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o the untrained eye, the pictures on physicist Timothy Duong’s computer screen don’t look like much—softball-sized globes of wrinkled gray matter flecked with bright spots of color. But these images—MRI scans of the brains of rhesus macaques—may hold the key to a revolution in modern medicine.
     “We have MRI, functional MRI (fMRI), micro PET, and other modalities such as optical retina imaging,” Duong says, showing off Yerkes’ Neuroscience Research Facility like a first-time homeowner. The $27 million building, with the only neuroimaging center in the country devoted to nonhuman primate studies, serves as home base for one of Yerkes’ expanding research frontiers: the brain.
     Why house so much imaging power at a primate center?
     “Most researchers must transport animals to an off-site facility—usually one dedicated to imaging human patients,” says Duong. “And then they don’t have access to the level of imaging and degree of specialization we have here to monitor brain development and function.”
     This ability will be key as the center embarks on a new research endeavor.
     Within the next four years, Yerkes geneticist Anthony Chan hopes to develop the first transgenic nonhuman primate model for inherited neurodegenerative diseases. If he is successful, the new imaging technologies will allow researchers to study changes in the brain in a way that has never been possible before.
     Chan, who developed the world’s first transgenic nonhuman primate at Oregon Health & Science University in 2000 (a monkey with a jellyfish gene inserted into its DNA), was recruited by Emory in 2002 to pursue a new goal: developing a primate model for Huntington’s disease.
     The disease does not normally occur in rhesus monkeys, but if the human genes associated with Huntington’s can be inserted in the animals, then the neurologic changes caused by the disease can be studied more effectively.
     Eventually, Chan’s studies will examine the entire spectrum of the disease, from detecting what makes the transgenic monkeys susceptible to illness, to studying the disease’s onset and progression using functional MRI to monitor changes in the brain.
A breed apart  
As Yerkes celebrates its 75th anniversary, Chan’s research is just one example of how the center is at the forefront of an emerging era in biomedical research. Called by many different names—genomic medicine, predictive health, or predictive medicine—this new age is one in which scientists believe they will be able to determine who will get certain diseases simply by looking at a person’s genome—the genetic code that governs physical development.
     And many are predicting the early advances in this new, gene-based medicine will be seen in neuroscience.
     At the April 8, 2005, Futurist Forum—a gathering of visionaries from around the nation who weighed in on Emory University’s strategic planning process—one speaker quipped, “When I first met Mike Johns, I told him the School of Medicine should be renamed the School of Neuroscience, because the brain is the commanding organ of the body—medical health starts with brain health,” said Floyd Bloom, professor emeritus at the Scripps Research Institute and former president of the Society for Neuroscience.
     And in this new era of medicine, says Yerkes Director Stuart Zola, brain health research will start not with neurologists and human patients but with nonhuman primates.
     “Yerkes intends to be established as a world leader in neuroscience research,” Zola says matter-of-factly. “We have a convergence of so many research capabilities that are going to be important for understanding how the brain is organized, how brain function translates to behavior, and what that really means.”
     In addition to Chan’s work, Lary Walker, research professor in neurology, plans to use transgenic models to research diseases like Alzheimer’s and Parkinson’s.
     “No organisms except humans develop Alzheimer’s disease,” Walker says. “We want to find out what is different between a rhesus monkey and a human that results in the human getting the disease while the rhesus doesn’t.”
Out of the shadows  
Taking on this brave new research world has required something of a fundamental climate change within Yerkes. The center has been accustomed to serving a vital, yet largely hidden role in fostering medical advances.
     “When I arrived here, there was a tendency to try to keep Yerkes off everyone’s radar,” says Zola, the center’s director since 2001. That old conventional wisdom had been shaped by years of animal rights protests, some ending literally at Yerkes’ front gate. This was not the kind of publicity center directors wanted, and so they avoided attention altogether.
     But now an entirely different approach is needed, Zola believes. The advances in genomic medicine have been accompanied by new challenges to medical research and to nonhuman primate research in particular, he says. If the promise of this new science is to be realized, the public must understand the value of the research conducted at Yerkes and the consequences for humankind if the work is restricted.
     “We need to be proactive,” he says. “We need to be aggressive about our profile in the community. We have important stories to tell. We’re doing research that is admirable, lifesaving, and humane, and the public needs to know that.”
Survival of the fittest  
The push of this new scientific momentum comes at a time when nonhuman primate research is facing new challenges.
     In September 2005, a group of international scientists announced the completion of the mapping of the chimp genome, which relied on DNA from a Yerkes chimpanzee. Chimps and humans share 98% of their genetic makeup, making chimps an ideal model for studying human neurologic development. This year, scientists also expect to finish mapping the genome of the rhesus macaque, the most widely used nonhuman primate in science.
     Mapping of the chimp genome was greeted with understandable excitement in the scientific community. The entire September 2005 issue of the journal Nature was devoted to coverage of its implications. But it also raised new questions—even among some scientists—about the ethics of conducting certain experiments on great apes. Few other countries permit the use of chimpanzees in biomedical research.

