Infectious Disease Postdoc/Clinician
Department of Pediatrics, University Hospital, Syracuse NY
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Reading Mr Russell's recent responses has been very revealing - in his zealous quest to deconstruct HIV and AIDS he manages to deconstruct most of his own arguments as well.
As mentioned in past responses - both ATL and AIDS were described prior to the discovery of their causative retroviruses.
Duesberg's anti-HTLV arguments are illogical for three reasons:
1. No-one is claiming that HTLV causes all cases of ATL. Fundamentally, ATL is just T cell leukaemia in adults...you can get the same thing from radiation exposure.
2. Cancer is not caused by a single mutation - the current understanding is that multiple errors are required to cause cancer. Duesberg is arguing from his experience with Src which is the most powerful oncogene yet discovered. One could argue that it was discovered first because of the very fact its effects were so profound. HTLV infection results in an increased risk of further mutations, which may then later result in cancer. By definition almost, cancer MUST be monoclonal, or else it's just a hyperplasia (e.g. the B cell mononucleosis seen in EBV infection is very different from the Burkitt's lymphoma seen in EBV infection).
The error rate for cellular DNA is so small that statistically speaking, the number of functional errors (i.e. affecting proto-oncogenes or tumour supressor genes) required for a human cancer, currently thought to be at least 5 or 6, could not have occured in a single cell in a single human being in the history of mankind. One of the most important events in oncogenesis is the increasing of the mutation rate or a reduction in the error correction. Such virus-cell interactions are common occurances in viral infections (e.g. p53 or Rb inhibition, immune surveillance evasion). This is why cells undergoing cycling are more likely to cause cancer (e.g. bowel mucosa, repairing sun-damaged skin, activated lymphocytes). Every DNA duplication has a risk of introducing mutations. This is also why viral infections that interfere with normal cellular function increase the risk of cancer.
In addition, certain behaviours are required to form a cancerous cell. Cancer cells must be able to divide, lack contact inhibition, not require contact to survive and invade new tissues (hence a good handful of gene mutations!). Lymphocytes can already survive autonomously in the bloodstream, invade tissues, and can avoid apoptosis without cellular contact. This is why leukaemias/lymphomas are so readily created (e.g. a single 15:17 translocation in Acute Myelocytic Leukaemia) and treated (retinoic acid for the above cancer results in around an 80% cure rate). RA-resistant cases have, as you would expect, more complex mutations. Knowing this, it's not surprisingly at all that the cancers with the best cure rates are leukaemias, they are very well characterised genetically, and relatively easily created by environmental exposures (including viral infections).
3. HTLV is far from a simple retrovirus (it encodes 2 accessory proteins, so is very different from Duesberg's RSV). It may not encode an oncogene, but it certainly encodes a another protein (tax) which interferes with a tumour suppressor - which can be pretty much the same thing. It targets the mitotic checkpoint protein MAD1.
To paraphrase Mr Russell, Prof Duesberg and Peter Vogt thought that retroviruses existed as exogenous entities and worked with them all their lives, presumably they knew what they were talking about. They did after all discover oncogenes by analysing genomes isolated from retroviruses which had captured mutated versions of cellular genes... Retroviruses after all have a life cycle almost perfectly suited to capturing cellular proto-oncogenes - in fact are required to explain the formation of the viral versions of genes like src.
Mr Russell cannot persist in cherry-picking the literature to suit his world view - he would be better off analysing all the literature to create a more appropriate world view. That would be called: "getting some form, any form of education at all in the field".
Far from being "trapped in a paradigm", I find that being able to explain the paradigm is rather liberating.
I should also take the opportunity to point out that I'm an infectious disease postdoctoral clinical research associate, not yet a Fellow even if the workload overlaps somewhat.
Nick Bennett firstname.lastname@example.org
Competing interests: None declared