N.Y.U. and Others Offer Shorter Courses Through Medical School





Training to become a doctor takes so long that just the time invested has become, to many, emblematic of the gravity and prestige of the profession.




But now one of the nation’s premier medical schools, New York University, and a few others around the United States are challenging that equation by offering a small percentage of students the chance to finish early, in three years instead of the traditional four.


Administrators at N.Y.U. say they can make the change without compromising quality, by eliminating redundancies in their science curriculum, getting students into clinical training more quickly and adding some extra class time in the summer.


Not only, they say, will those doctors be able to hang out their shingles to practice earlier, but they will save a quarter of the cost of medical school — $49,560 a year in tuition and fees at N.Y.U., and even more when room, board, books, supplies and other expenses are added in.


“We’re confident that our three-year students are going to get the same depth and core knowledge, that we’re not going to turn it into a trade school,” said Dr. Steven Abramson, vice dean for education, faculty and academic affairs at N.Y.U. School of Medicine.


At this point, the effort involves a small number of students at three medical schools: about 16 incoming students at N.Y.U., or about 10 percent of next year’s entering class; 9 at Texas Tech Health Science Center School of Medicine; and even fewer, for now, at Mercer University School of Medicine’s campus in Savannah, Ga. A similar trial at Louisiana State University has been delayed because of budget constraints.


But Dr. Steven Berk, the dean at Texas Tech, said that 10 or 15 other schools across the country had expressed interest in what his university was doing, and the deans of all three schools say that if the approach works, they will extend the option to larger numbers of students.


“You’re going to see this kind of three-year pathway become very prominent across the country,” Dr. Abramson predicted.


The deans say that getting students out the door more quickly will accomplish several goals. By speeding up production of physicians, they say, it could eventually dampen a looming doctor shortage, although the number of doctors would not increase unless the schools enrolled more students in the future.


The three-year program would also curtail student debt, which now averages $150,000 by graduation, and by doing so, persuade more students to go into shortage areas like pediatrics and internal medicine, rather than more lucrative specialties like dermatology.


The idea was supported by Dr. Ezekiel J. Emanuel, a former health adviser to President Obama, and a colleague, Victor R. Fuchs. In an editorial in the Journal of the American Medical Association in March, they said there was “substantial waste” in the nation’s medical education. “Years of training have been added without evidence that they enhance clinical skills or the quality of care,” they wrote. They suggested that the 14 years of college, medical school, residency and fellowship that it now takes to train a subspecialty physician could be reduced by 30 percent, to 10 years.


That opinion, however, is not universally held. Other experts say that a three-year medical program would deprive students of the time they need to delve deeply into their subjects, to consolidate their learning and to reach the level of maturity they need to begin practicing, while adding even more pressure to a stressful academic environment.


“The downside is that you are really tired,” said Dr. Dan Hunt, co-secretary of the Liaison Committee on Medical Education, the accrediting agency for medical schools in the United States and Canada. But because accreditation standards do not dictate the fine points of curriculum, the committee has approved N.Y.U.’s proposal, which exceeds by five weeks its requirement that schools provide at least 130 weeks of medical education.


The medical school is going ahead with its three-year program despite the damage from Hurricane Sandy, which forced NYU Langone Medical Center to evacuate more than 300 patients at the height of the storm and temporarily shut down three of its four main teaching hospitals.


Dr. Abramson of N.Y.U. said that postgraduate training, which typically includes three years in a hospital residency, and often fellowships after that, made it unnecessary to try to cram everything into the medical school years. Students in the three-year program will have to take eight weeks of class before entering medical school, and stay in the top half of their class academically. Those who do not meet the standards will revert to the four-year program.


Read More..

Syrian Resort Town Is Stronghold for Alawites





TARTUS, Syria — Loyalists who support the government of President Bashar al-Assad are flocking to the Mediterranean port of Tartus, creating an overflowing boomtown far removed from the tangled, scorched rubble that now mars most Syrian cities.







