About 10 million people around the world will die of cancer this year. Three million more will lose their life to AIDS. How does a biomedical research institution like Fred Hutchinson decide on the best ways to organize and fund its research efforts toward mitigating these and other global-health issues?
The center's scientific division directors and faculty members enjoy the freedom to set research agendas based on their interests and expertise, a system that has earned Fred Hutchinson its stature as world-class cancer center. But to launch broad scientific initiatives that build upon this stellar research base, a team of division directors, senior leadership and faculty must draw together their diverse perspectives together and chart a path to acquire the necessary resources.
Through a strategic-planning effort of this kind that began in June in collaboration with the Board of Trustees, the team has identified four research initiatives-early cancer detection, immunotherapy, tumor research and global health-that are natural outgrowths of existing center research and that draw on the expertise of numerous faculty from all divisions, said Dr. Lee Hartwell, center president and director.
"Our most important ongoing strategic initiative has been and will continue to be to support our faculty and their innovative research," he said. "Each faculty member builds his or her career and contributes to science by formulating and implementing their own scientific objectives.
"But given that we have an overarching institutional mission to eliminate cancer as a cause of human suffering and death, we also need to develop and support those areas of research most promising for our mission.
"For example, as a comprehensive cancer center, we must extend our excellence in leukemia research and treatment to solid tumors. We have a strong base of public-health scientists with solid tumor research programs, and we've formed partnerships with the University of Washington and Children's Hospital and Regional Medical Center to help us accomplish this goal.
"The center is already at the forefront of research to exploit the human immune system to fight cancer, a discovery that emerged from transplantation studies in the Clinical Research Division. We've recently created new shared resources that enable our researchers to manufacture and test these therapies. And our investigators lead and coordinate multiple global efforts to identify and test vaccines and other preventive measures for HIV/AIDS, and we've begun to establish new research collaborations in the Pacific Rim."
The initiative on early-detection research, Hartwell said, emerges from the evidence that diagnosing cancers early makes the greatest impact on survival and is a natural direction for a cancer center to pursue. Early detection is already an active area of research in the center's four scientific divisions, with projects underway by Drs. Nicole Urban, Martin McIntosh, Ruth Etzioni, Mark Roth, John Potter, Pete Nelson, Jerry Radich, Paul Lampe and others.
In addition, Hartwell said that the information now available from the Human Genome Project and the development of new techniques for conducting large-scale analyses of genes and proteins make the time ripe to capitalize on this exciting area of study.
Providing support for the new shared resources, pilot projects, fellowships and faculty recruitments and salary for each of these areas will require an influx of new funding-and creative new strategies to bring in that money, said Peggy Means, senior vice president for strategic development. More than $35 million of the annual budget now goes toward these expenses, an amount that has grown as the center has increased its commitment to providing faculty salary support.
Beyond federal funds
Until now, Means said, Fred Hutchinson has relied largely on federal grants or has raised primarily unrestricted funds from donors to fund these costs and new ventures. But the National Institutes of Health's leaner budget and a sluggish economy means that the center must rely more heavily on initiative-based fund raising.
"We will continue to fund our existing programs at their present levels, but there are many exciting new directions our faculty want to pursue that are very expensive and that we won't be able to support in the way we have in the past," she said. "To develop these new areas, we have to focus on strategic fund raising and partnerships, an effort we are undertaking with our Board of Trustees and Foundation Board."
Shift in thinking
Trustee Bob Gerth said that the scientific areas that have been selected for inclusion in the planning process are only a part of the science that makes the center a distinguished institution.
"Other areas of the center's science represent prominent and highly effective research areas," he said. "Those areas have therefore not been included in the current process as it is felt that they already have strong momentum and do not require the kind of strategic review that we're undertaking with the areas of focus."
Means said that strategic fund raising requires thinking about the work the center does in different ways.
"Part of our maturation as an institution is to be able to articulate our scientific goals in ways that motivate donors," she said. "We have to organize ourselves in ways that provide more accountability and feedback to potential investors in our work. In addition, we anticipate that some of the most expensive technology tools can best be obtained through partnerships with other institutions and with industry."
Gerth said that the present is a particularly important period for the center and its partner institutions to be conducting this type of planning.
"The opportunities for success have never been greater, but the specifics of how to cooperate and what techniques to prioritize are more complex and costly than ever before."
