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Biochemical, inhibition, inhibitor resistance studies XMRV reverse transcriptase

Discussion in 'XMRV Research and Replication Studies' started by Jemal, Sep 9, 2011.

  1. Bob

    Bob

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    Good question Daffodil... That's what I'd like to know! (I still haven't read the paper!)
     
  2. ukxmrv

    ukxmrv Senior Member

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    There have also been concerns raised about taking some of the anti-herpes drugs (like Valtrex, Valctye etc) and possible drug resistance for future anti-retrovirals.

    We just don't know what the future will bring and what we will discover.

    What I do know is that I am not getting any younger. I'm taking Valtrex because it is making enough difference now for me to take the risk. It may be proven later on that Valtrex causes resistance to specific anti-retroviral drugs. No idea and if so, will there be alternatives - who knows? .

    As time goes on (years that is) I may make the decision to start on anti-retroviral drugs without the benefits of clinical trials purely because of my age and very low quality of my current functioning. It's a risk that patients need information on to weigh up the benefits and risks. The question is will we get that information with in our current life spans?

    If XMRV is shown to play a major part in ME either as the cause or a co-infection how many of us will be alive to see the end of clinical trials and treatment and still have enough life left to benefit from this? We just don't know.

    I'm already taking a calculated risk. Dead is still dead, even if it is after 40/50 years of a disease and not a quicker death like the early HIV patients.
     
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  3. Bob

    Bob

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    I totally relate to your experiences KFG. It always amazes me how so many of us have almost totally identical experiences of this illness, and almost totally identical life-experiences after getting ill.

    I describe it as feeling like permanently having severe flu, and a serious hangover.

    I've been ushered out of a sneering doctor's surgery because I was complaining of ongoing lung problems that apparently did not exist according to the doctor. On that occasion, it turned out that I had an undiagnosed clinically under-active thyroid (a couple of years after getting ME). It's a shame that the doctor who ushered me out didn't study my blood test results that were on his system! If I had been well enough, they would have had to answer a case of medical negligence.

    On that one occasion, I was proved right because in the end I diagnosed myself with thyroid problems and they discovered that my previous blood tests were out of range. So on that occasion it wasn't 'all in my mind' because the evidence was written down on paper. The only difference between that situation and our ME situation is that we don't have a biological marker, so corrupt 'scientists' and doctors get to enjoy accusing us of being mentally ill. Just one simple biomarker makes all that difference. It would instantly turn from the patient being 'mentally ill' to corruption and negligence on the part of the medical community. No wonder Wessely is fighting so hard right now.

    I agree with you... I think it's premature to take antiretrovirals... There's so many questions to be answered yet... But that's just my opinion, and knowing this illness, I would never judge someone for doing so.

    But I would wish them well.
     
  4. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    Ha. Good point.
     
  5. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    Bob, I am going to press this issue even further. I don't think its even a matter for opinion as far as individual patients are concerned. Forgive the comparison, but I think it's more akin to someone making a euthenasia decision to end their live with, say, drugs. Until you are desperate enough, and in the position of the person having to make the decision, it is not really possible to have a valid opinion.

    What is the difference between someone with very severe ME and someone with moderate ME? I have moderate to severe ME, but I can only imagine what sort of existence someone with severe ME has. And believe me, even though I have endured this illness for twenty years, I still read stories on the forums that shock me.

    I agree with you completely about how we should always post with sensitivity and empathy. I cringe at my own acerbic posts (when I try to redress a perceived wrong), because I know how emotionally sensitive patients are. And while I applaud the tolerance of the vast majority of forum members towards those posters deliberately and systematically providing information which misleads and misdirects, I believe to allow these posters to continue is wrong. Many patients are simply in too fragile a condition to sort the wheat from the chaff.

