U.S. drone strategy in Yemen is fraught with peril









AL SARRAIN, Yemen — The U.S. drone flew over a cluster of mud houses on a ridge and, according to Yemeni officials, locked onto Adnan Qadhi, a mercurial man of many guises, including radical militant, peace mediator, preacher of violence and army general.


Villagers said Qadhi climbed out of his utility vehicle the night of Nov. 7 to make a cellphone call shortly before the missile struck. His photo — broad face peering from beneath a tilted red beret, stars on his epaulets — now hangs in a small grocery store in a land where farmers work narrow fields below the villas of politicians, tribal leaders and a former president that rise like fortresses on nearby hilltops.


Some here call him a martyr, others a fanatic. But the life and death of Qadhi, a senior officer in the 1st Armored Division who preached holy war in mosques and donned government-issued fatigues, epitomizes the political instability, tribal intrigue, crisscrossing allegiances and radical Islamist passions the United States must sort out when targeting militants in Yemen. At times, Washington risks being drawn into internal conflicts and becoming increasingly despised in the Arab world's poorest nation.





PHOTOS: A new breed of drones


Extremists here have a history of shifting tactics and circumstances. They were pressed into service by the government of former President Ali Abdullah Saleh when needed, then arrested and jailed when the political winds changed. Later they vanished from prisons by the scores, set loose across tribal lands. Yemeni security officials say that era is ending, and they're stepping up military offensives to rout extremists — fighters from Libya, Somalia and other nations, and assassins on motorcycles intent on killing intelligence officials.


At the same time, the Obama administration has intensified airstrikes against the Yemeni group Al Qaeda in the Arabian Peninsula, which plotted in 2009 and 2010 to blow up American airliners. A 2011 drone attack killed Anwar Awlaki, an American-born Muslim preacher and militant recruiter. Weeks later, a U.S. airstrike killed Awlaki's 16-year-old son, who tribesmen and relatives say had no links to terrorism.


The Long War Journal, a website that tracks U.S. drone activity, reports that since 2002, America has launched 57 airstrikes in Yemen, killing 299 militants and 82 civilians. The number of strikes has risen dramatically from four in 2010 to 40 so far this year.


FULL COVERAGE: Drones


"Why do these Americans come and interfere in Yemen?" said Radhwan Dahrooj, the grocer in Al Sarrain. "Why do they kill our people? If they have charges against someone why do they not arrest him and bring him to justice?"


Qadhi was sentenced to prison four years ago for plotting an attack on the U.S. Embassy in Sana, the capital, that killed at least 16 people, no Americans among them. With the help of clansmen and army officials, he was released shortly afterward and resumed his old life: militant and officer in the 1st Armored Division, led by Maj. Gen. Ali Mohsin Saleh Ahmar, a commander described in a 2005 U.S. diplomatic cable as "dealing with terrorists and extremists."


When uprisings against President Saleh swept the country in 2011, the brigade mutinied and battled with competing tribes and security units for control of Sana.


What began as a peaceful revolution against Saleh tipped the nation — already fighting a rebellion in the north and a secessionist movement in the south — into deeper turmoil. Al Qaeda in the Arabian Peninsula and its affiliate Ansar al Sharia exploited the unrest, taking over territory in the south. That gave Qadhi an opportunity to expand his militant ambitions even as he slipped into another of his guises, currying favor with the government by mediating a truce between Yemeni officials and an Al Qaeda faction.


The U.S., which this year has given Yemen $337 million in military and security aid, would not confirm that a drone targeted Qadhi. Yemeni officials and villagers, who heard a plane circling that night, said a U.S. airstrike killed him not far from his home in Beit al Ahmar. Though Qadhi was an active Al Qaeda recruiter and often accused Washington in his sermons of wanting to keep Yemen divided and in chaos, it is not clear what specific danger he was seen as presenting to the United States.


