Biotechnological Application in Medicine

Biotechnological Application in Medicine

  • Recombinant DNA technology has revolutionized healthcare by enabling the mass production of safe and highly effective therapeutic drugs. 
  • These recombinant therapeutics offer several advantages over products derived from non-human sources, including reduced risk of immunological responses. Currently, approximately 30 recombinant therapeutics have been approved for human use worldwide, with 12 of these available in the Indian market.

 

Impact of Recombinant DNA Technology:

  • Recombinant DNA technology allows for the production of therapeutic drugs on a large scale. 
  • These drugs are safer and more effective compared to traditional treatments. 
  • They are produced using genetically engineered organisms to express specific proteins with therapeutic properties.

 

Advantages of Recombinant Therapeutics:

  • Recombinant therapeutics do not induce unwanted immunological responses commonly seen with products derived from non-human sources. 
  • They offer precise targeting and enhanced efficacy, leading to improved patient outcomes. 
  • The production process can be tightly controlled, ensuring consistency and quality in each batch.

 

Approved Recombinant Therapeutics:

  • Globally, around 30 recombinant therapeutics have received approval for human use. 
  • These drugs target a wide range of medical conditions, including cancer, diabetes, autoimmune disorders, and genetic diseases. 
  •  In India, 12 of these recombinant therapeutics are currently available in the market, providing patients with access to advanced treatments.

 

Examples of Recombinant Therapeutics:

  • Some notable examples of recombinant therapeutics include insulin for diabetes management, erythropoietin for anemia treatment, and human growth hormone for growth disorders. 
  • Biologics such as monoclonal antibodies have also been developed through recombinant DNA technology for targeted cancer therapy and autoimmune diseases.

 

Genetically Engineered Insulin 

  • The management of adult-onset diabetes often requires regular administration of insulin. However, in the past, the availability of human insulin was limited, leading to the extraction of insulin from the pancreas of slaughtered cattle and pigs.  
  • This approach posed risks of allergic reactions due to the foreign protein.  
  • The development of genetically engineered insulin transformed diabetes treatment, offering a safer and more efficient solution.

 

Challenges with Animal Insulin:

  • Limited availability of human insulin led to the extraction of insulin from animal pancreases, primarily from cattle and pigs. 
  • Insulin from animal sources posed risks of allergic reactions and immune responses due to differences in protein structure.

 

Genetically Engineered Insulin:

  • Genetically engineered insulin involves the production of insulin using recombinant DNA technology. 
  • The main challenge was to assemble insulin into its mature, functional form. 
  • In 1983, Eli Lilly, an American company, successfully prepared DNA sequences corresponding to the A and B chains of human insulin. 
  • These DNA sequences were introduced into plasmids of Escherichia coli (E. coli) bacteria to produce insulin chains. 
  • The A and B chains were produced separately, extracted, and combined to form human insulin by creating disulfide bonds between them.

 

C Peptide in Insulin Synthesis:

  •  Insulin consists of two short polypeptide chains: chain A and chain B, linked together by disulfide bridges. 
  • In mammals, including humans, insulin is synthesized as a pro-hormone containing an additional stretch called the C peptide. 
  • The C peptide is not present in mature insulin and is removed during the maturation process. 
  • Its presence in pro-insulin helps in the proper folding and assembly of the insulin molecule. 
  • Despite not being present in mature insulin, the C peptide serves as a marker for insulin production in the body and is measured in diagnostic tests for diabetes management.

 

 

 

Advantages of Genetically Engineered Insulin:

  • Genetically engineered insulin is identical to human insulin, minimizing the risk of allergic reactions and immune responses. 
  •  Its production using bacteria such as E. coli allows for large-scale manufacturing, ensuring a stable and reliable supply of insulin for diabetic patients worldwide.

 

Administration of Insulin:

  • Insulin cannot be orally administered to diabetic patients due to its degradation by digestive enzymes in the gastrointestinal tract. 
  • Instead, insulin is typically administered via injection or through insulin pumps to ensure direct delivery into the bloodstream.

 

Gene Therapy

  • For individuals born with hereditary diseases, the prospect of corrective therapy was once a distant hope. However, gene therapy has emerged as a groundbreaking approach to address genetic defects and potentially provide long-term solutions.  
  • By inserting functional genes into a person's cells and tissues, gene therapy aims to treat and even cure genetic disorders, offering new hope to patients and their families. 
  •  Gene therapy encompasses a range of techniques aimed at correcting gene defects diagnosed in individuals, including children and embryos. 
  • The fundamental principle involves the insertion of normal genes into a person's cells and tissues to compensate for non-functional or defective genes. 
  • This corrective approach seeks to restore normal gene function and alleviate the symptoms associated with genetic disorders. 
  • The first clinical gene therapy was administered in 1990 to a 4-year-old girl with adenosine deaminase (ADA) deficiency. 
  •  ADA deficiency results from the deletion of the gene responsible for producing the ADA enzyme, crucial for immune system function. 
  • Existing treatments such as bone marrow transplantation and enzyme replacement therapy are not always curative, highlighting the need for alternative approaches like gene therapy. 
  • In ADA deficiency, lymphocytes from the patient's blood are cultured outside the body. 
  • A functional ADA gene, encoded by complementary DNA (cDNA), is introduced into these lymphocytes using a retroviral vector. 
  • The genetically engineered lymphocytes are then returned to the patient's body. 
  •  However, due to the limited lifespan of these cells, periodic infusions of genetically engineered lymphocytes are required. 
  • Gene therapy holds the promise of providing a permanent cure for genetic disorders if introduced at early embryonic stages. 
  •  By integrating functional genes into cells during early development, gene therapy could potentially offer lifelong benefits and eliminate the need for ongoing treatments.

