Philip Needleman, PhD, has accepted an appointment as associate dean, focusing on BioMed 21 initiatives.
BioMed 21 is a redirection of thinking about how knowledge moves from the laboratory to the hand of the physician at the patient’s bedside and how observations can be conveyed more effectively from clinicians to researchers.
We always have thought it important to be surrounded by more people who are actually doing genomics and who are using the information and technology in an applied way.” RICHARD K. WILSON, PHD
“Genes are critical to our predisposition to disease and to the safety and efficacy of drugs. Genetic studies increasingly will become a key component of clinical investigation.” KENNETH S. POLONSKY, MD
“Today, we’re diagnosing and treating diseases when they present clinically. Tomorrow, we’ll be deciding who is genetically predisposed to specific conditions, and we will be visualizing the underlying mechanisms that bring about those diseases, which will allow us to develop better treatments.” R. GILBERT JOST, MD
TO ANY LIST OF MOMENTOUS DATES in the history of life sciences at Washington University, 2003 must now be added as the year in which BioMed 21 debuted. From the 1909 Abraham Flexner visit that fueled a redefinition of American medical education through the completion of the Human Genome Project in 2002, few events have had the impact predicted for BioMed 21.
It is an initiative that will reshape university culture over the next 10 years to catalyze and support emerging forms of bioresearch and rapidly convert the knowledge of the genetic blueprint into effective, individualized treatments. Here’s what some of this new direction’s architects say about it:
Mark S. Wrighton “BioMed 21 represents a new paradigm in basic and life science research...we will address the most important questions in biomedical science and translate our findings into new therapies and potential technologies.”
Larry J. Shapiro “Resources channeled through BioMed 21 will enable Washington University scientists and physicians to harness genomics and other evolving disciplines to diagnose diseases more accurately, cure diseases more effectively, and care for patients more appropriately.”
Edward S. Macias “BioMed 21 will fuse our Hilltop engineering and arts and sciences faculty and medical campus faculty into teams with intellectual and technical vigor, poised to make discoveries that can enhance our effort to improve human health.”
Jeffrey I. Gordon “BioMed 21 reflects a transcendent view of the intellectual and technical resources of this university and is the beginning of a cultural revolution. We have the opportunity to define ourselves at a level of molecular detail formerly reserved for simpler organisms. This will provide new understanding of our evolution, our normal biology, and the origin of many of our common diseases.”
Mark Johnston “In 1953, the discovery of the structure of DNA brought biologists to the threshold of an understanding of the molecular basis for life. Fifty years later, with the blueprint of our species in hand, we find ourselves standing on a new threshold that beckons practical applications that will benefit humanity. We must walk boldly across that threshold.”
To successfully cross that threshold, make those discoveries and develop those therapies, BioMed 21 advances on many fronts:
• It collects and dedicates more than $300 million in resources. Included is NIH support, such as the newly announced $130 million, three-year award to Richard K. Wilson and the Genome Sequencing Center (GSC) that funds efforts to decipher the genome of nonhuman species, including the chimpanzee. Gifts from friends and supporters already include an endowment from the Danforth Foundation for start-up funds to stimulate research and a gift from John F. McDonnell and the JSM Charitable Trust to endow four new professorships. A gift from Dr. and Mrs. Philip Needleman will establish the new Philip and Sima K. Needleman Professorship.
• It is a building program that defines new spaces to house emerging interdisciplinary basic and clinical research programs, beginning with the $13.5 million reconstruction of existing space adjacent to the GSC to facilitate interactions between basic scientists, clinicians and the GSC. Later will come the construction of a $150 million, 250,000-square-foot building dedicated to translational research, to be built in stages. Bridging the basic and clinical sciences, the new building will be located in the center of the medical campus, near the new $37 million Farrell Learning and Teaching Center that is an important teaching component of BioMed 21. Also included is an $18 million, 40,000-gross-square-foot facility at the corner of Clayton and Taylor avenues designed to spur development of mouse models for human diseases.
• It’s also a faculty development program that will add more than 50 faculty members in areas including, but not limited to, patient-oriented research and imaging sciences.
• Concomitantly, a similar number of new students will join the student body. “The PhD, MD and combined MD/PhD students who train under the banner of BioMed 21 will be critical to its success. They will export technology and ideas as they develop their careers under this new, interdisciplinary paradigm,” says Philip D. Stahl. “Training young bio-- medical-scientists and physician-scientists will provide a substantial and long-term return on our investment.”
• BioMed 21 is a redirection of thinking about how knowledge moves from the laboratory to the hand of the physician at the patient’s bedside and how observations can be conveyed more effectively from clinicians to researchers.
• Perhaps most tellingly, it’s the creation of a new “intellectual space,” in Gordon’s words. At a university known for its collegiality and cross-disciplinary collaboration, BioMed 21 calls for unprecedented levels of cooperation between the broadest range of academic endeavors—from physics to pharmacology, from engineering to evolutionary biology.
Early plans for the structure of BioMed 21 aim to establish three new research units accessible to interested faculty members on both campuses: The Center for Genomics and Human Genetics, the Division of Clinical Sciences, and the Center for Biological Imaging. The conceptual nucleus around which these three new units orbit is to build upon the work of the Human Genome Project to rapidly advance the diagnosis and treatment of human illnesses.
THE FIRST PHYSICAL STEP toward BioMed 21 is the creation of a pilot program in the Center for Genomics and Human Genetics. Five researchers will relocate their laboratories into close proximity to the Genome Sequencing Center in the 4444 Forest Park Avenue Building. Gordon and Johnston, whose laboratories will be among the first to move, call this new arrangement an “intentional community.”
