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March 28, 2002
1. Jumping genes make "designer"
2. Should jumping genes be used
3. Nominee for health chief backs
stem cell research
Jumping genes make "designer" animals easy
19:00 27 March 02
Exclusive from New Scientist
A bit of fly DNA might be about to turn the trickle of genetically modified
animals into a flood. Biotech company Tosk of San Francisco says
it can add
genes to mammalian cells with unprecedented efficiency with the help
fruit fly DNA that can jump in and out of chromosomes.
The company's claims are being greeted with a mixture of enthusiasm
scepticism by other biologists, who warn its results have yet to be
independently confirmed. "But if it works the way they claim, it's
revolutionary," says Tom Rosenquist of Stony Brook University in New
Introducing genes into mammals is laborious and expensive at present,
technique is only used for research and to create animals that yield
high-value medical products. But if making GM mammals becomes cheap
easy, companies could soon be modifying everything from the farm animals
that produce our food to our pets. Tosk's method could even be used
correct genetic faults in people.
Human gene therapy - the hopes and fears
At the moment, GM mammals are usually made by injecting naked DNA directly
into an egg. But the success rate is extremely low: to get just one
animal, a skilled technician has to carry out dozens of injections
implant the resulting embryos. An alternative is to start with ordinary
cells and then try to clone the few that integrate the extra DNA. But
is not very efficient either.
Tosk's method cuts out this tedious manipulation, New Scientist has
The extra DNA is simply injected into an animal's bloodstream. Within
couple of weeks, it is integrated into a high proportion of cells in
different tissues, says Tosk's chief executive Patrick Fogarty.
Since some sperm and egg cells are also altered, normal breeding can
produce animals in which every cell carries the extra DNA. When mice
modified by injecting DNA into their tails, Fogarty claims, 40 per
their offspring on average carry the extra DNA - an amazingly high
Tosk's secret is jumping genes, or transposons, which are found in
organisms. They are genetic parasites: bits of DNA with no function,
the peculiar ability to spread themselves around by hopping in and
DNA with the help of a "cut-and-paste" enzyme called a transposase.
A typical transposon consists of a gene that codes for a transposase
by unique marker sequences. When the enzyme is produced, it homes in
markers, snips out the entire transposon and pastes it elsewhere in
One of the most active transposons is the P-element, found in fruit
For decades, scientists have used it to make transgenic flies by replacing
the transposase gene with the genes they want to transfer. But nobody
get it to work well in mammals.
Now Fogarty, who left Stanford University to start Tosk, says that
tinkering with the structure of the P-element, his team can get it
integrate into up to 80 per cent of mouse and human cells in culture.
delivery system consists of two bits of DNA: one containing the gene
introduced, flanked by the marker sequences, the other containing the
for the P-element transposase (see graphic).
Trillions of copies of these bits of DNA, encased in fatty globules
help them enter cells, are injected into an animal. The animal's cells
start producing the transposase, which cuts and pastes the extra gene
random site in the cell's genome.
The transposase gene itself is not integrated into cells' DNA, but
down after a couple of weeks. Once that has happened, the inserted
DNA stay put.
Made to measure
Tosk has just launched a service to make transgenic animals, and a
scientists have begun placing orders. "If it's true it's wonderful,"
biologist Laurence Bugeon of Imperial College, London, who has just
batch of mice from Tosk. Fogarty says they have also begun collaborations
with about a dozen corporate partners that will test the technique
cows and pigs.
So far, however, no details of the company's experiments have been
published, and it could be months before its claims can be independently
verified. Other scientists say that the company needs to do more experiments
to prove that gene integration is indeed happening through transposition.
Still, Tosk is not alone in developing transposons for gene delivery.
Published work using other transposons suggests that the technique
also become a valuable tool for correcting genetic defects in people.
Right now, the main approaches in gene therapy research are to infuse
DNA into cells or to use viruses to add DNA to the genome. But naked
survives only a short time, and there are obvious safety concerns with
viruses. Transposons could provide the best of both worlds: stable
integration without the dangers of viruses.
