10/4/00

Mark Shwartz, News Service (650) 723-9296; e-mail: mshwartz@stanford.edu

Bio-X awards $3 million in grants for imaginative interdisciplinary research and education projects

Some day, computers will be able to detect diseases inside your body . . . you'll have your own personal vaccine to fight cancer . . . and damaged synapses in your nervous system will be replaced by electronic chips.

Such medical breakthroughs may happen sooner than expected, thanks to a decision this week by the Bio-X program awarding members of the Stanford faculty nearly $3.03 million for innovative biological projects.

Bio-X, a unique faculty-run program designed to promote interdepartmental bioscience research, became a reality one year ago following a $150 million donation from former engineering professor Jim Clark -- the largest single gift to Stanford since the founding grant in 1885. Last spring, Bio-X awarded $7 million in grants to build and upgrade research facilities and laboratories.

At the same time, the newly formed Bio-X Interdisciplinary Initiatives Program Committee called on faculty members to propose imaginative new interdisciplinary, interactive research and educational projects in biology, medicine, computer science, engineering and other disciplines.

On Oct. 2, the committee announced that of 85 proposals submitted, 19 have been awarded seed grants averaging $158,000 over a two-year period. After that, researchers are expected to obtain independent funding, according to committee chair Harvey Cohen.

"One of the key criteria in our decision-making process was that a proposal had to be truly interdisciplinary," says Cohen, a professor of pediatrics in the School of Medicine.

A good example of that approach, he notes, is a proposal submitted by Carlo Tomasi, an assistant professor of computer science, along with Christopher Beaulieu and Sandy Napel, assistant and associate professors, respectively, of radiology in the School of Medicine. Their project -- one of the 19 grant recipients -- combines diagnostic radiology with state-of-the-art-computer imaging.

Over the past few years, Tomasi and his colleagues note in their proposal, medical imaging devices such as CAT scans and MRIs used to take pictures of the inside of the human body have been markedly improved compared with earlier devices. As a result, diagnostic radiologists who interpret the pictures often try to look at as many as 1,000 separate images of a single patient in a few minutes.

"Trying to interpret such a large amount of information accurately and thoroughly is unquestionably beyond human capacity," add the authors. "Fortunately, the information contained in medical images can be 'seen' by tireless and ever more powerful computers if they are appropriately programmed. Going beyond simple programming, we will develop tools that will allow our programs to 'learn' more about human anatomy and the differences between normal and abnormal."

Rather than artificial intelligence, Tomasi and his co-investigators describe their end-product as "augmented human intelligence" -- computers that will assist radiologists in quickly diagnosing diseases and abnormalities.

Another grant went to James Swartz, a professor of chemical engineering, who teamed up with Professors Ronald and Shoshana Levy of the School of Medicine. They proposed to develop a method that would rapidly synthesize patient-specific vaccines to treat a form of cancer known as B cell lymphoma.

"The scientists of the Levy lab have learned how to design a vaccine that recruits the victim's own immune system," Swartz points out.

"The challenge," he notes, " is that each patient needs a new and different vaccine. With conventional technology that new vaccine may take months to produce."

But using a technique called cell-free protein synthesis, Swartz will join with the Levy lab to develop a cost-effective vaccine that can be produced in just one week.

Education

Interdisciplinary education is another major component of Bio-X, explains Cohen, which is why one group received a grant to create a novel course for graduate students in biological and engineering sciences called "Introduction to Medical Sciences."

"The ability to understand human disease at the molecular and cellular level has blurred the boundaries between the basic biological and chemical sciences, engineering and clinical investigation," notes Jane Parnes, a professor of medicine.

"However, as the promise of new technologies for medicine has grown, interdisciplinary training in medicine for bioscientists and engineers has not kept pace," she writes. "We therefore propose to develop a course and potentially a series of courses designed to teach human pathophysiology and medicine to graduate students enrolled in Ph.D. programs in the basic or engineering sciences. The goal will be to equip biomedical scientists/engineers with an understanding of disease sufficient to allow them to optimally identify and pursue areas of medical research in which they can apply their more specialized training to clinical problems.

"Establishing these courses is not a trivial undertaking," she argues, "as the students will come from varied backgrounds and their interests within the scope of human disease might be very different. We have therefore assembled a group of faculty with expertise in medicine, engineering, education and learning methodologies to design a course or courses that will be effective for cross-disciplinary learning, as well as instruments for evaluating the effectiveness of such courses."

