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Chagas Disease Costs U.S. More Than Better-Known Illnesses
By DONALD G. McNEIL Jr., The New York Times, February 11, 2013
Chagas disease may be obscure, but the economic burden it imposes on the world is greater than that of better-known diseases, like cervical cancer or cholera, according to a new study. Even in the United States, the authors said, the costs of Chagas are commensurate with those of more publicized diseases, like Lyme disease.
(In the same league, perhaps, but not quite equal. In their study, published in Lancet Infectious Diseases, the authors calculated that Chagas cost the American economy $900 million a year. A 1998 study estimated that Lyme disease cost $2.5 billion.)
Chagas disease is caused by a trypanosome parasite transmitted by the bloodsucking “kissing bug,” which bites victims as they sleep. Transmission is endemic in much of Latin America, from central Mexico to northern Argentina. Kissing bugs have been found in the southern United States; the bugs tend to live in substandard housing and animal pens.
The parasites cause an initial flulike illness that can be cured if it is caught. But it is often not diagnosed, and the infection may become chronic. It may be silent for decades and then emerge as long-term damage to the heart or intestines. It can be fatal.
Up to 10 million people may be infected, many of whom have emigrated from Latin America seeking jobs in the United States, Canada and Europe — especially Spain.
The authors, from the University of Pittsburgh and Baylor University, estimated the economic burden by trying to calculate the cost of hospitalization and care, including pacemaker implants, for those with heart damage or other organ failure. The costs vary by country, of course, with the United States being the most expensive.
The researchers then added estimates of “disability-adjusted life years,” a measure of how many years of healthy life are lost. They “cost” more when they are subtracted from the life of a working-age adult in a high-wage country than from a retiree or an infant in a poor country.
The authors estimate that the global burden of Chagas is about $7 billion a year. By comparison, the burden of cervical cancer — a notorious killer of women, but almost only in poor countries, and usually as they age out of their working lives — is estimated at below $5 billion.
The burden of rotavirus, a diarrheal disease that kills many babies but rarely endangers anyone over age 5, is estimated at $2 billion. (By contrast, lung cancer’s burden is estimated at $83 billion a year, and breast cancer’s at $35 billion.)
Many millions have been spent developing a rotavirus vaccine and on ways to fight cervical cancer in poor countries.
Knowing that Chagas is a serious economic threat could push policy makers to spend more money on developing vaccines against it, said Dr. Peter J. Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine and a co-author of the new study. Dr. Hotez is also president of the Sabin Vaccine Institute, which is doing research on Chagas vaccines.
Mice Fall Short as Test Subjects for Humans’ Deadly Ills
By GINA KOLATA, The New York Times, February 11, 2013
For decades, mice have been the species of choice in the study of human diseases. But now, researchers report evidence that the mouse model has been totally misleading for at least three major killers — sepsis, burns and trauma. As a result, years and billions of dollars have been wasted following false leads, they say.
The study’s findings do not mean that mice are useless models for all human diseases. But, its authors said, they do raise troubling questions about diseases like the ones in the study that involve the immune system, including cancer and heart disease.
“Our article raises at least the possibility that a parallel situation may be present,” said Dr. H. Shaw Warren, a sepsis researcher at Massachusetts General Hospital and a lead author of the new study.
The paper, published Monday in Proceedings of the National Academy of Sciences, helps explain why every one of nearly 150 drugs tested at a huge expense in patients with sepsis has failed. The drug tests all were based on studies in mice. And mice, it turns out, can have something that looks like sepsis in humans, but is very different from the condition in humans.
Medical experts not associated with the study said that the findings should change the course of research worldwide for a deadly and frustrating condition. Sepsis, a potentially deadly reaction that occurs as the body tries to fight an infection, afflicts 750,000 patients a year in the United States, kills one-fourth to one-half of them, and costs the nation $17 billion a year. It is the leading cause of death in intensive-care units.
“This is a game changer,” said Dr. Mitchell Fink, a sepsis expert at the University of California, Los Angeles, of the new study.
“It’s amazing,” said Dr. Richard Wenzel, a former chairman at the department of internal medicine at Virginia Commonwealth University and a former editor of The New England Journal of Medicine. “They are absolutely right on.”
Potentially deadly immune responses occur when a person’s immune system overreacts to what it perceives as danger signals, including toxic molecules from bacteria, viruses, fungi, or proteins released from cells damaged by trauma or burns, said Dr. Clifford S. Deutschman, who directs sepsis research at the University of Pennsylvania and was not part of the study.
