Government evaluates distress of laboratory animals

The announcement last summer that the USDA-APHIS was considering changes to animal welfare regulations to promote the humane treatment of laboratory animals was, not surprisingly, received with mixed responses.

At issue are "gaps" in regulations derived from the Animal Welfare Act, such as the failure to clarify "distress," a term used throughout the regulations, unlike "pain," which is defined. Another point of contention: APHIS is considering modifications to the classification system used by institutional animal care and use committees (IACUC) for reporting the number of laboratory animals used annually in experiments, research, and teaching.

Debate over the adequacy of the guidelines promoting laboratory animal welfare has been brewing for years, according to Dr. Ron DeHaven, deputy director of APHIS Animal Care. He recalled a forum in 1995 on responsibility in medicine and research where "several hundred people" discussed the possibility of changing the government's classification system because it failed to provide substantive information.

Current federal regulations require that when an animal is used in a painful and/or distressful experiment, researchers must treat the animal with pain-relieving medications when doing so won't interfere with research results. In addition, any procedure likely to cause pain and/or distress in an animal must be preapproved by the IACUC after the researcher has found alternative test methods unworkable.

Although the regulations define a painful procedure for laboratory animals as "any procedure that would reasonably be expected to cause more than slight or momentary discomfort in a human being to which that procedure is applied," there is no such guidance for identifying or alleviating distress.

"We have focused largely in the past on the word 'pain' and largely ignored the word 'distress,'" Dr. DeHaven explained. "We have ensured that there is, to the extent practical, minimization of pain and consideration of alternatives to painful procedures, but we haven't given minimization of distress equal due. We're trying to remedy that."

Distress is an adverse condition resulting from an unrelieved stressor. The causes and signs of distress vary considerably with the animal; a complex mix of environment, personality, and responses to past stressful situations determines much of an animal's reaction.

This past July, APHIS announced it was considering changes to the welfare regulations, and asked the public a number of questions, including: Would a definition of "distress" help researchers and facility staff better identify and minimize distress in test subjects? Because professional standards have changed since the classification system was introduced nearly 30 years ago, would an updated system allow researchers to more accurately predict pain and distress experienced by laboratory animals? And, in addition to prospective reporting of all pain- and/or distress-causing experiments, as is the case now, should research facilities begin retrospective reporting to show how much pain and/or distress an animal experienced before and after an experiment?

APHIS has offered a working definition of "distress" that reads: "Distress refers to a state in which an animal cannot escape from or adapt to the internal or external stressors or conditions it experiences, resulting in negative effects on well-being."

More than 2,500 individuals and special interest groups replied to the agency's request for comments. The AVMA, National Association for Biomedical Research, and American College of Laboratory Animal Medicine are representative of groups that believe additional federal guidelines will not necessarily lead to improved treatment of laboratory animals. The Humane Society of the United States, however, argues that the classification system is significantly flawed, and has recommended comprehensive improvements.

There are those in the biomedical research community who worry that anything more than an academic explanation of distress, and minor adjustments to the classification system, will add to their regulatory burden by requiring additional reporting of a complex condition for which there is little agreement. As it stands now, NABR and ACLAM say the current reporting requirements exceed Congress' intent in the Animal Welfare Act.

For years researchers have sought to minimize distress in laboratory animals without the aid of a government definition, according to Barbara Rich, executive vice president of NABR. The association represents more than 350 public and private universities, medical and veterinary schools, teaching hospitals, voluntary health agencies, and pharmaceutical companies. Facilities have relied on the judgment of staff veterinarians and other personnel to identify and alleviate distress in animals on a case-by-case basis, she said.

"We've been using the term 'distress' all along," Rich explained. "It's not a new concept to try and limit distress, because we consider distress as likely to produce unwanted and maladaptive reactions and responses from an animal, so we want to avoid it."

Implemented in the early 1970s, the USDA system classifies laboratory animals into one of three categories based on the amount of pain and/or distress likely to be experienced during a procedure: little or no pain and/or distress, and pain-relieving medications are not used; might experience pain and/or distress, and pain-relieving medications are used; and unrelieved pain and/or distress. Experiments falling into the latter two categories require IACUC approval.

