hen 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."