News Analysis: Getting Polio Campaigns Back on Track





How in the world did something as innocuous as the sugary pink polio vaccine turn into a flash point between Islamic militants and Western “crusaders,” flaring into a confrontation so ugly that teenage girls — whose only “offense” is that they are protecting children — are gunned down in the streets?




Nine vaccine workers were killed in Pakistan last week in a terrorist campaign that brought the work of 225,000 vaccinators to a standstill. Suspicion fell immediately on factions of the Pakistani Taliban that have threatened vaccinators in the past, accusing them of being American spies.


Polio eradication officials have promised to regroup and try again. But first they must persuade the killers to stop shooting workers and even guarantee safe passage.


That has been done before, notably in Afghanistan in 2007, when Mullah Muhammad Omar, spiritual head of the Afghan Taliban, signed a letter of protection for vaccination teams. But in Pakistan, the killers may be breakaway groups following no one’s rules.


Vaccination efforts are also under threat in other Muslim regions, although not this violently yet.


In Nigeria, another polio-endemic country, the new Islamic militant group Boko Haram has publicly opposed it, although the only killings that the news media have linked to polio were those of two police officers escorting vaccine workers. Boko Haram has killed police officers on other missions, unrelated to polio vaccinations.


In Mali, extremists took over half of the country in May, declaring an Islamic state. Vaccination is not an issue yet, but Mali had polio cases as recently as mid-2011, and the virus sometimes circulates undetected.


Resistance to polio vaccine springs from a combination of fear, often in marginalized ethnic groups, and brutal historical facts that make that fear seem justified. Unless it is countered, and quickly, the backlash threatens the effort to eradicate polio in the three countries where it remains endemic: Pakistan, Afghanistan and Nigeria.


In 1988, long before donors began delivering mosquito nets, measles shots, AIDS pills, condoms, deworming drugs and other Western medical goods to the world’s most remote villages, Rotary International dedicated itself to wiping out polio, and trained teams to deliver the vaccine.


But remote villages are often ruled by chiefs or warlords who are suspicious not only of Western modernity, but of their own governments.


The Nigerian government is currently dominated by Christian Yorubas. More than a decade ago, when word came from the capital that all children must swallow pink drops to protect them against paralysis, Muslim Hausas in the far-off north could be forgiven for reacting the way the fundamentalist Americans of the John Birch Society did in the 1960s when the government in far-off Washington decreed that, for the sake of children’s teeth, all drinking water should have fluoride.


The northerners already had grievances. In 1996, the drug company Pfizer tested its new antibiotic, Trovan, during a meningitis outbreak there. Eleven children died. Although Pfizer still says it was not to blame, the trial had irregularities, and last year the company began making payments to victims.


Other rumors also spring from real events.


In Pakistan, resistance to vaccination, low over all, is concentrated in Pashtun territory along the Afghan border and in Pashtun slums in large cities. Pashtuns are the dominant tribe in Afghanistan but a minority in Pakistan among Punjabis, Sindhis, Baluchis and other ethnic groups. Many are Afghan refugees and are often poor and dismissed as medieval and lawless.


Pakistan’s government is friendly with the United States while the Pashtuns’ territory in border areas has been heavily hit by American Taliban-hunting drones, which sometimes kill whole families.


So, when the Central Intelligence Agency admitted sponsoring a hepatitis vaccination campaign as a ruse to get into a compound in Pakistan to confirm that Osama bin Laden was there, and the White House said it had contemplated wiping out the residence with a drone missile, it was not far-fetched for Taliban leaders to assume that other vaccinators worked for the drone pilots.


Even in friendly areas, the vaccine teams have protocols that look plenty suspicious. If a stranger knocked on a door in Brooklyn, asked how many children under age 5 were at home, offered to medicate them, and then scribbled in chalk on the door how many had accepted and how many refused — well, a parent might worry.


In modern medical surveys — though not necessarily on polio campaigns — teams carry GPS devices so they can find houses again. Drones use GPS coordinates.


