The coming Kuhnian revolution in biology

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References

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    The anomalies arising from Human Genome Project data banks are described by Miklos and Rubin (The role of the Genome Project in determining gene function: Insights from model organisms. Cell 86: 521–529, 1996) Also presented is a scheme for reducing complex function to small clusters of functionally related genes. The hope is that major physiological functions in different species will all exhibit identical or nearly identical patterns of gene utilization. If correct, such reduction may prove useful, but it appears limited in that the search for causality seems to remain focused on the identity of the genetic entities. A more interesting acknowledgment of complexity, in this case in the brain, comes from Edelman and his group. They are evolving models of the brain that also identify subsystem activities, but that attempt to show how “…the complex brain can deal with context and go ‘beyond the information given’.” Going beyond the information given clearly implies going beyond the genome and the need for some epigenetic function having to do with emergent behavior. (Tononi.G., Scorns, O., and Edelman, G.M. 1996. A complexity measure for selective matching of signals by the brain Proc. Natl. Acad. Sci. USA 96: 3422-3427)

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    The high correlation (>95%) between chromosomal abnormalities and cancer has been noted for many years, but has been mostly abandonded as a cause of cancer in favor of theories that favor powerful single gene effects, oncogenes and mutated tumor suppressor genes. (Boveri, T. 1914. Zur Frage der Enstehung maligner Tumoren. Gustav Fischer Verlag, Jena, Germany; German, J. (Ed.) 1974. Chromosomes and Cancer. John Wiley & Sons, New York; Cram, L.S. et al. 1983. Spontaneous neoplasti evolution of Chinese hamster cells in culture: Multistep progression of karyotype. Cancer Res. 43: 4828–4837.

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    Epigenesis has been given a modem definition as follows: “Classical genetics has revealed the mechanisms for the transmission of genes from generation to generation, but the strategy of the genes in unfolding the developmental programme remains obscure. Epigenetics comprises the study of the mechanisms that impart temporal and spatial control on the activity of all those genes required for the development of a complex organism from the zygote to the adult.”( Holliday, R. 1990. Phil. Trans. Royal Soc. Lond. 8326: 329–338). As such, it establishes the basis for a level of organizational control above the genome; a level that is now well established in fact, but continues to evade decisive theoretical insight.

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    Dyson, F. 1993. Science in trouble. Am. Scholar 62: 513–525; For an analysis of specific troubles coming from biotechnology, see Strohman, R. 1994. Epigenesis: The missing beat in biotechnology Bio/Tecftnology 12: 156-164.

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    The process involved in editing premessage RNAfrom the genome involves major surgery by enzymes that cut and splice the RNA. In other words, in higher organisms the functional gene is not really in the DNA but emerges only as a result of this higher order cellular manipulation of genetic messages. Therefore, even this linear paradigm of the gene harbors, in higher organisms, a nonlinear component. For a discussion of this and of other epigenetic processes that intervene to change patterns of gene expression, see a recent review by Tim Cavalier-Smith (Trends Genet. 13:7-9,1997).

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    The terms “linear” and “nonlinear” offer sources of confusion because they mean different things in different scientific settings. In mathematics, linearity means simply that we can know the value of the whole by adding up the sum of the parts. So, for example, if we know the values of the initial conditions of a system and these conditions don't interact with one another, we can predict the system's future behavior. A nonlinear system, then, is one in which initial conditions interact so that outcome prediction is difficult at best, even when a complete knowledge of initial conditions is possible. In biology, initial conditions are often taken simply as genomic information and an additive (noninteractive) environmental component. But this is oversimplified in the extreme. Biological systems are nonlinear. For a more fulsome explanation of these two terms and for the clearest (and shortest) explanation of how non-linear systems, while being difficult to predict, are nevertheless determinative, consult ref. 24.

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    Jablonka, E. and Lamb, M.J. 1995. Epigenetic Inheritance and Evolution. Oxford University Press, Oxford; Russo, V.E.A., Martienssen, A.and Riggs, A.D. (eds.). 1996. Epigenetic Mechanisms of Gene Regulation. Cold Spring Harbor Press. Cold Spring Harbor.

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    “The attitude of physiological genetics is that characters are determined 100% by physiological processes, but that genes are the ultimate internal physiological agents.” ( Wright, S. 1945. Genes as physiological agents. Am. Naturalist July-August 783: 289–302).

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    “We know about the components of genomes…We know nothing, however, about how the cell senses danger and initiates responses to it that are often truly remarkable.” ( McClintock, B. 1984. Significance of responses of the genome to challenge. Science 226: 792–801).

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    Bak, P. 1996. How Nature Works. MIT Press,Cambridge; Kelso, J.A.S. 1995. Dynamic Patterns. MIT Press, Cambridge; Goodwin, B.C. 1994. How the Leopard Changed its Spots: The Evolution of Complexity. C. Scribner's Sons, New York.

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    Lenoir, T. 1982. The Strategy of Life. University of Chicago Press, Chicago. Teleomechanists were a group of German experimental biologists who successfully countered preformationist ideas of development in the early nineteenth century, and who began a search for systemic laws governing the emergence of complex behavior in organisms. They failed, not because of lack of good experimentation, but for lack of a detailed theory capable of embracing the experimental complexity they discovered. They may be seen as the forerunners of modern epigenetic biologists and of the current attempts to apply complex adaptive systems theory in the life sciences.

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