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Introduction
Biotechnology is technology based on biology, especially
when used in agriculture, food science and medicine.
Principles of Biotechnology
The two core techniques that enabled us to combine the
genetic elements of two or more living cells or that enabled
birth of modern biotechnology are:
(i). Genetic Engineering: Techniques to alter the
chemistry of genetic material (DNA and RNA), to introduce
these into host organisms and thus change the phenotype of
the host organism. The recombinant DNA thus created is
called rDNA or chimeric DNA which has properties of DNA
from multiple sources.
Recombinant DNA
Technology
Recombinant DNA technology alters the phenotype of an
organism (host) through a genetically altered vector. This
cloning vector is introduced and integrated into the genome of
the organism. So, basically, the process involves the
introduction of a foreign piece of DNA into the genome which
contains our gene of interest. The gene which is introduced is
the recombinant gene and the technique is called the
recombinant DNA technology. Here we will learn about key
tools of recombinant DNA technology.
Biotechnological
Application in
Medicine
The recombinant DNA technological processes have made
immense impact in the area of healthcare. The most obvious
commercial applications are diagnosis of disease and
commercial production of pharmaceuticals for disease
therapy, valuable proteins (enzymes or hormones), gene
therapies and powerful vaccines. Genetically engineered
bacterial cells are grown in vats to obtain proteins or drugs at
commercial scale such as human insulin, human growth
hormone, etc. RDT enables mass production of safe and more
effective therapeutics
do not induce unwanted
immunological
responses. At present,
about 30 recombinant
therapeutics have been
approved globally and
12 of these are presently
being marketed in India
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 gene clinical gene therapy was given in 1990 to a
4year 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 permanent
cure.
Molecular Diagnosis:
For effective treatment of a disease, early diagnosis and
understanding the path physiology is very important.
The term diagnosis refers to the act or process of determining
the nature and cause of a disease through evaluation of
patient history, examination and review of laboratory data. In
short, diagnosis is what the disease is
For e.g. you can have a diagnosis of asthma.
Pathophysiology is the study of changes in normal,
mechanical, physical and biochemical functions caused by a
disease
Presence of a pathogen (bacteria viruses) is normally
suspected only when the pathogen has produced disease
symptoms. By this time, the conc. of pathogen is already
very high in the body. Methods of detection fall under two
categories:
Methods of Diagnosis
Traditional Modern
Transgenic Animals:
Animals that had their DNA manipulated to possess and
express an extra gene are known as transgenic animals. The
genome of their animals has been changed and they can carry
genes from other species. Examples of transgenic animals
include rats, rabbits, pigs, sheep, cow, monkey and fish
although over 95% transgenic animals are mice.
How are transgenic animals produced?
1. DNA microinjection
2. Retrovirus-mediated gene transfer
3. Embryonic stem cell mediated gene transfer.
Why are these transgenic animals being produced?
1. Some transgenic animals are produced for specific
economic trait.
2. Other transgenic animals are produced as disease
models (animals genetically manipulated to exhibit
disease symptoms so that effective treatment can be
studied.
Benefits from
transgenic animals
can be studied under
3 heads
Cows that
produce
Medicine human
protein
enriched
milk
Larger
sheep that
Agriculture grow more
wool.
Goats that
produce
Industry spider milk
for
material
production
1. Medicine:
Normal physiology and development: Transgenic
animals can be specifically designed to allow the study
of how genes are regulated, and how they affect the
normal functions of the body and its development E.g.,
Study of complex factors involved in growth such as
insulin-like growth factor. By introducing genes from
other species that alter the formation of this factor and
studying the biological effects that result, information
is obtained about the biological role of the factor in the
body.
Study of disease: Many transgenic animals are
designed to increase our understanding of how genes
contribute to the development of disease. These are
specially made to serve as models for human diseases
so that investigation of new treatment for diseases is
made possible. Toady transgenic models exist for many
human diseases such as cancer, cystic fibrosis,
rheumatoid arthritis and Alzheimer’s
Biological Products: Medicines required to treat
certain human diseases can contain biological products,
but such products are often expensive to make.
