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Le Infezioni in Medicina, n. 1, 52-56, 2012 Le infezioni From miasmas to germs: nella sto- a historical approach ria della medicina to of infectious

Infections transmission in the Dai miasmi ai germi: un approccio storiografico alle teorie history of della trasmissione delle malattie infettive medicine Marianna Karamanou1, George Panayiotakopoulos2, Gregory Tsoucalas1, Antonis A. Kousoulis1, George Androutsos1 1History of Medicine Department, Medical School, University of Athens, Athens, Greece; 2Clinical Pharmacology, Medical School, University of Patras, Patras, Greece

n INTRODUCTION tance [4]. In Ancient Rome fever had three tem- ples, in Palatine Hill, in Vicus Longus and in hroughout centuries philosophers and sci- Sacra Via and was supplicated as the Goddess entists tried to explain the way of infec- Febris who protected people from fever and Ttious transmission. Witchcraft, [5]. demons, gods, comets, earthquakes were the In 6th century BC, the pre-Socratic philosophers first unproved theories, followed by tangible Pythagoras, Alcmaeon, and Empedocles inau- scientific ones such as miasma’s , conta- gurated the period in where the envi- gious theory, theory ronment was understood to play a vital role in and germ theory till the of microbiol- health and disease. A century later, Airs, waters ogy in mid . and places of the Hippocratic texts, correlated a variety of symptoms and diseases with geo- Early transmission theories and the miasma graphical and meteorological conditions, for theory example malaria, catarrh and diarrhea were be- Primitive ideas about contagiousness dealt lieved to be due to the effect of seasonal with the general notion of transmission changes on stagnant water or marshy places [6]. through contact. were probably rare Such concepts survived and in time consolidat- in small primitive tribes but they became terri- ed in the belief that a pathological state of the fying events once population density increased atmosphere is associated with infectious dis- enough to produce and sustain them. At that eases and this line of thinking developed fur- time people’s ignorance led to magical or reli- ther into the of contagion [7]. gious explanations of disease, sent by the gods Air became contaminated with “miasmas”, poi- as punishment for their sins [1]. Among many sonous vapors produced by putrefying organic primitive tribes, as well as in the highly devel- matter and a person could become infected oped sacerdotal practices of ancient cultures, when miasmas invaded the body and disturbed we find suggestive fragments of infectious dis- its vital functions. eases transmission embedded in a matrix of re- In his manuscript about -based regula- ligion[2, 3]. Characteristically, in Ancient Persia tion for selecting building sites, entitled De ar- we see an emphasis on demonology. The dis- chitectura, the Roman architect Marcus Vitru- ease is caused by evil spirits and must be con- vius Pollio (70 BC-15 BC) revokes the miasma trolled by exorcism. The cult of Nergal, a de- theory and warned against swampy places: mon portrayed in hymns and myths as a god of “For when the morning breezes blow toward war, fever and pestilence, was of a great impor- the town at sunrise, if they bring with them

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mist from marshes and, mingled with the mist, duced his own theory of disease, the contagious the poisonous breath of creatures of the marsh- theory. According to his writings, some dis- es to be wafted into the bodies of the inhabi- eases, such as syphilis and gonorrhea were on- tants, they will make the site unhealthy” [8]. ly transmitted by direct contact, other diseases (130- c. 201 D) the most famous physi- were transmitted by fomites as clothing, that cian of the Roman period emphasizes also the had been in contact with the sick and in the miasma theory as he recognizes plague, tuber- third category he placed diseases such as tuber- culosis and skin diseases as contagious [9]. culosis and capable of infecting per- As we pass from the classical to the early cen- sons at a distance from the sick and transmitted turies of the Christian era, we find the conta- by air [1]. For Fracastoro, germs are conceived giousness of leprosy playing a major role in the not as living but as chemical basis of the Old Testament. In Leviticus Book, a substances liable to evaporation and atmos- sanitary code almost free from any elements of pheric diffusion; each disease was specific and supernaturalism, we notice a system for control- had its specific germ; the germ propagated in ling leprosy involving differential diagnosis, the tissue of the infected host and caused dis- isolation, and disinfection that re- ease by setting up chemical putrefactive mains the most brilliant application of rational changes in those tissues; in order a germ to pro- of ancient times. In the Byzantine duce , it must find a corresponding period the spread of leprosy is also mentioned analogy in the tissues of the host [11]. in the writings of Aretaeus of Cappadocia (1st Fracastoro’s theory is considered to be the first century AD). He states that the breath is the ve- theoretical statement of the contagious theory hicle for disease transmission. In the 6th century of the disease, three centuries before Pasteur’s AD the also named and Koch’s researches, a victory of rationalism “Justinian Plague” furnished new information’s but in that period a difficult concept for people to the concept of contagion [10]. The historian to accept; they continued to believe in the mias- Evagrius Scholasticus (537-594) described the ma theory that persisted well into the 1800s. plague and considered it transmitted by contact, visiting infected houses or even by interperson- From spontaneous generation to germ theory al relationship in the market place [2]. Despite the discovery of the microscopic world by Anton van Leeuwenhoek (1632 – 1723), in The contagious theory of the 17th century little progress had been made In the medieval period epidemic disease was on the road to truth and reason. In that histori- associated in people’s mind with comets, cal period the revival of the spontaneous gener- eclipses, earthquakes or major astrological dis- ation theory was widely accepted by most turbances that charged the air with poisonous members of the scientific community. It pro- vapors known as “miasmas”. The miasma the- posed that simple life arises spontaneously ory was again the dominant theory of conta- from non living matter (abiogenesis); for exam- gion because of people’s observation that the ple mice can arise from grain and maggots from epidemics and mainly the plague tended to oc- decaying meat. The idea of spontaneous gener- cur during the hot summer months where the ation may be tracked back in the teaching of air in the cities was humid and filled with the in 4th century BC. According to this odours of garbage, decomposing animals and theory stated in The and in . The Generation of Animals, living things came During the 16th century, Girolamo Fracastoro from non living things because the non living (1478-1553) poet, physician and mathematician material contained pneuma or vital force [12]. attempted to analyze the concept of contagion A strong opponent to that theory was the Ital- and infection. In his major clinical work On ian physician (1626-1697). In his Contagion, Contagious Diseases and Their Cure, work entitled on the Generation of In- published in 1546, Fracastoro distinguished sects, published in 1668, he developed an exper- three forms of contagion and speculated that in- iment in order to disprove that maggots arose fections are caused by transferable seed-like be- spontaneously from decaying meat (Figure 1). ings, seminaria or germs, which could in- Redi began by putting pieces of meat into six fection. Having observed the epidemics of jars, he covered with lids three of the jars and syphilis, plague and typhus that devastated he left open the other three. The meat in the Italy during the16th century, Fracastoro intro- closed jars decayed but no maggots appeared;

