The Wall Street Journal
July 12, 2006

Ex-Executive Backs Big Push to Get A Jump on Cancer
Mr. Listwin Runs Foundation In the Style of a Start-Up;
Scientific Hurdles Remain

The 'Fingerprints' of Tumors

By DAVID P. HAMILTON

A few years after his mother died of ovarian cancer in 2001, a Silicon Valley millionaire named Don Listwin decided it was time for a radical new assault on cancer.

The problem, as the former Cisco Systems Inc. executive saw it, wasn't a lack of money, since the U.S. already spends roughly $10 billion a year on cancer research. Instead, Mr. Listwin began to think that the most promising way to beat cancer using technology to detect early tumor cells before they spread was languishing from neglect. Two years ago, he established the Canary Foundation to begin an industrial-style attack on the thorny problem of early cancer detection.

Echoing the work of titans such as the Bill and Melinda Gates Foundation,millionaires like Mr. Listwin, 47 years old, are adding to a growing movement among wealthy entrepreneurs to give away their money while they're still relatively young. Many are focusing on medical causes that arise from their personal experience.

Following his diagnosis with prostate cancer in 1993, former financier and convicted securities-law violator Michael Milken established the Prostate Cancer Foundation to support research into the disease. More recently, he founded FasterCures, a Washington-based "actiontank" that attempts to accelerate the translation of basic scientific discoveries into medical treatments. Scott Johnson, a former Silicon Valley entrepreneur with multiple sclerosis, founded the Myelin Repair Foundation to speed the development of new MS therapies.

Mr. Listwin, whose estimated $100 million fortune derives largely from holdings of Cisco stock, has a personal interest in early detection. His father survived a grueling bout with cancer several years ago. When his mother fell ill at the age of 67, her complaint was twice misdiagnosed as a bladder infection, he says. (Ovarian cancer frequently isn't detected until the disease is advanced.)

"I'm pretty convinced I'm going to get it," Mr. Listwin says of cancer. "I'd like to get to a point where my son gets to have a blood test rather than having to rely on today's early detection."

In contrast to much larger charitable organizations, which frequently support research without trying to direct it, Canary takes a hands-on approach. Some of the researchers Mr. Listwin recruited were initially wary of his approach,concerned that his foundation might be a rich man's hobbyhorse that would serve as a distraction from important research questions.

For years, a handful of cancer specialists such as Nobel laureate Lee Hartwell ,director of the Fred Hutchinson Cancer Research Center in Seattle, have argued that it makes far more sense to nip cancer in the bud than to spend billions of dollars developing new drugs that may only extend the lives of patients by a few months. "We can already cure cancer when it's detected at an early stage," Dr. Hartwell says. "If we can move late-stage [patients] to the early stage, we're almost done."

Canary's program faces big hurdles. The most fundamental is simply proving its basic scientific premise: that the right set of high-tech tests can reliably detect cancer at an early stage.

Existing early-detection tests including mammography for breast cancer, colonoscopy for colon cancer and the prostate-specific antigen (PSA) blood test for prostate cancer have helped some people. But the tests can be intrusive,uncomfortable and often inaccurate, missing early tumors or mistakenly flagging benign conditions.

New Technology

Canary is focused on new technology that could "fingerprint" early tumors by scanning blood samples for unusual patterns of proteins or gene activity. While scientists have tentatively identified many such fingerprints - called "biomarkers" - few are ready to be used in diagnostic tests.

That's the problem that Mr. Listwin wants to tackle, approaching the task like a startup business. Canary sets short-term goals and chooses researchers to work on them, often funding them with far less red tape than at traditional foundations.

Earlier this year, for example, several researchers presented Canary with their ideas for future early-detection technologies. Instead of just thanking them at the end of the meeting, Mr. Listwin wrote $50,000 checks for the two researchers whose ideas were deemed best, and asked them to come back and report on their experiments.

At many foundations, costs for administration and fund-raising can eat up a substantial portion of budgets - a sore point with many donors. Mr. Listwin covers such operational costs himself, about $1.5 million a year, to assure potential donors their gifts will flow directly to research.

A native of Saskatoon, Saskatchewan, Mr. Listwin moved to Silicon Valley in 1986. A few years later he was working his way up at Cisco, eventually becoming an executive vice president. He left the company in 2000, taking the top job at software startup Openwave Systems Inc., near the height of the Internet bubble. He held that job until 2004, when he resigned to devote time to Canary.

His business experience, Mr. Listwin grew convinced, could help him guide his foundation in ways others hadn't. For instance, instead of assembling a board of advisers to review grant proposals from outside researchers, he brought on scientists who could not only oversee the research, but carry out much of it themselves. He tapped small companies and venture capitalists, hoping to speed the commercialization of new cancer diagnostics. He has taken steps to involve federal regulators too.

"He's bringing together the whole spectrum," says Larry Kessler, an official in the Food and Drug Administration's Center for Devices and Radiological Health, who has attended two Canary-sponsored meetings. "I've not seen anything like it."

