Nothing in Nature is more fascinating than the development of a complex, multicellular organism that progressively acquires the essential attributes of its parents. When one considers the complexity of molecular, cellular and tissue interactions that are necessary to orchestrate embryonic development, one must indeed be amazed at Nature’s handiwork. However, despite the fact that most infants are born normal, In this country, that can boast of the best health care system in the world, every three minutes there is a baby born with a birth defect. Each year, in the United States alone, at least 120,000 babies are born with major structural birth defects. In addition, one in eight babies is born too soon. Premature birth is the number 1 cause of infant mortality— with nearly 20% of all infant deaths due to complications attendant to congenital anomalies.
For the past 50 years scientists have pursued fundamental knowledge about the developing embryo and application of that knowledge to reduce the burden of disabilities. The current mantra for contemporary research addressing the causes of congenital malformations is one that strives for “bench to bassinet” outcomes. Biomedical advances are increasingly being made by research teams, using interdisciplinary approaches and supported by open access to powerful databases and on-line tools. In the last decade, biomedical and research breakthroughs, notably in genetics and stem cells, have helped transform the care of children, and have improved both diagnosis and treatment for numerous diseases. These breakthroughs have included advances in newborn screening for inborn errors of metabolism; early diagnosis of primary immunodeﬁciencies; stem cell therapeutics for childhood neurological diseases; prenatal stem cell transplantation; and improved diagnosis of genetic disease in preimplantation embryos. To To be sure, ﬁve Nobel Prizes in Physiology and Medicine in the past decade alone have had a profound effect on enlarging our understanding of embryonic development. In 2001 the award was given for discoveries of key regulators of the cell cycle, while the 2002 award recognized discoveries concerning genetic regulation of organ development and programmed cell death. In recent years the Nobel committee paid tribute to the discovery of RNA interference-gene silencing (2006) and the illucidation of principles for introducing speciﬁc gene modiﬁ cations in mice by the use of embryonic stem cells (2007). Most recently, the prize was awarded for the development of in vitro fertilization (2010).
“Science is facts; just as houses are made of stone, so is science made of facts; but a pile of stones is not a house, and a collection of facts is not necessarily science.” — Jules Henri Poincaré (1854-1912) French mathematician.
A pediatrician who practiced in the 1950s would not recognize the children’s health care landscape today: babies born 3 month too soon and weighing less than 1 1/2 lb, survive; diseases such as polio and bacterial meningitis that often killed or crippled children are so rare that most physicians have never treated them; new imaging technologies provide powerful prenatal diagnostic tools to enable identiﬁ cation of birth defects in utero; fetuses are now operated on for life-threatening disorders; expectant mothers are treated with drugs and vitamins to prevent certain birth defects. What all these advances have in common, is that they were made possible by biomedical research—the very types of research being conducted within the University of Louisville Birth Defects Center.
The remarkable successes of biomedical research notwithstanding, the frequency of congenital craniofacial anomalies remains distressingly high. Despite an impressive broadening of our understanding of the molecular machinery orchestrating embryonic development, the fundamental mechanisms governing growth and development of the embryo remains poorly deﬁned. When depicting far off lands at the edge of the known world, maps from the Middle Ages declared “Here There Be Dragons.” While our understanding of the molecular mechanisms that coordinate development of the embryo/fetus has dramatically increased in the past several decades, our knowledge remains uncomplicated by a full appreciation of the regulatory intricacies involved in normal, muchless abnormal, development. Here there be dragons indeed!
“It is a capital mistake to theorise before one has data. Insensibly one begins to twist facts to suit theories instead of theories to suit facts.” — Arthur Conan Doyle (1859-1930) British physician and novelist
While many examples of individual research support can be acknowledged (see individual faculty proﬁles that follow), two organizations require singular recognition:
1) Each year Kosair Charities (www. kosair.org) donates millions of dollars to help support health care organizations in Kentucky and southern Indiana that specialize in treating children. During the past several years, the University of Louisville Birth Defects Center received signiﬁcant support from Kosair Charities. On behalf of the University and the Center, I wish to acknowledge this support which has made an important and positive impact on our ability to address the missions of the Center.
2) For the past 8 years the National Center for Research Resources (http://www.ncrr.nih.gov) at the NIH has supported a Center of Biomedical Research Excellence (COBRE) whose purpose was to foster interdisciplinary, health-related research aimed at illuminating the molecular etiologies of developmental defects and disabilities, and to enhance the competitiveness of junior investigators for independent funding. Because of success in achieving these goals, the COBRE was refunded by the NCRR in 2008 for an additional 5 years in the amount of $8.8 million.
“Science is organized common sense, where many a beautiful theory was killed by an ugly fact.” — Thomas Huxley (1825-1895) British biologist
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