Saturday, May 23, 2015

I was rather incredulous

‘He explained his call to my astonishment that Beadle, Tatum, and I were to be the co-recipients of the Nobel prize in medicine this year. I was rather incredulous: he insisted the AP was quoting the rumors and he was quite sure it would be announced Thursday.’ This is part of Joshua Lederberg’s diary entry on the day he heard he had been awarded the Nobel Prize. Lederberg, who was born 90 years ago today, was an American scientist who pioneered work in bacterial genetics but who also advanced the influence of science and scientists in public policy development.

Lederberg was born 23 May 1925 in Montclair, New Jersey, the oldest of three sons. His father, a rabbi, and mother had emigrated from Palestine the year before. The family moved to Manhattan when Lederberg was still an infant. He attended Stuyvesant High School,  which specialised in science and technology, and went on to Columbia University, where he studied zoology. There he came under the influence of biochemist Francis J. Ryan, who nurtured his passion to ‘bring the power of chemical analysis to the secrets of life’. In 1943, he enrolled in the Navy’s V-12 training program, which combined an accelerated premedical and medical curriculum, and was able to work at the clinical pathology laboratory at St. Albans Naval Hospital, gaining first-hand experience with parasites.

Lederberg returned to Columbia, finished his degree, and began training as a medical student, also continuing research under Ryan. He was soon much inspired by Oswald Avery’s DNA discoveries, and took a leave of absence to work with Edward L. Tatum, at Yale, an expert in bacteriology and the genetics of micro-organisms. At Yale, he made significant discoveries, including a new understanding of how bacteria evolve and acquire new properties, such as antibiotic resistance.

Lederberg then began mapping the E. coli chromosome, to show the exact locations of its genes. With Tatum’s support, he submitted research on genetic recombination in bacteria as his doctoral thesis, receiving a PhD degree from Yale in 1947. A year earlier he married a fellow scientist, Esther M. Zimmer. Instead of returning to finish a medical degree, he accepted a position as Assistant Professor of Genetics at the University of Wisconsin. There, he was soon making breakthroughs, discovering, with Norton Zinder, how genetic material could be transferred from one strain of the bacterium Salmonella typhimurium to another using viral material. In 1954, he was promoted to Professor.

Two years later, the Society of Illinois Bacteriologists simultaneously awarded Joshua Lederberg and Esther Lederberg the Pasteur Medal, for ’their outstanding contributions to the fields of microbiology and genetics’. And in 1958, Lederberg, shared the Nobel Prize in Physiology or Medicine with George Wells Beadle and Edward Lawrie Tatum. Lederberg’s prize was cited ‘for his discoveries concerning genetic recombination and the organization of the genetic material of bacteria’; and his colleagues were cited for ‘their discovery that genes act by regulating definite chemical events’.

Just days before news of the Nobel Prize, Lederberg  accepted an offer to become the first chairman of the newly-established Department of Genetics at Stanford University’s School of Medicine where he continued to lead research in bacterial genetics. But his interests also widened, relating genetics to the wider context of human health and biology, winning a place for biologists within the burgeoning US space programme. Beyond biological research, he became involved in expanding the role of computers in scientific research, bringing science into matters of public policy, and advising government on such issues. From 1966 to 1971, he wrote a weekly column - Science and Man - for the Washington Post.

in 1966, Lederberg divorced his wife, with whom he had had no children; two years later he married psychiatrist Marguerite Stein Kirsch. They had one daughter. Lederberg became University Professor Emeritus at Rockefeller University in 1990. There, he resumed his own research, continued to advise government and to lecture widely about science issues as they relate to public policies, such as those concerned with bioterrorism and infectious diseases. He died in 2008, Further information is available online from Wikipedia, Nasa, DNA from the beginning, a New York Times obituary, or the National Library of Medicine’s Profiles in science website.

The National Library of Medicine holds an archive of Lederberg’s papers, some of which it has made freely available online. Among these files are images of, and extracts from, Lederberg’s diaries (which range from 1948 to 1963).

20 January 1945
‘I had the evening all to myself, and particularly the excruciating pleasure of reading Avery ’43 on the deoxyribose nucleic acid responsible for type transformation in Pneumococcus. Terrific and unlimited in its implications. Viruses are gene-type compounds, but they cannot grow on synthetic or even dead media, and their capacity for production is limited to reproduction. The TF of Pneumococcus has every characteristic of a mutation. The obvious questions still to be considered are the fraction of serum that is involved in the reaction system; the induction of mutation in the TF by use of x-ray and more controllable methods; the problems of its antigenic specificity and relations to the specific polysaccharide whose manufacture it regulates or initiates. Also the possibility of activity of TF in vitro or in killed systems must be investigated, although the presence of phosphatases and desoxyribonucleases present a difficult problem. I can see real cause for excitement in this stuff though.’

Lederberg wrote a note on the transcript of the following diary entry as follows: ‘I was not keeping a diary at those days but this particular event led me to make notes on it just at the time.’
26 October 1958
‘I was to work at the lab until about 12:30, then pick up Phyllis and Margaret for lunch and then see Phyllis off to her plane: --> Columbus->Denver->SFO->Sydney. At 11:30 + or - there was a call from a Mr. Lindquist of the “Tijding...” newspaper in Stockholm - the New York correspondent. He explained his call to my astonishment that Beadle, Tatum, and I were to be the co-recipients of the Nobel prize in medicine this year. I was rather incredulous: he insisted the AP was quoting the rumors and he was quite sure it would be announced Thursday. It’s no surprise, of course, that Beadle should be honored this way and it is a perceptive courtesy for Tatum but I am still quite astonished (as I was for the NAS last year) to be added on. I just had the impression that this kind of dignification in biology should go to the venerables and veterans and it is a bit of a shock to be classed that way. Of course in physics quite young men, e.g. Willis Lamb have been marked this way too. But I’m worried enough at keeping up a lab career that this kind of stigma has some dreadful connotations: I guess I just don’t believe in memorializing the live and kicking. On the whole I’m a little afraid the fuss and bother more than outweigh the egotistic satisfactions, the cash and the prestige factors that might help in getting my lab going. Perhaps I’m exaggerating the fuss; I was glad enough to be off the cover of Time, however! Anyhow I should have guessed sooner: several clues make some more sense now! - George Klein’s enigmatic correspondence (saying earlier he’d see me this year, then denying he was coming to the U.S.); Leo Goldberg’s request for a photograph; a telephone interview yesterday or Friday by Dag Nystadter reporter; George’s request for a bibliography last spring ( I suppose it did occur to me that George did have something of the sort in his mind then, but hardly this year.) Anyhow the trouble is it is by no means certain and there must be some possibility it is a mistake; I am rather nervously awaiting the AP bulletin to be picked up locally as I’m sure I’ll have no peace after that! I do feel as much as ever that the nonsense ought to be abolished but I don’t have the courage to meet it head on and I’m afraid it would raise even more fuss and perhaps affront Ed and Beadle in a rather nasty way. The best I can do is to be as inconspicuous about it as possible and make some reference to the obsolescence of personal distinction in scientific life.’

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