69117 Heidelberg, Germany
Hamburger studied at the University of Heidelberg. In 1925 he received a Doctor of Philosophy degree.
69117 Heidelberg, Germany
Hamburger studied at the University of Heidelberg. In 1925 he received a Doctor of Philosophy degree.
http://www.amazon.com/gp/product/B0006WQN58/?tag=2022091-20
1977
(Here is a critical account of the experimental work of Ge...)
Here is a critical account of the experimental work of German biologist and Nobel laureate Hans Spemann, one of the founders of experimental embryology.
http://www.amazon.com/gp/product/0195051106/?tag=2022091-20
1988
http://www.amazon.com/gp/product/1489967451/?tag=2022091-20
2014
educator embryologist scientist author
Viktor Hamburger was born on July 9, 1900 in Landeshut, Silesia, Germany (now Kamienna Góra, Poland), to a middle-class family. He was one of two sons born to Max and Else Hamburger, who had moved from Breslau (later Wroclaw, Poland) to take over the family textile industry. Hamburger’s parents were well-educated: his father was an avid art collector and friend of many important German artists and his mother was an ardent naturalist.
Hamburger enrolled at the University of Heidelberg in 1919. There he attended seminars of Hans Driesch and received his first introduction into experimental embryology from Curt Herbst.
In 1920 Hamburger enrolled at the University of Freiburg as a graduate student and was accepted into Hans Spemann’s laboratory. In 1925 Hamburger received a Doctor of Philosophy degree for studying the relationship between nerve and limb development.
For his PhD dissertation, completed in the spring of 1925, Hamburger undertook to study the role of the nervous system in the development of peripheral organs such as the limbs (using the frog, Rana fusca). Earlier work had suggested that ablation of developing eye tissue had resulted in, among others, defects in limb development. In repeating the earlier experiments, Hamburger found no clear relationship between eye and leg development. However, his experiments did suggest a novel idea: innervation was not necessary for normal limb bud differentiation (though it was necessary for later functional development of the limbs). He established this principle unambiguously later, while working at the Kaiser-Wilhelm Institute for Biology in Berlin-Dahlem.
Later in life Hamburger received many honorary degrees including a doctorate from Washington University in 1976 and a doctorate from Rockefeller University in 1996.
Benjamin WillierAfter Freiburg, Hamburger spent several months working at the Stazione Zoologica in Naples before taking up a postdoctoral position in Göttingen with Alfred Kühn. Kühn assigned Hamburger to one of his many ongoing projects, studying color vision in fish, The project never got very far but the stay in Göttingen did help Hamburger establish a number of contacts among leading German biologists who passed through Kühn’s laboratory.
Moving from Göttingen to the Mangold laboratory at the Kaiser-Wilhelm Institute for Biology in 1926, Hamburger found himself in the center of much new, exciting work, especially in the area of developmental genetics. The embryology department was on the first floor of the institute building, while Richard Gold-schmidt’s genetics department was on the floor above. Hamburger regularly attended the afternoon teas with the genetics group, where he became close friends with Curt Stern, later to become one of the twentieth century’s leading geneticists.
Although Hamburger’s attempt in collaboration with Stern to carry out some breeding experiments with the fruit fly, Drosophila, did not yield any useful results, the relationship between genetics and embryology that this work inspired became a guiding principle for his later work on interspecific crosses among species of salamanders, which involved observing changes in developmental timing (similar to Goldschmidt’s work on interspecific crosses in the gypsy moth, Lymantria). After arriving in the United States, he also studied the developmental genetics of a mutation in chickens known as "creeper" because they have developmental problems of the limbs that produce creeping-like motion.
In 1932 the Rockefeller Foundation invited Spemann to nominate a candidate for a one-year postdoctoral fellowship to the United States. Spemann nominated Hamburger. The main aim was to adapt the methods and techniques of experimental transplantation developed for amphibians in the Freiburg lab to work on chick embryos in Chicago. Hamburger came to the Frank Rattray Lillie lab in the fall of 1932.
