October 1, 2009 (Vol. 29, No. 17)
Jonathan Simons M.D.
Research-Funding Model Being Used to Bankroll Potential Breakthrough Discoveries
In healthcare reform, policymakers need to appreciate that true cost savings can be best achieved through accelerated research that ultimately allows us to cure more and treat less. It is time for a careful examination of the institutions and the processes that allocate resources for medical research, with the aim of giving greater emphasis, and more funding, to research that can deliver better patient outcomes.
One problem inherent in government-funding mechanisms in place today is the tendency to promote only the safer projects and not the more risky research projects that could lead to new approaches to prevention, treatment, and, ultimately, a cure.
We believe that a well-proven mechanism already exists in a venture philanthropy model pioneered at the Prostate Cancer Foundation (PCF) and adopted with demonstrable success by other philanthropic organizations supporting research including the Lance Armstrong Foundation (testicular cancer), the Michael J. Fox Foundation (Parkinson’s disease), The Multiple Myeloma Foundation, the Melanoma Alliance, and others. Applying the principles of venture philanthropy more broadly—preferably (and most expediently) through extant organizations—should maximize the value returned on our research investments.
Perhaps the first principle of venture philanthropy is that there are no universal rules. Venture philanthropy has its roots in the worlds of business and finance, where success depends on the ability to spot the opportunity that others have overlooked. Each situation is unique and must be approached without preconceived solutions.
Leverage has gone from darling to pariah in financial circles, but it remains essential to success in venture philanthropy. In this context, success requires finding ways to encourage innovation and avoid inertial and negative thinking by leveraging the specialized knowledge of a motivated community of interest.
Notwithstanding the first principle stated above, that there are no universal rules for judging innovation, certain patterns have emerged in the 16 years we have practiced venture philanthropy that seem to have general applicability, at least as a framework for analysis. We have explicitly followed six principles in the funding programs we have created:
- Eliminate the endowment model: rather than building interest equity, build urgent discovery equity. A cash in, cash out model puts resources where they are most needed for patients, with the most valuable return on investment—progress. The PCF is in business of putting itself out of business, not building a self-perpetuating organization.
- Streamline the funding application process: time is money. Traditional grant applications can be hundreds of pages long and their preparation often consumes an unjustifiable amount of researchers’ time. As William Strunk Jr. stated in The Elements of Style, vigorous writing is concise. A cogent research plan can be evaluated in five pages or less. Thus, our applications are strictly limited to a five page maximum. We take no more than 30 days for review and approval, and we make funds available within 60 days of approval.
- Demand information sharing and encourage collaboration: the traditional process of peer review and publication, while fulfilling an absolutely vital role in the scientific process, can impede the free flow of information and slow progress toward vital new discoveries. All researchers receiving funds from the Prostate Cancer Foundation must agree to share their results freely within one year of funding at our annual scientific meeting, regardless of publication status.
- Actively recruit the best and brightest young minds into the field: talented young scientists must be attracted to a field of research early in their careers when they are making choices that typically last a lifetime.
- Encourage flexibility and mid-course adjustments: it is fundamental to the discovery process that new results suggest new directions for investigation. Use of funds in exploration of promising new leads should not be delayed by requirements for re-review and approval. If we approved the original application, we should trust the scientific judgment of the investigator and not waste time with reapplication for changes suggested by new findings.
- Encourage and reward game-changing hypotheses and innovative new research methods: large institutional and government funding programs are well-suited to supporting advances that ultimately constitute the vital aspects of incremental scientific progress. However, they may not be the best way to liberate breakout ideas, discoveries that can transform a field and generate new therapies and cures that can make an urgent impact in the lives of so many.
Products in Development
A novel microfluidic MEMS device developed by Daniel Haber, M.D., Ph.D., and Mehmet Toner, Ph.D., of Harvard/ Massachusetts General Hospital to detect circulating tumor cells (CTC) provides an excellent example of the research underwritten and results generated with venture philanthropy funding from the PCF.
CTCs are present at low levels in the bloodstream of cancer patients—as low as one in a billion cells. Current detection methods successfully detect CTCs in only half of samples known to contain them. Typically they capture only one CTC per mL of blood, and CTCs constitute only 0.1% of all captured cells. The presence of so many nonCTC cells interferes with characterization, and the detection process usually kills the cells, preventing culture.
The new device consists of approximately 80,000 microposts covered with antibodies against the epithelial cell adhesion molecule (EpCAM), permitting them to selectively bind CTCs. The bound cells are visualized with fluorescent staining and optical microscopy. The device enables a simple blood test to detect and characterize the CTCs responsible for metastasis. Staining techniques for specific molecules such as prostate specific antigen provide reliable confirmation of the source of the CTC.
Although not yet approved for clinical use, the device has the potential to play a key role in numerous aspects of cancer diagnosis and treatment including detecting and evaluating metastatic disease, selecting and individualizing initial surgical and medical therapies, monitoring disease progression, detecting the occurrence of therapy-induced mutations and the consequent development of resistance, and understanding the fundamental biology of metastasis.
The CTC detector is a single example of the many breakthrough discoveries supported with venture philanthropy funding. During the last 16 years, venture philanthropy has played a transforming role in moving prostate cancer research from what was essentially a scientific dead end to one of the most active and productive areas of cancer research. While this is significant progress, urgent needs for practical solutions remain.
The demonstrated success of the venture philanthropy model clearly warrants a larger role for innovative investment strategies focused on delivering game-changing results with tangible value.
Jonathan Simons, M.D. ([email protected]), is president and CEO of
the Prostate Cancer Foundation. Web: www.pcf.org.