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Vivisection |
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What have guinea pigs ever done for us?
Millions of lives have been saved by animal experiments, say
scientists. Vivienne Parry examines the key research
Vivienne Parry
Thursday September 1, 2005
Guardian
If you read some of the anti-vivisection websites, you could easily believe
that there had been no benefits from animal research. Even the discovery of
penicillin, tested on mice, which has indisputably saved millions of lives,
is dismissed. Why? Because, it is claimed, penicillin is toxic to guinea
pigs and rabbits and it was luck that made Oxford chemists Chain and Florey
pick mice for their experiments. Should it negate the fact that without
mice, a drug of enormous benefit to both humans and animals might never have
been developed? Absolutely not. Nevertheless it remains controversial - last
week a guinea pig farm was forced to close by animal rights protesters.
Millions of animals were used in early medical research. Some experiments
make shocking reading now and did involve pain and distress of a sort that
would be unacceptable and illegal now. Some of the research might not have
been translatable, some indeed was misinterpreted or ignored, but there were
a great many animal experiments that led to extraordinary breakthroughs in
treatments, such as vaccines, transfusion, insulin, anti-retrovirals and
asthma medications. There were also great leaps in surgical techniques,
which have benefited both people and animals.
We and our families have already benefited from these advances, so to
dismiss these experiments as being flawed and without value flies in the
face of reason. Today, even though medical research has expanded enormously,
the number of animals used in experiments has fallen by half in the last 30
years, reflecting not just alternative research methods, such as computer
simulation and cell cultures, but a properly questioning use of animals in
which the minimum possible specimens are used. So what has animal research
done for humans?
1. Penicillin
In 1928, Alexander Fleming noticed that staphylococcus bacilli would not
grow on a culture medium accidentally contaminated with a mould, Pencillim
notatum. But test tube experiments failed to show the antibiotic properties
he expected. Ten years later, Oxford chemists Ernest Chain and Howard Florey
were working on antibacterial substances. Penicillin wasn't a top priority.
But when Chain injected two mice with it, they remained healthy. Delighted
by this apparent lack of toxicity, Florey then decided to give his full
attention to penicillin.
The animal experiment
Only by 1940 was enough penicillin available for testing. Eight mice were
infected with a deadly dose of 110 million streptococci bacteria. One hour
later, four of them were injected with penicillin. These survived but the
untreated ones died. Florey said, "It looks like a miracle".
Why animals?
The amount of penicillin needed to treat a human is 3,000 times greater than
for a mouse. Without these early whole animal proofs on toxicity and
effectiveness, penicillin would not have been developed further.
What's it done for humans?
It revolutionised the ability to treat bacterial infections, which were a
major cause of death. This simple animal test led directly to the saving of
literally millions of lives, both human and animal.
2. Blood transfusion
The first successful blood transfusion was performed on a dog by Richard
Lower in 1666 and perfected in dogs by 1907. Clotting was prevented by the
addition of sodium citrate and citrated blood was shown to be safe for
transfusion to dogs in 1914.
The animal experiment
In 1915, two doctors, Rous and Turner at the Rockefeller Institute, New
York, demonstrated the optimum concentrations of citrate and sugars for
preservation of red blood cells, in dogs and rabbits and showed that the
preserved blood could be stored for as long as three weeks in rabbits and
safely transfused back into the animals. Later work established longer
storage times for human blood.
Why animals?
Much blood transfusion research is done in test tubes, but animals were used
to establish the safety of citrated blood.
What it's done for humans?
Blood transfusion is used after injury and surgery and to treat cancers and
anaemia. Open heart surgery would not be possible without it.
3. Tuberculosis
A century ago, TB was a common cause of death. In 1907, there were 117,000
cases in Britain. It was also endemic among farm animals. Robert Koch
isolated and identified the bacteria responsible, showing that it reproduced
the disease when introduced into experimental animals.
The animal experiment
In 1943, Waksman and Schatz, soil microbiologists working at Rutgers
University, New Jersey, injected streptomycin, the product of a soil
bacteria isolated in a sick chicken, into guinea pigs infected with TB. It
completely suppressed the TB without harming the guinea pigs.
Why animals?
Antibiotics need to be trialled in living organisms as there is no way of
knowing whether they will penetrate tissue at the site of an infection. TB
is unusual in having multiple infection sites.
What it's done for humans?
This was the first effective treatment for TB, both human and animal. It
saved millions of lives.
4. Macular degeneration
Macular degeneration is the commonest cause of blindess in adults in the
developed world. It is caused by the abnormal growth of blood vessels behind
the macular, the part of the retina responsible for detailed vision.
The animal experiment
In 1998, a team in Liverpool announced a new surgical treatment for this
condition. It involves opening the eye, detaching the retina and moving it
to a new position, where it is held in place with a tuck. Called macular
relocation, this technique was perfected in the eyes of monkeys, cats and
rabbits starting in the 1960s.
Why animals?
Although vision surgery can be practised on the eyes of human cadavers,
there is no way of knowing whether vision has been restored successfully.
What's it done for humans?
Macular relocation is one of a large number of sight-saving surgical
procedures, many now performed routinely, which are based on techniques
perfected in animals.
5. Asthma
Asthma is the result of an allergic reaction of the airways. It is a chronic
illness affecting 3 million people in Britain, including one in eight
children. It kills around 2,000 people every year in the UK.
