Boston
WOULD you tuck into a genetically modified steak? No? What if the cow had
been engineered to be BSE-resistant, guaranteeing it was free of the prions that
cause vCJD?
Researchers have been trying to create prion-free cattle for years. Now they
may be on the brink of achieving it. Jorge Piedrahita’s team at Texas A&M
University has managed to remove the prion gene from cow cells and clone the
cells to create embryos, although so far there have been no pregnancies. At
least two biotech companies are also racing to create such cows.
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“People are suggesting this could be the way to go to eliminate BSE
transmission to humans,” says Keith Campbell of Nottingham University. But it’s
not clear whether affordable prion-free cows could be created in commercially
viable numbers even if the demand was there from farmers and consumers. Nor is
it clear what effects knocking out the prion protein will have on the health of
the animals.
Prion diseases such as BSE and CJD are caused by a misshapen form of the PrP
protein that deforms the normal PrP protein, which then builds up in the brain
to disastrous effect. Cows lacking the gene that codes for PrP should be immune
to prion diseases because there’ll be no normal protein to go awry.
But knocking out the gene isn’t easy. Scientists have to modify
cells—no easy feat—and then transfer their nuclei to eggs. And since
it has proved impossible to obtain “immortal” embryonic stem cell lines from
cattle or sheep, scientists have to work with skin cells that can only divide a
limited number of times. “The cells have undergone so much selection that the
nucleus can’t be reprogrammed properly,” says Piedrahita, explaining why his
implanted embryos have so far failed to result in pregnancies.
“The challenge is to link the technology of gene targeting with nuclear
transfer,” says John Clark of the Roslin Institute near Edinburgh. His group has
managed to knock out the PrP gene in sheep cells and has used these to create
embryos, although all four lambs that were born died soon afterwards.
But Clark thinks the lambs died because of problems with the cloning process,
not because they were missing the PrP gene. The precise function of PrP remains
unclear, but several strains of PrP-free mice have been created. While some
develop gait problems in old age, others seem normal.
Despite the difficulties, everyone agrees that the hurdles are not
insurmountable, and that PrP-free animals are bound to become a reality. “As far
as I’m concerned, it’s a matter of time,” says Campbell.
Right now, though, the technology is prohibitively expensive for agricultural
purposes. According to Ron Gillespie of Advanced Cell Technology (ACT) in
Massachusetts, a company that is also trying to make prion-free cows, creating a
cloned cow costs about $20,000. And because only one of an animal’s two
PrP genes can be deleted at a time, a cloned female and a cloned male, each with
one gene removed, must mate to create a completely PrP-free animal. Even then,
only one in four of their progeny will have no PrP genes at all.
But if the technology progresses and breeding herds are established, the
price will drop. “We think it’s a real programme in agriculture,” says Michael
West, chief executive of ACT.
Others disagree. “There’s no prospect, in our view, for solving the BSE
crisis. It’s wholly impractical,” says Harry Griffin of the Roslin Institute.
“The only context we would envision [for PrP-free cattle] is if the concern was
heightened about using animals for therapeutics.”
That’s likely to be the first use for such animals. Hematech of Connecticut,
for example, wants to use GM cattle for producing therapeutic products such as
human proteins. To guarantee its products are BSE-free, the company wants to
make them in PrP-free cows. “It’s certainly something we are pursuing,” says
chief executive James Barton.