JBUON 2014; 19(1): 319-323 ISSN: 1107-0625, online ISSN: 2241-6293 • www.jbuon.com E-mail: [email protected] HISTORY OF ONCOLOGY The fascinating germ theories on cancer pathogenesis G. Tsoucalas1, K. Laios1, M. Karamanou1, V. Gennimata2, G. Androutsos1 1Department of History of Medicine, Medical School, University of Athens, Athens; 2Department of Microbiology, Medical School, University of Athens, Athens, Greece Summary bel Prize in 1926 that was attributed to the Danish scientist Johannes Fibiger for his work on the nematode Spiroptera as a For more than 100 years, the germ theory of cancer, pro- causative agent in cancer. Even if those theories were the result posing that microorganisms were at the origin of the disease, of fantasy and misinterpretation, they paved the way for the dominated medicine. Several eminent scientists like Etienne scientific research in oncology. Burnet, Mikhail Stepanovich Voronin, Charles-Louis Mal- assez, and Francis-Peyton Rous argued on the pathogenesis presenting their theories that implicated cocci, fungi and par- Key words: carcinogenesis, germ theories, Johannes Fibiger, asites. The impact of these theories was culminated by the No- parasitic theory Introduction transmission was explained. It is long discussed for cancer that heredity is a legend that will vanish Apart from the exogenous, strange for today’s when contagion will be proved” [1]. medical world, misconceptions about cancer (can- cer villages, cancer houses, cancer countries, can- The germs of cancer: coccus and fungi cer races), the microbial theory of cancer held a significant place in the scientific community dur- Several scientists believed that cancerous ing the second half of the 19th century, similarly to germ had a preference for wetlands and could be tuberculosis during the previous decades. In 1907, transmitted to humans under favourable condi- Pasteur’s follower Etienne Burnet (1873-1960) tions, while others supported that the favourite wrote in his treatise La Lutte contre les microbes host of cancer could have been the rat, the rabbit or (The fight against microbes): “Cancer is almost to the fish. In many cases, the Pasteur Institute rep- the point where tuberculosis was, when Villemin resented by Ilya Ilyich Metchnikoff (1845-1916) demonstrated contagion and inoculability....and and Amédée Borrel (1867-1936), was called to take now Pasteur gave us a stronger scientific reason; a position. Bacilli, fungi, sporozoites and viruses the study of cancer can only be benefited from were at the core of cancer theory at that time [2]. this. Cancer is inoculated with a fragment of can- During 1887 and 1889 Scheuerling and Rap- cer, like tuberculosis is inoculated with a tubercle. pin discovered, independently, intracellular micro- Cancer had its Villemin and waits for the discov- organisms (bacilli), which upon culture appeared ery of its microbe; it waits for Robert Koch”. For to contribute to the development of malignant cancer villages and cancer houses, Burnet stated: tumours [3]. At approximately the same time, “They point out the contagion; they do not indicate Professor Charles Richet (1850-1935) isolated heredity. We had the same illusion on tuberculo- “micrococcus pyosepticus” [4], and Eugene Doy- sis; for a long time a hereditary transmission was en (1859-1919) “micrococcus neoformans”, which believed, without any evidence. After the discovery caught the attention of the public, but left the sci- of bacillus and the ways of contagion, tuberculosis entific community with mixed opinions [5]. Correspondence to: Marianna Karamanou, MD, PhD. 4, Themidos street, 14564, Kifissia, Athens, Greece. Tel: +30 6973606804, Fax: +30 210 8235710, E-mail: [email protected] JBUON 2014; 19(1): 319 320 History of Oncology Several scholars investigated the role of cer- of penetration, while the fifteenth day he extracted tain species of fungi in carcinogenesis. In France, the remaining fragment. From that moment on, the Bra and Charles Mongour (1866-1917) were par- small wound grew and became slightly indurated. ticularly intrigued by several types of tumours Months later, the wound widened, and a carcinoma that grow on pears, which could easily be mistaken of the tongue appeared, resulting in the death of for malignant tumours. As they explored this con- the patient ten months after the onset of the dis- cept, they isolated a fungus, “nectria dictissima”, ease” [7]. from which they prepared an anticancer vaccine. The coccidian theory raised a heated debate. Mikhail Stepanovich Voronin (1838-1903) though, During the 11th International Congress of Medical implicated “plasodiophora brassicae” in carcino- Sciences which was held in 1894 in Rome, Rib- genesis, a microorganism that grew on cauliflower bert, André Cornil (1837-1908) and several other roots. His observation caught the attention of Be- scientists strongly opposed against the coccidian hla who strongly believed that the co-existence of theory supporting that the so-called presence of cauliflower and tumours was a mere