Papanicolaou – the great giver of life

On January 5, 1928, the Greek biologist Georgios Papanikolaou announced that he had created a method for detecting cancer at an asymptomatic stage. This test, which has reduced mortality from cervical cancer by an order of magnitude, is called the Pap smear, or Pap test for short, after the author.

Georgios Papanicolaou was born May 13, 1883 in Kimi on the island of Euboea and spent his childhood years in a happy family atmosphere. After elementary school, he went to Athens to study at the gymnasium, from which he graduated in 1898. Then he was enrolled in the medical faculty of the University of Athens, after which he received a diploma in 1904 at the age of 21.

The problems of the young Papanicolaou began with the fact that the young biologist did not like his future father-in-law, Colonel Androgeni. Firstly, the daughter of Colonel Andromache was too in love with Georgios and got married somehow suddenly, having barely met, without asking her father’s opinion. Secondly, Papanikolaou was the son of a doctor and graduated from the medical faculty in Athens, and did not open his own practice, but went to Germany, studied there with Weisman “some kind of genetics”, and defended his dissertation on it. Although the Colonel did not give a blessing to the marriage, nor a dowry, he decided that if his daughter saw her husband less often, this could destroy their marriage as a result.

Using his connections at the Greek court, Androgeni arranged for his son-in-law to be a physiologist on the expedition of Prince Albert I of Monaco. The eccentric prince was an oceanologist, spent 10 months a year at sea on his research yacht, where Papanicolaou was accepted, naturally, without his wife.

But for Georgios, the expedition on the Yrondel II yacht was the happiest time in his life. He studied the genetics of the inhabitants of the sea near the Canary Islands, and the employer Albert I doted on him. With a heavy heart, he released Georgios when he was forced to go to war (First Balkan War).

When the mobilization was proclaimed, Papanikolaou, as a junior lieutenant of the medical service in the reserve, served until the end of the Balkan wars (1912-1913). The reaction of the Greek diaspora to the call of the motherland was impressive. There were many Greeks from America who fought as volunteers. Papanicolaou’s interactions with Greek Americans gave him an insight into the New World. Everyone assured him that if he was interested in research work, in America he would find suitable conditions and means to carry out his intentions. And so, as soon as peace was concluded in 1913, Georgios went to New York, taking his wife with him.

Since no one in America could pronounce either the name or the surname of our heroes, Andromache became Mary, and Georgios asked to be called “Doctor Pap.” He could not work as a real doctor – without knowledge of the language and with a Greek diploma. For several months he and his wife were sellers in a clothing store, and in the evenings Georgios played the violin in a restaurant.

Some time later, “comrades in arms” arranged for him a position as a scientific columnist in the only Greek magazine in all of America, Atlantis. Papanicolaou went to interview Thomas Hunt Morgan about linked genes. Scientists from different countries know each other by surnames. And Morgan asked the journalist if he was related to that Papanicolaou who wrote articles on genetics.

Hearing that the columnist was the same Papanicolaou, Morgan gave him a recommendation to the pathology laboratory at Cornell University Hospital. There, the boss assigned a Greek biologist to study the effects of alcohol on guinea pigs. He was allowed to take some animals for his own experiments. Since Georgios was researching chromosomes, he needed those guinea pigs that were ovulating. In other laboratories, 50 animals were slaughtered to take a single ovulating pig. Papanicolaou never dreamed of such resources. He could not afford a single mistake.

It occurred to him that on different days of the cycle, the composition of cells in the epithelium of the vagina and the uterus is different. And Georgios began to take a vaginal swab from the pigs, using the instrument of an otolaryngologist – a nasal mirror. By scraping reserve cells from the epithelium with such a probe (Papanicolaou said “exfoliative”), it was possible to examine them under a microscope and accurately determine the day of ovulation. But since it works with guinea pigs, it could be done in women to track endocrine changes.

The structure of the genital organs of pigs and humans is very different. To select cells from the surface of the vagina and cervix of the woman, a probe of a different design was needed – a special kind of brush. Such a Papanicolaou probe worked on his wife Andromache, that is, Mary. She left the store and helped her husband in the laboratory – he could not have other laboratory assistants. By 1923, a new painless and harmless method of analysis was ready.

The clinic took a huge number of tests. Adding his own to the usual smear on the flora, Papanicolaou received material from hundreds of women. And in one of these smears, a cancer cell was found quite by accident. The patient had no symptoms of cervical cancer. Apparently, cancer cells have just emerged in the epithelium, the tumor has not yet grown deep into the tissue. At this stage, the cancer could be stopped without surgery.

In those days, cervical cancer was the most common malignant tumor among women, especially among the poor. They too infrequently underwent examinations, and if cancer was found in them, it was usually at an inoperable stage.

Papanicolaou felt that he was in for a huge stroke of luck. After studying hundreds of cases, he made a report on the possibility of early detection of cancer of the female genital organs with a simple and cheap smear. The performance on January 5, 1928 was accompanied by photographs and was unusually capacious and energetic. This is a sample discovery story. Unfortunately, its author was considered a second-class researcher, and the conference was second-class – it was devoted to the issues of “improving the human race.” Eccentrics gathered there, sharing ideas about a healthy lifestyle and eugenics. Papanicolaou looked like a black sheep among them.

The luminaries of gynecology noticed his report, but they believed only in a biopsy, which is guaranteed to detect a tumor. The idea that tumors could not be allowed to mature seemed wild to them. Unfortunately, the head of Papanicolaou, who ordered to curtail all work on the smear, thought the same way.

Our hero obeyed only in appearance: he secretly continued to take smears, improving the method of staining preparations. Papanicolaou was just waiting for his boss to retire. In 1939, this finally happened. The new leader saw commercial potential in the “Greek idea” and assigned a team of real gynecologists to work on the smear. They convinced all the women in New York City to get a “Pap test,” as they called the Pap test for simplicity. It was found that it reveals early oncopathology in 95% of cases. Thanks to him, mortality from cervical cancer immediately decreased by 70% (by the end of the 20th century – 14 times). Papanicolaou became famous all over the world. By 1957, investors were willing to give him money to start a cancer research institute to be named after him.

All these years, Papanikolaou did not part with the dream of returning to his homeland and founding an institute in Greece. In addition, Eleftherios Venizelos is trying to convince him to return to Greece for a full-time job at the Department of Zoology, Faculty of Physics and Mathematics at the University of Athens. However, these negotiations failed because Venizelos did not win the next parliamentary elections (1920).

In 1928, Papanicolaou gave a lecture in Michigan entitled “A New Method for Diagnosing Cancer” in which he presented the technique and results of his research. This pioneering work was not well received, especially by pathologists. In 1943, Papanicolaou, together with F. Traut, published a monumental monograph “The diagnosis of uterine cancer using vaginal smears”, in which, in addition to the characteristics of cancer cells, it also emphasizes that precancerous conditions can be diagnosed and treated in a timely manner.

During the Second World War, Papanikolaou participated as a special adviser to the Association for the Relief of the Greeks during the War and significantly contributed to its work. Thanks to his authority and connections, pharmaceutical firms were of great help to hospitals in Greece, which at that time were experiencing difficulties due to the lack of equipment, medicines and sanitary material.

In 1961, Papanicolaou moved to Miami to establish the Papanicolaou Cancer Research Institute at the University of Miami, but died on February 19, 1962, before the center opened. He almost did not live to receive the Nobel Prize, for which he had already been nominated.

Before the Pap test, 14 women per 100,000 died of cervical cancer, now less than one. Several hundred million people around the world take Pap smears regularly, and several tens of thousands of women owe their lives to a Greek geneticist.

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