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5-Animals: GE mice are key tool in quest for new drugs



                                 PART I
------------------------------- GENET-news -------------------------------

TITLE:  Mice Are Key Tool in Quest for New Drugs
SOURCE: Associated Press, by Matt Crenson/ Environmental News Network
        http://www.enn.com/today.html?id=9999
DATE:   06 Mar 2006

------------------ archive:  http://www.genet-info.org/ ------------------


Mice Are Key Tool in Quest for New Drugs

BAR HARBOR, Maine -- When it comes to the price of mice, you pay more for
defects. A mouse with arthritis runs close to $200; two pairs of
epileptic mice can cost 10 times that. You want three blind mice? That'll
run you about $250. And for your own custom mouse, with the genetic
modification of your choosing, expect to pay as much as $100,000.

Always a mainstay of scientific research, mice have become a critical
tool in the quest for new drugs and medical treatments.

It turns out that a mouse's genes are so similar to a person's that with
proper manipulation -- either by man or nature -- they can produce an
animal with an ailment akin to virtually any human medical condition.
Mice with Alzheimer's disease, obesity, diabetes, cancer and countless
other ailments are being used to study both the illnesses themselves and
potential treatments.

As many as 25 million mice are now used in experiments each year. Where
do they come from?

From the mouse industry, of course.

There are many vendors: The Jackson Laboratory, a nonprofit supplier in
Bar Harbor, Maine, ships more than 2 million a year. Commercial breeder
Charles River Laboratories of Wilmington, Mass., makes about $500 million
annually selling and caring for lab animals, most of them mice.

Yet the mouse business is a challenging one. What was once a relatively
simple business of breeding and shipping animals has become an extremely
challenging enterprise that requires cutting-edge technology and a
mastery of difficult logistics.

"It's not just putting two animals together any more," said Terry Fisher,
general manager for business development and surgical services at Charles
River Laboratories, a Wilmington, Mass., which offers laboratory animals
and services to pharmaceutical companies and researchers.

At the Jackson Laboratory, Rob Taft maintains a collection of 2,850
different mouse strains -- but he rarely sets eyes on most of them.

Two-thirds of Taft's collection consists of embryos, frozen at 320
degrees below zero in tiny glass tubes about the size of a cocktail
straw. The half-dozen freezers that hold the embryos are a biological
Library of Congress, a genetic repository containing virtually every
publicly available strain of lab mouse ever produced.

All of them are for sale.

Any qualified researcher can call the Jackson Lab, where Taft is the
associate director of reproductive sciences, and order 100 diabetic mice,
50 anemic mice or a dozen mice with cystic fibrosis. Taft simply pulls a
straw out of the collection, thaws it, and implants the embryos in a
female mouse. Three weeks later, he has a made-to-order litter of mouse pups.

Mice gained their new significance not long after the completion of the
human genome project in 2001. Scientists rushed to finish sequencing the
mouse's DNA sequence the following year, and when they put the two
genetic codes side-by-side they found something they'd always suspected
-- the genes of mice and humans are virtually identical. The obvious
differences between us and them lie not in the genes themselves but in
where, when and how those genes are activated.

"It means that the anatomy and physiology of a mouse is pretty darn
similar to what you see in a human," said Roy Woychik, director of the
Jackson Laboratory.

Essentially, mice and humans are made from different combinations of the
same parts.

Companies now have to know the genetic makeup of every mouse that goes
out the door. They have to guarantee that their mice are free of viruses,
bacteria, parasites and other pathogens that could affect the outcome of
an experiment. And they have to be able to store hundreds or thousands of
different strains, either "on the hoof" or frozen as sperm or embryos.

Lab mice live the ultimate hothouse existence. They are kept in special
rooms with filtered ventilation systems and air locks, or in cages known
as "isolators" that keep them completely free of contamination from the
outside world. Any technician who comes in direct contact with mice has
to go through a thorough decontamination process beforehand that involves
a shower and a full change of clothes. All the food, water and bedding
for mice is sterilized by heating, irradiation or both.

Lab mice are smaller and tamer than wild mice, and much more sensitive to
temperature and other environmental changes. The animals are so delicate
that distributors ship them in special climate-controlled trucks and go
to great lengths to avoid sending them by air freight. One company,
Taconic Farms of Germantown, N.Y., serves West Coast customers with a
nonstop truck that leaves New York every Thursday evening and arrives in
California the following Monday morning.