Fred Hutchinson's four research initiatives
The four initiatives capitalize on the center's strengths in laboratory-based, clinical and public-health research and will involve researchers from each scientific division. Here are descriptions of the initiatives and some examples of divisional connections. Future Center News articles will address each of these areas in more detail.
The immunotherapy initiative seeks to develop immune-based approaches for treating cancer and other diseases. The center's bone-marrow transplantation researchers were the first to discover that donor immune-system cells can eliminate cancer cells in patients with leukemia. Scientists in the Clinical Research Division have exploited this phenomenon to develop a modified transplantation technique called the "mini-transplant" and have adapted components of the immune system, including antibodies and T cells, to attack tumor cells.
"Our scientists are among the country's leaders in using antibodies to target radiation and chemotherapy to cancer cells, and we are continuing to build on this antibody-based research," said Dr. Fred Appelbaum, director of the Clinical Research Division.
Members of the division also have pioneered the use of T cells as search-and-destroy troops for melanoma and other diseases.
"We'd like to continue and expand these studies-but they are very labor- and cost-intensive," Appelbaum said. "It involves money to support doctors, nurses, facilities to manufacture these therapies and the costs associated with complying with the regulations required to test them. Raising money for this research is essential to our ability to build our strength in this area."
The early-detection initiative seeks to identify protein signatures in the blood that foretell the risk, presence and prognosis of cancer or other diseases. Many of these studies are based on the emerging field of proteomics, the study of all of the proteins produced by an organism. This initiative depends on laboratory researchers to identify cancer-specific proteins, biostatisticians to interpret large sets of data, epidemiologists to compare protein signatures of healthy people and those with cancer and clinical researchers who will use new diagnostic and prognostic tests in the clinic.
Much of the basis for understanding the earliest events of cancer will emerge from studies of model organisms such as fruit flies or worms, said Dr. Mark Groudine, director of the Basic Sciences Division.
"Studies of the fundamental mechanisms that control how and when cells divide have yielded major insights into cancer," he said. "Using this approach, researchers in the Basic Sciences Division have identified several key proteins that are misregulated in cancer cells. Indeed, these very insights provide the candidates that will be targeted in the early-detection initiative."
In addition, Groudine said that basic research on how cell lineages arise from single cells-a situation analogous to how a tumor develops from a single cancer cell-would provide insight into the early stages of cancer development.
Dr. John Potter, director of the Public Health Sciences Division, noted that cancer is a complex and time-dependent process that occurs largely in older individuals.
"Because cancer takes place in genetically and behaviorally heterogeneous populations, the signals that emerge, even from early lesions, are likely to be complex and involve multiple biologic pathways," he said. "This means that to understand the process fully and to develop robust markers, it will be necessary to monitor large numbers of individuals at multiple time-points for periods of years."
The global-health initiative seeks to increase the center's research efforts on health problems that affect vast segments of world. Fred Hutchinson already leads the HIV Vaccine Trials Network, an international effort to develop and test preventive vaccines; houses the Statistical Center for HIV/AIDS Research and Prevention, which collects, manages and analyzes data from international clinical trials and behavioral studies to eliminate HIV as a threat to human health; and engages in numerous international research collaborations for the study and prevention of cancer.
Potter said that as a world leader in cancer prevention, the center is now committed to devoting more resources and effort to developing cancer-prevention and screening strategies that can be easily adopted by developing countries.
"For example, we've got a good screening strategy for colon cancer-colonoscopy-but it is expensive," he said. "We've got to develop accurate screening and early detection methods for the world's prevalent cancers that are cheaper and that will work in developing countries, where rates for many cancers are extremely high and rising."
The Tumor Research initiative aims to build strong laboratory-based and treatment-based programs that focus on cancers affecting organs and tissues other than the blood. Such studies will complement Fred Hutchinson's bedrock of leukemia research and its epidemiological and genetic studies of breast, ovarian, prostate and other solid cancers.
Dr. Barbara Trask, director of the Human Biology Division, said that research on solid tumors is already an established area of research in numerous center laboratories. Among the findings to emerge from this work are the discovery or analysis of genes that play a key role in pre-disposing individuals to breast, prostate and pancreatic cancer.
"More than half of the faculty in Human Biology is involved in some aspect of solid tumor research," she said. "Fund raising to expand this area is critical for the center to achieve the same world-class recognition for its research on the prevention, diagnosis and treatment of solid tumors as it has earned in hematological (blood) cancers."