Further response to James Parker 1 April 2004
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Eleni Papadopulos-Eleopulos,
Biophysicist
Royal Perth Hospital, Western Australia, 6001,
Valendar F Turner, John Papadimitriou, Barry Page, David Causer, Helman Alfonso, Sam Mhlongo, Todd Miller, Christian Fiala

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Re: Further response to James Parker

Further response to James Parker

 

In his rapid response “Re: Re: Horizontal Transmission? Reply to Perth”, 26th7 March 2004, James Parker wrote: “Proving Koch's postulates to everyone's satisfaction is a problem when dealing with diseases which have a long period of latency. While it is perhaps easier to comprehend in the case of FeLV infected cats where this may be up to 4 years, in the HIV 'infected' human this may be 12-15 years or longer.”

 

In a 1977 paper entitled “Leukemia, Lymphoma, and Fibrosarcoma of Cats as Models for Similar Diseases of Man” by Essex, Hardy and their associates, they wrote: “About a third of the feline lymphoproliferative tumors are negative for both visually discernible virus particles (by electron microscopy) and virus structural proteins (by serological techniques).   Thus, since the evidence that this proportion of the spontaneous tumors are also caused by the feline leukemia virus (FeLV) is very strong, a nonproducer model is also available for study.” (1)  This means that FeLV does not fulfil even the 1st Koch postulate.  

 

Most, if not all, of the evidence which is said to prove horizontal transmission has been published by Jarrett, Hardy, and Essex and their colleagues.   In their 1977 paper, Essex, Hardy, et al wrote: “The evidence that spontaneous leukemia and lymphoma of cats are caused by horizontally transmitted viruses is now overwhelming…The first suggestions for this came when a few clusters of these diseases were reported…Further proof that both FeLV and the diseases it causes are horizontally transmitted was obtained by demonstrating that FeLV infections could be prevented by the removal of carrier animals from the exposure environment…To test the effect of natural exposure of older cats to FeLV, we placed ten 4-month-old cats in a leukemia-cluster household…All ten displayed evidence of infection by several criteria”. (1)

 

Since the disease may be caused by other factors, it means that either decreasing or increasing the incidence of the disease in a household by either removal or addition of cats is not proof that the disease is caused by FeLV or that FeLV is horizontally transmitted as succinctly illustrated in Mark Bartlett’s rapid response “Re: Re: Re: Horizontal Transmission ? Reply to Perth”, 28 March 2004.    The ‘test and removal’ program tells us even less about the specificity of the antibody tests.   One can also place a sure "bet" that introducing ten healthy sailors to an 18th century, scurvy ridden ship would also result in "evidence of infection by several criteria". And that such "infection" would be cured by their timely removal.

 

Jarrett wrote in a 1975 paper: “Infection has been conclusively proved to be accomplished horizontally from cat to cat (Jarrett et al, 1973b)”.(2)   In the 1973 paper, Jarrett, Hardy, Essex et al performed several experiments in which cats inoculated  with FeLV were housed with non-inoculated cats.    In 3 out of the 4 experiments, the inoculum consisted of culture fluid containing “105 particles per ml was concentrated 100 times.   Each cat received 0.5 ml.”   For the other experiment, “the inoculum used was a platelet preparation” of FeLV. (3)     Both the inoculated cats and the non-inoculated cats were repeatedly examined over a period of time for the appearance of disease and infection.

 

Disease

A small number of the inoculated and non-inoculated cats developed neoplasm.   However:

As we already mentioned in our rapid response “Re: Horizontal Transmission?” 23 March 2004, 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” (4).

In 1975 Jarrett wrote: “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%”. (2)

We have already pointed out that FeLV does not fulfil Koch’s 1st postulate.

 

In other words, no relationship exists between FeLV and leukemia, no proof exists that FeLV causes the disease.  Jarrett, Hardy, Essex et al themselves concluded “Thus the incidence of leukemia in cats bears little relation to the frequency of FeLV infection.”

 

Infection

Some but not all of the inoculated and non-inoculated cats were reported as infected.    A positive result in one or more of the following was considered proof of infection:

Antibodies to group-specific antigens.

Particles visualized by electron microscopy (usually “virus-positive platelets on EM”).

Antibodies to FOCMA (feline oncornavirus-associated cell-membrane antigen).

