On January 5, 1928, Greek biologist Georgios Papanikolau announced that he had found a method for detecting cancer at an asymptomatic stage – Pap test as we know it today.
This analysis, which subsequently reduced the mortality rate from cervical cancer by order of magnitude, is honorably called a Papanikolau smear, or a Pap test for short.
It all started with the fact that the young biologist Georgios Papanicolaou was not liked by his future father-in-law, colonel Mavrogeni. Firstly, the colonel’s daughter, Andromachi, was in love with Georgios and somehow went to marry him suddenly, without seeking her father’s opinion. Secondly, Papanikolau was the son of a doctor and graduated from the medical faculty in Athens, but he did not want to be a doctor. Instead, he went to Germany, studied genetics under Weismann, and wrote a dissertation. In Greece, at the beginning of the 20th century, genetics was not an occupation that would allow feeding the family. Finally, it was merely a misalliance. The colonel was a member of the top military leadership, and he did not consider the unemployed biologist hailing from the rural Euboea Island a match to his daughter.
The colonel neither did give his blessing to this marriage nor provided a dowry. He came up with a plan so that she saw her husband as rarely as possible. Using connections in the Greek court, Mavrogeni arranged for his son-in-law a position of physiologist at the Prince Albert I of Monaco’s expedition. The eccentric prince was an oceanologist, hanging out at sea for 10 months a year on his research yacht, so let Papanikolaou keep him company – far away from Andromachi.
But for Georgios, the expedition on the Yrondel-II yacht became the happiest time in his entire life. He studied the genetics of the inhabitants of the sea near the Canary Islands, and the employer – Albert I – grew quite fond of the geneticist. Thus, only with a heavy heart, the prince released Georgios when the latter decided to go to war.
It was the First Balkan War: Greece, Bulgaria, Serbia, and Montenegro agreed to expel the Turks from Europe and divide all European possessions of Turkey among themselves. Papanikolaou entered the service as a doctor on a warship. Greek sailors distinguished themselves in that war – they expelled the Turkish fleet from the Aegean Sea and were already preparing to bombard Istanbul when frictions arose between the allies. For example, the Greeks took Thessaloniki and annexed this central industrial city, while the Bulgarians wanted the city for themselves.
Papanicolaou did not want to fight with brothers in faith. In the fleet, he had friends among American volunteers – former Greek citizens who emigrated to the United States in the past and now came to the aid of their homeland. They, too, were not going to fight with the Bulgarians and began packing, urging Papanikolau to come along. And so, as soon as peace was made in 1913, Georgios and his wife relocated to New York. Since no one in America could pronounce the names of our heroes, Andromachi introduced herself as Mary, and Georgios asked people to call him “Doctor Pap.” He could not work as a real doctor – with a Greek diploma and no knowledge of English whatsoever. For several months he and his wife worked as salespersons in a clothing store, and in the evenings, Georgios played violin in a restaurant. Then his former comrades-in-arms invited him to a position of scientific columnist in Atlantis, the only Greek-language magazine published in America. Once, Pap went to interview Thomas Hunt Morgan about his linked genes research. Scientists from different countries often know each other by last names. And Morgan asked the journalist if he was related to Papanikolaou, who wrote articles on genetics.
Discovering that the columnist is the very Papanikolaou whose articles got his attention in the past, Morgan gave him a recommendation to the pathology laboratory at the Cornell University Clinical Hospital. There, the chief instructed the Greek biologist to study the effects of alcohol on guinea pigs. He was allowed to take several animals for his experiments. As Georgios investigated the chromosome damages, he needed the ovulating female guinea pigs. In some of the other labs, dozens of animals could be slaughtered to find a single ovulating pig. Papanikolaou’s allowance was never as high. He could not afford a single miss. It occurred to him that on different days of the cycle the composition of cells in the epithelium of the vagina and uterus varies slightly. Georgios began to take swabs from the pigs’ vaginas using the otolaryngologist’s tool – a nasal mirror. After scraping reserve epithelial cells (Papanicolaou called them “exfoliative”) with such a probe, it was possible to study them under a microscope and accurately determine the day of ovulation. As a scientist, Georgios wondered – since this works with guinea pigs, is it possible to use similar manipulations in the case of human women to track endocrine changes in their bodies?
