|
[Excerpts from Reports prepared for and presented to the Commissioners on
specified Heads of Inquiry]
Part I [Omitted]
Part II.
PROPAGATION OF CATTLE PLAGUE.
Of the numerous and complicated questions relating to the propagation of
Cattle Plague which were included in the plan of the present inquiry
as originally laid down, I have been able to investigate
experimentally,
those only which refer to the nature and properties of the contagious
principle of the disease as they are exhibited in the effects of
inoculation, and to the length of the period of incubation.
1.
Effects of inoculation.
The question which stands first in its
practical bearing on the employment of inoculation as a means of
eradicating
or preventing Cattle Plague is the following: - Is it
possible by inoculation to produce a form of disease which, while it
is protective against future attacks, is yet so mild that it admits of
certain cure under ordinary circumstances, or in other words, that
the affected animals, as a rule, recover with reasonable care as to
hygienic conditions ?
This question does not at present admit of an
answer. It is true that although the results of the countless
inoculations of Cattle Plague, which have been performed since the
practice was first introduced in 1754,*
{Of these an excellent account is given in Prof. Unterberger's "Beitrage zur Geschichte der
Rinderpestimpfung." Dorpat, 1865.} show that there is no appreciable
difference either as regards symptoms, progress, or duration, between
the disease produced by inoculation and that which results from
natural infection, provided that two fatal cases, or two cases of
equal severity are compared with each other, yet the proportion of
fatal and severe cases is much smaller in inoculated animals than in
those naturally infected. So much so that in the majority of the
former the malady is deprived of its malignant character, and tends to
spontaneous recovery.
But this fact loses its practical value by its
inconstancy. While during certain epizootics, and in certain
countries, the results of inoculation on the large scale have been so
favourable as to lead even the opponents of inoculation to hope that
they were mistaken, in others the mortality has been almost as great
among inoculated animals as among those infected naturally. Until we
are able, not only to say on what these variations depend, but to
control them - until we have found out a method of producing a
mitigated form of the disease at will, the problem will remain
unsolved.
The practice of inoculation has had its
strenuous and ardent advocates in every country of Europe - men
who have not only made investigations themselves, but have pressed
upon governments the expediency of testing its value by experiments on
a large scale. Al1 such proposals have been discouraged by the leading
members of the veterinary
profession, for reasons which are of a similar nature to those which
were urged against the practice of inoculation of smallpox at the end
of the last century. In countries or districts in which the epizootic
prevalence of Cattle Plague is so general that all animals are certain
to be exposed to innumerable sources of infection, it is admitted that
the practice of inoculation as a prophylactic is at least defensible,
for its effect would be to reduce the duration of the epizootic to
that of an individual case, and to settle once for all the loss to the
community which would be occasioned by it. It is also very generally
admitted that in countries in which the disease is constantly enzootic
(supposing such countries to exist, of which there is no evidence,)
inoculation is proper, no less on the ground of the probability that
every animal will take the disease than for the sake of other
countries.* {With reference to the Steppes of Southern Russia special
considerations are applicable. In the first place it has been shown on
the clearest evidence that in the grey cattle of the Steppes the
disease assumes a much milder form than in other breeds, and
consequently that inoculated animals recover from its effects in much
larger proportion than others; secondly, if it be admitted that the
Steppes are the home of Rinderpest and the source from which all
epizootics spring, it is clear that if all the Steppe cattle imported
into Prussia and Austria were rendered insusceptible of the disease
by inoculation, and thereby incapable of communicating it, it would
eventually cease to exist in Europe. This is the idea, which has been
so perseveringly insisted on by that enthusiastic advocate of
inoculation in Russia, Professor Jessen.} But the introduction of inoculation as a general prophylactic measure
is condemned by all the authorities. It would be unjustifiable, it is
said, not only because the result is extremely uncertain, but also
because inoculation cannot be carried out without the constantly
recurring risk of originating outbreaks, the extent and
destructiveness of which can neither be controlled nor foreseen.
So long as the main question remains unanswered -
so long as we do not
know how to produce at will a curable form of disease by inoculation,
the conclusiveness of this argument does not admit of dispute. In
the present state of our knowledge, it would not even be proper to
recommend inoculation of sound animals in plague-stricken herds,
as a means of bringing an outbreak of limited extent to a speedy
conclusion. We are so unacquainted with the circumstances which
determine the severity of its effects, that at present no man would be
warranted in advising it, for the probable loss which would be
sustained by the inoculation of any given number of animals could only
be guessed at, not estimated.
During the course of the present inquiry 11 animal have been devoted to
experiments, having reference exclusively to inoculation. Of these, of
which nine were yearlings and two cows, six recovered and five died.
In the first inoculations (Nos. 1, 2, 4, and 6), the method which is
usually practised in Russia was followed. A curved needle of the same
form and size as that used by Russian inoculators, perforated near its
point, and armed with a seton soaked with virus, and composed of about
half a dozen lengths of white worsted thread twisted together, was
passed through a fold of the integument of the neck, previously
pinched up between the thumb and finger. The needle having been
withdrawn, the thread was allowed to remain in the wound for 48 hours,
its ends having been previously tied together. In all these cases the
wounds became swollen and inflamed, and in some, subcutaneous
abscesses were formed which it was afterwards necessary to open with
the knife. The discharge in which the threads were steeped was derived
from the eyes and nostrils of a cow in the last stage of Cattle
Plague. The period of incubation varied from 48 to 60 hours, and the
total duration of the disease from eight to ten days. All of them
recovered, the improvement commencing from the sixth day.
