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The children of the future may be conceived
and spend their first few days of development on a computer-controlled
chip.
In a move recalling Aldous Huxley's
famous production lines for making babies in Brave New World,
researchers in the US
are building a "chip" that can automatically carry
out all the steps involved in IVF, from fertilizing
eggs to preparing embryos for implantation.
Ultimately, such devices - which amount
to artificial reproductive tracts - may even be able to
sort and test embryos for genetic flaws.
So far researchers David Beebe and Matthew
Wheeler have built prototypes that can carry out the major
steps involved in IVF, though not all on the same chip.
Far more mouse embryos develop successfully on these devices
than by traditional methods.
The researchers say they expect the
technology will first be used for livestock production,
but their eventual aim
is to use it for human embryos.
The work could be the first step towards
a future in which IVF becomes the norm, says George Seidel,
a reproductive physiologist at Colorado State University
in Fort Collins.
"Fifty or 100 years from now, our
in vitro procedures for parts or even all of pregnancy may
end up being safer than dealing with the various things
that occur in the body - in terms of viruses that the mother
comes across, toxins, and so on."
Dumped In
A Dish
In conventional IVF, sperm and eggs
are dumped into a Petri dish where the fertilized eggs grow
until they're ready to be implanted. As embryos need different
culture media at different stages, embryologists transfer
them from one dish to another via a pipette.
"It's like being plucked out of
the Atlantic Ocean and stuck into the Pacific Ocean,"
says Beebe, a biomedical engineer at the University of Wisconsin,
Madison.
So Beebe and Wheeler, an embryologist
at the University of Illinois at Urbana-Champaign, designed
a device to mimic conditions inside a female's reproductive
tract.
The device, made of a transparent elastomer,
resembles a small glass slide and contains a network of
tiny channels, each around 0.2 milliliters in depth and
width. The researchers connect the channels to programmable
syringe pumps, which can move embryos around and add or
remove fluids.
Acid Test
To test the device, the team cultured
mouse embryos to see how many developed to the "blastocyst"
stage, ready to be implanted.
"In 48 hours, in the traditional
Petri dish, none of them made it to the blastocyst stage.
In our channels, about 75 per cent made it," says Beebe.
"The embryos were transplanted into hosts and live
pups were born. So there doesn't appear to be any detrimental
effect."
The researchers also used the device
to remove the "zona pellucida" shell that encases
early embryos. In human IVF, this "assisted hatching"
can be used to encourage implantation. Traditionally, the
embryo is put into an acid medium and quickly removed when
the embryologist sees the zona break up.
But waiting this long may damage the embryos. By washing
acid over mouse embryos "parked" in a microchannel
on a chip, the team found even with a brief exposure, the
zona broke up after the acid was removed. "People have
been leaving embryos in the acid too long," says Beebe.
Embryo Weeding
In a separate experiment, the team matured
mouse eggs inside the channels, then fertilized them by
squirting sperm over them. Eventually they hope to integrate
all the steps into a single artificial reproductive tract.
Crucially, the chip-like device not
only allows many embryos to be cultured at once, it allows
each one to be individually manipulated and tracked in separate
channels. That should make it easier to weed out poor-quality
embryos before implantation.
Embryologists already inspect embryos
under the microscope, and some IVF clinics also measure
their consumption of oxygen and glucose and the amount of
carbon dioxide they release. All this could be done more
routinely on a reproductive chip, says Beebe.
"Major
Questions"
In time, the device could even make
it easier to carry out pre-implantation genetic diagnosis,
where a few cells are removed to screen embryos for genetic
disorders. "That involves more sophisticated manipulation
than our current devices can do. But it is something we
are working on," says Beebe.
But quality control raises ethical issues,
says Tom Shakespeare of the Policy, Ethics and Life Sciences
Research Institute in Newcastle.
"If we are talking about maximizing
the chances of becoming pregnant and carrying to term, then
there's less argument. But if we are talking about either
reducing genetic diversity or indeed enhancing selection
then there are major questions."
New
Scientist May
23, 2001
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