Cystic Fibrosis and Gene Therapy

Jennifer Senn

Copyright 1998


The average life span of a person with Cystic Fibrosis is 25-30 years of age. Although the more traditional treatments of this disease are adequate, is there something else that could be even better? Gene therapy is fast becoming one of the more studied aspects of genetics today. Let's take a look at some details of Cystic Fibrosis and gene therapy.

Technical Aspects

Cystic Fibrosis (CF) is the most common fatal genetic disease in the United States today. CF is an autosomal recessive disease that occurs approximately one out of 3,300 live births (Cystic Fibrosis Foundation, 1998). Autosomal means that the gene for CF is not carried on the sex chromosomes and males and females are both afflicted by this disease. Recessive inheritance is when both parents "carry" the abnormal gene in their DNA but they themselves do not show evidence of the disease. The mother and father have one normal gene and one abnormal gene and don't show signs of disease because the normal gene dominates the abnormal gene. To have CF, a child must inherit two abnormal genes, one from each parent. Remember that chromosomes are made up of DNA or deoxyribonucleic acid. DNA is made up of genes, and genes are made up of building blocks called base pairs. The specific gene responsible for CF was identified in 1989 on human chromosome 7 (Pseudomonas Genome Project, 1998). A mutation, or change in the genetic material, resulting in a substitution or loss of one of the base pairs causes the CF gene to be abnormal (Cystic Fibrosis Foundation, 1995).

CF does not affect all people the same way. The basic problem for all patients however is an abnormality in glands, which produce mucus or sweat. The mucus produced by people with CF is thick and sticky instead of thin and watery. The major systems most affected by CF are the respiratory and the digestive. In the respiratory system, the mucus causes breathing difficulties, frequent respiratory infections and eventually permanent lung damage. The mucus builds up providing bacteria with a place to flourish. The most common infection comes from a bacterium called Pseudomonas aeruginosa. The body's response to P. aeruginosa includes inflammation, which causes episodes of intense breathing problems (Pseudomonas Genome Project, 1998). Normally the body will get rid of excess mucus by coughing before it's a problem but with the thick mucus involved in CF the body has a harder time to get rid of the thicker mucus. Lung disease is the usual cause of death in most patients (National Institutes of Health, 1995). In the digestive system, mucus can block the supply of enzymes used to break down food. The result of the blockage of such enzymes is malnutrition. The patient will have an excessive appetite but will not experience any weight gain. What is also evident is a failure to grow, CF was often misdiagnosed vaguely as "failure to thrive" when physicians didn't know the reason for this poor growth. Sweating is also a problem in people with CF. One of the basic defects in CF is the faulty transport of sodium and chloride (salt). People with CF lose excessive amounts of salt when they sweat. This causes the natural balance of salt in the body to be off balance, which may cause abnormal heart rhythms (National Institutes of Health, 1995).

For most people, diagnosis of CF is usually made within the first three years of life (Cystic Fibrosis Foundation, 1995). Although CF is present at birth, the symptoms don't always show up right away or are often confused with other childhood illnesses. The most common way to diagnose CF is by the sweat test. Because CF causes abnormal levels of salt in sweat, the salt content is measured. If the test shows a high salt content, this is a positive test for CF. The sweat test can be used only to determine whether or not a person has CF. There is no relationship between the salt level in the sweat and the severity of the disease (Cystic Fibrosis Foundation, 1995).

The traditional treatments of CF depend on the severity of the disease and the organs involved. When the lungs are involved, chest physical therapy is used. This involves vigorous percussion on the back using cupped hands to dislodge the thick mucus from the lungs (Cystic Fibrosis Foundation, 1995). Varying the positions of the patient and where the therapy is given drains the mucus from various parts of the lung. Antibiotics are also sometimes given to help with the respiratory infections that might occur. Antibiotics may be given orally (pills), through IV (intravenously), or by the use of medicated inhalers. When the digestive system is involved and the patient isn't getting enough nutrients, they may have to eat a diet rich in nutrients. They may also have to take supplements to replace the enzymes needed to digest. All of these treatments are traditional ones that are widely accepted by the general public. Since the gene causing CF was discovered, treatment of this disease may come from a more 'untraditional' method.

Here enters gene therapy. Gene therapy offers the best hope for a life-saving treatment by tackling the root cause of CF, rather than only treating the symptoms (Cystic Fibrosis Foundation, 1998). The basic concept behind gene therapy is to identify the defective gene and to correct the defect with a normal gene. There are two forms of gene therapy that may be used as a method of treatment. The first is called germ line gene therapy. This form not only helps the individual being treated, but also his or her children as well. Germ line therapy would change the genetic pool and future generations would have to live with that change (Genentech Inc., 1998). The other form of therapy is called somatic gene therapy. Somatic means of, relating to or affecting the body. This therapy involves changing the defective gene in the individual but the change won't be inherited by the next generation. Somatic gene therapy would be the therapy of choice since it doesn't have the ethical considerations that germ line therapy creates.