Washington has no precise rules on the criteria for targeting militants with drone strikes. But President Obama has said that an extremist must present an imminent threat to the U.S. or its allies, as Yemen's Al Qaeda branch is considered to do, and that arrest would be impossible.


A former senior U.S. intelligence official said Qadhi's arrest for the 2008 embassy attack would not have been enough to put him on an assassination list. White House counter-terrorism advisor John Brennan has said that militants battling solely to overthrow the government in Sana are not targeted. But Qadhi's 1st Armored Division was certainly a threat to the Yemeni government and the country's stability.


Yemeni officials said the nation's new president, Abdu Rabu Mansour Hadi, approved the strike against Qadhi after determining that an attempt to arrest him in his neighborhood could have led to more deaths. The officials said they were unaware of intelligence linking Qadhi to any active plot.


The danger in the drone program is the potential for U.S. intelligence and airstrikes to be manipulated by Yemenis seeking to weaken the competing clans and political factions. For example, Obama and his top generals felt misled in 2010 when Obama signed off on an airstrike against a senior militant that killed six people, including the deputy governor of Mareb province. The strike was based entirely on intelligence provided by the Yemenis, who had not told the U.S. that the governor would be there, a former senior U.S. official said.


Since Hadi took office in February, the cooperation and trust between the Yemeni government and the U.S. has vastly improved, U.S. and Yemeni officials say.


There are many potential drone targets. For decades, young men have left Yemen to become foot soldiers and bomb makers among the militants in Afghanistan, Algeria, Pakistan, Iraq and Libya. Some of them have come home.


One was Rashad Mohammed Saeed, who left at 15 and became a confidant of Osama bin Laden, fighting beside him in Afghanistan. He returned to Yemen around 2000 and in an interview said he had put aside his weapons to start the Renaissance Union Party, made up of former militants who run for parliament seats.





Read More..

Just got a new iPhone, iPad or Android device for Christmas? Gameloft cuts popular iOS and Android games to 99¢









Title Post: Just got a new iPhone, iPad or Android device for Christmas? Gameloft cuts popular iOS and Android games to 99¢
Rating:
100%

based on 99998 ratings.
5 user reviews.
Author: Fluser SeoLink
Thanks for visiting the blog, If any criticism and suggestions please leave a comment




Read More..

A huge collection of odd TV stuff needs a home






LOS ANGELES (AP) — James Comisar is the first to acknowledge that more than a few have questioned his sanity for spending the better part of 25 years collecting everything from the costume George Reeves wore in the 1950s TV show “Superman” to the entire set of “The Tonight Show Starring Johnny Carson.”


Then there’s the pointy Spock ears Leonard Nimoy wore on “Star Trek” and the guns Tony Soprano used to rub out a mob rival in an episode of “The Sopranos.”






“Along the way people thought I was nuts in general for wanting to conserve Keith Partridge’s flared pants from ‘The Partridge Family,’” the good-natured former TV writer says of the 1970s sitcom as he ambles through rows of costumes, props and what have you from the beginnings of television to the present day.


“But they really thought I needed a psychological workup,” Comisar, 48, adds with a smile, “when they learned I was having museum curators take care of these pieces.”


A museum is exactly where he wants to put all 10,000 of his TV memorabilia items, everything from the hairpiece Carl Reiner wore on the 1950s TV variety program “Your Show of Shows” to the gun and badge Kiefer Sutherland flashed on “24″ a couple TV seasons ago.


Finding one that could accommodate his collection, which fills two sprawling, temperature-controlled warehouses, however, has sometimes been as hard as acquiring the boots Larry Hagman used to stomp around in when he was J.R. on “Dallas.” (The show’s production company finally coughed up a pair after plenty of pleading and cajoling.)


Comisar is one of many people who, after a lifetime of collecting, begin to realize that if they can’t find a permanent home for their artifacts those objects could easily end up on the trash heap of history. Or, just as bad as far as he’s concerned, in the hands of private collectors.