The ramped-up immune system releases its own proteins in such overwhelming amounts that capillaries begin to leak. The leak becomes excessive, and serum seeps out of the tiny blood vessels. Blood pressure falls, and vital organs do not get enough blood. Despite efforts, doctors and nurses in an intensive-care unit or an emergency room may be unable to keep up with the leaks, stop the infection or halt the tissue damage. Vital organs eventually fail.
The new study, which took 10 years and involved 39 researchers from across the country, began by studying white blood cells from hundreds of patients with severe burns, trauma or sepsis to see what genes were being used by white blood cells when responding to these danger signals.
The researchers found some interesting patterns and accumulated a large, rigorously collected data set that should help move the field forward, said Ronald W. Davis, a genomics expert at Stanford University and a lead author of the new paper. Some patterns seemed to predict who would survive and who would end up in intensive care, clinging to life and, often, dying.
The group had tried to publish its findings in several papers. One objection, Dr. Davis said, was that the researchers had not shown the same gene response had happened in mice.
“They were so used to doing mouse studies that they thought that was how you validate things,” he said. “They are so ingrained in trying to cure mice that they forget we are trying to cure humans.”
“That started us thinking,” he continued. “Is it the same in the mouse or not?”
The group decided to look, expecting to find some similarities. But when the data were analyzed, there were none at all.
“We were kind of blown away,” Dr. Davis said.
The drug failures became clear. For example, often in mice, a gene would be used, while in humans, the comparable gene would be suppressed. A drug that worked in mice by disabling that gene could make the response even more deadly in humans.
Even more surprising, Dr. Warren said, was that different conditions in mice — burns, trauma, sepsis — did not fit the same pattern. Each condition used different groups of genes. In humans, though, similar genes were used in all three conditions. That means, Dr. Warren said, that if researchers can find a drug that works for one of those conditions in people, it might work for all three.
The study’s investigators tried for more than a year to publish their paper, which showed that there was no relationship between the genetic responses of mice and those of humans. They submitted it to the publications Science and Nature, hoping to reach a wide audience. It was rejected from both.
Science and Nature said it was their policy not to comment on the fate of a rejected paper, or whether it had even been submitted to them. But, Ginger Pinholster of Science said, the journal accepts only about 7 percent of the nearly 13,000 papers submitted each year, so it is not uncommon for a paper to make the rounds.
Still, Dr. Davis said, reviewers did not point out scientific errors. Instead, he said, “the most common response was, ‘It has to be wrong. I don’t know why it is wrong, but it has to be wrong.’ ”
The investigators turned to Proceedings of the National Academy of Sciences. As a member of the academy, Dr. Davis could suggest reviewers for his paper, and he proposed researchers who he thought would give the work a fair hearing. “If they don’t like it, I want to know why,” he said. They recommended publication, and the editorial board of the journal, which independently assesses papers, agreed.
Some researchers, reading the paper now, say they are as astonished as the researchers were when they saw the data.
“When I read the paper, I was stunned by just how bad the mouse data are,” Dr. Fink said. “It’s really amazing — no correlation at all. These data are so persuasive and so robust that I think funding agencies are going to take note.” Until now, he said, “to get funding, you had to propose experiments using the mouse model.”
Yet there was always one major clue that mice might not really mimic humans in this regard: it is very hard to kill a mouse with a bacterial infection. Mice need a million times more bacteria in their blood than what would kill a person.
“Mice can eat garbage and food that is lying around and is rotten,” Dr. Davis said. “Humans can’t do that. We are too sensitive.”
Researchers said that if they could figure out why mice were so resistant, they might be able to use that discovery to find something to make people resistant.
“This is a very important paper,” said Dr. Richard Hotchkiss, a sepsis researcher at Washington University who was not involved in the study. “It argues strongly — go to the patients. Get their cells. Get their tissues whenever you can. Get cells from airways.”
“To understand sepsis, you have to go to the patients,” he said.
This article has been revised to reflect the following correction:
Correction: February 11, 2013
An earlier version of this article misstated the position of Dr. Richard Wenzel. He is a former chairman of the department of internal medicine at Virginia Commonwealth University. He is not currently the chairman.
An artist's rendering of a placental ancestor. Researchers say the small, insect-eating animal is the most likely common ancestor of the species on the most abundant and diverse branch of the mammalian family tree.
