2165. The Big Search to Find Out Where Dogs Come From

By James Gorman, The New York Times, January 18, 2016

A lone wold known to play with dogs

OXFORD, England — Before humans milked cows, herded goats or raised hogs, before they invented agriculture, or written language, before they had permanent homes, and most certainly before they had cats, they had dogs.

Or dogs had them, depending on how you view the human-canine arrangement. But scientists are still debating exactly when and where the ancient bond originated. And a large new study being run out of the University of Oxford here, with collaborators around the world, may soon provide some answers.

Scientists have come up with a broad picture of the origins of dogs. First off, researchers agree that they evolved from ancient wolves. Scientists once thought that some visionary hunter-gatherer nabbed a wolf puppy from its den one day and started raising tamer and tamer wolves, taking the first steps on the long road to leashes and flea collars. This is oversimplified, of course, but the essence of the idea is that people actively bred wolves to become dogs just the way they now breed dogs to be tiny or large, or to herd sheep.

The prevailing scientific opinion now, however, is that this origin story does not pass muster. Wolves are hard to tame, even as puppies, and many researchers find it much more plausible that dogs, in effect, invented themselves.

Imagine that some ancient wolves were slightly less timid around nomadic hunters and scavenged regularly from their kills and camps, and gradually evolved to become tamer and tamer, producing lots of offspring because of the relatively easy pickings. At some point, they became the tail-wagging beggar now celebrated as man’s best friend.

Some researchers question whether dogs experience feelings like love and loyalty, or whether their winning ways are just a matter of instincts that evolved because being a hanger-on is an easier way to make a living than running down elk. Raymond Coppinger, a professor emeritus of biology at Hampshire College, noted in his landmark 2001 book, “Dogs,” that “best friend” is not an “ecological definition.” And he suggested that “the domestic house dog may have evolved into a parasite.”

Researchers also point out that of the estimated one billion dogs in the world, only a quarter of them are pets. The vast majority of dogs run free in villages, scavenge food at dumps, cadge the odd handout and cause tens of thousands of human deaths each year from rabies. They are sometimes friendly, but not really friends.

Modern dogs are different from modern wolves in numerous ways. They eat comfortably in the presence of people, whereas wolves do not. Their skulls are wider and snouts shorter. They do not live in pack structures when they are on their own, and so some scientists scoff at dog-training approaches that require the human to act as pack leader.

Wolves mate for the long haul and wolf dads help with the young, while dogs are completely promiscuous and the males pay no attention to their offspring. Still, dogs and wolves interbreed easily and some scientists are not convinced that the two are even different species, a skepticism that reflects broader debates in science about how to define a species, and how much the category is a fact of nature as opposed to an arbitrary line drawn by humans.

Tracing the Origins

If current divisions between species are murky, the past lies in deep darkness. Scientists generally agree that there is good evidence that dogs were domesticated around 15,000 years ago. By 14,000 years ago, people were burying dogs, sometimes along with humans. But some biologists argue, based on DNA evidence and the shape of ancient skulls, that dog domestication occurred well over 30,000 years ago.

And as to where the process occurred, researchers studying dog and wolf DNA — most of it modern but some from ancient sources — have argued in recent years that dogs originated in East Asia, Mongolia, Siberia, Europe and Africa.

One reason for the conflicting theories, according to Greger Larson, a biologist in the archaeology department at the University of Oxford, is that dog genetics are a mess. In an interview at his office here in November, he noted that most dog breeds were invented in the 19th century during a period of dog obsession that he called “the giant whirlwind blender of the European crazy Victorian dog-breeding frenzy.”

That blender, as well as random breeding by dogs themselves, and interbreeding with wolves at different times over at least the last 15,000 years, created a “tomato soup” of dog genetics, for which the ingredients are very hard to identify, Dr. Larson said.

The way to find the recipe, Dr. Larson is convinced, is to create a large database of ancient DNA to add to the soup of modern canine genetics. And with a colleague, Keith Dobney at the University of Aberdeen, he has persuaded the Who’s Who of dog researchers to join a broad project, with about $2.5 million in funding from the Natural Environment Research Council in England and the European Research Council, to analyze ancient bones and their DNA.

