News and Publications

Year In Review - 2000

President's Introduction

his has been a year of significant transition at The Scripps Research Institute, all the while maintaining its impressive array of scientific accomplishments, facilities expansion to accommodate ongoing growth, and important new faculty appointments. Sadly, this year marked the passing of TSRI's Dean of Graduate Studies and Chairman of the Department of Cell Biology, Norton B. Gilula, Ph.D., after a valiant struggle with cancer. While he has made an indelible imprint on the quality and character of the Institute, we all miss his keen insights, sound scientific judgement, generosity of spirit, leadership ability, and friendship. It is a great loss to the scientific community here.

Jeffery Kelly, Ph.D., Lita Annenberg Professor, Department of Chemistry, and The Skaggs Institute for Chemical Biology, has been appointed Acting Dean, Graduate Studies Program, and Acting Vice President, Academic Affairs, taking over many of Dr. Gilula's responsibilities. While conducting an active program of laboratory studies, Jeff will assist me with policy decisions that relate to the direction of scientific activities at the Institute. In addition, Sandra L. Schmid, Ph.D., has replaced Dr. Gilula as Chairman, Department of Cell Biology. She has been a member of TSRI's faculty for more than 10 years where she has distinguished herself as an outstanding scientist whose work is widely respected in the international scientific community.

TSRI continues to enjoy a collegial and productive relationship with Novartis, which recently granted a five-year renewal on its industrial collaboration agreement with the Institute. Clearly, this arrangement is of paramount importance to the continuation of TSRI's long-range initiatives and we expect many more years of fruitful efforts.

With more than 1,000 manuscripts submitted for publication by TSRI's scientists, it is difficult to single out a small number of scientific accomplishments from this substantial group of discoveries. However, an iteration of a few will connote the breadth of achievements in a multiplicity of research arenas.

Carlos Barbas, Ph.D., Professor, Department of Molecular Biology, and a member of The Skaggs Institute, has developed a method of producing and combining proteins as modular building blocks capable of functioning as genetic switches to turn on or off genes on demand. Barbas calls this "an operating system for genomes." Its goal is to develop a new class of therapeutic proteins that can inhibit or enhance the synthesis of proteins, providing a new strategy for fighting diseases of either somatic or viral origin. The lab is currently developing proteins that may inhibit the growth of tumors, halt HIV, and even make healthier corn. They have demonstrated that they can use their alphabet of proteins to specifically turn on or off genes at will.

A team of scientists studying a human DNA repair enzyme, led by John Tainer, Ph.D., Professor, Department of Molecular Biology and The Skaggs Institute, has discovered an evolutionary adaptation that highlights a fundamental advantage in the way human cells repair damage to their DNA. They have demonstrated that a key DNA repair enzyme is optimized to remain bound to its toxic, damaged DNA products until the next enzyme in the DNA repair pathway can take over. This adaptation allows for DNA repair in human cells to be coordinated between subsequent enzymes in the pathway, rather than having harmful DNA damage intermediates exposed in the cell. This has implications, for example, in cancer chemotherapy regimes because it may be possible to overwhelm DNA repair processes when the amount of damage is very high.

Work in my laboratory this year, in collaboration with Peter Schultz, Ph.D., Professor, Department of Chemistry and The Skaggs Institute, and Director, Genomics Institute for the Novartis Research Foundation, has shown that gradual genetic changes may be the source of many, if not all illnesses of aging, including breast cancer, osteoporosis, Alzheimer's disease and arthritis. The study concludes that human aging and its associated diseases can be traced to a gradual increase in cell division errors in tissues throughout the body. This functional change begins slowly in middle age and increases gradually with advancing age. While scientists had previously believed that aging is a disease in which cells stop dividing, this study suggests that aging is a disease of quality control. With advancing age, altered gene expression results in cells with diminished function. Errors in cell division lead to the altered expression of a collection of key genes in the cells. Altered gene expression gradually causes the loss of tissue function which results in aging.

Researchers led by Chi-Huey Wong, Ph.D., Professor, Department of Chemistry and The Skaggs Institute for Chemical Biology, have a new tool to address the growing problem of antibiotic resistance. They have focused on aminoglycosides, a family of antibiotics that includes such drugs as neomycin. Bacteria, which create the proteins they need to survive, are constantly evolving and mutating in ways that circumvent the activity of antibiotics. To circumvent the problem, Wong has found a way to bind the antibiotic to the bacteria's RNA. This prevents the formation of proteins that allow the bacteria to become resistant to antibiotics. The approach could yield a drug 1,000 times more effective than the original antibiotic.

The buildout of the facility to house the new Institute for Childhood and Neglected Diseases continued this year with the first scientists expected to take occupancy of their laboratories in January, 2001. When fully occupied, this facility will house some 150 scientists and support staff. John and Rebecca Moores' unique contribution of a collection of 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 institute.

Scientists and clinicians selected to participate in The Skaggs Clinical Scholars Program, established with a contribution of $2 million from the Skaggs Family, have completed their first year of collaboration. Chaired by Ernest Beutler, M.D., Chairman, Department of Molecular and Experimental Medicine, 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 a TSRI scientist. The broader goal is to expand the body of knowledge related to human disease and to develop effective therapeutic interventions.

A number of prominent researchers joined the scientific staff at TSRI this year, bringing the number of faculty members to more than 275. They include Joel N. Buxbaum, M.D., former Professor of Medicine, NYU School of Medicine; Bruce Beutler, M.D., former Professor, University of Texas Southwestern Medical Center at Dallas; Dong-Er Zhang, Ph.D., former Assistant Professor, Department of Medicine, Harvard Medical School; Heidi Stuhlmann, Ph.D., former Assistant Professor, Brookdale Center for Developmental and Molecular Biology, Mount Sinai School of Medicine; John R. Yates, Ph.D., former Associate Professor, Molecular Biotechnology, University of Washington; Mark R. Mayford, Ph.D., former Assistant Professor, Department of Neurosciences, University of California, San Diego; Aniko Bartfai, Ph.D., former Associate Professor, Department of Psychology, Stockholm University; Ulo Langel, Ph.D., former Associate Professor, Department of Neurochemistry and Neurotoxicology, Stockholm University; and Geoffrey Chang, Ph.D., who recently completed a postdoctoral fellowship at CalTech.

This year, as in years past, numerous TSRI faculty have been recognized by their peers with prestigious awards and honors. K. Barry Sharpless, Ph.D., Professor, Department of Chemistry and The Skaggs Institute, has been selected to receive the National Academy of Sciences Award in Chemical Sciences. The prize is awarded for innovative research that contributes to a better understanding of the natural sciences and to the benefit of humanity. Ian Wilson, D.Phil., Professor, Department of Molecular Biology and The Skaggs Institute, has been elected to fellowship in the Royal Society, the independent scientific academy of the UK founded in 1660, dedicated to promoting excellence in science. Chi-Huey Wong, Ph.D., Professor, Department of Chemistry and The Skaggs Institute, has been selected to receive a 2000 Presidential Green Chemistry Challenge Award, jointly presented by the Director of the U.S. Environmental Protection Agency, the Director of the White House Office of Science and Technology and the President of the American Chemical Society. The award program provides national public recognition for organizations that are successfully researching, developing and implementing outstanding green chemical technologies.

As we enter a new millennium, I feel that TSRI is in a unique position to exploit the riches of the sequencing of the human genome, to expand on the prodigious body of knowledge elucidated by our own faculty, to play a role in training the next generation of scientists through the Graduate Studies Program, and to ultimately have a positive effect on alleviating human suffering.

Richard A. Lerner, M.D.