Copyright 0 1995 by the Genetics Society of America Perspectives Anecdotal, Historical And Critical Commentaries on Genetics Edited by Jams F. Crow and William F. Dove

Two Genes, No Enzyme: A Second Look at BARBARAMCCLINTOCK and the 1951 Cold Spring Harbor Symposium

Nathaniel C. Comfort

Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 1I724 and Department of History, State University of New York, Stony Brook, New York 11 794

didn’t understand a word of it, but if BARBARAsaid this essay is attributed by GREEN(1992) to ALFRED STUR- “Iit, it must be true!” With these words, the great TEVANT, who, GREENsays, had attended theSymposium. Drosophila geneticist ALFRED STURTEVANTreportedly Yet the only STURTEVANT listeda participant as in 1951 gave his opinion of BARBARAMCCLINTOCK’S firstpublic is one FRANKSTURTEVANT, of Northwestern University! presentation of transposable elements, at the 1951 Cold The error is quite excusable; while his is the only pub Spring HarborSymposium (GREEN1992). A legend has lished version, this story has been repeated many times sprungup around MCCLINTOCK’Spresentation, ac- by many people, and doubtless in many versions. It is cording to which she gave her talk with great expecta- part of the legend, amythology that continues to grow, tion of acceptance and interest, only to be ridiculed even among demythologizers. and ignored by her colleagues. The subtext is that A re-examination of the 1951 Symposium can help MCCLINTOCKwas discriminated against, whether be- replace the myth with a more rational explanation of cause of her views or her sex. In her biography of the reaction to MCCLINTOCK’Spaper. It also shows how MCCLINTOCK,EVELYN FOX-KELLER writesthat MCCLIN- data and scientific theory are intertwined with the cul- TOCK’S talk “was met with stony silence. With one or ture of science. MCCLINTOCKwas not apassive recipient two exceptions, no one understood. Afterward, there of her colleagues’judgments. She defiantly and deliber- was mumbling-even some snickering-and outright ately challenged the paradigm viewof the gene-a complaints. It was impossible to understand. What was gutsy move, but one that brought upon herself some this woman up to?” (KELLER 1983, p. 139). of the confusion that so distressed her. MEL GREEN,writing in the 1992 Festschrift for It is certainly true thatMCCLINTOCK’S workwas highly MCCLINTOCK,The Dynamic Genome, seeks to redress the respected by the time she presented her data on trans- legend: “There is a widely extant viewpoint that BARBA- posable elements. Since the 1920s she had published RA’S research was much unappreciatedand appropriate paper after importantpaper on maizecytogenetics. recognition was too longdelayed. . . . I believe this view- With HARRIET CREIGHTONat Cornell, MCCLINTOCKpro- point to be a half-truth” (GREEN1992, p. 117). Some duced the firstvisual evidence of crossing-over, just of the legend springs from MCCLINTOCK’S own lips.In barely beating out CURTSTERN’S similar work on Dro- an interview with KELLER, MCCLINTOCKsaid, “It was sophila. Subsequent work took her ever deeper into just a surprise that I couldn’t communicate; it was a genomic instability and chromosome structure. First surprise that I was being ridiculed, or being told that I she showed the existence of ring chromosomes. Then was really mad” (KELLER 1983, p. 140). Unexplained, she showed that ring chromosomes were a special case MCCLINTOCK’Scool reception supports the idea that of broken chromosomes, one in whichthe endsbecame her colleagues were obtuse in failing to see the truth “sticky” and fused to each other. In 1936 MCCLINTOCK and beauty of her discovery, or worse, that they refused moved to the Universityof Missouri, where she was to accept her results because MCCLINTOCKwas outside hired byLEWIS STADLER,who with R. A. EMERSON, the geneticists’ old boys’ network. MCCLINTOCK’Smentor atCornell, was one of the reign- Some of the legend seems to stem from scientists ing lions of maize genetics. At Missouri, MCCLINTOCK wishing to squelch it. The quote at the beginning of discovered the “breakage-fusion-bridge” cycle, a fur- ther extension of her observations of chromosomal in- Address fw correspondace: Cold Spring Harbor Laboratory, 1 Bung- stability. The breakage-fusion-bridge cycle led MCCLIN- town Road, Cold Spring Harbor, NY 11724. TOCK to two important conclusions, one a prediction

