E-Book Price War Has Yet to Arrive

Thor Swift for The New York Times

A Google e-reader is displayed at a bookstore. Sales of e-books for the devices have slowed this year.

Right about now, just as millions of e-readers and tablets are being slipped under Christmas trees, there was supposed to be a ferocious price war over e-books.

Last spring, the Justice Department sued five major publishers and Apple on e-book price-fixing charges. The case was a major victory for Amazon, and afterward there were widespread expectations — fueled by Amazon — that the price of e-books would plunge.

The most extreme outcome went like this: Digital versions of big books selling for $9.99 or less would give Amazon complete domination over the e-book market. As sales zoomed upward, even greater numbers of consumers would abandon physical books. The major publishers and traditional bookstores were contemplating a future that would pass them by.

But doomsday has not arrived, at least not yet. As four of the publishers have entered into settlements with regulators and revised the way they sell e-books, prices have selectively fallen but not as broadly or drastically as anticipated.

The $10 floor that publishers fought so hard to maintain for popular new novels is largely intact. Amazon, for instance, is selling Michael Connelly’s new mystery, “The Black Box,” for $12.74. New best sellers by David Baldacci and James Patterson cost just over $11.

One big reason for the lack of fireworks is that the triumph of e-books over their physical brethren is not happening quite as fast as forecast.

“The e-book market isn’t growing at the caffeinated level it was,” said Michael Norris, a Simba Information analyst who follows the publishing industry. “Even retailers like Amazon have to be wondering, how far can we go — or should we go — to make our prices lower than the other guys if it’s not helping us with market share?”

Adult e-book sales through August were up 34 percent from 2011, an impressive rate of growth if you forget that sales have doubled every year for the last four years. And there have been more recent signs of a market pausing for breath.

Macmillan, the only publisher that has not settled with the Justice Department, said last week as part of a statement from John Sargent, its chief executive, that “our e-book business has been softer of late, particularly for the last few weeks, even as the number of reading devices continues to grow.” His laconic conclusion: “Interesting.”

Mr. Norris said Simba, which regularly surveys e-book buyers, has been noticing what it calls “commitment to content” issues.

“A lot of these e-book consumers aren’t behaving like lab rats at a feeder bar,” the analyst said. “We have found that at any given time about a third of e-book users haven’t bought a single title in the last 12 months. I have a feeling it is the digital equivalent of the ‘overloaded night stand’ effect; someone isn’t going to buy any more books until they make a dent in reading the ones they have already acquired.”

Another, more counterintuitive possibility is that the 2011 demise of Borders, the second-biggest chain, dealt a surprising blow to the e-book industry. Readers could no longer see what they wanted to go home and order. “The print industry has been aiding and assisting the e-book industry since the beginning,” Mr. Norris said.

It is possible that Amazon, which controls about 60 percent of the e-book market, is merely holding back with price cuts for the right moment. The next few weeks are when e-book sales traditionally take a big jump, as all those newly received devices are loaded up with content.

Amazon declined to comment beyond saying, “We have lowered prices for customers from the prices publishers set on a broad assortment of Kindle books.” Barnes & Noble declined to comment on its pricing strategy.

The question of the proper price for e-books has shadowed the industry ever since Amazon introduced the Kindle in late 2007 and created the first truly popular portable reading device. Amazon had a natural impulse to build a market and was an aggressive retailer in any case, so it took best sellers that cost $25 in independent bookstores and sold them for $9.99 as e-books. Consumers liked that. E-book adoption soared.

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Clashes Break Out in India at a Protest Over a Rape Case

Anindito Mukherjee/European Pressphoto Agency

The police used water cannons on demonstrators gathered in India’s capital city on Saturday.

Protesters scuffled with the police throughout the day. Some police vehicles were damaged, and the police eventually used tear gas, water cannons and sticks to disperse the crowd. Officials said 35 protesters and 37 police officers had been injured, two officers seriously, and that six buses and several police vehicles were damaged.

Outrage over the crime has continued to build across the country and the protesters in New Delhi promised to return in even greater numbers on Sunday, prompting Home Minister Sushil Kumar Shinde to hold a news conference on Saturday night to plead for calm.

“The government is committed to ensuring the safety of women in the capital as well as in the rest of the country,” Mr. Shinde said. “I appeal to this media, to all those who have come to support this dedication, to withdraw.”