And because scientists have become more attuned to the health of their
mice, insisting that they be free of anything that could affect the
result of an experiment -- or even worse, wipe out an entire colony of
animals -- suppliers constantly sample their populations for the
slightest sign of infection.

"We screen for everything under the sun," said Charlie Chungu, product
manager of the model organism division at Charles River Laboratories. He
oversees an army of technicians who culture tissue samples for bacteria,
test blood serum for signs of viral infection and dissect mice to make
sure their internal organs are in good condition.

When scientists began working with mice a century ago they didn't know
anything about DNA, and had only the foggiest notion of genes. They had
just rediscovered breeding experiments that had been performed on pea
plants 40 years earlier by the Austrian monk Gregor Mendel. Mendel had
worked out rules of inheritance that worked in plants; did they apply to
animals as well?

Mice were the obvious choice for breeding experiments. Small, docile and
more than willing to reproduce, they were also readily available from the
collections of Victorian mouse fanciers who bred the animals to have
interesting coat colors and patterns. Many of today's most popular lab
mouse strains are direct descendants of those original "fancy mice."

Over decades, researchers created inbred lines of lab mice by repeatedly
mating siblings to one another until every member of the strain was
virtually the same genetically. That standardization made it possible for
a researcher in Japan to replicate the experiment of a colleague in
California without having to worry about genetic variation affecting the
result.

It also gave each strain a distinct character that made it preferable for
certain experiments. The strain BALB/c, for example, is especially useful
for immunological studies. Another strain, C3H, is known for its
susceptibility to breast tumors.

Mouse breeding was much simpler before the genetic revolution. For much
of the 20th century new strains of lab mice were created either by
selective breeding or by chance. If a sharp-eyed lab technician or
graduate student spotted an unusual animal that turned out to have a
novel mutation, a new line would be produced in order to study that
particular gene.

Now researchers -- and increasingly biotechnology companies -- can create
their own mutations, inserting or deleting genes at will.

Companies such as Deltagen of San Carlos, Calif., will create a
"knockout" mouse that lacks a particular gene. Artemis Pharmaceuticals of
Cologne, Germany, offers to insert human genes into a mouse's genetic
code. PolyGene Transgenetics, a Swiss company, will insert genes whose
output can be turned up and down as if they were on a biological dimmer
switch.

And the award for sheer weirdness goes to Xenogen, an Alameda, Calif.,
outfit that can hitch the gene of interest to one that codes for the
protein that makes fireflies glow. The result: Whenever and wherever the
gene being studied switches on inside the mouse, it glows.

Depending on the specific genetic manipulation, the cost to create a
custom mouse is usually in the tens of thousands of dollars. Once the
line has been established, individual animals can run into the hundreds.

"Not that much to pay if you want to see how a disease affects a mammal
or how a drug is going to work," said Lee Silver, a Princeton University
biologist who has worked with mice since 1978.

The problem is, the new mouse strains are so specialized that there are
only a handful of buyers for any given custom mouse. Of the thousands of
strains it has in stock, the Jackson Laboratory makes money on a few
dozen and breaks even on a few hundred more. The common, high-demand
strains -- and federal grants -- subsidize the storage and maintenance of
the more exotic lines, and also help support the research of more than 50
scientists.

"If you're selling a million mice of a particular strain, it's not too
hard to make a marketplace," said Charles E. Hewett, chief operating
officer of the Jackson Lab. "A mouse that we're only going to sell a
dozen or so every year, that's much harder."

But biologists agree that those mice are vital to the advancement of
biology, which is why the federal government's National Institutes of
Health has invested millions of dollars in creating and maintaining lines
of genetically modified mice.

This year the NIH spent $10 million to purchase 250 strains of knockout
mice, along with detailed information about their physiology, from two
biotechnology companies, Deltagen and Lexicon Genetics of The Woodlands,
Texas. The acquisition is just an "hors d'oeuvre" for a much larger
international effort to create a knockout strain for every one of the
mouse's 20,000 to 25,000 genes, said Chris Austin, director of the
National Institute of Health's Chemical Genomics Center.

