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 (Pontecorvo and Sermonti 1954). Al- Ponte went to Sheffield to consult McIlwain about these though the earlier work with Penicillium might have ideas, a young student, J. A. Roper, was detailed to escort been a dead end, the search for a genetically tractable him from the railway station. Roper was present during micro-organism that followed was largely inspired by the discussions and later, when the Aspergillus work realization of the opportunities for genetic analysis started to flourish, it was he who became one of the most created by heterokaryosis (Pontecorvo 1947) and by important graduate collaborators and the discoverer of clear ideas on how the resolving power of genetic stable diploids (Roper 1952, 1994). analysis was limited by the number of offspring that Among the many remarkable features of Ponte’s could be screened (Pontecorvo 1956a). It is notable writings is the section of an article on the resolving that, of the novel processes of gene recombination that power of genetic analysis (Pontecorvo 1956b) in which came to light among micro-organisms between 1936 and he sought to give ‘‘chemical meaning to what we are 1946, i.e., bacterial transformation, conjugation, trans- resolving’’ by applying Benzer’s (1955) argument. With duction, and the parasexual cycle, only the latter does an estimated genome size of 4 3 107 bp and a total not generally involve merozygosis (Pontecorvo 1958b). genetic map length of .500 cm, Ponte found that the Perspectives 1441 minimum recombination frequency so far measured in be scaled down to increase the efforts with human cells, Aspergillus (1 3 106 or 104 cm) corresponded to ‘‘8 to which Martin says: ‘‘...our response was to continue nucleotides ... compared with 216 for Drosophila and that valiant effort during the day, and to sneak back to 12 for phage’’ and that ‘‘a whole section of allelism (a the lab at night to do REAL genetics with A. nidulans.’’ gene) could include as a minimum 1,000–8,000 nucleo- Despite the immediate failure of Ponte’s approach to tides in Aspergillus ...and ...further that this is the sort human genetics in vitro, one of his articles in this field of template required for making a protein’’ (p. 84). (Pontecorvo 1975) became a citation classic. This gave Evidently, these ‘‘very crude estimates’’ (later reduced to him sardonic and impish pleasure, mainly because it was 3, 40, and 2 nucleotides; Pontecorvo 1958a, Table 4) rejected by the Proceedings of the Royal Society B on were prescient. When sequenced, the two closest pairs the basis of review by an eminent Oxford cell biologist of sites separated by recombination in meiotic crosses and fellow FRS who should have known better, but who were found to be 11 and 12 nucleotides apart, respec- thought this valuable technical advance was too trivial tively (Glatigny et al. 1998; Wilson and Arst 1998). for such an august journal. Not only was the polyethylene The frequency of recombination in the 11 nucleotides glycol (PEG) fusion method (already in use for proto- separating hxA143 and hxA101 was 6.3 3 106, corre- plast fusion of plants and some bacteria) a considerable sponding to 5.7 3 107 between adjacent nucleotides improvement over the Sendai virus technique then in (C. Scazzocchio, personal communication, based on use for human cells, but also Hopwood (2007, p. 86-88) S. Lee,H.M.Sealy-Lewis and C. Scazzocchio, unpub- recounts how it came to be used for Streptomyces lished data). In the sequenced genome, linkage map/ protoplast fusion and how the conditions optimized recombination distances are rather variable between by Ponte for human cells proved to be beyond improve- regions, but suggest a recombination frequency of 1.3 3 ment. However, it may be unrealistic to claim that the 107 between adjacent nucleotides (A. J. Clutterbuck, wider use of PEG protoplast fusion in bacteriology personal communication). Considering that the number (most recently the transplantation of a bacterial ge- artigue of meiotic progeny screened for recombination is ex- nome: L et al. 2007) owes much to Ponte’s work. trapolated from viable counts, Ponte’s early calculations The many visitors who came to work with Ponte in agree surprisingly well with the specific fine-structure Glasgow carried away varied