What is Biotechnology?

India's Biotechnology Sector has seen significant growth, aiming for a USD 150 billion bioeconomy by 2025. To achieve this, strategies include capacity building, strategic partnerships, and fostering self-reliance. India’s strengths include a strong workforce and robust infrastructure. However, challenges like low R&D investment and marketization issues persist. It can be used in various fields like healthcare, agriculture, and the environment, utilizing genetic engineering, stem cell therapy, and 3D printing. Vaccines, including India's COVAXIN, play a crucial role, with initiatives like "Mission COVID Suraksha" ensuring pandemic readiness. To sustain growth, India must address Research and Development expenditure, foster partnerships, and align education with industry needs while enhancing research infrastructure.

In recent years, the Biotechnology Sector has experienced significant growth, thanks to the groundwork laid through decades of research, education, and product development. Efforts have been made to engage stakeholders and implement key policy changes to support this ecosystem, beyond just financial backing. Since its establishment in 1986, the Department of Biotechnology has released several Vision and Strategy documents, including the ones in 2000, 2007, 2015 and 2021. These documents aim to create a conducive environment for sector growth and ensure that cutting-edge biotechnologies benefit humanity through the development of technologies and products.

Biotechnology involves the application of biological knowledge and techniques, focusing on molecular, cellular, and genetic processes, to enhance products and services significantly. Biotechnology advancements have led to improved living standards, better healthcare, increased agricultural output, and the creation of job opportunities, among other benefits. India holds a 3-5% market share in the global biotechnology industry and is recognized as one of the top 12 biotech destinations worldwide, ranking 3rd in Asia. With a growing economy, heightened health awareness, and a vast population exceeding a billion, India's biotech sector is poised for substantial growth. Current estimates value the Indian biotech industry at USD 100 billion in FY22, projected to reach USD 150 billion by FY25. Presently, the industry comprises over 3500 biotech start-ups, with expectations to expand to 10,000 by 2024-25.

The National Biotechnology Development Strategy for 2021-2025 aims to position India as a global leader in biotechnology and achieve a USD 150 billion bioeconomy by 2025
Key strategies outlined in this include:

• Building Capacities: Enhancing the skill sets of the workforce and improving state-of-the-art infrastructure.
• Atal Jai Anusandhan Biotech (UNaTI) Missions: Launching biotech missions to align with national and global priorities, supporting National Development Plans (NDP) and Sustainable Development Goals (SDG).
• Building a Self-reliant India (Atmanirbhar Bharat) through Biotech Interventions by fostering self-sufficiency in biotechnology through strategic interventions.
• Leveraging Strategic Partnerships: Collaborating with national and international partners to capitalize on strengths.
• Preparing for the Future: Strengthening the knowledge base for future advancements.
• Taking Science to Society: Empowering rural sectors with biotechnological advancements.
• Effective Outreach and Communication: Building public trust through transparent and informative communication.
• Global Benchmarking and Performance Measurement: Evaluating performance against global standards.

• Abundant Scientific Human Resources: We have a large pool of scientists and engineers contributing to the field.
• Cost-Effective Manufacturing Capabilities: The industry benefits from efficient manufacturing processes, making it economically viable.
• Thriving Biotech Start-up Ecosystem: With approximately 3500 biotech start-ups, innovation and entrepreneurship are thriving in the sector.
• National Research Laboratories and Centers of Academic Excellence: These institutions provide valuable research infrastructure and intellectual capital.
• Biotechnology Parks and Incubators: Spread across the nation, these facilities support the translation of research into marketable products and services.
• Education and Training Infrastructure: Numerous universities, colleges, and institutes offer specialized degrees and diplomas in biotechnology-related fields.
• Strong Pharmaceutical Industry: India's well-established drug and pharmaceutical industry contributes to the biotech sector's growth and innovation.
• High Standards in Manufacturing: India boasts the highest number of USFDA-approved manufacturing plants outside the U.S., ensuring quality and compliance.
• Rich Biodiversity: The country's diverse gene pools offer significant opportunities for genomics and biodiversity research.
• Growing Clinical Capabilities: India is rapidly developing as a hub for clinical trials and contract research, attracting international attention and investment in this field.

