FILTER-PASSING VIRUSES, organisms small enough to pass through a bacterial filter made of unglazed porcelain or compressed infusorial earth. In these filters the grains of the china clay or infusorial earth used for their manufacture are sufficiently small and uniform to leave interstices, the cross section of which is 0.2 to o•8µ in diameter. If a liquid containing microbes whose smallest diameter exceeds 0.2µ be pressed through the filter, the microbes remain impacted in the smaller crevices. As O.2µ is also the limit of size of a particle which can be resolved by the best microscopes (see MICROSCOPY) when white light is used, filter passing organisms are either invisible or on the margin of visibility. Hence, most of them have been classed as "ultravisible viruses." Discovery.—The first discovery, that an ultramicroscopic or filterable virus was the cause of an animal disease, was made by Loeffler in 1 898 in the course of some experiments upon f oot-and mouth disease, in which a filter of infusorial earth was used to remove ordinary recognizable bacteria from the diluted contents of the superficial vesicles which are characteristic of this disease. The filtrate was free from any particles visible by the microscope and no bacteria developed in it on cultivation. Nevertheless, in jection of this filtrate into animals caused disease. Material re moved from the vesicles of the animal so infected and filtered again reproduced the disease in a fresh animal. Similar experi ments were carried out through a number of generations of ani mals, so that there was no doubt that a virus capable of propa gation in the animal body was contained in the filtrates. In the next few years the filterability of the virus was established in the case of infectious pleuro-pneumonia of cattle, South African horse-sickness and fowl plague.
The cause of yellow fever has been shown by Noguchi to be a spirochaete which, owing to its thinness and motility, can pass through a bacterial filter.
Up to 1927 the virus of about 4o diseases of man and domestic animals had been found to pass through a bacterial filter by reliable observers. The more important of these are the following : foot-and-mouth disease, contagious bovine pleuro-pneumonia, African horse-sickness, fowl plague, yellow fever, cattle plague, sheep-pox, epithelioma contagiosum of birds, swine fever, rabies, cow-pox (vaccinia), molluscum contagiosum of man, equine infectious pernicious anaemia, canine distemper, "blue tongue" of sheep, dengue fever, papataci or sand-fly fever, smallpox, trachoma, poliomyelitis, measles, typhus fever, trench fever, mumps, Rocky Mountain spotted fever and herpes labialis.
Recently, Olitzky has succeeded in propagating on special culture media seven varieties of small microbes from the filtrates through a "bacteria proof" filter of washings of the throats of individuals suffering from catarrhal diseases. One of them is credited, on substantial grounds, with being the cause of pandemic influenza (q.v.), another is supposed by its discoverer to be responsible for our common colds. The others do not appear to be of pathological significance.
There is now reason to suppose that filter able viruses play some part in the origin of cancer (see CANCER RESEARCH). When a fragment of a malignant tumour is im planted in the tissues of an animal of the same species it generally grows and ultimately kills the animal. The animal cells of which the cancer is composed are endowed with a faculty for growth, uncontrolled by those factors which determine normal tissue equilibrium. The possibility that this property was due to infec tion of the cells by a microbe has, in the past, occupied the atten tion of investigators, but no experimental basis for this view was afforded till 1911, when Peyton Rous described a sarcoma of the fowl which differed from mammalian tumours in that it was transmissible from chicken to chicken by means of a filtrate from a filter which kept back all of the malignant cells (much too large to traverse its pores) and also any bacteria of ordinary dimen sions. This filtrate could be dried at a low temperature and the powder retained its activity for years. It had no effect when injected into animals other than chickens, and it always produced the same type of tumour.
As the same result could not be obtained with a filtered extract of other malignant growths, this very important discovery was interpreted to mean that this fowl-sarcoma was a thing apart, although in structure and behaviour it closely resembled the mammalian sarcomata. Subsequently, its discoverer found that two other malignant tumours of fowls possessed similar proper ties, and quite recently Carrel has recorded the formation of malignant tumours in fowls following local irritation of the tissues with tar or arsenic, filtrates from which were also infective for chickens. Rous believed that the filterable agent which caused the tumours he studied was, probably, an extremely small mi crobe, but as he did not succeed in propagating it outside the body its nature remained undetermined. The nature of the in fective agent in the filtrate of Rous's tumour has recently been investigated by Gye, who believes he has succeeded in growing it in test tubes in a special medium. The culture has been carried on through several generations of transplantations. By this means the virus has been purified from the other constituents of the original implant. The inoculation of this purified virus alone did not give rise to a tumour, but if mixed with an extract of the fresh tumour, in which the virus has been killed by chemical agents and which alone was innocuous, a tumour occurred. In other words, he holds that the conjunction of two factors, living virus and some non-living chemical substance or substances, is necessary to provoke the cells of the animal to that anarchical development which is characteristic of malignant growth.
Gye also maintains that chicken sar coma is not peculiar, as hitherto believed, and that a particular mouse sarcoma will sometimes yield an infective filtrate. In this case, however, a special technique had to be employed, the origi nal method of Rous proving unsuccessful. This is a discovery of much significance and it seems possible that an extrinsic origin may be found in the case of other cancers in the near future.