Another series of inoculations (Nos. 13, 17, 18, 19, 20) was performed
by injecting the liquid virus
under the skin of the perineum by means
of a subcutaneous syringe, the quantity employed being in each case
half a drachm. By this method no local effects whatever were produced.
In No. 13 the liquid employed was serum of blood taken from the heifer
No. 11, three days after the first rise of temperature observed in
that animal. In this case as the period of incubation extended to six
days, being nearly three times as long as in the previous experiments,
it was judged expedient to repeat the inoculation with mucous
discharge from the eyes of No. 12. Immediately after this had been
done, the temperature began to rise, so that it may be presumed that
the second insertion was futile. The progress of this case was
remarkably rapid, death taking place early on the sixth day, a
circumstance which I believe to be attributable to the fact that the
animal was previously suffering from pulmonary disease arising from
strongyli, as well as from flukes in the liver.
In the other four cases serum was also employed, but was taken from the
cow No. 15, 17 hours after the first rise of the temperature. The
purpose of these experiments was to ascertain in the first place,
whether in Rinderpest the serum of blood is virulent, and secondly, to
compare the effects of matter, taken at the earliest stage of the
disease, while the mucous membranes still remain in a natural state,
and the animal is to all appearance in perfect health, with those
produced by the insertion of morbid secretions collected shortly
before death. In all of these animals the incubation period was longer
than in the former series, varying from four to seven days. No. 17,
which recovered, resembled very closely Nos. 1, 2, 4, and 6, both as
regards the progress and character of the symptoms. In Nos. 18, 19,
and 20, which died, the disease assumed much the same character as in
animals which had been naturally infected, the only remarkable
difference being that in No. 20 death occurred about half a day later
than usual.
In two other cases (Nos. 14 and 1.5) the operation was also performed by
subcutaneous injection, but here the liquid employed was lachrymal.
fluid. In No. 14 it had been kept for seven days in capillary tubes,
and had been taken between the fourth and fifth day of the disease, a
fact which seems to have some relation to the period of incubation,
which in this instance lasted for three days. In No. 15, the lachrymal
fluid was collected between the seventh and eighth day from No. 14,
the period of incubation was from 48 to 60 hours, and death took place
10 days after inoculation.
In addition to the animals above referred to, four of the calves sent by
the French Government to the Albert College, (to be further mentioned
in the section of this Report relating to vaccination,) were
inoculated by Mr. Duguid by subcutaneous injection on the l5th of
February. Of these, two were inoculated with lachrymal secretion
collected from No. 19 on the fifth day of the disease; the other two
with the same virus diluted with ten times its volume of milk.
The symptoms recorded in these animals show that there was no
difference either as regards the period of incubation, the duration of
the symptoms, or the mode in which the fatal termination occurred.
It need scarcely be stated, that the experiments hitherto made have been
so few that the conclusions drawn from them as to the effects of the
methods of inoculation employed must be rather negative than positive.
-
(1)
In the first place, it seems to be tolerably clear that it would be
incorrect to say that in any of the cases the disease was modified in
the same sense in which small-pox is said to be modified in
vaccinated persons, for even in the mildest cases, the development
and progress of the disease are essentially the same as those which
terminate fatally;
-
(2) nor can I for a moment believe that in the
mild cases, Nos. 1, 2, 4, and 6, there was any relation between the
character of the symptoms and the method of inoculation, not only
because in Russia where this method is constantly employed, no such
mitigation is observable, but because in a number of animals in which
the same method of inoculation has been practiced to my knowledge in
England, the resulting disease has assumed a most malignant character;
-
(3) it appears to me no less evident that the results were in no way
affected by the nature of the virus employed. For, on the one hand,
the experiments on serum of blood certainly afforded no ground for
believing that a mild form of disease could be produced by that
method, while on the other, the results obtained from Mr. Duguid's
inoculations with diluted virus, of the calves sent from France, do
not encourage any further investigation in that direction.
2. Period of Incubation.
From the experiments
already related it is seen that in animals inoculated with virus
collected during the third stage of the disease, the first indications
of infection exist about two days after inoculation; they also afford
some ground for believing that in those cases in which these
indications are deferred, the prolongation of the period of
incubation was in relation to the period at which the matter inserted
was taken.