• Low Research and Development (R&D) Investment: India's R&D expenditure is relatively low, ranging from 0.6-0.7% of GDP, hindering innovation and technological advancement.
• Intellectual Property Rights (IPR) Regime: Challenges in India's IPR regime include stringent patentability standards under Section 3(d) of the Patents (Amendment) Act, 2005, and the provision for compulsory licensing, which may discourage investment in research and development.
• Lack of Marketization: Many research projects face difficulties in transitioning from the development stage to commercialization due to inadequate funding beyond the initial research phase.
• Public Awareness: There is a lack of awareness among the general public regarding the benefits and potential of biotechnology, hindering its acceptance and utilization in various sectors such as healthcare, agriculture, and environmental conservation.
• Regulatory Framework: The Biotechnology Regulatory Authority of India Bill, 2013, aimed at establishing a regulatory body for biotechnology products,lapsed with the dissolution of 15th Lok Sabha, leading to uncertainty and delays in regulatory processes.
• Job Market Challenges: The biotechnology sector currently offers fewer job opportunities compared to the available workforce, leading to reduced interest among students in pursuing careers in this field. This discrepancy in job demand and supply needs to be addressed to foster growth and innovation in the sector.

• Healthcare
  • Gene Therapy: Gene therapy aims to correct defective genes responsible for genetic disorders
  • Pharmacogenomics: It investigates how genetic makeup influences drug response, with applications including customized medicine development, precise drug dosing, targeting disease-related genes, and safer vaccine creation through genetic engineering.
  • DNA Profiling/DNA Fingerprinting: DNA profiling is utilized in various applications, including establishing biological parentage, medical diagnosis, and maintaining accurate defense records
  • Bio-fortification: Biotechnology facilitates bio-fortification of staple crops like rice and wheat to address malnutrition
• Agriculture
  • Benefits of Bio-Fertilizers:
    • Reduces reliance on chemical fertilizers.
    • Enhances plant nutrient uptake.
    • Maintains soil health organically.
    • Promotes environmental sustainability.
    • Microorganisms in bio-fertilizers enrich soil organic matter.
    • Restores the soil's natural nutrient cycle.
  • Genetic Modification (GM) Crops:
    • Genetic engineering aims to confer resistance to insects and viruses.
    • Enhances tolerance to herbicides or drought conditions.
    • Improves nutritional content, appearance, texture, and shelf life.
    • BT cotton (Bacillus Thuringensis)
      • Bollgard I, based on single-gene technology, became India's first biotech crop approved for commercialization in 2002. It was succeeded by Bollgard II, featuring double-gene technology, in mid-2006.
      • BT cotton reduces input costs and increases cotton production.
    • GM mustard
      • The transgenic mustard hybrid DMH-11 has been developed by the Centre for Genetic Manipulation of Crop Plants (CGMCP) at Delhi University.
      • GM mustard has the genes that allow the plant cross-pollination and hybridization
      • However, there are apprehension that it may affect human health as well biodiversity negatively and hence proper studies are required to address these concerns.
  • Animal Husbandry:
    • Techniques like cloning, somatic cell nuclear transfer, and transgenic animals developed by advancements in biotechnology has benefitted this sector.
    • Goals include improving breed quality and imparting disease and climate resistance.
    • Example: Transgenic cows produce milk with a more balanced composition for human infants, increasing revenue through premium product sales.
    • DNA technology in vaccine development controls animal diseases, reducing farmers' upkeep costs.
  • Environment
    • Biofuel Production from Maize, Sugar, etc.
      • Enhances income opportunities for farmers while being environmentally friendly.
    • Bioremediation: Utilizes microorganisms, fungi, green plants, or their enzymes to restore the natural environment affected by contaminants.
      • Example: Bacteria used by the oil industry to clean up pollution caused by oil spills.
    • Biosensors: Applications include:
      • Detecting pesticides and contaminants in river or lake water.
      • Monitoring levels of toxic substances before and after bioremediation efforts.
      • Identifying drug residues in food products.

