Biotherapy Vol. 9, 1996. TRANSFER FACTOR IN THE ERA OF AIDS FOREWORD Giancarlo Pizza, Dimitri Viza Dogs bark only at the unknown. Heraclitus At the turn of the century, when reductionism and molecular biology have proven their efficacy to the satisfaction of many, transfer factor remains an irksome concept. Forty years after the original and seminal observation relating to the ability of leucocyte dialysates to transfer specific immunity from a sensitive donor to a naive recipient, thus forging the transfer factor concept and describing for the first time a lymphokine, the spectrum of activities of the dialysable leucocyte extracts has been considerably widened, whilst the controversy concerning the mode of action and the carrier molecules remains more vivid then ever. Indeed, to the initial antigen-specific transfer phenomenon, several other effects have been described since, calling for the identification of the carriers. It would seem that for each T lymphocyte subpopulation, viz. helper, cytotoxic and suppressor correspond dialysable lymphokines with antigen-specific, and probably also non-specific activities. However, because the molecular structure of the moieties responsible for the antigen-specific transfer remains elusive, and their putative mode of action challenges accepted beliefs, the transfer factor concept has become the target of unsubstantiated intellectual prejudice, and this despite the characterization of molecules within the dialysates exercising important non-specific effects on cell mediated immunity. As a consequence of the rejection of the concept, lack of funding followed suite, making further progress in the field quasi-impossible. Ironically, the logic forbidding the existence of transfer factor, applied to prions, a proteinaceous infectious agent whose activity contravenes accepted dogmas, should lead to similar wariness and critical rejection, making the Creutzfeldt-Jakob disease, bovine spongiform encephalopathy or scrapie mere antifacts, and thus preventing funding of research on this topic. Despite this state of affairs, investigators and clinicians throughout the world are still interested in the extraordinary properties of dialysable leucocyte extracts. One should see here the unabated health of the scientific spirit, since some scientists and clinical investigators have jeopardized their careers for the sake of their belief in facts, rather than in consensual theories. The Bologna Symposium bore witness to this spirit, viz. that a scientific problem cannot be buried under unsubstantiated rumours and the censorship of orthodoxy. Nonetheless, the 'transfer factor battle' will not be won until such a time when the molecular structure of all the moieties within the leucocyte dialysates will be unravelled and their mechanism of action at the cellular and molecular level understood. Meanwhile, the results of the laboratories that can afford to withstand the pressure of consensus and continue to work on the subject show that the observations published in the 70's and 80's were not mere artifacts due to the incompetence of the pre-AIDS era scientists. Rather, the clinical results reported herein suggest that transfer factor, the initial moiety, as well as the other lymphokines within the dialysable leucocyte extracts, have an important role to play in modem medicine, which from AIDS to Ebola faces the emergence of new viruses or the resurfacing of old pathologies such as tuberculosis, whilst strange prion-like entities threaten humans and their cattle.