The Principles of Humane Experimental Technique written by W.M.S. Russell and R.L. Burch in 1959 is arguably the most influential moment in alternatives to the use of animals in experimentation history. Although it had little impact when it was first published, the book, and the concepts introduced by Russell and Burch, would prove to be exceptionally important and fundamental, none more so than the concept of the Three Rs. Virtually all subsequently meaningful work that has been accomplished in the field of alternatives relies on the Three Rs  to some degree. For researchers and supporters of alternatives, The Principles of Humane Experimental Technique is usually considered the primary resource, and its historical significance to science on the whole cannot be understated.