2/17/04 NYT -- Specter of Cloning May Prove a Mirage.
February 17, 2004
Specter of Cloning May Prove a Mirage
By STEPHEN S. HALL
A rose is a rose is a rose, even if - like many commercial
plants - it is essentially a clone. But is a normal human
blastocyst, a microscopic bubble of proto-life that forms
about five days after sperm meets egg, the same as a cloned
blastocyst?
That may seem an arcane technical question in the debate
about human cloning, reignited last week with the
announcement by South Korean scientists that they had
cloned a human embryo and harvested embryonic stem cells
from it. But scientists, politicians and bioethicists have
been grappling for years with the biological and moral
subtleties encapsulated by that tiny dot of tissue.
The future of human therapeutic cloning in this country -
the laws governing it, the knowledge to be gained from it,
the ethical costs of doing it and the medicines it might
eventually bestow - may hinge on how society views that
question.
In last week's report in the journal Science, researchers
at Seoul National University described how they had created
some 30 cloned human blastocysts in order to harvest human
embryonic stem cells. Such a procedure has raised moral
concerns, not only because it requires the destruction of
the embryo to gather the cells, but because its mere
publication may provide technical guidance to several
well-known "cloning entrepreneurs" who have vowed to try
human cloning, despite widespread safety and moral
concerns.
In response to the South Korean experiment, Dr. Leon R.
Kass, chairman of the President's Council of Bioethics,
said, "The age of human cloning has apparently arrived:
today, cloned blastocysts for research; tomorrow, cloned
blastocysts for baby-making." Dr. Kass urged Congress to
pass a ban or moratorium on all forms of human cloning.
Several lawmakers called for just such a ban on all human
cloning research.
But it's unclear how imminent that "tomorrow" actually is.
While the South Korean paper offers a new technical trick
for creating a cloned human blastocyst, it does not resolve
any questions about how robust that blastocyst may be for
generating a healthy, normal human being.
"There's no doubt that there's still an awful lot of work
to be done before anybody would feel comfortable that it
could be done safely," said Dr. George Daley, a stem cell
researcher at Children's Hospital in Boston.
The South Korean group did not try to create a baby. The
promise of therapeutic cloning, still theoretical, derives
from the following premise. By introducing the DNA of an
adult human cell into a human egg whose nucleus has been
removed, the resulting hybrid cell can be induced to behave
like a fertilized egg. Like a normal embryo, it begins its
development as a single cell, but it contains the genetic
payload - and, presumably, the immunological identity - of
the adult patient. Treatment, not children, is the ultimate
point of the exercise.
But cloned embryos may not be genetically equivalent to
normal embryos. Dr. Rudolf Jaenisch, an expert on the
genetics of animal cloning at the Whitehead Institute for
Biomedical Research in Cambridge, Mass., has published
studies showing that cloned mice are riddled with genetic
abnormalities. Those glitches suggest that a cloned embryo
would have "little if any potential to ever develop into a
normal human being."
When an egg cell reprograms the DNA of an adult cell during
a cloning experiment, Dr. Jaenisch said, the process is
probably incomplete - raising the possibility that genes in
the cloned embryo are not activated (or "expressed") at the
right time, in the right amount, and properly suppressed
when not needed.
Gene regulation of this sort is especially significant in a
class of genes known as imprinting genes, which play a
crucial role in fetal development. "We think that 30 to 50
percent of imprinted genes are not properly expressed in
clones," Dr. Jaenisch said, "and imprinting genes are
mostly important for pre-natal development."
As a result, he said, the South Korean approach may be
"useful for therapy, but not useful for cloning." Dr.
Daley, who with Dr. Jaenisch published one of the first
animal experiments suggesting the promise of therapeutic
cloning, said, "All of the concerns and risks of mammalian
reproductive cloning have not changed with this paper."
Paradoxically, however, scientists working in the area
believe that the same genetic glitches that might prevent
an embryo from growing into a genetically normal organism
are unlikely to compromise the quality of stem cells that
might be harvested for medical use. "Cloned tissues are not
likely to have the same problems," Dr. Daley said, "but
that's yet to be proven."
