Jennings Worley III

Jennings Franklin Worley III passed away following a tragic bicycle accident on 28 November 2020 at the age of 62. Jennings was a collaborative and influential scientist with over 30 peer-reviewed publications who translated his deep understanding of ion channel biophysics and pharmacology to drug discovery.

Early life and academic career. Jennings was born in Washington, DC, and grew up in Maryland. He was always interested in sports and was captain of the football team at Largo High School. He received both his BS in zoology and PhD in physiology from the University of Maryland. As a graduate student in Bruce Kreuger’s lab, Jennings collaborated with Bob French to perform the first electrical recordings from voltage-dependent sodium channels incorporated into lipid bilayers. This work allowed the study of single channels in a way not possible with patch-clamp electrophysiology as some was published in Nature (303:172-175, 1983).

Jennings conducted postdoctoral work in Mark Nelson’s lab at the University of Miami and continued his work on ion channels in lipid bilayers. Jennings’s drive, good nature, and creativity was illustrated by the fact the bilayer set-up was put together in a hallway. Jennings met his wife, Terry, in Miami, and they married shortly before moving to the University of Vermont to continue postdoctoral work with Nelson. In 1987 he took a tenure-track position at the University of West Virginia as an assistant professor. He continued collaborative work with Nelson through the late 1980s, publishing extensively on the role of the calcium channel in smooth muscle contraction, including another paper in Nature (336:382-385, 1988)

Industry innovator. Although successful on the academic track, Jennings began to turn his interests toward applying his ion channel knowledge and expertise to drug discovery. At the suggestion of Nelson, Jennings took a research position in cardiovascular research at GlaxoSmithKline (GSK) in 1990. Jennings learned the importance of flexibility in the industrial setting almost immediately as GSK moved its cardiovascular research from the Research Triangle to the UK, but he easily pivoted to working on diabetes and metabolism. Jennings recognized early on that improved, more convenient methods were needed to support the screening and optimization of ion channel drugs. Jennings was technically adept and an innovator. While at GSK, he was an early adopter of the FLIPR (fluorescence imaging plate reader) to enable ion channel high-throughput screening, and he collaboratively worked with Kirk Schroeder and Brad Neagle (Essen Bioscience) in development of the first commercial-grade, high-throughput, automated electrophysiology instrument (IonWorksHT). Discovering his talent for technology development, Jennings in 2002 joined a biotechnology start-up, Amphora, that was developing microfluidic based chips and assays to screen for ion channels and GPCRs.

Contributions to drug discovery. Jennings joined Vertex Pharmaceuticals in 2004 to focus his expertise on ion channel drug discovery projects targeting CFTR for cystic fibrosis (CF) and voltage-gated sodium channels for pain. Over the years at Vertex, Jennings rose to the level of Senior Director of Discovery Core, an intradisciplinary department that invented and integrated automated processes to handle cells, assays, and compounds at scale. Notable was his collaboration with engineers and cell biologists to develop a high-throughput Ussing chamber array to measure chloride transport across primary human bronchial epithelial cultures from CF donors. Four approved CFTR modulator drugs with the potential to treat 90% of people with CF were discovered on this platform. He enjoyed interaction with CF patients and families and felt great satisfaction upon hearing patient stories about positive results from the CF therapies. The last project he worked on before he passed away was the discovery of a CFTR mRNA therapy to treat the remaining 10% of CF patients. He did not want to leave anyone with CF behind.

Impact on others. Despite these accomplishments, what people will likely remember most about Jennings is that he was wonderfully kind, humorous, and dedicated to science and the people around him. He only celebrated others’ successes, never his own. He felt fortunate to pursue a career that allowed him to ask profound questions and, by answering them, help others. He had many memorable sayings, but he would begin or end many conversations with the same questions: “What do you need and how can I help?” Whether hanging wallpaper for his graduate adviser’s nursery, shucking oysters during beach trips to Baja Mexico, mentoring young scientists on the art of drug discovery, or taking his son Alex to opening day for the Padres, Jennings was always there for others. He was a loving husband to Terry and father to Lauren and Alex. We will miss him.