Some of the earliest postings have mysteriously disappeared from the blog. One of these, The Phage in the Letter, is one of my favorites. So, I am re-posting it. Hope you enjoy.
Here is a favorite story of mine that I first heard when I was a graduate student in the mid 1960’s. The major protagonists are Sidney Brenner, who was one of the giants of the “golden age of molecular biology,” and Norton Zinder, also one of the top researchers of the day. Brenner was the first molecular biologist to propose the idea of a messenger RNA, a concept validated by experiments he later did with Mathew Meselson and Francois Jacob. Zinder’s major contributions included the discovery that a bacteriophage can transfer bacterial genes from one bacterial cell to another, a phenomenon referred to as “transduction.” And, apropos this anecdote, Zinder also isolated the f2 bacteriophage, the first bacteriophage known to contain a genome composed of RNA, rather than DNA. [In 1956, Heinz Fraenkel-Conrat at Berkeley, and Gerhard Schramm at Germany’s Max-Planck-Institute for Virus Research, independently discovered that the genome of tobacco mosaic virus is comprised of RNA rather than DNA. Each had found that rubbing the purified RNA of TMV—but not its protein— on wounded tobacco leaves, gave rise to a crop of complete virus particles. Thus, they became the first researchers to demonstrate that RNA can serve as the genetic material of a virus. ]
Bearing in mind how little was known in 1960, when Zinder isolated bacteriophage f2; the discovery of RNA phages had great potential for use in the study of fundamental molecular processes, such as protein synthesis, including its initiation and termination. Clearly, there were good reasons why molecular biologists of the day, including Brenner, wanted to obtain their own samples of f2 phage. So, as the legend goes, Brenner, among others, requested a sample of f2 from Zinder. And, Zinder wrote back to all, saying that the phage was not available.
Zinder may have thought that Brenner wanted the phage to study RNA replication, a topic that Zinder wanted to keep for himself. Now, here is the delightful part of the story. Knowing how carefree researchers can be in the laboratory, Brenner is said to have dipped Zinder’s letter in a culture of E. coli (the f2 host), thereby readily growing up a stock of f2 for himself.
Amusing as this story might be, the actual facts, at least according to a 1997 article by Brenner1, are as follows. First, after Zinder isolsted f2 phage from a New York sewer, he indeed declined to distribute the phage to the large number of researchers requesting it. Second, Brenner’s reason for wanting f2 was not to use it to work on RNA replication, but instead to use it to test bacteria for the presence of a sex factor. The bacterial sex factor is a gene that encodes a so-called pilus, which is present on male bacteria, enabling them to transfer genes to female bacteria. It also is the bacterial “organ” via which RNA phages enter bacterial cells, thus explaining Brenner’s stated interest in f2. [While it might be thought that f2 can only infect male bacteria, interestingly, male bacteria that are infected with f2 can transfer the virus to female bacteria via their pili. Thus, even bacteria have sexually transmitted infections.] Third, while Brenner may not have isolated f2 from Zinder’s letter, he indeed recommended a similar procedure to several other researchers. Brenner also confesses that he might have added to the original myth by hinting that the story actually might be true. In reality, Brenner isolated many RNA phages himself by taking sewerage from the Cambridge, Massachusetts, sewer treatment plant and plating it on bacteria expressing a sex factor.
The Micrograph shows an F-pilus emerging from an E. coli cell that is covered with icosahedral MS2 phage particles. At the end of the pilus, a filamentous fd phage has attached itself. The thicker thread emerging at the right is a bacterial flagellum. Figure 6.11, page 188, From Virology: Molecular Biology and Pathogenesis, by Leonard C. Norkin, ASM Press, 2010.
While Brenner’s work as a molecular biology pioneer may have justified a Nobel Prize, he received the award in 2002 for his later studies of the nematode Caenorhabditis elegans, in which his research group traced the fate of each cell from the zygote right through to the adult worm. Their work established C. Elegans as a model system that is now studied in hundreds of laboratories all over the world.
1Brenner, S. 1997. Bacteriophage Tales. Current Biology 7:R736-737.
Leonard Norkin Virology Site 