NEWS&ANALYSIS ANCIENT SAMPLES STUDIED Country
Approximate Morphological age (years) classification
Belgium Russia Belgium Alaska Belgium Russia Alaska Alaska Russia Russia Germany Switzerland Switzerland Switzerland Germany USA Argentina USA
36,000 33,500 30,000 28,000 26,000 22,000 21,000 20,800 18,000 15,000 14,700 14,500 14,500 14,500 12,500 8,500 1,000 1,000
Doglike Doglike Wolflike Wolflike Wolflike Wolflike Wolflike Wolflike Wolflike Doglike Doglike Wolflike Wolflike Wolflike Doglike Doglike Doglike Doglike
able DNA from ancient Middle Eastern canids and had no access to ancient specimens from East Asia. That’s a major flaw, says Savolainen, who remains convinced that dogs originated in southern China. “It’s not really an objective study.” He and others also fault the work for including just a few modern wolves from the Middle East and China but dozens from Europe. “[It is] the same as if you wanted to do a study of
Wolf or dog? Mitochondrial DNA from 18 fossils and from modern canids revealed that two considered doglike (italic) were not closely related to dogs at all.
the origins of humans and you didn’t have a single sample from Africa.” Furthermore, mtDNA, which is passed down from mother to daughter, “reflects a small part of the evolutionary history,” says Chung-I Wu, an evolutionary biologist at the University of Chicago in Illinois. Given how much human migration there was early in dog domestication, Wu suspects that male dogs coming from outside Europe might have been bred with European dams, leading to the mitochondrial story Wayne and Thalmann propose, but not the correct overall picture of dog domestication. “Two parts of the genome can tell two different stories.” Wayne and Thalmann are now trying to get good nuclear sequence data from dog and wolf fossils, as are Larson and other researchers (Science, 1 November, p. 543). But O’Brien is not sure that more complete genomes will settle the debates, given how much dogs and wolves must have muddied the genetic waters over history by interbreeding. “Genomic archaeology has its limitations and the dogs are testing it,” he says. “It may settle one day, but don’t count on it.” –ELIZABETH PENNISI
Goal of Ending AIDS Gains Traction SAN FRANCISCO, CALIFORNIA—A Who’s Who of HIV/AIDS researchers from six continents, major funders like the Bill & Melinda Gates Foundation, public health officials, and the first person ever cured of an HIV infection gathered here last week to explore the question: “What will it take to achieve an AIDS-free world?” Tremendous headway in science over the past few years has brought this once-fanciful idea into the realm of possibility, many agreed. But talk of “ending AIDS” alarms some experts, alert to the risks of overselling that promise and underplaying the huge logistical and financial challenges. Richard Horton, editor of The Lancet— which co-sponsored the unusual meeting with its sister journal Cell—noted that he recently spoke with an unnamed “senior AIDS person” who branded talk about an AIDSfree world as “nonsense,” “irresponsible,” and “dangerous,” warning that it might lead to complacency. “I agree completely, it’s much too soon for a victory lap,” said Anthony Fauci of the National Institute of Allergy
786
and Infectious Diseases (NIAID) in Bethesda, Maryland, who noted that last year alone saw 2.3 million new HIV infections, raising the global burden to 35.3 million people. But an AIDS-free world is not an audacious notion, Fauci said. “We have a scientific and public health basis for in fact talking about this.” Meeting participants debated what, exactly, an “AIDS-free High hopes. hopes Dramatic progress has sparked endgame talk. talk world” means. “Everyone is talking about the ‘end of AIDs,’ but everyone David Baltimore of the California Institute seems to have a different perspective,” of Technology in Pasadena. Steven Deeks, a clinician at the University ARVs certainly have made extraordinary of California, San Francisco, told Science. strides. Thanks to a massive infusion of The U.S. government has championed a goal funds, the number of HIV-infected people it calls the “AIDS-free generation,” in which receiving the drugs in sub-Saharan Africa has antiretroviral (ARV) drugs completely skyrocketed from 50,000 in 2002 to more than prevent transmission to babies and allow 7 million last year. A landmark study funded HIV-infected people to live near-normal by NIAID showed 2 years ago (Science, lifespans. Others contend that only a vaccine 23 December 2011, p. 1628) that the drugs can can end the epidemic, but this elusive goal prevent as well as treat infection; when people is “at least 10 years away,” said Nobelist take ARVs as prescribed, they suppress HIV