Mr. Shinde listed four steps the government would take immediately to improve security in New Delhi: increase the number of buses at night, track those buses with GPS devices, ensure drivers carry identity badges and increase the number of police officers on busy routes.

The police have arrested six suspects and Mr. Shinde said that the victim had given a statement to a magistrate on Friday night, and that the government had enough evidence to prosecute.

The woman was raped on Dec. 16 after she boarded a private bus with her boyfriend. A group of men onboard the bus, normally used to ferry schoolchildren, beat the couple with iron rods and raped the woman. The men then dumped them by the roadside.

The woman has had several rounds of surgery and a portion of her intestines had to be removed, doctors said. Mr. Shinde also said the government had canceled all permits for the transportation company that owns the bus on which the rape occurred. At the protest, people chanted “We want justice!” and held placards that said “Save Women Save India.”

“These rapists should be hanged publicly,” said Shaelly Tomar, a student at Delhi University who took part in the protest with several friends. “If that happens, nobody will dare to do it again.”

Tens of thousands of rapes are reported each year in India, while many more go unreported because rape victims are often shunned and unable to marry. Even so, reports of rape are on the rise, up about 25 percent in the past six years. Surveys have suggested that India is one of the most unsafe countries in the world for women.

The roots of the problem run deep in a conservative society that is having trouble adjusting to educational and economic advances by women, long confined to the home. Demographics also play a role, with half of India’s population under 25 and female infanticide and the neglect of girls creating a growing gender imbalance.

But India’s criminal justice system, riddled with incompetence, corruption and political meddling, seems unable to respond effectively.

Heather Timmons contributed reporting.

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Amazon Book Reviews Deleted in a Purge Aimed at Manipulation

Giving raves to family members is no longer acceptable. Neither is writers’ reviewing other writers. But showering five stars on a book you admittedly have not read is fine.

After several well-publicized cases involving writers buying or manipulating their reviews, Amazon is cracking down. Writers say thousands of reviews have been deleted from the shopping site in recent months.

Amazon has not said how many reviews it has killed, nor has it offered any public explanation. So its sweeping but hazy purge has generated an uproar about what it means to review in an era when everyone is an author and everyone is a reviewer.

Is a review merely a gesture of enthusiasm or should it be held to a higher standard? Should writers be allowed to pass judgment on peers the way they have always done offline or are they competitors whose reviews should be banned? Does a groundswell of raves for a new book mean anything if the author is soliciting the comments?

In a debate percolating on blogs and on Amazon itself, quite a few writers take a permissive view on these issues.

The mystery novelist J. A. Konrath, for example, does not see anything wrong with an author indulging in chicanery. “Customer buys book because of fake review = zero harm,” he wrote on his blog.

Some readers differ. An ad hoc group of purists has formed on Amazon to track its most prominent reviewer, Harriet Klausner, who has over 25,000 reviews. They do not see how she can read so much so fast or why her reviews are overwhelmingly — and, they say, misleadingly — exaltations.

“Everyone in this group will tell you that we’ve all been duped into buying books based on her reviews,” said Margie Brown, a retired city clerk from Arizona.

Once a populist gimmick, the reviews are vital to making sure a new product is not lost in the digital wilderness. Amazon has refined the reviewing process over the years, giving customers the opportunity to rate reviews and comment on them. It is layer after layer of possible criticism.

“A not-insubstantial chunk of their infrastructure is based on their reviews — and all of that depends on having reviews customers can trust,” said Edward W. Robertson, a science fiction novelist who has watched the debate closely.

Nowhere are reviews more crucial than with books, an industry in which Amazon captures nearly a third of every dollar spent. It values reviews more than other online booksellers like Apple or Barnes & Noble, featuring them prominently and using them to help decide which books to acquire for its own imprints by its relatively new publishing arm.

So writers have naturally been vying to get more, and better, notices. Several mystery writers, including R. J. Ellory, Stephen Leather and John Locke, have recently confessed to various forms of manipulation under the general category of “sock puppets,” or online identities used to deceive. That resulted in a widely circulated petition by a loose coalition of writers under the banner, “No Sock Puppets Here Please,” asking people to “vote for book reviews you can trust.”

In explaining its purge of reviews, Amazon has told some writers that “we do not allow reviews on behalf of a person or company with a financial interest in the product or a directly competing product. This includes authors.” But writers say that rule is not applied consistently.

In some cases, the ax fell on those with a direct relationship with the author.

