NationalLibraryOfScotland/medical-history-of-british-india huggingface dataset:
VIRUSES AS THE CAUSE OF DISEASE
169
The resemblance in structure and behaviour of the sarcoma of fowls to the
malignant growths of mammals gives rise to hesitation before admitting that it is
caused by an extrinsic virus, since mammalian malignant tumours have never
been found to yield an infective cell-free extract and have been usually regarded
as due to intrinsic tissue changes, though both mammalian and avian sarcomata
can be induced by external physical and chemical irritants, such as tar and certain
other substances.
If, therefore, an extrinsic virus is one of the essential causes of fowl sarcoma,
it must already be present in every susceptible fowl. The view that viruses which
produce disease are not essentially invading parasites, but are produced by the
host, is opposed by the regularity with which diverse viruses can be propagated
in the same kind of animal, and by the fact that the same virus may infect several
widely different species. For example, there are three distinct types of foot-and-
mouth disease virus which produce apparently identical symptoms in animals and
can only be distinguished by the fact that any one does not protect an animal
against infection with the other two ; nevertheless, each virus maintains its identity
whether propagated in the cow, pig, guinea pig, rat or hedgehog. It is difficult
to see how this could happen if the virus were produced by each species of mammal
from its own tissues.
Another filterable agent, in many respects resembling the virus of an animal
disease, is the bacteriophage which was independently discovered by Twort and
D'Herelle. The effect of a drop of a suspension of bacteriophage added to a young
liquid culture of susceptible bacteria is that the latter are dissolved and a large
amount of fresh phage is produced. The bacterium-free filtrate of the liquid
culture may often be diluted ten million times and still the same effect be produced
by a drop as by the original suspension.
D'Herelle and many other bacteriologists believe that the phage is a living
agent which infects young growing bacteria, multiplies in their interior, and is
set free when the bacteria die and break up.
Phage, though destroyed at a temperature of 70° to 75°C., as a rule survives at
60° to 65°C., when the bacteria with which it is associated are killed ; it also resists
drying and is remarkably resistant to the action of alcohol, acetone and chloro-
form. D'Herelle considers that all strains of phage are really one though differ-
ent strains become adapted to different bacteria, but more probably many phages
when first obtained are a mixture of distinct races, and most filtrates containing
phage are in the first instance derived from sewage or faeces, containing a great
variety of bacteria.
Some strains of bacteria harbour a phage although apparently insusceptible
to its destructive action. The activity is only manifested when a filterate is tested
on another susceptible strain. Thus many bacterial cultures have been shown to
produce phage, though the presence of phage is not apparent and may not even
170 THE INDIAN JOURNAL OF VETERINARY SCIENCE AND ANIMAL HUSBANDRY [VI, II
have been suspected. This phenomenon suggests the original production of the
phage by an uninfected culture, but it may merely be another instance of an ap-
parently normal organism ' carrying ' a parasite ; many parallel cases are known of
animals and plants ' carrying ' infective agents whilst themselves unaffected.
De Jong showed that cultures of certain sporing bacilli which produce a phage
may still be ' lysogenic ' after being heated at 100°C. for five minutes, whereas
the free phage is killed at 70°C. for five minutes. When the spores germinate the
phage is again liberated. This experiment suggests that the phage is preserved
by its inclusion in the resistant spore, and this evidence of its derivation from the
germinating spore de novo is not conclusive.
The chief reason for doubting the living nature of some phages and certain
viruses is the very small size of their filterable particles which makes it very
doutbful whether they can have a complex composition resembling that of
other living things.
Different strains of phage are very unequal in their filterability ; some have
relatively large particles with a diameter about half those of vaccina, while others
pass through very fine filters, like the virus of foot-and-mouth disease, for which
the diameter is estimated at about one tenth of the coarser phages.
The uniform and carefully graded collodion membranes introduced by Elford,
of which the average pore diameter can be calculated, enables much closer estimates
to be made than formerly of the size of particles which just pass or are just withheld.