“Some of the biggest bidders for Hollywood memorabilia right now reside in mainland China and Dubai, and our history could leave this country forever,” says Comisar, who these days works as a broker and purchasing expert for memorabilia collectors.


What began as a TV-obsessed kid’s lark morphed into a full-fledged hobby when as a young man writing jokes for Howie Mandel and Joan Rivers, and punching up scripts for such producers as Norman Lear and Fred Silverman, Comisar began scouring studio back lots, looking for discarded stuff from the favorite shows of his childhood. From there it developed into a full-on obsession, dedicated to preserving the entire physical spectrum of television history.


“After a couple years of collecting, it became clear to me,” he says, “that it didn’t much matter what TV shows James watched in the early 1970s but which shows were the most iconic. In that way, I had sort of a curator’s perspective almost from the beginning.”


In the early days, collecting such stuff was easy for anyone with access to a studio back lot. Many items were simply thrown out or given away when shows ceased production. When studios did keep things they often rented them out for small fees, and if you lost or broke them you paid a small replacement fee. So Comisar began renting stuff right and left and promptly losing it, acquiring one of Herman Munster’s jackets that way.


These days almost everything has a price, although Comisar’s reputation as a serious collector has led some people to give him their stuff.


If he simply sold it all, he could probably retire as a millionaire several times over. Just last month someone paid $ 480,000 for a faded dress Judy Garland wore in the 1939 film “The Wizard of Oz.” What might Annette Funicello’s original Mickey Mouse Club jacket fetch?


He won’t even think about that.


“I’ve spent 25 years now reuniting these pieces, and I would be so sick if some day they were just broken up and sold to the highest bidder,” he says.


He, and every other serious collector of cool but somewhat oddball stuff, face two major obstacles, say museum curators: Finding a museum or university with the space to take their treasures and persuading deep-pocketed individuals who might bankroll the endeavor that there’s really any compelling reason to preserve something like Maxwell Smart’s shoephone.


“People hold television and popular culture so close to their hearts and embrace it so passionately,” says Dwight Bowers, curator of entertainment collections for the Smithsonian’s National Museum of American History, who calls Comisar’s collection very impressive. “But they don’t put it on the same platform as military history or political history.”


When the Smithsonian acquired Archie Bunker’s chair from the seminal TV comedy “All in the Family,” Bowers said, museum officials took plenty of flak from those offended that some sitcom prop was being placed down the hallway from the nation’s presidential artifacts.


The University of California, Santa Cruz, took similar heat when it accepted the Grateful Dead archives, 30 years of recordings, videos, papers, posters and other memorabilia gifted by the band, said university archivist Nicholas Meriwether.


“What I always graciously say is that if you leave the art and the music aside for one moment, whatever you think of it, what you can say is they are still a huge part of understanding the story of the 1960s and of understanding the nation’s counterculture,” says Meriwether.


Comisar sees his television collection serving the same purpose, tracing societal changes TV shows documented from the post-World War II years to the present.


The Academy of Television Arts and Sciences Foundation looked into establishing such a museum some years back, and Comisar’s collection came up at the time, said Karen Herman, curator of the foundation’s Archive of American Television.


Instead, the foundation settled on an online archive containing more than 3,000 hours of filmed oral history interviews with more than 700 people.


While the archive doesn’t have any of Mr. Spock’s ears, anyone with a computer can view and listen to an oral history from Spock himself, the actor Leonard Nimoy.


Comisar, meanwhile, believes he’s finally found the right site for a museum, in Phoenix, where he’s been lining up supporters. He estimates it will cost $ 35 million and several years to open the doors, but hopes to have a preview center in place by next year.


Mo Stein, a prominent architect who heads the Phoenix Community Alliance and is working with him, says one of the next steps will be finding a proper space for the collection.


But, really, why all the fuss over a place to save one of the suits Regis Philbin wore on “Who Wants to be a Millionaire”?


“In Shakespeare’s time, his work was considered pretty low art,” Comisar responds.


