“In a scientific experiment, there are two possible outcomes: If the result confirms the hypothesis, then you've made a measurement. If the result is contrary to the hypothesis, then you've made a discovery.” - Enrico Fermi (1901-1953)
Those of us lucky enough to call ourselves developmental biologists have, for the past several decades, had front row seats at one of the most fascinating plays ever seen……..a play entitled ”Embryonic Development.” Intense scientific inquiry into molecular and cellular processes during development has revealed secrets long hidden by the developing embryo, transforming the field of developmental biology from a descriptive into a predictive science. Embryogenesis is no longer an arcane process. We are witnessing a play wherein genes, molecules and proteins are the actors, interacting—in ways that we increasingly understand—to create, by the final scene, a healthy baby.
Imagine each member of the audience of this play being shown the sequence of their own genome. They would see a line of A’s, T’s, G’s, and C’s three billion letters in length. The letters, represent the structural units of DNA used to spell out the genetic instructions used in development, each uniques sequence defining who we are. A printed version of this personal “Book of Life,” using the font size you see here, would be over 30,000 pages long. Astonishingly, this is packaged into a single cell, and using only 25,000 or so genes, this blueprint is used to construct a human being. Yet despite the immense complexity involved, most babies that are born are normal and healthy! One cannot help but be amazed at Nature’s handiwork!
The more that is revealed about our individual Book of Life, the more amazing the story becomes. Since the unveiling of the human genome in 2001, we have moved from asking what in our DNA makes us human to striving to know what in one’s DNA makes individuals unique. Indeed, recognition of the extent of human genetic variation was considered the 2007 “Breakthrough of the Year” by Science magazine. There are over 15 million locations, known as “single-nucleotide polymorphisms” (SNPs), in our genomes where a single base can differ from one person or population to the next. A catalog of common genetic variants that occur in human beings, called the HapMap, describes these variants and the location where they occur in our DNA. This information is being used by researchers to link genetic variants to the risk for specific diseases and should prove invaluable for defining risk factors for certain birth defects.
Another form of genetic variation occurs when differences in the number of copies of a particular region in the genome appear. Such changes can result in an altered number of copies of a gene or piece of regulatory DNA. Such “copy number variants,” as they are called, have been associated with susceptibility or resistance to disease. Copy number variants also appear to pose a risk to the developing fetus since such variants have been associated with autism, and idiopathic learning disability.
Despite these astounding advances in our knowledge, birth defects continue to affect about one in every 33 babies born in the United States each year, and are the leading cause of infant mortality. Each year, over 3 million children die before the age of five as a result of complications due to congenital anomalies. Nearly twenty five percent of all infant deaths in Kentucky are caused by congenital anomalies......one of the highest rates in the nation. Indeed, more babies die because of complications due to birth defects than from all other causes.
Despite ongoing research, the causes of nearly 70% of birth defects remain unknown! Nevertheless, significant advances have been achieved in our understanding of the causes and risk factors associated with congenital anomalies. For example, we now know that: obesity confers a higher risk of serious birth defects of the brain and spine; dietary supplementation with folic acid lowers the risk of having a baby with a neural tube defect; exposure to cigarette smoke increases the risk of giving birth to a low birth weight baby or one with a cleft palate; Accutane,™ a drug used to treat severe acne, during pregnancy causes severe birth defects; and consumption of alcohol (wine, beer, or liquor) is the leading known preventable cause of mental and physical birth defects.
The critical challenge for the Birth Defects Center at the University of Louisville’s to improve the diagnosis and treatment of birth defects as well as effect their prevention. To address this mission, investigators in the Birth Defects Center are engaged in the conduct of fundamental research on molecular and molecular genetic aspects of embryonic development and congenital malformations. In the pages that follow, it can be seen that the Birth Defects Center seeks to 1) examine how genes and the environment work together to cause birth defects, 2) enable prenatal molecular diagnosis of maternal genetic susceptibility to potential fetal hazards such as exposure to tobacco, alcohol and certain medications, and 3) define the etiology of developmental abnormalities such as autism, neural tube defects, orofacial clefting, holoprosencephaly, diabetic embryopathy, learning and cognitive disorders, and idiopathic infertility as well as others.
It is our hope that research activities conducted by members of the Birth Defects Center will result in a tangible improvement in our ability to diagnosis birth defects as well as lead to intervention strategies resulting in the reduction of the frequency of birth defects.
"The great tragedy of science — the slaying of a beautiful hypothesis by an ugly fact"- TH Huxley (1825-1895)
 Science 316:445 (2007).
 Psychiatr Genet. 18:101-109 (2008).
 The Lancet 354: 1676 (1999).
 March of Dimes, 2006
Robert M. Greene, Ph.D.
Director, University of Louisville Birth Defects Center
Professor and Chair,
Department of Molecular, Cellular and Craniofacial Biology
Associate, Department of Pediatrics