IMMUNITY AND CURATIVE INOCULATIONS
During the last twenty years the whole attitude of the study and
investigation of disease-causing microbes has advanced from the
preliminary step of merely identifying certain microbes as the causes
of certain diseases to a further step, viz. that of attempting to
defend the animal and the human body against their attacks in the
manner already so finely started by Pasteur. For many years disease
after disease was examined and found to be caused by special bacteria
or other microbes. Even non-infectious diseases or diseases only
communicable under very special conditions were found to be due to
microbes, so that it is probable that all disease that is not due to
congenital malformation or to mechanical injury, or to poison
fabricated in the weapons of larger animals and plants, or by man
himself, is due to microbes. "Life," says Lord Justice Moulton, "is
one ceaseless war against these enemies, and the periods of our
too-transient successes are known as health." One of the last diseases
traced to microbes is that sad condition known as "infantile
paralysis," by which so many of the brightest and best members of the
community have been crippled, from childhood onwards, through life.
Of late we have been making rapid strides in arriving at a knowledge
as to how Nature herself protects higher creatures from the excesses
and exuberance of destructive microbes, and we are now able to see
that it is in adopting her methods that our best hope of increasing
that protection lies. Nature is satisfied if the efficacy of her
defence is sufficient to save enough individuals to carry on the race.
Man desires in the case of his own fellows to out-do Nature and to
save all.
A century and a half ago, before the true character of infective
disease was understood, it was observed that an individual who was
attacked by the smallpox and recovered became incapable of receiving
the infection again. He was "protected" or "immune." The practice of
"inoculation" was introduced from the East by Lady Montague. The
infectious matter was introduced from a smallpox patient into the
person to be protected by rubbing it into a scarified part of the
skin. A much less severe attack of smallpox was thus produced than
that which usually followed the natural infection, which (though we do
not know precisely its mode of entrance) is more widely spread through
the blood. At the same time the condition of "immunity" after the
attack was brought about with equal efficacy. When Jenner introduced
inoculation with "cowpox" for the purpose of establishing "immunity"
in the vaccinated person, inoculation with smallpox itself was a very
usual practice. It was open to the objection that sometimes an
unexpectedly violent attack of the disease was produced, resulting in
death, and that the active infection was kept alive and ever present
in the community. The notion with regard to the mode in which
"immunity" was produced by either the Montacutian or Jennerian
inoculation was, even after the general knowledge of microbes as the
living contagion of disease had been arrived at, that the mild attack
due to inoculation "used up" something in the blood--in fact,
exhausted the soil, so that the infective matter or microbe could no
longer flourish in the blood. And this view was accepted as the
explanation of the "immunity" to the anthrax disease conferred on
cattle and sheep by Pasteur's inoculations of weakened, but still
actively growing, cultures of the anthrax bacillus. Another theory was
that they produced something in the blood by their own life-processes
which checked their further growth, just as yeast will not grow in
wort in which it has produced 8 per cent. of alcohol, and as a fire
may be choked by its own smoke or ashes.
We now know that both these explanations of "immunity" are incorrect.
Nature provides at least three varieties of defence within the blood
of higher animals against disease-producing microbes which have broken
through the outer line of fortification, the skin. These three methods
are effective in different cases (one in this disease, the other in
that), and, on the whole, are sufficient to preserve the races of
animals (including man) from complete destruction. These are (1) the
production in the blood of an antidote to the toxin or poison
elaborated by the invading microbe--an antitoxin, which chemically
neutralises the toxin; (2) the production in the blood of the attacked
animal of a "germicidal" poison which repels and kills the attacking
microbes themselves (not merely neutralising their poisonous
products); (3) the extermination of the intrusive, disease-producing
microbes by a kind of police, which scour the blood channels and
tissues and "eat up"--actually engulf and digest--the hostile
intruders. These latter agents, actual particles of the living animal
in which they exist, are the "eater-cells," or "phagocytes"--minute,
viscid, actively moving cells, resembling the animalcules called
"amoeba." They are only the one two-thousandth of an inch in
diameter, and are known as the white or colourless corpuscles of the
blood. They are far less numerous than the red blood-corpuscles, which
are the agents for carrying oxygen, but there are eight thousand
million of them in a large spoonful of blood. They are the really
important agents in protecting us from microbes, since they not only
engulf and digest and so destroy those intruders, but it is probable
(not certain) that they also are the manufacturers of the antitoxins
and of the germicidal poisons.
