Dolly's doctors hit cloning
LONDON DAILY TELEGRAPH
The doctors responsible for cloning the sheep
Dolly say they are outraged by scientists who plan to press ahead with
attempts at human cloning, calling any such attempt intolerable.
Dr. Severino Antinori, an Italian gynecologist,
and Dr. Panayiotis Zavos, an American "andrologist," announced last week
that they would start work on creating the first human clone "in the next
30 to 60 days." They insisted that the first cloned human baby will be
born next year. But Ian Wilmut, the scientist who stunned the scientific
world by leading the effort that produced Dolly, said in an interview:
"To try cloning on humans today would be criminally irresponsible. The
problems are far too serious."
Dr. Harry Griffin, another scientist at the
Roslin Institute near Edinburgh, Scotland, where Dolly was created, dismissed
reports that, five years after her birth, Dolly has aged prematurely,
is weak, cannot walk properly and suffers from intestinal problems. "None
of that is true," he said. "The truth is that Dolly is physically a normal
5-year-old sheep. She's been pregnant three times and produced six healthy
lambs, so no problems there." But Dr. Griffin utterly
rejected any suggestion that Dolly's good health meant the cloning of
humans could go ahead safely. "There are dozens of problems," he said
tersely. To understand those problems, you first have to understand a
little about "single nuclear transfer," the process by which Dolly was
created and which Drs. Antinori and Zavos are proposing to use to clone
Cloning is possible because of the strange
and surprising fact that each cell in the body has the capacity to make
every other cell: It contains a copy of the complete set of instructions
needed to build everything. It used to be thought that once a cell had
adopted a particular function -- once it had become part of the liver
or the brain or the lining of the stomach -- it was impossible to "reprogram"
it to build anything else. But Dolly proved that it could: She came from
a single cell taken from the udder of a 6-year-old Finn Dorset ewe.
The seven steps to a clone are, in theory,
- First, you need an unfertilized egg -- a human one
if a human is to be cloned, a sheep's egg if it is to be a Dolly.
- Second, you have to remove the DNA sequence -- that
is to say, the set of genetic instructions for building every part
of the adult organism -- from the nucleus of the egg. The Scottish
doctors simply sucked it out with a pipette.
- Third, you need another cell, to fuse with the egg.
That cell could come from anywhere in the body of the human or animal
to be cloned, because practically every cell contains the complete
set of chemical instructions needed for creating that particular individual.
- Step four is the insertion of that single cell into
- Step five requires the fusion of the new cell and
the egg. This is the crucial step that "switches on" the cell's DNA
-- the 30,000 to 40,000 genes which dictate the building of a new
body -- and persuades it to start the manufacture of an embryo. The
process normally requires the application of a small electrical current.
"That's what happened in the creation of Dolly," said Dr. Griffin.
"It mimics the changes that happen when sperm fertilizes an egg."
- The sixth step is to implant the egg, now flush with
genetic material, into the womb of a sheep -- or woman. If that implantation
is successful, the egg will divide and develop, so that after nine
months, in the case of a human, step seven occurs: the birth of a
While the theory is simple, there are practical problems
and difficulties with every one of those steps. "There are dozens of unknowns
with even sheep," said Dr. Griffin. "There are certainly going to be vastly
more with humans." To begin with, cloning has a success rate of about
1 percent or less. "We had to implant 277 eggs to get one cloned sheep,"
said Dr. Griffin. "Other laboratories that have cloned mice and pigs report
similarly high rates of failure.
"Now -- laying aside the serious ethical problems associated
with treating human embryos in this way -- where are you going to get
that number of human eggs to create them from? There simply isn't a surplus
anywhere. I don't see how Drs. Antinori and Zavos could possibly legitimately
get hold of the number of eggs they would need even to start." Step two
-- the removal of DNA material from an egg -- would not in itself be any
more difficult with a human cell than it is with one from a sheep.
The trouble is not with the technical manipulation, but
with its effects -- no one knows what they are, except that they are almost
certainly likely to be bad. The same is true of steps three to five. The
manipulation of the genetic material certainly has adverse effects on
how accurately the cellular machinery works. Dolly may be in good shape,
but she seems to be exceptional, more of a lucky fluke than anything else.
The majority of cloned animals have something wrong with
them. They die in the womb, or soon after birth. Typical defects are malfunctioning
lungs, a heart that doesn't work as it should, an imperfect immune system
and abnormal size. The scientists have theories about why so many clones
seem to go wrong. One is that molecules attached to the genetic material
which are important in ensuring that only some genes are "switched on"
at any given location in the body (so that, for instance, your brain cells
are in your head, rather than in your stomach), are scraped off or damaged
when the cell to be cloned is manipulated by the experimenters. Manipulation
by experimenters is inevitable, not just when DNA is removed from the
egg, but also when the new cell is inserted into it. The process disrupts
development in other ways.
Kevin Eggan, a professor at the Whitehead Institute for
Biomedical Research at the Massachusetts Institute of Technology, said
that even when they look normal, many cloned animals have damaged or imperfectly
copied genes, which, in people, could result in serious mental problems.
"Disruption of those genes in humans," he said, "could cause retardation,
among other difficulties." Dr. Rudolph Jaenisch, a colleague of Mr. Eggan's,
cautioned that there are between 30,000 and 40,000 genes in the human
genome. "Any one of them is, in principle, a target for faulty programming
in the cloning process. We have no idea how many are adversely affected
by it, and there's no way at present to find out. Tiny copying errors
can have horrible consequences."
Copyright © 2000 News World Communications,
Inc. Reprinted with permission of The Washington Times
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