The virus of Rous sarcoma has been presumed to be particulate as it is held back by the finer grades of filter, and recently Bar nard, using ultra-violet light, has obtained photographs of small globoid bodies about o• i µ in diameter from cultures of the virus. These small bodies occurred in masses, suggesting colonies. They were not discovered in the medium before inoculation or when the cultivation of the virus proved unsuccessful. Whether they represent the microbes or aggregations of colloidal particles pro duced from the proteins of the medium by chemical changes associated with the growth of the virus occurring therein, is not at present determined.
Filterable organisms are also responsible for many diseases of plants (see PLANT PATHOLOGY). In fact, their existence was first brought to light by Iwanowski in 1892 in connection with the mosaic disease of the tobacco plant. Iwan owski's discovery was lost sight of and the fact was rediscovered by Beijerinck in 1898. Many varieties of plants, including the potato, tomato, bean, peach, clover, pea, cucumber, turnip, spinach, datura, hyoscyamus, capsicum, sugar-cane, maize, sor ghum and various grasses suffer from mosaic diseases. In most mosaic diseases the only obvious lesion is bleaching of the leaves in patches of varying extent, but sometimes, as in "leaf roll" of potatoes, "curly top" of beet and "spike" disease of sandalwood trees, definite destruction of tissue leading to malformation occurs. The loss of chlorophyll interferes with the nutrition of the plant by limiting the leaf area capable of utilizing the radiant energy of the sun for the building up of carbohydrate from carbonic acid and water. To this handicap local necrosis of portions of the leaf and stalk is in some varieties superadded. The economic effect of these diseases may be, as in the case of the mosaic of sugar-cane, almost negligible or, as in the case of "peach yellows" and the "spike" of sandalwood, serious, as it destroys these trees.
Between these extreme instances, the infection results in more or less diminution of crop. Only the growing leaves are affected. Nevertheless the virus extends throughout the plant and some times to the seeds. Mosaic diseases are very infectious. Mere handling of a healthy plant after touching an infected one is, in some instances, sufficient to transmit infection. The disease is spread by leaf flies or beetles and by grafting (see ENTOMOLOGY, ECONOMIC) . The virus is not capable of maintaining itself in the soil. There is a large number of different viruses which produce mosaic diseases. Some of them infect more than one species of plant. They can also inhabit resistant species of plants without these manifesting any symptoms, but the disease can be trans ferred from resistant plants to susceptible species by insects or grafting. Many attempts have been made to propagate these plant viruses in the laboratory upon plant-juices without success, but the virus of one of the mosaic diseases of the potato appears to have been recently cultivated by Olitzky.
Little is known about most of these filterable viruses. They appear to be of various natures, and the only property common to them is minuteness. The para site responsible for yellow fever is a small spirochaete, those occasioning bovine pleuro-pneumonia and human poliomyelitis are globoid in shape and just on the margin of visibility with the best microscopes.
It is not improbable that many of them flourish only inside the cells of animals and plants, which may explain the difficulty in cultivating them in artificial media. In some cases, small bodies of definite size, shape and staining characteristics are always to be seen in the cells at the seat of the lesion (trachoma, molluscum contagiosum, variola, vaccinia, bird-pox, typhus and Rocky Moun tain spotted fevers) . Whether these represent the microbe or granules in the cell contents produced under the influence of the virus is a matter of opinion. Until cultivation outside the body is achieved this controversy will not be settled.
At present only the viruses of pleuro-pneu monia, poliomyelitis, yellow fever, chicken sarcoma and the mi crobe probably responsible for influenza have been certainly cultivated, although many claims to have accomplished this with other viruses have been made. Some of these viruses occur in the blood of the patient during the acute stage of the illness and are transported to a fresh host by the bite of blood-sucking insects. Transmission of Infection.—The infections of yellow fever (q.v.) and dengue are conveyed by the mosquito (Stegornyia f asciata) . That of papataci fever is transmitted by the sandfly (Phlebotomus papatasii) (see SANDFLY FEVER) and that of typhus and trench fevers by lice (see INFECTIOUS FEVERS) . With these three fevers, and also in the case of some of the mosaic diseases of plants which are transferred by leaf flies, some days elapse before the insect is capable of handing on the infection, indicating that an interval for the multiplication of the parasite is necessary. It is possible that a stage in the life-history of the parasite can only occur in the body of the insect host. Some filterable viruses, such as smallpox, cow-pox, foot-and-mouth disease and molluscum contagiosum, give rise to superficial lesions, and are spread by contact ; others occasion catarrh of the respiratory passages and are distributed by coughing and intimate contact, as in distemper, measles and pleuro-pneumonia.
Most filter-passing microbes which have been discovered hitherto cause disease of plants or animals. It would be strange if only parasitic forms existed, for the majority of the larger microbes are not pathogenic but are concerned with the multifarious putrefactive and fermentative changes in organic matter on the surface of the earth. Accordingly, it would be natural to suppose that sub-microscopic germs with similar activi ties would be ubiquitous. The indications, at present, are, how ever, against this supposition, and sub-microscopic dimensions seem to be an attribute, more especially, of germs which are parasitic upon animals and plants. (C. J. M.)
