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Robert Haselkorn1
Department of Molecular Genetics and Cell Biology, University of
Chicago, Chicago, Illinois, USA
Jim Darnell’s career in science covers the 60 or so years which were absolutely correct. Sol Spiegelman proposed
following the publication of the Watson-Crick structure of another reason the Volkin result was ignored: he said it
DNA. This remarkable book tells a story that parallels his was because it had not been predicted by Francis. What-
career, dealing at the beginning with the prehistory of ever the reason, it was ignored until the Brenner, Jacob,
research on RNA, DNA, and proteins and then shifting and Meselson experiment in 1960, when it was essentially
into high gear with a detailed look at the history of confirmed and re-interpreted to mean that the Volkin
bacterial messenger RNA and the author’s own specialty, RNA was a message carrying the gene sequence to the
the RNA of eukaryotic cells. Having been present at the ribosome, where it could be translated (somehow) into
creation, so to speak, and being blessed with an incredible the amino acid sequences of the phage proteins.
memory (or really good files), Darnell is able to produce Darnell is an experienced teacher and author of text-
an accurate flow, naming the right names and supporting books. His explanations of complex experiments are
every assertion with examples of good data from the superb, taking, for example, his description of the phage
historic record. The prehistory of Chapter 1 ends with the
genetic experiments in which Crick himself participated,
structure of DNA in 1953.
the ones that established the triplet nature of the genetic
The second chapter describes the discovery of messen-
ger RNA in bacteria. From my perspective, Darnell gets code. These experiments involved careful analysis of the
this just right. I was a postdoc in Roy Markham’s lab in rII region of phage T4, in which chemical agents were
Cambridge from 1959 –1961, just outside the city but able used to induce and then to revert deletion or insertion
to see Francis Crick and Sydney Brenner often, and mutations. Darnell’s recapitulation of these, from motiva-
friendly with Jim Ofengand, who was in the Brenner lab. tion to outcome, is a paradigm of clarity.
Brenner went off to Cal Tech in the summer of 1960 with A dicey aspect of the historical approach is the assign-
the express purpose of using the CsCl equilibrium cen- ment of credit, which occasionally requires disputing the
trifugation technique developed by Matt Meselson to see judgment of others, such as the Nobel committee. I find
whether “Volkin RNA” in T2-infected E. coli could be Darnell to be right on target in these cases, perhaps even
found associated with “old” ribosomes, that is, ones that too gentle in some. One example is the prize for the
existed before T2 infection. discovery of the enzyme that synthesizes RNA, awarded to
E. Volkin and L. Astrachan worked at Oak Ridge, where Severo Ochoa. The committee was completely misled,
32
P was available readily. By 1956, they had used the label believing that polynucleotide phosphorylase was the real
to study nucleic acid metabolism in E. coli infected with RNA polymerase, when in truth it degrades RNA. The real
phage T2. They found that early in infection an unstable RNA polymerase was first isolated by Sam Weiss and then
RNA could be labeled rapidly with 32P and that the label by Jerry Hurwitz and Audrey Stevens, which Darnell
turned over and ended up in T2 DNA. The base compo- correctly emphasizes.
sition of the RNA resembled that of the phage DNA. Here
is where their relative isolation in Oak Ridge cost them:
they interpreted their result to mean that the RNA was a
precursor of the DNA. Never mind that it would require 1
Correspondence: Dept. of Molecular Genetics and Cell Biol-
converting every ribose to deoxyribose and methylating ogy, University of Chicago, 920 E. 58th St., CLSC, Rm. 1039A,
every U to T. I suspect that it was this erroneous interpre- Chicago, IL 60637, USA. E-mail: r-haselkorn@uchicago.edu
tation that caused others to ignore the results themselves, doi: 10.1096/fj.11-1101ufm
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