Exploiting a Research Underclass in Phase 1 Clinical Trials

In November 1996, the Wall Street Journal reported that Eli Lilly was paying homeless alcoholics from a local shelter to participate in safety testing of new drugs at its trial site in Indianapolis.1 “These individuals want to help society,” asserted Lilly’s director of clinical pharmacology. The subjects, however, said they took part for easy money and free room and board. Although Lilly reportedly offered the lowest per diem in the business, it managed to attract poor subjects from all over the country.1 The medical director of the local Homeless Initiative Program said Lilly had created a “shadow economy” of paid human subjects. Today, the Lilly episode seems like an early warning about an emerging set of ethical problems. Over the past decade, clinical trials have moved from universities to private testing sites, the pressure to recruit subjects quickly has intensified, and ethical oversight has been outsourced to for-profit institutional review boards (IRBs). Payment to subjects has escalated, creating “shadow economies” in cities throughout North America and elsewhere. In 2005, Bloomberg Markets reported that SFBC International, a contract research organization, was paying immigrants to participate in drug trials under ethically questionable conditions in a dilapidated Miami motel. A few months later, nine apparently previously healthy subjects at an SFBC subsidiary in Montreal contracted latent tuberculosis during a trial of an immunosuppressant. In 2006, six healthy subjects required intensive care in a phase 1 trial of a monoclonal antibody at a London facility run by the contract research organization Parexel. For all the ethical debate over these cases, however, few commentators have addressed the most troubling question: Is it ethically problematic to pay poor people to test the safety of new drugs

Involuntarily Committed Patients as Prisoners

Part I relates several stories of involuntarily committed patients who were recruited into studies posing serious risks. Part II draws on these cases to argue that the involuntary commitment of these patients leaves them vulnerable to unethical treatment by researchers. Their inherently coercive circumstances present an overwhelming obstacle to voluntary consent, and their captive status makes them attractive targets for research that could be performed using less vulnerable subjects. Part III argues that most research on this patient population is improper under generally applicable principles of informed consent and fair subject selection. However, existing protections have proved insufficient to prevent unethical recruitment of these patients. Accordingly, Part IV builds on the Institute of Medicine\u27s call for expanding the definition of prisoner in federal regulations, arguing that civilly committed patients should be included within its ambit and that the Common Rule\u27s protections should be applied to all research involving involuntarily confined subjects

Modelling the effect of round window stiffness on residual hearing after cochlear implantation

Preservation of residual hearing after cochlear implantation is now considered an important goal of surgery. However, studies indicate an average post-operative hearing loss of around 20 dB at low frequencies. One factor which may contribute to post-operative hearing loss, but which has received little attention in the literature to date, is the increased stiffness of the round window, due to the physical presence of the cochlear implant, and to its subsequent thickening or to bone growth around it. A finite element model was used to estimate that there is approximately a 100-fold increase in the round window stiffness due to a cochlear implant passing through it. A lumped element model was then developed to study the effects of this change in stiffness on the acoustic response of the cochlea. As the round window stiffness increases, the effects of the cochlear and vestibular aqueducts become more important. An increase of round window stiffness by a factor of 10 is predicted to have little effect on residual hearing, but increasing this stiffness by a factor of 100 reduces the acoustic sensitivity of the cochlea by about 20 dB, below 1 kHz, in reasonable agreement with the observed loss in residual hearing after implantation. It is also shown that the effect of this stiffening could be reduced by incorporating a small gas bubble within the cochlear implant

Is It Ethical to Use Enhancement Technologies to Make Us Better than Well?

Background to the debate: A variety of biomedical technologies are being developed that can be used for purposes other than treating disease. Such “enhancement technologies” can be used to improve our appearance and regulate our emotions, with the goal of feeling “better than well.” While these technologies can help people adapt to their rapidly changing lifestyles, their use raises important ethical issues

An Ethical Path to a Covid Vaccine

https://www.nybooks.com/articles/2020/07/02/ethical-path-covid-19-vaccine/#fn-

How Much Should Governments Pay to Prevent Catastrophes? Longtermism's Limited Role

Longtermists have argued that humanity should significantly increase its efforts to prevent catastrophes like nuclear wars, pandemics, and AI disasters. But one prominent longtermist argument overshoots this conclusion: the argument also implies that humanity should reduce the risk of existential catastrophe even at extreme cost to the present generation. This overshoot means that democratic governments cannot use the longtermist argument to guide their catastrophe policy. In this paper, we show that the case for preventing catastrophe does not depend on longtermism. Standard cost-benefit analysis implies that governments should spend much more on reducing catastrophic risk. We argue that a government catastrophe policy guided by cost-benefit analysis should be the goal of longtermists in the political sphere. This policy would be democratically acceptable, and it would reduce existential risk by almost as much as a strong longtermist policy

The Epstein-Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family

AbstractThe cytoplasmic C-terminus of Epstein-Barr virus (EBV) latent infection membrane protein 1 (LMP1) is essential for B lymphocyte growth transformation and is now shown to interact with a novel human protein (LMP1-associated protein 1 [LAP1]). LAN is homologous to a murine protein, tumor necrosis factor receptor-associated factor 2 (TRAF2), implicated in growth signaling from the p80 TNFR. A second novel protein (EBI6), induced by EBV infection, is the human homolog of a second murine TNFR-associated protein (TRAF1). LMP1 expression causes LAPP and EBI6 to localize to LMP1 clusters in lymphoblast plasma membranes, and LMPI coimmunoprecipitates with these proteins. LAPI binds to the p80 TNFR, CD40, and the lymphotoxin-β receptor, while EBI6 associates with the p80 TNFR. The interaction of LMP1 with these TNFR family-associated proteins is further evidence for their role in signaling and links LMP1-mediated transformation to signal transduction from the TNFR family