The New York Times

The port city of Tartus is sheltered by a mountain range.






There are no shellings or air raids to interrupt the daily calm. Families pack the cafes lining the town’s seaside corniche, usually abandoned in December to the salty winter winds. The real estate market is brisk. A small Russian naval base provides at least the impression that salvation, if needed, is near.


Many of the new residents are members of the Alawite minority, the same Shiite Muslim sect to which Mr. Assad belongs. The latest influx is fleeing from Damascus, people who have decided that summer villas, however chilly, are preferable to the looming battle for the capital.


“Going to Tartus is like going to a different country,” said a Syrian journalist who recently met residents here. “It feels totally unaffected and safe. The attitude is, ‘We are enjoying our lives while our army is fighting overseas.’ ”


Should Damascus fall to the opposition, Tartus could become the heart of an attempt to create a different country. Some expect Mr. Assad and the security elite will try to survive the collapse by establishing a rump Alawite state along the coast, with Tartus as their new capital.


There have been various signs of preparations.


This month, the governor of Tartus Province announced that experts were studying how to develop a tiny local airfield, now used mostly by crop-dusters, into a full-fledged civilian airport “to boost transportation, business, travel and tourism,” as the official Syrian news agency, SANA, reported. The announcement coincided with the first attacks on the airport in Damascus, forcing it to close temporarily to international traffic.


More important, security forces are continuously tightening an extensive ring of checkpoints around the potential borders of an Alawite canton. The mountain heartland of the Alawites rises steeply to the east of Tartus, separating it from much of Syria. Across the mountains, the Orontes River creates a rough line separating Alawite territory from central Syria. Rebel military commanders from adjoining Hama Province said government soldiers vigorously maintain checkpoints on routes leading up into the mountains.


“If we bomb a checkpoint, it is back in place sometimes within hours,” said Basil al-Hamwi, a rebel fighter, speaking on the sidelines of a meeting of opposition military commanders in Turkey. “Once, in Hama Province, we destroyed five in one day and they were all back the next day. This area is even more important for them than Damascus.”


Mr. Hamwi and other rebel leaders said there were about 40 government checkpoints along more than 60 miles in Homs and Hama Provinces alone. Many Alawite commanders of Mr. Assad’s army have sent their families to their home villages, so they are particularly aggressive in protecting the area, said Hassan M. al-Saloom, a rebel battalion commander. They have formed committees to guard the outskirts of their villages, he said, and often negotiate local truces.


“Nobody goes inside, and they don’t come out,” he said.


There are widespread suspicions within the opposition that the military is shipping weapons into the Alawite hinterland, or has already positioned them. “The mountains and the coast make it hard to raid,” Mr. Saloom said.


Castles left by the Crusaders dot the coastal range, a testament to its strategic value.


If Mr. Assad fled to Tartus, he could seek protection from the Russian naval base here, or flee aboard a Russian vessel. Russia announced Tuesday that it was sending a small flotilla toward Tartus, possibly to evacuate its citizens who live in Syria. But Tartus residents said that the Russian families from the naval base had already left, while the officers do not leave the base, which is little more than an enclosure near the civilian port.


An employee of The New York Times reported from Tartus, and Neil MacFarquhar from Antakya, Turkey. Hania Mourtada contributed reporting from Beirut, Lebanon, and Hala Droubi from Dubai, United Arab Emirates.



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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.


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..

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..

The Lede Blog: Bahrain Welcomes European Delegation, Not Delegates' Calls to Free Dissidents

Last Updated, Saturday, 10:34 a.m. As The Lede reported on Wednesday, a delegation from the European Parliament visited Bahrain this week to discuss human rights, just as the kingdom jailed a rights advocate for documenting a protest on Twitter.

Bahrain’s state news media presented the visit as evidence that the kingdom is committed to human rights. One report showed the delegates meeting with the head of an official human rights organization established by royal decree, another their briefing by the royal who oversees the police force “on human rights reforms that have been implemented within the interior ministry.”

