Armond S. Goldman

Karl Landsteiner applied the sciences of biochemistry, pathology, microbiology, and immunology in medical research to great success during the first half of the 20th century. Although he is principally known for elucidating the major blood group antigens A and B and their isoantibodies for which he was awarded the Nobel Prize in Physiology or Medicine, Landsteiner made many other important medical discoveries. In that respect, he ascertained that paralytic poliomyelitis was due to a virus, the pancreas was damaged in cystic fibrosis, simple chemicals called haptens were able to combine with antibodies, and the Rh antigen that was later found to be the principal cause of hemolytic anemia of the newborn was found in most humans. Moreover, Landsteiner’s book “The Specificity of Serological Reactions” was a precursor to the molecular revolution in immunology that occurred after Second World War. Finally, he was one of the leaders of the American Association of Immunology and of the Journal of Immunology.

In 2003, we published evidence that the most likely cause of FDR’s 1921 neurological disease was Guillain–Barré syndrome. Afterwards, several historians and neurologists stated in their publications that FDR had paralytic poliomyelitis. However, significant criticism of our article or new support for that diagnosis was not revealed. One critic claimed that FDR’s cerebrospinal fluid indicated poliomyelitis, but we did not find evidence that a lumbar puncture was performed. The diagnosis of FDR’s neurological disease still depends upon documented clinical abnormalities. His age, prolonged symmetric ascending paralysis, transient numbness, protracted dysaesthesia (pain on slight touch), facial paralysis, bladder and bowel dysfunction, and absence of meningismus are typical of Guillain–Barré syndrome and are inconsistent with paralytic poliomyelitis. FDR’s prolonged fever was atypical for both diseases. Finally, permanent paralysis, though commoner in paralytic poliomyelitis, is frequent in Guillain–Barré syndrome. Thus, the clinical findings indicate the most likely diagnosis in FDR’s case remains Guillain–Barré syndrome.

In addition to the holdings at Bibliothèque Nationale de France and Musée du Pasteur Institut à Paris, major parts of la Bibliothèque de Louis Pasteur are in four institutions in the United States – Reynolds Historical Library at the University of Alabama at Birmingham, Alabama; Burndy Library on the History of Science and Technology at Huntington Library in San Marino, California; Harry Ransom Humanities Research Center at University of Texas in Austin, Texas; and Truman G Blocker History of Medicine Collections, The Moody Medical Library, University of Texas Medical Branch, Galveston, Texas. The circuitous paths that led each part of la Bibliothèque de Louis Pasteur to their present locations were traced and the lives of key individuals in medicine, science and the humanities who obtained these valuable documents were recounted. The documents in each institution were discussed and a plan was considered to make them accessible to scholars who wish to further explore the life of Louis Pasteur.

The evolution of immunological agents in milk is intertwined with the general aspects of the evolution of the mammary gland. In that respect, mammalian precursors emerged from basal amniotes some 300 million years ago. In contrast to the predominant dinosaurs, proto-mammals possessed a glandular skin. A secondary palate in the roof of the mouth that directed airflow from the nostrils to the oropharynx and thus allowed mammals to ingest and breathe simultaneously first appeared in cynodonts 230 million years ago. This set the stage for mammalian newborns to nurse from the future mammary gland. Interplays between environmental and genetic changes shaped mammalian evolution including the mammary gland from dermal glands some 160 millions of years ago. It is likely that secretions from early mammary glands provided nutrients and immunological agents for the infant. Natural selection culminated in milks uniquely suited to nourish and protect infants of each species. In human milk, antimicrobial, anti-inflammatory, and immunoregulatory agents and living leukocytes are qualitatively or quantitatively different from those in other mammalian milks. Those in human milk compensate for developmental delays in the immunological system of the recipient infant. Consequently, the immune system in human milk provided by evolution is much of the basis for encouraging breastfeeding for human infants.

The response to treatment was the diagnostic mainstay in ancient times when diseases were poorly understood. Now that the bases of most diseases are known, appropriate diagnostic means are available. However, many physicians still rely on therapeutic tests to establish diagnoses. Since most illnesses are self-limited and because of the placebo effect, many physicians and patients attribute the improvement to (he medication and believe that the correct diagnosis was made. However, inappropriate therapeutic tests often lead to diagnostic delays. rapid emergence of antibiotic-resistant bacterial pathogens, increased risks of adverse drug reactions, and unnecessary expenses. To reduce the frequency of unwarranted therapeutic tests, health-care professionals and educators must take steps to rectify the problem.

The science of immunology emerged in the last of the 19th and the first of the 20th century. Substantial progress in physics, chemistry and microbiology was essential for its development. Indeed, microorganisms became one of the principal investigative tools of the major founders of that science – Louis Pasteur, Robert Koch, Ilya Ilich Metchnikoff, Paul Ehrlich and Jules Bordet. It is pertinent that these pioneering scientists were born when questioning and exploration were encouraged because of the legacies of the previous century of enlightenment. Mentors greatly aided their development. Their discoveries were shaped by their individual personalities. In turn they developed other contributors to the nascent field. Their discoveries included the types of leukocytes, the roles of neutrophils in inflammation and defence, cellular lysis due to complement, the principles of humoral and cellular immunology, passive and active immunization, tissue antigens, anaphylaxis, anaphylactoid reactions and autoimmunity. Their work formed the basis of modern immunology that developed many decades later. Immunology has enormously impacted our understanding of the pathogenesis, diagnosis and treatment of infections, immune-mediated disorders and inflammation. Burgeoning advances forecast further important clinical applications of immunology. Yet, their applications will be problematic because few physicians sufficiently understand the science. We propose that understanding modern immunology requires a grasp of how that science developed – who made the discoveries, how they were made, their successes and failures, their interactions and debates all reveal the foundation of modern immunology.

Jules Bordet, a pioneering immunologist, lived until the dawn of molecular immunology. He was born in Belgium in 1870, obtained a medical degree in 1892, worked at l'Institut Pasteur in Paris from 1894 to 1901 and then established the Pasteur Institute of Brabant in Brussels. Before World War I, Bordet found that complement binds to antibody-antigen complexes regardless of the antigen or antibodies involved. Subsequently he developed the complement fixation test that was of diagnostic importance for several decades. For his research concerning complement he was awarded the 1919 Nobel Prize in Physiology or Medicine. During that period he also discovered anaphylatoxin, conglutinin, and the cause of whooping cough ( Bordetella pertussis). After World War I he found how thrombin forms, how platelets participate in clotting, lysozyme in human milk and much of the biology of bacteriophages. In addition, Bordet worked fervently to limit weapons of mass destruction and promote peace until his death in 1961.