Thalidomide-induced teratogenesis: history and mechanisms.

Nearly 60 years ago thalidomide was prescribed to treat morning sickness in pregnant women. What followed was the biggest man-made medical disaster ever, where over 10,000 children were born with a range of severe and debilitating malformations. Despite this, the drug is now used successfully to treat a range of adult conditions, including multiple myeloma and complications of leprosy. Tragically, a new generation of thalidomide damaged children has been identified in Brazil. Yet, how thalidomide caused its devastating effects in the forming embryo remains unclear. However, studies in the past few years have greatly enhanced our understanding of the molecular mechanisms the drug. This review will look at the history of the drug, and the range and type of damage the drug caused, and outline the mechanisms of action the drug uses including recent molecular advances and new findings. Some of the remaining challenges facing thalidomide biologists are also discussed.

Concern for truth: driving defensively when confronting a zombie epidemic.

The newly approved drug Diclegis(®), indicated for the treatment of nausea and vomiting associated with pregnancy, has a very interesting background story going back more than 50 years, in which science, celebrity individuals, the media, and the courts crossed paths. The story illustrates how concepts of truth, evidence, objectivity, and disinterested inquiry can become distorted in various ways, and this is especially relevant and prevalent in today's media environment of cable television, talk radio, and especially the Internet.

[Thalidomide epidemics: 50 years after]. / Thalidomidová epidemie - 50 let poté

Thalidomide tragedy and the subsequent epidemics of congenital anomalies is one of the most tragic but also enlightening chapters in the history of modern medicine. Many thousands of children were born with various anomalies - especially with limb deformities - because of the mass usage of thalidomide by pregnant women. The numbers of the spontaneous abortions and fetal deaths will remain unknown forever. In year 2012 we have a sad 50th anniversary of final recognition of thalidomide teratogenous potential. The causes of this tragedy and subsequent actions are summarized in our text.Key words: thalidomide, teratogenesis, congenital anomalies.

"Risk-free rest and sleep:" Jornal do Médico (Portugal) and the thalidomide disaster, 1960-1962. / "Descansar e dormir sem riscos": o Jornal do Médico (Portugal) e o desastre da talidomida, 1960-1962.

This article analyzes the way the Porto-based journal Jornal do Médico reported on the thalidomide disaster. The pages of the publication are researched from the beginning of 1960 to the end of 1962 with the aim of identifying and discussing two interconnected questions: the delay in publishing news on the harmful effects of the drug, which was sold in the country under the brand name Softenon®, and the discursive construction of a lack of accountability on the part of physicians for the phenomenon of medication iatrogenesis.

O artigo analisa como o periódico Jornal do Médico, editado na cidade do Porto, em Portugal, divulgou o desastre da talidomida. A pesquisa percorreu as páginas da fonte desde o início de 1960 até o final de 1962. Aqui, objetivam-se apontar e discutir duas questões interligadas: a morosidade em publicar matérias sobre os efeitos deletérios do medicamento, vendido no país sob a denominação Softenon®, e a construção discursiva da isenção da responsabilidade do médico no fenômeno da iatrogenia medicamentosa.

The teratogenic effects of thalidomide on limbs.

Thalidomide remains notorious as a result of the damage it caused to children born to mothers who used it to treat morning sickness between 1957 and 1961. The re-emergence of the drug to treat a range of conditions including erythema nodosum leprosum (a complication of leprosy) has led to a new generation of thalidomide damaged children being born in Brazil. Although thalidomide affects most of the developing tissues and organs of the body, the damage to the limbs is striking. Indeed phocomelia, the severe reduction or loss of the proximal long bones with retention of the distal hand/foot plate remains the stereotypical image of thalidomide. This review focuses on the type and range of damage thalidomide caused to the limbs, reviews current understanding of the mechanisms underlying thalidomide-induced limb malformations and outlines some of the challenges remaining in elucidating its teratogenicity.

