Bacterial Genetics Course, 1977 - Invasion of the Kan-hoppers

[Norma Neff]

The Bacterial Genetics Course in July 1977 occurred at a time when DNA technology was beginning to bring geneticists together. My experience at CSHL was the first time I had viewed genetics as a way of thinking rather than a collection of curiosities. Most students including myself had some previous experience in genetics courses and learning basic concepts, but the experimental focus in these traditional courses was on the specifics and subtleties of scoring phenotypes for each model organism. Biochemistry has always been a more universal effort using the same assays and units of activity whether the enzyme is isolated from bug or beast, but genetic systems seemed to maintain a historical tradition of isolation. Small unique sequence elements, combined with DNA isolation and detection methods, now became universal genetic markers such that ideas could be adapted readily from one system to another. The focus of the bacterial genetics course this summer was to learn how to accelerate mutagenesis, mapping and cloning using selectable drug-resistance markers (such as kanamycin) carried on a mobile insertion element (the Kan hop). The course instructors divided the responsibilities with John Roth and David Botstein spearheading the genetic effort, while Peter Wensenk and Ron Davis introduced us to DNA manipulation.

Learning to focus
Genetics has a complex language to expedite the exchange of ideas between investigators (negative interference). One of David Botstein's gifts as a teacher is his ability to make complicated experiments transparent using the retrospectoscope to demystify the schmerogram. Simple phrases such as "you get what you ask for" and "all you need to know is the difference between recombination and complementation" became the mantras of the newly converted.

The less is more experiment
One of the most useful ideas I took away from the course was an understanding of DNA ligation as demonstrated by Ron Davis. This project used electron microscopy to visualize the products of ligation reactions and compare them to the bacterial transformation numbers. In setting up ligations your native instinct is to put more and more of the insert and to use much too much vector in the reactions. Spreading the DNA and seeing the products was much more convincing than any lecture or gel.

Secret Santa
Having Frank Stahl as one of the students enhanced the daily "nuts & bolts" of the course. Frank would drop by with a cheery Zippy greeting "Are we having fun yet?" and offer up equal parts technical hints and philosophy as well as a few zingers to the instructors. The trick I learned from Frank of using a plating wheel and the corner of the triangle spreader with a zigzag motion to create a plate with uniform colony density still confounds and amazes the uninitiated. Frank's warmth and wit were surpassed only by his competitiveness as revealed by his intimidating presence in the volleyball games.

War stories at the Page Motel
This course was memorable not only for its education in transposition and cloning technology but also for several notable nights. John Roth was the favorite instructor of many of the students for affectionate remarks such as "Treat yourself to a few controls" and his saintly patience however brusque his demeanor. He was frequently found at night sitting outside the Page Motel telling scientific stories as if around a campfire. One night he talked about a report in PNAS of protein splicing using two defective beta-galactosidase genes expressed in E.coli. He said that the work had been done at CSHL and something about it bothered him, so he and Jerry Fink had sat up late one night and figured out that the results reported were due to the bacterial strain thought to be rec- was actually Rec+. John pointed out it was important to remember that not everything in the literature is true and sometimes errors are useful. Despite the problems with this report many including myself have used this paper as a teaching tool. The significance of this story is that when Mark Goebl called me about an odd sequence alignment of a gene my lab had cloned from yeast I knew this gene could be what the beta-galactosidase story had foreshadowed. I called Tom Stevens to pool our resources, leading to the first demonstration that protein splicing is a real phenomenon.

"When it gets dark enough, you can see the stars" (C. A. Beard)
Jim Dwyer in the New York Daily News ("Frenzy in Dreadful Darkness" July 6, 1997) characterized July 13, 1977 as the worst night of the worst summer in the modern history of New York. The city's residents were terrorized not only by the blackout of the city and subsequent looting, but also by the fear of the serial killer David Berkowitz (Son of Sam). Unlike the blackout on August 14, 2003, the Long Island Power Authority was able to isolate its grid from Con Edison and this effort resulted in little effect at the Laboratory except for intensive news watching. As a resident of New York City since 1984, I am still amazed by the resourcefulness and resiliency of New Yorkers in the face of terrors both foreign and domestic (Yankee Fans in the subway).

The night of the flying lobster
The banquet traditionally signals the end of a meeting or course at the Laboratory. A normally festive event, it can be boisterous and high-spirited. Occasionally leftover lobster bodies fly back and forth across the room, followed by dinner rolls and cheesecake. At the end of the banquet for the 1977 Bacterial Genetics Course another body went flying. In the spirit of dousing the winning coach with Gatorade, some of the participants in the course grabbed John Roth and tossed him in the harbor by the staff parking lot. The expected exuberant splash was replaced by a thud and a groan as the tide was out. I don't think there were any permanent scars but someone will have to query any surviving horseshoe crabs.