Ray David Owen 30 October 1915 * 21 September 2014

30 october 1915 . 21 september 2014The authors are among many indebted to Ray Owen for his unique and endearing responses to students and his incredible mentorship. To his friends (and that included almost everyone), Ray was a complex man with a simple affect. He was an uncommon mixture of a highly critical and careful scientist overlaid on the soul of a mensch. We recall Ray's many and important scientific accomplishments below, but will finish with a particular trait of the Owen lab: twice daily coffee.Ray David Owen was born in rural Genesee, Wisconsin (population 180) on October 30, 1915. His father was a dairy farmer, and Ray grew up with a farmer's habit of early rising and hard work. He helped work the family farm through three years at nearby Carroll College (Waukesha, Wisconsin), where he majored in biology; the biology department there consisted of a single faculty member. Ray had planned to become a teacher and even went so far as to practice teaching in his hometown. Perhaps most importantly, he met his future wife-June Weissenberg-at Carroll College. He was married to June in 1938, a marriage that lasted for 74 years, until her death.Ray began graduate work at the University of Wisconsin, and his earliest work that we could locate was on the iris color in pigeons (Hollander and Owen 1939a, 1939b). This study using chemical approaches to understand genetics proved to be an important harbinger of his later studies-an approach that he never gave up on. His early fondness for pigeons and doves continued in his own PhD work on the expression of hybrid antigens on crosses between guinea fowl and domestic fowl. This work represents first use of specially produced antibodies that detected neo-antigens on the hybrids that were not present on either parent, and this result foreshadows much of the work of the late twentieth century on the detection of neo-antigens in cancer. He also brought the pigeon models to his graduate students later in his career.Ray's most important single contribution is the famous twin cattle observation. It is important to note that this was not an experiment per se but an observation: an experiment of nature that only a thoughtful observer could interpret. Ray noticed that each of the twin offspring of a cow inseminated by two different bulls expressed blood groups consistent with both sires (Owen 1945). This observation could not be accounted for by then-current Mendelian genetic understanding. Ray, with his previous knowledge of cattle development, surmised that two things had happened: first, that there was a colonization of the blood system of each calf with its co-twin's hematopoietic stem cells; and second, that these acquired cells are capable of becoming established to provide a source of blood cells throughout life, despite their difference from the "host" blood cells. In Ray's oral history, he describes his development in 1946 of the idea of acquired unresponsiveness for a seminar at Caltech. These studies led to the idea of acquired immunological tolerance, which was profound. The paper was recognized but not widely cited until the observations of Anderson et al. (1951) and Billingham, Brent, and Medawar (1953). It is clear that the Medawar group appreciated the importance of the cattle observation. This is stated explicitly in Brent's obituary of Owen published in The Independent, as well as in a letter from Medawar to Owen after the awarding of the Nobel Prize to Medawar and Burnet.In 1946, with the blessing of his department chair, Ray took a leave from the University of Wisconsin and came to Caltech on a short-term appointment as a Gosney Fellow. The appointment transformed into a permanent faculty position a couple of years later, and Ray never returned to Madison.Although the discovery of acquired tolerance is of vast importance, Owen made many other contributions. During a sabbatical at Oak Ridge National Laboratory to work with Dan Lindsley (a Caltech PhD who became a noted Drosophila geneticist), he performed seminal experiments on bone marrow transplantation. …