Copyright Ó 2007 by the Genetics Society of America Perspectives Anecdotal, Historical and Critical Commentaries on Genetics Edited by James F. Crow and William F. Dove Guido Pontecorvo (‘‘Ponte’’): A Centenary Memoir Bernard L. Cohen1 *Institute of Biomedical and Life Sciences, Division of Molecular Genetics, University of Glasgow, Glasgow G11 6NU, Scotland N a memoir published soon after Guido Pontecor- mendation, Pontecorvo applied for and was awarded a I vo’s death (Cohen 2000), I outlined his attractive, small, short-term SPSL scholarship. Thus, he could again but sometimes irascible, character, his history as a apply a genetical approach to a problem related to refugee from Fascism, and his most significant contribu- animal breeding (Pontecorvo 1940a), the branch of tions to genetics. The centenary of his birth (November agriculture in which he had most recently specialized 29, 1907) provides an opportunity for further reflec- with a series of data-rich articles (e.g.,Pontecorvo 1937). tions—personal, historical, and genetical.2 But Ponte was stranded in Edinburgh by the outbreak of Two points of interest arise from the support that war and the cancellation of a Peruvian contract and Ponte received from the Society for the Protection of continued for about 2 years to be supported by SPSL. Science and Learning (SPSL). Formed in 1933 as the The first point of interest is a prime example of the Academic Assistance Council, SPSL aimed to assist the power of chance and opportunity. Renting a small room refugees who had started to arrive in Britain from the in the IAG guest house, Ponte there met Hermann European continent (among them Max Born, Ernst Joseph Muller, who had recently arrived from Russia. Chain, Albert Einstein, Rudolf Peirls, and Max Perutz). Muller was almost certainly the most able, perhaps the In 1938, facing dismissal on ‘‘racial’’ grounds from his only ‘‘pure’’ geneticist that Ponte had met (Pontecorvo position in Tuscany (a copy of the letter of dismissal is 1968a,b) and the effect of this meeting was so strong available from the author), Ponte arranged with Alick that Ponte promptly changed direction, registering Buchanan-Smith,3 whom he had met in Edinburgh as Muller’s Ph.D. student ( July 1939–April 1941). The during a 1937 tour of animal breeding centers, to work second point of interest is that in 1955, when at the Institute of Animal Genetics (IAG) while he appointed to the newly founded chair of genetics at sought another post and, on Buchanan-Smith’s recom- the University of Glasgow, Ponte immediately offered to repay his SPSL scholarship, something that only a few others had done. There being no more refugees, 1 Address for correspondence: IBLS Division of Molecular Genetics, the money was put toward a history of the SPSL. University of Glasgow, Pontecorvo Bldg., 56 Dumbarton Rd., Glasgow G11 6NU, Scotland. E-mail: [email protected] For someone with no background in experimental 2Additional sources for the stories of the refugee scientists include genetics, Ponte’s Ph.D. project must have provided a recorded interviews by Ponte and others in the sound archives of the challenging experience: the sterility of melanogaster 3 Imperial War Museum’s oral history project, ‘‘Britain and the Refugee Crisis, 1933–1947’’ (reference 004505/13) and Medawar and Pyke simulans hybrids was overcome by mating heavily X- (2001). There is also a recorded interview with Ponte in the Edinburgh irradiated simulans males with triploid, multiply marked, University Library collection on the history of the Institute of Animal females. Viable, diploid, ‘‘pseudobackcross’’ progeny Genetics. For authentic accounts of the early history of Aspergillus work, see Roper (1994) and Pontecorvo (1994). For a wider-ranging account, occasionally appeared in which one or more chromo- see Roper and Hopwood (1988). somes were homozygous for melanogaster markers while 3A. D. Buchanan-Smith (1899–1984), who trained in animal breeding the remainder were heterozygous, enabling at least at Iowa State University, was a remarkable character from a distinguished some further analysis of the genetical correlates of family. As well as being a lecturer in genetics he was a practical farmer and pig breeder (at Balerno) and was called on at various times in a long career species divergence in the form of interchromosomal to serve at senior levels in national agricultural administration, national and chromosomal/cytoplasmic interactions (Muller politics, the Scottish church and universities, and several educational and Pontecorvo 1940; Pontecorvo 1943a). While this charities. In the wartime army, he rose to the rank of brigadier and was director of personnel selection at the War Office. Much honored, he was work shed no important and lasting