Koss, Leopold G. M.D.
Department of Pathology
Montefiore Medical Center/
Albert Einstein College of Medicine
Bronx, New York
To the Editor:
I was delighted with the excellent article on Aurel Babeş' by Tasca et al. (1), paying homage to this remarkable and inventive man. A few additional comments may be appropriate. I discovered Babeş' contributions around 1960 quite by accident; I believe that a French colleague mentioned Babeş' to me. At that time, Dr. Papanicolaou was a consultant and frequent visitor to my laboratory at the Memorial Hospital for Cancer in New York but I do not recall whether I mentioned Babeş' to him.
The extraordinary contribution by Babeş' (2) clearly preceded Papanicolaou's first paper presented in 1928 (3). Babeş' proposed that a cytologic diagnosis of noninvasive cervical carcinoma was possible many years before this concept was generally accepted. I dug a bit deeper into the past and was able to secure copies of the titles of Daniel and Babeş' first and second presentations made in Bucharest in January and April 1927. In the first presentation, the authors suggested that the cytologic diagnosis of cervical cancer was possible but, just 3 months later, the authors stated firmly that their method was actually diagnostic of cervical cancer (Fig. 1).
Babeş' method was much more efficient than Papanicolaou's. Babeş' described direct smears of the cervix obtained by Daniel, who was a gynecologist, by means of a bacteriologic loop. The smears were fixed in methanol and stained with Giemsa with excellent results. It is amusing to reflect that Babeş' simple system of smear processing has now been widely adopted in aspiration cytology. Papanicolaou initially used vaginal pool smears obtained by using a small glass pipette, which he invented to study the menstrual cycle in rodents, a method subsequently applied to the human female. The smears were fixed in a 50–50 alcohol-ether mixture and stained with a complex polychromatic formula. It took several years before the inaccurate and very tedious method to screen vaginal smears was complemented and ultimately replaced by direct cervical samples obtained by using a scraper or spatula, first described by the Canadian gynecologist, J. Ernest Ayre (4).
Actually, Babeş' had a better initial following than Papanicolaou. An Italian gynecologist, Professor Odorico Viana from Verona, successfully used the Babeş' method and published his results in 1928 (5). Viana also insisted on biopsies of the cervix for confirmation of cytologic findings. Both Babeş' 1928 contribution and Viana's paper were translated into English by Dr. Larry Douglass while he was a fellow in my laboratory (6,7).
What happened after 1928? Nothing. Neither Babeş' nor Papanicolaou pursued their methods of diagnosis. Despite Viana's encouraging paper, Babeş' gave up completely and never returned to the topic. Papanicolaou returned to the cytologic diagnosis of cancer of the uterus around 1938, but only because he was prodded in this direction by the new Chair of Anatomy (this was Papanicolaou's affiliation at Cornell Medical School), Joseph Hinsey. Joe Hinsey, as a practical person, thought that there was possibly greater merit (and more money) in cancer of the female genital tract than in the menstrual cycle. To this effect, Hinsey organized a collaborative venture with Herbert Traut, who was then an associate professor in charge of gynecologic oncology at Cornell. The rest is history, which I summarized briefly in a previous publication (8).
Did Papanicolaou know about Babeş' work? I don't know for sure. The story narrated by Dr. Bernard Naylor, who worked closely with Papanicolaou during the last 9 months of his life and cited by Tasca et al. (9), was also related to me in a personal letter.
Papanicolaou died during the night, on the eve of the day when he was to read Babeş' major paper. It sounds like Babeş' revenge.
But actually Babeş' spirit may have hovered over Papanicolaou sometime before. Papanicolaou's name was repeatedly submitted to the Nobel Committee and rejected every time. The true reason for the rejection was most likely different from those cited in the Tasca paper, which merely repeats what Papanicolaou's biographer, Carmichael, said in his book (10). Several years ago, I met in Stockholm a person who was very close to the Nobel Committee in the 1950s when Papanicolaou's candidacy was seriously considered. This person informed me that the Nobel Committee delegated the in-depth investigation of Papanicolaou's merits and demerits to the late Professor Santesson, who was at that time the head of pathology at the Stockholm Cancer Institute (the Radiumhemmet). The investigator discovered Babeş' contributions that had never been cited by Papanicolaou and duly reported this fact to the Committee, which then rejected Papanicolaou's Nobel award. Is this story true? Perhaps some day when the secret archives of the Nobel Committee are open for inspection, some interested historian could confirm or deny this sequence of events. In the meantime, the lesson is clear: always cite papers written by your predecessors and contemporaries, if you ever wish to obtain the Nobel Award.
Leopold G. Koss, M.D.
1. Tasca L, Östör AG, Babeş' V. History of gynecologic pathology. XII. Aurel Babeş'. Int J Gynecol Pathol 2002: 21:198–202.
2. Babeş' A. Diagnostic du cancer du col utérin par les frottis. Presse Méd 1928; 29:451–4.
3. Papanicolaou GN. New cancer diagnosis. Proceedings of 3rd Race Betterment Conference.
Battle Creek, Michigan. 1928:528–30.
4. Ayre JE. Selective cytology smear for diagnosis of cancer. Am J Obstet Gynecol 1947; 53:609–17.
5. Viana O. La diagnosi precoce del cancro uterino mediante lo stricio. Clin Ostetrica (Italy) 1928; 30:781–93.
6. Douglass LE. A further comment on the contributions of Aurel Babeş' to cytology and pathology. Acta Cytol 1967; 11:217–24.
7. Douglass LE. Odorico Viana and his contribution to diagnostic cytology. Acta Cytol 1970; 14:544–9.
8. Koss LG. Cervical (Pap) smear. New directions. Cancer 1993; 71:1406–12.
9. Naylor B. Perspectives in cytology. From Battle Creek to New Orleans. Acta Cytol 1988; 32:613–21.
10. Carmichael DE. The Pap Smear: Life of George N. Papanicolaou.
Springfield: Charles C Thomas, 1973.