Department of Medical Physics, Royal Perth Hospital, Western Australia, 6001,
Valendar F Turner, John Papadimitriou, Barry Page, David Causer, Helman Alfonso, Sam Mhlongo, Todd Miller, Christian Fiala
Send response to journal:
Re: Re: Further response to James Parker FeLV Horizontal Transmission
In his rapid response “Re: Further response to James Parker FeLV Horizontal Transmission”, 5th April 2004, he wrote: “Having commented on test and removal of FeLV infected cats in paragraph three as reported in 1977 by Jarrett, Hardy and Essex, she dismisses this in paragraph four. 'Since the disease may be caused by other factors, it means that either decreasing or increasing the incidence of disease in a household by either removal or addition of cats is not proof that the disease is caused by FeLV...' What other factors ?”
We do not know “what other factors” and in regard to our argument it is not necessary to know. The important point is that there are factors other than FeLV which cause leukemia in the cats. (1)
James Parker wrote: “FeLV appears to produce a spectrum of reaction in cats which varies from the development of natural immunity with the development of feline oncarnovirus membrane associated antigen (FOCMA) antibodies to anaemia, runting syndrome, immunodeficiency, thymic atrophy, infectious peritonitis, panleukopoenia leukaemia and lymphosarcoma etc. In Hardy et al's paper in Nature ( Sept 23 1976 263 326-328 ) 'Prevention of the contagious spread of feline leukaemia virus and the development of leukaemia in pet cats all the FeLV associated conditions were removed from the 51 households under study. Also all the FeLV associated conditions remained in the 25 control households. This point is worthy of emphasis.”
Note that James Parker makes the assumption without any proof that various diseases are produced by FeLV (he uses the phrase “appears to produce”). Based on this assumption, he then proceeds to emphasise the “removal” experiments of Hardy et al. We repeat what we said in a previous rapid response (see “Further response to James Parker”, 1st April 2004) that “removal” programs cannot be used to prove horizontal transmission.
James Parker wrote: “When Jarrett wrote in 1975 ' in the Glasgow urban area between 10% and 40% of normal cats have antibody titres to FeLV whereas the leukaemia incidence is only 0.05%', he did not conclude that no proof exists that FeLV causes the disease (these are Perth inferences).”
We did not infer that Jarrett concluded that “no proof exists that FeLV causes the disease”. We quoted that Jarrett, Hardy, Essex et al themselves concluded: “Thus the incidence of leukemia in cats bears little relation to the frequency of FeLV infection.” Also we quoted again that in 1973, Hardy, Essex et al stated: “Whether the exogenous FeLV induces lymphosarcoma or activates an endogenous virus which does so, is an open question”.
James Parker wrote: “He had induced disease experimentally by inoculation of FeLV as far back as 1964 and also by the introduction of diseased animals in uninfected households.”
In 1964 Jarrett et al performed the following experiment:
“The mediastinal mass was removed aseptically and stored for 5 days at -40° C. It was then divided into smaller pieces and stored for 66 days in 50% glycerol and 0.1 M phosphate buffer (pH 6.8) at -10° C. A one-tenth suspension in 0.1 M phosphate buffer was prepared by hand grinding in a mortar and was centrifuged for 30 min at 2,000g. The supernatant was stored for one day at -40° C. Each of the four kittens of a litter was injected with 0.5 ml of this supernatant subcutaneously over the ribs within 12 h of birth.”
Pathological changes in the four cats were described which were said to be consistent with leukemia (lymphosarcoma). The authors concluded: “These findings may indicate the transmission of a spontaneous multicentric lymphosarcoma”. But they expressed doubts about this conclusion because “it is impossible to be completely sure that the inoculum did not contain a few living cells which survived freezing and homogenisation. Filtration and high-speed centrifugation were not used in this initial experiment as it was thought that they might decrease the titre of any infective agent which might be present.” (2) (Note that even if filtration was used, this does not exclude the possibility that factors other than a virus as Rous pointed out in 1911 (3)).
In another publication, “A Virus-like Particle associated with Leukaemia (Lymphosarcoma), Jarrett et al wrote: “The preceding communication reported the probable transmission of lymphosarcoma in cats. In the one animal which developed the full clinico-pathological syndrome, ultra-thin sections of cells forming the mesenteric node mass were examined with the electron microscope and particles were found….The nucleus filled most of the cell and in the cytoplasm of many cells there was a highly vesiculated area. This region was only evident in a proportion of the cells in any one section, but it was in it that virus-like particles were usually found. These particles were enclosed in the vesicles, often in groups, and were not apparent either free in the cytoplasm or in the intercellular spaces….The outer diameter of the nucleoid measured about 60 mm and that of the whole particle approximately 100 mm.”
It is clear that whatever these particles were, they could not have been retrovirus particles.
James Parker wrote: “Antibodies to gs antigen not proven to be specific, EM particles commonplace and not proven to be infectious and since the FOCMA antigens are cellular and not viral (Essex et al), finding antibodies to them cannot be considered proof for FeLV infection” and then added (Perth opinion).”
That is, he infers that this is just the “Perth opinion”. Would please James Parker provide references to the contrary, that is, which prove that the FOCMA antigens are viral, that the antibodies and the particles are specific to FeLV?
James Parker wrote: “FOCMA -Feline oncarnovirus ASSOCIATED membrane antigen. As Eleni Papadopulos-Eleopulos is probably well aware, there is an inverse correlation between antibody to this antigen and the development of FeLV related disease and elaboration of a vaccine based on this has been available for over 20 years.”
Would please James Parker provide references in which vaccines based on FOCMA led to the control of leukemia in cats?
Furthermore, since “of greater significance has been the observation that FeLV-negative lymphoid tumor cells have regularly been positive for FOCMA” (1), then would please James Parker explain why if such vaccines exist, they have anything to do with a virus, FeLV?
James Parker wrote: “Eleni Papadopulos-Eleopulos reporting on Jarrett et al's paper in J Nat Cancer Inst(1973 51 833-841) is critical of lack of proper controls. In discussing Experiment 6 ,in which a seriously ill cat in the terminal stages of alimentary lymphoblastic lymphosarcoma was put in a house with 4 healthy unrelated adult cats (FeLV negative), three of the cats developed positive EM for virus at week 3 and the fourth a positive FOCMA antibody titre (0.16) at week 4. She denies the claim of horizontal transmission because the seriously ill cat was not reported to be FeLV infected. On reviewing the paper in question I cannot find any evidence that this cat was or was not tested for FeLV. It was obviously presumed to be infected. If this experiment were repeated and the index cat appropriately tested positive would Eleni Papadopulos-Eleopulos then accept this as evidence of horizontal transmission of FeLV ?”
1. Essex M, (1980). Feline Leukemia and Sarcoma Viruses, in Viral Oncology, edited by George Klein, Ravin Press, New York, pp205-229.
2. Jarrett WFH, Martin WB, Crighton GW, Dalton RG, Stewart MF. (1964). Transmission Experiments with Leukaemia (Lymphosarcoma). Nature 202, 566-567.
3. Rous P. (1911). A Sarcoma of the Fowl transmissible by an agent separable from the Tumor Cells. J Exp Med 13:397-411.
Competing interests: None declared