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When PPLO Became Mycoplasma

The smallest cell has had a long career in the spotlight

Harold J. Morowitz

The Calvin Connection

Serendipity struck again when Melvin Calvin came to visit our department and was brought to our laboratory by the department chair, Ernest Pollard. Professor Calvin had won the Nobel Prize for his work unraveling the famed Calvin cycle at the heart of photosynthesis. When we met him, he was the chief consultant to the newly formed biology division of the National Aeronautics and Space Administration (NASA). Upon hearing of our search for cellular simplicity, he noted, “that’s just the kind of thing that NASA should be interested in.” This encounter resulted in grant support for our work for the next 15 years or so. Shortly after our entry in this new field, a paper appeared by Morowitz and Cleverdon entitled “An extreme example of the coding problem, Avian PPLO 5969.“ Using the data and techniques available at the time, we calculated that there were only 70 protein-coding genes in our little cell. And that was assuming the DNA was double-stranded, which we suspected but did not know at the time. (By modern estimates, the number of protein-coding genes in PPLO 5969—Mycoplasma gallisepticum—is not 70, but about 865. As we’ll see, it wouldn’t be the last time mycoplasmas fooled us.)

To understand the problems we encountered in trying to determine the genome size of PPLO, it is necessary to look into the background of this group of microbes. In the 1890s, two French investigators, Edmond Nocard and Emile Roux were studying pleuropneumonia in cattle. This was a disease of economic importance. Both Nocard and Roux had been trained by Louis Pasteur, taking us back to the beginning days of bacteriology. In 1898 they published the first report of mycoplasmas in a paper, “Le Microbe de la péripneumonie.“ To indicate what was special about these organisms we quote from Emmy Klieneberger-Nobel, the grande dame of the small community of PPLO researchers at the time we began our studies.

All this started in 1898 with a remarkable discovery by French bacteriologists, Nocard and Roux, namely that pleuropneumonia, a highly infectious disease of cattle, was caused by an organism that could pass filters that retained bacteria. It was at first not possible to cultivate this organism on customary bacteriological medium: but the authors soon produced a richer medium on which this organism, seen in their microscopes as little dots darting around in Brownian motion grew in the form of tiny delicate colonies. These were characterized by a dark center and lighter peripheral zone.

This brief description of very small size and growth outside of a host recalls the beginning of PPLO fame as the smallest living organism. Filtration placed them with the viruses, and independent growth classed them with the bacteria.

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