Life and Death: What Is the Major Mystery?

  • Werner A. Müller


Fundamental concepts linking programmed death to the evolution of multicellularity were advanced as early as 1881 by August Weismann, a zoologist and pioneer of genetic theories designed to explain development and cell differentiation. Weismann proposed that aging and decay are not inherent to life itself but are events that became integral to development only in the course of evolution of multicellular organisms. Only the multicellular organism inevitably would be doomed, through senescence—the process of aging.


Green Fluorescent Protein Embryonic Stem Cell Imaginal Disc Heat Shock Transcription Factor Green Fluorescent Protein Gene 
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  1. Blackburn, E. (1991): Structure and function of telomeres. Nature 350:569–573.PubMedCrossRefGoogle Scholar
  2. Harley, C.B., et al. (1992): The telomere hypothesis of cellular aging. Exp. Gerontol. 27:375–382.PubMedCrossRefGoogle Scholar
  3. Hayflick, L. (1980): The cell biology of human aging. Sci. Am. 242(1): 58–65.PubMedCrossRefGoogle Scholar
  4. Johnson, E, and Bottjer, S.W. (1994): Afferent influences on cell death and birth during development of a cortical nucleus necessary for learned vocal behavior in zebra finches. Development 120:13–24.PubMedGoogle Scholar
  5. Oppenheim, R.W., Prevette, D., Tytell, M., and Homma, S. (1990): Naturally occurring and induced neuronal cell death in the chick embryo in vivo requires protein and RNA synthesis: Evidence for the role of cell death genes. Dev. Biol. 138:104–113.PubMedCrossRefGoogle Scholar
  6. Raff, M.C., et al. (1993): Programmed cell death and the control of cell survival: Lessons from the nervous system: Science 262: 695–700.PubMedCrossRefGoogle Scholar
  7. Svendsen, C.N., and Rosser, A.E. (1995): Neurones from stem cells? Trends Neurosci. 18:465–467.PubMedCrossRefGoogle Scholar
  8. Wallace, D.C. (1992): Mitochondrial genetics: A paradigm for aging and degenerative diseases. Science 256:628–632.PubMedCrossRefGoogle Scholar
  9. Wickelgren, I. (1996): Is hippocampal cell death a myth? Science 271: 1229–1230.PubMedCrossRefGoogle Scholar
  10. Williams, G.T., and Smith, C.A. (1993): Molecular regulation of apoptosis. Genetic controls on cell death. Cell 74:777–780.PubMedCrossRefGoogle Scholar
  11. Zakian, V.A., et al. (1990): How does the end begin. Trends Genet. 6: 12–16.PubMedCrossRefGoogle Scholar
  12. Zwilling, R., and Balduini, C. (1992): Biology of Aging. Springer-Verlag, Heidelberg.Google Scholar

