THE COLLEGE HILL INDEPENDENT


In The Name of Science

monkey testing at Brown

by Will Fesperman

Illustration by Julie Kwon

published April 25, 2014


Around 38 monkeys live in research laboratories at Brown University. It is difficult to know for certain how many—the researchers won’t say. Thirty-eight is simply the latest available number, listed in a United States Department of Agriculture (USDA) report from 2013. This number changes throughout the year when University researchers buy new monkeys or kill existing ones.

     There is so much secrecy around animal research at Brown that at first I was unable to determine where the University’s monkeys actually live. A graduate student in neuroscience assured me that the location was “not secret in any way.” But I had to make multiple requests through the federal Freedom of Information Act (FOIA) to learn more. In the past few months, I accessed five grant applications filed by Brown researchers to the National Institutes of Health (NIH), which finances most of the University’s animal research. Last year, NIH gave Brown researchers $2.1 million for research involving monkeys. I also retrieved 21 documents about Brown’s animal research from NIH’s Office of Laboratory Animal Welfare.

     Most of the NIH grant applications I looked at had black stripes over the location of Brown’s primate facility. The researchers had the chance to redact such details before I saw the documents, and they did—in all but one case. For unknown reasons, one reseacher did not redact detailed information about the new primate facility that was then under construction. Brown’s monkeys are housed in the Sidney E. Frank Hall for Life Sciences, on the University’s main campus.

     In 2010, the USDA cited Brown for 11 violations of the Animal Welfare Act, which sets standards of care for animals used in research and entertainment. At least six of those violations involved monkeys.

“Their Primate Chair”

Brown uses most of its monkeys for neuroscience experiments. University researchers have used monkeys to study the brain’s primary motor cortex, visual processing in the temporal cortex, and optogenetics, a method of electrically stimulating the brain. Brown has been buying more monkeys in recent years: the University owned just two monkeys in 1999, while in 2012 40 monkeys were kept in Sidney Frank, as the building is known among Brown students.

     The monkeys have about 112,000 peers in labs across the United States. Some are used to study deadly diseases like HIV and tuberculosis. Last month, researchers at Rockefeller University and the Centers for Disease Control and Prevention used monkeys to test a new drug that could protect humans from contracting HIV for months. The experiments used 28 monkeys, half of which acquired the virus.

     At Brown, the BrainGate Neural Interface System is probably the most celebrated product of monkey research. BrainGate is a groundbreaking technology that has already allowed human test subjects to control robotic limbs with their thoughts. John Donoghue, a professor of neuroscience who directed the project, spoke about it on Dr. Mehmet Oz’s radio show in 2008. And in October, the project won a million-dollar prize for excellence in brain research from Israel Brain Technologies, a research and technology nonprofit.

     A video on Brown’s website shows a woman, paralyzed from the neck down, using the BrainGate interface. She uses her thoughts to control a robotic arm that holds a bottle of coffee. She brings the bottle to her lips and drinks the coffee on her own—for the first time in 15 years—then grins at the camera.

     When I met with BrainGate’s John Donoghue in the University’s Institute for Brain Science, he asked me a few times why I was writing this article. “Do you have a personal belief yourself about [non-human] primates being special?” he asked. A porcelain figure of a monkey rested on his desk, and on another table were coasters featuring antiquarian drawings of monkeys.

     Donoghue’s lab first tested the brain implants in a group of rhesus macaques, some of which still live in Sidney Frank. According to the NIH grant applications I looked at, monkey experiments like these require invasive surgical procedures and months of training.

     Surgery begins with the insertion of tiny electrodes into the monkeys’ brains. For this procedure, research assistants remove a section of skin, muscle, and bone, and then insert the equipment into the brain. Sometimes researchers replace the bone flap with titanium mesh, attaching the mesh to the skull with screws before closing the skin over top. If the skin is not “sufficiently intact,” Donoghue’s 2011 application states, dental acrylic is added to close the incision. The monkeys are anesthetized for all surgeries. Researchers also implant three titanium rods into the monkeys’ heads. These rods stick out of the sides and back of the head. The rods are meant to restrain the monkeys’ heads during training and data collection.

     After recovering from surgery, the monkeys are trained to “sit quietly in their primate chair,” as one grant application puts it, for hours at a time. While sitting in the chair—their arms separated by a barrier, their heads fixed in place—the monkeys learn to perform specific tasks, like pressing buttons, to receive “rewards” of water or juice. Donoghue’s grant application says the training is “not stressful” for the monkeys. Monkeys, the application states, “readily cooperate in performing the task, and session length is determined by the animal.” 

