In a secret lab at perhaps America’s most prestigious university, scientists and 18 primates are unlocking the secrets of the brain.

PRINCETON BOROUGH – Somewhere at Princeton University, 18 monkeys are kept in a mystery-shrouded lab. It’s a lab so secret, the university won’t even reveal which building it occupies or give a reporter a glimpse inside.

University officials say the insistence on such secrecy is largely for security reasons, based on worries that calling attention to the lab could make it a target of animal rights extremists.

At a time when activists are pressuring scientists to allow test animals to retire to nature preserves, Princeton researchers are continuing to look to monkeys for help, as they have since the 1970s.

In June, an Ohio-based animal research watchdog group unsuccessfully petitioned the university to halt aspects of its primate research it alleged are unethical and inhumane, such as the use of surgically attached skull restraints.

University officials, however, rebuff such calls, saying the monkeys are sensitively treated and are part of important basic research.

“We work very diligently to provide the best care for these primates that we can,” Princeton spokeswoman Lauren Robinson-Brown said. “We have many levels of internal controls, from strict guidelines in the facilities to our oversight board. And then we have federal regulations and inspections.”

Inside Princeton’s lab, neuroscientists study the brains, actions and behavior of the monkeys to gain better insight into the human brain and neurology.

“Everything we know about the human brain is based four-square on monkey work – the visual system, the nervous system, how (neural) circuits are put together really came from monkey work,” said a veteran Princeton researcher, who agreed to be interviewed on condition of anonymity.

Nationally, the number of nonhuman primates used in research grew to a record high 62,315 in fiscal year 2006, the most recent for which such data are available, according to the U.S. Department of Agriculture.

The agency has tracked those numbers annually since 1973 and provides a report to Congress on research animals each year.

But Princeton has reduced its nonhuman primate rolls from 71 to 18 since 2005, Robinson-Brown said. The retired primates were sent to a sanctuary in Texas.

Still, research goes on at Princeton and elsewhere.

In some cases, a monkey under full anesthesia undergoes delicate invasive surgery in which a tiny hole gets drilled through its skull, the anonymous Princeton researcher said.

The hole gives scientists a pathway for inserting an ultra-thin instrument called a microelectrode to stimulate, probe and measure activity in different parts of the brain once the monkey recovers from the two-hour procedure, he said.

Monkeys – macaque monkeys in Princeton’s case – are ideal for this type of experimentation because people and monkeys are primate cousins with remarkably similar brain structure, he said.

The scientist said he does not want his identity disclosed because, like the university, he wishes to avoid becoming a magnet for harassing threats or violence from animal rights extremists.

Cruel or Crucial?

The Princeton researcher agreed to be interviewed in the wake of criticism directed at the university over its monkey research by Stop Animal Exploitation Now (SAEN), an animal advocacy group in Milford, Ohio.

He said that many prospective discoveries would elude neuroscientists if they abandoned invasive animal research entirely.

For example, neuroscientists were certain that new brain cells don’t form in adult primates – people and nonhuman alike.

But a pair of Princeton researchers studying adult rhesus monkeys in the 1990s turned that established wisdom on its head with the discovery that the monkeys do grow new neurons.

Experts said that revelation has sparked a massive new area of research. It could lead to advancements on a broad range of issues, from how we learn as we age to rehabilitating stroke victims to helping solve the puzzle of Alzheimer’s disease.

But SAEN’s executive director, Michael A. Budkie, contends that some of the methods Princeton and other research labs commonly use, such as surgically attaching restraining devices to monkey skulls or otherwise limiting their movement, are unethical and cruel because they cause unnecessary pain and distress.

“Most people think this type of research simply isn’t happening anymore,” Budkie said.

Budkie wrote to Princeton President Shirley M. Tilghman last month asking that Princeton ban any procedures that surgically attach restraining devices to nonhuman primates, confine them to restraint chairs while they are under observation or deprive them of water for extended periods of time.

USDA spokeswoman Jessica Milteer said nonhuman primate research that uses surgically attached restraints, restraining chairs and water deprivation aren’t prohibited by federal law, as long as they are part of the authorized research protocol for a specific project.

Budkie pointed out that during a routine inspection in April 2006, the USDA flagged Princeton for twice – on consecutive days – failing to provide water for more than 23 hours to one of its nonhuman primates.

Princeton spokeswoman Robinson-Brown said that problem was an error of administrative oversight that was not part of the research design and the university corrected the issue right away.

Still, in an interview, Budkie questioned the justification for any surgically invasive research on monkeys by Princeton because, he said, many universities and research labs around the country conduct similar work.

The anonymous Princeton researcher countered that it’s not the research itself that is duplicated from lab to lab but the surgical and observation procedures.

“It is a property of basic research that you can ask a very large number of basic questions with very similar standard techniques,” he said.

However, this researcher said he hasn’t done nonhuman primate work for two years and doesn’t expect to return to it, in large part because technological advances have helped make a lot of – though not all – animal research unnecessary.

For instance, some previously invasive brain research on primates can now be done using increasingly detailed and accurate computer modeling.

Also, improvements to brain-scanning equipment like fMRI (functional Magnetic Resonance Imaging) machines offer scientists opportunities to study the brain in human volunteers who aren’t subjected to any invasive surgery, as well as in monkeys, he said.

Projects that use monkeys or other nonhuman primates, especially when they involve invasive surgery, should be – and at Princeton are – a last resort when computer modeling or other nonintrusive procedures aren’t viable alternatives, Princeton spokeswoman Cass Cliatt said.

Singer’s view

Even Princeton bioethicist Peter Singer, a trailblazer in the animal rights movement who generally opposes biomedical research on animals, doesn’t argue for an all-out ban on surgically invasive research on nonhuman primates – either at Princeton or more broadly.

“In general, I am opposed to the use of animals in research because the entire practice is based on speciesism – that is, a prejudice against taking seriously the interests of the animals involved,” Singer wrote in an e-mail.

“I would need to know more about what is happening to the monkeys to offer an opinion on any specific research,” Singer stated. He said that “individual experiments may be defensible, depending on the care given to the animals (including the way they are housed) and the purpose of the experiment.”

Singer said he has never called on Princeton to end use of nonhuman primates in research but noted that in recent years most of his animal advocacy has focused on another arena entirely – factory farming.

“As compared with the use of animals in research, the numbers of animals used (in factory farming) is vastly larger, and there is no possibility of arguing that the close confinement and other forms of animal abuse serve a useful purpose,” Singer said.

The anonymous Princeton researcher said he is glad to have ended his work on monkeys.

“Probably all researchers who do any animal research have a certain sense of respect for the animal and the sense that this is something we do because it’s necessary to answer our questions,” he said. “Wouldn’t it be nice to be able to move from that research? That’s a thought that’s never far away.”

Robert Stern is a staff writer for The Times of Trenton, N.J. E-mail rstern@njtimes.com.
“Everything we know about the human brain is based four-square on monkey work – the visual system, the nervous system, how (neural) circuits are put together really came from monkey work.” – Princeton scientist, speaking on condition of anonymity