Improving outcomes, reducing costs

Last week, two philanthropic organizations announced $45 million in grants to launch the Partnership for Personalized Medicine, a global initiative to develop personalized molecular diagnostics, which will be led by Hutchinson Center President and Director Dr. Lee Hartwell.

Hartwell was instrumental in developing the new initiative and will chair the Partnership's executive committee. The Virginia G. Piper Charitable Trust committed $35 million and the Flinn Foundation has granted $10 million to fund the initiative.

The cornerstone of the Partnership is the creation of a high-throughput proteomics laboratory that draws upon the scientific strengths of Translational Genomics Research Institute (TGen) and the Biodesign Institute at ASU, each of which will contribute significant laboratory space to the effort.

"The Piper trustees made this investment because Dr. Hartwell has a vision to transform the prevention, diagnosis and treatment of disease," said Dr. Judy Jolley Mohraz, president and CEO of the Piper Trust. "That vision draws together scientists, clinicians, engineers, statisticians, insurers and regulators to work collectively to make health care more targeted and affordable."

Hartwell spoke with Center News to share details about how the Partnership for Personalized Medicine developed and the Hutchinson Center's involvement in the initiative.

How Hartwell became involved

Center News: Tell us more about this project and how you became involved?
Dr. Lee Hartwell: This is the logical extension of work that I have been doing for the last seven years. The beginning was a workshop we held at the Hutchinson Center on molecular diagnostics in cancer. It really provided an answer to a question that was on my mind: How can we better exploit our knowledge of cellular and molecular biology to improve medical science? I suddenly realized that most of the national research resources and intellectual talent were focused on therapeutics for disease and that diagnostics was being undervalued. I think this is true for all diseases, but when you consider the value of early detection for cancer, it's dramatically apparent that investment in early detection could have at least as big an impact as therapeutics for late stage disease.

This set me off on a quest to promote the development of molecular diagnostics, especially proteomics, which was beginning to show promise. The National Cancer Institute contracted with the Hutchinson Center for me to help them develop programs in proteomics. Two programs were eventually launched, providing $120 million for proteomic research. I helped recruit the research team for the Canary Foundation for early detection research and, with the help of Rick Klausner, launched an early detection project for breast cancer with support from the Entertainment Industry Foundation. That project involved seven institutions including investigators at the Center, and is ongoing. Another project was the formation of the International Cancer Biomarker Consortium, which now includes about a dozen teams throughout the world.

CN: How did these activities lead to the new project in Phoenix?
LH: All of the previous projects were focused on technology development and the sharing of technology improvements because proteomic technologies were inadequate for blood-based biomarker discovery. In the last couple of years, the field has had some breakthroughs that change the equation. While we still have a long way to go, the field is now in a position to be productive. Our own investigators have made some of the key developments including Marty McIntosh's Computational Proteomics Analysis System (CPAS) for informatics, Sam Hanash's deep fractionation techniques, and Mandy Paulovich's use of MRM (multiple reaction monitoring) technology for assay development. All are beginning to pay off.

What intrigues me now are the downstream challenges. Assume we can discover biomarkers. How do we get them validated and approved? Economic incentives are inadequate for companies or venture capital to support the large costs of clinical trials to validate biomarkers, and without that validation we don't know what information they are providing. Consider PSA (prostate-specific antigen), which was approved as a biomarker for disease recurrence but is now being used for early detection. We don't know how much good or harm it is doing because it has never been validated for early detection. Most genetic tests are now entering patient care through a process called CLIA (clinical laboratory improvement amendments) approval wherein CMS (Centers for Medicare and Medicaid Services) authorizes a laboratory to perform a test, assuring reproducibility and good laboratory practice, but does not require validation. Without validation, reimbursement is uncertain.

The PPM plan

CN: Does the Partnership for Personalized Medicine solve these problems?
LH: Well, we won't know until we try, but that is the idea. The plan of the PPM is to build a factory-style laboratory for proteomic biomarker discovery and validation at TGen so we have high capacity to offer. Then we want to offer this capacity to health care systems throughout the world with the mantra "improving outcomes — reducing costs." We hope that ministers of health who are facing out-of-control health care costs will find that attractive. No one else is really addressing the question of reducing health care costs. Nearly all new technology developments cost the system more money. But I really believe that appropriately researched and designed diagnostic interventions can turn the tide.

CN: Will this project offer any new opportunities for Hutchinson Center investigators?
LH: Yes, I hope so. I think there will be many opportunities to collaborate with the expertise here at the Center. For example, my particular role is to develop the partnerships. This means an analysis of costs and benefits for particular diagnostic points of intervention. We plan to contract with Scott Ramsey to provide some of the needed economic expertise. At first, the new proteomics facility at TGen will, I am sure, seek input and potential collaboration from Marty, Sam, Mandy and others. Later, the TGen facility will have capacity beyond that at the Hutchinson Center and may be a place our investigators go to for high-throughput proteomics.

Location and leadership

CN: Why is this activity located in Phoenix?
LH: My connection with the Phoenix biomedical community began with my serving on the scientific advisory boards for TGen and the Biodesign Institute at ASU. At some point, I connected with the Piper Trust, which is dedicated to supporting the community of Maricopa County, Ariz. They had been planning an initiative in personalized medicine and asked me to help. They contracted with the Center for my effort, and I spent some time interviewing scientists and administrators from academic and health care institutions. The Partnership for Personalized Medicine grew out of that activity.

The Piper Trust and the Flinn Foundation, which is dedicated to supporting causes in Arizona, put up $45 million for the project. Also, the factory-style proteomics facility is not appropriate for universities or other academic institutions like the Hutchinson Center. There are two places in the country that specialize in high-throughput, high-quality-control genomic technologies — one is the Broad Institute in Cambridge, Mass., and the other is TGen in Phoenix.

CN: How does your role in Phoenix relate to your role at the Hutchinson Center?
LH: Some time ago, I gave up my laboratory at the Center because I found it incompatible with my role as Center director. I found that I could not run a laboratory research program part time. Since then, I have tried to contribute to medical science by promoting the field of biomarker discovery. This is another manifestation of that effort and is being handled much like other investigators at the Center who are collaborating with other institutions. A subcontract from TGen to the Center will cover my time.