This Week's Citation Classics: Host Induced Variation

Today epigenetics is all the rage, but it has its roots in a pair of papers appeared nearly simultaneously in 1952-1953.

Luria SE and Human ML. 1952. A nonhereditary, host-induced variation of bacterial viruses. J. Bact. 64: 557-569.

Bertani G and Weigle JJ. 1953. Host controlled variation in bacterial viruses. J. Bact. 65: 113-121.

Luria & Human and Bertani & Weigle independently discovered that bacterial hosts can affect the growth and phenotypic properties of their bacteriophages.

As Luria and Human put it, "In analyzing the relation between certain phages and certain mutants of their bacterial hosts, we have encountered a novel situation: the genotype of the host in which a virus reproduces affects the phenotype of the new virus. The phenotypic change suppresses the ability of the virus to reproduce in certain hosts but not in others....

Several B/4 mutants of Escherichia coli, strain B, when infected with phages T2 or T6, liberate these phages in a form designated as T*, which does not multiply in young cells of strain B or of its mutants. T* can multiply in a small proportion of old, starved cells of strain B, giving rise to a yield of the corresponding normal T phage."

This finding was quite puzzling at the time, especially since it appeared to subvert traditional Mendelian genetics. Later it was discovered that a number of different mechanisms were responsible for host-induced modification including DNA methylation, restriction modification, and glucosylation. Werner Arber, Daniel Nathans and Ham Smith eventually shared a Nobel prize for their discoveries relating to restriction modification.

When I was working in the Turner Lab at Yale, I noticed that some of my phages grew better on a novel strain when they were previously grown on native strain than when they were previously grown on a novel strain.
I found this phenomenon was kind of interesting and thought I might have been the first to discover this. I called it a "maternal effect". Naturally it was with considerable chagrin when I found out that Luria, Bertani, Weigle and Human had discoved this over 50 years before. On the other hand, I found it neat that I rediscoved something that those giants of microbiology had discovered. And I could console myself with the I was the first to find host-induced modification among RNA phages (maybe).

One more aspect of this discovery that deserves mention is that it highlights the congeniality of the phage group. Not only did each of these authors acknowledge the competing group in their citations, but Bertani and Luria even came up with a media recipe together. Today we call it LB broth.

Figure: Epigenetic Mechanisms Nature 441, 143-145 (11 May 2006)