    Troll Alerts
    Many ME patients, even with deteriorating analytical skills, still retain the ability to perceive patterns. Look for patterns. I have a couple of rules which I apply to determine whether posters are bona fide, without having to evaluate technobabblespeak (the language of trolls):
    1. Is there any pattern to their posts? Eg, do they only provide negative information to studies supporting a biological cause of ME
    2. Do the posters write with empathy? Is the empathy real or contrived? Do the posters have an understanding of the illness? When a poster says something like "the illness is not serious", alarm bells should be ringing
    3. What is interest of the poster? Do they have ME? Are they trying to help ME patients? If not, it is difficult to perceive a positive agenda. Why is someone without ME posting on this site on a regular basis? Don't they have a life? Ironically this sort of poster either has a pretty major psychological issue or they have a personal agenda which is often commercial. Remember, self interest is what drives people usually, not altruism.
     
    Bob likes this.
  6. Bob

    Bob

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    Hi Rusty,
    That's pretty much what I said in my long post earlier, so I do agree with you.
    When I say that I think it's premature to take anti-retrovirals, I'm thinking about it from a practical point of view.
    (i.e. We don't know which ones or which combinations are effective against XMRV, and we don't even know if XMRV causes ME yet.)
    Bob


    I know where you are coming from Rusty.
     
  7. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    Yeah, sorry, didn't mean to sound like I was contradicting you, Bob. I did agree with everything you said except, of course, where you said it was premature to take anti-retrovirals, for your own treatment. And I think what you said, needed to be said. I know you weren't pushing your opinion onto anyone.

    To some extent I agree even on that point. I am not in a position financially to take antivirals, and I guess I also would have some trepidation about their effectiveness when it comes to forking out the hard earned dollars if I did have some money. However I will defend vigorously those patients who have taken the step. The bottom line for me is that the use of ARVs is the only treatment with a chance of working that I have seen in 20 years. Given this, then it is immoral for researchers come onto this site, given their systematic failure to explore the disease for more than thirty or forty years, and engage in hollow debate aimed at snuffing out the smallest chance we have of rejoining society.

    Not only are most of the anti-ARV arguments somewhat silly and contradictory, they also seem to shift around. First it was because they have no effect, then because they are dangerous, now because they will lead to resistence (which of course has only been proven in a couple of mutant strains and in vitro).
     
  8. redo

    redo Senior Member

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    You know what. I agree with you. I agree that it's most likely not right to try from a patient perspective. Some have got better (Deckoff-Jones and more), but others have got worse. There are also other things which yet are to be identified. I think the chances for resistance and the chances it might go a-rye are too big that it's worth it. But that's not what I am arguing. What I am arguing is that it's up to the patient and doctor to make decisions about pawing new paths in general - about this and about other treatments. And that the informed patient should have the final word - if the doctor is out of options, if the patient has no life worth living as it is (of course, this doesn't mean all CFS patients)- and is motivated, and if the patient can bring forth a reasonable explanation showing how it could work.

    This brings us really in many ways to politics. Should parachuting be allowed, if yes, what about BASE jumping etc. Of course there's a bigger reward for getting well from CFS than doing a base jump successfully, but the risks could be higher for treatment than jumping.

    I feel that something which makes the doctors less fit than they should be, in the decision making, is that they often care a lot more about themselves than the patients. They normally think; will I get some sort of reprimand if it doesn't go as planed, and what's in it for me it it goes well. I feel that the patients life is too little at the center (speaking in general terms, not just for CFS, but for cancer, MS and more), and the consideration should be mainly focused at that. One could argue that it's the system's fault, and not the doctors - and I to a large extent agree to that. But that said, I think the doctors should be sticking up for their patients more than they do currently, despite the system being like it is.

    Hoping we haven't sent the thread too much off topic now :D
     
  9. alex3619

    alex3619 Senior Member

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    Hi redo, but who is the "system"? Individual doctors are not the "system", but collectively they are most of it. Some more gets thrown in from government, societal attitudes, and insurance interests. Individual doctors are failing the "system" by not speaking out. Government is failing the "system" by not making the medical profession more accountable. We, as patients, are failing the "system" by not demanding better treatment. The insurance industry is failing the "system" by allowing patients to get worse over time and so cost more in the long run ... maybe not to the individual insurers, but to society as a whole (in which case the insurers are failing societal expectations).

