In the not too distant future, the phrase “shooting up” could take on a whole new meaning. At least if the U.S. Army has its way. Wired‘s Danger Room blog reported a few days ago that the military is seeking bids for a high-tech form of vaccination that could be delivered quickly and efficiently to a large number of troops in the heat of battle. More specifically, the Pentagon wants a DNA vaccine that can be administered via a literal shot to the arm—and a jolt of electricity. All without causing too much “discomfort” to the patient, of course.

Suffice it to say that this futuristic-sounding vaccine would be a far cry from what you and I received as children. As last year’s swine flu epidemic made painfully clear, our current methods of vaccine development, which have remained essentially unchanged for decades, are woefully outdated. The vaccines take too long—upwards of seven months—to produce, are easily prone to failure if not prepared correctly and, in many cases, lose their potency after only a year. These failings have helped draw attention to DNA-based vaccines, cocktails of genetically engineered plasmids which offer the promise of inducing a stronger, and more targeted, immune response. Where regular vaccines are slow to develop and hard to combine, DNA vaccines can be made relatively quickly and mixed together to ward off multiple pathogens at once. They are also generally safer to produce and administer, more durable and can be scaled more easily.

Like other vaccines, however, they are still primarily injected into muscles and thus suffer from the same inefficiency problems. Because the DNA is not injected directly into the host cells but into the spaces between them (the “intracellular spaces”), the vaccine first needs to be taken up before the cells can mount a robust response and pump out the necessary disease-fighting proteins.

The two main alternatives cited in the Army’s solicitation are gene guns and intramuscular electroporation. The first gene gun was designed in the 1980s by a Cornell University scientist as a tool with which to transform plant cells by blasting them with microscopic DNA-coated gold or tungsten beads carried on a powerful whiff of helium gas.

Gene guns have since focused their crosshairs on animals and humans alike, particularly after the Army recently embraced them as their vaccine delivery method of choice. The main downside is that it can only deliver small quantities of DNA, not the two or more vaccines at a time that the Army wants. Intramuscular electroporation, which improves vaccine uptake by temporarily opening pores in their membranes through short bursts of electricity, can be used to supply sufficient amounts of DNA, but it comes at a cost: pain. So what ideal device would the Army like?

The optimal vaccination strategy would capitalize on the efficiency of electroporation, eliminate the discomfort associated with intramuscular injection, and be useful for simultaneous delivery of two or more DNA vaccines. A minimal successful outcome would provide effective delivery with reduced discomfort for one DNA vaccine.

For the moment, electroporation seems to be the method of choice among the companies operating in this burgeoning field. Inovio, a Pennsylvania-based startup that has emerged as one of the field’s dominant players, claims that its electroporation system can boost cellular uptake of a vaccine 1,000-fold or more. The company employs a handheld needle-electrode applicator tethered to an electric pulse generator to inject the vaccine into skin or muscle and deliver a few short zaps of electricity to jostle the cells into taking it up. Unlike most such electroporation systems, Inovio claims its own is relatively painless—”tolerable without anesthetic.” But it’s important to bear in mind that while DNA vaccines are making concrete progress, they still have quite a ways to go before they supplant conventional vaccines. (Plasmid purification, in particular, remains a challenge.) With any luck, the Army will have found its desired device by the time the first DNA vaccines hit the production line.

Image: alvi2047/Flickr

We’ve just heard that we’re going back to Comic Con this summer, with a panel topic and line-up even bigger and better than last year’s event.

We are teaming up with Jennifer Ouellette and the crew at the Science and Entertainment Exchange to produce a panel on “MAD SCIENCE,” i.e. Science as a double-edged sword, ethically and morally neutral in and of itself, but dependent upon who wields it, and how.

Beloved Internet Personality Phil Plait is lined up to moderate (after he gets his tattoo) and we’re expecting guests from Eureka, Battlestar Galactica, Fringe, Stargate: Universe and more.  Watch this space for additional details.