The size of the particles of some viruses has also been calculated, especially by
Bechhold, by their rate of deposition when centrifuged at 10,000—15,000 rev.
per min.
It has been possible to purify virus particles by first filtering and then cen¬
trifuging at high speed, washing the deposit and again centrifuging, as has been
shown by Ledingham.
By the new collodion ultra-filters the diameter of the particles of different
viruses has been estimated to vary from 200 mµ to 150 mµ, for vaccinia to about
8-10 mµ for foot-and-mouth disease (µ=mikron=1 thousandth of a millimetre ;
mµ=one thousandth of a mikron). It is difficult to understand how with such
dimensions they can have a composition of sufficient complexity to consist of living
matter. For comparison, the smallest bacteria have a diameter of 1.0—0.5µ
and the egg-albumen molecule has been estimated at 4.34 mµ diameter.
Doerr, in a recent treatise, while granting that some viruses have been shown
to be living denies the possibility of life in those of the smaller dimensions. It
so happens that the viruses of foot-and-mouth disease and louping-ill which are
among those with the smallest particles, exhibit all the typical essential characters
of viruses both in vitro and in the animal body, though causing very different dis-
eases and having very different ' life-histories '.
VIRUSES AS THE CAUSE OF DISEASE
171
The exact and quantitative experiments with filters have been made possible
by the high concentration in which certain viruses occur, and by opportunities
for determining the presence of the virus in different dilutions by inoculation of
susceptible small animals. The dilution of some fluids containing virus from the
animal body can be carried to 1 in 10 6 or even higher when dealing with foot-and-
mouth disease, vaccina and some other diseases without depriving them of infec¬
tivity.
The quandary arising from the very active and apparently vital functions of
virus particles in spite of their small size raises the question whether the accepted
definitions of life are universally applicable or whether some intermediate state
between what is called living and dead matter may not exist, as has been suggested
by Boycott.
Of the functions usually postulated for a living organism, assimilation appears
to be the most characteristic and indispensable. It is reasonable to assume that
the metabolism of an organism would be much simplified if it existed in a circulat-
ing medium which provided a constantly changing supply of materials resembling
its own components, such as might be afforded for an obligatory parasite living
inside the cells of its host. Such an existence would have very different require-
ments from a truly independent life.
Virus diseases are transmitted from one animal to another by very varied
means. Some, like canine distemper and certain influenza-like diseases of man, by
droplets in the breath, others like yellow and dengue fevers by the bites of insects,
others like louping-ill of sheep by the bites of blood-sucking ticks or of mites ;
again, the bite of the mammalian host is the usual mode of infection with rabies,
but for many others the method of transmission is still uncertain. In these res-
pects they do not differ from diseases due to bacteria.
It is characteristic of many diseases that, although the initial infection is caused
by a virus, many of the symptoms and complications are due to secondary infec-
tions with bacteria, and this is notably the case in the influenza-like group in man
in swine fever, canine distemper and swine influenza.
A virus may become remarkably adapted and sometimes permanently
attenuated, when transferred to a new host, as is well instanced in the change
of the virus of small-pox to vaccinia in cattle and rabbits, and of the rabies virus
in the rabbit.
The period of resistance shown by the host following an attack of disease is
sometimes very prolonged even life-long after small-pox, varicella, yellow fever
and canine distemper, but in some other cases the protection afforded is of com-
paratively short duration, in foot-and-mouth disease usually for one to two years,
whereas frequently recurring attacks due to the virus of herpes labialis are common.
172 THE INDIAN JOURNAL OF VETERINARY SCIENCE AND ANIMAL HUSBANDRY [VI, II
This immunity is to a great extent due to the production in the animal body
of ' antibodies' which can be found in the blood serum of recovered animals
just as occurs after bacterial infection. These antibodies can often be demons-
trated by the formation of a precipitate or by the agglutination of the virus parti-
cles when a suspension of the elementary bodies is mixed with the serum, or by
the neutralisation of the virus by the serum when both are injected into an animal.
