Cystic Fibrosis

Cystic Fibrosis has been the subject of high profile claims in favour of animal testing.  Read the reality here.

Patients deserve better science than animal experiments


Cystic Fibrosis is in many countries the most common inherited fatal disease.  It is caused by a defective gene, which normally regulates the transfer of sodium and fluid across cell membranes.  This gene, CFTR, also acts as a sodium channel, but is closed in cystic fibrosis patients.  There were over 300 different gene mutations identified by 1993, and the type of mutation influences the degree to which the sodium channel is affected, and therefore the severity of the illness. The victims develop an imbalance of biological acids, which results in the accumulation of a thick, sticky mucous in the lungs, where bacteria thrive.  For 95% of cystic fibrosis patients, this is the cause of death. [1]

In addition to lung disorders, the pancreas is also severely affected. It develops cysts and degenerates, making it less effective in absorbing nutrients. About 85 per cent of CF patients are unable to properly secrete pancreatic digestive enzymes. [2]

Drs. Lap-Chee Tsui and Jack Riordan identified the responsible gene which causes CF in humans using technological methods in June 1989, in collaboration with Dr. Francis.   The mutation is so small that apart from a single amino acid difference, the DNA of a cystic fibrosis patient will resemble the DNA of a healthy person completely. [3]

Animal Models

Attempts have been made to develop animal models which mimic cystic fibrosis and may be used to held develop treatments or even a cure.  However, they failed to overcome the biological nature of genetic illnesses, that they reflect the interaction of the defective gene and other genes with the environment. [4]

The mouse model was developed by implanting a foreign CFTR gene into a mouse embryo, transferring the embryo to another mouse, thus enabling birth of an animal with a defective gene, and breeding of further generations with the same defect.  The defective gene is recessive, which means that if a faulty and a normal gene are inherited, the normal one will be dominant, and cystic fibrosis symptoms don't develop - the individual will be a carrier.  If they then pass the defective gene on along with another defective gene from the other parent, cystic fibrosis will develop in the recipient.  Mice with two faulty genes were therefore seen as models for the human condition.

Respiratory symptoms

As the overwhelming threat to humans, lung infections were anticipated in these models.  Yet in `Science`, in August 1992, it was reported that CFTR (-/-) mice "don't have the mucus-clogged lungs and persistent lung infections that plague human CF sufferers. That could be because the lungs of mice are fundamentally different from those of humans - they have fewer mucus secreting glands and cells overall." [5]

It was also commented that "…symptoms of the CF mice are hardly identical to those of human CF" [6]. Koller, leader of one of the teams who pioneered this mouse model admitted, "it would be very unlikely to get a mouse model that is identical to humans", because, as another expert explained "there are just too many subtle physiological differences between the two species"  [7].

The differences between mouse and human lungs are significant, and this difference was predictable.  The mouse lung does not contain serous glands, yet these are the crucial glands in the human patient which secrete the mucus into the lungs.[8]

The lung damage in humans starts to develop after birth, starting with abnormalities in the gland ducts and the system which secretes mucus.  Chronic infection can result in the first years, and this will be the eventual cause of death in 95% of patients [9]. By contrast, the North Carolina developers of the mouse model admit: "our CFTR (-/-) mice die early in life of gastrointestinal obstruction, and not from pulmonary infections" [10].

Criticisms also came form the Edinburgh team who had also developed a CF mouse model: "[North Carolina] frequent prenatal death with intestinal obstruction, but not lung or gonadal pathology. By contrast, our ... mutants are viable and show mild intestinal obstruction in association with gut, lung and gonadal pathology, characteristic of cystic fibrosis" [11].

Such optimism is typical of animal research, but didn't go unchecked. Researchers from the University of Michigan were more sceptical and pointed out the varying symptoms among the Edinburgh colony [12]. They also stated that "The apparent differences in the first two mouse models of CF underscore the complexities of modelling human diseases in animals"  [13]

With the major symptom of cystic fibrosis still not reproduced convincingly, and no idea of what relevance any effective treatments have for humans, the mouse model is currently far from a success.  Furthermore, the biological differences - such as the complete lack of the serous gland - means it is always likely to be a failure.


The Pancreas

Another symptom of cystic fibrosis is pancreatic disorder.  About 85 per cent of CF patients are unable to properly secrete pancreatic digestive enzymes [14].  This has not been a feature of the mouse models. One team admitted their model showed only occasional pancreatic changes, and  the liver effects of focal bilary cirrhosis [15], a disorder which develops in an estimated 14-43% of human CF patients, was not seen in the mice. [16]

The Edinburgh team had similar problems which they tried to explain: "the ductal blockage that typifies most [human] cystic fibrosis patterns might be expected to be less severe in mice, or to develop later" [17].

