OJGen  Vol.4 No.5 , September 2014
The Fate of Ochoa’s School in the Origins of Oncogenetics in US (I)
ABSTRACT
It was in the early eighties that a genuine school of spanish biochemists around Severo Ochoa participated in the oncogene races. Malignant cell transformation and oncogenes were put in relation during that era. Several prominent scientists coming from Spain have established and maintained a strong tradition of studies in the enzymology of retroviruses and transcriptional events. In this short historical account, we briefly pay tribute to these famous forerunners, by emphasizing both the originality and quality of their work, as well as the many accompanying conceptual and methodological analysis. We start with àngel Pellicer (1948-) who, amongst other contributions, first established the landmark experimental transfection protocol and nucleated the onset of oncogenetics with his discovery that ras oncogenes were activated by mitogenic factors. Whereas Manuel Perucho (1948-) can be considered as one of the pioneers, if not the founder, of the cloning of human oncogene, through his experiments on H-ras, and he became a milestone in diagnostic detection to allow hospital technicians to screen for mutant ras genes. More known Mariano Barbacid (1949-) established that ras oncogene was a kind of common denominator for cancer, and clarified that their functional differences were by a single point mutation. In conclusion, this history demonstrates how eager spanish biochemists trained by Eladio Viñuela were to maintain the tradition of Severo Ochoa’s long-standing scientific reputation in the US.

Cite this paper
Wulff-Barreiro, E. (2014) The Fate of Ochoa’s School in the Origins of Oncogenetics in US (I). Open Journal of Genetics, 4, 392-406. doi: 10.4236/ojgen.2014.45037.
References
[1]   Cantor, D. (2012) Between Prevention and Therapy: Gio Batta Gori and the National Cancer Institute’s Diet, Nutrition and Cancer Programme, 1974-1978. Medical History, 56, 531-561.
http://dx.doi.org/10.1017/mdh.2012.73

[2]   Pickstone, J.V. (2007) Contested Cumulations: Configurations of Cancer Treatments through the Twentieth Century. Bulletin of the History of Medicine, 81, 164-196.
http://dx.doi.org/10.1353/bhm.2007.0011

[3]   Moscucci, O. (2005) Gender and Cancer in Britain, 1860-1910: The Emergence of Cancer as a Public Health Concern. American Journal of Public Health, 95, 1312-1321.
http://dx.doi.org/10.2105/AJPH.2004.046458

[4]   Vineis, P., Schatzkin, A. and Potter, J.D. (2010) Models of Carcinogenesis: An Overview. Carcinogenesis, 31, 1703-1709.
http://dx.doi.org/10.1093/carcin/bgq087

[5]   Coste, J. and Lepiège, A. (2009) Toward Epistemiology and History of Epidemiology. Revue d’épidémiologie et de Santé Publique, 57, 317-318.
http://dx.doi.org/10.1016/j.respe.2009.06.007

[6]   Fantini, B. (2006) Of Arrows and Flows, Causality, Determination, and Specificity in the Central Dogma of Molecular Biology. History and Philosophy of the Life Sciences, 28, 567-593.

[7]   Keating, P. and Cambrosio A. (2007) Cancer Clinical Trials: The Emergence and Development of a New Style of Practice. Bulletin of the History of Medicine, 81, 197-223.
http://dx.doi.org/10.1353/bhm.2007.0003

[8]   Beatson International Cancer Conference (2006) 24 Years : Ras and Human Cancer. 18-21 June 2006, Glasgow.

[9]   Angier, N. (2014) Natural Obsessions: Striving to Unlock the Deepest Secrets of the Cancer Cell. Houghton Mifflin Company, Boston.

[10]   Barbacid, M. (2003) Eladio Viñuela : Pionero de la biología molecular en España. In: ávila, J., Perucho, M. and López-Otín, C., Eds., El fago phi29 y los orígenes de la biología molecular en España, CSIC, Madrid.

[11]   Barona Vilar, J.L. (2010) El exilio científico republicano. PUV, València.

[12]   Giral, F. (1994) Ciencia española en el exilio (1939-1989): El exilio de los científicos españoles. Centro de Investigación y Estudios Republicanos (CIERE), Madrid.

