Gene Therapy

This is perhaps the most significant, and most controversial kind of genetic engineering.
It is also the least well-developed. The idea of gene therapy is to genetically alter
humans in order to treat a disease. This could represent the first opportunity to cure
incurable diseases. Note that this is quite different from using genetically-engineered
microbes to produce a drug, vaccine or hormone to treat a disease by conventional
means. Gene therapy means altering the genotype of a tissue or even a whole human.

Cystic Fibrosis (you must

learn this one!)
Cystic fibrosis (CF) is the most common genetic disease in the UK, affecting about 1 in
2500. It is caused by a mutation in the gene for protein called CFTR (Cystic Fibrosis
Transmembrane Regulator). The gene is located on chromosome 7, and there are
actually over 300 different mutations known, although the most common mutation is a
deletion of three bases, removing one amino acid out of 1480 amino acids in the
protein. CFTR is a chloride ion channel protein found in the cell membrane of epithelial
(lining) tissue cells, and the mutation stops the protein working, so chloride ions cannot
cross the cell membrane.
Chloride ions build up inside these cells, which cause sodium ions to enter to balance
the charge, and the increased concentration of the both these ions inside the epithelial
cells decreases the osmotic potential. Water is therefore retained inside the cells, which
means that the mucus secreted by these cells is drier and more sticky than normal. This
sticky mucus block the tubes into which it is secreted, such as the small intestine,
pancreatic duct, bile duct, sperm duct, bronchioles and alveoli.
These blockages lead to the symptoms of CF: breathlessness, lung infections such as
bronchitis and pneumonia, poor digestion and absorption, and infertility. Of these
symptoms the lung effects are the most serious causing 95% of deaths. CF is always
fatal, though life expectancy has increased from 1 year to about 20 years due to modern
treatments. These treatments include physiotherapy many times each day to dislodge
mucus from the lungs, antibiotics to fight infections, DNAse drugs to loosen the mucus,
enzymes to help food digestion and even a heart-lung transplant.
Given these complicated (and ultimately unsuccessful) treatments, CF is a good
candidate for gene therapy, and was one of the first diseases to be tackled this way. The
gene for CFTR was identified in 1989 and a cDNA clone was made soon after. The idea
is to deliver copies of this good gene to the epithelial cells of the lung, where they can
be incorporated into the nuclear DNA and make functional CFTR chloride channels. If
about 10% of the cells could be corrected, this would cure the disease.
Two methods of delivery are being tried: liposomes and adenoviruses, both delivered
with an aerosol inhaler, like those used by asthmatics. Clinical trials are currently
underway, but as yet no therapy has been shown to be successful.

Advantages and disadvantages

The Pros:

The most important factor in the development of gene therapy is the fact that, for genetic
disorders, there is only one way of curing the disease replacing the defective gene with
a healthy copy and therefore gene therapy is the only hope of finding cures for such
disorders

If gene therapy targets the reproductive cells of carriers of such genetic disorders as
cystic fibrosis, Parkinsons disease, or cancer, it is possible that any children the carrier
goes on to have would be free of the defective gene and on a bigger scale the disease can
be wiped out completely

Gene therapy, when successful, can have a number of advantages over drug therapy such
as providing a cure rather than easing the symptoms. These advantages are discussed in
detail in the section Advantages of Gene Therapy.

The Cons:
Issues based on the science behind gene therapy:

The current lack of knowledge and understanding of the treatment means that its safety is
unknown. The current scientific understanding is based on theory rather than solid fact.
This, however, can be improved with further research and practice.

In clinical trials already carried out the effects of the treatment have only been shortlived. To achieve long term results much more research is needed.

Drug therapy, although not offering the possibility of a cure, is a tried and tested method
and is therefore deemed safer

With current knowledge there is no guarantee that the vector carrying the healthy gene
will end up in the specific place it is intended there is a risk of causing even more
damage to the genetic make-up that can result in severe consequences for the patient

Ethical, religious and moral issues:

The intrusive nature of gene therapy means that we can discover information about our
genetic make-up that some would say we are never meant to know. From genetic
screening we can find out if we are at any significant risk of certain diseases. For some,
this knowledge could have a negative impact on their lives and if that knowledge was to
influence any life decisions in a negative way then it is questionable whether genetic
screening is morally correct.

Genetic screening can also be carried out on unborn babies if this screening showed
that a child was carrying a disease this may lead to the parents deciding to abort the child.
This is clearly a very morally questionable act as many would argue that a person does
not have the right to play God with another persons life.

Similarly, a couple who are aware of their genetic make-up and know that theyre both
carriers of a specific genetic disorder may decide against having children to avoid passing
on the defective gene. Again, many would argue that this goes against the natural order.

Gene therapy has the potential to be misused for instance the concept of designer
babies, where specific genes are selected in order to create the perfect child, can be
compared to Hitlers attempts to create a superior race.