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Subject: Biotech and Medical Sciences

  • Type 2 diabetes rising among young people, posing lifetime risks: Lancet

    Why in the News?

    A new series by The Lancet highlights a major shift in global health. Type 2 diabetes, which earlier affected mostly older people, is now increasing quickly among those under 40. Around 260 million young adults worldwide already have the disease.

    What distinguishes early-onset type 2 diabetes from adult-onset in impact?

    • Longer disease duration with increased complications: Being diagnosed at a younger age means living longer with the disease, increasing the risk of complications like kidney failure, heart disease, and nerve damage throughout life. A 25-year-old with diabetes may face multiple health issues by age 40, compared to someone diagnosed at 55.
    • Greater loss in life expectancy: Individuals diagnosed before the age of 30 can lose up to 15 years of life expectancy, whereas older adults diagnosed later typically lose fewer years. A young adult may not survive past their 60s if the disease is poorly managed, while an older adult may live well into their 70s or 80s.
    • More disruption to personal and economic life: Early onset affects critical life stages like education, job opportunities, and family planning, placing greater mental and financial stress. A person in their 20s may have to drop out of college or limit employment due to frequent medical care needs.

    Why is early-onset diabetes a major concern for Indian health systems?

    • Rising burden on already stretched public healthcare: India’s healthcare system is under pressure from both infectious and non-communicable diseases. Early-onset diabetes increases the demand for long-term care, monitoring, and medication. A 2023 ICMR study found that more than 25% of diabetes cases in India are now diagnosed before the age of 40.
    • Economic impact on productivity and workforce: Early-onset diabetes reduces an individual’s healthy working years and impacts productivity, especially in labour-intensive sectors. According to the ICMR 2023 study, diabetic workers lose an average of 7–8 additional workdays annually, leading to reduced output, absenteeism, and rising employer costs.
    • Greater lifetime healthcare costs and complications: Early diagnosis leads to decades-long care, including medication, check-ups, and complication management, increasing costs for families and public health insurance. Eg: A young diabetic using insulin, requiring eye and kidney screenings, adds a heavy burden on schemes like Ayushman Bharat.

    How do socio-economic and environmental factors drive its rise?

    • Unhealthy food environments and marketing: Easy availability and aggressive marketing of processed and sugary foods through social media influence poor dietary habits among youth. Eg: Fast food delivery apps and influencer-driven trends promote ultra-processed snacks in urban areas like Delhi and Mumbai.
    • Inequality in access to healthcare and lifestyle management: Low-income groups lack access to nutritious food, safe exercise spaces, and preventive healthcare, increasing risks of obesity and diabetes. Eg: Children in urban slums of Kolkata face limited health awareness and inactivity, raising early-onset diabetes risk.
    • Impact of early-life undernutrition and developmental challenges: Poor maternal nutrition, low birth weight, and childhood undernourishment raise the chance of developing type 2 diabetes later, even without obesity. Eg: In rural Madhya Pradesh, undernourished children show insulin resistance despite having a low BMI.

    Why is prevention more effective than treatment in tackling this issue?

    • Reduces lifelong health burden and complications: Preventing diabetes avoids decades of medication, monitoring, and risks of complications like kidney or heart disease. Eg: Promoting physical activity and healthy diets in schools can reduce diabetes risk and future hospital visits.
    • More cost-effective for individuals and health systems: Prevention strategies like awareness campaigns and food policies cost less than long-term drug therapy and hospitalisation. Eg: Taxing sugar-sweetened beverages, adopted in over 100 countries, has reduced sugary drink sales and lowered obesity-related costs.
    • Addresses root causes and promotes healthy behaviours: Focusing on prevention changes social and environmental conditions that lead to obesity and diabetes. Eg: Urban planning with parks, pedestrian paths, and fitness centres encourages active lifestyles, lowering diabetes risk.

    Way forward:

    • Strengthen preventive public health strategies: Implement nationwide programs promoting healthy eating, physical activity, and early screening in schools and communities to reduce risk factors from a young age.
    • Ensure equitable access to care and awareness: Expand access to affordable diagnosis, lifestyle counselling, and essential medicines in both urban and rural areas, especially targeting low-income and high-risk groups.

    Mains PYQ:

    [UPSC 2022] The increase in life expectancy in the country has led to newer health challenges in the community. What are those challenges, and what steps need to be taken to meet them?

