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Chip could create mass-produced clones

19:00 30 January 02
Sylvia Pagán Westphal

A chip that will automatically create hundreds of cloned embryos at a time 
is being developed by a Californian biotech company, New Scientist has learned.

If it lives up to its promise, the chip should help make cloning cheap and 
easy enough for companies to mass-produce identical copies of the best milk 
or meat producing animals for farmers. It might even be used for cloning 
human embryos.

The chip automates the laborious process of nuclear transfer, the key step 
in cloning. At present it takes hours of painstaking work with a microscope 
to remove the nucleus of an egg cell and replace it by fusing the 
denucleated egg with another cell.

"If somebody's got something like that, obviously it would make everybody's 
life easier," says Tanja Dominko of Advanced Cell Technology, the 
Massachusetts company that caused a stir late last year when it announced 
that it had created cloned human embryos.

Urchin eggs

In animals, cloning is still very wasteful. At best, around half of cloned 
embryos develop to the point where they can be implanted, and only a tenth 
of these survive to birth. Often more than a hundred nuclear transfers must 
be carried out to create a single clone.

Scientists usually start with a batch of 150 eggs, and denucleate them one 
at a time before moving on to the next step. That means eggs can be left 
sitting around for several hours, a delay that may reduce success rates.

But the nuclear transfer array developed at Aegen Biosciences, by the 
company's founders Richard Kuo and Gregory Baxter, could handle hundreds or 
even thousands of eggs at once. Kuo says they can routinely denucleate 30 to 
50 sea urchin eggs at a time. They plan to start testing cow eggs in the 
next few weeks.

The prototype is a thin silicon slice a few centimetres across etched with 
hundreds of tiny wells, one for each egg. The trick is to spin the chip in a 
centrifuge, forcing the eggs' dense nuclei through a small hole at the 
bottom of each well. About 90 per cent of the eggs can be successfully 
denucleated this way, Kuo says.

Kuo and Baxter are now working on the next step, which is to fuse a donor 
cell with the denucleated egg. A lid with appropriately positioned donor 
cells will be placed on top of the eggs. "Then they're ready to fuse," says 
Kuo, although he won't reveal details of the method. After fusion, eggs that 
develop far enough could be implanted manually into an animal's womb as normal.

Too expensive

"If it works with cow [eggs], that would be very neat," says Rudolph 
Jaenisch of MIT, who studies problems with cloning. But just because it 
works with sea urchins doesn't guarantee that it will work with the eggs of 
other species, he warns.

And Randall Prather of the University of Missouri, whose team recently 
announced the cloning of miniature pigs, says the chip won't help solve 
other problems, such as ensuring that the eggs you use have been kept in the 
right conditions. He thinks it might also be too expensive for many labs.

Kuo admits there is much work still to be done on the chip, but he believes 
it's worth the effort. One could submit different batches of eggs to various 
treatments, to find out which conditions improve success rates in cloning, 
he says. Such studies could also help researchers identify the factors in 
eggs that reprogram the added nucleus.

If the chip does improve success rates in animals, it is likely to be used 
to create cloned human embryos, where the problem is not dealing with many 
eggs at a time but getting hold of sufficient numbers of eggs. Companies 
such as Advanced Cell Technology hope to obtain embryonic stem cells from 
cloned embryos but have had only limited success.

The chips might also appeal to the mavericks who want to carry out human 
reproductive cloning despite all the warnings about the risks. The warnings 
are based on the health problems seen in the few clones that do survive, 
which have also prompted the FDA to ask companies not to sell food from 
clones until it has been proved to be safe.

19:00 30 January 02



esommer.net | esommer.net : blog | esommer.net : blog : archive | archive : 2002 | 2002 02 dyree(e) | Details 2002 02 dyree(e) | 200202 01 Friday new sci article on cloning chip