Oh, he’ll admit that “Mike and Molly,” the modern TV love story of a couple who fall for each other at Overeaters Anonymous, may never rank in the same category as “Romeo and Juliet.”


“But what about a show like ‘Star Trek’?” he asks.


Entertainment News Headlines – Yahoo! News





Title Post: A huge collection of odd TV stuff needs a home
Rating:
100%

based on 99998 ratings.
5 user reviews.
Author: Fluser SeoLink
Thanks for visiting the blog, If any criticism and suggestions please leave a comment




Read More..

Four firefighters shot, two fatally, in western New York












Four volunteer firefighters responding to an intense pre-dawn house fire were shot Monday morning, two fatally, leading to a shootout between a suspect and police in suburban Rochester, N.Y., police said.


"One or more shooters" fired at the firefighters after they arrived shortly after 5:30 a.m. at the blaze near the Lake Ontario shore, just east of Rochester, Town of Webster Police Chief Gerald Pickering said.











There was no active shooter at the scene later Monday morning, according to Monroe County Sheriff Patrick O'Flynn. The first Webster police officer who arrived on the scene exchanged gunfire with the shooter, Flynn said, but he had no other information on the shootout.


The West Webster Fire District received a report of a car and house on fire on Lake Road, on a narrow peninsula where Irondequoit Bay meets Lake Ontario, Flynn said.


"When they got there, they stated to take on rounds and the initial responders were struck," the sheriff said.


The two wounded firefighters were in critical condition at a Rochester hospital, Flynn said.


The fire started in one home and spread to two others and a car, officials said. The fire appeared from a distance as a pulsating ball of flame glowing against the early morning sky, flames licking into treetops and reflecting on the water, with huge bursts of smoke billowing away in a brisk wind.


Webster, a middle-class, lakeside suburb, now is the scene of violence linked to house fires for two Decembers in a row.


Last Dec. 7, authorities say, a 15-year-old boy doused his home with gasoline and set it ablaze, killing his father and two brothers, 16 and 12. His mother and 13-year-old sister escaped with injuries. He is being prosecuted as an adult.





Read More..

Pro-gun rights US petition to deport Piers Morgan






LONDON (AP) — Tens of thousands of people have signed a petition calling for British CNN host Piers Morgan to be deported from the U.S. over his gun control views.


Morgan has taken an aggressive stand for tighter U.S. gun laws in the wake of the Newtown, Connecticut, school shooting. Last week, he called a gun advocate appearing on his “Piers Morgan Tonight” show an “unbelievably stupid man.”






Now, gun rights activists are fighting back. A petition created Dec. 21 on the White House e-petition website by a user in Texas accuses Morgan of engaging in a “hostile attack against the U.S. Constitution” by targeting the Second Amendment. It demands he be deported immediately for “exploiting his position as a national network television host to stage attacks against the rights of American citizens.”


The petition has already hit the 25,000 signature threshold to get a White House response. By Monday, it had 31,813 signatures.


Morgan seemed unfazed — and even amused — by the movement.


In a series of Twitter messages, he alternately urged his followers to sign the petition and in response to one article about the petition said “bring it on” as he appeared to track the petition’s progress.


“If I do get deported from America for wanting fewer gun murders, are there any other countries that will have me?” he wrote.


Entertainment News Headlines – Yahoo! News





Title Post: Pro-gun rights US petition to deport Piers Morgan
Rating:
100%

based on 99998 ratings.
5 user reviews.
Author: Fluser SeoLink
Thanks for visiting the blog, If any criticism and suggestions please leave a comment




Read More..

N.Y.U. and Others Offer Shorter Courses Through Medical School





Training to become a doctor takes so long that just the time invested has become, to many, emblematic of the gravity and prestige of the profession.




But now one of the nation’s premier medical schools, New York University, and a few others around the United States are challenging that equation by offering a small percentage of students the chance to finish early, in three years instead of the traditional four.


Administrators at N.Y.U. say they can make the change without compromising quality, by eliminating redundancies in their science curriculum, getting students into clinical training more quickly and adding some extra class time in the summer.


