T his paper examines the development and termination of nebacumab (Centoxin ® ), a human IgM monoclonal antibody (mAb) drug frequently cited as one of the notable failures of the early biopharmaceutical industry. The non-approval of Centoxin in the United States in 1992 generated major concerns at the time about the future viability of any mAb therapeutics. For Centocor, the biotechnology company that developed Centoxin, the drug posed formidable challenges in terms of safety, clinical efficacy, patient selection, the overall economic costs of health care, as well as financial backing. Indeed, Centocor's development of the drug brought it to the brink of bankruptcy. This article shows how many of the experiences learned with Centoxin paved the way for the current successes in therapeutic mAb development. IntroductionOn April 15, 1992, the United States Food and Drugs Administration (US FDA) announced that it would not approve nebacumab (Centoxin ® ), a human IgM monoclonal antibody (mAb) for treatment of Gram-negative sepsis, developed by Centocor, a biotechnology company founded in 1979 to commercialise mAbs. Triggering wide scale dismay among financial investors and biotechnology executives, the news heralded not only possible bankruptcy for Centocor, its shares falling 41% in one day, 1 but also what seemed an obituary for mAb therapeutics overall. What made the shock particularly acute was the fact that the drug had already The birth pangs of monoclonal antibody therapeuticsThe failure and legacy of centoxin Lara Marks Department of Primary Care and Public Health; King's College London; London, UK received marketing approvals in a number of European countries during 1991 and had been recommended for approval by a FDA Advisory Committee in September 1991. Particularly devastating was the fact that the drug was designed to treat a medical condition known to be a leading and rising cause of death in intensive care units, and for which there was little effective treatment. 2,3While marking a very bleak and painful day for Centocor, in the long-term the drug's failure provided important lessons in the subsequent development, testing and regulation of therapeutic mAbs for the company, as well as the biotechnology industry and regulatory agencies. The event is particularly striking given that today mAb therapeutics form one of the fastest growing and most successful and lucrative segments within the biopharmaceutical sector. The success of this market is exemplified by Centocor's infliximab (Remicade ® ), a chimeric IgG mAb approved in 1998 for inflammatory and autoimmune diseases, which had global sales of US$8.1 billion in 2010. As of January 2012, nearly 30 mAb drugs had been approved in the US and Europe, with four of these (Remicade ® ), Humira ® , Avastin ® , Rituxan ® among the world's ten best selling drugs. 4,5 The history of Centoxin and the aftermath of its termination provides a useful insight into the trials and tribulations not only of mAb drugs, but also the challenges and obstacles faced by executiv...

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The ongoing social and political problems of Ireland at the end of this century, and the question of what form a unified nation might take, suggest that the position taken by Connolly may still be one worthy of serious consideration. The whole theme of socialism and capitalism, whether in conflict or cooperation, is one that retains a continuing relevance in postcolonial societies. This book, unfortunately, is of only limited use in analyzing the "pre-post-colonial" society of Ireland.In Model Mothers, Lara Marks examines the reality behind the belief common among late nineteenth-and early twentieth-century reformers that Jewish women were near-perfect mothers. A useful supplement to Ellen Ross's Love and Toil: Motherhood in OutcastLondon, Marks's book provides a comprehensive picture of maternity care in workingclass London. A lecturer in the history of twentieth-century medicine at Imperial College, University of London, Marks poses key questions about gender, ethnicity, and class.After her valuable overview of the nature of the Jewish community in London, Marks accounts for the drop in infant mortality found in Jewish areas of East London from the 1890s, an earlier and sharper drop than elsewhere in England. As environmental conditions were not noticeably different in Jewish neighborhoods, Marks concludes that Jewish mothers exerted more control over their surroundings. In part, Jewish cultural and religious practices contributed to better health. In addition, the Jewish community, concerned that Jewish language, religious,