MANGOLD (NéE PRöSCHOLDT), HILDE

(b. Gotha, Germany, 20 September 1898; d. Auenstein near Stuttgart, Germany, 5 September 1924),

developmental biology, experimental embryology, pattern formation.

Embryogenesis transforms the seemingly simple egg cell into an organized body of amazing complexity. A fundamental component of this process, called the organizer effect, was first documented in the doctoral dissertation of Hilde Mangold, published at the time of her death. This work, crucial for the 1935 Nobel Prize in Physiology or Medicine, ranks as the first breakthrough toward a mechanistic understanding of vertebrate development.

Life of Hilde Mangold . Hilde was born to Gertrud and Ernst Pröscholdt as the second of three daughters. Her father came from a family of artists who specialized in chinaware decoration but managed to acquire a soap factory

in Gotha, a provincial center of intellectual life. Hilde received the best education possible. She was one of the few girls to be admitted to the local high school and passed her final exam with best marks. Dissatisfied by a brief interlude at a “Pensionat” that trained prospective housewives, Hilde studied chemistry, philosophy, and fine arts at Jena University. After one term (winter 1918–1919) she shifted to Frankfurt and to zoology as her main subject.

There she was deeply impressed by a guest lecture by Hans Spemann, doubtless the leading experimental embryologist of that period. Spemann had just resigned from the Kaiser Wilhelm Institut für Biologie and moved to the idyllic setting of Freiburg (Baden, Germany). In the spring of 1920 Hilde moved there too. Impressed by her intellect and drive, Spemann accepted her for doctoral research after just one year of advanced training in biology. This training she shared with about a dozen fellow students, of whom two—Viktor Hamburger and Johannes Holtfreter—like Hilde herself were to leave indelible marks on developmental biology. The main teachers of this gifted and vividly interacting group were Fritz Baltzer and Otto Mangold.

In 1921, Hilde decided to marry Otto and adopted his family name. Despite considerable differences in years and in temper—Hilde vivacious, Otto steady and very systematic—the couple apparently developed a successful partnership in research as well as family life during the three years left to them. In December 1923 their son Christian was born and Hilde had to abandon work on her experiments—seemingly just for the time being. But she died on 5 September 1924, the victim of terrible burns suffered the previous day while trying to heat her baby’s meal on an alcohol stove. She was buried in the family grave at Gotha; the tombstone carrying her portrait in bronze is still extant.

The Organizer Effect . This effect, named by Hans Spemann, is illustrated in Figure 1. It was first observed in experiments using salamander (newt) embryos at the onset of gastrulation, the process whereby cells destined to yield internal organs get shifted inside the previously hollow embryo (called the blastula). The aim was to understand the mechanisms causing the increase in ordered complexity (later called pattern formation) during embryogenesis. The organizer effect was documented by transplanting material from a certain region—called the dorsal lip—of a donor blastula into the belly region of another embryo of the same stage, the host (see Figure 1). Often, such transplants would locally initiate gastrulation and thereby move inward, accompanied by huge numbers of surrounding host cells. After further development, this cell complex could develop into a more or less complete additional body, made up of transplant cells intermingled with host cells that otherwise should have formed nothing but belly surface. Apparently, the transplanted material was capable of triggering (inducing) and guiding the formation of a well-organized body—it acted as an “organizer.”

Under Spemann’s guidance, Hilde Mangold in 1921 and 1922 performed 259 of these technically demanding “lip transplantations” for her doctoral thesis. Of the seventy-three surviving cases, twenty-eight developed in their belly regions recognizable components of an additional body. The individual degree of organization ranged from a feeble rudiment of the spinal cord (the as-yet-superficial neural plate, see Figure 1b) to a well-defined additional body (see Figure 1c). All but two of these additional embryos were of a chimeric (composite) constitution (see Figure 1d). With the ascent of genetic, biochemical, and molecular methods, Mangold’s “mechanical” experiments seemed to fall into oblivion. However, once advanced molecular methods had passed their teething troubles, their practitioners came to appreciate her pioneering work—as documented by a dramatic rise in its citation frequency (Fässler and Sander, 1996).

