Books: From Bang to Whimper: A Heart Drug’s Story

On June 23, 2005, American medicine managed to take a small step forward and a giant step backward at precisely the same time, with government approval of the first medication to be earmarked for a specific racial group. It was BiDil, a drug designed to treat heart failure in blacks.

Enthusiasts hailed BiDil’s approval by the Food and Drug Administration as a landmark event in the nascent field of pharmacogenomics, which aims to create drugs tailored to fit an individual’s genetic makeup as precisely as a bespoke suit drapes its owner’s shoulders. Critics just winced and clocked one more misstep in medicine’s long history of race-related disasters.

You would think that the elucidation of the human genome would have cleared up most of the hoary untruths surrounding race and health. But as Jonathan Kahn makes clear in his worthy if convoluted review of the events surrounding the birth of BiDil, the genome has in many respects only made things worse.

It has been clear for decades that race has minimal relevance to the body’s inner workings. Research has repeatedly shown that the biologic variations among individuals of the same race are reliably great enough for race to retain little utility as a biologic predictor. You might as well sort people by height. Or, in the words of an editorial writer for Nature Biotechnology in 2005, “Pooling people in race silos is akin to zoologists grouping raccoons, tigers and okapis on the basis that they are all stripy.”

But old misconceptions die hard, particularly for entrepreneurs eagerly awaiting cash bonanzas from the genomic revolution.

Race may be irrelevant; it may be, as Dr. Francis Collins, the director of the National Institutes of Health, put it, “a weak and imperfect proxy” for genetic differences. But it is also a familiar concept — and asking people what race they are is substantially cheaper than genotyping them.

So in a peculiar paradox, race has come to serve in some circles as a crude surrogate for genetic analysis until actual genomic medicine comes along — a temporary bridge from now to later, known to be flawed but still a quasi-legitimate stand-in for the real thing.

Against this background unfolds the story of BiDil, a drama of greed and good intentions.

Several observations prompted the drug’s development. Among them was the common assertion from the last century that blacks with heart failure were more likely to die than whites. (Mr. Kahn does an impressive job of researching and debunking this statistic.) Then there was the belief that blacks often reacted badly to some of the newer drugs used for treating heart failure, and the results of a study dating from the 1980s suggesting that many black patients did well with two old standby drugs.

Those two drugs were (and are) on sale as generics, costing pennies a pill. But just suppose they were combined into a single pill that could be then specifically marketed to patients who just happened to be thought in particular need of effective medication? Now there was a pharmacologic and marketing plan that would extend a lucrative new patent for decades.

And so it came to pass that a collection of eager investors and some of the nation’s foremost cardiologists smiled on the results of an industry-sponsored trial performed on self-identified black subjects with heart failure: The two cheap drugs combined into the not-so-cheap BiDil reduced mortality by 40 percent compared with placebo. This figure was impressive enough to end the trial early and speed BiDil to market.

How did whites do on BiDil? Nobody bothered to check.

Mr. Kahn deserves credit for teasing out all the daunting complexities behind these events, including the details of genetic analysis, the perils of racial determinations and the minutiae of patent law. Unfortunately, though, he suffocates his powerful subject in a dry, repetitive, ponderous read.

A law professor with a doctorate in history and longstanding interest in race issues, Mr. Kahn trudges a partisan path through the drama in which he himself was a player. (He testified before an F.D.A. advisory committee that BiDil should be approved without racial qualifications.)

He heads bravely into many statistical thickets, but omits relevant clinical data; he repeatedly refers to the trial that led to BiDil’s approval, for instance, but I could find its numerical findings nowhere in the book and had to look them up. In a story that fairly drips with potential human interest, he offers the reader not one sip.

The issues raised on every page are so important and so thought-provoking that it would be irresponsible to warn interested readers away. Still, it would be almost as irresponsible to misrepresent the difficulty of the journey.

As it happens, BiDil itself has had a remarkably inglorious career. Despite its much-trumpeted release, patients did not request the medication, and practicing doctors did not prescribe it.

NitroMed, the company that developed it, sponsored no further studies and failed in 2009.

The drug still lingers on the market; Mr. Kahn writes that BiDil may be resurrected in sustained-release form — that other time-honored technique for wringing a few more years from a drug’s patent.

For a parable of early 21st-century medicine, as it treads water between past and future and never hesitates to reach for a buck, it doesn’t get much better than BiDil.

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IHT Rendezvous: Monitoring Mandela, and With Him the Soul of a Nation

PLETTENBERG BAY, South Africa – After almost three weeks of treatment for a recurrent lung infection, Nelson Mandela, the 94-year-old icon of South Africa’s triumph over apartheid, was discharged from hospital late Wednesday. But a terse statement from his physicians saying he would not return immediately to his remote, rural home at Qunu in the Eastern Cape region raised fresh questions that his family and his associates sought to answer a day later.

Page Two

Posts written by the IHT’s Page Two columnists.

Mr. Mandela’s health – and the very question of his longevity – are a national issue reflecting his role as the custodian of his moral legacy. As I write in my latest Page Two column, his survival offers reassurance to many. But there is little doubt about his frailty.

