Louis James Casarett (1927–1972)

Paul E. Morrow*, Margaret C. Bruce{dagger} and John Doull{ddagger},{ddagger}

* University of Rochester, 575 Elmwood Avenue, Rochester, New York 14642; {dagger} Chandler Medical Center, University of Kentucky Medical School, 800 Rose Street, Lexington, Kentucky 40536-0001; {ddagger} University of Kansas Medical Center, Department of Pharmacology, Toxicology, and Therapeutics, 3901 Rainbow Boulevard, Kansas City, Kansas 66160

Received September 7, 2000; accepted September 7, 2000

Lou Casarett was born in Rochester, New York. His forebears, the Casaretti family, emigrated from Italy to Rochester during the Civil War era. Lou attended primary and secondary schools in Rochester and during World War II, served in the U.S. Navy. In 1950, he obtained his B.S. degree from the University of Michigan. In 1951, Lou returned to Rochester, and Paul Morrow, who became a close personal friend, recalls with considerable pleasure picking Lou up each day to take him to and from the university as he had no car. Lou was a determined and successful graduate student who enthusiastically joined Professor Harold Hodge's research division, a predecessor of the University of Rochester's first Department of Pharmacology. Lou received his master of science degree in 1955 and his doctor of philosophy degree in 1958, both from the Division of Pharmacology and Toxicology of the Department of Radiation Biology at the University of Rochester. Dr. J. Newell Stannard was his advisor for both degrees.

In the early 1950s, Lou utilized microscopic autoradiographic methods pioneered in the late 1940s to define and semiquantify radioisotopic distributions at the tissue and cellular level. By the use of innovative freeze-dry techniques and quantitative studies of isotopic leaching during various histopathologic and autoradiographic procedures, Lou was able to advance the methodology, especially that applied to the study of alpha-emitters e.g., Po-210 and Pu-239. Important findings from Lou's autoradiographic investigations of animals exposed to radioactive dusts and from his subsequent studies of alveolar dust clearance in experimental animals include many aspects of lung cell-particle interactions such as endocytosis by lining cells, alveolar macrophage (AM) recruitment, the permeation of the lung epithelium to particles, and the role of perivascular and peribronchiolar lymphatics in the pulmonary clearance of insoluble particles. On the respiratory clearance of insoluble particles, Lou proposed 4 distinct phases: a rapid mucociliary clearance, a slower AM-mediated clearance, a still slower clearance of sequestered particles by AM, and a concurrent solubilization of sequestered particles. Lou cautioned against extrapolating from this model, based on experimental animal studies, to clearance mechanisms in lower, more realistic particulate exposures.

When Lou joined the faulty at Rochester, his special interest in matters educational began to be expressed. He developed a summer research program for undergraduate students wherein he solicited applications from many academic institutions around the country and then matched the students with appropriate mentors. In addition to laboratory work, the students met once a week for research seminars presented by faculty members. Although this type of program is widely used today, Lou's summer program at Rochester was one of the first in the nation, a fact noted by Newsweek magazine, which prepared a special article on the program in its second or third year of existence.

One particularly poignant event in Lou's teaching career occurred at the University of Rochester when a graduate student of his, George Metzger, developed testicular cancer. Although he received the most advanced therapy, Metzger's cancer rapidly progressed so that for his Ph.D. defense, his committee with an outside member, Dr. Roy Albert of NYU, met in a New York City hospital at George's bedside. George's defense was exceptional and he was awarded his doctorate in pharmacology. Sadly, he died shortly after the award and the department, in his honor, created the Metzger Award, an annual award given to a graduate student who has shown particular excellence in his doctoral research.

During his days at Rochester, Lou also took the lead in many extracurricular activities. He was an avid sportsman who especially liked boxing and tennis. He volunteered to organize and prepare many clambakes and social activities of the department. His abilities to organize and cook were also manifest at home, where he and his wife Peggy frequently entertained with gourmet dinners prepared for friends.

In 1967, Lou and Peggy moved from Rochester, New York to Honolulu, Oahu, where they joined the faculty of the new medical school in its formative stages. With his usual zeal, Lou, now an associate professor of pharmacology, played an active role in getting the Department of Pharmacology up and running and concurrently developed a graduate course in toxicology. For this new course, Lou very much wanted a toxicology textbook that would include not only the classes of toxic agents (metals, pesticides, solvents, etc.) but also the organ systems involved (liver, kidney, CNS, etc.) as separate sections of the book. Lou approached Professor John Doull at the University of Kansas, described his concept, and asked him to join him in the venture. John enthusiastically agreed and since Lou and John were serving together on the NIH Toxicology Study Section, they presented this idea to the Study Sections members at a seafood dinner in Bethesda. Members who approved the idea, such as Gabby Plaa and Sheldon Murphy, were quickly signed up as potential authors and Lou then negotiated with Joan Zulch for Macmillan to be the publisher. Subsequently, during a vacation in Hawaii with his family, John worked with Lou selecting potential contributors and addressing matters regarding the scope of the book. Tragically, as the first chapters were received, Lou was diagnosed with brain cancer. As his condition deteriorated, his wife Peggy worked with him reading him the newly drafted chapters that Peggy recalls were, for the most part, outstanding. Concomitantly, Professor Doull, aware of Lou's problem, became heavily involved in the reviews and decision making and working with Peggy and the contributors to the book.

