In the debate about animal use and alternatives within preclinical science, there appears to be some confusion about terms, and some discrepancy about what the common abbreviations stand for. This section is an attempt to discuss and describe some of the most relevant terms.

The 3Rs were formulated by Russell & Burch in the 1950's to describe ways to 'diminish or remove inhumanity' (and in the process increase the validity of science), by means of the Replacement, Reduction and Refinement of animal use. The definitions and interpretation of these terms have changed somewhat over the years from their original meaning. Replacement was from the outset divided into "absolute" (or full) and "relative" (or partial).
There is even some contemporary disagreement about which "R" certain procedures fall under. Russell and Burch acknowledged that there 'are clearly areas of overlap' between the Rs. For example, procedures performed on animals under terminal anaesthesia (also called non-recovery or acute experiments) were classified in their book as "relative replacement", yet they are considered by some today to be Refinement since animals are still used (perhaps because Russell and Burch were even willing to include recovery experiments in this category, as long as the treatment effect wore off before the animals regained consciousness).
Norecopa has constructed a detailed slide deck about the 3R principle and these developments, available in 5 languages so far.

The acronym NAT was introduced specifically to describe procedures that replace current animal use, i.e. Non-Animal Technologies. For example, a computer simulation of the classic nerve-muscle preparation which has been used for many years in undergraduate Physiology classes. A NAT Roadmap has been published for the UK.

The acronym NAM, on the other hand, is generally used for New Approach Methodologies, i.e. methods which were not developed explicitly to replace or reduce animal research*. Scientists who use animals today may (or may not) find them to be suitable alternatives, or supplements, to their in vivo research. NAMs often have little resemblance to an animal model (for example, use of the human placenta), but they are often valuable because they involve the use of human tissue.

*(some institutions, such as the UK NC3Rs and Utrecht University, use the acronym NAM both for Non-Animal Methods, which we refer to here as NATs, and New Approach Methodologies. The NC3Rs has started a resource network and provides a project overview for the latter)

A simple way to differentiate NAMs and NATs is to consider whether the starting-point for development of the method was an animal model or not. NATs are designed to replace animal models, whereas NAMs are more focused on addressing a scientific question, which may then involve the use of in vitro, in silico or in chemico methods, often with human tissue or data. 

Neither NATs nor NAMs are about refining animal models, or replacing one animal model with another one.

The 3Vs of Hanno Würbel (construct validity, internal validity and external validity) and the 3Ss of Carol Newton (Good Science, Sense & Sensibilities) are also highly relevant to this discussion.

It is also worth noting that the species covered by the word "animal" may vary, depending upon whether the context is a pure biological classification or a piece of legislation. In the latter case, "animal" may be restricted to a group (for example fish, wild-living or production animals) or those species believed at the time of writing to exhibit sentience. Legislation relevant to animal research may therefore differ between regions (e.g. the EU) and between (or even within) the legislation of individual countries (different groups of species may be protected in different scenarios).

The UK organisation Understanding Animal Research (UAR) has produced a fact sheet and infographic about NAMs and NATs</a>.

There is probably a tendency on both sides to oversell the benefits and applicability of, respectively, animal studies and non-animal technologies. Greater respectful dialogue between these parties will accelerate both the reduction and replacement of animal use, as well as refinement of those animal studies that still need to be performed.

Dutch scientist Judith Homberg and colleagues discuss how to optimise communication about both animal and animal-free research methods.