The Scientific Liaison Coalition (SLC) recently completed a webinar series on Predicting Adverse Effects Before They Occur: Teratogens as an Example. The webinars in this series feature two Teratology Society Past Presidents, Dr. Jan Friedman and Dr. Anthony Scialli and recordings are now available.
In Bed with the Devil: Recognizing Human Teratogenic Exposures
This webinar took place on November 28, 2017. A recording is available HERE.
Presented by Jan Friedman, MD, PhD, a clinical geneticist and Professor of Medical Genetics at the University of British Columbia (UBC). In the past decade, Dr. Friedman has been a pioneer in the development and application of cytogenetic and genomic tools to understand the genetic causes and clinical consequences, and improve diagnosis of, intellectual disability syndromes.
Dr. Friedman's presentation addresses the challenge to recognize that an exposure is teratogenic when the fewest possible babies have been harmed. Recognizing exposures that are teratogenic in humans requires: (1) babies who have been harmed by the exposure; (2) a way to associate the maternal exposure to the babies’ birth defects (hypothesis generation); and (3) a way to prove that the observed association is causal (hypothesis testing). Proving an association is probably causal as quickly as possible means making this call before the definitive study has been done. A weight-of-evidence approach is used, taking each study for what it is worth, but no more. Dr. Friedman has published more than 270 peer-reviewed papers and has written six books and edited two others. He is the Director of CAUSES Clinic at BC Children’s Hospital. This research clinic provides advanced DNA testing, clinical interpretation, genetic counselling, and personalized recommendations for treatment for children with complex, undiagnosed medical conditions.
The Next Thalidomide
This webinar took place December 20, 2017. A recording is available HERE.
Presented by Anthony B. Scialli, MD, a teratologist and board-certified obstetrician-gynecologist. Dr. Scialli is Adjunct Professor in the Departments of Obstetrics and Gynecology and of Pharmacology and Physiology at Georgetown University School of Medicine, where he was a full-time Professor and director of the Residency Training Program until 2003, and Clinical Professor in Obstetrics and Gynecology at George Washington University, where he continues to see patients.
Dr. Scialli's presentation addresses disease prevention. One reason to work in toxicology is to prevent episodes of human disease before they occur by identifying and avoiding exposures that are likely to be harmful. In developmental toxicology, this practice is sometimes called preventing the next thalidomide. Of course, one limitation on this idea is the fact that the next thalidomide has already occurred, several times in fact. It can be instructive to review these episodes and learn from them where the failures occurred. In some cases (isotretinoin, valproic acid), well-characterized warnings were not noticed by clinicians or patients. In other cases (diethylstilbestrol, warfarin), the sensitive developmental period in humans was outside the observation period of standard experimental protocols. In yet other cases (mycophenolate), the problem was the importance of the drug for the health of the patient and the need to wait for a critical epidemiological mass to establish causation. Fundamental to the use of traditional experimental protocols is the belief that laboratory animal response predicts human response, but it has been clear for decades that this belief is an artifice of the dosing regimens used in the experimental studies. By using high enough dose levels, any chemical can be made to look teratogenic, a principle enunciated by David Karnofsky in 1965. Because of this principle, experimental animal studies can look highly predictive if we accept any developmental endpoint at any dose as a positive, and if we are not too worried about false alarms. We hope that the use of alternative test strategies and better characterization of mechanisms of abnormal development will make experimental protocols more predictive of human response, but it is not a foregone conclusion that they will do so.
About the Scientific Liaison Coalition
The mission of the Scientific Liaison Coalition is “improving the ability of societies to partner with other domestic and international organizations with the goal of advancing science to improve human and environmental health” by efforts to: strengthen partnerships among health science organizations to increase awareness of toxicology and related sciences on human health; and enhance cooperation among societies with the goal of accomplishing tasks benefiting human health and disease prevention through joint and shared activities. Teratology Society Past President Mary Alice Smith, PhD, is currently the Chair of the Scientific Coalition, and Teratology Society Past President Thomas B. Knudsen, PhD, serves as an At-Large Society Representative on the SLC Governance Committee.
Links to recordings of all past SLC Webinars may be found in the Educational Webinars File Library on BDR Connection.