The initial problem on which Hamburger focused grew out of conflicting results obtained in 1909 by one of the students (Elizabeth Shorey) using the chick, and a decade later (1919) those of one of the graduate students (Sam Detwiler) at Yale. The question related to the effects of damaging or removing developing chick limb buds on the further development of sensory and motor nerve tracts in the spinal cord. Shorey, using electrocautery, noticed hypoplasia (diminished development) of both motor and sensory nerve columns. By contrast, Detwiler, using limb extirpation and transplantation methods, found that extirpation caused hypoplasia only in sensory nerve columns, and that transplantation of limb buds to other areas of the embryo resulted in hyperplasia primarily of sensory nerve ganglia. Lillie suggested that Hamburger reinvestigate the problem, using the Spemann techniques of microsurgery on the chick, to resolve the discrepancy.
Hamburger learned microsurgical methods for chick embryos from others in the lab, applying the glass needle end hair-loop techniques developed in Freiburg for limb bud extirpation to determine the effects of development of the adjacent nervous system. The results were clear: Shorey’s observation that both sensory and motor neurons responded to extirpation with hypoplasia, was confirmed.
In addition to the actual results, Hamburger was immediately impressed with the use of the chick as a model for investigating vertebrate development. In contrast to amphibians, where motor neurons are not organized into the easily-observed motor columns, in the chick embryo, the motor columns are clearly visible, and thus provide favorable material for analyzing changes in their numbers and size in a way that the amphibian embryo does not allow. From this point onward the chick became Hamburger’s primary model organism.
In the middle of his year in Chicago, the National Socialist government came to power in Germany, and within months had promulgated the "Law for the Restoration of the Professional Civil Service," removing all civil servants (which included university employees) of Jewish descent from their jobs. Hamburger was dismissed from his post at Freiburg. With an extension of the Rockefeller grant Hamburger was able to remain in Chicago until 1935.
Returning briefly to Germany to bring his family to the United States, he began searching for jobs. There were only three prospects: Odessa (USSR), Sao Paulo (Brazil) and Swarthmore College. He had decided that the best opportunities for research lay in the United States, but Swarthmore was a small liberal arts college where he would have a heavy teaching load. Fortuitously, a position opened up in 1935 at Washington University, and Hamburger jumped at the opportunity. At Washington he advanced from assistant professor (1935–1939), associate professor (1939–1941), and full professor (1941–1966), and after retirement in 1966, he was appointed Edward Malinckrodt Distinguished University Professor (1968) taking emeritus status in 1969. He served as department chairman for twenty-six years (1941–1966).
The vast bulk of Hamburger’s research work from 1935 onward focused on three major areas in chick development: the relationship between limb bud extirpation (and reimplantation) and its effects on the outgrowth of motor columns in the spinal cord; developmental genetics of the creeper fowl mutation; and the development of chick behavior, especially during the pre-hatching period.
One of the outcomes of Hamburger’s early extirpation work in Chicago was the accidental discovery (based upon his unconscious removal of different amount of limb bud tissue) that there appeared to be a quantitative relationship between the amount of limb bud tissue removed and the degree of hypoplasia in the lateral motor columns and the related sensory neurons. He also noted that when he transplanted limb bud tissue to other regions of the embryo (flank or belly) that hyperplasia of the motor neurons was enhanced.
In a paper of 1934 Hamburger interpreted this work in the framework of Spemann’s induction theory, by putting forward three major conceptual points: The developing peripheral tissue (in this care limb bud) stimulates (by way of an inducer substance) the growth of neurons toward the developing tissue; The inducer substance is transported by retrograde movement from the growing neuron tip back to the cell body to stimulate further growth; and The effect is quantitative: the greater the quantity of inducing tissue, the greater the rate of neuronal growth (and vice-versa, with removal of limb bud tissue).
Hamburger had sent a copy of his 1934 paper to an eminent colleague, Giuseppe Levi at the University of Turin Medical Faculty, who eventually passed it on to one of his young post-docs, Rita Levi-Montalcini. During the war, working in exile in the Italian countryside, Levi-Montalcini was intrigued with this paper and had repeated Hamburger’s experiments.
