s p e c i a l f e a t u r e – h i s t o r y o f n e u r o l o g y Hansen’s bacillus mice developed the disease. Koch announced in 1876 that he had proved this bacterium JMS Pearce MD, FRCP caused anthrax. He went on to identify the Emeritus Consultant Neurologist, Department of Neurology, Hull Royal Infirmary, UK. bacterial causes of tuberculosis (1882), and cholera(1883). Correspondence to: Gerhard Armauer Hansen (1841-1912) J.M.S. Pearce, 304 Beverley Road Anlaby, East Yorks, HU10 7BG, UK. worked at St. Jørgen’s hospital in Bergen, Email: [email protected] striving to find the cause of leprosy. Importantly, Hansen’s identification of M. leprae preceded Conflict of Interest statement: None declared. Koch’s seminal investigations.5 Leprosy is a Date first submitted: 23/1/18 chronic mycobacterial infection that affected Acceptance date: 4/2/18 millions of people, mainly in Brazil, India, and To cite: Pearce JMS, ACNR 2018;17(4);16-18 Indonesia. The Tuberculoid or paucibacillary type shows well-expressed cell-mediated immunity that controls bacillary multiplication by forming Figure 2: Gerhard Armauer Hansen. 1900s Abstract epithelioid-cell granulomas. The lepromatous (Photo by Mondadori Portfolio via Getty Images) Because of its gradually declining incidence or multibacillary type shows cellular anergy many UK physicians rarely encounter leprosy towards M. leprae, thus profuse bacillary Hansen also observed visual impairment which is thus easily overlooked. Hansen’s multiplication. Between these is a continuum, or blindness now known to result either from discovery of mycobacterium leprae, the first varying from borderline tuberculoid, through mycobacterial infiltration of the anterior identified human bacterial infection, was borderline, to those with little cellular response, segment of the eye, or from trophic changes of crucial importance. He struggled to find borderline lepromatous. caused by damage to trigeminal and facial acceptance, and arguments about priority of his nerves, resulting in lagophthalmos, deformed discovery were rife until his vital role was estab- Clinical Features eyelids or corneal anaesthesia. lished in the Leprosy congress in Berlin in 1897. Hansen had observed varied clinical features. Typically there was a variety of skin lesions: Hansen’s bacillus eprosy was the first proven instance of a large single well-defined red patch or asym- Hansen was born to a Danish family the eighth a bacterial infection causing a human metrical hypo-pigmented macules, plaques, of 15 children, at Bergen on July 29, 1841. His Ldisease. Its importance cannot be over- and nodules, often thickening of the forehead father Claus was a merchant who after a crisis emphasised, because it was the first direct and earlobes, loss of eyebrows, deformity of went bankrupt. His memoirs show details of evidence of the causal role of microorganisms the nose and loss of the upper incisor teeth. his childhood and professional life.6 He studied predicted but not proved by the Germ theory Neuropathy was accompanied by sensory loss Medicine at the University of Christiania (now of the 1800s that stated many diseases are and tender, thickened peripheral nerves. It Oslo), qualifying in 1866. In 1870, he went caused by the presence and actions of specific could resolve spontaneously or progress to to Bonn and Vienna to study histopathology. microorganisms. Germ Theory superseded borderline or lepromatous leprosy with hideous Returning to Bergen in 1868, he was appointed existing theories of disease: divine superstitions, deformities. assistant physician to the distinguished Daniel miasma and contagion, and thereby revolu- Cornelius Danielssen (1815-1894) at St. Jørgen’s tionised the practice of Medicine. The global hospital for lepers. He searched for the aetiology Figure 1: Patient (‘elephantiasis’) at St Jørgen’s hospital. prevalence has decreased from approximately (Photo MHSB02924: Lepramuseet St. Jørgens hospital). of leprosy, in blood, then in leprous tissues. It 600, 000 cases in 2001 to <200,000 in 2015,1 but was here that Hansen discovered the causative under-reporting is likely. It remains a worldwide agent of leprosy, M. lepra, in 1873.7,8,9 This was scourge.2 three years before Koch identified the anthrax The existence of ‘germs’, ‘microbes’, or bacillus and nine years before he showed that ‘microorganisms’ however, had preceded Germ tubercle bacillus caused human tuberculosis. Theory, for in 1676-7, using his first micro- The prevalence of leprosy in Bergen was scope, Antonie van Leeuwenhoek (1632–1723) high, estimated at c. 25 per 1,000 population. of Delft, observed tiny organisms — which he With Carl Wilhelm Boëck (1808-1875) of Oslo, called ‘animalcules’ — but he did not relate Danielssen had pioneered the scientific study them to disease. It was Louis Pasteur (1822-95) of