    This is the second time I have tried to post this more general reply to the question of ARVs. The last time the window imploded. Was this an omen?

    Taking ARVs to treat ME is a non-issue. So few of us are taking them.

    For me, this is not an option at this point. With my current understanding, current symptoms, and current resources, the risk/benefit ratio is wrong. For someone else in a different situation, the risk/benefit ratio could be different.

    I have no moral issues with taking ARVs. If a patient is properly monitored by a doctor who knows a lot about ARV treatment, and if the patient has given informed consent, then I don't think there are any medical ethics issues either. There may be insurance/government issues around cost, but thats another problem entirely.

    Every drug has risk. So little is known about our pathophysiology that we often have severe adverse reactions to drugs. I know I have. The CDC recognized this long ago with respect to CFS (but not ME, which was never discussed by them in this context so far as I know). So any one of those "safe" drugs we get prescribed could make us worse or kill us. Its all about managing risk/benefit ratios, where the risk and benefits are both informed guesses at best.

    As to severity of illness, I have to regularly remind myself that the worst patients with ME are not represented on any forum - they have no voice, cannot even use a computer. Nobody who has not lived through that can possibly understand the pain and desperation. I only dimly understand it because at my worst I came close to that, but I have never fully experienced it.

    The issue is not entirely about XMRV/HGRVs though. Many diseases have a suspected retroviral component. Sjogren's Syndrome is now suspected of being retroviral, and is known to co-occur with HIV and HTLV infection. Not all of these patients have HIV or HTLV though. Sjogren's Syndrome frequently co-occurs with ME. Why has there not been a systematic large scale study into reverse transciptase prevalence in ME patients? While the new paper on this is only easily available as an abstract you can see an old paper at:

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC499817/pdf/jclinpath00252-0045.pdf

    Sicca Syndrome, which is similar but lacks the antibodies found in autoimmune Sjogren's Syndrome, is also suspected of being retroviral in origin. However other viruses are also implicated, so I do wonder if the issue is not another virus that is opportunistic due to retroviral suppression of the immune system.

    Society has an Euthanasia by Stealth approach to ME. Deny treatment, deny research funding, deny social support, label with pejoratives, treat patients in ways which aggravate their symptoms - and watch the suicide rate climb. It does not matter that this is not deliberately targeted at a specific group of very sick people for the most part, the effect is the same. This is a policy that drives us to suicide, and drives us to abject poverty where even minimal requirements of basic medical care and nutrition are impossible and so the normal death rate will climb. This is Euthanasia by Stealth.

    It would be more honest for society to open up euthanasia clinics, at least that would minimize the pain and suffering. I would not agree with such a policy, but it would reduce the pain and suffering, and reveal the hypocrisy in how society treats us. Just to be clear though, while I think euthanasia should be a legal option, it should not be driven by societal imperatives.

    There is very little epidemiological research into ME. There are a few studies that have looked at suicide rates (using various CFS criteria), and the results are all over the place. In Australia no study has looked at suicide, but one has looked at attempted suicide (many years ago) and reported that one in six long term CFS (not ME) patients had admitted to attempting suicide. The highest reported rate of suicide in the USA was about 20% of deaths, in a country in which ME patients are usually ignored. In the UK, where patients are usually mistreated, the highest reported suicide rate is over 30% if I recall correctly.

    Usual medical care is a risk for anyone with ME. So is not taking ARVs. I strongly suspect that most cases of suicide in ME and CFS are labelled as caused by depression, the circumstances which drive us there are rarely examined. There is an old saying: "doctors bury their mistakes". What happens when those mistakes are society wide, and driven by economic and political imperatives? That is why I call it Euthanasia by Stealth. It is not genocide because there is no intent, but the result is still the same. The "system", ultimately, is the responsibility of everyone in the "system". The doctors have the biggest responsibility since society expects them to act to improve the health of everyone.