Not only, they say, will those doctors be able to hang out their shingles to practice earlier, but they will save a quarter of the cost of medical school — $49,560 a year in tuition and fees at N.Y.U., and even more when room, board, books, supplies and other expenses are added in.


“We’re confident that our three-year students are going to get the same depth and core knowledge, that we’re not going to turn it into a trade school,” said Dr. Steven Abramson, vice dean for education, faculty and academic affairs at N.Y.U. School of Medicine.


At this point, the effort involves a small number of students at three medical schools: about 16 incoming students at N.Y.U., or about 10 percent of next year’s entering class; 9 at Texas Tech Health Science Center School of Medicine; and even fewer, for now, at Mercer University School of Medicine’s campus in Savannah, Ga. A similar trial at Louisiana State University has been delayed because of budget constraints.


But Dr. Steven Berk, the dean at Texas Tech, said that 10 or 15 other schools across the country had expressed interest in what his university was doing, and the deans of all three schools say that if the approach works, they will extend the option to larger numbers of students.


“You’re going to see this kind of three-year pathway become very prominent across the country,” Dr. Abramson predicted.


The deans say that getting students out the door more quickly will accomplish several goals. By speeding up production of physicians, they say, it could eventually dampen a looming doctor shortage, although the number of doctors would not increase unless the schools enrolled more students in the future.


The three-year program would also curtail student debt, which now averages $150,000 by graduation, and by doing so, persuade more students to go into shortage areas like pediatrics and internal medicine, rather than more lucrative specialties like dermatology.


The idea was supported by Dr. Ezekiel J. Emanuel, a former health adviser to President Obama, and a colleague, Victor R. Fuchs. In an editorial in the Journal of the American Medical Association in March, they said there was “substantial waste” in the nation’s medical education. “Years of training have been added without evidence that they enhance clinical skills or the quality of care,” they wrote. They suggested that the 14 years of college, medical school, residency and fellowship that it now takes to train a subspecialty physician could be reduced by 30 percent, to 10 years.


That opinion, however, is not universally held. Other experts say that a three-year medical program would deprive students of the time they need to delve deeply into their subjects, to consolidate their learning and to reach the level of maturity they need to begin practicing, while adding even more pressure to a stressful academic environment.


“The downside is that you are really tired,” said Dr. Dan Hunt, co-secretary of the Liaison Committee on Medical Education, the accrediting agency for medical schools in the United States and Canada. But because accreditation standards do not dictate the fine points of curriculum, the committee has approved N.Y.U.’s proposal, which exceeds by five weeks its requirement that schools provide at least 130 weeks of medical education.


The medical school is going ahead with its three-year program despite the damage from Hurricane Sandy, which forced NYU Langone Medical Center to evacuate more than 300 patients at the height of the storm and temporarily shut down three of its four main teaching hospitals.


Dr. Abramson of N.Y.U. said that postgraduate training, which typically includes three years in a hospital residency, and often fellowships after that, made it unnecessary to try to cram everything into the medical school years. Students in the three-year program will have to take eight weeks of class before entering medical school, and stay in the top half of their class academically. Those who do not meet the standards will revert to the four-year program.


Read More..

Raging fire guts Kabul market









KABUL, Afghanistan -- Firefighters battled through the night to contain a raging fire that swept through a market in the Afghan capital.

No injuries were reported, but the blaze destroyed hundreds of stores and millions of dollars worth of merchandise, Afghan police and firefighters said at the scene. 


Dealers at the neighboring currency exchange, the city’s largest, said they evacuated cash, computer equipment and records from their shops as the flames approached during the night. But in the morning, the market was jammed with people haggling over thick stacks of notes as smoke billowed overhead.





Col. Mohammed Qasem, general director of the Kabul fire department, said he suspected an electrical short was to blame for the fire. 


Gas canisters used to heat the stores propelled the flames, along with the cloth and clothing sold by many of the vendors, Qasem said. “It made it very big in a short time.”