What the country’s official news agency did not report, however, is that the head of the delegation, Inese Vaidere of Latvia, called for the release of all “prisoners of conscience” currently being detained for their role in the protest movement.

Ms. Vaidere’s call was joined by at least two other members of the European Parliament who made the trip, Richard Howitt of Britain and Ana Gomes of Portugal. At the end of their visit, those members issued a joint statement calling on the government to immediately release up to 800 “political prisoners” and begin direct talks with the opposition.

Like the New York Times Op-Ed columnist Nicholas Kristof, who was denied entry to Bahrain last week after reporting on human-rights abuses on previous trips, Ms. Gomes was stopped at the airport in April, the last time she attempted to visit the kingdom to meet with rights activists.

Throughout their three-day visit, Ms. Gomes and Mr. Howitt posted a stream of updates on their Twitter feeds as the delegation met with Bahraini officials and detained opposition members. They both reported questioning the treatment of human rights activists like Said Yousif al-Muhafda, who was jailed on Monday for tweeting about a protest.

Mr. Howitt and Ms. Gomes also described meetings with detained rights activists. They included Nabeel Rajab, the president of the Bahrain Center for Human Rights — who was jailed for inciting antigovernment protests in speeches and Twitter updates — and the same rights group’s founder, Abdulhadi al-Khawaja — who was sentenced to life in prison by a military court last year for his role in the 2011 protests. Claims that the men are confined in luxurious surroundings are untrue, the parliamentarians reported.

Read More..

Instagram Reversal Doesn’t Appease Everyone


Peter DaSilva for The New York Times


Kevin Systrom, right, co-founder of Instagram, with employees in the company office in San Francisco last year.







SAN FRANCISCO — Facebook may have quelled a full-scale rebellion by quickly dumping the contentious new terms of use for Instagram, its photo-sharing service. But even as the social network furiously backpedaled, some users said Friday they were carrying through on plans to leave.








Eric Piermont/Agence France-Presse — Getty Images

Kevin Systrom, Instagram’s co-founder, said the company would complete its plans, then explain its ad policy.






Ryan Cox, a 29-year-old management consultant at ExactTarget, an Indianapolis-based interactive marketing software company, said he had already moved his photos to Flickr, Yahoo’s photo-sharing app, where he could have better control.


Mr. Cox said the uproar this week over whether Instagram owned its users’ photos was “a wake-up call.”


“It’s my fault,” he continued. “I’m smart enough to know what Instagram had and what they could do — especially the minute Facebook acquired them — but I was a victim of naïve optimism.”


“Naïve optimism” is as good a term as any for the emotion that people feel as they put their private lives onto social networks.


Companies like Google, Twitter, Yelp and Facebook offer themselves as free services for users to store and share their most intimate pictures, secrets, messages and memories. But to flourish over the long term, they need to seek new ways to market the personal data they accumulate. They must constantly push the envelope, hoping users either do not notice or do not care.


So they sell ads against the content of an e-mail, as Google does, or transform a user’s likes into commercial endorsements, as Facebook does, or sell photographs of your adorable 3-year-old, which is what Instagram was accused of planning this week.


“The reality is that companies have always had to make money,” said Miriam H. Wugmeister, chair of Morrison Foerster’s privacy and data security group.


Even as Instagram was pulling back on its changed terms of service on Thursday night, it made clear it was only regrouping. After all, Facebook, as a publicly held corporation, must answer to Wall Street’s quarterly expectations.


“We are going to take the time to complete our plans, and then come back to our users and explain how we would like for our advertising business to work,” Kevin Systrom, Instagram’s youthful co-founder, wrote on the company’s blog.


Instagram’s actions angered many users who were already incensed over the company’s decision earlier this month to cut off its integration with Twitter, a Facebook rival, making it harder for its users to share their Instagram photos on Twitter.


Users were apprehensive that the new terms of service meant that data on their favorite things would be shared with Facebook and its advertisers. Users also worried that their photos would become advertising.


