DARPA Safe Genes concept

CORRECTION: DARPA is not looking to directly alter human DNA, as this article originally suggested

WASHINGTON: If you talk with senior defense officials there is one threat they will acknowledge is at the top of their list but they rarely discuss in public — biological weapons. Now DARPA wants to develop defenses against biologically engineered threats before they are ever unleashed, the agency’s director made clear this morning. That includes proactively boosting troops’ immune systems to produce a wide array of antibodies and biochemically blocking hostile attempts to edit DNA.

“Our focus is about the protection aspect and the restoration, versus enhancement,” Steven Walker said when I asked him about human augmentation during a CSIS conference. “All these technologies, they’re dual use. You can use them for good; you can use them for evil — and DARPA is about using them for good, to protect our warfighters.”

Steven Walker

Super Immunity

That doesn’t mean the US military has forsworn the use of synthetic biology techniques on human beings. To the contrary, Walker is very interested in ways to enhance the immune system, effectively turning the body into its own pharmaceutical factory.

“Can you actually protect a soldier on the battlefield from chemical weapons and biological weapons by controlling their genome, [by] having the genome produce proteins that would protect the soldier from the inside out?” he asked.

Well, why not just brew the necessary vaccines, anti-viral treatments, and anti-toxins in a normal factory and issue them as needed to the troops? That’s how we’ve dealt with naturally occurring diseases. And DARPA is working on that too, Walker said, with a program “to build a vaccine in 60 days or less for 20,000 people for a virus you’ve never seen before.”

The problem is that developing, producing, stockpiling, and dispensing one treatment at a time — even in just 60 days — may not work fast enough against future bioweapons. As soon as you develop a defense against one form of artificial plague, the enemy can use gene-editing tools to create a different version, one whose biochemical structure is just different enough that the old antibodies don’t recognize it anymore.

Many diseases naturally mutate this way all the time. That’s why you can get a series of shots in childhood that protect you against measles or chicken pox for the rest of your life, but you need a new flu shot every year to stop the latest strain — and no one’s figured out how to stop the common cold. The so-called Spanish Flu of 1918-19 killed more people than World War I; imagine that as a weapon.

“To have a shot available for every case that might be out there is becoming more and more intractable, because [of] synthetic biology and the ability of folks anywhere in the world to make something that’s slightly different,” Walker said. “You can’t stockpile enough of the vaccine or the antivirus capability to protect the population against that in the future.”

Schematic of how CASPR Cas9 gene editing works

Undoing the Edit

DARPA is also looking at neutralizing or even reversing the effects of CRISPR Cas9 itself, the enzyme that made today’s breakthroughs in gene-editing possible in the first place. (It’s worth noting that China is now a leading country in gene editing science and its technology.)

“How do we reverse it [genetic editing] if it gets out into the wild and gets out of control?… That’s what the Safe Genes program is all about,” Walker said. “We’ve actually made a lot of progress there in being able to control gene edits.”

Walker didn’t go into specifics, but there’s plenty of non-military work in this area as well. It’s even led by some of the pioneers of gene editing themselves, who understandably would like a way to undo the effects if one of their experiments goes wrong.

The irony of gene editing is that the crucial tool wasn’t invented from scratch in the lab: It was found in nature. Many bacteria use CRISPR — a whole complex of DNA sequences — as a natural defense against invading viruses, allowing them to “recognize” the viral DNA as a foreign body and then use the Cas9 protein to cut it apart, “killing” the virus. (Though technically viruses aren’t living things in the first place). Scientists repurposed CRISPR Cas9 to snip apart and reorganize genes.

It turns out that, over millions of years of evolution, some viruses have developed an immunity to CRISP Cas9. They use so-called Anti-CRSPR proteins that shut down the enzyme so it can’t start slicing DNA — which would stop gene editing dead.

Lisa Porter

Benign Biotech

There are many more benign applications for biotechnology, said Walker’s boss, Lisa Porter, the deputy under secretary of defense for research & engineering.

“When we think biotech in DoD, we think chem/bio defense, and that’s an element of the problem — but there’s also a lot of opportunity space that people don’t necessarily realize unless they talk to the biologists,” Porter told the CSIS conference. “[So] we will be focusing, not just on the traditional tenets of biotech that we always do, but we’ll be expanding into, what are the opportunities for new materials, new applications?”

One biotech project she offered as an example is developing new materials to rapidly lay down new runways. That’s a matter of intense interest to the Air Force, which is increasingly worried its big central bases are easy targets for long-range missiles and wants new ways to either repair them or create alternative sites in a hurry.

What about human augmentation (boosted humans)? That gets a lot of concern and media attention, Porter said — and quite rightly: “You read about what China is doing and we should be concerned, because they don’t have the same set of moral and ethical norms that we have in our country.” (DARPA is careful to note in many of the web pages outlining genetic and related work that they work closely with recognized ethicists to ensure they are not crossing lines that should not be crossed.)

Porter, like Walker, did not mention any American plans to biologically enhance our own troops. But there are DARPA efforts that could, in the fast-changing world of biotech, lead to smarter, faster healing and stronger humans. Or try to stop what other countries have done to their troops.

The original version of this story suggested DARPA was studying techniques that would edit the human genome. In fact, DARPA is looking at techniques that would temporarily affect how genes are expressed, without altering the DNA itself.