MEN and women who can’t produce sperm or eggs could one day have “natural”
children of their own thanks to a form of cloning.
Gianpiero Palermo of Cornell University in New York has created artificial
human eggs that contains just one set of a would-be mother’s chromosomes. Such
eggs could be fertilised with the partner’s sperm, just like a normal egg.
And in Australia, Orly Lacham-Kaplan of Monash University in Melbourne has
shown that you can fertilise eggs, not with sperm, but with cells taken from
elsewhere in the body. But there are still considerable obstacles to overcome
before either technique could be used to create human babies.
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The trouble is that we inherit not just genes, but chemical marks, or
imprints, that turn some genes off. Chromosomes taken from body cells have
different patterns of imprinting to egg and sperm cells, and that could cause
developmental abnormalities. This may be why some clones have problems.
Because of the risks, adds Palermo, careful testing in animals and further
understanding of how imprinting works are needed before the new methods are
applied to humans. “It’s something we are evaluating,” he says. “We’re just
going one step at a time.”
If the technique can be made safe, it would help
the growing number of people who can conceive only with the help of donated eggs
or sperm—and are therefore not genetically related to their children. Some
women lose their eggs because of chemotherapy or ovarian surgery. But many women
are also finding themselves in this situation because they’ve put off childbirth
until it’s too late. And although existing fertility treatments can help men
with low sperm counts, they don’t work for men who make abnormal sperm, or no
sperm at all.
One solution would be cloning: transplanting genetic material from, say, a
skin cell of the would-be mother or father into an egg from which the DNA has
been removed. But because the baby would be identical to its parent, this
technique is highly controversial and likely to be banned in many countries.
So Palermo and his colleagues are trying to use cloning techniques to create
eggs that behave more as nature intended. Like normal cells in our body, a
mature human egg usually has two sets of chromosomes—one inherited from
the woman’s mother, the other from her father. When the egg is fertilised, it
retains one set in a so-called pronucleus, and spits out the rest in a little
package called the polar body. The fertilising sperm, which contains just one
set of chromosomes, then restores the full complement.
Palermo’s team has mimicked this process by transplanting a nucleus from a
body cell into a mature human egg that has had its genetic material removed. By
prodding the reconstituted egg with a pulse of electricity, they can make the
nucleus divide in half, forming two pronuclei
(see Diagram). The team removes
one pronucleus and then fertilises the egg by injecting a sperm.
So far, however, the resulting embryos have stopped developing after only one
or two rounds of cell division, they told a conference on human reproduction in
Switzerland this week. “This is preliminary work,” cautions Palermo, “but at
least in theory, it might be a way to provide eggs for sterile women.” However,
a child created this way would inherit the DNA-containing structures called
mitochondria from the donor egg, and would thus effectively have three parents
(see 91av, 12 May, p 7).
Meanwhile, a related technique being being developed by Lacham-Kaplan and her
colleagues might help infertile men. The team has succeeded in “fertilising” a
normal mouse egg using a cell taken from the body of a male. This is surprising,
because the body cell has two sets of chromosomes.
But the team found that when the egg is exposed to certain chemicals, it
spits out two polar bodies. One, as normal, contains the egg’s spare
chromosomes. But the other contains half the chromosomes of the transplanted
nucleus, leaving the fertilised egg with the usual two sets.
Even more surprising, such eggs go on to develop relatively normally in the
lab, up to the pre-implantation stage. Lacham-Kaplan is now trying to transfer
these embryos into surrogate mice.