 

Neither Hardy nor Jarrett nor Essex have ever proven that the antibodies which react with the group-specific antigens (gsa) are specific to these antigens or are cross-reacting antibodies present in the cats including auto-antibodies and other antibodies appearing as a result of lymphosarcoma or the many other diseases from which the household cats were suffering. Even if there were viral antibodies, they may have been antibodies directed against other retroviruses such as feline immunodeficiency virus or endogenous retroviruses  activated by the surrounding conditions including the stress of being in a crowded enclosure.   For example, in one experiment where the housing conditions are given, 10 cats were “kept together in a house 6x6x8 feet high” for 34 weeks.     As Jarrett himself pointed out: “…all of the mouse viruses have cross reacting gsa’s, as have all of the cat.” (2)

 

The finding in animal tissue of particles with the morphology of retroviruses is commonplace as Ludwig Gross has shown it repeatedly in his extensive work. (5).   However there is no proof that these particles are infectious, that is, that they are horizontally transmitted.

 

Since the FOCMA antigens are cellular and not viral (1), finding antibodies to them cannot be considered proof for FeLV infection.

 

Perhaps the main failure in their experiment was the lack of proper controls.    FeLV-negative cats should have been injected with inoculum obtained from diseased FeLV-negative cats.   These cats should have been housed with FeLV-negative cats and followed in exactly the same manner as their experimental cats.    The experimental and the control cats should have been kept in exactly the same conditions and fed the same foods.

 

Discussing their above experimental findings, Jarrett, Hardy, Essex et al wrote: “To determine that our results were not experimental artifacts…”, “A seriously ill cat, in the terminal stages of alimentary lymphoblastic lymphosarcoma, was put in a house 4x6x8 feet with 4 healthy, unrelated, adult cats of about 6 months of age.”    The 4 healthy cats were FeLV-negative.   “The sick cat, remaining recumbent during the 7 days it survived, never showed any aggression toward the other cats, which, in turn, did not show any particular interest in the sick animal.   For humane reasons, this sick cat was treated with pethidine during this time.   It died during the 8th night and, when found, was not suitable for detailed examination for virus.   The in-contact cats were allowed to live for a further 2 months…All cats became infected by this short exposure (table 8).”    However, the data in table 8 shows that at 0 and 2 weeks, all 4 cats were negative by both EM and FOCMA antibodies.   At 4 weeks, cats 1-3 were EM positive while cat 4 remained EM negative and all 4 cats remained FOCMA antibody negative.   At 6 weeks, cats 1-3 became negative for both EM and FOCMA antibodies while cat 4 was EM negative and FOCMA antibody positive.   At 8 weeks, cats 1-2 were EM positive and FOCMA antibody negative, cats 3-4 were EM negative and FOCMA antibody positive.   Even if we assume that this data proves infection of cats 1-4, the claim for horizontal transmission has not been proven since the seriously ill cat was never reported as being FeLV infected. 

                   

 

TABLE 8 - Virus and FOCMA antibody in 4 normal cats after contact with a cat with  naturally occurring lymphosarcoma

 

 

Cat

 

Time (wk)

 

     0                    2                  4                   6                  8                                        

 

Virus:Titer    Virus:Titer    Virus:Titer   Virus:Titer  Virus:Titer

 

1

2

3

4

 

0:0

0:0

0:0

0:0

 

0:0

0:0

0:0

0:0

 

+:0

+:0

+:0

0:0

 

0:0

0:0

0:0

0:16

 

+:0

+:0

0:4

0:16

           

Note: Virus = positive EM;  Titer =  FOCMA antibody titre

 

 James Parker wrote: “While I do not have an epidemiological study to present (I would defer to someone like Brian Foley), I have a newspaper cutting from the Toronto Globe & Mail (March 15 1994) with the large headline 'AIDS widow awarded $500.000'. This outlined a situation in which a man died of HIV related pneumonia, without knowing he was infected by a tainted blood transfusion received during previous surgery in 1984. His widow was probably infected in the last year of his life. Interviewed on the radio a week or so ago she is now receiving AIDS therapy. Does this answer the final question posed -which of the Perth group's views are dangerous and why ?”

 

No.

 

References

Essex M, Cotter SM, Stephenson JR, Aaronson SA, Hardy WD (1977). Leukemia, Lymphoma, and Fibrosarcoma of Cats as Models for Similar Diseases of Man. Proceedings of Cold Spring Harbour Conferences in Cell Proliferation, Vol. 4, 1197-1214.

Jarrett WFH (1975).  The Relation of Immune Response to Pathogenesis, Vaccination and Epidemiology in Virus Induced Leukaemia. Br J Cancer 31, Suppl. II, 147-151.

Jarrett W, Jarret O, Mackey L, Laird H, Hardy W, Essex M (1973). Horizontal Transmission of Leukemia Virus and Leukemia in the Cat.   J Natl Cancer Inst 51, 833-841.

Hardy WD, Old LJ, Hess PW, Essex M, Cotter S (1973).  Horizontal Transmission of Feline Leukaemia Virus.   Nature 244, 266-269.

Gross L.  Oncogenic Viruses.  2nd Edition, Pergamon Press, 1970.

Competing interests: None declared