First Human Embyro Cloned

November 27, 2001
NEWS ANALYSIS

A Breakthrough on Cloning? Perhaps, or Perhaps Not Yet
By GINA KOLATA with ANDREW POLLACK

When 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."