The footage depicting him these days seems to be exclusively from the archives. The precise state of his health remains unclear.
When a television station re-broadcast an interview with his wife, Graça Machel this month, suggesting that his “spirit” and “sparkle” were fading, the alarms spread far beyond South Africa’s borders until the channel apologized, saying her remarks dated to 2009.

The terms of Mr. Mandela’s discharge from the hospital seemed to reflect those uncertainties.

Mr. Mandela’s grandson, Mandla Mandela, was quoted by the news24 Web site on Thursday as saying he hoped “it won’t be too long before he’s with us back in Qunu, where he belongs.” But, he said, the trip could be strenuous and Mr. Mandela’s physicians would determine “when he will be fit and ready to come back home.”

Mac Maharaj, a spokesman for President Jacob Zuma, said doctors had concluded that Mr. Mandela was better off at his home in Houghton, in Johannesburg’s leafy, upmarket northern suburbs, “so that he’s close to all the facilities where we can give him high care,” News24 reported.

“Madiba was doing well, but as you know, when you’re recovering there are ups and downs, slight ups and downs, and the doctors are looking for a steady progress and that began to be registered over the last few days,” Mr. Maharaj said, using Mr. Mandela’s clan name, Madiba.

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Study Finds Modest Declines in Obesity Rates Among Young Children From Poor Families

A new national study has found modest declines in obesity among 2- to 4-year-olds from poor families, a dip that researchers say may indicate that the obesity epidemic has passed its peak among this group.

The study, by researchers from the Centers for Disease Control and Prevention, drew on the height and weight measurements of 27 million children who were part of the federal Women, Infants and Children program, which provides food subsidies to low-income mothers and their children up to the age of 5.

The study was based on data from 30 states and the District of Columbia and covered the years from 1998 to 2010. The share of children who were obese declined to 14.9 percent in 2010, down from 15.2 percent in 2003, after rising between 1998 and 2003. Extreme obesity also declined, dropping to 2.07 percent in 2010 from 2.22 percent in 2003. The study was published Tuesday in The Journal of the American Medical Association.

The report defined a 3-year-old boy of average height, almost 3 feet 2 inches tall, as being obese when he weighed 37 pounds or more. The same boy was categorized as being extremely obese when he weighed 44 pounds or more.

“The declines we’re presenting here are pretty modest, but it is a change in direction,” said Heidi M. Blanck, one of the study’s authors and the acting director of the Division of Nutrition, Physical Activity and Obesity at the disease centers. “We were going up before. And this data shows we’re going down. For us, that’s pretty exciting.”

The findings were another sign that one of the nation’s seemingly intractable health problems may be reversing course, at least among children. Single interventions like school exercise programs have not worked, and public health experts now say that only a broad set of policy measures has a chance of success.

Over the past year, several major cities, including Los Angeles, New York and Philadelphia, have reported obesity declines among some parts of their student populations.

The new study was one of the first to document a national decline in obesity among young children from low-income families. Researchers say that is particularly meaningful in a population that is disproportionately at risk. Twenty percent of poor children are obese, compared with about 12 percent of children from more affluent families, according to the centers.

It is unclear what drove the decline, but Dr. Blanck offered hypotheses. Breast-feeding, which often leads to healthier weight gain for young children, has increased since 2000. The percentage of 6-month-olds still being breast-fed increased to 47.7 percent among children born in 2009, up from 34.2 percent among children born in 2000.

Breast-feeding of infants from low-income families has risen over the years. In 1980, only 28 percent of infants from those families had ever been breast-fed, compared with 66 percent in 2011.

Dr. Blanck also pointed to changes in the environment, like those documented in a report about food marketing practices released by the Federal Trade Commission on Friday.

The agency found that the amount of money spent on food marketing to children declined by nearly 20 percent from 2006 to 2009, with the biggest drop in television advertising. The total spent on food advertising to youths in 2009 was $1.79 billion, the report said.

The report, based on data from 48 major food and beverage marketers, also found that cereals marketed to children ages 2 to 11 had about a gram less sugar per serving in 2009 than in 2006 and slightly more whole grain.

Marketing to children of the most sugary cereals — those with 13 grams or more sugar per serving — was virtually eliminated between 2006 and 2009, according to the report.

But drinks marketed to children still averaged more than 20 grams of added sugar per serving, the report found. Most of the improvements in beverages in the time period were in those sold in schools, the report said.

Dr. Blanck said she was hopeful that several national programs begun in the past few years would help extend the early declines. One initiative, Let’s Move! Child Care, initiated by Michelle Obama’s office, helps child care centers serve healthier food and include physical activity throughout day.

Changes in the foods that are subsidized in the Women, Infants and Children program, like less financing for fruit juice and more for fruits and vegetables, may also help, she said.

Read More..

Study Finds Modest Declines in Obesity Rates Among Young Children From Poor Families

A new national study has found modest declines in obesity among 2- to 4-year-olds from poor families, a dip that researchers say may indicate that the obesity epidemic has passed its peak among this group.

The study, by researchers from the Centers for Disease Control and Prevention, drew on the height and weight measurements of 27 million children who were part of the federal Women, Infants and Children program, which provides food subsidies to low-income mothers and their children up to the age of 5.

The study was based on data from 30 states and the District of Columbia and covered the years from 1998 to 2010. The share of children who were obese declined to 14.9 percent in 2010, down from 15.2 percent in 2003, after rising between 1998 and 2003. Extreme obesity also declined, dropping to 2.07 percent in 2010 from 2.22 percent in 2003. The study was published Tuesday in The Journal of the American Medical Association.

