Passing a revolutionary demand within a package of autocratic decisions is a setback for the revolution,” Abdel Moneim Aboul Fotouh, a more liberal former leader of the Muslim Brotherhood and a former presidential candidate, wrote online. And the chief of the Supreme Constitutional Court indicated that it did not accept the decree.

In Washington on Thursday, the State Department spokeswoman, Victoria Nuland, released a statement saying: “The decisions and declarations announced on November 22 raise concerns form many Egyptians and the international community,” and noting that “one of the aspirations of the revolution was to ensure that power would not be overly concentrated in that hands of any one person or institution.” The statement called for resolution “through democratic dialogue.”

David D. Kirkpatrick and Kareem Fahim reported from Cairo and Alan Cowell from Paris. Mayy El Sheikh contributed reporting.

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Tool Kit: Online Shopping Tips for the Holidays

Some people may be looking forward to leaving Thanksgiving dinner before the pie is served to join the Black Friday rush, which will begin during dinnertime Thursday, earlier than ever, at stores like Sears, Walmart and Lord & Taylor.

But for those who prefer to stay for the pie course, avoid the lines and freezing temperatures and shop from the comfort of their homes, there are just as many deals to be found online this year, especially for smart shoppers.

Last year, online shoppers spent $816 million on Black Friday, an increase of 26 percent from the year before, and an additional $2.3 billion over Thanksgiving weekend and Cyber Monday, according to comScore. It expects online spending to rise this year.

Online, there is no commute, no parking and no crowds — and shopping can be done in bed or at the Thanksgiving dinner table. Still, you cannot try clothes on, you have to wait for your purchase to arrive and there is always the nagging feeling that a better price is just one more click away.

To find your way around those problems, here are some tips from online shopping pros, retailers and shopping bloggers.

BARGAINS START EARLY “Cyber Monday is passé,” said Fiona Dias, chief strategy officer for ShopRunner.com, a network of e-commerce sites. “With online sales beginning as early as the Wednesday night before Thanksgiving, consumers who hold out for the best deal may find that what they are looking for has already sold out.”

Amazon.com, for example, started its Black Friday deals on Monday, but they end Saturday. SHOP ON TUESDAYS One of the secrets of online shopping is that prices change by the second. To maximize your chances of getting the best price year-round, shop on Tuesday, a variety of e-commerce experts say. For whatever reason, Tuesday is when most e-commerce sites, including Shopbop, Etsy and RetailMeNot, post discounts and new items.

No matter the day, online retailers often start sales in the wee hours, so shop early.

As for the time of year, women’s clothes, shoes and accessories are discounted most in January, February, August and September, according to Shop It To Me, an online shopping search site. For consumer electronics like laptops, shop in midsummer and late September, before and after the back-to-school rush, according to Decide.com, a price comparison site.

NEVER PAY FULL PRICE Online holiday shoppers should use 40 percent off as a benchmark for a good deal, said Marjorie Cader, a Shop It To Me spokeswoman, based on discount data the site has collected. Expect discounts that are about 5 percent better from online-only retailers than from those that also operate brick and mortar stores, she said.

Comparison shopping sites like TheFind or ShopStyle can locate the best prices; Google or coupon sites like RetailMeNot can also help find a discount.

Google, Amazon and even flash sale sites like Gilt.com do not always have the lowest prices. You might check small shopping blogs dedicated to your favorite brands, like Grechen’s Closet for contemporary women’s clothes or J. Crew Aficionada.

“Spend 20 minutes and ensure you are getting the best deal out there,” said John Faith, senior vice president of mobile at WhaleShark Media, which operates coupon sites, including RetailMeNot.

BE A HAGGLER This is the year haggling at the cash register could become acceptable, as offline retailers try to keep shoppers offline. If you find a better price online — by using an application like RedLaser or searching Amazon — ask whether the cashier will match it. Big retailers like Target have already said they will.

WAIT TILL THE LAST MINUTE Procrastinators might benefit during the holidays. Electronics sold online are least expensive in the week before Christmas, according to Decide, especially TVs, laptops and cameras.

And while Dec. 17 is the last day that most online retailers will offer free shipping in time for Christmas, Walmart, the luxury clothing seller Net-a-Porter and others will deliver the same day. In San Francisco and New York, eBay now offers same-day delivery from hundreds of stores, including Macy’s, Target and Toys “R” Us.

NEVER PAY FOR SHIPPING... Nine of ten retailers will offer free shipping on certain purchases this holiday season, and a third will offer free shipping on all purchases, according to the National Retail Federation.

Some, though, require that you enter a promotional code, so it’s wise to take a minute to look around the Web site or search a coupon site to find it.

