Embryo Project Encyclopedia Articles

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.

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.

"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."

Josef Warkany studied the environmental causes of birth defects in the United States in the twentieth century. Warkany was one of the first researchers to show that factors in the environment could cause birth defects, and he helped to develop guidelines for the field of teratology, the study of birth defects. Prior to Warkany’s work, scientists struggled to explain if or how environmental agents could cause birth defects. Warkany demonstrated that a deficiency or excess of vitamin A in maternal nutrition could cause birth defects. He also established that mercury in teething powders increased infant mortality rates. Warkany showed how substances outside the human body could adversely affect conception, growth, and development of the human fetus in utero.

In its 1993 decision Daubert v. Merrell Dow Pharmaceuticals, Inc., the US Supreme Court established the Daubert Standard for evaluating the admissibility of scientific knowledge as evidence in US federal courts. When it began in trial court, the case addressed whether or not Bendectin, an anti-nausea medication taken during pregnancy, caused birth defects. However, after the trial court dismissed the case for lack of admissible evidence, Daubert v. Merrell Dow Pharmaceuticals, Inc. advanced through appeals courts to the US Supreme Court, where the Justices defined the criteria by which scientific knowledge, which for them included a least theories based on evidence, expert testimony from scientists, and scientific techniques, could be introduced and used in court cases as evidence. The Daubert Standard states that the judge of a case is responsible for determining what claims are admissible as scientific knowledge and as evidence in the case. The admissibility should be determined by the falsifiability of the claims, by whether or not they had passed peer reviewed, by the general scientific acceptance of the claims, and for techniques, by their error rates of the techniques. Daubert v. Merrell Dow Pharmaceuticals, Inc. set a landmark precedent in the US judicial system and influenced most subsequent legal cases that appealed to science to establish facts in trials.

Isidore Geoffroy Saint-Hilaire studied anatomy and congenital abnormalities in humans and other animals in nineteenth century France. Under the tutelage of his father, Etienne Geoffroy Saint-Hilaire, Isidore compiled and built on his father's studies of individuals with developmental malformations, then called monstrosities. In 1832, Isidore published Histoire generale et particuliere des anomalies de l'organisation chez l'homme et les animaux (General and Particular History of Structural Monstrosities in Man and Animals), in which he defined the term teratology as the study of birth defects and deformities. Isidore Geoffroy Saint-Hilaire established teratology as a legitimate branch of scientific study.

Truman William Brophy developed a cleft palate surgical repair, later called the Brophy Operation, in the late nineteenth century US. The procedure improved facial aesthetics and speech in cleft palate patients. A cleft palate occurs during development when the palatal bones in the roof of the mouth don't completely fuse, leaving an opening, or cleft, in the upper lip and mouth. Brophy's cleft repair used compression inside and outside of the mouth to push the palatal bones into normal alignment shortly after birth. Brophy advocated surgery on newborns with cleft palates as soon as possible after birth, which met with opposition in the late nineteenth and early twentieth centuries when medical professionals did not operate on infants for non-life threatening conditions. However, Brophy's successful operations convinced many doctors to adopt his technique.

In 1980, Ernesto Ippolito and Ignacio Ponseti published their results on a histological study they performed on congenital club foot in human fetuses. The researchers examined the feet of four aborted fetuses and compared the skeletal tissues from healthy feet to those affected by congenital club foot. Infants born with club foot are born with one or both feet rigidly twisted inwards and upwards, making typical movement painful and challenging. Ippolito and Ponseti studied how the connective tissues, such as the ligaments and tendons stretching across the foot and ankle, function to pull the affected foot out of place as the fetus develops. Their findings helped researchers determine club foot’s potential causes and possible treatments by focusing on connective tissues.

Virginia Apgar worked as an obstetrical anesthesiologist, administering drugs that reduce women’s pain during childbirth, in the US in the mid-twentieth century. In 1953, Apgar created a scoring system using five easily assessable measurements, including heart rate and breathing rate, to evaluate whether or not infants would benefit from medical attention immediately after birth. Apgar’s system showed that infants who were previously set aside as too sick to survive, despite low Apgar scores, could recover with immediate medical attention. Additionally, Apgar researched the effects of anesthesia used during childbirth and advocated for the prevention and management of birth defects. Apgar’s work led to a decrease in infant mortality rates in the mid-twentieth century, and into the twenty-first century, hospitals around the world still used the Apgar score at one and five minutes after birth.