In addition to being a notoriously inefficient procedure,
animal cloning has produced many animals with conspicuous
developmental problems, like respiratory illnesses and
overly large placentas. Dolly the cloned sheep suffered
from premature arthritis before dying last year. Such
genetic dysfunction is one reason for nearly unanimous
scientific opposition to reproductive cloning. As Dr. Daley
put it: "As a scientist, I would be willing to support a
ban on reproductive cloning, if it allows us to pursue
legitimate therapeutic research. That is the most rational
way of approaching the debate."
But Dr. Jaenisch also made a distinction between cloned
embryos and the kind of blastocysts formed during normal
reproduction, including embryos fertilized in vitro. "When
you really think about an I.V.F. embryo that rests in a
deep freeze, it only has three fates," he said. "It can be
destroyed, it can be implanted into a woman or it can be
converted into embryonic stem cells. When you make
embryonic stem cells, you do destroy an embryo, and that is
an ethical issue.
"Cloned embryos also have three fates. "They can be
destroyed, they can be used to make normal embryonic stem
cells tailored to the needs of patients, but they cannot
make a normal baby. In my opinion, the destruction of a
cloned embryo to make embryonic stem cells poses less
ethical problems than the destruction of frozen embryos in
the I.V.F. clinic."
Dr. Thomas H. Murray, president of the Hastings Center in
Garrison, N.Y., says this scientific distinction has moral
import. "What are the ethical implications if embryos
created in this way are not viable, or severely impaired?"
he asked. "If Rudy Jaenisch is right, if embryos created by
cloning are a fairly abnormal ball of cells, that would
compel us to think very hard about what moral meaning to
attach to such an entity."
Such a scientific distinction, Dr. Murray also noted, could
"complicate" a split in the anti-abortion movement that
emerged several years ago during the debate over stem cell
research and cloning. Several prominent abortion opponents,
including Senator Orrin G. Hatch, Republican of Utah,
supported federal financing for stem cell research; Mr.
Hatch has also co-sponsored legislation allowing
therapeutic cloning while prohibiting reproductive cloning.
In fact, the biological distinction between cloned embryos
and normal embryos came up for discussion two years ago at
the President's Council on Bioethics. Dr. Paul McHugh, the
former head of psychiatry at Johns Hopkins University
School of Medicine, floated the notion that a cloned embryo
was distinct - in creation, composition and reproductive
intent - from a normally formed embryo. He coined the word
"clonote" to distinguish it from "zygote," the
single-celled embryo that results from fertilization.
"If you take the point that the clonote is something
different, it's something manufactured rather than
begotten, then you would want to study, use its best
potentials for humankind and not let its potentials for
error and slavery appear," he said at the time.
Despite the renewed calls last week for a ban on all forms
of cloning, including therapeutic cloning for medical
research, even the Bush bioethics council split sharply on
the issue. In discussions leading up to the panel's July
2002 report, "Human Cloning and Human Dignity: An Ethical
Inquiry," the committee failed to muster a majority in
favor of a blanket ban on both therapeutic and reproductive
cloning. Only 7 of 17 voting members supported a complete
ban; 3 others supported a moratorium. Indeed, the panel's
public discussion leading up to the report revealed
considerable sentiment in favor of therapeutic cloning, as
long as it was properly regulated.
The most provocative aspect of the South Korean research,
in Dr. Daley's opinion, was something that was not even
included in the paper, but was revealed by several of the
scientists at a news conference last Thursday. Dr. Woo Suk
Hwang and Dr. Shin Yong Moon said that when the researchers
tried to use the DNA from male adult cells or cells from
females unrelated to the egg donors, they failed to create
any embryos. The only successes in their cloning
experiments came from the use of so-called cumulus cells,
the adult cells that typically surround a maturing egg cell
in a woman's ovarian follicles.
The failure of the other cells to work, Dr. Jaenisch said,
merely underscores how much research remains to figure out
the best adult cells to use for therapeutic cloning.
Whether making human medicines or human babies through
cloning, in other words, "tomorrow" may still be a long way
off.
Copyright 2004 The New York Times Company. |
