PT - JOURNAL ARTICLE AU - Johan P Mackenbach TI - The origins of human disease: a short story on “where diseases come from” AID - 10.1136/jech.2005.038661 DP - 2006 Jan 01 TA - Journal of Epidemiology and Community Health PG - 81--86 VI - 60 IP - 1 4099 - http://jech.bmj.com/content/60/1/81.short 4100 - http://jech.bmj.com/content/60/1/81.full SO - J Epidemiol Community Health2006 Jan 01; 60 AB - Most of public health is based on the working hypothesis that disease is caused by exposure to noxious factors in the external environment. While this approach has produced great successes in primary prevention, a general theory of the origins of human disease cannot be found in the textbooks of public health or epidemiology. This paper suggests that, in all its manifestations, disease is a reaction of the human organism to, and/or a failure to cope with, one or more unbalancing changes in its internal environment. These are caused by one or more unfavourable exchanges with the external environment and/or failures in the structural and functional design of the organism. In the final analysis, human disease is attributable to the dependence of organisms on a fundamentally hostile external environment and to unfortunate evolutionary legacies. While this sketch of a theory suggests that there will ultimately be some hard limits to primary prevention, it also helps in identifying possible new approaches to prevention, including interfering with disease mechanisms, and remedying human organisms’ design failures.