gene therapy technique was developed involving a
drug-activated response. Genetically engineered with
a self-destruction signal, these "suicide" genes are
genetically altered to include a sequence that, when
triggered by a drug, will make the cell toxic.
Although attempting to sift out all the mature T
lymphocytes would make the procedure far safer,
practicalities leave it far behind. If a transplanted
bone marrow' s T-cells begin to attack the host' s
body, the drug can be administered and the foreign
cells will be destroyed before graft-versus-host
disease can develop.(2) Taking this procedure,
otherwise known as "prodrug activation" , a step
further could lead us to an entirely new approach to
curing diseases such as cancer. By introducing this
toxic gene expression into cancer cells, they can be
destroyed by administering the corresponding drug.
T his experiment was successfully conducted in mice,
where the prodrug gancyclovir triggered the
expression of the herpes virus thymidine kinase. Not
only did the cells containing the new sequence die,
but even neighboring cancer cells were observed to
die due to a bystander effect.
T he ability to express an introduced gene at any time
and for any duration by simply swallowing a pill
makes this type of gene therapy very practical; it
would offer an attractive and controlled form of
administering therapeutic proteins such as
monoclonal antibodies, interferons and even certain
growth factors . Adding a coding sequence to a cell is
the standard method of conducting gene therapy,
and has been most successful, but new approaches
take a more complex approach towards curing
disease. By actually altering the genetic sequence,
instead of simply supplementing it, genetic therapy
may be even more powerful in eliminating disease.
An approach to defeating such diseases as HIV,
hepatitis B, and hepatitis C involves using a
r i bozyme molecule to cut and destroy certain RNA
molecules that correspond to the particular virus.(1 )
An even more complicated approach involves
repairing the gene using chimeric oligonucleotides.
Homologous recombination is the natural process
that controls the replacement of a defective gene.
Gene therapy can harness this natural process and
have the body repair its DNA itself. DNA repair is
highly precise, and by using DNA oglionucleotides to
introduce site-specific changes in the genome, a
s ingle incorrect base can be corrected.
Diseases like sickle-cell anemia, that are caused by a
s ingle point mutation, are prime candidates for this
gene therapy Experimentation on mice have
provided promises.(3) Unfortunately, transferring the
chimeric oglionucleotide is very inefficient and must
be improved on to make the process practical.(4)
As strategies for local expression of the genetically
altered cells are developed, even more new
possibilities are opened. Arthritis patients could
release an anti-inflammatory response from proteins
in inflamed joints , and asthma sufferers could
s imilarly reduce the inflamation associated with their
ailment. Bio-artificial organs have been proposed,
and even tested in some animal trials, that could be
transplanted in whole and serve as centers for
producing particular proteins.( 1 )
Even certain aspects of the vector delivery system
for the sequences make interesting use of certain
diseases . The HI V virus and its ability to infect non-
dividing cells could be a boon for medicine. With this
ability, HIV could emerge as a very effective viral-
vector for delivery into even dormant cells, such as
neur ons , can be infected without instigating a heavy
immune response.(5) In tests with mice, the
expression was efficient and stable.(6) A deep
concern, of course, accompanies the use of HIV in
any form, and its safety would have to be thoroughly
confirmed before its use could proceed. Many of the
issues associated with gene therapy go far beyond
the scientific and medical ones.
A topic, where much of the ethical concern within
gene therapy has pooled, is the in utero use of gene
therapy. Correcting genetic defects in a fetus before
birth could allow many children to be born that
otherwise would never have survived, and many to
live a longer and more enjoyable life than would
otherwise be possible. Tests to cure homozygous
thalassemia, a hemoglobin disorder that would
normally kill the fetus before birth, and a severe
immunodeficiency due to a lack of the adenosine
deaminase enzyme are some of the first tests
planned.(7) However, a new risk is created-the
possibility that transplanted genes could end up in
the germ line and then be passed on to future
generations . Fears like thes e become even more real
when we consider how thin a line exists between
reality and ethics of gene therapy.
Can the benefits of such therapy be passed on to the
future generations? The current protocols are meant
for only somatic cells and hence would be apt to
name it "Somatic Gene Therapy" . However, if the
introduction of a tumor suppressor gene into a germ
line cures cancer permanently down the generations
forthcoming, it would perhaps be more acceptable
than somatic cell protocols.
Conclusion
What should this mean to the scientists and the
public today? S hould research be stopped in fear of
the possible abuses of such abilities? T his is the
same question science has asked itself many times
before, and gene therapy is no different. Genetic
technology poses risks along with its rewards, just as
any technology has in the past. To stop its
development and forfeit the benefits gene therapy
could offer would be a far greater mistake than
forging ahead could ever be. People must always try
to be responsible with their new technology, but
gene therapy has the potential to be the future of
medicine and its possibilities must be explored. If
one could permanently correct a mutation such as
those causing S ickle cell anaemia or Cystic Fibrosis
(8) in the germ line of an individual, giving the
additional benefit of keeping the future generations