The radical expansion of biology’s frontier raises an uncomfortable question: How do you guard against threats that don’t yet exist? Genetic engineering sits at the edge of a new era. The old era belonged to DNA sequencing, which is simply the act of reading genetic code—identifying and extracting meaning from the ordering of the four chemicals that make up DNA. But now we’re learning how to write DNA, and this creates possibilities both grand and terrifying.
Again, Craig Venter helped to usher in this shift. In the mid‑1990s, just before he began his work to read the human genome, he began wondering what it would take to write one. He wanted to know what the minimal genome required for life looked like. It was a good question. Back then, DNA-synthesis technology was too crude and expensive for anyone to consider writing a minimal genome for life or, more to our point, constructing a sophisticated bioweapon. And gene-splicing techniques, which involve the tricky work of using enzymes to cut up existing DNA from one or more organisms and stitch it back together, were too unwieldy for the task.
Exponential advances in biotechnology have greatly diminished these problems. The latest technology—known as synthetic biology, or “synbio”—moves the work from the molecular to the digital. Genetic code is manipulated using the equivalent of a word processor. With the press of a button, code representing DNA can be cut and pasted, effortlessly imported from one species into another. It can be reused and repurposed. DNA bases can be swapped in and out with precision. And once the code looks right? Simply hit Send. A dozen different DNA print shops can now turn these bits into biology.
In May 2010, with the help of these new tools, Venter answered his own question by creating the world’s first synthetic self-replicating chromosome. To pull this off, he used a computer to design a novel bacterial genome (of more than 1 million base pairs in total). Once the design was complete, the code was e‑mailed to Blue Heron Biotechnology, a Seattle-area company that specializes in synthesizing DNA from digital blueprints. Blue Heron took Venter’s A’s, T’s, C’s, and G’s and returned multiple vials filled with frozen plasmid DNA. Just as one might load an operating system into a computer, Venter then inserted the synthetic DNA into a host bacterial cell that had been emptied of its own DNA. The cell soon began generating proteins, or, to use the computer term popular with today’s biologists, it “booted up”: it started to metabolize, grow, and, most important, divide, based entirely on the code of the injected DNA. One cell became two, two became four, four became eight. And each new cell carried only Venter’s synthetic instructions. For all practical purposes, it was an altogether new life form, created virtually from scratch. Venter called it “the first self-replicating species that we’ve had on the planet whose parent is a computer.”
But Venter merely grazed the surface. Plummeting costs and increasing technical simplicity are allowing synthetic biologists to tinker with life in ways never before feasible. In 2006, for example, Jay D. Keasling, a biochemical engineer at the University of California at Berkeley, stitched together 10 synthetic genes made from the genetic blueprints of three different organisms to create a novel yeast that can manufacture the precursor to the antimalarial drug artemisinin, artemisinic acid, natural supplies of which fluctuate greatly. Meanwhile, Venter’s company Synthetic Genomics is working in partnership with ExxonMobil on a designer algae that consumes carbon dioxide and excretes biofuel; his spin-off company Synthetic Genomics Vaccines is trying to develop flu-fighting vaccines that can be made in hours or days instead of the six-plus months now required. Solazyme, a synbio company based in San Francisco, is making biodiesel with engineered micro-algae. Material scientists are also getting in on the action: DuPont and Tate & Lyle, for instance, have jointly designed a highly efficient and environmentally friendly organism that ingests corn sugar and excretes propanediol, a substance used in a wide range of consumer goods, from cosmetics to cleaning products.
Other synthetic biologists are playing with more-fundamental cellular mechanisms. The Florida-based Foundation for Applied Molecular Evolution has added two bases (Z and P) to DNA’s traditional four, augmenting the old genetic alphabet. At Harvard, George Church has supercharged evolution with his Multiplex Automated Genome Engineering process, which randomly swaps multiple genes at once. Instead of creating novel genomes one at a time, MAGE creates billions of variants in a matter of days.
Finally, because synbio makes DNA design, synthesis, and assembly easier, we’re already moving from the tweaking of existing genetic designs to the construction of new organisms—species that have never before been seen on Earth, species birthed entirely by our imagination. Since we can control the environments these organisms will live in—adjusting things like temperature, pressure, and food sources while eliminating competitors and other stresses—we could soon be generating creatures capable of feats impossible in the “natural” world. Imagine organisms that can thrive on the surface of Mars, or enzymes able to change simple carbon into diamonds or nanotubes. The ultimate limits to synthetic biology are hard to discern.
All of this means that our interactions with biology, already complicated, are about to get a lot more troublesome. Mixing together code from multiple species or creating novel organisms could have unintended consequences. And even in labs with high safety standards, accidents happen. If those accidents involve a containment breach, what is today a harmless laboratory bacterium could tomorrow become an ecological catastrophe. A 2010 synbio report by the Presidential Commission for the Study of Bioethical Issues said as much: “Unmanaged release could, in theory, lead to undesired cross-breeding with other organisms, uncontrolled proliferation, crowding out of existing species, and threats to biodiversity.”
