influenza (Pfeiffer) was the cause of the disease. The year 1920 found expert opinion sharply divided into two schools, one up- holding the etiological significance of Pfeiffer's bacillus, the other maintaining that the evidence pointed rather to an invisible " filter-passing " virus as the causative agent. This question is ably discussed by Sir Frederick Andrewes, F.R.S., in the Report of the British Ministry of Health (1920) above referred to.
Recent research has proved that there are several serologically distinct organisms included under the heading of Bacillus influence and that these vary in virulence for experimental animals. It seems beyond question that pathological changes resembling those of hu- man influenza may be produced by the inoculation of "some of these strains. The same, however, can be claimed for filtrates of body fluids, exudates and secretions from human influenza cases, and also for " Nogouchi " cultures from these. The liability of laboratory animals to lung injuries during experimental manipulation intro- duces a source of error that is very difficult to exclude, and that is equally operative in experiments with Pfeiffer's bacillus and with " filtrates." No final answer can be hoped for until a future outbreak finds us prepared to start our investigations before the crest of the wave, though much spade-work can and should be done in non- epidemic periods to narrow down the field of inquiry. One thing is certain: that, with adequate technique, Pfeiffer's bacillus can be isolated from almost every case of influenza. A r61e of vast impor- tance in the production or accentuation of pulmonary complications is played by " secondary invaders," the bacterial flora of the normal respiratory tract, a potentially pathogenic group well calculated to exploit the tissue injuries induced by the influenzal virus. These bacteria were found to vary in different areas ; but certain of them, notably the streptococcus mucosus, the streptococcus hcemolyticus, the pneumococcus and the staphylococcus, were almost universal. Rarer types were mcningococci, pneumo-bacilli, pyocyaneus and others. The vast numbers of these organisms that sometimes invaded the injured lung tissues must be seen to be believed. It was common to find them in the blood-stream as " terminal infections " and they were cultivable from the heart-blood after death.
Epidemiology. In the absence of final knowledge as to the causative agent, many points of fundamental importance still remain obscure. Was the pandemic of 1918-9 a sudden awakening to virulence of some germ already widely distributed in western Europe or was it a " new arrival " operating in " virgin soil "? In spite of the weighty arguments for the former view set forth in the Report of the Ministry of Health, we incline to the latter. But the Question arises: " Where could such a germ come from?" It seems justifiable to assume that previous pandemics were due to the same agent. No doubt, somewhere, from one pandemic to another, some human individual or chain of individuals carries on the virus until the time shall be ripe for a fresh outbreak.
It is to be noted that the first wave coincided with the arrival of the first large drafts of American troops in Europe. These young contingents, gathered from the remotest ends of a vast continent, meeting for the first time with the dwellers of far cities or countries, each group harmlessly infested with its familiar bacterial commensals but unprotected against those carried by its new neighbours, these freshly improvised troops must have brought into common circula- tion pathogenic strains that had long remained dormant in isolated and relatively immunized communities. The crowded troopships afforded just the incubation places that would permit of the matura- tion of such an infection ; and Europe, with its crowded concentra- tion areas and billets offered an unequalled opportunity for its spread. The last influenzal pandemic had occurred just 28 years before. There might be a few scattered " carriers " and perhaps some residual immunity among the middle-aged and the elderly; but the adolescents and the young adults would, in 1918, be " virgin soil." It was just these lower age-groups that suffered most.
How, then, explain the second wave with its greater severity? and the third ? Surely, if immunity played a part, these waves would have been much less extensive, much more benign, and con- fined to those persons who had previously escaped. These are good, but not final, arguments. It is at least possible that the pas- sage of the first wave might leave behind it a virus of exalted viru- lence, many " carriers " and many " allergic " subjects whose behaviour to reinfection might betray the phenomena of hyper- sensitiveness of the respiratory surfaces and a tendency to inflam- matory exudates on contact with the air-borne virus. Under such conditions a fresh outbreak would be specially likely to arise in the fall of the year, a period of rapid fluctuations of temperature when the chill evenings drive men into the warmth and close contact of crowded dug-outs, shelters and billets.