• Genetic Engineering or Recombinant DNA (rDNA):
  • Involves the manipulation of an organism's genetic makeup.
  • Technique include:
    • CRISPR Cas9 technology for Gene Editing : It is basically a molecular scissors used in targeted gene editing.
    • Gene cloning
    • Gene therapy
    • Genetic modification of crops
• Assisted Reproductive Technologies (ART): It includes
  • In vitro fertilization (IVF): Fertilization of an egg by sperm outside the body.
  • Embryo Transfer Technology: Transfer of embryos to a recipient mother, either from a donor mother or from in vitro fertilization.
  • Artificial insemination: Direct delivery of sperm into the cervix or uterus.
  • Gamete intrafallopian transfer (GIFT): Injection of egg and sperm directly into the fallopian tube for fertilization.
  • Surrogacy: Carrying an embryo in another woman's uterus (gestational carrier or surrogate mother).
  • Artificial Wombs: Technology to support the survival of premature or sick human babies outside the mother's womb.
• Mitochondrial Replacement Therapy/Pro-nuclei Transfer:
  • It involves the use of mitochondrial DNA from a healthy donor to prevent the transmission of mitochondrial diseases from mother to child
• Stem Cell Therapy ( separately below )
  • It involves the use of stem cells to treat or prevent various diseases or medical conditions.
• 3D printing. ( separately below )

Genetic Engineering, or Recombinant DNA (rDNA) technology, involves manipulating the genetic makeup of organisms for various applications:

• Production of Genetically Modified Organisms (GMOs):
  • Examples include GM crops or transgenic animals.
• Production of Therapeutic Mammalian Proteins and Hormones:
  • This includes the production of human insulin, growth hormone, and other therapeutic proteins.
• Recombinant DNA Vaccines:
  • Examples include the Hepatitis B vaccine and other vaccines produced using recombinant DNA technology.
• Gene Therapy:
  • Utilized to correct genetic diseases by introducing functional genes into cells.
• Production of Interferons:
  • Interferons are produced against various pathogens such as viruses, bacteria, and parasites.
• Efficient Production of Bioenergy and Biofuels:
  • Genetically engineered microorganisms are used to produce bioenergy and biofuels.
• Genetically Engineered Organisms (GEO) for Bioremediation:
  • Genetically engineered organisms are employed for bioremediation purposes, helping to clean up environmental contaminants.

Genome Sequencing involves sequencing the entire genome (the complete set of DNA) of an individual, offering several benefits and facing various challenges:
Benefits:

• Predictive and Preventive Healthcare: Enables early detection of genetic predispositions to diseases, allowing for proactive preventive measures.
• Precision Medicine: Tailors medical treatments and interventions based on individual genetic makeup, leading to more effective outcomes.
• Scientific Research: Mapping the genetic diversity of India aids in understanding evolution and genetic variations among populations.
• Prevention of Biopiracy: Protects indigenous genetic resources from exploitation by unauthorized parties.
• Boost to Genomics Field: Enhances India's capacity to generate, analyze, and utilize large-scale genome data, fostering advancements in genomic research and technology.

Challenges:

• Technological Issues:
  • Analytical software tools and data storage solutions require constant advancement to handle the vast amount of genomic data.
• Financial Issues:
  • Genome sequencing may receive less priority compared to national security and social welfare initiatives, hindering funding and resources allocation.
• Legal Issues:
  • Data privacy concerns, including anonymity and misuse of genetic data, necessitate robust legal frameworks and regulations.
• Cybersecurity:
  • Vulnerability to cyber breaches poses risks to the security and confidentiality of genomic data.
• Genetic Stereotyping and Stigmatization:
  • Misinterpretation or misuse of genetic information may lead to discrimination and stigmatization based on genetic predispositions.
• Interpretational Issues:
  • Shortage of trained clinicians and genetic counselors capable of interpreting genomic data in the best interests of patients may impede effective utilization of genome sequencing in healthcare.

• Genome India Project by the Department of Biotechnology (DBT):
  • Aims to sequence the genomes of 10,000 individuals representing the diverse population of India.
  • The sequencing of 10,000 Indian genomes has been completed.
  • The dataset will be stored at the Indian Biological Data Centre (IBDC) located in Faridabad.
• IndiGen Program by the Council of Scientific and Industrial Research (CSIR):
  • Focuses on genome sequencing of 1,000 Indian individuals.