One transposon derived from fish, called Sleeping Beauty, has been
successfully to deliver genes to the livers of mice with haemophilia
Scientist, 22 November 1997, p 11). But even in culture Sleeping Beauty
integrates at a low rate - just five to six per cent of cells. Tosk
transposon is about 10 times as efficient, an enormous difference.
Of course, there are major concerns
that need to be
addressed if transposons are ever to become tools for gene therapy.
you look at the general principles, it's a wonderful system," says
Mulligan of Harvard Medical School. "Time will tell."
Sylvia Pagan Westphal
Should jumping genes be used in people?
19:00 27 March 02
Exclusive from New Scientist Print Edition
It is one thing to use jumping genes from flies to make transgenic animals,
but quite another when it comes to gene therapy in people. The idea
having a bit of fruit fly DNA inserted into your cells is uncomfortably
reminiscent of the movie The Fly.
In principle, the added DNA should consist only of the desired genes
by short marker sequences - so you would not have much fly in you.
DNA is inserted randomly. One fear is that it could land in the wrong
knocking out vital genes and making cells cancerous.
The chances of that are minuscule, says Perry Hackett of the University
Minnesota. Only about 1.5 per cent of our DNA consists of genes, we
copies of most of them and cells usually commit suicide if they have
serious defect. In all the gene therapy experiments that have been
out, there has never been any evidence of such problems, he says.
A more realistic worry, if Tosk's method is as good as the company claims,
is integration of a gene into the human germline. If the extra gene
in a patient's sperm or egg cells, it could be passed on to any children
that person has.
Regulatory agencies such as the US Food and Drug Administration do not
any gene therapy trials that might result in germline alteration. To
minimise the chances of this, Tosk's Patrick Fogarty says it should
possible to target organs where the gene is needed, such as the heart
But it might not be that easy. Even the relatively inefficient viruses
already used in gene therapy occasionally seem to find their way into
(New Scientist, 14 March 1998, p 7). In 2000, the American Association
the Advancement of Science concluded that it is "very likely" that
therapy trials authorised in the US have already had unintentional
on the germline.
Some argue that germline transmission is desirable, though. A person
genetic disease might welcome a cure that also protects their future
children. "Personally I think gene therapy without a germline component
unethical," Fogarty says. "However, I wouldn't want any of the current
technologies used in the human germline."
The effects of random integration are more of a worry if the germline
affected. A relatively minor mutation could have serious consequences
were present in all a person's cells.
Fogarty says, however, that Tosk is working on a way to get its transposons
to insert genes into particular sites in the genome. If the company
can deliver an efficient way of targeting genes, it could undermine
the current arguments against germline gene therapy.
Nominee for health chief backs stem cell research
By Victoria Griffith in Boston
Published: March 26 2002 19:58 | Last Updated: March 26 2002 20:34
President George W. Bush extended an olive branch to the US scientific
community on Tuesday by nominating as head of the National Institutes
Health (NIH) an administrator who favours embryonic stem cell research.
If approved, Elias Zerhouni, executive vice-dean at Johns Hopkins School
Medicine, a centre for stem cell research, would occupy a position
for two years. The administration's failure to fill the job has caused
consternation among researchers who are concerned that the president
being properly advised on science issues.
The approval process may be controversial as abortion rights activists
indicated they may oppose Dr Zerhouni.
Two other key posts - head of the Centersfor Disease Control and the
the Food and Drug Administration - remain unfilled.
Finding a replacement for former NIH director Harold Varmus has been
challenge, since Mr Bush wanted to find a respected scientist who could
within his strict guidelines on embryonic stem cell research.
The administration also announced on Tuesday Mr Bush's selection for
surgeon general post - Arizona surgeon Richard Carmona. Dr Carmona
a made-for-television movie by using a helicopter to rescue a person
stranded on a cliff in 1992. He was once involved in a shoot-out after
stopping to help victims in a car crash and served as part of the elite
Green Beret force in Vietnam.
If his nomination is approved by the US Congress, Dr Carmona would
David Satcher, former president Bill Clinton's appointment, who announced
last year he was leaving the post. Among the surgeon general's obligations
are the oversight of responses to bioterrorism.
Mr Bush has already asked for a boost in funding for the NIH next year
more than $27bn (E30bn, #19bn).
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