In animals naturally infected the period of
incubation is probably
from four to five days. The following facts may be adduced in
illustration: A heifer (No. 10) was bought on the 2nd of January for
the purpose of experiments on vaccination. It was ascertained by
inquiry
from her former possessor, that the stable in which she had been kept
for several months contained no other bovine animal, and that she had
not been exposed in any way to Cattle Plague. On the 5th of January
she was placed in a coach-house which had been for some time
unoccupied at Notting Hill, along with two other yearlings (Nos. 11
and 12), three healthy cows occupying a contiguous three-stalled
stable. On the 6th she was observed to be unwell, and on the 8th I
found that the eruption of Cattle Plague on the lips had progressed
to such an extent that it must have existed for two or three days. The
two yearlings in the same coach-house were apparently well, but
it was thought advisable to remove them to the experimental stable. As
will be seen by a reference to the cases, they exhibited the initial
signs of Rinderpest on the 11th and 12th respectively, and died on the
16th and 18th. The three cows that remained at Notting Hill, under the charge of Mr. Badcock, were vaccinated by him on
the 13th; on the 15th they were reported to be ill, and were
subsequently removed to the Albert College. From the appearance of the
mucous membrane of the mouth there could, in my opinion, be no doubt
that the eruption had appeared on the 14th, and consequently, that the
disease must have commenced on the 12th - that is about the same
time as in Nos. 11 and 12. Thus after three days exposure to natural
infection, from the 5th to the 8th of January, the five animals became
affected on the 11th or 12th, and were all dead by the 18th, showing
that at least, in one instance, the period of incubation could not
have exceeded five days. This result is confirmed by the more exact
observations made in the heifer No. 15, in which the first rise of
temperature took place just four days after it was placed along with
diseased animals in an infected stable.* {Since the above was written
the following fact has come under my notice. A bullock was placed, on
the 26th of March, in the same stall with another animal, then at the
third day of Cattle Plague. The temperature remained natural until the
morning of the 31st, but at 3 p.m. on the same day it had risen to
104.0.}
PART III.
ACCOUNT OF EXPERIMENTS UNDERTAKEN WITH REFERENCE TO THE ALLEGED
PROTECTIVE POWER OF VACCINATION.
The steps which were taken at the beginning of
the present year, for the purpose of determining the question, whether
or not successful vaccination exercises any influence in modifying the
progress or mitigating the severity of Cattle Plague, have been
already sufficiently detailed in the introduction to this Report.
The first experiments relating to this special
inquiry were made during the last week in January, the results being
of such a nature, as to make it appear that Cattle Plague could be
communicated with perfect facility to vaccinated animals, either by
inoculation or natural infection, and that when so communicated its
character was not modified. The question was thus at once conclusively
settled; it therefore appeared unnecessary to incur further expense
with reference to it, so that, although a large number of animals were
purchased for vaccination (amounting in all to 26), only three were
exclusively devoted to the object for which they were originally
intended, the rest (with the exception of those which unfortunately
contracted the disease in the reserve stable at Notting Hill) being
employed for other experiments. Of these animals, one (No. 14) was
purchased of a gentleman, by whom it had been vaccinated in December
1865, at the suggestion of Dr. Harding of Grafton Street, for the
purpose of testing the value of vaccination as a prophylactic
against Cattle Plague, while the others ( Nos. 1 5 and 16) had been
generously presented to the Commissioners for the same purpose, by Mr.
Dumbrell of Ditcheling, Sussex. In all three cases, the evidence of
good vaccination was conclusive. Of the two fine cows presented by Mr.
Dumbrell, one had been vaccinated from the other. The success of both
operations was guaranteed by Mr. Holman of Hurstpierpoint, and
further indicated in the animal last vaccinated, by the regular form
and satisfactory character of the crusts which were still adherent,
and in the other by the appearance of the cicatrices. In both, the
operation had been performed by four insertions. With respect to the
purchased animal, although the visible results were not so
satisfactory, it was ascertained on the testimony of Dr. Harding that
vaccine matter derived from it had been employed with perfect success,
in the vaccination of several children.
The disease was communicated to two of these animals (Nos. 14 and 15) by
inoculation, to the other by natural infection. The calf No. 14. was
first inoculated on the night that it was brought to the college, with
liquid discharge from the eyes of No. 12. which had been kept for six
days in capillary tubes, there being at the time no diseased animal in
the stables. As on the third day, the temperature of the body remained
unchanged, the inoculation was repeated with virus taken directly from a
heifer, at the fourth day of Cattle Plague. The result showed that the
second inoculation was superfluous, for on the following morning, the
temperature had risen to 105o Fahr., and continued above that height
during the further progress of the disease. No other symptoms appeared
until two days later, when the animal became constipated and lost
appetite, and the mucous membrane of the mouth was for the first time
affected in the usual way. Although the disease followed its regular
course, it soon became obvious that the case was comparatively mild, for
on the sixth day, when the unfavourable symptoms, which are the
precursors of death, are as a rule to be looked for, no such change took
place. There was no marked prostration, the dejections were still of
greater consistence than natural, and liquid food was taken readily.
On the seventh clay diarrhaea came on, and the general state of the
animal was worse, the evacuations being abundant and foetid, and the
discharge from the mouth and nares more profuse; but these symptoms soon
receded, and convalescence set in.
The comparison of this case with those previously observed, in which the
disease had been communicated to healthy animals by inoculation,
afforded no ground for supposing that the progress of the symptoms had
been favourably modified by vaccination; for with the exception of No.
