DNA Manufacturing Enters the Age of Mass Production

Synthetic-biology startups adopt technologies from the computer industry

3 min read
DNA Manufacturing Enters the Age of Mass Production
Illustration: Elias Stein

Emily Leproust, CEO and cofounder of the buzzy biotech startup Twist Bioscience, is an industrialist on the nanoscale. “I remind everyone at Twist, we are a manufacturing company,” she says. “We manufacture DNA.”

Twist is part of the young industry of synthetic biology, in which living organisms are the product and a biology lab is the factory floor. By manufacturing strands of DNA—assembling the genetic code of life from its basic components—scientists are creating organisms the likes of which the world has never seen. And these new life forms can be decidedly useful: Biologists have produced yeast cells that excrete pharmaceuticals and algae that brew jet fuel.

img DNA Factory: Twist Bioscience’s machine builds DNA strands inside 600-nanometer wells on a silicon plate. Photo: Twist Bioscience

This burgeoning business sector has been hampered by the labor-intensive nature of DNA assembly, a painstaking process requiring trained personnel. Now, nimble startups are competing to fashion automated DNA assembly lines that would make Henry Ford proud, using techniques copied from the fabs that make computer chips. As their innovations bring down the cost of constructing DNA strands, these entrepreneurs are aiming for a low price point, which they say will cause a market boom. Twist Bioscience, which will begin commercial operations at its San Francisco headquarters in 2016, is a leading contender in that race to the bottom.

Genetic material is composed of molecules called nucleobases; the four types of bases in DNA are identified by the letters A, C, G, and T. The order of these letters serves as a code that instructs an organism how to build its cells and carry on the functions of life. In human beings, this code is about 3.2 billion letters long, while the yeast used in baking and beer brewing has a code of about 12 million letters. If you tweak the order of the letters, you tweak the organism’s instructions. Synthetic biologists have written new snippets of code and inserted them into yeast DNA, causing the microbe to churn out, for example, the omega-3 fatty acids found in fish oil supplements or the aromatic oils normally produced by roses.

Matter of Fact

Mycoplasma laboratorium: The name given to the first “synthetic organism,” a bacterium whose 1-million-base genome was assembled from scratch.

Constructing a strand of DNA isn’t complicated; in fact it’s a routine procedure performed in labs all over the world. But that procedure is typically carried out by hand, says Twist’s Leproust: “Microbiology is manual labor. You have a Ph.D. student moving liquid from one test tube to the next all day long.” So she and her cofounders invented a machine that automates the construction process.

The heart of the machine is a silicon plate pocked with 10,000 tiny wells, which are etched using the same photolithography techniques perfected by computer chip manufacturers. A different strand of DNA can be constructed in each 600-nanometerwide well. The machine does “the exact same chemistry” as a Ph.D. student would do, Leproust says, “only in a volume that’s 100 times smaller.”

Twist isn’t selling its machine but rather its DNA manufacturing services, which are aimed at researchers and startups seeking new genetic modifications that might prove useful. In 2015 the company began production runs for select customers; 2016 will see Twist’s full commercial launch. DNA assembly is priced on a cost-per-base model, and Leproust says her company’s 10-cents-per-base starting price is already the best in the industry. But she’s aiming for a 2-cent price point: “That’s the point at which researchers can significantly scale experiments and will no longer be limited by the cost of DNA,” she says. Today, customers typically order DNA strands of 300 to 1,800 bases in length, Leproust says.

  1. 1,600 Bases

    Length of gene for insulin (INS)

  2. 81,000 Bases

    Length of gene for breast cancer risk (BRCA1)

Another synthetic-biology startup in the San Francisco area, Zymergen, offers customers a broader set of services. The company not only constructs DNA snippets on the cheap, it also inserts that DNA into microbes and monitors the outcome. Chief science officer Zach Serber explains that the results can inform the next round of DNA design, letting customers iterate quickly as they look for their ideal organism. “You cast a wide net,” Serber says, “and when you find a variation that improves the microbe’s performance, then you double down.”

Such setups have led to excited talk of a synthetic-biology industry based on “organism fabs.” But the promise of mass-produced DNA doesn’t impress Rob Carlson, a biotech consultant and managing director of the BioEconomy Capital venture fund. “I don’t understand the business model,” he says.

