/ 30 June 2008

Inside the primate laboratory

Anna stares at the computer screen and considers her options. In front of her are two shapes — a flower and a diamond. If she picks the right one she will be rewarded with banana milkshake, but the wrong choice will briefly switch the lights off in her Perspex box. She opts for the diamond and is plunged into darkness.

During the next nine minutes Anna makes the same mistake over and over again. The neuroscientists who designed this experiment are testing how good Anna is at learning new rules. Over the past few weeks she has learned that the diamond was her ticket to a tasty drink, but this is the first test in which the rules have been reversed. Most of the subjects adapt quickly. But Anna is different.

In March she was subjected to precision brain surgery in which researchers destroyed a small area of her brain. To the untrained eye this has not affected her behaviour. But the experiments are showing that the specific brain region knocked out is crucial for subtle behavioural abilities.

If Anna was human, this experiment would not be possible. But the studies conducted on her and the other marmosets at one of the most controversial research facilities in the United Kingdom are providing vital insights into the brain malfunctions that cause conditions such as schizophrenia, obsessive compulsive disorder, attention deficit hyperactivity disorder and depression.

Animal rights campaigners condemn this research as cruel and unnecessary. Recently, renowned primatologist Dr Jane Goodall urged the European Union to do more to promote other routes to cures. She advocated a Nobel Prize for alternatives to animal testing. She said: “We should admit that the infliction of suffering on beings who are capable of feeling is ethically problematic and that the amazing human brain should set to work to find new ways of testing that will not involve the use of sentient beings.”

The European Commission is reviewing Directive 86/609, which governs animal research across the EU. Goodall and groups who oppose animal experimentation hope to pressure the commission to include a timetable for ending primate testing altogether.

“Primate use is deeply embedded into the system and the prospect of ending it brings significant resistance from some researchers,” said a spokesperson for the British Union of Anti-Vivisectionists (Buav).

We were granted access to the facility and allowed to visit every room and see every animal on the understanding that we did not reveal its location. The names of workers have been changed to protect their identities.

Despite being a world-class neuroscientist, Jessica, who runs the secret marmoset research facility at a leading UK university, rarely talks about her job. “I very seldom tell anyone what I actually do because you just don’t know who you are talking to,” she said. Police have found her name on a hit list compiled by animal rights extremists and she is afraid that her home and family might be targeted.

To minimise the chance of her identity being revealed, Jessica has never before talked to a journalist. But now she feels a duty to speak. “I’m fed up with the amount of misinformation that’s constantly put out,” she said.

She particularly objects to the photographs on anti-vivisection websites depicting monkeys terrified because protesters have broken in during the night or images that are deliberately cropped to make the cages look tiny.

They are often decades out of date, she said. “The disorders that we are trying to treat are crippling to people. I would love it if we could just tell the world what we do.”

Her anonymous building looks no different from any other set of academic offices. Inside the marmosets are housed in nine rooms, in cages nearly 3m high that are full of ladders, beams and ropes. The cages are bespoke, designed specifically with the needs of this species in mind. The monkeys, which are bred on site, live either in family groups of up to 15 or in pairs as they would be in the wild.

‘What we try to do is, as closely as possible, give them all the opportunities they would have in the wild,” said Peter, the lab’s animal welfare officer. The facility has been visited by marmoset specialists at UK zoos who wanted to learn from the state-of-the-art husbandry Peter has developed.

In the marmoset kitchen, Peter prepares the monkeys’ menu. Their basic diet consists of egg and Complan sandwiches along with pellets that give them the correct balance of minerals. But Peter also includes a dried fruit and nut mix, fresh apples, bananas, pears, grapes and peanuts.

Farley’s rusks, Heinz banana delight, malt loaf and the marmosets’ favourite — mini marshmallows — are also in the larder.

Groups who oppose the use of animals in research claim that scientists force their monkeys to perform by starving them and withholding water.

Peter vigorously denied this. Even without the treats they receive during the experiments, he said the animals receive a nutritionally balanced diet.

Breeding animals receive the same diet as the experimental monkeys.

Apart from Peter’s desire to treat the animals well and his obligation to do so under the husbandry regulations stipulated by the Home Office, he said treating the animals badly would be counter-productive because animals forced into participating in experiments would give unreliable results.

Every monkey has a numbered collar, but each one also has a name. The colony’s family tree goes back to 1978 and each year the researchers choose a theme for the names so that it is easy to tell when a monkey was born.

Gin and Tonic, for example are two marmosets from 2005, the drink-themed year. Hermione was born in 2003 — the Harry Potter year. This year’s dual theme is herbs and cars.

For those who oppose primate research though, even the best welfare conditions entail suffering. “We know that the heightened sentience, intelligence and emotional needs of monkeys makes even day-to-day life in a laboratory cage a grave animal welfare issue — quite aside from the horrifying suffering that can be caused by invasive brain studies or protracted poisoning tests,” said the Buav spokesperson.

And this is the crunch point for many people uneasy about experimenting on the brains of creatures so close in evolutionary terms to ourselves.

To investigate how the monkeys’ brains work the researchers must destroy parts of the brain tissue. To destroy some brain structures, the scientists must make up to eight brain lesions. The operations, under anaesthetic, last about three hours. The marmosets take about four hours to come round, at which point they are reunited with their cage mate.

One of the post-doctoral researchers introduces a pair of experimental animals, Anna and Hedwig, that underwent brain surgery in March and April respectively. The fur on Hedwig’s head is still growing back, but he is bounding around the cage like all the others.

The research in the lab is not aimed at testing the effectiveness of specific new drugs against the simian equivalents of human brain diseases or testing how toxic new products are. They are aimed at understanding the basic neural architecture of primates (including us) so that treatments for brain diseases become a possibility. One focus is on testing the monkeys’ behavioural flexibility and finding out which areas of the brain are responsible. It is these parts of the brain that are altered in conditions such as obsessive compulsive disorder, attention deficit hyperactivity disorder and depression.

Obsessive compulsive disorder patients feel compelled to repeat behaviours such as washing their hands. Anna, returning to the wrong symbol, is performing the equivalent behaviour, said Jessica. When obsessive compulsive disorder patients are given the same rule-changing task they act in the same way.

The difference with Anna is it is possible to work out which part of the brain is responsible and so offer options for treating people.

Jessica is adamant that the insights her team is providing would simply not be possible any other way. “I really don’t believe there is an alternative,” said Jessica. “Tissue cultures don’t behave. Imaging can’t get at cause and effect. Modelling can’t work unless you understand what you are trying to model.” No scientist would choose to work on animals unless there was no alternative, she said. It is expensive, bureaucratic and dangerous because of the lengths to which some who oppose the work are prepared to go. “You need to do something for the people who suffer from these debilitating psychiatric disorders. We can’t do that unless we understand how the brain controls our behaviour.”

Critics say using animals in research is simply old-fashioned science.

“Urgent action is needed to improve the protection of animals and to replace unethical and outdated animal experiments with non-animal techniques,” said Dr Gill Langley of the Dr Hadwen Trust, a non-animal medical research charity. She favours methods such as tissue culture, computer modelling and brain scans, which she says are more advanced and relevant to human patients. —