15 NOVEMBER 2013
VOL 342
SCIENCE
Published by AAAS
www.sciencemag.org
SOURCES (TOP TO BOTTOM): O. THALMANN ET AL., SCIENCE; ADAPTED FROM WAFAA EL-SADR/COLUMBIA UNIVERSITY
INFECTIOUS DISEASES
Downloaded from www.sciencemag.org on January 1, 2014
in May at The Biology of Genomes meeting in Cold Spring Harbor, New York, in which Wayne’s team also concluded that modern wolves are not dogs’ direct ancestors. The second surprise was geographic: The ancient remains most closely related to modern dogs were all European. For example, the closest wolf relative for the largest branch of modern dogs was 14,500 years old and hailed from a cave in Switzerland; ancient dogs from Germany were the closest relatives of another modern dog branch. “This provides crucial new information,” says Renato Mariani-Costantini, a pathologist at the “G. d’Annunzio” University of Chieti-Pescara in Italy who had previously published a mitochondrial DNA study of five prehistoric Italian dogs that suggested a European origin of canines. Some geneticists argue that dogs became domesticated once agriculture arose, but the new study reinforces the idea that domestication happened much earlier, among huntergatherers. Wayne and his colleagues calculate, based on mutation rates and observed genetic differences in their samples, that dog domestication began between 18,800 and 32,100 years ago, and that canines were well entrenched with people between 15,000 and 20,000 years ago, before humans farmed. The researchers were unable to get suit-
NEWS&ANALYSIS Far out. The Alpha Magnetic Spectrometer juts from the International Space Station.
PA R T I C L E P H Y S I C S
CREDIT: NASA
Hint of Dark Matter May Be Just Cosmic Ray Debris Suppose you thought you glimpsed Bigfoot in your yard. You might be disappointed if somebody suggested you’d actually seen a bear. You’d feel doubly let down if the bear turned out to be your neighbor. That’s how some physicists may feel about a new analysis of data from an ambitious space-based experiment that seemed to show hints of dark matter. The data come from the Alpha Magnetic Spectrometer (AMS), a $2 billion detector on the International Space Station that snares particles from space called cosmic rays. In April, AMS confirmed an apparent increase in the ratio of antielectrons (positrons) to electrons at high energies (Science, 12 April, p. 135). Those positrons could come
from particles of dark matter—the invisible stuff whose gravity binds the galaxies— annihilating one another. Or, skeptics countered, they could flow from some nearby pulsar, a spinning neutron star. But not even a pulsar is needed because there are no extra positrons, argue Kfir Blum and Boaz Katz of the Institute for Advanced Study in Princeton, New Jersey, and Eli Waxman of the Weizmann Institute of Science in Rehovot, Israel. Instead, they say, the positrons are all “secondary” cosmic rays produced when primary cosmic rays, such as protons from exploding stars, smack into hydrogen and helium in space. The theorists use measurements of other secondary cosmic rays such as boron nuclei
so powerfully that it becomes undetectable in blood, making heterosexual transmission rare. Studies have also proven that taking ARVs works as a preventive for uninfected people at high risk—a strategy known as pre-exposure prophylaxis (PrEP). Male circumcision curbs spread, too, as do needle exchange, opiate substitution, and other “harm reduction” efforts with injecting drug users. Two people even seem to have been cured. The first, Timothy Brown of Las Vegas, Nevada, cleared his HIV infection only after dangerous bone marrow transplantations to combat his leukemia; now, a baby may have been cured simply by starting ARVs shortly after birth (Science, 8 March, p. 1134). Yet the progress has stark limits. Deeks, who treats patients at San Francisco General Hospital, noted that “we don’t see AIDS anymore but we see a new version of HIV infection.” Even in people taking ARVs, low levels of HIV cause chronic inflammation
