A Look Inside Tarantino's <em>Django Unchained</em> Comic Book

Django Unchained opens in theaters today, but the big screen isn’t the only way to see the newest work by Quentin Tarantino. The issue of the Django Unchained comic book mini-series from DC/Vertigo Comics is available now in comic book stores (and online), and in advance of tomorrow’s film debut, Wired has a look at the Tarantino’s introduction to the comic, along with the original character sketches by artist R.M. Guéra and a six-page preview of the first issue.

The comic is an incredibly faithful adaptation of Tarantino’s movie script – the first issue is the first few scenes of the film, almost line for line. Drawing on the director’s story, the book’s interior art comes from Guéra, who made characters that hew closely to their actor counterparts but are their own characters entirely. The artist’s Django, the slave that becomes a bounty hunter, has a more steely cowboy vibe than smooth, cool Jamie Foxx; ruthless plantation owner Calvin Candie looks even more maniacal than Leonardo DiCaprio; and Candie’s house slave Stephen looks far more jowly and grizzled on the page than Samuel L. Jackson does on screen.

“Growing up I read the adventures of Kid Colt Outlaw, TOMAHAWK, The Rawhide Kid, BAT LASH, and especially, Yang (which was basically the Kung Fu TV show done as a comic), and Gunhawks featuring Reno Jones (a Jim Brown stand-in) and Kid Cassidy (a David Cassidy stand-in), which for my money was the greatest Blaxploitation Western ever made,” Tarantino says in the first issue’s intro. “And it’s in that spirit of cinematic comics literature that I present to you Django Unchained.”

Tarantino’s version of the story hits theaters Dec. 25.

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A huge collection of odd TV stuff needs a home

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

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

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

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

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

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

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

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

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

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

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

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

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

He won’t even think about that.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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Area sports cheating cases drag secretive NCAA into spotlight

The men and women of the NCAA enforcement staff prefer to work in secret.

They almost never speak publicly about tips they receive or evidence they gather against cheaters in big-time college sports. Rarely will they acknowledge the existence of an investigation.

Now several recent incidents — all in Southern California — have dragged them into the spotlight, raising questions about how they police athletes and coaches on campuses nationwide.

In one of the cases, at UCLA, the lead investigator has been accused of prejudging UCLA freshman Shabazz Muhammad before all of the facts were gathered.

Across town, a Los Angeles County Superior Court judge in a defamation suit has portrayed other NCAA officials as potentially malicious for the way they dealt with a USC assistant coach linked to the Reggie Bush sanctions.

Things could get worse. The judge could unseal files from that lawsuit, providing greater insight into this powerful, quasi-judicial organization.

"The NCAA does not operate like a prosecutor's office or a police department where there are clearly understood constitutional limits," said Geoffrey C. Rapp, a University of Toledo law professor and editor of the Sports Law blog. "They don't have a structure in place to ensure consistency."

The NCAA declined to answer questions, responding instead with a brief statement that read, in part, "We are committed to providing a fair enforcement process for our members."

The father of UCLA basketball player Kyle Anderson, who was investigated this fall, sees the process from a different angle.

"I'm a schoolteacher, and the big thing in school now is bullying," Kyle Anderson Sr. said. "That's exactly what the NCAA is … the prototype of a bully."

Money and television

The influx of television and donor money makes college sports vulnerable to corruption. Though almost no one denies the need for supervision, critics have often questioned the NCAA's enforcement policies.

The two-part procedure begins with an enforcement staff of 57, which includes "former coaches, student athletes and compliance officers — as well as investigators that are former practicing attorneys," the NCAA statement said.

Investigators gather information and submit a report for the second part: adjudication. The Committee on Infractions, its members drawn from colleges, conferences and the public, hears testimony and renders a decision.

The committee has been criticized for inconsistent penalties in recent cases against USC, Ohio State, Auburn and Penn State. The recent cases in Los Angeles deal primarily with the investigative part of the process.

Staff members face at least one major hurdle: They lack subpoena power, meaning they cannot compel outsiders such as former athletes and agents to talk.

To compensate, member schools have authorized the use of an ethics bylaw to penalize current athletes and coaches who refuse to cooperate.

"There's not, in my opinion, any sort of conspiracy on the part of the NCAA or the enforcement staff to incriminate people who have not committed violations," said Dan Matheson, a former investigator who now teaches at Iowa.

Not everyone agrees.

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Army Goes Goth With 'Super-Black' Materials

Get ready to break out the eyeliner and the candelabras, because the Army is going goth.

In its latest round of solicitations for small businesses, the Army is asking for proposals for super-black material. That is, material so black that it absorbs 99 percent of all light. But it isn’t really black paint, exactly. The plan is to use either an “antireflective coating or surface treatment process for metals” to absorb stray light “in the ultraviolet, visible, infrared, and far-infrared regions.” This, the Army hopes, will boost the quality of high-resolution cameras, while also cooling down sensitive electronics. Or to put it another way: The Army needs the color black to reflect its icy-cold heart.