Publishing her results, along with those of several other Italian workers after the war, Levi-Montalcini came up with a very different interpretation. She had noted something Hamburger had not: After an initial period of proliferation and growth in the non-extirpated side of the chick spinal cord a certain percentage of cells in the motor ganglia began to degenerate, a process she called neuronal death. This was apparently normal, leading Levi-Montalcini to postulate that the limb bud does not have an inductive capacity, but provides a "maintenance factor" that prevents massive neuronal death.
When Hamburger read Levi-Montalcini’s papers after the war, he was impressed with her work and immediately invited her to St. Louis to work in his lab and try to resolve the discrepancies. With funds provided by the Rockefeller Foundation, Levi-Montalcini came to St. Louis in 1947 for what was intended to be a one-year period. As the work proceeded with exciting results, Hamburger arranged for an extension of the Rockefeller funds, and eventually procured for Levi-Montalcini a faculty position at Washington University that she held for the next thirty years.
In repeating Hamburger’s experiments, Levi-Montalcini pointed out the general feature of neuronal death that Hamburger had missed, confirming the hypothesis that the limb bud produces a maintenance rather than an inducing factor. The obvious next step was to isolate and identify the chemical agent responsible, but that was difficult working with chick limb bud tissue, which exists in very small quantities. As it happened, in 1948 Hamburger received a paper from a former student, Elmer Bueker (then at Georgetown University Medical School), detailing an experiment in which he had transplanted a mouse sarcoma into a developing chick egg. Shortly afterward, he noted that the tumor had been thickly invaded by sensory neurons, suggesting that the tumor produced some sort of neuron-stimulating factor.
With Bueker’s permission, Hamburger and Levi-Montalcini repeated the experiment and observed a clear quantitative relationship between size of sarcoma and neuronal growth rate. Not being biochemically knowledgeable himself, Hamburger hired a young post-doc from the Washington University Medical School, Stanley Cohen, to identify the active fraction from the tumor. Cohen quickly managed to isolate a nucleo-protein fraction that would stimulate neuronal growth significantly, but it was not clear whether the nucleic acid or protein component was the active agent.
Using snake venom as a source of a nucleic-acid digesting enzyme (phosphodiesterase), Cohen showed that the protein fraction had the nerve stimulating property. In fact, the snake venom itself turned out to have a thousandfold greater potency for stimulating neuronal growth than the tumor protein. The system for studying and characterizing the active fraction, which came to be called the nerve growth factor (NGF), was enhanced further by using male mouse salivary glands as a source (which are far easier to obtain than snake venom). Using their system Cohen eventually fully characterized the protein making up NGF. As the work progressed, Hamburger stepped back from the day-to-day activity, leaving the project in the hands of Levi-Montalcini and Cohen.
In the 1940s and 1950s, while most classically trained embryologists at best paid lip service to the genetics of development, Hamburger’s work with the creeper mutant provided one model for how the problem could be approached. The creeper mutant was of interest because in the heterozygous state, the legs are greatly foreshortened due to retardation of growth during embryogenesis, whereas in the homozygous state the eye buds develop a peculiar abnormality known as coloboma (homozygous embryos usually die around the 72-hour stage). Because a single gene appeared to affect these two very different traits, Hamburger realized the creeper system could be used to dissect apart the ways in genes affect developmental pathways. When he transplanted proto limb- and eye-bud tissue from the creeper (heterozygous) strain to the flank of an embryo of a normal strain, the transplant developed the mutant phenotype, as expected. But when he transplanted an eye primordium from a homozygous strain to the eye region of a normal embryo, a perfectly normal eye developed.
Hamburger’s analysis suggested that the effect of the creeper mutation on limb and eye growth must be qualitatively different. The effect on limb growth was direct, that is, the gene must control some process such as division rate of cells making up the limb tissue, thus affecting (in this case retarding) growth. However, the effect of the creeper gene on eye development must be indirect, altering a secondary process such as development of vasculature of the eye region, rather than a defect in the genetic information for the eye itself. The outcome of this work suggested that experimental embryology could contribute in at least a small way to an understanding of the ways in which genes function in development.