According to a government report, of the 1,217,998 animals used for research in 1999, only 107,523 were relegated to the unrelieved pain and/or distress category.

But according to the HSUS, the lack of federal guidelines for identifying and relieving distress has led to a misrepresentation of laboratory animal suffering. Although acknowledging gains in minimizing pain in animals used for research and testing, the HSUS believes distress has largely gone untreated.

"The current statistics are so poor that they're not revealing. They don't give you an accurate picture of what's happening in animal research," said Martin Stephens, PhD, vice president of animal research issues at the HSUS. Dr. Stephens believes research facilities have too much latitude in how they alleviate distress in the animals they use.

Dr. Stephens said that rather than revealing the extent of pain and distress experienced by animals each year at research facilities, the current system more accurately reflects whether an anesthetic was used to reduce pain during the experiment. The system fails to provide data about pain and distress experienced after a procedure, he said. As a solution, the HSUS has proposed an expanded system that categorizes pain as minor, moderate, and severe. The model is similar to those employed by countries such as Canada, where categories include the degree of pain as well as examples of procedures causing various degrees of pain.

NABR, the AVMA, and ACLAM do recognize deficiencies in the current classification system—the absence of a category for therapeutic agents other than anesthetics and analgesics to relieve disease-induced conditions, for example—but reject the HSUS model as too subjective. The groups question whether substantial changes to the regulations would actually enhance laboratory animal welfare, or merely produce more paperwork for researchers.

NABR and ACLAM have, instead, proposed to APHIS their own closely related systems intended to simplify reporting. The ACLAM model, supported by the AVMA, proposes the following categories: no, minimal, or momentary pain/and or distress, and pain/distress-relieving measures not used; pain and/or distress is prevented by anesthetics, analgesics, or other agents or techniques; and animals experience pain and/or distress with or without pain-relieving agents or other techniques.

To better recognize distress in laboratory animals, the groups recommend that research facilities and IACUC refer to peer-reviewed scientific literature and such sources as the 1992 National Research Council/National Academy of Sciences paper "Recognition and alleviation of pain and distress in laboratory animals."

According to Dr. Mike Kastello, a member of ACLAM's board of directors, the debate over the need for additional regulations exposes a fundamental misunderstanding about how animals are used in research. "It's not a situation where anything goes, just because there's not a rule against it," he said, explaining that a distressed animal is not in a condition to yield useable scientific data. The goal of scientists in biomedical research is to have as normal a situation as possible, Dr. Kastello said.

APHIS is reviewing the more than 2,500 comments and is expected to make an internal decision on how to proceed by June. The agency is quick to note its unwillingness to impose additional regulatory requirements if there isn't a direct correlation with improved animal welfare.

"To the extent that there is an additional burden imposed on the biomedical research community, it's got to be justified by some return on that investment, and preferably that return is going to be improved animal welfare. And if there's not, then I don't think that we should go forward," Dr. DeHaven said.

Even modest changes in the regulations will be counted a small victory by the HSUS, which has an ambitious goal of ending pain and distress in laboratory animals by 2020. Through increased government oversight, the HSUS hopes to push the research community toward developing more alternatives to experimenting on animals. The United States, Dr. Stephens points out, lags behind other developed countries in funding for alternative research methods.

Those hopes of the HSUS were bolstered in September with news that the USDA had agreed to start the process for regulating laboratory birds, rats, and mice—the latter two account for more than 90 percent of the animals used in research—as part of an out-of-court settlement with an animal rights group.

NABR and others had unsuccessfully opposed the settlement, but APHIS was then delayed at least a year from beginning any formal rule making by a last-minute amendment in an agriculture appropriations bill (see JAVMA, Dec 1, 2000, page 1607).

Dr. DeHaven said lately he's been accused of caving in to animal rights groups. He acknowledges that the distress issue and lawsuit settlement are separate issues, but "no one is naïve enough to suggest that we can change one without having a dramatic impact on the other."

"Whatever we do with regard to pain and distress, we have to do it with conscious knowledge that, in fact, it could have far greater impact if we eventually were to regulate rats, mice and birds," he said. "Ultimately, we have to do what we think is the right thing for the right reasons, not because any particular group or individual wants it."