Joshua Lederberg

To cover Josh’s life and work in toto, and with any degree of authority, is the task of “apter craftsmen,” to use his own words. This tribute presents only selected highlights, though one must emphasize the boundless curiosity that his Ph.D. advisor, Edward Lawrie Tatum, and George Beadle, who both shared the Nobel Prize with Josh, likely saw in him and that others came to know in his later years in his role as a scientific statesman.¹

Josh, Beadle, and Tatum shared attributes of leadership and excellence, which helped them forge lasting scientific and social bonds. Josh, a rabbi’s son born in Montclair, New Jersey¹ found a kindred spirit in George Beadle, a farmer’s son born in Wahoo, Nebraska.² Beadle was a contemporary of major scientists like Barbara McClintock, the maize cytogeneticist who received a Nobel Prize for her discovery of mobile genetic elements (transposons) and Boris Ephrussi, whose achievements included the observation that the yeast petite phenotype had its genetic basis in the mitochondrion. Beadle was one of those rare scientists who switched model organisms with great ease, progressing from maize to fruit flies, where he was aided by the chemistry skills of Tatum, and eventually to the bread mold, Neurospora crassa. His collaboration with Tatum using Neurospora auxotrophs to develop the “one gene/one enzyme” hypothesis and the latter’s background on the nutritional requirements of bacteria set the stage for the entrance of the prodigy, Joshua Lederberg.

A young Joshua Lederberg

Josh’s groundbreaking work continued with, among others, Norton Zinder, Josh’s famous graduate student. Norton and Josh studied genetic exchange in Salmonella⁴ and published their seminal work demonstrating transduction.¹ Norton later identified the first phage that contained RNA as its genetic material.⁵ He was appointed as an RU professor in 1964.

One anecdote from the period when Josh was serving as the fifth president of RU illustrates his spirit of generosity. Earlier Nobel nominations for Barbara McClintock’s discovery of genetic transposition in maize (work done in the 1940s) had been unsuccessful and Marcus Rhoades, who concurred with the opinion that McClintock’s work was a forerunner to the operon model of Jacob and Monod, wrote to Josh asking him to “lead the charge” that culminated in her overdue Nobel prize (1983).⁸ Josh readily complied, emphasizing the value of “her work on the mechanism of control of gene action in maize, involving the action and interaction of two independent loci.”⁸

Josh’s connections with RU pre-dated his 1978 appointment as president. He was intimately familiar with the work of Oswald Avery (1944-2005) who, together with MacLeod and McCarty, identified DNA as the genetic material in bacterial transformation.⁹ In an interview, Josh recollected the trio’s publication from their time at RU as having been one of the molding influences on his career.¹ Some of Josh’s later research interests have been told to the RU newsletter, Benchmarks, by RU Associate Professor David Thaler.

Iwona Stroynowski (one of Josh’s students at Stanford in the late 1970s and now a professor at the University of Texas Southwestern Medical Center at Dallas) offered these comments, “At the time when restriction enzymes and gene splicing were in their infancy, Josh was asking his students when the first human being will be successfully cloned. Needless to say, we did not rise to his expectations and failed to acknowledge such a possibility as anything other than science fiction. Josh was never afraid to challenge established wisdoms and differentiate important ideas from details and he did so openly, no matter who listened.” Suffice it to end by also quoting Josh, “As the debate is alive…that is where the scientific method operates.”¹ In 2006, a grateful nation awarded him its highest prize, the Presidential Medal of Freedom.

Our sympathies and thoughts are with Josh’s loved ones: Marguerite, his wife of 40 years, Seymour and Dov, his brothers, Anne and David, his children, as well as Isabel and Jacob, his grandchildren.

Acknowledgments: Mary Jane Zimmerman, Josh’s secretary of 30 years, and David Thaler provided input.

References:

¹ http://profiles.nlm.nih.gov/BB/. The Joshua Lederberg Papers. Washington: National Library of Medicine (NIH).

² Berg P, Singer M., George Beadle, An Uncommon Farmer—The Emergence of Genetics in the Twentieth Century. New York: Cold Spring Harbor Laboratory Press; 2003.

³ Lederberg J, Tatum EL. Gene Recombination in Escherichia coli. Nature 1946;158:558.

⁴ Zinder ND, Lederberg J. Genetic Exchange in Salmonella. J Bacteriol 1952;64(5):679-99.

⁵ Loeb T, Zinder ND. A Bacteriophage Containing RNA. PNAS 1961;47:283-289.

⁶ Lederberg J, St Clair J. Protoplasts and L-type Growth of Escherichia coli. J Bacteriol 1958;75(2):143-60.

⁷ Joseleau-Petit D, Liebart JC, Ayala JA, D’Ari R. Unstable Escherichia coli L Forms Revisited: Growth Requires Peptidoglycan Synthesis. J Bacteriol 2007;189(18):6512-20.

⁸ Comfort NC. From Controlling Elements to Transposons: Barbara McClintock and the Nobel Prize. TIBS 2001;26(7):454-457.

⁹ http://profiles.nlm.nih.gov/CC/. The Oswald T. Avery Collection. Washington: National Library of Medicine (NIH).