     The monkeys cooperate because they are thirsty, and because liquid is the reward for participation. Researchers can restrict their access to water for days before the training session. In these cases, the monkeys’ water intake is less than what USDA regulations require. But the USDA exempts Brown and other research institutions from this requirement when experiments demand it. Such exemptions are routine; they are approved not by the USDA directly, but by Institutional Animal Care and Use Committees (IACUC). I looked at five annual reports since 2005, and every one of them included an identical statement: “Brown University has several IACUC approved protocol exceptions to USDA regulation in which access to water is regulated for [x number of] non-human primates…”

     IACUCs are required for every research institution under the Animal Welfare Act. Brown’s IACUC consists of a chair—Rebecca Burwell, an animal researcher at Brown—and three other members. One is James Harper, a veterinarian and the director of animal care, who declined to be interviewed for this article. As required by the Animal Welfare Act, the other two members have no connection to Brown.

     IACUCs determine whether proposed experiments meet federal animal welfare regulations and follow the Guide for the Care and Use of Laboratory Animals, published by the National Research Council, a private, non-profit organization. Experiments can deviate from these guidelines if “acceptable justification” is given, according to Brown’s Animal Welfare Assurance, filed with NIH in 2014. The document does not explain what counts as “acceptable justification.”

     The committee also decides whether the researchers really need to use animals. “If you can answer a question without using animals, you would want to do that,” Burwell told me, “because [animal testing] is labor-intensive and time consuming,” and introduces ethical concerns. Neuroscientists use monkeys when using human test subjects would be deemed unethical, and when the experimental question cannot be answered with what Burwell called a “lower species,” like rats or mice.

     Brown’s IACUC can’t control everything that happens in the lab. In 2009, Brown students performed three surgical procedures on unidentified animals without getting IACUC approval. According to a USDA report, two of the animals “experienced complications” during surgery and had to be euthanized.

Living Alone

Brown’s primate facilities are relatively new. Prior to 2007, the monkeys lived in the University’s BioMedical Center. With the construction of Sidney Frank came new monkey labs and housing. According to a grant application, the new primate facility features a “state of the art surgical facility” and offices for Brown professors, post-doctorates, and graduate students. Donoghue’s laboratory alone has three rooms for behavioral training. The building can only be accessed with a key card.

     The monkeys live alone in separate cages. If solitary housing is common in research labs, it presents a stark change from monkeys’ lives in the wild. Rhesus macaques, which are housed in Sidney Frank, are highly social animals in their Asian habitats. Macaques live in matriachal groups and communicate with a system of gestures and vocalizations. The effects of solitary captivity were the subject of a discussion among lab workers from the U.S. and Europe, published in the October 2004 issue of the Laboratory Primate Newsletter, a quarterly for primate researchers published by Brown.

     According to the lab workers, the majority of individually housed monkeys can be seen “rocking, self-biting, bar-biting, ear-pulling, hair-pulling, eye-poking, etc.,” as a result of being housed alone. And a study of 362 individually housed research primates, published in the American Journal of Primatology in 2003, concluded that behaviors like hair-pulling, self-biting, and self-injury increase with the number of years a monkey is held in solitary captivity.

     Labs try to counter these behaviors with environmental enrichment. In the same 2004 issue of the Laboratory Primate Newsletter, Jo Fritz summarized her research on music as a form of enrichment for captive chimpanzees in Arizona. “What a blast and great fun animal research can be,” she began. Fritz described in perky exclamations how researchers gave the chimpanzees “a tiny plastic piano with four keys!”

     A 2010 USDA inspection found that researchers at Brown violated the Animal Welfare Act by failing to provide enrichment for a “young juvenile” monkey. The same report gave Brown a citation for existing enrichment devices: white PVC pipes that were stained orange from contact with the rusty metal clamps on the monkeys’ cages. 

     The Animal Welfare Act requires group housing for monkeys, but the USDA—the agency responsible for enforcing the law—allows Brown and other research institutions to bypass this regulation. In 2012, all forty monkeys were exempt from pair housing. Brown’s annual statement of IACUC-approved exemptions said that if the monkeys were housed together they might damage the titanium rods sticking out of each other’s heads. Pair housing would also make it difficult to regulate how much water each monkey drank, the statement added.

“A Human Interest Story”

I asked Donoghue about his relationship with the monkeys he experiments on, but he declined to comment. He explained that such anecdotes belong in a “human interest story,” not a “press story.” When I pressed Donoghue on this, he appeared irritated: “It would be the same for mice or for rats or for monkeys,” he said. “This is a research environment.” People working with conscious monkeys must wear “a full-face shield and goggles,” a face mask, and “kevlar gloves and arm protectors,” according to Brown’s 2014 Animal Welfare Assurance.

