A critical consideration of some immunological problems with special reference to diphtheria

Abstract

I N this Address I hope to provide a reply to a question which was recently put to me by a colleague who said: " Do you still believe in the work you are doing with sera?" My questioner was clearly very sceptical of the value of serology as applied in practice, and the scepticism is one which is shared by many members of the profession. Opposed to it is the blind faith with which the value of immunological products, whether in the sphere of passive or active immunity, is accepted by so many others. Their most active protagonists will ask you to accept without question what they choose to tell you concerning them, and it will be my endeavour to analyse impartially some of the evidence on which their boldest assertions rest. I shall confine myself largely to consideration of what we know about diphtheria not alone because of the importance of this disease but because the value of immunological products for the treatment and prophylaxis of human disease is most usually assessed by the results which have been obtained with diphtheria antitoxin and diphtheria prophylactics. Let us first consider the evidence on which claims are based for the use of diphtheria antitoxin in the treatment of diphtheria. There are only two experiments on the clinical use of diphtheria antitoxin which would be capable of providing first class evidence of its therapeutic value. Of these the experiment performed at the Blegdams Hospital in Copenhagen by Fibiger (1898) is regarded by some as the most complete of its kind. His method was to treat all cases without selection a.dmitted on one day with antitoxin and the next day without antitoxin, alternating in this manner for a period of one year. In all, 484 cases were recorded, 239 with antitoxin and 245 without. Of the 245 untreated, 30 died, giving a case mortality or fatali ty rate of 12.2 per cent. Against this, 8 deaths among the 239 in the treated group gave a fatality rate of 3.3 per cent., a notable reduction. But in the light of modern experience Fibiger's results are much less convincing. He was dealing with a type of diphtheria in which the fatality-rate was only 12.2 per cent. in the untreated cases, a diphtheria of such mild character that its fatality-rate without specific treatment is already as low as the rate found to-day in many areas in which specific treatment is employed in conjunction with the chemica! and mechanical aids to therapy which have been developed since his time. This is illustrated in