* * * * *
If these three defensive processes given us by Nature are in working
order, that is to say, if we are "healthy," they should secure to us a
sufficient "immunity"--at at any rate, "recovery"--from any attack of
disease-producing microbes. But they are not in "unselected," widely
ranging mankind always equal (in their unaided natural state) to their
task.
The attempts to produce immunity by vaccination with weakened or
localised disease germs is really an attempt to train and develop to a
high point the activities of the phagocytes or eater-cells of the
blood.
The introduction of antitoxins by injection of them into the blood (as
in the treatment of diphtheria, lock-jaw, and snake-bite) is an
attempt to bring to the rescue of a patient who would sooner or later
produce his own antitoxins (but perhaps too late or in insufficient
quantity) the similar antitoxin obtained from the blood of another
animal which has been artificially made to produce in its blood an
excessive quantity of that substance.
Mithridates, King of Pontus, was, according to ancient legend, in
consequence of his studies and experiments, soaked with all kinds of
poisons to which he had become habituated by gradually increasing
doses, and he had at last reached a condition in which no poison could
harm him, so that when he was captured by the Romans and wished to
kill himself (which was the correct thing in those days for a fallen
king to do), he wept because he was unable to get any poisons which
would act upon him. He was "immune" to all poisons. This real or
supposed immunity resulting from the introduction into the living body
at intervals of a series of doses of a poison gradually increasing
strength has been called "Mithridatism," and animals and men so
treated have been said to be "mithradatized." The toleration of
poisonous drugs--such as tobacco and alcohol, and even of mineral
poisons, such as arsenic--was, until lately, regarded as merely a
special exhibition of that habituation of "adaptation by use" which
living things often show in regard to some of the conditions of their
life. Unusual cold, unusual heat, unusual moisture, salinity or the
reverse, unusual deprivation of food, unusual muscular effort may be
tolerated by animals without injury provided that they have been
"gradually accustomed" to the unusual thing, or, in other words, that
the unusual has been gradually made the usual; so that there is a
saying that eels after a time even get used to being skinned. There
was no attempt to explain the details of this process of habituation;
it was assumed to be a part of the general "educability" of living
matter.
The study of the education of living matter, in regard to various
conditions which can act upon it, has yet to be further carried out,
but the way in which the poisons made by disease germs and the like,
and the disease germs themselves, are dealt with in the blood and
tissues has, on account of its urgent importance, from a medical point
of view, been already profoundly studied by experimental and
microscopic methods of late years. The old notion as to "mithridatism"
was that an animal or a man would have to be separately prepared and
"immunised" by habituation for every distinct kind of poison. We now
know that this is not the usual way in which Nature confers immunity
to poisons. Most astonishing, and at first sight magical or
mysterious, powers exist in the living protoplasmic cells in and
around the blood of man and higher animals, which enable their
possessors to resist and combat the poison-producing microbes, and
also the poison itself, of all kinds, by which the race is liable to
be attacked.
Few of us realise what a wonderful and exceptional fluid the blood of
a higher animal is. The Australian natives attach so little importance
to it that they actually cut themselves and use their blood as a sort
of paste for sticking decorative feathers on to a pole! The Papuans
are more advanced, since they regard the flow of blood from a cut or
graze as an evil portent. And some respect to the greatness and wonder
of blood is shown by those persons among civilised peoples (more
frequently men than women) who faint when they see blood, or even at
the mention of its name! This stream of red fluid within us (of which
an average man has about fifteen pints in his vessels) courses at a
tremendous rate from the heart through all the endless branches and
networks of arteries, capillaries and veins, and back to the heart. It
feeds, cleanses, warms and takes "vital air" (the old name for oxygen
gas) dissolved in it to every particle of our bodies, fresh and fresh
at every pulse-beat as it rushes on. It not only absorbs crude
digested food through the walls of the gut, but conveys it to where it
is worked up and distributes the worked-up product. It removes the
quickly used-up substances from every part, and the choke-damp or
carbonic acid which would stop the whole machine, and kill us, were it
not got rid of through the lungs as the blood hurries through the
walls of these air-sacs, whilst other used-up materials are carried by
it to the kidneys and passed out of the body through them. Every part
of the body is brought into common life with every other part by this
impetuous blood-stream--which is here, there, and everywhere, right
round, and back again, in twenty-five seconds! It is obviously a very
serious thing if a poison-producing microbe gets into this
blood-stream and multiplies within it, or if poison-producing microbes
lodge somewhere beneath the skin in a wound, and keep on discharging
virulent poison into the blood! The mischief is spread all over the
body at once.
