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As Made-To-Order DNA Gets Cheaper, Keeping It Out Of The Wrong Hands Gets Harder

Sep 24, 2019
Originally published on September 24, 2019 1:30 pm

Patrick Boyle recalls that by the time he got his Ph.D. in biology in 2012, he had worked with just a few other people and managed to manufacture six genes, the basic units of heredity.

"Today, we are synthesizing more than 10,000 genes every month," he says, showing off a lab at a Boston biotech company called Ginkgo Bioworks.

Making genes from scratch used to be laborious and time consuming, but not anymore. That's why federal officials are now considering new measures to prevent this rapidly advancing technology from being misused to create dangerous viruses or bioweapons.

Genes are made up of DNA, a "code" determined by four chemical bases — known as A, C, T and G — that can be strung together to make the biological instructions that govern cells.

The human genetic code has about 3 billion pairs of these letters. The first effort to sequence, or "read" all of these letters took more than a decade and cost billions of dollars. These days, however, anybody's genetic code can be read for about $1,000.

The technology needed to "write" DNA is now undergoing a similar transformation. Over the last decade, the cost of synthesizing a pair of DNA letters has dropped from about one dollar to less than 10 cents.

"We can actually finally afford to write this code, and we can write much more of it," says Boyle. "We're coming up with thousands of new designs on a computer, printing out the DNA for them, booting up that DNA, seeing what it does and then iterating on those designs."

When he says printing out DNA, he means it literally. The technology used for Inkjet printing has been adapted to print short fragments of DNA onto glass slides. Those fragments then get assembled into larger and larger pieces in a highly automated process.

All this synthetic DNA can be inserted into bacteria, yeast, fungi or even mammalian cells. Ginkgo Bioworks' customers want to turn them into tiny factories that can spew out useful products like enzymes or food ingredients.

"One of our newest projects is to work on making animal proteins without the animals," says Jason Kelly, the CEO and co-founder of Ginkgo Bioworks.

In his view, what's happening with DNA now is analogous to what happened at the start of the computer industry.

"Except this time, it will be cells that will be programmed," Kelly says. "And they won't be moving information around. They'll mostly be building stuff."

This company uses so much DNA that it not only makes its own, but also buys some from another major manufacturer named Twist Bioscience.

Emily Leproust, Twist Bioscience's CEO, estimates that the global synthetic DNA industry is currently churning out approximately 3 billion pairs of DNA letters a year—or about the same amount found in each human cell.

She says her company produces about 10 percent of that, and its customers include pharmaceutical firms, agricultural companies and academic scientists trying to understand basic biology.

"You log on to the website, you upload the sequence you want and you can order one gene or 10 genes or a thousand genes," explains Leproust.

A couple weeks later, custom DNA arrives in the mail. At least, it does if the order gets through Twist Bioscience's rigorous security screening.

What makes DNA so powerful, after all, also makes it potentially dangerous. Someone could use it to change a harmless bacteria into one that makes a deadly toxin.

And scientists have already shown that it's possible to use bits of DNA to construct viruses like polio and Ebola.

James Diggans, Twist's director of biosecurity, says they check out every potential customer. They also analyze each requested DNA sequence, to see if there's anything worrisome in there, like a gene specific to some nasty germ.

"And then we make a decision about whether that sequence is appropriate to make for that customer," he says.

A handful of times, they've said no. Diggans won't give specifics on those occasions. He does note that they would not have made the pieces of DNA that one research team recently ordered from a different company and used to assemble horsepox virus.

That was controversial because horsepox is so close to the deadly human pathogen smallpox. "That is not something we would have been comfortable in producing," says Diggans.

As this example shows, companies have different standards. Many, but not all, belong to a consortium whose members have pledged to follow or exceed some biosecurity guidelines put out by the U. S. government.

Those guidelines came out almost a decade ago, and some say they no longer are adequate because of how the technology has changed.

For example, the guidelines call for screening big chunks of DNA. But Diggans says it's gotten so easy to put little pieces together that the smaller sequences really need to be screened as well.

"That's sort of an easy next step that the U.S. government could take," he says.

Diggans also would like to see new standards for desktop DNA synthesizers. Rather than ordering from a company, scientists can now buy one of these machines to create desired bits of DNA in their own lab.

"That machine needs to be able to screen and ensure that that manufacture occurs safely and legally," says Diggans, who compares what's needed to the controls in photocopier machines that prevent people from counterfeiting money.

Gigi Kwik Gronvall, a biosecurity expert at the Center for Health Security at Johns Hopkins University, agrees that the government should strengthen its guidelines.

Still, she says, some companies are losing patience with the screening because it can be expensive and time-consuming.

"The cost for making genes is going down, down, down, but the screening costs are kind of fixed," Gronvall says. "You can automate most of it, but if there is something that comes close to a hit, it sucks up the time and energy of a highly-paid employee to figure it out and figure out who is ordering it and if they are allowed to order it."

That's one reason why she thinks all researchers who receive federal funding should be required to order their synthetic DNA from companies that follow the guidelines.

"The idea there is to level the playing field," says Gronvall, "to make the business case that screening is not a burden for the companies. It becomes an advantage."

At the same time, she cautions that these measures are only a partial solution.

"It's going to be something that should be done to deter some people who might misuse these technologies. It's not going to get everybody," says Gronvall, who points out that DNA synthesis techniques are advancing rapidly and are available around the world.

A spokesperson for the Department of Health and Human Services told NPR that officials are in the process of reviewing and updating the government's guidelines for synthetic DNA manufacturers, but that it was too early to discuss what changes might be made.