Robert Wayne, an evolutionary biologist at U.C.L.A. who studies the origin of dogs and is part of the research, said, “There’s hardly a person working in canine genetics that’s not working on that project.”

That is something of a triumph, given the many competing theories in this field. “Almost every group has a different origination hypothesis,” he said.

But Dr. Larson has sold them all on the simple notion that the more data they have, the more cooperative the effort is, the better the answers are going to be. His personality has been crucial to promoting the team effort, said Dr. Wayne, who described Dr. Larson as “very outgoing, gregarious.” Also, Dr. Wayne added, “He has managed not to alienate anyone.”

Scientists at museums and universities who are part of the project are opening up their collections. So to gather data, Dr. Larson and his team at Oxford have traveled the world, collecting tiny samples of bone and measurements of teeth, jaws and occasionally nearly complete skulls from old and recent dogs, wolves and canids that could fall into either category. The collection phase is almost done, said Dr. Larson, who expects to end up with DNA from about 1,500 samples, and photographs and detailed measurements of several thousand.

Scientific papers will start to emerge this year from the work, some originating in Oxford, and some from other institutions, all the work of many collaborators.

Dr. Larson is gambling that the project will be able to determine whether the domestication process occurred closer to 15,000 or 30,000 years ago, and in what region it took place. That’s not quite the date, GPS location and name of the ancient hunter that some dog lovers might hope for.

But it would be a major achievement in the world of canine science, and a landmark in the analysis of ancient DNA to show evolution, migrations and descent, much as studies of ancient hominid DNA have shown how ancient humans populated the globe and interbred with Neanderthals.

And why care about the domestication of dogs, beyond the obsessive interest so many people have in their pets? The emergence of dogs may have been a watershed.

“Maybe dog domestication on some level kicks off this whole change in the way that humans are involved and responding to and interacting with their environment,” he added. “I don’t think that’s outlandish.”

Shepherding the Research

Dr. Larson is no stranger to widely varying points of view. He is an American, but recently became a British citizen as well. His parents are American and he visited the United States often as a child, but he was born in Bahrain and grew up in Turkey and Japan, places where his parents were teaching in schools on American military bases.

He graduated from Claremont McKenna College in California and received his Ph.D. at Oxford. In between college and graduate studies, he spent a year searching for the bed of an ancient river in Turkmenistan, and another couple of years setting up an environmental consulting office in Azerbaijan. He had an interest in science as an undergraduate, and some background from a college major in environment, economics and politics, but no set career plans. Instead, his career grew out of intense curiosity, a knack for making friends and a willingness to jump at an opportunity, like the time he managed to tag along on an archaeological dig.

He was staying in Ashgabat, Turkmenistan, and a local man who had helped him rent an old Soviet truck to explore the desert told him some Westerners were arriving to go on a dig, so he wangled his way onto one of the trucks.

“I think everybody there thought I was with somebody else,” Dr. Larson said.

By the time the group stopped to rest and someone asked him who he was, it was too late to question whether he really belonged. “I was a complete stowaway,” he said.

But he could move dirt and speak Russian, and he had some recently acquired expertise — in college drinking games — that he said was in great demand at night. By luck, he said, the researchers on the dig turned out to be “the great and the good of British neolithic archaeology.” One of them was Chris Gosden, the chairman of European Archaeology at Oxford, who later invited him to do a one-year master's degree in archaeology at Oxford. That eventually led to a doctoral program after he spent some time in graduate school in the United States.

The current project began when he became fed up with the lack of ancient DNA evidence in papers about the origin of dogs. He called Dr. Dobney, of the University of Aberdeen in 2011, and said, “We’re doing dogs.”

After receiving the grant from the council in England, he and Dr. Dobney organized a conference in Aberdeen, Scotland, to gather as many people involved in researching dog origins as they could. His pitch to the group was that despite their different points of view, everyone was interested in the best possible evidence, no matter where it led.