In the late 1950s and 1960s, at a time when many of his colleagues were thinking about retiring, Hamburger took up a whole new line of experimental work on the neurobiological origin of behavior. Two embryologically-based concepts guided this research: Behavior has an internally guided ontogenesis in the same way as physical organs and systems; and The ontogenesis of behavior and of the structural development of the nervous system are inseparable processes. Recognizing that much of embryogenesis is guided by internal factors, Hamburger decided to investigate the early origin of some simple chick behaviors. The behaviorist view would require, among other things, that the sensory and motor systems in the embryo would develop simultaneously; it would also see embryonic behaviors as coordinated with sensory input and thus nonrandom. Hamburger’s approach was to determine how neuronal development correlated with the development of observable behavior in the chick.
Investigating the timing of development, Hamburger noted that the chick motor system began to develop before the sensory system, starting at the anterior and proceeding to the posterior region of the spinal chord. Motor neuron development also coincided with the appearance, starting at about 3.5 days, of numerous movements of the head and beak and moving progressively to the wings and hind limbs. Hamburger and his students analyzed these movements, cataloguing their frequency, duration, and degree of complexity. The movements were found to be random and uncoordinated (one leg or wing would move, the other not) and cycling through periods of activity and quiescence. As embryogenesis progressed, the frequency and complexity of movements increased, while the periods of quiescence decreased.
The next step was to test the hypothesis of spontaneous (non-stimulus-based) movement by removing sections of the afferent (sensory) system leading from a developing limb (they chose the right leg), and nerve tracts from the brain in 2–2.5 day-old embryos. From the initiation of the experiment until around the tenth day, the activity of the leg was identical in the experimental and control (in which afferent nerves had not been removed) groups. To check these observations, Hamburger and several post-docs monitored the electrophysiological discharge of spinal cord motor neurons, finding their activity coincided in frequency and duration with observed spontaneous motility. These findings showed clearly that motor activity precedes any sensory input, refuting the orthodox behaviorist explanation.
One of Hamburger’s most important contributions to the field of embryology was to devise, with Howard Hamilton, a standardized stage series for chick development. A major problem for development of any organism is to have a well-grounded reference system for the stages through which the embryo passes, so that comparisons between experiments can be made at comparable points in the developmental process. The only existing stage series for the chick was a rather loose one drawn up in F. R. Lillie’s 1919 Development of the Chick.
Lillie’s series was based on chronology (hours of incubation), a criterion that can be misleading because incubators do not necessarily operate at the same temperature or maintain the same humidity levels, factors that affect growth rate. Hamburger and Hamilton decided early on that what would be most useful would be a stage series based on visible anatomical characteristics. They agreed further that the stages should be chosen on the basis of clear identifiability in external structures, successive stages should be spaced as closely together as possible, and wherever feasible, quantitative measurements such a beak or toe length should be used.
Serving as Zoology Department chairman at Washington University for twenty-five years, he acquired an outstanding group of faculty. Always a dedicated teacher, he taught at least one course every semester even while serving as department chairman. Two of those courses deserve special mention. One was a year-long, integrated course he developed and co-taught for many years on comparative anatomy and development, accompanied by two two-hour lab sessions per week. The other was a laboratory course in experimental embryology, in which students repeated many of the classic experiments; for this course Hamburger prepared his widely used Manual of Experimental Embryology, which went through two editions.
Another of Hamburger’s most important educational influences came through his association with the embryology course at the Marine Biological Laboratory in Woods Hole, first as instructor (1936–1941) and then as director of the course (1942–1947). When he took over as director, he converted what had been a traditional, descriptive course into an experimentally-based one, engendering considerable excitement on the part of students. Through this association Hamburger influenced a whole generation of developmental biologists to take up experimental work.
