When you burn your finger, the grimace on your face sends a universal message. From Finland to Fiji, virtually any human on earth need only see your face to know that you're in pain. Facial expressions, anthropologists have long known, are an international language.
But that language, it turns out, isn't exclusive to humans. Mice also express pain through facial expressions—and those grimaces are remarkably similar to yours or mine, according to a recent article published in the journal Nature Methods.
In that extremely controversial study, researchers used a wide range of methods to subject mice to various levels of pain. They immersed the animals' tails in hot water, used radiant heat on them, attached a binder clip to their tails, injected irritants into their feet, induced bladder inflammation with a chemical that causes painful cystitis in humans, and injected acetic acid, causing the mice to develop abdominal constriction and writhe. They performed surgery on the mice and did not provide postoperative analgesics.
The study's authors developed a Mouse Grimace Scale as a measurement tool to help quantify the level of pain experienced by mice. They concluded that when subjected to painful stimuli, mice showed discomfort through facial expressions in the same way humans do.
This painful experiment raised many questions among researchers. Criticism of the study was covered in a newsletter called Laboratory Animal Welfare Compliance and elsewhere. Critics have maintained that the experiments were cruel and unnecessary.
That study—and the debate surrounding it—highlights critical issues relevant to animal research. For example, mice are now the most commonly used animals in research, but they are not covered by the Animal Welfare Act, one of the few legal protections afforded by U.S. law to other animals used in laboratory experiments.
The original intent of the Laboratory Animal Welfare Act of 1966 was to prevent the unauthorized buying and selling of pet dogs or cats for research purposes. However, the types of enterprises covered, species of animals regulated, reporting requirements, and minimal animal-care guidelines were expanded in subsequent amendments.
Although those laws provide basic protections for some animals used in research, there are significant inconsistencies among U.S. regulations. For example, more than 90 percent of animals used in research are excluded from the Animal Welfare Act.
The law excludes birds, rats of the genus Rattus, mice of the genus Mus, and farm animals. Those exclusions are thought to be primarily attributable to the laboratory industry's successful lobbying efforts. In addition, there is no legal threshold for how much pain and suffering an animal can be exposed to in experiments.
Those were some of the issues discussed at a recent conference on animal research and alternatives. My colleagues at the Physicians Committee for Responsible Medicine and I organized "Animals, Research, and Alternatives" to bring together experts with diverse opinions to discuss animal-research issues. As a physician concerned about the prevention and alleviation of suffering in both humans and animals, I wanted to help facilitate informed, intelligent discussion about animal research.
Despite well over a century of debate, the ethical and scientific issues surrounding animal research have rarely been studied together in a balanced, organized forum. At our conference, more than 20 speakers shared expertise on the scientific, legal, ethical, and political imperatives regarding animal research.
The first presenter, John Gluck, a professor emeritus of psychology at the University of New Mexico and an affiliate faculty member at Georgetown University's Kennedy Institute of Ethics, set the tone for the conference. After years of conducting primate research, he began studying the ethics of animal research. He and other speakers explained that animals have their own set of needs, and that those needs are compromised when humans use animals in laboratory experiments.
Unlike human-research protections, which are now guided by a principled approach, laws governing the use of animals in research have resulted from a largely politicized, patchwork process. That has led to unclear and disparate policies. Meanwhile, studies have dramatically increased our understanding of animal cognition and emotion, suggesting that animals' potential for experiencing harm may be greater than has been appreciated, and that current protections need to be reconsidered.
Although today's laws require institutional committee systems to monitor animal research, individuals serving on Institutional Animal Care and Use Committees have no clear set of ethical principles in which to ground decisions about protocol approval. The scientific question being researched takes precedence over the welfare of the animals. This differs significantly from human-research protections, wherein the interests of individuals and populations are protected, sometimes to the detriment of the scientific question.
At the conference, we learned about intriguing advances in medical research, including a surrogate human immune system for predicting vaccine safety, and a revolutionary approach to breast-cancer research.
Susan Love, president of the Dr. Susan Love Research Foundation, which focuses on eradicating breast cancer, explained that most breast-cancer research in the field is still conducted on animals, even though humans are one of only a few species that develop breast cancer. She discussed the goal of the Army of Women (a partnership between the Avon Foundation for Women and Love's foundation) to challenge research scientists to move from ineffective animal models to breast-cancer-prevention research conducted on healthy women.
If we could better understand the factors that increase the risk for breast cancer, as well as methods for effective prevention, fewer women would require treatment for breast cancer. But animal experiments do not offer reliable and reproducible findings that can appropriately be applied to women. Whereas animal research is largely investigator-initiated, the Army of Women model tries to address the questions that are central to the care of women at risk for or affected by breast cancer. The model has facilitated the recruitment of women for studies such as a national project backed by the National Institutes of Health and the National Institute of Environmental Health to examine how environment and genes affect breast-cancer risk. This critical study, which began in 2002, could not have been accomplished with animal research.
