This is Dr William Weir's synopsis of the IiME Conference, written for the lay audience in N. Ireland. Permission to repost. INVEST IN ME CONFERENCE Synopsis of proceedings of 8th International Conference held on 31st May 2013. Dr William Weir FRCP (Lond) FRCP (Edin) The main theme of this conference focused on the three burning questions which all ME sufferers want answered, namely what causes ME, what is being done to discover this cause and what treatments might be effective? What was very encouraging was the impressive cast of speakers from around the world whose scientific credentials could not be challenged. Happily, none of them were psychiatrists, as gradually the psychiatric, biopsychosocial theory of ME causation is being consigned to the dustbin of history. There is now far too much high quality scientific evidence indicating that ME is due to immunological dysfunction and many of the speakers stated this principle very forcefully. There were four main categories of speaker. Firstly there were those who talked about the organization of studies, which included the collection and computerisation of data (such as case histories) and biological material (such as blood and other body fluid samples). Clearly, in the USA at least, work of this nature is now getting off the ground and a large effort is being made to establish a “biobank” of biological materials from patients which will be made available to researchers. Here in the UK a biobank has already been set up, based at the London School of Hygiene and Tropical Medicine to where blood samples are being sent for cold storage. Secondly there were the immunologists who described the immunological abnormalities seen in ME patients. One of the frustrations with ME is that, although there are always across-the-board abnormalities, those seen are never as consistent as they are, for example in AIDS where one particular type of immunologically active cell is consistently reduced. However one of the speakers came out with the opinion that: “if any doctor now thinks that these abnormalities are due to psychological disorder and that exercise is the cure, he/she should be deregistered” (He was from Australia). One phenomenon which is now well recognised is the “cytokine flare” which follows physical (and mental) exercise. Cytokines are substances produced by the immune system as part of a normal immune response to the presence of an invading bug, be it a virus or bacterium (or other, such as a malaria parasite). Interferon is the one most people have heard of. They make you feel ill as part of the body’s normal defence against infection. In ME however they appear to be produced inappropriately, and go on being produced in the apparent absence of a recognisable infection. Furthermore there is an abnormal increase - “flare” - after exercise which now explains the problem of post exertional malaise. Here, at last, is direct evidence that Graded Exercise Therapy (GET) is very likely to be harmful. Thirdly the issue of a possible virus infection was addressed. This would provide a logical explanation for the ongoing immunological activity – finally identifying the metaphorical fire from which all the immunological smoke was coming. The XMRV story was reviewed and provided real insights into the complexities of identifying a “new” virus. The term “new” meaning hitherto undiscovered, as it is fully appreciated that there are probably very many undiscovered viruses out there in the biological ecosystem, often being carried silently (ie without illness) by a large range of animals, including humans. The disease -causing potential of these viruses is unknown and may have very long incubation periods with infection preceding the development of disease by many years. For example It has been suggested that Parkinson’s disease is due to such a virus, and the same may be true of ME. As many will know, XMRV was finally recognised as a contaminant of the cultures in which attempts were being made to grow a new virus from samples taken from ME patients. The initial excitement over the discovery of XMRV was dampened when this was realized, but has not deterred the search for other viruses. To apply historical perspective, when influenza was first researched, a number of bacteria and viruses were initially but incorrectly proposed as the cause before the real villain was identified. Some very sophisticated techniques are now being used in the search for the real ME villain, one candidate being a form of retrovirus known as a “human endogenous retrovirus” (HERV). These are viruses which are already present in human genes, and usually inactive (ie not replicating). Nonetheless they probably can be turned on again and they have been postulated as causes of a wide range of diseases, including cancer and autoimmune disease. Thus ME may well be due to a HERV. Finally there was a presentation of the Norwegian study of rituximab therapy which shows promise in the treatment of ME. Twenty of twenty eight patients improved significantly although there was a lag period of two to three months before improvement occurred. Rituximab specifically targets the CD20 lymphocytes, taking them out of circulation but well before symptomatic improvement – suggesting that it is antibodies produced by the CD20 cells which cause the symptoms, but which require the 2-3 month period to clear from the body. This study on its own supports the immunological hypothesis of causation, further diminishing the psychiatric attribution of an “abnormal illness belief”. Rituximab does however have its drawbacks. It is potentially very toxic, also very expensive and no UK doctor would be able to prescribe it for ME at present. Further studies are in progress. Watch this space!