The discovery of enzymes, the biological catalysts that manage nearly every chemical reaction in living systems, was not a singular event but a complex scientific journey spanning centuries. These protein-based molecules accelerate processes like digestion and metabolism with remarkable speed and precision. Understanding when enzymes were discovered requires tracing the shift from observing their effects in ancient practices to isolating them in the laboratory and finally determining their exact chemical nature.
Recognizing the Phenomena of Biological Action
Long before scientists understood the concept of a biological catalyst, the effects of enzymatic action were recognized and utilized in daily life. Ancient civilizations relied on processes like fermentation to produce staples such as bread, beer, and cheese, unknowingly harnessing microbial enzymes. The ancient Egyptians were brewing beer as far back as 5,000 BCE, and leavening bread with wild yeast was a significant practical advancement.
The process of digestion was another long-observed mystery, with early theories often relying on mechanical action or “vital forces” to explain how food was broken down. In the 17th and 18th centuries, debate centered on whether digestion was purely chemical or mechanical. The transformation of starch into sugar by plant extracts and saliva was known in the late 1700s, but the mechanism remained unidentified.
Isolating the Early Ferments
The early to mid-1800s marked the first successful isolation of the active agents responsible for these biological transformations, which scientists referred to as “ferments.” In 1833, French chemists Anselme Payen and Jean-François Persoz isolated the first substance now classified as an enzyme. They extracted a material from malt that accelerated the conversion of starch into sugar and named this substance “diastase,” from the Greek word for “to separate.”
In 1836, German physiologist Theodor Schwann isolated a substance from stomach secretions responsible for the digestion of meat. Schwann named this agent pepsin, making it the first enzyme prepared from animal tissue. While both diastase and pepsin showed remarkable catalytic power outside a living organism, their true chemical composition remained unknown, fueling debate about whether these agents were living or non-living entities.
The Conceptual Shift to Cell-Free Catalysis
The distinction between “organized ferments” (living organisms like yeast) and “unorganized ferments” (chemical agents like pepsin) became a controversy in the late 19th century. Louis Pasteur championed the view that fermentation was inextricably linked to the life force of the yeast cell, a “vital act” that could not occur if the cell were dead. This belief meant that the catalytic power could never be separated from the living organism itself.
A conceptual shift occurred in 1878 when German physiologist Wilhelm Kühne coined the term “enzyme” (meaning “in yeast”) to distinguish these chemical agents from living organisms. Kühne’s term provided a name for non-living substances, like pepsin, even though Pasteur’s “vital force” theory still dominated the understanding of fermentation. The definitive answer to the mechanism of fermentation came in 1897 with the discovery by Eduard Buchner.
Buchner found that an extract prepared by grinding yeast cells with quartz sand could still ferment sugar, producing alcohol and carbon dioxide, even though all the living yeast cells had been destroyed. This landmark experiment proved that fermentation was purely a chemical process driven by substances that could function outside the cell, effectively shattering the “vital force” theory. The discovery of this cell-free fermentation marked the moment when the mechanism of biological catalysis was truly understood and is often cited as the birth of modern biochemistry.
Finalizing the Chemical Identity
With the functional mechanism settled, the final step in the discovery timeline was determining the chemical structure of enzymes. Despite the work of Buchner, many prominent chemists still believed that enzymes were a special class of unidentifiable compounds, not simple proteins. The definitive proof arrived in 1926 with the work of American chemist James B. Sumner.
Sumner successfully isolated and crystallized the enzyme urease from jack beans, which breaks down urea into ammonia and carbon dioxide. Upon detailed analysis, Sumner concluded that the crystalline urease was a protein. This assertion was met with skepticism because proteins were considered too complex and fragile to be the sole agents of such specific chemical reactions.
The skepticism was overcome in the early 1930s when John Howard Northrop and Moses Kunitz successfully crystallized and confirmed the protein nature of several other enzymes, including pepsin and trypsin. These later confirmations solidified the modern understanding that the vast majority of enzymes are, in fact, proteins, bringing the centuries-long process of discovery to a close.