The report defined a 3-year-old boy of average height, almost 3 feet 2 inches tall, as being obese when he weighed 37 pounds or more. The same boy was categorized as being extremely obese when he weighed 44 pounds or more.

“The declines we’re presenting here are pretty modest, but it is a change in direction,” said Heidi M. Blanck, one of the study’s authors and the acting director of the Division of Nutrition, Physical Activity and Obesity at the disease centers. “We were going up before. And this data shows we’re going down. For us, that’s pretty exciting.”

The findings were another sign that one of the nation’s seemingly intractable health problems may be reversing course, at least among children. Single interventions like school exercise programs have not worked, and public health experts now say that only a broad set of policy measures has a chance of success.

Over the past year, several major cities, including Los Angeles, New York and Philadelphia, have reported obesity declines among some parts of their student populations.

The new study was one of the first to document a national decline in obesity among young children from low-income families. Researchers say that is particularly meaningful in a population that is disproportionately at risk. Twenty percent of poor children are obese, compared with about 12 percent of children from more affluent families, according to the centers.

It is unclear what drove the decline, but Dr. Blanck offered hypotheses. Breast-feeding, which often leads to healthier weight gain for young children, has increased since 2000. The percentage of 6-month-olds still being breast-fed increased to 47.7 percent among children born in 2009, up from 34.2 percent among children born in 2000.

Breast-feeding of infants from low-income families has risen over the years. In 1980, only 28 percent of infants from those families had ever been breast-fed, compared with 66 percent in 2011.

Dr. Blanck also pointed to changes in the environment, like those documented in a report about food marketing practices released by the Federal Trade Commission on Friday.

The agency found that the amount of money spent on food marketing to children declined by nearly 20 percent from 2006 to 2009, with the biggest drop in television advertising. The total spent on food advertising to youths in 2009 was $1.79 billion, the report said.

The report, based on data from 48 major food and beverage marketers, also found that cereals marketed to children ages 2 to 11 had about a gram less sugar per serving in 2009 than in 2006 and slightly more whole grain.

Marketing to children of the most sugary cereals — those with 13 grams or more sugar per serving — was virtually eliminated between 2006 and 2009, according to the report.

But drinks marketed to children still averaged more than 20 grams of added sugar per serving, the report found. Most of the improvements in beverages in the time period were in those sold in schools, the report said.

Dr. Blanck said she was hopeful that several national programs begun in the past few years would help extend the early declines. One initiative, Let’s Move! Child Care, initiated by Michelle Obama’s office, helps child care centers serve healthier food and include physical activity throughout day.

Changes in the foods that are subsidized in the Women, Infants and Children program, like less financing for fruit juice and more for fruits and vegetables, may also help, she said.

Read More..

Israel to Review Curbs on Women’s Prayer at Western Wall

Rina Castelnuovo for The New York Times

Members of a group called Women of the Wall read from the Torah near the Western Wall in Jerusalem in December.

JERUSALEM — Amid outrage across the Jewish diaspora over a flurry of recent arrests of women seeking to pray at the Western Wall with ritual garments in defiance of Israeli law, Prime Minister Benjamin Netanyahu has asked Natan Sharansky, the chairman of the Jewish Agency, to study the issue and suggest ways to make the site more accommodating to all Jews.

The move comes after more than two decades of civil disobedience by a group called Women of the Wall against regulations, legislation and a 2003 Israeli Supreme Court ruling that allow for gender division at the wall, one of Judaism’s holiest sites, and prohibit women from carrying a Torah or wearing prayer shawls there.

Although the movement has struggled to gain traction in Israel, where the ultra-Orthodox retain great sway over public life, the issue has deepened a divide between the Jewish state and Jews around the world at a time when Israel is battling international isolation over its settlement policy. Critics, particularly leaders of the Reform and Conservative movements in the United States, complain that the government’s recent aggressive enforcement of restrictions at the wall has turned a national monument into an ultra-Orthodox synagogue.

“The prime minister thinks the Western Wall has to be a site that expresses the unity of the Jewish people, both inside Israel and outside the state of Israel,” Ron Dermer, Mr. Netanyahu’s senior adviser, said in an interview on Tuesday. “He wants to preserve the unity of world Jewry. This is an important component of Israel’s strength.”

Mr. Sharansky, whose quasi-governmental nonprofit organization handles immigration for the state and is a bridge between Israel and Jews around the world, said that Mr. Netanyahu asked him on Monday to take up the matter, and that he expected to have recommendations within a few months. He and Mr. Dermer said the agenda would include improvements for Robinson’s Arch, a discrete area of the wall designated for coed prayer under the court ruling, and the easing of restrictions in the larger area known as the Western Wall plaza, along with the more sensitive questions regarding prayer at the main site.

Mr. Sharansky said the Jewish Agency itself stopped having ceremonies for new immigrants in the plaza about two years ago after the Western Wall Heritage Foundation, which controls the site, said that men and women could not sit together. Under pressure from the international groups that provide its financing, the agency passed a resolution on Oct. 30 calling for a “satisfactory approach to the issue of prayer at the Western Wall.”