“We always have thought it important to be surrounded by more people who are actually doing genomics and who are using the information and technology in an applied way,” says Wilson. The five investigators, brought into contact with the GSC, will devise new ways to mine the data generated there.
They also hope to encourage other investigators to bring their innovative ideas to the GSC under the umbrella of a feasibility pro--gram that would support generation of preliminary data by the sequencing center—data that could be used as the foundation for new grant applications.
More broadly, members of the center will use comparative genomics to study the evolution of life on our planet and pursue research in systems biology, an emerging field that combines computational methods with quantitative experimental methods to examine the origins, structures and functioning of the complex genetic and molecular networks that regulate normal cellular functions.
Faculty and students in the center and others in the broader
university hope to use this information to gain new understanding about
how network disruption leads to disorders such as diabetes, obesity, cancer,
cardiovascular disease, Alzheimer’s
The center will function as a proving ground for developing strategies to effectively assemble, mentor and reward members of teams that work at the interface of multiple disciplines. Center members also hope to catalyze development of high-end computing resources and new software tools, as well as a core curriculum in systems biology, that would be distributed to medical school and Hilltop graduate programs.
THE SECOND UNIT OF BIOMED 21 to be established as a cross-department and cross-campus division modeled after the Division of Biology and Biomedical Sciences, is the Division of Clinical Sciences (DCS). Put simply, Kenneth S. Polonsky says the division’s purpose is “to improve the performance of patient-oriented investigation.”
By which Polonsky means two types of research studies. The first are those that move basic science insights into the clinical realm, striving to understand in the most practical terms why people develop diseases and how to treat those diseases. These include trials of pharmaceuticals and the effectiveness of biomarkers. The second type looks into treatment outcomes and epidemiology. By employing new genetic and imaging techniques, clinician scientists will learn to “stratify” patients, classifying them by phenotype and genotype to determine which drugs are most likely to be effective and cause the fewest side effects in a given individual.
“To be successful, we must do three things,” Polonsky says. “We must recruit eminent faculty who are experienced at doing patient-oriented research, both in- and outpatient. Then we must provide them with the core resources to perform their research, developing facilities for small-scale genetic studies as well as scanning and imaging capabilities. Finally, we need to train a new generation of physician-scientists who answer important biological questions in human subjects.”
Polonsky points out that the university has in place the NIH-funded General Clinical Research Center that supports clinical research performed there, and the Center for Clinical Studies that offers infrastructure for negotiating contracts, locating patients, providing nursing and coordination—two advantages that enhance the new division’s position.
An essential part of many of the trials to be conducted in the DCS is determination of the genetic makeup of the individuals participating, and Polonsky says close ties to the new Center for Genomics and Human Genetics are therefore vital, along with the involvement of the university’s clinical departments and the Department of Genetics. “Genes are critical to our predisposition to disease and to the safety and efficacy of drugs. Genetic studies increasingly will become a key component of clinical investigation,” he says. A key person in the DCS will be the individual recruited to fill the newly endowed Philip and Sima K. Needleman Professorship.
CENTRAL TO ADVANCES in genomic science, in diagnosis and treatment and in patient-oriented research are emerging imaging abilities from BioMed 21’s third unit, the Center for Biological Imaging. “Today, we’re diagnosing and treating diseases when they present clinically. Tomorrow, we’ll be deciding who is genetically predisposed to specific conditions, and we will be visualizing the underlying mechanisms that bring about those diseases, which will allow us to develop better treatments,” says R. Gilbert Jost. “We’ll see more medical developments in the next 10 years than we’ve seen in the past 50.”
He and others have identified two principal missions for the imaging center. Researchers will work to develop technologies that reveal much smaller details, moving from being able to resolve marble-sized anatomy to being able to make in-formation-filled images of cells and even individual molecules. The creation of sophisticated radiopharmaceuticals that target and illuminate specific cell populations or behaviors requires the work of talented chemists, and high-field-strength imaging devices need input from physicists, Jost says. Already in the works: desktop sized MRI, CT and PET scanners dedicated to imaging changes in living animal models as small as mice. Light microscopes also are evolving to provide investigators with the ability to observe physical processes in living animals.
The center also will establish a clinical arm, a new leading edge imaging facility dedicated to clinical research and located at Barnes-Jewish Hospital to support clinical trials for both in- and outpatients.
“That will be a facility unlike any other,” Jost says. In such an application, imaging can shortcut decisions about a drug’s effectiveness. Using sensitive scanners, tiny changes—in the size of a tumor, for example — that are otherwise undetectable can be closely measured and compared, quickly providing insights into a drug’s efficacy.
“Quick insights”: two words that describe much about BioMed 21. Ultimately, all of the initiative’s elements are designed to work together in support of one another, so that the whole is greater than the sum of its parts, so that what we learn readily becomes what we practice. It represents a way of organizing around the biggest questions in medical science, and it is an example of form following function, as a new web of intentional interactivity is devised to probe the network of thousands of genes and their proteins interacting with the environment to cause disease. And then to more quickly and effectively deliver all that we learn to patients for the benefit of their health.
Quoted in this story:
Mark S. Wrighton, PhD
Larry J. Shapiro, MD
Edward S. Macias, PhD
Jeffrey I. Gordon, MD
Mark Johnston, PhD
R. Gilbert Jost, MD
Kenneth S. Polonsky, MD
Philip D. Stahl, PhD
Richard K. Wilson, PhD