BIOTECHNOLOGICAL APPLICATIONS IN MEDICINE
The recombinant DNA technological processes have made immense impact
in the area of healthcare by enabling mass production of safe and more
effective therapeutic drugs. Further, the recombinant therapeutics do not
induce unwanted immunological responses as is common in case of
similar products isolated from non-human sources. At present, about
30 recombinant therapeutics have been approved for human-use the
world over. In India, 12 of these are presently being marketed.
Genetically Engineered Insulin
Management of adult-onset diabetes is possible by taking insulin at
regular time intervals. What would a diabetic patient do if enough
human-insulin was not available? If you discuss this, you would soon
realise that one would have to isolate and use insulin from other animals.
Would the insulin isolated from other animals be just as effective as
that secreted by the human body itself and would it not elicit an immune
response in the human body? Now, imagine if bacterium were available
that could make human insulin. Suddenly the whole process becomes
so simple. You can easily grow a large quantity of the bacteria and make
as much insulin as you need.
Think about whether insulin can be orally administered to diabetic
people or not. Why?
Insulin used for diabetes was earlier extracted from
pancreas of slaughtered cattle and pigs. Insulin from an
animal source, though caused some patients to develop
allergy or other types of reactions to the foreign
protein. Insulin consists of two short polypeptide
chains: chain A and chain B, that are linked together by
disulphid bridges(Figure-1). 
In mammals, including
humans, insulin is synthesised as a pro-hormone (like a
pro-enzyme, the pro-hormone also needs to be processed
before it becomes a fully mature and functional hormone)
which contains an extra stretch called the C peptide.
This C peptide is not present in the mature insulin and is
removed during maturation into insulin.The main
challenge for production of insulin using rDNA techniques
was getting insulin assembled into a mature form. In
1983, Eli Lilly an American company prepared two DNA sequences
corresponding to A and B, chains of human insulin and introduced them
in plasmids of E. coli to produce insulin chains. Chains A and B were
produced separately, extracted and combined by creating disulfide bonds
to form human insulin.
Gene Therapy
If a person is born with a hereditary disease, can a corrective therapy
be taken for such a disease? Gene therapy is an attempt to do this.
Gene therapy is a collection of methods that allows correction of a
gene defect that has been diagnosed in a child/embryo. Here genes
are inserted into a person’s cells and tissues to treat a disease.
Correction of a genetic defect involves delivery of a normal gene into
the individual or embryo to take over the function of and compensate
for the non-functional gene.
The first clinical gene therapy was given in 1990 to a 4-year old girl
with adenosine deaminase (ADA) deficiency. This enzyme is crucial for
the immune system to function. The disorder is caused due to the deletion
of the gene for adenosine deaminase. In some children ADA deficiency
can be cured by bone marrow transplantation; in others it can be treated
by enzyme replacement therapy, in which functional ADA is given to the
patient by injection. But the problem with both of these approaches that
they are not completely curative. As a first step towards gene therapy,
lymphocytes from the blood of the patient are grown in a culture outside
the body. A functional ADA cDNA (using a retroviral vector) is then
introduced into these lymphocytes, which are subsequently returned to
the patient. However, as these cells are not immortal, the patient requires
periodic infusion of such genetically engineered lymphocytes. However, if
the gene isolate from marrow cells producing ADA is introduced into cells
at early embryonic stages, it could be a permanent cure.