Asked whether he could imagine a day when women could wear prayer shawls and read a Torah at the wall itself, Mr. Sharansky said, “I imagine very easily a situation where everybody will have their opportunity to express their solidarity with Judaism and the Jewish people and the state of Israel in a way he or she wants, without undermining the other.”

“That’s as much as I want to say at this moment,” he added. “Now I have to share this vision with the appropriate bodies.”

Mr. Sharansky, a former Soviet dissident and widely respected figure, has been called upon before to broker peace with the diaspora over questions of religious pluralism, most recently during a harsh fight over conversion. Anat Hoffman, the chairwoman of Women of the Wall, reacted with cautious optimism to Mr. Netanyahu’s initiative, but said it would not stop the Israel Religious Action Center, of which she is executive director, from filing a Supreme Court petition as soon as next week challenging the makeup of the heritage foundation’s board.

“It’s a good thing that after 24 years the highest echelons in Israel are actually paying attention to this rift that is breaking diaspora Jews from Israel,” she said. “The table that should run the Western Wall should have everyone who has an interest in the wall sitting around it.”

Rabbi Shmuel Rabinowitz, the head of the heritage foundation, said in an e-mailed statement that he was unaware of the Sharansky initiative and therefore “does not have an opinion about it.”

While Ms. Hoffman said the women’s group would be satisfied if it were allowed to pray at the wall once a month with full regalia, her religious action center wants hours each day, between scheduled prayer times, when the gender partition is removed and people can freely enjoy the site as a cultural monument.

“If in the end what happens is that the Robinson’s Arch area will be run by the Jewish Agency instead of the antiquities department, then we’re talking about who’s going to take care of the air-conditioning in the back of the bus,” she said. “I don’t care about that. I don’t want to sit in the back of the bus. I want to dismantle the Western Wall Heritage Foundation.”

Abraham H. Foxman, the director of the Anti-Defamation League, said he discussed the wall and other questions of religious pluralism with Mr. Netanyahu in Jerusalem on Monday.

“This is a wise initiative, but it’s only a beginning,” Mr. Foxman said.

Irit Pazner Garshowitz contributed reporting.

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Israel to Review Curbs on Women’s Prayer at Western Wall

JERUSALEM — Amid outrage across the Jewish diaspora over a flurry of recent arrests of women seeking to pray at the Western Wall with ritual garments in defiance of Israeli law, Prime Minister Benjamin Netanyahu has asked Natan Sharansky, the chairman of the Jewish Agency, to study the issue and suggest ways to make the site more accommodating to all Jews.

The move comes after more than two decades of civil disobedience by a group called Women of the Wall against regulations, legislation and a 2003 Israeli Supreme Court ruling that allow for gender division at the wall, one of Judaism’s holiest sites, and prohibit women from carrying a Torah or wearing prayer shawls there.

Although the movement has struggled to gain traction in Israel, where the ultra-Orthodox retain great sway over public life, the issue has deepened a divide between the Jewish state and Jews around the world at a time when Israel is battling international isolation over its settlement policy. Critics, particularly leaders of the Reform and Conservative movements in the United States, complain that the government’s recent aggressive enforcement of restrictions at the wall has turned a national monument into an ultra-Orthodox synagogue.

“The prime minister thinks the Western Wall has to be a site that expresses the unity of the Jewish people, both inside Israel and outside the state of Israel,” Ron Dermer, Mr. Netanyahu’s senior adviser, said in an interview on Tuesday. “He wants to preserve the unity of world Jewry. This is an important component of Israel’s strength.”

Mr. Sharansky, whose quasi-governmental nonprofit organization handles immigration for the state and is a bridge between Israel and Jews around the world, said that Mr. Netanyahu had asked him on Monday to take up the matter, and that he expected to have recommendations within “a few months.” He and Mr. Dermer said the agenda would include improvements for Robinson’s Arch, a discreet area of the wall designated for coed prayer under the court ruling, and the easing of restrictions in the larger area known as the Western Wall plaza, along with the more sensitive questions regarding prayer at the main site.

Mr. Sharansky said the Jewish Agency itself stopped having ceremonies for new immigrants in the plaza about two years ago after the Western Wall Heritage Foundation, which controls the site, said that men and women could not sit together. Under pressure from the international groups that provide its financing, the agency on Oct. 30 passed a resolution calling for a “satisfactory approach to the issue of prayer at the Western Wall.”

Asked whether he could imagine a day when women could wear prayer shawls and read Torah at the wall itself, Mr. Sharansky said, “I imagine very easily a situation where everybody will have their opportunity to express their solidarity with Judaism and the Jewish people and the state of Israel in a way he or she wants, without undermining the other.”

“That’s as much as I want to say at this moment,” he added. “Now I have to share this vision with the appropriate bodies.”

Mr. Sharansky, a former Soviet dissident and widely respected figure, has been called upon before to broker peace with the diaspora over questions of religious pluralism, most recently during a harsh fight over conversion. Anat Hoffman, the chairwoman of Women of the Wall, reacted with cautious optimism to Mr. Netanyahu’s initiative, but said it would not stop the Israel Religious Action Center, of which she is executive director, from filing a Supreme Court petition as soon as next week challenging the makeup of the heritage foundation’s board.