"Descansar e dormir sem riscos": o Jornal do Médico (Portugal) e o desastre da talidomida, 1960-1962 / "Risk-free rest and sleep: " Jornal do Médico (Portugal) and the thalidomide disaster, 1960-1962

Resumo O artigo analisa como o periódico Jornal do Médico, editado na cidade do Porto, em Portugal, divulgou o desastre da talidomida. A pesquisa percorreu as páginas da fonte desde o início de 1960 até o final de 1962. Aqui, objetivam-se apontar e discutir duas questões interligadas: a morosidade em publicar matérias sobre os efeitos deletérios do medicamento, vendido no país sob a denominação Softenon®, e a construção discursiva da isenção da responsabilidade do médico no fenômeno da iatrogenia medicamentosa.

Abstract This article analyzes the way the Porto-based journal Jornal do Médico reported on the thalidomide disaster. The pages of the publication are researched from the beginning of 1960 to the end of 1962 with the aim of identifying and discussing two interconnected questions: the delay in publishing news on the harmful effects of the drug, which was sold in the country under the brand name Softenon®, and the discursive construction of a lack of accountability on the part of physicians for the phenomenon of medication iatrogenesis.

The redemption of thalidomide: standardizing the risk of birth defects.

In this paper we examine how a standardized drug distribution system contributed to a therapeutic and symbolic make-over of thalidomide. In the 1960s, thalidomide was seen as a horror drug that caused severe birth defects among over 10,000 babies who were exposed to it in utero. Currently, thalidomide is viewed as a potentially life-saving drug which is being distributed in the USA. We discuss this transformation from a social worlds perspective, showing how the standardized drug distribution system normalized the risk of foetal birth defects, while preserving the autonomy of health care professionals. The distribution system accomplished this transformation by focusing on the risk associated with female reproductive behavior, and by providing close reproductive surveillance of female patients. This standardized system solidified social inequalities and professional power relationships, revealing assumptions about trust, responsibility and risk.

[The thalidomide experience: review of its effects 50 years later]. / Talidomida: 50 años después.

This year is the 50(th) anniversary of the discovery that the drug thalidomide causes birth defects and should therefore be considered as a teratogen. However, despite the existence of several other drugs that are also human teratogens, thalidomide continues to cause concern among health professionals as well as the general population. The objectives of this article are to make a short historical review of the discovery that this drug severely alters the embryo development, the critical period of gestation and the identification of the real effect of thalidomide. For the first time an analysis is provided to identify the type of malformations for which thalidomide really increases the risk. The proportions of the different types of malformations groups from the series of patients considered to be affected by thalidomide from the literature were compared with the proportions of the same malformations groups in non-exposed infants from the Spanish Collaborative Study of Congenital Malformation (ECEMC). The aim of the analysis was to calculate the relative frequencies of 13 groups of malformations observed in series of patients exposed to thalidomide, by comparison with the same groups of defects in 1,491 patients with limb malformations from the ECEMC consecutive newborn infants, non-exposed to thalidomide. The results showed that the groups with the most classical limb malformations attributed to thalidomide (phocomelia, thumb absence/hypoplasia) had a significantly very higher frequency in exposed cases than in the ECEMC's cases. However, cases presenting with only lower limb malformations were 3 times less frequent in thalidomide cases than in those of ECEMC. Finally, other groups presented the same frequency as those observed in the ECEMC's cases. The results of the 2 last groups, strongly suggests that they were not due to the effect of thalidomide. In addition to the short historical review of the teratogenicity risk of thalidomide, and their new therapeutic properties, it is documented that, as it happens with all other currently known human teratogens, not all malformations observed in infants prenatally exposed to thalidomide were caused by this drug. Finally, it is discussed the paradox that the «feared¼ thalidomide drug causing a great human drama affecting about 10,000 infants has led to a formidable contribution to the scientific knowledge, and large range of therapeutic applications.