“My sister’s and best friend’s reviews were removed from my books,” the author M. E. Franco said in a blog comment. “They happen to be two of my biggest fans.” Another writer, Valerie X. Armstrong, said her son’s five-star review of her book, “The Survival of the Fattest,” was removed. He immediately tried to put it back “and it wouldn’t take,” she wrote.

In other cases, though, the relationship was more tenuous. Michelle Gagnon lost three reviews on her young adult novel “Don’t Turn Around.” She said she did not know two of the reviewers, while the third was a longtime fan of her work. “How does Amazon know we know each other?” she said. “That’s where I started to get creeped out.”

Mr. Robertson suggested that Amazon applied a broad brush. “I believe they caught a lot of shady reviews, but a lot of innocent ones were erased, too,” he said. He figures the deleted reviews number in the thousands, or perhaps even 10,000.

The explosion of reviews for “The 4-Hour Chef” by Timothy Ferriss shows how the system has evolved from something spontaneous to a means of marketing and promotion. On Nov. 20, publication day, dozens of highly favorable reviews immediately sprouted. Other reviewers quickly criticized Mr. Ferriss, accusing him of buying supporters.

He laughed off those suggestions. “Not only would I never do that — it’s unethical — I simply don’t have to,” he wrote in an e-mail, saying he had sent several hundred review copies to fans and potential fans. “Does that stack the deck? Perhaps, but why send the book to someone who would hate it? That doesn’t help anyone: not the reader, nor the writer.”

As a demonstration of social media’s grip on reviewing, Mr. Ferriss used Twitter and Facebook to ask for a review. “Rallying my readers,” he called it. Within an hour, 61 had complied.

A few of his early reviews were written by people who admitted they had not read the book but were giving it five stars anyway because, well, they knew it would be terrific. “I am looking forward to reading this,” wrote a user posting under the name mhpics.

A spokesman for Amazon, which published “The 4-Hour Chef,” offered this sole comment for this article: “We do not require people to have experienced the product in order to review.”

The dispute over reviews is playing out in the discontent over Mrs. Klausner, an Amazon Hall of Fame reviewer for the last 11 years and undoubtedly one of the most prolific reviewers in literary history.

Mrs. Klausner published review No. 28,366, for “A Red Sun Also Rises” by Mark Hodder. Almost immediately, it had nine critical comments. The first accused it of being “riddled with errors in grammar, spelling and punctuation.” The rest were no more kind. The Harriet Klausner Appreciation Society had struck again.

Mrs. Klausner, a 60-year-old retired librarian who lives in Atlanta, has published an average of seven reviews a day for more than a decade. “To watch her in action is unbelievable,” said her husband, Stanley. “You see the pages turning.”

Mrs. Klausner, who says ailments keep her home and insomnia keeps her up, scoffs at her critics. “You ever read a Harlequin romance?” she said. “You can finish it in one hour. I’ve always been a speed reader.” She has a message for her naysayers: “Get a life. Read a book.”

More than 99.9 percent of Mrs. Klausner’s reviews are four or five stars. “If I can make it past the first 50 pages, that means I like it, and so I review it,” she said. But even Stanley said, “She’s soft, I won’t deny that.”

The campaign against Mrs. Klausner has pushed down her reviewer ratings, which in theory makes her less influential. But when everything is subject to review, the battle is never-ending.

Ragan Buckley, an aspiring novelist active in the campaign against Mrs. Klausner under the name “Sneaky Burrito,” is a little weary. “There are so many fake reviews that I’m often better off just walking into a physical store and picking an item off the shelf at random,” she said.

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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..

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..

Obama Nominates Kerry for Secretary of State

WASHINGTON — With a patrician bearing, nearly three decades of service on the Senate Foreign Relations Committee, a highly decorated combat career in the Vietnam War, even a father who was a diplomat, John Kerry is the very picture of a secretary of state.

“In a sense, John’s entire life has prepared him for this role,” President Obama said on Friday at the White House, as he nominated Mr. Kerry to replace Hillary Rodham Clinton, the first step in filling out a national security team for his second term.

Mr. Obama praised Mr. Kerry, 69, a Massachusetts Democrat, for having been immersed in “every major foreign-policy debate for nearly 30 years.”

But though Mr. Kerry would bring even deeper experience to the job than Mrs. Clinton did, his appointment is likely to further centralize policy decisions in the White House, where for the past four years the president and a small circle of advisers have kept a tight grip on issues like Iran’s nuclear program, China, Pakistan, and the winding down of the war in Afghanistan.