that hastens morbidities from non-AIDS conditions like heart disease, kidney damage, and cancers, he said. Although proven interventions exist, all too often they don’t reach the people most in need or aren’t used properly. For instance, World Health Organization recommendations call for starting 25.9 million people on ARVs, but the drugs are available to fewer than half that number—and no funds exist to expand treatment. Stigma and discrimination leads many locales to ignore “key affected populations” like injecting drug users, sex workers, and men who have sex with men. People who have access to ARVs often fail to “adhere” as directed; in the United States, fewer than 25% of infected people have undetectable viral levels, and the situation is bleaker still in some poor countries. When it comes to prevention, few uninfected people have benefited from PrEP because clinicians rarely offer it and neither drugmakers
www.sciencemag.org
SCIENCE
VOL 342
Published by AAAS
to infer how many secondary positrons could be produced at a given energy. AMS never sees more than that number, they report in a paper in press at Physical Review Letters. The ratio of positrons to electrons only appears to increase at high energies, they argue, because the numbers of lower energy positrons dwindle as the particles lose energy swirling in magnetic fields and colliding with photons. The energy loss shifts them to energies lower than AMS measured. That last point is tricky. At first glance, higher energy positrons ought to drain away more rapidly than low-energy ones. But, Waxman argues, higher energy positrons could survive if they escape the galaxy’s disk and its magnetic fields and photons faster than they lose energy. Igor Moskalenko, a theorist at Stanford University in Palo Alto, California, says the assumption that highenergy positrons escape so quickly could mess up modeling of other aspects of cosmic rays. Waxman says he’s not worried because current models “include lots of assumptions that are not justified.” AMS researchers stick to their claim that secondary positrons alone cannot explain their data, says Andrei Kounine, an AMS team member from the Massachusetts Institute of Technology in Cambridge. But Stéphane Coutu, a cosmic ray physicist at Pennsylvania State University, University Park, cheers the new analysis. “Much too much emphasis has been placed on the dark-matter interpretation, the sexy thing,” he says. “What we need now are sober second looks such as this one.” –ADRIAN CHO
nor public health campaigns vigorously promote it. Epidemiologist Wafaa El-Sadr said we can only “treat our way out of the epidemic” if communities do more to find all infected people and then help them take their daily pills. “I don’t believe anyone in this room thinks there’s a silver bullet,” said El-Sadr, who is running a study in the Bronx to evaluate ways to improve ARV adherence. The meeting did not aim to draft a manifesto with action points to promote an AIDS-free world, but it did end up with a general consensus that it’s “an essential aspiration,” as Myron Cohen of the University of North Carolina, Chapel Hill, put it. “The cancer field has race to the cure, run for the cure, crawl for the cure, limp to the cure— there is no metaphor that the cancer field has not used,” Cohen noted. “I don’t say this to make fun of the field. They understand what they’re doing.” –JON COHEN
15 NOVEMBER 2013
787
Approximate Morphological age (years) classification
Belgium Russia Belgium Alaska Belgium Russia Alaska Alaska Russia Russia Germany Switzerland Switzerland Switzerland Germany USA Argentina USA
36,000 33,500 30,000 28,000 26,000 22,000 21,000 20,800 18,000 15,000 14,700 14,500 14,500 14,500 12,500 8,500 1,000 1,000
Doglike Doglike Wolflike Wolflike Wolflike Wolflike Wolflike Wolflike Wolflike Doglike Doglike Wolflike Wolflike Wolflike Doglike Doglike Doglike Doglike
able DNA from ancient Middle Eastern canids and had no access to ancient specimens from East Asia. That’s a major flaw, says Savolainen, who remains convinced that dogs originated in southern China. “It’s not really an objective study.” He and others also fault the work for including just a few modern wolves from the Middle East and China but dozens from Europe. “[It is] the same as if you wanted to do a study of
Wolf or dog? Mitochondrial DNA from 18 fossils and from modern canids revealed that two considered doglike (italic) were not closely related to dogs at all.
