NORFOLK, Virginia––Seven years after National Institutes of Health director Francis S. Collins and his predecessor Elias Zerhouni heralded a turn away from animal testing, U.S. laboratories are using more animals than ever before, especially mice and rats, say People for the Ethical Treatment of Animals investigators Justin Goodman, Alka Chandna, and Katherine Roe.
Goodman, Chandna, and Roe made their case in the February 25, 2015 online edition of the Journal of Medical Ethics, based on an analysis of “use of all vertebrate animals by the top institutional recipients of National Institutes of Health research funds over a 15-year period. These data show a statistically significant 72.7% increase in the use of animals at these U.S. facilities during this time period—driven primarily by increases in the use of mice,” they wrote, in a peer-reviewed article entitled “Trends in animal use at U.S. research facilities.”
British, Irish, & Bayer data
British Home Office, Irish Department of Health, and Bayer AG data on animal testing have shown similar trends.
The number of scientific procedures using animals in the United Kingdom increased from 2.71 million in 1995 to 4.12 million in 2012, according to data published by the Home Office in July 2014.
The number of animals used in Ireland zoomed from 38,000 in 2005 to 280,000 in 2010, the Irish Department of Health acknowledged in February 2012.
Bayer AG used 38,811 animals in 1989, according to numbers published in 1991 by the Investor Responsibility Research Center, but the IRRC data did not include rats, mice, and birds. In 2013, the German-based organization Doctors Against Animal Experiments announced in May 2014, Bayer AG “consumed, according to their own publications, more than 147,000 animals. In addition more than 23,000 animals were used by externally commissioned institutes.”
Rats, mice, fish and birds are believed to be included in the 2013 Bayer AG total. If these species were 90% of the animals used in both 1989 and 2013, Bayer AG use of animals would have declined by 50% in 24 years––but Goodman, Chandna, and Roe argue that while use of species covered by the U.S. Animal Welfare Act has dropped since tracking requirements were instituted 41 years ago, use of rats, mice, fish and birds has markedly increased.
Reductions of animal use in traditional areas
Far fewer animals are used in certain areas, such as teaching and product safety testing. These categories of animal use formerly used by far the greatest numbers of animals per experiment. Because of the reduction in animal use in teaching and product safety testing, the average number of animals used per experiment may now be lower than ever before since numbers have been tracked. At the same time, the total number of animal experiments appears to be steeply up, according to the Goodman, Chandna, and Roe findings, resulting in a net increase in overall animal usage.
“A number of countries have reported increased animal use in recent years,” Goodman, Chandna, and Roe wrote. However, “In the U.S.—one of the world’s largest users of animals in experiments—a lack of published data on the species most commonly used in laboratories (e.g., mice, rats and fish) has prevented such assessments.
“Some analyses,” Goodman, Chandna, and Roe continued, “suggest that there has been sizeable growth in animal use over the past several decades due to increased use of genetically modified mice, while others claim that U.S. animal use has decreased by as much as 50% over the past 25 years.
Data from open records requests
“While the Animal Welfare Act animal use reporting requirements make it impossible to reconcile these figures due to the exclusion of key species,” Goodman, Chandna, and Roe acknowledged, “institutions funded by the National Institutes of Health are required to submit a report that includes the average numbers of all vertebrate animals,” including mice, rats, birds, fish, reptiles and amphibians, “held and used for experimental purposes. The NIH does not analyze or publish these data, but the documents can be requested through federal and state open records laws.”
Goodman, Chandna, and Roe estimated animal use from the “approximate average daily inventory” of vertebrate animals reported by each NIH-funded institution “in the Animal Welfare Assurances filed at least once every four years by these institutions.
At the “top 25 largest public and private recipients of NIH funds for 2011,” Goodman, Chandna, and Roe found, total animal use increased over fifteen years from an average of 74,619 animals per year to an average of 128,846.
98.8% of lab animals not covered by Animal Welfare Act
“These patterns contradict industry claims of reduced animal use,” Goodman, Chandna, and Roe wrote, “but are consistent with international trends in experimental use of animals in recent years that show an increased use of mice and, in some cases, fish, while reporting declines in the use of cats, dogs, primates, rabbits, guinea pigs and hamsters.”
Perhaps most significantly, Goodman, Chandna, and Roe found that “98.8% of the animals at the institutions were not covered by the Animal Welfare Act. That experimentation on the most widely used animals—mice, rats and fish—is subjected to substantially less independent oversight may a contribute to the significant increases in their use.”
“We all drank the Kool-Aid”
Lamented Elias Zerhouni, who headed the NIH from 2002 to 2008, in a 2013 address to his former NIH colleagues, “We have moved away from studying human disease in humans. We all drank the Kool-Aid on that one, me included.”
Because of the relative ease of doing studies using genetically modified mice, Zerhouni warned, disease researchers have become excessively reliant on animal data.
“The problem is that it hasn’t worked,” Zerhouni said. “It’s time we stopped dancing around the problem. We need to refocus and adapt new methodologies for use in humans to understand disease biology in humans.”
