Responses to the article noted below:
Environmental Enrichment of Laboratory Rodents: The Answer Depends on the Question

Toth, Linda A.; Kregel, Kevin; Leon, Lisa; Musch, Timothy I., Comparative Medicine
, Volume 61, Number 4 August • Pages 314-321

Commentary
By Karen Froberg-Fejko, VMD

I was disappointed by “Environmental Enrichment of Laboratory Rodents: The Answer Depends on the Question.” I expected a much-needed article championing reasons why it is essential to provide environmental enrichment for rodents. To my dismay, the authors chose to weigh in on the side of those who see little value in providing EE for rodents. I offer my opinion as a lab animal professional who sees the glass as half full as opposed to half empty.

First, we must ask: what is enrichment? Definitions vary widely; however, we must accept that the intention of EE is to allow the expression of normal species behavior. Although there are wide variations in rodent species and strains in the response to EE, the dominant behaviors in rodents such as sheltering, nesting, foraging, and gnawing are hard-wired. Attempts to allow what is normal should be offered and noted, specifically in the materials and methods sections of publications to provide evidence supporting introduction of EE.

Mice respond differently to different environments, and the difficulty for us is to identify individual needs. The number of rodents used in research can present an overwhelming, but potentially rewarding challenge to animal caretakers. Instead of adopting a herd mentality, we need to carefully evaluate what is going on at cage level. We must recognize that “one size does not fits all,” and I would argue that the responsibility of monitoring the effects of EE must be placed upon the human caregivers. I have confidence in the honest evaluation by daily caregivers because they have hands-on experience and know what is effective. I realize human emotion has a finite role in a study design; however, because we are discussing the needs of rodents, there is no black and white, so we must rely upon observations of what appears appropriate until more research in this area has been conducted.

In my travels, investigators frequently state that their mice “LOVE their shelters.” I interpret this to mean that the sheltering option they have provided to their mice is having a positive effect. I believe that it is essential to validate the effects of different types of EE upon rodents, but due to fiscal challenges and other priorities, it is not happening. If we have to wait to validate EE, then the rodents will suffer. In the interim, I believe we should rely on our caregivers and investigators to accurately monitor and note changes on different types of EE offered to rodents.

Second, who should determine whether enrichment interventions benefit or harm the animal or the science? The authors of the article maintain that EE should not be imposed unilaterally or arbitrarily by any stakeholders. I submit we have a responsibility to impose best practice stipulations since rodents are not covered by the Animal Welfare Act. Rodents are the most utilized animal species in research, and there are no federal regulations to protect them. This makes the GUIDE an essential document, promulgating best practices that address the needs of rodents as opposed to settling for minimum standards of care.

The authors state that complex and unexpected effects of EE on research variables are possible. No one would argue that research variables must be minimized in order to collect valid data, and this concern is magnified in a tox or GLP environment due to the nature of this type of research. There is concern in a tox and GLP environment that providing environmental enrichment could potentially affect the outcome of a study. However, not offering the opportunity for animals to express species-specific behavior through enrichment can lead to the most important variable of all, stress. A barren environment is stressful. Stress affects every physiologic function of the body, and we must strive to minimize it.

There are many uncontrolled variables within a research environment including personnel rotations, differences in HVAC and caging systems, monthly fire alarms, vibrations, and changes in light levels. We must recognize them as an inherent part of lab animal research. I have had dams cannibalize their young because of building renovations. This behavior dissuaded with the addition of EE. My point is that EE can be extraordinarily beneficial to achieve a desired outcome. There are numerous published research articles and plentiful testimonials supporting the positive effects of EE. But it is important to recognize that institutions must invest in EE programs and staff training. A successful EE program requires careful planning, controlled implementation, close observation and frequent re-assessment. Performance goals should be planned and close evaluation must be documented. A well-managed EE program will undergo continual assessment. It requires time, money and commitment.

There is no doubt that the article has generated discussion surrounding the implementation of EE for rodents. It is our responsibility to stay close to ongoing research and support more studies in the future. Providing EE is good animal welfare, and we must strive for the delicate balance of good data collection conducted in the least stressful environment. I wanted to share a comment by an anonymous author which emphasizes the importance of EE: “For those who pledge to take responsibility for the welfare of animals and vow to use scientific knowledge and skills for the advancement of medical knowledge, the wise composer of this oath sees no conflict between relieving animal suffering and advancing science. Indeed there is none!”

The Standardized Environment Must Be Enriched
By Emily G. Patterson-Kane, Ph.D.

Toth et al (2011) musters a number of arguments against willy-nilly environmental enrichment. And my issues with them, spelled out below, are more a matter of attitude than fact. But when it comes to environmental enrichment, attitude may be more important than many people realize….

