History

I was fortunate to have been a student in the School (then College) of Pharmacy in the late 1950s.  During those years Pharmacy was located mainly on the third floor of Bagley Hall.  Forrest Goodrich (Foley) had just stepped down as the Dean of Pharmacy and Jack Orr assumed the Deanship in 1956.   Jack Orr wrote a definitive History of the School of Pharmacy at the University of Washington.

Other faculty members in the School of Pharmacy, and in other departments of the University of Washington had a profound effect on my education and career.  I will mention only some, while acknowledging that almost all were extremely supportive and inspirational.

Seymour B. Rabinovitch, Professor of Chemistry, dazzled freshmen students by lecturing for 50 minutes without a single pause to look at a note.  Nathan Hall was appropriately demanding of accuracy in pharmacy classes. I recall that he gave me a B when I thought I had an A coming, because ‘You needed to be taken down a notch’.  He was, of course, right.

John T. Elder was assigned by the Department of Pharmacology to teach pharmacology to pharmacy students.  Elder was a senior graduate student in the Department of Pharmacology.  He was a superb, entertaining, delightful instructor with a wealth of stories that illustrated the educational points in question.  He was keenly interested in students and was extremely inspirational.  His charisma was a major factor in my choice of pharmacology rather than medicinal chemistry as an area for graduate study.  At the time that was a very difficult choice. 

After he finished his Ph.D. degree, Elder joined the faculty of the Department of Pharmacology.  However, he left a few years later to move to Creighton University.  Elder’s commitment to the education of minority students was well recognized at Creighton.  He founded a nationally recognized program aimed at helping minority students gain the skills and knowledge needed for entry and success in medical school.

Undergraduate Research

In addition to the usual undergraduate training in Pharmacy, I got involved in research in several areas.

Pharmacognosy
Varro Tyler gave me a first taste of research in the Drug Plant Laboratory.  Tyler was a walking encyclopedia of botanical and pharmacognostical information.  The American Society of Pharmacognosy posted an obituary hononring him in 2001.

At the time I joined the Drug Plant Laboratory, Tyler and his graduate student, Lynn Brady, were developing a method of growing Claviceps purpurea in tissue culture.  It raised exciting possibilities in the days when the pharmacological properties of compounds related to lysergic acid were being intensively studied (before they became essentially illegal).  My research project in the Drug Plant Laboratory used paper chromatography to explore the question of whether the opium poppy, Papaver somniferum, when crossed with the mexican prickly poppy, Argemone mexicana, would produce morphine-like alkaloids when grown in the Pacific Northwest (answer, no). 

Medicinal chemistry
Professor Alain Huitric was directing an active research program and allowed me to engage in undergraduate research.  We synthesized some interesting compound related to molecular entities with very interesting psychopharmacological effects.  I was lucky to be named as an author on a paper of which William F. Trager was the first author.  Trager was a graduate student working with Huitric at the time. He finished his Ph.D. with Huitric and after postdoctoral work in London returned to the School of Pharmacy as a faculty member.

Graduate Training

Upon entry into graduate training in Pharmacology, I entered the lab of Theodore C. West.  Ted West was pioneering the use of to microelectrode recording in single cardiac cells.  Emphasis in the lab was on the electrophysiology of the sino-atrial (SA) node and autonomic regulation of automaticity of the SA node.  We demonstrated that it was possible to stimulate postganglionic autonomic nerve endings in the SA node without directly stimulating the SA node cells.

This led to the use of the SA node as a model of autonomic innervation of the heart.  It was a model that provided rapid feedback (by altered automaticity) on the effect of autonomic fibers on the SA node and facilitated analysis of the effects of various drugs on the release and actions of autonomic neurotransmitters.

The most important information that resulted from this particular line of research was a clear refutation from more than one approach of the then popular ‘hypothesis of Burn and Rand’ which stated that postganglionic sympathetic fibers release acetylcholine, which then by acting on preganglionic autoreceptors, causes the release of norepinephrine.

While Theodore C. West was the official mentor for my Ph.D. work, it must be mentioned that Professor Akira Horita was an intellectual mentor for all of the graduate students in the Department of Pharmacology in the 1960s and 1970s.  Aki, as he is affectionately known, was a mentor in the best sense of the word, serving as a role model, coach, scientific critic and teacher.  Aki is now retired from the Department.

Another retired professor who made a big impact on all the students in the early years of the Deparment of Pharmacology was Ted Loomis.  Ted was a Professor of Pharmacology and he was also the Washington State Toxicologist.  His presence, and the presence (at that time) of the Washington State Toxicology Laboratory, (now merged with the Washington State Patrol Crime Laboratory Division) added immeasurably to the intellectual and experiential training possibilities available to graduate students and postdoctoral fellows.

Postdoctoral training

What an incredible opportunity!  A postdoctoral fellowship from the National Science Foundation allowed me to pursue postdoctoral work in Bern, Switzerland.  I was fortunate that Ted West recommended me to Hans J. Schatzmann.  In pioneering work, Schatzmann had shown that digitalis inhibits the active transport of sodium and potassium. This was before the sodium/potassium pump was known.  In fact, Schatzmann’s seminal observation was critical in the elucidation of active membrane transport, of the sodium potassium pump, as well as the Na/K ATPase enzyme.

At the time I moved to Bern, Schatzmann was a ‘Privat Dozent’ (approximately equivalent to an Assistant Professor) in the Pharmacology Institute of the School of Medicine (under the direction of Professor Walther Wilbrandt).  During my first months in Bern, Schatzmann was on sabbatical leave in Japan so I pursued a project on my own.  The results demonstrated that the positive inotropic effect of digitalis may or may not depend on cardiac rate, depending on temperature (and other variables determined later).  I wrote up the manuscript with Schatzmann’s name included.  He demurred, saying that since he had not gotten his hands wet, he should not be an author.  However, he insisted on reviewing the manuscript.  That manuscript went through about six re-writes, with Schatzmann having the audacity to repeatedly correct my English!  I still recall how angry I was that he (whose mother tongue was definitely not English) had made me rewrite the manuscript repeatedly.  I still recall mailing it at the local post office thinking to myself that I never wanted to see that manuscript again.   As it turns out I did not see it again in manuscript form.  The lesson taught to me by Hans Schaztmann, and reinforced by the letter from the field editor of the Journal of Pharmacology and Experimental Therapeutics, was that it is better to properly write a manuscript in the first place.  In spite of that lesson, I have never had another manuscript accepted for publication without any corrections. 

During my second year in Bern, Schatzmann was appointed as the Professor of Veterinary Pharmacology at a newly built school of veterinary medicine at the University of Bern.  It was a palace, and reflected the importance of large animal veterinary medicine in the Canton of Bern.

Hans Schatzmann introduced me to the fascinating world of membranes and membrane transport, and a wonderful model system for studying them – human red blood cells.  The cells are easily obtained in relatively large quantities from normal humans  as well as from humans with interesting inherited and acquired diseases.  While working with Schaztmann, we demonstrated the existence of, and did some early characterization of the plasma membrane calcium pump.