The warlords of Waziristan made the connection specific, barring all vaccination there until Predator drones disappeared from the skies.


Dr. Bruce Aylward, a Canadian who is chief of polio eradication for the World Health Organization, expressed his frustration at the time, saying, “They know we don’t have any control over drone strikes.”


The campaign went on elsewhere in Pakistan — until last week.


The fight against polio has been hampered by rumors that the vaccine contains pork or the virus that causes AIDS, or is a plot to sterilize Muslim girls. Even the craziest-sounding rumors have roots in reality.


The AIDS rumor is a direct descendant of Edward Hooper’s 1999 book, “The River,” which posited the theory — since discredited — that H.I.V. emerged when an early polio vaccine supposedly grown in chimpanzee kidney cells contaminated with the simian immunodeficiency virus was tested in the Belgian Congo.


The sterilization claim was allegedly first made on a Nigerian radio station by a Muslim doctor upset that he had been passed over for a government job. The “proof” was supposed to be lab tests showing it contained estrogen, a birth control hormone.


The vaccine virus is grown in a broth of live cells; fetal calf cells are typical. They may be treated with a minute amount of a digestive enzyme, trypsin — one source of which is pig pancreas, which could account for the pork rumor.


In theory, a polio eradicator explained, if a good enough lab tested the vaccine used at the time the rumor started, it might have detected estrogen from the calf’s mother, but it would have been far less estrogen than is in mother’s milk, which is not accused of sterilizing anyone. The trypsin is supposed to be washed out.


In any case, polio vaccine is now bought only from Muslim countries like Indonesia, and Muslim scholars have ruled it halal — the Islamic equivalent of kosher.


Reviving the campaign will mean quelling many rumors. It may also require adding other medical “inducements,” like deworming medicine, mosquito nets or vitamin A, whose immediate benefits are usually more obvious.


But changing mind-sets will be a crucial step, said Dr. Aylward, who likened the shootings of the girls to those of the schoolchildren in Newtown, Conn.


More police involvement — what he called a “bunkerized approach” — would not solve either America’s problem or Pakistan’s, he argued. Instead, average citizens in both countries needed to rise up, reject the twisted thinking of the killers and “generate an understanding in the community that this kind of behavior is not acceptable.”


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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.






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Wired Science Space Photo of the Day: Hourglass Nebula











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Barbra Streisand goes on a “Guilt Trip” with Seth Rogen






LOS ANGELES (Reuters) – Road-trip movies have been dominated by teenagers on wild adventures or “Hangover” style bro-mances, but Barbra Streisand and Seth Rogen are driving the genre into new territories with mother-son comedy “The Guilt Trip” to usher in the holiday season.


“The Guilt Trip,” which hits U.S. theaters this week, follows struggling novice inventor Andy (Seth Rogen), who is guilted in to bringing his mother on a work-related road-trip across the country.






Streisand, 70, who broke out as an actress in 1968′s comedy “Funny Girl,” returns to her comedic roots as Joyce, Andy’s overbearing mother, who becomes closer to her son over the duration of their tense and comedic adventures on the road.


The actress told reporters at a recent press conference that it was her son Jason Gould who convinced her to do the project after reading the script with her, and Streisand found a deeper connection to the story.


“Mothers develop guilt trips,” Streisand said. “(When my own son was young) I was working a lot and I felt guilty as a parent that I cannot pick (up) my son everyday from school, bake him cookies, that kind of thing. And so you try and compensate.”


“I thought it was interesting to investigate this – trying to be his friend versus a mother…this movie, it hit on all those things that I thought I could explore.”


Rogen, 30, also related closely to the mother-son storyline, saying that while he has a “good relationship” with his own mom, even she can drive him “crazy” sometimes.


“That dynamic where your mother is trying and the more she tries, the more it bugs you, the more it bugs you, the more she tries….All that is very, at times, real to my relationship with my mother,” Rogen said.


