Abstract
For the last 50 years the dominant stance in experimental biology has been reductionism in general, and genetic reductionism in particular. Philosophers were the first to realize that the belief that the Mendelian genes were reduced to DNA molecules was questionable. Soon, experimental data confirmed these misgivings. The optimism of molecular biologists, fueled by early success in tackling relatively simple problems has now been tempered by the difficulties encountered when applying the same simple ideas to complex problems. We analyze three examples taken from experimental data that illustrate the shortcomings of this sort of reductionism. In the first, alterations in the expression of a large number of genes coexist with normal phenotypes at supra-cellular levels of organization; in the second, the supposed intrinsic specificity of hormonal signals is negated; in the third, the notion that cancer is a cellular problem caused by mutated genes is challenged by data gathered both from the reductionist viewpoint and the alternative view proposing that carcinogenesis is development gone awry. As an alternative to reductionism, we propose that the organicist view is a good starting point from which to explore these phenomena. However, new theoretical concepts are needed to grapple with the apparent circular causality of complex biological phenomena.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Akagi T., Sasai K., Hanafusa H. (2003). Refractory nature of normal human diploid fibroblasts with respect to oncogene-mediated transformation. Proceedings of the National Academy of Science of the United States of America, 100, 13567–13572
Alberts B., Johnson A., Lewis J., Raff M., Roberts K., Walter P. (2001). Molecular biology of the cell (pp. 1313–1362). New York, NY: Garland Publishing Inc.
Alberts B., Johnson A., Lewis J.G., Raff M., Roberts K., Walter P. (2002). Molecular biology of the cell (pp. 1015). New York, NY: Garland Publishing Inc.
Bassett D.E., Jr., Eisen M.B., Boguski M.S. (1999). Gene expression informatics—It’s all in your mine. Nature Genetics, 21, 51–55
Benson K. (2001). T.H. Morgan’s resistance to the chromosome theory’. Nature Reviews: Genetics, 2, 469–474
Bissell M.J. (1981). The differentiated state of normal and malignant cells or how to define a normal cell in culture. International Review of Cytology, 70, 27–100
Bissell M.J., Radisky D. (2001). Putting tumours in context. Nature Reviews: Cancer, 1, 46–54
Brisken C., Socolovsky M., Lodish H.F., Weinberg R. (2002). The signaling domain of the receptor rescues prolactin receptor-mutant mammary epithelium. Proceedings of the National Academy of Science of the United States of America, 99, 14241–14245
Brown P.O., Botstein D. (1999). Exploring the new world of the genome with DNA microarrays. Nature Genetics, 21, 33–37
Bunge M. (2004). Emergence and convergence (pp. 13–14). Tortonto: University of Toronto Press.
Clark W.H. (1991). Tumour progression and the nature of cancer. British Journal of Cancer, 64, 631–644
Cunha G.R., Bigsby R.M., Cooke P.S., Sugimura Y. (1985). Stromal-epithelial interactions in adult organs. Cell Differentiation, 17, 137–148
Curtis H.J. (1965). Formal discussion of: Somatic mutations and carcinogenesis. Cancer Research, 25, 1305–1308
Dawe C.J., Morgan W.D., Slatick M.S. (1966). Influence of epithelio-mesenchymal interactions of tumor induction by polyoma virus. International Journal of Cancer, 1, 419–450
Dawkins R. (1976). The selfish gene. Oxford, Oxford University Press
De Robertis E.A., Morita E.M., Cho K.W. Y. (1991). Gradient fields and homeobox genes. Development, 112, 669–678
DiBerardino M.A., Orr N.H., McKinnell R.G. (1986). Feeding tadpoles cloned from Rana nuclei. Proceedings of the National Academy of Science of the United States of America, 83, 8231–8234
Downie S.A., Newmann S.A. (1994). Morphogenetic differences between fore and hind limb precartilage mesenchyme: relation to mechanisms of skeletal pattern formation. Developmental Biology, 162, 195–208
Elenbaas B., Spirio L., Koerner F., Fleming M.D., Zimonjic D.B., Donaher J.L., Popescu N.C., Hahn W.C., Weinberg R.A. (2001). Human breast cancer cells generated by oncogenic transformation of primary mammary epithelial cells. Genes and Development, 15, 50–65
Farge E. (2003). Mechanical induction of twist in the Drosophila foregut/stomodeal primordium. Current Biology, 13, 1365–1377
Foulds L. (1969). Neoplastic development. New York, NY, Academic Press
Fujii H., Cunha G.R., Norman J.T. (1982). The prostatic inducer. Journal of Urology, 128, 858–861
Gilbert S.F. (1997). Developmental biology (pp. 594–596). Sunderland: Sinauer Associates. Inc.
