What Price Mice?

Because they are dedicated to the elimination of the use of all animals in medical experiments regardless of the human cost, animal protectionist groups have moved vigorously to seek the assistance of the federal courts. Inspired by their taste of success in other areas, these groups are now attempting to make the use of mice, rats, and birds in biomedical research prohibitively expensive and extremely burdensome. This raises the distinct possibility that such research is in danger of experiencing the strangulation by red tape that is threatening medical research in the United Kingdom.^{1 - 3}

The latest effort by animal protectionist groups is remarkably shrewd. In 1998 a recently established group calling itself the Alternatives Research and Development Foundation (ARDF), functioning under the umbrella of the American Anti-Vivisectionist Society, filed a petition for rulemaking with the US Department of Agriculture (USDA) asking that the USDA cancel the longtime exemption of mice, rats, and birds from its animal care regulations.⁴ The USDA published the petition in the Federal Register asking for public comment, but also presented a lengthy discussion of the USDA's own serious objections to the demands of the petitioners.⁵ Rather than await the USDA's decision on its petition, the ARDF moved to force the issue by filing suit in federal court claiming that the secretary of agriculture had arbitrarily and capriciously excluded mice, rats, and birds from the definition of "animal" in the Animal Welfare Act.⁶ Joining the ARDF as plaintiffs were a company describing itself as a manufacturer of laboratory tests to replace animal testing and a Beaver College student who claimed she had standing to sue because she had suffered an "aesthetic injury" from observing laboratory rats who had allegedly received "inadequate housing, water, food, and veterinary care."⁶

The separate attempts in August and September 2000 by the National Association for Biomedical Research (NABR) and Johns Hopkins University to become parties to the litigation were thwarted when, in a sudden reversal of position, the USDA joined with the plaintiffs to obtain stays of the court proceedings while they engaged in private settlement negotiations.⁷ This meant that the court would not rule on the intervention motions of the NABR and Johns Hopkins, and that the settlement negotiations could proceed behind closed doors with no representative of research institutions present. Other government agencies with important interests in the use of rodents in medical research were not consulted by the USDA or admitted to the settlement negotiations. These included the National Institutes of Health, which has allocated billions of taxpayer dollars for biomedical research; the Food and Drug Administration, which has an interest in the use of rodents in toxicity testing of new pharmaceuticals; the Centers for Disease Control and Prevention, which uses rodents and birds in epidemiological investigations; and the US Department of Defense, which must use rodents in tests to combat bioterrorism and biowarfare.

The settlement negotiations culminated with a complete capitulation of the USDA to the demands of the plaintiffs.⁸ The worst fears of researchers were realized when the USDA agreed to grant the plaintiffs' petition for rulemaking to amend the USDA regulation excluding birds, rats, and mice from coverage under the Animal Welfare Act. The filing by the parties on September 28, 2000, of a voluntary stipulation of dismissal without prejudice ended the litigation for now, and the government agreed to pay the plaintiffs $18 000 in attorney fees. Not unexpectedly, research scientists are asking, "What goes on here?"

Fortunately, not all is lost. The USDA chose to ignore the many entreaties expressed by biomedical organizations, university presidents, and scientists not to engage in an out-of-court settlement. Congress, however, did react to the disastrous settlement by adding language to the fiscal year 2001 Agricultural Appropriations bill prohibiting the USDA from spending any part of its appropriations to change the regulatory definition of "animal" in the regulations promulgated under the Animal Welfare Act. President Clinton signed the bill into law on October 28, 2000.⁹ Since the legislative "fix" was inserted into an appropriations bill, it is in effect for only 1 year. The research community now must engage in a concerted effort to obtain a permanent solution from Congress. Congress and the public must understand the dire human, scientific, and economic consequences of inhibiting the use of mice and rats in biomedical research and permitting the vociferous animal rights groups to set the national agenda in biotechnology.

