A virus is a submicroscopic infectious agent that can only replicate inside the living cells of an organism, making it an obligate intracellular parasite. The discovery of these entities occurred during the late 19th century, when microbiology focused almost entirely on bacteria as the cause of infectious diseases. Scientists expected to find a visible, culturable microbe for every ailment. The realization that an infectious agent could be invisible to microscopes and impossible to grow outside a living host cell required a revolutionary shift in scientific thought.
The Precursor Investigations
The initial systematic study leading to the discovery of the first virus focused on tobacco mosaic disease, which affected crops across Europe. In 1879, German agricultural biologist Adolf Mayer began investigating the disease, which caused a mottled, discolored pattern on the leaves. Mayer published a paper in 1886, describing the symptoms and demonstrating the disease’s infectious nature. He proved this by grinding diseased leaves and using the extracted sap to infect healthy tobacco plants.
Mayer’s transmission experiments established that a disease-causing agent was present in the sap. He struggled to identify the pathogen using established methods, as he could not observe any fungi or bacteria under a microscope. Following Robert Koch’s postulates, Mayer attempted to culture the agent on nutrient media without success. He hypothesized that the cause was either a very small, unseen bacterium or a soluble toxin.
The Filtration Breakthrough
The physical nature of this unseen infectious agent was demonstrated by the Russian scientist Dmitri Ivanovsky in 1892. Ivanovsky sought to confirm Mayer’s findings and isolate the causal organism of the tobacco mosaic disease. The key to his experiment was the Chamberland filter, a porcelain device designed with pores fine enough to trap all known bacteria from a liquid.
Ivanovsky filtered the infectious sap through this porcelain filter. Based on germ theory, the expectation was that the filtrate would be sterile. However, when he inoculated healthy tobacco plants with the clear, filtered liquid, the plants still developed the full symptoms of the disease. This result proved the infectious agent was significantly smaller than the smallest known bacterium. Ivanovsky concluded that the agent was either an ultra-small bacterium that passed through a faulty filter or a toxin secreted by a bacterium.
Defining the New Agent
The conceptual understanding of the agent as a new entity, distinct from bacteria, came from the Dutch microbiologist Martinus Beijerinck in 1898. Beijerinck independently repeated Ivanovsky’s filtration experiments, confirming the agent could pass through bacterial filters. He then conducted dilution experiments, demonstrating that the agent multiplied only in actively dividing plant cells. This finding was inconsistent with the properties of a non-living toxin, which would simply lose its effect through dilution.
Beijerinck also observed that the agent could not be grown in laboratory culture media. He concluded that the pathogen was not a particulate microbe but a unique form of living infectious material. He described this agent as Contagium vivum fluidum, or “contagious living fluid,” emphasizing its reproductive nature and ability to diffuse through agar gel. Beijerinck was the first to use the term “virus,” derived from the Latin word for “poison,” to specifically describe this filterable agent, establishing the foundation for virology.
The First Virus Identified
The specific pathogen identified through these investigations was the Tobacco Mosaic Virus (TMV). TMV is a rod-shaped virus with a helical structure, approximately 300 nanometers long and 18 nanometers in diameter. Its simple composition consists of a single strand of ribonucleic acid (RNA) encased within a protein coat, or capsid.
The simple chemical composition of TMV made it an ideal subject for further study, bridging biology and chemistry. In 1935, American biochemist Wendell Stanley successfully crystallized TMV. Since crystallization is typically applied to non-living chemicals, Stanley’s achievement suggested the virus was a protein molecule that retained its infectious properties even in an inert state. Later work revealed that TMV contained RNA, proving it to be an infectious nucleoprotein. Stanley’s work provided the first evidence that viruses occupied a space between living organisms and non-living biochemicals, launching the era of molecular biology.