The Case for Phasing Out Experiments on Primates

Whether they realize it or not, most stakeholders in the debate about using animals for research agree on the common goal of seeking an end to research that causes animals harm.^[1] The central issues in the controversy are about how much effort should be devoted to that goal and when we might reasonably expect to achieve it. Some progress has already been made: The number of animals used for research is about half what it was in the 1970s, and biomedical research has reached the point where we can reasonably begin to envision a time when it could advance without causing harm to animals. With some effort and aggressive development of new biomedical research technologies, full replacement of animals in harmful research is within our grasp. The goal will not be reached all at once, however, and phasing out invasive research on all nonhuman primates should be the priority.

Approximately 70,000 nonhuman primates are used for research in the United States each year, according to the U.S. Department of Agriculture, and another 45,000 are held or bred for research. They include macaques, baboons, marmosets, and other monkeys, as well as some chimpanzees. Moreover, these numbers are increasing in the United States and Canada. The rise is driven in part by the “high-fidelity” notion (supported by very little careful scientific justification) that primates are likely to be better models than mice and rats for studying human diseases, and partly by the sheer availability of primates.

The availability factor is a result of historical accident. In the 1960s, the United States invested in a significant infrastructure for primate research through creation of the National Primate Research Centers. The primate center program was the result of two unrelated occurrences. First, in the 1950s, hundreds of thousands of wild primates were captured and imported to support the race to develop a poliomyelitis vaccine. By 1960, with polio vaccines in use, this “race” was essentially over, but laboratories still had tens of thousands of primates. Then, they became swept up in another kind of race. The Russians had beaten the United States into space by launching the first satellite, creating panic that Russian science was outpacing U.S. science. American scientists made the argument that, because the Russians had a big primate research center, the United States should also have one or more primate centers. Seven facilities, formally recognized as government-supported institutions, were set up to provide support for and opportunities to do research in nonhuman primates.

The centers did not produce the hoped-for results. Three federal assessments found that the research conducted by the centers fell far short of expectations in terms of quality, and many deficiencies were also noted.^[2] In the early 1980s, these centers were “rescued,” in a sense, by the discovery that primates at the California Regional Primate Research Center were suffering from a simian version of AIDS. Suddenly, there was renewed focus on research in nonhuman primates. There are now eight National Primate Research Centers, the objective of which continues to be “to provide support for scientists who use NHPs in their research.”^[3]

Primates are used for a wide variety of research purposes. An analysis of one thousand federally funded studies that involved nonhuman primates found that research on HIV accounted for about 27 percent of the funding, followed by colony maintenance (likely because caring for primates is costly) at 15 percent, neurological research at 14 percent, and developmental research at 10 percent.^[4]

Arguments for Phasing Out Primate Research

Phasing out primate use should be a priority for ethical, scientific, and economic reasons. The ethical concerns fall into two categories. One of them is the nature of the primates themselves. They are well known for their cognitive and emotional abilities. Studies demonstrate that they have mathematical, memory, and problem-solving skills and that they experience emotions similar to those of humans—for example, depression, anxiety, and joy. Chimpanzees can learn human languages, such as American Sign Language. Primates also have very long lifespans, which is an ethical issue because they are typically held in laboratories for decades and experimented on repeatedly.  The other category of ethical concern is how primates are treated. Each year, thousands are captured from the wild, mostly in Asia and Mauritius, and transported to other countries. For example, China sets up breeding colonies, and the infants are sold to various countries, including the United States and European countries.  The animals experience considerable stress, such as days of transport in small crates and restrictions on food and water intake. Studies show that it takes months for their physiological systems to return to baseline levels,^[5] and then they face the trauma of research, including infection with virulent diseases, social isolation, food and water deprivation, withdrawal from drugs, and repeated surgeries.

Providing for the welfare of primates in a laboratory setting is very challenging. According to the Animal Welfare Act, each facility must develop and follow a plan for environmental enhancement to promote the psychological well-being of nonhuman primates. The plan must address social grouping; enriching the environment, with special consideration for great apes; caring for infants, young juveniles, and those primates showing signs of psychological distress; and ensuring the well-being of those primates who are used in a protocol requiring restricted activity.

