Cloning harbors serious, hidden problems, scientists say
By GARETH COOK ©2001 THE BOSTON GLOBE

Since the birth of Dolly, the first cloned sheep, scientists have made
stunning progress, creating seemingly healthy copies of mice, pigs,
goats and cows.

But Friday, almost five years to the day since Dolly's birth, a team of
scientists will announce evidence that these creations of modern
science can harbor serious hidden problems in their genetic code,
raising new concerns about plans to create a cloned human.

The finding, reported in Friday's issue of the journal Science, could
explain why so many clone pregnancies fail, and why some cloned
animals suffer strange maladies in their hearts, joints and immune
systems. And the research, which focused on how cells interpret
their genetic instructions, suggests cloning causes further problems
that have so far evaded detection.

"There are almost no normal clones," declared study author Rudolf
Jaenisch, a professor of biology at MIT.

The announcement comes at a crucial time, with Congress
considering sharp new limits on cloning technology, and under
pressure from a range of religious groups, biomedical companies,
and patients groups.

Current cloning techniques could be used to create a human
clone -- a person, the report hints, who could have a host of
unpredictable medical and developmental problems. The same
technology, however, can also be used for "therapeutic cloning,"
a process that creates healthy copies of a patient's cells -- not
whole beings -- and could eventually be used to treat diabetes,
Parkinson's disease, and many other disorders.

Some geneticists worry that in the political fight over cloning,
these findings could become ammunition against not only
human cloning, but also therapeutic cloning.

"This is exactly the kind of paper that can be misunderstood,
stopping treatments that could save millions of people from
diseases," said Robert Lanza, vice president of research for
Advanced Cell Technology, a Worcester-based company that
is heavily involved in cloning research and could be put out of
business by a broader ban.

The authors of the report investigated "gene expression," the
vital process in which cells use the parts of the genetic code
they need. Different kinds of cells -- the skin, muscles,
nerves -- have different genes turned on. This pattern is what
determines the identity of the cell.

To create a clone, researchers take a cell -- a skin cell, say -- from
an animal and then return the pattern of gene expression to its
most primitive setting, so it will behave like a fertilized egg cell,
ready to grow into a new animal.

To accomplish this, biologists transfer the DNA from one cell
into an egg cell that has been emptied of its own DNA. The egg
cell then seems to reset the gene expression of the injected DNA.
From there it will grow into an embryo, and eventually a live animal
with a genetic code identical to that of the donor.

But the reset doesn't seem to work perfectly. In the research
announced Friday, scientists cloned mice and then compared the
expression of six genes to normal mice. Of about 40 mice, the vast
majority had at least one abnormality, according to another study
author, David Humpherys of the Whitehead Institute and MIT.

Problems with gene expression can be completely harmless,
or instantly fatal, or somewhere in between. But with human cloning,
the stakes would be much higher.

"This may not be a critical fact in how a cow functions," said Mark
Westhusin, a leading cloning expert who is an associate professor
at Texas A&M. "But humans have to do more than stand out in a
pasture and chew grass."

And because an animal has tens of thousands of genes, it would
be practically impossible to prove definitively that a particular clone
is normal, even if it appears fine at first. Dolly, for example, seemed
completely normal before suddenly turning obese.

In this study, researchers used embryonic stem cells, a primitive
type of cell thought to be especially easy to reprogram. Jaenisch
said that the team plans to test clones made from other cells, but
expects to find similar problems.

He emphasized that the finding did not pose any problems for
therapeutic cloning. In this technique, a patient's cell is cloned,
resetting it to its primitive state and then allowed to divide for
several days, to a pre-embryonic stage.

This process yields stem cells, which can then be turned into
specialized cells that can be implanted back into the patient.
Because these cells are performing specialized functions, small
gene expression problems are less likely to pose difficulties, the
researchers said.

Therapeutic cloning, though, has drawn fire from religious and
other groups who argue that the process is tantamount to creating
and then snuffing out a new life. Others fear it will make it easier to
create the world's first human clone.

But "there is no reason to punish innocent patients just because
of the chance that someone might abuse the system," said Lanza.

Gareth Cook can be reached by e-mail at [log in to unmask]

http://www.charlotte.com/topnews/pub/clonning.htm

* * *

----------------------------------------------------------------------
To sign-off Parkinsn send a message to: mailto:[log in to unmask]
In the body of the message put: signoff parkinsn