[13]   Ochoa, S. (1960) Síntesis enzimática del ácido ribonucleico. Ciencia, 20, 1-14.
http://cedros.residencia.csic.es/imagenes/Portal/ciencia/1960_20_01-02-z2.pdf

[14]   Ochoa, S. (1980) A Pursuit of a Hobby. Annual Review of Biochemistry, 49, 1-31.
http://dx.doi.org/10.1146/annurev.bi.49.070180.000245

[15]   (2004) Folkman, Hunter, Massague, Vogelstein and Weinberg Win 2004 Prince of Asturias Awards. Cancer Biology & Therapy, 3, 585-592.
http://dx.doi.org/10.4161/cbt.3.7.1050

[16]   Wigler, M., Sweet, R., Sim, G.K., Wold, B., Pellicer, A., Lacy, E., Maniatis, T., Silverstein, S. and Axel, R. (1979) Transformation of Mammalian Cells with Genes from Procaryotes and Eucaryotes. Cell, 16, 777-785.
http://dx.doi.org/10.1016/0092-8674(79)90093-X

[17]   Perucho, M., Goldfarb, M., Shimizu, K., Lama, C., Fogh, J. and Wigler, M. (1981) Human-Tumor-Derived Cell Lines Contain Common and Different Transforming Genes. Cell, 27, 467-476.
http://dx.doi.org/10.1016/0092-8674(81)90388-3

[18]   Goldfarb, M., Shimizu, K., Perucho, M. and Wigler, M. (1982) Isolation and Preliminary Characterization of a Human Transforming Gene from T24 Bladder Carcinoma Cells. Nature, 296, 404-409.
http://dx.doi.org/10.1038/296404a0

[19]   Pulciani, S., Santos, E., Lauver, A.V., Long, L.K., Robbins, K.C. and Barbacid, M. (1982) Oncogenes in Human Tumor Cell Lines: Molecular Cloning of a Transforming Gene from Human Bladder Carcinoma Cells. Proceedings of the National Academy of Sciences of the United States of America, 79, 2845-2849.
http://dx.doi.org/10.1073/pnas.79.9.2845

[20]   Malumbres, M. and Barbacid, M. (2003) RAS Oncogenes: The First 30 Years. Nature Reviews Cancer, 3, 459-465.
http://dx.doi.org/10.1038/nrc1097

[21]   Morange, M. (2007) The Field of Cancer Research: An Indicator of Present Transformations in Biology. Oncogene, 26, 7607-7610.
http://dx.doi.org/10.1038/sj.onc.1210583

[22]   Morange, M. (1997) From the Regulatory Vision of Cancer to the Oncogene Paradigm, 1975-1985. Journal of the History of Biology, 30, 1-29.
http://dx.doi.org/10.1023/A:1004255309721

[23]   Wigler, M., Silverstein, S., Lee, S.L., Pellicer, A., Cheng, Y.C. and Axel, R. (1977) Transfer of Purified Herpes Virus Thymidine Kinase Gene to Cultured Mouse Gene Cells. Cell, 11, 223-233.
http://dx.doi.org/10.1016/0092-8674(77)90333-6

[24]   Wigler, M., Pellicer, A., Silverstein, S., Axel, R., Urlaub, G. and Chasin, L. (1979) DNA-Mediated Transfer of the Adenine Phosphoribosyltransferase Locus into Mammalian Cells. Proceedings of the National Academy of Sciences of the United States of America, 76, 1373-1376.
http://dx.doi.org/10.1073/pnas.76.3.1373

[25]   Pellicer, A., Wigler, M., Axel, R. and Silverstein, S. (1978) The Transfer and Stable Integration of the HSV Thymidine Kinase Gene into Mouse Cells. Cell, 14, 133-141.
http://dx.doi.org/10.1016/0092-8674(78)90308-2

[26]   Wigler, M., Pellicer, A., Silverstein, S. and Axel, R. (1978) Biochemical Transfer of Single-Copy Eucaryotic Genes Using Total Cellular DNA as Donor. Cell, 14, 725-731.
http://dx.doi.org/10.1016/0092-8674(78)90254-4