Rat-Size Ancestor Said to Link Man and Beast
By JOHN NOBLE WILFORD, The New York Times, February 7, 2013
Humankind’s common ancestor with other mammals may have been a roughly rat-size animal that weighed no more than a half a pound, had a long furry tail and lived on insects.
In a comprehensive six-year study of the mammalian family tree, scientists have identified and reconstructed what they say is the most likely common ancestor of the many species on the most abundant and diverse branch of that tree — the branch of creatures that nourish their young in utero through a placenta. The work appears to support the view that in the global extinctions some 66 million years ago, all non-avian dinosaurs had to die for mammals to flourish.
Scientists had been searching for just such a common genealogical link and have found it in a lowly occupant of the fossil record, Protungulatum donnae, that until now has been so obscure that it lacks a colloquial nickname. But as researchers reported Thursday in the journal Science, the animal had several anatomical characteristics for live births that anticipated all placental mammals and led to some 5,400 living species, from shrews to elephants, bats to whales, cats to dogs and, not least, humans.
A team of researchers described the discovery as an important insight into the pattern and timing of early mammal life and a demonstration of the capabilities of a new system for handling copious amounts of fossil and genetic data in the service of evolutionary biology. The formidable new technology is expected to be widely applied in years ahead to similar investigations of plants, insects, fish and fowl.
Given some belated stature by an artist’s brush, the animal hardly looks the part of a progenitor of so many mammals (which do not include marsupials, like kangaroos and opossums, or monotremes, egg-laying mammals like the duck-billed platypus).
Maureen A. O’Leary of Stony Brook University on Long Island, a leader of the project and the principal author of the journal report, wrote that a combination of genetic and anatomical data established that the ancestor emerged within 200,000 to 400,000 years after the great dying at the end of the Cretaceous period. At the time, the meek were rapidly inheriting the earth from hulking predators like T. rex.
Within another two million to three million years, Dr. O’Leary said, the first members of modern placental orders appeared in such profusion that researchers have started to refer to the explosive model of mammalian evolution. The common ancestor itself appeared more than 36 million years later than had been estimated based on genetic data alone.
Although some small primitive mammals had lived in the shadow of the great Cretaceous reptiles, the scientists could not find evidence supporting an earlier hypothesis that up to 39 placental mammalian lineages survived to enter the post-extinction world. Only the stem lineage to Placentalia, they said, appeared to hang on through the catastrophe, generally associated with climate change after an asteroid crashed into Earth.
The research team drew on combined fossil evidence and genetic data encoded in DNA in evaluating the ancestor’s standing as an early placental mammal. Among characteristics associated with full-term live births, the Protungulatum species was found to have a two-horned uterus and a placenta in which the maternal blood came in close contact with the membranes surrounding the fetus, as in humans.
The ancestor’s younger age, the scientists said, ruled out the breakup of the supercontinent of Gondwana around 120 million years ago as a direct factor in the diversification of mammals, as has sometimes been speculated. Evidence of the common ancestor was found in North America, but the animal may have existed on other continents as well.
The publicly accessible database responsible for the findings is called MorphoBank, with advanced software for handling the largest compilation yet of data and images on mammals living and extinct. “This has stretched our own expertise,” Dr. O’Leary, an anatomist, said in an interview.
“The findings were not a total surprise,” she said. “But it’s an important discovery because it relies on lots of information from fossils and also molecular data. Other scientists, at least a thousand, some from other countries, are already signing up to use MorphoBank.”
Michael J. Novacek, a paleontologist and provost for science at the American Museum of Natural History in New York City, said the system could assess each mammal on the basis of more than 4,500 possible traits, which is 10 times larger than previous databases. “At one point, I didn’t think we would ever finish,” Dr. Novacek said.
John R. Wible, curator of mammals at the Carnegie Museum of Natural History in Pittsburgh, who is another of the 22 members of the project, said the “power of 4,500 characters” enabled the scientists to look “at all aspects of mammalian anatomy, from the skull and skeleton, to the teeth, to internal organs, to muscles and even fur patterns” to determine what the common ancestor possibly looked like.
The project was financed primarily by the National Science Foundation as part of its Assembling the Tree of Life program. Other scientists from Stony Brook, the American Museum of Natural History and the Carnegie Museum participated, as well as researchers from the University of Florida, the University of Tennessee at Chattanooga, the University of Louisville, Western University of Health Sciences, in Pomona, Calif., Yale University and others in Canada, China, Brazil and Argentina.
