Ronald Hunt
During the past 30 years, research involving nonhuman
primates has helped unlock some of the great secrets of
biology. Investigations of monkeys and apes have helped
reveal how the brain "sees" the world and how we fall prey
to a host of diseases, including AIDS.
Yet, at the same time, the use of primates is a flash point in the emotional public debate over the ethics of using animals in research. And that tension-between a legacy of invaluable research and of present-day ethical concerns-is presenting a challenge to the New England Regional Primate Research Center as it enters its fourth decade.
The use of primates in research is dwindling today for a variety of reasons: the ethical controversy, the cost of using primates, and the emergence of molecular biology. Indeed, as biologists focus their sights on the cell and the gene, they are able to conduct many of their investigations in mice and even in isolated cells. But the history of groundbreaking discoveries is a compelling reminder of what can be learned from research in monkeys.
"A lot is being done at the molecular level," says Ronald Hunt, professor of comparative pathology and director of the New England Primate Research Center. "But a lot of things still need a whole animal."
The primate center occupies a heavily wooded campus 25 miles west of Boston in Southborough. Since it opened in 1966 with a grant from the National Institutes of Health, scientists from all over the world have come to the center with the aim of finding solutions to medical problems ranging from myopia to drug addiction to infectious diseases such as AIDS. The simian immuno- deficiency virus (SIV), the animal model for HIV, was first isolated at the center in the early 1980s.
The primate center is a child of the Cold War and, in particular, the mid-century rivalry in science between the United States and Russia. The idea for a group of regional primate centers arose when American scientists, including Harvard Medical School cardiologist Paul Dudley White, visited a Russian primate research facility in Sukhumi, on the Black Sea.
"They came back and were very impressed that Russia had this huge primate research facility and the U.S. had nothing. And this was at the same time as Sputnik. You know, Russia is ahead of us, we've got to catch up," says Hunt.
In 1961, Congress appropriated money to construct seven regional primate research centers and invited applications from host institutions across the United States. Harvard was chosen to receive a grant from NIH in 1962. Four years later, the New England Regional Primate Center opened its doors under the directorship of Bernard Trum.
The New England Regional Primate Center in Southborough
runs a prominent money-breeding program.
"Our charge from NIH was to serve as a regional
resource. Investigators that have research requiring monkeys
or their tissues can come here to do their research," says
Hunt, who became director in 1976. "It might be their red
blood cells, it may be their urine. It may be some hair. It
may be the whole animal."
In addition to serving the biomedical community, the center has reached out to researchers doing primary research on monkeys, studying their biology and behavior. "By better understanding the monkey, you uncover new knowledge that allows you to explore new biomedical research opportunities," Hunt says.
In fact, during the past 30 years, discoveries in monkey biology at the center have resulted in a number of biomedical breakthroughs. The first of these discoveries occurred in the late 1970s when the center's researchers discovered that a herpes virus, called virus T, was the cause of a lethal disease in a colony of owl monkeys. In the course of studying the new virus, the researchers discovered another herpes virus, one that caused leukemia. Until then, no one had ever observed that a virus could cause cancer in a mammal. Soon after, the Epstein-Barr virus was found to be associated with Burkitt's lymphoma in humans.
The discovery of virally transmitted cancer in monkeys gave rise to a new research program on how the herpes virus transforms white blood cells-or lymphocytes-into cancer cells. "Much of that is now molecular, in tissue culture," Hunt says. "But it began with a study of sick monkeys."
"We didn't know what was going on. Then all of a sudden, there was this new funny [immunosuppressive] disease happening in New York and San Francisco that didn't even have a name-the term AIDS had yet to be coined. HIV had not been discovered. No one knew what caused it-they had all sorts of wild ideas," Hunt says.
Hunt suspected a connection between the human and monkey outbreaks of immunosuppressive disease. He went to Baruj Benacerraf, then head of pathology at HMS, who sent a young researcher, Norman Letvin, now associate professor of medicine, to help Hunt unravel the similarities.
"We isolated a virus that we thought was the answer, but it wasn't," Hunt says.
However, at the same time, Hunt and his colleagues had been studying how leukemia was transmitted virally in monkeys. During their investigations, they came across a stunning result. When they took tissue from a leukemia- infected rhesus monkey, and put it into other monkeys, some monkeys began dying of cytomegalovirus infection. To find out what was causing the immunosuppressive disease, they analyzed tissue from the leukemic monkeys and isolated a virus.
"The more you understand the animal you're working with, the better your research is going to be." -- Ronald Hunt
The virus was SIV. SIV, which is a slow-acting virus (or lenti virus), is very similar to HIV and includes many of the same genes. "We now have a model system for studying [HIV]," says Hunt.
More than half of the 50 staff researchers at the primate center are currently involved in AIDS research under the direction of Ronald Derosiers, professor of microbiology and molecular genetics, R. Paul Johnson, assistant professor of medicine and Andrew Lackner, assistant professor of comparative pathology. Partly because of that commitment to AIDS research, basic research in primatology at the center has tailed off in recent years.
The number of biomedical research projects at the center also has declined in recent years. "My guess is that if you stick too much difficulty in the way of a particular type of research for whatever reason-because it's too expensive, because it's hard to get the animals-today science moves so fast that you immediately say I'm not going to work with [monkeys]. I'm going to work with something else," says Elio Raviola, Bullard professor of neurobiology.
Raviola, who has spent more than 20 years at the center studying myopia, thinks that turning away from research in primates is a mistake. "If at some point you don't use the primate, you don't have a model that is very close to the human. And then either you experiment directly on humans, or you use an inappropriate animal."
During the past 30 years, the center has evolved into an important breeding facility, and currently houses the largest breeding colony of the endangered cotton-top tamarin. The center also has begun a "pathogen free" breeding program; the breeding rhesus monkeys are monitored to be sure they are free of specific viruses and pathogens. "Our goal is to convert the whole colony of macaques into an SPF [specific pathogen free] colony," says Prabhat Seghal, senior veterinarian.
Such a colony could provide an invaluable resource for organ transplant and vaccine research as well as for basic research into human and animal disease. Hunt notes that the center today is greatly underused; only one-third of the center's 1,500 monkeys-rhesus, squirrel monkeys, baboons, tamarins- are being utilized for research. Many research projects, he notes, can utilize monkeys in a noninvasive way.
"For example, you could take monkeys in the breeding colony and give half of them beta carotene and five years from now, measure something-I don't know what to measure. Maybe there's someone bright on the faculty who does," says Hunt. "The fact that we have animals here-if somebody is interested in studying hair, we can at a nominal cost get some monkey hair for them. Our point is to raise the question: Are we fully taking advantage of the resources that are available?"
--Misia Landau