Drew Endy: The iGEM Revolution

## Massively collaborative synthetic biology Natural genomes are nearly impossible to figure out, Endy began, because they were evolved, not designed. Everything is context dependent, tangled, and often unique. So most biotech efforts become herculean. It cost $25 million to develop a way to biosynthesize the malaria drug artemisinin, for example. Yet the field has so much promise that most of what biotechnology can do hasn’t even been imagined yet. How could the nearly-impossible be made easy? Could biology become programmable? Endy asked Lynn Conway, the legendary inventor of efficient chip design and manufacturing, how to proceed. She said, “Go meta.” If the recrafting of DNA is viewed from a meta perspective, the standard engineering cycle---Design, Build, Test, Design better, etc.—requires a framework of DNA Synthesis, using Standards, understood with Abstraction, leading to better Synthesis, etc. “In 2003 at MIT,” Endy said, “we didn’t know how to teach it, but we thought that maybe working with students we could figure out how to learn it.” It would be learning-by-building. So began a student project to engineer a biological oscillator—a genetic blinker—which led next year to several teams creating new life forms, which led to the burgeoning iGEM phenomenon. Tom Knight came up with the idea of standard genetic parts, like Lego blocks, now called BioBricks. Randy Rettberg declared that cooperation had to be the essence of the work, both within teams (which would compete) and among all the participants to develop the vast collaborative enterprise that became the iGEM universe—students creating new BioBricks (now 10,000+) and meeting at the annual Jamboree in Boston (this year there are 2,500 competitors from 32 countries). “iGEM” stands for International Genetically Engineered Machine. Playfulness helps, Endy said. Homo faber needs homo ludens—man-the-player makes a better man-the-maker. In 2009 ten teenagers with $25,000 in sixteen weeks developed the ability to create _E. coli_ in a variety of colors. They called it _E. chromi_. What could you do with pigmented intestinal microbes? “The students were nerding out.” They talked to designers and came up with the idea of using colors in poop for diagnosis. By 2049, they proposed, there could be a “Scatalog” for color matching of various ailments such as colon cancer. “It would be more pleasant than colonoscopy.” The rationale for BioBricks is that “standardization enables coordination of labor among parties and over time.” For the system to work well depends on total access to the tools. “I want free-to-use language for programming life,” said Endy. The stated goal of the iGEM revolutionaries is “to benefit all people and the planet.” After ten years there are now over 20,000 of them all over the world guiding the leading edges of biotechnology in that direction. During the Q&A;, Endy told a story from his graduate engineering seminar at Dartmouth. The students were excited that the famed engineer and scientist Arthur Kantrowitz was going to lead a session on sustainability. They were shocked when he told them, “‘Sustainability‘ is the most dangerous thing I’ve ever encountered. My job today is to explain two things to you. One, pessimism is a self-fulfilling prophecy. Two, optimism is a self-fulfilling prophecy.”