In this week’s episode of Fringe, we have a woman, Valerie Boone, who suffers from a disease that makes her into a vicious cerebrospinal-fluid-drinking sort of vampire. It’s ugly stuff: she dances languidly at a night club, gets picked up by cocky young men, goes home with them, and then snaps their necks so she can drink their CSF. Nummy!

On the plus side, if you’re going to make a human body your soda fountain, CSF isn’t a bad choice. The pressure  inside the spinal cord is relatively low, just 200-300 mm of mercury. That’s pretty far below air pressure, so the CSF should come flowing out like water out of a straw once she tears it open with her scary pointy teeth.

But I hope she’s not too thirsty. The human body only produces 500 ml of CSF a day, and it typically has 130 mm at any given moment. CSF is produced from the choroid plexus, a paired organ attached to the brain. The fluid fills the fourth ventricle of the brain and flows out to surround the brain, filling the area between the pia mater and the dura mater, two membranes that line the brain and the skull, respectively. The CSF provides a cushion, and a degree of buoyancy to the brain, protecting it from sharp blows and whiplash. The CSF  also carries toxins and drugs away from the brain, and it helps transport hormones from one part of the brain to the other.

But even with all these roles, it doesn’t actually have a lot of substance. It’s fairly salty, but it has just 15-45 mg/dl of protein and 50-80 mg/dl glucose. Multiplied across  130 ml, she’s only getting, at most, 65 mg of glucose and 58.5 mg of sugar. She’d do better eating a Snickers.

We’re told  mid-episode that Ms. Boone is drinking the CSF because a disease is using up her own.  Technically speaking, the CSF is on a one way journey: From the brain to the dura mater, to blood vessels, which carry it off. But leaving that fact aside, there is some evidence that the body is aware of what’s going on with it’s CSF and tries to compensate for problems. Scientists experimented with altering the sodium concentration of CSF in sheep. They found that increasing the sodium concentration caused them to avoid salty food, while decreasing it led them to desire more. So maybe Ms. Boone should have been eating more potato chips, and fewer people?

As she became CSF depleted,  she would start to suffer headaches, loss of hearing, blurring of visions, tinitis, and numbness of the face. Sounds unpleasant. No wonder she was so cranky all the time.

As we’ve mentioned before, though, this is sometimes problematic when it comes to J.J. Abrams’s Fringe.  Still, we try not to critique.

Besides, Polite Dissent does such a good job of it already.  Head over to PD today for a recap of last night’s episode, including his ongoing homage to the Bulletin of Atomic Scientists.

We’ll leave the debates over the acting, direction, and overall adaptation to others (except to say that Jackie Earle Haley stole the show). But one aspect worthy of analysis is the story’s main conflict—the constant “looming” nuclear holocaust. Granted, we never actually see any evidence that the aforementioned holocaust is looming, save a few shots of Nixon upping Defcon levels—but we’ll address that later. When Alan Moore first published the book in 1986, the apocalypse on everyone’s mind was Cold War atomic bombs—which, as we’ve noted, no longer pack quite the same anxiety punch as, say, biological weapons. Today, gas masks and duct tape have replaced air raids and backyard shelters in the popular conscious, to the point where seeing mushroom clouds onscreen feels like you’re watching an ’80s homage.

Of course, none of this means that the nuclear threat is any smaller now than it was three decades ago: The danger of nuclear war is still present, and fear of missile attack still drives plenty of policy and military tech decisions worldwide. But, like Bird Flu, nukes seem to have a PR problem: Despite the fact that they could wipe us all out, the thought of them isn’t all that scary.

Which is really the main problem for Snyder and his estimated $125 million budget: No matter how faithful your script and powerful your characters, it’s tough to keep a story suspenseful when you’re working towards a climax that doesn’t pack a serious punch. Not helping is the fact that the film completely ignores the other side—the Russians. We get a few choice shots of Tricky Dick mumbling about war, but never once do we see Gorbachev ordering missile launches or troop mobilization.

