Thousands sign 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.

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Gifts That Keep Giving (if Not Exploding)

Gregory Tobias/Chemical Heritage Foundation Collections

A Chemcraft set from the mid-1950s. More Photos »

Ask scientists of a certain age about their childhood memories, and odds are they’ll start yarning about the stink bombs and gunpowder they concocted with their chemistry sets. Dangerous? Yes, but fun.

“Admittedly, I have blown some things up in my time,” said William L. Whittaker, 64, a robotics professor at Carnegie Mellon University who unearthed his first chemistry set, an A. C. Gilbert, in a junkyard around age 8. By 16, he was dabbling in advanced explosives. “There’s no question that I burned some skin off my face,” he recalled.

Under today’s Christmas tree, girls and boys will unwrap science toys of a very different ilk: slime-making kits and perfume labs, vials of a fluff-making polymer called Insta-Snow, “no-chem” chemistry sets (chemical free!), plus a dazzling array of modern telescopes, microscopes and D.I.Y. volcanoes. Nothing in these gifts will set the curtains on fire.

“Basically, you have to be able to eat everything in the science kit,” said Jim Becker, president of SmartLab Toys, who recalled learning the names of chemicals from his childhood chemistry set, which contained substances that have long since been banned from toys.

Some scientists lament the passing of the trial-and-error days that inspired so many careers. “Science kits are a lot less open-ended these days,” said Kimberly Gerson, a science blogger who lives outside Toronto. “Everything is packaged. It’s either ‘yes’ or ‘no.’ If you don’t get the right result, you’ve done it wrong and you’re out of chemicals.”

Others, though, say the new crop of science toys — even with their cartoonish packaging and heavy emphasis on neon goo — actually represent progress. More entertaining, educational and accessible than earlier products, which relied heavily on a child’s inner motivation, these toys may actually help democratize the learning of science and introduce children to scientific methods and concepts at an earlier age.

“I grew up in the 1960s, and a lot of the chemistry sets were kind of boring,” said William Gurstelle, a science and technology writer. “You’d go through the book, and at the end of the experiment you’d get some light precipitate at the bottom of the beaker. Maybe at most it changes color or something.”

Mr. Gurstelle’s books, which include “Whoosh Boom Splat” and “Backyard Ballistics,” teach people how to make dangerous projectiles, like a potato cannon that uses hair spray as launching fluid. But he had high praise for commercial science kits, which show children (among other things) how to make slime.

Jeff Swensen for The New York Times

William L. Whittaker at the Planetary Robotics Lab at Carnegie Mellon University surrounded by the robots he has created.

“Well, that’s a pretty cool thing to have when you’re done,” Mr. Gurstelle said. “You’re not going to really learn to be a chemist from a chemistry set when you’re in seventh grade; you’re just going to be inspired. The point is that new chemistry sets and new toys are just better, because the manufacturers have figured out how to make them more fun.”

Some toy makers, like SmartLab, Mr. Becker’s company, have used this philosophy to give classic toys a makeover. One of SmartLab’s takes on a chemistry set, for instance, is the Extreme Secret Formula Lab, which comes with “squishy-lidded bubble test tubes” and “an abundance of glow-in-the-dark powder.” The game of Mousetrap has been re-envisioned as the Weird and Wacky Contraption Lab, meant to bring out children’s Rube Goldberg talents. And the slot car tracks that Mr. Becker recalls snapping together in his youth have been translated into a robot called ReCon 6.0, which children can program to roam around.

Mike Kane for The New York Times

Jim Becker of SmartLab Toys.

“What we do is give kids the opportunity to learn through problem solving,” Mr. Becker said.

Of course, technology has also remade the experience of learning science. Children may be more likely to click on a science app than to go play outside.

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Online holiday shoppers spent $1 billion on 'Free Shipping Day'

Shoppers scrambling to buy last-minute presents but avoid the malls spent $1.01 billion on this year's Free Shipping Day.

The annual event is scheduled to take place on the last day that orders delivered by ground can be guaranteed to arrive by Christmas. This year, that was Monday, Dec. 17, when more than 1,000 retailers offered free shipping.

Free Shipping Day was the beginning of a hectic workweek for online merchants, who raked in $3.69 billion during last week's five weekdays, up 53% from the same period last year, according to research firm ComScore.

"The fact that Free Shipping Day occurred on a Monday, combined with the fact that so many retailers extended their promotions into the middle of the week -- with guaranteed shipping by Christmas -- helped deliver an encouraging late-season surge," said ComScore Chairman Gian Fulgoni.

The busiest online shopping day of the year was again Cyber Monday -- Nov. 26 this year -- with a record $1.47 billion of spending, followed by Tuesday, Dec. 4, and then Dec. 10 (also known as Green Monday).

During the holiday shopping season online retailers racked up a dozen days that each surpassed more than $1 billion in spending, topping last year's total of 10 days.

