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.

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.

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.

Sidney Q. Cohlan studied birth defects in the US during the twentieth century. Cohlan helped to discover that if a pregnant woman ate too much vitamin A her fetus faced a higher than normal risk of teratogenic effects, such as cleft palate. A teratogen is a substance that causes malformation of a developing organism. Cohlan also identified the teratogenic effects of several other substances including a lack of normal magnesium and prenatal exposure to the antibiotic tetracycline. Cohlan's experiments with vitamins and other chemicals brought attention to how nutrition and environmental agents adversely affect human pregnancy outcomes.

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.

This project focuses on the history of how teratogens, or agents which have the potential to cause birth defects, have been understood and tested for teratogenic potential in the US over the twentieth century. Prior to this time, teratogen studies were primarily concerned with cataloguing defects rather than exploring possible causes. At the turn of the twentieth century, experimental teratogen studies with the aim of elucidating mechanisms commenced. However, these early studies did not aim to discover human pregnancy outcomes and ways to prevent them, but simply focused on the results of exposing pregnant mammals to various physical and chemical insults.

Teratogens are substances that may produce physical or functional defects in the human embryo or fetus after the pregnant woman is exposed to the substance. Alcohol and cocaine are examples of such substances. Exposure to the teratogen affects the fetus or embryo in a variety of ways, such as the duration of exposure, the amount of teratogenic substance, and the stage of development the embryo or fetus is in during the exposure. Teratogens may affect the embryo or fetus in a number of ways, causing physical malformations, problems in the behavioral or emotional development of the child, and decreased intellectual quotient IQ in the child. Additionally, teratogens may also affect pregnancies and cause complications such as preterm labors, spontaneous abortions, or miscarriages. Teratogens are classified into four types: physical agents, metabolic conditions, infection, and finally, drugs and chemicals.

Infantile Autism: The Syndrome and Its Implications for a Neural Theory of Behavior (hereafter Infantile Autism) is a book written by Bernard Rimland, published in 1964. The book proposed a theory to explain the causes of autism. The book also synthesized research into autism and used Rimland's neural theory, described in the book, as a theory to explain some aspects of behavior, intelligence, and abnormality. Moreover, Infantile Autism contributed to a debate between Rimland and child psychologist Bruno Bettelheim in the 1960s over whether autism was caused by upbringing (see refrigerator mother theory) or by impaired brain development. Rimland's book convinced many autism researchers to look for abnormal psychological development.

Androgen Insensitivity Syndrome (AIS) is a human disorder in which an individual's genetic sex (genotype) differs from that individual's observable secondary sex characteristics (phenotypes). A fetus with AIS is genetically male with a 46,XY genotype. The term 46,XY refers to the chromosomes found in most cells of the fetus. Most cells have a total of 46 autosomes, or non-sex chromosomes, and a pair sex chromosomes, XX for genetic females, or XY for genetic males. Due to a defect on the androgen receptor gene (AR) located on the X chromosome, a fetus with AIS cannot process male sex hormones or androgens. The effect on the fetus is that, compared to genetically male fetuses without AIS, it doesn't develop normal male phenotypes. The resistance to androgens affects all of the fetus's organs during embryonic development and during puberty. Although genetically male, persons with AIS can be socially raised as either female or male (sex-of-rearing) yet identify with a gender discordant with their sex-of rearing. AIS and other states of intersexuality challenge physicians, scientists, and society to evaluate definitions of sex.

The one gene-one enzyme hypothesis, proposed by George Wells Beadle in the US in 1941, is the theory that each gene directly produces a single enzyme, which consequently affects an individual step in a metabolic pathway. In 1941, Beadle demonstrated that one gene in a fruit fly controlled a single, specific chemical reaction in the fruit fly, which one enzyme controlled. In the 1950s, the theory that genes produce enzymes that control a single metabolic step was dubbed the one geneÐone enzyme hypothesis by Norman Horowitz, a professor at the California Institute of Technology (Caltech) and an associate of Beadle's. This concept helped researchers characterize genes as chemical molecules, and it helped them identify the functions of those molecules.