Transgenic animals that produce useful biological
products can be created by the introduction of the
portion of DNA (or genes) which codes for a particular
product such as human protein (-1-antitrypsin) used
to treat emphysema. Similar attempts are being made
for treatment of phenylketonuria (PKU) and cystic
fibrosis. In 1997, the
first transgenic cow,
Rosie, produced human
enriched protein milk.
The milk contained the
human alpha-
lactalbumin and was
nutritionally a more balanced product for human babies
than natural cow milk
Vaccine Safety: Transgenic mice are being
developed for use in testing the safety of vaccines
before they are used on humans. Transgenic mice are
being used to test the safety of the polio vaccine. If
successful and found to be reliable, they could replace
the use of monkeys to test the safety of batches of the
vaccine.
Chemical Safety Testing: This is known as
toxicity/safety testing. The procedure is the same as
that used for testing toxicity of drugs. Transgenic
animals are made that carry genes which made them
more sensitive to toxic substances than non- transgenic
animals. They are then
exposed to the toxic
substances and the effects
studied. Toxicity testing in
such animals will allow us to
obtain results in less time.
2. Agriculture:
I. Breeding: Farmers have
always used selective breeding to produce animals that
exhibit desired traits. Traditional breeding is a time
consuming difficult task. When technology using
molecular biology was developed, it becomes possible
to develop traits in animals in a shorter time and with
more precision. In addition, it offers the farmer an easy
way to increase yields.
II. Quality: Transgenic cows exist that produce more
milk with less lactose or cholesterol, pigs and cattle
that have more meat on them, and sheep that grow
more wool. In the past, farmers used growth hormones
to spur the development of animals but the technique
was problematic, especially since residue of the
hormones remained in the animal product.
III. Disease resistance: Scientists are attempting to
produce disease resistant animals, such as influenza
resistant pigs, but a very limited number of genes area
currently known to be responsible for resistance to
diseases in farm animals.
Ethical Issues:
Bioethics:
Ethics includes a set of standards by which a community
regulates its behaviour and decides as to which activity is
legitimate and which is not. Therefore, bioethics may be
viewed as a set of standards
that may be used to regulate
our activities in relation to
the biological world.
The manipulation of living
organisms by the human race
cannot go on any further,
without regulation. Some
ethical standards are
required to evaluate the
morality of all human
activities that might help or
harm living organisms.
Going beyond the morality of
such issues, the biological significance of such things is also
important. Genetic modification of organisms can have
unpredictable results when such organisms are introduced into
the ecosystem.
Therefore, the Indian Government has set up a organisations
such as (Genetic Engineering Approval Committee) which
will make decisions regarding the validity of GM research and
the safety of introducing Gm-organisms for public services.
The major bioethical concerns pertaining to biotechnology
are summarized below:-
I. Use of animals in biotechnology causes great
suffering to them.
II. When animals are used for production of
pharmaceutical proteins, they are virtually reduced to
the status of a ‘factory’
III. Introduction of transgenic from one species into
‘integrity of species’
IV. Transfer of human genes into animals(and vice
versa) dilutes the concept of ‘humanness’
V. Biotechnology is disrespectful to living beings, and
only exploits them for the benefit of human beings.
VI. Biotechnology may pose unforeseen risk to the
environment including risk to biodiversity.
Patent:
A set of exclusive
rights granted by
state(national
government) to an
inventors or their
assignee for a limited
period of time in
exchange for a public
disclosure of an
invention. Patents are
supposed to satisfy three criteria of – Novelty, non-
obviousness and utility.
Novelty implies that the innovation must be new. It
cannot be part of ‘prior art’ or existing knowledge. Non-
obviousness implies that it may not be documented but is
otherwise well-known. The discored fact or product
should be of a particular use for the human beings.
A patent is granted for
a) an invention(including a product)
b) an improvement in an earlier invention
c) the process of generating a product
d) a concept or design
Initially, patents were granted for industrial inventions,
etc, but at present, patents are being granted for biological
entities and for products derived from them; these patents are
called biopatents. Primarily, industrialised countries, like
U.S.A., Japan and members of European Union, are awarding
Biopatents.