ALSO:

Stores offer same-day delivery to compete with Amazon

Best Buy extends deadline for founder to make takeover bid

Stores hope last-minute Christmas shoppers revive holiday sales

Follow Shan Li on Twitter @ShanLi

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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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RIM’s biggest problem: It’s still scrambling to catch yesterday’s hottest mobile app

The moment I first realized that RIM (RIMM) was truly in enormous trouble was back in 2010 when I heard then co-CEO Jim Balsillie downplay the importance of apps. Yes, you read that correctly. Balsillie actually told attendees at a Web 2.0 summit in 2010 that the Internet itself was the most important “app” for mobile devices and contended that the “Web needs a platform that allows you to use your existing Web content, not apps.” My feelings on this matter were only solidified when I attended the BlackBerry World conference in May 2011 and watched RIM executives proudly announce that the Playbook tablet would soon get its own version of Angry Birds sometime in the near future. In reality, Angry Birds didn’t release for BlackBerry until late December of that year, or two full years after it was originally released for iOS.

[More from BGR: WhatsApp goes free for iPhone for a limited time]

All of which brings me back to RIM’s current state: Despite the great looking hardware and user interface pictures we’ve seen from new BlackBerry 10 smartphones so far, the company still has an app problem. I was reminded of this when I read a post over at CrackBerry titled, “There’s still a chance for WhatsApp on BlackBerry 10.” The issue here isn’t whether RIM eventually does or doesn’t get WhatsApp on its platform — the issue is that RIM always seems to be one step behind when it comes to getting the hottest apps of the day on its devices.

[More from BGR: BlackBerry 10 browser smokes iOS 6 and Windows Phone 8 in comparison test [video]]

The most absurd example of this, of course, is Instagram. Yes, it’s very likely that BlackBerry 10 will support the popular photo-sharing app right out of the gate given the company’s partnership with Instagram owner Facebook (FB). But we still have no official confirmation that Instagram will be a BlackBerry 10 app just over a month before the new platform launches, and this is symbolic of the fact that RIM is always stuck at the back of line when it comes to app developers’ priorities.

Simply put, RIM can’t possibly hope to compete with Android, iOS or even Windows Phone 8 if its users will always wonder if they’ll be able to do all the cool things with their phones that their friends can do. In the unpredictable Wild West of today’s app market, where new apps seemingly go viral overnight to become global powerhouses, platform developers need to make sure they have quick and simple ways for app developers to port over their software. And until RIM figures out a way to get this done, it still has no shot in the long term.

This article was originally published by BGR

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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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TV firm All3Media to consolidate studios in Westchester

Britain's largest independent television production company, All3Media, will consolidate its Southern California studios in Westchester.

The company behind such shows as "Undercover Boss" and "Ramsay's Kitchen Nightmares" has agreed to rent two floors in a Howard Hughes Center office building near the 405 Freeway and Sepulveda Boulevard, real estate broker Jacob Bobek of Cushman & Wakefield said.

The lease for 51,000 square feet of space is valued at $16 million, Bobek said. All3Media's five Los Angeles-area studios are now in separate locations in Culver City and on the Westside, and the consolidation will reduce their total rented space about 20%.

More than half of All3Media's revenue comes from international operations, and the U.S. is its fastest-growing market, according to British industry website Broadcast. This month All3Media announced plans to pool its U.S. resources in a production hub headed by Eli Holzman.

The company will move about 220 workers to its new space at 6060 Center Drive in July, said broker Greg Lovett of Cushman & Wakefield, who also worked on the All3Media lease with landlord Equity Office Properties.

The floors All3Media will rent were previously occupied by video game maker Vivendi, Lovett said, which left behind about $750,000 worth of improvements turning the offices into creative-style space with exposed heating ducts and enhanced electric power supplies.

Nasty Gal adding L.A. office space

Fast-growing e-commerce company Nasty Gal will quintuple the size of its headquarters in a historic downtown Los Angeles office complex.

Nasty Gal, which sells women's clothes and accessories online, has agreed to expand its offices to 50,300 square feet in the PacMutual Building complex near Pershing Square. It will occupy the third and fourth floors of the "Carriage House," a Beaux Arts-style building that housed a garage, ballroom and dining facility when it was finished in 1926.

The landlord, Rising Realty Partners, bought the PacMutual complex in April. The three connected buildings were built for Pacific Mutual Life Insurance Co. as its headquarters starting at the turn of the 20th century. Previous owners endeavored to rent offices there to traditional white-collar companies, but Rising Realty has set out to also attract creative firms by emphasizing the historic nature of the property.

Nasty Gal's space will have 18-foot ceilings, exposed brick walls, marble floors and a vintage private elevator that was closed off by previous owners. Nasty Gal, which was founded six years ago, will also occupy part of the "Clock Building." That building is where Pacific Mutual once kept a large clock and a sign reading "Time to insure."

Rising Realty is refurbishing PacMutual and will add a "green wall" vertical landscape feature that will scale the Olive Street side of the six-floor Clock Building, said Christopher Rising, president of Rising Realty.

Terms of the seven-year agreement were not disclosed, but real estate data provider CoStar Group said the landlord is asking for about $2.73 a square foot per month.

"This new space will be a prolific extension of the Nasty Gal brand," said Carle Pierose of Industry Partners, the building's leasing agent.