light on genetic eventually elevated to the House of Lords as Lord Balerno of Currie. isolating mechanisms or on the nature of species Genetics 177: 1439–1444 (November 2007) 1440 B. L. Cohen differences—other species were more informative—it The power of somatic recombination for the recovery was a typically ingenious application of Muller’s great from diploids of segregants homozygous for recessive knowledge of the intricacies of Drosophila genetics and alleles and for mapping gene loci in the absence of his skill in devising experiments (Crow 2005) and is still meiotic sexual processes was soon applied by plant often cited. One report (Pontecorvo 1943b, p. 52) also pathologists to the study of host–pathogen relations contains a cryptic reference to Ponte’s temporary in- (Day 1960) and these techniques have been more re- ternment as an ‘‘enemy alien’’ where, referring to Muller cently embraced by mouse geneticists. For example, in and Pontecorvo (1941), he writes, ‘‘Unfortunately their recognition of his pioneering work, Haigis and Dove work was suddenly interrupted before completion.’’ The (2003) dedicated their publication ‘‘to the memory experience of X-ray-induced chromosome loss was soon of Guido Pontecorvo, who insisted long ago on the put to use in another context (see next paragraph) and importance of somatic recombination for mammalian again almost 30 years later (e.g.,Pontecorvo 1971). genetics.’’ Pontecorvo also emphasized ‘‘fields of higher Ponte is most widely known for his pioneering work order’’ in which neighboring functional units may be in microbial genetics. This resulted in the develop- integrated into one field of action (Goldschmidt 1955; ment of Aspergillus nidulans as a genetically tractable Pontecorvo 1958a, pp. 54–55). He thought the T locus model organism (Pontecorvo 1949; Pontecorvo et al. in mice was a particularly good example, about which 1949, 1953) and in recognition of the parasexual cycle Salome Gluecksohn Waelsch (1989, p. 724) chose to (Pontecorvo 1954; Pontecorvo and Sermonti 1954) quote his words: ‘‘...this is probably only a foretaste of and the possibilities that this offered for genetic anal- what we are likely to find when we pass from the analysis ysis in imperfect fungi and, via somatic cells, in hu- of ‘simple’ genes like those providing the information mans (Pontecorvo and Ka¨fer 1956; Pontecorvo for such a minor matter as the mere synthesis of an 1958b, 1959). Less widely known, Ponte introduced the enzyme, to the genetic organization necessary to carry term ‘‘mutational site’’ and first applied Haldane’s the information for morphogenetic processes.’’ terms cis and trans to the genomic arrangement of Chance and opportunity were also involved in forging alleles (Pontecorvo 1950). Surprisingly perhaps, the a human connection between the early work on turn to microbes owed something to Pontecorvo’s Ph.D. Aspergillus and later developments. Among the new studies: he started work with Penicillium around 1943 biochemical ideas at the time (when the molecular and proposed to use X-rays to create high-yielding nature of genes and enzymes was still largely obscure) penicillin-producing strains. But because all British was one due to Henry McIlwain (McIlwain 1946), then penicillin research and development had been offi- professor of biochemistry at the University of Sheffield, cially transferred to the United States, this initiative was who suggested that some enzymes (especially those discouraged. E. Sansome and M. Demerec, along with synthesizing metabolites like vitamins, required in small others in the United States, soon discovered or de- quantities) might be organized in a sort of assembly line veloped high-yielding strains, thereby enabling penicil- so that substrates and products of milli-micromolar lin to be made available in quantity. Despite the official reaction chains would be produced and consumed in discouragement, some fundamental studies of Penicil- close proximity (as is indeed the case with bacterial lium were pursued in collaboration with a member of polyketide synthetases, e.g.,Llewellyn and Spencer the botany department staff (later a noted horticultur- 2007). This was of direct interest because of the use of alist and broadcaster). Genetic evidence for Penicillium auxotrophy for vitamin-like substances (e.g.,biotin)as heterokaryosis was obtained (Pontecorvo and Gem- genetic markers. Were the genes also so arranged and, if mell 1944b), the significance of sectored colonies so, could fine genetic analysis reveal traces of the orga- explored (Pontecorvo and Gemmell 1944a), and, nization? This would provide a plausible rationale for with a later collaborator, parasexual cycle genetics was an Aspergillus genetics research program. In 1946, when demonstrated