Washington, DC (2/5/02)- The parthenogenetic creation of
primate embryos with subsequent production of stem cells suggests a new, perhaps
somewhat less ethically controversial direction in research aimed at treating
human diseases with stem cell-derived therapies. Meanwhile, cloning and stem
cell research continue to develop at a dizzying pace.
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Partheno-what?
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Parthenogenesis
is derived from the Greek words for 'virgin birth'. In modern biology,
it refers to a form of reproduction in which an ovum develops into a
new individual without having been fertilized. Many insect species are
known to reproduce by natural parthenogenesis. Examples include aphids,
bees and ants. In bees and ants, unfertilized eggs become drones.
Graphic (above):
primate parthenogenetic embryos
As long ago as 1900,
biologists were able to encourage artificial parthenogenesis in some
species. Jacques Loeb reported in that year that he was able to induce
unfertilized frog eggs to grow by scratching them with a needle. Since
that time various chemical and mechanical means have been used to produce
artificial parthenogenesis in numerous animals including rabbits. However,
in most cases the resulting developments abnormal.
Athena
in the Parthenon
While the ancient
Greeks may have been mystified by many elements of molecular biology,
they would have easily been able to grasp parthenogenesis, a concept
rooted in their oldest myths.
Graphic
(above): Athena bearing the aegis
Athena, daughter
of Zeus, was among the most important of the Greek deities. Her birth
was most unusual. Zeus swallowed his first wife Thetis when she became
pregnant, fearing a son would steal his throne. He developed a severe
headache and his fellow god Hephaestus was good enough to split his
head open with an ax. Athena emerged full grown, wearing a suit of armor,
from the head of Zeus.
Athena was the patron
goddess of Athens, and was associated with everything from warfare and
urban development to fertility and weaving. Her animal symbol the owl
gives rise to the still current association between owls and wisdom.
The Parthenon is the name of the temple of Athena on the Acropolis.
Other familiar words associated with Athena include the aegis (her shield)
and palladium (from Pallas Athena). NASA's "Project
Athena" is a K-12 global weather education project.
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A team of well-respected scientists from Mayo Clinic, Sloan Kettering Cancer
Center and Wake Forest University working with a Massachusetts biotechnology
company announced that they had managed to create primate embryos parthenogenetically,
that is, without fertilization. Moreover, they were able to tease stem cells
derived from the asexually derived embryos to produce numerous types of cells
including brain, heart and smooth muscle cells.
One particularly promising development was the report that the researchers
were able to produce midbrain dopamine neurons, a first. The hope is that
some day such cells could replace dysfunctional cells in the brains of patients
with central nervous disorders such as Parkinson's disease and Huntington's
disease.
Embryos are normally the product of sexual reproduction, when the male sperm
and female egg combine DNA. The current research involved stimulating a monkey
egg to grow without any help from sperm. The researchers used chemicals to
signal the eggs not to eject half of their chromosomes (as they would do in
sexual reproduction) and command the eggs to start dividing. In this case
the resulting mass of 100 or so cells, known as the blastocyst, cannot become
a viable organism when produced with the new technique. Four of 28 parthogenetic
eggs developed into blastocysts. The researchers were able to derive a single
stem cell line from one of the blastocysts. .
"Neurons and other cells derived from this renewable source could alleviate
some of the technical problems of human cell therapy, including rejection
of transplanted tissue." said Jose Cibelli, Ph.D., chief scientist at Advanced
Cell Technologies.
Stem cells are the holy grail of modern biology. These root cells can, with
proper stimulation, be used to produced virtually any type of cell in the
body. Until now, the best source of stem cells has been human embryos. These
have typically been obtained from fertility clinics. Considerable research
is also underway to clone stem cells derived from non-embryonic tissue. The
possibility of deriving stem cells from nonviable, asexually produced blastocysts
might solve, at least for some, the ethical debate currently raging on the
direction of therapeutic stem cell research..
"This study suggests an alternative to human therapeutic cloning. Differentiated
cell types derived in vitro by parthenogenesis eliminate the requirement to
produce or disaggregate a normal, competent embryo and may circumvent the
ethical concerns voiced by some, positively impacting the debate in stem cell
research," the researchers noted in Science.
Continuing Controversy
How long will it be before human parthenogenesis is achieved? Researchers
from the same biotech company that supported the current research, Advanced
Cell Technologies, created considerable controversy in November of last year
when they announced they had cloned human embryos. The embryos had not grown
beyond six cells and had not produced stem cells.
While the race is on to create parthenogenetic human embryos, considerable
doubts remain regarding the safety and efficacy of this approach. Researchers
believe that the male DNA that mixes with the females DNA in the egg probably
has an important role to play in gene activation in at least some kinds of
stem cells. For example, studies in mice produced parthenogenitically suggest
that those stem cells differentiate more readily into neurons than into other
cell types such a muscle. The hypothesis that such cells would indeed be immune-privileged
also remains unproven.
Publish or ???
There are also increasing concerns that the rush to be first is weakening
the safeguards provided by the traditional process of presenting data in peer-reviewed
journals. In some cases (e.g. Dolly the cloned sheep) potentially earthshaking
research findings are announced at press conferences rather than submitted
to scientific journals. This may be a good way to get the attention of the
venture capitalists (and stockholders) who support biotech startups, but does
not allow the review process that has become part of process of communicating
new scientific findings. Moreover, an initial publication in a journal has
traditionally been considered a starting point, with other researchers withholding
judgment until results can be reproduced independently.
Stem Cells Grow Human Blood Vessels
Efforts to derive stem cells from adult tissue are also progressing at a remarkable
rate. A report from the University of Minnesota Stem Cell Institute indicates
just how fast the field of therapeutic cloning is evolving. Researchers there
announced that they have managed to get a hitherto unknown type of adult bone
marrow stem cell to expand in the test tube into endothelial cells, and then
to get those cells to engraft in mice and contribute to new growth of blood
vessels.
"These lab results demonstrate the potential of adult bone marrow stem cells
to differentiate beyond mesenchymal cells, into cells of the endothelium.
What we have seen is the ability of these cells to feed the blood vessels
of tumors and to heal the blood vessels surrounding wounds. The findings suggest
that these adult stem cells may be an ideal source of cells for clinical therapy.
For example, we can envision the use of these stem cells for therapies against
cancer tumors by, for instance, introducing anti-angiogenesis genes. Or, they
could be used to heal wounds such as ulcers or diabetic wounds or to treat
atherosclerosis," said Catherine Verfaillie, M.D., director of the University
of Minnesota Stem Cell Institute.
The parthenogenetic monkey research appears in the February 1 issue of the
journal Science. The findings
of Dr. Verfaillie et al. appear the February 1, 2002 issue of Journal
of Clinical Investigation.
Graphic (below): From blastocysts to stem cell to blood vessel. click
to enlarge
In other developments:
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