    Let us not be fooled into thinking that taking ARVs is any kind of current issue. Clinical studies will move ahead if any retrovirus is strongly demonstrated to be involved in ME, and then we will have hard data. While I would not take ARVs as usual treatment, I am probably like many other patients in that I would be happy to take ARVs as part of a clinical trial. Taking ARVs is just one more risk: having ME is already high risk.

    In the meantime we should respect the wishes of anyone who has made the choice to take ARVs. I know I respect them.

    Bye
    Alex
     
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  10. Bob

    Bob

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    Great post Alex, thank you.
     
  11. redo

    redo Senior Member

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    When you ask I reply :Retro smile:. With the system, in the context I wrote, I mean those who set the rules for medical boards and those who sit on the medical boards. How medical licences can get revoked, or reprimands given, if a doctor steps out of line and does his best to help a patient. But for not giving a damn about their patients, they seldom get anything revoked, and rarely gets reprimands. There's something fundamentally wrong with that. This type of system only works when there's functioning procedure for every illness. If there is no procedure, and the doctor tries to help, it could mean trouble for them. You asked which system I was referring to when writing. And that's the one. And I also agree that there's a larger unofficial system, where doctors backtalk each other, and conformity is more often the pleasant way from a doctors perspective. The whole medical profession isn't exacly a breeding ground for new ideas, even when there are no exising ones for a certain disease.

    I agree. And have it's often I have thought about it. I was really going to become a MD before my illness, but seeing the way this iron claw hierarchy works (between doctors), I'd rather not. And I wont. I changed my mind, and I wont be part of it. I have also thought to myself that it's almost a crime to not speak out against it, if they are on the inside themselves. And the government is also to blame.

    +1 for your post Alex.
     
  12. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    Loved the post Alex.

    I am amazed that some forum members still cling to their beliefs in the system. I lost my innocence 6 months after I realized I had ME. Things have gone downhill since then. That was 20 years ago.

    Yet there are bright moments along the way: a good doctor, a caring psychiatrist, researchers who try to buck the system, ME patients who defy the odds with their life stories and messages of hope, mothers with ME raising autistic children against the odds, families moving to third world countries to survive, patients who suffer humiliations and illness yet manage to crack a joke and laugh at themselves and struggle on.

    That's what these forums are about!
     
  13. alex3619

    alex3619 Senior Member

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    Hi redo, much appreciated, and no disagreement from me with your arguments. ;) Bye, Alex
     
  14. In Vitro Infidelium

    In Vitro Infidelium Guest

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    What has that go to do with a discussion of a scientific paper ? Either the science is being discussed or it is not - there are no sensitivities involved that's the whole point of the scientific approach, of course on forums or sub forums where the purpose is discussion of personal suffering or difficulties or whatever, civility would require acknowledgement of the pain being expressed. But suffering of itself doesn't confer expressable scientific insight, and an expression of misery does not confer scientific authority. Those who want to be 'supportive', 'kind', 'sensitive', 'empathic' and 'thoughtful' have plenty of opportunity to demonstrate those qualities in other arenas without clogging up reasoned analysis with appeals to emotion.

    That's an absurd proposition, it creates a paradigm where one has to constantly second guess other people's, ignorance and/or, prejudice and/or wilful stupidity, it reduces scientific discussion to an exchange of platitudes and shared prejudices in which the display of disease stigmata confers holiness and any expression of disent with those who are stigmata empowered is presented as antithetical to the 'supportive', 'kind', 'sensitive', 'empathic' and 'thoughtful' true believers. "I'm sicker than you so don't disagree with me because my suffering has shown me the way".


    I see no confusion, just business as usual on an M.E/CFS forum with the usual pardigms rigidly complied with. Your assumption that I don't consider how what I write will be perceived by others is apparently based on your assumption that no one would write as I do, if only I truly understood - parhaps that's from your perspective, the real 'horror' - I will not play the emotional game (although of course there would be no reason to exclude someone from contributing on the basis of an incapacity to understand - say someone with ASD), I do undertstand how many M.E/CFS affected people will negatively perceive 95% of what I write - I'm not writing for popularity, I'm writing to convey a perspective, which may happen to appeal to a few readers.