     In 2010, one of Brown’s monkeys, #H310, went without water for 72 hours. According to the USDA inspection report, an unidentified researcher was “out of town” and “forgot to make arrangements with other laboratory staff to take care of the animal in his/her absence.” #H310 experienced “no adverse effects,” the report said.

     Marisa Quinn, vice president for public affairs and University relations, told me in an email that “corrective actions have been taken to mitigate the chance for future errors” since the 2010 incident. But a November 2012 letter from Clyde Briant, vice president for research, to the NIH Office of Laboratory Animal Welfare (OLAW) reports a similar violation. In September of that year, the letter says, a monkey did not have access to water for 48 hours, the result of a “breakdown of communication” among laboratory staff.

     According to the NIH award number listed in the letter, the monkey was being used in Donoghue’s research. Briant wrote that lab workers would receive “additional training” to prevent future incidents. An OLAW official replied two weeks later, simply acknowledging that OLAW had received the letter. “OLAW concurs with the actions taken by the institution” after the incident, the official wrote.

     I contacted twelve research assistants, graduate students, and undergraduates who have worked in primate labs at Brown, asking if they would talk about their experiences with monkey experimentation. Only three responded; of these three, only one was willing to talk to me, but he does not have direct contact with the monkeys and was unable to provide any information. “This is interesting, but risky business,” he wrote in an email.

     Rebecca Burwell, the chair of Brown’s IACUC, said that people who research on animals tend to keep a low profile to stay off activists’ radars. “People sometimes quit doing this work because their family is threatened,” Burwell added. While most advocates for animals use peaceful methods, some activists threaten researchers with violence. The intimidation ranges from protests outside researchers’ homes to death threats. Burwell and Donoghue both said they know researchers who have been targeted, though they themselves have not.

     But self-protection alone does not explain the researchers’ silence. Even the people who agreed to be interviewed for this article were hesitant to talk about Brown’s monkeys. I asked Burwell, whose research uses rodents, where the University gets its non-human primates. “I don’t want to answer the monkey questions,” she said.

Oversight

The USDA has little power to penalize research institutions for animal abuse. Brown didn’t receive any penalties for its violations in 2010 and other years, only orders to improve conditions by a certain date. When penalties do exist, they are minor. In 2012, the USDA held Harvard University responsible for the deaths of four monkeys, including one instance where a cage was put through a mechanical washer with a monkey still inside. The extent of the punishment was a $24,036 fine.

     Brown’s animal labs receive yearly, unannounced visits from USDA inspectors. The University’s facilities also undergo an inspection every three years by a private accreditation group, the Association for Assessment and Accreditation of Laboratory Animal Care, or AAALAC. “[AAALAC] isn’t required, but we want to be an accredited institution,” Burwell said. Unlike the USDA, AAALAC alerts labs before inspections occur. AAALAC does not release its inspection reports to the public, nor can they be released under the Freedom of Information Act. Harvard, after the multiple violations in 2012, remains fully accredited by AAALAC.

     Unlike Brown, public universities are obligated by law to release information like primates’ medical histories and veterinary logs. But Jean Barnes, director of the Primate Freedom Project, said they are rarely eager to do so.

     “Things got really tough in Los Angeles for a good while,” Barnes told me. “UCLA had sent me a long list, twenty pages, of primates that they had in their laboratory. Well, they just decided that they were not going to abide by the law any more. They started telling people that they didn’t have those primates in their lab.” UCLA had moved its non-human primates out of University facilities and into a nearby veteran’s hospital. “They would write back to [our requests] and say, ‘We don’t have that primate. We’ve never had that primate. We know nothing about that primate.’”      

Life and Death

Brown kills its monkeys with an overdose of sodium pentobarbital, a drug employed in many labs, shelters, and pet hospitals to euthanize animals. Some U.S. states also administer the drug for capital punishment, though not without controversy: advocates who oppose its use on humans claim the drug can cause a slow and painful death.

     I could not access records of how many monkeys were killed by year. But nearly every grant application I looked at ended with these lines: “Euthanasia. The animals will be euthanized with an overdose of pentobarbital (120 mg/kg).” What varied was the number of monkeys slated to be killed: Fourteen male and female monkeys in a 2001 application; six male monkeys, ages four to ten, in a 2003 application. Three monkeys in a 2006 application. In a 2011 application, ten monkeys.

     The American Veterinary Medical Association’s “Guidelines for the Euthanasia of Animals” instruct labs to give psychological support to people whose job it is to kill the animals. The document says labs should teach “grief-coping skills” in particular. The guidelines warn that people who repeatedly have to kill animals may show their psychological distress through “[skipping work], belligerence, or careless and callous handling of animals.”

