Testing human brain cells in non-human primates: the debate

July 25, 2005

Brussels, 22 Jul 2005

A group of scientists and ethicists has sounded a note of caution concerning experiments involving the placing of brain stem cells from humans in big apes and monkeys, particularly if the result leads to a large fraction of a chimpanzee's brain being composed of human neuron. Scientists have declined to recommend a halt to the research, proposing instead steps to minimise the chances of mishaps leading to potentially unsolvable moral dilemmas.

No such experiments are currently planned, but it is possible that such experiments will be conducted as part of studies into stem cell therapies. These therapies are intended to treat diseases with implantations of stem cells capable of maturing into various cells, including brain cells.

If stem cells show promise in treating human brain disease, potential therapies would need to be tested in animals. The delicate issue is that these experiments would go far beyond animal testing, as they could lead to creation of a human mind in a non-human primate body.

A panel of more than 20 scientists, philosophers and lawyers has deliberated for over two years on how far such research should be allowed to go. Its conclusions were published in the 15 July issue of the research journal Science. After acknowledging the general view that primates should not be used for experiments at all, the group, led by Dr R. Faden, a biomedical ethicist at Johns Hopkins University in the US, considered the kinds of research that should be permitted if the experiments were to be required by regulatory authorities.

In the future brave new world of neuroscience, surgeons hope to be able to replace lost or diseased parts of the brain with new, healthy neural stem cells grown in the lab. Testing this therapy first in animals would show how well the cells integrate themselves in the brain. Clinical trials usually depend on or involve previous tests with rats or mice that have some equivalent of the human disease. However, for some diseases, specifically those that affect the human brain, the rodent models do not usually provide enough case similarity. If stem cell therapies for Alzheimer's or Parkinson's disease were to be developed, regulatory authorities might specifically require tests in primates before going further in permitting clinical trials with human patients.

The debate is set to reopen previous polemic on whether primates are appropriate models to reproduce and develop therapies for human diseases, and namely human brain diseases like Parkinson and Alzheimer, two priority research lines in this field. The panel decided to set aside this older disagreement, opting by focusing instead on whether experiments with stem cells and the brain posed any new, unique ethical quandaries.

The most dramatic differences between humans and other primates are in the brain: the human brain is four times larger than that of a chimpanzee, for example, and biochemical pathways in the brain are unique. For example, gene expression in the human brain is dramatically different to that of any other primate. Humans are distinguished from all mammals by their lack of a particular sugar molecule on the surface of cells, especially in the brain. It is likely that this profoundly affects brain development and function. Moreover, the human brain is enriched with specific cell types implicated in communication, language, comprehension and autonomic functions, and characteristics of humanlike cognition.

The panel does not consider it likely that the adult brain of a primate would be significantly altered by human cells. However, the group were deeply concerned about the eventual outcomes if human cells were to be introduced into earlier developmental stage animals. And the closer the primate species is to humans, the higher the risk of some significant shift towards humanlike cognition. If human neural stem cells were to be inserted into the embryo of a chimpanzee, these cells may actually construct parts of the brain so that they are more similar to humans.

Dr Faden explained that the group 'couldn't rule out the possibility that certain experiments could potentially alter the cognitive or emotional status of the animal in ways that would be problematic from an ethical point of view'. The panel recommended for minimising the possibility that such experiments could change the animals' 'moral status' by changing their mental abilities.

Remarks: Reference publication: Greene et al., ETHICS: Moral Issues of Human-Non-Human Primate Neural Grafting, Science 2005 309: 385-386

CORDIS RTD-NEWS / © European Communities
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