“There’s every reason to believe that we’re going to have a very White House-centric foreign policy,” said David J. Rothkopf, the chief executive of the Foreign Policy Group. “Kerry is going to have to show his loyalty and willingness to work within the Obama system.”

In contrast to Mrs. Clinton, whom Mr. Obama named to his cabinet after they competed against each other in the 2008 presidential primaries, Mr. Kerry has been a loyal supporter of the Obama administration, guiding an arms-reduction treaty with Russia to ratification in the Senate and playing diplomatic troubleshooter for the White House in Afghanistan, Pakistan and Sudan.

He has also figured at critical moments in Mr. Obama’s career. At the 2004 Democratic National Convention that nominated him for president, Mr. Kerry gave the keynote speaking slot to Mr. Obama, then a little-known Illinois state senator, catapulting him to national prominence. In early 2008, Mr. Kerry endorsed him over Mrs. Clinton, and this fall he played the role of Mitt Romney in mock debates — sessions that by some accounts put the president’s teeth on edge.

“Nothing brings two people closer together than weeks of debate prep,” said Mr. Obama on Friday, looking at a grinning Mr. Kerry. “John, I’m looking forward to working with you instead of debating you.”

However lavish Mr. Obama’s praise, his instinctive choice for secretary of state was Susan E. Rice, the ambassador to the United Nations, who withdrew her name from consideration after Republicans threatened to block her nomination because of statements she made after the lethal attack on the American Mission in Benghazi, Libya.

Mr. Obama, his aides said, likes Ms. Rice’s blunt style and is in sync with her view of foreign policy, which places a premium on aggressively defending human rights.

As a result, Ms. Rice, who is staying in her post, remains a candidate for a major foreign-policy post in the second term, according to administration officials. Thomas E. Donilon, the national security adviser, is expected to stay on for a year or so, but Ms. Rice could be named to his job.

If she were to move into the White House, analysts said, that would pose a test for Mr. Kerry, given her access to Mr. Obama and their shared views on many foreign policy issues.

“The easiest model to see developing is one in which Kerry is on the road a lot, interfacing with foreign leaders, but the decision-making is done at the White House,” said Elliott Abrams, who held foreign-policy posts in the administrations of Ronald Reagan and George W. Bush.

Mr. Obama expressed confidence that Mr. Kerry would be confirmed by his Senate colleagues, a prediction that seemed safe, given that at a recent news conference, Senator John McCain, Republican of Arizona, one of Ms. Rice’s fiercest critics, jokingly referred to Mr. Kerry as “Mr. Secretary.”

Mrs. Clinton has not announced her resignation, but she has made it clear she would not stay beyond a single term. Because she is recovering from a concussion, she did not appear at the midday announcement. Mr. Obama said that he spoke to her on Friday morning, and reported that she was “in good spirits.”

In a statement, Mrs. Clinton said Mr. Kerry was a leader of the “highest caliber,” who had advocated on behalf of diplomacy and development in Congress.

Mr. Kerry is working with her to adopt the recommendations of a recent report that harshly criticized the State Department for lapses in security in Benghazi, she said. The Benghazi attack, analysts said, underscored the management challenge for a longtime senator like Mr. Kerry in taking over a sprawling worldwide bureaucracy. Former aides to Mr. Kerry point out that he did oversee a huge, if temporary, campaign operation in 2004, which, though criticized for tactical missteps, was not viewed as poorly managed.

Although Mr. Kerry is not a global celebrity like Mrs. Clinton, his background as a presidential nominee and his chairmanship of the Foreign Relations Committee have made him well known abroad, accustomed to meeting monarchs and presidents.

In October 2009, he was viewed as instrumental in persuading President Hamid Karzai of Afghanistan to accept the need for a runoff election. Mr. Kerry spent 20 hours over five days with Mr. Karzai, telling him over dinner and in long walks in the garden of the presidential palace in Kabul of his own frustrations at the ballot box in 2004.

“I told him, ‘Sometimes there are tough things,’ ” Mr. Kerry said in an interview at the time.

Before Syria exploded in violence, Mr. Kerry met several times with its president, Bashar al-Assad, hoping to draw him into a more constructive role in the Middle East. His failed effort at engagement may elicit some tough questions from Mr. McCain and other Senate hawks.

