Dissolving Illusions
The Encyclopedia Britannica (1922) – Vaccine Therapy“Vaccine Therapy”, Encyclopædia Britannica, The Encyclopædia Britannica Company, 1922, New York, Vol.
XV, pp. 319-321
VACCINE THERAPY. – Since the discoveries of Pasteur it has become recognized that a very large
number of the diseases from which human beings suffer are due to infection of the tissues by living microorganisms, most of which belong to the simpler forms of plant life.
Immunity from such infections may be natural or may be acquired. By natural immunity we understand anatural resistance to infection by certain micro-organisms which are known to have pathogenic properties for otherspecies of animals. It is know, for instance, that microbes which produce a rapidly fatal disease in one kind ofanimal are quite innocuous when introduced even in enormous numbers into another kind.
As an example of an acquired immunity may be taken the immunity conferred as a rule for a lifetime by anattack of measles or chicken-pox. The individual who has once overcome such an infection is usually immune froma further attack, even though exposed to infection.
It is this fact which led Jenner to try to confer immunity against smallpox by producing a modified mild
“attack” by vaccination with calf lymph. It is now admitted that such vaccination does confer immunity, and thateven should infection occur the disease runs a mild course.
Since the discovery of bacteria as causative agents of disease, much study has been devoted to the partplayed by cells and fluids of the tissues in recovering from bacterial infections. Evidence has been sought for
response on the part of the body to the bacterial invasion. It is Metchnikoff that we owe the knowledge that thewhite blood corpuscles and other cells of the body react to the introduction of bacteria into the tissues. Enormous
number of these cells congregate at the site of invasion and engulf the microbes (phagocytosis). As Sir John Burdon
Anderson aptly put it, the white blood corpuscles act as the policemen of the body.
It was soon learnt, however, that this is not the only way in which the body reacts to microbic infection.
Buchner was able to show that the tissue fluids and the blood serum in particular acquire new properties as a resultof bacterial infection, properties which render them highly injurious to the invading microbes. It was shown, forinstance, that if actively mobile typhoid bacilli are brought into contact with the blood serum of a normal individual
the bacilli are but little affected by the serum. On the contrary, if the bacilli are brought into contact with the serumof an individual convalescent from typhoid fever their mobility ceases, they are massed into clumps (agglutination)and finally killed (bactericidal action) and dissolved (bacteriolytic action). Sir Almroth Wright was able todemonstrate that a further property is acquired by the serum, namely an increased power to render the bacteria more
readily ingestible by the phagocytic cells (opsonic action). Exactly how and where these new properties are
acquired is not yet known, but one of the most striking facts emerging from the study of these reactions is that they
are directed against the particular micro-organism which has invaded the tissues the reactions are said to be specific.
Thus the blood serum of a patient convalescent from typhoid fever, which is strongly bactericidal for typhoidbacillus, behaves like a normal serum when brought into contact with any other kinds of bacteria. Similarly, while
an attack of typhoid fever confers immunity against a second infection by the typhoid bacillus, it confers noimmunity from infection by other bacteria, even those so closely related as the para-typhoid bacilli.
It must be admitted that recent work goes to confirm the opinion that there is a concomitant non-specificresponse common to the reaction against all microbic infections, but this does not detract from the importance ofrecognizing the highly specific nature of these immunity reactions.
A very important step forward was taken when it was demonstrated that the body responds to theintroduction into the tissues of dead bacteria in the same was as it does when living bacteria invade the tissues, forthis made possible artificial immunization. To attempt to confer immunity against any microbic disease by the
introduction of very small numbers of even attenuated living bacteria is fraught with manifest dangers, for thebacteria are capable of multiplication in the tissues and are no longer under control. To attempt to confer immunity

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The Encyclopedia Britannica (1922) – Vaccine Therapy

