Terror! PANIC! MAAYYYHEMMM!!!

by emptypockets

Plutonium Page, DemFromCT, and I were sitting in the TNH combination secret batcave/Hall of Justice/jacuzzi spa/bowling alley yesterday, monitoring the globe for emerging threats to our Dutcho-American way of life, when an alert appeared on the TNHoscope. "Alert!" said P.P. "ALERT! A-freakin-LERT!!" We jumped in the biodiesel-powered TNHmobile robo-dolphin and sped off to investigate.

In London, the Guardian had discovered and "revealed" that short synthetic single-stranded DNA sequences could be ordered custom-made, and (shockingly) these orders would then be carried out and, yes, even delivered to the person who ordered them. They further revealed that the "DNA letters" as they adorably call them arrived in "a small plastic phial with a tiny blob of white gel at the bottom."

"You mean a vial?" I asked.

"Yes, a phial."

"Those phenomous phillians!" I proclaimed.

"Phery vunny," they said.

The Guardian emphasized that "because the industry is so new and unregulated," DNA synthesis companies aren't doing background checks on their customers. Commercial DNA synthesis has been around for about a quarter-century (PDF). And as long ago as 1976, before DNA synthesis had been developed as a commercial application, the first completely synthetic gene was constructed and put into living cells (PDF). DNA synthesis today is positively quotidian, among the most trivial tasks in modern research.

The Guardian was clearly thinking about the recent de novo synthesis of poliovirus. They shake the old terror-stick and suggest bioterrorists could download a viral genome sequence from the internet, design several hundred short oligos, order the sequences and have them delivered (this is the step that scares them), anneal them into double-stranded DNA fragments, ligate them together in order, clone the whole thing into a vector, express it in some culture system, and then somehow release it into the public. Now, if you're Dr. Evil in his Underground Lab (which is what you'd have to be), what's the tricky part of that scheme? Hint: It's not getting the oligos synthesized. In fact, as I write this you can pick from any of four different oligo synthesizers on eBay for less than the cost of a new MacBook, and do it yourself at home.

The rest of the steps are trickier, though. Tricky enough, that for the up-and-coming evildoer it would be much easier to hide in a car trunk and start shooting people with a sniper rifle, or pack a truck full of explosives and drive into an office building, or hijack a plane and use it as a weapon. Those are real threats. This is not.

The Guardian kept shaking its bogeystick at us anyway:

"This is the most disturbing story I have heard for some time," said Phil Willis MP, chairman of the parliamentary science and technology committee. "There is clearly a massive loophole which needs to be dealt with by regulation or legislation."

Should a flag be raised if someone starts ordering hundreds of oligos designed against a nasty pathogen's genome? Sure. Is it "the most disturbing story" that Willis has heard for some time? Depends which cave in Afghanistan he's been living in the last five years.

A few years ago, the media provoked a similar scare about human cloning. Republicans in Congress called some total fruit loops from a cult called the Raelians, who believe that life on Earth was created by extraterrestrial genetic engineers, and who claimed they were about to clone a human in a secret lab in an undisclosed location. This scare is similar. There is a real issue here, buried under the hype. But, as Nature magazine also writes today, there's a lot of hype.

We returned to TNH-HQ happy to have dispensed with the latest threat against humanity. "Of course," DemFromCT said, "we might also have dismissed the threat of anthrax a few years ago, and been wrong about that." "But would regulations have helped?" I asked. "Let's ask AQ Khan," Plutonium Page said. And she was right -- there will always be dangers in the world. Sensible regulation can deal with some of them, but insensible panic will always make them worse. And there are some things you just have to pray won't happen -- and count on groups like us, the TNH Justice Squad, and you bloggers there at home, (and hopefully someday a competent government,) so that when or if those threats become real, there's a plan, there are trained personnel, and there is leadership to see us through.

Rest safe, America. Those 70-mer oligos won't be harming you today.

Comments

[Kagro X]

I know a Vil Willis. Is that the same guy?

[viget]

You have got to be kidding me. Oligo synthesis is now a bioterror threat? Boy, there will be tons of pissed off PIs if that's ever followed up on.

And creating an infectious vector of several kb from scratch like this is hella difficult (the number of possible combinations of ligating n oligos being very large; I have enough trouble just trying to ligate my inserts into my vectors!). Much easier to just PCR it from a template, but of course that would require having an infectious poliovirus template to work from, and I assume there are decent controls on the sharing of potential bioterror vectors.

[emptypockets]

Kagro, could be -- you should vone him and ask

viget -- I was hoping you'd stop by for this one. I know. That was my reaction too. The methods section in the supplemental material to the poliovirus paper are interesting, actually. (The Guardian was trying to make smallpox... fortunately they went to the trouble of putting nonsense mutations into the three oligos they ordered, I guess so they wouldn't spontaneously re-hydrate, mix, ligate, and um... somehow... regenerate the rest of the genome while they're at it...) The poliovirus reconstruction sounds like it was a real pain in the ass. They actually used a combination of straight annealing and ligating oligos and a modified pcr strategy to get it. I should have mentioned there are companies now (here's one I've heard of) that will synthesize double-stranded DNA up to 40kb for you. So, something like that I think it is reasonable to ask them to check what they're building. Although frankly for any bioterror threat -- or any natural biological threat -- I think trying to rapidly detect and contain it when it happens, through public health preparedness, is a far better use of funds than trying to keep it from ever happening. (Avian flu is not a bad example.)

[Commander Deathtrap]

I resent this. Some of us Evildoers do have the patience and determination to stick it out and not settle for shooting people out the back of a car trunk. Sloppy, cheap, and hastily slapped together plans shall not be hallmarks of this Evildoer!

[DemFromCT]

Holy virulence, Batman 'pockets! Can't we all just get along?

[viget]

'pockets--

I just read that Guardian article. Too hilarious. Apparently they put in the nonsense mutation so it wouldn't run afoul of some UK law against transporting potential bioterror agents, because the law had some clause about "DNA related to an infectious agent." But it's like you said, so are the oligos going to spontaneously rehydrate, ligate together and somehow be transcribed and translated to make an infectious virus particle?

That being said, I think for batch orders of many oligos or for orders of dsDNA that are longer than say, 1kb, a computerized screening process isn't a bad idea. But this needs to be done with consulting leading virologists and other scientists, it shouldn't be that everyone ordering oligos needs a background check or something.

On that note, the ridiculousness has ramped up a notch with irradiators. My wife often does hematopoeitic reconstitution of lethally irradiated mice, so she needs to have access to one of those. Apparently now to have access Homeland Security has a mandated background check and access controls to the facility. Like a would-be terrorist is going to steal the radioactive source and make a dirty bomb? Apparently, you wouldn't live very long if the source isn't properly shielded anyway.

[vachon]

Between massive loopholes and turning corners, I'm getting quite dizzy, phrancine.