The 3-unit course, which may be offered to graduate students as early as Spring 2001, will be coordinated by Parnes; Elizabeth Mellins, associate professor of pediatrics; Charles Kerns and Larry Leifer of the Stanford Learning Lab; and Decker Walker, a professor in the School of Education.

Bio-X also awarded four separate grants to projects designed to determine the molecular structure of proteins, the building blocks of life [see sidebar on Judith Frydman and molecular chaperones].

But not all the proposals involve medicine and human biology. Jeffrey Koseff, a professor of civil and environmental engineering, and Robert Dunbar, a professor of geological sciences, received a grant for studying coral reefs and their impact on world climate change.

"The healthy functioning of coral reefs is of great importance," write Koseff and Dunbar, "not only because of their amazing beauty, but also for the numerous marine organisms that comprise a reef's ecological community. Coral reefs are comparable to terrestrial rain forests in terms of productivity and their immense diversity."

Some researchers believe that coral reefs contribute to global warming by releasing large amounts of carbon dioxide into the oceans, while others contend that reefs actually absorb huge quantities of CO₂ from the sea.

"Although significant research effort has been directed toward resolution of this problem during the past 10 years," say Koseff and Dunbar, "the magnitude and even the sign of the coral reef ecosystem impact on air-sea CO₂ exchange remains unknown. We are, therefore, proposing a 'proof-of-concept'-type study on a reef system in the Red Sea in which we will develop methodologies for accurately determining total carbon, CO_w and alkalinity mass balances for entire reef systems."

A parallel grant focusing on the production of organic material in reef ecosystems was awarded to another research team.

"The committee really feels that these 19 grants will help define where Bio-X is going," says Cohen, "because all of the proposals came straight from our faculty."

"We hope to fund other projects in the not too distant future, if we can come up with additional sources of money," he concludes.

Bio-X Interdisciplinary Proposals Funded Oct. 2000
(listed by Principal Investigator and Proposal)

Fishman, Harvey (Medicine), The Artificial Synapse Chip: A Neural Interface to the Visual System

Utz, Paul J. (Medicine), Development of Biomolecular Microfluidics Systems for Multiplex Analysis of Protein: Protein Interactions

Kim, Daniel (Medicine), Image-Guided Radiosurgery for the Spine and Lung

Bronte-Stewart, Helen (Medicine), An Interdisciplinary Project to Develop a Quantitative, Kinematic Analysis for 3-D Limb Movement in Dystonia

Tomasi, Carlo (Computer Science), Imaging and Learning Techniques for the Detection of Anomalous Structures in 3-D Medical Images

Parnes, Jane (Medicine), Biomedical Science Course Development – Human Pathophysiology and Medicine for Graduate Students in Basic or Engineering Sciences

Frydman, Judith (Biological Sciences), Single-Molecular Probes of Chaperonin-Assisted Folding)

Shafer, Robert (Medicine), HIV Gene Sequence Analysis for Drug Resistance Studies: A Pharmacogenetic Challenge

Monismith, Stephen (Civil and Environmental Engineering), Hydrodynamic Influence on the Productivity of Reef Ecosystem

Koseff, Jeffrey (Civil and Environmental Engineering), Coral Reef Health and Interaction with the Global C Cycle: Innovative Technologies for Assessment

Swartz, James (Chemical Engineering), Rapid Synthesis of Vaccines for Treatment of B-Cell Lymphoma

Swain, Judith (Medicine), The Coccidiodes immitus Fungus: Exposure Modeling and Public Policy Through Favored Soil Habitat and Aeolian Dust Circulation

Luthy, Richard (Civil and Environmental Engineering), Contaminated Sediment Processes and Bioavailability

Kobilka, Brian (Medicine), Single Molecule Analysis of G Protein Coupled Receptor Activation

Latombe, Jean-Claude (Computer Science), Sampling Conformational Pathways

Nishimura, Dwight (Electrical Engineering), Magnetic Resonance Microscopy

Brunger, Axel (Molecular and Cellular Physiology), Automating Protein Structure Determination

Krasnow, Mark (Biochemistry), MSPT Trainee Program – Stimulating MD/PhD Training at Stanford

Smith, Todd (Physics), Investigating Questions of Neurite Differentiation and Actin-Based Cell Motility Using Near-Field Infrared Microscopy

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By Mark Shwartz