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Hans Spemann (27 Jun 1869 – 9 Sep 1941) was awarded the Nobel Prize in Physiology or Medicine in 1935 for seminal experiments that laid the foundations for the field of embryonic development.
Spemann was assisted by Hilde Proescholdt (later Mangold), a Ph.D candidate in Spemann's Freiburg laboratory.
Hilde Mangold (1898 – 1924; born Pröscholdt), German biologist.
Mangold made important conceptual and methodologcal contributions to the laboratory. Historians of Science generally refer to the Freiburg work as the Spermann-Mangold Experiment.
Hilde Mangold had married Otto Mangold, the most senior student in Spemann’s lab and bore a child. She is pictured here with her child in 1924. She died when a gasoline heater in her kitchen exploded in September of the same year.
Mangold's death occurred in the same year as publication of the seminal paper that focused developmental biology on a new path.
Uber Induktion von Embryonanlagen durch Implantation artfremder Organisatoren. Spemann, H., and H. Mangold. Roux Arch. f. Entw. mech. 100: 599-638. 1924.
Embryo Development. As shown, development proceeds from fertilization to the blastocyst stage after 5-6 days of culture..
Video courtesy of the Mitera Maternity Hospital (Athens, Greece, (2007). Time 02:34.
Washington, DC, USA. Science shows that the human brain and central nervous system form before the remaining portions of our overall body plan. This is a central insight and the province of developmental biology, particularly embryology, which deals with the development of organs and other anatomical structures from the point of conception.
While many questions remain to be answered, scientists have accumulated a great deal of knowledge on the sequence of human development following conception. Prior to the 20th century (and as recently as the 18th), the field of human embryology was in its formative stages. Ideas of preformation were prevalent; that is, the egg or sperm contains the homunculus — a preformed, miniature infant — that gows larger during development.
Uber Induktion von Embryonanlagen durch Implantation artfremder Organisatoren. Spemann, H., and H. Mangold. Roux Arch. f. Entw. mech. 100: 599-638. 1924.
The competing explanation was a proposal by Aristotle some 2,000 years before. Called epigenesis, it supposed that the form of an animal emerges gradually from a relatively formless egg. Instrumentation improved throughout the 19th century, ao biologists could actually observe embryos and watch a series of progressive steps. Epigenesis eventually displaced preformation as the favored explanation.
The Spemann-Mangold Experiments
Further progress came in fits and starts, occasioned by important events that seem deceptively simple in hindsight. The Spemann-Mangold experiments are an important example that set embrylogy on a truly modern path.
Hans Spemann (27 Jun 1869 — 9 Sep 1941), a German scientist, was awarded the Nobel Prize in Physiology or Medicine in 1935 for his discovery of the effect now known as embryonic induction. Spemann and his assistant, Hilde Mangold (1898 — 1924), a Ph.D candidate in his Freiburg laboratory, conducted seminal experiments that laid the foundations for the field of embryonic development.
The basic idea for embryonic induction had been proposed by several of Spemann’s predecessors (referred to then as Organization [C1]. However, there had not been a definitive demonstration of the phenomenon.
Embryonic induction is the interaction between two groups of cells, one of which influences the developmental fate of the other. Thus, various parts of the embryo direct the development of groups of cells into particular tissues and organs.
After considerable earlier work, Hans Spemann and Hilde Mangold (b. Hilde Proescholdt) performed a series of deceptively simple experiments. The entire series took place over a period of years and received full publication in 1924 [C2, sidebar].
To start, the scientists divided a salamander embryo in half.
One half, the one that gives rise to the salamander's belly (ventral) started to wither away.
The back (dorsal) half — the one that develops into its head, brain and spinal cord — continued to grow.
The surviving dorsal half regenerated the missing belly half and developed into a smaller, but complete and fully functional embryo.
They then conducted another experiment. This time, the removal of a few cells from the back half of one embryo for transplantation into the belly half of a different embryo.
This gave rise to a Siamese twin embryo where an extra head was generated from the transplanted cells.
Although the resulting embryo was smaller than normal, all its tissues and organs developed in the right proportions irrespective of its size, and functioned properly.
Portions of an area in the embryo, upon transplantation into a second embryo, organized or "induced" secondary embryonic primordia regardless of location.
