This section is from the book "Symposium Phenomena Of The Tumor Viruses", by U.S. Dept. of Health. Also available from Amazon: Tumor Suppressing Viruses, Genes, and Drugs: Innovative Cancer Therapy Approaches.
In addition, similar changes-i.e., a similar developmental cycle-take place in renal adenocarcinoma induced in chickens by the myeloblastosis virus. Thus, it appears that there is some uniformity in what might be described as the developmental cycle in this group of viruses.
Dr. Bonar: It is interesting that there seem to be some developmental relationships, even as there are morphologic and serologic relationships among the virus particles themselves. But someone suggested that we are dealing with a unique cell. This is certainly true, though I suppose we must regard each cell type as unique. In the normal course of events, as the myeloblast matures, it has the capacity to form granules. We do not know yet what relationship these structures in the myeloblasts may have to the bodies of similar appearance in erythroblastosis or other chicken tumors. It is tempting to speculate that the malignancy of the myeloblast is due to the inhibition of maturation of the granules and thereby the maturation of the cell.
Dr. Beard: I would modify that somewhat-not the inhibition of the maturation of the granules, but the inhibition of the maturation process of the total cell which includes maturation and the formation of granules.
Dr. Miroff (University of North Dakota): Dr. Bonar, you mentioned that you saw lipoid bodies in these infected cells. Do you find these generally associated with infected cells?
Dr. Bonar: They are rather frequent in these cells.
Dr. Miroff: Are they more prevalent when you see more virus particles?
Dr. Bonar: Generally they are not so numerous in the rapidly growing cultures. They are more apt to be seen in the circulating cells in the diseased chicken or in cells which are not growing. This has not really been quantitated, but it is my impression that they are less common in the growing cultures.
Dr. Gemile Haddad: In some of the pictures Dr. Bonar showed, the viroplasts were vacuolated and contained virus particles. I wonder whether the particles should be considered intracellular or extracellular. This may be only of academic importance, but if they are to be regarded as extracellular, the relationship would be analogous, say, to food in the human stomach, which is extraorganismal rather than intraor-ganismal.
Dr. Bonar: This is a matter largely of terminology but still of interest. The question might be asked whether the cristae of the mitochondria are intra- or extracellular on the same basis. I do not know how to answer your question.
Dr. Banfield (National Institutes of Health): In the structures which you referred to as the very early gray bodies with a dense membrane and a rather granular center, there is a similar structure, almost identical, which is seen in cells infected with molluscum contagiosum. These have been described by Dourmashkin, and he has attributed their origin to mitochondria, but with what evidence, I am not aware.
There is also a tissue-culture cell, grown by Dr. Dawe, that contains many bodies identical to the gray bodies and even contains particles like those which can be called virus-like particles. This is a cell derived from a mouse lymphoma.
Dr. Scherer: Have you observed that cells containing viruses undergo mitosis?
Dr. Bonar: Yes. It was probably because of the low magnification of those two cells in mitosis that you were not able to see the virus particles. However, they did contain the typical structures which we have observed in the purified virus preparations and which have been definitely associated with infectivity.
Dr. Dalton (National Institutes of Health): In all these situations as they have been described by Dr. Haguenau and you, the respective cells have been in tissue culture. As I understand it, this whole group of avian viruses is presumably derived from a common source or have basic similarities. Yet, it has already been described that, in erythroblastosis, particles do bud out from a surface membrane. What do you think about the possibility that the tissue-culture situation may be a special one and that, under conditions in the host in vivo, the actual life cycle might possibly be different?
Dr. Bonar: The results with erythroblastosis really suggest the need for considerable caution in judging the quantitative importance of various aspects of virus production. Dr. Heine in our laboratory has observed that different cultures of erythroblasts may show differences in the frequency of budding in relation to other possible modes of virus formation. In the examination of hundreds of pictures of myeloblasts, there were three suggestive of the occurrence of buds. Conceivably, then, this process may occur in myeloblastosis as well.
Examination of cells in various tissues of birds with myeloblastosis has not shown budding, but the sampling problem in electron microscopy is such that we may have missed it, and there are other tissues which we have not examined.
Dr. Murray (Columbia University): Since mitochondria seem to be so important to some of our discussions, would Dr. Palade have a suggestion or a statement as to the origin, the genesis of mitochondria? Would he tell us where they come from, where they go, and whether they are self-perpetuating?
Dr. Palade: The best evidence so far available indicates that mitochondria are self-perpetuating bodies resulting from other mitochondria that preceded them. It is interesting in this respect to note that in the life of an animal cell there is no stage at which the mitochondria disappear.
Experiments, performed sometime ago by Ethel Harvey, have been interpreted as evidence for the view that mitochondria can arise de novo in the cytoplasmic matrix.
Dr. Harvey centrifuged Arbacia eggs until they broke into two halves with all the mitochondria apparently sediinented in the heavy halves. The light halves, which, by the way, contained the lipide inclusions of the eggs, developed into embryos upon fertilization, and in the cells of these embryos, mitochondria could be convincingly demonstrated. Since the cells were derived from apparently mitochondrion-free eggs, it was concluded that their chondriome arose de novo. But more recently, light halves of Arbacia eggs have been examined by electron microscopy and found to possess mitochondria closely associated with their lipide inclusions. Therefore, the original interpretation of the experiment is now in serious doubt.
So here the evidence rests for the moment. We tentatively assume that any mitochondrion derives from a preceding mitochondrion, but we should realize that the assumption is based primarily on the lack of clear evidence to the contrary.
The virus-induced leukemia of Swiss mice is at present being studied in several laboratories, with different approaches. As part of this team work, the electron microscopists can provide information dealing with the control of biological experiments or with the purely morphologic description of the virus. Since the former findings on this leukemia have been reported (IS), this paper will deal only with electron microscope observations on material prepared with the techniques previously described (1,2).