Centenary of the Death of Józef Brudziński: on His Contribution to Early Bacteriology

VARIA

DOI: 10.34763/devperiodmed.20172103.293296 Piotr Polaczek*

CENTENARY OF THE DEATH OF JÓZEF BRUDZIŃSKI: ON HIS CONTRIBUTION TO EARLY BACTERIOLOGY

Braun Labs, California Institute of Technology, Pasadena, California

DEV PERIOD MED. 2017;XXI,3:293296

Józef Brudziński died December 18th, 1917 at the At the end of 19th century, bacteriologist as a profession, age of 43. In his short life, he achieved prominence as per se, did not exist, but a few scholars, mainly physicians, a pediatrician, neurologist, bacteriologist, and also as a were engaged in investigations of the micro+ora of the political #gure. In Poland, he is remembered as the #rst human gastrointestinal tract and its role in health and rector of Warsaw University (#g. 1) following its revival disease. %is work may mark the beginnings of probiotic a$er a century of turmoil (partition of Poland, several and microbiome research. Reminiscent of today, there uprisings, and World War I). He was also wholeheartedly was no shortage of hype, skepticism and controversies involved in organizing several pediatric hospitals in involved. Poland, at the time among the most modern in Europe. %eodor Escherich was the discoverer of Bacilllus coli His work as a pediatrician on neurological signs in commune, later renamed Escherichia coli in his honor. diagnosis of meningitis is widely known. Medical students He is credited with carrying out the #rst systematic study all over the world are familiar with the tongue-twister, of intestinal bacteria [2]. Escherich’s clinic attracted called Brudziński’s sign or relex, used in the diagnosis researchers not only from Europe, but practically from of meningitis. Less is known about his contributions to all over the world (#g. 2). According to one of Escherich’s bacteriology and his seminal work on intestinal bacteria. assistants and later a renowned physician, Bela Schick, One has to dig deep into the literature of the early 20th the bacterial era was inaugurated in pediatrics by century to gain insight into this equally important work. Escherich, who had a longstanding interest in bacterial In online searches, the name Brudziński complicates +ora of the gastrointestinal tract [3]. It was believed at matters, as the spelling of his name has many variations the time that bacteria are responsible for decomposition in the literature: Brudzińsky, Brudzinske, Brudsinski etc. of proteins to harmful putrefaction products that could %e approaching hundredth anniversary of his death be absorbed from the bowels into the blood stream, a is an appropriate time to call attention to his largely form of auto-intoxication. Escherich suggested #ghting forgotten early work that, along with that of a handful this condition by the in troduction of acid-producing of others pioneers, forms the foundation of what we now bacteria, #rst described by Louis Pasteur [4], and including call probiotic and microbiome research. carbohydrates to the diet based on a mutual antagonism Because in partitioned Poland, at the end of 19th between the saprophytic intestinal inhabitants and the century there were limited opportunities to study acid-producing bacteria. medicine, Brudziński le$ the country and enrolled in the In Escherich’s clinic, Brudziński [5, 6] was to test medical school programs in Dorpat, Estonia (now Tartu). this hypothesis by performing experiments aimed at %e russi#cation of the university and the expulsion of com bating intestinal putrefaction in dyspeptic infants German faculty, however, led him to move to Moscow using the acid-producing Bacillus lactis aerogenenes (now University. A$er graduation in 1897, he continued his Enterobacter aerogenes), which was known to ferment education at St. An na Children’s Hospital at the University sugars with the formation of lactic acid and gas. %is of Graz, Austria, under %eodor Escherich. Subsequently, organism had previously been found by Escherich to he worked at l’Hôpital des Enfantes Malades in Paris with be one of the two dominant bacteria in stools of healthy Jacques-Jo seph Grancher, Antoine Marfan, and Victor infants (%e other was E. coli. Note that this was before Henri Hutinel. It is interesting to note that both Escherich knowing that the dominant intestinal bacteria are strict and Grancher, a close collaborator of Louis Pasteur, anaerobes). Brudziński #rst examined fetid stools of several are thought to be the #rst pediatricians for infectious dyspeptic infants and found that most grew out Proteus diseases [1]. vulgaris. He then administered pure cultures of Bacillus

