Lessons from thalidomide

Abstract

All human life has intrinsic value, but a truth that seems universal and common across cultures all around the world is that we place the greatest value of all upon the health and wellbeing of children. It is widely asserted that the most important measure of a civilisation is the way in which it treats its most vulnerable. If this is so, it is difficult to imagine more vulnerable people than newborn babies, or babies in utero. It is natural, therefore, for us to take a keen interest in factors that can potentially influence developmental outcomes if the foetus is exposed during gestation. Congenital malformations or other adverse influences on human development have enduring effects upon a child's health and wellbeing, and potentially have significant impact upon that individual for the rest of his/her life. Moreover, it is clear that there are wider important factors involved in the consideration of the effects of exposure to factors that contribute to developmental abnormalities: for example, the profound impact upon maternal wellbeing. Although often thought of as a science involving the study of abnormalities in the physiological development of a human foetus, in the purest sense, teratology actually involves a wider perspective of the abnormalities of physiological development. More subtle issues that are also examined under the rubric can include syndromes where structural and morphological abnormalities are not present (e.g. foetal alcohol syndrome). Regarded by many as a forefather of modern teratology, James Wilson published five key principles of teratology in 1959.1 These principles asserted that the susceptibility of an embryo to the effects of a potential teratogen depends upon the developmental stage at which the agent is applied, that each teratogen appears to act in a specific way on a particular aspect of cellular metabolism, that the genotype of the animal influences to a greater or lesser degree the reaction to a teratogenic agent, that the agents that cause malformations also cause a rise in embryonic mortality and, finally, that teratogenic agents may have little or no deleterious action on the maternal organism. These principles remain scientifically sound today, and Wilson later augmented them with a sixth principle that related to dosage effects and teratogenic thresholds. It was not long after this time that one of the most infamous episodes in the history of teratology unfolded, culminating in the publication of a letter from an Australian obstetrician and gynaecologist (William McBride) who wrote to The Lancet in 1961, a letter of just over 110 words, which had a profound impact that is still keenly felt today.2 The letter succinctly described his concerns that there was a high prevalence of severe congenital abnormalities amongst the children of women who had been treated with thalidomide during pregnancy. He also noted a characteristic pattern of malformations involving structures derived from the mesenchyme, particularly the bones and the gut musculature. The rest is, of course, very famous history. Although McBride went on to experience less illustrious aspects of his professional career, many believe that it was after his observations that lasting changes for the better occurred, notably the requirement to test new drugs for potential teratogenicity in animals, enhanced structured and systematic post-marketing surveillance for drugs and a generalised enduring awareness amongst prescribers of the potential for the teratogenic effects of drugs. In this issue of the Journal we publish two articles that examine different perspectives on the provision of advice about the use of medicines during pregnancy, and also about the potential effects of medicines upon an infant breastfed by a woman undergoing drug therapy. The authors highlight issues and opportunities, and remind our readership of the importance of providing high quality, scientifically sound and objective advice. We are prompted to consider the importance of a systematic examination of the potential benefits and problems associated with the use of medications during pregnancy and lactation, and the extent to which pharmacists are regarded as authority figures in this area (and the inherent responsibility that accompanies this). The stakes are high and the people who need advice in this context are very much dependent upon good quality guidance to assist with decision-making. At times there may be no definitively ‘correct’ answer to provide: instead, thoughtful and carefully constructed advice based upon the best information to hand will need to be enough.