against disease by the introduction of dead microbes into the tissues is a different matter, for the dosage can beregulated and the bacteria cannot multiply in the tissues.
Thus it was Sir Almroth Wright proposed to confer immunity from typhoid infection by inoculation into
the healthy tissues of a standardized suspension of dead typhoid bacilli in physiological salt solution (typhoidvaccine). The immense benefit derived from such inoculations was fully demonstrated during the World War 19148. Wright’s studies in immunization had demonstrated that it was possible to confer immunity against microbic
infections by the inoculation of bacterial vaccines into healthy individuals. It seemed at first that nothing but harm
could result from the inoculation of such vaccines once the tissues had become infected. It appeared, indeed, as if to
do so were merely to add more poison to a system already being poisoned. Such, however, is not the case. Pasteur
was the first to show, in connexion with rabies, that beneficial results could be obtained by inoculating vaccine
during the incubation period of the disease. But it was discovered by Wright that the rapidity with which a specificresponse to the inoculation of a vaccine occurs depends on the dose of the vaccine given, and that this response
occurs very rapidly if the dose is an appropriate one, which opened up the whole field of vaccine therapy. Wrightshowed that the inoculation of too large a dose of vaccine can lead to a state of lessened resistance and that no
immunizing response follows. But this so-called negative phase can be modified as regard severity and duration by
the adjustment of the dose, even to the point of its virtual disappearance, and nevertheless a good immunizing
response follows. And such a satisfactory response occurs when vaccines are inoculated into an already infectedindividual. This means that, if the gravest generalized infections be expected, there is not in microbic diseases awholesale poisoning of the tissues of the body. There is infection of certain tissues and others remain healthy or, atall events, capable of immunizing response. And it is to the power of these healthy tissues to respond that we turn invaccine therapy. Just as the tissues of a healthy individual inoculated with an appropriate vaccine response byelaborating protective substances against the microbe or microbes contained in that vaccine, and such response
confers immunity of the individual, so do the healthy tissues of an infected individual respond to a vaccine
containing the infecting microbe, and such a response raises the resisting power of the individual to the infection.
Now infections by microbes can broadly be divided into two classes: (a) generalized, and (b) localized. By
a generalized infection we mean that the microbes and their products have ready access to the blood, and lymph
stream, and thus exert their baneful influence not only locally but at a distance on various tissues of the body. In a
localized infection, on the other hand, the microbes affect a particular region of the body only and the remaining
regions are not at all or only quite secondarily affected. From what has been said before, it is obvious that in thefirst class vaccine therapy has but a limited sphere of application; in the second class it has a very wide one. For it ison the satisfactory response of tissues that the success of vaccine therapy depends and this will bear definite
relationship to the healthiness of the tissues; further, the gravity of the infection must necessarily enter into account,just as a small war calls for but a small effort, whiles a great war, in which the life of a nation is at stake, calls for a
maximal and sustained effort.
When it is borne in mind that the substances elaborated in response to the inoculation of a vaccine arelargely carried to the site of infection by the blood stream, it will be realized that the success or failure of vaccine
therapy depends largely on the blood supply of the affected area. So long as the newly elaborated antibacterial
substances can come into contact with the bacteria, success may be anticipated, but when barriers to their arrival
exist, success is limited or denied by the extent or completeness of the barriers. Thus in acute lobar pneumonia theaffected area of the lung is occupied by an impenetrable clot of blood; little good can therefore be expected fromvaccine therapy once this clot has formed and as long as it remains. But this does not preclude the exploitation of
vaccine therapy in pneumonia in the earliest stages of the disease or after resorption of the clot has begun.
Fortunately, in the majority of infections there is not such general disturbance of the blood supply to the infectedarea; in such case it surely follows that a supply of blood rich in protective substances must constitute an advantage,
as against a supply of blood poorer in such substances. It will be realized from these remarks that the utmost care isneeded in the accurate bacteriological diagnosis of each infection before vaccine therapy is employed, and thevaccine must be prepared with care as to sterility and specificity.
The administration of the vaccine needs the knowledge not only of general medicine but of bacteriology
and the principles of active immunization against microbic infections.

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The Encyclopedia Britannica (1922) – Vaccine Therapy

The Vaccine. – For practical purposes bacterial vaccine may be defined as sterilized and enumerated
suspensions of bacteria, the liquid medium being either physiological salt solution or dilute nutrient broth. The
bacteria must be isolated in pure culture and strictly indentified by the usual tests. The microbes thus indentified areusually inoculated on to the surface of a solid medium (e.g. agar-agar) and, after growth has occurred, the bacterialcolonies are floated doff into sterile physiological salt solution. The suspension thus obtained is placed in ahermetically sealed tube and thoroughly shaken, if necessary by mechanical means, so as to break up the colonies
and obtain an even suspension. A small sample of the suspension is then removed for enumeration, the tube once
more hermetically sealed and the whole placed in a water bath at 60º C. for one hour. This temperature has beenfound to be sufficient to kill most of the pathogenic bacteria without profoundly altering their chemical composition.
Sterility of the vaccine is not, however, presumed and each one is subjected to cultural control before being certified
sterile.
The enumeration of the suspension may be carried out in various ways. The original method of Wright is
as follows:
Effective doses
Autogenous
vaccine advisable

Stock vaccine adequate

Acne bacillus

In some cases

Staphylococcus..

