NERVECENTER December 2013
Neuroscientists Navigate Divide on
Nonhuman Primate Research
Since a December 2011 Institute of Medicine report, which prompted a series of federal regulations strengthening limits on the use of chimpanzees in biomedical and behavioral research, many neuroscientists have been warily watching the impact of the new regulations.1 “As I see them, the regulations are rigorous, but reasonable; it’s possible to interpret them in a way that protects animal subjects and makes it possible for me to do my research,” says neuroscientist Stephen Lisberger, PhD, George Barth Geller Professor and Chair of Neurobiology at Duke University in Durham, North Carolina. Lisberger’s research with rhesus monkeys helps us understand how human beings learn—and, he believes, could ultimately contribute to our understanding of neurodegenerative and neuropsychiatric disorders. But Lisberger hastens to add that regulations often depend on who is interpreting them and that it’s been less possible for some of his colleagues to continue their work. Scott Wong, PhD, Interim Chief of the Division of Pathology and Immunology at the Oregon National Primate Research Center (ONPRC) in Beaverton, voices similar concerns. Wong is senior author on a study that discovered a multiple sclerosis–type disease in macaque monkeys.2 The discovery opens what many believe is an important research window into long-held theories about how the disease is triggered. Wong says the ONPRC does not have any chimpanzees, but worries that, “these regulations could work their way down to other nonhuman primates.” If that happened, say the researchers, the tightening restrictions could potentially compromise or even halt some neurological research, slowing progress on diseases from multiple sclerosis to Parkinson disease—and prolonging the agony of A8
patients and families. Some scientists also argue that removing nonhuman primates from clinical research could endanger patients, should researchers have to make the leap to human clinical trials from rodent studies and/ or computer modeling. On the other hand, critics of nonhuman primate research question whether scientists try hard enough to answer questions and meet standards raised by nearly every animal rights group, as well as by the IOM report and Europe’s so-called Bateson report (Review of Research Using Non-Human Primates).3 These groups ask: Does the research genuinely require the use nonhuman primates? And even if it does, is it of enough scientific importance to justify the costs and the ethical concerns? Most, if not all, of the animal rights groups would argue it is not.
The Science Question In 2012, The Hastings Center, a bioethics research institution, issued a report titled The Case for Phasing Out Experiments in Primates.4 Authored by two members of the Humane Society of the United States, the piece acknowledged that the Bateson report found most neurological research on nonhuman primates was of high scientific value. Nevertheless, the authors asserted that the IOM report, which concluded, “Most current use of chimpanzees for biomedical research is unnecessary,” should serve as a case study for how to examine all primate research.1 Yet many scientists say that because nonhuman primates are the closest genetic and physical link to humans, in certain cases studying these animals is the safest and best way to understand brain function, and to test diagnostic techniques and potential therapies. “I don’t think anybody likes working with nonhuman primates,” says Dennis Bourdette,
Will & Deni McIntyre / Science Source.
NEW REGULATIONS CONCERN SOME RESEARCHERS, BUT OTHERS QUESTION THE NECESSITY OF MOST RESEARCH ON NONHUMAN PRIMATES
A scientist feeds Rhesus monkeys (Macaca mulatta) at a research institution.
MD, Chair of Neurology and Director of the Multiple Sclerosis and Neuroimmunology Center at Oregon Health & Science University in Portland, who co-authored the multiple sclerosis study with Wong and publishes frequently on the disease. “The people who do it do so because they can answer important questions related to the health of people that cannot be answered with other animals.” Neuroscientist Kathy Grant, Head of the Division of Neuroscience at the ONPRC, agrees. “We now have funding to look at in-utero non-human primate brain development,” she says. “[We hope] we can provide physicians with a noninvasive, repeated longitudinal measure of normal brain development to see that a fetus is developing normally. And, this may be applicable to a lot of different neurological conditions, but you can’t do these projects in rodents—and what we’ve gleaned from these studies so far is remarkable and having real human impact.” Nobody discounts the value of rodent Volume 74, No. 4
• NERVECENTER
The Cost Question Perhaps not, but are the answers worth the financial cost? The Hastings Center report claims that the eight National Primate Research Centers receive $1 billion of the National Institute of Health’s $32 billion budget and that care and upkeep of nonhuman primates other than chimpanzees is $20 to $25 dollars a day, compared with $.20 to about $1.60 per day for small rodents.4
Few neuroscientists would argue that nonhuman primate research is cheap. Some counter, however, that nonhuman primate research makes up less than 1% of the animal research done in this country. And Lisberger, for one, believes the many fewer nonhuman primates makes the cost concern a red herring. “I have ten primates,” he says. “My colleagues who do rodents have 50,100,400 rodents. I would argue it’s less costly to do my research than rodent research.” Larry Sherman, Senior Scientist in the Division of Neuroscience at the ONPRC, says, “For me, the costs to society of diseases far outweigh the costs of the research.”