“State of denial”
Zerhouni spoke about six months after Stanford Institute for Immunity, Transplantation & Infection director Mark M. Davis, Ph.D., wrote in the December 19, 2008 edition of the peer-reviewed scientific journal Immunity that, “We seem to be in a state of denial, where there is so much invested in the mouse model that it seems almost unthinkable to look elsewhere.
“The mouse has been incredibly valuable,” Davis acknowledged. “That’s part of the problem. In humans it often takes years to find out anything. There are a lot more regulatory, financial and ethical hurdles,” but “Mice are lousy models for clinical studies,” Davis bluntly concluded. “We can’t depend on the mouse for all the answers, because in some cases it’s not giving us the right answers. But think about what we can do with people. People come to hospitals, get vaccinations, give blood and tissue samples for routine lab tests and clinical trials. We’re not learning nearly as much as we could from these samples. As with the recent history of human genetics, we could be much bolder.”
65 million years
Davis pointed out that mice and humans last had a common ancestor at least 65 million years ago, but the divergence is wider than that where immunology is involved. The numbers of mouse generations raised in laboratories during the past 100 years are approximately equal to the numbers of human generations who have lived since the dawn of civilization. The mice have been inbred for specific traits and isolated from exposure to diseases other than those that scientists deliberately give them.
By contrast, Davis wrote, “We’ve been selected by urbanization, with plagues such as the bubonic plague and smallpox that routinely killed huge numbers of people, and modern scourges like HIV and malaria that still infect and kill millions each year. Most humans are infected with six different herpes viruses, and who knows what else. And while we’re suffering away, getting colds and flu, the mice are living in the lap of luxury in miniature condominiums, with special filters on the cage tops to keep bad things out.”
In effect, Davis argued, lab mice have been reverse-engineered to respond less and less like humans who have been exposed to disease in real-world environments, where early or low-level exposure to some illnesses may confer immunity to others.
The Stanford Institute for Immunity, Transplantation & Infection, where Davis works, is among the users of an ultra-secure animal research complex opened in 1985, at cost of $11 million and years of controversy. As many as 50,000 mice and rats were used in experiments there in 1986 alone.
Activists opposed to building the complex alleged that the planners had used the hypothetical possibility of break-ins by would-be animal rescuers to rationalize security precautions that would actually be used to conduct dangerous experiments involving recombinant DNA and deadly diseases.
Considered state-of-the-art then, the complex represents the emphasis on mouse study that Davis termed obsolete.
Davis recommended an approach to immunology research based on “high-throughput” studies of clinical data, similar to the studies that decoded the human genome.
Francis S. Collins
Davis’ recommendations paralleled those issued in the February 15, 2008 edition of the journal Science by then-National Human Genome Research Institute director Francis S. Collins, who succeeded Zercouni as NIH chief.
Collins’ co-authors included Environmental Protection Agency research and development director George M. Gray and National Toxicology Program associate director John R. Bucher.
Collins, Gray, and Bucher jointly announced that the EPA, the National Toxicology Program, and the NIH had signed a memorandum of understanding to promote developing non-animal alternatives to the animal tests required to meet U.S. federal regulatory standards.
“Historically toxicity has always been determined by injecting chemicals into laboratory animals, watching to see if the animals get sick, and then looking at their tissues under the microscope,” Collins explained to reporters at the 2008 annual meeting of the American Association for the Advancement of Science in Boston. “Although that approach has given us valuable information, it is clearly quite expensive, it is time-consuming, it uses animals in large numbers, and it doesn’t always predict which chemicals will be harmful to humans.”
“We are not rats”
Besides, Collins added, “We are not rats and we are not even other primates.”
Collins, Gray, and Bucher revealed their memo of understanding nine days after the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICETAM) and the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) published a five-year plan for helping U.S. government agencies to phase out animal testing.
NICETAM and ICCVAM were created by Congress in increments as a gradual endorsement of the “Three R’s” principle of pursuing reduction, refinement, and replacement of animal use in biomedical research, outlined by William Russell and Rex Burch in The Principles of Humane Experimental Technique (1959).
The “Three R’s” were incorporated as a recommendation in the enforcement regulations for amendments to the federal Animal Welfare Act adopted in 1985.
The U.S. National Institutes of Health Revitalization Act of 1993 directed the NIH to support research to reduce, refine, or replace animal use. The ICCVAM Authorization Act of 2002 then formed ICCVAM to expedite the process.
Seventeen agencies participate in ICCVAM, including theNIH, the EPA, the Consumer Product Safety Commission, the U.S. Department of Agriculture, the Department of Defense, the Department of Energy, the Department of Health & Human Services, the Centers for Disease Control & Prevention, the Agency for Toxic Substances & Disease Registry, the Food & Drug Administration, the National Cancer Institute, the National Institute of Environmental Health Sciences, the National Library of Medicine, the Department of the Interior, the Department of Labor, the Occupational Safety & Health Administration, and the Department of Transportation.