• 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
NERVECENTER
A10
Eye Movement Disorders in Clinical Practice, will be released by Oxford University Press in January 2014.
worst of times. The prospects to make meaningful discoveries seem so grand, yet the obstacles facing young investigators are more daunting than ever before. What advice would you give to a young person contemplating a career as an investigator in academic neurology? SW: They should go after doing what they want to do. For example, if an opportunity comes up in a lab for somebody to work on epilepsy and a young person isn’t really interested in epilepsy but would simply like a position in that academic hospital, there is always a big temptation to go for the job anyway. This would be a mistake—you are going to be most productive, happy, and successful academically and clinically if you are pursuing a career on a topic that really interests you. People sometimes make the easier choice or take a job out of perceived necessity, rather than follow the more difficult course of pursuing one’s true interest. In the end, the easy way is too often the wrong way. AON: You are also a legendary educator at Harvard and beyond. What are the key ingredients for success as a teacher of medicine? SW: The key is that you have to like teaching. It has to be something you enjoy doing and you don’t mind being challenged in your assumptions; you find it stimulating and always thought provoking. Teaching is a two-way street, you can learn from the stu-
dent and the student can learn from you— and it is not just knowledge or insight you should aim to provide for your students, but also an awareness of how to teach. Teachers have to be creative, they need to put work and thought into it. If they do, it’s very rewarding. AON: What do you like to do outside of the hospital? SW: I’m athletic. I loved to run and I played English university tennis. When I came to America, I developed a passion for skiing. Then I took up small boat sailing and joined a racing group on Martha’s Vineyard. Now, I am addicted to golf. AON: Could you share with us a preview of your new book? SW: My book, Eye Movement Disorders in Clinical Practice, will be released by Oxford University Press in January 2014. It is a very personal book documenting my experiences as a neurologist over the last 50 years. Eye movement disorders, although common, raise difficult questions with regard to diagnosis, management, and treatment, and there are always many aspects to these disorders. My “clinical points to remember” reveal the personal preferences that have worked for me and, hopefully, will work for others. The book comes with video clips of 56 unusual cases that I have seen, treated, and recorded over the years, and which Nancy Lombardo and the NOVEL group at the University of Utah helped me publish electronically. My video collection actually began many years ago when David Cogan and I developed an annual teaching course in neuro-ophthalmology. We decided we would never show the same case twice and we video-recorded unique patient cases that we saw during the year. I have added cases every year since, and I am especially grateful to the patients whose permission has contributed so much to my book. An e-book will be published in the spring of next year, which will make it very easy to use video display to watch videos immediately. Readers who would like to view additional video of a variety of other eye movement disorders can access my website through the NOVEL website of the North American Neuro-Ophthalmology Society: http://NOVEL.utah.edu/Wray or by accessing my collection at Harvard Medical School, Countway Library: http://repository. countway.harvard.edu/Wray. •
She sat down with Stephen L. Hauser, MD, Editor-in-Chief of Annals of Neurology (AON), to discuss her career, the changes she’s witnessed in the field of neurology, and her new book on eye movement disorders. AON: Shirley, it must be gratifying to see so many prominent women in the current generation of academic neurologists. Do you feel like a pioneer, and do you think that there is now a level playing field for men and women in academic medicine? SW: It is wonderful to see more women academics in leadership positions, and I have been fortunate to work with two—Anne Young, former chair of neurology at MGH, and her successor Merit Cudkowicz, who has a real passion for neurology. These women are examples of the best in academic neurology. In the early days, when I was in London, I did feel like a pioneer. In the 1950s, I was only the second woman to go on the House at the National Hospital, Queen Square. I feel less of a pioneer in America, but there is still a real deficit of women in academic neurology and in the membership of the ANA. Is the playing field level? It’s not. When medical students, residents, and fellows ask about gender equality, I am still cautious. All things are not equal—by and large, a man will still get the job ahead of a woman unless she is already a step ahead. For example, he has an MD; she has an MD, PhD. Hard, but it is real. Mentors also play a role in helping female neurologists get ahead. But, you can’t just hope for a mentor. You have to earn one by giving as much in time and help as you hope to get. Mentors can make all the difference with personal phone calls and insightful letters of recommendation to help a young colleague move up. AON: You’ve worked with so many remarkable people: Ray Adams, E. P. Richardson, Charles Miller Fisher, Anne Young, and Verne Caviness, among others. What were the qualities that made them so effective? SW: They all shared a passion for their work in medicine and they shared, as well, a disarming humility that made them great communicators. It doesn’t hurt to be brilliant, but if you are both brilliant and modest, it’s unbeatable. AON: In many respects, these are the best of times and also the
•
DOI: 10.1002/ana.24075
Volume 74, No. 4
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
NERVECENTER
A10
Eye Movement Disorders in Clinical Practice, will be released by Oxford University Press in January 2014.