Firefighters from the Afghan defense department and NATO forces were sent to assist. But the city’s notorious traffic and the market’s narrow lanes made it difficult for responders to maneuver their vehicles, Qasem said.


Abdulrahman, who like many Afghans has only one name, squatted near a fire truck with his head in his hands  as responders aimed a hose at the blackened ruins of a building still smoldering at noon Sunday, more than 12 hours after the fire broke out.


He said the building had contained three shops that he owned and a warehouse full of glassware, crockery and kitchen utensils. 


“I lost everything,” he said.


Shirali Khan complained that police hadn't allowed him to remove the goods from his four clothing stores.


“They thought we were all robbers,” he said.  “There’s only ashes left.”


ALSO:


Pope pardons former butler convicted of theft


Bombing kills local official, 7 other people in Pakistan


Tensions high as vote on proposed Egyptian constitution continues


Special correspondent Hashmat Baktash contributed to this report.






Read More..

Disney Sets August 9 Release for ‘Cars’ Spin-off ‘Planes’






NEW YORK (TheWrap.com) – Disney will release “Planes,” a spin-off of Pixar‘s “Cars” franchise, August 9, 2013, in the United States. DisneyToon Studios is behind the film with Pixar/Disney Animation chief creative officer John Lasseter producing.


The film follows a fleet of planes, in particular Dusty. “Two and a Half Men” star Jon Cryer was to voice Dusty, but he has dropped out and the studio is now casting the part.






Disney initially intended to release “Planes” direct to video, but it will now send it into theaters domestically and overseas.


“Planes” will compete against a pair of films that summer weekend, both of which should have more adult followings. The big-ticket item will be Sony’s “Elysium,” Neill Blomkamp‘s follow-up to “District 9.” Also opening that weekend is “We’re the Millers,” a New Line drug-smuggling comedy starring Jason Sudeikis and Jennifer Aniston.


Next summer’s biggest animated movies should all be sequels save “Epic,” Fox’s story of a teenage girl caught in a forested battle. Beyonce Knowles‘ leads the voice cast. The other big openers are Despicable Me 2,” “Monsters University” and “Smurfs 2.”


Movies News Headlines – Yahoo! News





Title Post: Disney Sets August 9 Release for ‘Cars’ Spin-off ‘Planes’
Rating:
100%

based on 99998 ratings.
5 user reviews.
Author: Fluser SeoLink
Thanks for visiting the blog, If any criticism and suggestions please leave a comment




Read More..

Genetic Gamble : Drugs Aim to Make Several Types of Cancer Self-Destruct


C.J. Gunther for The New York Times


Dr. Donald Bergstrom is a cancer specialist at Sanofi, one of three companies working on a drug to restore a tendency of damaged cells to self-destruct.







For the first time ever, three pharmaceutical companies are poised to test whether new drugs can work against a wide range of cancers independently of where they originated — breast, prostate, liver, lung. The drugs go after an aberration involving a cancer gene fundamental to tumor growth. Many scientists see this as the beginning of a new genetic age in cancer research.




Great uncertainties remain, but such drugs could mean new treatments for rare, neglected cancers, as well as common ones. Merck, Roche and Sanofi are racing to develop their own versions of a drug they hope will restore a mechanism that normally makes badly damaged cells self-destruct and could potentially be used against half of all cancers.


No pharmaceutical company has ever conducted a major clinical trial of a drug in patients who have many different kinds of cancer, researchers and federal regulators say. “This is a taste of the future in cancer drug development,” said Dr. Otis Webb Brawley, the chief medical and scientific officer of the American Cancer Society. “I expect the organ from which the cancer came from will be less important in the future and the molecular target more important,” he added.


And this has major implications for cancer philanthropy, experts say. Advocacy groups should shift from fund-raising for particular cancers to pushing for research aimed at many kinds of cancer at once, Dr. Brawley said. John Walter, the chief executive officer of the Leukemia and Lymphoma Society, concurred, saying that by pooling forces “our strength can be leveraged.”


