Richard E. Shope

Serial Transmission of Virus of Infectious Papillomatosis in Domestic Rabbits

It was reported 1 that the virus of infectious papillomatosis produced warts which were readily transmissible in its natural host, the wild cottontail rabbit. However, warts which it regularly induced in domestic rabbits were not transmissible serially in either wild or domestic rabbits. A similar situation as regards the transmission of Rous Sarcoma 1 to turkeys, guinea fowls, and pheasants has been described. 2 , 3 The purpose of the present paper is to report the successful transmission of the virus of infectious papillomatosis serially in domestic rabbits. Warts from domestic rabbits, infected with papilloma virus of wild rabbit origin in the usual fashion, 1 were removed at various intervals, ground with sand, suspended in physiological saline and the resulting suspension used in attempts to infect other domestic rabbits. The technique of infection was the same that had been used unsuccessfully in earlier experiments. Thirty-two attempts to carry the virus beyond its first domestic rabbit passage have been made since the 26 fruitless efforts first reported. 1 Of these, 13 were successful, the domestic rabbits of the second serial passage developing one or more papillomas over the area of skin inoculated. Efforts to maintain the virus in domestic rabbits beyond its second serial passage were made in 7 instances and, of these, 4 were successful. Two series were carried through their fifth domestic rabbit passage and then discontinued. The remaining 2 series are still being passed; one has reached its 6th and the other its 10th domestic rabbit passage. The individual papillomas developing in rabbits infected with the domestic rabbit-passaged virus are identical in all respects with those resulting following similar infection with virus obtained from wild rabbit warts.

Ultrastructure and site of formation of rabbit papilloma virus.

Summary Thin sections of rabbit papillomas reveal pools of dense virus particles in only highly keratinized cells. Viral bodies were readily distinguishable only in papillomas which had been soaked in glycerine-saline for some time. Viral bodies in fresh warts were masked by keratin, melanin and other granules. The bodies are spherical with a non-homogeneous density. They appeared to vary from 25 to 35 mμ in diameter, the most frequent size being 33 mμ. Particles in tissues soaked 1 year or 6 years were identical and equally active in test animals. Sectioned pellets of virus purified by a fluorocarbon process revealed the same particles as those seen in the tissue.

An Infectious Fibroma of Deer

Summary A naturally-occurring fibroma of the skin of deer has been transimitted experimetally. The causative agent survives for at least 22 months in fibroma tissue stored in 50% glycerol-saline at 0°F and further-more is filterable through Berkefeld N filters, properties characteristic of a virus. The experimentally produced deer fibroma has an incubation period of approximately 7 weeks and a very slow rate of growth.

Shope Papilloma Virus: Reversion of Adaptation to Domestic Rabbit by Passage through Cottontail

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RECENT KNOWLEDGE CONCERNING INFLUENZA

Excerpt From the time of Pfeiffers announcement of its discovery in 18921to 1918H. influenzaewas quite generally regarded as the agent responsible for epidemic influenza. Because of this general b...

Evolutionary Episodes in the Concept of Viral Oncogenesis

During the course of the past ten or twelve years our thinking with regard to the etiology ofcancer has undergone great modification. What would have been considered revolutionary, unorthodox, and even dan- gerous views as short a time as twenty years ago are now attaining great respectability and, at the present time, have reached the point where they modify and influence the spending policies ofboth the federal government and the major fund-granting agencies so far as cancer research is concerned. I am referring, of course, to the currently great enthusiasm with which both the scientific and lay communities have leaped to accept the possi- bility that filterable viruses may be of basic etiological importance in cancer. A question which comes to the minds of those seriously interested in the solution ofthe cancer problem concerns the basis for the current con- cept ofviral oncogenesis and its validity. With our present great interest in the possibility that cancer may be a viral disease, are we perhaps being led up a blind alley and are our scientists being diverted in their investiga- tions from more promising approaches? I believe that it is self-evident that our current concept of viral tumorigenesis was not arrived at in any single step and that the results of much experimental work have con- tributed to our present thinking. There is, of course, no way of telling at this point what further modifications may be made in our thinking concerning viral oncogenesis, but we do know pretty well how we have reached our present concept. It has been arrived at through a series of studies, each ofwhich has constituted an episode in viral tumor research and each of which has changed to a greater or lesser extent our earlier thinking.