Outside scientists said that this formidable new systematic data-crunching capability might reshape mammal research but that it would probably not immediately resolve the years of dispute between fossil and genetic partisans over when placental mammals arose. Paleontologists looking for answers in skeletons and anatomy have favored a date just before or a little after the Cretaceous extinction. Those who work with genetic data to tell time by “molecular clocks” have arrived at much earlier origins.
The conflict was billed as “Fossils vs. Clocks” in the headline for a commentary article by Anne D. Yoder, an evolutionary biologist at Duke University, which accompanied Dr. O’Leary’s journal report.
Dr. Yoder acknowledged that the new study offered “a fresh perspective on the pattern and timing of mammalian evolution drawn from a remarkable arsenal of morphological data from fossil and living mammals.” She also praised the research’s “level of sophistication and meticulous analysis.”
Even so, Dr. Yoder complained that the researchers “devoted most of their analytical energy to scoring characteristics and estimating the shape of the tree rather than the length of its branches.” She said that “the disregard for the consequences of branch lengths,” as determined by the molecular clocks of genetics, “leaves us wanting more.”
John Gatesy, an evolutionary biologist at the University of California, Riverside, who was familiar with the study but was not an author of the report, said the reconstruction of the common ancestor was “very reasonable and very cool.” The researchers, he said, “have used their extraordinarily large analysis to predict what this earliest placental looked like, and it would be interesting to extend this approach to more branch points in the tree” including for early ancestors like aardvarks, elephants and manatees.
But Dr. Gatesy said the post-Cretaceous date for the placentals “will surely be controversial, as this is much younger than estimates based on molecular clocks, and implies the compression of very long molecular branches at the base of the tree.”
This article has been revised to reflect the following correction:
Correction: February 8, 2013
An earlier version of this article misstated one hypothesis regarding an extinction event 65 million years ago. The hypothesis states that 39 placental mammalian lineages — not 39 mammalian lineages – may have survived. It also misstated in one instance the name of an institution that some of the researchers are affiliated with. It is the American Museum of Natural History, not the American Natural History Museum.
By DONALD G. McNEIL Jr., The New York Times, February 11, 2013
Chagas disease may be obscure, but the economic burden it imposes on the world is greater than that of better-known diseases, like cervical cancer or cholera, according to a new study. Even in the United States, the authors said, the costs of Chagas are commensurate with those of more publicized diseases, like Lyme disease.
(In the same league, perhaps, but not quite equal. In their study, published in Lancet Infectious Diseases, the authors calculated that Chagas cost the American economy $900 million a year. A 1998 study estimated that Lyme disease cost $2.5 billion.)
Chagas disease is caused by a trypanosome parasite transmitted by the bloodsucking “kissing bug,” which bites victims as they sleep. Transmission is endemic in much of Latin America, from central Mexico to northern Argentina. Kissing bugs have been found in the southern United States; the bugs tend to live in substandard housing and animal pens.
The parasites cause an initial flulike illness that can be cured if it is caught. But it is often not diagnosed, and the infection may become chronic. It may be silent for decades and then emerge as long-term damage to the heart or intestines. It can be fatal.
Up to 10 million people may be infected, many of whom have emigrated from Latin America seeking jobs in the United States, Canada and Europe — especially Spain.
The authors, from the University of Pittsburgh and Baylor University, estimated the economic burden by trying to calculate the cost of hospitalization and care, including pacemaker implants, for those with heart damage or other organ failure. The costs vary by country, of course, with the United States being the most expensive.
The researchers then added estimates of “disability-adjusted life years,” a measure of how many years of healthy life are lost. They “cost” more when they are subtracted from the life of a working-age adult in a high-wage country than from a retiree or an infant in a poor country.
The authors estimate that the global burden of Chagas is about $7 billion a year. By comparison, the burden of cervical cancer — a notorious killer of women, but almost only in poor countries, and usually as they age out of their working lives — is estimated at below $5 billion.
The burden of rotavirus, a diarrheal disease that kills many babies but rarely endangers anyone over age 5, is estimated at $2 billion. (By contrast, lung cancer’s burden is estimated at $83 billion a year, and breast cancer’s at $35 billion.)
