• November 1, 2014

Animal Research: Why We Need Alternatives

Why We Need Alternatives to Animal Research 1

Bjorn Alander, Nordic, Aurora Photos

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Bjorn Alander, Nordic, Aurora Photos

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.

Hope Ferdowsian is a physician and director of research policy at the Physicians Committee for Responsible Medicine. For more information about the conference, go to www.researchalternatives.org.

Comments

1. whitefmo - November 08, 2010 at 10:19 am

While Dr. Ferdowsian's efforts to work towards alteratives to animals in research are admirable, her inability to present a clear picture of the manner in which mice and rats are treated in US universities is absymally incomplete.

She is correct to state that the "Laboratory Animal Welfare Act of 1966 was to prevent the unauthorized buying and selling of pet dogs or cats for research purposes," and indeed the law excludes rats of the genus Rattus, mice of the genus Mus. However, US universities receiving federal monies do not discriminate in regard to what species is covered by this act. All vertebrate species are covered.

The following is taken from the Indiana University School of Medicine IACUCU.
"Guidelines for Selecting Humane Endpoints during Experiments Using Living Animals"
The Animal Care and Use Committee is committed to minimizing pain and suffering in experimental animals, irregardless of the species of animal in which an experiment is conducted. The Committee recognizes that all vertebrate animals are capable of experiencing pain and distress. It is essential that the principal investigator consider the welfare of the animals when planning experiments. Section C and Item 9 of the Animal Care and Use Application form require investigators to provide specific information about humane cut-off points for experimental animals and to address the issues of pain and distress and how they can be minimized. These guidelines were prepared to assist investigators when completing these sections of the application form.


Also the Montreal pain study called into question has been found to comply with Canadian ethical guidelines for animal research. The Canadian Council on Animal Care, which regulates the use of laboratory animals, made the ruling after investigating the study led by Jeffrey Mogil at McGill University.

The council reviewed documentation about the study and interviewed an animal compliance representative at the university after criticism of the study was published in a U.S. subscription newsletter called the Laboratory Animal Welfare Compliance.

I also suggest that Dr. Ferdowsian take some time to read the material presented in The ILAR Journal, a quarterly, peer-reviewed publication of the Institute for Laboratory Animal Research (ILAR). As part of the ILAR mission, authors are invited to provide thoughtful and timely information for all who use, care for, and oversee the use of laboratory animals. Issue themes and article topics are pertinent for investigators in biomedical and related research, institutional officials for research, veterinarians, and members of animal care and use committees. ILAR is under the guise of the National Academy of Science. The website is http://dels.nas.edu/ilar.

2. grward - November 08, 2010 at 11:46 am

As a former animal researcher, I struggled with this issue for years. When I would fill out the Animal Care Proposal (which was required by my institutions in spite of the fact that I worked only with rats and mice, in contradiction to what Dr. Ferdowsian claims), I would be required to explain the benefits to humans of the proposed experiment. Sometimes, I had an idea of a way to improve the health of the rats and mice in my research and was discouraged from asking permission to try it out since, clearly, it would only benefit lab animals and not humans. No worries, however: I would simply say that anything that could improve lab animal health could increase our ability to use animals to do research benefiting humans. That would satisfy the committee and the proposed research would be approved.

The first point I want to make, though, is that the author is trying to wear two hats when only one can be worn at a time. You can't claim that research on animals should be forbidden for ethical reasons (a position which may be valid, in my opinion as I now approach my senior, more contemplative years) and also claim that this research should be forbidden because it doesn't benefit humans anyway. Is she saying that research on animals could be acceptable if it turns out to benefit humans? If so, how do we decide just which benefits to humans would be worthwhile, and what level of suffering to animals would be acceptable? Can we know the benefits of research to humans a priori? That would seem to go against everything we've learned about the serendipitous nature of research. Of all the research findings that have ended up impacting on our lives for the better, how many of them were clearly recognized as having that potential at the time? Have we reached the point in history when serendipity will no longer play a role? When did that happen? It would have been a stupendous turning point in the history of science: I'm amazed that I didn't notice it.

Second, if we use past success as a strict criterion of what to do in research in the future, we won't just throw out animal-based research: we'll need to throw out much human-based research as well. Sure, we may be failing because we're doing something that is bound to fail, but more often than not success eventually results from applying research models in a different way, or recognizing that their strengths lie in a different application. Rarely can we say that a whole research model must be scrapped because we now realize that it never had the potential to find anything at all useful. Again, if we've reached that point, I'm amazed that I didn't hear of it.

