Interview with Joel Hardman on the intellectual history of Pharmacology - page 2

Guenter Schultz came to our lab in 1971 on leave from the Pharmacology Department at the University of Heidelberg. He and I, with help from his wife Karin, developed a much more sensitive assay for cyclic GMP and applied it to studies on regulation of the nucleotide in smooth muscle of vas deferens. He returned to Heidelberg in 1973, ran a superb research program and eventually became Chair of Pharmacology at the Free University of Berlin. He and I have remained closest of friends. Many of his students and postdocs have taken chairs around Germany, and it is no exaggeration to say that Guenter, probably more than any other individual, shaped the face of modern Pharmacology in Germany.

In 1972, David Garbers came as a postdoctoral fellow in Sutherland’s laboratory and stayed at Vanderbilt after Sutherland moved to Miami in 1973. David obtained his Ph.D. at Wisconsin with Neal First and Henry Lardy and was strongly influenced by the rigorous enzymological research of William Cleland. In 1974 he joined the faculty in Physiology, and he moved with me to the Pharmacology Department in 1975. For several years, David taught a segment of the Receptors course for graduate students. That segment was a series of lectures on enzyme kinetics that were attended by people from several departments. They were superb and a significant contribution to the institution. He helped a lot of people as they were trying to study the effects of drugs on enzymes. His research program dealt with guanylyl cyclases from several sources and with reproduction biology, especially sperm-egg interactions. He moved to Dallas in 1990 and was elected to the National Academy of Sciences shortly thereafter in recognition of his work on guanylyl cyclases and their regulation and on sperm-egg chemoattraction.

Jack Wells came to our lab from the School of Pharmacy at Purdue for a sabbatical period in 1972 and stayed to join the Physiology faculty. He brought a strong background in medicinal chemistry, became a good biochemist, and for more than 30 years applied his skills to important research on phosphodiesterase inhibitors and adenosine receptor antagonists. Along with Garbers, he also joined me in the Pharmacology Department in 1975. Jack was highly sought after as a collaborator and advisor by many investigators at Vanderbilt and elsewhere.

Bob Weiss came from the Yale in 1975 to spend a sabbatical period in our lab and worked with Jack Wells and me on phosphodiesterase activity in ureteral tissue. Bob is a urologist and now head of his division at Yale.

What attracted you to the Pharmacology Department and to take the Pharmacology Chair?

I think I was ready to do something else. I had been offered a chair elsewhere, but I wasn’t inclined to move my family. In 1974, I spent a sabbatical leave in England with Edith Bulbring working on smooth muscle. Before I had left on sabbatical, I had been asked if I would consider the Chair and my answer was a firm “No.” But something in my attitude changed while I was on sabbatical. During that time, Leon Cunningham, then serving as Chair of the Pharmacology Chair Search Committee, wrote and asked if I would reconsider being a candidate for the Chair. I knew that Al Gilman at the time was being considered for the position as well.  I told Cunningham that if Gilman didn’t take the Chair, then I would consider it. Gilman didn’t want the Chair, so in 1975 I threw my hat into the ring. Vernon Wilson, Dean and Vice Chancellor then, offered me the position and I took it.  In addition to Garbers and Wells joining the Pharmacology Department, I was able to recruit two other new faculty members. Peter Reed came in late 1975, and after renovation of some space, Lee Limbird came in 1979.

 What was the nature of the Pharmacology department when you moved into it and how did it change?

The Pharmacology Department at the time I joined it had three identifiable units. Alan Bass, who had taken over as Chair in the early 1950s, had great vision and built the Department from a small inconspicuous one to an internationally respected one. One of the identifiable units that he had initiated was and is Clinical Pharmacology. Allan was instrumental in recruiting John Oates, who was housed in Pharmacology space and had his primary appointment there with a secondary one in Medicine until he became Chair of Medicine. John founded what was either the first or second Clinical Pharmacology division in the country. The first may have been Leon Goldberg’s unit at Emory. The Clinical Pharmacology Division under John grew to be the premiere such division in the world, and I think it can still claim that distinction.