The Knockout Mouse Project would record information about the
characteristics of each strain in an enormous public database that would
allow researchers to link genes with their functions.

"The number of different things that you can do with these mice is huge,"
Austin said. "One can say, 'OK, show me all the mice that are anemic,'
... and you immediately come up with a list of genes, many of which you
never would have thought of."

Some researchers believe studying knockout mice will even lead to the
development of new drugs, perhaps dozens of them. One of the first steps
in drug development is the identification of what biologists call a
target -- a biological molecule that is involved in the disease process
and can be blocked or otherwise affected by a small, relatively harmless
compound.

Good targets are hard to come by. But knockout mice are virtual target
factories, because they are missing a single gene, and thus a single
biological molecule. For example, if researchers found a knockout mouse
that stayed skinny no matter how much it ate, they would immediately have
a promising target for an obesity drug.

"You can manipulate the genes ... and use the mouse as a translator of
mammalian physiology," said Brian Zambrowicz, executive vice president of
research at Lexicon Genetics.

Lexicon has knocked out 3,000 mouse genes already, and has designs on
2,000 more. With each knockout, the company performs a detailed battery
of tests to determine how the function of the deleted gene corresponds to
human physiology in six areas: opthalmology, cardiology, immunology,
cancer, metabolism and neurology.

If Lexicon can find just a few dozen new targets among the 5,000 genes it
is knocking out, it could easily revolutionize the pharmaceutical
industry. Zambrowicz claims that the company has already identified 70
new targets, which is pretty impressive when you consider that the 100
top-selling prescription drugs on the market exploit no more than a few
dozen.

Still, it remains to be seen whether a leap can be made from mice with
knocked-out genes to therapies for humans. In the past, discoveries that
looked promising in rodents have often failed in human patients.

"These mice are not going to tell us everything, and sometimes they tell
us nothing. But as a starting point," Austin said, "mice play a central
role."


                                 PART II
------------------------------- GENET-news -------------------------------

TITLE:  A mouse could save your life
SOURCE: The Independent, UK, by Steve Connor
        http://news.independent.co.uk/world/science_technology/
article349459.ece
DATE:   06 Mar 2006

------------------ archive:  http://www.genet-info.org/ ------------------


A mouse could save your life

The recent pro-vivisection demonstrations are prompting many in the green
movement to rethink their stance on animal testing. Steve Connor argues
that an intelligent debate is long overdue

If you are confused about the rights and wrongs of animal experiments,
you can be forgiven. Protests on the streets of Oxford for and against
the university's new scientific research centre have done little to
dispel the smog of propaganda that has descended over the animal debate.

We have been told testing on animals reveals nothing about people. We
hear about alternative research that is just as good if not better than
animal experiments. We learn about the children who have suffered because
scientists and drug companies are obsessed with the irrelevant results of
experiments on animals.

Yet few realise that Britain has one of the toughest laws in the world
governing animal experiments. Animals can only be used when
scientifically justified - their use in cosmetics testing was stopped in
1997 in Britain. Scientists and their research institutes also have a
legal obligation to use alternatives to animals whenever possible. If
they can use alternatives, not only is it incumbent on them to do so, but
it can be cheaper.

There are fewer animal experiments now than 20 or 30 years ago mainly
because of developments in techniques that can replace the use of living
animals. Scientists can sometimes carry out a test on people rather than
laboratory animals, or they can try to "model" a living system or medical
problem using powerful computer software. But, as the cosmologist Stephen
Hawking once said: "Computers can do amazing things. But even the most
powerful computers can't replace animal experiments in medical research."

Organisations opposed to animal experiments take the opposite view. They
say that not only do alternatives to animals exist, but they are better.
They also claim that relying on the results of animal research is
dangerous. "Reliance on animal experimentation amounts to gambling with
our children's' health," says the antivivisection group Europeans for
Medical Progress (EMP). "Time and time again, misleading results from
animal experimentation have proved tragic or fatal when applied to
children and babies. And there are much better options."

The thought that animal experiments directly harm people, that they are
next to useless for medical progress and that their only outcome is
unnecessary suffering is surprising, if not alarming. But what evidence
is there to back up such claims?

