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Date:  26 February 2001

OF  MICE  AND  MORONS?  HUMAN  BRAIN  CELLS  IN  MICE

The reporter suggests the research below, by Irving Weissman of Stanford University,  raises questions about human identity. With Weissman looking "to produce mice in which almost all the brain cells... are human", it ought to raise questions about human ethics.

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Financial Times (London) February 24, 2001, Saturday London

 Man or mouse? Well, it's not that simple any more: Clive  Cookson, Science Editor, examines the implications of  experiments in California where human cells have been  successfully implanted into the brains of mice:

The biological gap between people and other animals is shrinking fast, in the glare of science.

The most dramatic illustration so far is a group of mice in a Californian laboratory, whose brains contain a mixture of animal and human cells. The way human and animal cells thrive together inside the "chimaeric brain" already raises troubling questions about human identity. But Irving Weissman of Stanford University, who carried out the experiment with colleagues from the Salk Institute and
 StemCells, a California biotechnology company, is thinking of taking the research further into unknown and controversial territory. He can see a way to produce mice in which almost all the brain cells (neurones) are human.

In the present generation of mice, up to a quarter of the neurones are the descendants of immature human brain cells - stem cells - that were injected into their heads just after they were born. They behave like normal mice. Prof Weissman's proposed experiment would involve injecting human stem cells into the embryos of a mouse strain in which the neurones die off during development. The idea is that the growing human cells will replace the dying mouse cells and eventually produce a brain made up of human neurones. Constrained by the small space inside a mouse's skull, and inheriting the anatomy of the animal's brain, it is hard to see how such a brain could develop traces of human characteristics such as mind or intellect. But an imaginative science fiction writer could build horrifying scenarios about human brains trapped inside animals' bodies - or vice versa - so Prof Weissman has wisely asked a Stanford University bio-ethics committee to review the experiment before he begins detailed planning.

"The group grilled me about the reasons for doing this," he says.  "They have not yet come up with any recommendations - and I might not do the experiment even if I could, because I do have questions about it myself."

On the positive side, an experimental animal whose brain is genetically human and makes human proteins would be an enormously powerful scientific resource. "For example, by genetically modifying the stem cells (before injecting them into the mouse) you could rationally and quite rapidly ask what genes are required for particular behaviours," Prof Weissman says. The animal would also be a valuable tool for pharmaceutical researchers wanting to test the effect of drugs on the human brain before starting clinical trials.

Prof Weissman and colleagues are in the forefront of the worldwide surge in research into stem cells as vehicles for regenerative medicine. The aim is to repair diseased or damaged tissues, from the brain to internal organs such as liver and heart. The field has been controversial so far because most scientists believe the best sources of stem cells are human embryos created through in-vitro fertilisation or aborted foetuses, though some researchers have recently reported success in extracting stem cells from adult tissue such as bone marrow. The Californian researchers used technology developed by Nobuko Uchida and colleagues at StemCells to isolate the rare stem cells from human foetal brains, then culture them before injection into the brains of neonatal mice. These animal tests are a prelude to clinical trials in which the brain stem cells will be injected into human patients - with Parkinson's disease likely to be the first target. Half a dozen biotechnology companies, including ReNeuron in Britain and Layton Biosciences in the US, and several academic groups are developing stem cell treatments for brain disease.

The latest announcement came earlier this week from Paul Sanberg of the University of South Florida. His research team has injected human stem cells, extracted from umbilical cord blood, into rats paralysed by strokes and shown that they can restore some mobility. But no other group has created animals with so many human brain cells as Prof Weissman's. Ten years ago scientists would not have dreamt that a brain could combine cells from the mammalian species that diverged 70m years ago. "I was totally shocked by our results," says Prof Weissman. But DNA sequencing has recently shown how alike we are - only about one per cent of the estimated 30,000 human genes are not present in mice.

The perceived gap between mice and men has been shrinking ever since Charles Darwin showed that we have a common ancestor. Who knows where the trend will end?

 

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