Embryo Project Encyclopedia Articles

Isotretinoin is a molecule and a byproduct (metabolite) of vitamin A, and in greater than normal amounts in pregnant women, it can cause fetal abnormalities including cleft lips, ear and eye defects, and mental retardation. Isotretinoin is commonly called by its trade name Accutane, and it's a chemical compound derived from vitamin A, or retinoic acid. Doctors prescribe isotretinoin to treat severe acne. For pregnant women, too much vitamin A or isotretinoin can also cause greater than normal rates of stillbirths and fetal disintegrations after the ninth week of gestation. Women who use isotretinoin during the first trimester of their pregnancies, even in small amounts, risk defects to their fetuses such as external ear malformations, cleft palates, undersized jaws (micrognathia), a variety of heart defects, buildups of fluids inside the skulls that leads to brain swelling (hydrocephalus), small heads and brains (microcephaly), and mental retardation.

Frederik Ruysch, working in the Netherlands, introduced the term epithelia in the third volume of his Thesaurus Anatomicus in 1703. Ruysch created the term from the Greek epi, which means on top of, and thele, which means nipple, to describe the type of tissue he found when dissecting the lip of a cadaver. In the mid nineteenth century, anatomist Albrecht von Haller adopted the word epithelium, designating Ruysch's original terminology as the plural version. In modern science, epithelium is a type of animal tissue in which cells are packed into neatly arranged sheets. The epithelial cells lie proximate to each other and attach to a thin, fibrous sheet called a basement membrane. Epithelia line the surfaces of cavities and structures throughout the body, and also form glands. Although they lack blood vessels, epithelia contain nerves and can function to receive sensation, absorb, protect, and secrete, depending on which part of the body the epithelia line. During development, epithelia act in conjunction with another tissue type, mesenchyme, to form nearly every organ in the body, from hair and teeth to the digestive tract. Epithelia are an essential part of embryonic development and the maintenance and function of the body throughout life.

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.

Fortunio Liceti studied natural philosophy and medicine in Italy during the first half of the seventeenth century. Liceti wrote greater than seventy works on a wide range of topics, including the human soul, reproduction, and birth defects observed in animals and human infants. In the seventeenth century, people commonly addressed birth defects using superstition and considered them as signs of evil, possibly caused by spiritual or supernatural entities. Liceti described infants with birth defects as prodigies and monsters to be admired and studied rather than feared. Liceti’s works established monsters as a possible subject of scientific inquiry and served as models for the future study of birth defects, a field later called teratology. Liceti was one of the first scholars to attempt to systematically categorize birth defects based on their causes, including multiple causes unrelated to the supernatural.

De ovi mammalium et hominis genesi (On the Genesis of the Ovum of Mammals and of Men) is an 1827 pamphlet by Karl Ernst von Baer about the anatomical observation and description of the egg (ovum) of mammals, like dogs and humans. The pamphlet detailed evidence for the existence of the ovum at the beginning of the developmental process in mammals. Prior to von Baer's publication, there was much debate about how organisms develop, as some claimed that organisms grow from a corpuscular element already preformed in the body (preformationism), and others said that organisms developed from a fluid material undergoing a process of progressive formation (epigenesis). Researchers at the time struggled to observe the early stages of development, and those such as von Baer had to observe the phenomenon through microscopes and then provide interpretations of the phenomena they observed.

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.

Apoptosis, or programmed cell death, is a mechanism in embryonic development that occurs naturally in organisms. Apoptosis is a different process from cell necrosis, which is uncontrolled cell death usually after infection or specific trauma. As cells rapidly proliferate during development, some of them undergo apoptosis, which is necessary for many stages in development, including neural development, reduction in egg cells (oocytes) at birth, as well as the shaping of fingers and vestigial organs in humans and other animals. Sydney Brenner, H. Robert Horvitz, and John E. Sulston received the Nobel Prize in Physiology or Medicine in 2002 for their work on the genetic regulation of organ development and programmed cell death. Research on cell lineages before and after embryonic development may lead to new ways to reduce or promote cell death, which can be important in preventing diseases such as Alzheimer's or cancer.