The rise of experimental neuroembryology a personal reassessment

Abstract

Tbe Germans have a penchant for condensing their collective wisdom in proverbs: “All is well that ends well”, “Pride comes before a fall”, and “that which wants to become a hook bends early”. At age 14 I was exploring the countryside around the small German town in which I grew up. I collected plants, animals, fossils and brought home salamander and frog eggs and watched them develop and metamorphose. There was never any doubt in my mind that I would become a naturalist. Years later, I made the conscious choice to study Zoology. I felt that the Natural Sciences brought me closer to their subject matter than the Cultural Sciences, as the Humanities were then called. Animals and plants could be ordered in a rational taxonomic system, and frog embryos displayed a reassuring regularity. There was hope to understand some of the rules that govern these phenomena. Surely, others would find history more dramatic. No doubt, the lives of Caesar, Napoleon or George Washington could be more fascinating than those of my tadpoles. But to unravel the mysteries of their genius seemed to me beyond my ken. I discovered my calling at age 19, in a graduate seminar at the Zoological Institute in Heidelberg. Its Director, the distinguished experimental embryologist Curt Herbst, admitted me, a second-year student, probably on the recommendation of an older friend. At any rate, this was a refreshing sign of informality that prevailed then at German Universities. We read and discussed some publications of Wilhelm Roux, who was the founder of Experimental Embry&ogy. Despite his long-winded and somewhat pompous style I detected my “elective pity” to his causal analytical way of thinking and I looked forward to experimenting on living embryos. When I moved to Freiburg, at the foot of the Black Forest, hiking and skiing were much on my mind, but I had also found out that the Director of the Zoological Institute, Hans Spemann was a distinguished experimental embryologist. He had discovered embryonic induction, in the case of lens induction by the optic vesicle, and he had designed a method of transplantation on early amphibian embryos in the pursuit of problems of dete~ination of organ primordia. Two fellow students arrived in Freiburg at the same time, in 1920: Johannes Holtfreter, who became Spemann’s most innovative student and my lifelong friend, and Hilde Proescholdt, who later became Mrs Mangold. She was fortunate in having the organizer experiment assigned to her as her Ph.D. thesis. The organizer experiment consisted of the transplantation of the so-called dorsal lip of the blastopore of the gastrula (an early stage of the amphibian embryo) to the flank of another gastrula, where it induced a secondary neural plate (the precursor of the nervous system) and eventually the formation of an entire secondary embryo. I think the designation “organizer” for the tiny piece of embryonic tissues that accomplishes this feat is entirely justified. Some detractors of Spemann have implied that this term has vitalistic implications. This is not the case. The formation of the secondary embryo can be fully understood in terms of the then well-established mechanisms, such as assimilative and contact inductions, self differentiation and so forth. I still remember the great excitement in the laboratory when Hilde Proescholdt showed us late in the spring of 1921 her first success, a well-formed induced secondary embryo. And we were deeply saddened when she died in an accident in 1924, shortly after the publication of the famous organizer paper by her and Spemann, 33 that earned Spemann the Nobel Prize in 1935. Spemann’s approach to the causal analysis of development has influenced me profoundly. His emphasis was first and foremost on ~ndamental problems of a general nature. The specific experiment served the solution of a general problem. When he had discovered embryonic induction by