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George Nicholas Papanicolaou 1883-1962
His scientific innovations, including the Pap smear, helped establish the field of cytology.
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George Nicholas Papanicolaou, MD, developed a simple test, the Pap smear, which since its introduction has led to a 70% reduction in cervical cancer deaths.
Papanicolaou was born on May 13, 1883. He was the third child of Nikolas and Maria Papanicolaou. He and his two sisters and brother were raised in Kymi, a small town on the island of Euboea, Greece. Papanicolaou attended the University of Athens, where he studied literature, philosophy, languages and music.
At the urging of his physician-father, Papanicolaou pursued a career in medicine, eventually earning his medical degree in 1904. Later that year, he was conscripted into the army and was admitted to the academy for reserve officers.
When he was discharged two years later, Papanicolaou faced a decision: practice medicine in Kymi or continue as a military physician. He was not interested in either option. Instead, Papanicolaou convinced his father to finance additional education in Jena, Germany. He arrived there in 1907 to study under Ernest Haeckel, an early supporter of Darwin’s theory of evolution. He also studied with August Weismann of Freiburg, a geneticist. Papanicolaou enrolled at the Zoological Institute in Munich and was awarded a PhD in 1910 for his thesis, “Sex differentiation of the daphnia.”
He returned to Greece to pursue an academic career in biologic research. On the ferry home, he met Andromache (Mary) Mavroyeni. The couple fell in love, and married on Sept. 25, 1910.
Shortly after their wedding, Papanicolaou accepted a position at the Oceanographic Museum of Monaco. He worked as the physiologist for a scientific expedition on an oceanographic research ship.
In search of career opportunities
With the death of his mother in 1912, Papanicolaou returned to Greece. He stayed to serve as an army physician during the Balkan War. While in the army, he met several American volunteers who told him about the many career opportunities in the United States. The Papanicolaous arrived in New York City in 1913.
Because they had limited funds, the couple took positions at Gimbel’s department store. Papanicolaou’s retail career was short, however, and within a few weeks, he found a laboratory position at New York Hospital. By 1914, he was working at Cornell Medical College under Charles Stockard, MD, chairman of the anatomy department. Papanicolaou’s wife Mary soon joined him at Cornell as his assistant. The work that Papanicolaou pursued during his 45-year tenure at the college established the field of modern diagnostic cytology.
It was while at Cornell that Papanicolaou developed a method for studying exfoliated epithelial cells in relation to the menstrual cycle. He was studying guinea pig oocytes and he needed to harvest the eggs just before ovulation. The only way to collect the eggs was to sacrifice the animals, killing many animals whose eggs were not at the right point. He awoke one morning with the realization that guinea pigs have a menstrual cycle; it just had not been charted before. He knew that females of all higher animals have a periodic vaginal discharge. In the case of guinea pigs, it was probably too scanty to be visualized.
Papanicolaou used a nasal speculum to collect samples, and examined the smears under his microscope. What he saw was exciting: diverse cell forms and a sequence of distinctive cytologic patterns. Papanicolaou was able to chart the cyclic ovarian and uterine changes each day, allowing him to predict ovarian status. He could then harvest the oocytes at the appropriate time. He published his research on the cytologic patterns in guinea pigs in the American Journal of Anatomy in 1917.
Theory met with skepticism
Eventually, he began taking similar scrapings from women, and he soon noticed malignant cells in smears taken from women with cancer. By 1928, he had gathered enough data on cervical carcinoma cells and their detection to make a presentation on the topic at the Race Betterment Conference in Battle Creek, Mich. He expected a warm reception; instead, he was greeted with skepticism. At the time, most physicians and scientists thought the idea of examining scraped dead cells for cancer was ridiculous. The prevailing theory was that a biopsy and tissue exam was the only way to detect the disease.
Despite the initial rejection of his idea, Papanicolaou persevered. In 1939, he collaborated on a clinical study with Herbert F. Traut, MD, a gynecologic pathologist at Cornell, to validate the diagnostic potential of the vaginal smear. They enrolled all women admitted to the gynecologic service of the New York Hospital. Each woman underwent a smear that Papanicolaou interpreted.
Papanicolaou detected many asymptomatic cancer cases. Some were in such an early stage that they were undetectable on biopsy. Papanicolaou and Traut published their findings in a 1943 monograph titled, “Diagnosis of uterine cancer by the vaginal smear.”
The vaginal smear later became known as the Pap smear. Because the Pap smear could detect cancer before it became symptomatic, physicians could now keep the cancer from spreading. As a result, the mortality rate from cervical cancer dropped significantly.
In 1954, Papanicolaou published the “Atlas of Exfoliative Cytology,” a comprehensive work that featured his observations. It included his cytological findings in health and disease in multiple organ systems.
Long-time dream
Although he retired from Cornell, Papanicolaou’s career was not finished. In 1961, Papanicolaou realized a long-time dream: the establishment of a cytologic research institute: He was named Cancer Research Institute of Miami director and by January 1962, research had begun.
Papanicolaou died of a heart attack on Feb. 19, 1962, at age 78. His research institute was later renamed in his honor.
Papanicolaou wrote more than 150 articles and received numerous awards and honors. He was elected as an honorary Fellow of the Academy of Athens. In 1960, he was nominated for the Nobel Prize in Physiology and Medicine, and he was awarded the United Nations Prize in 1962. Three nations have dedicated postage stamps in his honor, including his native Greece and the United States. – by Colleen Owens
For more information:
- Barter JF. The life and contributions of Doctor George Nicholas Papanicolaou. Surg Gynecol Obstet. 1992;174:530-532.
- Palatianos GM, Cintron JR, Narula T. George N. Papanicolaou, MD. Father of modern cytology. A 30-year commemorative. J Fla Med Assoc. 1992;79:837-838.
- Vilos GA. After Office Hours. The history of the Papanicolaou smear and the odyssey of George and Andromache Papanicolaou. Obstet Gynecol. 1998;91:479-483.
- For more information regarding the Papanicolaou Society of Cytopathology, visit www.papsociety.org.