13, all of those animals had recovered, and most of them without any
severe symptoms, whereas here the animal was so ill on the seventh day,
that it was thought to be dying. In No. 13 the progress of the malady
was more rapid, but there the unfavourable result appeared mainly
attributable to previously existing disease.
|
|
[Section
omitted]
Admitting, then, that the active poisonous matter of contagious
diseases generally consists of living matter, and that this living
matter enters the blood, let us inquire how the living particles may
pass into the vascular system where there is no inoculation, no
solution of continuity, as far as can be ascertained, in the vascular
walls. We may explain the fact, that of a number of persons equally
exposed to the influence of a
contagious poison,
some will contract the disease while others will escape, by supposing
that in the latter case the living particles are prevented from
passing through the vascular walls, or, coming into contact with the
blood, that they do not grow and multiply, but become destroyed, and
the substances resulting from their destruction excreted, and at once
removed from the body.
How,
then, do the living particles pass through the vascular walls and
enter the blood; and what are the circumstances that would favour or
interfere with their passage? Thin-walled capillary vessels, as is
well known, come very near to the surface in many parts of the body.
Those of parts of the mucous membrane of the nose, mouth, and
conjunctiva, even in a state of perfect health, are covered with a
very thin layer of protective epithelium, while those of the air cells
of the lung are practically speaking bare. In many morbid states the
epithelial covering of the mucous membranes enumerated above is very
soft, and sometimes is reduced to a thin layer of a soft pulpy mucus,
in which any foreign particles would very readily become embedded. It
is reasonable to suppose that the contagious germs would find in this
soft mucus a nidus favourable for their reception, and at the same
time soluble materials adapted for their nutrition. They would grow
and multiply, and probably minute off-sets from them would soon find
their way to the external surface of the capillary walls.
I
have shown that there is strong reason for concluding that when the
capillaries are much stretched, as when fully distended with blood, as
in the early stages of inflammation, particles of living matter,
probably derived from the white blood corpuscles, make their way
through the walls with some of the serum, and grow and multiply in
their new position external to the vessels.*{On
the Germinal Matter of the Blood, with Remarks on the Formation of
Fibrin. - Trans.
Mic. Soc.
Dec. 1863.} An
"exudation," therefore, does not consist of mere fluid, but
contains particles of living growing matter, which pass with the fluid
through the capillary walls from the blood. These particles become the
spherical granular cells which are often seen external to the vessels
in inflammation. Each absorbs nutriment, and just as in the case of
all other kinds of living matter grows, and divides, and subdivides.
This view concerning the origin of many of the corpuscles in exudation
is supported by the fact that in pneumonia, and in some other
conditions in which the capillary distension is very great, blood
corpuscles, which are much larger than the particles of living matter
just referred to, pass through the capillary walls without the vessels
being torn across. And every one who has made very minute injections
is familiar with the fact that minute longitudinal rents or fissures
may be made quite wide enough for a red blood corpuscle to pass
through edgeways without destruction of the vascular tube. It is,
therefore, certain that particles of minute size may pass through
capillary walls without the occurrence of actual rupture.
Now
the state of things referred to above - a soft, moist state of the
mucous surfaces, a dilated condition of the capillaries, combined with
a weak, flaccid state of their walls, which would follow
long-continued congestion, and which is intimately connected with a
weak heart's action and feeble condition of the nervous system, -
are those which would facilitate the passage of such living
germs as I am supposing, and is it not probable that these are the
very conditions which exist in the organism about to be the victim of
a contagious fever? In such cases the composition of the blood is
altered, and its fluid constituents manifest a tendency to permeate
the vascular walls more readily than in a perfectly healthy state.
This state of blood would doubtless affect the nervous centres
presiding over the contraction of the arterial walls and regulating
the flow of blood through them, thereby influencing the nutrition of
the part, and in this way a relaxed state of the arterial walls and a
congested state of capillary vessels might be induced, or, already
existing, might be increased. It is this low and but too often ill-defined
weak state of health that we should endeavour to detect by most
careful observation, and at once treat. Nay, it seems to me almost
certain that every serious contagious and non-contagious acute disease
dangerous to life to which we are subjected is preceded by a condition
or system which in many particulars is a departure from health. If
this can be altered, the liability to the supervention of the acute
attack no longer exists. It is in the direction of anticipating the
occurrence of actual, serious, well-marked disease that those most
earnest in advancing medicine may reasonably hope to do useful work.
And it seems certain, that the more minutely we investigate, the more
likely shall we be to learn how to discover and appreciate that slight
departure from the healthy state which precedes, and often by some
considerable time, the development of many of the most serious and
most fatal maladies.
Of
the Multiplication and Reproduction of the Contagious Material in the
infected organism. - From the observations already advanced
concerning the size of the smallest active particles capable of
growing and multiplying, it will be inferred that the
quantity of material capable of giving rise to a contagious disease is
wonderfully small, and that within the organism this minute portion of
matter multiplies a million-fold.
One or more particles having entered the blood would of course
circulate with that fluid. It is possible that the particles would
multiply to some extent while actually circulating; but it is probable
that many of them would fail to traverse the capillary vessels, being
obstructed by the masses of germinal matter which project into their
interior and in which, or
in the white blood corpuscles, they might even become embedded.