These phenomena are of the same kind as the precipitation occurring when the blood
serum of an animal which has been inoculated with a foreign protein (antigen)
is mixed with the same protein in vitro, and are not peculiar to true infection.
It is not intended here to do more than refer to the enormous and increasing
number of filterable viruses known to cause infective disease in plants and found
in their juices. These, like mosaic disease of tobacco, spotted wilt of tomato and
crinkle and leaf-roll of potato may cause very serious disease, or in other cases
may be present throughout the plant without producing any visible effect, as in
some infections of the potato.
There is good evidence that two viruses may co-exist in the same plant, and
as a result the symptoms may be either much more or much less severe than when
either virus is present alone.
Some viruses are transmitted by insects such as aphis or thrips, while others
pass by unknown means. In some of these diseases of plants peculiar ' inclusion
bodies' are found in certain cells, but their relation to the virus is undetermined.
It is known that these ' bodies ' as well as some of the symptoms due to a virus
can in special cases be imitated by the addition of certain inorganic salts to the
soil, but the disease is not then transmissible. Some plant viruses are highly
resistant to drying chemical action and alcohol, and in many ways the viruses of
plants resemble those of animals.
The problems which the behaviour and properties of viruses raise are of great
practical and theoretical interest, and are by no means yet solved.
INHERITANCE AS A FACTOR IN POULTRY DISEASE*
BY
W. V. LAMBERT,
Iowa State College, Ames.
[Reprinted from the Poultry Science May, 1935, Vol. XIV, No. 3.]
(Presented at Annual Meeting, August 7-10, 1934.)
During the past three decades the poultry industry in the United States has
undergone tremendous changes. From the family flock basis, where birds were
kept principally as a source of meat and eggs, it has gradually changed until today
poultry keeping in its various aspects is the primary enterprise of thousands of
farmers. With this change many problems that were not of great concern in the
family flock have developed. Of first rank among these problems is that of flock
mortality, which instead of being on the wane seemingly is becoming a more
serious menace year by year.
SIGNIFICANCE OF DISEASE LOSS
The seriousness of mortality in commercial flocks has been emphasized in
economic studies of poultry farming in various states. In New Jersey in 1915-16
the mortality was 7 per cent [App et al., 1919]; in Oregon in 1926-28 the average
mortality was 13 per cent [Scudder et al., 1931]; 16.9 per cent in New Hampshire
in 1929-30 [Woodworth and Reed, 1932]; 21 per cent in Utah 1929-30 [Thomas
and Clawson, 1931 ]; 27 per cent in New York in 1930-31 [Misner, 1931]; and 21 per
cent. in Iowa in 1933 [Vernon and Whitfield, 1933]. In egg-laying contests
mortality has been equally severe. Stafseth and Weisner [1931] observed 18.98
per cent mortality among 10,000 pullets in eight successive years at the Michigan
contest. Furthermore, they point out that poultry diseases are increasing and
that the losses during the later years of the contest were greater than in the earlier
years. In the Vineland egg-laying contest Black [1933] reports mortality rates of
24.51, 29.75 and 23.36 for the years 1929-30, 1930-31 and 1931-32, respectively.
The seriousness of such losses to the industry cannot be over-emphasized. Ob-
viously if the poultryman is to succeed he not only must raise good pullets but he
must keep them alive. Lippincott and Card [1934] state that pullet mortality
and, to a less extent mortality in older hens, is one of the most serious problems
confronting poultrymen. Furthermore, they say that while good sanitary mea-
sures have enabled flock owners to bring mortality in growing chicks reasonably
well under control, that the problem of reducing or preventing mortality in laying
stock is still to be solved. They believe that one of the most promising methods of
* Journal Paper No. J231 of the Iowa Agr. Exp. Sta., Ames, project No. 251.
