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Papanicolaou secured a research position at Cornell that may have been just as surreal as carpet selling: he was assigned to study the menstrual cycle of guinea pigs, a species that neither bleeds visibly nor sheds tissue during menses. Using a nasal speculum and Q-tips, Papanicolaou had nonetheless learned to scrape off cervical cells from guinea pigs and spread them on glass slides in thin, watery smears.<\/p>\n\n\n\n
The cells, he found, were like minute watch-hands. As hormones rose and ebbed in the animals cyclically, the cells shed by the guinea pig cervix changed their shapes and sizes cyclically as well. Using their morphology as a guide, he could foretell the precise stage of the menstrual cycle often down to the day.<\/p>\n\n\n\n
By the late 1920s, Papanicolaou had extended his technique to human patients. (His wife, Maria, in surely one of the more grisly displays of conjugal fortitude, reportedly allowed herself to be tested by cervical smears every day.) As with guinea pigs, he found that cells sloughed off by the human cervix could also foretell the stages of the menstrual cycle in women.<\/p>\n\n\n\n
But all of this, it was pointed out to him, amounted to no more than an elaborate and somewhat useless invention. As one gynecologist archly remarked, \u201cin primates, including women,\u201d a diagnostic smear was hardly needed to calculate the stage or timing of the menstrual cycle. Women had been timing their periods\u2014without Papanicolaou\u2019s cytological help\u2014for centuries.<\/p>\n\n\n\n
Disheartened by these criticisms, Papanicolaou returned to his slides. He had spent nearly a decade looking obsessively at normal smears; perhaps, he reasoned, the real value of his test lay not in the normal smear, but in pathological conditions. What if he could diagnose a pathological state with his smear? What if the years of staring at cellular normalcy had merely been a prelude to allow him to identify cellular abnormalities?<\/p>\n\n\n\n
Papanicolaou thus began to venture into the world of pathological conditions, collecting slides from women with all manners of gynecological diseases\u2014fibroids, cysts, tubercles, inflammations of the uterus and cervix, streptococcal, gonococcal, and staphylococcal infections, tubal pregnancies, abnormal pregnancies, benign and malignant tumors, abscesses and furuncles, hoping to find some pathological mark in the exfoliated cells<\/p>\n\n\n\n
Cancer, he found, was particularly prone to shedding abnormal cells. In nearly every case of cervical cancer, when Papanicolaou brushed cells off the cervix, he found \u201caberrant and bizarre forms\u201d with abnormal, bloated nuclei, ruffled membranes, and shrunken cytoplasm that looked nothing like normal cells. It \u201cbecame readily apparent,\u201d he wrote, that he had stumbled on a new test for malignant cells.<\/p>\n\n\n\n
Thrilled by his results, Papanicolaou published his method in an article entitled \u201cNew Cancer Diagnosis\u201d in 1928. But the report, presented initially at an outlandish \u201crace betterment\u201d eugenics conference, generated only further condescension from pathologists. The Pap smear, as he called the technique, was neither accurate nor particularly sensitive. If cervical cancer was to be diagnosed, his colleagues argued, then why not perform a biopsy of the cervix, a meticulous procedure that, even if cumbersome and invasive, was considered far more precise and definitive than a grubby smear? <\/p>\n\n\n\n