George Androutsos

A brief history of apoptosis: from ancient to modern times.

The purpose of this article is to sketch the evolution of research on cell death and apoptosis from ancient to modern times. Early use of the term can be found in the texts of Hippocrates, whereas the first description of apoptotic cell death should be attributed to Rudolf Virchow. Glucksman, in 1951, rediscovered and reviewed cell death during embryonic development. Milestone discoveries in biology in the 20th century led biologists to the discovery of apoptotic mechanisms, soon after the definition of apoptosis by Kerr in 1972. The involvement of programmed cell death in the pathogenesis of various diseases and abnormalities gave a huge boost in the research of apoptosis. Nowadays, research is focused on the elucidation of apoptotic mechanisms, since the possibility of modulating cell death by targeting specific factors involved in the whole process could be the key for cure of diseases such as cancer, Alzheimer’s disease, and AIDS.

Alfred Francois Donné (1801-78): a pioneer of microscopy, microbiology and haematology.

Alfred François Donné is widely known in the scientific community as the discoverer of Trichomonas vaginalis, since he was the first to illustrate the parasite that later was recognized to cause vaginal infections. However, his other, less-known findings are equally important: he was also the inventor of the photoelectric microscope, with the assistance of his student Léon Foucault, as well as the first to apply photography to microscopic preparations (Daguerreotype). His research in microscopy extended to almost all human fluids that could be investigated and culminated in his famous Atlas, which was illustrated with numerous photographs. Donné was also the first to describe the microscopic appearances of leukaemia based on blood preparations acquired from patients. Finally, his work in the hygiene of child upbringing and nutrition is very significant.

Different strokes: Pap-test and Babes method are not one and the same

We would like to thank Dr. Pampuccian for his challenging criticism on our article, and must acknowledge that Dr. Aurel Babes did indeed make an important contribution to the methodology of his times while researching cervical cancer. However, we are not fully convinced that Aurel Babes should be credited along with George Papanicolaou in the development of the Pap-test. As Dr. Pampuccian states, techniques for studying cells from imprints and secretions had already been described before Babes and Papanicolaou’s publications on cervical cytological preparations. For that reason, Babes’ technique was not innovative in relation to his era’s previously published studies. On the contrary, Papanicolaou’s method was indeed innovative. It concerned a palpably different approach based not on scrapings but on smears from aspiration of vaginal fluid. The method initially aimed at the dating of the female hormonal cycle and later for the diagnosis cervical lesions and for the screening of cervical precancer and cancer lesions. The technique suggested by Ayre was not an abrasive method and does not involve scraping of visible lesions, as it was the method suggested by Aurel Babes who used clearly a platinum loop. For the aforementioned reasons, such an abrasive method that Babes and Daniel suggested could never be used as a screening method for cervical cancer. Dr. Pampuccian compares the two papers of George Papanicolaou and Aurel Babes. We believe that Dr. Pampuccian make some unfortunate comments regarding Dr. Papanicolaou’s paper. The quality and importance of the study is not always connected with the journal in which it is published or whether it contains grammar and spelling errors. By 1928, Dr. Papanicolaou had already published three major papers in prestigious journals such as Science and the American Journal of Anatomy. Also, Dr. Pampuccian assumes that the sample size presented by George Papanicolaou is very small, although there is no support for that argument. On the contrary, Dr. Papanicolaou made it clear in his Battle Creek presentation the extensiveness of his work on vaginal smears: ‘‘I studied smears from various pathological cases, including all kinds of infections staphylococcus, streptococcus, gonococcus, various inflammatory conditions of the vagina, of the uterus, of the tubes, cases of tubercle abscesses, cases of ovarian cysts and other conditions of the ovaries, and also cases of pregnancy and of tubal pregnancy, of abortions and finally cases of benign and malignant tumor.’’ Dr. Papanicolaou extended his studies beyond diagnosed cases of cancer to other non-malignant cases showing that he already confirmed that his method successfully screened of asymptomatic cases. Moreover, Papanicolaou worked on vaginal smears for almost a decade before presenting his results in the Battle Creek conference, as we prove below, and from 1923 already with human vaginal smears. To dismiss his paper because of an supposedly small sample size is a curious historical interpretation. A careful study of Papanicolaou’s papers proves that he started working on vaginal smears long before Aurel Babes. Babes presented his findings on 20 cases in Romania in a local conference of the Bucharest Gynecological Society in 1927 and published 20 cases in Presse Medicale in 1928, 3 months after the presentation of Papanicolaou’s paper in the Battle Creek conference. (The proceedings of the 1927 Bucharest conference were not widely disseminated.) In addition, Papanicolaou had been working with and on his method for more than 10 years. His first two publications with Stockard in 1917, entitled ‘‘The existence of a typical oestrous cycle in the guinea pig: with a study of its histological and physiological changes’’ and ‘‘A rhythmical ‘heat period’ in the guinea pig,’’ involved the use of vaginal smears for the study of the oestrous cycle in guinea pigs. Unlike Babes’ work, Papanicolaou efforts on vaginal smears shows a remarkable continuum. In 1923, Papanicolaou told an incredulous audience of physicians about the technique of gathering cellular debris from the lining of the vaginal tract *Correspondence to: E. Magiorkinis, B.Sc., M.D., Ph.D., L. Aianteiou 3-PB 1541, Salamina 18900, Greece. E-mail: mayiork@med.uoa.gr Received 17 December 2009; Accepted 28 December 2009 DOI 10.1002/dc.21347 Published online 6 May 2010 in Wiley Online Library (wileyonlinelibrary.com).

Proteinuria: From Ancient Observation to 19th Century Scientific Study

PURPOSE We present the evolution of ideas on the concept of proteinuria from antiquity through the 19th century. MATERIALS AND METHODS We conducted a thorough study of texts, medical books and reports along with a review of the available literature in PubMed. RESULTS Observations on proteinuria date back nearly 2,500 years to the works of Hippocrates. In the 17th and 18th centuries physicians and clinical chemists, particularly Frederick Dekkers, Domenico Cotugno and Charles Wells, further increased the knowledge of proteinuria. Contrary to popular belief the first appearance of the term albuminuria in print should be attributed to Martin Solon in 1837. CONCLUSIONS Observations on proteinuria span approximately 2,500 years. The work of physicians during the 17th and 18th centuries led to its establishment as a separate clinical entity associated with renal disease.

Highlights from the history of hormonal cytology

In 1847 Felix-Archimede Pouchet effectively launched the study of the physiology of cytology. Now 160 years later, the authors briefly trace the development of hormonal cytology to our present knowledge and practice. In the course of the paper the contribution of George Papanicolaou is stressed because of his monumental contribution to a major segment of medical practice of great emotive import.