NationalLibraryOfScotland/medical-history-of-british-india huggingface dataset:
NATURAL IMMUNITY AND DISEASE RESISTANCE : THE
GENETICAL POINT OF VIEW.
BY
F. FRASER DARLING, PH.D., N.D.A., N.D.D.,
Chief Officer, Imperial Bureau of Animal Genetics.
(Reprinted from the Imperial Bureau of Animal Genetics Quarterly Bulletin, Vol. 2, No. 4.)
One of the foci of attention when improvement of live stock is being considered,
is the immunity of certain species and the resistance of certain stocks to the multi-
farious diseases which beset the path of the animal breeder. The question and its
attendant problems are inevitably to the fore with those engaged in the uphill task
of raising economic stocks of domestic animals in tropical and sub-tropical countries.
It had long been observed that in the tropics European breeds of cattle and sheep
were infinitely more susceptible to certain types of infection and contagious diseases
than the indigenous breeds, when the science of genetics made its advent into the
world of affairs ;.yet, apparently, it was only from this time on that interest centred
upon the possibilities of breeding resistant strains and stocks of animals, of embody-
ing in the same animal high qualities of disease resistance and economic performance.
In the past three decades it cannot be said that this laudable ideal has been
attained, in fact success has been so meagre that one wonders at the still optimistic
conjectures regarding the production of naturally immune and disease resistant
stocks. The time is ripe for a survey of what we mean exactly by the terms
immunity, resistance and susceptibility, of what critical evidence exists as to the
possession of immunity and resistance, and of the problems involved in any attack
on the genetical front. It is possible that impartial consideration may destroy
much of our optimism.
Immunity to a disease, which may be exhibited by an animal, means that
under no natural conditions of environment can the animal contract the disease, no
matter how close to infection it may come. Such immunity is often a specific
character ; for example, cattle may have rinderpest but the disease is never found
in man or the horse. Tuberculosis is common in cattle, but is an exceedingly rare
disease in sheep in proportion to the opportunities of infection. This specific
immunity may be due to serveral factors such as temperature of the animal, specific
action of the body fluids other than the blood, the condition of the skin and mucous
membranes. The blood is an important factor in many ways. Its phagocytic
capacity towards a certain organism may be all-powerful, the blood serum may
( 88 )
NATURAL IMMUNITY AND DISEASE RESISTANCE
89
itself be inimical or there may be present natural anti-toxins. There may also be
lack of suitable nutriment in the blood for a given organism to establish itself and
produce the diseased condition. At the same time, it would appear that varieties
or strains within a species and individuals within a family do exhibit definite
immunity, but such a condition, probably, is rarer than the ostensible examples
brought forward from time to time. From the genetical point of view, species
immunity is of little importance, unless it is ever found possible to promote fertility
in certain hybrids, or to supplant one species by another in husbandry.
The rarity of racial immunity has been emphasised already. For all practical
purposes it would be better to dispense with the term and speak of racial resistance
to given diseases or groups of diseases. Leaving absolute immunity entirely alone,
there seems to be much reliable data relating to the degrees of resistance or
susceptibility. For instance, it will not be questioned that the Negro is more
susceptible to tuberculosis and pulmonary complaints than the white man. Holmes
has found, however, that diseases of the nose and throat are not so common in
American Negroes as amongst the rest of the population, and he attributes this to
the tougher mucous membranes of the nose and throat in the Negroid race.
Among the white peoples, the Jews enjoy a high degree of resistance to tuberculosis,
whilst from American figures the Irish appear more than ordinarily susceptible.
Lundborg, in 1920, enunciated that racial homogeneity was a powerful factor
preventing certain diseases, including predisposition to tuberculosis. Pure-bred
Jews and gypsies have a high resistance under very unsanitary conditions, but the
resistance is dissipated when they intermarry with other stocks. Mortality from
tuberculosis is high in the North of Sweden where Swede, Finn and Lapp intermix.
In the South of Sweden, its incidence is much less. Similarly, the disease is less
common in Iceland, Sardinia and Sicily, where the populations are relatively pure,
but it is rife in Poland and Austria, where the populations are very mixed. This
hypothesis tends to cut across that which postulates a much higher incidence of
tuberculosis in the blonde races than in the darkhaired sallow-skinned ones.