Box 1. History of the Developmental Biology

  1. Aristotle. De Anima. In Hicks, R.D. (1965) Aristotle’s De Anima, Adolf M. Hakkert Publ., Amsterdam.Google Scholar
  2. Aristotle. Historia Animalium. In Smith, J.A., and Ross, W.D. (eds.) (1949): The works of Aristotle translated into English, Vol. IV, Historia animalium, translated by Thomson, D.W.; at the Clarendon Press, Oxford.Google Scholar
  3. Bonner, J.T (1962): Ideas in Biology. Harper & Row, New York.Google Scholar
  4. Boveri, T. (1904): Ergebnisse über die Konstitution der chromatischen Substanz. Gustav Fischer, Jena, Germany.Google Scholar
  5. Boveri, T. (1910): Die Potenzen der Ascaris-Blastomeren bei abgeänderter Furchung. Festschrift für Richard Hertwig, vol3. Gustav Fischer, Jena, Germany.Google Scholar
  6. Dampier, W.C. (1948): A History of Science and Its Relations with Philosophy and Religion. 4th ed., The Claredon Press, Cambridge.Google Scholar
  7. Driesch, H. (1892): The potency of the first two cleavage cells in echinoderm development. Experimental production of partial and double formations. In Willer, B.H., and Oppenheimer, J.M. (eds.) Foundations of Experimental Embryology, pp. 38–50. Hafner, New York.Google Scholar
  8. Driesch, H. (1908): The Science and Philosophy of the Organism. I. Gilford Lectures 1907; II. Gilford Lectures 1908. A & C. Black, London.Google Scholar
  9. Gardner, E.J. (1965): History of Biology. Burgess, Minneapolis.Google Scholar
  10. Gould, S.J. (1977): Ontogeny and Phylogeny. Belkamp, Harvard Univ. Press, Cambridge, MA.Google Scholar
  11. Haeckel, E. (1892): The history of creation. Translation of Natürliche Schöpfungsgeschichte. Kegan Paul, Trench, Trubner; London.Google Scholar
  12. Hamburger, V. (1988): The Heritage of Experimental Embryology: Hans Spemann and the Organizer. Oxford Univ. Press, New York.Google Scholar
  13. Harvey, W. (1651): De generatione animalium. English translation by R. Willis. Encyclopedia Brittanica, Inc., Great Books of the Western World, Chicago; reprinted 1952.Google Scholar
  14. Müller, W.A. (1996): From the Aristotelian soul to genetic and epigenetic information. Int. J. Dev. Biol. 40:21–26.PubMedGoogle Scholar
  15. Sander, K. (1991a): Landmarks in developmental biology: Wilhelm Roux and his programme for developmental biology. Roux’s Arch. Dev. Biol. 200: 1–3.CrossRefGoogle Scholar
  16. Sander, K. (1991b): Wilhelm Roux’s treatise on “qualitative” mitoses—a “classic” by either definition. Roux’s Arch. Dev. Biol. 200:61–63.CrossRefGoogle Scholar
  17. Sander, K. (1991c): Wilhelm Roux on embryonic axes, sperm entry and the grey crescent. Roux’s Arch. Dev. Biol. 200:117–119.CrossRefGoogle Scholar
  18. Sander, K. (1991d): When seeing is believing: Wilhelm Roux’s misconceived fate map. Roux’s Arch. Dev. Biol. 200:177–179.CrossRefGoogle Scholar
  19. Sander, K. (1991e): “Mosaic work” and “assimilating effects” in embryo-genesis: Wilhelm Roux’s conclusions after disabling frog blastomeres. Roux’s Arch. Dev. Biol. 200:237–239.CrossRefGoogle Scholar
  20. Sander, K. (1991f): Wilhelm Roux and the rest: Developmental theories 1885–1895. Roux’s Arch. Dev. Biol. 200:331–333.Google Scholar
  21. Sander, K. (1992a): Shaking a concept: Hans Driesch and the varied fates of sea urchin blastomeres. Roux’s Arch. Dev. Biol. 201:265–267.CrossRefGoogle Scholar
  22. Sander, K. (1992b): Hans Driesch’s “philosophy really ab ovo” or why to be a vitalist. Roux’s Arch. Dev. Biol. 202:1–3.CrossRefGoogle Scholar
  23. Sander, K. (1993): Entelechy and the ontogenetic machine-work and views of Hans Driesch from 1895 to 1910. Roux’s Arch. Dev. Biol. 202:70–76.CrossRefGoogle Scholar
  24. Spemann, H. (1938): Embryonic Development and Induction. Yale Univ. Press, New Haven, CT. (Reprinted by Hafner, New York, 1962).Google Scholar
  25. von Baer, K.E. (1828): Über Entwicklungsgeschichte der Thiere. Königsberg, Germany.Google Scholar

Box 2. Experiments with Eggs and Early Embryos, Cloning, Chimeras, and Transgenic Animals

