Bhopal gas tragedy: scientific challenges and lessons for future

Abstract

Some of the challenges of BGT were answered by two multi-disciplinary projects of the ICMR on Pathology and Toxicology and Pathophysiology. Unlike other chemical disasters, the aerosol inhaled by the Bhopal victims contained a mixture of MIC and its trimers and dimers, as well as aqueous and thermal decomposition products, including HCN. A coordinated GC-MS study of the blood and autopsy tissues and chemicals in the Tank residue confirmed their role. Autopsy studies revealed the pathological changes in the acute, sub-acute and chronic phases progressive changes of pulmonary edema and bronchiolitis, followed by chronic pulmonary fibrosis. Cerebral edema resulted in 'acute histotoxic anoxia'. Intensive experimental studies with the help of newer tools of molecular biology might throw more light on the underlying mechanisms and newer therapeutic approaches. The initial finding of cherry-red discoloration of lungs led to a suspicion of cyanide toxicity. Eventually, elevated blood and tissue cyanide levels confirmed the prompt therapeutic response to NaTS and accompanying increase of urinary NaSCN excretion. However, periodic clinical recurrences and relapses pointing towards 'chronic cyanide toxicity' remained enigmatic. Specific changes the 2-3 DPG levels and Blood Gases were explained on the basis of N-carbamoylation of end-terminal valine residues of Hb. Soon, several other end-terminal α-amino groups of tissue proteins were also found to be N-carbamoylated. Had the attempts at demonstrate S-carbamoylation of glutathione and other SH radicals of tissue enzymes like rhodanese succeeded, perhaps the underlying mechanism of chronic cyanide toxicity due to MIC might have been resolved. Based on the practical lessons learnt in Bhopal, an attempt will be made to present the salient pathological and toxicological findings, followed by a brief outline of the principles of planned laboratory management for alleviation of human suffering from future chemical disasters.