Stores including Walmart, Toys “R” Us and Nordstrom allow you to shop online and pick up your order locally.

...OR FOR RETURNS Sites like Zappos.com and Piperlime send prepaid shipping labels, but beware.

“When it comes to returns, read the fine print,” said Brian Hoyt, a spokesman for WhaleShark Media. Some merchants include a prepaid return label but subtract the price from your refund, and others charge a restocking fee as high as 30 percent for consumer electronics.

Many companies, including Gap and J. Crew, also let you return an online purchase to a local store. And until Dec. 31, PayPal will cover the return shipping cost if the merchant does not, as long as you pay with PayPal and make the return within 30 days.

SEARCH WISELY Try searching synonyms, like “coat” instead of “jacket.” On sites like eBay, try leaving out words — if you are looking for an Yves Saint Laurent handbag on eBay, search for “Saint Laurent” or “Laurent bag.”

“If you search for ‘Yves Saint Laurent,’ you’ll be fighting over pieces with a bigger group of people,” said Sophia Amoruso, founder and chief executive of the e-commerce retailer Nasty Gal, who suggested purposefully misspelling brand names as well. “Think of what an uninformed person might list a really great designer piece as, and you can get an amazing gem for an incredible price.”

EBay Fashion also lets shoppers search by taking a cellphone picture of a fabric to find similar designs.

GET INSPIRED Search for “black sequin dress,” and you’ll get 128 results on Zappos.com, 2,618 on Amazon.com and a truly overwhelming 18 million on Google.

One solution: Trust online curators to suggest items. Etsy creates lists of recommended items. On Pinterest, you can peruse items culled by others. Other sites to search for inspiration: Polvyore, Fancy, Svpply, Lookbook.nu and We Heart It.

TRY IT ON, VIRTUALLY You can visit sites that show real people wearing the clothes you’re interested in buying, like Go Try It On, Fashism and Rent the Runway and sites that show video, including Asos, MyHabit and Joyus. Or, as long as a site offers free shipping and returns, order two sizes and return one.

SHOP INTERNATIONALLY “Don’t let international shopping scare you off,” said Caroline Nolan, the writer of Pregnant Fashionista, a maternity shopping blog.

Many international e-commerce sites, like Asos, ship free to the United States. And because the seasons are different, winter clothes in Australia, for instance, go on sale just as Americans are starting to shop for winter, she said. FarFetch has items from small boutiques worldwide and 1stDibs is good at finding rare items like an antique from Paris. On eBay, you might have luck finding items made by a European designer by switching to eBay’s site for a particular country.

MAKE SITES WORK FOR YOU On Shop It To Me, you can enter your favorite designers and sizes and the site will send you personalized e-mails with promotions and sales. Many sites allow shoppers to place a symbol like a heart on best-liked items or save them to a wish list. On a site like Pinterest, shoppers can build a list.

“You always think you’ll remember where you saw something or what brand it was, but really you never do,” said Noria Morales, style director at SugarInc, a network of fashion and lifestyle blogs.

Even better, sites like Shopbop and Polyvore send alerts when items you have saved go on sale or are running low. EBay sends alerts when new items are listed for a search you have saved.

BE DILIGENT No one has time to read 50 e-mails a day from retailers. But for your favorite e-commerce sites, it is worth signing up for e-mails, as well as tracking them on Facebook and Twitter, where they often post exclusive deals. Many online shoppers have more luck hunting for items than trusting services to send alerts, said Grechen Reiter, owner of Grechen Media, a network of shopping blogs.

“It is the thrill of the hunt that gets us going, after all,” she said.

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Inquiry Sought in Death in Ireland After Abortion Was Denied

DUBLIN — India’s ambassador here has agreed to ask Prime Minister Enda Kenny of Ireland for an independent inquiry into the death of an Indian-born woman last month after doctors refused to perform an abortion when she was having a miscarriage, the lawyer representing the woman’s husband said Thursday.

The lawyer, Gerard O’Donnell, also said crucial information was missing from the files he had received from the Irish Health Service Executive about the death of the woman, Savita Halappanavar, including any mention of her requests for an abortion after she learned that the fetus would not survive.

The death of Dr. Halappanavar, 31, a dentist who lived near Galway, has focused global attention on the Irish ban on abortion.

Her husband, Praveen Halappanavar, has refused to cooperate with an investigation being conducted by the Irish health agency. “I have seen the way my wife was treated in the hospital, so I have no confidence that the H.S.E. will do justice,” he said in an interview on Wednesday night on RTE, the state television broadcaster. “Basically, I don’t have any confidence in the H.S.E.”

