"Announcement Today by Scientists at Advanced Cell Technologies Changes
medical Science Forever
Cloned early-stage human embryos& human embryos generated only from eggs,
in a process called parthenogenesis now put therapeutic cloning within
reach"

Below is the story announced today about how the ACT scientists conducted
the research and why they did, as told by  Jose B Cibelli -vice president
of research, Robert P. Lanza - vice president of medical and scientific
development, and Michael D. West - president and CEO of Advanced Cell
Technology, a privately held biotechnology company in Worcester, Mass.

"THEY WERE SUCH TINY DOTS, YET THEY HELD SUCH immense promise. After
months of trying, on October 13, 2001, we came into our laboratory at
Advanced Cell Technology to see under the microscope what we'd been
striving for; little balls of dividing cells not even visible to the
naked eye. Insignificant as they appeared, the specks were precious
because they were, to our knowledge, the first human embryos produced
using the technique of nuclear transplantation, otherwise known as
cloning.

With a little luck, we hoped to coax the early embryos to divide into
hollow spheres of 100 or so cells called blastocysts. We intended to
isolate human stem cells from the blastocysts to serve as the starter
stock for growing replacement nerve, muscle and other tissues that might
one day be used to treat patients with a variety of diseases.
Unfortunately, only one of the embryos progressed to the six-cell stage,
at which point it stopped dividing. In a similar experiment, however, we
succeeded in prompting human eggs on their own, with
no sperm to fertilize them to develop parthenogenetically into
blastocysts. We believe that together these achievements, the details of
which we reported November 25 in the online journal e-biomed: The Journal
of Regenerative Medicine, represent the dawn of a new age in medicine by
demonstrating that the goal of therapeutic cloning is within reach.

Therapeutic cloning which seeks, for example, to use the genetic material
from patients own cells to generate pancreatic islets to treat diabetes
or nerve cells to repair damaged spinal cords is distinct from
reproductive cloning, which aims to implant a cloned embryo into a
woman's uterus leading to the birth of a cloned baby. We believe that
reproductive cloning has potential risks to both mother and fetus that
make it unwarranted at this time, and we support a restriction on cloning
for reproductive purposes until the safety and ethical issues surrounding
it are resolved.

Disturbingly, the proponents of reproductive cloning [see Reproductive
Cloning: They Want to Make a Baby] are trying to co-opt the term
"therapeutic cloning" by claiming that employing cloning techniques to
create a child for a couple who cannot conceive through any other means
treats the disorder of infertility. We object to this usage and feel that
calling such a procedure therapeutic" yields only confusion.

What We Did

WE LAUNCHED OUR ATTEMPT to create a cloned human embryo in early 2001. We
began by consulting our ethics advisory board, a panel of independent
ethicists, lawyers, fertility specialists and counselors that we had
assembled in 1999 to guide the company's research efforts on an ongoing
basis. Under the chairmanship of Ronald M. Green, director of the Ethics
Institute at Dartmouth College, the board considered five key issues [see
The Ethical Considerations] before recommending that we go ahead.

The next step was to recruit women willing to contribute eggs to be used
in the cloning procedure and also collect cells from individuals to be
cloned (the donors). The cloning process appears simple, but success
depends on many small factors, some of which we do not yet understand. In
the basic nuclear transfer technique, scientists use an extremely fine
needle to suck the genetic material from a mature egg. They then
inject the nucleus of the donor cell (or sometimes a whole cell) into the
enucleated egg and incubate it under special conditions that prompt it to
divide and grow [see Therapeutic Cloning: How It's Done].

We found women willing to contribute eggs on an anonymous basis for use
in our research by placing advertisements in publications in the Boston
area. We accepted women only between the ages of 24 and 32 who had at
least one child. Interestingly, our proposal appealed to a different
subset of women than those who might otherwise contribute eggs to
infertile couples for use in in vitro fertilization. The women who
responded to our ads were motivated to give their eggs for research, but
many would not have been
interested in having their eggs used to generate a child they would never
see.

We asked potential egg contributors to submit to psychological and
physical tests, including screening for infectious diseases, to ensure
that the women were healthy and that contributing eggs would not
adversely affect them. We ended up with 12 women who were good candidates
to contribute eggs. In the meantime, we took skin biopsies from several
other anonymous individuals to isolate cells called fibroblasts for use
in the cloning procedure.

We had a glimmer of success in the third cycle of attempts when the
nucleus of an injected fibroblast appeared to divide, but it never
cleaved to form two distinct cells. So in the next cycle we decided to
take the tack used by Teruhiko Wakayama and his colleagues, the
scientists who created the first cloned mice in 1998. (Wakayama was then
at the University of Hawaii and is now at Advanced Cell Technology.)
Although we injected some of the eggs with nuclei from skin fibroblasts
as usual, we injected others with ovarian cells called cumulus cells that
usually nurture developing eggs in the ovary and that can be found still
clinging to eggs after ovulation. Cumulus cells are so small they can be
injected whole. In the end, it took a total of 71 eggs from seven
volunteers before we could generate our first cloned early embryo. Of the
eight eggs we injected with cumulus cells, two divided to form early
embryos of four cells and one progressed to at least six cells before
growth stopped.

