SPEMANN, HANS

(b. Stuttgart, Germany, 27 June 1869; d. Freiburg im Breisgau, Germany, 12 September 1941),

embryology.

Spemann was the eldest of four children of a well-known book publisher, Johann Wilhelm Spemann, and the former Lisinka Hoffmann. His father’s family, of Westphalian peasant stock, had a number of members in the legal profession, and his mother’s family contained several doctors. There were three other children in the family, and he grew up in a fairly large house well provided with books, with parents who led an active social and cultural life. Spemann attended the Eberhard-Ludwigs-Gymnasium, where he was particularly attracted by classics. He first decided, however, to study medicine; and for that purpose he attended the University of Heidelberg as soon as he had completed his year of military service in the Kassel hussars.

At Heidelberg, Spemann formed a friendship that without doubt greatly influenced the direction of his life. Gustaf Wolff, a few years older than he, had begun experiments on the embryological development of newts and had shown that if the lens of the eye is removed, a new lens may be formed—not from the tissue that gives rise to the lens in normal development, but from the edge of the retina. This “Wolffian lens regeneration” intrigued Spemann throughout most of his life, and it still retains some of the air of mystery that originally surrounded it. At that time (1892) Wolff interpreted it as strong evidence against Darwin’s “selection theory” and as proof of “organic purposiveness.” Thus Spemann was introduced, at the beginning of his academic career, to the animal that was to remain his favorite experimental material; acquired an insight into the character of a well-planned and clean experiment; and developed an inclination toward what might now be considered a somewhat mystical conception of the nature of biological processes. He retained strong traces of these influences throughout his life.

As a young biologist Spemann began work in 1894 at Würzburg as a doctoral student and teacher, and was the favorite pupil of Theodor Boveri. It was there, just after taking his doctorate, that he married Clara Binder. After fourteen years at Würzburg, Spemann became professor at Rostock (1908–1914). He spent the years of World War I as director of the Kaiser Wilhelm Institute of Biology in Berlin-Dahlem; and in 1919 he succeeded Weismann as professor at Freiburg im Breisgau. He remained at Freiburg for the rest of his life, retiring in 1938 and dying in his country house nearby in 1941. He was awarded the Nobel Prize for physiology and medicine in 1935.

Spemann combined great persistence, foresight, and careful planning with beautifully precise manipulative skill and an insistence on Sauberkeit (cleanliness, in all aspects). His first two major works in biology were fully thought out, before he started writing them, to answer quite clearly defined questions. The time for this creative thinking had been forced on him by a lung illness that necessitated a rest cure in Switzerland.

For one line of work Spemann chose the object about which he had first learned from his friend Wolff—the lens of the amphibian eye—but asked himself a question more basic than any raised by Wolff’s work on regeneration: how the lens came to develop in the first place. It is formed from the outer layer of cells in the embryo (the ectoderm, which also gives rise to the skin and the nervous system), and it appears at the point where an outgrowth from the brain reaches the surface. At an early stage of development, the region from which this outgrowth arises is exposed on the surface of the egg, and Spemann was able to kill this group of cells by burning with a minute hot needle. He found that the remainder of the embryo could develop normally without the retina that should have developed from the brain outgrowth and, most important, also without the lens. This discovery strongly suggested that the brain outgrowth, when it reaches the ectoderm, exerts an influence that causes the cells to develop into the lens.

In order to study further the reality of this postulated “induction” of the lens by the retina. Spemann had to perfect his experimental methods. He invented a number of very simple but elegant and refined instruments, mostly made from glass, which made it possible to carry out complicated surgical operations on eggs and embryos only a millimeter or two in diameter. In this way he became almost solely responsible for founding the techniques of microsurgery, certainly one of his greatest contributions to biology. Using such instruments, Spemann could remove the region of ectoderm from which the lens would be expected to form, and substitute some other piece for it before the development of the retina; he found that this foreign ectoderm was induced by the retina to develop into a lens.

Spemann’s other early problem did not demand as much technical originality, but led even deeper into the major questions of development. The newt’s egg, when laid, is enclosed in an oval capsule of jelly. A thin hair—Spemann maintained that it should be from the head of a blond infant less than nine months old—can be tied around it and pulled tight enough to cut the egg in half or compress it to a dumbbell shape. Spemann found that if this constriction is carried out soon after laying, each separate half of the egg may develop into a complete larva; or, alternatively, one may develop into a whole larva and the other only into a more or less formless mass of cells. If the constriction is not complete, and produces only a dumbbell, one may obtain an embryo with a single tail and two complete heads.

The important point is that a half egg (or half region) never produces a half embryo, but always either a complete embryo (or organ such as the head) or nothing at all. The production of a complete embryo from half the egg shows clearly that at this early stage the various parts of the egg are not fixed in their “developmental fate” (“Determined”). On the other hand, if the same constriction experiment is carried out considerably later, after gastrulation but still before the first embryonic organs can be recognized, the halves form only half embryos, each part developing exactly as if there had been no constriction. Some process of “fixing the developmental fate of the parts” must have occurred between the early stage and the later; and Spemann called this process “determination.”