As a senator, Mr. Kerry compiled a strong record on climate change, and environmental groups issued enthusiastic responses to his nomination. But Mr. Obama, pressed at a recent news conference, said climate change would take a back seat to the economy, at least for now.

For Mr. Kerry, exerting influence internally is likely to be the greatest challenge of the job he has long coveted. Friends and former aides predicted he would carve out a role, just as Mrs. Clinton did.

“John was someone who from an early age dreamed of being president,” said Jim Gomes, a former chief of staff to Mr. Kerry. “As someone who grew up in a Foreign Service family, who testified before Senate Foreign Relations after coming home from Vietnam and who wanted to serve on Foreign Relations, this is a pretty terrific Plan B.”

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As Shoppers Hop From Tablet to PC to Phone, Retailers Try to Adapt

Ryan O’Neil, a Connecticut government employee, was in the market to buy a digital weather station this month. His wife researched options on their iPad, but even though she found the lowest-price option there, Mr. O’Neil made the purchase on his laptop.

“I do use the iPad to browse sites,” Mr. O’Neil said, but when it comes time to close the deal, he finds it easier to do on a computer.

Many online retailers had visions of holiday shoppers lounging beneath the Christmas tree with their mobile devices in hand, making purchases. The size of the average order on tablets, particularly iPads, tends to be bigger than on PCs. So retailers poured money and marketing into mobile Web sites and apps with rich images and, they thought, easy checkout.

But while visits to e-commerce sites and apps on tablets and phones have nearly doubled since last year, consumers like Mr. O’Neil are more frequently using multiple devices to shop. In many cases, they are more comfortable making the final purchase on a computer, with its bigger screen and keyboard. So retailers are trying to figure out how to appeal to a shopper who may use a cellphone to research products, a tablet to browse the options and a computer to buy.

“I’ve been yelling at customers for two years, saying, ‘Mobile, mobile, mobile,’ ” said Jason Spero, director of mobile sales and strategy at Google. “But the funny thing is, now we’re going to say: ‘Don’t put mobile in a silo. It’s also about the desktop.’ ”

The challenges are daunting, though. It is technically difficult to track consumers as they hop from phone to computer to tablet and back again. This means customers who, say, fill shopping carts on their tablets have to do all the work again on their PCs or other devices. The biggest obstacle, retailers say, is that the tools used to track shoppers on computers — cookies, or bundles of data stored in Web browsers — don’t transfer across devices.

Instead, retailers are figuring out how to sync the experience in other ways, like prompting shoppers to log in on each device. And being able to track people across devices gives retailers more insight into how they shop.

The retailers’ efforts are backed by research. While one-quarter of the visits to e-commerce sites occur on mobile devices, only around 15 percent of purchases do, according to data from I.B.M. According to Google, 85 percent of online shoppers start searching on one device — most often a mobile phone — and make a purchase on another.

At eBags, customers are shopping on their tablets in the evening and returning on their work computers the next day. But eBags has not yet synced the shoppers across devices, so customers must build their shopping carts from scratch if they switch devices.

“That is a blind spot with a lot of sites,” said Peter Cobb, co-founder of eBags. “It is a requirement moving forward.”

At eBay, one-third of the purchases involve mobile devices at some point, even if the final purchase is made on a computer.

At eBay, once shoppers log in on a device, they do not need to log in again. Their information, like shipping and credit card details and saved items, syncs across all their devices. If an eBay shopper is interested in a certain handbag, and saves that search on a computer, eBay will send alerts to her cellphone when a new handbag arrives or an auction is about to end.

“They might discover an item on a phone or tablet, do a saved-search push alert later on some other screen and eventually close on the Web site,” said Steve Yankovich, who runs eBay Mobile. “People are buying and shopping and consuming potentially every waking moment of the day.”

ModCloth, an e-commerce site for women’s clothes, said that while a quarter of its visits come from mobile devices, people are not yet buying there in the same proportion, though they are becoming more comfortable with checking out on those devices.

“She’s visiting us more on the phone, but she’s actually transacting somewhere else,” said Sarah Rose, vice president of product at ModCloth.

For example, a shopper will skim through new arrivals on her phone while on the bus and add items to her wish list, then visit that evening on her tablet to make a purchase, Ms. Rose said.

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Your Money: Walking the Tightrope on Mental Health Coverage

Insurance covers more mental health care than many people may realize, and more people will soon have the kind of health insurance that does so. But coverage goes only so far when there aren’t enough practitioners who accept it — or there aren’t any nearby, or they aren’t taking any new patients.

