30 September 2009
The invention: A cytologic technique the diagnosing uterine cancer,
the second most common fatal cancer in American women.
The people behind the invention:
George N. Papanicolaou (1883-1962), a Greek-born American
physician and anatomist
Charles Stockard (1879-1939), an American anatomist
Herbert Traut (1894-1972), an American gynecologist
Cancer in History
Cancer, first named by the ancient Greek physician Hippocrates
of Cos, is one of the most painful and dreaded forms of human disease.
It occurs when body cells run wild and interfere with the normal
activities of the body. The early diagnosis of cancer is extremely
important because early detection often makes it possible to effect
successful cures. The modern detection of cancer is usually done by
the microscopic examination of the cancer cells, using the techniques
of the area of biology called “cytology, ” or cell biology.
Development of cancer cytology began in 1867, after L. S. Beale
reported tumor cells in the saliva from
a patient who was afflicted
with cancer of the pharynx. Beale recommended the use in cancer
detection of microscopic examination of cells shed or removed (exfoliated)
from organs including the digestive, the urinary, and the
reproductive tracts. Soon, other scientists identified numerous striking
differences, including cell size and shape, the size of cell nuclei,
and the complexity of cell nuclei.
Modern cytologic detection of cancer evolved from the work of
George N. Papanicolaou, a Greek physician who trained at the University
of Athens Medical School. In 1913, he emigrated to the
In 1917, he began studying sex determination of guinea pigs with
Charles Stockard at New York’s Cornell Medical College. Papanicolaou’s
efforts required him to obtain ova (egg cells) at a precise
period in their maturation cycle, a process that required an indicator
of the time at which the animals ovulated. In search of this indicator,
Papanicolaou designed a method that involved microscopic examination
of the vaginal discharges from female guinea pigs.
Initially, Papanicolaou sought traces of blood, such as those
seen in the menstrual discharges from both primates and humans.
Papanicolaou found no blood in the guinea pig vaginal discharges.
Instead, he noticed changes in the size and the shape of the uterine
cells shed in these discharges. These changes recurred in a fifteento-
sixteen-day cycle that correlated well with the guinea pig menstrual
“New Cancer Detection Method”
Papanicolaou next extended his efforts to the study of humans.
This endeavor was designed originally to identify whether comparable
changes in the exfoliated cells of the human vagina occurred
in women. Its goal was to gain an understanding of the human menstrual
cycle. In the course of this work, Papanicolaou observed distinctive
abnormal cells in the vaginal fluid from a woman afflicted
with cancer of the cervix. This led him to begin to attempt to develop
a cytologic method for the detection of uterine cancer, the second
most common type of fatal cancer in American women of the
In 1928, Papanicolaou published his cytologic method of cancer
detection in the Proceedings of the Third Race Betterment Conference,
held in Battle Creek, Michigan. The work was received well by the
news media (for example, the January 5, 1928, New YorkWorld credited
him with a “new cancer detection method”). Nevertheless, the
publication—and others he produced over the next ten years—was
not very interesting to gynecologists of the time. Rather, they preferred
use of the standard methodology of uterine cancer diagnosis
(cervical biopsy and curettage).
Consequently, in 1932, Papanicolaou turned his energy toward
studying human reproductive endocrinology problems related to
the effects of hormones on cells of the reproductive system. One example
of this work was published in a 1933 issue of The American
Journal of Anatomy, where he described “the sexual cycle in the human
female.” Other such efforts resulted in better understanding of reproductive problems that include amenorrhea and menopause.
It was not until Papanicolaou’s collaboration with gynecologist
Herbert Traut (beginning in 1939), which led to the publication of
Diagnosis of Uterine Cancer by the Vaginal Smear (1943), that clinical
acceptance of the method began to develop. Their monograph documented
an impressive, irrefutable group of studies of both normal
and disease states that included nearly two hundred cases of cancer
of the uterus.
Soon, many other researchers began to confirm these findings;
by 1948, the newly named American Cancer Society noted that the
“Pap” smear seemed to be a very valuable tool for detecting vaginal
cancer. Wide acceptance of the Pap test followed, and, beginning
in 1947, hundreds of physicians from all over the world
flocked to Papanicolaou’s course on the subject. They learned his
smear/diagnosis techniques and disseminated them around the
The Pap test has been cited by many physicians as being the most
significant and useful modern discovery in the field of cancer research.
One way of measuring its impact is the realization that the
test allows the identification of uterine cancer in the earliest stages,
long before other detection methods can be used. Moreover, because
of resultant early diagnosis, the disease can be cured in more
than 80 percent of all cases identified by the test. In addition, Pap
testing allows the identification of cancer of the uterine cervix so
early that its cure rate can be nearly 100 percent.
Papanicolaou extended the use of the smear technique from
examination of vaginal discharges to diagnosis of cancer in many
other organs from which scrapings, washings, and discharges
can be obtained. These tissues include the colon, the kidney, the
bladder, the prostate, the lung, the breast, and the sinuses. In
most cases, such examination of these tissues has made it possible
to diagnose cancer much sooner than is possible by using
other existing methods. As a result, the smear method has become
a basis of cancer control in national health programs throughout the