It is my pleasure to present the report of the Committee on the Faculty Research Lecture and our nominee for Faculty Research Lecturer. The fifty-ninth annual Faculty Research Lecture will be scheduled for presentation in the spring of 2001.

Our candidate was born in Little Rock, Arkansas. He has a B.S. from Louisiana State University, Baton Rouge. His Ph.D. is from UC Berkeley, and he did postdoctoral work at Berkeley, the Rockefeller Foundation, and Northwestern University. From his days in the Ozarks, he has been and enthusiastic hiker. Since his days in Berkeley, he has been an avid runner. Since 1980, UC Davis is privileged to have him on its faculty.

Throughout his career, our candidate has made chemistry work for him in order to understand the actions of biological molecules and molecular complexes. He has probed and modified enzymes, antibodies and viruses, revealing their secrets and putting them to work in service to the public.

Enzymes are the tens of thousands of distinct proteins that catalyze most of the chemical reactions of an organism. Enzymes are the principal means by which the information of genes finds form and provides function. Our candidate has a knack for discovering new and important, but rare, enzymes. He has charted how these enzymes convert substrates to products. Through diligent and clever organic synthesis, he and his colleagues created numerous compounds that alter or prevent the function of specific enzymes.

Antibodies also are proteins. Antibodies help defeat infections but also can be analytical tools because they bind specific chemical structures. Our candidate has harnessed antibodies to create exquisitely sensitive and specific methods for detecting and quantifying minute amounts of compounds in complex mixtures.

Virus particles are ensembles of nucleic acid, proteins, and other molecules. They infect cells and often cause disease. Our candidate has modified certain viruses to make them useful infectious agents.

The University of California at Davis Faculty Research Lecturer for 2001 is Bruce Dupree Hammock, Professor the Entomology. The outcome of Professor Hammock's efforts has been a wealth of new basic knowledge and a surprising diversity of practical applications. His results have powerfully impacted biology, agriculture, and medicine.

Bruce Hammock has been the author of more than 250 publications in the past decade, with more than 430 for his career to date. He also has more than a dozen patents. Threads, of three decades duration, course through the research of Professor Hammock. We present some details of just one of these threads here.

Bruce Hammock's first publications describe aspects of the metabolism of insect juvenile hormone and related insect growth regulators. Juvenile hormone maintains the caterpillar as a caterpillar. When juvenile hormone levels decrease, the caterpillar ceases feeding and initiates metamorphosis, ultimately leading to the butterfly. In a startling discovery, Dr. Hammock showed that the concentration of juvenile hormone in the caterpillar is partially regulated by precise control of juvenile hormone degradation rather than primarily by control over its synthesis, as had been found for other hormones studied up to that time.

Professor Hammock postulated that hormone degradation is mediated by a highly specific esterase, juvenile hormone esterase. He exploited the 1948 dictum of Linus Pauling concerning tight binding by enzymes of molecules that resemble the transition state between substrate and product. Transition state analogues for juvenile hormone that he designed and synthesized are among the most specific and potent inhibitors known for any enzyme. These inhibitors prevent esterase action and the normal course of insect development. Treated caterpillars maintain their juvenile hormone and continue to feed, growing very large and supporting Dr. Hammock's hypothesis. At this point, the results, in the form of giant caterpillars, were not favorable to crop agriculture.

In a paper in the prestigious journal Science, Prof Hammock described his pioneering work on the use of immobilized transition state analogues to purify low abundance enzymes. Juvenile hormone esterase was purified more than 1000-fold. Prof. Hammock's technology, the use of transition state analogues for affinity chromatography, has been applied to a variety of other low abundance enzymes in many laboratories. Tests with his "affinity purified" juvenile hormone esterase showed that only a few picomoles of this protein would stop caterpillars from feeding and ultimately kill them. Possessing the purified enzyme, Professor Hammock and his colleagues subsequently cloned the juvenile hormone esterase gene.

While on sabbatical leave at Oxford, Dr. Hammock genetically engineered an insect virus, a baculovirus, to produce juvenile hormone esterase when it infects the insect larva. This genetically engineered insecticide led to the precocious production of the insect's own juvenile hormone esterase. The development of this viral anti-feeding agent for insects was the cover story of an article in the journal Nature.

Recent effort in Professor Hammock's laboratory has introduced genes for potent, insect specific neurotoxins into insect viruses. These viruses, in their unmodified form, kill insects too slowly to be of agricultural value. Insect neurotoxins are quick and effective. The thread of Dr. Hammock's research that we describe here wound its way from basic studies of caterpillar metamorphosis, to the demonstration of juvenile hormone esterase, to the construction of potent insect viruses. Clever chemistry, careful molecular biology, and good biology created a new concept in bio-control of insects by insect viruses, a result favorable to crop agriculture.