the origins of humans and you didn’t have a single sample from Africa.” Furthermore, mtDNA, which is passed down from mother to daughter, “reflects a small part of the evolutionary history,” says Chung-I Wu, an evolutionary biologist at the University of Chicago in Illinois. Given how much human migration there was early in dog domestication, Wu suspects that male dogs coming from outside Europe might have been bred with European dams, leading to the mitochondrial story Wayne and Thalmann propose, but not the correct overall picture of dog domestication. “Two parts of the genome can tell two different stories.” Wayne and Thalmann are now trying to get good nuclear sequence data from dog and wolf fossils, as are Larson and other researchers (Science, 1 November, p. 543). But O’Brien is not sure that more complete genomes will settle the debates, given how much dogs and wolves must have muddied the genetic waters over history by interbreeding. “Genomic archaeology has its limitations and the dogs are testing it,” he says. “It may settle one day, but don’t count on it.” –ELIZABETH PENNISI
Goal of Ending AIDS Gains Traction SAN FRANCISCO, CALIFORNIA—A Who’s Who of HIV/AIDS researchers from six continents, major funders like the Bill & Melinda Gates Foundation, public health officials, and the first person ever cured of an HIV infection gathered here last week to explore the question: “What will it take to achieve an AIDS-free world?” Tremendous headway in science over the past few years has brought this once-fanciful idea into the realm of possibility, many agreed. But talk of “ending AIDS” alarms some experts, alert to the risks of overselling that promise and underplaying the huge logistical and financial challenges. Richard Horton, editor of The Lancet— which co-sponsored the unusual meeting with its sister journal Cell—noted that he recently spoke with an unnamed “senior AIDS person” who branded talk about an AIDSfree world as “nonsense,” “irresponsible,” and “dangerous,” warning that it might lead to complacency. “I agree completely, it’s much too soon for a victory lap,” said Anthony Fauci of the National Institute of Allergy
786
and Infectious Diseases (NIAID) in Bethesda, Maryland, who noted that last year alone saw 2.3 million new HIV infections, raising the global burden to 35.3 million people. But an AIDS-free world is not an audacious notion, Fauci said. “We have a scientific and public health basis for in fact talking about this.” Meeting participants debated what, exactly, an “AIDS-free High hopes. hopes Dramatic progress has sparked endgame talk. talk world” means. “Everyone is talking about the ‘end of AIDs,’ but everyone David Baltimore of the California Institute seems to have a different perspective,” of Technology in Pasadena. Steven Deeks, a clinician at the University ARVs certainly have made extraordinary of California, San Francisco, told Science. strides. Thanks to a massive infusion of The U.S. government has championed a goal funds, the number of HIV-infected people it calls the “AIDS-free generation,” in which receiving the drugs in sub-Saharan Africa has antiretroviral (ARV) drugs completely skyrocketed from 50,000 in 2002 to more than prevent transmission to babies and allow 7 million last year. A landmark study funded HIV-infected people to live near-normal by NIAID showed 2 years ago (Science, lifespans. Others contend that only a vaccine 23 December 2011, p. 1628) that the drugs can can end the epidemic, but this elusive goal prevent as well as treat infection; when people is “at least 10 years away,” said Nobelist take ARVs as prescribed, they suppress HIV
15 NOVEMBER 2013
VOL 342
SCIENCE
Published by AAAS
www.sciencemag.org
SOURCES (TOP TO BOTTOM): O. THALMANN ET AL., SCIENCE; ADAPTED FROM WAFAA EL-SADR/COLUMBIA UNIVERSITY
INFECTIOUS DISEASES
Downloaded from www.sciencemag.org on January 1, 2014
in May at The Biology of Genomes meeting in Cold Spring Harbor, New York, in which Wayne’s team also concluded that modern wolves are not dogs’ direct ancestors. The second surprise was geographic: The ancient remains most closely related to modern dogs were all European. For example, the closest wolf relative for the largest branch of modern dogs was 14,500 years old and hailed from a cave in Switzerland; ancient dogs from Germany were the closest relatives of another modern dog branch. “This provides crucial new information,” says Renato Mariani-Costantini, a pathologist at the “G. d’Annunzio” University of Chieti-Pescara in Italy who had previously published a mitochondrial DNA study of five prehistoric Italian dogs that suggested a European origin of canines. Some geneticists argue that dogs became domesticated once agriculture arose, but the new study reinforces the idea that domestication happened much earlier, among huntergatherers. Wayne and his colleagues calculate, based on mutation rates and observed genetic differences in their samples, that dog domestication began between 18,800 and 32,100 years ago, and that canines were well entrenched with people between 15,000 and 20,000 years ago, before humans farmed. The researchers were unable to get suit-
NEWS&ANALYSIS Far out. The Alpha Magnetic Spectrometer juts from the International Space Station.