STAYING OUT OF THE SPOTLIGHT


Streisand, who is one of the few actresses to win a Tony, Emmy, Grammy and Oscar award over her six-decade career, last took a leading role in 1996′s “The Mirror Has Two Faces,” which she also directed and produced.


The actress initially had reservations about signing onto the movie and said she gave the movie studio numerous clauses “because I kept wanting an out some way.”


Her requests included having a set “no more than 45 minutes away from my house” and later morning starts, as “my husband (James Brolin) and I stay up until two or three in the morning so we don’t function…at six in the morning.”


Streisand’s requests were granted, and thus came about a road trip movie where the actors never actually went on the road. The film ended up largely being shot on a sound stage with Streisand and Rogen in a car against a green screen while backdrops of landmarks such as the Grand Canyon, were added in later.


With the exception of a supporting role as Ben Stiller’s mother in 2004′s “Meet The Fockers” and 2010′s “Little Fockers,” Streisand has stayed out of the spotlight in recent years, and attributes that as one of the keys to her long-standing success.


“I don’t make many movies and I don’t make that many appearances. Less is more. Maybe that keeps a little mystery,” Streisand said, adding that she likes to “stay at home a lot.”


While she hasn’t signed onto another project just yet, she said what keeps her satisfied as an artist is engaging in work that is “private” as opposed to being on public display.


“I love recording and I love making films as a filmmaker,” she said. “Because it uses every bit of what you have experienced or know, whether it’s graphics, composition, decorating, psychology, storytelling, whatever it is. It’s a wonderful thing.”


(Editing by Piya Sinha-Roy and Lisa Shumaker)


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Tepid Sales of Microsoft’s Windows 8 Point to Shaky Market


Mario Tama/Getty Images


Plenty of consumers already own PCs and seem content to make do with what they have.







BELLEVUE, Wash. — It used to be that a new version of the Windows operating system was enough to get people excited about buying a new computer, giving sales a nice pop.








Ted S. Warren/Associated Press

Earlier versions of Windows all came out during periods when the PC’s status as the center of computing seemed far more secure.






Not this time. Windows 8, the latest edition of Microsoft’s software, failed to pack shoppers into a Microsoft store in a mall here last week, at a time when parking lots in the area were overflowing. The trickle of shopping bags leaving the store with merchandise was nothing like the steady stream at a bustling Apple store upstairs.


Claude Ballard was among the customers at the Microsoft store who tried out Surface, a new Microsoft-designed Windows tablet. Mr. Ballard, who described himself as a “semiretired” computer systems manager for a real estate firm, said he was intrigued by the eye-catching design of Windows 8 — but not enough to scrimp to buy a new computer this year.


“It’s economics, really,” he said. “It’s going to be a better year for my mechanic than it is for me.”


Weak PC sales this holiday season suggest that the struggles of Microsoft and other companies that depend heavily on the computer business will not abate soon. Plenty of consumers already own PCs and seem content to make do with what they have, especially in a shaky economy in which less expensive mobile devices are bidding for a share of their wallets.


While there are also many tablets running Microsoft’s new, touch-friendly Windows, they have so far failed to emerge from the shadow of competing products from Apple and Amazon and other devices that are being snapped up by holiday shoppers.


Emmanuel Fromont, president of the Americas division of Acer, the world’s No. 4 PC maker, said sales of the company’s Windows 8 PCs had been lower than expected. He said one factor was the system’s unfamiliar design, which appeared to be making consumers cautious.


“There was not a huge spark in the market,” Mr. Fromont said. “It’s a slow start, there’s no question.”


The clearest evidence of Windows 8’s disappointing introduction comes from the research firm NPD, which estimates that sales of Windows machines have actually dropped from a year ago.


According to NPD, stores in the United States sold 13 percent fewer Windows devices from late October, when Windows 8 made its debut, through the first week in December, than in the same period last year.