The second identifiable unit of the Department was Psychopharmacology.  It was located at the Tennessee Neuropsychiatric Institute, or TNI. Allan Bass had talked the State Department of Health into allowing some of the space at Central State Mental Hospital, where patients with mental illness were treated as in-patients, to be set aside and renovated for use in research. In the mid-1960s he recruited Fridolin Sulser, Jim Dingell, “Dutch” Verster, Al Robison, Wolf Dettbarn, Dan Buxbaum and Dennis Schmidt to work at TNI. The Psychiatry and Psychology Departments also had several faculty members based at TNI including Bob Barrett and John Griffith. For several years, there was a vigorous and spirited environment at TNI, and graduate students found it an attractive place to work.

But by the time I came into the Pharmacology Department, there had been attrition in the TNI team. Al Robison had moved to Houston to take the Chair of Pharmacology. Wolf Dettbarn had moved to the Jerry Lewis Neuromuscular Center, “Dutch” Verster had left Vanderbilt, Jim Dingle had gone to the NIH and Dan Buxbaum had moved to the Dean’s office. Several investigators in Psychology and Psychiatry also had left TNI.

Fridolin Sulser, Elaine Sanders-Bush, Nancy Leith, Ron Kuczenski, Bob Barrett and Dennis Schmidt were at TNI along with a few members of the Psychiatry Department when I came into the Department. They were finding over time that it was harder and harder to attract graduate students, in part because of the distance from the University campus to TNI, which was on Murfreesboro Road near the airport. Relationships between members of the Pharmacology and Psychiatry Departments were not going well, the physical plant was deteriorating, and morale in general at TNI was low. In the mid- to late 1980s, Elaine Sanders-Bush moved into Medical Center North, Nancy Leith went to work for a drug company, Bob Barrett moved into the VA Hospital and Dennis Schmidt moved into the Psychiatry Department, leaving only Fridolin Sulser and his team at TNI. When Michael Ebert became Chair of Psychiatry, he tried to revive TNI, but the unit eventually was closed and Sulser moved his lab into the Psychiatry Department in Medical Center North.

The third identifiable unit in the Pharmacology Department when I joined it was the so-called “core unit.” Its faculty included Rama Sastry, Erwin Landon, Ray Harbison , who subsequently moved to Arkansas, and Henry Wilcox, who had worked with Murray Heimberg when he was in the department and later joined Heimberg in Missouri. Milton Bush was emeritus then but still had a small lab.

My goal, when I first took the chair of the department, was to strengthen the core unit in two areas. One was research on calcium, which recently had been recognized as an important second messenger along with cyclic nucleotides. And the other area was receptor biology, which had just been demonstrated to have biochemical handles that facilitated the study of interactions between drugs or neurotransmitters and receptors.

My first recruit was Peter Reed, who was on the faculty at the University of Massachusetts. He had worked with Henry Lardy at Wisconsin. David Garbers, who knew Peter there, had given me a heads-up about his talent. Peter worked with the calcium ionophore A-823187, and using it had demonstrated effects of calcium within cells. But he wasn’t particularly happy at U. Mass. While there, he had recruited a graduate student, John Murray, who moved with him, obtained M.D. and Ph.D. degrees and eventually joined the Vanderbilt faculty in Medicine. A year after Peter was recruited to the faculty, he took over as Director of Graduate Studies, a job he did with such passion and in such a effective way that few years later, he was appointed Associate Dean of the Graduate School.

Lee Limbird joined our faculty in 1979 from Bob Lefkowitz’s laboratory at Duke. She brought the tools and know-how of radio-ligand binding technology for receptor identification and characterization and shared these with our faculty and students. Her lab became a magnet for graduate students, and she became one of the Department’s and School’s most productive faculty members.

Over the years, additional faculty joined the department. Marty Waterson, and Linda Van Eldik came as members of the Howard Hughes Medical Institute in the mid-1980s. Marty had worked on calcium binding proteins broadly and had provided the first sequence of calmodulin. Linda had been focused on the S-100 proteins. Both of them examined structure-function relationships involving the target proteins for calcium binding proteins. Marty helped increase the institution’s recognition of the value of several emerging technologies. He and Linda left Vanderbilt in the early nineties when Marty took the Pharmacology chair at Northwestern.

Mike Skinner later joined our faculty, recruited primarily by the Reproduction Biology program at Vanderbilt. Mike was interested in inter-cellular communication in testes and the regulation of Sertoli cell function by molecules secreted from peritubular cell. He moved to UCSF in the nineties.



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