This scenario illustrates the difficulties faced by IACUCs that try to answer complex humane and ethical questions using established federal policies and guidelines. In my opinion, neither the question posed by the new member nor the answer of the established IACUC Chairman is controversial. This situation is a crossroads between a strict interpretation of federal standards and an expanded interpretation of a more progressive culture of humane science in animal welfare.

It is clear from both the literature and anecdotal accounts that a combination of subjective and objective observations and knowledge of the disease pathology must be applied to determine the level of pain and distress in an animal model. During my residency, in 1992, I had the opportunity to observe MPTP-treated rhesus monkeys. Their care and husbandry required a great deal of time and attention to detail. It was clear that these animals were debilitated. However, grading and 'treating' distress was more difficult than assessing pain and administrating analgesics. This animal model demonstrates one of the issues that still must be addressed by our federal regulatory agencies: how do you meet USDA category guidelines for animals that are clearly distressed, but will not benefit from the use of analgesics?

IACUCs have the freedom to evaluate any given procedure and categorize it as C, D, or E depending on the circumstances in which the procedure is employed. The MPTP-treated animals are distressed but receive intensive postprocedural care to address their condition. Although this care is not pharmaceutical, it is beneficial. Thus, they are not a good fit for Category C. Category D would seem to be the most logical, if postprocedural care is included in the list of agents used to address pain and distress.

Listing the animals in Category E, however, seems to be the most appropriate based on the USDA guidelines. Nevertheless, Great Eastern should be concerned about having nonhuman primates listed as Category E on an internet-accessible annual report. It is very possible that this issue will have a significant impact on the outcome of the discussion. The opinion of the USDA inspector may be beneficial since the school appears not to have had problems reporting these animals as category C in the past; change might not be required. However, more discussion between the biomedical research community and the regulatory authorities is necessary to address these complex issues.

Although the animals undergoing the gene therapy trial will be debilitated, their condition is not the result of a major surgical procedure. Thus, the protocol does not fall under the guidelines outlined in USDA Policy #14 (ref. 1). I agree with the Chair's interpretation of this policy.

This situation (and the many others like it) indicate that the USDA needs to revaluate its current policies. It is important that views like those expressed by the new IACUC member are given adequate time for discussion and consideration. I hope that more consideration will be given to animal care and its ability to address postprocedural issues.