The conditions to which they are exposed in the capillary vessels
would be more favourable to their rapid multiplication than those
present in the circulating blood, and they would therefore grow and
increase considerably in this situation.
We
have now to enquire more precisely into the circumstances under which
the wonderful increase of the poison
is brought about. There are two view essentially different from one
another, which may be supported by different arguments.
-
1.
It might be maintained that the contagious material actually
passing into certain portions of the living germinal matter of the
organism might excite in these new actions, and cause them to
divide and sub-divide very actively, and communicate to them the
same properties which the original particles possessed, somewhat
in the manner in which the wonderful powers existing in connexion
with the germinal matter of the spermatozoon are communicated to
that of the ovum and affect to some extent every one of the
multitudes of masses resulting from its division.
-
2.
The contagious particle or particles having gained access to the
fluids of the uninfected organism may absorb nutrient matter, grow
and multiply, giving rise to a progeny exactly like themselves in
every particular.
In
the first case the actual living matter of a healthy organism is
caused to take upon itself a new and peculiar action in consequence of
the influence of another kind of germinal matter upon it. In the
second the contagious material simply grows and multiplies at the
expense of the pabulum.
It
is open to discussion which of these two views is supported by the
greatest number and most pregnant facts. I incline strongly to accept
the latter as the more probable of the two.
It
may, however, be fairly asked, if, when a pus corpuscle from the
surface of the conjunctiva of a person suffering from purulent
ophthalmia, or when a particle of gonorrheal pus comes into contact
with an uninfected conjunctiva and grows and multiplies, establishing
a similar morbid condition to that in operation upon the surface where
it grew, the multitudes of resulting pus corpuscles are the direct
descendants of the pus corpuscle or are derived from the germinal
matter of the cells of the conjunctiva which are modified in
consequence of its action upon them?
It
seems to me probable that the corpuscles capable of exciting a new
action upon an unaffected surface are the direct descendants from the
original corpuscles which excited that action. Not only so, but I
believe they take the nutrient material which was destined for the
nutrition of the normal cells, and live at their expense. Just as in
the case of cancer, the adventitious rapidly growing germinal matter
takes the nutriment destined for the normal tissue, and even feeds
upon the latter in consequence of its powers of growth being much more
active.
It is most probable, I think, that in the case of the specific pus
corpuscles growing upon a mucous surface the germinal matter of the
normal cells may increase and multiply too. Indeed, in some instances
I am sure that this is the case. So that there are two distinct
processes going on; 1, the multiplication of the specific corpuscles,
and 2, the multiplication of the germinal matter of the normal cells
modified in consequence of the altered circumstances to which they are
exposed. And it therefore follows that not every one of the pus-like
bodies formed is capable of exciting the specific action, but the
specific bodies outstrip in the rate of their multiplication, to so
great an extent, the masses resulting from the normal germinal matter,
that the number of descendants of the latter would be comparatively
insignificant and would soon be completely overwhelmed by the former.
Upon
the whole, then, I
venture to think that the millions of contagious particles produced in
the organism in an eminently contagious disease, are all the direct
descendants of the very few, or perhaps even single particle first
introduced; just as the millions of bacteria and fungi developed in
certain decomposing organic matters in the course of a few hours may
have been produced from one or at most a very few particles.
And that although in the secretions upon the mucous surfaces, and in
internal parts, there may be many masses of germinal matter resulting
from the increased access of pabulum already many times referred to,
these latter do not form the active elements of the contagious
material or contagium.
Concerning
the possibility of the particles of contagium passing into the
substance of normal living germinal matter.
- It is true that in the substance of many masses of germinal matter
found in the secretions and discharges of animals dying from Cattle
Plague, and of many other diseases, some minute particles which would
ordinarily be termed granules, which refract the light very highly,
and probably have been often mistaken for minute oil globules, may be
invariably observed in great number. The nature of these particles is
not known. They are however met with in almost all kinds of living
matter with which I am acquainted, and different kinds are observed.
In Fig. 71 at a. some are seen in a very minute amoeba. In Fig. 15
some are seen in masses of germinal matter from the milk. It seems to
me probable that some of these particles have originated in the
germinal matter itself, while others have passed into it from without.
Now
it is certain that such particles are very numerous, and are commonly
found in masses of germinal matter so situated as to render their
entrance from without, not only possible, but probable. The fact of
the amoeba opening itself as it were, and then enclosing upon foreign
particles, and embedding them in its very substance, is well known.
Nor is this a phenomenon peculiar to the amoeba, but it is possessed
by other kinds of germinal matter. And now that the supposed
importance and even the actual existence in many cases of the cell-wall
have been disproved, and the active, spontaneous movements which used
to be called amoebiform, because it was supposed they were peculiar to
the amoeba, have been proved to be common to living matter in general,
it is probable that this and other properties, equally characteristic
of all kinds of matter in a living state, will be admitted.
It
must then be regarded as at least possible that particles of
contagious living matter less than 1/100000 of an inch in diameter
might pass into the substance of a white blood, lymph, or chyle
corpuscle, and thus embedded, the particle might be carried to all
parts of the system. The matter itself might increase and multiply in
the corpuscle, destroying it and living at its expense until the new
collection attained a size larger than that of the corpuscle.