Instagram is barely two years old but has 100 million users. Last spring, Facebook announced plans to buy it in a deal that was initially valued at $1 billion. The deal was closed in September for a somewhat smaller amount.


For some users, Mr. Systrom’s apology and declaration that “Instagram has no intention of selling your photos, and we never did” was sufficient.


National Geographic, which suspended its account in the middle of the uproar, held a conference call with members of Facebook’s legal and policy teams. Afterward, the magazine, which has 658,000 Instagram followers, said it would resurrect its account.


Also mollified was Noah Kalina, who took wedding photographs earlier this year for Mark Zuckerberg, the founder of Facebook. In a widely circulated post on Twitter, Mr. Kalina said the new terms of service were “a contract no professional or nonprofessional should ever sign.” His advice: “Walk away.”


On Friday, the photographer said he had walked back. “It’s nice to know they listened.”


Kim Kardashian, the most followed person on Instagram, said on Tuesday that she “really loved” the service — note the past tense — and that the new rules were not “fair.” She had yet to update her 17 million Twitter followers on Friday, but since she is pushing her True Reflection fragrance it is a safe bet that she has forgiven and forgotten.


Read More..

The Neediest Cases: The Daughter of a Sick Woman Falls Prey to a Craigslist Scam





Sitting side by side on their living room sofa, Patricia Morales and her daughter, Katherine, could be any mother-daughter duo. Both have dark hair, dark eyes and welcoming, infectious smiles.







Librado Romero/The New York Times

Patricia Morales, 62, at home in the Bronx. Her treatment for ailments like rheumatoid arthritis and hepatitis C led to depression.






2012-13 Campaign


Previously recorded:

$3,375,394



Recorded Wednesday:

182,251



*Total:

$3,557,645



Last year to date:

$3,320,812




*Includes $709,856 contributed to the Hurricane Sandy relief efforts.

The Neediest CasesFor the past 100 years, The New York Times Neediest Cases Fund has provided direct assistance to children, families and the elderly in New York. To celebrate the 101st campaign, an article will appear daily through Jan. 25. Each profile will illustrate the difference that even a modest amount of money can make in easing the struggles of the poor.


Last year donors contributed $7,003,854, which was distributed to those in need through seven New York charities.







The Youngest Donors


If your child or family is using creative techniques to raise money for this year’s campaign, we want to hear from you. Drop us a line on Facebook or talk to us on Twitter.





But the ties that bind them go beyond their genes, beyond the bodies they were born with.


“It’s called a neck ring. It’s a silver curved barbell, one inch,” Katherine, 20, said as she swept aside her shoulder-length black hair to show the piercing in the back of her neck, a show of solidarity with her mother. She had it done when she was 16. “I wanted to know what it felt like for my mom.”


Her mother then turned around and outlined with her finger two lengthy scars that run down her back.


“I’ve had a lot of physical problems,” Ms. Morales, 62, said. Shaking her head at her daughter’s piercing, she added, “I’ve had rods put in my upper and lower spine, but I could never do that.”


The rods were surgically planted to treat herniated discs, the result of having a cruel combination of osteoporosis, hepatitis C, fibromyalgia and rheumatoid arthritis. Ms. Morales contracted hepatitis C from a blood transfusion she received in 1972 after the birth of her only son, she said.


“I didn’t even know about it until 10 years ago,” she said. “My liver blood count was a little high.”


Since the diagnosis, Ms. Morales, a former schoolteacher, has ridden the arduous highs and lows common to patients with hepatitis C. Her treatments for the disease, which debilitates the liver over time, have included pills and injections that can cause depression. Ms. Morales, a single parent, found an unforgiving salve in alcohol.


“I was depressed; I was totally drunk,” she said. “I didn’t want to live anymore.”


Then, about a year ago, she reached a turning point when visiting her hepatitis C specialist.