The Ethical Questions Probably the most heated disputes revolve around the long list of troubling ethical concerns that animal rights groups point to. They include the cognitive and emotional awareness of the nonhuman primates, the processes by which studies are approved, the removal of the nonhuman primates from the wild, and their treatment in captivity. Certainly, there have been numerous, high-profile cases of animal mistreatment— cases that none of the researchers quoted here would defend. But at the national primate centers, say the researchers, nearly all of the animals are purpose-bred for research, have been for generations—and have healthcare that many humans would envy. “As far as I know, the people doing research on nonhuman primates in neuroscience are ensuring proper care and treatment,” says Lisberger. “The animals receive enrichment and socialization, analgesics and anes-
thesia as appropriate, and probably have more direct veterinary care than the average human does with their healthcare.” Grant adds that researchers are working to minimize the use of the nonhuman primates. “We have a number of collaborations that go across groups—geneticists, imaging, immunologists—who are all working on the same monkeys,” she says. As for the animals’ cognitive and emotional awareness, “I think about this all the time,” says Sherman. “None of us take using an animal lightly; we are sometimes asking the animal to sacrifice a life for our studies … . My personal justification is I’ve seen many human beings suffer from these diseases and my calculus is that it is worth sacrificing a limited number of animals for the millions of people suffering. I realize not everyone agrees.” •
research or computer modeling, the two research avenues that many argue can replace much of the work with nonhuman primates. But many scientists believe the power of those two avenues—especially the computer models—has been overstated. “These are biological systems, they’re complicated and we don’t know all the details yet to create an appropriate computer model,” says Wong. “There is a huge effort at primate centers to develop intercenter databases to get a better understanding of disease processes and reduce the number of animals we will need. If we can characterize genotypes and phenotypes better, we can avoid using large cohorts.” “Everyone who does the kind of work I do spends more time on computers doing theoretical analyses than we do working with monkeys; we leverage the data to the fullest possible extent, but there’s only so much you can do with computers,” says Lisberger. “You can streamline your research and answer more focused questions [with computer models],” says Bourdette. “But you can’t replace the animal research for clarifying any ideas you generate.”
ANDREW SCHWARTZ DOI: 10.1002/ana.24074
References 1. Institute of Medicine, Committee on the Use of Chimpanzees in Biomedical and Behavioral Research. Chimpanzees in biomedical and behavioral research: Assessing the necessity. Washington, D.C.: National Academies Press; 2011. 2. Axthelm MK, Bourdette DN, Marracci GH, et al. Japanese macaque encephalomyelitis: a spontaneous multiple sclerosis-like disease in a nonhuman primate. Ann Neurol. 2011;70:362-373. 3. Review of research using nonhuman primates: Report of a panel chaired by Sir Patrick Bateson, FRS. Wellcome Trust. 2011. Available at www. wellcome.ac.uk/stellent/groups/corporate site/@policy_communications/documents/ web_document/wtvm052279.pdf. Accessed October 1, 2013. 4. Conlee KM, Rowan AN. The case for phasing out experiments on primates. Hastings Cent Rep. 2012;42(6 Suppl):S31-S34.