“If we have to eat crow, we eat crow,” he said. “It’s science.”

A 32,000-Year-Old Skull

Mietje Germonpré, a paleontologist at the Royal Belgian Institute of Natural Sciences, is one of the many scientists participating in the dog project. She was one of a number of authors on a 2013 paper in Science that identified a skull about 32,000 years old from a Belgian cave in Goyet as an early dog. Dr. Wayne at U.C.L.A. was the senior author on the paper and Olaf Thalmann from the University of Turku in Finland was the first author.

It is typical of Dr. Larson’s dog project that although he disagreed with the findings of the paper, arguing that the evidence just wasn’t there to call the Goyet skull a dog, all of the authors of the paper are working on the larger project with him.

In November in Brussels, holding the priceless fossil, Dr. Germonpré pointed out the wide skull, crowded teeth and short snout of the ancient skull — all indicators to her that it was not a wolf.

“To me, it’s a dog,” she said. Studies of mitochondrial DNA, passed down from females only, also indicated the skull was not a wolf, according to the 2013 paper.

Dr. Germonpré said she thinks dogs were domesticated some time before this animal died, and she leans toward the idea that humans intentionally bred them from wolves.

She holds up another piece of evidence, a reconstruction of a 30,000-year-old canid skull found near Predmostí, in the Czech Republic, with a bone in its mouth. She reported in 2014 that this was a dog. And she says the bone is part of evidence the animal was buried with care. “We think it was deliberately put there,” she said.

But she recognizes these claims are controversial and is willing, like the rest of the world of canine science, to risk damage to the fossils themselves to get more information on not just the mitochondrial DNA but also the nuclear DNA.

To minimize that risk, she talked with Ardern Hulme-Beaman, a postdoctoral researcher with the Oxford team, about where to cut into it. He was nearing the end of months of traveling to Russia, Turkey, the United States and all over Europe to take samples of canid jaws and skulls.

He and Allowen Evin, now with the National Center for Scientific Research in Montpellier, France, also took many photographs of each jaw and skull to do geometric morphometrics. Software processes detailed photographs from every angle into 3-D recreations that provide much more information on the shape of a bone than length and width measurements.

Dr. Germonpré and Dr. Hulme-Beaman agreed on a spot in the interior of the skull to cut. In the laboratory, he used a small electric drill with a cutting blade to remove a chunk the size of a bit of chopped walnut. An acrid, burning smell indicated that organic material was intact within the bone — a good sign for the potential retrieval of DNA.

Back in Oxford, researchers will attempt to use the most current techniques to get as much DNA as possible out of the sample. There is no stretch of code that says “wolf” or “dog,” any more than there is a single skull feature that defines a category. What geneticists try to establish is how different the DNA of one animal is from another. Adding ancient DNA gives many more points of reference over a long time span.

Dr. Larson hopes that he and his collaborators will be able to identify a section of DNA in some ancient wolves that was passed on to more doglike descendants and eventually to modern dogs. And he hopes they will be able to identify changes in the skulls or jaws of those wolves that show shifts to more doglike shapes, helping to narrow the origins of domestication.

The usual assumption about domestic animals is that the process of taming and breeding them happened once. But that’s not necessarily so. Dr. Larson and Dr. Dobney showed that pigs were domesticated twice, once in Anatolia and once in China. The same could be true of dogs.

Only the Beginning

Although the gathering of old bones is almost done, Dr. Larson is still negotiating with Chinese researchers for samples from that part of the world, which he says are necessary. But he hopes they will come.

If all goes well, said Dr. Larson, the project will publish a flagship paper from all of the participants describing their general findings. And over the next couple of years, researchers, all using the common data, will continue to publish separate findings.

Other large collaborative efforts are brewing, as well. Dr. Wayne, at U.C.L.A., said that a group in China was forming with the goal of sequencing 10,000 dog genomes. He and Dr. Larson are part of that group.

Last fall, Dr. Larson was becoming more excited with each new bit of data, but not yet ready to tip his hand about what conclusions the data may warrant, or how significant they will be.

