In 1959, William Russell and Rex Burch introduced the 3R principle (Replacement, Reduction and Refinement) in their book ‘The Principles of Humane Experimental Technique’.

  • Replacement: to replace the use of laboratory animals by alternative methods to animal testing. Examples are the use of in vitro methods (such as human cell- and tissue cultures) and in silico models (via computer simulations).
     
  • Reduction: to reduce the number of laboratory animals. An example of reduction is the accurate calculation of the number of laboratory animals required for a scientific study. However, it is important to note that the number should be sufficiently high to obtain statistically reliable results. Another example includes the sharing of laboratory animals, so that certain organs can be used for one study and the carcass and/or the remaining organs for another study or for educational purposes.
     
  • Refinement: to refine experiments by minimizing the inflicted pain and distress to the laboratory animals as much as possible and maximizing their well-being. Examples to reduce the stress level in laboratory animals include group housing of social animals, sufficient cage enrichment, respect for the natural day/night cycle of the laboratory animal ...

Sometimes a fourth R for "Responsibility" is added referring to the "Culture of Care" philosophy in laboratories to which each scientist should contribute. According to this philosophy, scientists and lab technicians are committed to work in an ethical and correct way, obtaining as much scientific progress as possible while minimizing animal suffering.