Protection of Rabbits Against Naturally Acquired Infectious Myxomatosis by Previous Infection with Fibroma Virus

It is generally agreed that the viruses of rabbit fibroma and rabbit myxoma are closely related immunologically and that infection with the benign fibroma virus usually protects rabbits against fatal infection with the myxoma virus. 1-8 This suggested that the fibroma virus might make a satisfactory immunizing agent for practical use in the control of infectious myxomatosis. The possibility was tested by McKenney and Shillinger 9 with discouraging results, and they concluded that the infection of rabbits with fibroma virus did not constitute a satisfactory or practical means of immunizing against infectious myxomatosis. However, careful consideration of the experiments of McKenney and Shillinger suggests that their difficulties lay more in the maintenance of a potent infective fibroma virus for use in their experiments than in an actual failure of fibroma virus to enhance the resistance of rabbits to myxomatosis. Partly because of McKenney and Shillingers adverse report on the practicability of using fibroma virus prophylactically and partly to determine whether fibroma-recovered rabbits would prove as resistant when exposed to cases of infectious myxomatosis as they had when inoculated with myxoma virus, the experiment to be reported in this paper was conducted. The testicles from a rabbit inoculated intratesticularly 7 days earlier with strain A fibroma virus were removed aseptically and stored for one month in 50% glycerol in the refrigerator. (The period of storage in glycerol is not important providing it does not exceed 2 months.) At the end of this time they were washed in 3 changes of physiological saline, ground with sterile sand and suspended in physiological saline to make a 5% suspension. After the suspension had stood for 10 minutes in a tall glass graduate, the supernatant fluid was decanted for use as fibroma virus.

The influence of host and intermediate reservoir host in determining the epidemiologic pattern of bovine pseudorabies and swine influenza

Introduction. Very li t t le is known concerning the preservat ion of infective agents from one outbreak of disease to the next . As a rule, a lapse of m a n y months or even years takes place between epidemics, a nd similar long periods of t ime m a y separate sporadically occurring cases of disease from one another . Thus, some infectious diseases are of a n n u a l occurrence ; others, such as measles and whooping cough, t end to appear in epidemic form at roughly two-year intervMs; while as much as two decades or more m a y separate one outbreak of pandemic inf luenza from the next . No satisfactory explanat ion of the periodicity of infectious diseases has ever been furnished, nor has the whereabouts of the causative agents between epidemics been satisfactorily explained. The origin and source of infectious agents responsible for the s tar t ing of fresh outbreaks of disease have largely remained obscure, so far as most h u m a n diseases are concerned. I n the realm of an imal diseases, however, the above s ta tement is no t so str ict ly true, because for several of these an explanat ion, a t least t en ta t ive ly considered correct, is a t hand. I propose this af ternoon to discuss two of these diseases, bovine pseudorabies and swine infhlenza, and to compare the ways in which their epidemiologic pa t te rns are influenced by the three factors involved in each case; namely, the causative virus, the host, and the in termedia te reservoir host. B u t before

THE EPIDEMIOLOGY OF THE ORIGIN AND PERPETUATION OF A NEW DISEASE.

I. The Origin It is peculiarly appropriate that a Ricketts Lecture should deal with matters pertaining to the origin and perpetuation of an infectious disease because the work for which Howard Taylor Ricketts is best known concerned these very matters. Rocky Mountain Spotted Fever, when Ricketts began his investigations of it, was a mysterious, frequently fatal, typhuslike ailment occurring each spring and early summer in parts of the western United States. No one knew from whence it came each year, what its cause was, why it was seasonal, or where it disappeared to. Ricketts, by scientific sleuthing, requiring much imagination, originality, and scientific skill, solved the entire mystery ofthe origin and perpetuation ofthe disease. The story, after it was completely unraveled and worked out, seemed perfectly simple, as do many great scientific discoveries after they are finally made. Even today, however, over fifty years after his pioneering work, one can only marvel at the skillful and ingenious manner in which he discovered the causative agent of spotted fever, learned the secrets of its method ofperpetuation through a cycle involving ticks and small rodents, and explained its cyclical reappearance each year. He later worked with typhus fever and found in this disease an agent similar to the one he had shown in spotted fever. It was during these studies that he acquired the laboratory infection ofwhich he died on May 3, 1910. His contributions to our knowledge of that group of infectious diseases caused by organisms of the type that resulted in his death were numerous

Cholesterol in Blood of Horseshoe Crab and Woolly Bear Caterpillar.

It is generally considered that the blood of all animals contains both free cholesterol and cholesterol esters, the former existing in corpuscles and plasma and the latter occurring only in the plasma or serum. Since this conception is founded upon the results of determinations carried out on the blood of higher animals it seemed of interest to determine whether lower and more primitive forms would also contain these constituents in their blood corpuscles and serum. The horsehoe crab (Limulus polyphemus) and the woolly bear caterpillar (Isia isabella) were chosen as suitable experimental animals both as to position in the animal scale and as to the ease with which sufficient blood could be obtained. The work on the horseshoe crab was carried out on 2 adult animals, and that on the caterpillars on pooled blood samples from 40 animals. Bloors 1 method was used in determining total cholesterol and Bloor and Knudsons 2 in determining cholesterol ester, both modified as to amount of material tested and amount of extractive used in anticipation of very low values. The results obtained are given in Tables I and II. Summary. The blood serum of Limulus polyphemus was found to be entirely free of cholesterol or cholesterol esters and thus differs from the blood sera of higher animals. The blood cells, however, contained free cholesterol and were similar to blood cells of higher animals in that they contained no cholesterol esters. Both blood cells and serum of the woolly bear caterpillar contained free cholesterol but no cholesterol ester was present.