“Be open and experiment!”

The enormous changes that have characterized scientific research, funding, and education over the past few decades have at times daunted even the most successful and well-established of biomedical scientists. It is certainly understandable if these changes overwhelm students and young professionals just now entering their careers. Charles “Chip” Rutledge, who began graduate studies in pharmacology a half-century ago, has witnessed these changes from a number of vantage points, including research, education, and science administration and development. He speaks of his own navigation of change in terms of self-reliance, a concept he took to during his youth in Kansas, and it is with a mid-western sort of modesty that he describes each challenge undertaken along his career path as little more than an exercise in common sense. But in this way, Rutledge reminds us that successful science, with all its varied challenges, is fundamentally the exercise of common sense borne of a natural inquisitiveness a fairly apt definition of self-reliance. For young people now entering science careers and confronted with uncertain career paths, Rutledge offers the same sort of Emersonian advice that he himself has always relied on. “My advice is to get excited about what you’re doing right now,” he says.” …And keep your eye open for other things.”

–HBS

MI: Talk about the beginning of your career in science.

CR: I enrolled in pharmacy school in the fall of 1955, then a four-year program, at the University of Kansas. I took pharmacology in my junior year with Professor Duane Wenzel. He was the only pharmacologist among the four pharmacy faculty members at Kansas then, the others being responsible for medicinal chemistry, physical pharmacy, and dispensing pharmacy. In the beginning of the junior year, Professor Wenzel asked if anyone among us students would like to do research on a part-time basis, and I volunteered. He had a grant from the Army to study the effects of various performance-enhancing drugs. Pharmacy students volunteered as subjects it was a double-blind study and I had set up some methods for following performance pressing a lever or tracking a moving object. I later published the study in the Journal of Pharmaceutical Sciences as part of an MS degree in pharmacology.

MI: Was there a switch in your thinking from wanting to be a pharmacist to wanting to pursue your eventual career in pharmacology?

CR: No, I had always hoped to be a scientist, but pharmacy was my backup. I liked the idea of being in a profession based on chemistry and biology that could dramatically improve the quality of life of patients afflicted with various diseases. However, my first choice was to be engaged in advancing the sciences of pharmacy.

MI: Had you come from a science-minded family?

CR: My father studied business. My grandfather had been in the first engineering class enrolled at Kansas University. His family had homesteaded, right after the end of the Civil War, on farmland west of Topeka, Kansas, but he worked and studied hard and he graduated, in 1891, as one of the first of the KU civil engineers. He then worked for the Santa Fe Railroad, surveying the land as the track was laid all the way down to Galveston Texas. In my very early years, we lived in Hays, Kansas, but after the war started, the family moved to Kansas City. Dad was too old to go into the service by then, but he had gone into the defense industry working for North American Aviation In Kansas City. I went to school in Kansas City, Kansas, and ended up going to the same high school as my mother.

MI: Were you interested in science by the time you were in high school?

CR: Oh, yes. We had an excellent science field club, and I was involved in all kinds of projects and even had my first research published, by the Kansas Academy of Science, while I was still in high school. I made taxonomic observations on mites obtained from the ears of field mice. I enjoyed doing the experiments, although my writing skills were apparently not so good. But my interest in science even remedied that, because the science club director sent me to my English teacher, who then assigned and corrected an essay from me every day for a semester.

The other big influence on my early life was the Boy Scouts. I learned a lot of my leadership skills from the Scouts, spending about twenty years in scouting, from about the age of nine, to twenty-nine, ultimately becoming a troop Scout Master. There was also a Scouts honor service organization, called Order of the Arrow, which was based on the Indian tradition of proving yourself a worthy brave. I was one of the first of the members to be promoted to the Honor of the Vigil in Kansas, which is really when I learned a lot of leadership skills. Candidates for the Vigil were asked, under primitive outdoor conditions, to describe how they would go about pursuing a life of service. And that was meaningful to me. I learned to multitask in scouting because I was always pursuing multiple merit badge projects. It was really a course in self-reliance, which became very helpful for me as I went on to college and graduate school.

