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Georgios Papanikolaou
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==Discoveries== [[File:Pap test abnormal.JPG|thumb|An abnormal [[pap test]]]] In 1914, Papanikolaou and his wife worked at the Department of Anatomy at the [[Cornell Medical College]] of [[Cornell University]] and contributed to the [[Histology|histological]] and [[Physiology|physiological]] changes associated with the [[oestrus cycle]] in the [[guinea pig]].<ref name=":2">{{Cite book |last=Minetor |first=Randi |url=https://books.google.com/books?id=yUqyDwAAQBAJ&pg=PA247 |title=Medical Tests in Context: Innovations and Insights |date=2019 |publisher=ABC-CLIO |isbn=978-1-4408-6098-0 |pages=247 |language=en}}</ref> In 1917, Papanikolaou along with [[Charles 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 the [[vaginal mucosa]] and can be detected by [[cytologic]] examination of [[vaginal smears]].<ref name=":3">{{Cite book |last=Josimovich |first=J. B. |url=https://books.google.com/books?id=9vv2BwAAQBAJ&pg=PA7 |title=Gynecologic Endocrinology |date=2013-11-11 |publisher=Springer Science & Business Media |isbn=978-1-4613-2157-6 |pages=7 |language=en}}</ref> This technique (termed the ''Papanicolaou technique''<ref name=":3" />) was groundbreaking and also facilitated the discovery of an [[Ovarian hormones|ovarian hormone]].<ref name=":3" /> 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.<ref>{{cite news | url=https://www.abc.net.au/news/health/2023-07-08/andromache-mary-papanicolaou-pap-smear-test-cervical-cancer/102484690 | title=Every day for 21 years, Mary got a vaginal test. Her 'generosity' helped save 'millions of lives' | newspaper=ABC News | date=7 July 2023 }}</ref> 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.<ref name=":2" /> In 1925, with funds from the [[National Research Council (United States)|National Research Council]] and the Maternal Health Committee, Papanikolaou recruited 12 hospital staff volunteers, together with a number of pregnant [[gynecological]] 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.<ref name=":4">{{Cite book |last=Fabbri |first=Christiane Nockels |url=https://books.google.com/books?id=PWhoDQAAQBAJ&pg=PA85 |title=From Anesthesia to X-Rays: Innovations and Discoveries That Changed Medicine Forever: Innovations That Changed Medicine Forever |date=2016 |publisher=ABC-CLIO |isbn=978-1-61069-574-9 |pages=85 |language=en}}</ref> Upon examination of a slide made from a smear of one of the participant's [[vaginal 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."<ref name=":4" /> 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 in [[Battle 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 in [[uterine cancer|carcinoma of the uterus]].<ref>Papanicolaou GN, Traut HF. "The diagnostic value of vaginal smears in carcinoma of the uterus". ''American Journal of Obstetrics and Gynecology''. 1941; 42:193.</ref> 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, the ''Atlas of Exfoliative Cytology'', thus creating the foundation of the modern medical specialty of [[cytopathology]].<ref name=":5">{{Cite journal |last1=Chandrasekhar |first1=Vijayalakshmi |last2=Krishnamurti |first2=Chandrasekhar |date=2018 |title=George Papanicolaou (1883–1962): Discoverer of the Pap Smear |journal=The Journal of Obstetrics and Gynecology of India |language=en |volume=68 |issue=3 |pages=232–235 |doi=10.1007/s13224-018-1102-z |issn=0971-9202 |pmc=5972093 |pmid=29896006}}</ref> The complete works of Papanicolaou as the founder of exfoliative cytology include 5 books and 158 original articles, all of which are summarised in his [[monograph]]s.<ref name=":1" /><ref>{{Cite journal |last1=Diamantis |first1=Aristidis |last2=Magiorkinis |first2=Emmanouil |last3=Koutselini |first3=Helen |date=2014 |title=50 Years After The Death Of George Nicholas Papanicolaou (1883-1962): Evaluation Of His Scientific Work |url=https://hrcak.srce.hr/ojs/index.php/amha/article/view/19347 |journal=Acta medico-historica Adriatica |language=en |volume=12 |issue=1 |pages=181–188 |pmid=25310617 |issn=1334-6253}}</ref> ===Controversy=== Romanian physician [[Aurel Babeș]] made similar discoveries in the cytologic diagnosis of [[cervical cancer]].<ref name="ReferenceA">[[Michael O'Dowd|O'Dowd Michael J.]], [[Elliot Philipp|Philipp Elliot E.]] ''The History of Obstetrics & Gynaecology''. London: Parthenon Publishing Group; 1994: 547</ref> He discovered that if a [[platinum]] loop (rather than a [[cotton swab]], as used by Papanikolaou and by modern doctors<ref name=":2" />) 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 in [[Bucharest]] on 23 January 1927. His method of cancer diagnosis was published in a French medical journal, ''[[La Presse Médicale]]'', on 11 April 1928,<ref>{{cite journal|first=Aurel|last= Babeș |author-link=Aurel Babeș| title=Diagnostic du cancer du col utérin par les frottis| journal=[[La Presse Médicale]] |volume=29 |year=1928|pages= 451–454}}</ref> but Papanicolaou was not aware of Babeș's research.