Sheep cloning a success
(February 1997)
February brought us news of the world's first
cloned sheep. Workers at the Roslin Institute in Edinburgh have succeeded in a
task which, up until now, has only worked with mice. The implication appears to
be that what can be done with sheep can probably be done with humans, opening
up a whole range of "Brave New World" scenarios, and jokes about
Elvis have been resurrected as well - unlike Mr Presley, so far.
Credit is shared between the Roslin Institute,
part of Britain's Biotechnology and Biological Sciences Research Council, and
PPL Therapeutics, an Edinburgh biotechnology company, whose shares rose in
value after the announcement.
Dr Ian Wilmut announced on February 22 that he
had taken the DNA from a sheep's ovum, replaced it with the DNA from an adult
sheep, and grew it into a living lamb. The DNA was taken from the udder of the
"donor" sheep, but the major breakthrough was in getting the DNA to
become inactive, or quiescent, to use the geneticists' term. He then took an
ovum from another sheep, and removed all of the DNA from it.
The next step was to fuse the ovum with an
adult udder cell, after which the udder cell DNA took over the ovum, and
controlled its growth and division. Wilmut then implanted the embryo in yet a
third sheep, who gave birth to a lamb which is genetically identical to the
original DNA donor. Dolly was born in July last year, and during the last week
of February, was responsible for more headlines bearing the phrases "Hello
Dolly" and "Send in the Clones", than Hollywood and Broadway
ever inspired.
The next few months should see a flurry of
bio-ethicists straining to make themselves heard about what the implications of
this are, but the guidelines are already in place to deal with issues which
surround human clones, so problems are unlikely, at least in the short term. In
the longer term, the costs of breeding a master race are likely to be so large
that no "secret program" will be possible, but a number of television
script writers were probably reading the scientific press as February ended.
Scientific background
No less than three sheep were produced by much
the same cloning method, but only Dolly was able to command serious scientific
attention, as the other two sheep had been developed from cells taken
respectively from a fetus and from an embryo. Given the existence of Dolly, the
other sheep were of limited interest.
The genes in a cell become committed at an
early stage of development, and while you can take a nucleus from one egg and
put it in another egg, with some hope of achieving a result, the standard view
has been that you could not take an adult cell and expect the genes to develop
in any sort of normal way to grow an individual. When a cell has
differentiated, specialised to form some kind of tissue, that should be enough
to block it ever growing to a whole individual.
Against this, single plant cells can be taken
and cultured to produce a whole plant, but somehow, plants all seemed to be a
whole lot less complicated. Even when Wilmut's group succeeded in establishing
clones from cell lines taken from early embryos (blastocysts), the standard
barriers to successful cloning seemed still to be in place. Mouse embryos could
be cloned if you took nuclei from the eight-cell stage, but no later, because
the genetic material had been switched to a pathway of development, and could
not be switched back.
Another problem was getting the cell division
cycles of the donor cell and the host cell lined up-remember that a key feature
is putting the donor nucleus into a cell where the surroundings are egg-like-so
that later cell divisions do not produce cells with non-standard numbers of
chromosomes. Wilmut's team managed to hold the donor cells in an arrested
division state called the diploid G0 phase of the cell cycle by serum
starvation.
The effect of this was to get a better
synchronisation between the host cell and the new nucleus, but Wilmut's group
may also have been fortunate in another respect-the sheep embryo does not begin
committing cells (called transcription of the genome) until the 8-16 cell
stage, against the 2 cell stage in mice, so there is more time for
synchronisation to develop.
If this factor is important, then it casts
doubt over whether or not other mammal species can be cloned in the same way,
as the start of transcription of the genome varies between species. In the
first few days of March, a monkey cloning breakthrough was reported which may
or may not prove significant in the longer run.
The best analysis suggests that the cloning of
human beings by this method would be possible in somewhere from one to ten
years from now. The first calls for banning actually went out before the story
broke in Nature, with an email from an unnamed "Harvard academic" who
urged that Nature not publish details of the procedures until more thought had
been given to questions of bio-ethics. Soon after the publication, President
Clinton urged a moratorium on all such experiments. In Washington, Jeremy
Rifkin demanded that the attempt to clone humans be placed on a par with rape,
child abuse and murder.
On the other hand, Axel Kahn, a French geneticist (also in the news this month over transgenic corn) has suggested that side-issue of the technique might help a woman who had a serious mitochondrial disease to have a healthy child by inserting a nucleus into a donor cell. While this is not cloning, it may still be more acceptable than some of the other scenarios which are floating around.