But he is growing increasingly confident that they will find what they want, and come close to settling the thorny question of when and where the tearing power of a wolf jaw first gave way to the persuasive force of a nudge from a dog’s cold nose.

“I’m starting to drink my own Kool-Aid,” he said.

2083. On the Dangers of Human Induced Evolutionary Change

By Elisabeth Alter, The New York Times, November 10, 2015

THERE are four locked doors guarding a specialized lab at the Harvard School of Public Health. The doors are meant to prevent insects inside the lab from venturing out — which is essential, because researchers behind those doors are re-engineering mosquitoes by cutting and pasting bits of DNA with tools unimaginable a decade ago.

If researchers can figure out the right combination of genes, they’ll manufacture a mosquito resistant to malaria, which could save hundreds of thousands of lives every year. But geneticists, bioethicists and others who understand the implications of this new technology are apprehensive. To an astonishing degree, these new tools, which include a technique called Crispr-Cas9, allow us to bend evolution to our will. But will we harness these new technologies to help our planet? Or spark an ecological catastrophe?

In university labs, corporate R&D centers and even inside amateur D.I.Y. laboratories, researchers are creating genetically modified organisms at an unprecedented pace. This biotechnological revolution is so fast-moving that it hasn’t yet fully filtered into the public’s awareness or policy makers’ oversight. The implications of Crispr are now intensely debated by medical researchers, especially since Chinese scientists used the method earlier this year to modify human embryos. But there are few similar conversations about the implications of these technologies for ecosystems, even though those impacts will most likely be more transformative for our planet’s future.

These new tools are much more precise and easy to use than past versions. Researchers can cut and paste DNA into just about any animal, plant or fungus. Whereas modified genes were once likely to be stamped out if by chance they made it into the wild, today’s technologies can supercharge a genetic chain reaction: A technique called “gene drive” ensures a modified gene will be inherited with nearly 100 percent success. This is valuable in making sure that a desirable new gene, like one resistant to the malaria parasite, spreads once introduced into a mosquito population. It also means a mistake can’t easily be taken back.

As scientists, policy makers and citizens, we need to start debating how much genetic tinkering we should allow in the wild and what regulations need to be in place. On the one hand, these new tools could help us cope with many risks to humans and animals, including climate change. Coral could be buffered against warming ocean water through the introduction of heat-tolerant genes. Genes from successful species could be used to help rescue imperiled ones. The method could be used as a form of molecular CPR, helping species adjust to our changed planet more quickly than they could on their own.

But the ecological risks of these manipulations are real and poorly understood. We can’t fully predict the consequences of releasing self-propagating genes into the wild. 

Encoding a self-destruct gene, for example by altering sex-determining genes so the population eventually ends up entirely male, could be a way to battle invasive species like zebra mussels or coral-destroying sea stars. But such genes could potentially leak to places where these species actually play important ecological roles — and could even jump to other species through interbreeding. Re-engineered genes that escape from crop weeds and spread as a result of gene drive could devastate other ecosystems. Moreover, our understanding of how genomes function is still far from the point where we can change genes and be certain we aren’t creating bigger unintended consequences.

First, we need to clarify who has jurisdiction over gene-editing projects. Our current system is inadequate and confusing. A transgenic mosquito release in Florida by the company Oxitec is being evaluated by the Food and Drug Administration; a similar proposal for a moth release in New York is being overseen by the Department of Agriculture. Agencies vary widely in their review processes, and the current uncertainty about who’s in charge means that some ventures can fall through the cracks. The White House needs to issue clear guidelines.

Second, we need to pay for studies that explore the potential impacts of these technologies on the environment. Right now, there’s little incentive to explore the risks. The National Academies of Sciences, Engineering and Medicine and other groups evaluating those risks have virtually no data to work with. A recent report by the Wilson Center notes that from 2008 to 14, less than 1 percent of synthetic biology funding went toward risk research in the United States, lower than in other emerging technologies. Foundations that are investing mightily in gene-editing technologies should commit to footing some of the bill for research on the environmental risks.