• Stem Cell Therapy involves the use of stem cells to treat or prevent various diseases or medical conditions.
• Stem cells are cells that have the unique ability to differentiate into various specialized cell types within the body.There are different types of stem cells:
  • Totipotent Stem Cells: These can differentiate into all possible types of stem cells.
  • Pluripotent Stem Cells:
    • These cells have the ability to differentiate into many different cell types.
    • Examples include Embryonic Stem Cells (ESCs).
  • Multipotent Stem Cells:
    • They can differentiate into a limited range of cell types, usually within a particular tissue or organ.
    • Adult stem cells and cord blood stem cells are considered multipotent.
  • Oligopotent Stem Cells:
    • These cells can differentiate into a few different cell types.
    • Examples include Bone Marrow Cells.
  • Induced Pluripotent Stem Cells (iPSCs):
    • These are adult somatic cells that have been genetically reprogrammed to exhibit properties similar to embryonic stem cells.
    • iPSCs can differentiate into various cell types and hold potential for regenerative medicine and disease modeling.
• Advantages
  • Stem cells have the ability to divide and multiply rapidly, allowing for the generation of large numbers of cells for therapeutic purposes.
  • Embryonic stem cells can renew indefinitely, providing a potentially endless supply of cells for research and therapy.
  • Stem cells offer great potential for discovering treatments and cures for a variety of diseases and medical conditions through regenerative medicine and tissue engineering approaches.
  • The use of adult stem cells, such as iPSCs, in therapy allows for the patient's own cells to be used, minimizing the risk of rejection and immune responses.

• 3D printing is a technology that transforms digital information from a file into a physical object through a printer. The mechanism involves creating a 3D image using computer-aided design (CAD) software, sending the CAD file to the printer, which then lays down successive layers of liquid, powder, paper, or metal material to build the model from cross-sections.

Applications of 3D printing are diverse:

• Medical: Bio-printing of tissue and organs, personalized drug dosages.
• Manufacturing: Production of machine and robot parts.
• Food: NASA is exploring 3D-printed food to address food shortages.
• Prototyping: Researchers and industries use it to create 3D models.

Advantages of 3D printing include customization, constant prototyping, increased productivity, affordability in the long run, elimination of storage costs, and employment opportunities for technicians and designers. In healthcare, bioprinting could revolutionize organ transplantation.
However, there are also disadvantages:

• Decrease in manufacturing jobs, particularly low-skill jobs.
• Limited size of printed objects.
• Violation of copyrights, leading to counterfeiting.
• Risk of producing dangerous items, facilitating the creation of weapons by criminals or terrorists.

A vaccine is a biological agent that prevents infectious diseases caused by pathogens such as viruses, bacteria, or parasites. It works by guiding the body to defend itself against pathogen attacks by generating an immune response. Vaccines are typically administered in liquid form through injection, oral doses, or intranasal routes.
How vaccines work:

• Introduction of Pathogen Components: The vaccine introduces a small component or non-harmful form of the pathogen into the body, known as the foreign antigen or immunogen.
• Immune Response: The body's immune system responds to the pathogen by producing antibodies, killer cells, or both.
• Formation of Memory Cells: A small group of "memory" B-cells and T-cells remain in the body, ready to initiate a strong immune response upon future exposure to the pathogen. These memory cells enable a quicker and more robust immune response if the individual encounters the real pathogen later.

By mimicking the second type of response to a disease-causing organism without causing the initial symptoms, vaccines protect individuals from infection or disease. They are composed of either the entire pathogen or some of its components in a non-pathogenic form.
Types of vaccine: Vaccines can be synthesized in many ways based on which they are classified:
Live attenuated vaccines

• Pathogens like viruses or bacteria are weakened through genetic manipulations, limiting their growth and preventing disease in the host. These vaccines induce a broad immune response similar to that seen in natural infections.
• Examples include Oral Sabin polio vaccine, MRV Vaccine (Measles, Mumps, Rubella, and Varicella), Nasal influenza vaccine, Bacille Calmette-Guerin (BCG) vaccine, Varicella vaccine, Rotavirus vaccine.

Inactivated or Dead Vaccines:

• Disease-causing pathogens are killed or inactivated through thermal or chemical processes. These vaccines elicit a robust immune response similar to natural infections.
• Examples include Typhoid vaccine, Influenza vaccine, Salk polio vaccine, Hepatitis A vaccine.
• COVAXIN: India's homegrown COVID-19 vaccine, is developed by Bharat Biotech in collaboration with the Indian Council of Medical Research (ICMR) and the National Institute of Virology (NIV). This vaccine, based on inactivated virus technology, is produced and manufactured within Bharat Biotech's high-containment facility at Bio-Safety Level 3 (BSL-3). It is developed using the Whole-Virion Inactivated Vero Cell derived platform technology.

