86 NATURE 

of the past half-century? I need not discuss the 
various doctrines and conceptions of inflammation that 
formed the basis of pathological teaching of possibly 
most of us, but it is very obyious from even cursory 
analysis of the works of the great masters that the 
phenomena of inflammation gradually but surely came 
to be regarded in the light of natural defence mechan- 
isms. That this was so is abundantly evident at the 
commencement of the present century, and in illustration 
I might cite the inaugural address of Marchand, a 
valued teacher of my own, on assuming the chair of 
Cohnheim at Leipzig in 1900. ‘The title of his address 
was “ Die natiirlichen Schutzmittel des Organismus,”’ 
and it was an attempt*to summarise in the sense of 
defence mechanisms the various changes produced in 
the course of the inflammatory process. These changes 
he regarded as essentially defence mechanisms depending 
on the reactivity of the local tissues. 
On the whole I receive the impression from reading 
the works of these masters that their methods of work 
were too local and circumscribed to render the results 
capable of general applicability to the phenomena of 
bacterial invasion. They had little conception then 
of the vast potentialities for defence residing not only 
in the fluids circulating in the inflamed part but also 
in the emigrated leucocytes and possibly also in the 
fixed tissue cells. Since those days the immunologist 
has had his innings, but I am of opinion that again 
we shall return to the consideration on ampler lines of 
local condition and function in the widest sense if we 
are to understand thoroughly the rationale of natural 
immunity. Already one sees a tendency towards the 
combined histological and serological attack on these 
problems. 
I pass to Metchnikoff, whose attempt to extend the 
sphere of phagocytic action from the physiological to 
the pathological field, and to read into it the idea of a 
protective mechanism with an application to all higher 
animals possessing circulating amceboid elements, 
constituted the first large-scale conception calculated 
to raise the lore of inflammation from one of purely 
local to one of the most general application. It was, 
in fact, the commencement of immunity as a general 
science. To him the leucocyte came to be endowed 
with particular qualities and properties according to 
the reactivity of the host. It was, moreover, the source 
par excellence of any and all bactericidal substances 
that might be present in cell-free fluids of the body. 
The constant polemics into which his rigid adherence 
to the conception of the all-sufficiency of the phagocyte 
led him are now matters of history, but it has to be 
remembered that these very polemics with the rising 
school of humoralists led by Nuttall, Buchner, and a host 
of others, gave the stimulus to uncounted researches 
on the properties and sources of growth-inhibitory and 
bactericidal bodies in tissues and fluids. Metchnikoff 
sought to retrieve the position of the phagocyte by 
many ingeniously contrived experiments, but it was 
obvious that opinion was definitely ranged alongside 
the newer humoral ideas, while the ultimate source 
of the alexin and the intermediary body or substance 
sensibilisatrice, the co-operative action of which with 
a thermolabile alexin was later demonstrated, were left 
more or less open questions. The final demonstration 
by Denys and Leclef, Mennes, and others, showing the 
NO. 2777, VOL. IIT | 
[JANUARY 20, 1923 
dependence of phagocytic action in immune serum on 
the presence of a substance sensibilisatrice, and the ex- 
tension of the principle to normal serum by Wright and 
Douglas, constituted a reasonable enough compromise 
between the opposing views. We know, however, that 
absolutely independent phagocytic action cannot be 
excluded as a defence factor, especially when organisms 
of low virulence are in question, and researches on 
spontaneous phagocytosis have demonstrated that in 
a given collection of leucocytes exposed to organisms 
some individuals undoubtedly appear to possess much 
higher phagocytic powers than others. We have not 
reached the end of this particular problem. 
After the phagocyte came the alexin of the cell-free 
fluids. The complex nature of the normal alexin and 
its presence both in plasma and in cell-free serum are 
now fairly generally accepted facts. It should be noted, 
however, that the complex nature of the normal alexin 
is much more difficult to demonstrate than that of the 
so-called bacteriolysin in immune serum, and, as we 
shall see, there is now evidence that certain normal sera 
possess considerable bactericidal and growth-inhibitory 
effects which are not destroyed by the usual inactivation 
temperatures. In fact, the test-organism in all these 
matters is of prime importance. Here it is sufficient 
to note that the normal alexin can kill or dissolve 
certain organisms while others are unaffected or at 
most suffer growth inhibition. 
I pass to the leukins or the bactericidal substances 
present in extracts of leucocytes. The study of these 
arose largely out of the views expressed by Buchner 
and Metchnikoff that the source of the alexin might 
possibly be found in such. The chief work on this 
defence mechanism, which has not attracted perhaps 
the attention it deserves, has been that of Hahn, 
Schattenfroh, Petterson, Kling, Manwaring, Schneider, 
and Petrie. I would note simply that these extracts do 
not lose their power of killing certain test organisms 
after heating, say, at 60° F. They can resist very 
much higher temperatures, even up to 80° F. The 
constitution of these leukins or endolysins is still un- 
certain. Some have attempted to show that they possess 
complementing powers in the presence of inactivated 
sera, but others have entirely failed to confirm such 
action. Petterson would say that these extracts contain 
both an alcohol-soluble and an alcohol-insoluble fraction, 
and that the one can inhibit the action of the other. 
These effects, however, are almost certainly to be 
reckoned in the category of inhibition phenomena ex- 
plicable on colloidal principles. The chief interest of 
the leukins lies in the effects they produce on different — 
groups of organisms, and in the similarity of such 
effects to those produced by very analogous extracts 
prepared from tissues, which were demonstrated twenty — 
years ago by Conradi, Korschun and Morgenroth, 
Tarassewitsch, and others. These leukins have, as a 
rule, been tested against organisms of the typhoid-coli 
group and organisms of the subtilis group, to which 
anthrax belongs. 
Curious differences have been shown by extracts of — 
leucocytes of various animal species in their action on 
bacterial types. Thus guinea-pig leucocytic extracts 
are said to possess little or no bactericidal action on 
B. typhosus, while those from the rabbit are distinctly 
potent. Petrie, however, using extracts prepared from 

