Voices off: Stanley Milgram's cyranoids in historical context

This article revisits a forgotten, late project by the social psychologist Stanley Milgram: the ‘cyranoid’ studies he conducted from 1977 to 1984. These investigations, inspired by the play Cyrano de Bergerac, explored how individuals often fail to notice when others do not speak their own thoughts but instead relay messages from a hidden source. We situate these experiments amidst the intellectual, cultural, and political concerns of late Cold-War America and show how Milgram’s studies pulled together a variety of ideas, anxieties, and interests that were prevalent at that time and have returned in new guises since. In discussing the cyranoid project’s background and afterlife, we argue that its strikingly equivocal quality has lent itself to multiple reinterpretations by historians, psychologists, performers, artists and others. Our purpose is neither to champion Milgram’s work nor amplify the critiques already made of his methods. Rather it is consider the uncertain, allusive, and elusive aspects of the cyranoid project, and to seek to place that project ‘in context’, whilst asking where ‘context’ might end. We show how the experiments’ range of meanings, in different temporal registers, far exceeded the explanatory rubric that Milgram and his intellectual critics provided at that time; and ponder the risk for the historian of making anachronistic or teleological assumptions. In short, cyranoids, we argue, invite our open-ended exploration of ‘voices off stage’ in social and psychological relations, and offer a useful tool for thinking about historical context and the nature of historical interpretations

A comprehensive study of the rare diseases and conditions targeted by orphan drug designations and approvals over the forty years of the Orphan Drug Act

Abstract Background Rare diseases affect more than 30 million Americans. The passage of the Orphan Drug Act (ODA) in the United States in 1983 represented a launching point for a rare disease drug development revolution for these patients. Financial incentives provided by the ODA through its Orphan Drug Designation Program, in addition to remarkable scientific advances over the past 40 years, have led to hundreds of drug approvals for rare diseases. Our research examines the rare diseases that have been targeted by orphan drug designations and subsequent approvals since the law was enacted. Methods Using an internal FDA database, we classified and analyzed all orphan drug designations and approvals from 1983 to 2022 by disease and therapeutic area. Results Over the 40 years of the ODA, 6,340 orphan drug designations were granted, representing drug development for 1,079 rare diseases. Additionally, 882 of those designations resulted in at least one FDA approval for use in 392 rare diseases. Much of this development has been concentrated in oncology as seven of the top ten most designated and approved diseases were rare cancers. Conclusions Researchers have estimated that there may be 7000–10,000 rare diseases that have been identified and described. Based on our study, we can conclude that around 5% of rare diseases have an FDA-approved drug and up to 15% of rare diseases have at least one drug that has been developed and shown promise in their treatment, diagnosis or prevention. Funding of basic and translational science for rare disease drug development should continue in order to bring therapies to the millions of affected patients who remain without treatment options

Using four decades of FDA orphan drug designations to describe trends in rare disease drug development: substantial growth seen in development of drugs for rare oncologic, neurologic, and pediatric-onset diseases

Abstract Background Orphan drug designations are a useful proxy to investigate trends in rare disease drug development. Drug developers must receive a designation before they are eligible for the economic incentives of the Orphan Drug Act in the United States. We created a database of all orphan drugs designated between 1983 and 2019 that included numerous drug characteristics, including therapeutic area. In addition, we constructed a “broad disease” categorization of designations as an alternative to therapeutic area, based on disease etiology and age of onset rather than organ system. By looking at the pattern of orphan drug designations over the past four decades, this analysis studied the impact of the evolving rare disease drug development landscape and considers the future of rare disease therapies over the coming decades. Results Between 1983 and 2019, a total of 5099 drugs and biologics received orphan drug designation. Designations more than doubled between the 1980s and 1990s, almost doubled between the 1990s and 2000s, and almost tripled in number between the 2000s and 2010s. The top three therapeutic areas represented in the orphan drug designations were: oncology (1910, 37%), neurology (674, 13%), and infectious diseases (436, 9%). The broad disease categorization found that the proportion of designations for pediatric-onset diseases has increased in the most recent decade to 27%. Conclusions Analysis of the last four decades of orphan drug designation indicates seismic shifts have occurred in the rare disease drug development space. The number of designations granted more than quadrupled between the 1990s and 2010s. While these substantial increases led to growth in the absolute number of designations within all therapeutic areas (bar one) and broad disease categories, the relative proportions have seen considerable change over time. In the most recent decade, there have been notable increases in the proportion of drugs in oncology, pediatric-onset diseases, and neurologic disorders. The dramatic rise in overall orphan designations over the past four decades suggests we may continue to see an upward trajectory in designations leading to an increased number of approvals for drugs and biologics designed specifically for diagnosing, preventing, and treating rare diseases in the coming decades