1) Environmental enrichment is not well-defined

No abstract concept is uniformly defined. Environmental enrichment aims to create environments for animals that don’t suck. Each person proposing a definition has their own idea about what sucks the most about the captive environments they are working with, and honestly, there is a lot to choose from. Thus, the diversity in definitions reflects just how badly environmental enrichment is needed. (I and quite a few others are not, as it happens, a fan of the term “environmental enrichment”. I am, however, a huge fan of designing captive environments that don’t suck.)

2) Environmental enrichment can take many forms

Because there are many deficits, there are many solutions; we don’t always know what they are, so we have to try different methods before we strike the right one. Even a solid floor can be enriching to an animal that previously lived on a wire floor. Hanging wire-floored cages were the very model of scientific standardization, as long as you didn’t care that your rats were miserable, had sore feet, underdeveloped brains and compromised immune systems. It may seem like a small gain now, but environmental enrichment as a concept and rallying cry played a large part in achieving it, for the benefit of animals and science. (Actually, there are still a substantial number of labs that cling to their hanging cages, out of a sheer unwillingness to adapt to the new standard of care and shift their baseline.)

3) Varied housing impairs standardization

“Enrichment” is essentially an argument for a transitional period during which we determine the optimal environment, moving us from housing that causes suffering and impairs scientific validity to housing that supports good welfare and good validity. I have to say that most areas of research suck at standardization, so it is entirely a valid area of concern. I once read pretty much every study that used an open field with rats, and the only ones that used a field of the same size, shape and color seemed to be the ones actually using the same piece of equipment. The number of studies that even report home cage parameters are negligible to this day. I also read almost every study that ran a rat through a Hebb-Williams maze, an admirably standardized piece of equipment. So standardized, in fact, that we haven’t the slightest idea what it actually measures—and even more dangerously, we think we do. (If it measures intelligence-or some- euphemism-for-intelligence, how does extreme hunger or foot shock make animals more “intelligent”?)

4) Evidence that enrichment is beneficial is mixed

Evidence of gravity is mixed if you stand near the edge of the Grand Canyon and there is a good updraft. Serious and learned reviews since at least the 1970s have shown that barren housing impairs nearly all of the structures and functions of an animal (yes, even a domesticated one) and thus its ability to serve as a model of normal function. The only real question is: how do we fix this?

5) Housing type effects research outcomes

Well, duh. Housing is important and housing is part of the research model. The role housing plays is 1) it makes the animal normal except in an area where deviations from normality are an explicit part of the model, 2) it occurs in a manner that is well-defined and reported to the point of allowing replication, 3) housing is standardized to the extent that the need for unnecessary replication is minimized. If housing is not a large part of the model, minor to moderate changes should not have major outcomes unless the model is poorly understood, the model has poor validity, or standard conditions introduce major abnormalities. (I am not suggesting making changes arbitrarily. But I am rejecting any notion that they should not be made at all just because they can affect your data.)

Conclusion
Standardization cannot be considered in isolation from validity. And, I would argue that in most cases, animal research has disappeared up its own uniformity and is now rather unwilling to come out. Normal animals make valid models, and barren environments make abnormal animals. Thus, the standardized housing for any species must be free from any factor that causes deviations from normal function. The standardized environment must be enriched.

And, if we do not yet know exactly how to properly house every kind of animal we use, perhaps it is damn well time we figured it out. The authors state that developing enrichment that prevents stereotype is “a complex task”. And giving enrichment to large colonies of animals can be challenging. Well… tough. Using these animals carries with it the absolute duty to use the most effective and humane methods. If we admit ourselves incapable of knowing what these methods are, then maybe that is the very first research question we should answer. Do not pass go, do not collect two hundred dollars. If we are merely unwilling to ensure the task is carried out… well, expect no sympathy.

That said, we need to admit that this is a difficult time for many researchers. We do not yet have an array of accepted, proven enrichment cages suitable for standardization. Baselines need to be shifted, which is not an easy task and can’t be done every time someone wants to toss a new toy in the cage. And yes, standardization has become harder to achieve. It is reasonable for researchers to require that enrichment of proven worth be implemented according to a scientifically responsible protocol that is respectful of the primary research goal—that being the reason everyone is there in the first place.

Why is this not always happening? Perhaps it is because a lot of researchers have dug their heels in and are essentially not allowing enrichment, even when it does meet these criteria. Thus technicians who are with the animals all day want to sneak in any small enrichment they can. Administrators make rules that you must enrich, because enrichment is good and they want to make sure that you  do it. You see, if you want a careful and measured—a scientific—approach, when you do finally make a change, it needs to be large, proactive and effective. Not just a toy, but a whole new cage type, or room, or building. “Adequate” is not enough. You have to be willing to embrace and create a new standard. Only then will you be accepted as the leader, the boss, the rule-maker when it comes to working out how to get there.

Volume 10, January 2012

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