“It’s a good thing that after 24 years the highest echelons in Israel are actually paying attention to this rift that is breaking diaspora Jews from Israel,” she said. “The table that should run the Western Wall should have everyone who has an interest in the wall sitting around it.”

Rabbi Shmuel Rabinowitz, the head of the heritage foundation, said in an e-mailed statement that he was unaware of the Sharansky initiative and therefore “does not have an opinion about it.”

While Ms. Hoffman said the women’s group would be satisfied if it were allowed to pray at the wall once a month with full regalia, her religious action center wants hours each day, between scheduled prayer times, when the gender partition is removed and people can freely enjoy the site as a cultural monument.

“If in the end what happens is that the Robinson’s Arch area will be run by the Jewish Agency instead of the antiquities department, then we’re talking about who’s going to take care of the air-conditioning in the back of the bus,” she said. “I don’t care about that. I don’t want to sit in the back of the bus. I want to dismantle the Western Wall Heritage Foundation.”

Abraham H. Foxman, the director of the Anti-Defamation League, said he had discussed the wall and other questions of religious pluralism with Mr. Netanyahu in Jerusalem on Monday.

“This is a wise initiative, but it’s only a beginning,” Mr. Foxman said.

Irit Pazner Garshowitz contributed reporting.

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News Analysis: Scientists to Seek Clues to Violence in Genome of Gunman in Newtown, Conn.

In a move likely to renew a longstanding ethical controversy, geneticists are quietly making plans to study the DNA of Adam Lanza, 20, who killed 20 children and seven adults in Newtown, Conn. Their work will be an effort to discover biological clues to extreme violence.

The researchers, at the University of Connecticut, confirmed their plans through a spokeswoman but declined to provide details. But other experts speculated that the geneticists might look for mutations that might be associated with mental illnesses and ones that might also increase the risk for violence.

They could look at all of Mr. Lanza’s genes, searching for something unusual like gene duplications or deletions or unexpected mutations, or they might determine the sequence of his entire genome, the genes and the vast regions of DNA that are not genes, in an extended search for aberrations that could determine which genes are active and how active they are.

But whatever they do, this apparently is the first time researchers will attempt a detailed study of the DNA of a mass killer.

Some researchers, like Dr. Arthur Beaudet, a professor at the Baylor College of Medicine and the chairman of its department of molecular and human genetics, applaud the effort. He believes that the acts committed by men like Mr. Lanza and the gunmen in other rampages in recent years — at Columbine High School and in Aurora, Colo., in Norway, in Tucson and at Virginia Tech — are so far off the charts of normal behavior that there must be genetic changes driving them.

“We can’t afford not to do this research,” Dr. Beaudet said.

Other scientists are not so sure. They worry that this research could eventually stigmatize people who have never committed a crime but who turn out to have a genetic aberration also found in a mass murder.

Everything known about mental illness, these skeptics say, argues that there are likely to be hundreds of genes involved in extreme violent behavior, not to mention a variety of environmental influences, and that all of these factors can interact in complex and unpredictable ways.

“It is almost inconceivable that there is a common genetic factor” to be found in mass murders, said Dr. Robert C. Green, a geneticist and neurologist at Harvard Medical School. “I think it says more about us that we wish there was something like this. We wish there was an explanation.”

Scientists are well aware of the fraught history behind the questions of biology and violence.

In the early 20th century, claims that criminal behavior was inherited arose during the eugenics movement and led to sterilizations of mental patients and felons.

On Christmas Day in 1965, two researchers published a paper saying men with an extra Y chromosome, the chromosome that confers maleness, were “super males” and born criminals. The hypothesis was helped along by the fact that these men “fit the classic Hollywood criminal — big, awkward, thuglike and with low I.Q.’s,” said Dr. Philip Reilly, a lawyer and clinical geneticist who has studied this history.

The idea persisted for about 15 years, Dr. Reilly said, but eventually the epidemiological evidence convinced scientists that these men were no more violent than men without an extra Y chromosome.

In 1993, in a paper published in the journal Science, researchers reported that a mutation leading to a lack of the enzyme monoamine oxidase caused violence in a Dutch family. Every family member who inherited the mutation was a violent criminal; those without it had no criminal behaviors.

“It was a stunning piece of work,” said James Blair, the chief of the unit on affective cognitive neuroscience at the National Institute of Mental Health. But, he added, it turned out not to be generalizable. For the most part, “it was just this family,” he said.

The National Institutes of Health was embroiled in controversy about 20 years ago simply for proposing to study the biological underpinnings of violence. Critics accused researchers of racism and singling out minorities, especially black men.

Shortly after, the N.I.H. took back financing for a conference at the University of Maryland to examine genetics and criminal behavior. The conference was canceled.

But genetics has come of age in recent years with new and powerful methods to determine DNA sequences and analyze the results. Studies of people at the far end of a bell curve can be especially informative, because the genetic roots of their conditions can be stark and easy to spot, noted J. H. Pate Skene, a Duke University neurobiologist.

“I think doing research on outliers, people at an end of a spectrum on something of concern like violent behavior, is certainly a good idea,” he said, but he advised tempering expectations.

“I would call it a caution, not about whether to do this research but about what to expect,” he added.

