Balto and Togo during the cold winter of Alaska (1925): the two canine heroes in the fight against diphtheria.

In recent years, diphtheria has re-emerged in areas with inadequate vaccination coverage, and Europe has not been spared with several cases among migrants. Diphtheria is a potentially fatal infection caused mainly by toxigenic strains of Corynebacterium diphtheriae. Due to the high mortality rate, especially among young children, the fight against diphtheria is considered one of the first conquests of immunization. In the history of medicine, there is a unique case of an unconventional response to a diphtheria outbreak in which sled dogs were used to overcome the supply difficulties of diphtheria antitoxin. The mass media followed the medical response to the outbreak and raised audience awareness of public health issues. The facts of Nome, Alaska, in 1925 can serve as a catalyst to rethink conventional responses to diphtheria outbreaks in low-income countries today and promote mass media awareness of public health importance.

Sir Marc Armand Ruffer, MD: The early years, 1878-1896.

A founder of paleopathology, the study of disease in ancient human remains, Sir Marc Armand Ruffer, MD (1859-1917) served in Egypt, from 1896 to 1917, as a public-health administrator, epidemiologist, and pathologist. He was professor of Bacteriology at the Cairo Medical School, President of the Sanitary, Maritime, and Quarantine Council, member of the Indian Plague Commission, and author or co-author of 40 papers in palaeopathology. However, little is known of his early professional life, which encompassed his education, medical training, and research in England and France. The pre-Egyptian period, 1878 to 1896, was a time of extraordinary activity. Acquiring four academic Degrees at Oxford University and clinical experience at the University College Hospital, London (1878-1889), he was the clinical assistant of Louis Pasteur during the anti-rabies campaign (autumn 1889), interim President of the British Institute of Preventive Medicine (1893-1896), and immunology researcher (1890-1895), in London and Paris, under the guidance of Élie Metchnikoff (1845-1916). Ruffer developed the diphtheria antitoxin in Britain. In addition to a dissertation on hydrocephalus, he composed or co-authored 34 papers. A prolific writer, linguist, clinician, and administrator, he explored several medical sub-disciplines before concentrating on palaeopathology.

The 1925 Diphtheria Antitoxin Run to Nome - Alaska: A Public Health Illustration of Human-Animal Collaboration.

Diphtheria is an acute toxin-mediated superficial infection of the respiratory tract or skin caused by the aerobic gram-positive bacillus Corynebacterium diphtheriae. The epidemiology of infection and clinical manifestations of the disease vary in different parts of the world. Historical accounts of diphtheria epidemics have been described in many parts of the world since antiquity. Developed in the late 19th century, the diphtheria antitoxin (DAT) played a pivotal role in the history of public health and vaccinology prior to the advent of the diphtheria-tetanus toxoids and acellular pertussis (DTaP) vaccine. One of the most significant demonstrations of the importance of DAT was its use in the 1925 diphtheria epidemic of Nome, Alaska. Coordinated emergency delivery of this life-saving antitoxin by dog-sled relay in the harshest of conditions has left a profound legacy in the annals of vaccinology and public health. Lead dogs Balto and Togo, and the dog-led antitoxin run of 1925 represent a dynamic illustration of the contribution made by non-human species towards mass immunization in the history of vaccinology. This unique example of cooperative interspecies fellowship and collaboration highlights the importance of the human-animal bond in the one-health initiative.

Early Developments in the Regulation of Biologics.

This article is a history of the policy positions and legal interpretations adopted by the Public Health Service (PHS) under the 1902 Biologics Control Act. PHS generally interpreted the scope of the Act narrowly because it lacked authority to deny marketing licenses for ineffective biologics and wanted to minimize the number of worthless drugs with the imprimatur of a governmental license. In addition, PHS implemented important regulatory strategies not expressly authorized by the Act.

What you don't know about vaccines can hurt you.