    Linkage: This question directly addresses “newer health challenges” and the steps required to meet them. The need for “urgent investment in prevention, early diagnosis and targeted care” mentioned in the article directly aligns with the “steps to be taken” aspect of this question.

  • Agricultural Fungicides causing C. Tropicalis Infections

    Why in the News?

    Researchers at Fudan University found that overuse of the fungicide tebuconazole is causing azole-resistant Candida tropicalis to emerge — a deadly fungus with a 55–60% mortality rate.

    About Candida tropicalis:

    • Overview: Candida tropicalis is a fungal pathogen prevalent in tropical and subtropical regions, including India.
    • Type: It is a yeast species that causes invasive candidiasis, affecting the bloodstream and internal organs.
    • High-Risk Groups: The fungus is opportunistic, primarily infecting immunocompromised individuals such as cancer patients and those in ICUs.
    • Mortality Rate: The infection has a high mortality rate, estimated at 55–60% when it becomes systemic.
    • Drug Treatment: Standard treatments include azole-class antifungals such as fluconazole and voriconazole (widely used during COVID-19 induced Black Fungus).
    • Adaptability: The pathogen shows strong genomic plasticity, allowing it to survive hostile environments and develop drug resistance.

    Reasons for Spread and Resistance:

    • Agricultural Influence: Studies show that azole fungicides like tebuconazole, used in farming, contribute to azole-resistant C. tropicalis
    • Environmental Exposure: These fungicides accumulate in soil and water, promoting the evolution of resistant strains.
    • Genetic Adaptations: Resistant strains develop aneuploidy (extra chromosomes), aiding resistance but reducing growth in drug-free environments.
    • Efflux Pumps: Some strains duplicate genes like TAC1, boosting drug-efflux pumps (e.g., ABC transporters) to eject antifungals from the cell.
    • Increased Virulence: Resistant strains have proven more virulent in animal studies, posing greater public health risks.

     

  • Substandard Cancer Drugs: A Global Public Health Alarm

    Why in the News?

    A global investigation has revealed that vital chemotherapy drugs used in over 100 countries have failed quality tests, posing life-threatening risks to cancer patients.

    Various Drugs Used for Cancer Treatment:

    • Cisplatin is a platinum-based drug discovered in the 1960s. It binds to DNA in cancer cells and is widely used to treat testicular, ovarian, bladder, and lung cancers. It is known to cause kidney damage, hearing loss, and immune suppression.
    • Oxaliplatin is another platinum compound mainly used to treat advanced colorectal cancer. It works similarly to cisplatin but may also cause nerve-related side effects.
    • Cyclophosphamide is used for treating breast cancer, leukaemia, sarcoma, and lymphoma. It damages cancer cell DNA and lowers white blood cell counts, weakening the immune system. It can also cause bladder inflammation.
    • Doxorubicin, known as the “Red Devil”, is derived from soil bacteria and used against breast cancer, leukaemia, and sarcomas. It disrupts DNA replication but has serious side effects, including heart damage and hair loss.
    • Methotrexate blocks enzymes involved in DNA synthesis and is used for leukaemia, lymphoma, and various tumors. It is often followed by leucovorin, which helps protect normal cells from damage.
    • Leucovorin is not a chemotherapy drug but a supportive agent used with methotrexate to reduce toxicity. It is a form of vitamin B9 introduced in the 1950s.

    Recent Quality Test Failure

    • Investigation: A 2024 investigation revealed that chemotherapy drugs sold in over 100 countries failed basic quality standards.
    • Failure of Generics: The drugs tested were generics. Also, 189 unexpired samples were tested; 20% failed.
    • Indian Pharma Under Radar: 17 manufacturers were flagged, with 16 based in India. Drugs failed for containing either too little (under 88%) or too much (over 112%) active ingredient.
    [UPSC 2005] It begins as a single cell and grows into a merciless disease that claims millions of lives year after year. But scientists are steadily unlocking its mysteries, and the fight against it may now have reached a dramatic turning point. New discoveries promise better therapies and hope in the war against …” The disease referred to in the above quotation is:

    Options: (a) Cancer (b) AIDS (c) Tuberculosis (d) Alzheimer’s disease

     

  • In-Body CAR T-Cell Therapy

    Why in the News?

