George Papanicolaou, a Greek cytologist, arrived in NY in 1913 and to support himself, sold carpets. Finally after a long hunt he ended up getting a research job at Cornell. He was assigned to study menstrual cycle of guinea pigs. Not a very exciting job, but Papanicolaou gave everything into it. He scraped cervical cells off Guinea pigs using nasal speculum and Q-tips. Under a microscope, he found that the cells of guinea pig changed shape with their ebb and rise of hormones and Papanicolaou was able to foretell the precise stage of the menstrual cycle of a Guinea pig to the day.
Papanicolaou realised that he could try the same technique on women and recruited his wife Maria, to donate her cervical smears. She contributed her share everyday and expectedly he found that cells sloughed off by the human cervix could also foretell the stages of the menstrual cycle in women. A discovery of absolutely no value, since women could calculate their cycle quite accurately and had been doing so for centuries. But Papanicolaou had other ideas, he wondered if these smears could be used to test for any pathological conditions. Papanicolaou now began collecting cervical smears of women with various gynaecological conditions like- fibroids, cysts, tubercles, streptococcal and gonococcus infections, etc. hoping to find some pathological mark in exfoliated cells. Papanicolaou found that cervical cancer was prone to shedding abnormal cells of "aberrant and bizarre forms" with bloated nuclei, ruffled membranes and shrunken cytoplasm. Thrilled by his result, Papanicolaou published his method in an article "New cancer Diagnosis" in 1928 and called the test "pap smear". The technique was neither accurate not particularly sensitive and his colleagues argued that it was better to perform a biopsy of the cervix than rely on an unreliable test. Undaunted, from 1928 to 1950, Papanicolaou worked tirelessly, spending hours viewing cells under a microscope and typing reports on specimens. Later a gynaecological pathologist, Herbert Traut joined him to interpret his smears and a Japanese fish and bird painted, Hashime Murayama was hired to paint watercolours of his smears.
Then at a Christmas party in 1950, he was challenged by a tipsy gynaecologist to pinpoint the precise use of his smear and in the heat of the moment Papanicolaou had a thought- to use Pap smear not to find cancer, but to detect its antecedent or precursor. Papanicolaou speculated that his test thought imperfect might capture the disease at its first stages and give a woman a chance to receive preventive care and greatly decrease the likelihood of ever developing cancer.
In 1952, Papanicolaou convinced the national cancer Institute to launch a clinical trial to test his technique. 1,50,000 women of Shelby county participated. Temporary "Pap clinics" were setup at nearly every corner in the county. The samples were analysed at university of Tennessee and 555 women were found to have cervical cancer. Astonishingly 557 women were found to have pre-invasive cancers curable by relatively simple surgical procedure. What Papanicolaou had noted was that cancer did not arise directly out of a normal cell. Instead, cancer often slouched toward its birth, undergoing discrete, transitional stages between fully normal and frankly malignant cell. Identifying and eradicating this premalignant stage before the cancer spreads is the basis for the pap smear.
The Pap smear test is today widely recommended and has proved quite effective, thanks to the persistence and tenacity of Papanicolaou.
Inspired by: The Emperor of all Maladies: A biography of cancer – Siddhartha Mukherjee.