 

 

 

Molecular Diagnosis

  • Early diagnosis of diseases is crucial for effective treatment and management. Conventional diagnostic methods often fail to detect diseases in their early stages.  
  • However, advancements in molecular diagnostics, including techniques like Polymerase Chain Reaction (PCR) and Enzyme Linked Immuno-sorbent Assay (ELISA), have revolutionized early disease detection by amplifying minute amounts of DNA or detecting specific antigens or antibodies associated with pathogens.

 

Polymerase Chain Reaction (PCR):

  • PCR is a molecular technique used to amplify small amounts of DNA, allowing the detection of pathogens even before symptoms manifest. 
  • By repeatedly heating and cooling the DNA sample, PCR amplifies specific DNA sequences, making them detectable. 
  •  PCR is utilized in diagnosing diseases such as HIV/AIDS by detecting viral DNA at low concentrations, enabling early intervention and treatment. 
  • It is also employed in identifying gene mutations in suspected cancer patients and diagnosing various genetic disorders with high sensitivity and specificity.

 

Principle of PCR for Detecting Low DNA Amounts:

  • PCR can detect very low amounts of DNA through amplification. 
  • Even when disease symptoms are not yet visible, PCR can identify pathogens by amplifying their nucleic acids to detectable levels. 
  • The technique involves cycles of denaturation, annealing, and extension, where DNA strands are separated, primers bind to target sequences, and DNA polymerase synthesizes new strands, exponentially amplifying the DNA.

 

Autoradiography in Genetic Analysis:

  • Single-stranded DNA or RNA molecules tagged with radioactive probes can be used to detect specific gene sequences. 
  • These probes hybridize to complementary DNA in cell clones, and detection is achieved using autoradiography. 
  • Mutations in genes can be identified as clones with mutated genes will not appear on photographic film due to lack of probe complementarity.

 

Enzyme Linked Immuno-sorbent Assay (ELISA):

  • ELISA is based on the principle of antigen-antibody interaction and is used to detect infections by pathogens. 
  • It detects antigens (proteins, glycoproteins, etc.) produced by pathogens or antibodies synthesized against them. 
  • ELISA is widely used in diagnosing infectious diseases and monitoring immune responses to pathogens.

 

Transgenic Animals

  • Transgenic animals, whose DNA has been manipulated to incorporate and express additional genes, represent a significant advancement in biomedical research.  
  •  While various species have been genetically modified, mice comprise the majority of existing transgenic animals. 
  • These genetically modified organisms serve diverse purposes, ranging from studying normal physiology and disease development to producing valuable biological products.

 

Understanding Normal Physiology and Development:

  • Transgenic animals are engineered to elucidate how genes regulate normal physiological processes and development. 
  • By introducing foreign genes that influence factors like insulin-like growth factor, researchers can study their biological effects and role in the body's functions.

 

Study of Disease Models:

  • Many transgenic animals serve as models to explore the genetic basis of human diseases. 
  • These animals are designed to mimic human conditions such as cancer, cystic fibrosis, rheumatoid arthritis, and Alzheimer's disease, facilitating research on disease mechanisms and potential treatments.

 

Production of Biological Products:

  • Transgenic animals are harnessed to produce valuable biological products, including human proteins used in medical treatments. 
  • By introducing genes coding for specific products like human alpha-1-antitrypsin, transgenic animals can produce therapeutic proteins such as those used in treating emphysema and cystic fibrosis.
  • Examples include Rosie, the transgenic cow producing human protein-enriched milk, offering a more nutritionally balanced option for infants.

 

Vaccine Safety Testing:

  • Transgenic mice are developed for assessing the safety of vaccines before human trials. 
  • These animals are utilized to test vaccine batches for safety, potentially replacing the use of primates in vaccine safety assessments. 
  • For instance, transgenic mice are employed in testing the safety of the polio vaccine, ensuring its efficacy and safety for human use.

 

Chemical Safety Testing (Toxicity Testing):

  • Transgenic animals play a crucial role in toxicity testing, providing insights into the effects of toxic substances. 
  • Genetically modified animals are engineered to be more sensitive to toxic substances than non-transgenic counterparts, expediting toxicity testing and yielding results in a shorter timeframe. 
  • This approach enhances our understanding of chemical safety and aids in evaluating the potential risks associated with exposure to toxic compounds.