impressions, but one com- ronamraju experiments and with the overall genomic data. His mon theme has been expressed by K. M. D claims for the (then) unparalleled resolution attained (personal communication), who wrote that: ‘‘Before my by fine genetic analysis were not misplaced, but they had departure for Glasgow, I recall reading Haldane’s copy ontecorvo been anticipated—remarkably, Haldane (1920, pp. 7–8) of Ponte’s book, Trends in Genetic Analysis (P had calculated that in Drosophila, the shortest distance 1958a), and was struck by its simplicity and clarity. between loci is ‘‘... about 100 times the diameter of a Indeed, his writing style was much better than that of hydrogen atom ....’’ As noted above, Ponte’s other most important idea was 4A flavor of the (sometimes amusingly quirky) text is conveyed by the the realization (Pontecorvo and Ka¨fer 1956) that the following quotations: On the misuses of genetics (a favorite hobbyhorse): parasexual cycle could be applied to human genetic ‘‘... the closer relationship between biochemistry and genetics. For this weareindebtedmostlytoBeadleandTatum...a technique of immense analysis through the use of cultured somatic cells, a and versatile power.... Unfortunately, by and large, this technique has possibility to which his own research efforts were dedi- not been put to the best possible use in one of the directions for which it cated from about 1958 until long after official retirement has exceptional value, i.e., the study of the primary actions of the genetic material and their relations to its fine structure. In this respect, it has been age. These attempts to get somatic cell genetics under way made mainly into a tool for the unexciting description of intermediary were unsuccessful through prematurity, but were influen- metabolism ...’’ (Pontecorvo 1958a, p. 4). Self-deprecation: ‘‘A discussion on the relations between arrangement and activity of the tial through collaborators, some of whom later helped the chromosomalmaterialshould,ofcourse, include a consideration of field to flower, and one of whom, George M. Martin heterochromatin. The trouble here is that the study of heterochromatin (personal communication), provided this reminiscence: is at a prescientific level (e.g.,Pontecorvo 1944)’’ (Pontecorvo 1958a, p. 67). Almost an invocation of alternative splicing: ‘‘... the same idea I came to work with Ponte in 1961 because of my interest which I tried to convey very crudely some years ago, that is that new in mapping human genes via mitotic recombination integrations (i.e., genes) would arise epigenetically as a consequence of using cultures of human diploid fibroblasts. It quickly minor changes in chromosome spiralisation resulting from previous activities.’’ (Pontecorvo 1958a, p. 69). A tribute to (or a sly dig at) an became apparent that we could not do serial sub-cloning influential member of the British genetics establishment: ‘‘The study of or repeated replicate plating because of what later recombination suffers from the same disease as Italian literature: that of became known as the ‘‘Hayflick limit’’ of proliferation, having reached its highest peak too early in its life. The result is but Ponte’s view was always that we had not yet devised the subsequent scholasticism. The Divine Commedia of recombination was correct culture conditions. (He was at least partially Darlington’s Recent Advances in Cytology.’’ (Pontecorvo 1958a, p. 132). correct, as culturing these cells under ambient oxygen is And finally, on the resolution of genetic analysis: ‘‘It is quite possible, now known to be sub-optimal.) therefore, that ‘‘negative interference’’ could be the result of the closeness of the mutants necessary to detect it. If this were so we would Even would-be human geneticists were expected to have reached in biology a situation of indeterminacy analogous to that well-known in physics: beyond a certain limit we could not increase at the work with Aspergillus as a form of training in the same time the accuracy of determination of the relative positions and of parasexual cycle, but Ponte determined that this should the recombination between two markers.’’ (Pontecorvo 1958a, p. 89). 1442 B. L. Cohen

Figure 2.—Ugo Fano, Salvador Luria, and Pontecorvo at Cold Spring Harbor, 1946 (Ó Lisa Pontecorvo).