And finally, we need to encourage a public conversation about these technologies. At the end of the day, the escape of a few Harvard mosquitoes will not be the most pressing problem our ecosystems will face. But to confront the big challenges, we’ll need an informed and educated public, sophisticated oversight and a broad conversation about what kinds of advances and risks we want to embrace. We need protections that are stronger than multiple doors.

Elizabeth Alter is an assistant professor of biology at City University of New York, York College.

2054. Dogs Originated from Domestication of the Gray Wolf 15,000 Years Ago, Probably in Asia

By James Gorman, The New York Times, October 19, 2015

 A Gray Wolf

Where do dogs come from?

Gray wolves are their ancestors. Scientists are pretty consistent about that. And researchers have suggested that dogs’ origins can be traced to Europe, the Near East, Siberia and South China.

Central Asia is the newest and best candidate, according to a large study of dogs from around the world.

Laura M. Shannon and Adam R. Boyko at Cornell University, and an international group of other scientists, studied not only purebred dogs, but also street or village dogs — the free-ranging scavengers that make up about 75 percent of the planet’s one billion dogs.

Dr. Shannon analyzed three different kinds of DNA, Dr. Boyko said, the first time this has been done for such a large and diverse group of dogs, more than 4,500 dogs of 161 breeds and 549 village dogs from 38 countries. That allowed the researchers to determine which geographic groups of modern dogs were closest to ancestral populations genetically. And that led them to Central Asia as the place of origin for dogs in much the same way that genetic studies have located the origin of modern humans in East Africa.

The analysis, Dr. Boyko said, pointed to Central Asia, including Mongolia and Nepal, as the place where “all the dogs alive today” come from. The data did not allow precise dating of the origin, he said, but showed it occurred at least 15,000 years ago. They reported their findings Monday in Proceedings of the National Academy of Sciences.

Greger Larson of Oxford University, who is leading an international effort to analyze ancient DNA from fossilized bones, said he was impressed by the scope of the study. “It’s really great to see not just the sheer number of street dogs, but also the geographic breadth and the number of remote locations where the dogs were sampled,” he said. He also praised the sampling of different kinds of DNA and the analytic methods.

But in the world of dog studies, very little is definitive. The most recent common ancestor of today’s dogs lived in Central Asia, Dr. Boyko said, although he cannot rule out the possibility that some dogs could have been domesticated elsewhere and died out. Or dogs domesticated elsewhere could have gone to Central Asia from somewhere else and then diversified into all the canines alive today, he said.

Dr. Larson, who was not involved with the study, said he thought the Central Asia finding required further testing. He said he suspected that the origins of modern dogs were “extremely messy” and that no amount of sampling of living populations would be definitive. He said a combination of studies of modern and ancient DNA was necessary.

Dr. Boyko said the research for the first time studied three sources of DNA from purebred and village dogs worldwide. The team analyzed DNA from all the chromosomes in the cell nucleus, from the Y chromosome specifically, found only in males, and from mitochondria, cellular energy machines outside the nucleus that are inherited from the mother.

Dr. Boyko traveled to a number of the locations where blood was drawn from village dogs. He said: “The great thing about working with dogs is that if you show up with food you don’t usually have trouble recruiting subjects. Usually.”

He added: “We showed up in Puerto Rico at a fishing village and the dogs turned up their noses at roast beef sandwiches. They were used to eating fish entrails.”

1404. Book Review: How Antibiotics Can Do Harm

By Abigail Zuger, The New York Times, April 28, 2014 

You never get something for nothing, especially not in health care. Every test, every incision, every little pill brings benefits and risks.

Nowhere is that balance tilting more ominously in the wrong direction than in the once halcyon realm of infectious diseases, that big success story of the 20th century. We have had antibiotics since the mid-1940s — just about as long as we have had the atomic bomb, as Dr. Martin J. Blaser points out — and our big mistake was failing long ago to appreciate the parallels between the two.

