Animal Subjects Case Studies 1. Laboratory Decisions You are entering your second year as a graduate student in a biosciences program at a top rated research university. For your second year you are expected to work in a lab on biological systems that you are interested in and may provide experience with techniques you should be familiar with for your PhD. You have narrowed down the choices to two different labs. The lab of Dr. A works exclusively with cell cultures derived from animal, and never with live animals. Dr. A is known to object to the use of live animals in many types of experiments. The lab of Dr. Z, on the other hand, studies similar cell systems but uses a combination of cell cultures and live animal models, usually mice. Recently Dr. Z has expanded the animals used to include some dogs. Dr. Z evidently doesn’t object to using live animals in research. Even though there is a difference in approach, assume each lab will provide you with much of the same type of laboratory experience. Discussion Questions 1. Which lab would you prefer to work in? Why? Does the use of animals in these labs concern you? 2. Dr. Z’s new research protocol will subject the dogs to a noticeable degree of pain and discomfort, resulting in the need to euthanize the dogs. What effect does this information have on your decision of labs? 3. Do you think there are significant differences in what you can learn from in vitro studies versus in vivo studies that require live animals? What would justify focusing on in vivo studies and thus risking harm to animals? 2. Animal Models of Human Disease One of the great promises in medical research is the use of transgenic animals to better model human genetic diseases. The first attempt to produce an animal model of human genetic disease by transgenic means was the development, by embryonic stem cell technology, of a mouse that was designed to replicate Lesh‐Nyhan’s disease. Lesh‐Nyhan’s disease is a particularly horrible genetic disease, leading to devastating and untreatable neurologic and behavioral disorders. Patients rarely live beyond their third decade, and suffer from spasticity, mental retardation, and choreoathetosis (involuntary movements). The most striking aspect of the disease, however, is an irresistible compulsion to self‐mutilate, usually manifested as biting fingers and lips. As it turned out the resulting mouse model of the disease was asymptomatic, but still useful for research. Using cloning techniques, the mouse was reproduced for numerous studies. However, it is clear that a better animal model, a higher‐fidelity model of the disease, would be one that was symptomatic. Assume for the sake of argument that the relevant metabolic pathways could be replicated, and the resulting animal could be cloned successfully for various trials. The creation of such animals would generate both invaluable research and inestimable amounts of pain and suffering from these animals. (This case study was adapted from Bernard E. Rollin, “Biotechnology and Animals: Ethical Issues in Genetic Engineering and Cloning.” In A Companion to Genethics, edited by Justine Burley and John Harris. Blackwell, 2002, pp. 70‐81.) Discussion Questions: 1. Should higher‐fidelity animal models of genetic diseases, such as Lesh‐ Nyhan’s disease which have severe symptoms, be produced? Why or why not? 2. If such mice were in fact produced, how should the pain and suffering experienced by these animals be managed or alleviated? 3. Does the fact that the animal is produced through transgenic and cloning technology provide additional or heightened ethical concerns? Explain. 4. Imagine that the transgenic animals used for research on Lesh‐Nyhan’s disease can progress from mice to dogs to monkeys, and possibly to chimpanzees. Is there a point at which the research should no longer continue in this chain of potential animals? Why or why not? 3. The Human Neuron Mouse In the 1980s Dr. Irvig Weissman, a professor of pathology and developmental biology at Standford, developed a SCID‐hu mouse which allowed the study of human immune system functioning under laboratory conditions in mice. In early 2000, Weissman was considering developing experiments that would result in a human‐mouse hybrid, named the “Human Neuron Mouse”. He was familiar with an inbred strain of mouse that formed brains in early fetal development, but, died before birth because most or all of the developing neurons died. However, the glial cells, which make up about 90 percent of the brain, remained unharmed. Weissman’s proposal was to transplant human brain stem cells into the fetal mice just before the mice’s own neuron cells died. If successful, the experiments would result in mice with human derived neuron cells and mouse glial cells. The Human Neuron Mouse would promise a humanized model organism ideal for studying human neurons in vivo. To date the experiments that would lead to the Human Neuron Mouse have not been attempted, yet the proposed experiments generated substantial debate about the ethics of creating such a human‐mouse hybrid. Some argued that the potential research and medical benefits favored the development of the