A nationwide dearth of research monkeys has forced vaccine researchers at Harvard to scale back their studies, potentially compromising their rate of discovery, according to scientists.

The supply of research monkeys has been increasingly unable to meet the rapidly increasing demand over the past few years, making large-scale primate research projects difficult to organize and expensive to maintain.

And so many researchers have had to curtail their work to focus on more limited and specific questions than they might otherwise address.

“We have to design the experiments very carefully because of the lack of monkeys and their cost,” said Harvard Medical School (HMS) Associate Professor Judy Lieberman, who is part of a group researching an oral AIDS vaccine. “Because of that, they don’t answer all the questions you might have.”

HMS researcher R. Paul Johnson is conducting a study on how various vaccines affect the localization of T-cells to mucosal surfaces—an path of inquiry important in discovering a successful vaccine for mucosally-centered diseases such as AIDS. He planned his research to employ about 10 monkeys—enough to answer only one sort of question.

“I’ll be able to accomplish over the next three to five years the research I’m planning to do, but I think its more a case that the experiments have not been designed optimally because of the shortage,” he said. “As a result, we’re having to address these questions piecemeal.”

More test subjects would have allowed him to undertake a more comprehensive, multivariate study of vaccine effectiveness, he said.

The shortage centers on rhesus macaque monkeys, which are used in more than half of primate research projects across the nation, according to Ronald C. Desrosiers, who directs of the New England Primate Research Center (NEPRC), which is part of HMS. Researchers favor rhesus monkeys for disease treatments tests because of their biological similarity to humans.

“You can get some guidance from small animals like mice, but experience has shown that attributes don’t transfer well,” Lieberman explained. Before applying research to humans, most disease treatment researchers refine their work through primate study.

Her project, planned on a larger scale than Johnson’s, requires 86 monkeys at the Yerkes Regional Primate Research Center in Atlanta, Ga. But the study attempts only to determine whether test vaccines effective in preventing the virus.

Should she and her colleagues wish to explore their results even a bit further—such as to determine whether the test vaccines also offer effective treatment—they would need more monkeys, she explained.

Acquiring the necessary number of animals would be exceedingly difficult in the face of the shortage and the price increase it has yielded.

Rhesus monkeys presently cost $5,000 each to purchase, she said, and care during research contributes considerably to the overall cost of a primate study. Purchasing the dozens of monkeys for her present study would not have been possible without a hefty research grant, she said.

Finding such funding—and acquiring animals in a tight market—has stymied several similar studies, she said.

“It’s a very common problem for people who are developing new therapies and new vaccine,” she said. “It’s a combination of the availability of the animals plus the high cost of the experiments.”

Desrosiers said NEPRC—which allots animals to researchers from within and without the Center at the discretion of a special committee—has been relatively successful in meeting demand for monkeys so far.

“We have done okay and have been able to satisfy the needs of most of the scientists that we service. But it has been difficult obtaining rhesus monkeys on the open market,” he said in an e-mail.

But, he added, the Center may be relatively successful in meeting demand because many researchers, like Johnson, are already asking for fewer monkeys than they would request if there were no shortage.

“We have been able to meet over 80 percent of official requests,” he said. “But it is only fair to point out that these requests take into consideration the limited availability of rhesus monkeys.”

And researchers said they do not expect excessive demand for the rhesus monkeys to subside anytime soon—particularly under recent governmental pressure to pursue research combatting bioterrorism threats.

“It’s only going to get worse with the recent shift of resources to new biodefense initiatives,” Johnson said.

Continuing to meet the rising demand for monkeys will require a support system that does not exist at present, Desrosiers said.

“I think the need will continue to increase, and that appropriate plans and funding are not in place to increase the supply through increased breeding,” he said. “This requires an increase in facilities and infrastructure.”

The rhesus monkeys reproduce slowly, compounding the present shortage.

So far, NEPRC has been successful in securing the support it needs, he said. Anticipating a shortage, the Center has lobbied for more support and applied for a grants from the division of the National Institutes of Health responsible for funding primate research.

To date the NEPRC facility has received sufficient funding to breed more rhesus monkeys and to build new facilities, he said.

Still, for researchers working toward a cure for diseases like AIDS—even those who have been able to proceed with their projects—the monkey shortage has stands as a major obstacle, costing money and, more importantly, time.

“It’s become the major roadblock for vaccine trials,” Lieberman said.

—Staff writer Nathan J. Heller can be reached at heller@fas.harvard.edu.