Genetics 140 1161-1166 (August, 1995) more [before transposons], MCCI.INTO(:Kwould have become a major figure in the history of genetics” (FED- and the other hermost profound discovery. The obser- OROFF and BOTSTEIN1992). vation of the “stickiness” of the broken ends of chro- The 1951 Symposium took place in the years between mosomes led MCCLINTOCKto the prediction of special OSWALDAVERY’S demonstration that the transforming structures onthe ends of chromosomesneeded to principle in Pneumococcus was DNA, and the double maintainthe stability lost when thechromosomes revelations of ALFRED HERSHEYand MARTHA CHASE’S broke. She called them telomeres, the study of which “blender experiment” andWATSON AND CRICK’Smodel today is undergoing rapid growth. When MCCLINTOCK of the DNA double helix. The nature of the gene was left Missouri for Cold Spring Harbor in 1941, she took the central question in many biologists’ minds. Bacterio- with her strains of maize that underwent the breakage- phage and bacteria were the model systems of choice, fusion-bridge cycle. From them MCCLINTOCKdeduced with Neurospora and Drosophila close behind. Scien- the existence of transposable elements. The first set of tists working with these organisms were heavily invested experiment$ in which she observed transposition were in the classical T. H. MORGANmodel of the gene. MOR- done in 1944 (MCCI~INTOCK1984). She spent the next GAN’S group had shown the enormous intellectual pro- six years pursuing, confirmingand verifying her results. ductivity of viewing genes as unitary, particulate struc- By 1951 MCCLINTOCKwas among the best-respected tures, arranged linearly and statically alongthe cytogeneticists in the country. Even ten years earlier, chromosomes. BEXDLEAND TATUM’Sone-gene oneen- when the director of the Carnegie Department, MILI- zyme hypothesis, first developed in the early 1940s, lay SLAV DEMEREC,told staff scientist E. CARLETON MAG atop this foundation. It confirmed that geneswere uni- DOU‘EILthat he had succeeded in hiring MCCI.INTOCK, tary by showing they had unitary effects on metabolic MACDOWELI.“jumped up in theair and said, ‘We pathways. MILISLAVDEMEREC, director of the Cold should mark today’s date with red letters in the Depart- Spring Harbor Biological Laboratory and organizer of ment calendar!’ That expresses the feeling that is gen- the 1951 Symposium, acknowledged that the gene con- eral among our members” (DEMEREC1942). In 1939 cept had been unraveling in recent years. Genes, DIG- she was elected vice-president, and in 1945 president, MEREC said, “are regarded as much more loosely de- of the Genetics Society of America. By 1951 she had fined parts of an aggregate, the chromosome, which in received the Achievement Award of the Association of itself is a unit andreacts readily to certain changesin the University Women,been awarded two honoraryde- environment”(DEMEREC 1951). Whatever the gene’s grees, and been a member of theNational Academy of precise molecularnature, the working model of the Sciences for seven years. “The influence of her early gene was of a unitary entity that acted independently to work is greater than that of any of her peers, with the produce a physiologically active molecule. While many possible exception ofAL.FRED STURTEVANT,” wrote NINA at the time recognized that it was an oversimplification, FEDOROFFand DAVIDBOTSTEIN. “Had she done no the view of the genomeas a static, linear series of partic- Perspectives 1163 ulate, independently acting genes proved so successful of the original gene” (GOLDSCHMIDT 1951, p. 1). in explaining genetic observations and generating new Though he cited examples drawn from work on muta- experiments that few had cause to doubt it. ble genes in Drosophila and other organisms, promi- One who did doubt it was R~CHARDGOLDSCHMIDT. nent among GOLDSCHMIDT’Sremarks are several glow- For decades, GOLDSCHMIDT had been a gadfly to the ing mentions of MCCLINTOCK’Sdescription of the Ac/ genetics community. Brilliant and cantankerous, GOLD- Ds system in maize. For GOLDSCHMIDT, transposable ele- SCHMIDT delighted in challenging assumptions and ments provided a shining example of position effects pointing out logical inconsistencies in the evolving ge- and a dynamic genome. He referred to transposable netic theory. Since 1938, GOLDSCHMIDThad been ar- elements as “invisible” (i.e., submicroscopic) rear- guing against the theory of the gene. His observations rangements and position effects. To his fullsatisfaction, of Bar eye in Drosophila led him to conclude that the MCCLINTOCKhad proved that in Zea, “mutable loci are chromosome, not