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TSRI Scientific Report 1998-1999


President's Introduction

Richard A. Lerner, M.D.

Private philanthropy continues to have a central role in defining the shape and character of The Scripps Research Institute as well as other major research universities throughout the United States. As a nation, we can take pride in our unparalleled record of generosity. In 1998, individual donors contributed almost $135 billion, and between 1996 and 1998, total giving increased by more than $41 billion.

In the biomedical sciences, private contributions are particularly important to fields of study that thrive on bold new ideas and strategies. Funding new opportunities in emerging fields--including genomics, interfaces between disciplines, neurosciences, and translational research--is an important way in which private philanthropy can increase its impact. In addition, providing funding for young scientists at the beginning of their careers can have high payoffs and far-reaching implications.

This outpouring of generosity and interest on the part of the American public in investing in biomedical research comes at a uniquely opportune time in the history of scientific discovery. Today, scientists in large numbers around the globe are in the midst of a new and exciting process of charting the innermost regions of the human body, the most complex and inherently unknowable region in the universe. Scientists at TSRI will build on their prodigious accomplishments in molecular biology, cell biology, structural biology, computational chemistry, and bioorganic chemistry to exploit the discoveries from biology's most important and ambitious effort: the Human Genome Project. All human genes are expected to be deciphered in the next several years. With the language of the genome as a common currency, the science of biology will flourish as never before.

Positioning themselves for the time in which the entire DNA sequence will be determined, scientists at TSRI will help bridge the gap between known DNA sequences and the mechanisms that underlie disease by determining the function of gene products. As much as is already known, we are in the very early stages of genomics research. Here, we will expand on the body of knowledge developed in our laboratories to bring resources to bear on these disciplines of the "postgenomic" world.

Forging new areas of research, creating new opportunities for collaboration, takes courage, the spirit of innovation, and funding. The work is often long-term and unpredictable. The riskier the venture, the more unlikely the project will be funded by the federal government, making the role of private philanthropy even more important.

At TSRI, we are indeed fortunate to count a number of remarkable philanthropists as true partners in the scientific endeavor. The effects of the extraordinary generosity of the Skaggs family in establishing The Skaggs Institute for Chemical Biology have already been felt in a significant way throughout the institution. With a full complement of 25 principal investigators, the Skaggs Institute supports research in 5 departments; their specific areas of concentrated effort and broad expertise include nucleic acid dynamics, protein structure, antibody catalysis, and organic synthesis. Although the ultimate goals for research at the interface of chemistry and biology are cures for diseases and the improvement of human health, many of the scientists' efforts are focused on basic science, providing scientific underpinnings for the next generation of molecules targeted against disease. A newer initiative made possible by the Skaggs family will more closely integrate clinical and basic research within the Scripps organization. The Skaggs Clinical Scholars Program has already begun to refocus basic research discoveries on human conditions and to instill a new sense of camaraderie between clinicians and basic researchers in the shared task of applying research to alleviate human disease. An initial group of Skaggs Scholars has been selected, and the work has begun in earnest.

Planning also continues for TSRI's new Institute for Childhood and Neglected Diseases, with the recent purchase of a 53,000-square-foot facility on a 4.5-acre parcel on the east side of North Torrey Pines Road. The unusual lead gift for this new effort--a collection of 26 exceptional automobiles--was contributed by San Diego Padres owner and businessman John Moores and his wife, Becky. A subsequent gift, a collection of important U.S. coins donated by the Moores, was recently auctioned, and the proceeds will fund the new initiative. The Institute for Childhood and Neglected Diseases will build on the strength that TSRI has achieved at the nexus of biology and chemistry through the Skaggs Institute to apply the new molecular understanding of biology to address, reduce, and treat recalcitrant illnesses in 2 major categories: childhood diseases and neglected diseases that affect populations primarily in developing countries.

A $10 million commitment from Helen L. Dorris of San Diego, founder of the Harold L. Dorris Neurosciences Foundation, has enabled TSRI to establish the Harold L. Dorris Neurological Research Center. The largest contribution that TSRI has received for furthering research in the neurosciences will help to foster rapid advances in the fundamental understanding of the brain. Under the leadership of the Center's recently appointed director, Tamas Bartfai, Ph.D., former head of CNS research at Hoffmann-La Roche, Basel, Switzerland, the Center will bring a dedicated effort to providing education and conducting research on neurologic disorders, including schizophrenia and Alzheimer's disease, and to advancing knowledge of the how the brain ages.

Sustaining the progress of medical research is an enterprise that depends on a productive and collaborative partnership between scientific research organizations, the federal government, and private philanthropy. We as an institution are particularly grateful to those individuals who understand in a deep and profound way the difference one person can make in the life of an organization, and we stand in awe of the dedication and generosity of such individuals.


Senior Vice President's Overview

William H. Beers, Ph.D.

This past year was another year of substantial growth, impressive scientific accomplishment, and important new faculty appointments at The Scripps Research Institute. In addition, on the 10th anniversary of the founding of its graduate program, TSRI received significant validation of its position in the academic arena. This past year, on the basis of a survey sent to department heads and directors of graduate studies at universities throughout the United States, the TSRI graduate program was ranked by U.S. News and World Report as one of the finest in the country. Kudos to Dean Norton B. Gilula for his leadership in creating a program that after the short period of a decade so successfully competes with programs at the most elite American universities.

A facility to house TSRI's new Institute for Childhood and Neglected Diseases was purchased this year. The facility will house some 150 scientists and support staff when it is completed and occupied in January 2001. John and Rebecca Moores' unique contribution of a collection of 26 rare automobiles and a collection of important U.S. coins was auctioned on TSRI's behalf, the proceeds of which have provided the lead gift toward the establishment of the next institute.