She said the White House Office of Science and Technology Policy would be coordinating government agencies' efforts and would engage with the private sector.

: 9/24/19

In a previous version of this story, several references to James Diggans' last name were incorrectly spelled as Diggins.

Copyright 2019 NPR. To see more, visit https://www.npr.org.

DAVID GREENE, HOST:

DNA encodes all of our genetic information. So you might find it surprising that it is getting easier to make DNA in a lab. In fact, some companies are cranking out huge amounts of cheap, made-to-order DNA. So what are the chances, though, that it could be misused? NPR's Nell Greenfieldboyce takes a look.

NELL GREENFIELDBOYCE, BYLINE: DNA is amazing. It's a kind of code made up of molecules known by their first letters - A, C, G and T. Strung together, these letters can form genes, biological instructions that can get cells to do stuff, like make insulin or grow hair.

Patrick Boyle is showing me around a Boston biotech company called Gingko Bioworks.

PATRICK BOYLE: You know, I finished my Ph.D. in 2012, and over my - the course of my entire Ph.D., working with a few other people, we synthesized six genes.

GREENFIELDBOYCE: But, oh, how times have changed.

BOYLE: Today, we're synthesizing more than 10,000 genes every month.

GREENFIELDBOYCE: The workers here are like computer programmers, only the code they write is DNA code. Their designer DNA gets inserted into cells, like bacteria, yeast, fungi, to try to make them spew out chemicals that can be used as new drugs or food ingredients.

BOYLE: We're coming up with thousands of new designs on a computer, printing out the DNA for them, booting up that DNA, seeing what it does and then iterating on those designs.

GREENFIELDBOYCE: When he says printing out DNA, he means it literally.

(SOUNDBITE OF PRINTER)

GREENFIELDBOYCE: The technology used for inkjet printing has been adapted to print short fragments of DNA onto glass slides. Those fragments then get assembled into larger and larger pieces in a highly automated process.

BOYLE: So many of the robots that you see behind you are basically pipetting, you know, liquid around to put different fragments together to build the correct, full design.

GREENFIELDBOYCE: Over the last decade, the cost of making a pair of DNA letters - those A, C, T and Gs - has dropped from $1 to less than 10 cents.

BOYLE: We can actually, finally, afford to write this code, and we can write much more of it.

GREENFIELDBOYCE: This company now uses so much DNA, it not only makes its own but also buys some from another manufacturer named Twist Bioscience. Its CEO is Emily Leproust. She says her company's other customers are pharmaceutical firms, agricultural companies and academic scientists trying to understand basic biology. Anyone can just order DNA online.

EMILY LEPROUST: So you log on the website, you upload the sequence you want and you can order one gene or 10 genes or a thousand genes.

GREENFIELDBOYCE: A couple weeks later, your custom DNA arrives in the mail. At least, it does if your order gets through this company's rigorous security screening. Because here's the thing - DNA is so powerful that it's potentially dangerous. Someone could use it to transform a harmless bacteria into one that makes a deadly toxin. And bits of DNA can be assembled into a virus, like Ebola. Twist director of biosecurity is James Diggans. He says they check out every potential customer and each requested DNA sequence, looking to see if there's anything worrisome in there, like a gene specific to some nasty germ.

JAMES DIGGANS: And then we make a decision about whether that sequence is appropriate to make for that customer.

GREENFIELDBOYCE: A handful of times, they've said no. Diggans won't give specifics. He does say they would not have made the pieces of DNA that one research team recently ordered from a different company and used to assemble the horsepox virus. This was controversial because horsepox is so close to the deadly human pathogen smallpox.

DIGGANS: That is not something we would have been comfortable in producing.

GREENFIELDBOYCE: This just illustrates a key issue - companies have different standards. Many, but not all, follow some biosecurity guidelines put out by the U.S. government that were designed to keep people from doing anything dodgy.

Those guidelines came out about a decade ago and are kind of out of date. For example, the guidelines call for screening only big chunks of DNA. Diggans says, it's gotten so easy to put little pieces together, they really need to be screened as well.

DIGGANS: And so we think that's sort of an easy next step that the U.S. government could take.

GREENFIELDBOYCE: There's also new desktop DNA synthesizers. Rather than ordering from a company, scientists can now buy one of these machines to create desired bits of DNA in their own lab.

DIGGANS: That machine needs to be able to screen and ensure that that manufacture occurs safely and legally.

GREENFIELDBOYCE: Just like photocopier machines have built-in controls to stop people from counterfeiting money.

Gigi Gronvall is a biosecurity expert at the Center for Health Security at Johns Hopkins University. She agrees that the government should strengthen its guidelines and thinks all researchers who receive federal funding should be required to order their synthetic DNA from companies that follow them.

GIGI GRONVALL: The idea there is to level the playing field, so to make the business case that screening is not a burden for the companies, it becomes an advantage.

GREENFIELDBOYCE: Still, she says, these measures are only a partial solution.

GRONVALL: It's going to be something that should be done to deter some people who might misuse these technologies. It's not going to get everybody.

GREENFIELDBOYCE: Just because the technology is advancing rapidly and is available around the world.

A spokesperson for the Department of Health and Human Services said that officials are in the process of reviewing and updating the guidelines for synthetic DNA manufacturers but that it was too early to discuss what changes might be made.

Nell Greenfieldboyce, NPR News.

(SOUNDBITE OF MUSIC) Transcript provided by NPR, Copyright NPR.