    A new study published in Science journal shows that “In-Body CAR T-Cell Therapy” marks a breakthrough by enabling direct immune cell reprogramming for faster, safer treatment of cancer and autoimmune diseases.

    What is CAR T-Cell Therapy?

    • Overview: CAR T-cell therapy is a treatment where a patient’s own T cells are genetically modified to detect and kill cancer cells.
    • Science behind it: Scientists extract T cells and add a Chimeric Antigen Receptor (CAR) gene, which enables them to identify cancer cells.
    • Working: These modified T cells are infused back into the patient, where they multiply and actively attack cancer.
    • Effectiveness: The therapy has shown high success against certain blood cancers and is now being studied for autoimmune disorders like lupus.
    • Issues: The traditional therapy is expensive (₹60–70 lakh), slow, and requires chemotherapy and specialised lab facilities.

    Recent Breakthrough: In-Body CAR T-Cell Therapy

    • Approach: A new technique uses mRNA-loaded lipid nanoparticles (LNPs) to deliver instructions directly inside the body.
    • Targeting Cells: These nanoparticles are programmed to locate and enter killer T cells, converting them into CAR T-cells internally.
    • Benefits offered: This method eliminates the need for cell extraction, chemotherapy, or viral vectors, making it faster and safer.

    Significance for India:

    • Scalable Innovation: This platform may lower treatment costs and offer wider access in countries like India with high cancer and autoimmune burdens.
    • Infrastructure Relief: Its in-body nature avoids dependence on advanced labs, making it suitable for resource-constrained settings.
    [UPSC 2019] What is Cas9 protein that is often mentioned in news?

    Options: (a) A molecular scissors used in targeted gene editing* (b) A biosensor used in the accurate detection of pathogens in patients (c) A gene that makes plants pest-resistant (d) A herbicidal substance synthesized in genetically modified crops

     

  • How DNA identification works?

    Why in the News?

    Following the tragic crash of the Air India Boeing 787 Dreamliner in Ahmedabad, authorities concluded the identities of the victims using DNA analysis.

    What is DNA?

    • Overview: DNA (Deoxyribonucleic Acid) is the molecule that carries genetic instructions essential for the development, growth, and reproduction of all living organisms.
    • Location in the Body: It is present in nearly every human cell and is unique to each person, except for identical twins.
    • Structure: DNA is made up of four chemical bases—Adenine (A), Cytosine (C), Guanine (G), and Thymine (T)—arranged in sequences that encode genetic data.
    • Biological Fingerprint: Due to its individual uniqueness, DNA acts like a biological fingerprint, useful in crime investigations and disaster victim identification.

    How DNA Identification Works?

    • Use in Forensics: DNA is extracted from human remains when visual identification is not possible due to burns, decomposition, or trauma.
    • Reference Matching: Extracted DNA is compared with:
      • Family reference samples (from parents, children, siblings)
      • Personal belongings (like a toothbrush, razor, or hairbrush)
    • Sample Reliability: Bones and teeth are preferred in degraded conditions, as they preserve DNA more effectively.
    • Forensic Accuracy: Specialized forensic labs analyze and match DNA sequences, confirming identity with high levels of accuracy.

    Common DNA Analysis Methods:

    1. Short Tandem Repeat (STR) Analysis:
      • Focuses on short, repeating sequences of DNA that vary among individuals.
      • Requires nuclear DNA, typically from well-preserved samples.
      • Considered the gold standard for forensic identification.
    1. Mitochondrial DNA (mtDNA) Analysis:
      • Extracts DNA from mitochondria, not the nucleus, making it more resilient in degraded samples.
      • Inherited only from the mother, allowing tracing through the maternal lineage.
    1. Y-Chromosome Analysis:
      • Targets Y chromosomes, passed from father to son.
      • Useful for identifying male victims when paternal relatives are available.
    1. Single Nucleotide Polymorphism (SNP) Analysis:
      • Detects single-letter changes in the DNA sequence.
      • Applied when DNA is highly degraded and other methods are less effective.
      • Can be used with reference items like personal hygiene tools.
    [UPSC 2000] Assertion (A): DNA Finger-printing” has become a powerful tool to establish paternity and identity of criminals in rape and assault cases. Reason (R): Trace evidence such as hairs, saliva and dried semen are adequate for DNA analysis.

