Review lecture. Immunosuppressive agents, with special reference to antilymphocytic serum.

1. I n t r o d u c t i o n ‘Immunosuppressive agents’ are precisely what their name implies: agents tha t weaken or abolish the immunological response. The term itself promises more than any agent has in fact achieved. Strictly speaking, an immunosuppressive drug or treatm ent should be one th a t inhibits the immune response and no other. A central theme of this lecture is tha t only antilymphocytic serum (hereafter ALS) comes anywhere near fulfilling the requirements of this definition. The immuno­ suppressive action of all other agents in common use is a byproduct of some much more general toxic or inhibitory influence which happens to affect, amongst many others, the cells th a t transact the immunological response. For this reason immunosuppressive agents have not yet begun to do for immunology what specific metabolic inhibitors have done for the analysis of cellular metabolism to resolve a complex biological performance into separate episodes or cellular events. Our knowledge of how they work is purely empirical; it has been pieced together from the evidence of practical experience, rather than founded on a prior theoretical understanding of how they work. Immunosuppressive agents owe their importance to the sheer pressure of medical necessity. Diseases or disabilities tha t are due to immunological failure or insufficiency—-e.g. to a congenital insufficiency of blood proteins of the class to which antibodies belong—are less common and less perplexing than those which can be attributed to a miscarriage or abnormal manifestation of the immunological response. Hay fever, asthma, urticaria and the allergies generally, including drug and bacterial allergies; anaphylaxis and serum sickness; haemolytic disease of the newborn; blood transfusion incompatibilities and tha t rather different form of incompatibility which prohibits the grafting of tissues from one individual to another; the so-called ‘auto-immune’ diseases, whether primary or secondary, including auto-immune thyroiditis and some of the so-called collagen diseases all these are, to a greater or lesser degree, miscarriages or misadventures of the immunological response. There can therefore be no question of the strength of the practical incentive to bringing the immunological response under control.