Carlson is skeptical that cheap DNA assembly will lead to a proliferation of startups with ideas for profitable microbes. “So you can make and test a whole bunch more DNA—but that’s not the hard part,” he argues. “Going from test tube to bench scale to commercial scale, that’s 90 percent of cost.” For a startup to build a business around a yeast that cranks out a pharmaceutical, for example, it must manage massive tanks full of microbes. Reducing the cost of the initial DNA manufacturing would only give the company pocket money, Carlson says: “Hooray, they get to buy beer, or more pizza on Friday.”

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Biggest Tech Companies Now Building the Biggest Data Pipes

Facebook will lay a record-capacity submarine cable across the Atlantic

4 min read

Google's Grace Hopper subsea cable landing in the seaside town of Bude in England

Google

Old-fashioned telecommunication carriers are falling behind in the global bandwidth race as global giants of content and cloud computing are building their own global networks. Facebook has commissioned electronics and IT giant NEC Corporation to build the world's highest capacity submarine cable. When finished it will carry a staggering 500 terabits—some 4000 Blu-Ray discs of data—per second between North America and Europe on the world's busiest data highway.

For decades, transoceanic cables were laid by consortia of telecommunication carriers like AT&T and British Telecom. As cloud computing and data centers spread around the world, Google, Amazon, Facebook and Microsoft start joining cable consortia, and in the past few years Google began building its own cables. The new cable will give Facebook sole ownership of the world's biggest data pipeline.

Transoceanic fiber-optic cables are the backbones of the global telecommunications network, and their change in ownership reflects the rapid growth of data centers for cloud computing and content distribution. Google has 23 giant data centers around the globe, each one constantly updated to mirror the Google cloud for users in their region. Three years ago, flows between data centers accounted for 77 percent of transatlantic traffic and 60 percent of transpacific traffic, Alan Mauldin, research director at TeleGeography, a market-research unit of California-based PriMetrica, said at the time. Traffic between data centers is thought to be growing faster than the per-person data consumption, which Facebook says increases 20 to 30 percent a year.

Vying for maximum bandwidth at the intersection of Moore's Law and Shannon's limit

Fiber-optic developers have worked relentlessly to keep up with the demand for bandwidth. For decades, data capacity of a single fiber increased at a faster rate than the number of transistors squeezed onto a chip, the definition of Moore's Law. But in recent years that growth has slowed as data rates approached Shannon's limit, a point at which noise in the transmission system overwhelms the signal. In 2016 the maximum data rate per fiber pair (each fiber carrying a signal in one direction) was around 10 terabits per second, achieved by sending signals at 100 gigabits per second on 100 separate wavelengths through the same fiber.

Developing more sophisticated signal formats offered some improvement, but not enough to keep pace with the demand for bandwidth. The only way around Shannon's limit has been to open new paths for data delivery.

In 2018, Facebook and Google placed bets on broadening the transmission band of optical fibers by adding signals at a hundred new wavelengths to squeeze 24 terabits through a single fiber. Each bought one pair of fibers on the Pacific Light Cable stretching from Hong Kong to Los Angeles. The leader of the consortium, Pacific Light Data Communications, of Hong Kong, retained four other pairs in the six-pair cable. Although the cable was soon laid, the U.S. Federal Communications Commission has refused to license its connection to the U.S. network because of security concerns arising from its Chinese connections.

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Study: Recycled Lithium Batteries as Good as Newly Mined

Cathodes made with novel direct-recycling beat commercial materials

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iStockphoto

Lithium-ion batteries, with their use of riskily mined metals, tarnish the green image of EVs. Recycling to recover those valuable metals would minimize the social and environmental impact of mining, keep millions of tons of batteries from landfills, and cut the energy use and emissions created from making batteries.

But while the EV battery recycling industry is starting to take off, getting carmakers to use recycled materials remains a hard sell. "In general, people's impression is that recycled material is not as good as virgin material," says Yan Wang, a professor of mechanical engineering at Worcester Polytechnic Institute. "Battery companies still hesitate to use recycled material in their batteries."

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