Many millions have been spent developing a rotavirus vaccine and on ways to fight cervical cancer in poor countries.
Knowing that Chagas is a serious economic threat could push policy makers to spend more money on developing vaccines against it, said Dr. Peter J. Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine and a co-author of the new study. Dr. Hotez is also president of the Sabin Vaccine Institute, which is doing research on Chagas vaccines.
Mice Fall Short as Test Subjects for Humans’ Deadly Ills
By GINA KOLATA, The New York Times, February 11, 2013
For decades, mice have been the species of choice in the study of human diseases. But now, researchers report evidence that the mouse model has been totally misleading for at least three major killers — sepsis, burns and trauma. As a result, years and billions of dollars have been wasted following false leads, they say.
The study’s findings do not mean that mice are useless models for all human diseases. But, its authors said, they do raise troubling questions about diseases like the ones in the study that involve the immune system, including cancer and heart disease.
“Our article raises at least the possibility that a parallel situation may be present,” said Dr. H. Shaw Warren, a sepsis researcher at Massachusetts General Hospital and a lead author of the new study.
The paper, published Monday in Proceedings of the National Academy of Sciences, helps explain why every one of nearly 150 drugs tested at a huge expense in patients with sepsis has failed. The drug tests all were based on studies in mice. And mice, it turns out, can have something that looks like sepsis in humans, but is very different from the condition in humans.
Medical experts not associated with the study said that the findings should change the course of research worldwide for a deadly and frustrating condition. Sepsis, a potentially deadly reaction that occurs as the body tries to fight an infection, afflicts 750,000 patients a year in the United States, kills one-fourth to one-half of them, and costs the nation $17 billion a year. It is the leading cause of death in intensive-care units.
“This is a game changer,” said Dr. Mitchell Fink, a sepsis expert at the University of California, Los Angeles, of the new study.
“It’s amazing,” said Dr. Richard Wenzel, a former chairman at the department of internal medicine at Virginia Commonwealth University and a former editor of The New England Journal of Medicine. “They are absolutely right on.”
Potentially deadly immune responses occur when a person’s immune system overreacts to what it perceives as danger signals, including toxic molecules from bacteria, viruses, fungi, or proteins released from cells damaged by trauma or burns, said Dr. Clifford S. Deutschman, who directs sepsis research at the University of Pennsylvania and was not part of the study.
The ramped-up immune system releases its own proteins in such overwhelming amounts that capillaries begin to leak. The leak becomes excessive, and serum seeps out of the tiny blood vessels. Blood pressure falls, and vital organs do not get enough blood. Despite efforts, doctors and nurses in an intensive-care unit or an emergency room may be unable to keep up with the leaks, stop the infection or halt the tissue damage. Vital organs eventually fail.
The new study, which took 10 years and involved 39 researchers from across the country, began by studying white blood cells from hundreds of patients with severe burns, trauma or sepsis to see what genes were being used by white blood cells when responding to these danger signals.
The researchers found some interesting patterns and accumulated a large, rigorously collected data set that should help move the field forward, said Ronald W. Davis, a genomics expert at Stanford University and a lead author of the new paper. Some patterns seemed to predict who would survive and who would end up in intensive care, clinging to life and, often, dying.
The group had tried to publish its findings in several papers. One objection, Dr. Davis said, was that the researchers had not shown the same gene response had happened in mice.
“They were so used to doing mouse studies that they thought that was how you validate things,” he said. “They are so ingrained in trying to cure mice that they forget we are trying to cure humans.”
“That started us thinking,” he continued. “Is it the same in the mouse or not?”
The group decided to look, expecting to find some similarities. But when the data were analyzed, there were none at all.
“We were kind of blown away,” Dr. Davis said.
The drug failures became clear. For example, often in mice, a gene would be used, while in humans, the comparable gene would be suppressed. A drug that worked in mice by disabling that gene could make the response even more deadly in humans.
Even more surprising, Dr. Warren said, was that different conditions in mice — burns, trauma, sepsis — did not fit the same pattern. Each condition used different groups of genes. In humans, though, similar genes were used in all three conditions. That means, Dr. Warren said, that if researchers can find a drug that works for one of those conditions in people, it might work for all three.
The study’s investigators tried for more than a year to publish their paper, which showed that there was no relationship between the genetic responses of mice and those of humans. They submitted it to the publications Science and Nature, hoping to reach a wide audience. It was rejected from both.