Health plan to move headquarters to Rancho Cucamonga

Inland Empire Health Plan, a not-for-profit public health plan serving residents of Riverside and San Bernardino counties, will move its headquarters from San Bernardino to Rancho Cucamonga.

The company has agreed to rent 207,000 square feet in the Atrium at Empire Lakes, where it will consolidate its operations from five buildings into one, real estate broker Josh Gorin of Studley Inc. said. The 15-year lease with landlord Torchlight Investors is valued at about $84 million.

The health plan is a joint powers entity serving 565,000 residents through government-sponsored programs including Medi-Cal. It is expected to serve 900,000 members by 2014 as federal healthcare reforms take effect and the company enters the newly established California Health Exchange.

IEHP will begin moving most of its 1,000 employees to the Atrium at 10801 6th St. in the second quarter of next year.

The health plan lease is a large one for the Inland Empire, which has been plagued with empty office space since the economic downturn. Vacancy in the area near L.A./Ontario International Airport is about 30%, Gorin said.

"They are leasing a tremendous amount of space in a highly depressed market," he said.

roger.vincent@latimes.com

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6 die in Syria car bombing; gunman slays state journalist

BEIRUT — A car bomb exploded in eastern Damascus on Saturday, an insurgent spokeswoman said, and the Syrian government reported that a gunman killed a state television journalist in the capital.

The car bomb exploded in the capital's Kaboun area and left six people dead and 10 wounded, an opposition spokeswoman in Damascus identified as Lena Shami said by Skype.

There was no way to independently confirm the death toll.

The official Syria Arab News Agency also reported the bombing, blaming terrorists, the government's usual description of rebels seeking to overthrow President Bashar Assad. Shami the bombing on the government, which she said was targeting the area's Sunni residents. Sunnis make up a majority of the nation's population and also of the rebellion.

Meanwhile, a Syrian state television cameraman was slain outside his home in Damascus, SANA reported.

Haidar Smoudi was the ninth state-employed journalist killed by "armed terrorist groups," the news agency said. There was no claim of responsibility in the shooting, but anti-government groups have been suspected of carrying out attacks on state-employed journalists.

The 21-month-old rebellion has claimed as many as 40,000 lives, according to the opposition. A United Nations panel recently described the conflict as increasingly sectarian and gave details of abuses by both government forces and rebels.

Rami Abdul-Rahman, an activist with the London-based Syrian Observatory for Human Rights, a pro-opposition group, denounced the killing of Smoudi.

"We condemn completely the targeting of unarmed journalists who are considered pro-regime, just as we condemn the killing of any unarmed civilian, no matter their affiliation," he said.

On the diplomatic front, Russia, seen as one of Syria's chief supporters, indicated yet again that it was distancing itself from Assad. Russian Foreign Minister Sergei Lavrov told reporters late Friday that Moscow would not be opposed to any country offering Assad asylum, the Associated Press reported.

"If there is anyone willing to provide him guarantees, they are welcome," Lavrov told reporters on a plane returning from a Russia-European Union meeting in Brussels. "We would be the first to cross ourselves and say: 'Thank God, the carnage is over!' If it indeed ends the carnage, which is far from certain."

The remarks followed Russian President Vladimir Putin's comments Thursday making it clear that Russia saw Syria's stability, not "the fate of the Assad regime," as its priority.

ned.parker@latimes.com

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Ashton Kutcher files for divorce from Demi Moore

LOS ANGELES (AP) — Ashton Kutcher filed court papers Friday to end his seven-year marriage to actress Demi Moore.

The actor's divorce petition cites irreconcilable differences and does not list a date that the couple separated. Moore announced last year that she was ending her marriage to the actor 15 years her junior, but she never filed a petition.

Kutcher's filing does not indicate that the couple has a prenuptial agreement. The filing states Kutcher signed the document Friday, hours before it was filed in Los Angeles Superior Court.

Kutcher and Moore married in September 2005 and until recently kept their relationship very public, communicating with each other and fans on the social networking site Twitter. After their breakup, Moore changed her name on the site from (at)mrskutcher to (at)justdemi.

Kutcher currently stars on CBS' "Two and a Half Men."

Messages sent to Kutcher's and Moore's publicists were not immediately returned Friday.

Moore, 50, and Kutcher, 34, created the DNA Foundation, also known as the Demi and Ashton Foundation, in 2010 to combat the organized sexual exploitation of girls around the globe. They later lent their support to the United Nations' efforts to fight human trafficking, a scourge the international organization estimates affects about 2.5 million people worldwide.

Moore was previously married to actor Bruce Willis for 13 years. They had three daughters together — Rumer, Scout and Tallulah Belle — before divorcing in 2000. Willis later married model-actress Emma Heming in an intimate 2009 ceremony at his home in Parrot Cay in the Turks and Caicos Islands that attended by their children, as well as Moore and Kutcher.

Kutcher has been dating former "That '70s Show" co-star Mila Kunis.

The divorce filing was first reported Friday by People magazine.

___

Anthony McCartney can be reached at http://twitter.com/mccartneyAP.

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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.

Read More..