In the days after the Newtown, Conn., school shooting, parents and politicians took to the airwaves to make broad-based proclamations about the sorry state of mental health care in America. But a closer look reveals a more nuanced view, with a great deal of recent legislative progress as well as plenty of infuriating coverage gaps.

The stakes in any census of mental health insurance coverage are high given how many people are suffering. Twenty-six percent of adults experience a diagnosable mental disorder in any given year, and 6 percent of all adults experience a seriously debilitating mental illness, according to the National Institute of Mental Health. Twenty-one percent of teenagers experience a severe emotional disturbance between the ages of 13 and 18.

According to this year’s Society for Human Resource Management survey of 550 employers of all sizes, including nonprofits and government entities, 85 percent offer at least some mental health insurance coverage. A 2009 Mercer survey found that 84 percent of employers with more than 500 employees covered both in-network and out-of-network mental health and substance abuse treatments.

For now, some people who have no health insurance or who buy it on their own may avoid purchasing mental health coverage too, or may avoid seeking treatment for things like addiction or depression. This happens for many of the same reasons that there has historically been less mental health coverage than there has been for other illnesses. The earliest objections among insurance providers and employers had to do with whether mental disorders existed at all, according to Howard Goldman, a professor of psychiatry at the University of Maryland school of medicine. Then there were questions about whether treatment actually worked. Next, concerns arose over cost and how often people would avail themselves of costly mental health treatments.

But a subset of adults who have good insurance coverage still avoid treatment for mental illness to this day, according to Edward A. Kaplan, senior vice president and national practice leader for the Segal Company, a benefits consultant that works with many unions. “Culturally, a lot of people driving trucks don’t believe in it and suffer through,” he said. “And a lot of transport unions don’t trust employers and think they will look at it and use it to retaliate against the workers.”

For many of the people who do have mental health coverage, there is now a bit more of it at a lower cost than there might have been five years ago, even if mental health insurance over all remains much less generous than it was many years ago when employees did not pay as much out of pocket. That’s because a 2008 federal law requires employers with more than 50 employees that do offer mental health coverage to have no more restrictions than there are for physical injuries or surgery, and no higher costs.

This so-called parity bill now applies to a crucial provision of President Obama’s Affordable Care Act. Insurance plans in the exchanges that will offer health coverage to millions of uninsured individuals starting in 2014 must cover many items and services, including mental health disorders and substance abuse.

The combination of parity and expanded care is crucial, according to Anthony Wright, the executive director of Health Access, a consumer advocacy organization in California. After all, parity doesn’t do much good if the mental health coverage need only be equivalent to a meager health insurance plan that covers very little.

Then again, what good is parity in mental health insurance if you can’t get the treatment you need? Plenty of psychiatrists in private practice accept no insurance at all, though it is not clear how many; their professional organizations claim to have no recent or decent data on the percentage of people in private practice who take cash on the barrelhead, write people a receipt and send them off to their insurance company to request out-of-network reimbursement if they have any at all.

According to a 2008 American Psychological Association survey, 85 percent of the 2,200 respondents who said they worked at least part time in private practice received at least some third-party payments for their services. That doesn’t mean they take your insurance, though.

Nor does it guarantee that they or other mental health practitioners are anywhere near you or have any imminent openings for appointments. This can be a challenge for people who live far from major cities or big medical centers and need treatment for mental illnesses like severe depression or schizophrenia or disorders like autism.

But it is a particular problem for parents of autistic children who need specialized treatment that is relatively new or that not many people are trained to do. Amanda Griffiths, who lives in Carlisle, Pa., and is the mother of two autistic boys, called 17 providers within two hours of her home before finding one who was qualified to evaluate her younger son and was accepting new patients his age.

“No amount of insurance is going to magically make a provider appear,” she said.

And it remains a struggle to persuade insurance companies and employers to cover treatment that is new or expensive, even if it’s likely to be effective. Ira Burnim, legal director of the Bazelon Center for Mental Health Law, points to something called assertive community treatment, a team-based approach that has proved useful for adults with severe mental illness and holds promise for children, too. There, the challenge is to define what kinds of interaction with a patient outside of an office setting is billable and write rules for coverage.