Or, the foreign living particles in the white blood corpuscle might
interfere with its division and sub-division, and the germinal matter
of the corpuscle itself, attain a size larger than ordinary. Or the
presence of the bodies supposed might cause the death of some of the
particles of germinal matter and the formation of oil globules and
other substances which might go on accumulating until the white
corpuscle became too large to traverse the smaller capillaries. The
phenomena above referred to, would not only seriously interfere with
the growth and nutrition of the white blood corpuscles, but would
prevent the material undergoing conversion into red blood
corpuscles. And in consequence of the diminution in number of the red
blood corpuscles, and the reduction of the total quantity of blood in
the system, various secondary phenomena would follow.
But
in whatever way the minute particles of germinal matter supposed to be
included in the white blood corpuscle might cause their enlargement or
interfere with their function, impediment to the free circulation of
the blood in the capillaries must be induced. The minute particles now
stationary would rapidly increase and multiply, and some might make
their way through the vascular walls towards the surface or into the
surrounding textures.
The
minute particles embedded in the germinal matter sometimes so closely
resemble minute vegetable germs that in some cases it is difficult to
believe they are not of this nature and have gained access from
without. In other cases these particles are of the nature of nucleoli,
and have originated in the germinal matter itself, while I am quite
certain that some of the minute highly refracting particles embedded
in the white blood corpuscles, pus corpuscles, and some other masses
of germinal matter, result from changes occurring in the germinal
matter itself, and are closely allied to fibrin.* {See
my paper "On the Germinal Matter of the Blood; with Remarks on the
Formation of Fibrin." Trans.
Mic. Soc.
Dec. 1863.} I
am, however, not able without further investigation to pursue this
part of the inquiry.
Without,
therefore, pretending to be able to identify the actual materies
morbi of the Cattle Plague, or to distinguish it positively from
the other forms of germinal matter present in the fluids, on the
different free surfaces, and in the tissues of vast numbers, I think
the facts and arguments advanced in this paper tend to prove;
-
first,
that it is germinal matter;
-
secondly,
that the particles are not directly descended from any form of
germinal matter of the organism of the infected animal, but that
they have resulted from the multiplication of particles introduced
from without;
-
thirdly,
that it is capable of growing and multiplying in the blood;
-
fourthly,
that the particles are so minute that they readily pass through
the walls of the capillaries, and multiply freely in the
interstices between the tissue elements or epithelial cells;
-
and
lastly, that these particles are capable of living under many
different conditions - that they live and grow at the expense of
various tissue elements, and retain their vitality, although the
germinal matter of the normal textures after growing and
multiplying to a great extent has ceased to exist.
The
reader wil1 naturally ask which of all the particles seen in the
secretions from the nose and eyes, intestines, vagina, &c., are
the particles of contagium, for it has been proved that in all
these the contagious property resides. He will probably have gathered
from the statements made that I regard some of the most minute
particles present to be alone the active agents, while the epithelial
particles themselves, the fungi and bacteria, are probably as passive
as the oil globules or crystals of triple phosphate commonly met with.
Particles which I believe to be contagious are represented in Figs.
21, 25, 26, 33, 35, 36, 67, and the granular matter amongst the
bundles of fibrous tissue, represented in Figs. 18 and 19, I think
consists entirely of particles, the smallest of which would induce the
Cattle Plague, if introduced into the blood of an uninfected animal.
Figs. 7, 8, 33, 35, 36, represent particles of the suppose "contagium"
or active contagious matter in the vessels. It would, I think, be
quite possible to devise experiments which would determine positively
which is the real contagious matter.
The real contagious material has passed unnoticed and has really
formed part of what has been called debris and granular matter. By the
carmine fluid we can however distinguish particles of germinal matter
from fat globules, myelin particles, and other debris. Nor are
observations and experiments upon this most interesting question
concerning the nature of contagium limited to Cattle Plague. Although
this disease affords, in very many ways advantages for study far
greater than many other contagious maladies, and deserves on many
grounds the most thorough and extended scientific investigation, it is
probable that many of the questions of the greatest general interest
may be successfully worked out by studying other contagious maladies
affecting man or animals.
Of
the particles of Contagium.
- It has been proved experimentally that from the breath of the
diseased animal and from the air in the neighbourhood, matter can be
obtained which possesses contagious properties. I have endeavoured to
ascertain if such particles as I suppose to constitute the contagium
could be actually demonstrated by microscopical investigation with the
aid of the highest powers. Mr. Crookes has for some time past been
investigating this part of the subject, and has obtained some very
interesting and important experimental results. He has had the
kindness to give me a tube in which a piece of wool had been placed
and exposed to the breath of a deceased animal and fully impregnated
with contagious matter, and another tube through which the breath of
an animal dying from the disease had been passed. I moistened the wool
and the tube with perfectly pure glycerine and subjected this to
examination with the 1/50th.
