Hans Spemann on vitalism in biology: translation of a portion of Spemann's autobiography.
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Biomedical subjects
Publications and source records attributed to V Hamburger.
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The Nerve Growth Factor (NGF) is the progenitor of a family of growth factors which is still expanding. The history of its discovery is very colorful; it is a rare combination of scientific reasoning, intuition, fortuities, and good luck. In addition, I believe that the collaboration of three scientists with very different backgrounds contributed to the success: I had grown up in a laboratory of experimental embryology, Dr. Levi-Montalcini came from neurology, and Dr. Stanley Cohen was from biochemistry. The decision where to begin the history of a discovery is always arbitrary. I shall give my reasons why I begin this story with my wing bud extirpations on chick embryos and the analysis of the effects of the operation on the development of spinal nerve centers, published in 1934. Of course, I am aware of the fact that the analysis of neurogenesis had been pioneered by Dr. R. G. Harrison and his students at Yale University since the beginning of this century. It should be mentioned that their experiments had been done on amphibian embryos. My own interest in problems of neurogenesis dates back to my Ph.D. thesis in the Zoology Department of Professor H. Spemann at the University of Freiburg in (the Federal Republic of) Germany; it dealt with the influence of the nervous system on the development of limbs in frog embryos. After I had obtained some inconclusive results I did the crucial experiment of producing nerveless legs. I removed the lumbar part of the spinal cord and the spinal ganglia before the outgrowth of nerve fibers. The nerveless legs developed normally in every respect, but the muscles atrophied eventually.
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The German anatomists, M. Ernst and A. Glücksmann, deserve credit for the discovery of widespread cell death in embryonic tissues, including the nervous tissue. In 1934, V. Hamburger described a significant hypoplasia in dorsal root ganglia (DGR) and lateral motor columns, following the extirpation of limb buds in chick embryos. In the early 1940s, Dr. Rita Levi-Montalcini in Turin (Italy) repeated the experiment and suggested that the hypoplasia might result from the death of young differentiated neurons. In a joint reinvestigation, published in 1949, large numbers of degenerating neurons were described in brachial DRG, following wing bud extirpations. In the same embryos, Dr. Levi-Montalcini observed massive neuronal death in cervical and thoracic DRG which had not been affected by the operation. This was the discovery of naturally occurring neuronal death. Long after the discovery of Nerve Growth Factor (NGF) it was recognized that NGF and natural neuronal death are two sides of the same coin: the latter results from an insufficient supply of the former by the target tissues.
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Extirpation of the wing bud in 2-day chick embryos results in a conspicuous degeneration of neurons in both populations of brachial dorsal root ganglia (DRG). Daily injections of 1 to 6 micrograms of nerve growth factor (NGF), beginning at 4 1/2 days of incubation, rescued all small, late differentiating (DM) neurons and approximately 50% of large, early differentiating (VL) neurons, which would have died otherwise. The fact that NGF is an effective substitute for the hypothetical trophic maintenance factor for DRG which is normally produced by limb tissues strengthens our belief that NGF is identical with this factor. The control experiment, i.e., wing extirpation without NGF injections, revealed an inconsistency with previous data. Experiments on a number of different neuronal units had shown rather consistently that the period of experimentally induced neuron degeneration, caused by removal of the target, is synchronous with the period of normally occurring neuronal death in the same neuronal unit. This synchrony rule is violated by the VL population of brachial DRG. In this unit, the peak of degeneration resulting from wing bud extirpation occurs considerably earlier than the peak of normally occurring neuronal death. The competition hypothesis for the explanation of neuronal death had been based, in part, on the synchrony rule. We discuss the question of whether the deviation from the synchrony rule observed in our material represents a serious challenge to the competition hypothesis.
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