Synthetic PhiX174 Bacteriophage (Hessel, Quinn & Jaschke)

From the Curators: First artificially synthesized outside of a living organism by the J. Craig Venter Institute in 2003 after a painstaking five-year process, bacteriophage PhiX174 (or φX174) is a virus, benign in humans, that infects and eventually destroys the E. coli bacteria. Autodesk’s 2014 synthesis of a man-made version of PhiX174 is notable for its relative ease–it took Andrew Hessel, a distinguished researcher in their Bio/Nano Programmable Matter team, a matter of weeks and approximately $1,000. The process began digitally, with Hessel developing the virus using technology similar to the 3-D AutoCAD architecture and engineering software pioneered by Autodesk. The larger goal, both for Autodesk and other industry players, is to make tools for such processes widely available to the market. However, design strategies intended for the greater good can also hold catastrophic potential, and this axiom is especially potent in the field of synthetic biology. Where some see unfettered potential for the positive application of designs for synthetic life others–including Hessel himself, who wrote about the prospect of hacking the President’s DNA in a speculative essay for The Atlantic in 2012–worry about bio-weapons in the wrong hands. In this case, Autodesk’s PhiX174–an experiment to demonstrate potential rather than immediate commercial application–has been destroyed.

The 5,386 base pairs of φX174’s genome have been mapped, mutated, sequenced, synthesized, and redesigned since the 1950s. φX174 is a virus that infects E. coli, and its abundance, small size, and association with the common gut- and laboratory-dwelling bacterium have made it a superstar among model organisms. Its was the first genome ever to be synthesized in a test tube, in 1967, using DNA replication enzymes purified from E. coli. Its genome was also the first to be fully sequenced, in 1977, uncovering many of the peculiar details of φX174’s biology—primarily the fact that some of its genes were located within other gene sequences.

Possible alien messages encoded in φ174’s protein B?

The Japanese scientists Hiromitsu Yokoo and Tairo Oshima were intrigued by these overlapping genes. Could such an entangled sequence be the result of random evolution, or was there perhaps an intelligent designer at work? Was there a message hidden in the 121 (notably, the square of a prime number) amino acids of one of the overlapped genes? Such an encoded message, they argued, would be a much better method for interplanetary communication than radio signals, since they can replicate themselves and persist on a planet for much longer. Perhaps φX174 was designed by an extraterrestrial population with the patience to wait for Earth’s intelligent creatures to learn how to sequence DNA.

While Yokoo and Oshima didn’t manage to decode the 11 x 11 square of protein B into any decipherable alien message (see image), they did anticipate the growth of synthetic biology. They write in their 1979 paper about the possibility of designing and synthesizing a genome as complex as φX174: “Biochemistry on our planet is still not advanced enough to synthesize such sophisticated biomolecules, but, judging from the recent progress in biological sciences, it is most likely that our civilization will gain enough information to carry out such a project within a few decades.”

Twenty-five years later, in 2003, Craig Venter and his team announced that they had chemically synthesized the whole genome of φX174. Thanks to years of research at the Venter Institute to speed up DNA synthesis, the assembly of the genome took only 14 days. Scientists had synthesized viruses before this demonstration, but Venter’s team wanted to debut their new, faster method with the historically important φX174.

Today, when biology labs regularly synthesize several thousand DNA base pairs at a time, φX174 still holds symbolic power. Autodesk drew on this power to demonstrate the potential of the contemporary synthetic-biology supply chain, built over the past 10 years. They “built” a virus by buying its DNA online from a third-party genetic synthesis company for just over $1,000. The process likely took little more time than what was needed to find the sequence in a database, upload it to a website, and wait for the DNA to be shipped. Like Yokoo and Oshima’s analysis, this demonstration doesn’t advance the technology of DNA synthesis or our knowledge of the virus, but it does anticipate a potential future where viruses can easily be built to spec.

Over 50 years, scientists have used φX174 to mark milestones in molecular biology and to symbolize the promise of biological design, by both humans and extraterrestrials. As a virus—though one that doesn’t infect humans—it also feeds our fears about the more dangerous possibilities of designing living things. Will we someday design “sophisticated biomolecules” as dangerous to us as φΧ174 is to E. coli?

It’s not impossible. After all, there are a few scientists today working to evolve more virulent viruses, and biosafety breaches can happen. I’m not very interested, however, in predicting or debating the likelihood of any particular biosecurity threat. Instead, I’m fascinated by how these biological demonstrations, provocations, and design fictions shape how we understand living things and what we imagine to be possible. For now, naturally occurring biomolecules remain much more sophisticated—and dangerous—than those we can design, but φX174 will continue to stand for our biological hopes and fears, and it will continue to symbolize our quest to sequence, synthesize, and design DNA.