Although
in each case I have seen particles resembling those already referred
to many times in my report, I cannot attach much importance to these
two isolated observations, or look upon them as trustworthy, for in
the first place the number of minute particles of various kinds
present makes it difficult to identify with any confidence the
supposed particles of contagium; secondly, as there are
undoubted sporules of fungi, I could not prove that the very minute
particles which I should be inclined to regard as the contagium had
not been developed from these; thirdly, it is desirable never to place
much reliance upon only one or two observations of this character.
At
the same time it is only right to state that the piece of wool in one
of the tubes through which the air had been first filtered exhibited a
much greater number of minute particles, resembling those which I
regard as particles of contagium, than were obtained from the second
piece of wool at the other end of the same tube by which the air was
subjected to a second filtration. I do think, however, it might be possible
to determine the question from this experimental side. The
microscopical part of the investigation presents so many practical
difficulties that I should not like to enter upon it without
performing in the first instance a great many preliminary experiments,
so as to ascertain by experience the most convenient and delicate
methods of examination.
In
conclusion, I will attempt to account for the phenomena which succeed
one another, in what I believe to be the order of their occurrence in
a case of Cattle Plague, from the time when the contagious poison
enters the body to the death of the animal.
With
regard to the nature of the contagium itself evidence has been adduced
to show that it consists of very minute particles of matter in a
living state, each capable of growing and multiplying rapidly when
placed under favourable conditions; that the rate of growth and
multiplication of these minute particles far exceeds that at which the
normal germinal matter of the blood and tissues multiplies, and that
they appropriate the pabulum of the tissues, and even grow at their
expense.
Let
us suppose that some of the living particles of contagium derived from
the infected animal, so light that they may have been wafted long
distances by currents of air, but yet capable of effectually resisting
the influence of external conditions to which they may have been
exposed in their transit, reach an uninfected animal. Coming into
contact with the soft and moist mucous surfaces, and finding a nidus
suitable for their lodgment, and pabulum fit for their nutrition, they
grow and multiply.
It
is at least doubtful if such living particles could take the further
course about to be described, if the organism were in a perfectly
healthy state. But in the present state of our physiological knowledge
of man and domestic animals it is difficult or impossible to
distinguish the state in which there is a susceptibility or
predisposition to take a contagious malady, from conditions of system
which, not necessarily characterised by robust health, are nevertheless,
consistent with work, activity, and longevity. In fact we do not
possess, at the present time, sufficiently exact data to enable us to
appraise with anything approaching to correctness and certainty the
value of individual life.
In
an animal about to be infected with Cattle Plague it appears probable
that, the minute living particles having
reached the surface of the mucous membrane, perhaps already rendered
suitable for their nutrition by previous morbid changes, gradually
multiply amongst the soft epithelial particles until some of those
produced reach the walls of the capillaries almost immediately
beneath. It is possible that some of them may be drawn down the
windpipe during inspiration, or even into the air cells of the lung.
In the latter case they would gain a very ready access to the surface
of the capillary wall.
We
may suppose that at the time the particles come into contact with the
vascular wall the capillaries happen to be distended, and consequently
their walls so thin as to permit small particles to pass through them.
Such a state would obviously favour the entrance of minute particles
into the blood. One can conceive them gradually extending like
particles of an amoeba, and slowly insinuating themselves through the
capillary wall, or they might become embedded in the germinal matter
of the capillaries, and in this way gain access to the blood. Having
reached the interior of the vascular system, they would circulate with
the blood, and for a time would give rise to no symptoms whatever; but
in consequence of possessing highly active powers of growth they would
grow and multiply, increasing at a greater rate in proportion as their
numbers increased [i.e.
exponentially].
They would soon derange the normal changes going on in the blood; many
would probably soon become adherent to the wall as they traversed the
more minute capillary vessels, and growing and multiplying in this
situation would seriously impede the circulation of the blood, partly
perhaps acting mechanically, partly by deranging the nutritive changes
occurring in the vessels and in the tissues external to them.
Derangement of nervous action would soon follow, and upon sensitive
surfaces impaired or perverted sensation, and in the voluntary
muscules feeb1e and irregular contractions would result, while the
movements of the involuntary muscular fibre which give rise to
rumination would cease to be excited, and various phenomena consequent
upon the cessation of this important process would follow. Perhaps
rigors, partly the restult of direct, partly of reflex, action, might
occur about this time.
The
heart's action increasing in frequency during the early period of the
disease would perhaps slightly retard the tendency to the capillary
stagnation; but the causes which led to the original congestion
continuing, the impediment would gradually increase, and the
capillaries would become more dilated. Increased erudition, and here
and there haemorrhage, would occur; the germinal matter of the
capillary vessels and small veins, and that of the tissues external to
these absorbing the transuded fluid would increase considerably in
amount, and it is probable that this change is intimately connected
with the increased development of heat, which almost constantly occurs
at this stage of the disease.
The
circulation now becoming weaker, while the accumulation in the
capillary vessels still continued, complete
stagnation of the blood in certain of the capillaries would occur, and
the number of foci would gradually increase. The blood in the vessels
first affected would lose its colouring matter, while its white
corpuscle s and the living particles of contagious material would
increase and multiply. Perhaps from being surcharged with materials
requiring excretion, or perhaps in consequence of these not being in a
proper state for elimination, the blood does not flow freely through
the vessels of the various excreting organs, liver, lungs, and
kidneys, and the action of other secreting glands soon ceases from the
same circumstance.