Another curious thing is that the program is being run out of the Army’s Program Executive Office Ammunition at the Picatinny Arsenal, a main center for the Pentagon’s experiments in all sorts of weapons: from rifles and tank cannons to directed-energy weapons. But the purpose of the solicitation isn’t much more specific than described. “Simply put, it’s too early yet to speculate on where the technology(s) will go,” Frank Misurelli, an Army spokesman at Picatinny said in a statement provided to Danger Room. ”Possibly in a few months, after an contract has been awarded, more information may become available.”

But for whatever the Army wants to fade to black, it seems that regular black isn’t good enough. This is because most black paint will absorb only around 90-95 percent of light, with the other 5-10 percent reflected back outwards. For a high-resolution camera, that stray light can bounce back into the lens and interfere with the quality of an image. It’s even a problem for NASA’s ultra-deep-space sensors. In the extreme coldness of space, black paint turns a silver-y color, which increases heat and can interfere with infrared-detecting instruments.

But wait, doesn’t black get really hot when hit with light, like wearing black clothes during the summer? The answer is: sorta. Black is really good at absorbing heat, but is also really good at radiating heat away. This is why cooling fins, radiators and engines for cars and trucks are often painted black. In 2011, NASA developed a carbon-nanotube coating that absorbed between 98-99.5 percent of light, depending on the wavelength. Nor do the coating’s thin layers of nanotubes change color in extreme cold. They absorb more light, and help radiate heat away from instruments, keeping them cold.

The Army could go another route. A second option uncovered by Britain’s National Physical Laboratory involves immersing an object in a solution of nickel and sodium for several hours, which blackens the color, and then taking it out and dunking it in nitric acid for a few seconds. According to New Scientist, this creates an alloy pock-marked with tiny microscopic craters that prevent light from bouncing away.

Finally, the Army also hopes to expand the materials to “optical glass surfaces” — camera lenses, in other words — while testing to see whether “it will be able to survive in a military environment.” The material should also come in “multiple surface colors” and be able to “selectively exhibit earth color instead of broadband absorption.” And another hope is to use the materials to absorb water to cool down equipment. See, it’s tough out there being goth, but it doesn’t mean you can’t do it in comfort.

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Pro-gun rights US petition to deport Piers Morgan

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

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

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

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

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

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

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

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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, Kabul.

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 them, 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 firetruck 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.”

Special correspondent Hashmat Baktash contributed to this report.

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Wired Science Space Photo of the Day: Hourglass Nebula

This Hubble telescope snapshot of MyCn18, a young planetary nebula, reveals that the object has an hourglass shape with an intricate pattern of "etchings" in its walls. A planetary nebula is the glowing relic of a dying, Sun-like star.

The results are of great interest because they shed new light on the poorly understood ejection of stellar matter that accompanies the slow death of Sun-like stars. According to one theory on the formation of planetary nebulae, the hourglass shape is produced by the expansion of a fast stellar wind within a slowly expanding cloud, which is denser near its equator than near its poles.

Image: Raghvendra Sahai and John Trauger (JPL), the WFPC2 science team, and NASA [high-resolution]

Caption: Hubble Heritage site

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Nick Cassavetes Sued For Allegedly Stiffing Twin Canadian Pop Duo on $300K Movie Loan

LOS ANGELES (TheWrap.com) – Nick Cassavetes, Canadian twins and incest – besides three phrases that you probably didn’t expect to read in the same sentence today, they’re also elements of a bizarre new lawsuit that hit the California court system this week.

In a lawsuit filed Tuesday in Los Angeles Superior Court, TwinSpin music – home to twin Canadian pop duo Carmen & Camille – claim that “The Notebook” director failed to pay back a $ 300,000 loan to help make the upcoming drama “Yellow.”

The complaint alleges that the writer-director backed out of an agreement to give the duo parts in the movie and to feature a song of theirs in the Sienna Miller-Ray Liotta film.

The film chronicles a woman who’s addicted to pain pills and is fired from her teaching job for engaging in sexual shenanigans on school grounds. Oh, and she also had a love affair with her brother at one point. According to the suit – which also includes TwinSpin manager John Thomas as a plaintiff – TwinSpin and Cassavetes entered into an agreement in September 2010, in which TwinSpin would loan Cassavetes $ 300,000 to start production on the film.

In return, the suit says, Cassavetes agreed to pay the loan back with interest – for a total of $ 345,000 – the next month. Cassavetes also agreed to cast the duo in speaking roles in the film, use a song of theirs on the soundtrack, and to give Thomas a producer’s credit, the complaint claims.

But the money never came, the suit says – and neither did the roles, the song and the credit, without which the loan never would have been given.

“But for these representations, Plaintiffs never would have entered into the Loan Agreement or otherwise granted the Loan,” the lawsuit reads. “Plaintiffs are informed and believe that Cassavetes never had any intention of casting ‘Carmen & Camille’ in the Picture, or featuring a song by ‘Carmen & Camille’ in the Picture, of providing the producer credit to plaintiff Thomas, or of repaying the loan on a timely basis.”

Cassavetes’ agent has not yet responded to misrepresentation request for comment.

Alleging breach of contract, breach of covenant of good faith and fair dealing, fraudulent misrepresentation and negligent misrepresentation, the suit is asking for damages of $ 500,000, the amount that the plaintiffs believe is currently owed to them by Cassavetes, with accruing interest.

(Pamela Chelin contributed to this report)

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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..