The Royal Society

Weighing Molecules with Light | The Royal Society

Professor Philip Kukura’s Royal Society lecture explored how modern light‑based methods, especially mass spectrometry, let scientists weigh individual molecules— from tiny explosives to massive therapeutic viruses. He began by tracing the historical need for standardized mass, from barley‑based pounds to Dalton’s atomic theory, showing that precise molecular weight acts like a unique QR code for chemical identity. Kukura explained the physics of a mass spectrometer: vaporising a sample, ionising it, and steering charged particles through electric fields so that heavier ions take broader turns, landing at distinct detector positions. This simple “ski‑turn” analogy underpins the ability to differentiate compounds such as RDX explosives from the metabolite 3‑hydroxystanozol, enabling airport security and anti‑doping tests. The talk then highlighted how the technology scales. Traditional small‑molecule drugs like aspirin are easily profiled, but newer biologics—antibody therapies such as Keytruda and gene‑delivery vectors like Zolgensma—contain thousands to millions of atoms and are water‑soluble, challenging conventional gas‑phase analysis. Pioneers like Carol Robinson introduced native mass spectrometry, preserving native conformations and extending accurate mass measurement to these complex therapeutics. Kukura concluded that as medicines become larger and more sophisticated, precise molecular weighing remains essential for purity verification, regulatory compliance, and the development of next‑generation treatments, cementing mass spectrometry as a cornerstone of modern life‑science research.