Peggy recalls sending one somewhat-tardy contributor several Hawaiian picture postcards: "Thinking of you, wish your chapter were here." When all the chapters were finally received, Peggy turned them over to John Doull who took the major responsibility for getting the book to press and for sustaining the momentum with subsequent editions. John's wife Vera did the valuable task of indexing the book. Thus, the textbook was completed due to the perseverance of Peggy, the assumption of the major responsibility for organizing the book and shepherding it into print by John Doull, and the enthusiastic and capable participation of several of Lou's professional friends and colleagues, including Curtis Klassen and Mary Amdur, who subsequently became coeditors of the book. The emergence of Casarett and Doull's Toxicology: The Basic Science of Poisons in 1975 was a landmark event in toxicology and a fitting memorial to Lou Casarett's dedication to toxicologic education. As Dr. Harold Hodge, first President of SOT wrote in the foreword of this book: "This is the time for exploring the avenues of instruction in toxicology. Drawing from their teaching experience, Drs. Casarett and Doull have pooled their special interests and added contributions from other specialists. A useful plan of organization became apparent to them, grouping toxicologic phenomena according to organ systems. Dr. Casarett fervently brought this book to completion conceding nothing to his terminal illness, because he bore the conviction that this form serves its purpose well, a conviction shared by Dr. Doull. Their choices are commended; toxicology needs such a textbook."

Always gregarious and outgoing, Lou was readily accepted by Hawaiian locals who were traditionally wary of "outsiders." He quickly earned the trust and respect of people in many walks of life, both within and outside of the university. Among the community activities he became involved in was that of drug abuse, a major problem on Oahu. He and a graduate student, Randy Baselt, developed a urine analysis program for the island's methadone clinic. Without this backup, the methadone treatment program probably would have not been successful. Moreover, Lou helped set up an analytical laboratory capable of identifying the drugs in use on the streets so that emergency rooms were able to determine what kind of drug problems they were facing. These volunteer efforts led to Lou serving on the Health and Community Services Council, the State Commission on Drug Abuse, the Governor's Ad Hoc Committee on Education in Alcoholism and Drug Abuse, and several other municipal, state, and university committees. Lou's major research interest at the medical school was the toxicology of pentachlorophenol, a pesticide for the ubiquitous problem of dry-wood termites on the Hawaiian Islands. His academic and civic activities in Oahu certainly must have endeared him to many.

While at the University of Hawaii, Lou took sole responsibility for graduate education in radiation biology, developed a graduate research program in pharmacology and toxicology, and served as chairman of the department's curriculum committee. Lung clearance mechanisms continued to be a major research interest. His final treatise on the subject was published in 1972 in Essays in Toxicology, Vol. II. entitled "The Vital Sacs: Alveolar Clearance Mechanisms in Inhalation Toxicology." For years, he had been intrigued by the possibility that alveolar macrophages might also be derived from sources other than the bone marrow, a radical concept at the time. He argued that lung cells are likely to have the capacity for differentiation, dedifferentiation, adaptation, and for multiple functions. "To insist on specific anlagen is to deny a basic property of biological entities and to ignore what has been learned in analogous cell populations in other organs." Subsequent studies have confirmed Lou's viewpoint regarding a pulmonary source for AM (e.g., M. J. Evans and S. G. Shami, 1989, in Lung Cell Biology, Vol I. Lefant and Massaro, Eds., pp. 1–36, Marcel Dekker Inc., New York).

Despite his untimely death at age 45, Dr. Lou Casarett's contributions to toxicology were manifold, selfless, and important. Doubtless, it would be his wish to be remembered for his efforts in education. A dedicated, accomplished teacher, he took the initiative many times in his brief career to institute or improve how toxicology was taught. His friends knew him as an engaging, cheerful, modest individual who greatly enjoyed both intellectual and social pursuits. The Society of Toxicology is pleased to cite the accomplishments of this outstanding toxicologist.

ACKNOWLEDGMENTS

The authors would like to cite the important contributions made to this profile by Sue Shami (Lung Cell Biologist influenced by Lou's work), Newell Stannard (Professor Emeritus and Lou's former faculty advisor at Rochester), Randy Baselt (Forensic Toxicologist and former graduate student of Lou's at Hawaii), and Vicki Casarett (Lou's niece) and to thank the Departments of Pharmacology at the Universities of Hawaii and Rochester for archival materials.

NOTES

1 To whom correspondence should be addressed. Fax: (913) 588-7501. E-mail: jdoull{at}kumc.edu. Back





This Article
Extract
FREE Full Text (PDF)
Alert me when this article is cited
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Disclaimer
Request Permissions
Google Scholar
Articles by Morrow, P. E.
Articles by Doull, J.
PubMed
PubMed Citation
Articles by Morrow, P. E.
Articles by Doull, J.