BRED TO SUFFER - Transgenic animal disease models
In this second main section of the Bred to Suffer report, we look at transgenic animal disease models and expose their massive failure rate, as well as outlining the ethical, moral and religious concerns.
Animals have been genetically manipulated to model all of the diseases mentioned above and many more. In fact many scientists think that animals can now be engineered to represent practically any human complaint simply by adding or disabling bits of DNA.
Many species of animals are used in this research. But mice are the favourite
(at present) and their use is rocketing - up by 960% over the past 10 years,
with this rate of increase predicted to continue for the foreseeable future.
Sheep, cattle, pigs and chickens have all been genetically modified to increase their production of milk and meat, which is already beyond the limits their bodies can bear without damage. They have also been engineered to secrete therapeutic protein products (which could be obtained more safely and cheaply from transgenic micro-organisms or plants) for human medicine; a process called 'gene pharming'. These abuses are outside of the scope of this report, but see The Gene and the Stable Door - a Compassion in World Farming Trust report, available at www.ciwf.co.uk.
Suffering at every step: creation of transgenic animals
In order to create a new strain of transgenic mice, young females are injected with powerful hormones to make them superovulate. After mating, they are killed to extract the embryos, which are microinjected with the foreign DNA. These altered embryos are then surgically implanted into many surrogate mothers, who have also been hormone-injected to assist implantation and who will later be killed before or after giving birth. Many of the resulting baby mice are malformed and die before or shortly after birth. The surviving babies have to be tested to see if they have the new gene: this can be done by saliva or faecal sampling but is more often conducted by cutting off the tips of their tails or a notch from their ears.
Massive failure rate: millions of animals killed as 'rubbish'
Only 1-10% of the baby mice will have successfully incorporated the new gene.
The other 90-99% will be destroyed as 'failures'. This translates into so much
killing that many of the animal technicians responsible for killing all the
'waste' animals find it traumatic and are left feeling 'physically and emotionally
A gene is not a unit, but part of an integrated system. When introduced into
a foreign environment it may take effect in the wrong tissue, switch on at the
wrong time, or be uncontrolled in its effects and inflict damage on non-target
organs or tissues. As a consequence, there is always a likelihood that the animals
will suffer unpredicted side effects in addition to the intended suffering resulting
from their designer disease. For example, 'giant' mice were given a human growth
hormone gene to make them bigger than normal. But they also suffered unplanned-for
liver and kidney damage, grossly deformed hearts, spleens and genitalia, together
with high infant mortality and a shortened life-span.
Often, scientists create a 'model' by removing or disabling a gene. The resulting
animals are called 'knockouts'. The effects cannot be predicted in advance.
Researchers can guess, for example, that knocking out a receptor gene for thrombin
(a blood-clotting enzyme) in mice will affect their control of blood coagulation.
But only by creating the animals can they discover that such a deletion causes
half of the altered embryos to bleed from multiple sites so that they die in
Models of dubious value
Just as physically damaging animals results in poor 'models' of human disease, human conditions cannot be replicated in mice simply by giving them a human gene or two.
For example, none of the current 'cystic fibrosis' mouse strains accurately
models the human condition, in which the major symptoms are excess mucus in
the lungs, leading to lung infections. The mice, in contrast, suffer principally
from bowel disorders and are clearly not a very helpful model of the disease.
As already discussed, many human cancers have been 'replicated' in animals
by inserting some of the genes involved. 'One might expect that these animals
would mimic human symptoms, not just the genetic mutations. In fact, that is
usually the exception, not the rule.'
Even the industry's own Lab Animal magazine stated, 'Mice are actually poor
models of the majority of human cancers.'
The whole concept of modelling diseases on the basis of their genetic component
alone is fundamentally flawed. There is indeed a genetic element to our susceptibility
to many diseases, but our genes are not an automatic ticket to illness or health.
