Monkey business

How Stephen Lisberger became the poster boy for UCSF's animal welfare problems

STEPHEN LISBERGER IS a scientific star. His decades-long research into how the brain registers and responds to visual stimuli is considered groundbreaking. His colleagues are effusive in their praise. William Newsome, a Stanford University neuroscientist who investigates similar terrain, told the Bay Guardian that "it could take decades, or even centuries" to assemble a complete, working map of the brain's essential functions. "And Steve is one of the few people in the world who's making progress on this."

The federal government thinks he's worth a fair chunk of taxpayer change: The National Institutes for Health gave Lisberger $1.6 million in grants this year, and since 1992, an NIH database shows, he's received 31 grants worth a total of more than $12 million.

But Lisberger's work involves fairly invasive experiments on live subjects, and since you can't exactly stick electronic probes into the brains of human beings, Lisberger uses rhesus monkeys, those red-faced staples of biomedical research. His experiments have made him the bane of many critics of animal experimentation and over the past decade he's become the poster boy for opponents of animal experimentation at UCSF.

Lisberger declined to be interviewed for this story, so we gleaned the outlines of his work from federal documents and UCSF records.

It's not a pretty picture.

According to the scientific protocol for his experiments, filed with UCSF, Lisberger's monkeys undergo several different surgeries, under anesthesia, to prepare them for the research. First, each monkey has a restraint device attached to its head with a combination of metal plates, bolts, and screws. That will later allow the monkey's head to be locked in place for experiments. One or two holes are drilled in the skull, and then cylindrical recording chambers are secured over those holes so that microelectrodes that will allow precise neural activity to be measured can be inserted into the brain with ease. (The electrodes themselves don't cause discomfort because the brain lacks pain receptors.)

Sometimes, small wire coils are sutured to the monkeys' eyeballs. Other times the monkeys have spectacles attached to their faces that either magnify or miniaturize everything they see.

The monkeys in Lisberger's lab are put on a fluid-restriction program, so that each day they are scheduled to "work" they will obey commands for "rewards" of water or Tang. Each monkey is taught to move from its cage to a "primate chair," and once in the chair, its head is locked into the restraining device. Then the animal is prompted to move its eyes in certain ways to receive a reward. Monkeys typically work for two to four hours a day on alternating weeks, often for three years or more.

Lisberger's protocol states that his work could eventually lead to "the cure for many diseases of learning and memory such as Alzheimer's Disease."

Suzanne Roy, from In Defense of Animals, says she started looking into Lisberger's experiments in the late 1990s, after IDA got anonymous complaints from people who said they worked for UCSF. "What struck me was the highly invasive nature of them and the duration of them ... " she said. "He's making the monkeys so thirsty they'll move their eyes in a certain way for a juice reward. How could anyone do this to an intelligent monkey?"

In 2002 Roy asked Lawrence A. Hansen, a neuropathologist at UC San Diego who is unusual in his willingness to question animal research, to evaluate Lisberger's protocol. "I have never previously encountered experiments that would deliver quite so much suffering to higher primates for so comparatively little scientific gain...." Hansen wrote afterward. "While I do not doubt that these experimental manipulations will generate valid scientific data, such information is purchased at too high a moral and ethical cost. Even the primary investigator seems to feel it necessary to disguise his actual motivations, which are those of a fundamental research scientist, by invoking a link to a cure for Alzheimer's disease. This is one of the more ludicrous stretches from basic science to human application that I have ever encountered in my 20 years of research into Alzheimer's disease and other neurodegenerative diseases affecting human beings."

When we spoke to Hansen recently, he criticized Lisberger's grant applications and said, "He's picked a part of the brain that's not even involved in Alzheimer's."

Lisberger's studies are "basic science," meaning that they aim to answer larger scientific questions about how something works in this case, the brain rather than to invent or test a treatment. Although it might be somewhat easier to stomach an experiment that might cure Alzheimer's than one that seeks to understand how the brain functions, it is hard to dispute that this is valid science: How can medical researchers cure problems they fundamentally don't understand?

But even if you agree that the goals of Lisberger's research justify his use of animals, you might be troubled by Lisberger's record. Documents show that some animals enrolled in his research have a difficult time coping with the physical stress involved and that Lisberger has resisted efforts to make his experiments more animal-friendly.

Clinical notes gathered by IDA and other groups show that Lisberger's monkeys routinely undergo six or eight surgeries just to deal with their various implants and the infections they sometimes cause, or to remove scar tissue that has built up on the monkeys' dura, the protective layer between skull and brain, because of repeated electrode insertions. Several monkeys in Lisberger's lab have shown a significant decrease in body weight, and others have displayed a habit of self-mutilation, biting at their limbs and tearing out their hair.

Several years ago, when the internal committee that oversees animal research at UCSF raised concerns about whether monkeys in Lisberger's experiments would receive sufficient water, particularly if they were "worked" on consecutive weeks, Lisberger responded in writing. "I am not willing to tie my laboratory's flexibility down by setting guidelines or limits, or by agreeing to a negotiation with the veterinary staff when we do this," he wrote in a June 1998 letter. "I believe that the experimental schedule in my laboratory is an issue of academic freedom and that the Committee on Animal research lacks that [sic] standing to regulate this schedule."

In fact, the Animal Welfare Act was amended in 1985 to give the committee the primary responsibility for watchdogging researchers and ensuring that measures are taken to minimize the suffering of lab animals.

Less than two years after that bitter exchange, UCSF was cited by federal inspectors for AWA violations linked to Lisberger's experiments. In one report the inspector wrote, "In my professional opinion, the nutritional requirements for these animals were not met for either food or water." He also noted that a monkey identified as #17652 who, according to other documents, was enrolled in a Lisberger experiment had remained assigned to the protocol and was even placed on "long-term water restriction," despite the fact that he had chronic diarrhea.

UCSF temporarily suspended Lisberger's study and paid a $2,000 fine to settle the matter. And, despite his gaffes, UCSF defends Lisberger.

Vice Chancellor Ara Tahmassian described Lisberger's lab as a "model program" and said Lisberger is one of the only UCSF researchers who has hired veterinary technicians to work exclusively in his lab and "make sure that everything that happens is done in accordance with proper standards of care." He added, "It's critical for him, because of the nature of his research, that his animals are properly taken care of." Tahmassian also said that, in an academic setting, "there are times that individuals do believe that an oversight committee such as IACUC is getting into areas of science which the faculty members don't believe is in their jurisdiction.... It doesn't mean that the IACUC is going to just back off."

IACUC members also told us that, these days, Lisberger is cooperative. "I think the committee has a very good working relationship with Dr. Lisberger," IACUC chair Linda Noble said.

Even if Lisberger has cleaned up his act, it's hard to see why UCSF would put him in charge of training the scientists of tomorrow how to work with animals. Yet, according to online course information, Lisberger sometimes lectures UCSF students on "Philosophical/ethical issues in animal experimentation," relevant regulations, and "pain minimization."

TW

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