the gene,was the unitary element of actually position effects produced by genetically con- heredity (GOLDSCHMIDT1938; DUNN1965). GOLD- trolled and repeating transpositions and transloca- SCHMIDT argued from translocation data that the posi- tions” (GOLDSCHMIDT1951, p. 4). GOLDSCHMIDT waxed tion of a locus on the chromosome determined its func- poetic in his analogy for how genetic function derived tion. When a locus moved to a differentsite, its function from position: “If the A-string on a violin is stopped an changed. GOLDSCHMIDTargued in 1938 that “the whole inch from the end the tone C is produced. Something conception of the gene”was “obsolete.” GOLDSCHMIDT has been done to a locus in the string, it has been and BEADLEtook up opposing sides in a debate that changed in regard to its function. But nobody would lasted over a decade. GOLDSCHMIDT’Swas a dynamic conclude that there is a Gbody at that point” (GOLD- genome, not a static one. By playing the devil’s advo- SCHMIDT 1951, p. 7).MCCLINTOCK’S data must have cate, GOLDSCHMIDTforced geneticists to reconsider seemed a godsend to GOLDSCHMIDT,an example tailor- their assumptions. Though his style was combative and made to support his attack on the gene concept. his views extreme, position effects havebeen supported In her own paper, directly following GOLDSCHMIDT’S by molecular analyses. To besure, GOLDSCHMIDT in the Symposium volume, MCCLINTOCKreturned the seemed to set up a straw man; his notion of the prevail- favor.Both implicitly and explicitly, she repeatedly ing gene concept seemed to be a globular molecule aligned herself with GOLDSCHMIDT. Twenty-three pages situated on the chromosome, an almost literal “bead into her paper, she said, “It will be noted that use on a string.” This caricature doubtless made it easier of the term gene has been avoided in the foregoing for him to ridicule the gene theory, but it also made discussion of instability”(MCCLINTOCK 1951, p. 36). his alternative impossible for most geneticists to accept. She went on to say that this “does not imply a denialof For all his crotchetiness, GOLDSCHMIDTwas and is an the existence within chromosomes of units or elements important figure in genetics. DEMERECgave GOLD- having specific functions. The evidence for such units SCHMIDT the honor of presenting the opening talk of seems clear.” But the gene concept, she said, “stems the 1951 Symposiumin a special session entitled “The- from studies of mutation.” She then made the link ory of the Gene.” The session was filled out by MCCLIN- with GOLDSCHMIDTexplicit: “The author agrees with TOCK herself, LEWISJ.STADLER, who also critiqued the Goldschmidt that itis not possible to arrive at any clear gene model, but in a way less infuriating to geneticists, understanding of the nature of a gene, or the nature and N. H. HOROWITZand URS LEUPOLD,speaking on of a changein a gene,from mutational evidence alone” new evidence for and implications of the one-gene one- (MCCLINTOCK1951, p. 36). MCCLINTOCKinvoked enzyme theory. The “Theory of the Gene” session thus GOLDSCHMIDTagain in her conclusion: “Evidence, de- had three scientists critical of the standard model and rived from Drosophila experimentation, of the influ- one supportive of it. Much of the rest of the meeting ences of various knownmodifiers on expression of phe- was given over to the microbial geneticists. Three ses- notypic characters has led Goldschmidt (1949, 1951) sions weredevoted entirely to bacteriophage and bacte- to conclusions that are essentially similar to those given ria, with many more papers on microbial genetics sprin- here” (MCCLINTOCK 1951,p. 46). In thebattle between kled throughout the remaining sessions. Most of the GOLDSCHMIDTand BEADLE,it could not have been more remainder concerned Drosophila or Neurospora. On plain with whom MCCLINTOCKallied herself. both sides of the podium, discussion was dominated by It is clear what appealed to MCCLINTOCK inGOLD classical genetics, microorganisms, and the one-gene SCHMIDT’S work. Like MCCLINTOCK,GOLDSCHMIDT was one-enzyme vision of genetic function. arguing for a dynamic genome, a self-regulating system In theopening paper of the Symposium, GOLD- defined by the interactions among its parts.To both,the SCHMIDT revisited the arguments many had heard be- static concept of linear beads on a string, though it had fore. He had new evidence to support it, however. He enormous predictive value,was a vast oversimplification. took on BEADLE’Smodel early on, accusing