coincidence. sporozoites in cancerous tumours was simply an Other researchers were fascinated by certain spe- optical illusion. Specifically, they thought that the cies of forest mushrooms, to which they attributed “coccidianists” misinterpreted simple degener- the occasional cancer epidemics in woodland are- ation products for parasites, when looking under as, a form of cancer that they described as profes- the microscope [8]. However, a strange observa- sion-related cancer: the “logger’s cancer” [6]. tion directed the research of Pasteur’s followers to more original parasite theories. In 1891, a young Sporozoitic and miasmatic theories of Parisian scientist, Dr. H. Morau, was working on cancer cancer inoculation studies, while at the same time the experimental study of cancer was developed in At the same time sporozoites were attracting London by E. F. Bashford (1873-1923), in Copenha- considerable attention, as Charles-Louis Malassez gen by Jensen, in Germany by Paul Ehrlich (1854- (1842-1909), Joachim Albarran (1860-1912), Jean 1915), and in the Pasteur Institute by Borrel [9]. Darier (1856-1938), Bosc and Mathieu Jaboulay In all cases, it had appeared that cancer could be (1861-1913) emphasized their importance in car- transmitted from one subject to another only when cinogenesis. In his book Le Cancer, maladie infec- tieuse à sporozoaires (Cancer, infectious disease by the two subjects belonged to the same species, thus sporozoites) [7], Bosc claimed to have dissected sev- suggesting an infectious pattern of transmission. eral cancerous tumours containing these protozoa. According to Burnet the cell is infected by a “virus” This observation led to the belief that a pansperm- that lives together (symbiosis) with the affected cell ia could provoke a cancerous growth. Bosc stated and therefore cancer could be a miasmatic disease. that a ubiquitous coccidian, the “coccus oviforme” This theory was also supported by Amédée Borrel, could have been the pathogen. This could be found Pasteur’s follower, who became the head director in water, ground, most animal species, or even air, of the Institute of Hygiene of Strasbourg in 1919. but predominantly in rabbit’s liver. In the country- Borrel was expert in Parasitology and his research side around the farms, the soil was contaminated was oriented in tumor’s cytology and parasitolo- with spores and cysts rich with carcinogenic coc- gy. In 1903, he presented his thesis rejecting the cidia. Contamination of the air and the food chain various theories on parasite-induced oncogenesis by this protozoan, could explain the high incidence and supported instead the pathogenic role of small of cancer in certain rural regions, while the wide nematodes encysted in the tumours [10]. use of rabbit liver in several cooking sauces at the The origins of the virus-related cancer theory time heightened suspicions of its implication in could be found in the work of the American sci- carcinogenesis. Dogs, cats, rats, fowls, amphibians, entist Francis-Peyton Rous (1879-1970) (Photo 1), insects, and fish could have also served as vectors who had studied medicine at Johns Hopkins Uni- of this “coccus oviforme”. Barbel, tench, bassfish, versity and at the University of Michigan. In 1909 gudgeon and trout were hypothesized on the other he was appointed at the Rockefeller Institute for hand to be unrelated. The most carcinogenic were Medical Research, and one year later, experimen- thought to be the aquatic animals. Bosc wrote an tally showed that a virus was responsible for the unusual story: “While a young man was eating a development of cancer in chicken (Rous sarcoma trout felt suddenly a bone penetrating his tongue virus) [11]. While Rous became famous for this dis- and immediately he removed a small piece. A few covery, it remained unknown that he was preceded days later, he felt a little discomfort at the point by the French bacteriologist Émile Roux (1853- JBUON 2014; 19(1): 320 History of Oncology 321 Photo 1. The distinguished Nobel prized scientist Fran- Photo 2. The Danish Nobel laureate scientist Johannes cis-Peyton Rous. Fibiger. 1933), who, in 1903, in his article published in Bul- gion. In fact, Burnet reported that some children letin de l’Institut Pasteur described a transmissible defi ed their family homes if they had been “hit” by form of cancer in birds [12]. cancer. In 1931, Professor Lumière even spoke of During 1913, a student of Robert Koch (1843- parents avoiding public areas in fear of contact- 1910) and Emile Von Behring (1854-1917), the ing cancer. Those endorsing the parasite theories anatomist and physiologist Johannes Fibiger argued against the existence of hereditary cancer, (1867-1928) in Copenhagen, astonished the scien- since nothing could be done to avoid it, while a se- tifi c world by publishing the results of his work on ries of measures (e.g. improved hygiene and serum the carcinogenic eff ect of “spiroptera neoplastica”, therapy) could be taken against a contagious form which was isolated from a captured rat. Specifi cal- of cancer.