RESUMO
Biological threats are complex and multifaceted, as evidenced by the ongoing COVID-19 pandemic. Their effective prevention and countering require multiple lines of collaborative action and sustained cross-sectorial coordination. This paper reviews the conclusions of Graham Pearson's 1997 JAMA article titled 'The Complementary Role of Environmental and Security Biological Control Regimes in the 21st Century', taking into account the international policy developments that have occurred over the past two decades. The paper underscores the utility of the concept of a 'web of prevention' for elucidating the need for continuous interaction between the international biosafety and international biosecurity regimes, in order to ensure that the life sciences are used only for peaceful purposes. The terms 'biosafety' and 'biosecurity' are used to denote the primary purpose of the two regimes: the international biosafety regime seeks to prevent the unintentional (accidental) release of pathogens and toxins, including naturally occurring disease, whereas the biosecurity regime seeks to prevent the deliberate release and misuse of pathogens and toxins. The paper concludes by recommending practical steps for strengthening the implementation of all elements of the web of prevention and upholding the norms against the hostile misuse of life sciences.
RESUMO
PURPOSE: A novel regimen designed to maximize antileukemia activity of carboplatin through inhibiting repair of platinum-DNA adducts was conducted in poor prognosis, acute leukemia patients. EXPERIMENTAL DESIGN: Patients received fludarabine (10 to 15 mg/m(2) x 5 days), carboplatin (area under the curve 10 to 12 by continuous infusion over 5 days), followed by escalated doses of topotecan infused over 72 hours (fludarabine, carboplatin, topotecan regimen). Twenty-eight patients had acute myelogenous leukemia (7 untreated secondary acute myelogenous leukemia, 11 in first relapse, and 10 in second relapse or refractory), 1 patient had refractory/relapsed acute lymphoblastic leukemia, and 2 patients had untreated chronic myelogenous leukemia blast crisis. Six patients had failed an autologous stem cell transplant. Patients ranged from 19 to 76 (median 54) years. Measurement of platinum-DNA adducts were done in serial bone marrow specimens. RESULTS: Fifteen of 31 patients achieved bone marrow aplasia. Clinical responses included 2 complete response, 4 complete response with persistent thrombocytopenia, and 2 partial response. Prolonged myelosuppression was observed with median time to blood neutrophils >/=200/microl of 28 (0 to 43) days and time to platelets >/=20,000/microl (untransfused) of 40 (24 to 120) days. Grade 3 or greater infections occurred in all of the patients, and there were 2 infection-related deaths. The nonhematologic toxicity profile was acceptable. Five patients subsequently received allografts without early transplant-related mortality. Maximum tolerated dose of fludarabine, carboplatin, topotecan regimen was fludarabine 15 mg/m(2) x 5, carboplatin area under the curve 12, and topotecan 2.55 mg/m(2) over 72 hours. An increase in bone marrow, platinum-DNA adduct formation between the end of carboplatin infusion and 48 hours after the infusion correlated with bone marrow response. CONCLUSIONS: Fludarabine, carboplatin, topotecan regimen is a promising treatment based on potential pharmacodynamic interactions, which merits additional study in poor prognosis, acute leukemia patients.