Mundie, one of Gates’ successors, to retire from Microsoft

NEW YORK (Reuters) – Craig Mundie, one of two Microsoft Corp executives who took over Bill Gates‘ role at the company, has relinquished control of Microsoft’s large research organization and is to retire from the company in 2014.

Mundie is taking on a new role as a senior adviser to Chief Executive Steve Ballmer, according to a memo circulated internally earlier this month but only made public on Monday.

Eric Rudder, another Microsoft veteran, is taking on responsibility for Microsoft Research, Trustworthy Computing, and the Technology Policy Group, which were all run by Mundie.

A 20-year Microsoft veteran, Mundie was one of two men hand-picked by co-founder Gates to take over leadership of the technical side of Microsoft when he retired from day-to-day work at the company in 2008.

Mundie took over responsibility for the company’s long-term research activities, while Ray Ozzie became chief software architect. Ozzie left Microsoft in 2010. According to Ballmer’s memo, Mundie will retire from Microsoft in 2014, when he will be 65.

Mundie’s new role was first reported on Monday by the All Things D tech blog.

(Reporting By Bill Rigby; Editing by Steve Orlofsky)

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Reaction to the death of actor Jack Klugman

Celebrities on Monday reacted to the death of "Odd Couple" star Jack Klugman, who died Monday at age 90. Here are samples of sentiments expressed on Twitter:

___

"R.I.P. Jack Klugman, Oscar, Quincy a man whose career spanned almost 50 years. I first saw him on the Twilight Zone. Cool guy wonderful actor." — Whoopi Goldberg.

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"You made my whole family laugh together." — Actor Jon Favreau, of "Swingers," ''Iron Man" and other films.

___

"I worked with Jack Klugman several years ago. He was a wonderful man and supremely talented actor. He will be missed" — Actor Max Greenfield, of the "New Girl" on Fox.

___

"So sorry to hear that Jack Klugman passed away. I learned a lot, watching him on television" — Dan Schneider, creator of Nickelodeon TV shows "iCarly," ''Drake and Josh" ''Good Burger," ''Drake & Josh."

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Bill O’Reilly Has Top 2 Spots on Hardcover Best-Seller List

“Abe would have liked this book,” the Fox News television host Bill O’Reilly said confidently of his blockbuster best-seller “Killing Lincoln: The Shocking Assassination That Changed America Forever.” Even the ending?

Robert Wright for The New York Times

Bill O’Reilly is the co-author of “Killing Kennedy” (No. 1) and “Killing Lincoln” (No. 2).

Mr. O’Reilly reasoned that Lincoln would have liked this fast-paced, thrillerlike retelling of his death “because it is simple and he was a really simple guy, straightforward guy. He didn’t like a lot of subterfuge or a lot of nonsense.”

“I don’t know if Kennedy would have liked the book,” he added with a tad of reflection about “Killing Kennedy: The End of Camelot,” his other history book written with Martin Dugard that is currently dominating the nonfiction best-seller lists, “because it really lays him out as far as what he did, and some of it wasn’t very nice. But in the end he comes off as fairly heroic.”

No one could accuse Mr. O’Reilly, 63, of playing down his own appeal — and perhaps justifiably so. He anchors the highest-rated news program on cable, his political and personal writings like “A Bold, Fresh Piece of Humanity” (2008) and “Pinheads and Patriots” (2010) have been huge sellers, and now, in his latest franchise, he has become arguably the most popular history author in America.

In the 65 weeks since “Killing Lincoln” was released in fall 2011, Mr. O’Reilly has owned territory near the top of The New York Times’s best-seller list for hardcover nonfiction. It would have been an extraordinary run by itself, but in October he released “Killing Kennedy,” which has since sold about one million copies.

For the last full week of the year he snagged both the No. 1 and 2 spots on the list, a rare feat.

But few authors manage more than one book on the hardcover list because even regulars like the historian David McCullough and the journalist Michael Lewis do not grind it out at the pace of Mr. O’Reilly, who has produced about a book a year over the past decade and intends to keep going. Others have had two atop the paperback nonfiction best-seller list, an act most recently accomplished by President Obama, whose two memoirs “Dreams From My Father” (1995) and “The Audacity of Hope” (2006) both spiked with his election in 2008.

Of course few authors also have the television platform Mr. O’Reilly has and which he uses for 30 seconds nightly to promote his books to his nearly three million viewers.

In person Mr. O’Reilly sheds his on-air bellicosity but maintains the forward energy of a barreling freight train. During an interview, held at his corner office at Fox headquarters in Manhattan, Mr. O’Reilly barely looked up as he autographed a pile of bookplates to be put into copies to be sold on his Web site for a premium for charity. He is determined, he explained, to take advantage of the holiday season.

Thirty minutes later he pointed to the pile completed and said: “That’s about 10 grand for charity right in that pile. Not bad.” That money, he said, is likely to go to the Coalition for the Homeless, a New York-based group that has successfully sued the city and won a court-ordered “right to shelter” — just the kind of policy initiative that Mr. O’Reilly and might gleefully label “radical” or “leftist” on his program.

