George Nicholas Papanicolaou

George Nicholas Papanicolaou was born in Kimi on the island of Euboea. It is near the southern town of Karystos known for the ancient physician Diokles of Karystos (Diocles of Carystus) said to have been "second only to Hippocrates." He was the son of Nicolas Papanicolaou, a physician, and Maria, a cultured lady with a love for the classics. As a boy he loved outdoor life, particularly mountain hiking av boating. He had one brother and two sisters. He attended school in Athens from the age of 11, and in 1898 entered the University of Athens to study humanities and music. However, complying with his father's wish, he continued his studies at the medical faculty and received the M.D. from the University of Athens in 1904. He subsequently served as an assistant surgeon in the military until 1906.

For the next year he took care of patients at a leper colony north of his hometown of Kimi. However, Papanicolaou wanted to work in medical science, and in 1907 he went to Jena, Germany, for postgraduate study at the Zoological Institute in Munich, the greatest zoological research centre in the world at that time. His first teacher at the Institute in Munich was Professor Ernst Heinrich Philipp August Haeckel (1834-1910), known one of Europe's greatest early proponents of Darwinism. He earned a PhD in Zoology from the University of Munich in 1910.

En route to Paris, Papanicolaou stopped for a visit at the Oceanographic Institute of Monaco and accepted an unexpected offer to join its staff. He worked for one year as a physiologist and then returned to Greece upon the death of his mother. Here he married Andromache Mavroyeni who went by the name Mary, the daughter of a high-ranking military officer.

During the Balkan War, 1912-1913, he served as second lieutenant in the medical corps of the Greek army, fighting the Turks. With his wife and future research companion, he then went to the United States of America. They landed at Ellis Island on October 19, 1913 with just enough money for their visas and speaking no English.

After serving for two years as second lieutenant in the medical corps of the Greek army during the Balkan War, fighting the Turks, he visited the United States, and when World War I broke out in 1914, he decided to stay there. His first job in the US was as a rug salesman. He played violin at restaurants, and was a clerk for a Greek-language newspaper, while Mary worked as a tailor. However, Papanicolaou soon found appointment as assistant in the pathology department of New York Hospital, and in 1914 he became assistant in anatomy at Cornell Medical College. When World War I broke out in 1914, he decided to stay in the USA. Papanicolaou obtained American citizenship in 1927.

His research was devoted almost exclusively to the physiology of reproduction and exfoliative cytology, at the New York Hospital and the Cornell Medical College, two affiliated institutions, each of which has named a laboratory in his honour. He was designated professor emeritus of clinical anatomy at Cornell in 1951. In November 1961 Papanicolaou moved to Florida and became director of the Miami Cancer Institute, but died three months later of acute myocardial infarction. The institute was renamed the Papanicolaou Cancer Research Institute in November, 1962. An indefatigable worker, Papanicolaou is said never to have taken a vacation. He was described as a modest man.

In 1947 he received the Amory Prize from the American Academy of Arts & Sciences for his development of exfoliative cytology and its application to rapid and simple methods of diagnosis of cancer of the organs of the genitourinary tract.

In 1978, the U.S. put his picture on a stamp.

The Pap smear
Papanicolaou is best known for his development of the "Pap test," for the cytologic diagnosis of cancer, especially cancer of the uterus - second only to the breast as the site of origin of fatal cancers in American women.

The work that eventually resulted in his life-saving smear and test, began in 1916 when he began the study of sex chromosomes in guinea pigs. it occurred to him that guinea pigs, like humans, must have a menstrual cycle, even though no bleeding had been observed. If so, one should be able to obtain the necessary information from the vaginal secretions. Thus what was probably the first Pap smear — from a guinea pig.

In 1923, Papanicolaou told an incredulous audience of physicians about the technique of gathering cellular debris from the lining of the vaginal tract and smearing it on a glass slide for microscopic examination as a way to identify cervical cancer. That year he had undertaken a study of vaginal fluid in women, in hopes of observing cellular changes over the course of a menstrual cycle. In female guinea pigs, Papanicolaou had already noticed cell transformation and wanted to corroborate the phenomenon in human females. It happened that one of Papanicolaou's human subjects was suffering from uterine cancer.

Upon examination of a slide made from a smear of the patient's vaginal fluid, Papanicolaou discovered that abnormal cancer cells could be plainly observed under a microscope. "The first observation of cancer cells in the smear of the uterine cervix," he later wrote, "gave me one of the greatest thrills I ever experienced during my scientific career."

At a 1928 medical conference in Battle Creek, Michigan, Papanicolaou introduced his a low-cost, easily performed screening test for early detection of the cancerous and precancerous cells. However, this potential medical breakthrough was initially met with scepticism and resistance from the scientific community, and it was not until the early 1950s that large-scale screening using Pap smear began. This resulted in a historic drop in the incidence of cervical cancer among American women.

Much of his work was done in collaboration with the biochemist Charles Rupert Stockard (1879-1939) and E. Shorr. His studies on human beings, from 1939, was done to a large degree in collaboration with the gynaecologist Herbert Frederick Traut (1894-1963).

We thank John A. Paraskos, MD, and Patrick Jucker-Kupper, Switzerland, for information submitted.

• G. N. Papanicolaou and C. R. Stockard:
  The Existence of a Typical Oestrous Cycle in the Guinea Pig; with a Study of its histological and Physiological Changes.
  American Journal of Anatomy, 1917, 22: 225-283.
  The vaginal smear test for oestrus. It demonstrates the histological changes occurring in the vagina during the menstrual cycle.
• G. N. Papanicolaou:
  New Cancer Diagnosis.
  Proceedings of the Third Race Betterment Conference, January 2-6. 1928. 1928: 528-534.
• G. N. Papanicolaou and Herbert Traut:
  The diagnostic value of vaginal smears in carcinoma of the uterus.
  American Journal of Obstetrics and Gynecology, St. Louis, 1941, 42: 193-206.
  Smear diagnosis of carcinoma of the cervix. Papanicolaou first reported in 1928 that he could recognise cancer cells but the importance of his findings was not generally accepted and he abandoned the work for some years.
• G. N. Papanicolaou and Herbert Traut:
  Diagnosis of Uterine Cancer by the Vaginal Smear. New York, 1943.
• G. N. Papanicolaou:
  Atlas of Exfoliative Cytology. Cambridge, Massachusetts, 1954.
• G. N. Papanicolaou:
  Dedication of the Papanicolaou Cancer Research Institute.
  Journal of the American Medical Association, 1962, 182: 556-559.
• H. Speert:
  Obstetric and Gynecologic Milestones. New York, 1958, p 286.
• D. E. Carmichael:
  The Pap Smear: Life of George N. Papanicolaou. Springfield, Illinois, 1973.