The Nobel Prize—Fables and Facts . In 1935, the Nobel Prize for Physiology or Medicine was awarded to Hans Spemann, expressly “for his discovery of the organizer effect in embryonic development.” Some competitors, such as Sven Hörstadius, argued that this effect had been discovered already during a few exploratory experiments by Warren Harmon Lewis (1907) but—owing to a mistaken hypothesis of Wilhelm Roux (see Sander 1990, 1991)—Lewis had failed to recognize the effect, and never laid claim to it! The restriction of the prize to Spemann was considered unfair by some because it was Hilde Mangold who had delivered the experimental evidence. However, the prize can be awarded only to living persons.

Spemann himself no doubt deserved the honor because between 1914 and 1918 he had paved the way for Mangold’s success. He developed all the techniques

required, among them the delicate transplantation of small cell groups and the marking of transplant cells by taking the transplants from a different species—but as

a newly installed professor (1919) he lacked the time to apply them in combination himself. He had, however, made predictions as to the outcome, of which one alternative—neural induction by the submerged transplant—was to prove correct. Spemann failed, however, to foresee the induction of a complete body and the chimeric constitution of individual organ rudiments (see Figure 1d)—clearly the most striking and overarching components of the organizer effect. They were revealed de novo by Hilde Mangold’s experiments, and certainly should have earned her a share in the Nobel Prize. This, alas, was not to come true, but her name lives forth in the term Spemann-Mangold organizer, which became universally accepted.

BIBLIOGRAPHY

WORKS BY MANGOLD

“Ueber die Induktion von Achsenorgananlagen durch Transplantation eines Organisators.” PhD diss., Albert-Ludwigs-Universität Freiburg, Germany, 1922. Typescript (no figures); stored at the Universitätsarchiv Freiburg.

With Hans Spemann. “Über Induktion von Embryonalanlagen durch Implantation artfremder Organisatoren.” Archiv für mikroskopische Anatomie und Entwicklungsmechanik 100 (1924): 599–638. First and fundamental description of the organizer effect.

OTHER SOURCES

Fässler, Peter E. “Hans Spemann and the Freiburg School of Embryology.” International Journal of Developmental Biology 40 (1996): 49–59.

_____. Hans Spemann (1869–1941)—Experimentelle Forschung im Spannungsfeld von Theorie und Empirie. Berlin: Springer Verlag, 1997. Fully documented biography of Spemann.

_____, and Klaus Sander. “Hilde Mangold (1898–1924) and Spemann’s Organizer: Achievement and Tragedy.” Roux’s Archives of Developmental Biology 205 (1996): 323–332. Reprinted in Sander, 1997.

Hamburger, Viktor. “Hilde Mangold, Co-discoverer of the Organizer.” Journal of the History of Biology 17 (1984): 1–11. Report by a famous labmate of Hilde Mangold.

_____. The Heritage of Experimental Embryology: Hans Spemann and the Organizer. New York: Oxford University Press, 1988.

_____. “Memories of Professor Hans Spemann’s Department of Zoology at the University of Freiburg.” International Journal of Developmental Biology 40 (1996): 59–63.

Hörstadius, Sven. Über die Determination des Keimes bei Echinodermen. Stockholm: Albert Bonnier, 1928. Claims that the organizer effect was discovered by W. H. Lewis in 1907.

Lewis, Warren Harmon. “Transplantation of the Lips of the Blastopore in Rana palustris.” American Journal of Anatomy 7 (1907): 137–143.

Sander, Klaus. “Von der Keimplasmatheorie zur synergetischen Musterbildung—Einhundert Jahre entwicklungsbiologischer Ideengeschichte.” Verhandlungen der Deutschen Zoologischen Gesellschaft 83 (1990): 133–177. Illustrated history of developmental concepts.

_____. “When Seeing Is Believing: Wilhelm Roux’s Misconceived Fate Map.” Roux’s Archives of Developmental Biology 200 (1991): 177–179. Reprinted in Sander, 1997. Describes an error that may have prevented earlier discovery of the organizer effect.

_____, ed. Landmarks in Developmental Biology, 1883–1924: Historical Essays from Roux’s Archives. Berlin: Springer-Verlag, 1997.

_____, and Peter E. Fässler. “Introducing the Spemann-Mangold Organizer: Experiments and Insights That Generated a Key Concept in Developmental Biology.” International Journal of Developmental Biology 45 (2001): 1–11. A richly illustrated report.

Spemann, Hans. Experimentelle Beiträge zu einer Theorie der Entwicklung. Berlin: Verlag Julius Springer, 1936. Spemann’s exposition of his lifelong research on amphibian embryogenesis. Reworked translation: Embryonic Development and Induction. New Haven, CT: Yale University Press, 1938.

Klaus Sander