2. DEFINITIONS

2.1. Refinement

Russell and Burch (1992) defined Refinement as:
Any decrease in the incidence or severity of inhumane procedures applied to animals (p 65). Its object is simply to reduce to an absolute minimum the amount of distress imposed (p 134).

Balls et al. (1995), Buchanan-Smith et al. (2005) and Russell (2005) extended this definition by emphasizing that Refinement enhances the subject's well-being.

In the present review, the term "refinement" is used for:
Any modification in the housing and handling practices of animals that

• reduces or eliminates the subject's distress response to a specific condition (e.g., permanent single-housing) or situation (e.g., enforced restraint during a life-threatening procedure), and/or
• enhances the subject's well-being.

2.2. Distress

In this review, distress is interpreted as:
Inability to adapt to a condition or to a situation that induces an alteration in the subject's physiological and psychological equilibrium.

The following gestures and behaviors are taken as indicators that a nonhuman primate is distressed:

• Retreating to an upper back corner, crouching in the back of the cage, alarm vocalizing, fear-grinning, aggressive yawning, and self-biting in response to a potentially life-threatening situation (e.g., personnel approaching the cage). The subject is in a state of anxiety because a harmful event may happen, and frustration because there is no option to escape (Figure 2).

Figure 2 Rhesus macaque Betty is quasi-cornered as personnel approach her cage. She responds with fear, anxiety and defensive aggression to this distressing situation. Note that Betty has lost part of her hair [alopecia] as a result of compulsive hair-pulling.

• Fear-grinning, struggling, and urinating in response to being forcefully restrained. The subject is in a state of fear because an uncomfortable or painful event is about to happen, and frustration because there is no option of escape (Figure 3).
  
  

Figure 3 Rhesus macaque Ella is subjected to enforced manual restraint during routine blood collection. Ella exhibits signs of intense fear, indicating that she is distressed.

• Self-biting. This behavioral pathology occurs under the following circumstances:
  a) Stereotypic self-biting
  The subject is extremely bored, shows no signs of excitation, and repeats the same movement patterns over and over again - for example, circling, pacing, bouncing or somersaulting - interjected by sham biting of specific body parts (Figure 4a,b). This behavior often goes unnoticed because there is no visible abrasion or laceration, and the subject usually does not show the behavior when there is a distraction, for example when personnel is present.

	Figure 4a,b This juvenile male rhesus macaque shows a behavioral distress reaction to permanent confinement in a barren cage. He bit his upper arms, wrists, and thighs 636 times during a 60-minute video recording. Each "attack" lasted from a split second to as long as six seconds.

b) Compulsive self-biting
The subject is extremely frustrated - with high emotional arousal, e.g., shaking, intense staring, piloerection - for example, when fear-inducing personnel approach the cage, with the subject having no option to escape or attack. The animal will predictably bite specific parts of his or her body, for example always the right wrist or always the left upper thigh. This leads to noticeable abrasion over time - first local alopecia, followed by mild inflammation - but may also result in serious injuries. Typically, an animal self-inflicts lacerations of the same body part several times on different occasions (Figure 29a,b), often necessitating the amputation of the repeatedly injured limb.
Self-biting and other forms of self-injurious behaviors also occur in human primates in association with depression, anxiety and incarceration (Scott and Gendreau, 1969; Sluga and Grünberger, 1969; Wells, 1974; Bach-Rita, 1974; Yaroshevsky, 1975; Villalba and Harrington, 2003).

• Hair-pulling. The subject pulls single hairs or tufts of hair from his or her own fur or from the fur of a cage mate, manipulates the hair with the fingers, lips and tongue, chews the hair and finally ingests it. Hair-pulling often leads to localized alopecia (Figure 2).
  Hair-pulling is also relatively common in humans (Ko, 1999). It is classified as a mental disorder [trichotillomania], (Hallopeau, 1894), associated with clinically significant distress (American Psychiatric Association, 1987) depression, frustration, boredom, or other emotional turmoil (Christenson and Mansueto, 1999). It stands to reason that hair-pulling in nonhuman primates is also a sign of distress.
    
• Depression in response to being harassed by the cage mate. The subject consistently avoids the partner and spends most of the time crouching in a corner of the cage (Figure 50).
  In this review, repetitive gestures (e.g., saluting), behaviors (e.g., ear-pulling) and movements (e.g., pacing) without obvious function [stereotypies] are not being considered as unequivocal indicators of distress, even though they reflect species-inadequate housing conditions.

2.3. Well-Being

In this book well-being is defined as :
A state of ease in which the subject's needs for survival are met.
For nonhuman primates in professionally accredited research facilities, the physiological needs are usually met while the behavioral needs for survival are often not addressed. This review, therefore, focuses on well-being that is derived from the performance of behaviors that would be crucial for the subject's survival in the wild.

3. SIGNS OF REFINEMENT

Refinement is successful if it:

• buffers distress as reflected in a reduction or elimination of self-biting or hair-pulling;
• buffers distress as reflected in the reduction of fear, anxiety and frustration;
• enhances well-being by providing species-adequate opportunities for the expression of behaviors that have a distinct survival value:
  a) being with and interacting with another conspecific (social behavior);
  b) searching for, retrieving and processing food (foraging);
  c) accessing high refuge areas (vertical flight response).
  
  Manipulating objects or toys, gnawing inedible objects, and looking into mirrors and monitors have a temporarily entertaining effect, rather than survival value. Since it is questionable that the performance of such behaviors enhances well-being, they have not been included as signs of refinement in this review.

Figure 5 Nonhuman primates such as baboons have a biologically inherent need to be in the company of conspecifics. Photo by Annie Reinhardt.

4. DISTRESSING CONDITIONS