Human Neuron Mouse. Research into human neural development and longevity might provide breakthroughs for various developmental and neurodegenerative diseases of the brain. It would certainly aid in the understanding of the basic biochemical functions of neuron signaling and the effect of different drugs on neural transmitters. Others argued that the proposed hybrid was too humanized, and raised too many unanswered questions about the moral status of the human‐mouse hybrid. Since the hybrid would effectively have an entire brain developed from human neural stem‐ cells suggests the possibility that the brain may develop more human‐like functions. Even though it was unlikely a fully human brain would result, the differences that did develop would have serious ethical implications for how one ought to treat the Human Neuron Mouse. (For more detailed discussion of the ethical issues involved, see the target article and peer commentary in Thinking About the Human Neuron Mouse, by Henry T. Greely, Mildred K. Cho, Linda F. Hogle, Debra M. Satz. American Journal of Bioethics, May 2007; 7(5):27; available online at www.bioethics.net/journal.) Discussion Questions: 1. In your view, would it be ethical to develop the Human Neuron Mouse? Explain your answer. 2. How seriously should we take the argument that the Human Neuron Mouse is “too humanized” to be ethical? What kind of brain functions would make the hybrid too humanized? If the Human Neuron Mouse was developed and it in fact had developed more human‐like cognitive and conscious functions, should it be treated differently? 3. If the same research was proposed for developing a human‐mouse hybrid that involved a different biological system, for example a digestive system modeled on human cells, would this raise the same moral questions about the research? 4. The goal of creating humanized animal models is to provide usable and biologically analogous organisms for research purposes, there is always the risk of making the animal model too much like humans for ethical comfort. Discuss how much is too much when it comes to humanizing animals for research. 4. The Painless Mouse Lacy Brand worked extensively with animals in his research, especially mice. But he was tired of hearing about how animals shouldn’t be used in research because they suffer pain. What researchers needed was an animal that could serve as a proper research model but itself not feel pain. Mice have been created without a functioning immune system, so Lacy thought why not a mouse without a functioning nociceptive system? In his spare time Lacy worked out what he thought was a viable model for a painless mouse. It would require some research on the genetics of the nociceptive system, and many generations of mice to produce the right mouse, but he was confident his plan would work. After writing up the proposed experiments Lacy submitted it to his University’s Institutional Animal Care and Use Committee which reviews and approves or denies research proposal involving animal subjects. Discussion Questions 1. Assume that Lacy’s research proposal to produce a “painless mouse” is viable even if it would take many generations of mice, would it resolve the ethical dilemmas involved in animal pain and research? 2. If you were a board member of the IACUC reviewing Lacy’s proposal, would you permit the research? What ethical concerns would you raise? 3. Does this research proposal exhibit a general disregard for the value of animal life? That is, does it merely treat animals as a tool to be manipulated for the needs of humans? Is this cause for concern? 5. Animal Activism Animal activism against the use of animals in research has a long history, as far back as the antivivisectionist movement in the late 19th century. In more recent times activists have adopted a number of different strategies, with varied results. For example, in the early 1980s, Thomas A. Gennarelli, a professor at the University of Pennsylvania, was studying the effect of head injuries in baboons. His goal was to identify an animal model in which to study physiological and anatomical effects of head trauma in humans. Baboons were strapped to tables and fitted with monitors, and their heads were cemented inside a helmet. A hydraulic piston then suddenly twisted or jolted their heads which could simulate up to 2,000 times the force of gravity. The monkeys were typically comatose and paralyzed after the intervention, although some died. The surviving animals were sustained for two months, at which point they were sacrificed and the effect of the injuries on their brains was studied. However, in May 1984, members of the Animal Liberation Front (ALF) invaded Gennarelli’s laboratory, stole videotapes of the experiments, and released them to the public. People for the Ethical Treatment of Animals (PETA) released an edited version of the tapes, showing the injured and distressed monkeys. The ALF made two other raids, this time stealing thirteen animals from the University of Pennsylvania veterinary school. In the public outcry that followed, the adequacy of the anesthesia used on the baboons was questioned, as was the general treatment