Sage plants roots at the Center

Dr. Stephen Friend—a veteran of the biotech industry and academic research—has a unique perspective on the complexity of gathering and then unraveling the genomic information behind complex diseases. The data required is much too massive for one company or institution to develop and fully decipher to make breakthrough discoveries quickly.

In Friend’s perfect world, the huge amounts of genomic data being generated by researchers around the globe—information that is often proprietary in private industry—would be shared. Free, open data could lead more swiftly to breakthroughs and potential cures.

That’s why Friend has left industry to start Sage Bionetworks, a nonprofit institute working to create an open-access Internet database for researchers worldwide to share their genomic data and casual disease models—a public commons of sorts for human biology.

Hosted by the Hutchinson Center, Sage scientists have set up shop in the Arnold Building where they will work next to computational biologists in the Public Health Sciences Division. Friend serves as Sage president and as an affiliate investigator in PHS. Dr. Lee Hartwell sits on the Sage board.

As Sage’s host site, the Center will have many opportunities for collaboration and will get easy, early access to Sage data and models. The two institutions may seek grants together as well.

“I’m excited by Sage’s goal to build predictive models of cancer,” said Dr. Mark Groudine, deputy director of the Center. “Collaboration between our computational biology program and Sage investigators will strengthen our ability to predict clinical outcomes based on molecular data.

“The future of basic medical research will come, in part, from our ability to integrate and synthesize massive amounts of molecular and clinical data from multiple teams of investigators,” Groudine said. “If successful, the platform that Sage is building will provide an environment in which we will be able to share data and interact with colleagues, leading to important advances in human diagnostics and therapeutics.” 

The road from Rosetta to Sage

Friend first came to the Hutchinson Center 14 years ago to help start the Seattle Project, which delved into how genetic approaches could help find and validate drug targets.

Friend spent two years at the Center as head of molecular pharmacology. During that time, RNA profiling technology developed by the Seattle Project showed so much promise that in 1997 the Center spun out a biotech company called Rosetta Inpharmatics. Friend became its president.

Now, after spending the past decade in the private sector, Friend has returned to the Center as co-founder and president of Sage, along with 15 scientists who were the core of the Genetics Group at Rosetta.

Co-founded by Friend, Hartwell and Dr. LeRoy Hood, Rosetta sought to use pattern recognition technology to understand disease status and identify drug targets. In 2000, Rosetta Inpharmatics went public. It was purchased a year later by Merck & Co., Inc.

By that time, said Friend, it was becoming clear that linear approaches to generating data to understand diseases were probably inadequate to develop new therapies. Dr. Eric Schadt, then the scientific director at Rosetta and now a co-founder of Sage, responded by pursuing an integrative genomics approach to building network models of disease.

The core idea is to use natural genetic variations each individual has across their entire genome as a perturbation and by collating these with changes in intermediate traits such as RNA levels and clinical traits, such as risk of metastasis, to build causal network models of disease that are predictive. Networks represent the deeper layers of interacting proteins in the cell as opposed to the more classic linear pathways most scientists grew up learning from textbooks. Their work has been featured in Nature, Nature Genetics and other journals this past two years.

Merck invested $150 million to test Schadt’s network models of disease. “The models proved sufficiently predictive that the majority of new targets in disease areas such as cardiovascular disease and diabetes at Merck have been generated by those models,” Friend said.

A year ago, Merck decided to move Rosetta’s efforts to build network disease models into a public forum with open access. Last month, Friend and Schadt launched Sage as a platform to support collaborative research in a “precompetitive” environment.

Merck’s willingness to donate to Sage previously proprietary information and share this information reflects a new trend to encourage research of human biology to exist in a more open and less proprietary fashion. Sharing of disease models among researchers in academia and industry should allow a distributed network of scientists to jointly make and refine new discoveries. 
 
Sage can provide only a fraction of the information that might be needed to make a given prediction. That’s why Sage will encourage researchers who use the system to contribute information to make the system even more predictive as time goes by.

Collaborative spirit at the Hutchinson Center

As Friend and Schadt planned Sage, they decided to partner with existing academic research institutions rather than start a free-standing institute. “We knew we wanted to interact on a daily basis with the scientists who will be contributing data and using Sage to test their models,” Friend said.

“We could have launched Sage at many places,” he said. “Looking across the country at the spirit of institutions, it is a fact that the Hutchinson Center has a time-honored interest in collaboration and joint projects that makes it a very attractive place to be.

“In many other places, people will ask, ‘Why should I be involved, why should I try this?’. Hutchinson Center scientists are inclined to say, ‘Why not?’”

While Sage is being launched at the Hutchinson Center, it plans to establish sites at additional academic research institutions and ultimately employ 30 to 50 people.

Anonymous contributors donated several million dollars to help start Sage. Merck made a significant donation of data, core computers and equipment. The institution is leasing space from the Center and paying an administrative fee.

Sage expects to take three to five years to develop an open-access platform accessible over the Internet. During this initial phase, researchers who want to use Sage’s data and models will be able to collaborate directly with Sage scientists at one of the institute’s host sites. As Sage’s first host site, the Center will be able to make use of Sage data and models sooner rather than later.

“We’re getting an early chance to work with a group at forefront of computational biology that is actively seeking collaborations,” said Dr. Ross Prentice, director of the Public Health Sciences Division. “It’s kind of an experiment, but it is very exciting.”

Friend already has given three presentations about Sage to various groups at the Center and welcomes requests for more. Look for an ongoing series of lectures by Sage scientists to be announced this fall, as well as a lecture series by outside experts on network models of disease. For more information about Sage, visit www.sagebase.org. Friend can be reached at (206) 667-2101 or friend@sagebase.org.

“The scientists at Sage love to describe what we’re doing,” Friend said, “and we’re eager to learn how we can help projects already under way at the Hutchinson Center.”