Spemann called these areas "organiser centres" or "organisers". Later he showed that different parts of the organiser centre produce different parts of the embryo. For a fuller explanation of the Spemann-Mangold experiment, see the citations [C3].
Recent Work On Underlying Mechanism
Many questions remained after the classic Spemann-Mangold experiments. How can it be that just half an embryo can maintain its tissues and organs in the correct proportions and do this despite being smaller than a normal sized embryo? Scientists have arrived at a better understanding of the mechanisms involved.
Previous studies have shown that the growth and development of cells and organs within the embryo is somehow linked to a special group of substances called morphogens. These are substances that govern the pattern of tissue development, fixing the positions of the various specialized cell types within a tissue.
In developmental biology, the term morphogen has an even more rigorous sense to mean a signaling molecule that, depending on concentration, acts directly on cells to produce specific cellular responses.
These morphogens are produced in one particular area within the embryo and then spread throughout the entire embryo in varying concentrations. The concentration of morphogen sets the fate of any particular embryo cell type (which tissue and organ they will develop into).
Prof. Naama Barkai and her colleagues at the Weizmann Institute of Science [N1] developed a mathematical model to describe interactions that occur within an embryo's genetic networks. The data obtained from this model suggest that the way morphogens spread throughout the embryo in different concentrations is different than previously thought.
The team predicts that an inhibitor molecule, which is secreted from a localized source at one side of the embryo and can bind the morphogen, acts as a type of ferry that 'shuttles' the morphogen to the other side. Therefore, the mathematical model suggests that it is the interactions between the two substances that enable the embryo to keep the relative proportion between organs constant, irrespective of its size. The research team validated these predictions by experiments conducted on frog embryos.
The importance of the role of these morphogenic substances, as well as their mechanism of action, is evident by the fact that they have been conserved throughout evolution, where different variants can be found to exist in species ranging from worms to fruit flies and up to higher species including humans. Therefore, understanding the processes that govern embryonic cell development could have many implications. For example, it may lead, in the future, to scientists being able to repair injured tissues.
[N1] The full team consisted of Profs. Naama Barkai, Benny Shilo and research student Danny Ben-Zvi of the Molecular Genetics Department at the Weizmann Institute of Science (Rehovot, Israel), together with Prof. Abraham Fainsod of the Hadassah Medical Organization at the Hebrew University (Jerusalem, Israel).
[C1] Ethel Browne, Hans Spemann, and the Discovery of the Organizer Phenomenon. Howard M. Lenhoff. Biol. Bull. 181: 72-80. (August, 1991). [ Download PDF ]
Abstract
Ethel Browne Harvey (1885-1965) will be familiar to some as a researcher on the embryology of sea urchins. Few, however, know her as Ethel Browne who, as a graduate student, published, in 1909, a remarkable paper demonstrating for the first time the induction by a transplant of a secondary axis of polarity in the host. This process was later named “organization” by Spemann and Mangold (1924) in a paper that led to Spemann’s being awarded the Nobel Prize. Why did the Nobel Committee, or other embryologists for that matter, not connect Browne’s discovery with that of Spemann and Mangold? Did they consider the development of hydra as being too remote from that occurring in embryos of vertebrates? Did the 1909 paper of Ethel Browne in any way influence the thinking of Spemann or Mangold, although it was never referred to in any of Spemann’s papers? In light of new information about Spemann’s knowledge of Browne’s work, we also can ask a number of questions about the interplay of basic prejudices in the reception accorded Browne’s work.
[C2] Uber Induktion von Embryonanlagen durch Implantation artfremder Organisatoren. Spemann, H., and H. Mangold. Roux Arch. f. Entw. mech. 100: 599-638. 1924.
[C3] Spemann's organizer and self-regulation in amphibian embryos. Edward M. De Robertis. Nature Reviews Molecular Cell Biology 7, 296-302 (April 2006). doi: 10.1038 / nrm1855.
Abstract
In 1924, Spemann and Mangold demonstrated the induction of Siamese twins in transplantation experiments with salamander eggs. Recent work in amphibian embryos has followed their lead and uncovered that cells in signalling centres that are located at the dorsal and ventral poles of the gastrula embryo communicate with each other through a network of secreted growth-factor antagonists, a protease that degrades them, a protease inhibitor and bone-morphogenic-protein signals. But how does this happen? How exactly is the half embryo able to maintain its tissues and organs in the correct proportions despite being smaller than a normal sized embryo?
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