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Imitation of Life

Can a computer program reproduce everything that happens inside a living cell?

Brian Hayes

The Smallest Life Forms

Bacteria of the genus Mycoplasma are attractive for experiments of this kind because they are the smallest and arguably the simplest self-replicating organisms. (Viruses are smaller, but they can reproduce only by hijacking the biochemical machinery of a host cell.)

When mycoplasmas were first observed in the 19th century, they were thought to be fungi (hence the prefix myco-, from the Greek root μυκης, meaning fungus). The organisms are now classified among the bacteria, but they are peculiar members of that kingdom. They lack the rigid cell wall that encases other bacteria, having only a lipid membrane. One consequence is that mycoplasmas are resistant to many antibiotics, notably those that work by interfering with the synthesis of cell wall components. Mycoplasmas cause a number of human ailments as well as diseases of other animals and also plants. Perhaps the best known of the human pathologies is a lung infection sometimes called “walking pneumonia.”

M. genitalium, the organism chosen for the Covert group’s computer model, has been known to science only since 1980, when it was isolated from a few patients with urethritis. Even among mycoplasmas, M. genitalium is a diminutive cell, with a diameter of roughly half a micrometer. The better-known bacterium Escherichia coli, by contrast, is two micrometers long, with a volume roughly 50 times as large. M. genitalium is also tiny in terms of its genetic complement. The single circular chromosome has 580,076 base pairs of DNA and just 525 identified genes (even fewer than Morowitz estimated). The E. coli genome is about 4.6 million base pairs with 4,300 genes.

The compact cells and concise genome of mycoplasmas make them a useful test bed not just for software but also for “wetware” explorations of the minimal apparatus needed to sustain life. One notable experiment of this kind was reported in 2010 by J. Craig Venter, Clyde A. Hutchison III, Hamilton O. Smith and others at the J. Craig Venter Institute. They sequenced the genome of a particular mycoplasma, storing the list of bases as a computer file; then they made a few edits that would serve as an identifiable “watermark” and synthesized DNA corresponding to the altered sequence. Finally—and this was the hard part—they inserted the manufactured DNA into cells of another mycoplasma species, replacing the native genetic material. The cells grew and reproduced entirely under the direction of the artificial genome. The experiment can be viewed as a step toward creating a wholly synthetic life form.

In some respects, simulating life with a digital computer is even harder than synthesizing it from chemical components. Given the right ingredients, a biologist might be able to assemble a living cell without fully understanding all the details of how the parts interact. The computer programmer, however, must describe every molecular event.

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