( 173 )
174 THE INDIAN JOURNAL OF VETERINARY SCIENCE AND ANIMAL HUSBANDRY [ VI, II
attack is the breeding and selection of resistant strains, though they point out that
progress is likely to be slow until the vital significance of the problem is generally
realized.
Flock mortality is due, obviously, to diseases of various types and any pro-
gramme for disease control must recognize and take into consideration the
different kinds of diseases responsible for this mortality.
METHODS OF CONTROL
Three possible methods of disease prevention and control are available to
poultrymen. The first, and perhaps the foremost in importance, is proper hygiene
and sanitation for the flock. A second method is through the use of various
therapeutic agents and the third method is genetic. The genetic or breeding
method is concerned with the development of strains free from defects and
disturbances of function, and, likewise, with the creation of strains having a
high natural resistance to parasites and other infectious agents.
The genetic method of disease control, therefore, implies two rather distinct
categories of disease, namely the non-infectious or those diseases due to derange-
ments of structure or function, and the infectious. It is the purpose of the writer
to review the present status of our knowledge of the genetic aspects of disease and
this review will be presented under the above general headings. Certain diseases,
such as neurolymphomatosis, the etiology of which is still undetermined, will
be considered separately.
THE NON-INFECTIOUS DISEASES
Non-infectious disturbances involving deviations from the normal or desir-
able type in structure and function have been shown to be hereditary in many
cases, and it is probable that most diseases of this sort will be shown to have
some hereditary basis. Examples of such inherited defects in poultry are the
creeper fowl [Landauer and Dunn, 1930], congenital loco [Knowlton, 1929], con-
genital palsy [Hutt, 1934], dwarfism [Mayhew and Upp, 1932], and stickiness
[Byerly and Jull, 1932]. Since many of these conditions are lethal or else produce
some other serious detrimental effect in the affected individual they are responsible
for reduction in reproductive efficiency and a corresponding economic loss. Hence
it is essential for the welfare of the poultry industry to prevent the wide-spread
dissemination of such genes through the population. The eradication of such
diseases is purely a genetic problem, and any intelligent plan for disease control
in the poultry industry certainlv must consider the breeding programme if such
defects are to be eliminated.
While clear-cut genetic evidence is lacking, it is probable that numerous
weaknesses of the reproductive system, which result in much pullet mortality,
are hereditary. A study of the causes of mortality in any of the egg-laying con-
tests will show that much mortality is due to such causes as prolapsis of the
oviduct, rupture of the oviduct, and to other causes in which an infective agent
INHERITANCE AS A FACTOR IN POULTRY DISEASE
175
apparently is not involved. In their attempt to increase production many poul¬
trymen have neglected to take into consideration the inherent stamina of their
birds, which seemingly is a very vital factor if high egg production is to be main-
tained over long periods of time with little mortality. Dunnicliff [1914] has
pointed out the importance of this factor in. his analysis of the Hawkesbury egg-
laying contest. He says that some strains show much greater susceptibility to
ovarian weaknesses than do others. In the Hawkesbury contest the competition
committee, adopted the policy of awarding a special trophy to the pen laying
the most eggs without the replacement of a bird. Some high producing pens went
through three years without the replacement of a single bird. As a result of his
analysis Dunnicliff concludes that breeding for constitution will have to be con-
sidered much more closely than in the past, and he is hopeful that close atten-
tion to the salient points of breeding will result in eventual solution of this
most difficult problem.
Kennard [1933] has demonstrated the importance of selection based upon
the simple expedient of using hens as the progenitors of the pullets to be retained
as layers. By this method he was able to bring about an appreciable decrease in
pullet mortality, and he attributes a part of the increase in pullet mortality,
observed generally by poultrymen to the practice of selecting their breeding stock
from pullets. As a permanent solution of the problem of pullet mortality, he
advocates careful breeding and selection, combined with a type of management
that will insure that young birds reach maturity free of parasites and unexposed
to diseases.
