Jeffrey Lohmiller Senior Director Taconic Biosciences
Six Pillars That Can Help You Choose the Right Approach
Health standards have always played a critical role in the use of research lab animals. Evolving industry needs and advancements in research and the animals that support it have made health standards a more prominent consideration. The complexity of biomedical research and the sophistication of animal models make selecting and maintaining models at the right health standard essential.
Sign of the Times
One trend influencing animal health standards is the growing use of immunodeficient and genetically engineered models. It’s increasingly common to use models with multiple cell deficiencies to study how they impact disease development; but a more immunocompromised animal is less tolerant of opportunistic organisms and confounders that can alter its immune response. Similarly, genetic modifications to a model may alter or reduce the immune system’s effectiveness. As a result, models with a more restrictive health status are increasingly desired.
Certain therapeutic areas are impacting the health standards evolution. Immunology research is on the rise and often requires animals at a more restrictive health status, free of an increasing number of organisms that could affect the immune system and make study results tougher to reproduce. In oncology research, the increasing use of models in which human cells or tissues are present is necessitating animals with more precise health standards as well.
Heightened attention on the role of the microbiome in disease development, nutrition, drug metabolism, etc. is another factor influencing animal health standards. The pharmaceutical and nutrition industries are expending great resources to understand the organisms that form the human gut flora and how they impact immune response and disease development. The potential link between the microbiome and numerous disease states— including autoimmune diseases, diabetes, heart disease and cancer— is impacting the animal health standards researchers require. A desire to understand the microbiome’s effect on drug metabolism, toxicity, and drug-to-drug interactions also impacts animal health requirements, as it’s becoming desirable to obtain models in which the microbiome is controlled through initiating studies using models of the ultimate restrictive health standard, germ free.
As new findings emerge about bacteria and other organisms, they also influence animal health standards. Segmented filamentous bacteria (SFB) was once considered innocuous, but now there is growing evidence it can alter the immune system. Knowing whether SFB is present or absent in a model allows the investigator to control for this variable, making results more reproducible. Likewise, while there is no consensus about the impact of Proteus on disease, because it is known to be a swarming bacteria that quickly overgrows culture plates, more researchers are requesting its absence.
The 6 Pillars of Health Standard Selection
For these reasons, the health standard is an increasingly important criterion in choosing a research animal model. The following six pillars can effectively guide the selection of the right animal health standard for a particular study.
- Study Objective. For an infectious disease study, an investigator may want to start with a control group of animals free of the bacteria being studied, whereas for therapeutic areas known to be impacted by immune response, such as immunology, oncology, and inflammatory disease, a more restrictive heath status may be preferred. When conducting studies focused on the role of the microbiome, it may be useful to choose a health standard that precisely defines the organisms present.
- Study Timeframe. For longer-term studies, the ability to obtain animals of a consistent health standard over time can improve reproducibility of results. Consistent health standards over the long term require the lab animal breeder to use well-defined breeding and husbandry procedures and perform rigorous health testing and monitoring.
- Study Environment. The facility where animals will be housed and studied is an important consideration, since a more restrictive health standard poses more requirements on the infrastructure and operational stringency. For instance, space constraints make it difficult to segregate animals from different vendors, which is necessary for maintaining one or more strains at a higher health standard. Isolators, individually ventilated cages, sterilized materials, stringent husbandry practices, and regular health testing can help lab staff maintain animals at a more restrictive standard.
- Budget. The budget can impact the facility’s ability to employ sufficient practices to maintain more restrictive health standards consistently, as well as the appetite for purchasing models at a higher status. Animals bred under higher health status conditions are more costly to produce and available in smaller supply, so it is necessary to balance health standard, cost, and availability in choosing the best model.
- Stress. The level of stress the animal will experience during the study— from radiation, invasive surgery, dietary restrictions, exposure to infectious agents, or transportation—can influence the choice of health standard. The greater the stress, the more likely the model will need to be free of commensal or opportunistic organisms.
- Breeding Partner Capabilities. It is generally best to choose an animal model from a broad portfolio of well-defined models available at various health standards, supported by well-documented data about the presence or absence of organisms. If the breeder offers a model with a particular genetic background on multiple health statuses, the investigator can continue a long-term study with a more consistent model, only updating the health standard if needed. Expect the breeder to demonstrate well-defined quality control processes and procedures and rigorous health testing, and to provide not only a list of excluded agents, but a report of all agents tested for at all locations.
As biomedical research grows more complex and animal models become more sophisticated, animal health standards will become more important in the model selection process. In selecting the right health standard for a model, investigators can be guided by six pillars: the study objective, study timeframe, study environment, budget, stress level of the animal, and capabilities of the breeding partner, particularly with respect to portfolio breadth, availability of a single model at different health statuses, and rigor of the breeding and health testing processes. By understanding how the health standard may impact the model and the study results and by keeping these six pillars in mind, investigators can select the best model for each research endeavor.