A second research thread, briefly stated, stems from the 1970s. Bruce Hammock showed, contrary to what had been accepted, that at least some forms of the enzyme epoxide hydrolase are not bound to the membranous endoplasmic reticulum of mammalian cells. A paper published in the prestigious journal Science in 1980 provided unequivocal evidence for this unbound enzyme, which other researchers had overlooked for a decade. Prof Hammock again used cleverly designed substrates and inhibitors to understand the workings of epoxide hydrolases. This research, extending into the present, revealed how this and other enzymes detoxify some of the numerous natural toxins in our diets, including mutagens and carcinogens. Most recently, Prof Hammock's epoxide hydrolase inhibitors are finding potential applications in the treatment of hypertension.

A third thread is highly sensitive and highly specific detection of pesticides in environmental samples. In 1979 Professor Hammock outlined the potential of antibodies for pesticide analysis at a meeting of the American Chemical Society. His laboratory developed the basic technology and advanced it through to practical application. The Environmental Protection Agency, the Food and Drug Administration, and many other governmental and private agencies now use this technology. Even today, over half of the publications on the applications of antibodies for pesticide and other residue analysis were derived from work in Professor Hammock's laboratory. Currently he is extending this technology to the analysis of medical samples and the development of biosensors.

Professor Hammock and his research program are widely appreciated by his professional colleagues. His laboratory has been funded continuously on the same National Institute of Environmental Health Sciences grant in toxicology that he prepared as a postdoctoral fellow in 1973. In 1997, this grant was renewed with an outstanding score and was selected to receive a MERIT (Method to Extend Research in Time) Award from the granting agency, meaning an award for 10 years rather than the usual 5. He currently also is funded by the U.S. Department of Agriculture, NRICGP Award, for his work in entomology.

Of greatest note, Dr. Hammock organized and serves as Program Director of the National Institutes of Environmental Health Sciences Superfund Basic Research & Training Program which received the top peer review ranking in the nation in each of its four funding cycles. This project encompasses over 30 Ph.D. scientists at Davis and integrates engineering, ecology, hydrogeology, biodegradation, and assessment components of hazardous waste problems including agricultural chemicals. The Superfund program also includes a strong outreach component that reaches target populations such as farm workers exposed to agricultural chemicals to determine their risk and effects on human health.

Dr. Hammock also has been successful in acquiring extramural funds for the general enhancement of campus research capabilities. For example, he recently was one of several co investigators on successful grants to establish a mass spectroscopy center at Davis and to improve the campus capability in peptide and DNA chemistry. He participated in preparation of a proposal to the U.S. EPA to establish the EPA Center for Ecological Health Research. This Center was awarded to Davis after intense competition among major universities and is now in its fifth year of operation. He has contributed centrally to numerous other campus research initiatives.

Professor Hammock has received many awards in recognition of his research.

1972-73 NSF Fellowship, U.C. Berkeley.

1973-74 Rockefeller Foundation Postdoctoral Fellowship.

1978-84 National Institutes of Health Research Career Development Award.

1982-87 Frasch Foundation Award in Agricultural Chemistry.

1987-92 Burroughs Wellcome Toxicology Scholar Award.

1988-89 Fogarty Foundation Fellow, NIH.

1988-89 Visiting Fellow, Lady Margaret Hall, Oxford University

1993 Burroughs Wellcome International Fellowship, NERC Laboratory, Oxford

University

1993 International Award in Pesticide Chemistry, American Chemical Society

1994 Kenneth A. Spencer Award in Agricultural Chemistry

1995 Alexander von Humboldt Foundation Award in Agriculture

1996 Alfred M. Boyce Lecturer, University of California, Riverside

1996 Hong Memorial Lecturer in Molecular Biology, School of Life Sciences,

Illinois Univ., Urbana

1997 NSF International Fellowship, US/Australia

1997 MacMaster Fellowship in Agricultural Research

1997 Pacific Branch of the Entomological Society of America Award, Zeneca

Ag Products

1998 Entomology Society of America Recognition Award in Insect Physiology,

Biochemistry and Toxicology

1999 Agriculture Research Service Sterling B. Hendricks Memorial Lecturer

1999 Election to the National Academy of Sciences of the United States of

America

We of the Committee acknowledge our debt to Audrey Ashford, DeeDee Kitterman Michael Parrella and Valerie Williamson for gathering materials and other contributions. Please accept as the Committee's nominee for Faculty Research Lecturer, for the year 2001, Professor of Entomology Dr. Bruce D. Hammock, insect physiologist, protein biochemist, organic chemist, bioanalytical chemist, skilled research leader, intellectual force, and campus citizen. This is the highest honor for research that the UC Davis faculty can bestow on one of its own.

Gary Snyder

George Bruening, Acting Chair

Samuel Armistead

Donald Rothchild

Sandra Gilbert