As
the capillary congestion extended from the point at which it commenced
as from a centre, and as
the
centres of congestion themselves in the various tissues increased in
number, alterations in the chemica1 composition of the mass of the
blood still circulating in the system must result, and this would
still further
aid to the mischief.
After
the blood has remained stagnant in the vessels for a short time, it
undergoes change in colour, and the dark appearance at first seen
passes through various shades until a dusky greenish hue familiar to
all who have observed post mortem appearances results.
In
a severe case the patches of capillary congestion increase in number
from day to day, and are much more numerous in some parts of the body
than in others. In this disease the mucous membrane of the alimentary
canal seems to be specially affected, and in many cases the changes
resulting from stagnation of the blood lead to complete
disorganization of the tissue. There is no inflammation, but death of
a portion of the tissue may occur from complete cessation of the
circulation in the vessels which supply it. In the majority of cases,
however, the animal dies before the morbid changes have reached this
degree; but it is common enough to find a shrinking and wasting
portion of the mucous membrane corresponding to the congested vessels,
as, for example, in the fourth stomach. In the small intestine the
effects of the stagnation of blood in the capillaries are often
complete destruction of a number of the villi, a morbid change which
would alone cause the death of the animal.
The
congested state, however, is not confined to the mucous membrane of
the gums, mouth, air tubes, and almost the whole tract of the
alimentary canal. It affects also the capillaries of the skin,
inducing first a red rash, commonly distinct upon the almost naked
skin of the udder, but by no means limited to this part of the
body, and in many cases leading to morbid changes in the cutis and
cuticle constituting the eruption.
In
consequence probably of the alteration effected in the mass of the
blood by the occurrence of the local congestions, and partly perhaps
from the congestion in the capillaries of the mucous membrane of the
bronchial tubes and the lungs themselves, partly in consequence of
impaired muscular and nervous action, the process of respiration
becomes seriously interfered with. A remarkable emphysematous
condition of the lung, which in some cases extends to the areolar
tissue of the body, results.
It
need scarcely be said that many of these changes act and react upon
one another. The heart's action gradually becoming more and more
feeble, fails to propel the now seriously altered blood, even through
those capillaries which still remain pervious, the temperature falls
several degrees, and the action of the great nervous centres becomes
more and more feeble and at length ceases.
Perhaps
the extreme degree of congestion resulting from changes induced by the
enormous multiplication and accumulation of the minute particles of
contagium in many capillaries of the skin and mucous membranes, may be
an indication of a tendency to its elimination from these points; and
it seems not improbable that if a sufficient proportion of the blood
could be kept circulating in the majority of the capillary vessels,
while at the same time, time was allowed for the elimination of the
poison from these surfaces, and especially if the free action of the
excreting organs could be encouraged, by which the materials in the
blood resulting from the action of the Contagium in that fluid would
be at once eliminated, the life of the animal might be much prolonged
or saved. But when stagnation of the blood has actually occurred in a
great number of spots in different parts of the body, more especially
if in consequence of this and the contact of irritating materials
resulting from decomposition of the food, disorganization of the villi
has actually taken place, recovery would seem to he impossible. And
even if the recovery of an animal after a severe attack of fever could
be brought about by great care, practically this would be useless,
because the expense of a long convalescence and the nourishment
requisite to restore him to his previous weight would exceed the value
of the beast.
The
particles of contagium, which have greatly multiplied in the stagnant
fluid within the capillaries, readily make their way through the
capillary walls, probably with a small quantity of serum, and become
mingled with the cells, &c.; which are being detached from the
surface; while in the case of the cuticle, where these cells form a
firm investment, the particles of contagium multiply and cause
portions to be detached in flakes. From every part of the alimentary
canal as well as from the skin and probably from the glands connected
with those surfaces, the pouring out of the living particles of
contagium proceeds, and continues till death occurs. These retain
their vitality for a long time after death, and it appears probable
that they are not at once destroyed, even when the decomposition of
the surrounding organic matters has commenced.
In
the fourth section of my report, I have made use of many facts
obtained in the course of other inquiries, and the observations on the
pus corpuscle and the movements of living matter were advanced in the
lectures I delivered at the Royal College of Physicians, in 1861 and
1865.
If
any apology were needed for the introduction of speculative notions is
this report upon the Cattle Plague, I would venture to remark that I
found it impossible to prosecute my inquiries and discuss the various
questions which presented themselves for solution without resorting to
hypothesis, and I think that one method by which we are likely to
succeed in gaining real information upon the essential nature and mode
of propagation of contagious diseases, as well as upon other complex
physiological and pathological questions, is by testing the validity
of various hypotheses which obtrude themselves upon the mind of the
observer, one after another, as the inquiry slowly proceeds step by
step.
I
have to regret that my report contains some repetition, and that I
have been precluded from condensing it into a much smaller space.
These great faults would have been corrected had I been able to devote
more time to its preparation.
LIONEL
S. BEALE.
|