As physicians, we've all learned in detail about the science behind vaccinations, but I suspect few of us have been taught about the history of vaccinations. Sure, we all know that Dr. Jonas Salk developed the poliovirus vaccine, but I wasn't aware that he inoculated himself, his wife, and his three children with his then experimental vaccine. When our editorial committee decided to focus on vaccinations as our theme for this month's Greene County Medical Society's Journal, I perused the internet for interesting topics. I came across a fascinating website, historyofvaccines.org; this website is a project of the College of Physicians of Philadelphia, touted as being the oldest professional medical organization in the United States. I credit the majority of the information in this article to the above website and the rest to the National Institutes of Health (nih.gov) website; I trust that the information is valid and true, based on the agencies behind these websites. Below are some interesting tidbits about vaccine preventable diseases that I found noteworthy to pass on to our readers.

[Throat disease in the periphery of Europe: the introduction of diphteria antitoxin in Romsdal county]. / Halsesyke i Europas utkant--da difteriantitoksinet kom til Romsdals amt.

Diphteria played a key role in establishing the bacteriological model for explaining infectious disease. This understanding of bacteriological factors spurred research that culminated in the development of diphteria antitoxin, the first effective therapeutic cure for an epidemiological disease. Prior to the introduction of antitoxin, isolation and disinfection were regarded as the key defences against diphteria. The opportunity to combine antitoxin therapy with existing methods for combatting the disease was a key factor for the rapid spread of the antitoxin. Diphteria antitoxin was first used in Romsdal county in 1895. Initially the serum had to be ordered from manufacturers abroad, which restricted its application in the district. Few available doctors and long transport routes were reasons that prevented the antitoxin from reaching its full potential. Industrial manufacturing methods were an obstacle to serum production in peripheral areas. In Norway, production of serum gradually got underway in Kristiania, which was one factor that caused mortality from diphteria to decline faster there than in other parts of the country. In this article we will elucidate the relationship between the centre and the periphery in the spread of medical advances by studying the implementation of diphteria antitoxin in Romsdal county.

[From the ancient serotherapy to naked antibodies: a century of successful targeted therapies]. / De la sérothérapie aux anticorps recombinants << nus >> : plus d'un siècle de succès en thérapie ciblée.

Monoclonal antibodies and molecular engineering have renewed the ancient serotherapy, multiplying the possibilities of therapeutic interventions and providing many new clinical successes! Standing back about this history allows us to better understand the evolution of concepts underlying the therapeutic use of antibodies, as well as the maturation of the tool itself. The different principles of therapeutic targeting will be successively tackled, from their sometimes hundred year-old conception until the most recent clinical developments: antibodies neutralizing toxins and soluble antigens, anti-microbial antibodies, cytotoxic antibodies, tumour-specific antibodies, cell function -modifying antibodies, etc. This overview will finally offer the opportunity to introduce a new pharmacological classification of the entire class of unconjugated -therapeutic antibodies.

Enacting cultural boundaries in French and German diphtheria serum research.

The experimental development of a therapeutic serum against diphtheria between 1891 and 1894 was characterized by a scientific competition that pitted Emil Behring from the Institute for Infectious Diseases in Berlin against Emile Roux and Elie Metschnikoff from the Pasteur Institute in Paris. In general, their competition can be regarded as an extension of the fundamental differences that separated the research schools of Robert Koch and Louis Pasteur. However, to characterize the competition for a diphtheria-serum as "national rivalry" fails to account adequately for the mutual adoption of experimental practices by the Berlin and Parisian protagonists, whose contributions to the development of a therapeutic serum were intertwined in complex ways. Nor can it be characterized as "cooperation," given their fierce public disputes over scientific concepts and the fact that these disputes also shaped the peculiarities of the experimental procedures in Berlin and Paris. A close analysis reveals a complex picture of the dynamic interaction between the conceptual and experimental activities of Behring, Roux, and Metschnikoff- interaction that defined as well as bridged the "French" and "Prussian" experimental systems of diphtheria-serum research.

Locating therapeutic vaccines in nineteenth-century history.