of the baboons. The validity of the scientific hypothesis underlying the research was also criticized. Animal activists conducted sit‐ins at the National Institutes of Health, which was funding Gennarelli’s research. In direct response to this case, Congress enacted new laws mandating more rigorous oversight and protections for the welfare of laboratory animals. In recent years some activists have become more aggressive. Activists have organized rallies or vigils outside the houses of animal researchers. In addition, two reported events of bombs being placed at the homes of prominent animal researchers received national news coverage. In response Congress has recently enacted a law that punishes threats to animal researchers. But activists have also adopted other, less violent tactics. One tactic is to infiltrate animal laboratories and care facilities in order to record the treatment of animals. Individuals would apply for jobs in animal care facilities and covertly videotape the cage areas, procedures on animals, and other aspects of the laboratory use of animals. Then the individuals would quit the job and hand over the tapes to organizations like PETA, who then distributes them over the internet or other media outlets. In some cases, they exposed questionable practices and noncompliance to Federal regulations governing animal care. They also caused much consternation in the animal research communities. Discussion Questions 1. Regardless of your views on the ethics of animal research, what do you think about the efforts of animal activists to expose the use of animals in laboratories? Is it generally good that there are people like this pushing for reform? 2. If the efforts of groups like PETA are effective in exposing mistreatment of animals or other violations of existing law, does this justify their actions? Would the legal reforms mentioned have been enacted by Congress if ALF or PETA did not instigate the raids? Would institutional boards have been concerned enough to look into the matter? 3. Clearly bombing the house of an animal research goes to far. What about invading laboratories or the use of spies, as mentioned in the case study; is this unethical? Explain. 4. How should animal researchers respond to efforts of animal activists? Should they actively engage them in a public forum or simply ignore them? 6. Science Fair You are asked to judge a science fair at a local High School. One project catches your attention. It is an interesting study of differential feeding habits and its effects on growth patterns in mice. The student hypothesized that feeding mice limited pet chow in combination with limited water intake would change growing patterns and some behavioral patterns in mice. The students bought six mice from a local pet store and split them into two groups. Both groups were given the same pet chow and water, but one group had unlimited access to the food and water, whereas the other was limited to measured quantities of chow and water each day. Each week for three weeks the student weighed and measured each mouse, and evaluated their activity in a mouse play set which included a running wheel and a simple tunnel maze. The amount of time spent on each machine was timed during a thirty‐minute session for each mouse. At the completion of the three weeks the mice were to be killed and dissected to examine organ development. The student found, as expected that the group with unlimited access to food and water increased in size by 20% compared to the limited group, but they were also less active during the sessions in the play set. The student also found that mice in the unlimited group had what appeared to be normal organ development, whereas the mice in the limited group had some abnormal organ development; the organs were proportionally smaller, and several had unexpected growths. The student wasn’t sure if the growths were a result of the food regime or just coincidental because of the low number of mice used. The study was interesting, not just because it was well designed and ambitious but because it was the only project to use live animals. After checking with the school officials you find out that the High School policy discourages the use of animals in science projects, but they can be done on the approval and supervision of a biology teacher, which is how this student proceeded. Discussion Questions 1. As far as you can tell the mice were treated well and terminated humanely, without undue pain. What would you say to the student about the use of animals in this science fair project? Would you caution the student? Would you recommend different techniques? Would you discourage the use of animals in this way? 2. Does the fact that this experiment was for a science fair or used such a small number of mice and thus is unlikely to be published or advance knowledge, raise any ethical concerns about this use of animals in experiments? 3. Should live animals be used as teaching tools for High School science education? Why or why not? When is it appropriate to introduce live animals as experimental subjects in science education?
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