It is not surprising, then, that the long course of natural selection
and survival of the fittest has resulted in the fixing in the blood
and the living cells immediately connected with it of extraordinary
protective powers. The floating scavenger cells (eater-cells or
phagocytes, first recognised as such and so named by Metchnikoff) are
already found in the blood of quite simple animals in worms,
shell-fish and insects. I have watched them with the microscope at
work in transparent minute living water-fleas eating up, and digesting
microbes which had got into the water-flea's blood. In higher animals
what we call "inflammation" is a condition--the result of a new and
advantageous mechanism--which consists in a local retarding of the
blood-current, effected by the action of the nerves on the muscular
walls of the blood-vessels, and the consequent escape of the
eater-cells into the injured or infected tissue, there to eat up and
destroy the injurious microbes or other particles. Special and
remarkable properties--chemical activities of an extraordinary
character--have been gradually developed in the floating phagocytes
and in similar non-floating fixed cells over which the blood flows.
These special chemical activities are of several distinct kinds. The
first is the power to convert the poison of a microbe into a destroyer
of that poison--toxin into antitoxin. The atoms of these poisons are
elaborately composed combinations of the organic elements. By a
"shake" or a "twist" (so to speak) administered by the living cells of
the blood the combination is altered, and the toxin becomes an
antitoxin, destroying by chemically combining with it the very toxin
from which it was formed. This is a far more efficacious method than
the supposed mithridatic "habituation" or "toleration" of a poison,
with small doses of which you have to be gradually prepared. The
healthy blood converts any one of a large series of microbe poisons
into antitoxins. It is true that apparent "opposites" are often
closely allied in Nature. Evil smells and tastes are closely allied to
sweet perfumes and flavours, and what is healthy and agreeable to some
men acts as virulent poison to others (_e.g._ shell-fish, egg,
quinine, opium). The smallest change in the substance administered or
the smallest difference in the living substance of an individual (what
is called "idiosyncrasy") makes all the difference between "poison"
and "meati."
If the phagocytes and similar cells in the blood of a man or animal
exposed to the poison produced by localised microbes (such as those of
tetanus, diphtheria and septic growths) cannot produce enough
antitoxin so as to quickly destroy the poison, we can, and do,
nowadays, save his life, by injecting into his blood the required
antitoxin, obtained from another animal which we have caused (by
injection of the toxin) to produce the antitoxin in excess. That is
one sort of "immunity" or "resistance" which we can confer, and is
largely in use at the present day--the "antitoxin" treatment.
The second poison-repelling chemical activity of the blood, produced
by the living cells in and about it, consists in the blood becoming
directly poisonous to injurious microbes. It becomes "bactericidal,"
produces a bactericidal poison (called an alexin) which is usually
present in normal blood, but is greatly increased when large numbers
of certain poisonous microbes (_e.g._ those of typhoid fever) get into
the blood. Again, by other chemical substances produced in it, the
blood may, without actually killing the invading bacteria, only
paralyse them, and cause them to "agglutinate" (that is, to adhere to
one another as an inactive "clot" or "lump"). As the "agglutinating"
poison is peculiar (or nearly so) for each kind of microbe, we can
tell whether a patient has typhoid by drawing a drop of his
blood into a tube, and adding some fresh living typhoid bacilli
to it. If the patient had typhoid he will have begun to form the
"typhoid-agglutinating" or "typhoid-paralysing" poison in his blood,
and the experiment will result in the "agglutination" (sticking
together in a lump) of the typhoid bacilli. And so we prove, in a
doubtful case, that the patient has typhoid.
