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It is impossible to give reliable general rules for the validity of extrapolation from one species to another. This can often only be verified after the first trials in the target species (humans)..Extrapolation from animal models will always remain a matter of hindsight. (Emphasis added.) From the Handbook of Laboratory Animal Science.

"Cystic fibrosis is benefiting from the fact that scientists can now reproduce in mice the precise genetic defects that cause the disease in humans" Dr Mark Matfield.

This statement is an example of a claim which could be made by anyone, who does not cite references nor check the scientific data, and is certainly not according to the
scientific fact.

INTRODUCTION
Dr Herbert Stiller, specialist in neurology and psychiatry, psychotherapy, wrote, "Life expectancy has been sinking again in the industrial countries and the number of sick persons (and) the number of deformed children rising with some rapidity. Shortly after the War, one could reckon on deformities, or genetic defects in one percent of new-born babies. Today, thirty years later, one finds genetic deficiencies in every thirdchild...thirty-three percent. An increase in deformities ranging from 20 to 30 fold in a single generation gives cause for thought. The increase in harmful effects on health seems paradoxically to go hand in hand with an increase in the number of scientists." [SAV note - scientists / bio-medical researchers (vivisectors) NOT doctors / GPs](1).  Scientists have located the genetic defects of many inherited diseases, including cystic fibrosis and familial breast cancer. Trying to "model" these diseases in animals, researchers widely use animals--mostly mice--with spontaneous or laboratory-induced genetic defects. However, genetic diseases reflect interactions between the defective gene and other genes and the environment.  Consequently, nearly all such models have failed to reproduce the essential features of the analogous human conditions.(2) For example, transgenic mice carrying the same defective gene as people with cystic fibrosis do not show the pancreatic blockages or lung infections that plague humans with the disease,(3) because mice and humans have different metabolic pathways.(4,5).

HISTORY TILL 1987
Beginning in 1985, Canadian scientists Drs. Lap-Chee Tsui and Manuel Buchwald first traced the defective gene in cystic fibrosis (CF), also known as mucoviscidosis, to chromosome 7. In June 1989, Drs. Lap-Chee Tsui and Jack Riordan, in collaboration with Dr. Francis Collins announced the discovery of the gene responsible for cystic fibrosis. This small mutation in the DNA is found in 70% of chromosomes from CF patients, but is absent in all normal people(6,7).

In Great Britain the Cystic Fibrosis Research Trust, after twenty-five years of dosing rats repeatedly with Reserpine (a drug used in people for high blood pressure, and which causes suicidal tendencies and cancer of the breast, effects impossible to predict
from animal studies) and the study of "juvenile" atrophy of the pancreas in the German Shepherd dog, has yet to find "precisely how cystic fibrosis of the pancreas in humans is caused". But the Trust is "grateful to the public" which it says is "most generous" enabling the continuance of its work which has reached an "exciting" point. (In a letter from the Trust dated May 1 1987)(8).

AETIOLOGY and PATHOGENESIS
Cystic fibrosis is an inherited genetic disease in humans, which affects the cells of various glands -including mucus-secreting glands and sweat glands in the skin (epithelial glands)(9).

The cystic fibrosis gene was discovered in humans in August 1989(10) by Lao Chee Tsui, a Canadian genetisist(11). From DNA sequence analysis of DNA clones from CF patients, the gene which mutated in cystic fibrosis was identified. As loss of, or damage to, the cystic fibrosis gene results in absence of a plasma cell membrane protein - the Cystic Fibrosis Transmembrane Regulator - the cystic fibrosis gene became known as the CFTR gene(12). By 1992, over 170 different mutations had been found in the CFTR gene(13), and by the end of the following year (1993),the number of possible mutations had increased to morethan 300(14).

Analytical studies have shown that both parents can be carriers of a faulty gene without being affected by the disease(15).

In affected CF sufferers, the lack of the CFTR gene (that enables chloride ions to be transmitted across the cell membrane) results in production of thick mucus which obstructs the intestinal glands, the pancreas, and the lungs. Respiratory infections are common, and can be severe. Sweat glands in the skin (epithelial cells) contain excessive amounts of sodium and chloride(15).

In human CF patients, pathological changes have been noted in both the gallbladder and the liver - with an estimated 14 to 43 per cent of CF sufferers being affected by focal bilary cirrhosis(16).

About 85 per cent of CF patients are unable to properly secrete pancreatic digestive enzymes(16).

About 85 per cent of male CF patients are infertile due to abnormalities of the reproductive tract(16).

Newborn babies with CF appear to be "normal", but abnormal airway secretions appear in the first weeksof life. Ten per cent of newborn babies with CF suffer from a condition known as "meconium ileus" -intestinal obstruction caused by putty-like mucus(16).

Lung infections kill about 95 per cent of human CF patients(17,18).

ANIMAL "MODELS" OF CYSTIC FIBROSIS
Researchers from the University of North Carolina in America admitted, in 1985, "there are no satisfactory animal models for the disease [CF]"(19). A view which was reiterated five years later in an editorial in the journal, `Science`, which read, "there is no animal model available for cystic fibrosis"(20).

Gross build up of mucus in the lungs is one of the most serious affects of CF in humans (and as there are no animal "models" of the disease) researchers attempted inducing chronic lung infection in mice and rats with the bacterium, Pseudomonas aeruginosa(20). (Thus, the animal experimenters examined the effects of CF rather than the cause).

After the discovery and sequencing (in 1989) of the CF gene in humans(21), researchers claimed to have found the mouse equivalent to the gene which, when faulty, causes cystic fibrosis in humans(22), but, in the year 2001, Tsui (who by then was head of genetics and genomic biology at the University of Toronto) informed BioMedNet News that, in fact, CF is, actually, polygate. Tsui stated, "It`s no longer one gene - one disease. It`s only through genomics and systematic analysis that we can understand all the complexities"(23). Nevertheless, researchers set about trying to find a way of producing genetically-engineered mice by changes to the stem cells in a mouse embryo(24). The proposed method of genetic alteration (note in a mouse, not a human) is suggested as follows :-

By flushing, a pre-implantation embryo could be taken from the uterus of a pregnant mouse. After removal of the embryo, the stem cells may be separated and cultured as cell lines(25). The genetic changes could then, hypothetically, take place in the cell lines. If a new gene is added to a stem cell, or an existing gene is broken up by inserting another piece of DNA into it, or a gene is removed, the same change will, possibly, be present in all of the "daughter" cells into which the modified cell develops. The modified cells are most often re-inserted into the developing embryo by micro- injection, As the embryos are still in the stem cell stage, the modified stem cells will be incorporated as part of that embryo. The embryo is then put back into a female mouse and allowed to develop into a foetus(26).

By the end of 1991, it was reported that the "most favoured" approach was to "knock out" the mouse equivalent of the gene which, when faulty in humans causes CF(27). But six months earlier, J Travis had already announced, "Cystic fibrosis... [is one of] the genetic disorders that researchers are trying to recreate in mice with knockout technology... the researchers have encountered some problems... certain genes are more reluctant than others to exchange places in stem cells... the rate at which modified stem cells are successfully transformed into a mouse embryo is low... It may take a year or two to create a particular knockout strain but it can take even longer to understand the pathology of the mice"(28).
                                                                                                                  continued
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