Spemann was thus led to take two further steps that, in combination, opened a new era in the understanding of biological development. From the constriction experiments it seemed to follow that, long before any particular organs can be recognized in the embryo, some process of “determination” decides, more or less irrevocably, the nature of the end product into which any given region will develop. It might seem obvious to ask what the nature of this process is. But Spemann was too wary to get involved in such philosophical traps and too good an experimentalist. He posed the more restricted but more manageable problem of whether we can discover any causal antecedent that brings about this determination.

Calling on the microsurgical techniques elaborated in his study of the lens, Spemann devised experimental procedures that did indeed reveal a causal sequence of events leading up to the determination of the main organ that appears in early stages of development: the central nervous system. By transferring small fragments of tissue from one location in the embryo to another, he (and some of his student collaborators, particularly Hilde and Otto Mangold) showed that any part of the ectoderm of the embryo, if brought into contact with the mesoderm before or at the time of gastrulation, would be induced to become neural tissue; whereas if it were not allowed to contact the mesoderm, it would not become neural tissue, even if its original location in the embryo would have led one to expect it to develop in that way. By this achievement Spemann had discovered the first known example of a causal mechanism that makes it possible to control precisely the direction in which a part of the embryo will develop; by surgical manipulation of its neighboring cells, it can be determined whether this embryonic part will develop into nerves or into skin.

When a piece of ectoderm is placed in contact with the mesoderm, it is induced to form not a mere mass of neural cells but a part of a neural organ, such as the brain, with a greater or lesser degree of organization. This finding led Spemann to approach the problem of the mechanism of “the induction of determination” with considerable caution. His biological philosophy, while not explicitly vitalist, tended to fall within the “organicist” framework characteristic of German biology at the turn of the century. He seems at first to have felt that the process of induction occurs in cells that are so biologically complex that an attempt to analyze it would necessarily entail an oversimplification. He therefore used, as a name for the region that develops into mesoderm and that induces the neural plate, the word “Organisator,” and he stated, “It creates [schafft] an organization field out of the indifferent material in which it lies.”

In later experiments, devoted to the study of induction in other regions of the embryo, Spemann again found that what is induced usually is an organ, with its own characteristic shape. But some of these experiments, in which fragments from frogs’ eggs were transplanted to newts’ eggs, or vice versa, led to what should probably be considered Spemann’s second major contribution: the discovery that the character of the induced organ depends much more on its own intrinsic (presumably genetic) constitution than on that of the inducer. Thus a frog inducer, acting on newt tissues, produces a newt organ. The reacting material is by no means indifferent, as he had earlier thought. Further under the influence of younger, more analytically oriented students, Spemann gradually accepted the importance of experiments designed to discover the extent to which the effects of his “Organisator” can be produced when the cells of it have been killed or chemically extracted. He never seems, however, to have considered induction from the point of view that now seems so natural: as involving the genetic potentialities of the cells. Perhaps only T. H. Morgan, among his contemporaries, would have been tempted to approach the subject from that angle during the period when Spemann was most active. The communication between German experimental embryologists and American geneticists was so slight that the connection was made only toward the end of Spemann’s life. It was, however, the precision and rigor of Spemann’s experiments that led him to formulate clear questions concerning the causal sequences of particular and well-defined developmental performances by identifiable groups of cells, and thus to provide the foundations on which the more recent advances have been based.

BIBLIOGRAPHY

I. Original Works. All but the very last of Spemann’s publications were summarized by the author himself in his Experimentelle Beiträge zu einer Theorie der Entwicklung (Berlin, 1936), translated into English as Embryonic Development and Induction (New Haven, 1938). An autobiography is Forschung und Leben, Errinerungen(Stuttgart, 1943).

II.Secondary Literature. An extensive discussion by a long-time pupil and collaborator is O. Mangold, Hans Spemann, ein Meister der Entwicklungs physiologie, sein Leben und sein Werk (Stuttgart, 1953). Less extensive surveys of Spemann’s work, and discussion of it by authors not so closely associated with him, are in J. Needham, Biochemistry and Morphogenesis 2nd ed. (London, 1969); L. Saxén and S. Toivonen, Primary Embryonic Induction (London, 1962); and C. H. Waddington. Principles of Embryology (London, 1956).

Biographical writings are F. Baltzer. “Zum Gedächtnis Hans Spemann,” in Naturwissenschaften. 30 (1942), 229–239; and O. Mangold, “Hans Spemann als Mensch und Wissenschaftler.” in Wilhelm Roux Archiv für Entwicklungs-mechanik der Orangismen, 141 (1942). 385–425; and “Hans Spemann,” in Freiburger Professoren des’ 19. und 20. Jahrhunderts (Freiburg, 1957), 159–182.

C. H. Waddington