Acellular or Subunit Vaccines:
Acellular vaccines contain parts of the bacteria or viruses, such as polysaccharides or proteins, recognized by the immune system as ‘foreign’ and evoke an immune response against them. They do not contain whole cells. Types of acellular vaccines include:

• Toxoid Vaccine: Some pathogenic bacteria produce toxins or harmful proteins when they infect the body. Toxoid vaccines are made by chemically inactivating these toxins, rendering them non-poisonous but still capable of eliciting a strong immune response.
  • Examples: Diphtheria vaccine, Tetanus vaccine, Pertussis vaccine
• Conjugate Vaccine: Earlier vaccines using bacterial polysaccharides were less effective in infants and young children. Researchers found that linking bacterial polysaccharides to carrier proteins could enhance their efficacy, particularly in younger age groups. Additional proteins from the carrier further strengthen the immune response.
  • Examples: Haemophilus influenza type b (Hib) conjugate vaccine, Meningococcal C conjugate vaccine
  • Pneumococcal conjugate vaccine: These vaccines are effective against pneumonia as well as meningitis and sepsis.
• Recombinant Vaccine: A fragment of DNA from the disease-causing microorganism is inserted into a carrier vehicle, allowing large-scale production of well-defined proteins used in vaccines.
  • Examples: Hepatitis B vaccine, Human papillomavirus (HPV) vaccine
• DNA/RNA Vaccine: Genetic material (DNA or RNA) from the pathogen is introduced into human cells, where it prompts the cell machinery to produce the pathogen's protein. This protein triggers an immune response, providing protection against the pathogen.
  • Various nucleic-acid vaccines, including an HIV vaccine, are currently in developmental and clinical evaluation stages.

Viral vector vaccines
Viral vector vaccines utilize a harmless virus to transport the genetic code of the antigen to the host's cells, prompting the immune system to combat the antigen. Essentially, they serve as a gene delivery mechanism, delivering information about the antigen to trigger the body's immune response.

Benefits:

• Viral vector vaccines generally induce a robust immune response.
• Often, only a single dose of the vaccine is required to establish immunity.
• Boosters may be necessary to sustain immunity over time.

Examples:

• Ebola vaccine, Sputnik V
• Covishield : It was developed by Oxford-AstraZeneca, and is being manufactured by the Serum Institute of India.

Messenger RNA (mRNA) vaccines:
Messenger RNA (mRNA) vaccines function by delivering RNA material that instructs the body to produce a specific type of protein unique to the virus, without causing illness. This protein triggers an immune response, leading to the generation of antibodies that recognize the protein. Consequently, if the person encounters the virus in the future, their body would possess the necessary tools (antibodies) to combat it.

Benefits:

• Rapid vaccine production: mRNA technology allows for the swift creation of large quantities of vaccine material.
• Adaptability: The technology can be easily adjusted to target new antigens by modifying the mRNA formulation.
• High-quality vaccine production: mRNA vaccines can be produced efficiently and in large quantities.

Examples:

• Pfizer-BioNTech COVID-19 vaccine

The Department of Biotechnology (DBT) under the Ministry of Science & Technology has launched "Mission COVID Suraksha" with the aim of ensuring pandemic readiness in the country. Through this mission, DBT has achieved several milestones:

• Delivery of Four Vaccines:
  • ZyCoV-D: The world's first and India's indigenously developed DNA vaccine.
  • CORBEVAXTM: India's first protein subunit vaccine.
  • GEMCOVAC™-19: The world's first and India's indigenously developed mRNA vaccine.
  • iNCOVACC: The world's first and India's indigenously developed intranasal COVID-19 vaccine.
• Augmented Manufacturing of Covaxin:
  • Covaxin manufacturing capacity has been increased to meet the demand for vaccines.
• Infrastructure Development:
  • Necessary infrastructure has been created to support the smooth development of future vaccines.

Financial support and expert scientific and technical oversight were provided for various COVID-19 vaccine development activities under the Mission COVID Suraksha.

Moving forward, there is a pressing need to address India's low research and development expenditure, which currently stands at 0.6-0.7% of GDP. This can be achieved through several strategic initiatives. Firstly, fostering robust research-academic partnerships is essential. Additionally, increasing venture capital for high-risk scientific endeavors and encouraging higher R&D spending by industries are crucial steps. Strengthening the connection between research outcomes and commercialization processes is imperative, alongside ensuring that Indian products meet international standards through quality assurance measures. Moreover, aligning educational curricula with industry demands is necessary to better prepare students for the workforce. Furthermore, the establishment and enhancement of state-of-the-art research facilities and translational centers are vital for driving innovation and technological advancement in the country.