In his 1907 paper, "Experiments in Transplanting Limbs and Their Bearing Upon the Problems of the Development of Nerves," in the Journal of Experimental Zoology that he edited, Ross Granville Harrison tested the development of nerves in transplanted tissue. He studied neural development by examining two competing theories. Victor Hensen proposed a syncytial theory as a way to explain neural development, suggesting that all the nerves of an embryo were connected directly by cytoplasm laid down early in development, and leaving no room for later modification. Santiago Ramón y Cajal proposed a competing outgrowth theory that nerves develop from the central nervous system, pushing through tissues by growing nerve fibers and growth cones. Harrison's experiment refuted many of the claims of the syncytial theory although it did not produce evidence that could directly prove the outgrowth theory.
Conrad Hal Waddington's Organisers and Genes, published in 1940, is a summary of available research and theoretical framework for many concepts related to tissue differentiation in the developing embryo. The book is composed of two main conceptual sections. The first section explores the action and nature of the organizer, while the second section delves into genes and their influence on development.
Conrad Hal Waddington was an embryologist and theoretical biologist. His early experimental work investigated aspects of embryonic induction and the properties of the organizer first identified by Hans Spemann and Hilde Mangold, while his later studies focused on genetic assimilation. Waddington is probably best known for developing the concept of the epigenetic landscape, and he also held significant interest in many different areas ranging from the visual arts and poetry to philosophy. Throughout his career, Waddington maintained that the arts were integral to science, and he continued to draw inspiration from the arts for his own work.
"A Diffusible Agent of Mouse Sarcoma, Producing Hyperplasia of Sympathetic Ganglia and Hyperneurotization of Viscera in the Chick Embryo," by Rita Levi-Montalcini and Viktor Hamburger, appeared in 1953 in the Journal of Experimental Zoology. The paper provided the first evidence that nerve growth factor is a diffusible substance. Nerve growth promoting tumors were implanted into developing embryos to determine whether the tumors stimulated growth by direct contact or by a diffusible substance. The tumors were implanted into different parts of the embryo; one set of experiments implanted the tumor directly in the embryo, while another set of experiments placed the tumor on an exterior membrane. The membrane provided a barrier to direct contact with the nervous system, and allowed some chemical interaction between the tumor and the embryo. The tumor stimulated growth in both orientations, demonstrating that nerve growth factor was a chemical agent. The paper ends with two possible conclusions for the mechanism of nerve growth, the tumor may have been directly stimulating the ganglia by a diffusible signal, or it may have reduced the resistance of the chick tissues to the nerve growth. The term "nerve growth factor" is not explicitly used in this paper, and is referred to as a "diffusible agent" or a "growth promoting agent."
Alexis Carrel was a doctor and researcher who studied tissue cultures. He continued Ross Granville Harrison's research and produced many improvements in the field of tissue culture and surgery. He was the recipient of the 1912 Nobel Prize in Physiology or Medicine for his development of surgical techniques to repair blood vessels. Carrel was born on 28 June 1873 in Sainte-Foy-les-Lyon, France, to Anne-Marie Ricard and Alexis Carrel Billiard. His father died when he was five years old. Carrel earned a bachelor's degree in letters in 1889 and another in science in 1890 from St. Joseph's Day School in Lyon, France. He entered medical school at the age of seventeen and was regarded as a good but not exceptional student. The assassination of Sadi Carnot, a French politician visiting Lyon who was stabbed in the abdomen and died from the loss of blood, further interested him in surgery.
Johannes Holtfreter made important discoveries about the properties of the organizer discovered by Hans Spemann. Although he spent much time away from the lab over many years, he was a productive researcher. His colleagues noted that the time he spent away helped revitalize his ideas. He is credited with the development of a balanced salt medium to allow embryos to develop; the discovery that dead organizer tissue retains inductive abilities; and the development of specification, competence, and distribution of fate maps in the developing frog embryo. He was the sole author on all but three of the more than sixty papers he published. Johannes Holtfreter was born on 9 January 1901 in Richtenberg, Germany. He was the middle of three children, the only boy, and grew up collecting and drawing butterflies and other animals in the surrounding area. When World War I began, his family moved to Strausland, Germany, to avoid the war.
Beatrice Mintz is a brilliant researcher who has developed techniques essential for many aspects of research on mouse development. She produced the first successful mouse chimeras and meticulously characterized their traits. She has worked with various cancers and produced viable mice from the cells of a teratoma. Mintz participated in the development of transgenic mice by the incorporation of foreign DNA into a mouse genome. Her techniques have been widely applied to other studies of mouse development and are so common that many of the publications that utilize her techniques no longer remember to cite the source.
In "The Outgrowth of the Nerve Fiber as a Mode of Protoplasmic Movement," Ross Granville Harrison explores the growth of nerve fibers in vitro. The purpose of this experiment was to test two possible hypotheses for the growth of nerve fibers. Santiago Ramón y Cajal suggested that nerve growth is due to the extension of nerve fibers as they push through tissue. Victor Hensen's syncytial theory proposed an opposing view of nerve growth. He proposed that each neuron was connected by threads of cytoplasm and the successful connections stimulated further differentiation of the correct neural connections. Using hanging drop tissue cultures, Harrison provided significant evidence for Ramón y Cajal's theory by showing discrete cell membranes between cells and observing the growth of individual neurons.
Joseph Needham was an embryologist and biochemist who is most noted in science for his studies on induction in developing embryos. Needham worked with Conrad Hal Waddington to attempt to identify the compound responsible for the organizer's activity. Although he was not successful in discovering the chemical, he and Waddington learned much about the organizer. Needham was a meticulous writer, writing reviews and books about contemporary research. In later years, Needham traveled to a newly opened China and studied their history, writing a number of books on Chinese culture, science, and history. Born Noel Joseph Terrence Montgomery Needham on 9 December 1900 in London, his parents were Alicia Adelade Montgomery and Joseph Needham. His parents' relationship ended poorly while he was a child and he was often forced to mediate between them, a skill he utilized in later years. He pursued science and philosophy, subjects that also interested his father.
Robert William Briggs was a prolific developmental biologist. However, he is most identified with the first successful cloning of a frog by nuclear transplantation. His later studies focused on the problem of how genes influence development.