Christian Bohr. Discoverer of Homotropic and Heterotopic Allostery

Abstract

This essay recounts and revisits the scientific contributions of Christian Bohr, highlighting his pivotal role in discovering allostery about 120 years ago. Bohr's meticulous experimentation led to identifying two distinct forms of allostery: homotropic (single-ligand) and heterotropic (multi-ligand), the latter widely recognized as the Bohr Effect. His insights into oxygen binding to hemoglobin, as also modulated by carbon dioxide presence, laid the foundation for part of modern pharmacological advancements. Today, allosteric principles drive drug development, improving specificity and potentially minimizing adverse effects, with numerous allosteric modulators emerging in pharmaceutical pipelines. The treatise spans 13 chapters and an appendix with definitions on allosteric terms. It begins with Bohr's background, laboratory environment, and pivotal experiments in 1903 that demonstrated allosteric mechanisms. It traces Bohr's scientific journey—from medical training to his professorship in Copenhagen—and his collaborative research with Karl Hasselbalch and August Krogh. The work situates Bohr within the broader historical context, examining influence of earlier, 19th-century, and later physicochemical and physiological thoughts on his discoveries. Further chapters discuss dose-response relationships, including Hüfner's hyperbolic equation and Henri's enzyme kinetics, parallel to Bohr's findings. Bohr's S-shaped oxygen-hemoglobin binding curve, analyzed in 1904, marked a critical advancement in understanding homotropic allostery. Subsequent developments, such as Hill's equation and the Monod-Wyman-Changeux model, settled both types of allostery description. My study concludes with Bohr's abandonment in 1910 of his secretion theory and his legacy. Despite his early death in 1911, Bohr's contributions remain fundamental, warranting revitalized recognition for his discovery of allostery.