Georgios Papanikolaou | |
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Born | 13 May 1883 |
Died | 19 February 1962(1962-02-19) (aged 78) Miami, Florida, U.S. |
Nationality | Greek |
Alma mater | University of Athens University of Munich |
Known for | Cytopathology Pap smear |
Spouse | |
Awards | Lasker-DeBakey Clinical Medical Research Award (1950) |
Scientific career | |
Fields | Zoology,Pathology,Biology,Microscopy |
Institutions | Cornell University New York Hospital |
Georgios Nikolaou Papanikolaou (orGeorge Papanicolaou/ˌpæpəˈnɪkəlaʊ/;Greek:Γεώργιος Ν. Παπανικολάου[papanikoˈlau]; 13 May 1883 – 19 February 1962) was aGreekphysician,zoologist andmicroscopist who was a pioneer incytopathology and early cancer detection, and inventor of thepap smear for detection ofcervical cancer.
After studying medicine in Greece and Germany, in 1913 he emigrated to the United States and was on the faculty atCornell Medical College. He first reported that uterine cancer cells could be detected in vaginal smears in 1928, but his work was not widely recognized until the 1940s. An extensive trial of his techniques was carried out in the early 1950s. In 1961 he was invited to theUniversity of Miami to lead and develop there the Papanicolaou Cancer Research Institute.
Papanikolaou was born inKymi, Greece, on 13 May 1883. He attended theUniversity of Athens, where he studied literature, philosophy, languages and music. Urged by his physician father, he pursued a medical degree, which he received in 1904. He was then conscripted into military service. When his military obligation ended in 1906, he returned to Kymi to practice medicine with his father.
In 1907 he began studying inGermany underErnst Haeckel at theUniversity of Jena for one semester before moving to theUniversity of Freiburg, where he was supervised byAugust Weismann. He then attended theUniversity of Munich, where in 1910 he received aPhD degree inzoology.[1][2]
Papanikolaou then returned toAthens, where he marriedAndromachi Mavrogeni, who would later become his laboratory assistant and research subject.[3][4][5] He next departed forMonaco, where he worked for theOceanographic Institute of Monaco and participated in the Oceanographic Exploration Team of PrinceAlbert I of Monaco in 1911.[6]
Two years later, in 1913, along with his wife, he immigrated toNew York City in order to work in thepathology department atNew York Hospital and the Department of Anatomy atCornell University'sMedical College.[7]
Papanikolaou was also inspired by the philosophy ofImmanuel Kant andFriedrich Nietzsche,Arthur Schopenhauer andJohann Wolfgang von Goethe,[8][9] writing papers on philosophical matters for an Athenian literary quarterly.[8]Nietzsche's philosophical thought was particularly crucial in shaping his character.[9]
The importance of his work was recognized in 1942 with publication, along with Herbert F. Traut (1894–1963), ofDiagnosis of Uterine Cancer by the Vaginal Smear. The book discusses the preparation of vaginal and cervical smears, physiologic cytologic changes during themenstrual cycle, the effects of various pathological conditions, and the changes seen in the presence of cancer of thecervix and of theendometrium of theuterus. He thus became known for his invention of the Papanicolaou test, commonly known as thePap smear orPap test, which is used worldwide for the detection and prevention ofcervical cancer and other cytologic diseases of the femalereproductive system.
In 1961, he moved toMiami, Florida, to develop the Papanicolaou Cancer Research Institute[10][11][12] at theUniversity of Miami, but died there on 19 February 1962[13][14] due to amyocardial infarction.[15] His wifeAndromachi Papanikolaou, known as Mary, continued his work at the Papanicolaou Cancer Research Institute after his death; she died in Miami on 13 October 1982.
In 1914, Papanikolaou and his wife worked at the Department of Anatomy at theCornell Medical College ofCornell University and contributed to thehistological andphysiological changes associated with theoestrus cycle in theguinea pig.[16] In 1917, Papanikolaou along withCharles R. Stockard demonstrated that, in the guinea pig, the histologic cyclic changes that occur in the reproductive tract during the estrus cycle also occur in thevaginal mucosa and can be detected bycytologic examination ofvaginal smears.[17] This technique (termed thePapanicolaou technique[17]) was groundbreaking and also facilitated the discovery of anovarian hormone.[17]
Papanikolaou then began examining the human reproductive system. His wife Mary, was a crucial partner in this research. She was working in the same laboratory as an unpaid laboratory technician. Every day Mary provided a vaginal sample for the research. She also prepared her own samples in the laboratory for further analysis. She provided daily samples for twenty-one years, eventually encouraging her friends to also provide samples for the research.[18]
In 1920, Georgios Papanikolaou realized that he could tell the difference between normal and malignant cells on the cervix by viewing smears on a slide under a microscope.[16] In 1925, with funds from theNational Research Council and the Maternal Health Committee, Papanikolaou recruited 12 hospital staff volunteers, together with a number of pregnantgynecological and surgical patients, for a systematic study of cervical cell morphology. The participants were regularly tested to determine normal hormonal changes and to diagnose early pregnancy.[19] Upon examination of a slide made from a smear of one of the participant'svaginal fluid, Papanikolaou discovered that abnormal cancer cells could be plainly observed under a microscope. "The first observation of cancer cells in the smear of the uterine cervix," he later wrote, "gave me one of the greatest thrills I ever experienced during my scientific career."[19]
In 1928, Papanikolaou told an incredulous audience of physicians about the noninvasive technique of gathering cellular debris from the lining of the vaginal tract and smearing it on a glass slide for microscopic examination as a way to identify cervical cancer. That year, he had undertaken a study of vaginal fluid in women, in hopes of observing cellular changes over the course of a menstrual cycle. In female guinea pigs, Papanicolaou had already noticed cell transformation and wanted to corroborate the phenomenon in human females. It happened that one of Papanikolaou's human subjects was suffering from uterine cancer.