There is growing public anger that certain companies are
being granted patents for products and
technologies that make use of the genetic
materials, plants and other biological
resources that have long been
identified, developed and used by
farmers and indigenous people of a
specific region/country.
Rice is an important food grain, the presence of which
goes back thousands of years in Asia’s agricultural history.
There is an estimated 200,000 varieties of rice in India alone.
The diversity of rice in India is one of the largest in the world.
Basmati rice is distinct for its aroma and flavour and 27
documented varieties of Basmati are grown in India. There is
reference to Basmati in ancient texts, folklore, and poetry, as
it has been grown for
centuries.
Biopriacy is the term used
to refer to the use of bio-
resource by multinational
companies and other
organisations without proper
authorisation from the
countries and people
concerned without
compensatory payment
The Indian Parliament has recently cleared the second
amendment of the Indian Patents Bill that takes such issues
into consideration, including patent terms emergency
provisions and research and development initiative.
Case Study-1
Case Study: Herceptin (Trastuzumab) - A Breakthrough in
Breast Cancer Treatment
Background:
Herceptin, also known by its generic name Trastuzumab, is a
monoclonal antibody therapy used in the treatment of HER2-
positive breast cancer. HER2 (human epidermal growth
factor receptor 2) is a protein tha t promotes the growth of
cancer cells. HER2-positive breast cancer is more aggressive
and less responsive to traditional treatments. The
development of Herceptin represents a significant milestone
in biotechnology and medicine.
Development and Manufacturing:
Herceptin was developed using
biotechnological techniques.
Monoclonal antibodies are produced
by cloning a single type of immune
cell to create a uniform, targeted
therapy. The process involves
identifying and selecting the specific
antibodies that can bind to the HER2
protein, inhibiting its activity.
Herceptin was developed by Genentech, a biotech company,
and was approved by the FDA in 1998.
Mechanism of Action:
Herceptin works by binding to the HER2 receptor, preventing
it from promoting cancer cell growth. It also stimulates the
immune system to attack HER2-positive cancer cells. This
targeted approach minimizes harm to healthy cells, reducing
side effects compared to traditional chemotherapy.
Clinical Efficacy:
Clinical trials demonstrated that Herceptin significantly
improved survival rates and reduced the risk of cancer
recurrence in HER2-positive breast cancer patients. This
marked a breakthrough in breast cancer treatment, offering
new hope to patients with this aggressive form of the disease.
Market Impact:
Herceptin became one of the best-selling biotech drugs in the
world. Its success had a profound impact on the biotechnology
and pharmaceutical industry, showcasing the potential of
personalized medicine and targeted therapies. It also paved
the way for the development of other monoclonal antibody-
based drugs for various diseases.
Challenges and Controversies:
The high cost of Herceptin raised issues of accessibility and
affordability for patients. Furthermore, there were concerns
about potential side effects, which led to ongoing research to
optimize treatment regimens.
Ongoing Research and Future Prospects:
Herceptin's success has inspired ongoing research in
biotechnology and oncology. It has served as a foundation for
the development of other HER2-targeted therapies and
expanded its use to other cancers. Additionally, research into
improving the safety and efficacy of monoclonal antibody
therapies continues.
Conclusion:
The case of Herceptin exemplifies the significant impact of
biotechnology in medicine. Monoclonal antibody therapies
like Herceptin have transformed the treatment landscape for
HER2-positive breast cancer patients and have influenced the
development of numerous other biotech drugs. The success of
Herceptin underscores the potential of biotechnology to
provide targeted, more effective, and less harmful treatments,
leading the way to a brighter future in medicine. However,
addressing challenges related to cost and access remains a
critical issue for the
broader adoption of
such
biotechnological
breakthroughs in
healthcare.
Case
Study-2
Case Study: Gene Therapy for Cystic Fibrosis
Background:
Cystic fibrosis (CF) is a life-threatening genetic disorder that
affects the respiratory and digestive systems. It is caused by
mutations in the CFTR gene, which results in the production
of defective CFTR proteins. These proteins are responsible for
regulating the flow of salt and fluids in and out of cells,
particularly in the respiratory and digestive tracts. Patients
with CF experience thick, sticky mucus build-up in their
airways, leading to chronic lung infections and breathing
difficulties.