Autistic children can benefit from an intensive treatment called applied behavior analysis, but many insurance companies haven’t wanted to cover what can be a $60,000 or $70,000 annual cost. They claim that the treatment, which can include intensive one-on-one interaction and assistance with both basic and more complex skills, is either too experimental or an educational service that schools should provide. This can be a tricky area for parents to navigate, because it isn’t always clear which part of an overall health insurance policy ought to cover various possible treatments.

A law school professor named Lorri Unumb faced a bill that big several years ago when her son Ryan was found to be autistic and she discovered that her insurance would not pay for treatment. After moving to South Carolina and meeting families there who had not been able to afford the therapy, she spent two years persuading state legislators to pass a law that forced insurance companies to pay for the treatment. “I did not really know how to write a bill,” she said. “I had watched ‘Schoolhouse Rock’ before, and that was kind of my inspiration and guidance.”

Autism Speaks, a national advocacy organization, saw what she accomplished and hired her to barnstorm the country in an effort to get similar laws passed. There are now 32 states that have them, though there’s a crucial catch: they don’t apply to the many large employers who pool their own resources in so-called self-funded insurance plans.

If you work in such a company, it may be up to you to lobby your human resources department to cover applied behavioral analysis or whatever mental health therapy you or your child may need. Sometimes a personal appeal will succeed; Mr. Kaplan, the benefits consultant, noted that when a parent called about a child, an employer might be particularly sensitive.

But a part of Ms. Unumb’s job these days is to assist parents with appeals where employers have said no or appear likely to. She has accompanied parents to meetings with their human resources departments all over the country to request that the employer expand coverage for everyone. She has a 115-page presentation that she draws on, pointing out that at its core, autism is a medical condition diagnosed by a doctor, the very thing health insurance is supposed to cover.

At $60,000 or more annually for children with particularly acute treatment needs, the coverage does not come cheaply. But Autism Speaks estimates that that expense, spread over thousands of employees, raises premium costs 31 cents a month.

Ms. Unumb notes that for many autistic children, intensive early intervention can allow them to function in mainstream classrooms and prevent a host of problems there and once they finish school. “You pay for it now or you pay for it later,” she said. “And you pay for it a lot more if you choose later, in more ways than just financial.”

Read More..

Your Money: Walking the Tightrope on Mental Health Coverage

Insurance covers more mental health care than many people may realize, and more people will soon have the kind of health insurance that does so. But coverage goes only so far when there aren’t enough practitioners who accept it — or there aren’t any nearby, or they aren’t taking any new patients.

In the days after the Newtown, Conn., school shooting, parents and politicians took to the airwaves to make broad-based proclamations about the sorry state of mental health care in America. But a closer look reveals a more nuanced view, with a great deal of recent legislative progress as well as plenty of infuriating coverage gaps.

The stakes in any census of mental health insurance coverage are high given how many people are suffering. Twenty-six percent of adults experience a diagnosable mental disorder in any given year, and 6 percent of all adults experience a seriously debilitating mental illness, according to the National Institute of Mental Health. Twenty-one percent of teenagers experience a severe emotional disturbance between the ages of 13 and 18.

According to this year’s Society for Human Resource Management survey of 550 employers of all sizes, including nonprofits and government entities, 85 percent offer at least some mental health insurance coverage. A 2009 Mercer survey found that 84 percent of employers with more than 500 employees covered both in-network and out-of-network mental health and substance abuse treatments.

For now, some people who have no health insurance or who buy it on their own may avoid purchasing mental health coverage too, or may avoid seeking treatment for things like addiction or depression. This happens for many of the same reasons that there has historically been less mental health coverage than there has been for other illnesses. The earliest objections among insurance providers and employers had to do with whether mental disorders existed at all, according to Howard Goldman, a professor of psychiatry at the University of Maryland school of medicine. Then there were questions about whether treatment actually worked. Next, concerns arose over cost and how often people would avail themselves of costly mental health treatments.

But a subset of adults who have good insurance coverage still avoid treatment for mental illness to this day, according to Edward A. Kaplan, senior vice president and national practice leader for the Segal Company, a benefits consultant that works with many unions. “Culturally, a lot of people driving trucks don’t believe in it and suffer through,” he said. “And a lot of transport unions don’t trust employers and think they will look at it and use it to retaliate against the workers.”

For many of the people who do have mental health coverage, there is now a bit more of it at a lower cost than there might have been five years ago, even if mental health insurance over all remains much less generous than it was many years ago when employees did not pay as much out of pocket. That’s because a 2008 federal law requires employers with more than 50 employees that do offer mental health coverage to have no more restrictions than there are for physical injuries or surgery, and no higher costs.

