T. B. Wallington

DEVELOPMENTS IN IMMUNOLOGY SINCE JENNER AND PLANS FOR THE IMMUNOLOGY EXHIBITION

T.B. WALLINGTON B.A., F.R.C.P Immunologist, Member Jenner Educational Trust.

IMMUNITY EXPLAINED

Hippocrates noted that those who had recovered from plague were used to nurse its victims. Variolation, the deliberate infection of children with smallpox in the hope that they would avoid a more severe attack later in life, was well established medical practice in the eighteenth century. Dr Edward Jenner was the first clinical scientist to design an experiment to demonstrate the phenomenon of acquired immunity when in 1796 he inoculated James Phipps with serum from a cowpox pustule on Sarah Nelmes’ finger and later challenged the boy’s immunity with smallpox virus. Pasteur immortalised its importance in 1880. With the insight of the knowledge of the germ theory of infection he realised the principle of specific immunization using attenuated bacteria and viruses and named the procedure vaccinationin honour of Jenner’s discovery. Pasteur and those who followed him are the harvest of the seed, and the question posed to biological science by Jenner’s experiment: how is specific immunity to smallpox achieved? It is still producing fruit and now we know a great deal more about the working of the human immune system and can understand why Jenner’s experiment was successful. We hope that Jenner’s contribution to medical science, which is celebrated in the Jenner Museum, will be bought into even sharper focus in the museum with its displays linking it to modern immunology. I will outline our plans to achieve this in a hands-on exhibition of modern immunology which we hope will be opened for the bicentennial of vaccination itself in May 1996. The short title of the exhibition is "Immunity Explained". The project is co-ordinated by the Management Committee of the Museum and the British Society for Immunology who have recruited a team of immunologists willing to take the project forward. The exhibition will illustrate the structure and working of the immune system through displays

dealing with various states of health and disease. From these will come an understanding of how and why Jenner succeeded in vaccinating against smallpox. The link will be made by illustrating certain of the major discoveries of immunology in a section of the exhibition entitled the History of Immunology. Our plan is probably best illustrated by outlining our ideas for each module of the exhibition.

HISTORY OF IMMUNOLOGY Like other sciences, immunology has been through periods of frenzied activity and new discovery and quieter phases seemingly in the intellectual doldrums. Its development so far can reasonably be divided into three eras. The first was the realisation of immunity which started with Louis Pasteur and the germ theory in 1880 after quite a long period of seeming inactivity following Jenner’s discovery. Pasteur first discovered the principle of attenuation in experiments with chicken cholera and his rabies vaccine was the first deliberately attenuated vaccine used in humans. Pasteur understood the principle of immunity but not its mechanism. He thought infection deprived the infected person of essential nutriments, spoiling them as the seat for a further infection. It required the work of Roux, Yersin, von Behring and Kitatsato on bacterial toxins and the precipitating substances found in the sera of immune animals for immunity to be linked to the production of antibodies. At the same time the rôle for phagocytic cells in the immune response was described by Metchnikoff (1884), whilst the work of Koch (1891) on immunity to tuberculosis laid the foundation of the present understanding of specific cell mediated immunity. All of these discoveries were made in the latter half of the nineteenth century and immunology then moved into the relative doldrums. The next important era might be described as the era of immunobiology starting in 1937 with the discovery of the histocompatibility complex by Gorer and then quickly in 1939 with the discovery that antibodies are globulins and the beginnings of the understanding of their chemistry. In 1944 Medawar put transplantation immunology on the scientific map. In 1953 the phenomenon of immunological tolerance was described by Billingham, Brent and Medawar. Discoveries starting in 1956 with Glick’s work on the bursa of Fabricius defined lymphocytes as the cells responsible for the immune response and divided them into sets and subsets with specific functions in immunity. The present era is of course that of the molecular biochemist and rapidly we are learning just how all of those phenomena work. By picking from these landmark discoveries we hope to draw a map for

people visiting the exhibition which will link Jenner to the immunologists that followed him.

THE IMMUNE SYSTEM What is our present understanding? We will describe the cells, tissues and molecules that comprise the immune system. Such a display provides great possibilities for brilliant visual material. We hope that we will be able to use interactive computer technology with great effect. Such a display could be quite extensive with separate sections covering modern knowledge of antibodies, phagocytes, interleukins, and of course other topics.

They will be picked to link in with the pointers that history has given us.

WHAT IMMUNITY DOES In the context of Jenner it is important to tackle the topic of immunity to infection. Here inherited, developmental and acquired abnormalities that lead to immunodeficiency diseases can be illustrated powerfully to show in human terms why the immune system is so important. The effects of HIV are but one area of pressing interest here.

ALLERGIES This, like HIV, is viewed as a good point of contact and understanding with the general public. Almost everyone knows about hay fever and recognises it as an allergy. A suitable museum display could be a way for raising several interesting issues, in particular the distinction between harmful and protective immunity and the idea of malfunction causing disease: immunopathology.

ARTHRITIS This also is of course part of the common experience. Much arthritis is auto immune, the result of a fault in the immune system. We now know a lot about the mechanisms of auto-immune disease, but much is still to be considered. This is an area of very active medical research within immunology with great promise for the control of disease which we are sure will interest visitors to the Museum.

TRANSPLANTATION A grand example of how animal experimentation aided human medicine is through the discovery of histocom- patibility genes/antigens and immunosuppressive drugs. These discoveries can be linked to what has

been achieved in kidney, liver, heart, corneal and bone marrow transplantation.

OVERALL INTENT OF THE EXHIBITION This could be a very big exhibition indeed. We have the concept that we may have a core of exhibits to which rotating displays are added from time to time. If these are of sufficiently high quality then other museums we are sure will be interested in using them. Interest has already been expressed. I hope that in this short outline of our plans I will have interested you in this endeavour. I hope also that you will consider it an appropriate part of our efforts to mark the bicentennial of Jenner’s discovery of vaccination.

REFERENCES

Baxby, D., Paoletti, E. (1992) Potential use of non-replicating vectors as recombinant vaccines, Vaccine 10: 8-9.

Baxby D. (1993) Recombinant poxvirus vaccines, Reviews in Medical Microbiology4: 80-88.

Baxby D. (1982) The natural history of cowpox, Bristol Med. Chir. J.,97: 12-16.

Baxby D. (1981) Jenner’s Smallpox Vaccine, The Riddle of Vaccinia virus and its Origin,214pp., London: Heinemann.

Lakhani S. (1992) Early Clinical Pathologists: Edward Jenner (1749-1829), J. Clin. Path.45: 756-758.

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Morris, S. (1992) Edward Jenner,48pp., New York: Bookwright Press.

Fisher, R. B., (1991) Edward Jenner,361pp., London: A. Deutsch.

Perry, C. B., (1993) Edward Jenner,23pp Bristol: University Press.