Anna stares at the computer screen and considers her options. In front of her are two shapes - a flower and a stripy 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 last few weeks she has learned that the diamond was her ticket to a tasty, sugary 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 at all; she moves, eats and socialises normally. 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 UK are providing vital insights into the brain malfunctions that cause psychiatric conditions such as schizophrenia, obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD) and depression.
Animal rights campaigners condemn this research as cruel and unnecessary. This week, the renowned primatologist Dr Jane Goodall urged the EU 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 and experimenting that will not involve the use of live, 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, who have been known to make overblown and unscientific statements about the 'critical necessity' of their research," said a spokesperson for the British Union for the Abolition of Vivisection (BUAV).
The Guardian was granted access to the controversial facility. We were allowed to visit every room in the complex and see every animal on the understanding that we did not reveal its location. The names of workers at the site 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 openly 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 if her involvement becomes more widely known 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 which 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 with mirrored windows looks no different from any other set of academic offices. Inside there is the familiar faint university whiff of the academic coffee room, but here it is mingled with the pungent smell of monkey urine. The marmosets are housed in nine rooms, in cages nearly 3 metres (9ft) 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 pairsm, as they would 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 that Peter has developed. "I think a lot of people have the idea that you have mad scientists with primates in cages stuck on their desks. That's just not what it is," he said.
In the marmoset kitchen, Peter prepares the monkeys' daily 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 exactly the same diet as the experimental monkeys.
"It is restricted. We restrict the times when they have treats. But we are not starving the animals by any stretch of the imagination and we are not dehydrating the animals," he said. Apart from Peter's desire to treat the animals well and his obligation to do so under the strict 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. "This may sound strange, but I work here because I love animals. It's as simple as that," Peter said.
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 make 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. That involves shaving the marmoset's head, drilling tiny holes into its skull, inserting a needle and injecting a tiny quantity of toxin. To destroy some brain structures, the scientists must make up to eight brain lesions. All of this happens in an operating theatre on site using equipment and anaesthetic the same as would be used in human brain surgery.
The operations, under anaesthetic, last around three hours. Typically, the marmosets take around four hours to come round, at which point they are reunited with their cage mate. They are monitored as they recover from the anaesthetic and a vet is on call for all the monkeys day and night.
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. "You are a mallow monster - yes," said Sarah in a high-pitched baby voice as she hands a marshmallow through the bars of the cage. She knows 20 animals by sight and said they have unique personalities.
It is Anna's turn for her behavioural test. "I would honestly say that they like testing. If, for some reason, you don't test one for a day they are not happy with you," said Sarah. She places a small Perspex box next to an opening in the cage and Anna jumps in immediately to grab the marshmallow on offer. Sarah takes her to the experimental room where Anna spends a few minutes pressing on the computer screen. Despite failing to receive the milkshake, Anna shows no sign of being stressed by the exercise and she is back in her cage with Hedwig within 10 minutes.
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 even 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 OCD and ADHD.
OCD patients feel compelled to repeat behaviours such as washing their hands. Anna, returning time and again to the wrong symbol in her computer test, is performing the equivalent behaviour, said Jessica. When OCD patients are given the same rule-changing task they act in the same way. The difference with Anna is that it is possible to work out which part of the brain is responsible for the behaviour and so offer options for treating the symptoms in people.
Jessica is adamant that the insights her team is providing into how the human brain works would simply not be possible any other way. "I really don't believe there is an alternative at the moment," she said. "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 this huge number of people who suffer from these really 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.
Backstory
Research using non-human primates is the most controversial area of animal research, but it accounts for a tiny minority of experiments. No great apes (chimpanzees, orangutans and gorillas) have been used in experiments in the UK since 1986 and it has been government policy not to use them since 1997. No prosimians (for example, bush babies and lemurs) have been used for several years. Baboons have not been used since 1998. Scientists argue that animal research is highly regulated to ensure it is carried out as humanely as possible. Home office inspectors make unannounced visits to licensed laboratories to check standards of animal welfare. A five-year licence can take six months of detailed work to put together and submit to the Home Office. The research is expensive. Housing a marmoset for a year costs around £4,000; a larger macaque monkey around £18,000.
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