Neurologist with Vision SHIRLEY WRAY BRINGS A UNIQUE VIEWPOINT TO THE UNDERSTANDING OF NEURO-OPHTHALMOLOGY— AND THE FIELD OF NEUROLOGY
Shirley H. Wray, MD, PhD
December 2013
Shirley H. Wray, MD, PhD, has long had an interest in neuro-ophthalmology. After completing her neurology training in London, she came to Massachusetts for a fellowship in neuro-ophthalmology at the Howe Laboratory of Ophthalmology, Massachusetts Eye and Ear Infirmary—and she’s been in Boston ever since. She joined the faculty of Harvard Medical School, where she is currently Professor of Neurology, in 1969. Her career has included many teaching awards and mentorship roles, and she has developed an extensive library of educational materials and videos on neurovisual disorders. A9
Neuroscientists Navigate Divide on
Nonhuman Primate Research
Since a December 2011 Institute of Medicine report, which prompted a series of federal regulations strengthening limits on the use of chimpanzees in biomedical and behavioral research, many neuroscientists have been warily watching the impact of the new regulations.1 “As I see them, the regulations are rigorous, but reasonable; it’s possible to interpret them in a way that protects animal subjects and makes it possible for me to do my research,” says neuroscientist Stephen Lisberger, PhD, George Barth Geller Professor and Chair of Neurobiology at Duke University in Durham, North Carolina. Lisberger’s research with rhesus monkeys helps us understand how human beings learn—and, he believes, could ultimately contribute to our understanding of neurodegenerative and neuropsychiatric disorders. But Lisberger hastens to add that regulations often depend on who is interpreting them and that it’s been less possible for some of his colleagues to continue their work. Scott Wong, PhD, Interim Chief of the Division of Pathology and Immunology at the Oregon National Primate Research Center (ONPRC) in Beaverton, voices similar concerns. Wong is senior author on a study that discovered a multiple sclerosis–type disease in macaque monkeys.2 The discovery opens what many believe is an important research window into long-held theories about how the disease is triggered. Wong says the ONPRC does not have any chimpanzees, but worries that, “these regulations could work their way down to other nonhuman primates.” If that happened, say the researchers, the tightening restrictions could potentially compromise or even halt some neurological research, slowing progress on diseases from multiple sclerosis to Parkinson disease—and prolonging the agony of A8
patients and families. Some scientists also argue that removing nonhuman primates from clinical research could endanger patients, should researchers have to make the leap to human clinical trials from rodent studies and/ or computer modeling. On the other hand, critics of nonhuman primate research question whether scientists try hard enough to answer questions and meet standards raised by nearly every animal rights group, as well as by the IOM report and Europe’s so-called Bateson report (Review of Research Using Non-Human Primates).3 These groups ask: Does the research genuinely require the use nonhuman primates? And even if it does, is it of enough scientific importance to justify the costs and the ethical concerns? Most, if not all, of the animal rights groups would argue it is not.
The Science Question In 2012, The Hastings Center, a bioethics research institution, issued a report titled The Case for Phasing Out Experiments in Primates.4 Authored by two members of the Humane Society of the United States, the piece acknowledged that the Bateson report found most neurological research on nonhuman primates was of high scientific value. Nevertheless, the authors asserted that the IOM report, which concluded, “Most current use of chimpanzees for biomedical research is unnecessary,” should serve as a case study for how to examine all primate research.1 Yet many scientists say that because nonhuman primates are the closest genetic and physical link to humans, in certain cases studying these animals is the safest and best way to understand brain function, and to test diagnostic techniques and potential therapies. “I don’t think anybody likes working with nonhuman primates,” says Dennis Bourdette,
Will & Deni McIntyre / Science Source.
NEW REGULATIONS CONCERN SOME RESEARCHERS, BUT OTHERS QUESTION THE NECESSITY OF MOST RESEARCH ON NONHUMAN PRIMATES
A scientist feeds Rhesus monkeys (Macaca mulatta) at a research institution.
MD, Chair of Neurology and Director of the Multiple Sclerosis and Neuroimmunology Center at Oregon Health & Science University in Portland, who co-authored the multiple sclerosis study with Wong and publishes frequently on the disease. “The people who do it do so because they can answer important questions related to the health of people that cannot be answered with other animals.” Neuroscientist Kathy Grant, Head of the Division of Neuroscience at the ONPRC, agrees. “We now have funding to look at in-utero non-human primate brain development,” she says. “[We hope] we can provide physicians with a noninvasive, repeated longitudinal measure of normal brain development to see that a fetus is developing normally. And, this may be applicable to a lot of different neurological conditions, but you can’t do these projects in rodents—and what we’ve gleaned from these studies so far is remarkable and having real human impact.” Nobody discounts the value of rodent Volume 74, No. 4
• NERVECENTER
The Cost Question Perhaps not, but are the answers worth the financial cost? The Hastings Center report claims that the eight National Primate Research Centers receive $1 billion of the National Institute of Health’s $32 billion budget and that care and upkeep of nonhuman primates other than chimpanzees is $20 to $25 dollars a day, compared with $.20 to about $1.60 per day for small rodents.4
Few neuroscientists would argue that nonhuman primate research is cheap. Some counter, however, that nonhuman primate research makes up less than 1% of the animal research done in this country. And Lisberger, for one, believes the many fewer nonhuman primates makes the cost concern a red herring. “I have ten primates,” he says. “My colleagues who do rodents have 50,100,400 rodents. I would argue it’s less costly to do my research than rodent research.” Larry Sherman, Senior Scientist in the Division of Neuroscience at the ONPRC, says, “For me, the costs to society of diseases far outweigh the costs of the research.”