Social companionship is the most important psychological factor for most primates. Federal law requires institutions to house primates in groups unless there is justification, such as debilitation as a result of age or other conditions, for housing them alone. But a recent analysis of documents from two large facilities obtained by The Humane Society of the United States demonstrates that primates spent an average of 53 percent of their lives housed alone. In many instances, a metal shape hung for a month on the bars of a metal cage was deemed to constitute adequate “enrichment.”^[6]

There have been only a few detailed examinations of the scientific value of primate use, and most were undertaken in Europe.^[7] While there has been no general review of the usefulness of primate research in the United States, chimpanzee research has recently come in for very careful evaluation and serves as a case study for how all primate use should be examined. The Institute of Medicine’s landmark 2011 report, Chimpanzees in Biomedical and Behavioral Research: Assessing the Necessity, concluded that “most current use of chimpanzees for biomedical research is unnecessary.”^[8] (See “Raising the Bar: The Implications of the IOM Report on the Use of Chimpanzees in Research,” in this volume.) Most countries have banned research on chimpanzees, and there has been great pressure in Europe to end other primate use. A group chaired by Sir Patrick Bateson, current president of the Zoological Society of London and professor of animal behavior at Cambridge University, as well as former secretary of the Royal Society, published a report in 2011 that reviewed research using nonhuman primates in the United Kingdom. It is important to note that around 70 percent of all primate use in the United Kingdom is conducted to satisfy legislative or regulatory testing requirements and not necessarily because primates are essential for satisfying scientific goals.

The Bateson report recommended that all proposed primate studies be assessed using the following parameters: scientific value, probability of medical or other benefit, availability of alternatives, and likelihood and extent of animal suffering.^[9]  The report indicated that if a proposed use would cause severe suffering, it should be allowed only if there is a high likelihood of benefit. The report considered approximately 9 percent of the studies it examined to be of low importance and to inflict high levels of suffering.^[10] The report was critical of some of the neuroscience research, which represented nearly half of the research surveyed. It found that half of the thirty-one neuroscience studies took a high toll on animal welfare, although most were also considered to be of high scientific value. Two of the studies were of concern because they posed a “high welfare impact,” but moderate-quality science and little medical benefit.^[11] The report recommended that more consideration be given to alternatives to nonhuman primates, including brain imaging, noninvasive electrophysiological technologies, in vitro and in silico techniques, and even research on human subjects.^[12] The report recommended other ways of reducing the number of primates needed for research, including data sharing, publication of all results, and periodic review of outcomes, benefits, and impact of the research. “Researchers using NHPs have a moral obligation to publish results—even if negative—in order to prevent work from being repeated unnecessarily,” the report states.^[13]

In addition to the ethical and scientific arguments for ending research involving primates, there are economic reasons. Primates are very expensive to maintain. The eight National Primate Research Centers alone receive $1 billion of the National Institutes of Health’s total $32 billion budget. The care and upkeep of primates other than chimpanzees is twenty to twenty-five dollars per day, compared with twenty cents to about $1.60 per day for small rodents. We argue that much of the research with nonhuman primates is either of questionable value or has not been carefully evaluated and justified. Therefore, these funds might be better spent on other research models, including several technologies that could replace nonhuman primates and other animals. Francis Collins, director of the NIH, argued in 2011 that new high-throughput approaches could overcome the drawbacks of animal models—they are slow, expensive, and not sufficiently relevant to human biology and pharmacology.^[14]

Several such technologies are available. The U.S. Army recently announced that it would end the use of monkeys for chemical casualty training courses and replace them with alternatives such as simulators that mimic the effects of nerve gas on victims.^[15]

Following Chimpanzees

The process that culminated in the phasing out of invasive research on chimpanzees in the United States in 2011 can and should be applied to all other nonhuman primates. Public opinion and ethical challenges drove that process. Even before the 2011 IOM report, scientists in the United States were having difficulty justifying why they should perform experiments on chimpanzees when their colleagues in other countries had stopped doing so. Unlike nonhuman primates in general, the number of chimpanzees in U.S. labs has been declining since reaching its peak in the late 1990s.