Perhaps it will be fruitless to search for one or a few major gene mutations that always lead to extreme violence, Dr. Beaudet said. But what if a significant fraction of the shootings were linked to gene variants? What if scientists were to discover genes that were risk factors, increasing a person’s chance of violent behavior but not foreordaining it?

“If we know someone has a 2 percent chance or a 10 percent chance or a 20 percent chance of violent behavior, what would you do with that person?” Dr. Skene said. “They have not been convicted of anything — have not done anything wrong.”

But a genetic profile might play a role if someone were convicted of violent offenses, Dr. Beaudet countered. Criminals are routinely denied parole based solely on psychiatric evaluations. Perhaps a genetic test could add to the certainty of the decision, he said.

Ultimately, understanding the genetics of violence might enable researchers to find ways to intervene before a person commits a horrific crime. But that goal would be difficult to achieve, and the pursuit of it risks jeopardizing personal liberties. Some scientists shudder at the thought of labeling people potential violent criminals.

“The idea of screening with a view of preventing those kinds of incidents is basically unthinkable,” said Dr. Steven E. Hyman, director of the Stanley Center for Psychiatric Research at the Broad Institute of Harvard and M.I.T. “You would fail. You would stigmatize.”

Some day, he added, it might be important to know the phenotypes — the characteristics — of violent killers and have their DNA, but not for the reasons many think.

“I am always happy to store DNA and phenotype information and freeze cells, thinking that one day we would have usable clues,” Dr. Hyman added. “But that would be biology, not prevention.”

Read More..

News Analysis: Scientists to Seek Clues to Violence in Genome of Gunman in Newtown, Conn.

In a move likely to renew a longstanding ethical controversy, geneticists are quietly making plans to study the DNA of Adam Lanza, 20, who killed 20 children and seven adults in Newtown, Conn. Their work will be an effort to discover biological clues to extreme violence.

The researchers, at the University of Connecticut, confirmed their plans through a spokeswoman but declined to provide details. But other experts speculated that the geneticists might look for mutations that might be associated with mental illnesses and ones that might also increase the risk for violence.

They could look at all of Mr. Lanza’s genes, searching for something unusual like gene duplications or deletions or unexpected mutations, or they might determine the sequence of his entire genome, the genes and the vast regions of DNA that are not genes, in an extended search for aberrations that could determine which genes are active and how active they are.

But whatever they do, this apparently is the first time researchers will attempt a detailed study of the DNA of a mass killer.

Some researchers, like Dr. Arthur Beaudet, a professor at the Baylor College of Medicine and the chairman of its department of molecular and human genetics, applaud the effort. He believes that the acts committed by men like Mr. Lanza and the gunmen in other rampages in recent years — at Columbine High School and in Aurora, Colo., in Norway, in Tucson and at Virginia Tech — are so far off the charts of normal behavior that there must be genetic changes driving them.

“We can’t afford not to do this research,” Dr. Beaudet said.

Other scientists are not so sure. They worry that this research could eventually stigmatize people who have never committed a crime but who turn out to have a genetic aberration also found in a mass murder.

Everything known about mental illness, these skeptics say, argues that there are likely to be hundreds of genes involved in extreme violent behavior, not to mention a variety of environmental influences, and that all of these factors can interact in complex and unpredictable ways.

“It is almost inconceivable that there is a common genetic factor” to be found in mass murders, said Dr. Robert C. Green, a geneticist and neurologist at Harvard Medical School. “I think it says more about us that we wish there was something like this. We wish there was an explanation.”

Scientists are well aware of the fraught history behind the questions of biology and violence.

In the early 20th century, claims that criminal behavior was inherited arose during the eugenics movement and led to sterilizations of mental patients and felons.

On Christmas Day in 1965, two researchers published a paper saying men with an extra Y chromosome, the chromosome that confers maleness, were “super males” and born criminals. The hypothesis was helped along by the fact that these men “fit the classic Hollywood criminal — big, awkward, thuglike and with low I.Q.’s,” said Dr. Philip Reilly, a lawyer and clinical geneticist who has studied this history.

The idea persisted for about 15 years, Dr. Reilly said, but eventually the epidemiological evidence convinced scientists that these men were no more violent than men without an extra Y chromosome.

In 1993, in a paper published in the journal Science, researchers reported that a mutation leading to a lack of the enzyme monoamine oxidase caused violence in a Dutch family. Every family member who inherited the mutation was a violent criminal; those without it had no criminal behaviors.

“It was a stunning piece of work,” said James Blair, the chief of the unit on affective cognitive neuroscience at the National Institute of Mental Health. But, he added, it turned out not to be generalizable. For the most part, “it was just this family,” he said.

The National Institutes of Health was embroiled in controversy about 20 years ago simply for proposing to study the biological underpinnings of violence. Critics accused researchers of racism and singling out minorities, especially black men.

Shortly after, the N.I.H. took back financing for a conference at the University of Maryland to examine genetics and criminal behavior. The conference was canceled.

But genetics has come of age in recent years with new and powerful methods to determine DNA sequences and analyze the results. Studies of people at the far end of a bell curve can be especially informative, because the genetic roots of their conditions can be stark and easy to spot, noted J. H. Pate Skene, a Duke University neurobiologist.

“I think doing research on outliers, people at an end of a spectrum on something of concern like violent behavior, is certainly a good idea,” he said, but he advised tempering expectations.