In a tense debate in the Irish Parliament on Wednesday evening, Robert Dowds of the Labour Party said Dr. Halappanavar’s death had forced politicians “to confront an issue we have dodged for much too long,” partly because so many Irish women travel to Britain for abortions.

“The reality is that if Britain wasn’t on our doorstep, we would have had to introduce abortion legislation years ago to avoid women dying in back-street abortions,” he said.

After the debate, the Parliament voted 88 to 53 against a motion introduced by the opposition Sinn Fein party calling on the government to allow abortions when women’s lives are in danger and to protect doctors who perform such procedures.

The Irish president, Michael D. Higgins — who is restricted by the Constitution from getting involved in political matters — also made a rare foray into a political debate on Wednesday, saying any inquiry must meet the needs of the Halappanavar family as well as the government.

In 1992, the Irish Supreme Court interpreted the current law to mean that abortion should be allowed in circumstances where there was “a real and substantial risk to the life of the mother,” including the threat of suicide. But that ruling has never been codified into law.

“The current situation is like a sword of Damocles hanging over us,” Dr. Peter Boylan, of the Irish Institute of Obstetricians and Gynecologists, told RTE last week. “If we do something with a good intention, but it turns out to be illegal, the consequences are extremely serious for medical practitioners.”

Dr. Ruth Cullen, who has campaigned against abortion, said that any legislation to codify the Supreme Court ruling would be tantamount to allowing abortion on demand and that Dr. Halappanavar’s death should not be used to make that change.

Dr. Halappanavar contracted a bacterial blood infection, septicemia, and died Oct. 28, a week after she was admitted to Galway University Hospital with severe back pains. She was 17 weeks pregnant but having a miscarriage and was told that the fetus — a girl — would not survive. Her husband said she asked several times for an abortion but was informed that under Irish law it would be illegal while there was a fetal heartbeat, because “this is a Catholic country.”

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Inquiry Sought in Death in Ireland After Abortion Was Denied

DUBLIN — India’s ambassador here has agreed to ask Prime Minister Enda Kenny of Ireland for an independent inquiry into the death of an Indian-born woman last month after doctors refused to perform an abortion when she was having a miscarriage, the lawyer representing the woman’s husband said Thursday.

The lawyer, Gerard O’Donnell, also said crucial information was missing from the files he had received from the Irish Health Service Executive about the death of the woman, Savita Halappanavar, including any mention of her requests for an abortion after she learned that the fetus would not survive.

The death of Dr. Halappanavar, 31, a dentist who lived near Galway, has focused global attention on the Irish ban on abortion.

Her husband, Praveen Halappanavar, has refused to cooperate with an investigation being conducted by the Irish health agency. “I have seen the way my wife was treated in the hospital, so I have no confidence that the H.S.E. will do justice,” he said in an interview on Wednesday night on RTE, the state television broadcaster. “Basically, I don’t have any confidence in the H.S.E.”

In a tense debate in the Irish Parliament on Wednesday evening, Robert Dowds of the Labour Party said Dr. Halappanavar’s death had forced politicians “to confront an issue we have dodged for much too long,” partly because so many Irish women travel to Britain for abortions.

“The reality is that if Britain wasn’t on our doorstep, we would have had to introduce abortion legislation years ago to avoid women dying in back-street abortions,” he said.

After the debate, the Parliament voted 88 to 53 against a motion introduced by the opposition Sinn Fein party calling on the government to allow abortions when women’s lives are in danger and to protect doctors who perform such procedures.

The Irish president, Michael D. Higgins — who is restricted by the Constitution from getting involved in political matters — also made a rare foray into a political debate on Wednesday, saying any inquiry must meet the needs of the Halappanavar family as well as the government.

In 1992, the Irish Supreme Court interpreted the current law to mean that abortion should be allowed in circumstances where there was “a real and substantial risk to the life of the mother,” including the threat of suicide. But that ruling has never been codified into law.

“The current situation is like a sword of Damocles hanging over us,” Dr. Peter Boylan, of the Irish Institute of Obstetricians and Gynecologists, told RTE last week. “If we do something with a good intention, but it turns out to be illegal, the consequences are extremely serious for medical practitioners.”

Dr. Ruth Cullen, who has campaigned against abortion, said that any legislation to codify the Supreme Court ruling would be tantamount to allowing abortion on demand and that Dr. Halappanavar’s death should not be used to make that change.

Dr. Halappanavar contracted a bacterial blood infection, septicemia, and died Oct. 28, a week after she was admitted to Galway University Hospital with severe back pains. She was 17 weeks pregnant but having a miscarriage and was told that the fetus — a girl — would not survive. Her husband said she asked several times for an abortion but was informed that under Irish law it would be illegal while there was a fetal heartbeat, because “this is a Catholic country.”

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