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

Tuberculosis Tuberculosis (TB) is caused by Mycobacterium tuberculosis, identified by Robert Koch in 1882; M. bovis can also cause zoonotic TB. It spreads mainly by airborne droplet nuclei when a pulmonary TB patient coughs, sneezes or speaks; close household contact is important. Infection may remain latent or progress. Primary TB in children often forms a Ghon focus with draining hilar lymph nodes, together a Ghon complex; reactivation/post-primary TB usually appears in apical/posterior segments and may form Simon foci. Symptoms include chronic cough, fever, night sweats, weight loss, haemoptysis; extrapulmonary TB may affect lymph nodes, spine, pleura, kidneys. Diagnosis combines sputum smear/culture, chest X-ray, Mantoux tuberculin skin test for latent infection, IGRA (QuantiFERON/T-SPOT), and in India CBNAAT/CB-NAAT is central for rapid diagnosis and rifampicin resistance under NTEP/NDTB. Treatment follows DOTS/NDTB: HRZE for 2 months followed by HR for 4 months for drug-susceptible TB; MDR-TB and XDR-TB require longer, more toxic regimens with fluoroquinolones, linezolid and bedaquiline. India bears a high MDR-TB burden. Prevention includes DOTS, contact tracing, BCG vaccination, latent-TB preventive therapy, nutrition, DOTS-Plus, and India’s TB Elimination 2025 target under NTEP.

Nitrogen fixation Biological nitrogen fixation converts atmospheric N₂ to NH₃ by nitrogenase. The standard Mo-dependent nitrogenase has a MoFe protein (dinitrogenase) and an Fe protein (dinitrogenase reductase, Fe-S); some organisms use alternative Fe-Fe or Fe-only nitrogenases. In *Rhizobium*-legume symbiosis, bacteria form root nodules, fix N₂, and supply amino acids; Frankia fixes N₂ in actinorhizal plants; free-living cyanobacteria such as Anabaena and Nostoc fix N₂ in paddy fields and water. Non-biological fixation includes atmospheric lightning, which provides energy to convert N₂ and O₂ to NO/NO₂, eventually nitrates, and the Haber-Bosch process, which synthesises ammonia from N₂ and H₂ at high pressure/temperature with iron catalyst, energy-intensive. Industrial fixation uses Haber-Bosch ammonia; part of ammonia is oxidised by the Ostwald process to nitric acid, used for ammonium nitrate and nitrophosphate fertilisers, while ammonia and CO₂ are converted to urea by the Bosch-Meiser process. India produces about 25 million tonnes of urea a year but still imports a substantial quantity. Overuse of synthetic fertilisers, however, can disrupt nutrient cycles through eutrophication and nitrous-oxide emissions, reducing long-term soil productivity.

Gene therapy Gene therapy delivers functional genes, corrects mutations, or modulates gene expression to treat disease. Germline gene therapy targets gametes, zygotes or early embryos, so the change can be inherited; it is ethically restricted and not clinically approved. Because no approved human germline gene therapy exists, the clearest examples are experimental germline genome-editing attempts, such as CRISPR/Cas9 correction of β-thalassaemia or cystic fibrosis mutations in human embryos, and the controversial 2018 CRISPR-edited embryos for HIV resistance; mitochondrial replacement therapy is a related heritable mitochondrial technique but not classic gene therapy. Somatic cell gene therapy targets non-reproductive cells and is not inherited. Ex vivo therapy removes patient cells, modifies them, and reinfuses them: ADA-SCID, β-thalassaemia/sickle-cell disease ex vivo editing, and CAR-T cell therapy, which is being developed in India for haematological malignancies. In vivo therapy delivers vectors, often AAV or lentiviral, directly to tissues: AAV-mediated RPE65 gene therapy for inherited retinal dystrophy, Zolgensma for spinal muscular atrophy, and ocular gene therapy trials in India. In India, gene therapy is regulated under ICMR guidelines and the Drugs and Cosmetics Act/CDSCO framework, requiring safety, vector control and ethical approval.

Thus TB control, nitrogen fixation and gene therapy intersect in biomedical significance: TB elimination requires rapid diagnostics and DOTS; sustainable agriculture needs efficient nitrogen fixation; gene therapy offers future tools for TB vaccines, mycobacterial gene targeting and nitrogen-fixing crop improvement, while One Health links M. bovis, nutrient cycles and human health.