Viktor Hamburger, widely regarded as the preeminent embryologist and developmental neuroscientist of his era, died on June 12th after a brief illness suffered a few weeks before his 101st birthday.

Viktor was raised in a well-to-do family in the small town of Landeshut in the Prussian province of Silesia, now a part of Poland. The natural beauty of the area engaged him at an early age and, although he considered geology, led him to choose a career in biology. He matriculated at the University of Heidelberg in 1919, primarily because his parents thought his Aunt Clara Hamburger, a zoologist there, might keep an eye on him. Captivated by a visit to Freiburg (and perhaps the prospect of diminished oversight from his aunt), he soon transferred to the university there where he finished his degree and began graduate work in the laboratory of Hans Spemann. Spemann, who would later win a Nobel Prize for his experiments with Hilde Mangold on the embryonic 'organizer,' was the acknowledged leader of German embryology in the 1920s, and promptly inspired his student to study development with the ingenious microsurgical methods that were Spemann's technical trademark. Viktor obtained his Ph.D. degree summa cum laude in 1925 for a thesis on the effects of nerves in developing frog larvae; although the work was not especially notable, it began his lifelong interest in neural development. After postdoctoral work at Goettingen (where he met his future wife, Martha Fricke), and then at the Kaiser Wilhelm Institute in Berlin, he returned to Freiburg when Spemann offered him an instructorship in 1928.

In 1932, Viktor won a Rockefeller fellowship to study for a year at the University of Chicago with Frank Lillie, a friend of Spemann's and a major figure in American embryology. In contrast to Spemann, Lillie worked on the developing chick, the experimental preparation that Viktor subsequently exploited in his own laboratory for nearly 50 years. While in Chicago, he received a letter from Martin Heidegger (the existentialist philosopher), then Chancellor at Freiburg, discharging him from the faculty there because of his Jewish ancestry. The Rockefeller Foundation had established an emergency fund for German scholars displaced by the rise of the Nazis, which allowed Viktor to emigrate permanently to the United States.

In 1935, he was offered an assistant professorship in the Department of Zoology at Washington University, where he remained for the rest of his career. As Viktor liked to note, he was a 'sessile organism.' (The comment was typically made in the process of decrying the international motility of younger colleagues.) His penchant for staying put was interrupted only during the summers, when from 1936 to 1946 he taught in and then directed the embryology course at the Marine Biological laboratory in Woods Hole, or in later years when he traveled to Europe for social rather than scientific reasons.

The work that Viktor produced during the 70 years that he was active in the laboratory was of great importance. (Although he officially became the Mallinkrodt Distinguished Professor emeritus in 1969, Viktor continued training students and publishing key papers well into his 80s.) His major contributions were in the field of normally occurring cell death during the development of the vertebrate nervous system. Working in the chick embryo with the microsurgical techniques he had learned from Spemann, Viktor demonstrated in a series of experiments that most primary motor and sensory neurons die during the development of the spinal cord and its associated ganglia, a highly counterintuitive observation that has now been confirmed in many parts of the nervous system in virtually all vertebrates that have been examined. Just as importantly, he showed that neurons depend on their peripheral targets to thrive and grow, and that neuronal survival is based on competition. This work led in turn to the postulation of a target-derived signal that mediates these phenomena.

In 1947, Hamburger invited Rita Levi-Montalcini, then working with the anatomist Guiseppe Levi in Turin, to join him in St. Louis. Levi-Montalcini had been studying some of the same issues, but had obtained different results. Typically, Viktor suggested a collaboration, which seemed the most straightforward way to resolve their disagreement. Working together proved enormously fruitful, leading Levi-Montalcini to continue at Washington University for nearly 30 years, and to their joint discovery (with the biochemist Stanley Cohen) of the protein they eventually named 'nerve growth factor.'

The importance of this molecular signal in the trajectory of developmental neuroscience in the latter half of the twentieth century can hardly be overestimated. Work on nerve growth factor over the 30 years following the seminal papers announcing its discovery in the early to mid-1950s stimulated a series of observations documenting what the protein did, its natural sources and its mechanism of action. Most of these studies were carried out by Levi-Montalcini and her colleagues; Viktor retreated from further work on nerve growth factor in about 1955, primarily because of his distaste for the protracted biochemical labor that he imagined would be required to isolate and fully identify the active agent (a task that was not fully accomplished for another 35 years).

This body of closely integrated work that began with studies on cell death in the 1930s established a new field of trophic interactions and the underlying molecular biology of these processes, one of the central themes in contemporary neuroscience. Nerve growth factor and the other members of a family of more recently identified molecules called neurotrophins not only support the early survival of the relevant nerve cells, but continue throughout life to modulate neuronal connectivity. These concepts have long since become part of the neurobiological canon. The lifelong trophic interplay between neurons and targets, for which nerve growth factor and its actions remain the paradigm, is the foundation of ongoing work in literally hundreds of laboratories exploring issues that range from neural development and plasticity to the pathophysiology of neurodegenerative diseases.

After a period in the 1960s and 70s during which Viktor studied the early motor behavior of the chick embryo (another important, if less noted, field that he was proud to have initiated), he came back to work further on nerve growth factor, demonstrating additional aspects of its influence in the developing chick embryo. Only in his mid-80s did he stop going to his lab on a daily basis, working instead from his modest but elegant home near the university, documenting his firsthand information about a time and place in embryology that he felt would otherwise be forgotten. His memoir of Spemann's contributions, published in 1988, is a prime example of this effort1. In this last chapter in his scientific life, Viktor served, quite consciously, to strengthen the intellectual links between the nineteenth and early twentieth century work of Wilhelm Roux, Spemann, Otto Mangold, Johannes Holtfreter and others, and modern developmental biology and developmental neuroscience.

For these remarkable achievements, Viktor was widely honored. He won early election to the National Academy of Sciences, was awarded the National Medal of Science in 1989, and received numerous other accolades and honorary degrees. The one award that escaped him, however, was the Nobel Prize given in 1986 for the discovery of nerve growth factor to Levi-Montalcini and Cohen. Although there was unanimous agreement that Levi-Montalcini and Cohen were eminently deserving of the award, knowledgeable people in the field were taken aback that the Nobel committee had not recognized Hamburger as the co-discoverer of this agent and the intellectual force behind the avenue of work that led to its discovery. (See ref. 2 for a detailed account.)

In addition to his gift for science and the good fortune to be able to exercise this passion for the better part of 70 years, Viktor was blessed with a social instinct that made him, over his long life, the treasured friend of an extraordinary number of people. These friendships, which he cultivated with the same care that he devoted to science, included not just colleagues but individuals in the arts (he was an astute collector), in literature (he read widely and wrote beautifully), and among that sometimes reviled cadre of academics, university administrators. As head of his department for more than two decades, Viktor became close friends with a series of deans, provosts and chancellors who valued his key role in the rise of Washington University from a largely local campus to a leading liberal arts institution.

Viktor Hamburger was a giant not only in his accomplishments as a scientist, but as a human being. His keen intellect, his unflagging integrity and his openness to people and ideas profoundly influenced several generations of colleagues and friends to a degree that is rare in the academy, rare in science, and indeed rare in any human enterprise.