Esther Lederberg, Discover of Lambda Prophage, RIP

Biologist Esther Lederberg died recently--unfortunately, it wasn't very well covered (the NY Times was only a month late...). This is a real shame, since I don't think the history of molecular biology would have been the same without her.

While many people are familiar with, or at least have heard of her ex-husband, Joshua Lederberg, Esther Lederberg made seminal discoveries about the prophage Lambda. Lambda is a virus (or 'bacteriophage') that infects bacteria. Lambda can behave lytically--it injects its DNA into the bacterial cell, hijacks the cellular machinery to produce more virus, and then explodes the cell ('lysis') releasing the bacteriophages into the enviroment, where they can infect other bacteria.

What makes lambda phage so interesting is that it is a lysogen: once the DNA is injected into the cell, rather than producing more phage, it integrates into the bacterial genomic DNA, and lurks quietly. Everytime the bacterium divides and reproduces, the integrated lambda phage is also copied. In other words, all of the descendants of the infected bacterium have lambda DNA. When the cell is stressed, the lambda phage can behave lytically, take over the cell and produce more phage. Because of this switch in life history strategy, as well as the ability to integrate in the bacterial DNA, lambda was a model system for understanding some of the molecular and genetic basics of regulation and DNA function. Later, lambda phage would be used as one part of the bacterial geneticist's toolkit to perform various genetic manipulations.

Without her discovery, the history of, and I think the progress in, molecular biology and microbiology would have been very different.

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When I was a grad student I spent a lot of time working with cDNA libraries cloned in lambda. I quite enjoyed the routine of plating phage on bacterial lawns. Now that we are in the age of complete genome and transcriptome sequences, there is vastly less need for this kind of approach.

By PhysioProf (not verified) on 10 Dec 2006 #permalink

My undergrad thesis was constructing a P22 challenge phage assay - without lambda or the complete experience of plating lawn after lawn after lawn, I wouldn't have the appreciation for the patience required to stick things out.

Thanks Mike, for making mention of Ester Ledeberg's passing. The irony of contributing an invaluable discovery and research tool to mol bio, and being virtually unknown beyond the bench, is duly noted.

One of the most fascinating things I find about lambda is the way it controls its genome expression. Particularly the fact that it can transcribe both backwards and forwards along the genome, to produce various proteins to stop transcription of different parts of the genome in order to control what is transcribed. This is what allows is to switch off completely whilst inside the bacteria until conditions inside the bacteria change enough for it to release itself.