A genetic test for the dogs

If you are like many of the millions of owners of mixed-breed dogs in this country, the question of whether there's a little pug in your beagle or some terrier in your poodle has crossed your mind more than once. Now, thanks to the research of former Hutchinson Center scientists Drs. Elaine Ostrander and Leonid Kruglyak, a simple test to determine the genetic profile of your dog is on the way.

Three years ago, Ostrander and Krugylak published a paper in the journal Science on their discovery of a technique that can identify about 100 canine breeds using a cheek swab. That test has become a unique product to identify the pedigree of mixed-breed dogs. This summer, Mars Inc., the multinational giant that sells M&M's candy, Uncle Ben's rice and Pedigree dog food, is expected to launch Wisdom Panel MX, a DNA-based test that will be available through veterinary clinics.

The Center stands to benefit financially from sales of the test because it holds patents related to the breed-related genome discovery and owns a substantial portion of a private company formed to license and develop the technology resulting from the research.

Just how successful Wisdom Panel will be is unknown, but the potential was enough to interest Mars to spend the money to develop it. One local investment company estimates the available annual market at $75 million. According to Mars, half of the United States' estimated 70 million dogs are mixed breed. Many dog owners want to know the breed content of their pets, and according to the company, the test will answer that question and reveal characteristics of health, behavior and appearance.

"If sales of Wisdom Panel can generate revenue for the Center that helps pay for more research and clinical programs that bring in more high-quality researchers and clinicians, the more the better," said Spencer Lemons, vice president of Industry Relations and Technology Transfer.

How research on the genetics behind cancers common to dogs and humans became a commercial breed-test product is itself a unique story of technology transfer at the Center. The process from bench to dog bedside was relatively fast and has already proven profitable to the Center.

Technology transfer is the process of patenting a basic scientific discovery, assessing its potential for private development, licensing key intellectual property to an outside entity, and, hopefully, reaping financial rewards from a product.

"The primary mission of technology transfer is to develop new products and services that can benefit the public, whether through licensing of existing patented discoveries or creation of new companies," Lemons said. "The Mars test fits that bill perfectly."

By the time Science published Ostrander and Kruglyak's paper in May 2004, the Center had held a patent on their discoveries for several months.

The paper was based on work the pair had done to look for genetic commonalities among some pure dog breeds recognized by the American Kennel Club. One goal was to find the genes responsible for diseases common to both dogs and humans, including several types of cancers. The dog genome is easier to parse for cancer-mapping studies because of the relatively closed genetic makeup of distinct breeds. Eventually, the research led to an understanding of the relatedness, one to another, of about 100 breeds of the 150 recognized by the AKC, including sub-lineages of some breeds.

From science to market research

With the Center's blessing, Ostrander and Krugylak went looking for a venture partner to help turn their basic science into a marketable product. Their quest soon brought them to the office of renowned molecular biologist Dr. Leroy Hood, president of the Institute for Systems Biology. After listening to their proposal, Hood called Carl Weissman, president and chief executive officer of Accelerator, a small company near the Center that identifies, evaluates, finances and manages emerging biotechnology.

"One of the ways that Accelerator hears about new biotech opportunities is from faculty at our anchor institution, the Institute for Systems Biology," Weissman said. "So, one day, Leroy Hood called me up and said, 'Elaine Ostrander and Leonid Krugylak are here in my office and they've got what sounds like a fantastic idea for a biotech company. Would you have the time to sit down and talk with them?'"

"At the time I was actually a little bit awestruck because Elaine is one of the preeminent geneticists in the world, and Leonid is without question one of the top genetics statisticians anywhere," Weissman said. "These are two unbelievably well-known people and I'd only been in the job at that point for about six months."

Weissman felt that first meeting went very well. "To be honest, the last thing I expected them to say to me was, 'Hey Carl, we've got a way to sequence dog genomes and tell you what the breed content of your dog is.' At first I was like, all right, now what do I do? I've been sequestered in a room with these two really, really smart people and they've told me that they want to do a dog-breed test."

Weissman asked one of his employees, who also worked for a local venture-capital firm, to assess the market for a dog-breed test. "I think she thought I was sending her on a fool's errand at first, but as we researched the market, it turned out the numbers could make this a viable product." Their research showed that up to 24 percent of owners of mixed-breed dogs would be willing to pay up to $100 for a test to identify the breeds in their dogs. Given that more than 3 million mixed-breed dogs are born every year in the United States, they calculated a possible annual market of $75 million, Weissman said.

Pushing the potential

He helped the scientists develop a business plan that they pitched to Accelerator's investor board. However, the board was uncomfortable entering the consumer veterinary market and turned down the proposal to form a company to further develop the technology.

Weissman remained a believer in the potential of a dog-breed test. In the meantime, Ostrander introduced him to Graeme Blackwood, a senior executive colleague at Mars. Blackwood said the company would be interested in commercializing a dog-breed test. The scientists and Weissman decided to meet with Lemons, who had just arrived at the Center to lead Technology Transfer, to discuss what to do next.

Ostrander said she and Krugylak didn't have commercialization in mind when they began their research. "As soon as we realized that our data was of high enough quality to identify individual breeds, we knew we had a product," she said. "Leonid ran some calculations to show it worked for mixed-breed dogs, too."

In the fall of 2004, the discussion culminated in the creation of a company — Argus Genetics, LLC — for the expressed purpose of being a conduit between the Center and any licensee of the technology. Ostrander, Krugylak, the Center, Weissman and a colleague at Accelerator are shared owners of Argus.

Weissman and the team negotiated a license and commercialization agreement with Mars on behalf of Argus, which includes some of the scientists' time to further develop the test and a share of the profits on eventual sales, as well as some development "milestone" payments to Argus. The team sealed the deal in June 2005.

Ostrander and Weissman said working with Mars was straightforward and a great experience. In the end, Weissman said, it wasn't surprising that Mars, one of the world's largest privately held companies, would negotiate with a tiny entity like Argus. It has other pet and veterinary products and interests, and Weissman believes Mars had been waiting for the right opportunity to come along to enter the canine- diagnostics arena.

Ostrander, now chief of the cancer genetics branch of the National Human Genome Research Institute at the National Institutes of Health, said Wisdom Panel is a "very powerful tool for the millions of dog owners who buy their mixed-breed pets from a pound. Veterinarians can tell the owners what diseases to look for, and not just cancers, but also for Addison's (an endocrine disease) and muscular diseases."

Krugylak currently is a professor of ecology and evolutionary biology in the Lewis-Sigler Institute for Integrative Genomics at Princeton University.

Praise for Technology Transfer

"It is certainly exciting to see this idea of using molecular markers to identify signatures of different breeds — which had its origins in basic evolutionary genetics— make it all the way to a commercial product that has the potential to provide useful information to and satisfy the curiosity of millions of dog owners," he said.

Both scientists continue to work in canine genetics. Last month, they shared the media spotlight for another paper published in Science in which they demonstrated the role of the IGF-1 gene in controlling body size in small vs. large dogs.

Weissman had hearty praise for Lemons and the Center's Technology Transfer program. "First of all, it was an absolute pleasure to negotiate with Spencer. He's an extremely creative guy; not stuck in some old paradigm of the way tech transfer used to be. This deal would never have happened using the traditional approach to tech transfer that many academic institutions still use."

"The Hutchinson Center and Argus came to a very quick agreement about how we would share the upside, and I think that the Center, in the end, will benefit tremendously."