BEADLEof Yet MCCLINTOCKundersold herself somewhat by align- “extrapolation from the mutant action to the existence ing herself so closely withGOLDSCHMIDT. Her model was 1164 N. C. Comfort considerably more sophisticated than GOLDSCHMIDT’S. containa pentosenucleoprotein that continually re- Unlike GOLDSCHMIDT, MCCLINTOCKbelieved in genes; leases polynucleotide into the cytoplasm. This polynu- she just didn’t believe they were the entire story. Her cleotide, presumably RNA, was presented in the context “controlling elements” were presented as a new sort of of the one-gene one-enzyme theory as direct evidence genetic material, not genes but regulators of genes. that unitary genes have discrete, independent effects in While GOLDSCHMIDT deniedthe BEADLE and TATUM the cytoplasm. MARSHAK suggested that MCCLINTOCK’S model, MCCLINTOCKwas working outside of it. Activatorwas involved with the formation of nucleopro- Equally clear, however, iswhy MCCLINTOCK’Swork teins from raw histones and polynucleotides, much like would have receiveda cool reaction from the assembled a conventional gene. MCCLINTOCK’Sdata, he says, are audience. The differences between MCCLINTOCK’Sand readily explained on the basis of the hypothesis ifwe GOLDSCHMIDT’Sviews wouldhave been obscured by suppose that Ds and the other similar factors represent their obvious mutual admiration. Hadn’t MCCLINTOCK chromosome segments containing greater amounts of avoidedeven the use of the term gene for the first DNA than those which were previously associated with two thirds of her talk? Hadn’t she concludedby saying the locus in question. . . . If the “activator” is involved in the production of the pentosenucleoprotein[,] as for GOLDSCHMIDT’Sconclusions were essectially the same example from raw materials such as histones and poly- as her own? To an audience full of Neurosporists, Dro- nucleotidesstored in the nucleolus[,] an alterationin sophilists and phageologists, it must have seemed that the amount of the substance we have assumed to govern they had just hadto endure their second GOLDSCHMIDT the rate of activity of the locus will result and hence a talk! mutated condition: or if the intensity of the activator action varies, in a mutable condition. In this connection Although many geneticists were relaxing their con- it appears significant that the simultaneous presence in cept of the gene,all wereemploying it. Whatever a gene the genome of a Ds or Ds-like region together with an was, it was unitary and it acted independently. Eleven “activator” results in a “fusion-breakage event” which papers in the Symposium concerned the mutagenic ef- further suggests involvement of transport andutilization fects of radiation and chemicals. Further, “mutation” of nucleolar materials (MARSHAK1951, p. 157). and “gene” were defined in ways that were internally In this rather convoluted passage, MARSHAK attempts consistent but entirely self-contained. A mutation dis- to explain MCCLINTOCK’Sobservations from a BEADLE- rupteda gene. In his paper on pseudoallelism and and-TATUM point of view. Although MCCLINTOCKem- crossing over, E. B. LEWISdefined the geneas a physical phasized that Ac and Ds were not conventional genes, unit within which there is no crossing over. A static, MARSHAK’S explanation hinges on Ac being involved in discrete unit was inherent in his definition: “The defi- the production of nucleic acids-in short, acting like nition of any particulate unit must be in terms of its a gene. Significantly, MARSHAK says that “while other indestructibility by some breakage or splitting process” interpretations may seem equally plausible, this one . . . (LEWIS1951, p. 174). LEWIS’Sconcept of a gene com- is amenable to being tested experimentally,” suggesting plex became a paradigm in Drosophila developmental that MCCLINTOCK’Sinterpretation is not. genetics, but the regulation of the bithorax complex In their paper on chemically induced mutations in by chromosomal components has proved to be a key Neurospora, K. A. JENSEN,INGER KIRK, G. KOLMARK, element in understanding its operation. While GOLD- and M. WESTERGAARDoffer a different interpretation SCHMIDT and MCCLINTOCK’S1951 visionof genetic reg- of MCCLINTOCK’Sresults. They cite MCCLINTOCK’Scon- ulation differs from the modern conception, the paral- trolling elements as evidence for their theory that muta- lels are in many ways more striking than thedifferences. ble genes might result from unstable precursors accu- MCCLINTOCK’Scontrolling elements