Bacillus thuringiensis is a naturally occurring soil bacterium first described in 1901 by Ishiwata (who isolated it from diseased silkworms in Japan) and independently rediscovered in 1911 by Ernst Berliner from larvae of the Mediterranean flour moth near the German town of Thuringia (from which the species name "thuringiensis" derives). The bacterium produces two types of insecticidal proteins: delta-endotoxins (Cry proteins — "crystal" proteins) produced as large crystalline inclusions during sporulation (the crystals are visible under phase contrast microscopy alongside spores), which are the primary insecticidal agents; and Vip proteins (Vegetative Insecticidal Proteins) produced during vegetative growth. The Cry proteins represent a remarkably large and diverse family of insecticidal proteins, with over 700 cry genes identified producing proteins with specificity for different insect orders (Lepidoptera, Diptera, Coleoptera, Hymenoptera) and even some targeting nematodes. This specificity means different Bt strains can be selected for controlling specific target pest insects while minimising effects on non-target organisms.

The two-stage activation process of Bt Cry proteins is central to understanding both their insecticidal specificity and their safety for non-target organisms. Stage 1 (solubilisation): In the alkaline insect midgut (pH typically 9-11 in lepidopteran larvae), the crystalline Cry protein inclusions (protoxin, typically 130-140 kDa) dissolve rapidly, a process that would not occur at the acidic or neutral pH of the mammalian digestive system. Stage 2 (proteolytic activation): Midgut proteases (serine proteases including trypsin-like enzymes) cleave the solubilised protoxin, removing the N-terminal and C-terminal domains to generate the active core toxic fragment (approximately 60-70 kDa), which contains the three functional domains required for receptor binding and pore formation. Stage 3 (receptor binding): The activated toxin binds with high affinity to specific receptor proteins on the apical brush border membrane of midgut epithelial cells — cadherin-like proteins (CADR) and aminopeptidase-N (APN) are the primary receptors in most susceptible insects, and their presence and the toxin's ability to bind them determines insect susceptibility. Stage 4 (pore formation): Following receptor binding, toxin monomers oligomerise (assemble into clusters) and insert into the membrane lipid bilayer, forming pores approximately 1 nm in diameter. Stage 5 (cell death): Pore formation collapses membrane potential and allows unregulated ion and water flux across the epithelial membrane, causing cell swelling, osmotic lysis, and ultimately complete destruction of the midgut epithelium, leaving the insect unable to feed and susceptible to fatal septicaemia.

The discovery and characterisation of Bt cry genes enabled one of the earliest and most commercially successful applications of plant genetic engineering. By isolating cry genes from Bacillus thuringiensis and engineering them for optimal expression in plant cells (including codon optimisation, since the codon usage of bacteria differs from that of plants, and addition of appropriate plant promoters and terminators), researchers created transgenic crop plants capable of producing Bt toxin proteins throughout their tissues (or in specific tissue types depending on the promoter used), providing continuous, systemic protection against target insect pests without requiring repeated pesticide spray applications. Bt cotton was the first genetically modified crop approved for commercial cultivation in India (in 2002), expressing the Cry1Ac gene conferring resistance to the American bollworm (Helicoverpa armigera), which was previously a devastating and difficult-to-control pest requiring multiple insecticide applications per growing season. Bt cotton adoption in India dramatically reduced insecticide use on cotton (cotton previously consumed approximately 50% of all insecticides used in Indian agriculture despite occupying only about 5% of cultivated land), significantly reduced farmer production costs, and increased crop yields, making Bt cotton one of the most economically impactful agricultural biotechnology innovations deployed in India. Bt maize, expressing Cry1Ab for protection against the European corn borer (Ostrinia nubilalis), is widely grown in North America and many other regions. Bt brinjal (eggplant), expressing Cry1Ac for resistance to the fruit and shoot borer (Leucinodes orbonalis), has been approved for commercial cultivation in Bangladesh.

The long-term effectiveness of Bt technology — both as traditional spray biopesticides and as transgenic Bt crops — faces the challenge of insect resistance evolution, a natural consequence of applying strong selection pressure (highly effective insecticide) to large insect populations with short generation times and abundant genetic variation. Several insect pest populations have evolved resistance to Bt toxins in the field, including populations of Helicoverpa zea (corn earworm) that have developed resistance to Bt maize expressing Cry1Ab in the US, and Pectinophora gossypiella (pink bollworm) that evolved Cry1Ac resistance in some regions where Bt cotton is grown. Resistance typically evolves through mutations in the genes encoding the midgut receptor proteins that Bt toxins bind — mutations reducing receptor expression or altering receptor structure prevent toxin binding and membrane insertion, conferring resistance without necessarily impairing other aspects of insect biology. Resistance management strategies include the "refuge strategy" (requiring farmers to plant non-Bt crop areas adjacent to Bt crop fields, maintaining a population of susceptible insects that interbreed with any resistant individuals, diluting resistance alleles), stacking multiple Bt toxins with different receptor specificities in the same crop (pyramiding — resistant individuals must simultaneously carry resistance to all toxins to survive), and integrating Bt crops with other integrated pest management approaches.