Advances in science has led to a situation where dangerous pathogens that are enormously beneficial for research can also be greatly destructive. However, scientific institutions are not prepared to handle such a burden. Proposals advanced by scientific societies are voluntary by nature but do not alone provide robust global protection. This monograph outlines an advanced oversight arrangement, provisionally labeled the Biological Research Security System (BRRS), which is designed to help prevent destructive applications of biology, whether inadvertent or deliberate. Unfortunately, in order to provide adequate protection, constraints might be necessary on freedom of action at the level of fundamental research, and infringing on autonomy of researchers. In addition a great deal of conceptual innovation, legal specification, institutional design and political accommodation would admittedly be required to establish oversight processes. The author concludes that due to the demands and burdens imposed, that human societies might accept lesser standards of protection and rather acquiesce to more limited and incremental measures.