Finally, the creation of "virtual" methods, as I'm sure the author realizes, requires vast knowledge of the system being investigated. Furthermore, such methods raise all sort of questions that can often be answered only by returning to the living system. Where did much, if not most, of that knowledge come from? The potential usefulness of these virtual systems is often a function of how much research was already carried out on the living systems, and much of that research probably had little apparent direct applicability at the time it was done.

I do concede that much experimentation is ill-planned and poorly executed and, as a result, is often worse than useless. The solution is to modify the present system of research, including the reward structure in place that encourages quantity of publications over quality. To claim that it proves that animal research cannot be justified is beside the point, because we can never know just what research will turn out to be important in the future. If it is unethical to use animals for research, then animal research should be banned for that reason, regardless of whether it could save human lives or not, since we can never have the information we need to establish such a claim. In other words, first-rate ethicaql reasoning should not be supported by third-rate, faulty epistemological reasoning.

3. boiler - November 09, 2010 at 02:06 pm

The PETA attacks on animal research share a lot with right-wing attacks on the humanities. Both of them point to a few research projects that seem particularly wrongheaded, and based on that they call for the abolition of the whole field. Both of them also highlight a few examples of alternative research, which are supposed to prove that the benefits provided by the field are available elsewhere. In either case, this is a kind of cherry picking that evades the difficult ethical questions that underly their positions. An honest right-wing critique of the arts would discuss a useful, thoughtful social critique and ask whether its virtues justify its cost. An honest attack on animal research would consider a revealing, productive animal study and ask whether its benefits outweigh the harm caused to its subjects. It would also examine treatments which have been discovered through animal research, and ask whether those treatments have really been worth their cost to the animal subjects.

Personally, I support animal research. But I find myself preferring the extremes of people like Singer, who make a clear case for its moral unacceptability, than pieces like that above, which are essentially trying to slip out of the ethical consequences of their positions.

4. gahnett - November 09, 2010 at 02:12 pm

I think animal research represents a compromise through the use of metaphors. There will be situations in which things are somewhat the same but they're also always different in some way.

Currently, the biggest challenge facing human health research are complex diseases of the type that must be investigated in integrative systems. Therefore, there is no replacement for investigating whole organismal systems, with the idea that mammalian systems like the mouse are the closest to human systems. Moreover, we spent the past century developing genetic tools to interrogate interactions that have contributed tremendously to our current awareness. Recent developments in bioengineering technologies, in particular nanomedical research, appears to be an as yet untapped resource for improving therapies. To think that we can replace animal model research is a bit naive at this point.

Moreover, as far as I know, I personally know of no investigator who does this sort of work who gets off on hurting animals. In fact, most of us would love to mitigate pain as much as possible. However, if the goal is to alleviate human pain and suffering, whole organismal research is a required compromise.

5. recruited - November 09, 2010 at 06:20 pm

As a biomedical researcher, I regard the use of animals in my research as a last resort. We do everything possible to avoid using animal systems.

But sometimes there is no substitute. I don't like it, but we have to do what is necessary to answer our questions.

It is a balance. But we try our best to minimize this.

6. fergbutt - November 09, 2010 at 06:37 pm

It's not as if animals were making plans for tomorrow. They are the beasts that you wear everyday as shoes. They are the biting insects you swat at your kid's soccer game. They are the food on your plate. If you want to really test your ethical stance, consider the unborn fetus. It's OK to choose death for our own kind, but not for lab rats?

7. louisie - November 10, 2010 at 09:38 am

Arguably one of the world's most pressing needs - a vaccine for or "cure" (enhanced treatment of) HIV or AIDS - is being researched via work on non-human primates and could only be accomplished this way. Similarly, from new ways to treat antiobiotic resistant malaria to novel surgical approaches that benefit seriously ill children, animal models provide an essential and crucial way to advance science and medicine for the benefit of humanity.

That important role does not negate the need for ethical and humane treatment of all animal models. Every researcher and vet who I know works with animal models is especially conscientious of this fact and there is a very strong culture of "animals first" among the scientists I know who actually carry out such research in the lab (on behalf of PIs who get the funding, establish the protocols, and intrepret the research findings).

