A Practical Approach, Second Edition=Ronald D. Ho.pdf

PATHOGENESIS OF ABNORMAL DEVELOPMENT 81the genome, in most cases it will be only indirectly. And some teratogens, such as deformationsand vascular disruptive phenomena, are unrelated to any genetic alteration.The methods of molecular biology are used to study the structure and nature of the genes, andtheir products that result in congenital malformations. After we achieve an understanding of thebasic science of genes that produce congenital malformations, there is frequently a long and difficultroad before this information can be utilized to treat or prevent birth defects.Developmental toxicology is much different. If we can identify an environmental agent as ateratogen, our first task is to prevent exposure to the agent. In many instances that is a readilyattainable goal, especially if the agent is a drug or chemical over which society has control. Yetknowing that alcohol is a teratogen does not and has not solved the problem. Similarly environmentalcontaminants, such as mercury, are not readily controlled. Maternal disease states that are teratogenic,such as diabetes or teratogenic infections, represent more difficult problems, but they arestill solvable. The answer for the teratologist is epidemiological studies that identify developmentaltoxicants or animal studies that indicate or confirm the potential for harm. From the humanstandpoint, understanding the pathophysiology is irrelevant. Yet, as scholars it is important to studyand understand the mechanisms of teratogenesis and the pathophysiology from a scientific andclinical perspective. Drugs and chemicals with similar pathophysiological effects may represent arisk. Greater knowledge might thus permit chemists to prepare drugs that have the therapeuticbenefit sought, while eliminating the teratogenic risk, as has been attempted with valproic acidanalogs.The approach for solving the problem of genetically transmitted congenital malformations ismuch different. Basic science research into the nature of the normal and abnormal genes involvedin the genetically transmitted malformations will be the key to preventing or treating the geneticdefect. Since there is a cascade of gene products that can be unveiled once the gene is identified,understanding the totality of a particular gene’s role in development may permit the replacementof the deficient products attributable to the abnormal gene. There is even the possibility of insertingthe normal gene; although presently largely theoretical, it is a real possibility.So developmental toxicologists have to examine their field and recognize that it consists of thefollowing components:Epidemiological studies to identify agents that are causally associated with the production of birthdefects.Basic science research dealing with the mechanisms of teratogenesis and the pathophysiology ofabnormal development.Ecological interests to identify potential new environmental toxicants.Social and political actions to make certain that the information about environmental reproductive risksis acted upon promptly by governmental agencies.Responsibility for educating the public about environmentally induced birth defects as well as toeducate their scientific, clinical, and regulatory colleagues about these risks.REFERENCES1. Brent, R.L. and Jensh, R.P., Intrauterine growth retardation, Adv. Teratol., 2, 139, 1967.2. Wilson, J.G. Environment and Birth Defects, Academic Press, New York, 1973.3. Brent, R.L., Environmental factors: miscellaneous, in Prevention of Embryonic, Fetal and PerinatalDisease, Brent, R.L. and Harris, M.J., Eds., DHEW Pub. No. (NIH) 76-853, Department of Health,Education, and Welfare, Bethesda, 1976, p. 211.4. Brent, R.L., The magnitude of the problem of congenital malformations, in Prevention of Physicaland Mental Congenital Defects. Part A. Basic and Medical Science, Marois, M., Ed., Alan R. Liss,New York, 1985, p. 55.© 2006 by Taylor & Francis Group, LLC