Although Ponte had a reputation for filing official papers in the wastepaper basket, he was (fortunately) more particular with his personal correspondence, of Figure 1.—Pontecorvo with Jacques Monod at Cold Spring which a substantial archive exists and which throws Harbor, 1946 (Ó Lisa Pontecorvo). interesting light on this symposium. From letters of February 1946, it is clear that he was in close, collabo- many who were born and brought up in England, and rative contact with Boris Ephrussi, who did not initially it reminded me of Dobzhansky, who was equally skilled receive an invitation to attend, although one had arrived in English although his mother tongue was Russian.’’ 4 by early March. More unexpectedly (to the writer) is the L. Cavalli-Sforza (personal communication) stressed revelation that Ephrussi was requesting scientific advice other qualities: ‘‘Two extraordinary things about Ponte and support from Pontecorvo (e.g., on X-ray and were his intelligence, and the human warmth he kept chemical mutagenesis in Drosophila) and that the idea under his sharply critical mind .... But he was not the of trying to select yeast mutants resistant to acriflavine self-promoting kind.’’ originated in Glasgow. Thus, Ponte was indirectly re- Not self-promoting perhaps, but neither was he sponsible for the discovery of ‘‘petite’’ yeast which, in inclined to hide his light under a bushel, as shown by the hands of Ephrussi and his colleagues, played such his consistent record of contributing (when he had an important role in the clarification of organelle something useful to say) to meetings of genetics, bio- inheritance. chemistry, and microbiology societies. With European The Pontecorvo legacy in Glasgow has been mixed. scientists struggling to reestablish themselves after the When the Department of Genetics was established and war, attendance at the 1946 Cold Spring Harbor sym- for many years thereafter, Glasgow operated like most posium (no. 11, ‘‘Heredity and Variation in Microor- United Kingdom universities on a model in which the ganisms’’) provided an important opportunity to meet professor was not only primus inter pares among col- one another again and to get to know, and be known by, leagues but also the King-Emperor of a Protectorate. the North American proponents of the burgeoning Thus, the very creation of a genetics department, discoveries in microbial genetics. Leading figures at although welcome on academic grounds (except, ap- the 1946 meeting (with benefit of hindsight) included parently, to the dean of medicine!) entailed a potential D. Bonner, S. Cohen, M. Delbruck, B. Ephrussi, A. D. loss of empire by botany, zoology, microbiology and Hershey, J. Lederberg, the Lindgrens, S. E. Luria, biochemistry, and it would have been both impolitic and A. Lwoff, J. Monod, D. D. Perkins, J. Preer, F. J. Ryan, uncongenial for Ponte to seek to greatly broaden the T. M. Sonneborn, G. Streisinger, E. L. Tatum, and E. M. range of the department’s undergraduate courses, which Witkin. Important new results were reported on virus were devoted mainly to teaching core genetics to science and phage structure and function; mutation in bacteria, students. While there was a good flow of postgraduates, bacteriophage, and fungi; and biochemical variation. the undergraduate honors class remained small, largely Ponte’s contribution, a review of genetic systems based because Ponte thought it irresponsible to train people on heterokaryosis, was rather different from most of the for nonexistent employment; thus, only the most de- rest, many of which were reports of specific experi- termined one or two supplicants were allowed to enroll ments, some in tedious detail. A small selection from his each year, later entrants having to surmount the chal- apparently unique record of the participants is pre- lenge of a full double-degree course of genetics with sented in Figures 1 and 2. botany or