8. frankschmidt - November 10, 2010 at 10:18 am

Nature cares about only one thing: evolutionary success. Evolutionary success means "passing on your genes to your offspring," so by that measure laboratory rats and mice, and indeed all domesticated plants and animals, benefit from their use by humans.

This is not to justify cruelty to any organism (including humans), but the article betrays a biological hubris that is unjustified by the research she cites.

9. veronica594 - November 10, 2010 at 04:21 pm

I share Dr. Ferdowsian's view that animal research alternatives are needed due to both ethical and scientific issues. These are two clear reasons for moving away from animal research--and there is no reason why they cannot be discussed together.

It is abundantly clear that animal research harms animals, no matter how careful some researchers may be. Studies find that animals suffer even from routine handling and from living in a lab atmosphere.

And we now know that the translation of animal research to human medicine is exceedingly poor. Decades of experiments have failed to find cures for nearly all of the most debilitating diseases. At least 85 HIV/AIDS vaccines have been tested successfully in monkeys and other animals, but every single one has failed in human trials. The same is true of more than 100 stroke treatments, dozens of diabetes cures, and more than 20 paralysis treatments. And more than 90 percent of drugs that pass animal tests fail in human trials.

The National Research Council, the Institute of Medicine, and the National Cancer Institute have all joined the efforts to move away from animal testing to in vitro and other nonanimal research methods. Their reasons may be mostly science-based, but this move toward modern research methods will greatly benefit all involved.

10. ellenhunt - November 10, 2010 at 05:10 pm

It is just flat wrong to say that there have not been results. The opposite is true. There are too many instances of treatments moving into humans too quickly, bypassing primate models, and causing death or extreme illness. Ask the family of Jolee Mohr for instance.

The HIV/AIDS vaccine tests failed because the protocols for administration in rhesus need to be overhauled and nobody will do it because the field is hidebound. HIV/AIDS is a disease that does not have any cure in nature. Thus, at it's root, the concept of an HIV vaccine is specious at best.

I also have to seriously question people who carry on about the ethics of animal models while ignoring the meat at the butcher counter. The amount of flesh passing through labs is a tiny fraction of what goes through slaughterhouses each year. I just don't understand this business of screaming foul of such insignificance while munching lobster for dinner (dropped alive into boiling water) or bacon for breakfast. Believe me, the pigs know what is going on when they get near a slaughterhouse.

11. marcbeko - November 11, 2010 at 09:17 am

Many thanks for a very interesting an important essay - this might also be of interest to some of you:

http://animals.change.org/blog/view/the_animal_welfare_act_are_animals_really_better_off

12. marcbeko - November 11, 2010 at 09:25 am

Many thanks for a very interesting and important essay - this might also be of interest to some of you:

http://animals.change.org/blog/view/the_animal_welfare_act_are_animals_really_better_off

13. ericgriffith - November 11, 2010 at 04:54 pm

Thank you for publishing this informative and encouraging article. I am pleased to see a diverse group of experts coming together to discuss this topic at the "Animals, Research, and Alternatives" conference. Hopefully the dual concerns of ethical and scientific issues will speed the development of alternatives to animal research and thereby alleviate and prevent suffering in animals.

14. marjcramer - November 13, 2010 at 07:05 am

Dr. Ferdowsian gives an in depth overview of the medical, human health and ethical issues involved in animal experimentation. We have come a long way in the past 20 or 30 years and we need to look critically at the concepts of having another species be our surrogate. As a surgeon who has done animal experimentation I can understand the reflex response of some people that animal experiments are helpful because they use “whole systems.” Unfortunately these whole systems end up not being helpful given the multitude of differences between species. Modern advances in technology allow us to make rapid, more refined advances than would be possible using outdated 19th and 20th century medicine.

15. gplm2000 - November 15, 2010 at 04:43 pm

Thanks for the laughs guys and girls! Although unnecessary pain should be avoided for all animals, it is ridiculous to whine about that of animals for research to improve the lives of humans.

16. barrysto - December 08, 2010 at 05:50 pm

There is no doubt that animals need to be used in research. Unless you are fond of testing on humans in third world countries which is also common practice even though not too many people are talking about it.
I do, however, opose the pointless torturing which occured in the experiment discussed in this article. The whole experiment sounds like a little buy thinking "what would happen if I pokes the cat's eyes?"
I am not involved with tests using animals but I am a pet owner and I do everything I can (including paying for pet insurance) to make sure my pets are healthy and happy.

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