A British team based in Cambridge also developed a mouse model using the same method as the Edinburgh and North Carolina teams.  Although they claimed to have discovered blockage in the pancreatic ducts, this appeared late in the development of the mice (in contrast to humans), and the changes were not severe enough to alter enzyme secretion [18] - the problem which affects 85% of human CF patients.



A common problem in the mouse model but not seen among humans is in the intestine.  Among the North Carolina mice "…most die within 30 days after birth from intestinal blockages…". [19]  The Cambridge team reported an intestinal obstruction of the small intestine called meconium ileus, which was acknowledged to be not a feature in most human CF patients. They concluded, "The reason for this difference is not known" [20]


The Reproductive System

85% of male cystic fibrosis sufferers are infertile due to an abnormality on the reproductive tract [21], a proportion that is believed by some experts to be even higher at 95%. [22]  The animal model is in complete contrast, with no evidence of abnormality at all. [23]

Incredibly, after one male mouse was found with an increase in one of the constituents of mucus in the sperm ducts, the researchers were claiming that this isolated example indicated "that this mouse model may be valuable for studying male infertility"![24]  The causes of this isolated case could have been one or more of several factors.

As Dr Ray Greek, of Americans For Medical Advancement said:  “ 'cystic fibrosis mice' suffer principally from bowel disorders rather than lung infections; the main symptom of the condition in humans, so are clearly not a reliable model of the disease. The whole concept of using animals as models for human diseases is fundamentally flawed. Patients and their families deserve better science based on the sound clinical and in vitro methodologies we have at our disposal.”

The advances that have been made will no doubt be claimed by some people to be as a result of animal experiments.  Yet the history of drug development shows this is unlikely.



The problems of the pancreas were discovered by performing autopsies on patients, [25] whereupon it was found that pancreatic cysts were routine for CF patients.  Observing patients uncovered the link between excessive salt in the sweat, which led to the 'sweat test' which is still used.[26]

In the 1940s observation by doctors, of children with cystic fibrosis during a heat wave led to the discovery that low sodium in the lungs was typical, and following studies on the urine and sweat of these patients, the body chemistry which caused the interruption of salt transport was identified.[27]  The exact mechanism was identified by test tube methods during the 1980s.[28]

The isolation of the responsible gene in 1989 relied on technological methods and did not involve animals.  From this we can now identify cystic fibrosis by DNA analysis, even before birth. [29]

Taking cells from the lungs or inside of the nose for study soon followed. These cells have been grown and have been shown to be valuable material for study.  Their supply is virtually unlimited, and has provided a superior study material to the transgenic mouse model.  As a doctor summed up:

"The animals do not exhibit the same changes in the pancreas that humans do. Neither do they face the lung infections that cystic fibrosis patients do. Considering the fact that the pancreas and the lungs are the main organs affected, one can say that the transgenic model of cystic fibrosis is a failure.  Moreover, the mice died of intestinal disorders before the lung abnormalities manifested.  This was fruitless experimentation. It was impossible to ascertain whether the gene prevented anything since animals do not get cystic fibrosis." [30]

It was a great disappointment that the eagerness with which animal experiments are considered meant that cystic fibrosis research was still done on animals, when not only was a non-animal method available, but it was an easily grown matter of human source.

The pancreatic disorders linked with the illness were discovered in humans to reduce the availability of enzymes which are essential for digestion, so patients have now been given these orally. [31]

Now the role of defective proteins in hampering the flow of salt and water through channels within cells in lungs and other organs is understood, treatments are being developed.  In a healthy person, naturally occurring antibiotics kill bacteria which is breathed in. In the CF patient, the antibiotics are too salty to be effective. Xylitol was developed in the hope that this sugar could be introduced into the lungs to improve the effect of the natural antibiotics.  It has been found to be effective in human trials and owes nothing to animal use. [32]

A discovery was made in the 1940s when studying tuberculosis patients, which later proved valuable to cystic fibrosis patients.  It was noticed that the TB sufferers could cough up the secretions on their lungs more easily if given aerosol treatments.  This has been found also to be effective in the commonly addressed problem of thinning the heavy secretions on the lungs of the CF patient.  This was later tested on rats, although this was pointless, as the human results were already known.  [33]

Dr Henry Heimlich, the doctor who gave his name to the 'Heimlich manoeuvre', has developed a device which causes a similar effect.  He has explained on many occasions "why clinical research can not only be much more successful than any animal research but how it can be done safely."  He has now developed the Micro-Trach, a simple device which stimulates a natural cough which loosens the membranes and disturbs the accumulating mucous.  After trials this device has been found to be "literally turning lives around for these children." [34]

More aerosol treatments were developed without animals by using material collected from patients and testing it against potential treatment in test tube-type experiments. [35] DNase I from slaughterhouse pigs was found to be effective, although it did cause adverse reactions.  Human DNase I is now used and is safer. [36]

Pulmozyme is a medical treatment which has been used to treat lung congestion.