  1. Briggs, R., and King, T.J. (1952): Transplantation of living nuclei from blastula cells into enucleated frog eggs. Proc. Natl. Acad. Sci. USA 38:455–463.PubMedCrossRefGoogle Scholar
  2. Brun, R.B. (1978): Developmental capacities of Xenopus eggs, provided with erythrocyte or erythroblast nuclei from adults. Dev. Biol. 65:271–284.PubMedCrossRefGoogle Scholar
  3. Campbell, K.H.S., McWhir, J., Ritchie, W.A., and Wilmut, I. (1996): Sheep cloned by nuclear transfer from a cultured cell line. Nature 380:64–66.PubMedCrossRefGoogle Scholar
  4. Cappecchi, M.R. (1980): High efficiency transformation by direct microinjection of DNA into cultured mammalian cells. Cell 22:479–488.CrossRefGoogle Scholar
  5. DiBernadino, M.A. (1988): Genomic multipotentiality of differentiated somatic cells. In G. Eguchi, et al. (eds.) Regulatory Mechanisms in Developmental Processes, pp. 129–136. Elsevier, Amsterdam, New York.Google Scholar
  6. First, N.L., and Prather, R.S. (1991): Genomic potentials in mammals. Differentiation 48:1–8.PubMedCrossRefGoogle Scholar
  7. Gordon, J.W. (1988): Transgenic mice. In Malacinsky G.M. (ed.) Developmental Genetics of Higher Organisms: A Primer in Developmental Biology, pp. 477–498. Macmillan, New York.Google Scholar
  8. Gossler, A., et al. (1986): Transgenesis by means of blastocyst-derived stem cell lines. Proc. Natl. Acad. Sci. USA 83:9065–9069.PubMedCrossRefGoogle Scholar
  9. Gurdon, J.B. (1962): The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. J. Embryol. Exp. Morphol. 10: 622–640.PubMedGoogle Scholar
  10. Gurdon, J.B. (1968): Transplanted nuclei and cell differentiation. Sci. Am. 219(6):24–35.PubMedCrossRefGoogle Scholar
  11. Hanahan, D. (1989): Transgenic mice as probes into complex systems. Science 245:1265–1274.CrossRefGoogle Scholar
  12. McGrath, J., and Solter, D. (1984): Inability of mouse blastomere nuclei transferred to enucleated zygotes to support development in vitro. Science 226:1317–1319.PubMedCrossRefGoogle Scholar
  13. Mintz, B. (1957): Does embryological development of primordial germ cells affect its development? Symp. Br. Soc. Dev. Biol. 7:225–221.Google Scholar
  14. Solter, D. (1996): Lambing by nuclear transfer. Nature 380:24–25.PubMedCrossRefGoogle Scholar
  15. Thompson, S., et al. (1989): Germ line transmission and expression of a corrected HPRT gene produced by gene targeting in embryonic stem cells. Cell 56:313–321.PubMedCrossRefGoogle Scholar
  16. Wagner, E.E (1990): Mouse genetics meet molecular biology at Cold Spring Harbor. New Biologist 2:1971–1074.Google Scholar
  17. Wagner, E.F., and Keller, G. (1992): The introduction of genes into mouse embryos and stem cells. In Russo, V.E.A., et al. (eds.) Development: The Molecular Genetic Approach, pp. 440–458. Springer-Verlag, Heidelberg.Google Scholar
  18. Wakimoto, T., and Karpen, G.H. (1988): Transposable elements and germ-line transformation in Drosophila. In Malacinsky, G.M. (ed.) Developmental Genetics of Higher Organisms: A Primer in Developmental Biology, pp. 275–303. Macmillan, New York.Google Scholar

Box 3. The PI Signal Transduction System

  1. Ciapa, B., et al. (1992): Phosphoinositide metabolism during the fertilization wave in sea urchin eggs. Development 115:187–195.PubMedGoogle Scholar
  2. Gallicano, G.I., et al. (1993): Protein kinase C, a pivotal regulator of hamster egg activation, functions after elevation of intracellular free calcium. Dev. Biol. 156:94–106.PubMedCrossRefGoogle Scholar
  3. Larabell, C., and Nuccitelli, R. (1992): Inositol lipid hydrolysis contributes to the Ca2+ wave in the activating egg of Xenopus laevis. Dev. Biol. 153: 347–355.PubMedCrossRefGoogle Scholar
  4. Otte, A.P., et al. (1988): Protein kinase C mediates neural induction in Xenopus laevis. Nature 334:618–620.PubMedCrossRefGoogle Scholar
  5. Whitaker, M., and Swann, K. (1993): Lighting the fuse at fertilization. Development 117:1–12.Google Scholar

Box 4. Models of Biological Pattern Formation

  1. Edelstein-Keshet, L., and Ermentrout, B.G. (1990): Contact response of cells can mediate morphogenetic pattern formation. Differentiation 45:147–159.PubMedCrossRefGoogle Scholar
  2. Haken, H. (1978): Synergetics. Springer-Verlag, Heidelberg.Google Scholar
  3. Meinhardt, H. (1982): Models of Biological Pattern Formation. Academic Press, New York.Google Scholar
  4. Meinhardt, H. (1995): The Algorithmic Beauty of Seashells. Springer-Verlag, Heidelberg.Google Scholar
  5. Murray, J.D. (1989): Mathematical Biology. Springer-Verlag, Heidelberg.Google Scholar
  6. Prigogine, I., and Nicolis, G. (1967): On symmetry-breaking instabilities in dissipative systems. J. Chem. Phys. 46:3542–3550.CrossRefGoogle Scholar
  7. Turing, A.M. (1952): The chemical basis of morphogenesis. Philos. Trans. Roy. Soc. London B 237:37–72.CrossRefGoogle Scholar
  8. Steinberg, M.S., and Takeichi, M. (1994): Experimental specification of cell sorting, tissue spreading, and specific spatial patterning by quantitative differences in cadherin expression. Proc. Natl. Acad. Sci. USA 91:206–209.PubMedCrossRefGoogle Scholar
  9. Wolpert, L. (1969): Positional information and the spatial pattern of cellular formation. J. Theor. Biol. 25:1–47.PubMedCrossRefGoogle Scholar
  10. Wolpert, L. (1978): Pattern formation in biological development. Sci. Am. 239(4):154–164.PubMedCrossRefGoogle Scholar
  11. Wolpert, L. (1989): Positional information revisited. Development 1989 (Suppl.):3–12.Google Scholar