zoology. This extraordinary burden ensured Perspectives 1443 that, from 1959 until 1972 or 1973, Glasgow produced reputation that my collaborators and I have, especially no genetics graduates at all. This weakness, however, was abroad, people in my field do not connect my name with ... somewhat balanced by a pioneering interdepartmental Glasgow at all . By establishing a Chair of Genetics this would soon be put straight, and it would be easier to at- course in molecular biology, which flourished from the tract visiting research workers, lecturers, etc.... There are mid-1960s, the setting up of which contributed sub- already 5 chairs in the country: Edinburgh (Waddington), stantially to interdepartmental harmony. Ponte’s key Birmingham (Mather), London, U.C. (Haldane and role (with Michael Stoker, John Paul, Bob Williamson, Penrose), and Cambridge (Fisher). I think it would do and later, Adam Curtis) in the origination of this course Glasgow good to go ahead. perhaps underlines a paradox of his promotion to Yours sincerely, G. Pontecorvo ‘‘Professor and Head of Department’’ because this And fortunately the university agreed with him about traditionally implied an empire-building role for which as promptly as its procedures allowed. he was temperamentally and philosophically unsuited. Although very grateful to Glasgow University for the Generally at odds with the entrenched, conservative shelter and support that it offered, Ponte did occasion- elements of the academic administration, the form ally apply for other posts and received several unsolic- filling, letter writing, and committee sitting required ited inquiries and offers. However, except for the final of someone in his professorial position were anathema move to the Imperial Cancer Research Fund (described ohen (see his letter about the library committee in C in Cohen 2000), which gave complete freedom from 2000) and contributed much to his later decision to administration, all came to nothing. The possibilities resign from the Glasgow professorship. (between 1948 and 1964) for which I have some Glasgow genetics remains a flourishing undergradu- evidence included: an invitation from Demerec to join ate and postgraduate department of study, and the the Cold Spring Harbor Laboratory; inquiries from parallel but overlapping undergraduate honors courses Imperial Chemical Industries and from the Institute of in genetics and in molecular biology continue to Brewing Research; an application for the Quick Chair of flourish. But in 1994 all the separate biology depart- Biology at Cambridge; and an inquiry from Leiden ments were absorbed into the present conglomerate University. And, when asked by University College, (IBLS, now a faculty headed by a dean), and current London, to comment on the suitability of a chair plans entail the abandonment of the 1960s Pontecorvo candidate (a former Ph.D. student of whom he held a Building (with its continuously moving Paternoster lift) not-so-high opinion), Ponte proposed himself instead and the move of genetics staff into refurbished accom- (!). Remarkably, he was elected to, but did not actually modation nearer the campus center, allowing more succeed, R. A. Fisher in the Balfour Chair of Genetics at opportunity to mingle (or even collaborate!) with other Cambridge. This came about because the Electors were biologists. Pontecorvo, who believed that the essential powerless except to elect, without even the candidate’s unity of biology ‘‘makes a nonsense’’ (a favorite phrase) agreement, and the relevant powers would not or could of its division into independent, semicompeting aca- not satisfy his teaching and accommodation needs. demic departments, might well have welcomed such Ponte was put forward by Medawar as a possible candi- changes. date for Haldane’s chair at University College, London; Despite Cavalli-Sforza’s kind words above, Ponte was was offered a position at the John