*Józef Brudziński was the author’s great-grandfather. An earlier version of this article was posted in a blog, “Small things considered”, sponsored by the American Society for Microbiology (ASM). 294 Piotr Polaczek lactis aerogenes , which proved successful. %e foul smell %e research exempli#ed above, relatively high-pro#le subsided, and they regained their natural acidic smell. at the time, received recognition in the literature, but Proteus was now absent. A similar e/ect was achieved was also met with a dose of skepticism, as demonstrated by feeding patients large amounts of milk and sugar. by the following [13]: He concluded that the symptoms of auto-intoxication “Recently, renewed attention has been called to the observed in dyspeptic children were due to absorption in possibility of in"uencing intestinal fermentation and the intestine of toxins derived from Proteus . Brudziński putrefaction by the administration of cultures of bacteria. An also performed experiments with animals. Proteus injected old method was to administer brewer’s yeast. More recently under the skin of mice was lethal, while no symptoms Brudziński, Metchniko$ and Tissier have employed cultures were observed if mixed with food of young dogs and of organisms that occasion lactic acid fermentation. %e kittens. To identify the source of Proteus found in the same applies to the administration of sour milk, buttermilk, stools, Brudziński examined samples of raw and boiled koumiss, and similar preparations. %e value of this form milk for the presence of the bacteria. Proteus grew only of treatment has not yet been determined. It is doubtful in previously boiled milk, seldom in fresh milk, and whether the extravagant claims re cently put forward will never in acidic milk. be substantiated by further investigation.” Research on bacterial micro+ora of the gastrointestinal %e concept of in+uencing the composition of intestinal tract was quite proli#c at the time. Two newly discovered micro+ora with the use of mutually antagonistic bacteria species of intestinal bacteria were added to the list. Ernst was also discussed in terms of individual contributions. Moro discovered a gram-positive bacterium, Bacillus Alexander Poehl, a chemist and pharmacist from St. acidophilus (now Lactobacillus acidophilus ), claiming Petersburg was the #rst to discover that sour milk diminishes that it is a dominant species in breast-fed infants [7]. intestinal putrefactions [14]. Only later were cultures of lactic- At the Pasteur Institute, Henri Tissier observed a Y-shaped acid producing bacteria used in attempts to sup press this bacterium, and, because of its tendency to branch, named it condition. Metchniko/’s contribution to researching the Bacillus bi!dus (now Bi!dobacterium ) [8]. Tissier disputed topic was questioned in another report [15]: Moros’ assertion of the dominance of B. acidophilus , “Poehl, Brudziński, Fischer, Rovighi and Embden claiming that B. bi!dus is of primary importance. %e then turned their attention to sour milk and found that controversy ended with Moro’s own admission that B. bi!dus that too would inhibit intestinal putrefaction to a certain is present in far greater numbers in breast-fed babies, extent at least. %is work is in reality the foundation upon and both agreed that B. acidophilus was predominant which Metchniko$ built his sour milk therapy. His claim in stools of cow’s milk fed babies. to recognition appears to depend largely on the fact that Meanwhile, Elie Metchniko/, also working at the he popularized this form of administration of lactose and Pasteur Institute, turned his attention to the newly lactic acid” . discovered Bacillus bulgaricus (now Lactobacillus delbruckii Yale researchers Rettger and Cheplin [16] provided a subsp. Bulgaricus [9, 10, 11]. %is species is not only a more detailed list of workers in the #eld with the timeline powerful acid producer but is also resistant to high acid of their published work: concentrations. %e large numbers of centenarians living Poehl (1887) noted that sour milk when ingested decreased in Bulgaria, where lactobacilli-containing yogurt was a intestinal putrefaction. %is observation was con!rmed by dietary staple, convinced Metchniko/ that B. bulgaricus Rovighi (1892), Embden (1894), Brudsiński [sic] (1900) and may provide the secret to longevity by replacing the Fischer (1903). Tissier and Martelly (1902) stated that the toxin-generating bacteria in the colon. Whether this chief agent in e$ecting inhibition of putrefying bacteria is longevity may be attributed to the health bene#ts of probably the lactic acid produced by the lactic acid bacilli. yogurt or was simply a consequence of unreliable birth Tissier and Gasching (1903) found that acid-producing records is a matter of contention. Mechniko/ was not a bacilli are able in a sugar-containing medium to arrest physician and contributed little to experimental work, the growth of putrefactive organisms, thus con!rming the but was a staunch advocate of the health bene#ts of sour conclusions of Bienstock (1899) . milk. %is caused a media frenzy. %e popular French %us, at the turn of 19 th and 20 th century, work on daily, Le Matin, with front page headline: “Vive la Vie!” the bacterial gastrointestinal micro+ora thrived. Elie (Long live Life!), announced that Metchniko/ found Metchniko/ took notice of Brudzinski’s work. He an elixir of eternal youth [12]. Subsequent studies with mentioned it brie+y in his philosophical book Études B.bulgaricus in other laboratories put into question optimistses , translated into English under a provocative title: whether it can survive in the sto mach, much less colonize Prolongation of Life: Optimistic Studies [17]. In addition, the colon. Metchniko/’s conviction, bordering on in a scienti#c report, Bacteriotherapie Intestinale [18], obsession, with the notion that acid producing bacteria Metchniko/ devoted a large section to Brudzinski’s studies, may prolong life did not go unnoticed. As a result, commenting that while the bacteriological studies were he has been proclaimed the father of probiotics. His marred by the fact that they did not include anaerobic regimen of daily consumption of sour milk probably bacteria, this in no way detracted from the importance did not prolong his life by as many years as he had of the clinical experiments he carried out. He expresses wished for. He died in 1916 at the age of 71. However, astonishment, that no one followed up on this work. his accomplishments in immunology – notably, the Finally, he concludes that at the end of 19 th century, the discovery of phagocytosis, for which he was awarded bases of bacterial therapies had already been established the Nobel Prize in 1908 – earned him immortality. and had given rise to several interesting applications. Centenary of the death of Józef Brudziński: on his contribution to early bacteriology 295

