For nearly 40 years, Dr. Collier and his colleagues have been at the forefront in providing the scientific community with a growing understanding of the mechanisms of action of bacterial toxins. Working initially with diphtheria toxin, he was the first to demonstrate that a toxin could enter human cells and inactivate an intracellular target molecule. Specifically he showed how the diphtheria toxin interfered with protein synthesis in the cell by inactivating an intracellular target called elongation factor-2. This revolutionary discovery led to the more expansive conclusion that most major bacterial toxins act by modifying intracellular targets.
Dr. Collier then went further, by elucidating the fundamental structures of toxins and how they function inside a cell. Intracellularly acting toxins were found to consist of two units, A and B, which together contribute to cell damage. In this A-B paradigm, the B subunit allows for cell binding and forms a pathway for the A subunit to cross a membrane and enter the cell interior, where it gains access to its target. There, the A subunit modifies its target molecule, causing death of the cell or, in some cases, a toxic disruption of an important cellular function. As a result of these early discoveries, similar studies were undertaken with other toxins. In addition, for the first time in the field of toxinology, Dr. Collier's team elucidated the three-dimensional structures of toxins, eventually pioneering the use of crystallographic structural analysis in the design of bacterial vaccines. Subsequently, Dr. Collier has gone on to offer scientists new insights into different mechanisms by which channels or pores are formed in cellular membranes, allowing for the translocation of bacterial toxins into cellular compartments.
On a practical level, this pioneering research has contributed to the development of vaccines, including pertussis (whooping cough), because his identification of active sites on toxins has allowed them to be detoxified and then used as vaccines. In addition, the design of immunotoxins to specifically destroy certain cancer cells is a direct result of Dr. Collier's work. And most recently, as a result of work begun years before by his laboratory to investigate the toxin of the anthrax bacteria, new therapeutic strategies to defeat anthrax are now being developed.
"Dr. Collier's outstanding contributions to the field of infectious disease research began with his early work on diphtheria toxin, in the process helping us understand that what he discovered about diphtheria is applicable to most bacterial toxins," says Richard Colonno, Ph.D., vice president, Infectious Disease Drug Discovery, Bristol-Myers Squibb. "While his science has been insightful, elegant and indeed, in many ways extraordinary and groundbreaking, the practical applications of his work have been just as impressive and critical. They range from discoveries that have led to the development of vaccines, to the creation of immunotoxins to fight cancer, and now, to pioneering work on the anthrax toxin that could lead to new therapeutic approaches in the war against bioterrorism. He has understood the public health promise and implications of his basic scientific breakthroughs and has been in the forefront of finding practical and meaningful applications of his work. We're proud to be able to recognize his achievements on behalf of the scientific and medical community and on behalf of all those individual patients who have been helped as a result of those discoveries."
Dr. Collier received his B.A. from Rice University in 1959 and his Ph.D. in biology from Harvard University in 1964. He held teaching positions at the University of California, Los Angeles, beginning in 1966 before joining Harvard Medical School in 1984, taking up his current position in 1989. At Harvard, he has also served as Faculty Dean for Graduate Education, Chairman of the Division of Medical Science and Acting Head of the Department of Microbiology and Molecular Genetics.
He has been recognized for his many contributions with a number of honors including the Eli Lilly Award in Microbiology and Immunology in 1972, the Pierce Immunotoxin Award in 1988, the Paul Ehrlich Prize in 1990, the Selman A. Waksman Award in Microbiology from the National Academy of Sciences in 1999, and with his election to the National Academy of Sciences, the American Academy of Arts and Sciences and the American Academy of Microbiology. His work on anthrax and other toxins also has led to his membership on a number of distinguished panels exploring biowarfare and science, including an Advisory Panel for the Defense Advanced Research Projects Agency and the NIAID Blue Ribbon Panel on Bioterrorism.
The Bristol-Myers Squibb Unrestricted Biomedical Research Grants Program, under which the Distinguished Achievement Award is presented, was initiated in 1977. It marked its 25th anniversary in 2002, reaching a milestone of $100 million in no-strings-attached funding in six biomedical research areas: cancer, cardiovascular, infectious disease, metabolic disease, neuroscience and nutrition. The recipient is selected by peer review. The award, a $50,000 cash prize and a silver commemorative medallion, is given annually in each of the six therapeutic areas. Dr. Collier will officially receive the infectious disease award at the annual Bristol-Myers Squibb Distinguished Achievement Award dinner to be held in New York City on October 16, 2003.
Bristol-Myers Squibb is a global pharmaceutical and related health care products company whose mission is to extend and enhance human life.
Kathleen Poss, Ph.D.
Unrestricted Grants Program
Princeton, New Jersey
Princeton, New Jersey
Harvard Medical School