Those figures do not include sales in Microsoft’s own stores, which were the only place to buy a Surface tablet during that period, but because the stores are scarce, analysts believe it is unlikely they made a big difference.


“I think everybody would have hoped for a better start,” said Stephen Baker, an analyst at NPD. “The thing is, this market is not the same market that Windows 7 or Vista or even XP launched into.”


Those earlier versions of Windows all came out during periods when the PC’s status as the center of computing seemed far more secure. In the intervening years, smartphones and tablets have become much more serious rivals for a share of consumer spending on technology. Sales of PCs have been declining for much of the year.


While most people are not getting rid of their PCs altogether in favor of mobile devices, analysts believe they are postponing purchases of new ones.


“What you’re seeing is not a retirement of PCs, but a push-out in the replacement cycle,” said A. M. Sacconaghi, an analyst at Sanford C. Bernstein. “If people used to buy PCs every four years and are now buying them every five years, that could lower PC sales by 20 percent over time. That’s substantial.”


Mr. Sacconaghi predicted that global PC shipments would be down 3 percent in 2012.


The shift in spending to tablets is one reason that Windows 8 is so critical for Microsoft’s future. The company overhauled its operating system with a radically different, tile-based interface that is easier to navigate on touch-screen devices. Microsoft intends the software to be flexible enough that it can still be used on conventional laptops and desktops, including newer models with touch screens.


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Meat company owner sues USDA for right to slaughter horses









Rick de los Santos wants to reopen an animal slaughter business that's been banned in the U.S. for years. Along the way, he's also opened a can of worms.


The Roswell, N.M., meat company owner sued the federal government last week, alleging that officials ignored his application to resume domestic horse slaughter for food because the practice had become an emotional political issue throughout the West.


After waiting a year for permits, De los Santos, 52, says he's using the courts to force the U.S. Department of Agriculture to resume inspections necessary to open what would be the nation's first new horse slaughterhouse since 2007.





"I've submitted all the paperwork and have been told all along 'Oh, it won't be long now,'" said De los Santos, who owns Valley Meat Co. "I followed all their guidelines. I put more than $100,000 in upgrades and additions on my facilities to handle equine slaughter. And then the government comes back and tells me, 'We can't give you the permits. This horse issue has turned into a political game.'


"So what else do you do? I figured it was time to go to court."


The slaughterhouse owner, whose business had been slaughtering cattle, is also suing the Humane Society of the United States, Front Range Equine Rescue and Animal Protection of New Mexico, accusing those groups of defamation and causing loss of income during the dispute.


The dispute over killing horses has raged for years. Equine advocates have accused the Bureau of Land Management of failing to protect tens of thousands of mustangs that wander government-owned land in 10 Western states. Many of the animals are corralled each year and sent to long-term holding facilities. And reports surfaced this fall that the BLM was knowingly selling wild horses for slaughter, an outcome banned annually by Congress. The agency is investigating the claim.


In 2007, the last three domestic slaughterhouses in the United States were closed. Since then, unwanted domestic animals have been shipped to Mexico and Canada for slaughter.


Many animal protection groups and public officials were outraged at the idea of resuming domestic horse slaughter, including New Mexico Gov. Susana Martinez, a Republican, who has opposed the plan.


Many animal advocates says horse slaughter has no business in the U.S.


"Everything is wrong with this idea," said Sally Summers, founder of Horse Power, a Nevada-based equine advocacy group. "The economy has done just fine without this type of slaughter. And these plants are toxic to the community. They hurt these towns; they don't help them."


Summers said that many of the drugs that U.S. owners give their horses to ensure longevity and peak performance are carcinogenic. "This stuff gets into the water table through the drains," she said. "It's a nightmare. This man is smoking a pipe and I don't know what's in it."


The USDA declined to comment last week on the pending litigation. The agency has until January to respond to the suit, filed in federal court in late October.


De los Santos says his lawsuit will show that a recent "marked change in cooperation" by the USDA is due to pressure the government is receiving on the horse issue.


