While John Snow's life was unfolding in England, another scientific career was emerging in Italy, remarkably similar  to that of John Snow.  Eventually, the Italian scientist, Filippo Pacini, would gain prominence for his discovery of Vibrio cholera, but not until 82 years after his death, when the international committee on nomenclature in 1965 adopted Vibrio cholerae Pacini 1854 as the correct name of the cholera-causing organism.  Until then, many credited Robert Koch (1843-1910) with this seminal discovery.  

PACINI'S EARLY YEARS

Filippo Pacini (1812-83) was born in Pistoia, Italy on May 25, 1812.  His father was a cobbler of humble means, who nevertheless provided his family with a strict religious education.  From early on, Pacini's parents wanted him to become a bishop and be committed to religious studies.  At age 28 he abandoned his ecclesiastical career and turned to medicine.  He accepted a scholarship in 1830 to the Scuola Medica Pistoia, a medical school founded in 1666 in Pistoia.  He eventually became a physician and experienced dissector, and specialized in the use of the microscope. In 1849 at age 37, he became chair of  General and Topographic Anatomy at the University of Florence, where he remained for the duration of his career.  

PACINIAN CORPUSCLES

While still in medical school, he observed in his anatomy course some small ovoidal bodies attached to various  nerves.  They were hardly visible to the naked eye, but nevertheless caught his attention.  He used his meager savings to purchase a microscope and subsequently discovered and described "Pacinian corpuscles" -- encapsulated nerve endings widely distributed in the human body. Later they were found to be sensitive to pressure and to vibrations up to 400 cycles per second. Pacini first mentioned the corpuscles at a scientific meeting in Florence in 1835.  By 1844, his work became widely recognized in Germany and elsewhere, and the corpuscles were named for him. At the same time, the Grand Duke of Tuscany donated a more powerful microscope to the University of Florence for Pacini's use.   

DISCOVERY OF CHOLERA ORGANISM

Cholera came to Florence in 1854 during the Asiatic Cholera Pandemic of 1846-63. Pacini became very interested in the disease.  Immediately following the death of cholera patients, he performed an autopsy and with his microscope, conducted histological examinations of the intestinal mucosa. During such studies, Pacini first discovered a comma-shaped bacillus which he described as a Vibrio.  He published a paper in 1854 entitled, "Microscopical observations and pathological deductions on cholera" in which he described the organism and its relation to the disease.  His microscopic slides of the organism were clearly labeled, identifying the date and nature of his investigations (see figure).  

 While later found to be important, Pacini's work was completely ignored by the scientific community.  It is unlikely that John Snow knew of this earlier publication, presented in far-away Italy four years before Snow's death.  Nor 30 years later would Robert Koch come across Pacini's report. 

PACINI'S LATER YEARS

Pacini further developed his ideas on cholera in a series of publications in 1865 (seven years after the death of John Snow), 1866, 1871, 1876 and 1880.  He correctly described the disease as a massive loss of fluid and electrolytes due to the local action of the vibrio on the intestinal mucosa, and recommended in extreme cases the intravenous injection of 10 grams sodium chloride in a liter of water -- later found to be very effective.  

As a supporter of the germ theory, Pacini insisted that cholera was contagious. Yet similar to debate throughout Europe, his ideas were contradicted by influential Italian physicians who believed in the miasmatic theory.  Until one year after his death in 1883, Pacini's cholera data were ignored by the scientific community.   

Like John Snow, Pacini never married.  For a long time he took care of his two sisters who were both seriously ill.  He died very poor on July 9, 1883, having spent all of his money on his scientific investigations and medical care for his sisters.  

THE FAME OF ROBERT KOCH

As one a founder of the science of bacteriology, Robert Koch (1843-1910) enjoyed worldwide fame, including acknowledgement of his discovery in 1882 of the tubercle bacillus that caused tuberculosis and in 1884 the cholera bacillus, Vibrio cholerae.  For his many scientific achievements in 1905 he received the Nobel Prize for Physiology or Medicine. But how could there by two discoverers of the cholera organism when one reported his findings 30 years before the other?  The answer follows.  

The German physician Robert Koch, like most of the scientific community, was unaware of Pacini's work at the University of Florence.  Yet both independently came to a similar conclusion.  Since Koch's findings eventually became accepted by his scientific peers, and were widely know in the popular press, he became the acknowledged discoverer of the cholera organism.    

REDISCOVERY OF CHOLERA ORGANISM

During 1883, cholera was epidemic in Egypt.  Koch traveled with a group of German colleagues from Berlin to Alexandria, Egypt in August, 1883. Following necropsies, they found a bacillus in the intestinal mucosa in persons who died of cholera, but not of other diseases. He reasoned that the bacillus was related to the cholera process, but was not sure if it was causal or consequential. He stipulated that the time sequence could only be resolved by isolating the organism, growing it in pure culture, and reproducing a similar disease in animals.  He was not able to obtain such a pure culture, but did try to infect animals with choleraic material. None became infected.  His thoughts and early findings were sent in a dispatch to the German government and shared with the German press.

Late in 1883, Koch requested authorization for his team to sail to Calcutta, India to continue their work.  The epidemic had subsided in Egypt but was still very active in India. The team continued their research work.  On January 7, 1884, Koch announced in a dispatch that he had successfully isolated the bacillus in pure culture.  One month later he wrote again, stating that the bacillus was not straight like other bacilli, but "a little bent, like a comma."  He also noted that the bacillus was able to proliferate in moist soiled linen or damp earth, and was susceptible to drying and weak acid solutions.  Finally, he pointed out that the specific organisms were always found in patients with cholera but never in those with diarrhea from other causes, were relatively rare in early infection, but were extensively present in the characteristic "rice water stools" of advanced cholera patients.  He was, however, still unable to reproduce the disease in animals, reasoning correctly that they are not susceptible.  In May, 1884 Koch and his colleagues returned to Berlin where they were treated as national heroes.

PERSISTENCE OF MIASMA THEORY

Despite the earlier work of Dr. John Snow, many still believed that cholera was caused by miasmata.  Just 10 years earlier at a major 1874 international sanitary conference, representatives of 21 governments voted unanimously that "ambient air is the principal vehicle of the generative agent of cholera."  With Koch findings, however, the tide of scientific and public opinion began to increasingly to change, although slowly.  Scientists were divided in Germany, almost entirely negative to Koch's theory in France, and nearly so in England.  In the international sanitary conference of 1885 attended by Robert Koch along with representatives of 28 countries, the British delegation successfully blocked any "theoretical discussion on the etiology of cholera," thereby denying  evidence that British John Snow had so carefully described in his 1855 book, Italian Filippo Pacini had witnessed in his microscopic studies, and German Robert Koch had cultured in his field and laboratory studies. 

The grip of prevailing dogma was difficult to loosen.  Yet  with time the scientific clarity of Snow, Pacini and Koch swayed scientific opinions and the miasma theory of cholera was finally laid to rest.  

Sources:  

Bentivoglio M, Pacini P. Flippo Pacini: a determined observer. Brain Research Bulletin 38(2), 161-165, 1995.

Howard-Jones N. Robert Koch and the cholera vibrio: a centenary. British Medical Journal 288, 379-381, 1984. 

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