Kevan Martin puts his many years of research interests in a nutshell: “We want to find out how the brain works.” According to the Zurich Professor of System Neurophysiology, our brain began a real “leap” in development six to seven million years ago: its size tripled within three million years. The main beneficiary of this was the neocortex, the part of the cerebral cortex that, in an evolutionary sense, is youngest.. Researchers at the Institute of Neuroinformatics (INI) of ETH Zurich and Zurich University focussed their interest on this success story. Kevan Martin explains that “The neocortex largely makes us what we understand by ‘being human’. It is where speech, the ability to remember, the faculty of judgement and the ability to plan as well as emotional processes are located. But however fundamental this control centre is to our life, we are still groping in the dark as far as its functioning is concerned.”

Animal brains as a model

Work at the system level to shed light on this darkness is now progressing at the INI as part of the National Key Research Program “Plasticity and Repair of the Nervous System”, among others. It is hoped this will contribute in the long term to the treatment of accident-related brain injuries or illnesses such as schizophrenia or depression. Work on the simulation of brain functions is also being undertaken at the INI. For example they have created a robot arm that can be controlled by thoughts. The central questions are: how do the various regions work, how are they networked together and how are the instructions transmitted?

On the one hand studies are conducted on human volunteers. However on the other hand invasive experiments are necessary, for which animals are the only option. Daniel Kiper, a lecturer at the INI, says “We use macaques, cats and rats to determine for example the interaction between the sensory and motor systems or functional principles in the visual centre.” Of course humans and animals cannot be compared one to one in this respect, but Kiper thinks that “There are illuminating parallels in the fundamental neurobiological processes in the neocortex nonetheless.”

Anatomical studies are indispensable

The teams at the INI measure the animals’ brain activity with various tests. Some of these involve using fine probes to measure the electrical activity of cells in the cerebral cortex. Martin says “I can understand that such measurements may disconcert the onlooker. However, one must know that they do not involve any pain because the brain does not contain any pain receptors.” Nevertheless it is a fact that the animal must die at the end of an experiment of this kind: “Unfortunately we cannot avoid that,” says Kevan Martin. “Examination of the anatomy under the microscope yields key information about the signal pathways of the nerve tracts. These are made visible by using differential staining agents.”

For the projects to continue, the cantonal Animal Experimentation Commission repeatedly asked for new decision-making bases early in 2006, including among others three external expert’s reports by specialists nominated by the Commission. Kevan Martin says “Two of the three expert’s reports reached clearly positive judgements.” Nonetheless the Commission suddenly halted the macaque experiments last November by objecting to the continuation of authorisations granted in the meantime by the cantonal veterinary surgeon. The scientific journal “Nature” reported the case at the time. The Animal Experimentation Commission’s justification was that the experiments would violate the creatures’ dignity; this was a reference to the amended Swiss Animal Protection Act that will probably come into force in 2008. It includes a regulation that an animal’s dignity must be protected. Hans Sigg, Animal Protection Officer at UZH and ETH adds: “The objectors are giving the term ‘dignity’ a considerably wider interpretation than is specified by the definition in the Animal Protection Act.”

The dignity obstacle

The Zurich Commission also decided that the expected scientific results do not justify the distress caused to the animals. Moreover it said that the great similarity between primates and humans demands they be treated with the greatest possible respect in experiments. This action also caused astonishment at the INI because the long-term studies had always been approved for a decade, the six-monthly checks of the primate housing have never led to complaints and the ethical guidelines are strictly obeyed at the INI. However, the problematic argument of the “creature’s dignity” confronts the researchers with an obstacle that is hard to surmount. Kevan Martin says: “What ‘dignity’ is and when it is violated can be interpreted in almost any way you like. Various ethics commissions have dealt with this difficult concept in the past but in no case did they reach a consensus. At the same time the Animal Experimentation Commission refuses to discuss the matter. It has never availed itself of the opportunity to inspect our experiments thoroughly on the spot either.”

Klaus Peter Rippe, philosopher and President of both the Animal Experimentation Commission of the canton of Zurich and of the Swiss Federal Ethics Committee on Non-Human Biotechnology (EKAH) occupies a key position in the present case. Kevan Martin thinks that “Prof. Rippe has made a U-turn in the direction of the animal rights movement. By doing this he has endangered an entire research field in Switzerland." He says the Commission President also values fundamental research less than applied research in the medical field, which is why the barrier is higher for animal experiments such as those at the INI. According to Martin: “Anyone who draws a distinction between basic and applied science ignores the fact that the two are inseparably linked. Every successful therapy is the tip of an iceberg consisting primarily of fundamental research.”

Female macaque Bluesy in her enclosure at the Institute of Neuroinformatics: INI researcher Daniel Kiper uses her to study the processing of visual information in the brain. large

Precautions to avoid suffering

The Commission also complained that the animals were forced by being deprived of water and rewarded with apple juice to do things they would not do voluntarily. In Daniel Kiper’s opinion this is unfounded. Any trainer would also work with reward strategies, for example with dogs. But how does the INI deal with the animals’ suffering? The researcher stresses that “We avoid the animals suffering wherever possible. They are cared for considerately and it goes without saying that our relationship with them must be a partnership – in our own interest as well. After all, the animals must cooperate if an experiment is to succeed.”

Kevan Martin gives an assurance that the euthanasia of the animals at the end of the experiment – which can last for several years – is painless and stress-free, and in any case ETH Zurich and Zurich University are far above the worldwide standard with regard to their infrastructure. The macaques at the Institute’s site on the Irchel campus live in groups in large, lavishly equipped enclosures that also lead out into the open air. There would be no grounds for complaint even if the INI’s primate experiments were carried out in Great Britain, whose animal protection standards are among the most stringent anywhere. That’s why the international research community is now watching the events in Zurich with even more concern.

Simulation has its limits

How do the Zurich researchers reply to the objection frequently expressed that progress in research and methodology enables us to dispense with distressing animal experiments nowadays? Daniel Kiper says that “A certain level of knowledge can be achieved via computer simulation, through the non-invasive measurement of brain currents or by studying cell cultures, but these methods have strict limits.” With an EEG (electroencephalogram), for example, the real origin of the pulses is not clear. He adds that: “One cubic millimetre of the neocortex contains 50,000 nerve cells with four kilometres of ‘wiring’. No computer can simulate exactly what happens there, either today or for a long time to come.” A small and very controlled number of animal experiments are essential to obtain a comprehensive idea of the cortical functions. The Animal Experimentation Commission’s objection has been in the hands of the Zurich Health Authority since November 2006. Until they reach a decision, this branch of research at the Institute is stymied. What will happen if the Zurich government backs the Animal Protection Commission’s veto? Kevan Martin’s answer: “Then I see a bleak future for neocortex research in Zurich. There would be an exodus.”