Innes Institution; no wallflower when it came to protecting or promoting invited to apply for the Edinburgh botany chair, invited science and position, as shown by the following extracts to consider Harvard; invited by Medawar to join the from a 1953 letter to the university principal: National Institute for Medical Research at Mill Hill; and Dear Sir Hector, finally, consulted about a possible move to botany at Imperial College, London. By contrast, a 1962 offer ½paraphrased ... I found the enclosed report of the Institute of Biology on The Remuneration of Biologists most from the Albert Einstein Medical College in New York instructive ...the remuneration of the other members of was accepted and many preparations for the move were the Genetics Department staff worked out to be about undertaken, only for it to fall through for family and visa average for the corresponding age-groups in universities. reasons. It is rare for history of this sort to be made ½from here not paraphrased However, my own salary is public, but we may read it as clear evidence of the high grossly below the average for my age-group. I find that at my age (46) the average is about £1,700. I have £1550, yet I regard in which Ponte was held in academic circles. am not a biologist of ability 10% below average. Medawar’s involvement is known to have reflected anx- There are two ways in which the University could put ieties about ‘‘the brain-drain’’; the scientific establish- this matter straight. One would be only to my own advan- ment that he represented was anxious not to lose Ponte tage, i.e., raising my salary. The other one would be both from the United Kingdom. to the University’s and to my own advantage: i.e., establish- I am indebted to Lisa Pontecorvo for the suggestion that her father’s ing a Chair of Genetics (with adequate salary of course). centenary should be marked in some way and for access to and I have come to the conclusion that the time is now ripe permission to use unpublished material. People who contributed for the second alternative ... . The unpleasant, but particular reminiscences or information are named in the text, and unfortunately true, fact is that in spite of the personal their help is gratefully acknowledged. 1444 B. L. Cohen

LITERATURE CITED Pontecorvo, G., 1950 New fields in the biochemical genetics of mi- croorganisms. Biochem. Soc. Symp. 4: 40–50. enzer B , S., 1955 Fine structure of a genetic region in bacterio- Pontecorvo, G., 1954 Mitotic recombination in the genetic system phage. Proc. Natl. Acad. Sci. USA 41: 344–354. of filamentous fungi. Caryologia 6(Suppl): 192–200. ohen C , B. L., 2000 Guido Pontecorvo (‘‘Ponte’’), 1907–1999. Ge- Pontecorvo, G., 1956a Allelism. Cold Spring Harbor Symp. Quant. netics 154: 497–501. Biol. 21: 171–174. row C , J. F., 2005 Hermann Joseph Muller: evolutionist. Nat. Rev. Pontecorvo, G., 1956b Resolving power of genetic analysis. Nature Genet. 6: 941–945. 178: 83–84. ay D , P. R., 1960 Variation in pytopathogenic fungi. Annu. Rev. Mi- Pontecorvo, G., 1958a Trends in Genetic Analysis. Columbia Univer- crobiol. 14: 1–16. sity Press/Oxford University Press, New York/London. latigny of omao uber cazzocchio G , A., P. H ,M.J.R ˜ ,R.H and C. S , Pontecorvo, G., 1958b The versatility of heredity. J. Linn. Soc. 1998 Altered specificity mutations define residues essential for Lond. Zool. 44: and Botany 56: 116–122. substrate positioning in xanthine dehydrogenase. J. Mol. Biol. Pontecorvo, G., 1959 Is genetic analysis via mitotic segregation 278: 431–438. possible in man? Symp. Genet. Biol. Italica 9: 1–4. Goldschmidt, R. B., 1955 Theoretical Genetics. University of Califor- Pontecorvo, G., 1968a Hermann Joseph Muller. Annu. Rev. Genet. nia Press, Berkeley, CA. 2: 1–10. Haigis, K. M., and W. F. Dove, 2003 A Robertsonian translocation Pontecorvo, G., 1968b Hermann Joseph Muller. Biogr. Mem. Fel- suppresses a somatic recombination pathway to loss of heterozy- lows R. Soc. 14: 349–389. gosity. Nat. Genet. 