|MARCH 21, 2001|
Scientific institutions don't like being in the news for anything other than devising life-saving cures and unlocking the secrets of the physical universe.
The Oregon Regional Primate Research Center is no exception.
When 2001 began, the scientists in Hillsboro got things their way. Gerald Schatten, a scientist who recently left the center, hit the front page of The New York Times on Jan. 12 for creating the world's first genetically altered non-human primate.
Two months later, the spotlight returned to the 200-acre campus--not for a scientific breakthrough, but because a leading primate behaviorist hired by the center had said that, in some respects, the center was in the Dark Ages when it came to animal care (see "Monkey in the Middle," WW, March 21, 2001). Carol Shively's report, made public by WW, was particularly critical of ORPRC for two reasons: the center's use of a procedure known as electro-ejaculation and its practice of housing many of its research animals in individual cages.
Officials at the center and at Oregon Health & Science University, the its corporate parent, spent much of the year playing defense and trying to discredit critics. Even as recently as last week, ORPRC director Susan Smith refused to comment on the Shively report.
Behind the scenes, ORPRC took steps to reform. It changed its electro-ejaculation procedure, and records obtained by WW indicate that the modified process no longer induces the monkeys to bite themselves or pull out their hair. ORPRC also began to house its research animals socially, as Shively and the U.S. Department of Agriculture had both recommended.
But the new records obtained by WW also show there are other problems with a group of primates used in nutrition and eye research. Since 1998, these 24 rhesus monkeys--two feet of firecracker personality and sharp teeth--have shown signs of distress, repeatedly chewing their own flesh, ripping the skin from their digits and pulling out their hair.
Such behavior "shows extreme social deprivation," says James Mahoney, former director of the Laboratory for Experimental Medicine and Surgery in Primates in Sterling Forest, N.Y. "They're just shadows of what they're supposed to be. They're not really monkeys, but aberrant living creatures that metabolize--and that's about it. They are not representative of their species."
In September 2000, the primate center asked Shively to evaluate the psychological well-being of its monkeys. The move came after a whistleblower named Matt Rossell left the center, flinging about accusations of shabby animal care. Videotapes that Rossell secretly made captured a grunting and screeching monkey undergoing electro-ejaculation, a procedure used to gather sperm for reproductive biology studies. The procedure looked beastly.
In her report, Shively seemed to agree.
"The awake electro-ejaculation procedure observed by me while visiting the primate center did not appear to be humane and should be terminated immediately," wrote the professor of pathology and psychology at Wake Forest University in Winston-Salem, N.C. Shively, who's been a primate researcher for almost two decades, later told WW that watching the procedure left her "shaken and upset."
In January 2001, the USDA ordered the center to re-examine its practices. As a result, sperm-donor monkeys are now given valium and aspirin before being strapped into a chair and having an electrical charge applied to their penises. Records show they are no longer biting themselves or pulling out their hair.
The group of 24 rhesus monkeys, however, has continually showed signs of aberrant behavior. They're not being subjected to electro-ejaculation: Rather, they're at the center of Martha Neuringer's efforts to help newborn humans get proper nutrients.
Neuringer's science, which focuses on the physiological effects of nutrition, is solid and elegant (see "The Acid Test," page 20). The downside is that the monkeys making the science possible have sometimes paid a heavy price.
Each of Neuringer's monkeys was taken from its mother at birth. For the majority of its life, each has lived in a 5.3-square-foot cage.
Until 1998, the monkeys presented few clinical problems, according to ORPRC records. That year, however, several of the monkeys began biting themselves and "overgrooming," or plucking out their hair--both indices of animal pain and distress.
Self-biting, as it's called, is abnormal and almost never occurs at the Wisconsin Regional Primate Research Center, according to Joe Kemnitz, its director.
ORPRC officials say that self-biting cases are rare, too, at their facility, which opened in 1962. Yet the center's records indicate that all but one of Neuringer's monkeys have bitten themselves. WW tallied almost 250 instances in which monkeys bit themselves, most of them during the past four years. In some cases the biting was so severe that surgery was required, according to ORPRC records. Five monkeys, for example, had to have digits amputated. One monkey, who ripped open a vein, was later euthanized.
In addition, primate-center records show 185 documented instances of these monkeys pulling out their own hair.
Neuringer declined to be interviewed for this article. But in an interview with WW last January, she conceded that the animals have at times been in pain and attributed their behavior to the onset of puberty.
Captive animal behavior is often mysterious, even to scientists who work in the field. In the mid-1980s, Viktor Reinhardt, then a veterinarian at the Wisconsin primate center, had seen enough of monkeys chewing on themselves. So he housed monkeys two to a double-sized cage. Within days, the monkeys were calm. Reinhardt expanded the idea to include larger social groups, creating quasi-social troops of research animals. More calm monkeys.
