Monthly Archives: March 2014

Researchers disagree over the whens and wheres of canine domestication

Les Hirondelles Photography/Flickr/Getty Images

Scientists investigating the transformation of wolves into dogs are behaving a bit like the animals they study, as disputes roil among those using genetics to understand dog domestication.

In recent months, three international teams have published papers comparing the genomes of dogs and wolves. On some matters such as the types of genetic changes that make the two differ the researchers are more or less in agreement. Yet the teams have all arrived at wildly different conclusions about the timing, location and basis for the reinvention of ferocious wolves as placid pooches. Its a sexy field, says Greger Larson, an archeogeneticist at the University of Durham, UK. He has won a 950,000 (US$1.5-million) grant to study dog domestication starting in October. Youve got a lot of big personalities, a lot of money, and people who want to get their Nature paper first.

In January, Erik Axelsson and Kerstin Lindblad-Toh, geneticists at Uppsala University in Sweden, and their colleagues reported in Nature that genes involved in the breaking down of starch seemed to set domestic dogs apart from wild wolves. In the paper and in media interviews, the researchers argued that dog domestication was catalyzed by the dawn of agriculture around 10,000years ago in the Middle East, as wolves began to loiter around human settlements and rubbish heaps (see Nature http://doi.org/mv4; 2013).

But Larson, who has worked with Lindblad-Toh on other projects, says that their claim is dubious. He notes that bones that look similar to those of domestic dogs predate the Neolithic revolution by at least several thousand years, so domestication must have occurred before then. Why waste space [in a paper] saying something that is patently untrue? he says.

Axelsson concedes that the changes in starch digestion in dogs could have occurred after they were domesticated. But he also counters that the Neolithic era lasted for thousands of years, and that dogs may have been domesticated during the earliest steps towards agrarian life when human hunter-gatherers settled down and began eating more starch-rich wild plants.

A second study, published last month in Nature Communications, argues that dogs were domesticated 32,000years ago when they began scavenging with Palaeolithic humans in southern China. A team led by Ya-ping Zhang at the Kunming Institute of Zoology in China drew that conclusion from studying the whole genomes of several grey wolves, modern European dog breeds and indigenous Chinese dogs.

But Larson says that there is no evidence to suggest that wolves ever lived in southern China, so how do you domesticate a wolf if there arent any? And Jean-Denis Vigne, an archeozoologist at the National Museum of Natural History in Paris, agrees, noting that in earlier work, Zhangs team completely ignored what has been published, even in the frame of genetics.

Peter Savolainen, a geneticist at the KTH Royal Institute of Technology in Solna, Sweden, who co-authored the Nature Communications paper, argues that Chinese scientific literature suggests that wolves did once live south of Chinas Yangtze River, but have since become extinct. But he acknowledges that the date that his team reported like all molecular dating efforts relies on several assumptions, such as the number of genetic mutations that develop in each generation.

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Dog Genetics Spur Scientific Spat

As the justices prepare to hear arguments in the Myriad Genetics case, observers are debating the impact of the outcome on personalized medicine and whole-genome sequencing

Flickr/Be-Younger.com

When Daniel Weaver pitches Genformatic to potential investors, he feels obliged to note a future legal uncertainty. The two-year-old company, based in Austin, Texas, offers whole-genome sequencing and analysis to researchers and physicians, with plans to apply the technology to medical diagnostics. But Weaver fears that the company could become ensnared in a thicket of thousands of patents. Who knows how much it would cost in legal fees just to sort through that? he says.

Weaver and others in his line of business are looking to the US Supreme Court to prune that thicket. On 15 April, the court will hear arguments in a long-running lawsuit intended to answer one question: are human genes actually patentable? Yet the implications of the courts decision expected by the end of June may be narrower for business and medicine than many people hope and think. The case is limited to patents that cover the sequence of a gene, rather than methods used to analyze it (see A plethora of patents). Symbolically, this case is a pretty big deal, says Robert Cook-Deegan, a policy researcher at Duke University in Durham, North Carolina. But the practical consequences of it are limited.

The case, Association for Molecular Pathology v. Myriad Genetics, tackles the validity of patents owned by Myriad Genetics, a medical diagnostics company based in Salt Lake City, Utah, on isolated DNA that encompasses the human genes BRCA1 and BRCA2. Certain forms of these genes increase the risk of breast, ovarian and other cancers. Myriad says that its patents are necessary to protect its investment in research. But physicians and patients charge that the intellectual-property restrictions have limited development of and access to medical tests based on the genes. In 2009, the American Civil Liberties Union and the Public Patent Foundation, both based in New York, sued Myriad. The case has been rumbling through the courts ever since.

To many in biotechnology, it has ramifications beyond specific genes. The case highlights concerns that a network of individual gene patents could threaten the future of personalized medicine and whole-genome sequencing by blocking companies and clinicians from reporting a patients genetic risk factors for different diseases. Its as if somebody had a patent on the X-ray images of the pelvic region of a human being, says Weaver. You could administer the test, but you wouldnt be able to inform the patient about that region. Its crazy.

By some estimates, the number of patents on human DNA is indeed extensive. In 2005, researchers reported that 20% of human genes had been patented. Two weeks ago, another team raised that estimate to at least 41%. But some dispute these numbers and their implications. Christopher Holman, a law professor at the University of Missouri-Kansas City, read through 533 of the 4,270 patents referenced in the 2005 study, and found that more than one-quarter were unlikely to limit genetic testing. The literature is full of this kind of problem, he says.

His analysis was backed up by Nicholson Price, an academic fellow at Harvard Law School in Cambridge, Massachusetts, who found that few, if any, DNA patents would be infringed by companies or clinics sequencing whole genomes of individuals for medical insight. Many, for example, apply only to the selective isolation of specific stretches of DNA, says Price, whereas whole-genome sequencing is an untargeted sweep of the entire genome.

Myriads contested patents are part of a dying breed, says David Resnick, a patent attorney at the law firm Nixon Peabody in Boston, Massachusetts. They were filed in 1995, before much of the human genome was sequenced and put into the public domain. Many other US gene patents issued before the human genome was sequenced are no longer enforced, because the companies that hold them have stopped paying maintenance fees. This case is a conversation we should have had 20 years ago, says Resnick. Its moot now.

Cook-Deegan thinks that whole-genome approaches may still be threatened if courts interpret patent claims broadly. Christopher Mason, a genomics researcher at Weill Cornell Medical College in New York, says that companies and clinics should not have to bear the risk of a court case. If youre so sure those patents wont be a problem, he says, when I get sued, youll pay my court fees.

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Supreme Court Set to Hear Arguments on Whether Human Genes Can Be Patented