Embryo Project Encyclopedia Articles

In 1861, William John Little published, “On The Influence of Abnormal Parturition, Difficult Labors, Premature Birth, and Asphyxia Neonatorum, on the Mental and Physical Condition of the Child, Especially in Relation to Deformities,” hereafter “Abnormal Parturition,” in the Transactions of the Obstetrical Society of London. In the article, Little discussed the causes and types of what he refers to as abnormal births, and theorized how those births affect an infant’s likelihood of exhibiting a deformity. Little defined abnormal births as those involving an atypical maternal or fetal presentation, such as a slow birthing process or a fetus exiting the birth canal feet first rather than head first. In his article, Little published one of the first definitional frameworks to describe a condition causing rigidity and stiffness in the limbs that is often associated with birth-related trauma, which was then called Little’s disease, but is modernly known as spastic Cerebral Palsy.

The March of Dimes Foundation, or the March of Dimes, is a non-profit organization headquartered in Arlington, Virginia, focused on the health of pregnant women and infants in the US. Former United States president Franklin Delano Roosevelt founded the March of Dimes, then called the National Foundation for Infantile Paralysis, in 1938 to address polio. Polio is a viral illness that infects the spinal cord and may lead to paralysis. Roosevelt contracted polio in 1921, which left him permanently paralyzed from the waist down. During the 1960s, after scientists introduced polio vaccines, March of Dimes shifted its focus to prevent preterm birth and birth defects. As a non-profit organization, March of Dimes provides community service, funds for research, and efforts to educate the public about preterm birth and birth defects. While March of Dimes’ original goal was to help reduce the spread of polio in the US, it was also one of the first organizations to lead a campaign to prevent birth defects and infant mortality.

William John Little was one of the first orthopedic surgeons to research congenital malformations and their causes in the nineteenth century and presented preliminary research on a condition modernly known as cerebral palsy, a condition of varying severity that affects a person’s ability to move. Little worked throughout the United Kingdom for the majority of the time he practiced medicine, and eventually founded one of the first orthopedic infirmaries, the Royal Orthopedic Hospital in London, England. Throughout his career, Little studied congenital malformations, which are medical conditions inherited before birth, as well as how certain medical circumstances during delivery affect the neonate. In 1861, he described a condition with motor, behavioral, and cognitive irregularities in neonates, linked with oxygen deprivation during birth. Little’s research on that condition, originally called Little’s disease, and modernly, spastic cerebral palsy, was one of the first accounts of cerebral palsy in infants.

In 1616 in Padua, Italy, Fortunio Liceti, a professor of natural philosophy and medicine, wrote and published the first edition of De Monstruorum Causis, Natura et Differentiis (On the Reasons, Nature, and Differences of Monsters), hereafter De monstruorum. In De monstruorum, Liceti chronologically documented cases of human and animal monsters from antiquity to the seventeenth century. During the seventeenth century, many people considered such monsters as frightening signs of evil cursed by spiritual or supernatural entities. Liceti categorized monsters based on their potential causes, several of which he claimed were unrelated to the supernatural. Historians later noted that some documented monsters were infants with birth defects. In De monstruorum, Liceti elevated the status of monsters to potential subjects of scientific inquiry and provided an early model for the study of birth defects, a field later called teratology.

Mesoderm is one of the three germ layers, groups of cells that interact early during the embryonic life of animals and from which organs and tissues form. As organs form, a process called organogenesis, mesoderm interacts with endoderm and ectoderm to give rise to the digestive tract, the heart and skeletal muscles, red blood cells, and the tubules of the kidneys, as well as a type of connective tissue called mesenchyme. All animals that have only one plane of symmetry through the body, called bilateral symmetry, form three germ layers. Animals that have only two germ layers develop open digestive cavities. In contrast, the evolutionary development of the mesoderm allowed in animals the formation of internal organs such as stomachs and intestines (viscera).

The Spemann-Mangold organizer, also known as the Spemann organizer, is a cluster of cells in the developing embryo of an amphibian that induces development of the central nervous system. Hilde Mangold was a PhD candidate who conducted the organizer experiment in 1921 under the direction of her graduate advisor, Hans Spemann, at the University of Freiburg in Freiburg, German. The discovery of the Spemann-Mangold organizer introduced the concept of induction in embryonic development. Now integral to the field of developmental biology, induction is the process by which the identity of certain cells influences the developmental fate of surrounding cells. Spemann received the Nobel Prize in Medicine in 1935 for his work in describing the process of induction in amphibians. The Spemann-Mangold organizer drew the attention of embryologists, and it spurred numerous experiments on the nature of induction in many types of developing embryos.

In 1893, Julia Barlow Platt published her research on the origins of cartilage in the developing head of the common mudpuppy (Necturus maculosus) embryo. The mudpuppy is an aquatic salamander commonly used by embryologists because its large embryonic cells and nuclei are easy to see. Platt followed the paths of cells in developing mudpuppy embryos to see how embryonic cells migrated during the formation of the head. With her research, Platt challenged then current theories about germ layers, the types of cells in an early embryo that develop into adult cells. In most organisms' development, three types of germ layers are responsible for the formation of tissues and organs. The outermost layer is called ectoderm, the middle layer mesoderm, and the innermost layer endoderm, although Platt called it entoderm. Platt's research provided a basis for scientists to clarify the destination or function of the germ layers in vertebrates' development.

Thalidomide is a sedative drug introduced to European markets on 1 October 1957 after extensive testing on rodent embryos to ensure its safety. Early laboratory tests in rodent populations showed that pregnant rodents could safely use it, so doctors prescribed Thalidomide to treat morning sickness in pregnant women. However, in humans Thalidomide interfered with embryonic and fetal development in ways not observed in rodent tests. Pregnant women who take Thalidomide are at grater than normal risk for spontaneous abortion and for giving birth to children with developmental anomalies such as shortened, absent, or extra limbs, as well as a variety of heart, ear, and internal organ defects. The failure of rodent models to inform scientists of Thalidomide's teratogenicity in humans ignited debate about the proper use of cross-species testing during drug development.

Vitamin A (retinol) is an essential vitamin in the daily functioning of human beings that helps regulate cellular differentiation of epithelial tissue. Studies have shown that an excess of vitamin A can affect embryonic development and result in teratogenesis, or the production of birth defects in a developing embryo. Excess intake of vitamin A and retinoids by pregnant women often results malformations to fetuses' skulls, faces, limbs, eyes, central nervous system. Additionally, doctors often use derivatives of vitamin A, known as retinoids, as medicine to treat a number of skin conditions and carcinomas, the most common form of human cancers.

The article Experimental Studies on Congenital Malformations was published in the Journal of Chronic Diseases in 1959. The author, James G. Wilson, studied embryos and birth defects at the University of Florida Medical School in Gainesville, Florida. In his article, Wilson reviewed experiments on birds and mammals from the previous forty years to provide general principles and guidelines in the study of birth defects and teratogens, which are things that cause birth defects. Those principles included what species are convenient for conducting teratological research, what principles act in human embryological and fetal development, and what agents impact those processes. Wilson's article was one of the first attempts in the twentieth century to synthesize basic research conducted in the field of teratology. The article helped to establish teratology as a field in medicine during the twentieth century.