That the CF sufferer's lungs were clogged with mucus rich in DNA was known since the 1950s, [37] and led to treatment with DNase, which is an enzyme which breaks down DNA. This was taken from the pancreas of slaughterhouse cattle, and caused allergic reactions in patients. [38]

In 1990 it was suspected that the large amounts of white blood cells that accumulated in the lungs to fight infection caused the release of DNA, thus worsening the mucus problem.  A review of clinical (human) studies from the 1950s led to the idea that a genetically engineered DNase might be a potential treatment. A researcher from Genetech collected a mucus sample from a colleague who was a CF sufferer, and combined it separately with a salt solution and DNase.  While kept in a water bath at body temperature, he was able to observe within minutes that the salt solution sample remained unchanged, while that mixed with DNase soon liquified.[39]

Successful human trials resulted which established dose levels, and in 1993 it was approved under the trade name Pulmozyme. [40]  No comment was made of any studies in transgenic mouse models, which implies they were either considered irrelevant, or contradicted the clinical facts. The year after approval, the US Cystic Fibrosis Foundation participated in research which showed the treatment to cause a slight improvement in lung function and a dramatic decrease in lung infections. [41]

Osteopaths are also able to treat the illness by corrective adjustment, which breaks up mucous plugs, allows greater respiration and thoracic drainage, arterial supply, venous drainage and even better neurological control of the areas of the body affected.

It is incredible, given the balance of information, that claims are being made of the success of animal experiments in fighting cystic fibrosis. There are no animal models, and the genetically altered mouse models are unworkable. Everything we know about cystic fibrosis, how it works, how it is caused, how it threatens the health and life of people, and how it can be treated, comes from clinical methods.

Lobbying organisations, paid by those who benefit financially from the continued use of animals in experiments have been effective in bringing the plight of patients suffering from CF and other conditions to the forefront.  Then, without medical or historical facts, they claim that animal experiments have been and will be the way to help these people. The truth is very different.

 Other illnesses have been the subject of high profile claims in favour of animal testing.  Read the reality here.


1 Collins,PS. Wilson,JM. 1992. Nature. vol 358. p708;  Barinaga,M. 1992. Science. vol 257. p1047.     2 Snouwaert,J N. Brigham,KK et al. 1992. Science. vol 257. pp1083-1088   3 New Scientist. 1989. 21st October. pp54-58         4 Food and Chemical toxicology, 1985;23:139-143.              5 Snouwaert,J N. Brigham,KK et al. 1992. Science. vol 257. pp1083-1088                        6 Barinaga,M. 1992. Science. vol 257. p1047          7 Barinaga,M. 1992. Science. vol 257. p1047

8 Hospital update 1994Jan       9 Snouwaert,J N. Brigham,KK et al. 1992. Science. vol 257. pp1083-1088             10 Snouwaert,J N. Brigham,KK et al. 1992. Science. vol 257. pp1083-1088                               11 Dorin,JR et al. 1992. Nature. vol 359. pp211-5 41                             12 New Scientist. 1992. 19th Sept. p6                            13 Wilson,JM. Collins,FS. 1992. Nature. vol 358. p708          14 Santia,G. Geddes,D. 1994. Postgraduate Medical Journal. vol 70. pp247-251.15 Collins,PS. Wilson,JM. 1992. Nature. vol 358. p708                   16 Snouwaert,J N. Brigham,KK et al. 1992. Science. vol 257. pp1083-1088           17 Dorin,JR et al. 1992. Nature. vol 359. pp211-5

18 Ratcliffe,R et al. 1993. Nature Genetics. vol 4. pp35-41                     19 Ratcliffe,R et al. 1993. Nature Genetics. vol 4. pp35-41     20 Ratcliffe,R et al. 1993. Nature Genetics. vol 4. pp35-41              21 Santia,G. Geddes,D. 1994. Postgraduate Medical Journal. vol 70. pp247-251    22 Snouwaert,J N. Brigham,KK et al. 1992. Science. vol 257. pp1083-1088     23 Snouwaert,J N. Brigham,KK et al. 1992. Science. vol 257. pp1083-1088                           24 Dorin,JR et al. 1992. Nature. vol 359. pp211-5                        25 Santia,G. Geddes,D. 1994. Postgraduate Medical Journal. vol 70. pp247-251.                   26 Pediatrics 1953;12:549-563

27 Pediatrics, 1953; 12:549-563 & 1951; 8:648-656              28 American Journal of Physiology 1991;261:491-4 & Proc Nat Acad Sci 1992; 89:5171-75                29 New England Journal of Medicine1990;322:291-6             30 Dr C R Greek, Americans For Medical Advancement 2002                31 New England Journal of Medicine 1981;305:1489-93, Persp Ped Path 1976;2:241-278, Arch Dis Child 1991;66:698-701                                            32 New England Journal of Medicine 1981;305:1489-93

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