This so-called parity bill now applies to a crucial provision of President Obama’s Affordable Care Act. Insurance plans in the exchanges that will offer health coverage to millions of uninsured individuals starting in 2014 must cover many items and services, including mental health disorders and substance abuse.

The combination of parity and expanded care is crucial, according to Anthony Wright, the executive director of Health Access, a consumer advocacy organization in California. After all, parity doesn’t do much good if the mental health coverage need only be equivalent to a meager health insurance plan that covers very little.

Then again, what good is parity in mental health insurance if you can’t get the treatment you need? Plenty of psychiatrists in private practice accept no insurance at all, though it is not clear how many; their professional organizations claim to have no recent or decent data on the percentage of people in private practice who take cash on the barrelhead, write people a receipt and send them off to their insurance company to request out-of-network reimbursement if they have any at all.

According to a 2008 American Psychological Association survey, 85 percent of the 2,200 respondents who said they worked at least part time in private practice received at least some third-party payments for their services. That doesn’t mean they take your insurance, though.

Nor does it guarantee that they or other mental health practitioners are anywhere near you or have any imminent openings for appointments. This can be a challenge for people who live far from major cities or big medical centers and need treatment for mental illnesses like severe depression or schizophrenia or disorders like autism.

But it is a particular problem for parents of autistic children who need specialized treatment that is relatively new or that not many people are trained to do. Amanda Griffiths, who lives in Carlisle, Pa., and is the mother of two autistic boys, called 17 providers within two hours of her home before finding one who was qualified to evaluate her younger son and was accepting new patients his age.

“No amount of insurance is going to magically make a provider appear,” she said.

And it remains a struggle to persuade insurance companies and employers to cover treatment that is new or expensive, even if it’s likely to be effective. Ira Burnim, legal director of the Bazelon Center for Mental Health Law, points to something called assertive community treatment, a team-based approach that has proved useful for adults with severe mental illness and holds promise for children, too. There, the challenge is to define what kinds of interaction with a patient outside of an office setting is billable and write rules for coverage.

Autistic children can benefit from an intensive treatment called applied behavior analysis, but many insurance companies haven’t wanted to cover what can be a $60,000 or $70,000 annual cost. They claim that the treatment, which can include intensive one-on-one interaction and assistance with both basic and more complex skills, is either too experimental or an educational service that schools should provide. This can be a tricky area for parents to navigate, because it isn’t always clear which part of an overall health insurance policy ought to cover various possible treatments.

A law school professor named Lorri Unumb faced a bill that big several years ago when her son Ryan was found to be autistic and she discovered that her insurance would not pay for treatment. After moving to South Carolina and meeting families there who had not been able to afford the therapy, she spent two years persuading state legislators to pass a law that forced insurance companies to pay for the treatment. “I did not really know how to write a bill,” she said. “I had watched ‘Schoolhouse Rock’ before, and that was kind of my inspiration and guidance.”

Autism Speaks, a national advocacy organization, saw what she accomplished and hired her to barnstorm the country in an effort to get similar laws passed. There are now 32 states that have them, though there’s a crucial catch: they don’t apply to the many large employers who pool their own resources in so-called self-funded insurance plans.

If you work in such a company, it may be up to you to lobby your human resources department to cover applied behavioral analysis or whatever mental health therapy you or your child may need. Sometimes a personal appeal will succeed; Mr. Kaplan, the benefits consultant, noted that when a parent called about a child, an employer might be particularly sensitive.

But a part of Ms. Unumb’s job these days is to assist parents with appeals where employers have said no or appear likely to. She has accompanied parents to meetings with their human resources departments all over the country to request that the employer expand coverage for everyone. She has a 115-page presentation that she draws on, pointing out that at its core, autism is a medical condition diagnosed by a doctor, the very thing health insurance is supposed to cover.

At $60,000 or more annually for children with particularly acute treatment needs, the coverage does not come cheaply. But Autism Speaks estimates that that expense, spread over thousands of employees, raises premium costs 31 cents a month.

Ms. Unumb notes that for many autistic children, intensive early intervention can allow them to function in mainstream classrooms and prevent a host of problems there and once they finish school. “You pay for it now or you pay for it later,” she said. “And you pay for it a lot more if you choose later, in more ways than just financial.”

Read More..