leprosy.10 St. Jørgen’s hospital was estab- and Robert Koch (1843-1910) who showed that lished in the 14th-century and became a famous microbes caused infectious diseases. Pasteur leprosy research centre. Danielssen believed showed in 1863 that microorganisms caused leprosy was hereditary, but Hansen suspected fermentation of milk and grapes, and the putre- it was infectious. faction of meat. He therefore suggested human Having observed yellowish granular masses disease was caused by the multiplication of in leprous tissues in 1869, in 1873 he discovered germs in the body.3 the rod shaped bodies that looked like bacteria Koch proved that Bacillus anthracis that he in ‘lepromata’, later identified as M. Leprae. observed in the tissue of anthrax victims was ‘Danielssen at first disputed Hansen’s evidence the cause of anthrax4 and crucially was trans- of an infectious cause. Hansen read a paper missible. He extracted this bacterium from a in 1874 to the Medical Society of Christiania, sheep which had died of anthrax, then repeat- claiming these bodies were the cause of edly injected generations of mice with it; the leprosy. It was published in the Norsk Magazin 16 > ACNR > VOLUME 17 NUMBER 2 > NOVEMBER-JANUARY 2018 s p e c i a l f e a t u r e – h i s t o r y o f n e u r o l o g y for Laegevid–enskaben, as an 88-page mono- Although Hansen had described acid, alcohol Grecorum, which in turn replaced the Greek graph in 1874. However, written in Norwegian, resistant bacilli in leprous lesions, he struggled lepra taken from the biblical word tsara’ath. its readership was limited and failed to excite in vain to culture M. Leprae or to satisfy Koch’s It was often mistranslated as leprosy, though interest in the medical world. We can recognise postulates*. Frustrated, in 1879, he inoculated literally it signified any disease with a scaly his scientific caution, for at first he was uncer- the eye of a woman with material drawn from skin, such as psoriasis, scabies, and syphilis. tain whether these rod-shaped bodies were a leprous nodule. But because he had failed Before Hansen’s discovery, Robley Dunglison, bacteria, perhaps because he failed to culture to obtain informed consent Hansen was found personal physician to Thomas Jefferson, or stain them adequately: guilty of unethical conduct when tried at Court showed the bewildering variety of names in in Bergen. He lost his position as physician of his textbook, The Practice of Medicine:18 There are to be found in every leprous the Bergen hospitals, but retained his job as II ELEPHANTIASIS GRECORUM tubercle extirpated from a living indi- leprosy medical officer for the entire country SYNON. Lepra tuberculosa, L.Aegyptiaes, vidual — and I have examined a great of Norway. Henry Vandyke Carter (a major L. Alba, L. Hebaeorum, L. leon-tina, number of them — small staff-like contributor to Gray’s Anatomy, and leprolo- L. Mosaica, Tsarath of Moses, Leontiasis, bodies, much resembling bacteria, lying gist in India) visited Hansen’s laboratory and Satyriasis, Lepra, Leuce, Mor-phaea alba, within the cells; not in all, but in many vigorously supported him and his conclusions Baras, Vitiligo; Fr. Lèpre tuberculeuse, of them. Though unable to discover that leprosy was due to an infectious bacillus, Elèphantiasis des Grecs, Ladrerie, Tete de any difference between these bodies in his article On leprosy and elephantiasis. veau, Mal rouge de Cayenne; Ger. Weisse and true bacteria, I will not venture to (London: Eyre and Spottiswoode,1874). At a oder Mosaiche Aussatz, Knolligre Aussatz. declare them to be actually identical. Leprosy congress in Berlin (1897) Hansen was In the bible, Lepers were ‘unclean’ and Further, while it seems evident that finally recognised17 as the discoverer of the isolated from the community. Their plight is these low forms of organic life [i.e., lepra bacilli, the cause of leprosy. Leprosy is shown in Leviticus (13.2): bacteria] engender some of the most often named ‘Hansen’s disease.’ acute infectious diseases, the attributing When a man has on the skin of his body of the origin of such a chronic disease a swelling or a scab or a bright spot, and as leprosy to the apparently same it becomes an infection of leprosy on matter must, of course, be attended the skin of his body, then he shall be with still greater doubts. It is worthy of brought to Aaron the priest or to one notice, however, that the large brown of his sons the priests. … All the days elements found in all leprous prolif- wherein the plague shall be in him he erations in advanced stages … bear a shall be defiled; he is unclean: he shall striking likeness to bacteria in certain dwell alone; without the camp shall his stages of development…”11 habitation be. And in Matthew (8:3): But after consulting Robert Koch, he improved his techniques and in 1880 did stain the bacilli.