According to Kozelka, tetanus in the Chinese is very rare, measles is considered
a mild disease among Caucasian people, but in North American and Melanesian
peoples it is very severe. Negroes do not show such a high mortality to yellow
fever as Europeans and the Japanese seem resistant to scarlet fever. It is probable,
and in fact the only reasonable explanation for such resistances recorded above
seems to be, that races have acquired resistance to certain diseases because they
have been subjected to infection over a long period of time and they have become
groups raised from stocks which have successfully lived through infection. They
are rigorously selected populations. An example of the effect of selection on later
90 THE INDIAN JOURNAL OF VETERINARY SCIENCE AND ANIMAL HUSBANDRY [ II, I
resistance is given by the history of the outbreak of an acute type of swine erysipelas
in East Anglia in 1921-1922. During this time 70 to 80 per cent. of the young stock
affected succumbed to the disease, but after a few years the death rate fell to the
normal 10 to 15 per cent. Even so, there are environmental factors, known and
unknown, which have to be considered. The saprophytic causal organism may have
found conditions suitable for its spread at that time, or it may itself, for unknown
reasons, become more virulent in its action. Again, the proportion of the survivors
in the subsequent population was not determined, for the assessment of its genetical
significance in influencing the degree of resistance displayed by the present popula-
tion.
We must consider the rôle played by diatheses in the resistance of disease.
Crew has given this definition :—
" A diathesis may be defined in genetic terms as that state resulting from the
expression of a particular hereditary constitution, and conditioned by certain
environmental agencies which determine the individual's reaction, successful or
unsuccessful, to specific environmental stimuli. An individual exhibiting a parti-
cular diathesis will, in virtue of its genetic constitution, and in the presence of the
exciting agent and under appropriate conditions, exhibit a particular reaction which
is of such a kind as to render the individual less competent than its fellows,
efficiently to live fully in the particular environment in which it and they exist
Idiosyncrasies, diatheses, constitutions, are conceptions well based on genetic fact
and are to be regarded as chemical, immunological, physical, physiological and
psychological peculiarities exhibited by an individual in relation to its environment
or by different tissues or functions to one another."
There can be no doubt that the constitutional factor is of great importance in
the incidence of disease amongst a population, but it is not practical to confine the
term constitution to morphological characters alone. To quote Crew further :—
" The constitutional factor in resistance and susceptibility would seem to be a
certain kind of fundamental biochemical state within the cell and not something
of the nature of an antibody always present in the blood.
" Thus, an acquired immunity can remain after demonstrable antibodies have
disappeared from the circulation. One must assume, therefore, that the persistent
resistance is due to some definite physiological modification within the body cells
themselves, and that this modification results in the production of a condition that
is equivalent to that which exists in the cells of the naturally resistant. It is
possible, but not probable, that such acquired modification, becoming reinforced,
may become transmitted to succeeding generations."
NATURAL IMMUNITY AND DISEASE RESISTANCE
91
Grasset studied the various factors relating to the transmission of acquired
immunity and he came to the conclusions, that contrary to the natural immunity
of fixed character, equally transmissible by male or female, the transmission of
acquired immunity is confined to the female since, owing to the filtering action
of the placental barriers, antibodies are allowed to pass through while antigens are
retained and prevented from reaching the fœtus. Apart from any other considera-
tion this phenomenon throws a light upon the molecular size of the antibodies and
antitoxins and demonstrates that they are smaller than the corresponding antigens
or toxins. The resulting protection in the young is purely passive and temporary ;
acquired immunity in the ancestor does not exceed one generation and is not
incorporated among the hereditary characters, even if a succession of immunisations
is carried out over a number of generations ; passive immunity derived from
maternal sources is sufficient to ensure a protection whilst the individual is develop-
ing its own defence ; only the aptitude to create an immunity is hereditarily trans-
missible as a fixed character ; this reactive faculty, though there may be no occasion
for its application, is transmitted as a latent character from generation to genera-
tion, although subject to considerable individual variation in the same species; and
the reactive character may be influenced by several external or internal factors
which have the effect of increasing or decreasing the natural aptitude for response
to immunity.
When we consider the expressions of disease resistance shown by races of
domestic animals, we tend to find ourselves in some confusion. The Algerian
sheep is credited with immunity against anthrax. In Kenya a condition in sheep
and goats described as " Nairobi fever " affects native stock to the extent of a
70 per cent. mortality, whereas only about 30 per cent. of Merinos die. Such
findings as those, however, are not the result of critical experimentation and the
possible variables have not been duly considered. Only too often the record of an
observed set of empirical phenomena has gone into general opinion as fact. That
cattle type, popularly known as the " zebu," has been particularly unfortunate in
gathering upon itself records of disease resistance which critical analysis has been
unable to conform. In a previous issue of the Quarterly Bulletin Matson drew
attention to this state of affairs and made some enlightening remarks from his own
experience. In 1916 Pucci recorded that two " zebus " in a herd of seventy Brown
Swiss cows were the only individuals unaffected by an outbreak of foot-and-mouth
disease. This was merely an observation, but it is remarkable how many times
this has been quoted as evidence of the immunity of " zebus " against foot-and-
mouth disease. Matson says that Indian cattle are no more immune to this disease
than are European, but he suggests that in a tropical environment the zebu may
enjoy higher vitality than the European beast and thus escape the disease during
92 THE INDIAN JOURNAL OF VETERINARY SCIENCE AND ANIMAL HUSBANDRY [ II, I
a particular outbreak, thus pointing to the elaboration of antibodies being a func-
tion of metabolic activity.