This essay places some therapeutic vaccines, including particularly the diphtheria antitoxin, into their larger historical context of the late nineteenth century. As industrially produced drugs, these vaccines ought to be seen in connection with the structural changes in medicine and pharmacology at the time. Given the spread of industrial culture and technology into the field of medicine and pharmacology, therapeutic vaccines can be understood as boundary objects that required and facilitated communication between industrialists, medical researchers, public health officials, and clinicians. It was in particular in relation to evaluation and testing for efficacy in animal models that these medicines became a model for twentieth-century medicine. In addition, these medicines came into being as a parallel invention in two very distinct local cultures of research: the Institut Pasteur in Paris and the Institut für Infektionskrankheiten in Berlin. While their local cultural origins were plainly visible, the medicines played an important role in the alignment of the methods and objects that took place in bacteriology research in France and Germany in the 1890s. This article assesses the two locally specific regimes for control in France and in Imperial Germany. In France the Institut Pasteur, building on earlier successful vaccines, enjoyed freedom from scrutinizing control. The tight and elaborate system of control that evolved in Imperial Germany is portrayed as being reliant on experiences that were drawn from the dramatic events that surrounded the launching of a first example of so-called "bacteriological medicine," tuberculin, in 1890.

The administrative stabilization of vaccines: Regulating the diphtheria antitoxin in France and Germany, 1894-1900.

It is well known that the development of a diphtheria anti-toxin serum evolved in a competitive race between two groups of researchers, one affiliated with Emil Behring in Berlin and Marburg, and another affiliated with Emile Roux in Paris. Proceeding on the basis of different theoretical assumptions and experimental practices, the two groups developed a therapeutic serum almost simultaneously. But the standardized substance they developed took on very different forms in the two countries. In Germany the new serum was marketed in the private sphere and subjected to state regulations, becoming a kind ofprototype of industrial medications. In France, however, the same substance was marketed as a gift of science to humanity and distributed through the communal health care system. This article demonstrates how a new medication emerged from the efforts to produce, market, regulate, distribute, and apply it in the two respective countries. It attributes the difference to the negotiations between the respective actors (scientists, industrialists, politicians, officers, and the public) and institutions (firms, academies, private and public institutes, legislative bodies, professional corporations). I develop this argument on three different levels: First, I stress the importance of the institutional foundations of serum production; second, I illustrate the decisive role played by existing "ways of regulating" in the rapid development of new legal statutes; and third, I describe the consequences that flowed from the respective administrative organization of marketing and dissemination. In sum, I explore how an experimental object was transformed into an object of the public health system and stabilized by administrative means.

Monitoring the stable at the Pasteur Institute.

Diphtheria serum production in France was dominated by the Pasteur Institute, which equipped a facility at Garches to produce the antitoxin on a large scale. This article treats the background to the founding of this facility, as well as its day-to-day functioning around 1900. The treatment integrates an examination of the practical undertaking of serum production by the Pasteur Institute with an analysis of the popular perception of the Institute and the mixed financing of the whole venture. We particularly emphasize the "industrial" features of this manufacturing process that involved living units of production, showing how bioassays influenced the destiny of the animals producing the serum. Finally, we argue that this monitoring of the horses, seen as serum-producing units, also provided information on the diseases the sera were intended to treat.

The elusive role of scientific medicine in mortality decline: diphtheria in nineteenth- and early twentieth-century Philadelphia.

The designation of the Klebs-Loeffler bacillus as the cause of diphtheria in the early 1890s and the subsequent development of the antitoxin treatment in the years immediately following were at the time and continue to be viewed as triumphs of scientific medicine. I focus on these two developments to illustrate the problems that arise in attempting to answer the questions regarding the role that changes in medical practice--in this case, the use of antitoxin as a cure--played in lowering death rates at the time. Changes in diagnostic techniques, the selection of cases to be included, and ultimately the agendas of the persons constructing them affected the numerators and denominators of these rates. The data suggest that the antitoxin had some effect on already declining diphtheria death rates, but because of changes in understandings of the disease and contemporaries' presentation of the data, the size of that effect and its role in mortality decline more generally elude us. Our analysis of the past depends on numbers that reflect not only changing treatments but also changing understandings of disease at the end of the nineteenth century.