worst of times. The prospects to make meaningful discoveries seem so grand, yet the obstacles facing young investigators are more daunting than ever before. What advice would you give to a young person contemplating a career as an investigator in academic neurology? SW: They should go after doing what they want to do. For example, if an opportunity comes up in a lab for somebody to work on epilepsy and a young person isn’t really interested in epilepsy but would simply like a position in that academic hospital, there is always a big temptation to go for the job anyway. This would be a mistake—you are going to be most productive, happy, and successful academically and clinically if you are pursuing a career on a topic that really interests you. People sometimes make the easier choice or take a job out of perceived necessity, rather than follow the more difficult course of pursuing one’s true interest. In the end, the easy way is too often the wrong way. AON: You are also a legendary educator at Harvard and beyond. What are the key ingredients for success as a teacher of medicine? SW: The key is that you have to like teaching. It has to be something you enjoy doing and you don’t mind being challenged in your assumptions; you find it stimulating and always thought provoking. Teaching is a two-way street, you can learn from the stu-
dent and the student can learn from you— and it is not just knowledge or insight you should aim to provide for your students, but also an awareness of how to teach. Teachers have to be creative, they need to put work and thought into it. If they do, it’s very rewarding. AON: What do you like to do outside of the hospital? SW: I’m athletic. I loved to run and I played English university tennis. When I came to America, I developed a passion for skiing. Then I took up small boat sailing and joined a racing group on Martha’s Vineyard. Now, I am addicted to golf. AON: Could you share with us a preview of your new book? SW: My book, Eye Movement Disorders in Clinical Practice, will be released by Oxford University Press in January 2014. It is a very personal book documenting my experiences as a neurologist over the last 50 years. Eye movement disorders, although common, raise difficult questions with regard to diagnosis, management, and treatment, and there are always many aspects to these disorders. My “clinical points to remember” reveal the personal preferences that have worked for me and, hopefully, will work for others. The book comes with video clips of 56 unusual cases that I have seen, treated, and recorded over the years, and which Nancy Lombardo and the NOVEL group at the University of Utah helped me publish electronically. My video collection actually began many years ago when David Cogan and I developed an annual teaching course in neuro-ophthalmology. We decided we would never show the same case twice and we video-recorded unique patient cases that we saw during the year. I have added cases every year since, and I am especially grateful to the patients whose permission has contributed so much to my book. An e-book will be published in the spring of next year, which will make it very easy to use video display to watch videos immediately. Readers who would like to view additional video of a variety of other eye movement disorders can access my website through the NOVEL website of the North American Neuro-Ophthalmology Society: http://NOVEL.utah.edu/Wray or by accessing my collection at Harvard Medical School, Countway Library: http://repository. countway.harvard.edu/Wray. •
She sat down with Stephen L. Hauser, MD, Editor-in-Chief of Annals of Neurology (AON), to discuss her career, the changes she’s witnessed in the field of neurology, and her new book on eye movement disorders. AON: Shirley, it must be gratifying to see so many prominent women in the current generation of academic neurologists. Do you feel like a pioneer, and do you think that there is now a level playing field for men and women in academic medicine? SW: It is wonderful to see more women academics in leadership positions, and I have been fortunate to work with two—Anne Young, former chair of neurology at MGH, and her successor Merit Cudkowicz, who has a real passion for neurology. These women are examples of the best in academic neurology. In the early days, when I was in London, I did feel like a pioneer. In the 1950s, I was only the second woman to go on the House at the National Hospital, Queen Square. I feel less of a pioneer in America, but there is still a real deficit of women in academic neurology and in the membership of the ANA. Is the playing field level? It’s not. When medical students, residents, and fellows ask about gender equality, I am still cautious. All things are not equal—by and large, a man will still get the job ahead of a woman unless she is already a step ahead. For example, he has an MD; she has an MD, PhD. Hard, but it is real. Mentors also play a role in helping female neurologists get ahead. But, you can’t just hope for a mentor. You have to earn one by giving as much in time and help as you hope to get. Mentors can make all the difference with personal phone calls and insightful letters of recommendation to help a young colleague move up. AON: You’ve worked with so many remarkable people: Ray Adams, E. P. Richardson, Charles Miller Fisher, Anne Young, and Verne Caviness, among others. What were the qualities that made them so effective? SW: They all shared a passion for their work in medicine and they shared, as well, a disarming humility that made them great communicators. It doesn’t hurt to be brilliant, but if you are both brilliant and modest, it’s unbeatable. AON: In many respects, these are the best of times and also the
•
DOI: 10.1002/ana.24075
Volume 74, No. 4
![[Syncope from the viewpoint of a neurologist].](/assets/img/hold.png)