The Ethical Questions Probably the most heated disputes revolve around the long list of troubling ethical concerns that animal rights groups point to. They include the cognitive and emotional awareness of the nonhuman primates, the processes by which studies are approved, the removal of the nonhuman primates from the wild, and their treatment in captivity. Certainly, there have been numerous, high-profile cases of animal mistreatment— cases that none of the researchers quoted here would defend. But at the national primate centers, say the researchers, nearly all of the animals are purpose-bred for research, have been for generations—and have healthcare that many humans would envy. “As far as I know, the people doing research on nonhuman primates in neuroscience are ensuring proper care and treatment,” says Lisberger. “The animals receive enrichment and socialization, analgesics and anes-
thesia as appropriate, and probably have more direct veterinary care than the average human does with their healthcare.” Grant adds that researchers are working to minimize the use of the nonhuman primates. “We have a number of collaborations that go across groups—geneticists, imaging, immunologists—who are all working on the same monkeys,” she says. As for the animals’ cognitive and emotional awareness, “I think about this all the time,” says Sherman. “None of us take using an animal lightly; we are sometimes asking the animal to sacrifice a life for our studies … . My personal justification is I’ve seen many human beings suffer from these diseases and my calculus is that it is worth sacrificing a limited number of animals for the millions of people suffering. I realize not everyone agrees.” •
research or computer modeling, the two research avenues that many argue can replace much of the work with nonhuman primates. But many scientists believe the power of those two avenues—especially the computer models—has been overstated. “These are biological systems, they’re complicated and we don’t know all the details yet to create an appropriate computer model,” says Wong. “There is a huge effort at primate centers to develop intercenter databases to get a better understanding of disease processes and reduce the number of animals we will need. If we can characterize genotypes and phenotypes better, we can avoid using large cohorts.” “Everyone who does the kind of work I do spends more time on computers doing theoretical analyses than we do working with monkeys; we leverage the data to the fullest possible extent, but there’s only so much you can do with computers,” says Lisberger. “You can streamline your research and answer more focused questions [with computer models],” says Bourdette. “But you can’t replace the animal research for clarifying any ideas you generate.”
ANDREW SCHWARTZ DOI: 10.1002/ana.24074
References 1. Institute of Medicine, Committee on the Use of Chimpanzees in Biomedical and Behavioral Research. Chimpanzees in biomedical and behavioral research: Assessing the necessity. Washington, D.C.: National Academies Press; 2011. 2. Axthelm MK, Bourdette DN, Marracci GH, et al. Japanese macaque encephalomyelitis: a spontaneous multiple sclerosis-like disease in a nonhuman primate. Ann Neurol. 2011;70:362-373. 3. Review of research using nonhuman primates: Report of a panel chaired by Sir Patrick Bateson, FRS. Wellcome Trust. 2011. Available at www. wellcome.ac.uk/stellent/groups/corporate site/@policy_communications/documents/ web_document/wtvm052279.pdf. Accessed October 1, 2013. 4. Conlee KM, Rowan AN. The case for phasing out experiments on primates. Hastings Cent Rep. 2012;42(6 Suppl):S31-S34.
Neurologist with Vision SHIRLEY WRAY BRINGS A UNIQUE VIEWPOINT TO THE UNDERSTANDING OF NEURO-OPHTHALMOLOGY— AND THE FIELD OF NEUROLOGY
Shirley H. Wray, MD, PhD
December 2013
Shirley H. Wray, MD, PhD, has long had an interest in neuro-ophthalmology. After completing her neurology training in London, she came to Massachusetts for a fellowship in neuro-ophthalmology at the Howe Laboratory of Ophthalmology, Massachusetts Eye and Ear Infirmary—and she’s been in Boston ever since. She joined the faculty of Harvard Medical School, where she is currently Professor of Neurology, in 1969. Her career has included many teaching awards and mentorship roles, and she has developed an extensive library of educational materials and videos on neurovisual disorders. A9
