Constitutional hyperrecombinability and its consequences.

HANDLING human chromosomes is my métier. I meric constrictions). This pivotal discovery in a cell culture laboratory on the Gulf Coast of Texas in the early realized that long ago; however, preparing an article for Perspectives led me to ask myself how this 1950s—that immersion of mitotic cells in a hypotonic medium will make the chromosomes suitable for microcame to be. I, like others who took the premedicine curriculum in college in the 1940s, had learned about scopic analysis—was made by serendipity. Serendipity is a happy word that means (i) finding something of value Boveri’s discovery of the transmission of developmental determinants via chromosomes and of the stages of meithat was not being sought (ii) by someone who has a mind suitably prepared to perceive its value (cf. Ingram osis and mitosis, as well as more than a few things that were to be unlearned in due time, e.g., that cells rest 2004). Pomerat, long with an interest in the mammalian nucleus and its activities during the cell cycle, and T. C. between mitoses and that the human has 48 chromosomes! Early on, an unusual event convinced me that Hsu, a newcomer to mammalian cell biology but with an interest in genetics, specifically Drosophila genetics, the nucleus was the place to direct my attention and, specifically, that handling chromosomes experimentally were prepared; they perceived the importance of their observations, and fortunately they reported them (Hsu could be just plain exciting: In Galveston one day in the latter part of 1951, I was surprised to see the charismatic and Pomerat 1953), thereby opening the modern era of human, including medical, cytogenetics. pioneer in cell culture, Charles Pomerat, ordinarily sedate and rather slow moving, smiling and jigging happily This story is interesting historically, but why do I introduce my article by relating it? Although I had left the between the benches of his research laboratory. He was waving above his head a handful of freshly printed phoPomerat laboratory before the discovery of the hyposmotic treatment was made, it did happen in the place tographs and calling out to his associates: “Chromowhere I first realized my calling to cell research. Just somes! Human chromosomes!” Those little bearers of that realization seems in some unconscious way to have the determinants of human development about which provided me with continuing reassurance that handling he was so excited that day were not tightly entwined chromosomes was what I should be doing. It has always in the cells, hopelessly inaccessible to the eye of the seemed appropriate that I should be doing so and has microscopist as they had been until then, but rather been a continuing source of contentment. nicely separated from each other. What had happened? Preparation for a life finding out : As I have related The best explanation seems to be that a technical elsewhere (German 2003), I was permitted to work in assistant erroneously had made the laboratory’s stock Pomerat’s laboratory from my earliest days as a medical of balanced salt solution hypotonic. When T. C. Hsu, student (1945), and I had spent the entire summer of Pomerat’s new postdoctoral fellow, used what he 1948 there learning to devise, carry out, and record thought was Tyrode’s solution to rinse some cultures of laboratory experiments by using mammalian cells in human cells prior to fixing and staining them, the cells culture and raising antisera to human reticulo-endothenaturally had imbibed water. Those cells that by chance lial cells. I suppose it was because we were situated in a had been in mitosis had expanded their volume so much medical environment that Pomerat on several occasions that their chromosomes had become sufficiently separeferred to our work with cells as wissenschaftliche Medirated to permit their being counted and the observation zin, contrasting it to klinische Medizin. It was my interest of their individual morphology (relative lengths, centroin and enthusiasm about cells and their culture, first awakened there, that 14 years later was to direct me into human cytogenetics, thence human genetics. The 1Author e-mail: [email protected]