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This is an archive article published on January 29, 2006

Custom-made microbesat your service

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Bacteria that blink like lights or form multicoloured patterns of concentric circles resembling an archery target, or even reproduce photographic images? These are not strange-but-true specimens from nature, but rather the early tinkering of synthetic biologists who seek to create living machines and biological devices that can perform novel tasks.

“We want to do for biology what Intel does for electronics,” said George Church, genetics professor at Harvard and a leader in the field. “We want to design and manufacture complicated biological circuitry.” Much of the early work was eye-catching, if useless, like the blinking bacteria, but it could have a major impact on medicine and industry.

For instance, Christina D. Smolke of the California Institute of Technology, is trying to develop circuits of biological parts to sit in the body’s cells and guard against cancer. If they detect a cancer-causing mechanism activated, they would switch on a gene to have the cell self-destruct. J Craig Venter, who sequenced the human genome, wants to create microbes that produce hydrogen for use as fuel.

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Scientists have been putting genes into bacteria and other cells for three decades. “This has a catchy new name, but anybody over 40 will recognise it as good old genetic engineering applied to more complex problems,” said Frances H. Arnold, chemical engineering professor at Caltech.

Some synthetic biologists say they will go beyond genetic engineering, which often involves putting a single foreign gene into a cell. The human insulin gene, for instance, is put into bacteria, which then make insulin for use as a drug. But there have been genetic engineering projects involving multiple genes, so the number of genes alone is not enough to define synthetic biology. “We’re talking about taking biology and building it for a specific purpose, rather than taking existing biology and adapting it,” Professor Keasling of Berkeley said.

Also new is an engineering approach — the desire to make the design of life forms more predictable. That could be because many leaders of the field are not biologists by training. Ron Weiss of Princeton is a computer scientist. Michael Elowitz of Caltech trained as a physicist, and Drew Endy of the Massachusetts Institute of Technology as a structural engineer. Endy and colleagues at MIT have started a “Registry of Standard Biological Parts.” The parts, called BioBricks, are strings of DNA that can perform functions like turning on a gene or causing a cell to light up. In theory, these components can be strung together to build complex devices.

Scientists at the University of California, San Francisco, and the University of Texas used some BioBricks to engineer bacteria so that a sheet of them could capture an image as photographic film does. What make the engineering approach possible are inner workings of a living cell. Genes have instructions for producing proteins, which carry out most cell functions. Some can bind to DNA, turning particular genes on or off.

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Some newer efforts involve trying to manipulate entire colonies of microbes to cooperate with one another. They take advantage of something called quorum sensing, a natural communication system

A challenge is that the genes of the circuit can interact with the native bacterial genes in unexpected ways. There is also great variability among living creatures. The blinking bacteria, for instance, do not light up in unison, but at greatly varying rates. Even a newly formed daughter cell will not blink in sync with its mother cell, despite being almost identical genetically.

Some scientists say it might be difficult to make biological engineering as predictable as bridge construction. “There is no such thing as a standard component, because even a standard component works differently depending on the environment,” Professor Arnold of Caltech said. The unpredictability could lead to safety risks.

(New York Times)

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