     Not all research primates are euthanized; some are retired to sanctuaries. But sanctuaries are crowded and don’t always have the space to take in new monkeys. “Most [sanctuaries] are operating at or close to capacity,” said Sarah Baeckler Davis, executive director of the North American Primate Sanctuary Alliance. “Primates are very expensive to care for,” she said, and as a result, sanctuaries often cannot take in a monkey unless the lab pays at least part of the expense.

     Donoghue said that Brown researchers have begun requesting funds in their grant applications to retire monkeys to sanctuaries. His most recent application in 2011 did not request such funds; it stipulated that the monkeys would be euthanized. But Dan Brooks’s application from 2010 stated that three monkeys had indeed been retired from Brown to primate sanctuaries. James Harper, the Director of Animal Care, would not say where exactly these monkeys ended up. “We do not keep records of who went where,” he wrote in an email.

     Donoghue told me the monkeys might have gone to sanctuaries in Texas and the Pacific Northwest, but, to the best of his knowledge, the Texas sanctuary has since closed.

     Sanctuaries are growing as primate research becomes increasingly unpopular,  Baeckler Davis said. “Chimp research, the writing’s on the wall that that’s over…[Primate research] is starting to be less publicly supported.” As a result, labs are more likely to retire their monkeys and more willing to pay sanctuaries for their care, she said. But so far, only “several” of Brown’s monkeys have been retired, according to Harper. And retirement is not always an option. Donoghue said that sometimes researchers need to kill monkeys to examine their brain tissue after an experiment.

     Brooks’s 2010 grant application suggests that some Brown researchers have begun to consider the ethics of killing monkeys. While other applications merely state a drug and dosage for euthanasia, Brooks’s application briefly weighs the costs and benefits of killing. Brooks, then seeking his Ph.D., stated that “the tradeoff of using in-vivo electrode tracking versus killing additional well trained animals must be considered seriously.” In-vivo electrode tracking is a method that implants hardware in the monkeys’ brains, and usually requires that they be euthanized after the experiment. According to Brooks, such techniques may become unnecessary “with the advent of advanced neuroimaging methods,” which are non-invasive. Then labs could reuse the same monkeys for many experiments, or use human subjects instead.

     Of course, Brooks may simply want to save money and time: it can take months to train new monkeys for experiments, and a rhesus macaque costs around $6000. He did not respond to a request for an interview.

The Beginning of the End?

There has already been some movement away from using primates in research. Last year NIH announced that it would retire most of its 360 chimpanzees and phase out many research projects that used them. Burwell declined to comment on this decision. Donoghue supported the move, but said that NIH should keep some chimpanzees in case of “future viral diseases” like AIDS that might require them for research. Such experiments are already illegal in the European Union, which in 2010 banned research on great apes—that includes chimpanzees, bonobos, orangutans, and gorillas, but not macaques or other monkeys.

     In addition to bans on testing, there is also a movement toward granting legal rights to primates. In 2008, the Spanish parliament considered a resolution that would have given great apes the rights to life, liberty, and freedom from torture. Steven Wise, president of the Nonhuman Rights Project, expects courts to grant legal rights to some non-human animals within his lifetime. “I think that once you make the first breakthrough, judges and legislatures everywhere will start looking at it, and then the process will start to take hold,” he told me. “Things can go on for a long, long time. And then they start to crumble. And they start to crumble quickly.”

     Michael Rule, a graduate student in one of Brown’s primate labs, had this to say in a blog post in 2010: “The fact that science seems increasingly evil as we look back further into the past, suggests that science is always doing things that will be considered evil by future generations.”

Coming to Grips

In our conversation, I asked Donoghue how he justifies his work ethically. He asked me a question back: “If it’s your grandparents or your younger sister that might die because a disease was not understood, is [animal research] worthwhile?” For Donoghue, the question is not whether monkeys are intelligent or complex enough that caging and killing them is wrong, but whether human lives are worth more than non-human lives. He justifies research on non-human animals this way: “We’ve decided that in science [researching on non-human animals] is how we get the information.”

     He said that to give “special treatment” to monkeys because they are similar to humans is anthropocentric and “almost sounds like racism.” “Then I’m just as justified in saying that only humans matter, and no other animals matter,” he added. In place of such anthropocentrism, Donoghue says he follows an ethic of respect for all animal life. But this respect plays out in different ways for humans as compared to other animals. Donoghue takes for granted that non-human animals can be used and killed for invasive experiments, while humans cannot.

     When I asked if some non-human primates have an interest in being free, he replied, “I have no way of knowing that. It’s like asking if ants have a basic interest in being free.”

     Yet Donoghue acknowledged that animal research poses “an ethical dilemma.” “We should come to grips with that,” he said. “I think we have to do it individually and as a society.”