Gilbert S.F. (2003). Developmental biology (pp. 143). Sunderland: Sinauer Associates Inc.
Gilbert S.F. (2003b). The “Re-discovery”, of Morphogenic fields, http://www.devbio.com/ article.php?id=18&search=morphogenetic%20field
Gilbert S.F., Sarkar S. (2000). Embracing complexity: Organicism for the 21st century. Developmental Dynamics, 219, 1–9
Gould M.N. (1995). Rodent models for the study of etiology, prevention and treatment of breast cancer. Seminars in Cancer Biology, 6, 147–152
Greenspan R.J. (2001). The flexible genome. Nature Reviews: Genetics, 2, 383–387
Griffiths P.E. Gray R.D. (2000). Darwinism and developmental systems. In S. Oyama P.E. Griffiths, R. D. Gray (Eds.), Cycles of contingency: Developmental systems and evolution MIT Press.
Gullino P.M., Pettigrew H.M., Grantham F.H. (1975). N-nitrosomethylurea as mammary gland carcinogen in rats. Journal of the National Cancer Institute, 54, 401–414
Gurdon J.B. (1968). Transplanted nuclei and cell differentiation. Scientific American, 219, 24–35
Guzman R.C., Osborn R.C., Swanson S.M., Sakthivel R., Hwang S.-I., Miyamoto S., Nandi S. (1992). Incidence of c-Ki-ras activation in N-methyl-N-nitrosourea-induced mammary carcinomas in pituitary-isografted mice. Cancer Research, 52, 5732–5737
Hahn W.C., Weinberg R.A. (2002a). Mechanisms of disease: Rules for making human tumor cells. New England Journal of Medicine, 347, 1593–1603
Hahn W.C., Weinberg R.A. (2002b), Modelling the molecular circuitry of cancer. Nature Reviews: Cancer, 2, 331–342
Hull D. (1974). The philosophy of biological science. Englewood Clifts, NJ Prentice Hall pp. 8–44
Humpherys D., Eggan K., Akutsu H., Friedman A., Hochedlinger K., Yanagimachi R., Lander E. S., Golub T.R., Jaenisch R. (2002). Abnormal gene expression in cloned mice derived from embryonic stem cell and cumulus cell nuclei. Proceedings of the National Academy of Science of the United States of America, 99, 12889–12894
Illmensee K., Mintz B. (1976). Totipotency and normal differentiation of single teratocarcinoma cell cloned by injection into blastocysts. Proceedings of the National Academy of Science of the United States of America, 73, 549–553
Jacob F. (1982). The possible and the actual. Seattle, WA, University of Washington Press.
Kim J. (1999). Making sense of emergence. Philosophical Studies, 95, 3–36
Kupiec J.J. (1997). A Darwinian theory for the origin of cellular differentiation. Molecular and General Genetics, 255, 201–208
Mayr E. (1982). The growth of biological thought: Diversity, evolution, and inheritance. Cambridge MA, Belknap Press, pp 1–146
McCullough K., Coleman W., Ricketts S., Wilson J., Smith G., Grisham J.W. (1998). Plasticity of the neoplastic phenotype in vivo is regulated by epigenetic factors. Proceedings of the National Academy of Science of the United States of America, 95, 15333–15338
McKinnell R.G., Lust J.M., Sauerbier W., Rollins-Smith L.A., Williams J.W. 3., Williams C.S., Carlson D.L. (1993). Genomic plasticity of the Lucke renal carcinoma: a review. International Journal of Developmental Biology, 37, 213–219
Morange M. (2003). History of cancer research. Encyclopedia of life sciences. London, Nature Publishing Group
Moss L. (2003). What genes can’t do. Cambridge MA, MIT Press
Needham J. (1931) Chemical embryology. Cambridge, Cambridge University Press
Needham J. (1936). New advances in chemistry and biology of organized growth. Proceedings of the Royal Society of Britian, 29, 1577–1626
Orr J.W. (1955). The early effects of 9:10-dimethyl-1:2-benzanthracene on mouse skin, and their in relation to the mechanism of chemical carcinogenesis. British Journal of Cancer, 9, 623–632
Orr J.W. (1958). The mechanism of chemical carcinogenesis. British Medical Bulletin, 14, 99–101