Again, it has been frequently asserted that some strains of " zebu " cattle are
immune to rinderpest. Such has yet to be substantiated. However, the differing
degrees of resistance and susceptibility exhibited by different Indian cattle types
provide an interesting study. For example, the cattle of the hills are more
susceptible to many diseases than the cattle of the plains. In fixing the dose of
anti-rinderpest serum for the simultaneous method it has been found necessary
to give a much larger dose of serum to hill cattle than to plains cattle. According
to Walker, this resistance of the plains cattle does not seem to be due to enzootic
causes entirely, the diseases being as rife in the hills as in the plains. Pool has
stated that in Indian rinderpest outbreaks, Himalayan hill cattle free from
admixture with plains cattle show very nearly a 100 per cent. mortality rate,
whereas most plains breeds show a mortality of 20 to 30 per cent. European
cattle in India appear to have as high a mortality rate as the Himalayan cattle
and require more than four times the dose of serum per unit weight for immunisa-
tion. It is interesting to note, however, that McCall in Tanganyika found that
it was just as easy to immunise half-bred and three-quarter bred European cattle
as it was to immunise full-blooded " zebus." Concerning the temperature factor
in disease resistance it may not be out of place to mention that McCall found that
the body temperature of native cattle averaged about 101° F., whilst that of
imported European stock kept under similar conditions averaged just on 103° F.
Imported Afrikanders registered an average of almost 102° F.
There has been much controversy and loose talk in relation to trypanosomiasis
and the possibility of breeding immune strains of domestic stock. This disease
seems to be found throughout the tropics wherever the tsetse fly can find a habitat,
and most species of domestic animals seem prone to infection by one or other
member of the protozoan group responsible for the condition. The high resistance
of certain native cattle types has, from time to time, led to assumption of the
existence of absolute immunity. An experiment carried out a few years ago by
the Nigerian Veterinary Service shows the rashness of any such assumption. In
certain badly infested fly areas of the West African coast there lives in apparent
good health a dwarf, humpless type of cattle, and the Nigerian Department
considered this believed immunity to be worthy of further investigation. To
quote the story as given in the Report:—
" To ascertain definitely what degree of immunity if any was possessed by
these animals, as well as to carry out some breeding experiments, two small lots
were brought to the Vom Laboratory during the year
NATURAL IMMUNITY AND DISEASE RESISTANCE
93
" The first lot of three was immunised against rinderpest by the method of
double inoculation and all reacted severely and died, the cause of death being, in
every case, due to a breakdown to a previous infection of trypanosomiasis in
combination with the rinderpest reaction.
" The second lot of six were immunised against rinderpest by a combination of
the methods of formalised spleen pulp vaccination and double inoculation. No
reaction followed this method of immunisation, but in four out of the six
trypanosomiasis was observed on blood examinations.
" The result of these two experiments clearly demonstrates that these dwarf
cattle do not possess an immunity to trypanosomiases and in reality harbour the
infection in a dormant form which can become revivified as the result of an attack
of some other disease, such as rinderpest. Many of the humped cattle of the
Northern Provinces of Nigeria are in the same state of premunisation against
trypanosomiasis."
Similarly it is reported that the humpless West African Shorthorn cattle of
the northern territories of the Gold Coast show remarkable absence of clinical
symptoms of trypanosomiases. Stewart, in the 1929-30 Report of the Veterinary
Department of the Gold Coast, says that, " Crossing experiments between West
African Shorthorn cattle and English or Zebu bulls tend to show that the resistance
is transmitted, though much diluted in the English crosses."
The story of an interesting individual herd comes from Tanganyika. In 1913
a native took his herd from a fly-free area into a dense fly belt. Heavy mortality
resulted, but his herd was not completely wiped out. Until 1920 he was joined
by others, whose cattle shared the same fate. Calves were born from the survivors
but unfortunately the death rate exceeded the birth rate. The Report says :—
" The herd at present consists of five cows and heifers, two heifer calves and
one bull calf. They are closely related in that all are the progeny of three mothers
and probably several are by one sire.
" There is now no serviceable bull, but the cows were recently served by the
Government bulls which were introduced but quickly succumbed.
" The eight animals are bitten daily by many tsetse, so must be immune to
the ordinary forms of trypanosomes, although such immunity is no doubt of the
relative nature known in English as immunity-tolerance and in French as premuni¬
tion, in that parasites are merely suppressed but not eliminated. Such an
immunity is likely to break down, and this probably occurred with one cow last
year."