At a 1928 medical conference inBattle Creek, Michigan, Papanikolaou introduced his low-cost, easily performed screening test for early detection of cancerous and precancerous cells. However, this potential medical breakthrough was initially met with skepticism and resistance from the medical community. Papanicolaou's next communication on the subject did not appear until 1941 when, with gynecologist Herbert Traut, he published a paper on the diagnostic value of vaginal smears incarcinoma of the uterus.[20] This was followed two years later by an illustrated monograph based on a study of over 3,000 cases. In 1954, he published another memorable work, theAtlas of Exfoliative Cytology, thus creating the foundation of the modern medical specialty ofcytopathology.[21] The complete works of Papanicolaou as the founder of exfoliative cytology include 5 books and 158 original articles, all of which are summarised in hismonographs.[9][22]
Romanian physicianAurel Babeș made similar discoveries in the cytologic diagnosis ofcervical cancer.[23] He discovered that if aplatinum loop (rather than acotton swab, as used by Papanikolaou and by modern doctors[16]) was used to collect cells from a woman's cervix, and the cells were then dried on a slide and stained, it could be determined if cancer cells were present. This was the first screening test to diagnose cervical and uterine cancer.
Babeș presented his findings to the Romanian Society of Gynaecology inBucharest on 23 January 1927. His method of cancer diagnosis was published in a French medical journal,La Presse Médicale, on 11 April 1928,[24] but Papanicolaou was not aware of Babeș's research.[25][26] On the other hand, Babes was aware of Papanikolaou's studies.[27] Moreover, themedical community has established that the two techniques are different in their design.[16] Babeș's technique of preparing, staining and examiningvaginal smears was substantially different from Papanicolaou's and would never have lent itself to massscreening for cervical cancer without modification.[28]
Recent scientific papers have analyzed the ways that Babeș's method differed from Papanikolaou's and note that the paternity of the Pap test belongs solely to Papanicolaou.[29][30][31]
Although a few scholars believe that Babeș was the true pioneer in the cytologic diagnosis of cervical cancer,[23] Papanikolaou is still widely considered the pioneer in the field by mainstream scholarship.[25][32][33] InRomania, cervical testing is referred to as theMéthode Babeș-Papanicolaou in honor of both scientists.[34]
Papanikolaou was nominated five times for theNobel Prize, but never won. This was likely because the prize is rarely awarded for diagnostic tools, as well as because a death of one of Papanikolaou's great admirers, who was a member of theNobel Prize Committee, occurred around that time and also due to the committee's reluctance to award a Nobel Prize for another cancer discovery following a former embarrassing award in 1926 toJohannes Fibiger, who claimed that worms caused cancer.[35] Nevertheless, Papanikolaou received many other prestigious prizes and awards for his discoveries,[16] such as theAlbert Lasker Award for Clinical Medical Research (the American equivalent to theNobel Prize in Physiology[8]), which he received in 1950.[36] In total, he received hundreds of honorary awards.[37]
These include honorary awards by theAmerican Academy of Arts and Sciences, theAssociation of American Medical Colleges and theAmerican Cancer Society.[9][21] In 1949, the Medical School of theUniversity of Athens named Papanikolaou an honorary doctorate, while theAcademy of Athens in November 1957 proclaimed him an honorary member. In 1962, he was also posthumously given an award by theUnited Nations, after being nominated by theWorld Health Organization.[9][21][38]
In 1958 thePapanicolaou Award, the highest award given by theAmerican Society of Cytopathology, was established in Papanikolaou's honor, and it has since been awarded annually.[39]
In 1978 Papanikolaou's work was honored by theU.S. Postal Service with a 13-cent stamp for early cancer detection.[16]
Between 1995 and 2001, his portrait appeared on theobverse of the Greek₯10,000banknote, until its replacement by theeuro.[40]
In 2011A Man of Science, a statue portraying Papanicolaou, was permanently installed inWeill Cornell Medicine's main lobby at 1300 York Avenue, inNew York City.
On 13 May 2019, the 136th anniversary of his birth, aGoogle Doodle featuring Papanikolaou was shown in North America, parts of South America, and parts of Europe and Israel.[41] His and his wife Andromachi's efforts in the fight againstcervical cancer, along with those ofHelen Octavia Dickens andHashime Murayama, featured in thedocumentary filmThe Cancer Detectives, which first aired onAmerican Experience on 26 March 2024.[42]
The method by Babes was radically different from that by Papanicolaou. Dr. Papanicolaou should receive the credit for the use of exfoliative cytology, the wet fixation, the staining technique, the systematic classification of cells with intermediate stages between the normal and the cancerous cell, and the envisioning that the method could be applied to large numbers of women in the cancer-bearing period of life to detect cervical cancer in its early stages, i.e., the "Pap test" as is commonly employed.