Science and Nature said it was their policy not to comment on the fate of a rejected paper, or whether it had even been submitted to them. But, Ginger Pinholster of Science said, the journal accepts only about 7 percent of the nearly 13,000 papers submitted each year, so it is not uncommon for a paper to make the rounds.
Still, Dr. Davis said, reviewers did not point out scientific errors. Instead, he said, “the most common response was, ‘It has to be wrong. I don’t know why it is wrong, but it has to be wrong.’ ”
The investigators turned to Proceedings of the National Academy of Sciences. As a member of the academy, Dr. Davis could suggest reviewers for his paper, and he proposed researchers who he thought would give the work a fair hearing. “If they don’t like it, I want to know why,” he said. They recommended publication, and the editorial board of the journal, which independently assesses papers, agreed.
Some researchers, reading the paper now, say they are as astonished as the researchers were when they saw the data.
“When I read the paper, I was stunned by just how bad the mouse data are,” Dr. Fink said. “It’s really amazing — no correlation at all. These data are so persuasive and so robust that I think funding agencies are going to take note.” Until now, he said, “to get funding, you had to propose experiments using the mouse model.”
Yet there was always one major clue that mice might not really mimic humans in this regard: it is very hard to kill a mouse with a bacterial infection. Mice need a million times more bacteria in their blood than what would kill a person.
“Mice can eat garbage and food that is lying around and is rotten,” Dr. Davis said. “Humans can’t do that. We are too sensitive.”
Researchers said that if they could figure out why mice were so resistant, they might be able to use that discovery to find something to make people resistant.
“This is a very important paper,” said Dr. Richard Hotchkiss, a sepsis researcher at Washington University who was not involved in the study. “It argues strongly — go to the patients. Get their cells. Get their tissues whenever you can. Get cells from airways.”
“To understand sepsis, you have to go to the patients,” he said.
This article has been revised to reflect the following correction:
Correction: February 11, 2013
An earlier version of this article misstated the position of Dr. Richard Wenzel. He is a former chairman of the department of internal medicine at Virginia Commonwealth University. He is not currently the chairman.
An artist's rendering of a placental ancestor. Researchers say the small, insect-eating animal is the most likely common ancestor of the species on the most abundant and diverse branch of the mammalian family tree.
Rat-Size Ancestor Said to Link Man and Beast
By JOHN NOBLE WILFORD, The New York Times, February 7, 2013
Humankind’s common ancestor with other mammals may have been a roughly rat-size animal that weighed no more than a half a pound, had a long furry tail and lived on insects.
In a comprehensive six-year study of the mammalian family tree, scientists have identified and reconstructed what they say is the most likely common ancestor of the many species on the most abundant and diverse branch of that tree — the branch of creatures that nourish their young in utero through a placenta. The work appears to support the view that in the global extinctions some 66 million years ago, all non-avian dinosaurs had to die for mammals to flourish.
Scientists had been searching for just such a common genealogical link and have found it in a lowly occupant of the fossil record, Protungulatum donnae, that until now has been so obscure that it lacks a colloquial nickname. But as researchers reported Thursday in the journal Science, the animal had several anatomical characteristics for live births that anticipated all placental mammals and led to some 5,400 living species, from shrews to elephants, bats to whales, cats to dogs and, not least, humans.
A team of researchers described the discovery as an important insight into the pattern and timing of early mammal life and a demonstration of the capabilities of a new system for handling copious amounts of fossil and genetic data in the service of evolutionary biology. The formidable new technology is expected to be widely applied in years ahead to similar investigations of plants, insects, fish and fowl.
Given some belated stature by an artist’s brush, the animal hardly looks the part of a progenitor of so many mammals (which do not include marsupials, like kangaroos and opossums, or monotremes, egg-laying mammals like the duck-billed platypus).
Maureen A. O’Leary of Stony Brook University on Long Island, a leader of the project and the principal author of the journal report, wrote that a combination of genetic and anatomical data established that the ancestor emerged within 200,000 to 400,000 years after the great dying at the end of the Cretaceous period. At the time, the meek were rapidly inheriting the earth from hulking predators like T. rex.
Within another two million to three million years, Dr. O’Leary said, the first members of modern placental orders appeared in such profusion that researchers have started to refer to the explosive model of mammalian evolution. The common ancestor itself appeared more than 36 million years later than had been estimated based on genetic data alone.