were non-genes, mulating- in the nucleus, the result of blocked steps in genetic particles outside the framework of one-gene a BEADLEand TATUM-Style biochemical pathway: one-enzyme biochemical genetics. We know from the work on biochemical mutants of MCCLINTOCKdid not go unnoticed in the Sympo- Neurospora that when a specific intermediate step in the sium. Several speakers in later sessions referred to her synthesis of a vitamin or an amino acid is blocked by work, either in their papers or in the reprinted discus- mutation, a precursor may accumulate in the cells. We sion that followedmany of the papers. STADLER,of also know that some of these precursors are highly stable course, cited her graciously, though hedid so nonanalyt- and may be extractedfrom themycelium, and that others are very unstable and areconverted into by-products, like ically. JACKSCHULTZ cited her 1933 work on association the purple pigment in our adenineless strain, whereas of nonhomologous chromosomes during prophase of others disappear completely. We want to suggest that meiosis and NORMANGILES cited her seminal 1945 pa- some of the unstable precursors may act as mutagens per on thecytology of Neurospora. Two others referred during the decomposition. This would be a very specific type of mutagens [sic], since, as primary gene products, to MCCLINTOCK’Swork on transposons. ALFRED MAR- they may be produced within the nucleus. It does not SHAK, commenting on DAVIDBONNER’S paper on gene- seem improbable that some of these precursors would enzyme relationships in Neurospora, cited MCCLIN- be so unstable that they may only react over a very short TOCK’S work in connection with observations that nuclei distance, thus inducing mutations in loci only within a Perspectives 1165

short distance from the “blocked” gene. The so called systems.” She wrote that “it was the patternof behavior, unstableor mutable loci now under investigation by rather than the change in expression of the particular McClintock(1950) may be due to such an “unstable precursor” mechanism UENSENet al. 1951, p. 258). phenotypic character,that was obviouslyof impor- tance” (MCCLINTOCK1951, p. 43). She felt it was neces- Neither ~~RSHAKnor JENSEN et al. ignored MCCLIN- sary “to consider these various widely different levels TOCK’S work; neither, however, accepted her interpreta- of unitary control and how they may operate in the tion of her data. MARSHAKand JENSEN were working working nucleus, and also to consider the natureof the within the dominant paradigm of the BEADLEand TA- changes that can affect their operation” (MCCLINTOCK TUM model, and attemptedto jam MCCLINTOCK’S 1951, p. 37). This was pretty cosmic stuffto a biochemi- anomalouscontrolling elements into that prevailing cal geneticist or phage group member. and familiar conceptual framework. These examples The controversy between the MCCLINTOCK/GOLD- neither illustrate cloddishness on the part of MARSHAK SCHMIDT view of the gene and the BEADLE/TATUMview or JENSEN, nor demonstrate that MARSHAK and JENSEN was resolved with the advent of modern molecular tech- “misunderstood” MCCLINTOCK’Swork. Rather, they niques. As is often the case, both sides were partlyright. suggest scientists who listened to and believed MCCLIN- Transposition became widely accepted in the 1970s as TOCK’S data but thoughther interpretation overly spec- SAEDLER,STARLINGER, SHAPIRO, BOTSTEIN, FINK, FEDOR- ulative and even untestable. E. B. LEWIShad a similar OFF and others identified transposable elements in mi- reaction. He said of MCCLINTOCK,“Everybody recog- crobial and animal systems and elucidated the mecha- nized her as a great scientist. You could trust what she nism of transposition. It became clear that transposable found out experimentally, but it was the speculation elements can encode proteins that regulate other that gotout of hand. This reinforced her mystical ideas. genes. Ac was shown to encode transposase, which acti- Youjust couldn’t fit it into the standardgenetic theory” vates Ds. Genome instability, position effects, and geno- (E. B. LEWIS,personal communication). LEWISeven mic regulation have become hot topics as molecular suggests that MCCLINTOCKand GOLDSCHMIDT may have techniques allow confirmation and modification of been seen as supporting the anti-genetic stance of T. D. MCCLINTOCK’Sideas. MCCLINTOCK’Svision of biology LYSENKO-aview MCCLINTOCKand GOLDSCHMIDT needed to be filtered through the accepted methodol- would have found absurd, but one that illustrates