Granted, world annihilation isn’t dull—it’s still enough to keep an audience engaged for 2 hours and 43 minutes. Plus Snyder never misses a chance to smack us with stakes-raising reminders of devastation (we counted at least 8 shots with the Twin Towers in the background). And when the destruction does come to the Big Apple (why do TV shows and movies always love to decimate New York?) Snyder saves us the book’s graphic images of strewn corpses and bombed-out buildings, instead focusing on the internal struggle among the Watchmen ranks. Nine million people sacrificed for the greater good, meh—but we’ll watch one lovable sociopath in a ski mask.

So should Snyder have updated his apocalypse with biotech? He’d have faced the wrath of fans had he done so. Plus who would think nuclear war could ever get boring? It’s enough to make you wonder what the next big all-consuming fear will be. Oh, wait, we know that already: thinking robots.

Image courtesy of Warner Bros.

We see nerve gas often enough on TV and the silver screen that it’s worth understanding out just how it works. VX gas can be deadly when ingested or when it makes contact on the skin. Depending on how much exposure a victim has suffered, it can kill in 10 minutes or a couple of hours. It functions by interfering with the break down of acetylcholine in the muscles. Normally when a nerve fires, acetylcholine is released to cause the muscle to contract. After the contaraction, an enzyme is released to break down the acetylcholine, allowing the muscle to relax. The phosphorous in the VX gas bonds with the enzyme, causing the acetylcholine to stay in place, leading to muscle contractions and spasming. Death can result from asphyxiation, but also from the victim harming themselves while in convulsions.

In the show, the brilliant Dr. Hood comes upon a victim seconds after she has been exposed to the chemical. He does exactly the right thing: He triggers the emergency shower immediately, stripes off the exposed clothing and gets as much of the VX off her as possible. The poison can be countered with an antidote, so people exposed to the gas can be saved if they’re treated in time. They’re only hope is that their exposure is low enough that they can get to the hospital. A high dose can kill in 10 minutes, a low one might take hours to kick in. VX, even in gas form, is heavier than air, so the key to surviving it is to get to fresh air and high ground (which means you have to do the opposite of what you would do in case of a dirty bomb or atomic explosion, where the goal is to avoid radioactive fallout by going inside and staying on the lower floors, as fallout can settle on roofs, so make sure you can tell your apocalyptic scenarios apart!)

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Making a bioweapon requires more than just finding a disease thats suitably lethal and contagious. You need an infectious agent that can be stored under a range of conditions for at least some time, which can dispersed effectively, and which can be made in bulk. You can’t just grab one human, inject him with something at your convenience, and then send him back to infect all the rest — this might work once or twice, but then a simple quarantine protocol for all new arrivals or escapees would drastically limit the effectiveness of the weapon. You need some way to infect lots of people in a short period of time. In the shadowy world of bioweapon development, the favored approach is aerosolization: essentially creating a spray or mist of particles containing the infectious agent, which is then inhaled directly into the lungs.

This is not as easy as it sounds: a lot of agents can’t be effectively aerosolized for a number of reasons, including a short life span outside a living host, or because they are damaged during the aerosolization process. (This is why anthrax is a perennial concern to those tracking bioweapons as it naturally forms robust, long-lived, and infectious spores) When the U.S. stopped developing bioweapons in 1969, it had weaponized just seven agents. The Soviet Union worked on developing another 10 or so. Given that Skynet kills so many people and animals on Judgment Day, the pool of surviving diseases to weaponize would have been sharply reduced, limiting its options. (Most infectious diseases are essentially crowd diseases. Eliminate the crowds, or the animal reservoirs a disease can persist in, and you eliminate the the disease) All this means that one bioweapon, let alone two, would be a tall order, making it valuable enough to Skynet to send a terminator into the past to protect it.