31: 33–39. Pontecorvo, G., 1971 Induction of directional chromosome elim- Haldane, J. B. S., 1920 Some recent work on heredity. Trans. ination in somatic cell hybrids. Nature 230: 367–369. Oxford Univ. Jr. Sci. Club 1: 3–11. Reprinted in Selected Genetic Pontecorvo, G., 1975 Production of mammalian somatic cell hy- Papers of J. B. S. Haldane, edited by K. R. Dronamraju, 1990, brids by means of polyethylene glycol. Somatic Cell Genet. 1: pp. 441–449. Garland Publishing, New York & London. 397–400. Hopwood, D. A., 2007 Streptomyces in Nature and Medicine. Oxford Pontecorvo, G., 1994 Foreword, pp. xxiii–xxv in Aspergillus: 50 University Press, Oxford. Years On, edited by S. D. Martinelli and J. R. Kinghorn. Elsev- Lartigue, C., J. I. Glass,N.Alperovich,R.Pieper,P.P.Parmar ier, Amsterdam. et al., 2007 Genome transplantation in bacteria: changing Pontecorvo, G., and A. R. Gemmell, 1944a Colonies of Penicillium one species to another. Science 317: 632–638. notatum and other moulds as models for the study of population Llewellyn, N. M., and J. B. Spencer, 2007 Enzymes line up for as- genetics. Nature 154: 532–534. sembly. Nature 448: 755–756. Pontecorvo, G., and A. R. Gemmell, 1944b Genetic proof of het- McIlwain, H., 1946 The magnitude of microbial reactions involv- erokaryosis in Penicillium notatum. Nature 154: 514. ing vitamin-like compounds. Nature 158: 898–902. Pontecorvo, G., and E. Ka¨fer, 1956 Mapping the chromosomes by Medawar, J., and D. Pyke, 2001 Hitler’s Gift: Scientists Who Fled Nazi means of mitotic recombination. Proc. R. Phys. Soc. 25: 16–20. Germany. Piatkus Books, London. Pontecorvo, G., and G. Sermonti, 1954 Parasexual recombination Muller, H. J., and G. Pontecorvo, 1940 Recombinants between in Penicillium chrysogenum. J. Gen. Microbiol. 11: 94–104. Drosophila species the F1 hybrids of which are sterile. Nature Pontecorvo, G., E. Forbes and O. B. Adam, 1949 Genetics of the 146: 199. homothallic ascomycete Aspergillus nidulans. Heredity 3: 385. Muller, H. J., and G. Pontecorvo, 1941 Recessive genes causing Pontecorvo, G., J. A. Roper,L.M.Hemmons,K.D.Macdonald and interspecific sterility and other disharmonies between Drosophila A. W. J. Bufton, 1953 The genetics of Aspergillus nidulans. Adv. melanogaster and simulans (Abstr.). Rec. Genet. Soc. Am. 10: 157. Genet. 5: 141–238. Pontecorvo, G., 1937 Criteri adottati nel miglioramento dei bovini di Roper, J. A., 1952 The production of heterozygous diploids in fila- razza Chianina, pp. 1–44 in La Razza Chianina ed il suo Miglioramento. mentous fungi. Experientia 8: 14–15. Ispettorato Provinciale dell’ Agricoltura di Arezzo, Firenze, Italy. Roper, J. A., 1994 The early history, pp. 3–20 in Aspergillus: 50 Years Pontecorvo, G., 1940a A study of persistency in a herd of Ayrshire On, edited by S. D. Martinelli and J. R. Kinghorn. Elsevier, cows. J. Dairy Res. 11: 113–120. Amsterdam. Pontecorvo, G., 1943a Hybrid sterility in artificially produced re- Roper, J. A., and D. A. Hopwood, 1988 Guido Pontecorvo and his combinants between Drosophila melanogaster and D. simulans. Proc. contributions to genetics. Cancer Surv. 7: 229–237. R. Soc. Edinb. Ser. B 61: 385–397. Waelsch, S. G., 1989 In praise of complexity. Genetics 122: 721– Pontecorvo, G., 1943b Viability interactions between chromosomes 725. of Drosophila melanogaster and Drosophila simulans. J. Genet. 45: 51–66. Wilson, R. A., and J. H. N. Arst, 1998 Mutational analysis of AREA, Pontecorvo, G., 1947 Genetic systems based on heterocaryosis. a transcriptional activator mediating nitrogen metabolite repres- Cold Spring Harbor Symp. Quant. Biol. 11: 193–201. sion in Aspergillus nidulans and a member of the ‘‘Streetwise’’ GA- Pontecorvo, G., 1949 ‘‘Balanced’’ heterokaryons in Aspergillus nidu- TA family of transcription factors. Microbiol. Mol. Biol. Rev. 62: lans (Abstr.). Heredity 3: 385. 586–596.