The history of this herd is to be watched, for the close relationship of the
animals indicates the hereditary nature of this tolerance. The yearling bull is to
G
94 THE INDIAN JOURNAL OF VETERINARY SCIENCE ANE ANIMAL HUSBANDRY [ II, I
be used in future, rather than introduced males which would be susceptible to the
disease.
Another group of diseases which may be roughly classed as tick-borne diseases
are analogous to trypanosomiases in that a host other than the domesticated
animal is usual for the completion of the life cycle of the parasite. Piroplasmosis
or redwater is a good example of such diseases and it is present throughout the
tropics. The condition of resistance of tropical cattle is well described by an
excerpt from the Report of the Veterinary Department of the Gold Coast for
1929-30, which says :—
" This disease (Piroplasmosis) commonly affects calves. Native cattle possess
a high resistance, many pass through symptomless attacks, a minority lose condi-
tion and a few die. The fatal cases are nearly always complicated by severe worm
infections. After passing through an attack of Piroplasmosis as a calf, the animal
is thereafter resistant, the resistance being continually strengthened by exposure to
reinfection."
The usual method of control of tick-borne diseases is by passing the domesti-
cated stock through arsenical dips at intervals less than the average time taken for
one feeding period in the life history of the tick. Thus, in several areas in the
tropics both European and native cattle are kept free of ticks and consequently of
the diseases carried thereby. However, if native cattle reared under tick-free
conditions are moved to tick-infested areas, they appear to succumb to such
diseases as redwater almost as readily as European stock.
At the same time, it would seem that native cattle in the tropics have some
protection against tick infestation in that their coat is very dense and composed
of very short hairs. Ticks find a difficulty in ensconcing themselves in a skin of
this kind. This observation is borne out by the finding that of all the European
breeds of cattle tried, the Jersey is least troubled by ticks, and there can be little
doubt that the Jersey is the shortest coated of European cattle.
The previously-quoted Annual Report from the Gold Coast contains an interest-
ing reference to racial resistance among cattle to a fungoid skin disease,
streptothricosis, which is common throughout the stock-breeding areas of the
Colony. " It is particularly virulent in grade stock which seldom recover, serious
in Zebu cattle but rarely fatal to West African Shorthorns, among which
spontaneous recoveries are not uncommon. . . . The disease appears to be
seasonal, most new infections commencing during the late rains when the wet
conditions obviously predispose to the spread of the parasite."
When we approach the consideration of resistance and susceptibility to
tuberculosis we soon become aware of the extraordinary complexity of a critical
NATURAL IMMUNITY AND DISEASE RESISTANCE
95
genetic analysis of disease. The absence of the disease from a stock in a given
environment does not allow one to presuppose a high resistance. It may be that
the germ has not been introduced, or that the environment itself or the methods
of husbandry are not such as will allow establishment of the disease. Miller has
drawn attention to this point by instancing the reputed comparative infrequence
of tuberculosis in the Hereford compared with the Shorthorn. The Hereford is
largely grass bred and fed, whilst the Shorthorn is frequently housed and is thus
laid open to infection in a greater degree. Similarly, tuberculosis has a greater
incidence in dairy than in beef cattle. The dairy cow probably receives more
housing than the average beef animal, and the intensified physiological strain of
lactation in the dairy cow is only too often inadequately met by a low standard of
nutrition. Naturally, such a condition lowers resistance and would account for the
high incidence of tuberculosis in dairy cattle, yet it could not be stated critically
that they are more inherently susceptible to tuberculosis than are other types.
Relative to this point we may mention the observed high resistance of tubercle-
free Shetland cows brought to the mainland where, because of this, they are much
used as nurse cows, in beef Shorthorn herds. Over a long period of time they have
become genetically adapted to a low standard of nutrition in the islands. As nurse
cows on good land where nutrition is adequate and is understood, the Shetland
cattle attain, possibly, a state of physical well-being far above the normal, which
provides them with a high degree of resistance to tuberculosis.
As possible evidence of racial resistance to this disease among cattle. Miller
has cited the statements of Kitasato, that a definitely greater resistance to
controlled artificial infection is exhibited by certain Japanese breeds of cattle, than
is shown by European breeds under the same conditions. Hutyra and Marek
record that the Steppe cattle of Southern Russia, comparatively free from tuber-
culosis in those parts where they are indigenous, show a very pronounced resistance
against artificial infection. Dechambre and Guérin report that certain races of
cattle possessed of a light-coloured coat and hide contract tuberculosis more easily
than do those with dark skins, even when they are placed in the same infected
byres. The most susceptible appear to be the light roan Shorthorn and the French
Race des Landes.
From the foregoing general discussion it would seem that two main observa-
tions are worthy of consideration, though it must be realised that the interpreta-
tion of these is difficult since the phenomena are superimposed upon other factors
such as an inherent or acquired immunity or again the mode of infection.
Firstly, it would appear that there is much evidence that the quality of the
feeding and the power to metabolise the food are associated with a capacity to