Box 5: Signal Molecules Acting through Nuclear Receptors (See also Chapter 17)

  1. Beato, M., Herrlich, P., and Schütz, G. (1995): Steroid hormone receptors: Many actors in search of a plot. Cell 83:851–857.PubMedCrossRefGoogle Scholar
  2. Chen, Y.P., Huang, L., and Solursh, M. (1994): A concentration gradient of retinoids in the early Xenopus embryo. Dev. Biol. 161:70–76.PubMedCrossRefGoogle Scholar
  3. Conlon, R.A. (1995): Retinoic acid and pattern formation in vertebrates. Trends Genet. 11(8):314–319.PubMedCrossRefGoogle Scholar
  4. Eichele, G. (1989): Retinoic acid induces a pattern of digits in anterior half wing buds that lack the zone of polarizing activity. Development 107:863–867.PubMedGoogle Scholar
  5. Kastner, P., Mark., M., and Chambon, P. (1995): Nonsteroid nuclear receptors: What are genetic studies telling us about their role in real life? Cell 83:859–869.PubMedCrossRefGoogle Scholar
  6. Maden, M., et al. (1989): Cellular retinoic acid-binding protein and the role of retinoic acid in the development of the chick embryo. Dev. Biol. 135: 124–132.PubMedCrossRefGoogle Scholar
  7. Mangelsdorf, D.J., et al. (1995): The nuclear receptor superfamily: The second decade. Cell 83:835–839.PubMedCrossRefGoogle Scholar
  8. Mangelsdorf, D.J., and Evans, R.M. (1995): The RXR heterodimers and orphan receptors. Cell 83:841–850.PubMedCrossRefGoogle Scholar
  9. Umesono, K., and Evans, R.M. (1989): Determinants of target gene specificity for steroid/thyroid hormone receptors. Cell 57:1139–1146.PubMedCrossRefGoogle Scholar

Box 7. Some Cellular and Molecular Methods of Recent Developmental Biology (See also Bibliography for Box 2)

  1. Barinaga, M. (1994): Knockout mice: round two. Science 265:26–28.PubMedCrossRefGoogle Scholar
  2. Chisaka, O., and Capecchi, M.R. (1991): Regionally restricted developmental defects resulting from targeted disruption of the mouse homeobox gene Hox-1.5. Nature 350:473–479.PubMedCrossRefGoogle Scholar
  3. Cubitt, A.B., et al. (1995): Understanding, improving and using green fluorescent protein. Trends Biochem. Sci. 20:448–455.PubMedCrossRefGoogle Scholar
  4. Friedrich, G., and Soriano, P. (1991): Promoter traps in amphibian stem cells: A genetic screen to identify and mutate developmental genes in mice. Genes Dev. 5:1513–1523.PubMedCrossRefGoogle Scholar
  5. Gossen, M., Bonin, A.L., and Bujard, H. (1993): Control of gene activity in higher eukaryotic cells by prokaryotic regulatory elements. Trends Biochem. Sci. 18:471–475.PubMedCrossRefGoogle Scholar
  6. Prasher, D.C. (1995): Using GFP to see the light. Trends Genet. 11: 320–323.PubMedCrossRefGoogle Scholar
  7. Wagner, E.F. (1990): Mouse genetics meet molecular biology at Cold Spring Harbor. New Biologist 2:1971–1074.Google Scholar
  8. Wakimoto, T., and Karpen, G.H. (1988): Transposable elements and germ-line transformation in Drosophila. In Malacinsky, G.M. (ed.) Developmental Genetics of Higher Organisms: A Primer in Developmental Biology, pp. 275–303. Macmillan, New York.Google Scholar

Copyright information

© Springer-Verlag New York, Inc. 1997

Authors and Affiliations

  • Werner A. Müller
    • 1
  1. 1.Zoologisches Institut—PhysiologieUniversity of HeidelbergHeidelbergGermany

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