Parthogenesis

WE ALSO SOUGHT TO DETERMINE whether we could induce human eggs to divide
into early embryos without being fertilized by a sperm or being
enucleated and injected with a donor cell. Although mature eggs and sperm
normally have only half the genetic material of a typical body cell, to
prevent an embryo from having a double set of genes following conception,
eggs halve their genetic
complement relatively late in their creation cycle. If activated before
that stage, they still retain a full set of genes.
Stem cells derived from such parthenogenetically activated cells would be
unlikely to be rejected after transplantation because they would be very
similar to a patient's own cells and would not produce many molecules
that would be unfamiliar to the person's immune system. (They would not
be identical to the individual's cells because of the gene shuffling that
always occurs during the formation of eggs and sperm.) Such cells might
also raise fewer moral dilemmas for some people than would stem cells
derived from cloned early embryos.

Under one scenario, a woman with heart disease might have her own eggs
collected and
activated in the laboratory to yield blastocysts. Scientists could then
use combinations of growth factors to coax stem cells isolated from the
blastocysts to become cardiac muscle cells growing in laboratory dishes
that could be implanted back into the woman to patch a diseased area of
the heart. Using a similar technique, called androgenesis, to create stem
cells to treat a man would be trickier. But it might involve transferring
two nuclei from the man's sperm into a contributed egg that had been
stripped of its nucleus.
Researchers have previously reported prompting eggs from mice and rabbits
to divide into embryos by exposing them to different chemicals or
physical stimuli such as an electrical shock. As early as 1983, Elizabeth
J. Robertson, who is now at Harvard University, demonstrated that stem
cells isolated from parthenogenetic mouse embryos could form a variety of
tissues, including nerve and muscle.

In our parthenogenesis experiments, we exposed 22 eggs to chemicals that
changed the concentration of charged atoms called ions inside the cells.
After five days of growing in culture dishes, six eggs had developed into
what appeared to be blastocysts, but none clearly contained the so-called
inner cell mass that yields stem cells.

Why We Did It

WE ARE EAGER FOR THE DAY when we will be able to offer therapeutic
cloning or cell therapy arising from parthenogenesis to sick patients.
Currently our efforts are focused on diseases of the nervous and
cardiovascular systems and on diabetes, autoimmune disorders, and
diseases involving the blood and bone marrow.

Once we are able to derive nerve cells from cloned embryos, we hope not
only to heal damaged spinal cords but to treat brain disorders such as
Parkinson's disease, in which the death of brain cells that make a
substance called dopamine leads to uncntrollable tremors and paralysis.
Alzheimer's disease, stroke and epilepsy might also yield to such an
approach.

Besides insulin-producing pancreatic islet cells for treating diabetes,
stem cells from cloned embryos could also be nudged to become heart
muscle cells as therapies for congestive heart failure, arrhythmias and
cardiac tissue scarred by heart attacks.

A potentially even more interesting application could involve prompting
cloned stem cells to differentiate into cells of the blood and bone
marrow. Autoimmune disorders such as multiple sclerosis and rheumatoid
arthritis arise when white blood cells of the immune system, which arise
from the bone marrow, attack the body's own tissues. Preliminary studies
have shown that cancer patients who also had autoimmune diseases gained
relief from autoimmune symptoms after they received bone marrow
transplants to replace their own marrow that had been killed by high-dose
chemotherapy to treat the cancer.

But are cloned cells or those generated through parthenogenesis normal?
Only clinical
tests of the cells will show ultimately whether such cells are safe
enough for routine use in patients, but our studies of cloned animals
have shown that clones are healthy. In the November 30, 2001, issue of
Science, we reported on our success to date with cloning cattle. Of 30
cloned cattle, six died shortly after birth, but the rest have had normal
results on physical exams, and tests of their immune systems show they do
not differ from regular cattle. Two of the cows have even given birth to
healthy calves.

The cloning process also appears to reset the "aging clock" in cloned
cells, so that the cells appear younger in some ways than the cells from
which they were cloned. In 2000 we reported that telomeres the caps at
the ends of chromosomes from cloned calves are just as long as those from
control calves.
Telomeres normally shorten or are damaged as an organism ages.
Therapeutic cloning may
provide "young" cells for an aging population.

A report last July by Rudolf Jaenisch of the Whitehead Institute for
Biomedical Research in Cambridge, Mass., and his colleagues gained much
attention because it found so-called imprinting defects in cloned mice.
Imprinting is a type of stamp placed on many genes in mammals that
changes how the genes are turned on or off depending on whether the genes
are inherited from the mother or the
father. The imprinting program is generally "reset" during embryonic
development.

Although imprinting appears to play an important role in mice, no one yet
knows how significant the phenomenon is for humans. In addition, Jaenisch
and his co-workers did not study mice cloned from cells taken from the
bodies of adults, such as fibroblasts or cumulus cells. Instead they
examined mice cloned from embryonic cells, which might be expected to be
more variable. Studies showing
that imprinting is normal in mice cloned from adult cells are currently
in press and should be published in the scientific literature within
several months.

Meanwhile we are continuing our therapeutic cloning experiments to
generate cloned or parthenogenetically produced human embryos that will
yield stem cells. Scientists have only begun to tap this important
resource. "

FROM:
 http://dailynews.yahoo.com/h/nm/20011125/sc/science_clone_dc_2.html

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