[27]   Pellicer, A., Robins, D., Wold, B., Sweet, R., Jackson, J., Lowy, I., Roberts, J., Sim, G.K., Silverstein, S. and Axel, R. (1980) Altering Genotype and Phenotype by DNA-Mediated Gene Transfer. Science, 209, 1414-1422.
http://dx.doi.org/10.1126/science.7414320

[28]   Lowy, I., Pellicer, A., Jackson, J.F., Sim, G.K., Silverstein, S. and Axel, R. (1980) Isolation of Transforming DNA: Cloning the Hamster Aprt Gene. Cell, 22, 817-823.
http://dx.doi.org/10.1016/0092-8674(80)90558-9

[29]   Pelham, H.R.B. (1982) A Regulatory Upstream Promoter Element in the Drosophila Hsp 70 Heat-Shock Gene. Cell, 30, 517-528.
http://dx.doi.org/10.1016/0092-8674(82)90249-5

[30]   Corcés, V., Pellicer, A., Axel, R. and Meselson, M. (1981) Integration, Transcription, and Control of a Drosophila Heat Shock Gene in Mouse Cells. Proceedings of the National Academy of Sciences of the United States of America, 78, 7038-7042.
http://dx.doi.org/10.1073/pnas.78.11.7038

[31]   Sund, H. (1977) Pyridine Nucleotide-Dependent Dehydrogenases. Proceedings of the 2nd International Symposium, University of Konstanz, 28 March-1April 1977, FEBS Symposium, De Gruyter.

[32]   Marco, R. (2006) The Scientific Roots of José A. Campos-Ortega, a German Neurobiologist Born in Spain. Developmental Dynamics, 235, 855-860.
http://dx.doi.org/10.1002/dvdy.20700

[33]   Wigler, M., Perucho, M., Kurts, D., Dana, S., Pellicer, A., Axel, R. and Silverstein, S. (1980) Transformation of Mammalian Cells with an Amplifiable Dominant-Acting Gene. Proceedings of the National Academy of Sciences of the United States of America, 77, 3567-3570.
http://dx.doi.org/10.1073/pnas.77.6.3567

[34]   Perucho, M., Hanahan, D., Lipsich, L. and Wigler, M. (1980) Isolation of the Chicken Thymidine Kinase Gene by Plasmid Rescue. Nature, 285, 207-210.
http://dx.doi.org/10.1038/285207a0

[35]   Perucho, M., Hanahan, D. and Wigler, M. (1980) Genetic and Physical Linkage of Exogenous Sequences in Transformed Cells. Cell, 22, 309-317.
http://dx.doi.org/10.1016/0092-8674(80)90178-6

[36]   Guerrero, I., Villasante, A., Corcés, V. and Pellicer, A. (1984) Activation of a c-K-Ras Oncogene by Somatic Mutation in Mouse Lymphomas Induced by Gamma Radiation. Science, 225, 1159-1162.
http://dx.doi.org/10.1126/science.6474169

[37]   Shimizu, K., Goldfarb, M., Perucho, M. and Wigler, M. (1983) Isolation and Preliminary Characterization of the Transforming Gene of a Human Neuroblastoma Cell Line. Proceedings of the National Academy of Sciences of the United States of America, 80, 383-387.
http://dx.doi.org/10.1073/pnas.80.2.383

[38]   Nakano, H., Yamamoto, F., Neville, C., Evans, D., Mizuno, T. and Perucho, M. (1984) Isolation of Transforming Sequences of Two Human Lung Carcinomas: Structural and Functional Analysis of the Activated c-K-Ras Oncogenes. Proceedings of the National Academy of Sciences of the United States of America, 81, 71-75.
http://dx.doi.org/10.1073/pnas.81.1.71

[39]   Winter, E., Yamamoto, F., Almoguera, C. and Perucho, M. (1985) A Method to Detect and Characterize Point Mutations in Transcribed Genes: Amplification and Overexpression of the Mutant c-Ki-Ras Allele in Human Tumor Cells. Proceedings of the National Academy of Sciences of the United States of America, 82, 7575-7579.
http://dx.doi.org/10.1073/pnas.82.22.7575

[40]   Barbacid, M., Troxler, D.H., Scohijck, E.M. and Aaronson, S.A. (1978) Analysis of Translational Products of Friend Strain of Spleen Focus-Forming Virus. Journal of Virology, 27, 826-830.

