Exploring the Norton Zinder Collection: Penicillin, Auxotrophic Mutants, and Tricks of Memory

By Antoinette Sutto, Robert D. L. Gardiner Historian, sutto@cshl.edu

The story of science is often narrated as a clear progression of experiment and discovery, even though historians of science have pointed out that the reality was and is often much messier. The significance of a particular question or experiment is not always fully evident at the time, notes might be sloppy or incomplete (or lost) and even the best memories can err.

In the mid-1980s, Eugene Garfield of Current Contents invited Joshua Lederberg to write a “Citation Classic” essay on work that he and Norton Zinder had done back in the 1940s. Current Contents was (and is) an index to recently published scientific papers. It was originally published weekly by the Institute for Scientific Information in paper format, with a focus on biology and medicine. Current Contents is currently published in digital and print form by Clarivate Analytics. The “Citation Classic” essays, inaugurated as a part of Current Contents in 1977, were a weekly series of retrospectives on papers that had proven to be significant in the field. The goal was to “provide a kind of living history,” by allowing authors to comment on their past work and introducing readers to important papers they might not be aware of or whose significance they might not fully appreciate.¹ An archive of all of them with a brief introduction by Garfield is available here.

Lederberg and Zinder’s paper described a method for isolating auxotrophic mutants in bacteria.² Auxotrophic bacteria are bacteria that cannot produce one or more organic compounds that they need to survive and reproduce; they are used for genetic studies. They were difficult to isolate because, as Lederberg pointed out in the “Citation Classics” essay, “How would you select for organisms that grow poorly as compared to the wild type?” The solution had been provided by a comment from Gladys Hobby, a microbiologist known for her work on penicillin and other antibiotics. Hobby noted that “penicillin killed only rapidly growing cells, leaving stationary cells alive…her observations suggested that that penicillin, if applied to growing bacteria in a restricted medium, might leave the auxotrophic mutants still living,” since unlike the wild (i.e. not auxotrophic) type they would not be growing due to the medium not providing them with all the materials they needed.³

Lederberg and Zinder learned from Salvador Luria that Bernard D. Davis had made the same discovery independently, and the three of them decided to publish their respective papers (that by Lederberg and Zinder and that by Davis) side by side in the same journal. The journal’s editor also suggested that reprints of the two papers should be combined in one cover. Davis said later that he thought that this was “a model for how simultaneous independent discoveries might be handled.”⁴

As a result, when Garfield invited Lederberg to write his “Citation Classics” retrospective about the paper in 1987, Lederberg wanted to include Davis. Ultimately, they decided to publish two separate essays back to back, just like the original papers.

Material from the Zinder Collection at the CSHL Archives documents the thought process that went into the pair of retrospective essays and shows Lederberg and Zinder trying to reconstruct the precise sequence of thoughts and events that went into the original publication.

Lederberg wrote a note addressed to both Zinder and Davis in late June of 1986, enclosing a draft of the essay.⁵ Zinder wrote back on July 2 with a few brief questions and comments about the draft. Lederberg had stated that they were preparing the results for publication when Luria visited their lab and told them about Davis’s work. Zinder told that him in general “since your memories are your memories, feel free to write as you please.” At the same time, “my memory, which may be fallible, says that before Luria we did not plan immediate publication. To be part of my thesis.”⁶ Lederberg replied by annotating and returning Zinder’s note, remarking that “you may be right” about the plans (or not) for publication, and that he would check his own correspondence to see if he had anything that might “clear that up.” Zinder replied via his own notes on Lederberg’s note that that was “certainly a peculiar if not uncomfortable fact, if true. Indeed you might have written to Francis in dispair[sic] of my ever doing anything else?”⁷ This last comment was a little cryptic, and when Lederberg wrote back to say he hadn’t found any correspondence about publication plans, he asked “what is the despair you refer to? You first arrived at U-Wis in July. By Nov. we were already negotiating with JBC [Journal of Biological Chemistry], JACS [Journal of the American Chemical Society]…”⁸

Zinder and Lederberg’s exchange of notes in the summer of 1986 is a simple story, but it points to some important ideas. First, the archival material behind the published essay suggests how even straightforward stories of experiment and publication can be more complicated and contingent than they appear in retrospect. Lederberg and Zinder had differing memories of whether they had intended to publish their result right away. If Zinder’s memory was correct and they hadn’t intended to write it up right away, they might have left it as a part of Zinder’s thesis had Luria not come by and told them about Davis’s work, and Davis would probably have published first. Next, Lederberg’s comment about consulting his correspondence to see if he could hammer out what had actually happened and the fact that he didn’t follow Zinder’s comment about despair highlight a second important point, that personal memory could, as Zinder said, be “fallible.” What the people involved remember about the process of research, discovery and publication might not always be correct in all respects.

Notes

[1] Eugene Garfield, “Introducing Citation Classics: The Human Side of Scientific Reports,” Current Contents January 3, 1977, pages 5-7. http://www.garfield.library.upenn.edu/essays/v3p001y1977-78.pdf

[2] Joshua Lederberg and Norton Zinder, “Concentration of biochemical mutants of bacteria with penicillin,” Journal of the American Chemical Society 70, 12 (1948): 4267-4268.

[3] Joshua Lederberg, “This Week’s Citation Classic: Lederberg J & Zinder N. Concentration of biochemical mutants of bacteria in penicillin. J. Am. Chem. Soc. 70: 4267-8, 1948,” Current Contents: Life Sciences 30 No. 33, August 17, 1987, page 16. http://garfield.library.upenn.edu/classics1987/A1987J461000001.pdf

[4] Lederberg, “This Week’s Citation Classic”; Bernard D. Davis, “This Week’s Citation Classic: Davis B D. Isolation of biochemically deficient mutants of bacteria by penicillin. J. Amer. Chem. Soc. 70: 4267, 1948,” Current Contents: Life Sciences 30 No. 33, August 17, 1987, page 17. http://garfield.library.upenn.edu/classics1987/A1987J461000002.pdf

[5] CSHL Archives, Norton Zinder Collection, Series: Rockefeller University, Box 38, Folder: unlabeled, xerox of note from Lederberg to Zinder and Bernie (Bernard) Davis, June 25, 1986.

[6] CSHL Archives, Norton Zinder Collection, Series: Rockefeller University, Box 38, Folder: unlabeled, xerox of handwritten note, Zinder to Lederberg, dated 7/2 [1986] and Lederberg, print-out of draft of Citation Classics essay, June 25, 1986.

[7] CSHL Archives, Norton Zinder Collection, Series: Rockefeller University, Box 38, Folder: unlabeled, xerox of handwritten note, Zinder to Lederberg, dated July 2, 1986, with annotations by Lederberg on the right and further notes in response from Zinder, dated 7/5.

[8] CSHL Archives, Norton Zinder Collection, Series: Rockefeller University, Box 38, Folder: unlabeled, handwritten note, Lederberg to Zinder, “1948 Penicillin,” July 7, 1986.