“I was 210 pounds,” she said. “The doctor said: ‘You have to stop drinking. You have to lose weight.’ ”


To help combat the depression, her doctor referred her to Jewish Association Serving the Aging, a beneficiary agency of UJA-Federation of New York, one of the organizations supported by The New York Times Neediest Cases Fund. She began weekly counseling sessions with a social worker and started taking an antidepressant medication. The federation drew about $600 from the fund in May so that Ms. Morales could buy a mattress.


“I had a horrible bed,” she said. “I felt like I was sleeping on rocks, and with rods in my back, I was waking up every hour.”


After several months of therapy and starting a diet, Ms. Morales was on her way to losing 60 pounds. Today, she weighs 148.


Light was starting to show itself again when the family took an unexpected financial hit this summer. While taking time off from attending Hostos Community College, Katherine Morales looked for work on Craigslist.


“I saw my mom, and I realized I needed to get a job,” Katherine said shyly. “This guy asked me to be his personal assistant, and he asked me to wire money.”


Offering $400 a week, the man requested help transferring almost $2,000 from what he said was his wife’s account. He transferred the money to Katherine’s account, asking her to wire it to a bank account in Malaysia.


Shortly after she wired the money, the bank froze the account, which Katherine and her mother shared. It was then that Katherine realized she had been the victim of a scam. The money transferred into her account turned out to have been stolen, and she was responsible for repaying it.


Katherine went to detectives immediately with more than 20 pages of evidentiary e-mails, but found that she was unable to file a complaint.


“They told me it wasn’t enough,” she said. “These things happen all the time.”


They lost almost $2,000.


Ms. Morales lives on a fixed income. She receives just over $700 a month from Social Security and $200 month in food stamps. The rent for the apartment she shares with her daughter in the Throgs Neck neighborhood of the Bronx is $230, and Ms. Morales has a monthly combined phone and cable bill of $140. Ms. Morales has a son, but he is unable to help the family.


Falling behind on her bills, Ms. Morales turned once again to JASA for help paying a combined phone and cable bill of nearly $200, a grant the agency drew from the Neediest Cases Fund.


“It was terrible, because my intention was to help my mom,” said Katherine, who has since found a part-time job at a vitamin shop.


Ms. Morales has been feeling much better, but she is nervous about an appointment with her hepatitis C specialist in January.


“I’m taking things one day at a time, but I’m looking forward to someone taking care of me,” she said. “I want to live a little bit longer, but not that long.”


“Why are you putting a time limit on it?” Katherine said, jokingly. “Seventy’s the new 20!” she added, nudging her mother in the side. “Remember, the doctor said you wouldn’t live past your late 50s, but you did.”


Read More..

The Neediest Cases: The Daughter of a Sick Woman Falls Prey to a Craigslist Scam





Sitting side by side on their living room sofa, Patricia Morales and her daughter, Katherine, could be any mother-daughter duo. Both have dark hair, dark eyes and welcoming, infectious smiles.







Librado Romero/The New York Times

Patricia Morales, 62, at home in the Bronx. Her treatment for ailments like rheumatoid arthritis and hepatitis C led to depression.






2012-13 Campaign


Previously recorded:

$3,375,394



Recorded Wednesday:

182,251



*Total:

$3,557,645



Last year to date:

$3,320,812




*Includes $709,856 contributed to the Hurricane Sandy relief efforts.

The Neediest CasesFor the past 100 years, The New York Times Neediest Cases Fund has provided direct assistance to children, families and the elderly in New York. To celebrate the 101st campaign, an article will appear daily through Jan. 25. Each profile will illustrate the difference that even a modest amount of money can make in easing the struggles of the poor.


Last year donors contributed $7,003,854, which was distributed to those in need through seven New York charities.







The Youngest Donors


If your child or family is using creative techniques to raise money for this year’s campaign, we want to hear from you. Drop us a line on Facebook or talk to us on Twitter.





But the ties that bind them go beyond their genes, beyond the bodies they were born with.