    Options: (a) Both A and R are true, and R is the correct explanation of A (b) Both A and R are true, but R is not a correct explanation of A (c) A is true, but R is false (d) A is false, but R is true

     

  • Magnetic Isolation and Concentration Cryo-electron Microscopy (MagIC)

    Why in the news?

    Researchers from Rockefeller University introduced MagIC, a new method that allows cryo-EM to work with samples up to 100 times more dilute, making it easier to study rare or hard-to-purify molecules.

    About Cryo-Electron Microscopy (Cryo-EM):

    • Cryo-EM is a powerful microscope method used by scientists to see the 3D shapes of very small things like proteins, viruses, and cell parts.
    • In cryo-EM:
      • The sample is frozen very fast to keep it in its natural shape.
      • An electron beam is used instead of light to capture detailed images at extremely cold temperatures.
    • It helps in:
      • Understanding how diseases work
      • Designing new medicines
      • Studying cell processes
    • Problem: Cryo-EM usually needs a lot of the molecule to work well.
      • If the sample is too dilute (too weak), it’s hard to get good images.
    • Why MagIC helps: It solves this big problem by concentrating and organizing particles using magnetism and smart software, making cryo-EM work even for rare or tiny amounts of molecules.

    What is MagIC (Magnetic Isolation and Concentration cryo-EM)?

    • Overview: It is a new method developed by scientists in the U.S. to make it easier to study rare biological molecules under a special microscope called cryo-EM.
    • Sampling involved: Normally, cryo-EM needs the molecules in a sample to be very concentrated, which is hard when the molecules are rare or hard to collect.
    • MagIC solves this problem by using:
      • Tiny magnetic beads (50 nanometers wide) that stick to the molecules researchers want to study.
      • A magnet that pulls these beads together into one area.
    • This way, even when the solution has less than 0.0005 milligrams per milliliter of the molecules, scientists can still get useful images.

    Key Features of MagIC:

    • Magnetic Pulling: After molecules stick to the tiny magnetic beads, a magnet pulls them into clusters, making them easier to see.
    • Low Sample Requirement: Only 5 nanograms of sample per grid are needed. That’s a very tiny amount—much less than earlier methods.
    • Faster Imaging: The magnetic beads are easy to see, so scientists can quickly find areas with useful particles in the microscope.
    • Smart Software – DuSTER (Duplicated Selection to Exclude Rubbish):
      • It helps remove bad or blurry images and keep only the clear ones.
      • It picks each particle twice and only keeps it if the location matches both times.
    • MagIC works with samples that are 100 times more dilute than what cryo-EM could handle before.
    [UPSC 2023] ‘Aerial metagenomics’ best refers to which one of the following situations?

    Options: (a) Collecting DNA samples from air in a habitat at one go* (b) Understanding the genetic makeup of avian species of a habitat (c) Using air-borne devices to colect blood samples from moving animals (d) Sending drones to inaccessible areas to collect plant and animal samples from land surfaces and water bodies

     

  • HKU5 Bat Viruses pose potential Pandemic Risk

    Why in the News?

    A new study warns that HKU5 bat coronaviruses, closely related to Middle East Respiratory Syndrome coronavirus (MERS-CoV), are just one mutation away from infecting humans.

    Back2Basics: Middle East respiratory syndrome (MERS)

    • Middle East respiratory syndrome (MERS) is a viral respiratory disease caused by Middle East respiratory syndrome coronavirus (MERS‐CoV) that was first identified in Saudi Arabia in 2012.
    • It is a species of coronavirus which infects humans, bats, and camels.

    About HKU5 Virus and Its Characteristics:

    • Classification: HKU5 is a bat coronavirus that belongs to the merbecovirus subgenus, which also includes the MERS-CoV (Middle East Respiratory Syndrome coronavirus).
    • Origin: It was first identified in the Japanese pipistrelle bat in Hong Kong. “HKU” in the name refers to the University of Hong Kong, where the virus was identified.
    • Virology: HKU5 is an enveloped, positive-sense, single-stranded RNA virus, structurally similar to other high-risk coronaviruses.
    • Spread: The virus has been detected in bats across Asia, Europe, Africa, and the Middle East, indicating widespread natural reservoirs.
    • Cell Entry Mechanism: Like SARS-CoV-2, HKU5 uses the ACE2 receptor to infect cells, but current strains bind effectively only to bat ACE2, not human ACE2.
    • Recent Developments: In 2025, a new variant called HKU5-CoV-2 was isolated in China, and lab studies show it can infect human airway and gut cells, though less efficiently than SARS-CoV-2.
    • Genetic Similarity: HKU5 is genetically close to both MERS-CoV and SARS-CoV-2, though it has not yet been detected in humans.