how ogy and language of genetics and molecular biology in far out they seemed to mainstream geneticists. MCCLIN- order forit to significantly influence our understanding TOCK’S peers were struggling to re-interpret anomalous of the gene. Further, thenew techniques made it possi- data into terms with which they were comfortable. ble to confirm what had seemed speculations, and to Other factors doubtless also contributed to theconfu- do it in multiple species. sion about and lack of acceptance of MCCLINTOCK’S MCCLINTOCKwas universally admired as an experi- conclusions. Her model systemmay have had some mentalist, but to some she seemed to be extrapolating alienating effect, but it would seem to have been small. too much from her data. Those unfamiliar with her True, STADLERwas the only other maize geneticist on work probably associated her paper with the one pre- the program, yet there were several other plant geneti- ceding it and considered MCCLINTOCKjust another cists and several cytologists. And although maize was Goldschmidtian. MCCLINTOCKherself encouraged this becoming an unfashionable organism in genetics, it perception by explicitly aligning herself with the notori- wasn’t so far out of style as to be incomprehensible. ously controversial GOLDSCHMIDT.And GOLDSCHMIDT MCCLINTOCK’Spresentation may have been something was, in fact, the closest to MCCLINTOCK in hisconcept of a barrier,however. Non-trivial, surely,was her paper’s of the gene. But unlike GOLDSCHMIDT,MCCLINTOCK considerable length. Itfilled 35 pages in the Symposium didn’trefute the paradigm-she stepped outside it. volume and was by far the longest of anyat themeeting. Among those who knew and respected her, some tried MCCLINTOCKpresented a welter of data, with long sec- to squeeze her findings into their conception of the tions of background on each important mutation and gene, while some, like STURTEVANT-Or whoever it detailed descriptions of her crosses. Her talk was essen- was-didn’t understand a word of what she said. tially historical in structure, rather than the more con- Thanks to ROB MARTIENSSEN for critical reading and discussion of ventional format of Introduction, Results and Conclu- the manuscript, to CAROL GREIDERfor critical reading and more, sion, so it tended to ramble. Also, she used highly and to CLARE BUNCEfor archival research. The portraits of BARBARA unconventional language. Beyond dispensing with the MCCLINTOCKand RICHARD GOLDSCHMIDT were provided by the Cold word “gene,” she invented new terms to describe her Spring Harbor Laboratory Research Library Archives. new phenomena. In addition to “activators” and “dis- sociators”-terms that even those scientists who tack- LITERATURE CITED led her data handled with verbal kid gloves, such as DEMEREC,M., 1942 Letter to W. M. GILBERT,Executive Director of quotation marks and “so-cal1eds””she spoke of “al- the Carnegie Institution of Washington, 6 April 1942. MCCLIN- tered states,” “out-of-phase timing,” and “controlling TOCK file, Cold Spring Harbor Laboratory Archives. 1166 Comfort N. C.

DEMEREC,M., 1951 Foreword. Cold SpringHarbor Symp. Quant. ofhetics, edited by N. FEDOROFFand D. BOTSTEIN.Cold Spring Biol. 16: v. Harbor Laboratory Press, Cold Spring Harbor, NY. DUNN,L. C., 1965 A ShortHistmy ofGenetics McGraw-Hill, NewYork. JENSEN,K.A.,I.KIRK,G.KOLMARK~~~M.WESTERGAARD,~~~~Chemi- FEDOROFF,N., and D. BOTSTEIN,1992 Introduction, pp. 1-4 in The cally induced mutations in Neurospora. Cold SpringHarbor Qnamic Genome: Barbara McClintock ‘s Ideas in the Centu? of Genet- Symp. Quant. Biol. 16: 245-261. ics, edited by N. FEDOROFFand D. BOTSTEIN.Cold Spring Harbor KEI.I.ER, E. F., 1983 A Feeling for the Organism. W. H. Freeman, New York. Laboratory Press, Cold Spring Harbor, NY. LEWIS,E. B., Pseudoallelism and gene evolution. Cold Spring GOLDSCHMIDT, 1938 PhysiologzculGenetics. McGraw-Hill,New 1951 R., Harbor Symp. Quant. Biol. 16: 159-174. York. MARSHAK, A,,1951 Discussion. Cold Spring Harbor Symp. Quant. GOLDSCHMIDT,R., 1951 Chromosomes and genes. Cold Spring Har- Biol. 16: 156-157. bor Symp. Quant. Biol. 16: 1-11. MCCLINTOCK,B., 1951 Chromosome organization and genic ex- GREEN,M., 1992 Annals of mobile DNA elements in Drosophila. pression. Cold Spring Harbor Symp. Quant. Biol. 16: 13-47. The impact and influence of Barbara McClintock, pp. 117-122 MCCLINTOCK, B.,1984 The significance of responses of the genome in The Dynamic Genome: Barbara McClintock’s Ideas in the Centuly to challenge. Science 226: 792-801.