Raymond E. Counsell was born in Vancouver, British Columbia, Canada. He received his Bachelor of Science in Pharmacy degree from the University of British Columbia in 1953 and his PhD in Medicinal Chemistry and Organic Chemistry from the University of Minnesota in 1957. From 1957 to 1964 he served as Senior Research Chemist at G. D. Searle and Company in Skokie, IL.
Searle’s research was heavily involved in steroid chemistry. Ray was placed in Frank Colton’s group which was active in the development of contraceptive agents and anabolic steroids. Ray was encouraged to develop his own research program. His early efforts involved pursuing structure-activity relationships among the 19-norsteroids which have the basic structure known as estrane. This led to one of his earliest papers entitled “Isomeric Estrane Derivatives” published in Tetrahedron in 1961. This paper was notable for providing the first chemical and biological properties for substituted 5α, 10α-estranes. Other studies on anabolic steroids were conducted in collaboration with colleague Dr. Paul Klimstra and summarized in their chapter in Alfred Burger’s third edition of Medicinal Chemistry (1970).
His next major effort involved a search for agents to regulate cholesterol biosynthesis for the treatment of atherosclerosis. Based on publications which indicated that feeding cholesterol to animals limited the rate at which the sterol was synthesized in the liver led Counsell to design and synthesize agents that would mimic cholesterol in this feedback process. This encouraged him to prepare a series of azacholesterols. One of these was 20,25-diazacholesterol which appeared promising in animal studies, but had a brief exposure in the clinic because of side effects (muscle cramping). Subsequent studies by Counsell and his students revealed 20,25-diazacholesterol to be a potent inhibitor of cholesterol side-chain cleavage, a key step in the biosynthesis of the female and male sex hormones (J. Med. Chem., 1972). In recent years 20,25-diazacholesterol under the name of Ornitrol or Diazacon has been used as a contraceptive to control pigeon populations as well as those of other annoying small animals under the auspices of the USDA National Wildlife Research Center.
In 1963, Counsell was asked to consider joining the Nuclear Medicine group at the University of Michigan Medical School to establish a new program in the design and synthesis of radiopharmaceuticals for tumor and organ imaging (currently known as Molecular Imaging). An award from the American Cancer Society provided support for his appointment as Associate Professor of Medicinal Chemistry in the College of Pharmacy and Department of Internal Medicine in the Medical School with full tenure. Research funding from N.I.H. provided the resources to establish his research program. His groups efforts led to radioiodinated 19-iodocholesterol which became the first agent to noninvasively visualize the adrenal gland and associated tumors in humans ( J. Nucl. Med., 1970). Prior to that, a radioiodinated analog of chloroquin gave rise to the first agent to produce clinical images of malignant melanoma in patients (J.A.M.A., 1968). This agent was licensed to Mallinckrodt Pharmaceutical where it was marketed under the name of Iomethin-131 and used for many years by the National Eye Institute for the diagnosis of uveal melanoma.
Counsell’s continued interest in synthesizing agents to regulate steroid hormone biosynthesis led his laboratory to prepare and evaluate inhibitors of the enzyme aromatase, a key enzyme in the biosynthesis of the estrogen hormones. This led to a number of potent inhibitors which were among the few known at the time (J. Med. Chem., 1978). These studies were conducted by Robert Brueggemeier for his doctorate and have been expanded by him in his laboratory at Ohio State University.
Further studies with radioiodinated derivatives of cholesterol led to the recognition of the importance of plasma lipoproteins in their biodistribution and tissue uptake by receptor-mediated endocytosis. This led to the concept that certain types of lipoproteins could be useful carriers for radiodiagnostics (see perspective article in J. Med. Chem., 1982). This concept was perfected by colleagues Weichert and Longino in the Department of Radiology. This technology was subsequently licensed by the University of Michigan and has given rise to two products known as Fenestra LC for liver imaging and to a pegylated version known as Fenestra VC for vascular contrast enhancement. (For animal use only at this time).
Counsell’s most recent efforts have involved radioiodinated phospholipid analogs for tumor imaging. Early publications (J. Med. Chem., 1989) demonstrated the remarkable ability of these agents to selectively concentrate in tumors. Several more years of chemistry, animal studies and tests in patients finally gave rise to the most tumor selective agent known as NM-404 (J. Med. Chem., 2006). The University of Michigan has licensed a company known as Cellectar to commercialize NM-404 for the diagnosis and treatment of cancer.
Dr. Counsell’s studies have been reported in over 250 peer-reviewed publications and 21 book chapters, and he holds over 50 U. S. Patents. During the course of his investigations, 25 graduate students have received Ph.D. degrees from the University of Michigan along with 12 others who received their Masters degree with Dr. Counsell serving as their thesis chair. Thirty-five postdoctoral fellows have also trained with Dr. Counsell.
Dr. Counsell has served on the editorial boards of the Journal of Medicinal Chemistry, Journal of Pharmaceutical Sciences and the Quarterly Journal of Nuclear Medicine. In addition he has served as a senior editor for the Journal of Medicinal Chemistry and as a section editor for the Annual Reports in Medicinal Chemistry. He has been active in the American Chemical Society Division of Medicinal Chemistry and served as chair from 1970-71, the Academy of Pharmaceutical Sciences where he served as Chair of the Section of Medicinal Chemistry from 1970-71, the Society of Nuclear Medicine, and the International Association of Radiopharmacology where he served as president from 1994-95.
In the Department of Pharmacology, Dr. Counsell served as acting chair from 1987-88, as associate chair from 1988-90, and as interim chair from 1990-94. He has also been active in the Interdepartmental Program in Medicinal Chemistry and one in which he assisted Professor Burckhalter organize in the 1960s. This graduate program received an N.I.H. Training grant in 1968 which has continued to this day. He served as interim chair of the interdepartmental program from 1973-76.
Among his honors and awards are listed the Horner Gold Medal in Pharmacy (1953), the American Cancer Society Research Associate Award (1964-71), American Cancer Society Eleanor Roosevelt International Fellowship (1972), the Czerniak Prize of Nuclear Medicine and Radiopharmacology, the Fogarty International Fellowship (1986), the T. O. Soine Memoral Award (1981) and Alumni Outstanding Achievement Award (1989) from the University of Minnesota. He has been elected as a fellow in the Academy of Pharmaceutical Sciences (1973), AAAS (1980), and the American Association of Pharmaceutical Sciences (1987). In 2003 he was awarded the Technology Transfer Career Achievement Award from the University of Michigan.
During his academic career he served on numerous university and National committees. From 1968 to 1972 he was a member of the NIH Medicinal Chemistry Study Section A and from 1975 to 1979 he was a member of the Pharmacology-Toxicology Program Committee of NIGMS. From 1979 to 1983 he was a member of the Committee on Medical Radioisotopes for Los Alamos Scientific Laboratories.
On September 1996 the Regents of the University of Michigan named Dr. Counsell Professor Emeritus of Pharmacology and Medicinal Chemistry.