[41]   Barbacid, M., Stephenson, J.R. and Aaronson, S.A. (1976) Gag Gene of Mammalian Type-C RNA Tumor Viruses. Nature, 262, 554-559.
http://dx.doi.org/10.1038/262554a0

[42]   Larraga, V. and Muñoz, E. (1975) Molecular-Organization in Bacterial Cell-Membranes. Specific Labelling and Topological Distribution of Glycoproteins and Proteins in Streptomyces-Albus Membranes. European Journal of Biochemistry, 54, 207-218.
http://dx.doi.org/10.1111/j.1432-1033.1975.tb04130.x

[43]   Barbacid, M., Robbins, K.C. and Aaronson, S.A. (1979) Wild Mouse RNA Tumor Viruses. A Nongenetically Transmitted Virus Group Closely Related to Exogenous Leukemia Viruses of Laboratory Mouse Strains. The Journal of Experimental Medicine, 149, 254-266.
http://dx.doi.org/10.1084/jem.149.1.254

[44]   Barbacid, M., Beemon, K. and Devare, S.G. (1980) Origin and Functional Properties of the Major Gene Product of the Snyder-Theilen Strain of Feline Sarcoma Virus. Proceedings of the National Academy of Sciences of the United States of America, 77, 5158-5162.
http://dx.doi.org/10.1073/pnas.77.9.5158

[45]   Barbacid, M. (1981) Cellular Transformation by Subgenomic Feline Sarcoma Virus DNA. Journal of Virology, 37, 518-523.

[46]   Pulciani, S., Santos, E., Lauver, A.V., Long, L.K., Aaronson, S.A. and Barbacid, M. (1982) Oncogenes in Solid Human Tumours. Nature, 300, 539-542.
http://dx.doi.org/10.1038/300539a0

[47]   Reddy, E.P., Reynolds, R.K., Santos, E. and Barbacid, M. (1982) A Point Mutation Is Responsible for the Acquisition of Transforming Properties by the T24 Human Bladder Carcinoma Oncogene. Nature, 300, 149-152.
http://dx.doi.org/10.1038/300149a0

[48]   Sukumar, S., Notario, V., Martin-Zanca, D. and Barbacid, M. (1983) Induction of Mammary Carcinomas in Rats by Nitroso-Methylurea Involves Malignant Activation of H-Ras-1 Locus by Single Point Mutations. Nature, 306, 658-661.
http://dx.doi.org/10.1038/306658a0

[49]   Szybalska, E.H. and Szybalski, W. (1962) Genetics of Human Cell Lines, IV. DNA-Mediated Heritable Transformation of a Biochemical Trait. Proceedings of the National Academy of Sciences of the United States of America, 48, 2026-2034.
http://dx.doi.org/10.1073/pnas.48.12.2026

[50]   Pollack, R., Salas, J., Wang, R., Kusano, T. and Green, H. (1977) Human-Mouse Hybrid Cell Lines and Susceptibility to Species-Specific Viruses. Journal of Cellular Physiology, 77, 117-119.
http://dx.doi.org/10.1002/jcp.1040770113

[51]   Perucho, M., Salas, J. and Salas, M.L. (1977) Identification of Mammalian DNA-Binding Protein P8 as Glyceraldehyde-3-Phosphate Dehydrogenase. European Journal of Biochemistry, 81, 557-562.
http://dx.doi.org/10.1111/j.1432-1033.1977.tb11982.x

[52]   Guerrero, I., Villasante, A., Corces, V. and Pellicer, A. (1985) Loss of the Normal N-Ras Allele in a Mouse Thymic Lymphoma Induced by a Chemical Carcinogen. Proceedings of the National Academy of Sciences of the United States of America, 82, 7810-7814.
http://dx.doi.org/10.1073/pnas.82.23.7810

[53]   Santos, E., Martin-Zanca, D., Reddy, E.P., Pierotti, M.A., Della Porta, G. and Barbacid, M. (1984) Malignant Activation of a K-Ras Oncogene in Lung Carcinoma but Not in Normal Tissue of the Same Patient. Science, 223, 661-664.
http://dx.doi.org/10.1126/science.6695174

 
 
Top