The defective gene in the case of CF carries the code for a protein called the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). This protein regulates the movement of salt and water in and out of cells and the alteration of this protein is what causes the thick, sticky mucus typical of CF (Pseudomonas Genome Project, 1998). In theory, this defective gene would be replaced by a gene that was normal and this protein would then be able to do what it's suppose to do. However, gene therapy comes with some limitations as well as abilities. One of the first limitations is how to get the 'normal' gene to replace the defective one. Replacing the defective gene in one cell wouldn't be good enough since there is more than one cell involved in the disease. Once the corrected gene was inserted into the cell, the next problem is getting it to go to the right place. Each cell in the human body contains 22 pairs of autosomal chromosomes, or chromosomes that are not associated with sex chromosomes. Remember that the gene for CF is found only on chromosome 7. To do this, gene delivery vehicles called vectors, which contain the corrected gene, are used. The first vector used was an attenuated or weakened adenovirus. Adenoviruses are responsible for a number of respiratory illnesses but since they are weakened they are harmless to use for gene therapy. The use of this virus was the first evidence that it's possible to get the healthy gene for CF into the lungs (Fackelmann, 1994).

Now that there is a way to get the gene into a patient, there is still the problem of getting it to go to the right spot on the chromosome. For the most part, the healthy gene will insert itself randomly in the cell DNA. The new gene might alter the phenotype, or the expression, of the gene because of changes in the position or chromosomal environment of the gene. This is called position effect (McClean, 1997). Depending on where the new gene inserts, since it is a random insertion, it can be harmful or helpful. Before gene therapy can be used to treat CF patients, researchers must find a better way to deposit these healthy genes into the body. The first gene therapy experiments involve lung cells because they are readily accessible and lung damage is the most life-threatening problem. Researchers know that the gene can be safely transferred into CF airways of the lungs and will express itself. They now need to take information from experiments and refine the delivery methods to carry healthy genes to damaged cells in other organs affected by CF (Cystic Fibrosis Foundation, 1998).

Pros and cons

The obvious con of gene therapy involves the germ line therapy. This therapy not only changes the gene expression for the individual but it also affects following generations. No one knows what this will do to the gene pool that exists afterwards. Another con would be that researchers aren't sure how long the results of gene therapy will work. They also don't know how often the therapy would have to be repeated to get results. As of now, the technology being used isn't adequate enough for gene therapy to be used in people for a range of diseases. All gene therapy at this stage is experimental and cannot be used for any disease. Another point that should be made is about the ethics involved in changing a human beings make-up. Is this the right thing to do, even though it may help a person afflicted with CF?

A pro of gene therapy is that it doesn't cover up what's wrong but fixes the 'problem'. It has the capability of producing a normal life for the individual that receives the therapy. Another pro is that gene therapy is a fast growing field of its own and more and more is learned about it every day. The technology is there to develop it, so the technology is there to bring it to life. When gene therapy can be actively used, it will be regulated to prevent unnecessary treatment that may be harmful to the patient. Part of the Hippocratic Oath states, "that I will lead my life and practice my art in uprightness and honour; that into whatsoever house I shall enter, it shall be for the good of the sick to the utmost of my power...that I will exercise my art solely for the cure of my patients".

Personal Opinion

My opinion about gene therapy is somewhat on the pro side and a little on the con side. First of all, I don't believe that gene therapy should be used in cases where the disease can be helped by traditional methods. I think that gene therapy should be a last resort, used by doctors when all else fails. A sort of last ditch approach to what may be a cure. I don't believe that prospective parents who want to decide what 'kind' of baby they want should use it. If such parents want a blonde-haired, blue-eyed baby, one of the parents should be that way and they should just play the odds. Gene therapy shouldn't be used to manipulate the genetic make-up of an individual for personal gain. Instead gene therapy should be used to help an individual afflicted with a disease that is fatal. CF is just one example. If they could find someway to use gene therapy for AIDS patients, I'm all for it. If it can further a person's life and enhance life for a person that would otherwise have no chance, gene therapy may be their only answer.

The whole issue of cloning is taking this technology too far. The human race will survive the best way it can, I believe in survival of the fittest. A species is balanced so that everything is in its place and there is harmony. When you start messing around with a gene pool that is doing okay on its own, why mess with it? I believe that all things natural happen for a reason. Who are we to change that? What makes us so superior as to change the natural force of things? If gene therapy helps an individual to live, use it. Otherwise, just leave well enough alone.


  1. Fackelmann, K. A. "Gene Therapy for CF Reaches Human Lungs." Science News. Sept. 3, 1994: v149, n 10, p. 149 (1).
  2. National Institutes of Health: National Heart, Lung, and Blood Institute (1995). "Facts about Cystic Fibrosis". NIH Publication #95-3650.
  3. Cystic Fibrosis Foundation, "Facts about Cystic Fibrosis." Obtained from the WWW 10/31/98: (A HREF="">
  4. Cystic Fibrosis Foundation, "Gene Therapy". Obtained from the WWW 10/31/98:
  5. Genentech Incorporated, "Gene Therapy-An Overview". Obtained from the WWW 10/31/98:
  6. McClean, Phillip. "Variation in Chromosome Structure". Obtained from the WWW 10/15/98:
  7. Pseudomonas Genome Project, "Cystic Fibrosis". Obtained from the WWW 10/31/98:
  8. Cystic Fibrosis Foundation, "An Introduction to Cystic Fibrosis for Patients and Families" in Respiratory Diseases and Disorders Sourcebook". Health Reference Series, V. 6, 1995. Sect. 5.1, p. 240.
  9. WWWebster Dictionary. Obtained from the WWW 11/2/98:

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