The Discovery of Bacterial Sex: a Tribute to E. coli K-12

The most famous lab rat in all of molecular biology is Escherichi coli. And the most popular strain of E. coli is the K-12 strain. Why? It was so convenient: it grew quickly, doubling every 20-30 minutes; it was easily isolated and identified; and it was harmless. These features made it a perfect choice as an experimental model.

The pleasant surprise for the pioneers of bacterial geneticists was that the K-12 strain held  treasures.“In retrospect, we know how lucky was the choice of strain K-12,” wrote Joshua Lederberg, “With the methods used in 1946, only one E. coli strain in twenty, chosen at random, would have been successfully crossed, owing to the idiosyncrasies of the F-plasmid which govern its sexual behavior.” Simply put, only K-12 was fertile, because it carried the F-factor, required for fertility. Stranger yet, when the F-factor is transmitted, the receptor cell, the female, transforms into a fertile male! Bacterial sex is infectious! And more like a sex-change infection than an STD.The discovery of F-factor was the first treasure of K-12.

In 1951, Esther Lederberg discovered the next revelation: the lysogenic Lambda bacteriophage. Lambda is naturally “lysogenic” in K-12. “Lysogeny” is the quiet, hidden state of bacterial viruses, when the viral DNA is completely integrated within the chromosome of its bacterial host. When K-12 bacteria are stressed by exposure to UV light, the lambda phage DNA dislocates and new, fully active phages reproduce and kill the host cell. What does that sound like? Shingles. After recovering from chicken pox, you aren’t free of the virus: it hides out in peripheral nerve cells for many decades until stress activates the long-latent virus, and you get (maybe) shingles. The capacity of the Lambda genome to integrate into the E. coli genome, and then separate, upon activation, led to fundamental discoveries about gene regulation and control.

Esther Lederberg was so impressed with K-12, and so grateful for the treasures it provided for her research, that she named her beach house after it. In 1964, she christened her beach house Kappadodici, Italian for “K-12.” Originally, she hoped to design an hexagonal shape for the beach house, that would reflect the hexagonal shape of the head of the Lambda phage virus. This was impractical, so she settled for a semi-hexagonal symmetry.Box32 011 (Coastal house Esther designed - half hexagon)

Box22 024 Pescadero house looking South

Esther Lederberg and a carpenter, framing the beach house.

9 main_entrance

Front door entrance.

3 ocean_view_housefront    Ocean view from the back of the beach house.

4 south_side_of_house.jpg South side of the beach house.

Esther Lederberg Gunther Stent 1965
Esther Lederberg, Gunther Stent, Walter Bodmenr, and Joshua Lederberg. 1965 at the site of the Bean Hollow, Pescadoro beach house.

Naming her beloved beach house Kappadodici wasn’t just a whimsical gesture. Esther really loved her bacteria and meant it as a sincere tribute. Stanley Falkow, chairman of the Department of Microbiology and Immunology at Stanford during the latter half of Esther Lederberg’s career, recalled that she had an abiding affection for bacteria. She belonged to an exceptional breed of scientists who possessed “a feeling for the organism,” as Barbara McClintock described the special connection between the scientist and her experimental subject. Evelyn Fox Keller, McClintock’s biographer, wrote: “this intimate knowledge, made possible by years of close association with the organism she studies, is a prerequisite for her extraordinary perspicacity.” Esther displayed this profound vision that sustained her through a long and successful—if not celebrated—life in science.

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