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 acronyms stand for. In addition, the use of animals in science is often referred to as "animal testing", despite the fact that regulatory use of animals accounts for less than 20% of animal use in the EU. The potential for replacing animal use in such testing is relatively large and efforts are being made to develop alternatives. On the other hand, animal research (basic and applied) which constitutes the vast majority of animal use, is more diverse and there are often fewer obvious opportunities for complete replacement, although large efforts are being made here, too. This section is an attempt to describe some of the most relevant terms applicable to animal testing and research:

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. The NC3Rs provides a resource network and a project overview for NAMs.

*Some institutions, such as the UK NC3Rs , Utrecht University, and the RSPCA in their report on Supporting Replacement in Academia, use the acronym NAMs for Non-Animal Methods, which covers both what we refer to here as Non-Animal Technologies and New Approach Methodologies. The FDA use NAMs to mean "New Approach Methods". See also the definition of NAMs from the British Toxicological Society.

A simple way to differentiate the pure definitions of 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 formulated by 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.

"Animal" can cover different species, 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 situations.

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

There is probably a tendency on both sides to oversell the benefits and applicability of, respectively, studies that use animals or animal material, and technologies that do not.
Greater respectful dialogue between these parties will accelerate 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.

Further information

The term NAM (New Approach Methodologies) was coined at a workshop in Helsinki in 2016 organised by ECHA, whose proceedings were entitled New Approach Methodologies in Regulatory Science (Maurice Whelan, personal communication). The workshop 'addressed the use of data and information from new approach methodologies (NAMs) to support regulatory decisions for the use of chemical substances'. The proceedings state:
For many in the workshop, the term “new approach methodologies – NAMs” was novel. To increase understanding, there is a need to define and scope NAMs. For instance, the workshop heard a description of NAMs as being: in silico approaches, in chemico and in vitro assays including high-throughput and high-content techniques, omics with a focus on metabolomics, the use of exposure data in terms of volume and use etc. There is no current comprehensive overview of where and how NAMs are being defined and used, and how they could be applied in the future. A taxonomy of methods for NAMs would be a great benefit.

In 2018, ICCVAM in their Strategic Roadmap for Establishing New Approaches to Evaluate the Safety of Chemicals and Medical Products in the United States defined NAMs as follows: 'More recently, the term ‘new approach methodologies’ (NAMs) has been adopted as a broadly descriptive reference to any non-animal technology, methodology, approach, or combination thereof that can be used to provide information on chemical hazard and risk assessment. These new approaches include integrated approaches to testing and assessment (IATAs), defined approaches for data interpretation, and performance-based evaluation of test methods.'

Further reading

• Magee (2024): New Approach Methodologies - Where are we, what opportunities are we currently pursuing and what risks must we avoid?