Josephine Elliot Clark-Curtiss: a lifetime of pioneering microbiology research

Headshot of Josphine Clark-Curtiss

Josephine Clark-Curtiss, Ph.D., whose career spanned half a century, worked tirelessly to help mitigate the spread of dangerous infectious diseases. After a valiant personal battle against ovarian cancer, she passed away on Nov. 6, 2023, leaving a legacy of pioneering genetic research on mycobacterial diseases like leprosy and tuberculosis.

Clark-Curtiss joined the University of Florida’s Emerging Pathogens Institute in 2015, where she researched the pathogenesis of tuberculosis and worked on developing a vaccine for the disease. She served as a professor of medicine in UF’s Division of Infectious Diseases and Global Medicine, with a joint appointment in the Department of Molecular Genetics and Microbiology, until her retirement in 2022.

Clark-Curtiss’s childhood role models included scientists and healers. She planned to become a medical doctor and earned a bachelor of science in biological sciences from St. Mary’s College in South Bend, Indiana, before she discovered a passion for research.

After receiving her PhD in microbiology from the Medical College of Georgia, she began as a postdoctoral researcher in 1973 at the University of Alabama in Birmingham with Roy Curtiss III, who would later become her husband. She analyzed the genetic bases for the transfer of antibiotic resistance among enterobacteria, a large family of bacteria that includes salmonella and E. coli.

Recombinant DNA technology, which uses enzymes and laboratory techniques to isolate and manipulate segments of DNA, also emerged around this time. As part of the Curtiss research team, she constructed and characterized the first biologically contained “safe” strains of E. coli, paving the way for investigators in the U.S. to conduct research on approved bacterial strains.

Continuing at the University of Alabama as a research faculty member, Clark-Curtiss and her colleagues built the first recombinant DNA library of any mycobacterial strain through their work on Mycobacterium leprae and M. tuberculosis, the bacteria that cause leprosy and tuberculosis, respectively. Her research team was early in identifying specific genes that encoded M. leprae proteins and was the first to point out a repeated DNA sequence in the genetic code of M. leprae. This segment is now known as RLEP and is used to diagnose leprosy.

Profile picture of Josphine Clark-Curtiss

In 1983, Clark-Curtiss joined the research faculty at Washington University in St. Louis’ Department of Microbiology and Immunology, where she continued her molecular genetics research on M. leprae. She and her husband stayed for over two decades, raising three children, before moving to Arizona State University in 2005.

At the Biodesign Institute’s Center for Infectious Diseases and Vaccinology in Arizona, Clark-Curtiss worked in collaboration with Curtiss, her husband, to develop a tuberculosis vaccine. They researched methods for delivering M. tuberculosis protective antigens using recombinant attenuated Salmonella vaccines (RASVs)—essentially, segments from weakened strains of Salmonella.

RASVs are orally administered and engineered to pass through the gastrointestinal tract just like wild salmonella. Instead of causing disease symptoms, however, RASVs produce antigens to stimulate an antibody immune response and do not colonize the host long-term. Tests with laboratory mice showed the RASV tuberculosis vaccines protected mice from aerosolized M. tuberculosis as well as, or slightly better than, BCG vaccine—the gold standard for tuberculosis vaccines.

In 2015, Clark-Curtiss left Arizona State University as an Emeritus Professor and came to UF, where she continued working to improve the RASV tuberculosis vaccine. She was driven by a belief that immunization was a better option than the continual development of antibiotics that bacterial pathogens would inevitably acquire resistance to.

Clark-Curtiss’s research team at UF also worked to understand the mechanisms of tuberculosis pathogenesis, or how the disease develops. By infecting cultured human immune cells with M. tuberculosis, they were able to identify what genes in the bacteria are expressed and subsequently what metabolic pathways are activated. They also characterized the regulatory systems that control gene expression.

Supporters of Clark-Curtiss’s pioneering molecular genetic research included the World Health Organization and the Damien Foundation. She was also the first person to obtain a grant from the National Institutes of Health for genetic analysis of mycobacterial pathogens. Clark-Curtiss served on the US-Japan Leprosy Panel, chaired the Mycobacteriology Division of the American Society for Microbiology, and became a member of the Albert Einstein Society of the National Academies of Sciences, Medicine, and Engineering.

Over the course of her career, Clark-Curtiss was a mentor to many, including 18 postdoctoral scholars, over 50 undergraduate research scholars, and many new faculty members.

Written by: Jiayu Liang