“I would call it a caution, not about whether to do this research but about what to expect,” he added.

Perhaps it will be fruitless to search for one or a few major gene mutations that always lead to extreme violence, Dr. Beaudet said. But what if a significant fraction of the shootings were linked to gene variants? What if scientists were to discover genes that were risk factors, increasing a person’s chance of violent behavior but not foreordaining it?

“If we know someone has a 2 percent chance or a 10 percent chance or a 20 percent chance of violent behavior, what would you do with that person?” Dr. Skene said. “They have not been convicted of anything — have not done anything wrong.”

But a genetic profile might play a role if someone were convicted of violent offenses, Dr. Beaudet countered. Criminals are routinely denied parole based solely on psychiatric evaluations. Perhaps a genetic test could add to the certainty of the decision, he said.

Ultimately, understanding the genetics of violence might enable researchers to find ways to intervene before a person commits a horrific crime. But that goal would be difficult to achieve, and the pursuit of it risks jeopardizing personal liberties. Some scientists shudder at the thought of labeling people potential violent criminals.

“The idea of screening with a view of preventing those kinds of incidents is basically unthinkable,” said Dr. Steven E. Hyman, director of the Stanley Center for Psychiatric Research at the Broad Institute of Harvard and M.I.T. “You would fail. You would stigmatize.”

Some day, he added, it might be important to know the phenotypes — the characteristics — of violent killers and have their DNA, but not for the reasons many think.

“I am always happy to store DNA and phenotype information and freeze cells, thinking that one day we would have usable clues,” Dr. Hyman added. “But that would be biology, not prevention.”

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Bits Blog: Instagram Does an About-Face

11:14 p.m. | Updated
SAN FRANCISCO — In the aftermath of the uproar over changes to Instagram’s privacy policy and terms of service earlier this week, the company did an about-face late Thursday.

In a blog post on the company’s site, Kevin Systrom, Instagram’s co-founder, said that where advertising was concerned, the company would revert to its previous terms of service, which have been in effect since October 2010.

“Rather than obtain permission from you to introduce possible advertising products we have not yet developed,” he wrote, “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.” Users had been particularly concerned by a clause in Instagram’s policy introduced on Monday that suggested Instagram would share users’ data — like their favorite places, bands, restaurants and hobbies — with Facebook and its advertisers to better target ads.

They also took issue with an update to the company’s terms of service that suggested users’ photos could be used in advertisements, without compensation and even without their knowledge.

The terms of that user agreement said, “You agree that a business or other entity may pay us to display your user name, likeness, photos (along with any associated metadata) and/or actions you take, in connection with paid or sponsored content or promotions, without any compensation to you.”

Following a reaction that included customers defecting to other services, Mr. Systrom told Instagram users on Tuesday that the new policy had been misinterpreted. “It is our mistake that this language is confusing,” he wrote, and he promised an updated agreement.

That statement apparently was not enough. With more people leaving the service, the company, which Facebook bought for $735 million this year, reacted again by returning to the old rules.

Acknowledging those concerns late Thursday, Mr. Systrom wrote: “I want to be really clear: Instagram has no intention of selling your photos, and we never did. We don’t own your photos — you do.”

Mr. Systrom said the company would still be tweaking its privacy policy to quell users’ fears that their photos might pop-up on third-party sites without their consent.

But Mr. Systrom did not clarify how Instagram planned to monetize its service in the future. Facebook is under pressure to make Instagram earn income.

“It’s a free service — they have to monetize somewhere,” said John Casasanta, a principal at Tap Tap Tap, the maker of Camera+, a photo-filter app that has shunned advertising and instead charges users for premium features. “The days of the simple banner ads are gone. Their user data is too valuable.”

It was unclear whether reverting its terms of service would be enough to satisfy high-profile users like National Geographic, which stopped using its Instagram account in light of the moves, or other users who have aired their grievances on Twitter and Facebook.

The controversy has driven traffic and new users to several other photo-sharing applications.

Pheed, an Instagram-like app that gives users the option to monetize their own content by charging followers to see their posts, gained more users than any other app in the United States on Thursday. By Thursday morning, Pheed had jumped to the ninth most downloaded social-networking app in Apple’s iTunes store, just ahead of LinkedIn.

O. D. Kobo, Pheed’s chief executive, said Thursday morning that subscriptions to the service had quadrupled this week and that in the last 24 hours users had uploaded 300,000 new files to the service — more uploads than any other 24-hour-period since Pheed made its debut six weeks ago.

Another runaway success was Flickr, Yahoo’s photo-sharing service, which redesigned its app last week to make it easier to share photos on Twitter. In a stroke of good fortune, it released the app to positive reviews just as Instagram announced it would no longer sync with Twitter, a Facebook rival.

The day before Instagram announced changes to its terms of service, Flickr’s mobile app was ranked at around 175 in Apple’s overall iTunes app charts. Since that day, the application skyrocketed to the high 20s.

Of course, most of these services are still tiny compared to Instagram, which claims to have more than 100 million members who have uploaded upward of 5 billion photos using its service. And it was unclear if the services’ newfound members had also deleted their Instagram accounts or were merely dabbling in other offerings. But the migration, whether temporary or permanent, was a reminder of the volatility of success and that the fall to bottom can sometimes be as swift as the rise to the top.