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Chip Rutledge at his desk in the Department of Pharmacology, University of Colorado School of Medicine (June 1975)

MI: In addition to the self-reliance, did your family support your career pursuits?

CR: My parents were supportive and thought I could do pretty much whatever I decided, but my dad was not that thrilled about me becoming a professor. He was a businessman, and he was in favor of my becoming a pharmacist, because everyone would always need drugs, but a university career seemed less certain in his view. But by the time I was in the PhD graduate program, he was convinced that I’d be successful, and my mother always encouraged me to do whatever it was I was thinking about doing.

MI: And what were you thinking about doing when you applied to doctoral programs?

CR: Well, I applied to a few pharmacology programs where Duane Wenzel, my advisor at Kansas, knew some people, including Boston University. While I was in Boston for the interview, I phoned Jane, my fiancee, who was living in Boston, and we got to thinking that I should call the department at Harvard to see if I could interview with them, as well. On the day scheduled for my visit to the Harvard Department of Pharmacology, there was a terrible snow storm. The buses and subways were not running, and everything was shut down. The secretary of the Department at Harvard told me on the phone that she didn’t think anyone would be there, due to the storm. But I had spent a lot of time out-of-doors in the winter and the storm didn’t seem that bad to me. Jane and I walked from Cambridge to the Medical School campus in Boston. Norman Weiner directed graduate studies at the time, but he was away on sabbatical leave in England, and I ended up being interviewed by Otto Krayer, Chair of the Pharmacology Department.

MI: What did you talk about with Otto Krayer?

CR: He asked me first about my research at Kansas and my master’s thesis, and I told him about my methods for measuring the effects of performance-enhancing drugs in humans, but I remember that he then asked me what I read for pleasure and relaxation. I had recently been reading New England authors, particularly Emerson, and he was interested in talking about that. I spoke about Emerson’s essay on self-reliance, which he clearly had read. At the end of our conversation, he said that the Department normally accepted only two students per year, and that the quota had already been met. I took him at his word and was prepared to conclude the interview, but he added that it was possible to make an exception if I could complete the application within the following couple of weeks. It was a rush, but I submitted my application materials within that time and was taken into the program.

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Ralph Waldo Emerson

MI: What was your experience like as a graduate student in Otto Krayer’s department?

CR: That was a well-recognized department, with outstanding faculty. They ran a very rigorous PhD program I published three papers from my first-year rotations. I worked with Roger Kelleher in Peter Dews’s laboratory, and we looked at the effects of amphetamines and barbiturates on pecking behavior in pigeons. This paper is still cited in the behavioral pharmacology literature. Then I worked with Werner Flacke and Milton Alper to develop a gas chromatographic method to measure halothane levels. I did a lab rotation with Norman Weiner that led to my PhD thesis. One of my most memorable experiences was a laboratory rotation with Otto Krayer. He and Werner Mosimann demonstrated many physiological preparations, developed by physiologists and pharmacologists in Germany, to demonstrate pharmacological actions of drugs. These demonstrations included the perfused hind limb of the frog, the perfused Straub frog heart, the guinea pig ileum, and the Langendorf heart preparation. Krayer also showed me the dog heart–lung preparation for which he was especially well-known, demonstrating the effects of cardiac glycosides. Krayer had brought to the Department about seventeen faculty, each in a distinct special area of pharmacology. There was hardly any overlap, and very little collaboration, among these faculty members. In addition to the faculty with whom I did my rotations, the department included Ullrich Trendelenburg in autonomic pharmacology; John Blinks in cardiovascular pharmacology; Jan Koch Weser as a clinical pharmacologist; and Jean Marshall in smooth muscle pharmacology. All of these people were recruited by Krayer and went on to have very successful careers in pharmacology, almost all as chairs of their own departments.

