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To: Jon Koplik who wrote (2746)11/13/2003 10:32:57 AM
From: Jon Koplik  Respond to of 3576
 
(Part 2) 11/8/03 NYT article on cloning and cloning difficulties.

Scientists Seek Efficient Cloning Process

November 8, 2003

Meanwhile, Clonaid, a company founded by the leader of a
religious sect that believes space aliens created life on
Earth, claims it has produced five babies through cloning.
Clonaid grabbed headlines last December by announcing the
first such baby had been born, but that claim has been
dismissed by scientists for lack of proof.

Most scientists who deal with cloning oppose using it to
make human babies. ``Human reproductive cloning is unsafe,
unethical and ought to be illegal everywhere in the
world,'' declared Gerald Schatten of the University of
Pittsburgh.

Schatten is close to the debate because he's been trying to
clone monkeys, which belong to the same overall
classification -- primates -- as humans. The implications
of any success for the prospects of human cloning are
clear, and Schatten said he's already exploring ways to
make sure that if he succeeds, others won't be able to use
his work to produce human babies.

Schatten wants to make identical monkeys for medical
research, providing a more human-like version of the
genetic uniformity found in mouse strains. But so far, his
efforts have failed even to produce a pregnancy. What's
going on?

To understand the apparent answer, you have to know a
little about cloning. The basic idea is to take the
DNA-bearing nucleus of an animal's cell and plop it into an
unfertilized egg. The implanted DNA drives the egg to
develop into an embryo, which is placed in a surrogate
mother, where it grows into a newborn -- the genetic clone
of the animal whose DNA you started with.

An egg has its own nucleus, so that has to be removed
before the egg receives the new one. Normally that doesn't
pose a problem. But with monkeys, it does.

Schatten's scientific team reported earlier this year that
removing the nucleus from a monkey egg also removes two key
proteins. Without them, the egg doesn't stand a chance of
growing into a new monkey.

Schatten figures this problem will be overcome and newborn
monkeys will eventually follow. And he's philosophical
about bumping into the hurdle in the first place.

``I feel like nature has given us a scientific reprieve''
to block human cloning with current techniques, giving time
to develop laws, he said.

With barnyard animals, researchers can produce newborn
clones, just not as consistently as they'd like. The
problem becomes apparent after embryos are planted in
surrogate moms.

``We can make thousands of embryos,'' says Steve Stice of
the University of Georgia. ``The real cost and real problem
for us is when we transfer that embryo and we don't produce
a (successful) pregnancy, because that costs us time and
money.'' And the agricultural industry won't be interested
in cloning if it's not efficient enough at producing
newborns, he said.

It took 29 implanted embryos to produce Dolly, and since
then, ``we haven't been able to increase efficiency as we
thought,'' said Jose Cibelli of Michigan State University.

In cattle these days, only one in seven to one in 15
transferred embryos produces offspring, Stice said.

At Cyagra Inc. of Worcester, Mass., which has produced more
than 100 calf clones for dairy and beef farmers, marketing
manager Steve Mower says the track record is about 15
percent.

``We have to do better,'' he says, and the company is
aiming at efficiencies of 60 percent to 70 percent.

It's not just cows. It took 113 implanted embryos to
produce just three cloned mules this year, an efficiency
just below 3 percent, said one of the cloners, Ken White of
Utah State University.

To deal with the efficiency problem, some scientists are
scrutinizing the raw materials, looking for ways to
identify the most promising eggs and the best cell nuclei
from animals to be cloned. Cibelli, for example, is looking
for chemical markers that can identify a nucleus that's
ready to be introduced into the egg.

``We're getting good results,'' Cibelli said.

In fact,

many scientists believe the nucleus of the donor cell holds
the key for why cloning works so sporadically, as well as
why clones show unusual rates of birth defects.

For scientists, Dolly the sheep was stunning because she
showed that the DNA in the nucleus of an adult animal cell
could undergo an amazing career change. After all, its job
had been to drive the everday activities of an adult cell,
with certain genes active and others switched off to
achieve that goal. But once it was placed in an egg, it had
to reprogram its gene activity to start the process of
creating all the tissues of a whole new individual.

``If you have a nucleus that has been committed to be skin
for a number of years, then in a matter of minutes you have
to turn it into an embryonic nucleus that can make
anything,'' Cibelli said. ``Not all the genes will be ready
to be reprogrammed.''

If the changeover isn't complete enough, the egg and
resulting fetus just won't be equipped for developing
normally, scientists say. That can doom a pregnancy.

Even in animals that make it to birth, faulty reprogramming
could lead to observed abnormalities in clones like
breathing problems and defects of the liver, heart and
brain. Some abnormalities may also be due to manipulations
of the embryo before implantation.

Despite the appearance of defects in some clones,
scientists point out that many animal clones turn out just
fine.

``We have seen cloned cows that are thriving at the moment,
and indistinguishable from non-cloned animals,'' Cibelli
said. Stice said that's been the experience of his clones.
``The vast majority of them are just fine,'' he said.
``They look like any other pig or cow out there.''

Visitors to a home in Texas say roughly the same thing
about a calico cat that frolics there. It's cc, the
domestic shorthair who gained fame in February 2002 when
she was announced as the first clone of a cat. This year,
she moved in with Duane Kraemer, one of the Texas A&M
researchers who made her birth possible.

She's an ``absolutely normal cat in every aspect we can
determine,'' Kraemer said. She does have a heart murmur,
like the cat she was cloned from. Neither animal has had
any trouble with it, Kraemer said.

Scientists say they hope to achieve cloning in more
species. Mark Westhusin of Texas A&M, who directed the
research that produced cc, said he's trying to clone
white-tailed deer to help ranchers who supply game for
hunters. White of Utah State hopes to clone an endangered
wild sheep called the argali, known for its massive curved
horns.

AviGenics Inc. of Athens, Ga., is trying to clone chickens.
Genetic Savings and Clone Inc., based in Sausalito, Calif.,
is not only gearing up to clone more cats but also trying
to duplicate a dog for the first time. For technical
reasons, dogs are harder to do than cats.

But ``we think there's some likelihood we'll produce a dog
clone within the next year,'' said Ben Carlson, the
company's vice president for communications.

Maybe that'll happen and maybe not. But the cloning field
is moving so fast, it's hard to rule anything out, says
Gary Anderson of the University of California at Davis.

So when he's asked if the DNA reprogramming problem that
hinders cloning can be overcome, he turns unpredictability
into optimism.

``One wouldn't want to say we're stuck, we can't do
anything about it,'' Anderson said. ``You're proven wrong
almost every day.''

------

On the Net:

Cloning background: arhp.org

nlm.nih.gov

Copyright 2003 The New York Times Company.