Washington Post ... Cloned Embryos Could Help Explain Basis for Diseases

[Murray Charters <mcharters@xxxxxxxxxxxxxx>]

Washington Post ... Cloned Embryos Could Help Explain Basis for Diseases
Scientists Expect to Determine Causes, Develop Therapies by Watching Progress 
of Illness in Cells Implanted in Mice

By Rick Weiss
Washington Post Staff Writer
Monday, February 23, 2004; Page A08

When South Korean researchers announced two weeks ago they had made the world's 
first cloned human embryos, they
emphasized they had no intention of allowing those embryos to grow into cloned 
babies. Their goal -- like that of
others doing similar work -- is to develop new therapies for Parkinson's 
disease, diabetes and other ailments.

The idea is to make a cloned embryo from a patient's healthy cells and then 
retrieve from the embryo stem cells that
could be used to repair the patient's failing organ -- an approach known as 
therapeutic cloning. Because the cells
would come from an embryo genetically identical to the patient, the theory 
goes, they would not be rejected by the
patient's immune system.

This potential to regenerate ailing organs has been a powerful -- though so far 
unsuccessful -- selling point as
scientists and advocates have tried to persuade Congress and the Bush 
administration to loosen federal restrictions
that preclude the use of federal funds for work involving cloned embryos.

In moments of candor, however, many scientists concede that therapeutic cloning 
is far down the list of reasons they
want to clone human embryos. In the long run, the promise is real, they insist. 
But the technical and regulatory
hurdles are so high that it could be a decade before the first proposal is 
ready for consideration by the Food and Drug
Administration.

The agency has already said it will want answers to tough questions before it 
will consider allowing cloned embryo
cells to be injected into patients: Will the cells go where they're supposed to 
go in the body? Could they turn into
the wrong kinds of cells once they're in the body? Will they start multiplying 
uncontrollably and form cancers?

By the time those and other questions get addressed in animal studies, an 
entirely new approach to regenerative
medicine -- one that may not depend on cloned embryos at all -- might have 
emerged.

But there are avenues of research that scientists do want to pursue immediately 
with cloned human embryos. They fall
under the category of basic research and so are unlikely to get patients and 
politicians excited, researchers
acknowledge. But they are experiments that could reveal in spectacular detail 
the basic causes of many diseases. And
they could speed the development of new drugs through already well-established 
pharmaceutical pipelines, without having
to break the new technical and regulatory ground that therapeutic cloning does.

Although the goals of these experiments are less sexy than the almost magical 
regrowing of sick organs, scientists are
starting to talk about them more -- in part out of frustration that Congress 
remains unconvinced embryo cloning
deserves federal support.

Instead of making cloned embryos as a source of healthy stem cells for 
transplantation into patients, scientists are
proposing to make cloned embryos that explicitly bear the genetic glitch or 
glitches at the root of a patient's
disease.

They would start with a diseased cell from a patient -- a degenerating nerve 
cell, for example, from a person with Lou
Gehrig's disease, a neurological disorder that robs people of control over 
their muscles. Using cloning techniques,
scientists would transform that cell into an embryo, which after a few days 
would produce stem cells. Each stem cell
would bear the genetic roots of the disease and each would have the potential, 
as stem cells do, to turn into any kind
of cell or tissue.

In the case of Lou Gehrig's, scientists already have found a handful of genes 
that appear to play a contributing role.
But as with many diseases, they don't know which are most important. They also 
don't know what environmental influences
might determine whether a person with those genes would get the disease or not.

With stem cells from a cloned Lou Gehrig's embryo, however, scientists believe 
they could quickly answer those
questions -- and a host of others.

Here's how it would work: Researchers already know how to force stem cells to 
become nerve cells, so in one set of
experiments they would do so with stem cells taken from a cloned Lou Gehrig's 
embryo and watch those cultured nerves as
they degenerate in a laboratory dish. That alone would be an unprecedented 
opportunity to watch the disease unfold
outside a person, and to test whether certain classes of chemicals or drugs 
might slow or prevent the process.

But even better, said Irving Weissman, director of Stanford's Institute for 
Cancer/Stem Cell Biology and Medicine,
scientists could inject those fresh but doomed neurons into the brains of mice 
and watch how the cells grow, die and
respond to various drugs.

"You could study them not only in a dish but in the context of the kind of 
organ in which they normally find
themselves," Weissman said.

Studies could go much further than that, others said. Scientists already know 
how to "fix" broken genes in stem cells
by splicing out the bad copies and replacing them with normal copies. 
Researchers could start doing that one at a time
with the handful of genes suspected of playing a role in Lou Gehrig's. Then 
they could see whether fixing one gene, or
another, or a combination of several, prevented the degeneration of nerves.

They could do the same with genes in muscle cells from a Lou Gehrig's embryo. 
After all, the disease is all about
communication between brain cells and muscle cells. And although scientists 
suspect that muscle cell genes may
contribute to the disease along with nerve cell genes, it is not known how big 
a role each plays.

With key genes identified, it would be much easier to design a drug or other 
therapy that could target the biochemical
essence of the disease.

Finally, since defective genes alone often are not enough to cause a disease 
but do so only after a specific
environmental trigger -- exposure to pollutants, stress hormones or cigarette 
smoke, for example -- scientists could
add those influences in lab dishes or in mice and see how they contribute.

"You could study the multistep progression of the disease," said Robert Lanza 
of Advanced Cell Technology in Worcester,
Mass., a company pursuing human embryo cloning with private money. "This use of 
clones has been totally missed by the
public but is of extreme importance to really understand the molecular basis of 
disease."

SOURCE: The Washington Post


* * *

----------------------------------------------------------------------
To sign-off Parkinsn send a message to: mailto:listserv@xxxxxxxxxxxxxxxxxxxx
In the body of the message put: signoff parkinsn