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

Hans Spemann

The German experimental embryologist Hans Spemann (1869-1941) was awarded the Nobel Prize in Physiology or Medicine for his discovery of the organizer effect in embryonic development.

Hans Spemann, son of Wilhelm Spemann, a publisher, was born in Stuttgart on June 27, 1869. After a period in his father's business and military service, he became a medical student at the University of Heidelberg, spent a period at the University of Munich, and in 1894 transferred to Würzburg. There he abandoned medicine for science, studied under Theodor Boveri, who greatly influenced his future research, and graduated in 1895.

Spemann then began research in the Zoological Institute at Würzburg, where he became a lecturer in 1898. In 1908 he was appointed professor of zoology and comparative anatomy in the University of Rostock, and in 1914 associate director of the Kaiser Wilhelm Institute for Biology at Berlin-Dahlem. He was called to the chair of zoology in the University of Freiburg in Breisgau in 1919, from which post he retired in 1935. Spemann devoted his scientific career to the study of the causes that act on the cells of the earliest embryos, leading to their differentiation and specialization for different functions.

Foundation of Experimental Embryology

The science of experimental embryology (or developmental mechanics) was founded about 1890 by Wilhelm Roux and Hans Driesch. Roux destroyed one of the two blastomeres formed by the first division of a fertilized frog's egg. He found that the other blastomere continued to develop, but it formed half an embryo. Then Driesch separated the two blastomeres of a sea urchin's egg and removed one entirely. The remaining blastomere formed, not half an embryo, but a normal embryo of small size.

It was well known that the eyeball developed from the optic cup, a protuberance from the primitive brain, and that the lens arose in the epidermis overlying the optic cup. Why the epidermis thickened and became transparent at the appropriate point was unknown, and the question was whether there was some unknown connection between optic cup and potential lens. In 1901 Carl Herbst found that, in abnormal embryos showing a single (median) optic cup, only one lens developed and that at a point opposite the cup. This strongly favored an influence exerted by the cup on the overlying ectoderm.

Spemann's Classical Experiments

This paper by Herbst fired Spemann's enthusiasm, and in the same year he demonstrated that the epidermis showed no change if the eye rudiment was destroyed. He suggested that proof of the correlation could be obtained if the optic cup was brought into contact with a foreign part of the epidermis, either by transplanting the optic cup or the epidermis overlying it. W. H. Lewis performed these experiments satisfactorily in 1904. During the next 6 years Spemann published his experiments on the eye and also his technique and instruments for "microsurgery." It was shown that practically any part of the epidermis could form a lens if it was activated by some influence in the optic cup.

Spemann then experimented on the amphibian gastrula, the early embryo consisting of undifferentiated cells forming a hollow sphere, with a mouth (the blastopore) opening to the exterior. He frequently transplanted minute pieces of the gastrula from one area of its surface to another, and he always found—with one exception—that the transplants developed according to their new positions. The exception was a transplant from the upper lip of the blastopore, which in its new position developed into a small secondary embryo. In 1918 Spemann thought that the whole of the secondary embryo was formed by the implanted material, so that the ectoderm (upper layer) of the implant formed the medullary plate (subsequently forming the central nervous system), and the lower layer developed into the notochord and muscular system. He concluded therefore that the blastopore region was already differentiated at that stage, while all other cells in the gastrula were still undifferentiated.

Further work then led Spemann to think that possibly the primitive nervous system of the secondary embryo was formed by induction from the ectoderm of the host tissue. To decide the point it was necessary to distinguish implanted tissue from host tissue. Until then his transplants had been from one part to another of the same embryo, but in 1921 he decided that the answer lay in using two embryos, of the same age but of different species. In 1924 Spemann and Hilde Mangold published their results. For the implant and the host they used respectively gastrulas of the newts Triton cristatus (almost colorless) and Triton taeniatus (highly pigmented). Implant and host cells were thus easily distinguished. In innumerable experiments they found that the graft disappeared below the gastrula surface to form the mesodermal elements (notochord and muscles) of the secondary embryo. Above it the ectoderm of the host was induced to form, from host material, the neural tube of the secondary embryo.

Organizer Effect

From these "heteroplastic transplants" Spemann concluded that the upper lip of the blastopore, when brought into contact with other cells of the gastrula, could exert an influence to induce them to become differentiated to form a medullary plate. This influence he called an "organizer." In all vertebrate embryos it is the first step in the series of differentiations that result in the fully formed fetus. He therefore termed the influence of the blastopore lip the "primary organizer." The formation of the optic cup being a sequel to this action, he called the organizer in the optic cup a "secondary organizer." Further development is due to chains of induction by successive orders of organizers. Spemann believed that the action of the organizer was transferred by a chemical substance; but he, and other scientists such as Joseph Needham and C. H. Waddington, succeeded only partially in identifying it.

Spemann was awarded the Nobel Prize in 1935, and he received many other honors, including the title of Geheimrat (Privy Councilor). He died at Freiburg on Sept. 9, 1941.

Further Reading

There is a biography of Spemann in Nobel Lectures, Physiology or Medicine, 1922-1941 (1965), which also includes his Nobel Lecture. For his work see his Embryonic Development and Induction (1938); see also C. H. Waddington, The Nature of Life (1961), and J. Needham, Biochemistry and Morphogenesis (1942). □

Hans Spemann

1869-1941

German zoologist and embryologist who received the 1935 Nobel Prize for Physiology or Medicine for his discovery of embryonic induction. Fascinated with newts, his early experiments were on the evolution of the eye lens of amphibians. This delicate work led him to develop small, precise surgical instruments and techniques—the foundation of microsurgery. His experiments with newt's eggs showed that at early stages cells were not specialized, and he discovered the first known example of a causal mechanism controlling the development of an embryo.