MI: You mentioned that your wife had supported your idea to apply to Pharmacology at Harvard. What was her reaction to your full devotion to your graduate work?

CR: While I was in graduate school, Jane was teaching mathematics in two local high schools. In our forty-nine years of marriage, we have always functioned as a team, and at that time, I supported her teaching career and she supported my working toward a PhD.

MI: You decided to go abroad after completing your PhD at Harvard. What drew you to Arvid Carlsson, who was then decades away from winning the Nobel Prize?

CR: Arvid Carlsson had come to give a talk at Harvard, and I was very impressed with what he was doing in biogenic amines. My PhD work with Norman Weiner was on the effect of reserpine on norepinephrine metabolism in the isolated perfused heart. I wrote to Carlsson to see if he would accept me as a postdoctoral fellow, and he said yes, provided that I got a fellowship. I received a NATO postdoctoral fellowship, and in July, 1966, we boarded the Gripsholm and headed for Gothenburg, Sweden. Jane and I had been learning Swedish before we left Harvard, which helped us ultimately in getting settled in Gothenburg. I was also fortunate in being able to work with Jan Jonason and Gunilla Wilen, already members of the laboratory in Gothenburg. Together, we were able to publish five papers based on the effects of drugs on the metabolism of norepinephrine and dopamine in isolated brain slices. Our first paper was accepted in JPET while my last paper from my graduate work was also in press, in JPET. Jane gave birth to our first child, David, that same year, in November.

MI: So you launched five research projects into publication and had your first baby that year?

CR: It was very productive time! I was very fortunate, too, that Norman Weiner, who had in the interim accepted the chair of the department at Colorado, offered me a job as Assistant Professor, so I didn’t have to worry about getting back to the States for interviews while I was in Sweden. Norman brought a lot of great people into the new department, including Perry Molinoff, John Perkins, Peter Wicks, and Bob Murphy, all of whom became very prominent throughout their careers in the discipline.

During my eight years in Colorado, I proceeded from Assistant to Associate Professor, working in part to develop a model to explain the amphetamine-induced release of norepinephrine, for which I had an NIH grant. I also provided leadership for the interdisciplinary basal ganglia grant, which, I just heard, has been renewed, making it a project of forty years duration. In my eighth year, I was offered the Chair of the Department of Pharmacology and Toxicology back at Kansas University. At Kansas, we built the department up to about six or seven faculty members and had a strong basic science program. Ed Smissman, who had developed medicinal chemistry at Kansas, was instrumental in establishing interdisciplinary science at Kansas, and he in turn brought in Takeru Higuchi, known as the “father of physical pharmacy,” to head pharmaceutical chemistry. Les Mitscher came from Ohio State to continue building the Department of Medicinal Chemistry. So, we built up a really top-notch interdisciplinary research group at Kansas, and I continued there for twelve years. It was during that time that I came onto the Council of ASPET and eventually became Treasurer.

MI: Team building seems to have been a theme in your career, even as you were a graduate student and then a postdoctoral fellow—and a foreigner—in Sweden. How does this proclivity to collaborate mesh with the emphasis on self-reliance that you talked about earlier?

CR: Self-reliance enables you to accomplish personal goals, and team building allows you to accomplish much larger goals that would be impossible if you were working alone. You need new ideas and additional resources that others bring to the project to be successful on a larger scale. With experience, you learn multiple administrative skills and how to apply each one depending upon the circumstances. Self-reliance and team building are just two such skills.

MI: After your time at Kansas, you decided to move to Purdue. What was your mission and reasons for moving on at that time?

