WHY do baby clones keep dying? That question is haunting cloning researchers
in the wake of last week鈥檚 otherwise encouraging news from Japan: the birth of
eight genetically identical cow clones from only 10 implanted embryos. This
success rate is unprecedented, yet four of the calves died within days of
birth.
From the beginning of cloning, for each cow or sheep clone that has survived,
at least an equal number have perished late in pregnancy, or soon after birth.
The exception seems to be cloned mice鈥攂ut in this species, unhealthy
embryos may be reabsorbed, which could mask the problem.
Cloners hoped that the death rate would plummet as they developed their
skills. But George Seidel, a reproductive physiologist at Colorado State
University in Fort Collins, says the continuing death toll suggests a deeper
problem. 鈥淭his isn鈥檛 going to go away by itself,鈥� he says.
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Despite the four deaths, getting four healthy calves from 10 embryos (
Science, vol 282, p 2095) puts cloning鈥檚 efficiency on a par with
established technologies such as IVF. Dolly the sheep was the only survivor from
29 implanted embryos.
The success of the researchers led by Yukio Tsunoda and Yoko Kato at Kinki
University in Nara may be due to the combination of techniques they used, or to
their dexterity. Like the Scottish team that produced Dolly, they starved the
donor cell they wished to clone into a state of genetic hibernation and used an
electric jolt to fuse it with an egg from which the genetic material had been
removed. And like the Hawaiian team that has cloned scores of mice
(see page 28),
they used female reproductive cells, such as the cumulus cells that
surround developing eggs, as donors.
But if cloning is to be used widely in animal production, the problems with
infant mortality could prove a real obstacle. Indeed, on 15 December, the Farm
Animal Welfare Council, which advises Britain鈥檚 Ministry of Agriculture,
Fisheries and Food, recommended a moratorium on cloning in commercial
agriculture until welfare problems can be resolved.
In their paper, the Japanese researchers attribute the deaths to
鈥渆nvironmental causes鈥�. But they have few clues as to what, exactly, was to
blame. 鈥淲hy four died, we don鈥檛 know,鈥� admits Tsunoda. Two calves breathed in
large amounts of amniotic fluid during birth, one died of pneumonia stemming
from heat stroke, and the fourth perished from other complications during
delivery. Several experts think that some part of the cloning procedure is
responsible for producing 鈥渨eak鈥� animals.
One is Jean-Paul Renard of INRA, the French agricultural research agency, in
Jouy-en-Josas near Paris. Earlier this year he cloned a calf called Marguerite
from a fetal muscle cell. She died when six weeks old from an infection that she
acquired soon after birth (This Week, 18 April, p 20).
鈥淲e鈥檙e looking for evidence that cloning is related to these effects,鈥� he says.
Seidel suggests that the deaths might be related to 鈥渄opey calf syndrome鈥�. A
tiny minority of normal calves and as many as 15 per cent of those conceived by
IVF die shortly after birth due to immune, cardiovascular and other
complications. 鈥淵ou get beautiful calves,鈥� says Seidel. 鈥淏ut some turn out to be
a lot weaker than others.鈥�
In bovine IVF, the condition may be triggered by chemicals in the media in
which test-tube embryos are cultured. Cloning involves a series of mechanical
and chemical assaults, such as zapping the egg with electricity, which may
affect development. To study the problem, Seidel wants to compare the activity
of genes in embryos produced by cloning to that in naturally fertilised embryos.