At the heart of this search for new cancer drugs are patients like Joe Bellino, who was a post office clerk until his cancer made him too sick to work. Seven years ago, he went into the hospital for hernia surgery, only to learn he had liposarcoma, a rare cancer of fat cells. A large tumor was wrapped around a cord that connects the testicle to the abdomen. “I was shocked,” he said in an interview this summer.


Companies have long ignored liposarcoma, seeing no market for drugs to treat a cancer that strikes so few. But it is ideal for testing Sanofi’s drug because the tumors nearly always have the exact genetic problem the drug was meant to attack — a fusion of two large proteins. If the drug works, it should bring these raging cancers to a halt. Then Sanofi would test the drug on a broad range of cancers with a similar genetic alteration. But if the drug fails against liposarcoma, Sanofi will reluctantly admit defeat.


“For us, this is a go/no-go situation,” said Laurent Debussche, a Sanofi scientist who leads the company’s research on the drug.


The genetic alteration the drug targets has tantalized researchers for decades. Normal healthy cells have a mechanism that tells them to die if their DNA is too badly damaged to repair. Cancer cells have grotesquely damaged DNA, so ordinarily they would self-destruct. A protein known as p53 that Dr. Gary Gilliland of Merck calls the cell’s angel of death normally sets things in motion. But cancer cells disable p53, either directly, with a mutation, or indirectly, by attaching the p53 protein to another cellular protein that blocks it. The dream of cancer researchers has long been to reanimate p53 in cancer cells so they will die on their own.


The p53 story began in earnest about 20 years ago. Excitement ran so high that, in 1993, Science magazine anointed it Molecule of the Year and put it on the cover. An editorial held out the possibility of “a cure of a terrible killer in the not too distant future.”


Companies began chasing a drug to restore p53 in cells where it was disabled by mutations. But while scientists know how to block genes, they have not figured out how to add or restore them. Researchers tried gene therapy, adding good copies of the p53 gene to cancer cells. That did not work.


Then, instead of going after mutated p53 genes, they went after half of cancers that used the alternative route to disable p53, blocking it by attaching it to a protein known as MDM2. When the two proteins stick together, the p53 protein no longer functions. Maybe, researchers thought, they could find a molecule to wedge itself between the two proteins and pry them apart.


The problem was that both proteins are huge and cling tightly to each other. Drug molecules are typically tiny. How could they find one that could separate these two bruisers, like a referee at a boxing match?


In 1996, researchers at Roche noticed a small pocket between the behemoths where a tiny molecule might slip in and pry them apart. It took six years, but Roche found such a molecule and named it Nutlin because the lab was in Nutley, N.J.


But Nutlins did not work as drugs because they were not absorbed into the body.


Roche, Merck and Sanofi persevered, testing thousands of molecules.


At Sanofi, the stubborn scientist leading the way, Dr. Debussche, maintained an obsession with p53 for two decades. Finally, in 2009, his team, together with Shaomeng Wang at the University of Michigan and a biotech company, Ascenta Therapeutics, found a promising compound.


The company tested the drug by pumping it each day into the stomachs of mice with sarcoma.


Read More..

Genetic Gamble : Drugs Aim to Make Several Types of Cancer Self-Destruct


C.J. Gunther for The New York Times


Dr. Donald Bergstrom is a cancer specialist at Sanofi, one of three companies working on a drug to restore a tendency of damaged cells to self-destruct.







For the first time ever, three pharmaceutical companies are poised to test whether new drugs can work against a wide range of cancers independently of where they originated — breast, prostate, liver, lung. The drugs go after an aberration involving a cancer gene fundamental to tumor growth. Many scientists see this as the beginning of a new genetic age in cancer research.