Mr. Listwin's transition to philanthropist effectively began when his mother died. Aggrieved by the multiple misdiagnoses of her ovarian cancer, Mr.Listwin says he briefly entertained visions of suing her doctor. As he learned more about ovarian cancer and the way it spreads, however, he calmed down and began looking for ways to fund research that could advance the fight against the disease.

Internet searches soon led him to the Fred Hutchinson cancer center, known as "the Hutch." There Nicole Urban, an epidemiologist, was trying to discover biomarkers in ovarian cancer.

Mr. Listwin helped support Dr. Urban's work. At one point, when she needed a laboratory to pursue her studies, Mr.Listwin arranged a $1 million grant to the Hutch, contingent on Dr. Urban getting research space.

Mr. Listwin found that he and the Hutch's director Dr. Hartwell had a common interest in early detection. Mr.Listwin eventually offered a larger gift, to help fund the core of a biomarker discovery and analysis program.

He was determined to build coordination into the Hutch's early- detection research. "These guys are notoriously princes of their own fiefdoms," he says. "I wanted a program office, so the left hand knew what the right hand was doing."

As he learned more about early detection, Mr. Listwin found the work was making little headway. Despite scientists' growing understanding of cancer genetics and new tools for analyzing proteins and other biomarkers, few laboratories have been able to translate their discoveries into tests that can reliably spot early tumors.

The process is difficult and expensive. A newly discovered biomarker protein requires researchers to develop a test that can identify the target as it floats among a soup of similar molecules in human blood or tissue. Then scientists must use that probe on thousands of patient samples to ensure that it can reliably distinguish between people who developed cancer and those who didn't.

For the most part, industry hasn't picked up the slack. That's partly because no single biomarker is likely to detect cancer with 100% accuracy. For instance, PSA, the blood test for prostate cancer,measures a single biomarker. The test has a high "false positive" rate 70% to 75% of the time it incorrectly suggests a man has cancer, according to the National Cancer Institute. Since scientists believe effective early-detection diagnostics will likely use a combination of several biomarkers, most companies havehad relatively little incentive to invest heavily in individual markers.

Mr. Listwin decided he could mount an even broader effort to encourage development of early-detection methods. He called around for advice from other philanthropists, including Mr. Milken, and donated a total of $13 million to the Hutch and $1 million each to cancer programs at Stanford University and the University of California at San Francisco. Eventually,he began to recruit scientists for Canary,which he named after the birds coalminers once carried as early detectors of dangerous gases.

Mr. Listwin limited his invitations to West Coast researchers, figuring that keeping travel times short would make it easier for the team to meet regularly in person. At gatherings every six weeks or so, the group - which includes several cancer and cell biologists, an epidemiologist (Dr. Urban from the Hutch), an expert in diagnostic imaging and a former Intel Corp. engineer - brainstormed ways to speed work in early detection.

The Canary team members agreed that existing biomarker-discovery efforts were too scattershot to be truly useful. So,among other things, the scientists devised a plan to identify and analyze new biomarkers derived from lines of cultured tumor cells, then divided up the work between their laboratories.

Started just a few months ago, that project is slated to produce an analysis of newly unearthed biomarkers by the end of the year. "We were thinking, we could spend a year and a half soliciting grants, or just do it and get it done," says Stanford University researcher Pat Brown, a member of the Canary team.

Attracting Attention

Canary's efforts have started to attract attention in the broader early-detection research community. Dr. Kessler of the FDA, who works in the office that would review any diagnostic test resulting from the program, learned of Canary from the Hutch's Dr. Urban.

Dr. Kessler spoke about FDA regulation of diagnostic tests at two Canary symposia, and earlier this year invited Mr. Listwin to FDA headquarters in Rockville, Md., for a day of meetings. "I didn't want him to come up with a product and then have to say, 'It isn't going to happen,'" Dr. Kessler says.

Mr. Listwin's support helped establish the Hutch as an early- detection center,and bolstered that approach to fighting cancer. Earlier this year, the National Cancer Institute announced a five- year,$100 million effort to standardize the discovery and analysis of new protein biomarkers for cancer. The Hutch's Dr.Hartwell played a key advisory role in establishing that program, says Anna Barker, NCI's deputy director for advanced technology.

Canary is staying focused on specific, short-term projects. It is evaluating a group of 20 or so markers in ovarian cancer, with results due by the end of next year. If the data are positive, Dr.Urban says, they may be enough to apply for FDA approval for the new test.

Commercializing these tests presents another challenge. Many individual biomarkers are tied up by patents and licensing agreements that complicate efforts to assemble them into one product. Mr. Listwin has already hired consultants to analyze the intellectual-property challenges, with an eye toward acquiring rights to the markers Canary needs.

If Canary can't win rights to all the biomarkers its scientists want, Mr.Listwin says the foundation still has options. Some of the patents and licenses in question aren't enforceable in other nations, he notes. He points to a recently signed partnership with the British Columbia Cancer Agency and suggests Canary would be happy to help establish biomarker diagnostics as a standard of care wherever it can.

"Perhaps we start saving lives in China first, or Singapore, or Canada," he says. "The real issue is proving it works. If we do that, the public will demand it."

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