Although some small primitive mammals had lived in the shadow of the great Cretaceous reptiles, the scientists could not find evidence supporting an earlier hypothesis that up to 39 placental mammalian lineages survived to enter the post-extinction world. Only the stem lineage to Placentalia, they said, appeared to hang on through the catastrophe, generally associated with climate change after an asteroid crashed into Earth.
The research team drew on combined fossil evidence and genetic data encoded in DNA in evaluating the ancestor’s standing as an early placental mammal. Among characteristics associated with full-term live births, the Protungulatum species was found to have a two-horned uterus and a placenta in which the maternal blood came in close contact with the membranes surrounding the fetus, as in humans.
The ancestor’s younger age, the scientists said, ruled out the breakup of the supercontinent of Gondwana around 120 million years ago as a direct factor in the diversification of mammals, as has sometimes been speculated. Evidence of the common ancestor was found in North America, but the animal may have existed on other continents as well.
The publicly accessible database responsible for the findings is called MorphoBank, with advanced software for handling the largest compilation yet of data and images on mammals living and extinct. “This has stretched our own expertise,” Dr. O’Leary, an anatomist, said in an interview.
“The findings were not a total surprise,” she said. “But it’s an important discovery because it relies on lots of information from fossils and also molecular data. Other scientists, at least a thousand, some from other countries, are already signing up to use MorphoBank.”
Michael J. Novacek, a paleontologist and provost for science at the American Museum of Natural History in New York City, said the system could assess each mammal on the basis of more than 4,500 possible traits, which is 10 times larger than previous databases. “At one point, I didn’t think we would ever finish,” Dr. Novacek said.
John R. Wible, curator of mammals at the Carnegie Museum of Natural History in Pittsburgh, who is another of the 22 members of the project, said the “power of 4,500 characters” enabled the scientists to look “at all aspects of mammalian anatomy, from the skull and skeleton, to the teeth, to internal organs, to muscles and even fur patterns” to determine what the common ancestor possibly looked like.
The project was financed primarily by the National Science Foundation as part of its Assembling the Tree of Life program. Other scientists from Stony Brook, the American Museum of Natural History and the Carnegie Museum participated, as well as researchers from the University of Florida, the University of Tennessee at Chattanooga, the University of Louisville, Western University of Health Sciences, in Pomona, Calif., Yale University and others in Canada, China, Brazil and Argentina.
Outside scientists said that this formidable new systematic data-crunching capability might reshape mammal research but that it would probably not immediately resolve the years of dispute between fossil and genetic partisans over when placental mammals arose. Paleontologists looking for answers in skeletons and anatomy have favored a date just before or a little after the Cretaceous extinction. Those who work with genetic data to tell time by “molecular clocks” have arrived at much earlier origins.
The conflict was billed as “Fossils vs. Clocks” in the headline for a commentary article by Anne D. Yoder, an evolutionary biologist at Duke University, which accompanied Dr. O’Leary’s journal report.
Dr. Yoder acknowledged that the new study offered “a fresh perspective on the pattern and timing of mammalian evolution drawn from a remarkable arsenal of morphological data from fossil and living mammals.” She also praised the research’s “level of sophistication and meticulous analysis.”
Even so, Dr. Yoder complained that the researchers “devoted most of their analytical energy to scoring characteristics and estimating the shape of the tree rather than the length of its branches.” She said that “the disregard for the consequences of branch lengths,” as determined by the molecular clocks of genetics, “leaves us wanting more.”
John Gatesy, an evolutionary biologist at the University of California, Riverside, who was familiar with the study but was not an author of the report, said the reconstruction of the common ancestor was “very reasonable and very cool.” The researchers, he said, “have used their extraordinarily large analysis to predict what this earliest placental looked like, and it would be interesting to extend this approach to more branch points in the tree” including for early ancestors like aardvarks, elephants and manatees.
But Dr. Gatesy said the post-Cretaceous date for the placentals “will surely be controversial, as this is much younger than estimates based on molecular clocks, and implies the compression of very long molecular branches at the base of the tree.”
This article has been revised to reflect the following correction:
Correction: February 8, 2013
An earlier version of this article misstated one hypothesis regarding an extinction event 65 million years ago. The hypothesis states that 39 placental mammalian lineages — not 39 mammalian lineages – may have survived. It also misstated in one instance the name of an institution that some of the researchers are affiliated with. It is the American Museum of Natural History, not the American Natural History Museum.