Streptococcus

Minimal(million)

Maximal(million)

Generally

5500

Generally

50

1000

In most cases

150

Pneumococcus

Generally

550

Influenza bac.

Generally

If polyvalent

10500

B. of Friedlander

Generally

..

5100

B. coli

Generally

..

1100

M. catarrhalis

Generally..

5100

Bordet’s bac.

..

Generally

50500

Diphtheria bac.

Often

Often

1050Gonococcus..

Generally

150

Antinomyces..

Generally

125Meningococcus..

Polyvalent

501000M. melitensis..

Generally

30100

B. tyhposus

..

Yes

10100

B. paratyphosus A..

Yes

10100

B. paratyphosus B..

Yes

10100

Tubercle bac.

(?)

Nearly always used

1/500,000 mg

1/1000 mg

It has been the practice for some 25 years to enumerate the corpuscles of the blood in a counting chamberof known depth and ruled with squares of known size. Wright, therefore, mixed an equal quantity of blood and the3Dissolving Illusions
The Encyclopedia Britannica (1922) – Vaccine Therapy

bacterial suspension. Films of the mixture are made and appropriately stained for microscopic examination. An
adequate number, about 500 usually suffices, of red blood corpuscles are counted in a series of fields of themicroscope and at the same time the number of bacteria seen is noted. The number of red blood corpuscles per cub.
mm. has previously been determined in a counting chamber, so that all that remains to be done is to work out theproportion of bacteria to red cells and so to arrive at the number of bacteria per cub. mm. or cm. of the suspension.
There are technical difficulties in the way of enumerating certain bacteria, e.g. the tubercle bacilli; in these cases thebacterial growth is weighed, and the dosage, instead of being expressed in millions of microbes per cub. cm., isgiven in milligrammes of their fractions, e.g. a usual dose of staphylococcus vaccine will be 250,000,000 cocci,
whilst that of the tubercle vaccine would be 0.0001 milligrammes.
A vaccine made from cultures obtained directly from the patient to be treated is said to be an autogenousvaccine. A vaccine made not directly from cultures obtained from the patient but from cultures of the same speciesof microbe as that which is infecting him is termed a stock vaccine. In general it may be affirmed that autogenous
vaccines are nearly invariably to be preferred to stock vaccines, whilst in the case of certain microbes they areindispensable. Stock vaccines, however, are usually effective, save time and expense and have very wide
application. Latterly attempts have been made to reduce the toxic action of the bacterial suspensions and so-called
sensitized and detoxicated vaccines have been recommended, but it is doubtful whether these procedures constitute a
useful advance.
The accompanying table gives a summary of the microbes from which vaccines are commonly prepared,
together with the minimal and maximal effective doses in which they are administered.
Vaccines are administered by hypodermic injection and the inoculations are painless.
Where the minimal effective dose is employed the inoculation is not followed by any local or constitutional
disturbance. If there is any sensible constitutional change, that change is in the direction of increased well-being.
When a medium dose is inoculated there may be a small amount of local tenderness and a transient aggravation of
the patient’s symptoms, or slight constitutional disturbance, malaise, headache and possibly a slight rise intemperature. But none of these negative phase effects are at all marked except where an excessive dose has beenemployed.
It is outside the sphere of this article to enumerate the various disease in which vaccine therapy finds
application, but a few in which vaccines have proved of exceptional value may be mentioned.
Boils, carbuncles and other staphylococcal infections usually yield readily to treatment by staphylococcal
vaccine. Erysipelas, puerperal septicæmia, acute surgical septicæmia and septic wounds are conditions benefited bytreatment with streptococcus vaccine. Certain forms of rheumatism, arthritis and fibrositis are relieved and theprogress of the disease is arrested by treatment with an appropriate vaccine, and the same may be said in the case ofcertain cases of bronchial asthma, chronic bronchitis and recurrent colds.
The distressing symptoms of inflammation of the bladder due to infection by the bacillus coli are relieved
and may entirely disappear under the treatment with an autogenous vaccine.
Tuberculous disease of the glands, skin and joints is amenable to treatment with a tubercle vaccine, and in
rigidly selected cases the same holds good for tuberculosis of the lung.
It may be confidently asserted that, with the increasing knowledge vaccine therapy will find wider
application and will become recognized as a valuable weapon in the combating of microbic diseases. (A. C. I.)

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