In the first half of the 20th century, crystallization of small simple molecules had become a vital process in understanding their chemical nature, but could crystallization also help in understanding the chemical nature of vital processes? Three scientists overcame the barrier of crystallizing proteins in different ways, and for their achievements they shared the Nobel Prize in Chemistry in 1946.

In 1926, James Sumner successfully crystallized an enzyme, called urease, for the first time, and with it he solved a contentious debate amongst biologists. For years researchers had studied the effects of enzymes – nature’s catalytic converters – without knowing anything definite about what they are, partly because they could not be isolated in the pure form. Despite several colleagues telling him that isolating an enzyme was a foolish task, Sumner proved urease could be crystallized, and that it could still carry out its catalytic reaction in the crystal state. Tests showed that urease is also a protein, making this the first ever protein to be crystallized.

Sumner’s findings were initially dismissed. However, building on this pioneering work, John Northrop developed the crystallization of pure enzymes and other proteins into an art form; and with it helped convince researchers that enzymes can be purified and isolated in tangible quantities. Northrop and his colleagues created the optimal conditions for successfully crystallizing a number of digestive enzymes, such as pepsin and trypsin. Through this, Northrop discovered interesting relationships between enzymes and related proteins, and this paved the way to developing a better understanding of how enzymes work.

The chemical make-up of viruses was as obscure as that of enzymes, before Wendell Stanley showed that the tobacco mosaic disease virus can be crystallized in the same way as proteins and enzymes. Stanley’s findings helped to open up an almost unlimited field of research – scientists could now crystallize a host of viruses, allowing them to investigate their precise structures and how to target them with treatments.