William Warren explained a surrogate in-vitro human immune system that his company has developed to help predict an individual's immune response to a particular drug or vaccine. The system essentially functions as a clinical trial in a test tube. In other words, it is a virtual human immune system that relies on human immune responses, which differ from those of other animals. The system includes a blood-donor base of hundreds of individuals from diverse populations. It can replace the use of animals for a range of research purposes, most notably vaccine testing. Technologies like those offered by this system could help accelerate the process of developing an HIV vaccine and other immunizations.
Other presenters addressed more of the ethical reasons for moving toward nonanimal alternatives. Lori Marino, a senior lecturer in neuroscience and behavioral biology at Emory University, discussed her noninvasive research on dolphin and whale cognition. She described how invasive research involving cetaceans can result in confinement and social deprivation, stress and disease, mortality, and destruction of social cultures. Although both invasive and noninvasive cetacean research attempts to better understand marine-animal cognition, Marino's research does not involve medical procedures, such as biopsy darting, or techniques that manipulate the mind, social milieu, or physical freedom of the animals.
Jaak Panksepp, a neuroscientist at Washington State University, discussed the overwhelming evidence that animals experience basic emotions. For example, mice like to be tickled, much as humans do. If our ears were sufficiently attuned, we could hear their laughter. Marc Bekoff, a professor emeritus of ecology and evolutionary biology at the University of Colorado at Boulder, pointed out that the emotional and moral lives of animals matter.
It is now widely acknowledged that animals do suffer, Bekoff explained. Decades of observational and experimental research have provided evidence that animals experience physical pain. Psychological suffering—chronic fear, anxiety, and distress—is another major issue, possibly the most neglected one in animal research.
Perhaps Jeremy Bentham (1748-1832), a legal scholar and social reformer, said it best: "The question is not, 'Can they reason?' nor, 'Can they talk?' but rather, 'Can they suffer?'"
Because animals are sentient beings, they share many qualities with humans. For example, animals demonstrate coordinated responses to pain and many emotional states similar to those of humans. Further, the structures and neuroendocrine mechanisms associated with certain psychiatric conditions are shared across a wide range of animals.
Based on these neuroanatomical and physiological similarities, researchers have described signs of depression in animals, including nonhuman primates, dogs, pigs, cats, birds, and rodents, among others. Learned helplessness, a form of depression that has been described in human patient populations such as victims of domestic violence, has also been identified in rodents, dogs, monkeys, and apes exposed to inescapable shocks. Post-traumatic stress disorder and depression have been described in chimpanzees.
The absence of certain neuroanatomical structures may also be significant because animals with less-organized neural circuits may have more-limited coping mechanisms useful in reducing the level of pain they feel. Other animal qualities may also be ethically relevant. For example, many animals demonstrate language skills, complex problem-solving abilities, empathy, and self-awareness.
At the conference, I presented my own observational study of chimpanzees. My colleagues and I have found that many chimpanzees who were used in laboratory research continue to exhibit symptoms of depression and post-traumatic stress disorder years after they have been released to sanctuaries.
Because the United States is the last nation conducting large-scale, invasive experiments on chimpanzees, we have to ask ourselves why—particularly when chimpanzee research has hit a dead end for humans. More than two decades of HIV-vaccine research using chimpanzees has failed to produce a human vaccine. The story is similar for hepatitis C. Hepatitis behaves very differently in humans than in chimpanzees. Chimpanzees are rarely affected by chronic hepatitis or complications associated with hepatitis, such as cirrhosis or hepatocellular carcinoma. Decades of cancer, malaria, cardiovascular disease, and other forms of research using chimpanzees have led to similar failures.
Meanwhile, chimpanzees have demonstrated their own rich preferences in life, including seeking solitude, experiencing new places, living free from fear of attack, and maintaining life-long contact with individuals they love.
The subject of animal research is complex. Each of our own opinions has been informed by education, experience, and personal perspective. Conversations surrounding the use of animals in research are understandably truncated by emotion. Often it seems like two sides talking past each other.
It's clear that we're making progress toward replacing the use of animals in invasive experiments, but we have a lot of work ahead of us. I am hopeful that our conference advanced the dialogue and will contribute to scientific and ethical progressadvances for both people and animals.
In years to come, when we have replaced animals in research, future generations will look back and wonder why this advance did not happen sooner. But they will also be thankful for those who improvedmade animals' lives better and strove for better, more ethical science.