(a) Mention the causative agent and means of spread of tuberculosis. Also describe symptoms, diagnosis, treatment and preventive…

(a) Tuberculosis

• Causative agent: Mycobacterium tuberculosis, a non-motile, acid-fast rod discovered by Robert Koch in 1882; M. bovis causes a zoonotic form.
• Spread: mainly by air. Droplet nuclei expelled when a pulmonary TB patient coughs, sneezes or speaks are inhaled by close contacts; less often through unpasteurised milk from infected cattle. Infection often stays latent, and active disease develops mainly when immunity is low (HIV, diabetes, malnutrition, smoking).
• Symptoms: cough for more than two weeks, sometimes with blood in the sputum (haemoptysis); evening fever, night sweats, loss of weight and appetite, chest pain and fatigue. Extrapulmonary TB affects lymph nodes, pleura, bones and spine, meninges, kidneys and intestine.
• Diagnosis: sputum smear microscopy for acid-fast bacilli; culture on Löwenstein–Jensen medium or in liquid MGIT; rapid molecular tests (CBNAAT/Xpert MTB/RIF, Truenat), which also detect rifampicin resistance; chest X-ray; Mantoux (tuberculin) skin test or IGRA for latent infection.
• Treatment: DOTS (directly observed treatment, short-course), free under India's National TB Elimination Programme, with nutritional support through the Ni-kshay Poshan Yojana. Drug-sensitive TB: 2 months of isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E), then 4 months of HR, six months in all. Multidrug-resistant TB (resistant to at least H and R) needs second-line drugs, such as the 6-month BPaLM regimen (bedaquiline, pretomanid, linezolid, moxifloxacin) approved in India in 2024. Incomplete treatment breeds resistance.
• Prevention: BCG vaccination of newborns (protects mainly against severe childhood TB); early detection and full treatment of patients, which cuts transmission; contact tracing and TB preventive treatment for household contacts and people living with HIV; cough hygiene, ventilation and avoiding overcrowding; pasteurised milk; better nutrition and control of HIV, diabetes and tobacco use.

(b) Biological, non-biological and industrial nitrogen fixation

Nitrogen fixation converts inert atmospheric N₂ (about 78% of air) into ammonia or nitrates that plants can use.

• Biological: carried out by prokaryotes with the enzyme nitrogenase (MoFe protein and Fe protein): N₂ + 8H⁺ + 8e⁻ + 16 ATP → 2NH₃ + H₂ + 16 ADP + 16 Pi. Oxygen destroys nitrogenase, so it is protected by leghaemoglobin in root nodules and by heterocysts in cyanobacteria. Symbiotic fixers are Rhizobium in legume nodules, Frankia in alder and Casuarina, and Anabaena azollae in the water fern Azolla; free-living ones are Azotobacter and Beijerinckia (aerobic), Clostridium (anaerobic) and cyanobacteria such as Nostoc; Azospirillum is associative on cereal roots.
• Non-biological (natural): the energy of lightning combines N₂ and O₂ into nitric oxide (N₂ + O₂ → 2NO), which is oxidised to NO₂; this dissolves in rain as nitrous and nitric acids and reaches the soil as nitrates. High-temperature combustion also forms nitrogen oxides.
• Industrial: the Haber–Bosch process makes ammonia from N₂ of air and H₂ from natural gas: N₂ + 3H₂ ⇌ 2NH₃ (exothermic), at about 450–500 °C and 150–250 atmospheres over an iron catalyst promoted with potassium and aluminium oxides. Ammonia is converted to urea, ammonium nitrate and ammonium sulphate fertilisers, and to nitric acid. The process is energy-intensive, and fertiliser run-off causes eutrophication.

(c) Gene therapy

Gene therapy is the introduction, replacement or correction of genes in a patient's cells to treat or prevent disease, using vectors such as retroviruses, lentiviruses and adeno-associated virus (AAV), or genome editing such as CRISPR–Cas9.

• Germline gene therapy: alters gametes, the zygote or an early embryo, so the change enters every cell and is inherited by future generations. It raises ethical and safety concerns (off-target changes, no consent from descendants) and is not permitted in humans in India and most countries. The CRISPR-edited babies announced in China in 2018 were condemned worldwide; heritable changes are made in transgenic animals such as mice.
• Somatic cell gene therapy: targets body cells, so the effect stays in the patient and is not inherited. It is of two types, ex vivo and in vivo.
• Ex vivo: cells are removed, genetically modified in culture and returned. Examples: the first gene therapy (NIH, 1990), in which a functional ADA gene was given to a four-year-old girl with ADA-deficiency SCID; CAR-T cell therapy, such as India's NexCAR19 (approved 2023) for B-cell lymphoma and leukaemia; and Casgevy, CRISPR-edited blood stem cells for sickle-cell disease.
• In vivo: the vector is given directly into the body. Examples: Luxturna, AAV carrying the RPE65 gene injected under the retina for inherited retinal dystrophy; and Zolgensma, AAV9 carrying the SMN1 gene for spinal muscular atrophy.
• Risks include insertional mutagenesis, immune reactions and high cost.