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5-Animals: Transgenic monkeys with jellyfish genes produced

-------------------------- GENET-news ---------------------------

TITLE:  Scientists place jellyfish genes into monkeys
SOURCE: New York Times, by Gina Kolata
DATE:   December 23, 1999

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Scientists place jellyfish genes into monkeys

Scientists in Oregon report today that they had installed
jellyfish genes in monkey embryos, using a technique that might
eventually be used to create monkeys with added human genes. Such
a technique would allow those genes to be studied for the
development of treatments for human diseases. But the scientists
say they are acutely aware that their research raises a host of
troubling questions about reproductive technology. If scientists
can add genes to monkey embryos, it should be possible to add
genes to human embryos, raising the emotionally fraught issue of
human genetic engineering.

"These are matters that need to be discussed," said Dr. Barry
Zirkin, who leads the division of reproductive biology at the
Johns Hopkins University School of Public Health in Baltimore,
who was not connected with the Oregon research. What stands out,
some experts said, is how simple the method is. If it is refined
to be highly effective in monkeys, it could be just a short step
to using it to add genes to human embryos. Some genes might
correct diseases or prevent them -- like an AIDS resistance gene,
or one that might make a person less susceptible to Alzheimer's
disease. Adding such genes might be akin to vaccinating a child.
The addition of other genes might be more problematic.

Dr. Inder Verma, a molecular biologist at the Salk Institute in
San Diego who also was not connected with the work, gave the
example of a gene like one for the glutamate receptor protein in
the brain, which may improve memory. "Suppose you put in an extra
glutamate receptor and turn it on before giving a test to a
monkey," Dr. Verma said. He said it would be interesting to know
whether the monkeys' memories improved.

What if it worked and then humans wanted that gene? "If something
can be done, people will do it," Dr. Verma replied, though he
added that he was comforted by the thought that there would be
very few people who could afford such genetic engineering, and
even fewer who would want it.

The current study being published today in the journal Molecular
Human Reproduction, is more of a demonstration of feasibility,
experts said. To add genes to monkey embryos, Dr. Gerald Schatten
of the Oregon Primate Research Center at Oregon Health Sciences
University in Beaverton, and his colleagues began by mixing
jellyfish genes with sperm cells from rhesus monkeys. The genes
stuck naturally to the outside of the sperm cells. Then the
scientists tried to use those sperm to fertilize eggs, asking
whether the added jellyfish genes became part of the developing
embryos. The gene encodes instructions for a protein that gives
jellyfish a green glow. If it got into the monkey embryos and
functioned, the embryo cells would glow green under a fluorescent

In one set of experiments, the scientists fertilized about 20
monkey eggs in vitro, mixing sperm and eggs in a petri dish. With
that method, which mimics natural fertilization, the sperm swims
to the egg and discards its protein coat as it enters. The extra
gene was discarded with the coat as the sperm penetrated the egg.
Only the sperm's genetic material got in. The scientists also
fertilized 81 eggs by directly injecting them with the gene
containing sperm. Then, they report, the jellyfish genes entered
the eggs with the sperm. The consequence was clear when the
scientists shined a fluorescent light on the embryos. "More than
a third of the embryos fluoresced," Dr. Schatten said.

Using seven of the monkey embryos created by direct sperm
injection into eggs, Dr. Schatten and his colleagues tried to
create pregnancies and got a set of stillborn twins and one live
male monkey. The scientists have not found evidence that the gene
was incorporated into any of the monkeys' cells. But, they and
others say, they have no doubt that the method will work, because
it was recently shown to work in mice. Earlier this year, in the
journal Science, Dr. Ryuzo Yanagimachi at the University of
Hawaii and his colleagues reported that they had mixed the same
jellyfish gene with mouse sperm, injected the sperm into mouse
eggs and created pregnancies. They reported that 11 of the 57
mice that were born had the jellyfish gene: when they examined
cells from the animals' tail tips under a fluorescent light, the
cells glowed green. Dr. Yanagimachi said that while he was
disappointed that the first monkeys did not have the added gene,
"this is just a matter of time before it can be done."

Monkeys, Dr. Schatten said, can be invaluable in studies of human
disorders. "When you think of their value as a disease model or
for understanding cognition or mental disorders or all sorts of
diseases and disorders that appear in people, this is a very
small first step," he said. But, he added, a darker side of the
work is the questions it raises about a popular fertility
treatment. The sperm injection method is a standby in fertility
clinics, where it is used 10,000 to 20,000 times a year in about
200 American clinics. Discovered by accident less than a decade
ago, the method, called intracytoplasmic sperm injection, or
ICSI, revolutionized the treatment of male infertility. It
allowed men whose sperm do not move, men whose sperm cannot
penetrate an egg, and men whose sperm are not even ejaculated, to
become fathers.

But ICSI (pronounced ICK-see) puts whole sperm, along with
whatever may be attached to them, into egg cells. Dr. Schatten
noted that viruses can attach themselves to sperm and no amount
of rinsing can get them off. With ICSI, these viruses would be
injected directly into eggs where, his work shows, their genes
could start to function. And while there is no proof so far that
babies born from ICSI procedures have unusual diseases, the
prospect has troubled some scientists. "It's a significant
concern," said Dr. Peter N. Schlegel, a specialist in male
infertility at the Weill Medical College of Cornell University.
But he noted that most of the monkey embryos did not take up the
genes that Dr. Schatten attached to the sperm.

Dr. Paul Turek, a specialist in male infertility at the
University of California in San Francisco, says he will add the
new information from the monkey experiments when he is counseling
patients who are considering ICSI. "They can decide whether they
want to go forward or not," he said. But Dr. Turek added that
while he would continue with ICSI for those who want it, he would
not give a blanket recommendation to everything that becomes
technologically possible just because there is a market for it.
"I fall back on the fact that I am an ethical religious man," he
said. As such, he said, he continually questions where the
boundaries lie. "People think technology is forging way ahead of
biology, ethics, and common sense," Dr. Turek went on. "All of us
think about this all the time. All of the clinicians wonder what
we are doing." 


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