Of course, the genital organs of guinea pigs and humans are very different. To select cells from the surface of the vagina and cervix of a woman, a probe of a different design was needed – a special kind of brush. Such a probe Papanicolaou tested on his wife Andromachi, that is, Mary. She left working in the store and started aiding her husband in the laboratory – he was not allowed to hire any assistants. By 1923, a new, painless, and harmless analysis method was ready.
The clinic conducted a vast number of tests. Adding his test to the usual flora smears, that Papanicolaou received from hundreds of women. In one of these smears, he discovered a cancer cell. The patient had no symptoms of cervical cancer. Apparently, the cancer cells just appeared in the epithelium; the tumor has not yet grown into the tissue. At this stage, cancer could have been stopped without surgery.
In those days, cervical cancer was the most common malignant tumor among women, especially the poor. They were screened too rarely, and if they had cancer, it was usually at an inoperable stage. Papanicolaou felt that he had made a huge discovery. After examining hundreds of cases, he made a report on the possibility of early detection of cancer in the female genitals using a simple and cheap test. His speech on January 5, 1928, was accompanied by photographs and was unusually capacious and energetic. This was a sample report about a scientific discovery. Unfortunately, its author was considered a second-rate researcher, and the conference itself was second-rate – it was devoted to the issues of “improving the human race.” Eccentrics gathered there, sharing their thoughts on healthy lifestyles and eugenics. Doctor Pap looked like a black sheep among them.
The luminaries of gynecology noticed his report, but they believed only in a biopsy, which was guaranteed to detect a tumor. The idea that tumors can be eliminated before maturing seemed wild to them. Unfortunately, Papanikolaou’s boss thought the same, so he ordered that all smear work be curtailed in favor of soldering the guinea pigs. Our hero obeyed only in appearance: he secretly continued to select smears, improving the technique of microscope samples preparation. Papanikolaou simply waited for his boss to retire and in 1939, this finally happened. The new leader saw the commercial potential of the “Greek venture” immediately and allocated a team of real gynecologists to work on smears. They convinced all New York women to do a Pap test, as they called Papanikolau’s smear for simplicity.
It was found that it allows diagnosing gynecologic oncology diseases early in 95% of cases. Thanks to this, the mortality rate of cervical cancer patients decreased immediately by 70% (by the end of the 20th century – by 14 times). Papanikolaou became globally recognized. By 1957, investors were ready to fund him to organize a cancer research institute, which would be called in his name.
All these years, Papanikolaou dreamed of founding an institution like this in Greece. First of all, he went for reconnaissance in Athens and did not recognize his homeland. The quality of hired labor was dire. Post-war Greece was inhabited by people who were not eager to work and who agreed to take only the leadership positions. Moreover, the political situation in Greece was volatile. At any moment, the Communists or the military junta could seize power. The former would nationalize the institute, and the latter would appoint someone like colonel Mavrogeni as a president.
Paris was another option, but even there, the quality of scientific personnel did not satisfy the hardworking Papanicolaou. With some regret, he returned to America and founded his institute in Miami. A month after the opening of the institution, Dr. Pap died of a heart attack. He did not live mere weeks before being awarded the Nobel Prize, for which he had already been nominated.
Prior to the widespread adoption of the Pap test, 14 women among every 100 thousand died of cervical cancer annually; today, this figure is less than one. Several hundred million people around the world take Pap test regularly, and several dozen thousands of women owe their lives to the Greek geneticist, who at first only wanted to save the expense of experimental material – guinea pigs.
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