In all the fanfare about the sequencing of the human genome, their contribution
has been massively exaggerated. Other factors such as diet, lifestyle and environmental
pollution are far more important in determining whether or not we will succumb
to a particular disease at a particular time. Most of us are carrying the genes
for a variety of serious diseases but are not suffering from them. This is because
these 'disease genes' are not switched on unless triggered through, for instance,
exposure to cigarette smoke, a high-fat diet or some other environmental risk
factor. Even if one identical twin suffers from a particular disease, the other
twin usually does not,
And a mouse with a gene for a human disease is still a mouse, whose 30,000
or so other genes will affect the expression and behaviour of the gene in question.
The gene will perform in a completely different way in the mouse from the way
it is expressed in its natural human environment. As Philip Abelson, editor
of the prestigious journal Science commented, 'Are humans to be regarded as
behaving biochemically like huge, obese, inbred, cancer-prone rodents?'
Even when scientists think they have a 'good model' it is difficult to determine
how much its attributes are due to its genes or to environmental factors. Wildly
differing results have been found to occur in different laboratories using the
same strains of animal in the same procedures.
Transgenic animals also used to test poisons and carcinogens
Transgenic rats and mice are used in toxicity tests, for example, to measure
the carcinogenic (cancer-causing) potential of various chemicals. The animals
are designed to be genetically susceptible to cancer and it is claimed that
this is beneficial to animal welfare because the tests should be less prolonged
and use fewer animals than the traditional 'chronic rodent bioassay', which
consumes 400-500 animals per compound. However, human hazard would be better
predicted by using human cells. 'Toxicogenomics' (or pharmacogenetics) is a
new technique using DNA arrays: tiny glass plates or 'chips' covered with a
matrix of DNA fragments are washed over with fluorescent 'probes' that can detect
which fragments have been affected by the substance in question. Thousands of
chips can be processed in a matter of hours. The results are more accurate and
sensitive than animal tests and (when human DNA is used) are directly relevant
Legal protection inadequate
Having read this far, it will be apparent that no laboratory animals are properly protected under the 1986 Animals (Scientific Procedures) Act. But there are certain problems unique to GM animals, which require changes in the law to afford them due consideration. This is, not least, because their use, certainly on its current scale, was not foreseen when that legislation was introduced. Even the Home Office recognised this inadequacy and, in 1999, published guidance notes for project licence applicants who were intending to create or use GM animals. These notes stipulate, for example, that mice should be at least five weeks old before they can be superovulated by repeat hormone injections - a week after which they will be killed for egg/embryo harvesting. The notes also specify a maximum of 0.5cm tail-tip removal, or a maximum 15% of total blood volume removal by tail-bleeding for DNA-typing. However, DNA can be typed by faecal or saliva-sampling: clearly these more humane methods should be mandatory. The massive wastage of animals as 'failures' should be prohibited. There are methods that achieve much greater levels of success and these should be mandatory. Equally significant is that the Home Office notes still classify the production and maintenance of GM animals as 'mild' severity procedures. Yet, as we have seen, the consequences of transgenesis cannot be predicted and often seriously compromise the welfare of the resulting animals.
Ethical, moral and religious concerns
Altering the genetic material of animals raises a whole host of ethical, moral and religious questions.
- Changing the genetic make-up of animals compromises their essential nature and fails to respect their unique identity.
- Deliberately designing animals to suffer, as disease models inevitably do, is morally repugnant.
- GM animals are more than likely to suffer in unexpected ways as well as in the ways intended by their manipulators. Altering animals' genes without knowing the consequent harm they will suffer raises fresh ethical problems.
- Because researchers want to protect their 'inventions', each of many thousands of GM animal strains are 'owned' by private patent-holders, who sell them as just so much laboratory equipment. The very idea of patenting life, particularly sentient life, is abhorrent to many.
- A moral dilemma that applies equally to all animal research is this: who
are we to decide whether the potential benefits to mankind outweigh the costs
to the animals? This 'dilemma' should be resolved, however, when policy-makers
understand that the 'potential benefits' are much more usually potential harms
to human beings themselves, from bogus and misleading animal results. As leading
surgeon Moneim Fadali states, 'conclusions drawn from animal research are
likely to delay progress, mislead and do harm to the patient'.
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