“It’s called a neck ring. It’s a silver curved barbell, one inch,” Katherine, 20, said as she swept aside her shoulder-length black hair to show the piercing in the back of her neck, a show of solidarity with her mother. She had it done when she was 16. “I wanted to know what it felt like for my mom.”


Her mother then turned around and outlined with her finger two lengthy scars that run down her back.


“I’ve had a lot of physical problems,” Ms. Morales, 62, said. Shaking her head at her daughter’s piercing, she added, “I’ve had rods put in my upper and lower spine, but I could never do that.”


The rods were surgically planted to treat herniated discs, the result of having a cruel combination of osteoporosis, hepatitis C, fibromyalgia and rheumatoid arthritis. Ms. Morales contracted hepatitis C from a blood transfusion she received in 1972 after the birth of her only son, she said.


“I didn’t even know about it until 10 years ago,” she said. “My liver blood count was a little high.”


Since the diagnosis, Ms. Morales, a former schoolteacher, has ridden the arduous highs and lows common to patients with hepatitis C. Her treatments for the disease, which debilitates the liver over time, have included pills and injections that can cause depression. Ms. Morales, a single parent, found an unforgiving salve in alcohol.


“I was depressed; I was totally drunk,” she said. “I didn’t want to live anymore.”


Then, about a year ago, she reached a turning point when visiting her hepatitis C specialist.


“I was 210 pounds,” she said. “The doctor said: ‘You have to stop drinking. You have to lose weight.’ ”


To help combat the depression, her doctor referred her to Jewish Association Serving the Aging, a beneficiary agency of UJA-Federation of New York, one of the organizations supported by The New York Times Neediest Cases Fund. She began weekly counseling sessions with a social worker and started taking an antidepressant medication. The federation drew about $600 from the fund in May so that Ms. Morales could buy a mattress.


“I had a horrible bed,” she said. “I felt like I was sleeping on rocks, and with rods in my back, I was waking up every hour.”


After several months of therapy and starting a diet, Ms. Morales was on her way to losing 60 pounds. Today, she weighs 148.


Light was starting to show itself again when the family took an unexpected financial hit this summer. While taking time off from attending Hostos Community College, Katherine Morales looked for work on Craigslist.


“I saw my mom, and I realized I needed to get a job,” Katherine said shyly. “This guy asked me to be his personal assistant, and he asked me to wire money.”


Offering $400 a week, the man requested help transferring almost $2,000 from what he said was his wife’s account. He transferred the money to Katherine’s account, asking her to wire it to a bank account in Malaysia.


Shortly after she wired the money, the bank froze the account, which Katherine and her mother shared. It was then that Katherine realized she had been the victim of a scam. The money transferred into her account turned out to have been stolen, and she was responsible for repaying it.


Katherine went to detectives immediately with more than 20 pages of evidentiary e-mails, but found that she was unable to file a complaint.


“They told me it wasn’t enough,” she said. “These things happen all the time.”


They lost almost $2,000.


Ms. Morales lives on a fixed income. She receives just over $700 a month from Social Security and $200 month in food stamps. The rent for the apartment she shares with her daughter in the Throgs Neck neighborhood of the Bronx is $230, and Ms. Morales has a monthly combined phone and cable bill of $140. Ms. Morales has a son, but he is unable to help the family.


Falling behind on her bills, Ms. Morales turned once again to JASA for help paying a combined phone and cable bill of nearly $200, a grant the agency drew from the Neediest Cases Fund.


“It was terrible, because my intention was to help my mom,” said Katherine, who has since found a part-time job at a vitamin shop.


Ms. Morales has been feeling much better, but she is nervous about an appointment with her hepatitis C specialist in January.


“I’m taking things one day at a time, but I’m looking forward to someone taking care of me,” she said. “I want to live a little bit longer, but not that long.”


“Why are you putting a time limit on it?” Katherine said, jokingly. “Seventy’s the new 20!” she added, nudging her mother in the side. “Remember, the doctor said you wouldn’t live past your late 50s, but you did.”


Read More..