The paper "Formation of Genetically Mosaic Mouse Embryos and Early Development of Lethal (t12/t12)-Normal Mosaics," by Beatrice Mintz, describes a technique to fuse two mouse embryos into a single embryo. This work was published in the Journal of Experimental Zoology in 1964. When two embryos are correctly joined before the 32-cell stage, the embryo will develop normally and exhibit a mosaic pattern of cells as an adult. Mosaics were easily characterized by mouse fusions from embryos of different colors; this produced clearly visible color patterns identifying the alternate cell types. Mintz referred to the fused mice as mosaic or later as allophenic, but they are more commonly known today as chimeras.
James Edgar Till is a biophysicist known for establishing the existence of stem cells along with Ernest McCulloch in 1963. Stem cells are undifferentiated cells that can shift, or differentiate, into specialized types of cells and serve as a repair system in the body by dividing indefinitely to replenish other cells. Till’s work with stem cells in bone marrow, which produces the body’s blood cells, helped form the field of modern hematology, a medical discipline that focuses on diseases related to the blood. He also worked on issues in the medical field including patient inclusion in clinical trials, matters of effective and ineffective clinical communication, and limitations of public access to medical and scientific research. Till’s work with stem cells furthered scientists’ understanding of abnormal blood cell development, which helped set the foundation for regenerative medicine.
Wilhelm Roux was an influential figure in the early history of experimental embryology. Although he originally studied medicine, he was invited to be a Privatdozentur, or unsalaried lecturer, at the Anatomical Institute in Breslau (Wroclaw), Poland, in 1879. He spent the next ten years at this institute, working his way from Dozent to associate professor and finally, in 1889, to director for his own institute, Institut für Entwicklungsgeschichte, or Institute for Developmental History and Mechanics. It was here that he performed what is perhaps his most famous series of experiments on green frog eggs in 1888 and published in Virchows Archiv, which he titled "Beiträge zur Entwicklungsmechanik des Embryo. Über die künstliche Hervorbringung halber Embryonen durch Zerstörung einer der beiden ersten Furchungskugeln, sowie über die Nachentwickelung (Postgeneration) der fehlenden Körperhälfte."
"In vitro Experiments on the Effects of Mouse Sarcomas 180 and 37 on the Spinal and Sympathetic Ganglia of the Chick Embryo" were experiments conducted by Rita Levi-Montalcini in conjunction with Viktor Hamburger and Hertha Meyer and published in Cancer Research in 1954. In this series of experiments, conducted at the University of Brazil, Levi-Montalcini demonstrated increased nerve growth by introducing specific tumors (sarcomas) to chick ganglia. Ganglia are clusters of nerve cells, from which nerve fibers emerge. This work led to the discovery of nerve growth factor (NGF) and later the Nobel Prize in Physiology or Medicine in 1986.
In "Selective Growth Stimulating Effects of Mouse Sarcoma on the Sensory and Sympathetic Nervous System of the Chick Embryo," Rita Levi-Montalcini and Viktor Hamburger explored the effects of two nerve growth stimulating tumors; mouse sarcomas 180 and 37. This experiment led to the discovery that nerve growth factor was a diffusible chemical and later to discoveries that the compound was a protein. Although this paper was an important step in the discovery of nerve growth factor, the term "nerve growth factor" was not used in this paper. It was instead referred to as a "growth promoting agent." The discovery of nerve growth factor earned Levi-Montalcini and Stanley Cohen, who also discovered epidermal growth factor, the 1986 Nobel Prize in Physiology or Medicine.
In 1980 Janet Rossant and William I. Frels published their paper, "Interspecific Chimeras in Mammals: Successful Production of Live Chimeras Between Mus musculus and Mus caroli," in Science. Their experiment involved the first successful creation of interspecific mammalian chimeras. Mammalian chimeras are valuable for studying early embryonic development. However, in earlier studies, clonal analysis was restricted by the lack of a cell marker, present at all times, that makes a distinction between the two parental cell types in situ. To battle this limitation, Rossant and Frels decided to make chimeras from embryos of two different species in order to have sufficient genetic differences so that, in any tissue type, the two cell types could be clearly identified. In their paper Rossant and Frels describe the successful creation of live chimeras between Mus musculus and Mus caroli. These two species of mice are more closely related than chimeras produced previously. The chimeras created in the experiment showed no sign of selection against one cell type or the other. Therefore, they are valuable for clonal analysis of development. Rossant and Frels were the first to successfully produce an interspecific mammalian chimera that experienced normal development.
The developmental stages of the chick embryo were examined by Viktor Hamburger and Howard L. Hamilton in "A Series of Normal Stages in the Development of the Chick Embryo," published in the Journal of Morphology in 1951. These stages were published to standardize the development of the chick based on varying laboratory conditions and genetic differences. The stages Hamburger and Hamilton assigned were determined by the visible features of the chick embryo. The first stage begins just prior to the primitive streak, with the formation of the embryonic shield, and the final stage, forty-six, ends at the hatching of the chick.
In "Versuche zur Analyse der Induktionsmittel in der Embryonalentwicklung," published in Naturwissenschaften in 1932, Hermann Bautzmann, Johannes Holtfreter, Otto Mangold, and Hans Spemann jointly reported on experiments each had conducted testing the activity of organizers killed by boiling, freezing, alcohol, and drying. Each of the authors had been independently conducting similar experiments, when Holtfreter made a breakthrough allowing him to produce many more successful transplantations. When he told Spemann the news, Spemann suggested that he tell Bautzmann, who had been working extensively on the question. Spemann then coordinated the joint paper to avoid a conflict among the researchers.
In this paper Viktor Hamburger and Rita Levi-Montalcini collaborated to examine the effects of limb transplantation and explantation on neural development. In 1947 Hamburger invited Levi-Montalcini to his lab at Washington University in St. Louis to examine this question. Independently, each had previously arrived at opposing conclusions based on the same data. Hamburger concluded that limb transplantations caused the ganglia to develop more connections and grow larger while Levi-Montalcini concluded that the ganglia first produce a large amount of neurons, then degenerate the unsuccessful neurons. She concluded that larger ganglia must be due to the increase in successful connections. This joint paper, published in the Journal of Experimental Zoology in 1949, corroborated the findings reported by Levi-Montalcini and established that nerve degeneration is an integral part of development.
Stanley Cohen published "Purification of a Nerve-Growth Promoting Protein from the Mouse Salivary Gland and its Neuro-Cytoxic Antiserum" in the Proceedings of the National Academies of Sciences in 1960. This paper outlined the successful purification and identification of nerve growth factor (NGF) as a protein, the developmental effects of depriving an embryo of NGF, and the discovery that NGF is also required for the maintenance of the nervous system.