Kamala Nehru, Jawaharlal Nehru’s wife, fell victim to the old enemy, tuberculosis (TB), in a far-off Swiss sanatorium in 1936. Her privileged social standing could not save Kamala. A stark reminder of the disease’s indiscriminate nature.

At the time, Nehru was confined to a colonial prison, a helpless, distant spectator to his wife’s battle with TB. His shackles prevented him from being by her side. In a cruel twist of fate, the man who would become his greatest adversary in the political arena, M.A. Jinnah, too, ultimately met his end against the same relentless enemy that claimed Nehru’s beloved, we later learnt.

The untimely demise of these privileged individuals, along with millions around the globe, is a chilling testament to the lack of effective therapeutics against the dreaded disease, despite its causative agent being uncovered in 1882. Today, almost a century later, the narrative of TB treatment has dramatically transformed. We aspire to eliminate tuberculosis from the world by the end of this decade. This year (2024), the theme of World TB Day was “Yes, we can end TB.” This was unimaginable for centuries. It is now possible because of the therapeutic regimen. A testament to medical advancements and a tribute to the tireless efforts of the medical community.

Revolution in treatment

TB is an unyielding nemesis caused by Mycobacterium tuberculosis, which has existed for at least 3 million years. It has been a thorn in the side of humanity since the beginning of civilisation. Before antibiotics, TB treatments were largely palliative, offering fresh air and rest to patients in sanatoriums at high altitudes or tranquil countryside locations. Alternatively, surgical procedures like lobectomy, artificial pneumothorax (collapsing the lung), and pneumonectomy were performed by expert cardiothoracic surgeons. These treatment options, however, had limited success, and their efficacy was often questionable.

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The discovery of antibiotics by Sir Alexander Fleming marked the beginning of a new chapter in the fight against this persistent foe. However, the real revolution in TB treatment was brought on by the ground-breaking work of Sir Austin Bradford Hill.

Hill’s own bout with TB during World War I may have thwarted his aspirations to become a physician, but it didn’t dampen his spirit. Hill made remarkable contributions to medical statistics. He pioneered the randomised control trial technique at the British Medical Research Council (BMRC). It led to one of the first randomised clinical trials to evaluate the efficacy of antibiotics against TB. He is also credited with the establishment of early ethical guidelines for clinical trials that set a new standard for scientific integrity in medicine.

Cornerstone of breakthroughs

Clinical trials performed using the randomisation technique have been instrumental in shaping modern medicine, providing a robust and unbiased method to evaluate the efficacy of various treatments and interventions. They have been the cornerstone of numerous medical breakthroughs, including the discovery of aspirin’s role in preventing heart attacks, the development of antiretroviral therapy for HIV treatment, and the application of cognitive behavioural therapy for mental health conditions to the latest COVID vaccines. 

Hill’s effective implementation of RCTs in testing streptomycin, the first antibiotic to prove effective against TB, was a game-changer. His meticulous work helped establish the optimal dosage of this life-saving drug, transitioning it from a lab discovery to a practical solution for TB. Hill’s efforts redefined the management of TB, moving it from the exclusive domain of specialised surgeons to the broader realm of primary care physicians. 

Hill’s contributions, however, went beyond TB. His eponymous ‘Bradford Hill Criteria’ form the bedrock of modern epidemiology. The nine criteria — strength, consistency, specificity, temporality, biological gradient, plausibility, coherence, experiment, and analogy — provide a robust framework for establishing a causal link between a specific factor and a health effect. From establishing alcohol as a risk factor for cardiovascular diseases to the risks of sugar-sweetened beverages and obesity, the criteria served as a guiding principle for examining the evidence in several areas.

Hill’s criteria were pivotal in establishing the link between smoking and lung cancer through a case-control study. His research provided irrefutable evidence, debunking the pseudoscience propagated by the tobacco lobby and causing a significant shift in public perception and policy towards tobacco.

Debt of gratitude

As we stand on the threshold of eliminating TB, even in the face of formidable challenges such as Multi-Drug Tuberculosis (MDR-TB) and Extensively Drug-Resistant Tuberculosis (XDR-TB), we owe a monumental debt of gratitude to Sir Austin Bradford Hill. His life and work serve as a testament to the power of scientific inquiry and resilience, continuing to inspire us as we aspire to achieve the ambitious goal of eradicating TB.

Today, as we reflect on the past, let’s honour the invaluable contributions of scientists like Bradford Hill. In their tireless research and relentless pursuit of knowledge, they have carved pathways to incredible change. His work is a testament to the power of science to effect positive change, a legacy that continues to inspire researchers around the world.

(Dr. C. Aravinda is an academic and public health physician. aravindaaiimsjr10@hotmail.com)