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Figura 1 - The eminent Italian physician Francesco Figura 2 - The French chemist and microbiologist Redi (1626-1697). (1822-1895).

however maggots and flies appeared in the the narrow sense, none are more worthy of at- opened jars. His did not convince tention than those relating to the origin of fer- the supporters of the spontaneous generation ments. Where do they come from these myste- theory which argued that it was unauthentic; rious agents? This is the problem that has led the lids excluded air and therefore the “vital” me to study the so-called “spontaneous genera- force necessary for spontaneous generation to tion” [15]. He demonstrated that fermentation occur. Redi modified his experiment by putting and growth of microorganisms in nutrient body nets instead of lids on the same jars and no did not proceed by spontaneous generation. He maggots appeared. These results gave a strong boiled meat broth in a flask, heated the neck of blow to the spontaneous generation theory but the flask in a flame until it became pliable, and many scientists still believed that microscopic bent it into the shape of an S. Air could enter forms of life were generated from non living the flask, but airborne microorganisms could substances [13, 14]. not, they would settle by gravity in the neck. As The theory of spontaneous generation was fi- Pasteur had expected, no microorganisms nally putting to rest in 1862 when the French grew. When he tilted the flask so that the broth chemist Louis Pasteur (1822-1895) proposed a reached the lowest point in the neck, where any germ theory of diseases, supporting that mi- airborne particles would have settled, the broth croorganisms are the cause of diseases (Figure rapidly became cloudy with life [16]. Pasteur 2). Actually, during that period scientists were had both refuted the theory of spontaneous working on the notion of the species trying to generation and demonstrated that microorgan- identify life. If (1809-1882) isms are everywhere, even in the air; the revo- went to Galapagos and he theorized on the lutionary germ theory was a reality [17]. birth of a new world and on the evolution of Finally, it was a German scientist species, Pasteur was riveted to his microscope (1843-1910) who developed the criteria and pro- revealing the origin of germs [15]. cedures necessary to establish that a particular During 1862 and 1864, Pasteur was working on microbe and no other cause a particular disease. ferments, carrying out revolutionary experi- His first demonstration with the bacil- ments and making observations that disproved lus was in 1876. Between 1877 and the end of the spontaneous generation: “Among the ques- the century he identified bacillus tions raised by my research on the ferments in and . In 1884 Koch and Friedrich

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Loeffler (1852-1915) formulate four criteria in n CONCLUSION order to establish a relationship between a causative microbe and a disease. According to The concept of disease transmission and conta- this, the must be found in abun- gion was well established before microorgan- dance in all organisms suffering from the dis- isms were identified. As the conception upon ease, but should not be found in healthy ani- diseases transmission reflects the society’s state mals, it must be isolated from a diseased organ- of progress, we passed from the miasma theory ism and grown in pure culture, the cultured mi- to the most important concept in the history of croorganism should cause disease when intro- modern medicine, the germ theory. duced into a healthy organism and a microor- ganism must be re-isolated from the inoculated, Key words: miasma theory, Girolamo Fracas- diseased experimental host and identified as toro, spontaneous generation, Louis Pasteur. being identical to the original specific causative agent [18]. The modern concept of disease Conflict of interest: none transmission was born.

SUMMARY

From miasma to germ theory we trace the evolu- gion theory and spontaneous generation theory up tion of conceptions in infectious disease transmis- to the revolutionary trans- sion. Starting from the unproved theories of conta- mission. giousness we move on to miasma theory, conta-

RIASSUNTO

In questo articolo viene tracciata l’evoluzione del con- attraverso la teoria dei miasmi, del contagio e della ge- cetto di trasmissione delle malattie infettive. Partendo nerazione spontanea, gli autori giungono infine a di- dalla teoria non provata della contagiosità, e passando scutere della teoria “rivoluzionaria” dei germi.

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