For an adult cell to be cloned, it must somehow be made "young" again. How the clock of life was turned back
By Andy Coghlan and David Concar
Dolly's birth shows that the biological development of cells is not as
irreversible as scientists once thought. To make her, Ian Wilmut and his
colleagues had to wind back the developmental clock of an adult udder cell.
Thanks to their manipulations, the cell obliged. Its nucleus shook off its
"udder cell" identity and was biochemically reprogrammed to begin life all
Such reincarnation at the genetic level goes against long-held beliefs about molecular biology.
As an organism grows, its cells divide and specialise by switching on certain genes inside their nuclei and shutting others down. It is a complex business involving specialised proteins that manipulate DNA and enzymes that chemically modify the strands with methyl groups. People assumed that genes were shut down for good, but Dolly's arrival appears to show that the process is reversible.
In pioneering experiments with frogs in the 1970s, a team led by John Gurdon at the University of Cambridge transplanted nuclei from the skin cells of adult frogs into frog eggs lacking their own nuclei. While some embryos grew into tadpoles, none reached adulthood.
Wilmut says the key to success lies in the unique way his team manipulates the cells that donate the genetic material. They starve the donor cell into a state of hibernation by placing it in a salt solution containing just enough growth factor to keep it alive. The cell stops dividing and copying its DNA, and shuts down all but the most vital of its genes. This seems to enable the nucleus-free egg to reprogram the new nucleus. During the first few hours of development, sheep embryos are slow to activate genes in their nuclei. This period of "genome silence" may also give the egg a breathing space to reprogram the new nucleus, says Jonathan Slack, an embryologist at the University of Bath. But working out the biochemistry--and limits--of this reprogramming will keep researchers busy for years. The new findings suggest the egg must contain proteins and enzymes powerful enough to remodel and repackage a specialised nucleus. But nobody yet knows what these molecules are, or whether clones could be made with any adult cells. "Brain and muscle cells are probably so [specialised] that you can't reset their clocks," says Wilmut.
Another big question is whether cells from a very old donor would work. Some molecular changes that build up during ageing--such as random damage to DNA--are likely to prove impossible for an egg to reverse.
>From New Scientist, 01 March 97
Fasten your seatbelts . . .
The news that a Californian woman who died from leukaemia a year ago will
become a mother 'from beyond the grave' will have worried many people
concerned about the uses to which new medical technologies are put. Yet it
should surprise few.
Julie Garber, who was 28 when she died, had some of her eggs removed and fertilised by an anonymous donor before undergoing cancer treatment. Her grandparents claim she wanted them to find a surrogate mother for her child after her death, and last week a 23-year-old woman obliged. The ethical dilemmas are myriad, and the US has been troubled by them since Jean and Howard Garber began advertising for a surrogate for their 'grandchild'. Many people are horrified that advances in reproductive biology can allow the birth of a child whose mother has been dead for well over a year.
They should be prepared for worse. For what this case amply demonstrates is that if a technology exists that meets a biological need, somebody, somewhere will use it, whatever the ethical opposition -- and probably whatever the cost. It happened with in vitro fertilisation, today widely accepted.
It's now happened with the late Julie Garber's embryo. It will happen with human cloning -- when the technology is good enough, and the price right. Making the impossible possible is bound to raise difficult questions. The benefits of biological innovation will come hand in hand with a host of dubious applications, against which people will demand to be protected. They should realise, though, that no amount of legislation can put the genie back in the bottle.
>From New Scientist, 06 December 97
In a few short years we'll have the power to control our own evolution
The fears of a clone
Even the President turned out to hear what's hot at the annual meeting of the American Association for the Advancement of Science in Philadelphia. By Peter Aldhous
Gina "Nanogirl" Miller
"The science of nanotechnology, solutions for the future."