Infectious mononucleosis, commonly known as mono or “the kissing disease,” is a viral illness causing symptoms like profound fatigue, fever, and a sore throat. The discovery of its cause involved medical and scientific milestones spanning nearly a century. This history traces the illness from initial clinical observations to the precise identification of its viral source. The progression involved physicians recognizing symptoms, hematologists defining a unique blood abnormality, and finally virologists identifying the specific infectious agent.
Early Recognition of the Syndrome
The earliest signs of the illness were documented in the late 19th century, long before physicians understood its specific nature. In 1885, Russian pediatrician Nil Filatov described an infectious process he termed “idiopathic adenitis.” These initial accounts focused on a febrile disease accompanied by prominent swelling of the lymph nodes.
The German physician Emil Pfeiffer provided a more definitive early description in 1889, documenting cases of a short-term febrile illness characterized by fever, sore throat, and cervical lymph node enlargement. Pfeiffer named the condition Drüsenfieber, which translates to “glandular fever.” These observations marked the first time the syndrome was recognized as a distinct clinical entity.
Formalizing the Diagnosis and Naming
The modern name and clinical definition of the disease emerged in the early 20th century, driven by advances in blood analysis. In 1920, American physicians Thomas Peck Sprunt and Frank Alexander Evans published a classic clinical description. Their paper, titled “Mononuclear leukocytosis in reaction to acute infection (infectious mononucleosis),” introduced the term “infectious mononucleosis.”
The name “mononucleosis” was chosen because the researchers observed an unusual proliferation of white blood cells in the peripheral blood of patients. They noted an increase in mononuclear cells, providing a distinct laboratory finding for the syndrome. These atypical cells are actually activated CD8+ T lymphocytes responding to the infection. This characteristic blood picture became a clinical criterion for diagnosis, allowing doctors to identify the condition before the actual virus was known.
Identifying the Epstein-Barr Virus
The search for the specific infectious cause of mononucleosis concluded decades later with the identification of a herpesvirus. In 1964, scientists Michael Epstein and Yvonne Barr, along with Bert Achong, identified a viral particle in cultured cells taken from Burkitt’s lymphoma. This virus was subsequently named the Epstein-Barr Virus (EBV).
The connection between EBV and infectious mononucleosis was established in 1968 by virologists Gertrude and Werner Henle. They developed a serological test to detect antibodies to EBV. When a technician in their laboratory developed mononucleosis, the Henles compared a stored blood sample taken before the illness with one taken after. The comparison demonstrated the technician developed EBV antibodies during the illness, suggesting the virus was the cause. Subsequent studies confirmed that primary EBV infection is responsible for approximately 90% of acute mononucleosis cases.