It was also through his association with other embryologists at Woods Hole that Hamburger and two other colleagues, Benjamin Willier (Johns Hopkins) and Paul Weiss (University of Chicago) developed the idea of a comprehensive review of the state of developmental biology in the mid-1950s, The Analysis of Development (Willier, Weiss, and Hamburger, 1955). Articles were written by specialists on particular processes (game-togenesis, early cleavage, nuclear-cytoplasmic interactions) and on the development of particular animal groups (Hamburger and Holtfreter, for example, wrote the comprehensive chapter on amphibian development).
After he closed his laboratory in the mid-1980s, Hamburger devoted his still prodigious energies to historical studies, including the monograph The Heritage of Experimental Embryology (Hamburger, 1988) and numerous articles, the last, in his ninety-ninth year, an introduction to and translation of a portion of Spemann’s autobiography, focusing on his supposed vitalistic tendencies.
Viktor Hamburger was known as one of the most influential neuroembryologists of the twentieth century. In collaboration with Rita Levi-Montalcini he discovered nerve growth factor. In 1951 Viktor and Howard Hamilton developed a standardized stage series to describe chicken embryo development. Now it is called the Hamburger-Hamilton stages.
Viktor's work The Analysis of Development, written in co-authorship with Benjamin Willier and Paul Weiss became the most influential compendium of experimental embryology of the mid-twentieth century.
Hamburger was inducted into the National Academy of Sciences in 1953. In addition, he was awarded a number of prizes in recognition of his work on neuroembryology: The F. O. Schmitt Medal in Neuroscience, The Ross G. Harrison Prize in Developmental Biology, the Louisa Gross Horwitz Prize in Cell Biology and Developmental Neurobiology, the Ralph Gerard Prize and Medal of the Society for Neuroscience, the Fidia-Georgetown Award in Neuroscience, the National Medal of Science, the Karl Spencer Lashley Award of the American Philosophical Society and the first Lifetime Achievement Award from the Society of Developmental Biology.
(Here is a critical account of the experimental work of Ge...)
1988Hamburger shared with his mentor Spemann and many of his generation an appreciation of biological phenomena in general, and embryology in particular, as dynamic, interconnected, and holistic processes, not reducible simply to chemical and molecular reactions. Unlike Spemann, who had no abiding interest in biochemistry or genetics, Hamburger understood that both were important as complementary ways of understanding the dynamics of development, in particular cellular differentiation.
In contrast to the more reductionist philosophy, however, for Hamburger the chemical and molecular basis of ontogenetic changes was the starting point, not the ending point, of investigation. It was necessary to know, but not sufficient to explain development as an interactive and integrated process. He understood clearly that development was not simply a series of mechanical or chemical process, but occurred at a number of organizational levels, from the molecule to the cell, tissue and organ-system.
Hamburger adhered to what might be called (he did not use the term himself) a holistic materialist philosophy. He had no patience with vague or vitalistic ideas, or mystical, immaterial directive forces like the "entelechy" put forward by older biologists such as Hans Driesch. His holistic view was non-mystical and practical. It respected the wholeness, that is, the integrity of the embryo.
Quotations:
"Our real teacher has been and still is the embryo, who is, incidentally, the only teacher who is always right."
"I promised the embryo that if it would reveal to me some of its secrets I would never homogenize it in a Waring blender. I think we have both kept our promises."
Viktor Hamburger was a member of many learned societies and institutions, including the American Society of Zoologists, American Association for the Advancement of Science, the American Society of Naturalists, the Society for Developmental Biology, and the International Society for Cell Biology and for Developmental Biologists. He was elected to the National Academy of Sciences in 1953, and the American Academy of Arts and Sciences. Viktor was an honorary member of Sigma Xi and Phi Beta Kappa.
In his scientific and personal life, Hamburger was known for his quiet, almost self-effacing manner, his incisive views and his dry wit. He worked intensively and with great concentration.
In 1928 Hamburger married Martha Fricke, a young biologist whom he had met in Göttingen. They had two daughters, Doris Sloan and Carola Marte.