Gene Therapy Approach: Researchers in the field of
biotechnology have developed a gene therapy approach to
treat cystic fibrosis. The primary goal of this approach is to
introduce a functional CFTR gene into the affected cells,
allowing them to produce normal CFTR proteins. The steps
involved in this gene therapy case study include:
Identifying the Genetic Mutation: First, scientists identify the
specific mutation in the CFTR gene responsible for the
patient's condition. Understanding the genetic basis of the
disease is crucial for designing a targeted therapy.
Developing a Delivery System: Biotechnologists develop a
viral vector, often based on adeno-associated viruses (AAVs),
that can safely transport the functional CFTR gene into the
patient's cells. These viral vectors are engineered to be non-
pathogenic and efficient at delivering the therapeutic gene.
Clinical Trials: Before the therapy is available to the general
public, it undergoes rigorous testing in clinical trials. Patients
with CF who meet the eligibility criteria participate in these
trials, where the gene therapy is administered, and its safety
and efficacy are assessed.
Administration of Gene Therapy: During the gene therapy
procedure, the viral vector carrying the functional CFTR gene
is introduced into the patient's airway cells, either through
inhalation or direct administration to the respiratory tract.
Monitoring and Follow-Up: Patients are monitored closely
after the gene therapy to assess its effectiveness and safety.
Key indicators, such as lung function and mucus production,
are evaluated over time.
Results and Outcomes: This gene therapy case study for
cystic fibrosis has shown promising results. Several clinical
trials have demonstrated improved lung function, reduced
pulmonary exacerbations, and enhanced quality of life for
patients receiving the treatment. While gene therapy for cystic
fibrosis is still undergoing refinement and regulatory
approval, it offers great hope for individuals with this life-
altering genetic disorder.
Challenges and Future Directions: Despite the success of
this biotechnological approach, there are challenges to
address, such as the long-term durability of the therapy,
potential immune responses, and variability in patient
responses. Additionally, ensuring the therapy is accessible and
affordable for all patients remains a significant concern.
As biotechnology continues to advance, it is likely that gene
therapy and other innovative approaches will further
transform the landscape of medicine, offering hope for
patients with genetic disorders like cystic fibrosis and many
others.
Conclusion: This case study illustrates the significant role of
biotechnology in medicine, with a focus on gene therapy for
cystic fibrosis. It exemplifies how biotechnological
advancements have the potential to revolutionize treatment
options for patients with genetic disorders and underscores the
importance of ongoing research, clinical trials, and regulatory
processes in bringing these therapies to the mainstream
medical practice.
Conclusion
Biotechnology has revolutionized the field of medicine,
opening new frontiers in diagnosis, treatment, and healthcare
delivery. It has enabled the development of cutting-edge
therapies, precision medicine approaches, and innovative
diagnostic tools, offering hope for patients with previously
untreatable or difficult-to-treat conditions. The application of
biotechnology in medicine has not only improved patient
outcomes but has also driven advancements in personalized
medicine, genomics, and regenerative medicine.
Biotechnology has played a critical role in areas such as gene
therapy, monoclonal antibodies, stem cell research, and
CRISPR-based gene editing, providing solutions to a wide
range of medical challenges. Additionally, biotechnology has
paved the way for targeted therapies, reducing side effects and
improving the efficacy of treatments.
While biotechnology in medicine has demonstrated significant
promise, it also comes with ethical, regulatory, and access-
related challenges. Ensuring equitable access to these
advanced therapies and addressing ethical concerns
surrounding genetic editing and data privacy are essential
aspects that the medical community and society must
consider.
The future of biotechnology in medicine holds great potential,
with ongoing research and innovation driving the
development of new treatments and technologies. As
biotechnological advancements continue, they will likely lead
to more personalized, effective, and accessible healthcare
solutions, ultimately improving the quality of life for patients
around the world. This convergence of biotechnology and
medicine represents a bright future for healthcare, offering
hope for individuals suffering from a wide range of medical
conditions.