Facebook and Instagram declined to say whether they had seen any significant number of account deletions or if they were concerned about losing ground in the photo-sharing market to rivals. Some photo apps took direct aim at Instagram. Camera+ even went so far as to include a snide, holiday-themed reference to Instagram’s stumbles in an app update on Wednesday.

“We’ll never do shady things with your shared pics, because it just isn’t right,” the update noted. “On that note, happy Christmas to all, and to all a good night!”

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Madrid Journal: Spain Turns Christmas Into a Season of Thrift

MADRID — This is the season when barren stone plazas and broad sidewalks here fill with Christmas markets peddling sweets, candles, holiday decorations and crafts. But alongside the festive stalls this year, another kind of market has sprung up in response to Spain’s hard times.

They are the “mercadillos,” or little markets, where the entrepreneurial-minded have found a niche by gathering and selling the unsold stock of more established retailers whose sales have plummeted, or unwanted clothing and other items from people in need of cash.

Buyers and sellers rely heavily on Facebook and other social networking sites to promote the improvised exchanges, which have transformed the way Spaniards shop for the holidays.

For the hard-pressed, the markets are a bargain hunters’ paradise, and for the jobless, they offer an economic lifeline and a chance to recast their fortunes.

Cristina Aresti and Sofía Bourne had never thought about working in fashion until they lost their jobs, joining the more than 25 percent of Spaniards who are unemployed. But this month they opened Abo Cool Market, a pop-up shop that sold secondhand women’s clothing over six days inside a Madrid furniture store.

The two women said they had intended to limit their sales to 500 items. But given the avalanche of offers from people wanting to sell off their wardrobes, they ended up selecting 800 pieces of clothing, with a combined retail value of more than $59,000.

“We just couldn’t believe how many people now want to sell clothing that they had hardly worn,” Ms. Bourne said. Among the most expensive items on sale — a totem of more prosperous times — was an unworn Gucci silk dress that still bore its original sales tag. It was on sale for $650, about a quarter of the original price.

Ms. Aresti and Ms. Bourne will keep 35 percent of their sales receipts; the rest will go to the women who supplied the clothing. The original owners then have the choice of either retrieving unsold items or donating them to charity groups.

Many of the people running this year’s mercadillos had little or no experience in retail sales. Ms. Bourne was laid off by a real estate company; Ms. Aresti lost her job as director of a company that organizes business conferences.

“I don’t yet know whether my future really lies in fashion,” Ms. Aresti said, “but there comes a point in such a hopeless job market when you’ve at least got to try to reinvent yourself.”

Even merchants with long experience in retail or fashion are borrowing some of the practices of the little markets as a way to lure customers.

“Store sales have been plummeting, so you need to go out of your way to make it fun and worthwhile for people to still do some shopping this Christmas,” said Cristina Terrón, a fashion stylist whose mercadillo sold some clothing she had initially selected for television and movie productions. “Something that started out of economic necessity is now also turning into a fashion.”

On average, Spanish households are set to spend $790 to $920 on Christmas shopping this year, down as much as 38 percent from 2007, before the onset of the economic crisis, according to a study published this month by Esade, a Spanish business school.

Jaime Castelló, a marketing professor and one of the authors of the study, said the crisis was not only reducing spending, but also speeding up changes in consumer habits.

About 70 percent of Spanish households said they would search online before buying any Christmas gifts, and 25 percent said they would not even step into a department store, according to the study. The mercadillos, Mr. Castelló suggested, were “another alternative in this crisis to the traditional buying channels.”

Ana María Menoyo Delgado, 26, said she had “lots of fun” searching the Christmas mercadillo Web sites as she worked her way through her holiday shopping list. At Abo Cool’s market, with her mother’s help, she ended up with two designer hand bags, a skirt and a coat, spending a total of $659.

While bargain hunting is part of the attraction, several buyers said they simply preferred the mercadillos to department stores.

“I can’t stand anymore walking into a conventional luxury store where you are likely to be welcomed by a pretty and young but utterly grumpy sales attendant,” Irene Trigueros, a commodities trader, said as she tried on a pair of secondhand sunglasses.

Some of the mercadillos have even been held in bars. “Having a cocktail while trying on some nice clothing seems to me a perfect way to end the day,” said Alberto Martínez, owner of the 1862 Dry Bar, who allowed his basement to become a mercadillo for three days this month.

Mr. Martínez did not charge any rent, but some of the larger mercadillos add to their revenue by renting out booths in their spaces to smaller sellers, normally for $200 to $400 a weekend.

In Alcobendas, on the outskirts of Madrid, a warehouse was transformed into La Galería del 32, a market that sold, among other things, wine, ham, sculpture, jewelry and handbags. The warehouse used to store electronics equipment and other goods until about three years ago, when the demand for storage space dried up as retail sales slumped.

“This kind of event is a great way for those who exhibit to attract more shoppers, while we earn something from renting the space rather than allowing it to stand empty,” said Leticia Martínez Rubio, one of the organizers.

A charity foundation, the Fundacíon Dar, also took part in the weekend event, encouraging shoppers to bring toys that the foundation would distribute to underprivileged children in the Madrid area.

“Beside having a successful weekend sale, I think it’s also important to keep some of the Christmas spirit,” Ms. Martínez Rubio said.

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