     Zola believes too many people are unaware of the important role chimps have played in many of the important medical discoveries of the past two decades, including helping scientists understand the basic makeup of HIV and how it infects cells and the development of a vaccine for hepatitis B.
     More recently, chimpanzees have been vital to testing monoclonal antibodies—genetically engineered agents that are almost identical to naturally occurring antibodies, cells our immune systems develop to fight infection. These antibodies one day may be used to “vaccinate” people against different cancers and autoimmune diseases.
     Now that we know the extent to which chimpanzees are genetically similar to humans, their research potential is even greater, says Zola. With both the chimp and human genomes sequenced, comparisons between the two are being used to identify genetic links to diseases that uniquely affect people.
     And those are just the research avenues already under way, Zola says. “It’s very likely within the next few decades that we will discover more.”
      Thirty-five years ago, it would have been impossible to predict that chimpanzees would hold the key to understanding the basis of AIDS or hepatitis B and C because the viruses that cause those illnesses had not been discovered yet, he points out. Now, advances in genetic and molecular research are rapidly delineating new treatment possibilities, many of which were unheard of a decade ago.
     It’s essential that researchers who work with primates become more vocal and active to ensure that the scientific benefits of research are weighed along with its challenges, Zola says.
     It’s one of the reasons he accepts outside speaking engagements and encourages other Yerkes scientists to serve on speaker’s bureaus and do other forms of advocacy in their areas of specialization, giving primate research a higher level of visibility.
Evolved leadership  
It also helps that the Woodruff Health Sciences Center is visibly committed to supporting the work at Yerkes, including it at a level on par with the center’s other academic components—the schools of medicine, nursing, and public health.
     “The three deans and I all sit at Mike Johns’ table for executive leadership,” says Zola. “None of the other seven national primate research centers have that kind of reporting organization.”
     And there are signs the evolution in communication strategy is working in support of the potentially revolutionary research under way at Yerkes. Although diminished in number, animal rights protesters were back again last spring, carrying placards and shouting personal insults at animal researchers. But for the second year in a row, supporters of animal research staged a counter-protest to balance the equation.
     A result of Zola’s aggressive PR campaign, perhaps? He sure thinks so.
     “I like to attribute the lack of enthusiasm in these animal rights demonstrations to the fact that the public has begun to understand what we do and why it’s important,” he says. “As long as we make it clear that we are serious about our stewardship of the welfare of the animals and we are definitive about our successes, there’s support to do this research. We will continue to tell our story in a clear and truthful way.”

Michael Terrazas is editor of Emory Report.
75 Years of Discovery
The expanded focus on neuroscience doesn’t mean Yerkes is reducing the broad array of research that put the center on the map long ago—research like that of world-renowned primatologist Frans de Waal, whose studies of primate social interactions recently earned him induction into the National Academy of Sciences. Or that of psychobiology chief Mark Wilson, who examines how hormones affect adult social behavior. Transplant surgeons Christian Larsen and Thomas Pearson are continuing to break new ground in developing medications to prevent organ rejection. Georgia Research Alliance Eminent Scholar Mike Kuhar is working on potential treatments for cocaine addiction. And researcher Mike Mustari’s work on nerve function and visual development may one day help physicians preserve the sight of children born with congenital eye diseases.
     Harriet Robinson, Yerkes’ chief of microbiology and immunology, who was recruited eight years ago from Boston University, is continuing her effort to develop a DNA vaccine to fight AIDS. Robinson’s two-step vaccine (a DNA prime and a recombinant poxvirus as a booster) has been in Phase I clinical trials for three years. Robinson says it could be 2012 at the earliest before any vaccine is ready for humans, but she estimates that Phase III efficacy
trials could come as soon as 2009.
     “There are 20 to 25 AIDS vaccines in development around the United States, and none has preclinical data as strong as ours,” she says. Robinson credits the foundation of knowledge that exists among Yerkes scientists for helping advance her own work, and that synergy could in the not-too-distant future break down even more disciplinary walls. For example, might Yerkes someday be involved in developing a vaccine for Alzheimer’s?
     “A few years ago there was a big splash about immunization therapy for Alzheimer’s,” says neurology researcher Lary Walker, adding that human trials of a vaccine ended when enrolled patients began developing encephalitis. But the approach still holds promise. Walker is using squirrel monkeys to continue Alzheimer’s immunization studies, with some preliminary success.
     The ability of faculty at Yerkes to work across disciplines and collaborate with each other, as well as with researchers throughout the Health Sciences Center and on national and international levels, will be key in achieving many of these goals.
     “Collaborations like these are the kinds of critical processes that differentiate institutions that produce Nobel Prize winners from those that don’t,” says Yerkes director Stuart Zola. “Institutions that foster Nobel Prize winners don’t necessarily have better labs or the latest equipment—what they have are places that nurture interdisciplinary thinking in order to look at issues in a new and bold way.”


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