NYT on this latest pig cloning stuff.
January 4, 2002
Breakthrough in Pig Cloning Could Aid Organ Transplants
By SHERYL GAY STOLBERG
WASHINGTON, Jan. 3 — Two rival
biotechnology companies announced
this week that they had cloned pigs
that are missing a specific gene, a feat that
experts say helps pave the way to transplanting
pig organs into people without causing immune
rejection.
With human organs in short supply, companies
have been racing to develop so-called knockout
pigs in which a gene that prompts rejection has
been removed, or knocked out. Although pigs
have been cloned before, until now scientists
have been able to add genes but not to take
them away.
Today, researchers at the University of Missouri, in collaboration with Immerge
BioTherapeutics, a biotechnology company in Charlestown, Mass., announced
that they had created four cloned miniature pigs, each lacking one of two copies
of the crucial gene. The piglets, all female and apparently healthy, were born in
September and October.
On Wednesday, PPL Therapeutics, the Scottish company that helped create
Dolly, the cloned sheep, said it had cloned five pigs that lack one copy of the
gene. The animals were born on Christmas Day at PPL Therapeutics's United
States branch in Blacksburg, Va., and the company has named them Noel, Angel,
Star, Joy and Mary. (The Missouri pigs have numbers.)
Experts say the animals represent an important milestone in the field of
animal-to-human transplants, known as xenotransplantation. But significant
hurdles remain before scientists will be ready to test pig organs in people.
First, the researchers must breed animals that lack both copies of the gene.
Second, transplant experts expect to face other problems involving immune
rejection, although less daunting ones. Third, critics warn that the pig organs
could introduce deadly viruses into the recipients.
"This is a very important step in what has been a long pathway," said Dr. David
H. Sachs, director of the Transplantation Biology Research Center at
Massachusetts General Hospital, who collaborates with Immerge BioTherapeutics
but did not work on this experiment. "But we are not there yet."
With more than 75,000 Americans waiting to receive human organs, and demand
far exceeding supply, scientists have long looked to animals as the answer to the
shortage.
"This is why cloning was developed," said Dr. David Ayares, chief operating
officer of PPL Therapeutics United States branch. "Xenotransplantation is the
holy grail of the cloning field, and the unmet clinical need that can be met here is
huge."
But immune rejection has been a huge barrier, and the field of xenotransplantation
is littered with failures, among them the "Baby Fae" case in 1984, in which a
baby died after receiving a baboon heart.
In recent years, scientists have focused their attention on pigs because they are
readily available and easily bred. But pigs carry a gene that is missing in humans.
The gene sets off production of an enzyme called 1,3-galactosyltransferase,
which makes a sugar that humans and other primates recognize as foreign. So
the primate immune system kills the pig organs.
The idea behind the recent cloning experiments was to create a supply of
identical animals that lack the problematic gene. But, said Dr. Randall Prather, the
reproductive biologist from the University of Missouri who led the Immerge
BioTherapeutics research, "until this time we haven't been able to remove a gene,
we have only been able to add genes."
To clone the animals, company scientists first developed a line of cells from a pig
fetus, said Dr. Julia Greenstein, chief executive of Immerge BioTherapeutics.
Scientists then took DNA that was designed to disrupt the gene that results in the
production of the sugar molecule, and introduced the DNA into the fetal cells.
The researchers identified cells that had taken up the DNA and put it in the
correct place. Those cells were frozen and shipped to Dr. Prather in Missouri. He
inserted them into pig embryos and transferred the embryos into surrogate
mothers, who gave birth to the four cloned piglets.
The company chose miniature pigs, Dr. Prather said, because they will weigh
only 250 to 300 pounds when grown and are therefore a better match for
humans than full-size swine, which can top 1,000 pounds. The results of his
experiment are reported in the current issue of the journal Science.
Immerge BioTherapeutics was formed in 2000 as a joint venture of Novartis
Pharma A.G. and BioTransplant Inc.
Dr. Ayares of PPL Therapeutics said his company's pigs would weigh 400
pounds when mature.
The PPL Therapeutics research, announced on Wednesday, on the eve of the
release of Dr. Prather's study, has not yet been published in an academic journal
and drew criticism as a result. A leading opponent of xenotransplantation, Alix
Fano, director of the Campaign for Responsible Transplantation, a New York
advocacy group, described the PPL announcement as "a publicity stunt" intended
to attract investors.
"It is to attract investors, but it's not a publicity stunt," Dr. Ayares said, adding
that it was the company's policy to announce the results of experiments before
they were published. He said the company was looking for an investment partner
and was trying to raise $15 million in venture capital to spin off its American
branch into a separate company.
Xenotransplant research has generated intense controversy, so much so that Dr.
Prather would not reveal the whereabouts of his four miniature pigs "because of
security," he said.
Animal rights activists oppose the work, and other critics say it is not safe
because of the threat of viruses.
One virus that has been especially worrisome to scientists is called PERV, or
porcine endogenous retrovirus. Immerge BioTherapeutics says its pigs do not
carry the PERV virus, but Ms. Fano said she was not convinced.
"Xenotransplantation is fraught with danger," she said. "This could trigger an
epidemic, exposing the public at large to viruses known and unknown."
Cloning itself is also controversial, and the results of Dr. Prather's experiments
are likely to fuel the debate over the safety of human cloning. To get the four
miniature piglets, Dr. Prather said, he and his team transplanted about 3,000
genetically modified embryos into 28 surrogates.
Seven piglets were born, but two died shortly after delivery, of respiratory
distress, he said. A third died at 17 days, during a routine blood collection
procedure. An autopsy of that animal showed a dilated right ventricle in the heart
and a thickening of the heart wall, Dr. Prather said.
Dr. Prather and Dr. Greenstein said the next step was for the company to breed
pigs that have both genes removed and then to work on other problems involving
immune rejection.
"It is down the road before we will have payoffs," Dr. Prather said. "But the
payoffs are now in sight."
Copyright 2002 The New York Times Company |