    If I accept your's and Rusty's and other posters' demands to comply with the group approved qualification for posting content and style, then I have to abandon my perspective, I consider that requirement of abandonment to be both an unjustifiable censorship, and an unwarranted limitation on the diversity of who qualifies as an M.E/CFS affected person. Just because I happen to have a chronic illness (that is my claim) that happens to be currently poorly amenable to current science, doesn't mean I've got start liking puppies and kittens and worrying about people who write on the intenet about how awful things are - for all I know everyone writing here except me is troll. I hate pets and people who whinge about their illness - I find my own ill health fundamentally boring, why on earth would I want have to start taking someone else's unredemable misery seriously. I fully respect people's right to address their illess in their own terms, and that they may wish a discourse more reflective of Oprah Winfrey than Richard Dawkins, but why does that non scientific discourse have to have any place in discussions of science ? As to having to explain things to people, why ? If someone is intent on writing about something, it is reasonable that they take some effort to educate themselves without relying on others to do the work for them - and if someone is going to risk writing unalloyed drivel about something they have no real knowledge of, then they must be prepared for some harsh criticism along the way - to say otherwise is to deny personal responsibility.

    IVI
     
  15. In Vitro Infidelium

    In Vitro Infidelium Guest

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    One, because science is structured such that even where a high probability is suggested (in this case XMRV is not a pathogen), until the null hypothesis (in this case XMRV is a pathogen) is demonstrated to be false, scientists to accept the null hypothesis as having a degree of validity. There is a fundamental difference between saying "research on XMRV as a pathogen at this time is not an effective use of resources" and saying "XMRV is not now and never could be a pathogen". And two, because there is no way of knowing what other viral agency may be currently affecting someone with an illness of unknown aetiology, nor of what future susceptibility that individual may have, nor of what communicability any resistant organsm may have.
     
  16. In Vitro Infidelium

    In Vitro Infidelium Guest

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    This is a gross logical fallacy - "one can't understand unless one has had the experience". It's merely a rhetorical conflation of "understanding" with "experience" such that semantic meaning is lost, one may as well say "it's not possible to have an experience without having that experience". Personally whenever I come across this particular fallacy, I'm always struck with an image of a teenager slamming a door shouting 'no one understands me' - sadly for the teenage pretty much everyone aroud then does understand, its just that the teenage mind has difficulty in recognising that fact. Human beings are immensely capable of understanding without direct experience, all of us, except a few with major cognitive dysfunction, have a 'theory of mind'. Ironically this experience/understanding fallacy frequently underwrites a legitimisation of a highly solipsistic perspective - which is evident in the argument given above - of course an individual must (within certain legal limitations) be free to set the terms on which they pursue medical interventions, but in the case of drug resistance the issue is not exclusively solipsitic - communicability of resistant pathogens has also to be considered and that is a community health consideration which would neccessarily take precedence over any solipsistic demand. Suicide may be private matter, using ones body as a drug resistant pathogen factory is a decidedly public issue.


    Ah well that's me identfied as 'teh evil' and my eke well vardaed

    IVI
     
  17. alex3619

    alex3619 Senior Member

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    Hi IVI, here we are going to have to disagree. People just do not understand a lot of what we say. Intelligent people. I can discuss many issues relating to the ME experience, for many hours, answer many questions ... and at the end their questions and behaviour do not show any information has been understood. This is at the limits of the human capacity for developing a theory of mind, of understanding what another is going through. Yet I can sometimes get through very quickly to some people who do not have ME - including cancer survivors. They get it. What is the difference then?