The humane care of laboratory animals was a concern of research institutions well before the Animal Welfare Act became law. In 1963 members of an Animal Care Panel working in the field of laboratory animal care authored the first Guide for Laboratory Animal Facilities and Care.¹⁰ These standards evolved into the Guide for the Care and Use of Laboratory Animals, the principal set of standards upon which the Public Health Service Policy on Humane Care and Use of Laboratory Animals is based.¹¹ The Public Health Service policy covers mice, rats, and birds and requires the filing of an Animal Welfare Assurance that commits research institutions to a responsible program of animal care. Moreover, a rigorous, expert reviewer–based accreditation program applying the same Guide for the Care and Use of Laboratory Animals standards is carried out by the Association for Assessment and Accreditation of Laboratory Animal Care International, a nonprofit accrediting organization that conducts in-depth, on-site evaluations of animal care and use programs—including rats, mice, and birds.¹²

Animal rights groups argue that if research institutions are already providing humane care to their mice, rats, and birds, application of the USDA regulations would not be burdensome. This is demonstrably not true. Although mice and rats always have been vital to medical researchers, there has been an enormous increase in their numbers because of the rapid success of the Human Genome Project and the consequent ability to develop transgenic mice that model the symptoms of human diseases. Application of the USDA regulations to the accelerated growth in the numbers of these species would divert scarce grant funds from actual research use, distract researchers from their scientific work, and overload them with documentation requirements that would not improve the humane care of mice, rats, and birds. For example, the regulations would require researchers using these species to keep records of the numbers simply being bred and held for later use in teaching and research. The rate at which these species reproduce makes them valuable for research purposes but keeping track of their daily census is an overwhelming task. The NABR estimates that there are approximately 25 million mice and rats used in laboratories in the United States.¹³ It is one thing to keep track of the offspring of a colony of primates and quite another to keep up with, for example, the litters of the 42 000 mice currently in the care of researchers at my own institution, Johns Hopkins University. Morover, this number is anticipated to increase exponentially as the need for transgenic mice increases.

Application of the USDA regulations to mice, rats, and birds also would require reports and documentation of the numbers of animals used in teaching or research involving no pain, distress, or use of pain-relieving drugs, including those undergoing routine procedures such as injections, tattooing, and blood sampling. This, too, would be an enormous time and financial commitment. Other USDA regulations already require that records be kept of the numbers of animals involved in experiments, teaching, research, surgery, or tests involving accompanying pain or distress and receiving appropriate anesthetic, analgesic, or tranquilizing drugs, as well as those animals for which the use of appropriate anesthetic, analgesic, or tranquilizing drugs would have adversely affected the procedures, results, or tests. More documentation requirements flow from the USDA regulations' demand for an explanation of the procedures producing pain or distress in these animals and the reasons such drugs were not used.

Genetic research promises to bring new therapies to alleviate human suffering from the acquired immunodeficiency syndrome, Parkinson disease and other neurological diseases, and virtually all other human and animal diseases. However, the promise of this new era of medical research is highly dependent on the ready availability of mice, rats, and birds. What clearly stands out is that there are no substitutes for their use as transgenic models. It is inescapable that if the benefits of the billions of dollars invested in genetic research are to be realized, the "price" of using mice must remain within the reach of medical scientists and bureaucratic impediments must not discourage, delay, or halt the march to eliminate the many disease scourges of humankind. This can be accomplished if a concerted effort is made by the nation's scientific societies, universities, and research institutions to seek a permanent legislative solution. A simple one comes to mind: laboratories coming under the jurisdiction of the Public Health Service should be exempted permanently from regulations promulgated under the Animal Welfare Act so that the one governmental agency with expertise in animal experimentation is responsible for the humane care of all laboratory animals. Imposing the absurd documentation requirements of the USDA on mice, rats, and birds, regulations that are ill-suited to these species, may serve the ends of animal rights advocates, but they most certainly do not serve the needs of patients or the public health.