What the human genome project will not tell us: the role of micro-organisms in disease.

The sum of living organisms, or biota that exist within 5 miles above and below the earth’s surface is mainly composed of microscopic life-forms, the vast majority of which have yet to be characterized. Bacterial cells that lack a nucleus, also referred to as prokaryotes, are the simplest and the smallest possible living creatures that are capable of independent existence, and make up the bulk of biota. After life originated on earth, prokaryotes alone existed for more than two billion years, until their mergers and combinations eventually led to the formation of eukaryotes or unicellular organisms that contain a nucleus. Proof that eukaryotes emerged as a result of symbiotic union between bacterial cells comes from finding three types of intracellular structures within these eukaryotic cells whose origins can be traced to a prokaryotic ancestor. The first is mitochondria, once independently existing bacteria that are the source of energy for most eukaryotic cells, in return for a permanent abode. Second, the green plastids called chloroplasts, which synthesize food from water and sunlight are present in plant cells, and are also thought to have existed previously as independent blue–green cyanobacteria. Finally, the whip like undulipodia on the surface of motile cells, share incredible structural uniformity, whether they exist as cilia lining the respiratory passages, or as flagella in sperm tails, and appear to be derived directly from one of the fastest moving bacteria called spirochetes. Thus, eukaryotic cells in the form of unicellular organisms collectively referred to as protists, emerged as a confederacy of bacteria 1.6 billion years ago. Transformation of prokaryotic cells into nucleated eukaryotes appears to be the single most dramatic event in biology since this became the blueprint for the design of the rest of the four kingdoms that include protists, plants, animals and fungi. Further evolution of the unicellular protists into multi-cellular organisms was an accident waiting to happen, even though it took another few hundred million years. During those early years, the lonely inhabitants of the earth were not mere silent spectators. Rather, these lowly bacteria defined the basic rules for cooperative existence thereby laying down the foundations for the birth and proliferation of all the incredible life forms that we witness today. In addition to their parental role as our ‘founding mothers’, there is increasing evidence that the earth’s environment as we know it now, owes its gaseous composition and precise temperature regulation directly to the activities of these microscopic forms of life. In other words, rather than being passive hostages, subservient to the whims of an indifferent, pre-determined environment, these diverse and interacting life forms profoundly influence the atmosphere, making and remaking its composition, and determining the conditions for our survival. If our earth is to be viewed as a self-sustaining meta-organism, then the lead role for maintaining homeostasis must be assigned to the symbiotic and cooperative operations of our microscopic ancestors and fellow passengers. Disruption of this symbiotic balance for any reason would result in the elimination of selective micro-organisms and the provision of an undue growth advantage to others * Tel.: +1-312-4558474; fax: +1-312-4558479.