PA R T I C L E P H Y S I C S
CREDIT: NASA
Hint of Dark Matter May Be Just Cosmic Ray Debris Suppose you thought you glimpsed Bigfoot in your yard. You might be disappointed if somebody suggested you’d actually seen a bear. You’d feel doubly let down if the bear turned out to be your neighbor. That’s how some physicists may feel about a new analysis of data from an ambitious space-based experiment that seemed to show hints of dark matter. The data come from the Alpha Magnetic Spectrometer (AMS), a $2 billion detector on the International Space Station that snares particles from space called cosmic rays. In April, AMS confirmed an apparent increase in the ratio of antielectrons (positrons) to electrons at high energies (Science, 12 April, p. 135). Those positrons could come
from particles of dark matter—the invisible stuff whose gravity binds the galaxies— annihilating one another. Or, skeptics countered, they could flow from some nearby pulsar, a spinning neutron star. But not even a pulsar is needed because there are no extra positrons, argue Kfir Blum and Boaz Katz of the Institute for Advanced Study in Princeton, New Jersey, and Eli Waxman of the Weizmann Institute of Science in Rehovot, Israel. Instead, they say, the positrons are all “secondary” cosmic rays produced when primary cosmic rays, such as protons from exploding stars, smack into hydrogen and helium in space. The theorists use measurements of other secondary cosmic rays such as boron nuclei
so powerfully that it becomes undetectable in blood, making heterosexual transmission rare. Studies have also proven that taking ARVs works as a preventive for uninfected people at high risk—a strategy known as pre-exposure prophylaxis (PrEP). Male circumcision curbs spread, too, as do needle exchange, opiate substitution, and other “harm reduction” efforts with injecting drug users. Two people even seem to have been cured. The first, Timothy Brown of Las Vegas, Nevada, cleared his HIV infection only after dangerous bone marrow transplantations to combat his leukemia; now, a baby may have been cured simply by starting ARVs shortly after birth (Science, 8 March, p. 1134). Yet the progress has stark limits. Deeks, who treats patients at San Francisco General Hospital, noted that “we don’t see AIDS anymore but we see a new version of HIV infection.” Even in people taking ARVs, low levels of HIV cause chronic inflammation
that hastens morbidities from non-AIDS conditions like heart disease, kidney damage, and cancers, he said. Although proven interventions exist, all too often they don’t reach the people most in need or aren’t used properly. For instance, World Health Organization recommendations call for starting 25.9 million people on ARVs, but the drugs are available to fewer than half that number—and no funds exist to expand treatment. Stigma and discrimination leads many locales to ignore “key affected populations” like injecting drug users, sex workers, and men who have sex with men. People who have access to ARVs often fail to “adhere” as directed; in the United States, fewer than 25% of infected people have undetectable viral levels, and the situation is bleaker still in some poor countries. When it comes to prevention, few uninfected people have benefited from PrEP because clinicians rarely offer it and neither drugmakers
www.sciencemag.org
SCIENCE
VOL 342
Published by AAAS
to infer how many secondary positrons could be produced at a given energy. AMS never sees more than that number, they report in a paper in press at Physical Review Letters. The ratio of positrons to electrons only appears to increase at high energies, they argue, because the numbers of lower energy positrons dwindle as the particles lose energy swirling in magnetic fields and colliding with photons. The energy loss shifts them to energies lower than AMS measured. That last point is tricky. At first glance, higher energy positrons ought to drain away more rapidly than low-energy ones. But, Waxman argues, higher energy positrons could survive if they escape the galaxy’s disk and its magnetic fields and photons faster than they lose energy. Igor Moskalenko, a theorist at Stanford University in Palo Alto, California, says the assumption that highenergy positrons escape so quickly could mess up modeling of other aspects of cosmic rays. Waxman says he’s not worried because current models “include lots of assumptions that are not justified.” AMS researchers stick to their claim that secondary positrons alone cannot explain their data, says Andrei Kounine, an AMS team member from the Massachusetts Institute of Technology in Cambridge. But Stéphane Coutu, a cosmic ray physicist at Pennsylvania State University, University Park, cheers the new analysis. “Much too much emphasis has been placed on the dark-matter interpretation, the sexy thing,” he says. “What we need now are sober second looks such as this one.” –ADRIAN CHO
nor public health campaigns vigorously promote it. Epidemiologist Wafaa El-Sadr said we can only “treat our way out of the epidemic” if communities do more to find all infected people and then help them take their daily pills. “I don’t believe anyone in this room thinks there’s a silver bullet,” said El-Sadr, who is running a study in the Bronx to evaluate ways to improve ARV adherence. The meeting did not aim to draft a manifesto with action points to promote an AIDS-free world, but it did end up with a general consensus that it’s “an essential aspiration,” as Myron Cohen of the University of North Carolina, Chapel Hill, put it. “The cancer field has race to the cure, run for the cure, crawl for the cure, limp to the cure— there is no metaphor that the cancer field has not used,” Cohen noted. “I don’t say this to make fun of the field. They understand what they’re doing.” –JON COHEN
15 NOVEMBER 2013
787
