Obituary of Professor Julian E. Davies

The Journal of Antibiotics https://doi.org/10.1038/s41429-025-00827-6 OBITUARY Obituary of Professor Julian E. Davies Ólafur S. Andrésson1 Douglas E. Berg2 Patrice Courvalin3 Michel De Wilde4 Morimasa Yagisawa5 Thomas J. White6 Vicky Davies Robin Davies Jeremy Davies ● ● ● ● ● ● ● ● We express our deepest sadness at the passing of Professor Julian E. Davies, our most esteemed mentor and beloved friend of microbiologists worldwide, on February 2, 2025 near Vancouver, British Columbia. Julian was born in Wales in January 1932, received his Ph.D. in organic chemistry from Nottingham University in 1956, and did postdoctoral work in natural product chemistry at Columbia University in New York and the University of Wisconsin. He was a lecturer at Manchester College of Science & Technology in 1959, a research associate with Bernard Davis at Harvard Medical School from 1962 to 1965 and with Francois Jacob at the Institut Pasteur from 1965 to 1967. In 1968 he established his own laboratory in the Department of Biochemistry at the University of Wisconsin-Madison (UW). Julian published an invited autobiography entitled “Gathering No Moss” to Annual Review of Microbiology in 2003. We will defer many details of his research results and his friendships to that autobiography. Here six of the scientists who worked with Julian during the 1970s describe our fond personal memories of our times with him, and his three grown children describe their wonderful family life in Madison, Geneva, Paris, and Vancouver as further illustration of his creative, energetic and joyful character. 1234567890();,: 1234567890();,: Received: 21 April 2025 / Accepted: 24 April 2025 © The Author(s), under exclusive licence to the Japan Antibiotics Research Association 2025 Overview by Patrice Courvalin Julian E. Davies, Ph.D. Professor Emeritus, University of British Columbia [January 9, 1932 – February 2, 2025] * Morimasa Yagisawa Extended author information available on the last page of the article Throughout Julian’s career, the research in his group reflected aspects of his personality: notably great curiosity, creativity, energy, and sociability. This research was varied, often collaborative, and, most importantly, innovative. As a great admirer of Louis Pasteur, Julian sought to ensure that his fundamental research would have translational and practical applications. His research programs over the years evolved from his first training in chemistry to microbiology, and molecular biology and genetics. Themes of his research included the Ó. S. Andrésson et al. discovery and mode of action of antibiotics, their biosynthesis, ribosome structure and function, the origins, evolution and spread of antibiotic resistance among often unrelated microbial taxa of antibiotic resistance: mobile DNAs (plasmids, transposons, integrons); analyses of antibiotic-producing microorganisms, by genetic, biochemical, and ultimately metagenomic methods, the likely environmental roles of these and other natural products, including cell signaling and microbial population control when at the low (sub-inhibitory) concentrations as in nature; and the extent and potential applications of microbial diversity. In early experiments (1964), Julian showed that streptomycin blocked translation of bacterial mRNAs by binding to 30S subunits of bacterial ribosomes, that resistance due to mutation in laboratory Escherichia coli was due to a change in the 30S ribosomal subunit, and that streptomycin and several other ribosome-targeting drugs could cause errors in mRNA translation (amino acid substitution). Left unsettled was how streptomycin also damages membranes of susceptible cells. Soon thereafter Julian, with his new group at UW, showed that resistance in many clinical isolates to the antibiotics streptomycin, and the neomycin and gentamicin groups usually resulted from specific enzymatic modification or inactivation of the drug (variously by adenylation, phosphorylation or acetylation), not by changes in the ribosomal targets of their action. In 1973 Julian and his first Ph.D. student, Raoul Benveniste discovered antibiotic modifying enzymes in extracts of antibiotic-producing bacteria (e.g., Streptomyces) whose activity profiles matched those from drug-resistant pathogens. Hence, the irony that the very sources of such lifesaving drugs also might have been the ancestral sources of the resistance genes that increasingly compromise their clinical usefulness. This hypothesis has received strong support over the years by findings (i) of broad range R (resistance) factor plasmids, transposons and other mobile DNAs that facilitate gene transfer among unrelated taxa, (ii) that genes cloned from antibiotic producers transferred into other strains in lab experiments do indeed confer expected resistance phenotypes, and (iii) in 1993, of DNAs that can confer resistance can be found in commercial antibiotic preparations. Other valuable research during this period included the isolation of restriction enzymes PstI and KpnI, that were useful for physical mapping and recombinant DNA cloning; and a finding that the npt gene of resistance transposon Tn5 (which Julian co-discovered in Geneva; see below), also conferred resistance to G418, an amionglycoside toxic to eukaryotes. This led to the widespread use of G418 and this npt gene for genetic manipulation and analysis of diverse fungal, plant and animal systems. Also, his was one of the early voices warning that the overuse and careless use of antibiotics would select resistant bacteria, making the antibiotics less and less effective. Practical applications of his basic research were important to Julian. This is illustrated by use of aminoglycosidemodifying enzymes to quantify aminoglycoside serum concentrations, genetic strategies for hyper-producing antibiotics, discovery of new useful restriction endonucleases, and construction of shuttle vector plasmids for Actinomycetes. The appeal of practical applications also led to his move from UW to Geneva in 1980, to become Research Director of the Swiss operation of Biogen, a pioneering international biotechnology company. He returned to Paris in 1985 to become head of the Laboratoire de Génie Microbiologique at the Institut Pasteur. There he began studies of mobile DNA elements and selectable markers in Mycobacterium smegmatis, a non-pathogenic and fastgrowing relative of M. tuberculosis, with important potential for vaccine development and analysis of M. tuberculosis virulence genes. Julian returned to university life in 1992, to become Chair of the Department of Microbiology at the University of British Columbia. There he started the TerraGen Discovery company in 1996, with the goal of finding new antibiotics and other useful compounds in environmental samples. Its core platform entailed encapsulation of individual spores and cells from natural product-producing microbes collected from environmental samples in gelatin beads for growth and scre (...truncated)