Faculty Bibliography

Anecdotal evidence of superior efficacy and lack of extrapyramidal symptoms in treating schizophrenia made clozapine a promising therapy in the United States during the early 1970s. In 1975, however, numerous fatal cases of clozapine-related agranulocytosis in Finland nearly ended the drug's development. Convinced of the significant benefits to patients, some clinicians in the United States advocated having clozapine available on a case-by-case humanitarian basis, which eventually helped resurrect the drug for Food and Drug Administration approval in 1989. This article builds on previous literature by utilizing oral histories from clinicians, researchers, and a patient's family member to understand how clozapine was saved. Exploring these stakeholders' perspectives has value to modern clinicians, who underprescribe the drug despite demonstrable benefits for treatment-resistant schizophrenia and suicide prevention.

The United States Preventive Services Task Force is perhaps America's best-known source of evidence-based medicine (EBM) recommendations. This paper reviews aspects of the history of one such recommendation-screening for colorectal cancer (CRC)-to explore how the Task Force evaluates the best available evidence to reach its conclusions.Although the Task Force initially believed there was inadequate evidence to recommend CRC screening in the 1980s, it later changed its mind. Indeed, by 2002, it was recommending screening colonoscopy for those aged 50 and older, "extrapolating" from the existing evidence as there were no randomized controlled trials of the procedure. By 2016, due in part to the use of an emerging analytic modality known as modeling, the Task Force supported four additional CRC screening tests that lacked randomized data. Among the reasons the Task Force gave for these decisions was the desire to improve adherence for a strategy-screening healthy, asymptomatic individuals-that it believed saved lives.During these same years, the Task Force diverged from other organizations by declining to advocate screening otherwise healthy Black patients earlier than age 50-despite the fact that such individuals had higher rates of CRC than the general population, higher mortality from the disease and earlier onset of the disease. In declining to extrapolate in this instance, the Task Force underscored the lack of reliable data that proved that the benefits of such testing would outweigh the harms.The history of CRC screening reminds us that scientific evaluation relies not only on methodological sophistication but also on a combination of intellectual, cognitive and social processes. General internists-and their patients-should realize that EBM recommendations are often not definitive but rather thoughtful data-based advice.

Bioethics has become a common course of study in medical schools, other health professional schools, and graduate and undergraduate programs. An analysis of past ethical scandals, as well as the bioethics apparatus that emerged in response to them, is often central to the discussion of bioethical questions. This historical perspective on bioethics is invaluable and demonstrates how, for example, the infamous Tuskegee syphilis study was inherently racist and how other experiments exploited mentally disabled and other disadvantaged persons. However, such instruction can resemble so-called Whig history, in which a supposedly more enlightened mindset is seen as having replaced the "bad old days" of physicians behaving immorally. Bioethical discourse-both in the classroom and in practice-should be accompanied by efforts to historicize but not minimize past ethical transgressions. That is, bioethics needs to emphasize why and how such events occurred rather than merely condemning them with an air of moral superiority. Such instruction can reveal the complicated historical circumstances that led physician-researchers (some of whom were actually quite progressive in their thinking) to embark on projects that seem so unethical in hindsight. Such an approach is not meant to exonerate past transgressions but rather to explain them. In this manner, students and practitioners of bioethics can better appreciate how modern health professionals may be susceptible to the same types of pressures, misguided thinking, and conflicts of interest that sometimes led their predecessors astray.