    Threats and Risks Associated with HKU5 Virus:

    • Near-Human Infectivity: HKU5 is considered just one mutation away from gaining the ability to infect humans via the ACE2 receptor.
    • Cross-Species Transmission: Certain HKU5 strains have already jumped into minks, demonstrating its capacity to cross species barriers.
    • Pandemic Potential: If HKU5 acquires mutations allowing efficient use of human ACE2, it could pose a significant zoonotic pandemic threat.
    • Relation to Deadly Viruses: Its structural similarity to MERS-CoV, which has a 34% fatality rate, places HKU5 in a high-risk category if human infection occurs.
    [UPSC 2015] H1N1 virus is sometimes mentioned in the news concerning which one of the following diseases?

    Options: (a) AIDS (b) Bird flu (c) Dengue (d) Swine flu*

     

  • IISc develops Nanozyme to prevent Abnormal Blood Clotting

    Why in the News?

    Researchers at the Indian Institute of Science (IISc) have created an artificial metal-based nanozyme that can help prevent dangerous blood clotting, especially in conditions like pulmonary thromboembolism (PTE) and COVID-19.

    What is Blood Clotting?

    • About: When we get a cut or injury, our body quickly stops the bleeding by forming a blood clot. This is done by special blood cells called platelets that stick together and seal the wound.
    • Control mechanism: This natural process is called blood clotting or haemostasis and is controlled by certain chemicals in our body like collagen and thrombin.
    • Post covid issues: But in some illnesses like pulmonary thromboembolism (PTE) or COVID-19, the body sends too many signals to make clots, even when there is no injury.
    • Oxidative Stress: This creates a problem called oxidative stress, where harmful molecules called Reactive Oxygen Species (ROS) build up in the blood. These ROS molecules over-activate the platelets, causing them to make too many clots inside blood vessels.
    • Hazards: This can block blood flow, leading to serious health issues like heart attacks, strokes, or lung problems. This condition is called thrombosis, and it can be life-threatening.

    Vanadium-Based Nanozyme and Its Features:

    • Purpose and Design: Scientists at IISc developed vanadium-based nanozymes to mimic natural antioxidant enzymes that reduce ROS levels.
    • How they work: The nanozymes control oxidative stress by copying glutathione peroxidase, an enzyme that removes ROS and protects platelets.
    • Optimal Structure: Spherical-shaped vanadium pentoxide (VO) nanozymes were found to be the most effective.
    • Test Results in Mice: These nanozymes reduced blood clots and improved survival in PTE-affected mice with no toxicity signs over five days.
    • Next Steps: Scientists plan to test the nanozyme in ischemic stroke and are optimistic about human clinical trials after promising lab results with human platelets.
    [UPSC 2015] With reference to the use of nano-technology in health sector, consider the following statements:

    1. Targeted drug delivery is made possible by nanotechnology.

    2. Nanotechnology can largely contribute to gene therapy.

    Which of the statements given above is/are correct?

    Options: (a) 1 only  (b) 2 only (c) Both 1 and 2* (d) Neither 1 nor 2

     

  • Thermophilic Bacteria in Rajgir Hot Spring could help fight Deadly Infections

    Why in the News?

    Researchers from the Vellore Institute of Technology (VIT) have discovered antibiotic-producing bacteria in the Rajgir hot spring in Nalanda, Bihar.

    What are Thermophilic Bacteria?

    • About: Thermophilic bacteria, or thermophiles (meaning “heat lovers”), are microorganisms that thrive in high-temperature environments ranging from 45°C to 70°C.
    • Adaptation: These temperatures can cause third-degree burns in humans, but thermophiles are biologically adapted to survive and grow in such conditions.
    • Habitats: They are commonly found in hot springs, deep-sea hydrothermal vents, and compost piles, which are mineral-rich and have low microbial competition.
    • Advantages: Some thermophiles produce potent antibiotics to outcompete other microbes and dominate their niche.
    • Global Example: Thermophiles from hot springs in Saudi Arabia have shown antibacterial activity against gram-positive pathogens.

