The Three Rs of Animal Research: What they Mean for the Institutional Animal Care and Use Committee and Why.

The Institutional Animal Care and Use Committee (IACUC) is entrusted with assessing the ethics of proposed projects prior to approval of animal research. The role of the IACUC is detailed in legislation and binding rules, which are in turn inspired by the Three Rs: the principles of Replacement, Reduction, and Refinement. However, these principles are poorly defined. Although this provides the IACUC leeway in assessing a proposed project, it also affords little guidance. Our goal is to provide procedural and philosophical clarity to the IACUC without mandating a particular outcome. To do this, we analyze the underlying logic of the Three Rs and conclude that the Three Rs accord animals moral standing, though not necessarily "rights" in the philosophical sense. We suggest that the Rs are hierarchical, such that Replacement, which can totally eliminate harm, should be considered prior to Reduction, which decreases the number of animals harmed, with Refinement being considered last. We also identify the need for a hitherto implicit fourth R: Reject, which allows the IACUC to refuse permission for a project which does not promise sufficient benefit to offset the pain and distress likely to be caused by the proposed research.

Improving interactions between animal rights groups and conservation biologists.

Invasive species are often considered to be a major threat to biodiversity, leading conservation biologists to often recommend their complete eradication. Animal rights groups typically categorically oppose killing animals, and their opposition has brought eradication attempts of gray squirrels in northern Italy (Europe) and mute swans in Vermont to a halt. As a result native red squirrels may disappear from Europe and ecosystem-wide impacts are expected to be caused by the swan. In contrast, cooperation between managers and animal rights groups has resulted in a successful control program for feral pigs in Fort Worth, Texas (U.S.A.). The philosophical differences between animal rights and conservation biologists' views make cooperation seem unlikely, yet documented cases of cooperation have been beneficial for both groups. We recommend that managers dealing with invasive species should consult with social scientists and ethicists to gain a better understanding of the implications of some of their policy decisions. In addition, we recommend that animal rights groups do more to support alternatives to lethal control, which are often excluded by economic limitations. Prevention of arrival of invasive species via application of the precautionary principle may be an especially productive avenue for such collaboration because it fits the goals and values of both groups.

Charting a path toward combination therapy for Alzheimer's disease.

It is acknowledged that progress in combined therapeutic approaches for Alzheimer's disease (AD) will require an unprecedented level of collaboration. At a meeting co-hosted by the Accelerate Cure/Treatments for Alzheimer's Disease Coalition and the Critical Path Institute, investigators from industry, academia and regulatory agencies agreed on the need for combinatorial approaches to treating AD. The need for advancing multiple targets includes recognition for novel adaptive trial designs that incorporate existing and new biomarkers to evaluate drug effects independently and in combination. A combination trial now being planned may test drugs targeting different pathogenic pathways or multiple targets along a common pathway. Collaborations and consortia-based strategies are pivotal for success and a regulatory framework is recommended for success.

The ethics of wildlife research: a nine R theory.

The commonsense ethical constraints on laboratory animal research known as the three Rs are widely accepted, but no constraints tailored to research on animals in the wild are available. In this article, we begin to fill that gap. We sketch a set of commonsense ethical constraints on ecosystem research parallel to the constraints that govern laboratory animal research. Then we combine the animal and ecosystem constraints into a single theory to govern research on animals in the wild.