While it would be rash to assume that most pullet mortality is due to hereditary
weaknesses, sufficient evidence has been advanced in man and other animals
[Pearl, 1928], as well as in poultry, to show that longevity and strong constitution
are inborn traits of certain families and strains. It would seem inevitable, there-
fore that any long-time plan of poultry improvement, if it is to be economically
successful, must consider the elimination of defects and the selection of strong
hardy strains as vital parts of its programme. Certainly the genetic method
of control is a most important one for diseases of this sort.
THE INFECTIOUS DISEASES
An infectious disease, in contrast to the non-infectious, requires the co-
operation of two agents, the host and the parasite for its expression. That heri-
table differences in resistance to such diseases exist has long been known, but
until the last ten years most of this evidence was statistical in nature, or was
confined to the demonstration of species and racial differences. In the last
decade, however, several investigators have shown that heritable difference in
resistance to bacterial diseases are common within the species. In poultry, Roberts
and Card [1926] have demonstrated the effectiveness of selective breeding upon
resistance to pullorum disease, and Lambert [1932] has shown similar results for
176 THE INDIAN JOURNAL OF VETERINARY SCIENCE AND ANIMAL HUSBANDRY [VI, II
fowl typhoid. Five generations of such selective breeding decreased the mortality
from fowl typhoid from 85 to 10 per cent. Roberts [1932] has recently reported
that the resistance of the pullorum stock has been maintained for seven conse-
cutive generations, the respective mortalities for the selected and unselected
stocks being 35 and 73 per cent. Furthermore, both Roberts and Card [1926]
and Lambert [1932] have shown that strain differences in resistance to both
these diseases exist in unselected flocks.
In other species, also, clear-cut demonstrations of the role of heredity in
disease resistance have been shown. Schott [1932] and Webster [1933] were able
to build up remarkable resistance to typhoid-like infections in mice, Irwin [1929]
to the Danysz bacillus in the rat, and Manresa [1932] to infectious abortion in
rabbits. Other demonstrations of the part of heredity in infectious disease have
been made by Frateur [1924], the Hagedoorns [1920] and by Gowen and Schott
[1933].
That a passive transfer of immunity was not responsible for the increased
resistance in the selected stock has been amply demonstrated by Irwin [1929],
Lambert and Knox [1932], Schott [1932] and Gowen and Schott [1933]. The
resistance has been shown to be transmitted by the male as well as by the female.
In addition, Lambert [1932] and Roberts and Card [1927] have pointed out that
in stocks selected for resistance to fowl typhoid and pullorum disease, chicks
hatching from the eggs of females who remain carriers of the pathogenic bacterium
are neither more nor less resistant than chicks produced from the eggs of non-
carrier females of these stocks.
The hereditary basis of resistance and susceptibility to infectious diseases
appears, from most of the results so far available, to be complex, probably being
dependent upon multiple factors. This, obviously, complicates the problem of
using the genetic method for producing commercially desirable lines of resistant
birds. It must be remembered, however, that very little research has been done
on this problem and that a blanket rejection of a method on the basis of difficulty
of accomplishment is unjustified. Certainly poultry furnishes the greatest oppor-
tunity for using the breeding method of any of our domestic animals of great
economic importance. In poultry, large progenies are available and this permits
of selection of large numbers and of elimination on a large scale. In addition, the
cost of the individual animal is low, a factor which often makes the use of
therapeutic agents, as costly vaccines, economically unjustifiable.
The whole question of the use of the breeding method in the case of infectious
diseases is one upon which more information is sadly needed. Cole [1932] has
pointed out that the ease with which preventive and therapeutic measures can
be applied has led to a neglect of any natural resistance present in our flocks,
a method of control which would be more satisfactory if naturally resistant stocks
can be developed.