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During the past half-century, experiments at Harvard Medical School’s (HMS) New England Primate Research Center (NEPRC) have yielded a long list of scientific accomplishments, including insights into addiction, HIV, and neurodegenerative disease. But recently, attention has shifted from breakthroughs in biomedical research and focused instead on lapses in the care of NEPRC’s more than 2,000 monkeys. In June 2010, a cotton-top tamarin was found dead in a cage that had just been cleaned. A necropsy revealed that the monkey had died of natural causes before the cage went through a sanitizing, high-temperature wash, but staff members had failed to notice the animal.

That incident, a direct violation of federal animal-welfare regulations, spurred a stern warning letter and the threat of possible fines if problems continued. When a Harvard-initiated comprehensive review exposed troubling gaps in basic procedures and supervision last summer, key leadership at the center was replaced, new research was temporarily suspended, and more rigorous checks and balances began to be implemented. University officials acknowledged that NEPRC had veered off course, but stated that the problems were being addressed and corrected. But three more monkeys have died since—drawing the scrutiny of regulators, the ire of animal activists, and unprecedented steps by senior HMS leadership to more fully explain the problems and the steps being taken to address them in order to ensure the safety of the animals and regain public trust.

“The events that have taken place represent totally unacceptable events in the context of our research activities. They are unacceptable; they are regrettable.…They are going to be fixed,” HMS dean Jeffrey S. Flier said in an interview with The Boston Globe in February, shortly after his return from an hours-long visit to the center triggered by the most recent incident: an elderly cotton-top tamarin, found in poor condition in a cage that was lacking a water bottle, had to be eu­thanized. (Harvard officials took the unusual step of disclosing the incident right away, even before a U.S. Department of Agriculture [USDA] inspector had visited the facility, and a worker involved in the monkey’s care was put on administrative leave.) “My sense is, whatever the procedures are that we put in place, they weren’t good enough to prevent this event,” Flier added. “So we are going even further with our procedures, to have an attempt to be more fail-safe.”

The problems at NEPRC and some of the corrective and disciplinary actions taken to right them have emerged piecemeal, but the first hints of systemic issues emerged through the probe Harvard initiated after the cage-washing incident. That review revealed a series of troubling gaps and breaks in the basic procedures and supervision that govern animal research. Some procedures were being conducted on animals without the necessary approval of an institutional committee. There was a pattern of incomplete medical records—including the absence of tuberculosis tests that are critical to maintaining the health of the colony. The two other fatalities also suggested possible training or procedural problems: last October, a common marmoset that escaped while being transferred for an imaging procedure was caught with a net and underwent imaging, but was later found dead; the day after Christmas, two squirrel monkeys were discovered severely dehydrated—staff members had not noticed a malfunctioning automatic watering system—and one had to be euthanized.

The incidents have sparked a federal investigation that includes the February 2011 death of a monkey (from an overdose of anesthesia) at another HMS primate-research facility, in Boston. “They’ve had a tough stretch, and it’s certainly something that’s gotten our attention, and we look forward to them correcting the situation,” David Sacks, a USDA spokesman, told the Globe. The department takes the unnecessary death of any animal seriously, he said. Since June 2010, federal inspectors have flagged seven instances at NEPRC of violations directly endangering animals’ health or safety, compared to 25 such “direct” noncompliance incidents at research facilities nationwide in fiscal year 2011, according to Sacks. The most recent USDA finding, from a March inspection, concerned the February monkey death‚ attributed to employee failure to provide a water bottle.

Animal activists reacted to the incidents with anger and dismay, calling on the USDA to levy large fines, and asking the National Institutes of Health (NIH) to investigate whether federal grant money was used in support of research that violated federal animal-welfare regulations. They also questioned whether the relatively simple problems that contributed to some of the incidents revealed shortcomings in procedures, training, and staff. “Even someone who is not well trained in veterinary care of animals…at the least, they should be making sure there’s a water bottle on the cage,” said Justin Goodman, associate director of the laboratory investigations department at People for the Ethical Treatment of Animals.

The concern over the situation at the primate center rapidly became a priority at the highest levels of Harvard. Flier intervened directly in the situation, and President Drew Faust said in a statement released in March that she was requesting regular progress reports: “This situation is unacceptable. When I was notified of developments at the primate center over the summer, I found them troubling and fully supported a thorough review of procedures and implementation of reforms.” After the most recent monkey death, she said, she requested weekly reports “specifying ongoing assessment of the sources of difficulties, proposed solutions, and timetables for plans of action.”

Animal research is extremely sensitive; institutions are typically secretive about operations at primate centers, largely from fear of retaliation by extremist animal-rights activists: elsewhere, researchers and facilities have been threatened or bombed. But the secrecy that shrouds the research also tends to fuel animal activists’ suspicions, perhaps even bolstering their arguments that such research, even when it is ethically conducted and overseen, should not be done. “Each and every death is unacceptable. We should be doing all that we can to avoid these cases,” said Kathleen Conlee, senior director for animal research issues at the Humane Society of the United States. “I think what gets lost in the shuffle, to some degree, is the deaths of animals due to research, not just accidents.”

But proponents argue that primate research is necessary—although it should always be held to the highest standards. They point to the checks and balances used to ensure that research is undertaken responsibly, and that each experiment is evaluated not only on its scientific merits but also on criteria such as whether the research uses the right species and the fewest possible number of animals, and is designed to cause the least amount of suffering. For certain scientific questions, such as developing a vaccine to prevent HIV or trying to solve major problems in neurodegenerative disease, other animal models are a poor approximation of a human being. Primates are “only used when lower animals won’t work, and they’re used in some research that’s been extraordinarily important to human health,” said Deborah Runkle, senior program associate for the American Association for the Advancement of Science.

In the weeks since the February death, NEPRC’s interim director, professor of medicine Frederick Wang, resigned after a six-month tenure, even though Faust and Flier credited his leadership for beginning to steer the center in the right direction. William W. Chin, HMS’s executive dean for research, is temporarily overseeing the center during the search for a successor. Harvard has made efforts to increase transparency: two new interim leaders gave the Globe a tour of the center, demonstrating firsthand some of the new procedures intended to increase the accountability and oversight of animal care, including afternoon checks of water availability. More supervisors and staff are being hired. And a seven-member, blue-ribbon panel of experts, including leaders of other primate centers and veterinary specialists, has been created to review the operations, logistics, and staffing at the center.

In a lengthy interview with the Globe in mid February, Chin said that incidents would be prevented by better systems and procedures. “Humans do make errors,” he pointed out. “Systems are built so you remove the human element of it, so you are less error-prone. I believe that it just takes time for all these things to take hold.”