A Focus on Replacement

Abstract

FRAME’s ultimate aim is the elimination of the need to use laboratory animals in any kind of medical or scientific procedures — with the full name of the charity being Fund for the Replacement of Animals in Medical Experiments. Of the Three Rs principles described by Russell and Burch in their 1959 book, The Principles of Humane Experimental Technique, replacement is undoubtedly the most important (and perhaps the most difficult) of the Three Rs to implement in practice, over the other two ‘Rs’ — reduction and refinement. The concept of absolute replacement involves substituting the use of animals with valid non-animal alternatives — hence the name of our journal, Alternatives to Laboratory Animals (ATLA). Promisingly, all of the articles featured in this current double issue of ATLA focus on this One R, which I am sure Russell and Burch would be pleased about, in the 60th Anniversary year of their book publication. In a paper by various centres around the world that are concerned with the validation of alternative methods, an extensive plan of work that was carried out by a number of Japanese laboratories is described. The aim of the study was to assess the robustness of a human corneal epithelium model for use in the eye irritancy testing of substances. The study assessed the within-laboratory and between-laboratory reproducibility, as well as the predictive capacity of the method. This in vitro method is a potentially useful non-animal alternative to the use of rabbits in the Draize eye irritancy test, according to the recently revised OECD Test Guideline 405. In many cases, the culture of in vitro cells and tissue for use in various alternative methods and models is carried out in the presence of fetal bovine serum. A number of serum substitutes are available, and their use is encouraged due to the ethical concerns surrounding the collection of serum from the fetal sources. This is particularly important in our move towards a future that is completely independent of any animal use in research and testing. In a paper by Hesler et al., an analysis of human serum from individuals rather than pooled sources is described. This has particular relevance to the development of patient-specific therapies in the future. In an insightful study from Portugal and the UK, the value of non-human primate-based approaches was compared with the value of human-based in vitro and in silico approaches (i.e. replacement methods) in the study of major depressive disorder. The data showed that, in the majority of cases, the human-based research approaches (both in silico and in vitro) received more citations in subsequent human research papers than did NHP studies. In further support of this replacement-focused ethos, the Lush Prize recently opened for nominations for its 2020 Prize, which will be presented at the Award Event in May 2020. The Lush Prize awards efforts in Research, Training, Public Awareness and Lobbying that are relevant specifically to this One R. For the past 6 years, we have been honoured to publish details of the outstanding Prize winners here in ATLA, and we are pleased to be currently planning a Special Issue for early next year, featuring the winners of the last Prize. Still on the theme of replacement, the next issue of ATLA will feature a report on our autumn event, the FRAME Annual Lecture, on the topic of human in silico trials for drug safety and efficacy evaluation. This lecture, commemorating FRAME’s 50th Anniversary year, is being given by Professor Blanca Rodriguez from the University of Oxford, UK, and we are looking forward to hearing about the exciting developments in this area.