The fix worked, Reinhardt says, because monkeys depend on contact with others for their psychological well-being.
Social housing, as the fix is known, slowly became a widely accepted practice in the early 1990s. When Shively inspected ORPRC last year, however, the overwhelming majority of its 1,000 research monkeys were housed in individual cages. (Approximately 300 more monkeys resided in a breeding colony, with 1,300 more living in the outdoor corrals.)
It was the sight of all these social creatures reduced to rattling about in small mesh enclosures without real social contact that brought out Shively's most intense criticism.
"I was exposed to no protocols that required social isolation," she wrote. "Rather, investigators were not giving priority to the social needs of the monkeys."
The primate center, Shively said, had not kept pace with advances in the industry. USDA officials largely agreed, telling WW in March that they expected ORPRC to begin social housing of its animals immediately.
Primate-center officials say they developed a 10-year-plan for social housing in 1994. But it was only this year that the center began in earnest to cage research monkeys in pairs. Almost 700 of its current population 3,100 monkeys are now housed in pairs.
In addition, in mid-December the center opened 10 open-air facilities, which can house as many as 600 monkeys in social troops. ORPRC plans to spend at least $8.5 million over the next five years on social housing.
Last week, during a tour of the center, the socially housed animals appeared as happy as you could expect a captive animal to be, bouncing about and banging against the metal of their "home cages" when a visitor drew too close.
Even Neuringer's 23 remaining monkeys, only four of whom are socially housed, were very active and, to the untrained eye at least, looked healthy.
But ORPRC records show that these monkeys have continued to bite themselves and pluck out their hair at a rate consistent with the prior three years. One had bitten itself 17 times in the first 11 months of 2001.
Center personnel have now given valium to half of Neuringer's monkeys, which some scientists characterize as a serious step that may do little more than mask underlying problems.
"You cannot chemically induce psychological well-being," says Irwin Bernstein, a University of Georgia professor of psychology.
This is an awkward time for biomedical researchers who use animals. Last month, the Humane Society of the United States released a poll showing that 60 percent of Americans oppose research using animals if the animals are exposed to moderate levels of pain.
In a way, Neuringer's monkeys are emblematic of the central conundrum of animal research: To perfect the human species, we breed and raise animals for experiments, and, once we've gleaned such information as they contain, we kill them. But, in the interim, the federal Animal Welfare Act requires scientists to minimize any pain and distress experienced by research animals. Physical pain is fairly easy to detect, at least among primates. But the law doesn't specify what constitutes psychological well-being or how to measure it.
"The regulations are inadequate," says Martin Stephens, vice president for animal-research issues for the U.S. Humane Society. "There is no definition of distress. Research facilities are getting a free ride on the psychological well-being issue."
Twice this year, the USDA has performed surprise inspections at the ORPRC. Twice it has issued the center a clean bill of health.
But, after learning about Neuringer's monkeys, Bob Gibbens, western regional director of animal care for the USDA's Animal and Plant Health Inspection Service, told WW that his inspectors will soon make another trip to Hillsboro.
THE ACID TEST
From the early 1990s until last year, Martha Neuringer used 24 monkeys to try to ensure that millions of human babies grew up with healthy eyes.
The 56-year-old scientist, who has been at the Oregon Regional Primate Research Center for 21 years, has been studying the effects of Omega-3 fatty acid deprivation on retinal development.
Neuringer works in collaboration with William Connor, a professor of medicine at Oregon Health & Science University. Neuringer handles the practical day-to-day work with the study in Hillsboro, while Connor deals with the biochemistry at OHSU's main campus. Neuringer brings $618,000 in grant money to the center each year and draws a $72,000 salary.
When the two scientists began their work, infant formula did not contain Omega-3 fatty acids, such as those found in breast milk. Nutritionists feared that infants' eye development was suffering as a result.
Neuringer and Connor figured that if rhesus monkeys were raised on a diet lacking those fatty acids, then their retinas would not develop properly. For example, they would react more slowly to light patterns than would normal retinas.
After proving their hypothesis last year, Neuringer and Connor published the results in Pediatrics. As a result, the world's major manufacturers of infant formula retooled their products to contain Omega-3. (Depending on whom you ask, rhesus monkeys share 95 percent or more of the human genome--so what is true in a rhesus is presumed to be true in a human.)
Neuringer's monkeys, however, still have work to do. They are being to study macular--a region of the retina--degeneration. --Philip Dawdy