A Breakthrough on Cloning? Perhaps,
or Perhaps Not Yet
From the New York Times, November 27, 2001
By GINA KOLATA with ANDREW POLLACKWhen Advanced Cell
Technology, a small biotechnology company in Worcester, Mass., announced on Sunday that it
had taken the first steps in producing human embryos through cloning, it could not report
lasting success; all the embryos it created had died.
It could not even report that it had used groundbreaking
techniques; its methods had already been used in animals.
Some scientists even suggested that what the company was
doing was not cloning at all.
But if there is a future in human cloning, either for
reproductive purposes or to create cell lines for use in treating diseases, people may one
day say it started in Worcester.
Despite the storm of protest that the company's
announcement has provoked, that would be just fine with Advanced Cell Technology. Its
president, Dr. Michael D. West, says the company feels pressure to keep the world informed
about what it is doing in so controversial a field. But he concedes that the desire to be
the first to claim to have created a human embryo by cloning was a factor in the company's
decision to publish its results so far.
Whatever the scientific significance of Dr. West's
announcement, its political significance was profound. President Bush denounced the work
as immoral, and there were loud calls for Congress to outlaw it.
Shadowing the raging dispute on whether such work should be
outlawed is a major scientific question: Is the human-cloning attempt a milestone or a
forgettable blunder? The answer, cloning experts say, is that it is impossible to know.
Work with animals has shown that cloning is something of an
art. There are no rules or formulas. Success, when it comes, can be unpredictable and
nearly inexplicable. It could be that human cloning is extraordinarily difficult and that
it will take years and thousands of attempts to make it work. Or it could be that a simple
change in the laboratory procedure will turn failure into success. That has been the
experience of scientists who work at cloning animals.
For Advanced Cell Technology, these uncertainties loom
large. The company is betting that it can perfect human cloning, creating embryos not for
reproductive purposes but as a source of stem cells. Human embryonic stem cells could, in
theory, grow into any of the body's tissues and organs, and the company wants to provide
them as replacement cells to patients suffering from any of a wide variety of diseases.
The small company has a track record of achievement in the
world of cloning animals; some of the leading cloning researchers are on its payroll.
But it also has a track record of astute dealings with the
news media. In interviews, Dr. West acknowledged that scientists for the company had
published their results in a little-known online publication - E- biomed: The Journal of
Regenerative Medicine - because E-biomed had agreed to arrange for distribution to
coincide with articles in Scientific American and U.S. News and World Report.
Like many other small biotechnology concerns, privately
held Advanced Cell Technology attracts investors with promise, not profits. And though Dr.
West said the company had just completed a round of fund-raising, he noted that it would
have continuing needs for money to finance its work.
"We're going to require hundreds of millions in
investments," he said, "before we become profitable."
In the work reported on Sunday, the company's scientists,
led by Dr. Jose Cibelli, used a standard technique that involves taking the genetic
material out of an unfertilized egg and inserting in its place the DNA of an adult cell.
In theory, the egg then uses the genes from the adult cell to direct its development,
turning into an embryo that is an exact genetic copy of the donor of the adult cell.
The company tried to clone with two types of adult cells:
skin cells and cumulus cells, which are cells that cling to human eggs. The researchers
added skin cells to 11 eggs; none divided even once. They added cumulus cells to eight
eggs; three divided once or twice, the others not at all.
Stem cells appear only after an embryo grows for about five
days and, more important, forms a blastocyst, a sphere of cells with a ball of stem cells
inside it. The Advanced Cell Technology embryos that were created by cloning were not even
close to that developmental stage.
Dr. Ronald M. Green, a Dartmouth professor who heads the
company's ethics board, says he prefers not even referring to the cells as embryos. He
would like to call them "cleaving eggs," he said.
In fact, scientists say, eggs can divide a few times
without making any use of their genes, so the fact that a few eggs divided a few times
does not at all mean that the
goal of the experiment - to add a new set of functioning genes to an egg - was even close.
But cloning failures can suddenly turn to successes, as
those who have cloned other species attest.
That was the experience of Dr. Randall Prather, a cloning
expert at the University of Missouri, in years of efforts to clone pigs. Over and over
again, Dr. Prather would start the cloning process, and then the cells, like those in the
Advanced Cell Technology study, would simply die.
Now he and others can clone pigs, but he does not know
which changes in his laboratory procedures made the difference. All he can say, Dr.
Prather remarked, is,
"Yeah, now it works."
Cloning also depends on scientists' having a delicate
touch, experts said.
One scientist now with Advanced Cell Technology, Dr. Tony
Perry, who worked on mouse cloning experiments at the University of Hawaii, said it took
endless hours of practice to do the careful manipulations of microscopic cells involved in
cloning. Some people develop a feel for the work, while others, no matter how hard they
try, are never very good.
"It requires a kind of eye-hand coordination" and
constant practice, Dr. Perry said, recalling months of practice, seven days a week, 10
hours a day. "If you lapse in your practice for two weeks," he said, "you
don't return to point zero, but you're a little bit rusty."
There are also puzzling and unpredictable differences
between species. Dr. Ryuzo Yanagimachi, who cloned the mice with Dr. Teruhiko Wakayama,
also now with Advanced Cell Technology, said about 2 to 3 percent of efforts to clone
cattle resulted in the birth of a live animal. Most of the rest die very early: only about
20 percent of the embryo clones make it to the blastocyst stage.
With mice, Dr. Yanagimachi said, about 50 to 60 percent of
the embryo clones make it to the blastocyst stage. But even more die afterward. In the
end, he said, the same percentage of mouse cloning attempts succeed as cattle cloning
attempts.
Given that the human cloning work ended in failure, some,
like Dr. Steen Willadsen, a cloning pioneer in Windermere, Fla., have asked why Advanced
Cell Technology even bothered to publish its results, orchestrating at the same time a
media blitz.
In theory, Dr. Willadsen said, the publication will offer
other researchers clues about "things not to do." But, he added, the crucial
unknown detail that doomed the attempt may not be so obvious, and may not even appear in
the paper. "There might be some trivial thing that is standing in their way," he
said.
"All one can say," Dr. Willadsen added, "is
it didn't work this time." |