Fig. 2. Escherich’s clinic in Graz, Austria. Theodor Escherich (center), Meinhard von Pﬂauner examining a child, and Józef Brudziński (far le) with Ernst Moro inoculang a laboratory animal.

“%e ceremony was short and simple. Precisely at Fig. 1. A photo of Józef Brudziński superimposed over the noon, General Besseler, wearing the decorations granted entrance gate to Warsaw University, where in 1916 for the reduction of Antwerp and the Polish fortresses he placed a white eagle, as a testament to the Polish character of the school. mounted the dais of the gala ballroom of the old Jagiellonian Castle, and in the name of Germany’s sovereign read the imperial manifesto in ringing, soldiery tones... President Brudziński of the recently elected City Council, who is rector of the University of Warsaw, advanced before the dais and in the Polish tongue gave thanks to the imperial decree... President Brudziński, who was in plain civilian %is early fascination soon began to wane, but was kept attire, without decorations, seemed to represent the spirit alive for some time, thanks in part to sensational news not of the ancient Poland and the Polish chivalry but of with the promise of prolonging life, only to die with the modern intellectual Poland.” advent of Fleming’s “miracle cure” – penicillin. %e early %e scienti#c careers of Brudziński and Moro followed pioneers in the #eld are now largely forgotten. Today, a remarkably parallel path; aside from their bacteriological as a consequence of antibiotics overuse and misuse and work under Escherich, both discovered neurological the growing threat of antibiotic resistant bacteria, we signs, now bearing their names. %e Moro re+ex in infants are witnessing the re-emergence of such studies, on a is a response to sudden loss of support and is believed vastly larger scale by a rapid expansion of pro biotic and to be the only unlearned fear in humans. Brudziński’s microbiome research. Technological advances allow us career ended with his premature death, while the career to study human-inhabiting bac teria as a collection of of Moro, whose wife was of Jewish origin, was cut short numerous species and to analyze functional, complex by the Nazi rule. interactions between the host and the microbiota, with new hope of preventing and treating a range of human REFERENCES diseases. 1. Escherich T. Die Darmbakterien des Säuglings und ihre As mentioned above, Brudziński, apart from Beziehungen zur Phsiologie der Verdauung. Enke Verlag, being a physician, was involved in other pursuits Stuttgart, 1886. such as organization of several hospitals in Poland, 2. Shulman ST. %eodor Escherich: the #rst pediatric infectious launching of the #rst Polish pediatric journal, Przeglad diseases physician? Clin Infect Dis. 2007;45(8):1025- Pediatryczny (Pediatric Review) in 1908, as well as actively 1029. participating in political life. In 1916, a declaration of 3. Schick B. Pediatric pro#les: Pediatrics in Vienna at the Emperors Wilhelm II of Germany and Franz Joseph of beginning of the century. J Pediatr. 1957; 50:114-124. Austria promised the creation of the Kingdom of Poland. 4. Pasteur L. Ann de Chim et Phys s 3 1858 lii p. 404. %is was regarded as one of main factors in the Polish 5. Brudzinski J. O wystepowaniu bac. proteus vulg aris e/orts to regain independence. On November 6 th , 1916, w stolcach niemowlat; proba leczenia przez podawanie under the headline: “Warsaw cheers promised freedom”, hodowli bakteryjnych. in Polish. Przeglad Lekarski %e New York Times reported [19]: (Kraków)1899;48:651-653 296 Piotr Polaczek

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Address for correspondence: Piotr Polaczek Braun Labs, California Institute of Technology, Pasadena, California 91125, USA. Phone: +1 (626) 395-6037 e-mail: [email protected]