In the summer of 2009, a team of Cambridge University undergraduates built seven strains of the bacterium Escherichia coli, one in each color of the rainbow. Red and orange carotenoid pigments were produced by inserting genes from plant pathogen Pantoea ananatis; a cluster of genes from Chromobacterium violaceum were likewise modified to yield green and purple. The students’ technicolor creations, dubbed “E. chromi” in reference to the organisms’ scientific name, won the Cambridge team the grand prize at that year’s International Genetically Engineered Machines (iGEM) competition, in which high-school and college students engineer biology.
The students’ goals were not merely chromatic. Instead, they were building parts for biological machines. They engineered the genes into standardized forms called BioBricks: pieces of DNA that, like genetic Legos, are designed to be mixed and matched at will. Several thousand of these BioBricks, fulfilling various functions, are already housed in the MIT-based Registry of Standard Biological Parts. Some BioBricks detect chemicals like arsenic; others act as “tuners” that determine the threshold level of chemical input needed to turn on a certain gene. By combining the new color-producing genes with existing parts, the thinking went, one might easily construct biosensors that, in the presence of environmental toxins, produce output visible to the naked eye.
“E. chromi” struck a chord with designers Alexandra Daisy Ginsberg, G ’06, and James King, who began a collaboration with the iGEM team. In a short video that was named best documentary at the Bio:Fiction synthetic biology film festival in 2011, Ginsberg and King imagined possible futures for living color. Soon, they suggested, scientists might search the natural world for new biological pigments and the genes responsible, revolutionizing dye production. “E. chromi” in probiotic yogurt might monitor human disease while traveling through the gut; microbes in the atmosphere might change color to indicate air quality.
“I think it’s a new term to most of the public, synthetic biology,” mused the host of National Public Radio’s Science Friday in the fall of 2009 when he interviewed the Cambridge team. “But I guess we’re going to be hearing a lot more of it.”
How to Build a Biological Machine
Armed with powerful new genetic tools and a penchant for tinkering, synthetic biologists have built a new menagerie. Photographic “E. coliroid” darken in response to light. Sensor bacteria record the presence of a chemical in a mouse’s gut by turning on certain genes. There are strains of E. coli that count input signals and others that carry out logical operations—steps toward biological computers. Still other strains smell like wintergreen and bananas instead of like the human gut. In 2005, festive researchers “wrote” the first verse of Viktor Rydberg’s Christmas poem “Tomten” into the genome of yet another E. coli strain, using triplets of DNA nucleotides to represent each letter; the resulting bacterium, they wrote, was “the first example of an organism that ‘recites’ poetry.”
Insofar as a common theme unites these diverse creations, it is the transformation of biology into an engineering discipline. Traditional genetic engineering amounted more or less to biological cut-and-paste: scientists could, for instance, transfer a cold-tolerance gene from an Arctic fish into a tomato. Synthetic biology aims for a more radical reorganization. Its organisms are built to be biological machines, with DNA and proteins standing in for circuit components or lines of computer code. In combination, the biological parts perform functions unknown to nature: processing signals, producing new chemicals, storing information.
“I like to say that biological carbon is the silicon of this century,” says Pamela A. Silver, Adams professor of biochemistry and systems biology at Harvard Medical School (HMS; see “Biology in This Century,” September-October 2011, page 72). Just as computers revolutionized the past hundred years, she says, biology is poised to transform the next. “The building of biological machines and biological computers—all of that should soon become a reality.”