Yeast as a model organism at Cold Spring Harbor Laboratory
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As I scuffed my shoes on scattered tree branches, bits of broken asphalt, and varied road debris with fast-moving lorries and sports cars whizzing past my right shoulder, it occurred that one of the principle scientific advantages of Cold Spring Harbor Laboratory is isolation. While the laboratory campus is on a busy road and only about a mile from the town with which it shares a name, that busy road has no sidewalks, and a pedestrian trying to make her way from lab to town and back again will find it a difficult journey. My sole attempt on the first day of my visit strongly dissuaded me from trying again, which proved a good thing. I felt trapped, with absolutely nowhere to go other than my small dormitory room, the campus cafeteria, and the room I had been allocated in the library, plus occasional excursions to the small private beach at the end of the campus road. And feeling trapped proved a felicitous mood for thinking about the peculiar environment for doing yeast research in this peculiar corner of the North Shore.
I was in Cold Spring Harbor for two reasons: first, to participate in a small meeting on model organism research; second, to investigate the archived records of the yeast genetics group active at the laboratory from 1977 to about 1985. I was “the yeast person” at the meeting, as Jim Hicks, Amar Klar, and Jeffrey Strathern had been “the yeast group” at Cold Spring Harbor.
The records of “the yeast group” are almost comically stuffed with what I came to think of as “accountancy tables”— loose-leaf notebook paper or gridded green graph paper divided up into columns of endless plus and minus symbols. The yeast group is best-known for making sense of yeast mating-type switching: a previously unseen genetic mechanism whereby either of two versions of a gene can be inserted into an active expression locus while the other version is stored elsewhere in an unexpressed region of the chromosome. The active version of the gene determines whether the yeast cell displays an “a” or “alpha” mating preference, and the intricacies of the molecular mechanism for switching mating type by swapping one region of DNA for another occupied a majority of thegroup's time.
In practice, that work involved scrutinizing stacks and stacks of plates torecord, ultimately, for whether a particular yeast strain did or did not growon a particular selective media. A colony's appearance or failure to appear became a plus or a minus sign in a column of an accountancy table, and rows of symbols became conclusions about gene regulation. Ranks of biochemical markers provided the vertical axis for these tables, yeast strains the horizontal. What stands out most from these records may be the evident monotony of the work. Ultimately most interesting, however, is how Polaroids of plates full of white spots, of variable shape and dimension, became a binary scale in the hands of yeast workers who established that they must make sense of individual patterns of growth in yes-or-no terms.
Thiscapacity to reduce yeast physiology to rows of plus and minus symbols, and to (relatively) quickly and easy tally up colonies as a primary tool of doing genetics, was a major part of why the second half of my visit to the lab involved a workshop on historical research of model organisms. Yeast is one of the thirteen organisms on the National Institutes of Health canonical list of model organisms to which special sharing regulations apply. Its place on that list was cemented, as the structure of the TRANSGENE project itself recognizes,when yeast genome sequencing was incorporated into the Human Genome Project and when yeast became the first fully sequenced eukaryote. The longstanding utility of that genome is only one of myriad major contributions yeast model organism research has made to contemporary biology research. And yet, among participants at that workshop, I was among those with the least literature upon which to draw, with only Robert Meunier and his work on zebrafish on less well-trod ground.
Why? Why is historical and philosophical attention to yeast as a model organism so disproportionate in comparison to the extensive use and obvious value of that model across somany biological subfields? One hypothesis arising from discussions at the workshop is that yeast is complicated; occupying such diverse scientific and social locations, its story (or stories) might be less linear and harder to tell than those of organisms whose trajectory is easier to follow. If so, that provides not one but two very good reasons to fill the gap—to address yeast,but also to address strategies for assembling complexities in how model organisms develop. Unlike Cold Spring Harbor Laboratory’s campus, yeast in the lab is anything but isolated from the outside world. Preserving and highlighting those diverse connections must be part of making sense of where and how yeast has moved in scientific knowledge production.