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Book Review
Nature Structural Biology 8, 18 - 19 (2001)
doi:10.1038/82991

Hershey heaven

Reviewed by: Angela N. H. Creager

Angela N. H. Creager is in the Department of History and Program in History of Science, Princeton University, Princeton, New Jersey 08544, USA. creager@Princeton.edu

We can sleep later: Alfred D. Hershey and the origins of molecular biology

Edited by Franklin W. StahlCold Spring Harbor Press, Cold Spring Harbor, New York, USA; 2000. 357 pages, US $39
. ISBN 0-87969-567-6.
When Alan Garen asked Alfred Hershey for his idea of scientific happiness, Hershey replied, "To have one experiment that works, and keep doing it all the time"1. The first generation of molecular biologists referred to this as "Hershey heaven." Both Hershey's wit and his scientific achievements receive their due in We can sleep later: Alfred D. Hershey and the origins of molecular biology. This volume, edited by Franklin Stahl, pays tribute to Hershey through essays and reminiscences by scientists who knew him and includes a selection of his writings. The recognition, as several contributors point out, is long overdue.

Hershey, who died in 1997 at the age of 88, is best known as one of the three founders of the 'phage group'. He shared the Nobel Prize in 1969 with Max Delbrück and Salvador Luria for their pioneering work establishing bacteriophage as the premier model system for molecular genetics. Yet Hershey's reticence kept him out of the public spotlight, and his research career at Cold Spring Harbor meant that he taught few students. The marvelous reflections on science, which he often included in his yearly reports as director of the Carnegie Institution's Carnegie Research Unit, reached a small audience. Consequently, this engaging volume introduces us to a little-known Hershey, filling in the details beyond his famous 1952 experiment and his quip about experimental bliss.

Hershey's versatility with genetic and chemical methods was remarkable even for the time. He and Raquel Rotman provided the first linkage map of a virus, bacteriophage T2, in 1949 (ref. 2). Three years later, the 'Hershey-Chase' experiment (performed with technician Martha Chase) provided decisive biochemical evidence that nucleic acids are the hereditary material3. Using a Waring blender to separate radiolabeled phage that had infected bacteria from the phage 'ghosts' which remained on the outside of the cells, Hershey and Chase showed that 32P-labeled nucleic acids entered the cells whereas 35S-labeled proteins largely remained on the outside.

Hershey's new evidence for the genetic role of nucleic acids in virus reproduction came as a surprise, despite the experiment published by Avery, MacLeod and McCarty in 1944 showing that DNA could genetically alter bacteria4. According to several contributors to the book, even Hershey expected his experiment to confirm that genes were composed of proteins. James Watson credits Hershey's results with providing the impetus for him to pursue the structure of DNA. The experiment's significance was reinforced by its pedagogical value; the Hershey-Chase experiment became a staple of molecular biology textbooks.

The blender experiment exemplified Hershey's ingenuity but did not exhaust it. In 1957 Hershey turned his attention to nucleic acid structure, using chromatography and ultracentrifugation to ascertain the size and shape of viral DNA. He demonstrated that the chromosome of phage (using T2 and lambda) consisted of a single double-stranded molecule. Hershey's further characterization of the lambda chromosome showed that it had "sticky ends" (in his apt phrasing).

Hershey's adeptness as an editor matched his elegant experimentation. The title of the volume is taken from a letter he wrote to contributors to Bacteriophage lambda, published in 1971 (ref. 5). Urging the authors of the 52 essays to complete and return their manuscripts, he ended the letter: "We can sleep later".

The subtitle of We can sleep later invokes a longstanding historical debate with respect to the origins of molecular biology. The 1966 Phage and the origins of molecular biology6, edited by John Cairns, Gunther Stent, and James Watson, offered a genealogy of molecular biology with Delbrück as founding father. The book's implicit message that molecular biology derived from the phage group drew fire from some. John Kendrew argued that structural biologists (such as those in his unit at Cambridge) had also played a crucial role in the founding of molecular biology7.

Gunther Stent subsequently offered a conciliatory view of the origins of molecular biology that combined the 'informational' school of phage genetics with the 'structural' school of X-ray crystallographers, a meeting of the minds that was conveniently personified by Watson and Crick8. This enlarged family tree still did not satisfy everyone; Origins of molecular biology: A tribute to Jacques Monod9, stressed the early importance of French microbiologists. Nonetheless, historical interpretations that emphasized these various 'origins' tended to demarcate molecular biology firmly from pre-existing fields, especially biochemistry (Delbrück famously disparaged biochemistry).

By all these accounts, Hershey makes an odd revolutionary. He is described by friends as a "biochemist's biochemist" as well as a pioneering molecular geneticist. His research defied any dichotomy between informational and structural approaches, and he retained a skeptical attitude towards the supremacy of nucleic acids. Attention to Hershey as one of the original molecular biologists complicates the story, showing the limitations of views that emphasize a single approach, dogma, or charismatic leader. By portraying a trailblazing biologist who combined structural, biochemical, and genetic methods in his quest to understand life at the molecular level, We can sleep later cautions us to keep a broad view of molecular biology's past — and its future.

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REFERENCES
  1. As quoted in Judson, H.F. The eighth day of creation: The makers of the revolution in biology, 275 (Simon and Schuster, New York; 1979).
  2. Hershey, A.D. & Rotman, R. Genetics 34, 44–71 (1949). | ISI |
  3. Hershey, A.D. & Chase, M. J. Gen. Physiol. 36, 39–56 (1952). | Article | PubMed | ISI | ChemPort |
  4. Avery, O.T. , MacLeod, C.M. & McCarty, M. J. Exp. Med. 79, 137–158 (1944). | Article | ChemPort |
  5. Hershey, A.D. , ed. The bacteriophage lambda. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York; 1971).
  6. Cairns, J. , Stent, G.S. & Watson, J.D. Phage and the origins of molecular biology. (Cold Spring Harbor Press, Cold Spring Harbor, New York; 1966).
  7. Kendrew, J. Sci. Am. 216, 141–43 (1967).
  8. Stent, G.S. Science 160, 390–395 (1968). | PubMed | ISI | ChemPort |
  9. Lwoff, A. & Ullmann, A. Origins of molecular biology: A tribute to Jacques Monod. (Academic Press, New York; 1979).
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