The Next Genetics Moonshot: Building a Human Genome from Scratch

Twisting double-helix molecule of DNA
Image: iStockphoto
Making a synthetic human genome will require assembling 3 billion base-pairs, each of which is represented as a rung on the twisting ladder of a DNA molecule.

Yes, it’s true that a group of leading geneticists is calling for the construction of a synthetic human genome. That means they want to take 3 billion chemical building blocks and assemble them into one complete package of DNA, encoding all the body parts and life processes that make up a functional human being. 

But the organizers want to make one thing very clear: “We’re not planning to make synthetic people,” says a somewhat exasperated Jef Boeke, one of the champions of this proposal. “We never were.” 

The disclaimer is necessary because of the breathless coverage in The New York Times a few weeks ago, in which the paper reported on a “closed-door” meeting where Boeke and his colleagues hammered out the goals of their proposal. That article raised concerns in some quarters that scientists were secretly plotting to create human beings without biological parents.

Instead, the organizers say their project follows the model of the Human Genome Project, a 13-year effort declared complete in 2003. In that mighty undertaking, geneticists sequenced an entire human genome, which means they took a sample of DNA and read out its sequence of 3 billion “letters,” the As, Gs, Cs, and Ts used to represent DNA’s four chemical units. Boeke and his collaborators call their new proposal the Human Genome Project-Write, and describe its aims in an article published today in Science.  

[This is as good a place as any for my full disclosure: Boeke plays folk music with my dad, and has known me since I was a baby sleeping in a guitar case lined with orange velvet. If I write anything negative about him, he has threatened to release pictures of me in diapers. No, not really.] 

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The original HGP is considered one of science’s greatest success stories not simply because researchers produced a complete genome. In the process of working toward that goal, they revolutionized the technology of genome sequencing, which has become exponentially faster and cheaper. Today, top-of-the-line sequencing machines can analyze an entire genome in less than a day, and the NIH estimates the cost of such a scan at about $1000.

Once the cost and time requirements of genome scans dropped, research scientists and doctors found endless ways to use them. In one recent example from the medical realm, pediatricians scanned the genomes of newborns in intensive care and diagnosed their ailments within 26 hours

Similarly, by rallying synthetic biologists around the ambitious goal of synthesizing a complete human genome, Boeke says HGP-Write will spur innovation in DNA manufacturing techniques. “With better technology, we can do more experiments and ask more questions,” Boeke says. 

Breakthroughs may come from young synthetic biology companies like Twist Bioscience and Gen9, which mass-produce DNA to their customers’ specifications. Such companies are pushing to bring down costs from today’s price of about 10 cents per “letter” of DNA. (That’s the price if you’re buying a relatively small quantity of DNA; if you’re buying in bulk you might get the price down to about 3 cents per letter.) 

The Science paper presents a target for cost reductions in DNA manufacturing, suggesting that technologists work toward a goal of synthesizing entire genomes for 1/1000th of the current cost within 10 years. 

The idea for HGP-Write began at a conference in New York City last year about synthetic genomes. Boeke (one of the conference organizers) and his collaborators presented their ongoing work on constructing a yeast genome from scratch, an effort that they expect to complete in the next couple of years. If the yeast project is successful, it will be the largest genome ever assembled from scratch.    

But one attendee at last year’s meeting was dreaming much bigger. Andrew Hessel, a researcher at the software company Autodesk, gave a presentation in which he argued that the best way to raise interest in synthetic biology would be to synthesize the human genome. “That was a magic moment,” Boeke says. “It wasn’t on the agenda at all, we were talking about (the worm) c. elegans and yeast.” 

HGP-Write isn’t a formal project yet, it’s just an idea. But the proposing team, which also includes Harvard synthetic biologist George Church, is hoping to convince U.S. funding agencies, philanthropists, and private companies to take up the cause. The group suggests that a cool $100 million would be sufficient to launch the project. The total costs are “difficult to estimate,” according to the Science paper, but would likely be less than the $3 billion spent for the original Human Genome Project. So it’s basically a bargain.  

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