The animal experiments
Not one, but many animal experiments made bronchodilators, which relax
smooth muscle in the airways, possible. First the frog work of Dale and
Loewi in the 1920s, which established the chemical nature of
neurotransmitters, such as noradrenaline, which act on receptors in the
lungs. Then, further extensive animal work in the late 60s, particularly on
guinea pigs, made safe long-lasting bronchodilators available.
Why animals?
There are no tissue cultures that mimic any of the symptoms of asthma,
although its cellular mechanisms are studied in vitro.
What's it done for humans?
Salbutamol and terbutraline, the most widely used bronchodilators, have
prevented many thousands of deaths and enabled those with asthma to live
more active lives.
6. Meningitis
Meningitis is a feared disease, especially in children. It is caused by a
variety of bacteria and viruses, but until recently, the most common in
childhood was Hib (Haemophilus influenzae).
The animal experiments
The Hib vaccine was technically very difficult to develop because of a
shortlived antibody response, especially in children, to the main Hib
antigen, a sugar. Coupling it with a protein, a technique previously shown
to protect mice against pneumonia, was shown to produce a more powerful
response in mice and rabbits.
Why animals?
Vaccines cannot be developed by tissue culture alone because they are used
to control infections that spread through the entire body. Animals are
pivotal to vaccine research.
What's it done for humans?
When the UK vaccination programme began in 1992, there were approximately
1,500 cases of Hib meningitis, mostly in babies, with 65 deaths and 150
children surviving with major handicap. Introduction of the vaccine has
reduced the number of cases by 90%.
7. Kidney transplants
Of the 5,000 people who develop kidney failure each year in the UK, one in
three would die without regular dialysis or a transplant.
The animal experiments
Surgical techniques for transplantation were perfected in dogs and pigs in
the 1950s and became routine in humans. However, rejection remained a
problem. Cyclosporine, which is extracted from a species of fungus, was
discovered in 1972 and found to be a potent immune suppressor in mice. Tests
in humans found that it prolonged the survival of grafted kidneys. Research
on transplants in dogs showed that combining cyclosporine with steroid
produces a three-fold increase in survival time.
Why animals?
It would be impossible to perfect surgical techniques for transplant in
tissue culture as an intact circulatory system is required.
What's it done for humans?
About 2,000 kidney patients each year benefit from kidney transplants and
more would do so if more organs were available.
8. Breast cancer
Breast cancer will affect one in 11 women during their lifetime and affects
around 40,000 women each year in the UK.
The animal experiments
Animal studies in the 1950s showed that hormone changes can induce breast
tumours in rats. This led to the development of tamoxifen which blocks the
growth of hormone dependent breast cancers. Further research with mice
showed its possible preventive role.
Why animals?
The initial use of animals here has now meant an alternative to animals for
breast cancer research. Tamoxifen work showed that lab grown cultures of
human tumour cells will respond to drugs that are effective in patients.
What's it done for humans?
Breast cancer is now the second most survivable female cancer, with a 77%
five-year survival rate. Following tamoxifen's introduction in the 90s,
there was a 30% fall in death rates. It has now been proved that tamoxifen
can also prevent breast cancer in high-risk women.
9. Parkinson's disease
Parkinson's Disease, which causes slowness and absence of movement as well
as tremor and rigidity, can be treated with the drug l-dopa, but its initial
effects do not last. There are a range of surgical treatments.
The animal experiments
Parkinson's was induced in macaque monkeys and then controlled by means of
an electrode to the subthalamic nucleus, the brain centre responsible for
the disease. Dr Tipu Azis of Oxford University applied the same techniques
to his human patients, fitting an electrode to their subthalamic nucleus,
and switching off their tremor.
Why animals?
Only people and higher animals naturally share the same symptoms of
Parkinson's, particularly tremor. There are now mouse models of Parkinson's.
What's it done for humans?
This technique has brought great benefits to 200,000 people with
Parkinson's.
10. Insulin
About 1.8 million people in the UK have diabetes, of which three quarters
have Type 2 or late-onset diabetes. People with Type 1 or insulin-dependent
diabetes have little or no insulin because the islet cells in the pancreas
which normally produce it, have been destroyed. People who developed this
form of diabetes, often as children or young adults, died very quickly.
The animal experiments
In 1889, von Mering and Minkowksi showed that removing the pancreas from a
dog produced diabetes. Insulin, however, proved difficult to isolate. In a
series of classic experiments, during the summer of 1921, Canadian doctor
Frederick Banting, along with student Charles Best, managed to extract
insulin. They injected their extract into a diabetic dog, close to death,
restoring it to health. But their extract caused high fever in patients.
Biochemist James Collip then developed a purification method but the only
way to check whether insulin was present and in what amount, was to measure
its ability to lower blood sugar in rabbits. Since insulin overdose is
fatal, this was essential. These extracts were first used in dogs, then in
patients in 1922. Banting and his supervisor, Professor John Macleod, won
the Nobel prize in 1923.
Why animals?
Insulin is common to many animal species. Hormones are carried in the blood,
which is why only live animals would work in these experiments.
What's it done for humans?
The development of insulin provided the first treatment for what had been a
lethal disease. It is not a cure, but it has kept millions alive since its
discovery.
What next?
Research on mouse models of motor neurone disease (MND) have demonstrated
the important of a growth factor called VEGF. A single injection of a virus
carrying a gene for VEGF delayed onset and slowed progression in MND mice.
Work on dogs, particularly dachshunds who are prone to spinal injury and
whose owners are glad to allow them to have new treatments, has prompted
human clinical trials for spinal injury. Fetal stem cells injected into the
brains of stroke injured rats were shown to migrate to injured areas. Such
research is essential. And if it could be done in other ways, it would be.
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