George Nickolas Papanicolaou received his early schooling in Kyme, and at age eleven was sent to Athens for further education. He received the Doctor of Medicine degree in 1904 from the University of Athens, then served as an assistant surgeon in the Greek army until 1906. After practicing for one year with his father, Papanicolaou did postgraduate work in biology at the universities of Jena, Freiburg, and Munich. The last awarded him the Ph. D. in zoology in 1910.
About 1910 Papanicolaou set out for Paris with his wife because opportunities for scientific investigation in Greece were limited. En route he visited the Oceanographic Institute of Monaco, where, after an unexpected offer of a staff position, he remained for a year as a physiologist. During the Second Balkan War he again served in the Medical Corps of the Greek army (1912 - 1913). He and his wife then immigrated to the United States, arriving at New York City on October 19, 1913, without definite plans. Through the influence of Thomas Hunt Morgan, professor of experimental zoology at Columbia University, Papanicolaou obtained a part-time position as assistant in the Department of Pathology and Bacteriology at New York Hospital.
In September 1914 he was appointed assistant and research biologist in anatomy at the Cornell Medical College under Charles R. Stockard. Mary Papanicolaou was soon given a job as her husband's technician. In 1917, Stockard invited Papanicolaou to collaborate in his work in experimental genetics. At that time great interest was focused on the role of chromosomes in the determination of sex. Papanicolaou began work in this area, using the ovum of the guinea pig. He established the correlation of the cytology of vaginal smears with ovarian and uterine cycles. This work resulted in a paper (1917) by Papanicolaou and Stockard that described the cellular changes observable in vaginal epithelium during the estrous cycle.
Their technique became a standard method for studying the sexual (estrous) cycle in other laboratory animals and influenced subsequent work in endocrinology and sexual physiology. Its application in the mouse as an assay of follicular hormone resulted ultimately in the first isolation of a sex hormone, estrogen.
In 1923, Papanicolaou extended his studies to humans by undertaking a systematic study of the cytology of human vaginal secretions in an effort to learn whether comparable vaginal cellular changes occur in women in association with the menstrual cycle. His first observation of distinctive neoplastic cells in the vaginal fluid of a woman with cancer of the cervix gave Papanicolaou what he later described as "one of the most thrilling experiences in my scientific career, " and led to redirection of his work. At this point Papanicolaou focused on careful cytologic study of specimens obtained from women with cancer of the uterus and with other diseases of the reproductive tract.
In 1928 his observations, entitled "New Cancer Diagnosis, " were presented at the Third Race Betterment Conference and were published later that year. He predicted the application of this technique to the diagnosis of cancer not only of the female reproductive system but also of other organ systems. For several years Papanicolaou's results were not generally accepted by the medical community, and in 1932 he turned his attention to other problems. For the next five or six years he investigated the effects of various hormones on reproductive cells.
In 1939, he began collaboration with Herbert F. Traut, a gynecologist who was convinced of the value of cytologic methodology. They accumulated an enormous amount of data that was published as Diagnosis of Uterine Cancer by the Vaginal Smear (1943). Acceptance of the findings followed, and the method was widely acclaimed. Superficial lesions could now be detected in their incipient, preinvasive phase, before the appearance of any symptoms. Papanicolaou later referred to his discovery as an example of serendipity; his early objectives were totally unrelated to cancer detection. The Papanicolaou smear soon achieved wide application as a routine screening technique. This was followed by a sharp reduction in the death rate from cancer of the uterus and of the cervix. Interest in this diagnostic method has spread rapidly throughout the world since 1947, when the first course in exfoliative cytology was offered at Papanicolaou's laboratory in New York City.
The principal value of the test lies in cancer screening, but it is also applied to the prediction of cancer radiosensitivity, the evaluation of the effectiveness of radiotherapy, and the detection of recurrence after treatment. Papanicolaou's work is among the most important in the field of cancer in modern times. Papanicolaou rose to the rank of professor of clinical anatomy at Cornell University in 1924, and became emeritus in 1949. He died in Miami on February 19, 1962.
George Nicholas Papanicolaou was conferred honorary membership in the Obstetrical and Gynecological Society of Athens and the New York Academy of Sciences.
Papanicolaou was a dedicated scientist, as modest as he was hardworking. He did not take vacations, worked seven days a week and relished immersing himself in the wonders of his research.
In Geece George Nickolas Papanicolaou married Mary Mavroyeni, the daughter of an army officer, on September 25, 1910. They had no children.