    This is not new to human experience either. You can "understand" what it is like for a soldier in a war zone being shot at, watching his colleagues die from explosions, and the psychological trauma that follows. I challenge you to demonstrate that we all understand that from our theory of mind in anything like the quality of that soldier. We can have compassion, we can "understand", but the understanding is superficial. We can have a sufficient grasp of the language describing the event that we can call that understanding, but our understanding is rooted in our cognitive history, our experience, and so is theirs. Just because we use the same words does not imply we have the same understanding beyond the capacity for rudimentary verbal communication.

    Chimpanzees meet the technical specification of having a theory of mind. Do you think a chimpanzee has the same understanding of your mind, of your human experience, that you do?

    Let me give you an ME related issue to this point. I put the date of onset of what we are fairly sure is ME as 1932 - it doesn't matter if this is true or not. Lets say that it isn't, that ME did not exist till 1984, and this was reclassified as CFS. A discussion with patients will have quickly revealed that we do not respond well to activity (mental or physical) that is beyond our threshold. Our health crashes. Tens of thousands of doctors would have heard this story. Hundreds of researchers would have heard this story. So far as I know the first scientific study that used this patient claim, that tested it by looking at post exercise results, was in 2003, followed by 2006. Why did it take 19 (71?) years? If I were to go out there and ask doctors today what happens to patients after exercise, how many could describe it? One percent?

    Theory of mind does not infer understanding. It infers a limited functional understanding, a capacity to reason at some minimal level about others. People misunderstand other people all the time because theory of mind is JUST A MODEL. We are self deluding if we think we truly understand, we only kind of understand.

    So the claim that this is a solipsist fallacy is itself counter-factual. It does not accord with what we claim we understand of mind nor meaning. It relies on a gross oversimplification of the issues, and then results from simplistic reasoning on the vastly reduced data set.

    The flip side is also a risk though. I think I understand other patient's experience, and my own theory of mind tells me I do ... but the map is not the territory. We are in danger of creating dialogue that portrays each other's experience in certain ways without it being true. I don't think there is much of that going on, but I wouldn't be surprised if there were some. I do know that it took me quite a while to be sure that my understanding reflected other's understanding ... much of what we experience cannot even be put into words, and it takes a long time to realize that my non-spoken understanding is reflected in another. It doesn't take long at all though to realize that my non-spoken understanding is not reflected in another, their behaviour and language reveals the lack of understanding.

    On the issue of writing with consideration for feelings, I understand both sides of the debate. Science can't worry about feelings ... but there are better and worse ways to put things.

    Bye
    Alex
    ex AI researcher candidate,
    formerly working on cognitive modelling using composite neural networks
     
  18. mellster

    mellster Marco

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    I have to side with Alex here. Humans are great at understanding science, but they cannot understand how somebody else "feels" unless they had a similar experience and I believe this is actually a natural darwinistic protective mechanism.
     
  19. kaffiend

    kaffiend Senior Member

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    The whole theory of mind concept in humans derives (much of it overstated and poorly understood by cognitive scientists) from the work of neurophysiologist Giacomo Rizzolatti, who discovered mirror neurons in the monkey.

    No "mirror neurons" have ever been found in humans. However, the monkey brain has neurons that discharge not only when the monkey executes goal-related hand actions like grasping objects, but also when observing other individuals. Therefore, action observation triggers automatic activation of the same neural mechanisms of actual action execution. Cognitive scientists have taken this to mean that action observation constitutes a form of embodied simulation of action. Human brains certainly do a lot of this type of work, but it's not clear the extent to which language is involved. So, understanding is a complex interplay of language and simulation, varying greatly depending upon the particular context and experiential background of the individual.

    Colleagues of mine using fMRI have found distinct networks for recalling actions from a story vs. personally experienced actions. As Alex writes, experiences related through others are filtered through our own "model", a model which is wrong (all models are wrong; some are better than others).

    From personal experience, I would not have believed how disabling this condition could be if I did not experience it first-hand. My mother has MS and I have a newfound appreciation for her fatigue levels and general disability.
     
  20. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    IVI, you respond to claims that you don't understand how we feel with a philosophical discourse??? I'm not sure how this is supposed to convince anyone.
     

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