But Mr. O’Reilly appears to relish not playing to type. Both on and over his desk, for example, are pictures of him and his daughter standing cozily with President and Mrs. Obama. “Michelle was very nice to my daughter,” he said.

Not being predictable is how he turned to history, he said. He was urged by publishers to do another memoir. It was an idea he dismissed “because I was repeating myself.”

This article has been revised to reflect the following correction:

Correction: December 24, 2012

An earlier version of this article misstated the title of President Obama’s first memoir. It is “Dreams From My Father,” not “Dreams of Our Fathers.” 

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Atheist Kids and Bullying: Just an Xbox and a Football Game Away From Redemption

I’ll never forget the year my eight-year-old daughter came home from school saying she got in trouble for going to the bathroom.

“I was afraid,” she said, “that the devil was coming out of the mirror to get me…. I wanted Aya to stay with me until I was done.”

Like any parent, I sat her down and asked her to tell me why she would ever think a mirror could spawn something as terrifying as that.

“Susie told me because I didn’t believe in god, the devil was coming to take my soul.”

MORE: Bullying the Bullies: What to Do to Save the Next Amanda Todd

“Susie” as we’ll call her, was a fellow eight-year-old student at my daughter’s Catholic school. Susie attended church every Sunday with her family—the same church that many of her classmates to this day all go to.

Was my daughter being bullied for being an atheist? I quickly dismissed it. After all, these were only eight-year-old girls, and it wasn’t like we talked about god hating with our morning cereal.

I soon noticed a new pattern of my daughter: She wouldn’t enter a bathroom without a friend or parent and began wetting the bed at night for fear of our extensive collection of bathroom mirrors pulling her into almighty hell at 2 a.m.

Sure enough, the religious eight-year-old was still pressuring my daughter to consider her morality, spirituality and reason for living daily in the school bathroom.

“When the child goes to school, and encounters for the first time other kids who don’t believe the same thing, whether it’s no belief or a different belief system, that can rock a kid’s world.”

I got on the phone and made sure the principal was aware of the bullying, that the child was reported and that my daughter would hopefully make the choice not to play with her anymore. The school thought I was a little crazy. Bullying was getting punched in the stomach in a dark place behind the school, not a little girl being taunted for not believing she was going to have life eternal. This was a new place they were afraid to gain control of. The principal, a former nun, kept a tight lip.

According to the American Society for the Prevention of Cruelty to Children, every day “an estimated 160,000 students in the U.S. refuse to go to school because they dread the physical and verbal aggression of their peers. Many more attend school in a chronic state of anxiety and depression.”

Courtney Campbell, Professor of Religion and Culture at Oregon State University, says he encountered the same case with his own children who were told at a very early age by some of their “friends” that they were “going to hell.” Though there were no physical beatings, the “psychic bullying” may have been worse.

“There is a phenomenon of religious-bullying at an early age, though in my own view/experience with raising my kids, it’s less of an issue than lookism [obese kids], size [‘big’ bullies], or gender, or clothes, or any of a number of things that kids do to manifest power over others,” says Campbell.

He points out that in most conservative/evangelical/fundamentalist Christian traditions, kids are taught at a very early age in their Sunday schools or summer bible camps that there’s only one path to happiness and salvation. That teaching, absorbed at a young age, is on its own rather threatening to the child.

“When the child goes to school, and encounters for the first time other kids who don’t believe the same thing, whether it’s no belief or a different belief system, that can rock a kid’s world,” Campbell adds.

Blame it on fear, maybe a calling out of one’s most sacred and learned family beleifs, but this form of push and shove is only getting more sophisticated.

Rachel Wagner, Associate Professor for the Department of Philosophy and Religion at Ithaca College and author of Godwired: Religion, Ritual and Virtual Reality, says we are overlooking a major player of the religious bullying model—video games.

“If we compare video games to rituals as similar kinds of interactive experiences that are meant to shape how we see ourselves and others in the world, then we can argue something more basic—that video games (like rituals) can teach people habits of encounter—and offer youth deeply problematic models of encounter with difference,” says Wagner, who adds that in her next book, she’ll argue that religion has always had the ability to be “played” like a game, a religious encounter she coins “shooter religion.”

While Wagner admits it’s very important to remember that all world religions also have “deep and abiding practices urging compassion, understanding, tolerance, and social justice,” in today’s media-soaked society, feeling the need to retreat into a simpler world where people can be reduced to camps can be terribly tempting.

Stacy Pershall, author of Loud in the House of Myself: Memoir of a Strange Girl, says that growing up in Prairie Grove, Arkansas, in an athletics-focused, Christian bible belt, she was used to being surrounded by “Jesus talk.”

Pershall, who was bullied for being a “strange girl,” when young, unathletic and atheist to boot, now works and empowers high school and college students as a writing teacher and mental health speaker.

“Although it still makes my heart pound a little to stand in front of a crowd and admit that I don’t believe in god (as I recently did at Catholic University in D.C.), somebody needs to do it. I get to be the adult who says to kids, ‘I’m an atheist, I have morals, I have friends, I’m happy, and I care about how you feel.’ That’s a wonderful, powerful thing. I get to tell bullied kids who might be considering suicide that they’re not alone, and that they have kindred spirits. It’s what the Flying Spaghetti Monster put me on Earth to do.”

