Share thisWith the growing presence of zebrafish in labs internationally, participants at a recent workshop discussed action items for consistent care and use standards that are scientifically-based.
The popularization of zebrafish as a research model began in the 1980s when George Streisinger and his colleagues, working at the University of Oregon, published a series of methods that made it possible for people to use the zebrafish to conduct genetic screens. The model experienced tremendous growth after the initiation of large-scale mutational screens by several groups, and the commencement of the sequencing of the entire genome by the Wellcome Trust and Sanger Institute quickly followed. In the fall of 1997, the Trans-NIH Zebrafish Coordinating Committee formed to “…promote the use of zebrafish as a model organism for the study of vertebrate development and disease.”¹ In 2000, 256 established zebrafish labs were listed at the Zebrafish Information Network (ZFIN) website. There are 611 labs listed there today,² and this is just a small sampling of the labs worldwide. Given this level of activity (Table 1), it was inevitable that attempts to regulate the care and use of zebrafish in research would expand.
Brief Summary of Regulations Governing the Care and Use of Zebrafish to Date
The first national law to regulate animal experimentation was passed as an Act of Parliament in the UK—the Cruelty to Animals Act of 1876.³ There were no such federal laws in the U.S. until the Laboratory Animal Welfare Act was passed in 1966. However, these regulations did not cover fish and neither did the Improved Standards for Laboratory Animals Act, passed as part of the Food Security Act (Farm Bill) of 1985. This act did mandate the establishment of Institutional Animal Care and Use Committees (IACUCs) based on the Guide for the Care and Use of Laboratory Animals (the Guide), and with the establishment of the Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals in 1986, fish came under the general regulatory umbrella in the U.S. Given that “…“the PHS Policy is intentionally broad in scope and does not prescribe specifics about the care and use of any species, assigning the task to IACUCs and allowing for professional judgment,”4 there were still no explicit guidelines regarding the care of fish used in research.
These laws focused on providing humane care for animals. To date there are no generally recognized, scientifically-based guidelines for standardization of care in support of either fish health and “well being” or the requirements of reliable, reproducible research. Although most scientific articles do delineate the basic parameters of animal conditions maintained during the performance of the experiments, this does not mean that we then know how these parameters affected the research outcomes. For instance, one can report that the fish were fed Tetramin flake food three times per day and artemia one time per day but there is very little knowledge in the industry regarding, first, the contents of Tetramin and second, how those ingredients affect attributes of the fish including growth, behavior, and longevity.
This raises several interesting questions regarding what would constitute optimum care and best husbandry standards. What kind of research zebrafish is the goal in the end? This question can be illustrated by taking a look at two examples of human excellence: the long distance runner, and the weight lifter. Both excel in a limited area of expertise; both are “healthy” by definition within that area of expertise; both train under a scientifically developed regimen to reach their highest performance standards. But it is hard to imagine more diverse outcomes for individuals each approaching their “optimum” level of health and performance. It is conceivable, even probable, that there will be varying “types” of zebrafish required depending on the research involved. If guidelines are established to support, say, an optimum (or median) weight, will labs have to appeal to their inspecting authorities to modify mandated standard practices? How will the inspecting authorities be able to review and approve (or deny) such requests? The current level of knowledge and education in this area (in the United States, certainly) is in most cases not sufficient to support such decisions.