The third chemical activity of the blood in dealing with poisonous
microbes is also one which is conferred upon it by its living cells
when excited by the presence of those microbes. It is the production
of a "relish" (for so it must be called) which attaches itself to the
microbes and renders them attractive to the eater-cells (the
phagocytes), so that those swarming amoeba-like floating particles
at once proceed to engulf the microbes with avidity. In the absence of
the relish (the Greek word for it used by Sir Almroth Wright, its
discoverer, is "opsonin"), the eater-cells are sluggish--too
sluggish--in their work. They resemble a child who will not eat dry
toast, or, at best, only slowly, but will devour rapidly many pieces
when the toast is buttered. It is of the utmost importance to us that
our white corpuscles, or eater-cells, should not be sluggish but
greedy.
There are some microbes which will produce deadly poison if grown in
the clear fluid (serum) of the blood of an animal (as, for instance,
the cholera-microbe when grown in the serum of the frog's blood), yet
when inoculated living into the blood of that animal never cause the
slightest illness! Why? Because they are at once eaten by the vigilant
phagocytes of the blood before they can produce any appreciable amount
of poison. That is easily demonstrated by experiment. Our main means
of defence against microbial disease, says Metchnikoff--though
cleanliness and precaution against access of microbes are all very
well in their way--is the activity of our phagocytes. Now it appears
that just as in the other cases I have been considering, so in the
production of "relish," the power to produce it resides in the blood
(and perhaps the cells of its vessels), but is not set at work until
the enemy is in the blood. Suppose there is an infection, an invasion
of the blood and tissues by one or other disease-causing microbe.
Gradually if the body is healthy the "relish" is produced and becomes
attached to the invading microbes. The phagocytes swallow them
greedily and make an end of the invasion.
It is proved that this aroused avidity of the phagocytes is due to no
change in the phagocytes themselves; since if they are transferred to
the serum of a normal man they show no such predilection for the
special invading microbe. The "opsonin," or "relish," is something
exuded into or produced in the blood fluid when the attacking microbe
arrives. It attaches itself to them: that is the essential fact. In
many of us the phagocytes are not at a given moment so "avid" of this
or that disease-microbe as they should be in order to protect us from
its multiplication and poison production. But it is found that by
injecting boiled and cooled (therefore dead) microbes of a particular
kind into the blood of a man, you can start the production of the
"relish" appropriate to that kind. The dead microbes answer this
purpose; they excite the production of the opsonin appropriate to them
and yet are not themselves dangerous, since they are dead. When
subsequently (or possibly concurrently in small quantity) living
microbes of the same disease enter the blood, the opsonin is ready for
them. They are, to put it picturesquely, like oysters at the
oyster-bar, peppered and vinegared "in no time," and then swallowed by
the phagocytes by the dozen. This seems almost too comic a view of the
deadly struggle of man and higher animals for health and freedom from
the swarming pests which everywhere invade him. Yet it is correct, and
involves a simple and fundamental truth. Our properties and appetites
are but the sum of those of the protoplasmic organisms--the cells--of
which we are built up. Our need for a relish with oysters is the same
thing as the need of the phagocyte for a relish with its microbes, not
something "poetically" compared to it. The story of "the oysters and
the carpenter" might be replaced by that of "the microbes and the
phagocyte." The saying, "Fine words butter no parsnips," finds a
parallel in the remark that "The drinking of drugs does not opsonise
microbes."
Half-way between us and the amoeba-like unicellular organisms we
find the earth-worm preparing his piece of lettuce (as Darwin showed)
with a juice exuded from his mouth, a "relish" reminding one of the
Kava drink of the South Sea Islanders. To "opsonise" or render
attractive by the application of chemical "relish" is a proceeding
which we find in operation in the feeding of the minute colourless
corpuscles which engorge the still more minute bacteria--and also in
the preparation of their food by various lower animals, and finally in
the elaborate flavouring and cooking of his food by civilised man!