Orr J.W., Spencer A.T. (1972) Transplantation studies of the role of the stroma in epidermal carcinogenesis. In: Tarin D. (eds), Tissue interactions in carcinogenesis. London, Academic Press, pp. 291–304
Pierce G.B., Shikes R., Fink L.M. (1978). Cancer: A problem of developmental biology. Cliffs NJ, Prentice-Hall
Rao M.S., Reddy J.K. (1996) Cell and tissue adaptations to injury. In: Sirica A.E.(eds), Cellular and molecular pathogenesis hiladelphia, PA Lippincott-Raven, pp. 57–78
Rideout W.M., Eggan K., Jaenisch R. (2001). Nuclear cloning and epigenetic reprogramming of the genome. Science, 293, 1093–1098
Rosenberg A. (1994). Instrumental biology, or, the disunity of science. Chicago, University of Chicago Press
Socolovsky M., Fallon A.E. J., Lodish H.F. (1998). The prolactin receptor rescues EpoR-/- progenitors and replaces EpoR in a synergistic interaction with c-kit. Blood, 92, 1491–1496
Sonnenschein C., Soto A.M. (1999). The society of cells: Cancer and control of cell proliferation. New York, Springer Verlag
Sonnenschein C., Soto A.M. (2000). The somatic mutation theory of carcinogenesis: why it should be dropped and replaced. Molecular Carcinogenesis. 29, 1–7
Soto A.M., Sonnenschein C. (2004). The somatic mutation theory of cancer: growing problems with the paradigm?. BioEssays, 26, 1097–1107
Steinmuller D. (1971). A reinvestigation of epidermal transplantation during chemical carcinogenesis. Cancer Research, 31, 2080–2084
Stewart T.A., Mintz B. (1981). Successful generations of mice produced from an established culture line of euploid teratocarcinoma cells. Proceedings of the National Academy of Science of the United States of America, 78, 6314–6318
Swann P.F. (1968). The rate of breakdown of methyl methanesulphonate, dimethyl sulphate and N-methyl-N-nitrosorurea in the rat. Biochemical Journal, 110, 49–52
Tarin D. (1972). Tissue interaction in carcinogenesis. London, Academic Press
van Obberghen-Schilling E., Roche N.S., Flanders K.C., Sporn M.B., Roberts A. (1988). Transforming growth factor beta-1 positively regulates its own expression in normal and transformed cells. Journal of Biological Chemistry, 263, 7741–7746
Waddington C.H. (1935). Cancer and the theory of organizers. Nature, 135, 606–608
Weaver V.M., Fischer A.H., Petersen O.W., Bissell M.J. (1996). The importance of the microenvironment in breast cancer progression:recapitulation of mammary tumorigenesis using a unique human mammary epithelial cell model and a three-dimensional culture assay. Biochemistry and Cell Biology, 74, 833–851
Weaver V.M., Lelievre S., Lakins J.N., Chrenek M.A., Jones J.C., Giancotti F., Werb Z., Bissell M.J.(2002). Beta4 integrin-dependent formation of polarized three-dimensional architecture confers resistance to apoptosis in normal and malignant mammary epithelium. Cancer Cell. 2, 205–216
Weaver V.M., Petersen O.W., Wang F., Larabell C.A., Briand P., Damsky C., Bissell M.J. (1997). Reversion of the malignant phenotype of human breast cells in three-dimensional culture and in vivo integrin blocking antibody. Journal of Cell Biology, 137, 231–245
Weinberg R.A. (1998). One renegade cell: How cancer begins. New York, Basic Books
Weinstein I.B. (2002). Cancer. Addiction to oncogenes—the Achilles heal of cancer. Science, 297, 63–64
Wilmut I., Schnieke A.E., McWhir J., Kind A.J., Campbell K.H. S. (1997). Viable offspring derived from fetal and adult mammalian cells. Nature, 385, 810–813
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Soto, A.M., Sonnenschein, C. Emergentism by default: A view from the bench. Synthese 151, 361–376 (2006). https://doi.org/10.1007/s11229-006-9030-3
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11229-006-9030-3