This was the question posed last year by the Advertising Standards
Authority (ASA) when it was investigating a complaint against EMP (then
called Europeans for Medical Advancement). For instance, the ASA was
interested in the evidence to support this claim by the group: "Treatment
of childhood leukaemia has also improved dramatically, thanks entirely to
ingenious research on cell and tissue cultures - not to animal experiments."

Or this statement: "The biggest obstacle in the search for cures for
cancer and many other diseases of childhood is our irrational dependence
on animal experimentation, which has cost far too many thousands of
lives." EMP also claimed the leukaemia drug Glivec had been discovered
entirely through test-tube research not involving animals.

When the ASA challenged the group to support these claims, EMP cited
research dating back to the 1940s and 1950s. Understandably, the ASA
ruled that people reading the group's literature are hardly likely to
consider 50 or 60-year-old research as recent improvements. The ASA also
found that Glivec, a recent treatment for chronic myeloid leukaemia, was
developed with the help of animal research.

But opinion masquerading as fact seems to be a hallmark of the animal
debate. EMP has stated, for instance, that "uncritical reliance on the
results of animal tests can be dangerously misleading and has cost the
health and lives of tens of thousands of humans".

This opinion on the subject of toxicity testing lies at the heart of the
argument against the use of animals in medical research. All drugs in use
today have been tested on animals before being given to people. The aim
is to ensure as far as possible that side-effects are kept to a minimum
and that potential toxicity is detected before a new drug goes on the market.

Of course there are drugs that have slipped through the safety net. They
may have not shown any adverse effects on animals, or even on the
patients who took part in the early clinical trials, but after some
months or years the side-effects of long-term use become apparent. Anti-
vivisectionists exploit the inevitable risk of missing potentially toxic
drugs using animal testing.

One of their favourite examples is the case of Thalidomide, a morning-
sickness drug which was tested on animals without any apparent side
effects before being found to cause limb deformities in the unborn babies
of pregnant women. Thalidomide is frequently cited as a drug that was
deemed safe in animal tests, illustrating the anti-vivisectionist mantra
that testing on animals tells us about animals, not about people.

In fact the animal tests on Thalidomide failed because they were not as
extensive as they should have been. After the drug was withdrawn,
scientists went back and tested the drug on rats, but this time the
researchers included pregnant animals - astonishingly pregnant animals
were not included in the original experimental protocol. The results were
unequivocal: Thalidomide caused spontaneous limb deformities in foetuses.
It was a finding that would almost certainly have resulted in the drug
being banned - had the fact been known - long before it was prescribed to
pregnant women.

Using animals to test the toxicity of new drugs stops as much as 80 per
cent of putative treatments from ever getting near to being given to
patients. As a screen against the side-effects of new drugs, animal
experiments are not perfect but without them there would be many more
dead or damaged people.

Another shibboleth of the anti-vivisectionist movement is the belief that
animal experiments have provided little, if any, insight into basic
science or medicine. Yet according to an extensive investigation in 2002
into animal experiments by the House of Lords, all reputable scientific
and medical organisations in every country of the world say that animal
research has been crucial in the understanding of health and disease. The
Department of Health's submission to the Lords' inquiry was clear about
the critical role played by animal experiments. "Research on animals has
contributed to almost every medical advance of the last century," it
said. "The NHS would be unable to function effectively were it not for
the availability of medicines and treatments that have been developed or
validated through research using animals."

So where exactly do we stand regarding the known facts about animal
research? It is widely accepted that Britain has one of the toughest sets
of regulations governing animal experiments anywhere in the world.
Indeed, many scientists claim that the bureaucracy involved in getting a
Home Office licence or amending it is so convoluted that it can take
anywhere between six months and a year - as opposed to weeks in other
countries.

In 2004, the last year for which we have full figures, there were 3,550
licensed projects in Britain and just over 2.85 million "procedures" on
animals, which can include relatively benign operations such as taking a
blood sample. The number of procedures has increased slightly in recent
years due to the use of genetically modified mice in studies to
understand the human genome. Genetically altered animals were used in
just over 914,000 regulated procedures in 2004 - about a third of all
procedures. About 67 per cent of all licensed experiments were carried
out on mice and 16 per cent on rats. Other mammals accounted for four per
cent.

No scientists derives enjoyment from inflicting suffering on animals, and
many researchers are working on alternatives. However these alternatives
are not yet at a stage to rival the complexity of the whole living organism.