The main drivers for efforts to phase out research on chimpanzees are their genetic, biological, and behavioral similarities with humans.^[16] Chimpanzees are humans’ closest relative. Chimpanzee cognition has been studied extensively, and their capabilities are considerable. As with other primates, the impact of laboratory life—including barren housing and social isolation—on chimpanzees can last decades due to their long lifespan and thus raises significant welfare concerns. There is evidence that some chimpanzees used in research suffer from a form of posttraumatic stress disorder similar to that of humans. In their 2008 article, Gay Bradshaw and colleagues described the plight of a chimpanzee named Jeannie who endured invasive research and social isolation for over a decade. She exhibited abnormal behavior, including self-injury, bouts of aggression, and, according to laboratory documentation, a “nervous breakdown.” When retired to a sanctuary, she recovered partially, but was ultimately diagnosed with complex PTSD. The paper concluded: “The costs of laboratory-caused trauma are immeasurable in their life-long psychological impact on, and consequent suffering of, chimpanzees.”^[17]

As we have done with chimpanzees, we need to critically analyze current uses of other nonhuman primates, the viability of alternative models, and the economic issues involved to forge the best way forward. A good starting point would be the formation of a working group of diverse stakeholders who agree that ending primate research is a worthwhile goal. Such a working group—possibly organized by the NIH and the National Academies—would analyze the necessity of primate use and identify existing and potential alternatives.

The stakeholder group could develop a concrete plan to work on common-ground issues. This would involve developing priorities, short-term outcomes, and related activities. The ongoing Human Toxicology Project Consortium’s work to ultimately replace all animals for toxicity testing is a good example of this approach. (See “No Animals Harmed:  Toward a Paradigm Shift in Toxicity Testing,” in this volume.) The mission of the consortium is to “serve as a catalyst for the prompt, global, and coordinated implementation of ‘21^st Century’ toxicology, which will better safeguard human health and hasten the replacement of animal use in toxicology.”^[18] Because science is ever-changing, there must be an ongoing analysis of new technologies and challenges, and regulatory authorities must adjust regulations accordingly. In the United States, many stakeholders express frustration with the fact that the Food and Drug Administration, for example, favors data from outdated tests, including those that involve primates and other animals.

Phasing out invasive research on all nonhuman primates would take courage on the part of leaders in science and policy. It is a formidable task, but similarly transformative changes in how we conduct biomedical research have been achieved. At various points in the past century and a quarter, restrictions have been placed on particular kinds of human and animal research because of ethical issues, despite objections that such restrictions would slow scientific progress; think, for instance, of the Helsinki Declaration to protect human subjects in research and the animal welfare laws in the United States and the European Union. However, these laws have not slowed the pace of discovery about biology and disease processes. If anything, there has been an acceleration of such discovery in the half-century since these restrictions went into effect.

In the early 1950s, Sir Peter Medawar pressed the Universities Federation for Animal Welfare to develop a report on how laboratory animal welfare could be improved and how distress and suffering in the research laboratory might be reduced. That initiative led to publication of a volume on humane experimental approach that is now regarded as the foundation for the concept of the Three Rs of replacement, reduction, and refinement of animal studies.^[19] Ten years later, in 1969, Medawar correctly predicted that laboratory animal use would peak within ten years and then start to decline. He argued that animal research would allow researchers to develop the knowledge and understanding that would lead, eventually, to the replacement of animal use in laboratories. In 2010, forty years after Medawar’s prediction, laboratory animal use is approximately 50 percent of what it was in 1970. Francis Collins has pointed to the down sides of animal-based research—that is “time-consuming, costly, and may not accurately predict efficacy in humans.”^[20] He has also suggested that nonanimal technologies might be quicker and more effective in new drug discovery programs. Given the trends and political will, we believe that we could reach Medawar’s prediction of complete replacement by 2050.

Now is the time for an internationally coordinated effort to define a strategy to replace all invasive research on primates. At the very least, we need to move quickly to reverse the increase in laboratory primate use in the United States and Canada. Until replacement is a realistic option, we must reduce the number of primates used and refine studies to reduce their suffering, for the sake of both animal welfare and science.

 

Kathleen M. Conlee is vice president for animal research issues with The Humane Society of the United States. She worked for several years at a primate breeding and research facility and also worked with great apes in a sanctuary setting. Her current work focuses on the long-term goal of replacing the use of animals in harmful research and testing, the ongoing development of nonanimal alternatives, and the short-term goals of ending invasive chimpanzee research and retiring chimpanzees from laboratories to sanctuaries. 

Andrew N. Rowan is chief scientific officer at The Humane Society of the United States and chief executive officer of The Humane Society International. He has written numerous books and peer-reviewed publications regarding animal research, including a book titled The Animal Research Controversy: Protest, Process and Public Policy (Center for Animals and Public Policy, Tufts University School of Veterinary Medicine, 1995). He is a biochemist in training, and a focus of his career has been promotion of the three Rs in animal research: replacement of nonhuman animals, reduction in number of animals used, and refinement to decrease animal suffering.

 

[[12]]12. Ibid., 4, 5, 16.[[12]