<ref name=":6">{{Cite journal |last=Spriggs |first=A I |date=1977-12-01 |title=History of cytodiagnosis. |journal=Journal of Clinical Pathology |language=en |volume=30 |issue=12 |pages=1091–1102 |doi=10.1136/jcp.30.12.1091 |issn=0021-9746 |pmc=476689 |pmid=604355}}</ref><ref>{{Cite journal |last=Koss |first=Leopold G. |date=1989 |title=The Papanicolaou Test for Cervical Cancer Detection: A Triumph and a Tragedy |url=http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.1989.03420050087046 |journal=Journal of the American Medical Association |language=en |volume=261 |issue=5 |pages=737–743 |doi=10.1001/jama.1989.03420050087046 |pmid=2642983 |issn=0098-7484}}</ref> On the other hand, Babes was aware of Papanikolaou's studies.<ref>{{Cite book |last1=Meisels |first1=Alexander |url=https://books.google.com/books?id=IpRsAAAAMAAJ |title=Cytopathology of the Uterus |last2=Morin |first2=Carol |date=1997 |publisher=ASCP Press |isbn=978-0-89189-383-7 |pages=10 |language=en}}</ref> Moreover, the [[medical community]] has established that the two techniques are different in their design.<ref name=":2" /> Babeș's technique of preparing, staining and examining [[vaginal smears]] was substantially different from Papanicolaou's and would never have lent itself to mass [[Screening (medicine)|screening]] for cervical cancer without modification.<ref>{{Citation |last1=Ramzy |first1=Ibrahim |title=CHAPTER 1 - Cytopathology: the history, the present and the future direction |date=2010-01-01 |url=https://www.sciencedirect.com/science/article/pii/B9780702031540000016 |work=Diagnostic Cytopathology (Third Edition) |pages=3–13 |editor-last=Gray |editor-first=Winifred |place=Edinburgh |publisher=Churchill Livingstone |language=en |doi=10.1016/b978-0-7020-3154-0.00001-6 |isbn=978-0-7020-3154-0 |access-date=2023-01-01 |last2=Herbert |first2=Amanda |editor2-last=Kocjan |editor2-first=Gabrijela}}</ref> 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.<ref>{{Cite journal |last1=Diamantis |first1=Aristidis |last2=Magiorkinis |first2=Emmanouil |last3=Androutsos |first3=George |date=2009 |title=What's in a name? Evidence that Papanicolaou, not Babes, deserves credit for the PAP test |url=https://onlinelibrary.wiley.com/doi/10.1002/dc.21226 |journal=Diagnostic Cytopathology |language=en |volume=38 |issue=7 |pages=473–476 |doi=10.1002/dc.21226|pmid=19813255 |s2cid=37757448 }}</ref><ref>{{Cite journal |last1=Diamantis |first1=Aristidis |last2=Magiorkinis |first2=Emmanouil |last3=Androutsos |first3=George |date=2010 |title=Different strokes: Pap-test and Babes method are not one and the same |url=https://pubmed.ncbi.nlm.nih.gov/20973044/ |journal=Diagnostic Cytopathology |volume=38 |issue=11 |pages=857–859 |doi=10.1002/dc.21347 |issn=1097-0339 |pmid=20973044|s2cid=823546 }}</ref><ref>{{Cite book |last1=Zheng |first1=Wenxin |chapter-url=https://books.google.com/books?id=hRegDwAAQBAJ&pg=PA572 |title=Gynecologic and Obstetric Pathology, Volume 2 |last2=Fadare |first2=Oluwole |last3=Quick |first3=Charles Matthew |last4=Shen |first4=Danhua |last5=Guo |first5=Donghui |date=2019 |publisher=Springer |isbn=978-981-13-3019-3 |pages=572 |language=en |chapter=History of Pap Test |quote=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.}}</ref> Although a few scholars believe that Babeș was the true pioneer in the cytologic diagnosis of cervical cancer,<ref name="ReferenceA" /> Papanikolaou is still widely considered the pioneer in the field by mainstream scholarship.<ref name=":6" /><ref>{{Cite journal |last1=Virtej |first1=P. |last2=Vasiliu |first2=C. |date=2003 |title=Cytodiagnosis in cervical neoplasia: from the Babes/Papanicolaou smear to the actual Bethesda System |url=https://pubmed.ncbi.nlm.nih.gov/14664403/ |journal=Clinical and Experimental Obstetrics & Gynecology |volume=30 |issue=4 |pages=173–177 |issn=0390-6663 |pmid=14664403}}</ref><ref>{{Cite book |last=Gardner |first=Kirsten E. |url=https://books.google.com/books?id=tiZ8O__3bDUC&pg=PA242 |title=Early Detection: Women, Cancer, and Awareness Campaigns in the Twentieth-Century United States |date=2006 |publisher=University of North Carolina Press |isbn=978-0-8078-7712-8 |pages=242 |language=en}}</ref> In [[Romania]], cervical testing is referred to as the ''Méthode Babeș-Papanicolaou'' in honor of both scientists.<ref>{{cite journal |last1= Naylor|first1=Bernard |last2=Tasca |first2= Luminița|last3=Bartziota|first3=Evangelina|last4=Schneider|first4=Volker|date=2001 |title=Cytopathology History: In Romania it's the Méthode Babeș-Papanicolaou |url=https://www.karger.com/Article/Abstract/326708 |journal=Acta Cytologica |volume=46 |issue=1 |pages=1–12 |doi=10.1159/000326708 |pmid=11843552 |s2cid=5580222 |access-date=13 May 2019 }}</ref>
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