    Key Findings from India:

    • Sampling Challenge: Samples were collected from water and soil at 43°C–45°C, making fieldwork difficult.
    • Microbial Analysis: In the sample, Actinobacteria made up 40–43% of the microbial population, double the typical amount in hot springs.
    • Significance: Actinobacteria are well known for producing key antibiotics like streptomycin and tetracycline.
    • AMR Context: The findings are crucial in the fight against antimicrobial resistance (AMR), which could cost $1 trillion globally by 2050, according to the WHO.
    • Antibiotic Potential:
      • Lab Testing: Seven Actinobacteria strains were found to inhibit pathogens such as E. coli, Salmonella, Klebsiella, Pseudomonas, and Staphylococcus aureus.
      • Compound Discovery: Scientists identified diethyl phthalate using GC-MS, which showed effectiveness against Listeria monocytogenes, a deadly foodborne pathogen.
      • Future Scope: The compound has potential for antibiotic development, but not all thermophiles produce antibiotics, so screening is essential.
    • Uses:
      • Industrial Use: The enzyme Taq polymerase, used in PCR tests (including during COVID-19), is derived from a thermophile called Thermus aquaticus.
      • Agricultural Use: A 2018 BHU study showed thermophiles from Chumathang hot springs (Leh) promote plant growth, revealing wider industrial and ecological value.
    [UPSC 2023] Consider the following statements:

    1. Some microorganisms can grow in environments with temperature above the boiling point of water.

    2. Some microorganisms can grow in environments with temperature below the freezing point of water.

    3. Some microorganisms can grow in highly acidic environment with a pH below 3. How many of the above statements are correct?

    Options: (a) Only one (b) Only two (c) Only three* (d) All four

     

  • TR1 Cells: The Hidden Warriors in Malaria Immunity

    Why in the News?

    Scientists at Stanford University discovered that TR1 cells play a dominant role in fighting malaria reinfections.

    Understanding the Body’s Immune Response:

    • What is the Immune System? It’s the body’s defence system that protects us from infections like malaria.
    • First Defence: The skin and body surfaces block germs from entering.
    • Innate Immunity: If germs get in, the innate immune system reacts fast, like an emergency response team.
    • Adaptive Immunity: Then, the adaptive immune system kicks in, targeting germs specifically and remembering them for future protection.
    • B-Cells and T-Cells:
      • B-cells make antibodies to fight germs.
      • T-cells attack infected cells and guide other immune cells.
    • Helper T-Cells: A type called CD4+ T-cells helps organise the defence. Earlier, scientists thought TH1 cells were key in malaria, but a new study shows TR1 cells are more important, especially in repeat infections.

    What are TR1 Cells?

    • Role of TR1 Cells: These are special T-cells that help control the immune system and prevent overreaction.
    • Major Response in Malaria: Though small in number, during malaria, TR1 cells become the main helper cells.
    • Study in Uganda: In young children with repeated malaria, TR1 cells grew in number and improved the body’s ability to fight malaria without severe illness.
    • Memory and Immunity: TR1 cells remember the malaria parasite and return stronger with each infection.
    • Types of TR1 Cells:
      • Naïve TR1 – not yet active.
      • Effector TR1 – fighting infection.
      • Memory TR1 – remembering past infections.
    • Epigenetic Role: TR1 cells may respond by switching genes on or off, not by changing the genes themselves.

    Key Findings of the Study:

    • Research Team: Scientists from Stanford University studied people in Uganda over many months and years.
    • Tracking Infections: They followed individuals through multiple malaria infections to see how immune cells behaved.
    • Gene Scanning: A special technique was used to read the genes of each immune cell — like scanning a barcode.
    • Findings: TR1 cells were accurate, long-lasting, and clearly connected to malaria (not other infections).
    • Why it matters: This discovery can help in making better malaria vaccines, boosting long-term protection, and even improving treatments for other serious diseases.
    [UPSC 2025] With reference to monoclonal antibodies, consider the following:

    I. They are man-made proteins. II. They stimulate the patient’s immune system to fight the specific disease. III. They are produced using animal cells only.

    Which of the statements given above are correct?

    Options: (a) I and II only (b) II and III only (c) I and III only (d) All the three *