Great uncertainties remain, but such drugs could mean new treatments for rare, neglected cancers, as well as common ones. Merck, Roche and Sanofi are racing to develop their own versions of a drug they hope will restore a mechanism that normally makes badly damaged cells self-destruct and could potentially be used against half of all cancers.


No pharmaceutical company has ever conducted a major clinical trial of a drug in patients who have many different kinds of cancer, researchers and federal regulators say. “This is a taste of the future in cancer drug development,” said Dr. Otis Webb Brawley, the chief medical and scientific officer of the American Cancer Society. “I expect the organ from which the cancer came from will be less important in the future and the molecular target more important,” he added.


And this has major implications for cancer philanthropy, experts say. Advocacy groups should shift from fund-raising for particular cancers to pushing for research aimed at many kinds of cancer at once, Dr. Brawley said. John Walter, the chief executive officer of the Leukemia and Lymphoma Society, concurred, saying that by pooling forces “our strength can be leveraged.”


At the heart of this search for new cancer drugs are patients like Joe Bellino, who was a post office clerk until his cancer made him too sick to work. Seven years ago, he went into the hospital for hernia surgery, only to learn he had liposarcoma, a rare cancer of fat cells. A large tumor was wrapped around a cord that connects the testicle to the abdomen. “I was shocked,” he said in an interview this summer.


Companies have long ignored liposarcoma, seeing no market for drugs to treat a cancer that strikes so few. But it is ideal for testing Sanofi’s drug because the tumors nearly always have the exact genetic problem the drug was meant to attack — a fusion of two large proteins. If the drug works, it should bring these raging cancers to a halt. Then Sanofi would test the drug on a broad range of cancers with a similar genetic alteration. But if the drug fails against liposarcoma, Sanofi will reluctantly admit defeat.


“For us, this is a go/no-go situation,” said Laurent Debussche, a Sanofi scientist who leads the company’s research on the drug.


The genetic alteration the drug targets has tantalized researchers for decades. Normal healthy cells have a mechanism that tells them to die if their DNA is too badly damaged to repair. Cancer cells have grotesquely damaged DNA, so ordinarily they would self-destruct. A protein known as p53 that Dr. Gary Gilliland of Merck calls the cell’s angel of death normally sets things in motion. But cancer cells disable p53, either directly, with a mutation, or indirectly, by attaching the p53 protein to another cellular protein that blocks it. The dream of cancer researchers has long been to reanimate p53 in cancer cells so they will die on their own.


The p53 story began in earnest about 20 years ago. Excitement ran so high that, in 1993, Science magazine anointed it Molecule of the Year and put it on the cover. An editorial held out the possibility of “a cure of a terrible killer in the not too distant future.”


Companies began chasing a drug to restore p53 in cells where it was disabled by mutations. But while scientists know how to block genes, they have not figured out how to add or restore them. Researchers tried gene therapy, adding good copies of the p53 gene to cancer cells. That did not work.


Then, instead of going after mutated p53 genes, they went after half of cancers that used the alternative route to disable p53, blocking it by attaching it to a protein known as MDM2. When the two proteins stick together, the p53 protein no longer functions. Maybe, researchers thought, they could find a molecule to wedge itself between the two proteins and pry them apart.


The problem was that both proteins are huge and cling tightly to each other. Drug molecules are typically tiny. How could they find one that could separate these two bruisers, like a referee at a boxing match?


In 1996, researchers at Roche noticed a small pocket between the behemoths where a tiny molecule might slip in and pry them apart. It took six years, but Roche found such a molecule and named it Nutlin because the lab was in Nutley, N.J.


But Nutlins did not work as drugs because they were not absorbed into the body.


Roche, Merck and Sanofi persevered, testing thousands of molecules.


At Sanofi, the stubborn scientist leading the way, Dr. Debussche, maintained an obsession with p53 for two decades. Finally, in 2009, his team, together with Shaomeng Wang at the University of Michigan and a biotech company, Ascenta Therapeutics, found a promising compound.


The company tested the drug by pumping it each day into the stomachs of mice with sarcoma.


Read More..