Were you ever bullied? Leave what you were bullied about in COMMENTS.

These are solely the author’s opinions and do not represent those of TakePart, LLC or its affiliates.

Related Stories on TakePart:

• 5 Things to Keep in Mind About Bullying

• A Bully’s Paradise: Hidden Halls, Dark Corners and No Supervision

• Mother Bullied to Abort Unborn Twins?

---

Amy DuFault is a writer and editor whose work has been published in EcoSalon, Huffington Post, Ecouterre, Organic Spa, Coastal Living, Yahoo!, The Frisky and other online and print publications. In addition to being a former co-owner of an eco-boutique, she coaches and connects the sustainable fashion community to feed her soul. She also dreams of singing in an all-girl punk band even though she has stage fright. @amytropolis | TakePart.com

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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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Poor Students Struggle as Class Plays a Greater Role in Success

Michael Stravato for The New York Times

Bianca Gonzalez earned an associate degree at a community college.

GALVESTON, Tex. — Angelica Gonzales marched through high school in Goth armor — black boots, chains and cargo pants — but undermined her pose of alienation with a place on the honor roll. She nicknamed herself after a metal band and vowed to become the first in her family to earn a college degree.

Michael Stravato for The New York Times

Angelica Gonzales, admitted to Emory, hoped to be the first college graduate in her family. She was suspended in her senior year after her grades fell.

“I don’t want to work at Walmart” like her mother, she wrote to a school counselor.

Weekends and summers were devoted to a college-readiness program, where her best friends, Melissa O’Neal and Bianca Gonzalez, shared her drive to “get off the island” — escape the prospect of dead-end lives in luckless Galveston. Melissa, an eighth-grade valedictorian, seethed over her mother’s boyfriends and drinking, and Bianca’s bubbly innocence hid the trauma of her father’s death. They stuck together so much that a tutor called them the “triplets.”

Low-income strivers face uphill climbs, especially at Ball High School, where a third of the girls’ class failed to graduate on schedule. But by the time the triplets donned mortarboards in the class of 2008, their story seemed to validate the promise of education as the great equalizer.

Angelica, a daughter of a struggling Mexican immigrant, was headed to Emory University. Bianca enrolled in community college, and Melissa left for Texas State University, President Lyndon B. Johnson’s alma mater.

“It felt like we were taking off, from one life to another,” Melissa said. “It felt like, ‘Here we go!’ ”

Four years later, their story seems less like a tribute to upward mobility than a study of obstacles in an age of soaring economic inequality. Not one of them has a four-year degree. Only one is still studying full time, and two have crushing debts. Angelica, who left Emory owing more than $60,000, is a clerk in a Galveston furniture store.

Each showed the ability to do college work, even excel at it. But the need to earn money brought one set of strains, campus alienation brought others, and ties to boyfriends not in school added complications. With little guidance from family or school officials, college became a leap that they braved without a safety net.

The story of their lost footing is also the story of something larger — the growing role that education plays in preserving class divisions. Poor students have long trailed affluent peers in school performance, but from grade-school tests to college completion, the gaps are growing. With school success and earning prospects ever more entwined, the consequences carry far: education, a force meant to erode class barriers, appears to be fortifying them.

“Everyone wants to think of education as an equalizer — the place where upward mobility gets started,” said Greg J. Duncan, an economist at the University of California, Irvine. “But on virtually every measure we have, the gaps between high- and low-income kids are widening. It’s very disheartening.”

The growing role of class in academic success has taken experts by surprise since it follows decades of equal opportunity efforts and counters racial trends, where differences have narrowed. It adds to fears over recent evidence suggesting that low-income Americans have lower chances of upward mobility than counterparts in Canada and Western Europe.

Thirty years ago, there was a 31 percentage point difference between the share of prosperous and poor Americans who earned bachelor’s degrees, according to Martha J. Bailey and Susan M. Dynarski of the University of Michigan. Now the gap is 45 points.

While both groups improved their odds of finishing college, the affluent improved much more, widening their sizable lead.

Likely reasons include soaring incomes at the top and changes in family structure, which have left fewer low-income students with the support of two-parent homes. Neighborhoods have grown more segregated by class, leaving lower-income students increasingly concentrated in lower-quality schools. And even after accounting for financial aid, the costs of attending a public university have risen 60 percent in the past two decades. Many low-income students, feeling the need to help out at home, are deterred by the thought of years of lost wages and piles of debt.

Kitty Bennett contributed research.

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News summary: Nintendo’s TVii replaces the remote

TVii LAUNCH: Nintendo if flipping on its TVii service Thursday, a month after sales started for its Wii U game console. The service turns the GamePad controller into a TV remote control, channel guide and Web video surfer.

SALES HOPES: Nintendo hopes the free service boosts sales of the console after recording 425,000 sales in the first week since its Nov. 18 launch.

HEAD START: It’s the first time a game console maker has put live TV controls into a device, but analyst Michael Pachter says competitors will copy the function soon.

Gaming News Headlines – Yahoo! News

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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..

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..