Neuroscientist Tamas Bartfai, former head of CNS research at Hoffmann-La Roche, Basel, Switzerland, was named director of the newly established Harold L. Dorris Neurological Research Center at TSRI. In addition, he will hold the Harold L. Dorris Chair in Neurological Research. The Center was formed last year with a $10 million commitment from Helen L. Dorris of San Diego to conduct research and provide education on neurologic disorders, including schizophrenia and Alzheimer's disease, and to advance knowledge of the process of aging of the brain.

TSRI scientists continue their prolific publication of important research results in prestigious scientific journals. This year, for example, a research group led by David Cheresh studied an investigational antiangiogenesis treatment, previously used against various forms of cancer, to assess the impact of the treatment on arthritic disease in an animal model. The results provided evidence for a central pathogenic contribution of angiogenic blood vessels to the maintenance and severity of arthritic disease and the potential usefulness of antiangiogenic therapy for the treatment of rheumatoid arthritis.

An article by Luca Guidotti and Francis Chisari published in Science proposes a new concept in viral immunology, namely that the immune system can cure viral infections without destroying the infected cells. Until now, scientists thought that viral clearance was due to the destruction of infected cells by cytotoxic T cells. This study indicates that nondestructive antiviral mechanisms can contribute to viral clearance by eliminating a virus from inside the cell without killing the cell.

Chi-Huey Wong and his colleagues devised a computer program for creating a range of oligosaccharides in a single simple reaction, a "1-pot" operation. Scientists think that speeding up the synthesis can help delineate the precise roles of these sugar chains. Dr. Wong and his group simplified the process of carbo-hydrate synthesis by developing a program called OptiMer. Although the technique initially will be used to facilitate reactions used in oligosaccharide synthesis to link sugars, it may be applicable to other types of organic reactions.

A research group directed by Kim Janda developed a portable biochemical kit to detect chemical weapons. Many of the rapid tests currently distributed in portable "suitcase laboratories" rely on the capability of artificially generated antibodies to quickly and accurately recognize specific substances. In the case of sarin, however, no one could obtain antibodies that reacted to this nerve gas. Dr. Janda and his colleagues, however, bound 2 conspicuous molecular fragments to the reactive binding sites of one of the natural decomposition products of sarin, methylphosphonic acid. After this reaction, the nearly spherical methylphosphonic acid molecule became far more noticeable, and the scientists were able to develop specific antibodies that recognize the modified molecules.

The Skaggs Clinical Scholars Program, established last year with a contribution of $2 million from the Skaggs family, selected its initial group of recipients. The goal of the program is to more closely integrate clinical and basic research within the Scripps organization by selecting research-oriented clinicians and funding meritorious collaborative research projects between each clinical scholar and an appropriate TSRI scientist. The broader goal is to expand the body of knowledge related to human disease and to develop effective therapeutic interventions. The method used to award funds is similar to the peer-review system used by the National Institutes of Health.

The 70,000-square-foot first phase of the laboratory building housing the Department of Molecular and Experimental Medicine opened this year, and TSRI scientists will fully occupy the 3-phase project in April 2000. The 5.5-acre, $43 million project in the Torrey Pines Science Park will contain 110,000 square feet of space when completed. The chairman of the Department of Molecular and Experimental Medicine is Ernest Beutler. The majority of studies in the department seek to understand life processes that, when disturbed, lead to disease.

A number of prominent researchers joined the scientific staff at TSRI this past year, as the number of faculty members increased to more than 260. Peter G. Schultz, a former professor of chemistry at the University of California, Berkeley, a principal investigator at Lawrence Berkeley National Laboratory, and an investigator with the Howard Hughes Medical Institute, joined the staff as a professor in the Department of Chemistry and The Skaggs Institute for Chemical Biology. He was also appointed director of the Novartis Institute for Functional Genomics, a discovery-focused research institute funded by the Novartis Foundation. Other new staff members include Ruben Abagyan, a former associate professor in the Department of Biochemistry, New York University; David Nemazee, a former professor in the Division of Basic Sciences, Department of Pediatrics, National Jewish Medical and Research Center, Denver; James C. Paulson, previously the chief scientific officer of Cytel Corporation, San Diego; James P. Quigley, a former professor in the Department of Pathology, State University of New York at Stony Brook; Peter Sims, former associate director and senior investigator, Blood Research Institute, Blood Center of South East Wisconsin; and Raymond C. Stevens, former assistant professor of neurobiology and chemistry, University of California, Berkeley, and senior principal investigator at Lawrence Berkeley National Laboratory.

TRSI scientists have been widely recognized by their peers for outstanding contributions to the scientists' respective fields of study, and this past year was no exception. Bernard M. Babior was elected to membership in the National Academy of Sciences. Election to the academy is considered one of the highest honors that can be accorded a scientist. Francis Chisari received the 1999 Rous-Whipple Award from the American Society of Investigative Pathology. This award, for experimental pathologists more than 50 years old who have had a distinguished career and are continuing to contribute to the field, is one of the most prestigious honors in the discipline of experimental pathology. Richard Lerner was a recipient of the 1999 William B. Coley Award from the Cancer Research Institute for distinguished research in basic and tumor immunology. In addition, Dr. Lerner was awarded the Windaus Medal for his contributions in natural product chemistry. Paul Schimmel was elected to membership in the American Philosophical Society, the oldest learned society in the United States devoted to the advancement of scientific and scholarly inquiry. He also received the Emily M. Gray Award of the Biophysical Society for his contributions to teaching and education in biophysics.

By any measure, the past year was an exceptional one at TSRI. The productivity of the scientific staff continues to increase, and the addition of new faculty creates new synergies and opportunities for novel research investigations. As we approach the new millennium, we are particularly well positioned to make significant contributions to the body of science that will translate to the enhancement of the quality of life.



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