Just as worrisome as bio-error is the threat of bioterror. Although the bacterium Venter created is essentially harmless to humans, the same techniques could be used to construct a known pathogenic virus or bacterium or, worse, to engineer a much deadlier version of one. Viruses are particularly easy to synthetically engineer, a fact made apparent in 2002, when Eckard Wimmer, a Stony Brook University virologist, chemically synthesized the polio genome using mail-order DNA. At the time, the 7,500-nucleotide synthesis cost about $300,000 and took several years to complete. Today, a similar synthesis would take just weeks and cost a few thousand dollars. By 2020, if trends continue, it will take a few minutes and cost roughly $3. Governments the world over have spent billions trying to eradicate polio; imagine the damage terrorists could do with a $3 pathogen.
During the 1990s, the Japanese cult Aum Shinrikyo, infamous for its deadly 1995 sarin-gas attack on the Tokyo subway system, maintained an active and extremely well-funded bioweapons program, which included anthrax in its arsenal. When police officers eventually raided its facilities, they found proof of a years-long research effort costing an estimated $30 million—demonstrating, among other things, that terrorists clearly see value in pursuing bioweaponry. Although Aum did manage to cause considerable harm, it failed in its attempts to unleash a bioweapon of mass destruction. In a 2001 article for Studies in Conflict & Terrorism, William Rosenau, a terrorism expert then at the Rand Corporation, explained:
Aum’s failure suggests that it may, in fact, be far more difficult to carry out a deadly bioterrorism attack than has sometimes been portrayed by government officials and the press. Despite its significant financial resources, dedicated personnel, motivation, and freedom from the scrutiny of the Japanese authorities, Aum was unable to achieve its objectives.
That was then; this is now. Today, two trends are changing the game. The first began in 2004, when the International Genetically Engineered Machine (iGEM) competition was launched at MIT. In this competition, teams of high-school and college students build simple biological systems from standardized, interchangeable parts. These standardized parts, now known as BioBricks, are chunks of DNA code, with clearly defined structures and functions, that can be easily linked together in new combinations, a little like a set of genetic Lego bricks. iGEM collects these designs in the Registry of Standard Biological Parts, an open-source database of downloadable BioBricks accessible to anyone.
Over the years, iGEM teams have pushed not only technical barriers but creative ones as well. By 2008, students were designing organisms with real-world applications; the contest that year was won by a team from Slovenia for its designer vaccine against Helicobacter pylori, the bacterium responsible for most ulcers. The 2011 grand-prize winner, a team from the University of Washington, completed three separate projects, each one rivaling the outputs of world-class academics and the biopharmaceutical industry. Teams have turned bacterial cells into everything from photographic film to hemoglobin-producing blood substitutes to miniature hard drives, complete with data encryption.
As the sophistication of iGEM research has risen, so has the level of participation. In 2004, five teams submitted 50 potential BioBricks to the registry. Two years later, 32 teams submitted 724 parts. By 2010, iGEM had mushroomed to 130 teams submitting 1,863 parts—and the registry database was more than 5,000 components strong. As The New York Times pointed out:
iGEM has been grooming an entire generation of the world’s brightest scientific minds to embrace synthetic biology’s vision—without anyone really noticing, before the public debates and regulations that typically place checks on such risky and ethically controversial new technologies have even started.
(igem itself does require students to be mindful of any ethical or safety issues, and encourages public discourse on these questions.)
The second trend to consider is the progress that terrorist and criminal organizations have made with just about every other information technology. Since the birth of the digital revolution, some early adopters have turned out to be rogue actors. Phone phreakers like John Draper (a k a “Captain Crunch”) discovered back in the 1970s that AT&T’s telephone network could be fooled into allowing free calls with the help of a plastic whistle given away in cereal boxes (thus Draper’s moniker). In the 1980s, early desktop computers were subverted by a sophisticated array of computer viruses for malicious fun—then, in the 1990s, for information theft and financial gain. The 2000s saw purportedly uncrackable credit-card cryptographic algorithms reverse-engineered and smartphones repeatedly infected with malware. On a larger scale, denial-of-service attacks have grown increasingly destructive, crippling everything from individual Web sites to massive financial networks. In 2000, “Mafiaboy,” a Canadian high-school student acting alone, managed to freeze or slow down the Web sites of Yahoo, eBay, CNN, Amazon, and Dell.
In 2007, Russian hackers swamped Estonian Web sites, disrupting financial institutions, broadcasting networks, government ministries, and the Estonian parliament. A year later, the nation of Georgia, before the Russian invasion, saw a massive cyberattack paralyze its banking system and disrupt cellphone networks. Iraqi insurgents subsequently repurposed SkyGrabber—cheap Russian software frequently used to steal satellite television—to intercept the video feeds of U.S. Predator drones in order to monitor and evade American military operations.
Lately, organized crime has taken up crowd-sourcing parts of its illegal operations—printing up fake credit cards, money laundering—to people or groups with specialized skills. (In Japan, the yakuza has even begun to outsource murder, to Chinese gangs.) Given the anonymous nature of the online crowd, it is all but impossible for law enforcement to track these efforts.
The historical trend is clear: Whenever novel technologies enter the market, illegitimate uses quickly follow legitimate ones. A black market soon appears. Thus, just as criminals and terrorists have exploited many other forms of technology, they will surely soon turn to synthetic biology, the latest digital frontier.