Antibiotics have cowed many of our old bacterial enemies into submission: We aimed to blast them off the planet, and we dosed accordingly. Now we are beginning to reap the consequences. It turns out that not all germs are bad — and even some bad germs are not all bad. In “Missing Microbes,” Dr. Blaser, a professor at the New York University School of Medicine, presents the daunting array of reasons we have to rethink the enthusiastic destruction of years past.

First and foremost, the war has escalated. Imprudent antibiotic use has resulted in widespread resistance among microbes; infectious disease doctors (I am one, as well as a casual acquaintance of Dr. Blaser’s) now operate in a state of permanent near panic as common infections demand increasingly powerful drugs for control.

Second, as always, it is the hapless bystanders who have suffered the most — not human beings, mind you, but the gazillions of benevolent, hardworking bacteria colonizing our skin and the inner linings of our gastrointestinal tracts. We need these good little creatures to survive, but even a short course of antibiotics can destroy their universe, with incalculable casualties and a devastated landscape. Sometimes neither the citizenry nor the habitat ever recovers.

And finally, there is the accumulation of disheartening evidence that the war against the old plagues is simply leading to worse wars against a whole series of new ones.

Parts of Dr. Blaser’s argument are familiar, such as the story of Clostridium difficile colitis, an increasingly common cause of diarrhea. This condition arises most often when a course of antibiotics skews the normal microbial population of the gut to favor a single toxin-producing organism. Sometimes yet more antibiotics will restore normal intestinal function. But sometimes no treatment works — nothing but infusing feces full of normal bacteria into the ailing intestines, a last-ditch strategy that has proved stunningly successful. Without it, otherwise perfectly healthy people can die.

Less familiar is the paradox posed by the little comma-shaped organism Helicobacter pylori, a denizen of the human stomach. Dr. Blaser is one of the world’s experts in these “ulcer bacteria,” which are associated not just with ulcers but also with stomach cancer. We have been slowly eradicating H. pylori with antibiotics — the organisms have become quite uncommon in developed countries.

But as they vanish, Dr. Blaser notes, a small epidemic of esophageal disease follows, with inflammation causing heartburn and even cancer. It turns out that this bad germ is also good, instrumental in protecting the human esophagus from trouble.

And that’s not all, folks, far from it.

We know that giving antibiotics to young chickens, cows and pigs means bigger, fatter animals brought to market. But we are doing pretty much the same thing to our own young, repeatedly dosing them up against all the infections of childhood (many of which do not require antibiotics to resolve). The results of an interconnected series of experiments in Dr. Blaser’s lab, with infant mice fed a variety of antibiotic regimens, lend strong support to the theory that exposure to antibiotics early in life has long-term effects on metabolism, and may contribute to our epidemic of childhood and adult obesity.

For other increasingly common conditions such as asthma, inflammatory bowel disease and celiac disease, Dr. Blaser offers an inversion of the so-called hygiene hypothesis, which holds that by removing us from contact with outdoor microbes, sanitized modern life has allowed the immune system to spiral out of control. Instead, he suggests, blame rests on the distortion of our internal microbial world.

Antibiotics are partly responsible, but so are other medical habits, such as our increasing use of cesarean sections. These aseptic procedures prevent newborns from acquiring their mothers’ organisms through the birth canal, possibly setting them up for a lifetime of trouble, with higher than normal risks of a range of immune-related problems.

Dr. Blaser presents this all at a rapid clip, not stinting on the technical language but infusing enough human interest to make his argument and data reasonably accessible. (He had writing help from Sandra Blakeslee, a veteran science journalist and a frequent contributor to Science Times.)

The discerning reader should not forget that the research he discusses is largely his own; we hear no dissenting voices or contradictory evidence, although much of the narrative remains scientifically hypothetical.

That said, however, the weight of evidence behind Dr. Blaser’s cautions about antibiotics is overwhelming. They are certainly lifesaving drugs — they saved his own life when he had typhoid fever, and he testified in Congress recently on the urgent need to develop better and stronger ones. But they are also immensely dangerous, both to individuals and to the firmly linked communities of microbes and men.