Some support a return to domestic horse slaughter. The American Quarter Horse Assn. says a 2011 report from the federal Government Accountability Office shows horse abuse and abandonment have been increasing since Congress essentially banned horse slaughter by cutting funding for USDA inspection programs in 2006.


The number of U.S. horses sent to other countries for slaughter has nearly tripled since domestic horse slaughter ceased. Most animal advocacy groups agree that some of the worst abuse occurs in the slaughter pipeline that often takes horses to inhumane facilities in Mexico.


Last year, 68,429 horses were shipped to Mexico and 64,652 to Canada, according to USDA statistics compiled by the Equine Welfare Alliance, a nonprofit group dedicated to ending horse slaughter. That compares with total exports of 37,884 of the animals in 2006.


De los Santos says he is tired of sitting in southern New Mexico and watching countless truckloads of horses en route to Mexico for slaughter.


"I've seen 130,000 horses a year on their way to Mexico — they go right through our backyard — and I wanted to tap into the market," he said. "I could have hired 100 people by now. Everyone in our community agrees we need this type of service. And I'm tired of waiting."


De los Santos says he is ready to start killing horses humanely.


"Everything that has four legs that walks can be slaughtered the same way, but we're ready to do this humanely," he said. "We've upgraded our knocking chutes for giving them that lethal hit."


He says he can't understand why everyone is so upset. Americans kill cows; why not horses?


"My wife says horse is on the menu all over Europe, but the moment you mention horse slaughter in the U.S., you've got a problem," he says.


john.glionna@latimes.com





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Terra/MODIS Color Image of Copahue Eruption Plume Across South America











For the first time since 2000, Copahue is erupting, sending an ash plume across southern South America. So far, the eruption is following the same patterns as the activity that ran from July to October 2000. That activity started with phreatic (water-driven) explosions, so it will be interesting to see if this eruption has new juvenile magma involved. Earlier this year, a study of the summit crater lake suggested new magma was intruding under Copahue and the SERNAGEOMIN report mentioned. that seismicity was rising before today’s eruption.


I grabbed the brand new Terra/MODIS imagery for South America and the plume from the Copahue was glorious – stretching over 350 km across Argentina to the east of the volcano. For a sense of scale on the image, the distance between Copahue and the Embalse los Barreales is ~225 km. The plume itself has been reported to be over 9.5 km / 30,000 feet tall.


UPDATE 12/22 5 PM EST: Eruptions reader Kirby pointed me to the SERNAGEOMIN webcam pointed at Copahue — check out the eruption live!


UPDATE 12/22 7 PM EST: ONEMI has not called for any evacuations on the Chilean side of Copahue — this article also has a nice gallery of pictures from the eruption as well.


Check out the original post with more details.




Erik Klemetti is an assistant professor of Geosciences at Denison University. His passion in geology is volcanoes, and he has studied them all over the world. You can follow Erik on Twitter, where you'll get volcano news and the occasional baseball comment.

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Reports: Rolling Stones guitarist Wood ties knot






LONDON (AP) — Two British newspapers say Rolling Stones guitarist Ronnie Wood has married his fiancee Sally Humphreys at a ceremony at London‘s Dorchester Hotel.


The Sun and the Daily Mirror carried photographs of the 65-year-old rocker with a pale boutonniere and a dark blue suit, and his 34-year-old bride in a traditional white gown and a clutch of matching white flowers.






The Sun quoted Wood as saying “I’m feeling great” as he and his bride kissed and posed for pictures outside the exclusive hotel in London’s upscale Mayfair district.


The newspapers said the guests included singer Rod Stewart and his wife Penny Lancaster as well as ex-Beatle Paul McCartney and his wife Nancy Shevell.


A call and an email to Wood’s U.S.-based agent weren’t immediately returned Saturday.


Entertainment News Headlines – Yahoo! News





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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.


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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.


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