C. Thomas Caskey (1938–2022)

A pioneer of the genetic code and then genomics, Dr. C. Thomas Caskey, passed away at the age of 83 on January 13, 2022 in Houston, Texas, after a brief illness. He is survived by his wife of 62 years, Peggy Pearce Caskey, his two children, Clifton Caskey and Caroline Caskey Goodner, and three grandchildren. He will be sorely missed by them and his many trainees and colleagues around the world. The breadth of Tom’s contributions to the fields of human molecular genetics and genomics during his approximately 60year career is extraordinary. He can be credited for: contributing key work to decipher the genetic code (Caskey 1970); cloning the third human gene to be so analyzed (Brennand et al. 1982, 1983); discovering short tandem repeat expansions in human disease (Caskey et al. 1992); building a robust and ubiquitously used DNA-based human identification system (Edwards et al. 1991); founding and leading an internationally acclaimed academic department focused on molecular and human genetics; leading a division atMerck Research Laboratories in drug and vaccine development; and advancing genomic medicine in the clinic. Throughout all these endeavors, he was tremendously active in the community, both at the policy level and as an inspirational and collaborative scientist. He trained andmentored an enormous number of individuals, making an indelible impression on more than one generation of scientists. His influence was pronounced in academics, industry, and even outside the world of science. Other articles paying tribute to Tom will surely celebrate his career achievements, describe his deep passion for competitive ocean sailing, and elaborate on his multitude of trainees that now populate the research enterprise. Within the scope of Genome Research, it is particularly appropriate to note his foundational work in genomics and his impact on both genomics and genetics as the fields co-evolved. Tom trained as an M.D., then worked with Marshall Nirenberg at the U.S. National Institutes of Health (NIH) on deciphering the genetic code (Marshall et al. 1967) and, with his colleague Ed Scolnick, on the role of release factors in peptide chain termination (Scolnick and Caskey 1969). He moved to Baylor College of Medicine in 1971 to explore the molecular bases of Mendelian diseases. For much of his ensuing career, Tom studied the molecular genetics of Lesch-Nyhan syndrome and the underlying gene, hypoxanthine phosphoribosyltransferase (HPRT1, previously known as HPRT), co-authoring more than 60 related publications. In 1982, he undertook a sabbatical with Sydney Brenner at the Laboratory of Molecular Biology, Cambridge, UK, with the specific aim of learning themolecular cloning techniques that would enable him to isolate the HPRT cDNA (Brennand et al. 1982). The momentum from this work consolidated his commitment to advancing genetics by focusing on technology development and application. In 1984, he founded the “Institute for Molecular Genetics” (later becoming the Department of Human and Molecular Genetics) at Baylor College of Medicine and soon recruited faculty, fellows, and clinicians, who together brought expertise that ranged from the basic sciences to clinical genetics. Through the work in his own laboratory, and his presence and influence in the clinic, he led the entire Institute in exploring the molecular causes of genetic diseases and building models that could be used for experimentation and therapeutic development. His leadership included the recruitment of model organism geneticists, based on his strong belief that studies in thesemodelswould provide insights that could translate to medical research and practice. Tom attended the earliest meetings on the conceptualization of the Human Genome Project, including the gathering at Alta (1984), the 1986 Cold Spring Harbor Symposium “The Molecular Biology of Homo Sapiens,” and the 1989 NIH and Department of Energy–supported Banbury Center meeting, at which plans to generate a genome-wide physical map were discussed (CookDeegan 1991). He embraced new methods to speed disease gene discovery and molecular diagnostics in his newly formed “Baylor Diagnostic Laboratories.” Meanwhile, he enabled the faculty to build programs in molecular cloning with novel vectors (e.g., cosmids and yeast artificial chromosomes), linkage mapping, and DNA sequencing. Hewas an early and passionate enthusiast for genome sequencing. In 1987, after reading about Yuji Kohara’s physical map of the E. coli genome (Kohara et al. 1987) based on bacteriophage clones, he immediately proposed the idea of pursuing a similar effort for the human X Chromosome. Shortly thereafter, following a visit to the laboratory of Craig Venter, he widely extolled the value of a full human genome sequence. He led by example and, in 1988, began a collaboration with Wilhelm Ansorge at the EMBL laboratories to sequence the entire human HPRT locus (∼44 kb) using the Pharmacia ELF Fluorescent DNA sequencing instrument. The results of this collaborationwere reported the same year as the launch of the Human Genome Project (Edwards et al. 1990) and embodied all of the methods Tom Caskey (left) and Norton Zinder (right) in November 1989 at the Banbury Meeting, “The Human Genome Project: NIH-DOE joint meeting.” (Image courtesy of Cold Spring Harbor Laboratory Archives.)