Dr. William Jusko and the Vanguard of the QSP movement

Bill’s first encounter with pharmaceutical sciences came as a pharmacy student in the lab of the renowned Dr. Gerhard Levy at the University at Buffalo. Dr. Levy encouraged Bill to pursue a career in research, who subsequently went on to become first an Assistant Professor of Pharmacology at Boston University followed by a return to the University at Buffalo in 1972 as the Director of the Clinical Pharmacokinetics Laboratory.

It was at the University at Buffalo where Bill became active in leading the nascent field from the use of basic models into the development and use of the complex quantitative systems pharmacology (QSP) models of today. His pioneering research elucidated novel insights into corticosteroid disposition and signaling and his mechanistic models of indirect responses and target-mediated drug disposition are fundamental to understanding the diverse actions of many drugs.

Along the way, he has been the recipient of multiple landmark awards, including the 2018 Oscar B. Hunter Career Award from the American Society of Clinical Pharmacology and Therapeutics, as well as the top 2020 award from the American Association of Pharmaceutical Scientists.

In this interview, Bill provides his unique perspective gained over a very productive career, both in terms of the science as well as his extensive experience in mentoring junior scientists.

What has surprised you the most about the way the field of pharmacology has changed during your career?
Jusko: The advancements in computation and technology, the movement towards molecular measurements for understanding of drug actions, and the need for collaboration have been the most significant changes to occur during my career. It is difficult for an individual to carry out simple, inexpensive studies these days. Instruments are complex (e.g. LC-MS/MS), data generated is often extensive (e.g. -omics), the literature is wideranging, and sophisticated computation is frequently necessary. I’ve been fortunate to have collaborators with expertise in molecular biology and bioanalysis to complement my role in searching for the ‘rules of biology’ of drug action through PK/PD modeling.

What do you envision as the future of personalized medicine?
Jusko: Early in my career, this area entailed therapeutic drug monitoring and development of pharmacokinetic nomograms for dosing patients. Over time our understanding of physiologic, disease, and drug interaction sources of variability in PK/PD has grown considerably with predictive software available. Today, the availability of pharmacogenetic screening capabilities and identification of diverse biomarkers for drug effects and disease severity has greatly advanced the field. Perhaps the next challenge will be to find rapid methods of assessing and understanding the epigenetic differences among patients and then using these measures, along with other factors and tools, to select and modify drug treatment regimens. 

You have a long track record of mentoring junior scientists. How has your mentoring style evolved over that time?
Jusko: Early in my career, I spent a greater portion of my time in the lab working alongside students and fellows. As they were performing studies with animals and human subjects and operating instruments, I was right there beside them to provide direct teaching, training, and assist in data generation. As my lab group grew, I began to rely on excellent technicians who supervised new students and carried out part of the experimental work. Unfortunately, I eventually lost my touch in mesmerizing rabbits for cardiac punctures to collect blood. My role evolved into largely generating ideas, writing grants, teaching theory, debugging computer code, and writing and revising manuscripts for publication. Over time, I believe I’ve developed a better eye for recognizing the diversity of skills and talents of trainees, and the patience to balance their interests and needs. My participation instead began to range from appreciable early supervision to the backseat of their later freedoms to explore independently inspired ideas (within reason and finances). For me, mentorship has always been more of a collaboration with junior scientists rather than my having a purely supervisory role.

How has your relationship with ASPET been beneficial during your career?
Jusko: I have been very pleased to be a member and participant in ASPET since 1974. Scientific organizations such as ASPET are wonderful for bringing scientists together, meeting old friends, and providing forums for cutting-edge research presented by both new and established scientists. The sponsorship of scientific journals is best handled by societies such as these. ASPET creates and encourages innovation and leadership opportunities, as well as offers various means of recognizing individuals for their accomplishments and contributions to the field.