Until alternatives do reach that stage, animal research will still be
needed if society is to enjoy the benefits of science and medicine.

Steve Connor is the Science Editor of 'The Independent'

What would we do without animal experiments?

- Polio: Research into polio vaccines required the living nerve-tissue of
animals to ensure that the virus used for vaccines causes the paralysis
typical of polio. No cultures of human or animal tissue work as well. The
inherent dangers of the live vaccine means that it also has to be tested
on animals. GM mice have replaced monkeys.

- Kidney disease: Some 5,000 people develop kidney failure each week in
the UK and a third would die without a transplant or regular dialysis.
Experiments on animals led directly to the development of dialysis
machines and to the drugs and techniques for successfully transplanting
organs without rejection.

- Cystic fibrosis: Modern genetics research is revolutionising the
understanding of inherited diseases, and much of the work can be done
without using animals. But, having identified six compounds that could
block the defective cystic fibrosis gene using non-animal experiments,
scientists had to use lab mice to find the most active drug.

- Tuberculosis: TB infects some two billion people in the world, killing
three million people each year. Mice with impaired immune systems are
central to attempts to make a viable vaccine against the bacterial
disease. All antibiotics used to treat patients have been tested on animals.


                                 PART III
------------------------------- GENET-news -------------------------------

TITLE:  BUAV TARGETS OXFORD UNIVERSITY STAFF AND STUDENTS OVER ANIMAL
        TESTING FACILITY: THROUGH LAUGHTER
SOURCE: British Union for the Abolition of Vivisection
        http://www.buav.org/press/2006/1322006.html
DATE:   13 Feb 2006

------------------ archive:  http://www.genet-info.org/ ------------------


BUAV TARGETS OXFORD UNIVERSITY STAFF AND STUDENTS OVER ANIMAL TESTING
FACILITY: THROUGH LAUGHTER

With threats against Oxford University's proposed animal testing facility
becoming increasingly confrontational, the BUAV (British Union for the
Abolition of Vivisection) are bucking the trend by using laughter, not
violence, to engage hearts and minds.

The peaceful campaigning organisation will today "introduce" Professor
Vitzerdooble to staff and students to persuade them that clinging to
animal-based research is out of touch with modern technology that can
save human lives without resorting to animal testing.

The mad Professor is a cartoon character, and star of a new animated film
'Testing Today', where he gives a lecture about the 'necessity' of animal
tests. He will be emailed to over 100 department heads, researchers, and
staff with a request to 'guest lecture' i.e. appear in their lectures.

Throughout the week, BUAV supporters will also canvas the campus with
thousands of leaflets, asking students to listen to Professor
Vitzerdooble's "lecture" by visiting www.testingtoday.info

Alistair Currie, Campaigns Director at the BUAV said: "We think that it's
crucial that students at Oxford University - the leaders of tomorrow -
are exposed to the real arguments of the anti-vivisection movement albeit
in a humorous way. Animal testing is not a 'necessary evil' as many might
claim. We want to spark debate and promote discussion, enabling them to
make informed decision based on facts not bias.

He added: "Although Professor Vitzerdooble is only two inches high, we
expect him to do a great job!"

To see the animated short film , please visit www.testingtoday.info and
for more information about the BUAV visit www.buav.org

ENDS


Notes to Editors:

The BUAV is unequivocally opposed to violence of any kind, whether that
be the violence of vivisection itself or the harassment and intimidation
that some people use as a means of protest. We believe that such methods
undermine the messages, damage the reputation of, and ultimately impede
the progress of the animal rights movement.

BUAV is the world's leading organisation campaiging against animal
experimentation. We oppose all violence to animals as well as humans, and
belive that animals are entitled to respect and compassion, which animal
experiments deny them. Our aim is to achieve lasting change by
challenging attitudes and behaviour towards animals. We do this in the
following ways:
Peacefully campaigning and lobbying to change laws and government policies.
Challenging negative perceptions around animal rights.
Providing information on and raising awareness of animal experimentation.

For more information about the BUAV, go to www.buav.org
tel: 020 7700 4888 or email: info@buav.org

For further information please contact:
Penaran Higgs, Press and Celebrity Officer

Tel: 020 7619 6978

Mobile (24 hours): 07850 510 955

Email: penaran.higgs@buav.org




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GENET
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