From: Electronic Telegraph Thursday 25 January 1996 Science
Over the barrier 'twixt man and beast
Roger Highfield, Science editor
The chimera, a fabulous beast made up of the body parts of many animals,
is one of the most enduring figures of legend. Modern science is beginning
to bring that myth to life - and while such innovation will
always prompt the spectre of the monster in the laboratory, it is only
by manipulating the mechanisms of life itself that science is helping to
conquer disease.
Blends of different mice that have recently been produced yield fundamental
insights into the way life develops, and mean that we can now investigate
the root of common hereditary diseases such as cystic
fibrosis. The benefits for medicine are potentially enormous.
One day it will even be possible, for instance, to mix the cells of two humans together, or pepper the mixture with foreign genes, which will open up an impressive range of new treatments for hereditary disease. But, inevitably this will raise a disturbing range of ethical problems and will provoke an equally disturbing response from some sections of the public.
"Public debate is very important in this area," Prof Evans said. He warned: "We should proceed with extreme caution."
Just over 10 years ago we saw the creation of a "geep", a blend of a
sheep and goat. Now the first experiment has taken place to mix baboon
bone marrow with that of a human [see right], the potential to manipulate
life this way raises important issues that demand wider debate. For example,
could ape-human chimeras ever be made? These would not be classical chimeras,
a hirsute human, for example, or a baboon's head married to a human body,
but an intimate mixture of ape and human
cells.
This uncomfortable possibility, albeit theoretical, has arisen from a recently discovered ability to isolate and grow a type of cell called a stem cell, the grandmother of all other cell types.
The ultimate stem cell is the fertilised egg. As it divides, its progeny
become more suited to a task or organ, ending with a wide repertoire of
possibilities, each of which carries out a specific job, whether in
brain, muscle or gut.
En route to an adult, more specialised stem cells develop. For example, there are blood stem cells, from which all the blood's red and white blood cells arise, and stem cells that proliferate to form and renew the skin.
One leading light in stem-cell research is Prof Martin Evans of Cambridge University. He was the first to isolate mouse embryonic stem cells and found that huge numbers could be grown over long periods in the laboratory. They provide new opportunities for genetic experiments yet each cell retains the ability to reconstitute an entire rodent.
Now Prof Evans believes that the follow-up work may have gone too far: Dr James Thompson and colleagues at the Wisconsin Regional Primate Centre in Madison, Wisconsin, have become the first to grow stem cells from an early primate embryo, in a technically challenging procedure in which the cells are bathed in special factors and grown on a bed of sterilised rat cells.
This opens the way to the creation of human embryonic stem cell line. "Public debate is very important in this area," Prof Evans said. He warned: "We should proceed with extreme caution."
Benefits, nevertheless, will arise from such research: for example, insights into the development of the foetus, and what can go wrong. By conducting genetic tweaking, it is also possible to persuade stem cells to grow into more specialised types to repair a ravaged body.
RESEARCHERS have already found a way to isolate and grow nervous system stem cells, or cells very much like them, for transplant into the brain.
"When we implanted these stem-like cells into special adult mouse models of specific brain injury, the cells appear to recognise the changed brain environment and become precisely the type of nerve cell that is missing," said Dr Evan Snyder of Boston Children's Hospital and Harvard Medical School. Another application would be to genetically engineer blood stem cells and use them to correct a hereditary disease such as haemophilia, said Mr Charles Harris of the Wisconsin team. Once stem cells have been armed with a gene responsible for a missing blood factor, they can be introduced into the marrow so that blood can clot again.
There is another route to the same end. Unlike adults, embryos have no immune system and tolerate big genetic differences. This raises the possibility that stem cells from an aborted embryo could be grown in the laboratory and mixed with that of a living embryo to create a human chimera, one consisting of a blend of cells rather than genetic blueprints - the usual result of genetic engineering, and sex, too.
By introducing a small percentage of normal stem cells into a foetus
that lacks the key enzyme ADA, and thus lacks immune protection, it could
be possible to correct the potentially fatal defect in the
resulting chimera. Embryonic stem cells could have an additional ADA
gene implanted and then be mixed with those of an afflicted embryo, indeed
any foreign gene could be dispersed this way throughout the body.
This sophisticated form of genetic manipulation has a disquieting spin-off. The eggs and sperm - and thus children - of a chimera could be the genetic descendants of an aborted foetus, or pass on implanted genes, a form of gene therapy that is outlawed in humans because it affects future generations.
"I find it difficult to see any potential justification for this," Prof Evans said. "It has so many dangers associated with it. It is illegal and should remain so."
The most extreme implication of this research would be a primate-human
hybrid, or a human-primate hybrid, depending on which species contributed
the most cells to the chimera. For example, it would be
possible to "humanise" primates by implanting human genes that make
their tissues suitable for transplant into man, helping to overcome the
acute shortage of donor organs.
AN AMERICAN team has already tested this idea by replacing 20 per cent of baboon bone marrow with human stem cells, so the monkeys have various lineages of human blood cells as a result. The team's success is down to a novel type of cell - present at levels of one per 200,000 in bone marrow - a so called "facilitating" cell that helps prevent a serious rejection problem, called graft versus host disease, and allows introduction of purified stem cells into other species.
"In the past, when researchers tried to transplant stem cells into genetically different recipients they were universally rejected," said team member Dr Suzanne Ildstad of the University of Pittsburgh.
In recent weeks, the team has attempted to produce a mixture of human and baboon blood cells for the radical new Aids treatment outlined on the right. But this also raises the issue of whether it would ever be possible to mix embryonic stem cells from primate and man. Such work could have bizarre consequences: for one, the resulting chimera could look human but produce primate sperm.
However, whether there would ever be any good reason for this horrendous experiment to be performed is doubtful.
Electronic Telegraph is a Registered Service Mark of The Telegraph plc
dan@southeast.net
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