CR: I wanted to have a greater impact on both the science of pharmacology and the profession of pharmacy. I could do that in the much larger program at Purdue and by being the Dean of the combined Schools of Pharmacy, Nursing, and Health Sciences. The profession of pharmacy was in a transition phase at that time, moving from a narrow focus on dispensing medication to a much wider scope in healthcare. It became crucial to bring the evolving sophistication of therapeutic medicine into pharmacy in order to inform and more productively involve healthcare providers and patients. One expression of these new concerns came from the Commission to Implement Change in Pharmaceutical Education of the American Association of Colleges of Pharmacy (AACP). I was privileged to take part in the Commission. We wrote a series of three papers that provided a scholarly treatise addressing the forces of change affecting the profession and why additional clinical training for pharmacists would help society. I became President of AACP in 1996, and by 2000, the national accreditation of pharmacists became limited to PharmD programs, no longer recognizing the baccalaureate degree as the entry level degree for the practice of pharmacy. That was a big change for the profession.

MI: The 1990s were also a time of great change for pharmacology. What were some of the changes, in terms of pharmacology, that your work at Purdue addressed?

CR: The year that I was President of AACP, I was also President of ASPET, so I was very much involved in the changes affecting the discipline of pharmacology. In getting people to accept change, you always have to find some aspect of the change that you know they’ll identify with. For example, change that I worked to bring about in the pharmacology curriculum for pharmacy students was the acceptance of more clinical perspective to areas previously presided over by the basic scientists. We did a lot at Purdue to expand collaborations in molecular biology, genetics, and chemical disciplines. There was some objection about the expansion of clinical initiatives, but I supported the general argument that these initiatives would favor the expansion of the basic sciences, such as molecular biology, for example. I think, in the context of such debates, you have to work always to propose a win-win situation. If you expand the basic science foundation of the clinical programs, both the basic scientists and the clinically oriented pharmacy faculty benefit. The key was to finance expansion in both areas. The additional clinical training, for example, was expensive and therefore justified tuition increases, which in turn helped more broadly to expand biomedical programs. In fact, we saw increased student enrollment in response to the expansion of the curriculum.

One of the biggest changes affecting pharmacology was the restructuring of departmental faculties. At Purdue, combination of the Department of Pharmacology and Toxicology with the Department of Medicinal Chemistry and Pharmacognosy resulted in the new Department of Medicinal Chemistry and Molecular Pharmacology. The strengths of both departments were successfully combined at Purdue primarily through the leadership of Richard Borch, a well-known organic chemist as well as a leader in oncology. He was thus positioned to support both chemists and pharmacologists in the new era.

I could talk about so many changes involving interdisciplinary collaboration over the past few decades. At Purdue, Discovery Park was a new initiative that was evolving as I was about to retire from my deanship. The Provost and President at Purdue wrote a grant to the Lilly Endowment and asked me to be Executive Director of Discovery Park, a role in which I was to bring scientists and engineers together to work in four basic areas, namely, the biological sciences, nanotechnology, a complex systems area that we called e-enterprise, and entrepreneurship. This latter program allowed for graduate students, undergraduates, and faculty to commercialize technology. I was tasked to recruit faculty and a director for each of four centers, and in a very short period of time, Discovery Park included five new interdisciplinary research buildings and its own administrative structure. It now attracts funds to support the activities of a thousand faculty and students and has provided some support for more than 140 start-up companies.

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Arvid Carlsson and Chip Rutledge at the Fifty Years of Dopamine celebration, June 1, 2007, in Gothenburg, Sweden

MI: The breadth of those activities, although certainly exciting, could be intimidating, especially for beginning students. What advice would you give to newcomers?

CR: My advice is to get excited about what you’re doing right now and never to be discouraged or intimidated. Do as good a job as you can and work as hard as you can. Try to be successful at what it is you’re doing, but keep your eye open for other things for what other people are doing and how you might contribute. Be open and experiment! Countless times, people would come to Discovery Park and simply ask us a question: Are you interested in this? Often, these same people had heard the word no. But I always try to receive this question positively, with curiosity. Stay cheerful and totally honest. In my experience, opportunities become available to those who are productive and enjoy what they are doing.

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