 

Ethical Issues

  • The advancement of biotechnology has revolutionized various sectors, offering promising solutions to complex challenges in agriculture, medicine, and industry. However, alongside scientific progress, ethical considerations have become increasingly significant. 
  •  Ethical standards and regulatory frameworks are essential to assess the morality of biotechnological activities and ensure responsible innovation.

 

Regulatory Framework:

  •  Establishing ethical standards and regulatory frameworks is crucial to evaluate the moral implications of biotechnological activities. 
  • Regulatory bodies like the Genetic Engineering Approval Committee (GEAC) in India play a pivotal role in assessing the ethical and safety aspects of genetic modification research and the use of genetically modified organisms (GMOs).

 

Environmental Concerns:

  • Genetic modification of organisms can have unforeseen consequences on ecosystems and biodiversity. 
  • Ethical considerations include the potential risks of releasing GMOs into the environment, such as ecological disruption and loss of biodiversity.

 

Human Health and Safety:

  •  Ethical dilemmas arise regarding the safety and long-term health effects of consuming genetically modified foods and medicines. 
  • Concerns include allergenicity, antibiotic resistance, and unintended health consequences of genetic modification.

 

Ownership and Control:

  • Questions of ownership and control emerge concerning the exploitation of biological resources and indigenous knowledge. 
  • Patenting of genetic resources and traditional knowledge by foreign entities raises ethical concerns about biopiracy and the equitable sharing of benefits.

 

Cultural Heritage:

  • Preservation of cultural heritage and traditional practices is essential in the face of biotechnological advancements. 
  • Ethical considerations include respecting indigenous rights, protecting cultural diversity, and preventing the commodification of traditional knowledge and resources.

 

Biopatent 

  • Bio patenting, the process of obtaining patents for biological materials and biotechnological inventions, raises profound ethical questions regarding ownership, control, and access to genetic resources and traditional knowledge. 
  • The granting of patents for genetic resources and traditional knowledge by foreign entities without adequate compensation or consent from indigenous communities has sparked debates on biopiracy and equitable benefit sharing.  
  • Understanding these ethical dilemmas is crucial in navigating the complex landscape of biotechnology and intellectual property rights.

 

Commodification of Genetic Resources:

  • Bio patenting involves the granting of patents for biological materials, including genes, organisms, and biotechnological processes. 
  • Concerns arise when genetic resources and traditional knowledge are commodified for commercial gain without adequate compensation or consent from indigenous communities.

 

Biopiracy:

  • Biopiracy refers to the unauthorized appropriation of biological resources or traditional knowledge from indigenous communities. 
  •  Instances of biopiracy involve the exploitation of indigenous crops, herbal medicines, and genetic resources by foreign entities for commercial purposes.

 

Intellectual Property Rights (IPRs):

  • Intellectual property rights (IPRs) play a significant role in bio patenting, granting exclusive rights to inventors or companies over their innovations. 
  • Ethical debates surround the balance between promoting innovation and ensuring access to essential resources and knowledge for the public good.

 

Equitable Benefit Sharing:

  • Ethical considerations include ensuring equitable benefit sharing from the commercialization of genetic resources and biotechnological innovations. 
  • Mechanisms such as prior informed consent (PIC) and mutually agreed terms (MAT) aim to safeguard the rights and interests of indigenous communities and biodiversity-rich countries.

 

Legal and Ethical Challenges:

  • Bio patenting raises legal and ethical challenges related to sovereignty, cultural heritage, and environmental sustainability. 
  • Balancing the promotion of innovation with ethical principles of justice, fairness, and respect for indigenous rights is essential in addressing bio patent issues.

 

Biopiracy

  • Biopiracy refers to the unauthorized use of biological resources and traditional knowledge by multinational companies and organizations without proper authorization or compensatory payment to the countries and communities from which these resources originate.

 

Disparity in Biodiversity and Traditional Knowledge:

  • Industrialized nations often possess financial wealth but lack biodiversity and traditional knowledge. In contrast, developing and underdeveloped countries are rich in biodiversity and traditional knowledge associated with bio-resources.

 

Exploitation of Traditional Knowledge:

  • Traditional knowledge related to bio-resources holds immense value and can be leveraged to develop modern applications. Additionally, it can streamline the commercialization process, saving time, effort, and resources.

 

Addressing Injustice and Inequity:

    There is a growing recognition of the injustice and inadequate compensation associated with the exploitation of bio-resources and traditional knowledge. Consequently, some nations are enacting laws to prevent unauthorized exploitation and ensure fair benefit-sharing.

 

Legislative Measures:

    The Indian Parliament has taken proactive steps to address biopiracy through legislative amendments, such as the second amendment of the Indian Patents Bill. These amendments aim to address issues related to patent terms, emergency provisions, and initiatives for research and development.