Such a theory, while presenting many difficulties, has many points in its favour as well. We find it impossible to believe that the so- called " influenza " to which deaths were attributed every year between 1892 and 1918 was the same disease as the fulminating pandemic that followed. Apart from the extreme contrast in in-
vasive power, a glance at the diagrams of Dr. T. H. C. Stevenson, illustrating the distribution of " influenza " mortality by age- groups (Proceedings of the Royal Society of Medicine, Jan. 1919), will suffice to emphasize the essential differences between, let us say, the graphs for 1917 and 1918, the one showing a preponderating death-rate amongst the old, the other, amongst the young. Such differences can hardly leap into existence within a few months. The known facts of increase and diminution of bacterial virulence lend no support to the idea that such a vast alteration is probable or even possible in so short a time.
Acquired Immunity. Many observers have brought forward evidence indicating that morbidity and mortality were less marked, in the second wave, amongst those who had been attacked in the first. The evidence bearing upon this point has been thoroughly ana- lyzed in the Report of the Ministry of Health, chap. vi. (1918- 9). After a careful examination of the facts and figures at their disposal, the authors state that " these data show a considerable immunizing power in the summer attacks and we conclude, although with natural hesitation, that it is probable, on the average, that an appreciable degree of active immunity was attained by those who passed through an attack in its first and mildest manifestations." This is not a very positive expression of opinion but all who study the figures will agree that the authors show a wise reticence. The evidences for immunity are of varying efficiency in different places, and the populations of many areas show no tendency at all to acquired resistance to infection as judged by a comparison be- tween the behaviour of those attacked and those missed by the first wave when confronted by the second.
We believe these data to be unsound as a basis for comparison. It is highly probable that many persons were infected during the summer and yet failed to show appreciable illness. The vast dif- ference that may exist between the numbers infected and the num- bers affected by a bacterial invasion can be judged from what we know of the mentngococcus and the diphtheria bacillus. And yet these non-pathogenic infections may confer active immunity as we know from the " Schick Reaction " in the case of diphtheria and from many other examples as well. It is very likely that the mere fact of a pre- vious " attack " is a fallacious guide in classifying populations for inquiry as to their relative immunities. After all, the best evidence of the acquisition of immunity is to be found in the phenomena of natural recovery of the individual and of the disappearance of pandemic waves from the community. The fact that these groups of pandemics are separated by long and fairly regular intervals, as a rule about 20 years, is not without significance in this connexion, since at least this period might be necessary to reduce the residual immunity from the last pandemic to an ineffective level.
Artificial Immunity. No vaccine can be entirely satisfactory unless it is known to contain the virus or germ of the disease in ques- tion. The vaccine issued by the War Office and afterwards by the Ministry of Health was confessedly of a provisional nature since the causative agent was still uncertain. Its formula was as follows :
Per cub. cm. of vaccine
Bacilli influenzas (Pfeiffer) 400,000,000
Pneumococci 200,000,000
Streptococci 60,000,000
Unless Pfeiffer's bacillus be accepted as the causative agent, this vaccine must be described as consisting entirely of the " secondary invaders." As such, its issue was entirely justifiable and its effects were such as might be expected : satisfactory in diminishing compli- cations and mortality but practically nil in preventing the disease. Vaccine, then, cannot, as a prophylactic, help us much at present ; nor can we, in the light of recent experience, hope for great results from general measures of hygiene. We have just passed through " one of the great sicknesses of history, a plague which within a few months has destroyed more lives than were directly sacrificed in four years of a destructive war." Lacking exact knowledge, we are vulnerable, and our watchword must be "Research." (S. L. C.)
INGE, WILLIAM RALPH (1860- ), British divine, was born June 6 1860 at Crayke, Yorks., the son of William Inge, sometime provost of Worcester College, Oxford. He was educated at Eton, and at King's College, Cambridge, and won numerous honours and prizes during his university career. From 1884 to 1888 he held an undermastership at Eton, and during the last two years of that time was fellow of King's College, Cambridge. From 1889 to 1904 he was fellow of Hertford College, Oxford, Bampton lecturer in 1889, and Paddock lecturer in New York in 1906. From 1905 to 1907 he was vicar of All Saints', Ennismore Gardens, until his appointment as Lady Margaret professor of divinity at Cambridge. In 1911 he became dean of St. Paul's, where his sermons attracted great attention owing to their original power, their caustic criticism of the tendencies of modern life, and a somewhat pessimistic tone which earned for him the sobriquet of " the gloomy dean."
Among his numerous historical and theological works may be mentioned Society in Rome under the Caesars (1886); Christian
