Today's mail-order molecule could help build the next great vaccine. Or it could unleash the next deadly epidemic.

That's the conundrum faced by the Bay Area's gene synthesis companies, which screen thousands of requests for custom-built DNA -- and the customers who want them -- to make sure that tomorrow's Hitler isn't ordering up the next smallpox, Ebola or yet-unnamed killer.

"If there's some weird order from some weird place, it raises a red flag," said Claes Gustafsson, co-founder and chief commercial officer of ATUM, a Newark-based gene synthesis company.

The companies' approach -- a shared database and screening techniques, established voluntarily by a trade association -- isn't perfect.

But it represents a rare instance of competitive companies successfully regulating their own cutting-edge field to protect us from possibly perilous pathogens. Their responsibility grows as it gets ever cheaper, faster and easier for almost anyone to stitch together the chemicals that make life.

"I think the fact that they have been so willing to monitor themselves helps us identify the places where there are gaps in regulation, where our vulnerabilities lie," said Mildred Cho of the Center for Biomedical Ethics at Stanford.

The burgeoning field of gene synthesis is possible because of this simple fact: Life is just information.

Four molecules -- each called a "base," the most irreducible unit of life, represented by the letters A (adenine), T (thymine), G (guanine) and C (cytosine) -- spell the words that write the dictionary of creation.

The sequence of these letters dictates whether you spell out the makings of a cowpox virus or the starting pitcher for the Yankees.

The ease of building these sequences -- and the lower costs as technology has improved -- has spurred the growth of companies like ATUM and San Francisco's Twist Bioscience, where armies of machines spit out accurate and custom-designed strands of DNA.

The benefits are many and profound, leading to new therapies, non-fossil fuels, and more resilient agricultural crops. While the promise of "gene editing" through CRISPR techniques has received a lot of attention, gene building could be a potentially more efficient technology. Rather than changing a gene sequence, you can build the sequence from scratch.

But along with these advances have come new biosecurity threats, where sequences are designed for harm. Some sequences have dual uses, either good or deadly. For instance, research based on the gene sequence of Ebola virus could help accelerate the design and production of new vaccines. But the same gene sequence, in the wrong hands, could unleash terror.

The federal government has a short list of regulated organisms. But the government's ban focuses on the organisms themselves, rather than the genetic instructions for making them.

Because the government has not published those sequences, the companies must decide for themselves whether a mail order request is potentially dangerous.

The companies face a challenge: How do they know when someone is building a biological bullet? While the government calls on companies to screen both customers and the ordered DNA sequences, this is a voluntary rather than regulatory approach.

To help, leading companies have organized and created their own database and biosecurity practices, in line with federal guidelines, through a trade association called the International Gene Synthesis Consortium. Members include two Bay Area companies -- ATUM and Twist Bioscience -- as well as 10 other major companies which provide an estimated 80 percent of the world's synthetic genes.

Each order is screened against the group's database, which includes whole genomes of pathogenic species, subspecies and toxin genes.

And every customer is screened using software, which combs through the U.S. government watch lists for terrorists and traffickers of weapons of mass destruction.

Companies also check for an institutional affiliation. They don't sell DNA to unaffiliated individuals or ship to P.O. boxes.

"If we received an order to make the Ebola virus, screening the customer would play a very important role, after the sequence was flagged as dangerous," said biochemist Emily Leproust, co-founder and CEO of Twist Bioscience.

"If it were the U.S. Centers for Disease Control ordering the virus, then after confirming all of the appropriate information, we would make the DNA and ship it," she said. "If, on the other hand, the order came from an individual who was ordering the DNA to be shipped to a P.O Box in Iran, we would not ship it."

The consortium has adopted a common "red-yellow-green" approach for their screening.

Safe sequences are considered "green," and the order is quickly filled. A "yellow" hit has a sequence that is similar to a pathogen but is not itself deadly. A "red" sequence belongs to a known pathogen.

For each yellow or red hit, the company writes or calls the customer's safety officer to learn if there is a legitimate reason for the order. If the person cannot be verified or has no legitimate reason to order that DNA, they may be reported to the FBI.

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"You never want to send it to an address for the cave in Afghanistan," said Gustafsson.

Fewer than 1 percent of orders are determined to be dangerous "red" hits, according to an analysis by the J. Craig Venter Institute, a La Jolla-based genomic research institute.

Federal enforcement falls short, asserted Xue-Nong Zhang of Epoch Life Science in Missouri City, Texas, which is not a member of the consortium but according to Zhang, abides by its own security measures. Zhang said he was even interviewed by the FBI more than a decade ago, and wrote that he found astonishing "the ignorance of the government and disconnection between different agencies."

The proliferation of companies is prompting questions about whether strategies for preventing the microbial mayhem need to be rethought.

An estimated 10 to 20 American gene-synthesizing companies aren't members, according to the consortium. Some, such as Epoch, may have their own internal guidelines; others don't, saying they lack the time and specialized knowledge, according to the Venter Institute analysis.

International players, particularly Chinese companies, are rapidly increasing their share of the market. And it is becoming easier for almost anyone to build a gene.

"With all the basic equipment needed to do gene synthesis flying around every corner of the world and free knowledge available unlimited, plus raw material providers synthesizing millions of bases of DNA every day unscrutinized -- how on earth are you going to prevent someone's use of this technology for harmful purpose?" asked Zhang.

The real problem might not be bioterrorists, but established scientists who make unintentional mistakes, added Stanford's Cho, who recommends extra attention by internal institutional reviewers.

Sam Weiss Evans, an assistant professor with the Program on Science, Technology, and Society at Tufts University, said regulators need to specify what part of a gene sequence -- and how much of this sequence -- makes it deadly.

But he warned that might not be enough. Because microbes' behavior is controlled by an intricate balance of gene expression, protein folding and other factors, the mere presence of a gene may not necessarily mean trouble, he said. And increasingly, companies make short DNA strands that are so tiny they lack any "fingerprint" that might identify them as part of something dangerous.

Finally, rules that focus solely on dangerous sequences miss the evil-doers who order benign strings of DNA and then reassemble them to create a threat, said Jennifer Doudna, a biochemist at the University of California, Berkeley, and a pioneer in CRISPR gene editing research.

"It is a very big challenge," said Doudna. "How can we be sure that you are checking all the ways that information can be encoded against all of the orders being placed around the world every single day?"

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