by Shanon Hunt
“And so?” Malloy barked. Get to the point, Jordan.
“I’m no mad scientist, but the only thing I can think of is that they weren’t trying to silence the pain gene entirely. They were trying to modulate it.”
“What does that mean?” Garcia asked.
“The RNA silencing is like an on–off lightswitch, right? Maybe instead they’re trying to create a dimmer switch. That might give them a new approach to pain management.”
“Is that possible?” Christ. All this science was so far beyond Malloy’s expertise, he was losing confidence in his ability to effectively manage this case, let alone solve it.
“Well, that’s the thing. The technology to engineer a new gene like gene Z is already known and available, though in all honesty I’ve never seen anything like this before. But what we can’t do yet—what no one in the whole world has been able to do yet—is to precisely deliver a megagene like gene Z into the DNA of a human. From the injection, the gene has to first find the right tissue. Then it has to find the right cells. Specific targeting like that is extremely difficult. But even if it manages to accomplish getting to the right place, it still has to cross the cell membrane into the nucleus.” Jordan stared into the screen. “It would be like trying to drive a freight train through a keyhole. It’s impossible. But if that’s not impressive enough, get this. In both victims, more than ninety-five percent of the target cells expressed the modified gene Z. It’s the most effective gene delivery system I’ve ever seen.” He looked down at his DNA toy and spoke in a low voice, as if only to himself. “How the hell did Dr. Frankenstein do that?”
Spooky as hell.
From across the room, Wang spoke for the first time. “Do the spinal ports have anything to do with it?”
“Kinda,” Jordan replied, standing up straight. “The drug is targeting neurons. Brain cells. And the easiest way to get a drug to a brain cell is intrathecally, through the cerebrospinal fluid. Great big genes like this wouldn’t be able to cross the blood–brain barrier to get to the right cells. But again, a port is just another overcomplication. You don’t even need it. You could easily just stick a needle directly into the spine.”
Several people groaned.
“So why have the port at all?” Wang asked.
“Two reasons I can think of. One, if the patient is getting a lot of injections or infusions over time, a port reduces infections and injection site reactions. But this is usually for inpatient care, like at cancer centers. The other reason is if the patient is self-injecting. A port provides a precise point for the needle when the drug’s being delivered by someone without medical training. But obviously it’d be pretty hard to self-inject at that angle. In this case, they’d probably need a friend or family member to inject them.”
Jordan sat back down and again reangled his camera.
“Jordan, this is extremely interesting.” Malloy rubbed his temples. “But we have eight people dead, and we need to find the source of this drug before others die. How do we begin?”
The question was really more to himself. He wasn’t expecting the boy to produce an answer.
“I don’t know, but this guy had to come from somewhere with money. This is cutting-edge biotech, not cheap and not widely available. It had to come from a biotech or university with a huge grant or some kind of special funding that could build a super-high-tech lab. This wasn’t developed in some lunatic biohacker’s garage, that’s for sure.”
A lunatic biohacker. Malloy snapped his fingers. “Exactly. That’s exactly who we’re looking for—a lunatic biohacker. A do-it-yourself biology lab built by someone with money.” Some shop set up in the middle of nowhere. Hiding.
Chapter 14
Allison felt the weight of the Spiragene team’s stares as she stepped over to select an Evian from the untouched refreshment table. She picked up a napkin imprinted with the Spiragene logo. Austin never would have approved such a ridiculously ornamental expense for Quandary. She was out of her league.
Hiding a grimace, she took her seat at the end of the table.
Barbara Gilbert shot her a winning smile. “After Chung-Hee has reviewed the Quandary portfolio, we hope you’ll indulge us for just a couple minutes to tell you a little about our latest design ideas. We haven’t had a chance to discuss some of our new technologies with Austin or Brad, so perhaps you could relay our excellent progress to them when you see them.”
Allison clutched the Evian bottle in both hands, wondering how long she’d be able to pull off this charade. “Of course. And how long has it been since Austin has visited?”
Gilbert looked at Hwong. “Has he even been to our new location?” She looked back at Allison. “Austin and Quandary are the reason we have this beautiful new building, and he hasn’t even been here to appreciate it. It’s been over a year, I think. Maybe you can drag him over some time.”
Her coquettish smile made Allison wonder if Austin had slept with her, and she tried to suppress a flash of jealousy. She willed her tense shoulders to relax, hoping Gilbert wouldn’t notice her uneasiness. How had Austin become such a mystery?
Hwong stepped up to the front of the room. “We currently have three ongoing projects for Quandary, so I thought I’d review them in order. We’ve finished the work on the other five projects. You don’t want to hear about those, do you?”
Allison relaxed her grip on her bottle and sat up taller. “I won’t need an update, but I was wondering if you could provide me with reports? I couldn’t find them on our server.”
“Oh yes, that’s probably because we don’t send the reports to Quandary. Brad requested that we only load them onto the secure shared drive, due to the stringent nondisclosure agreement with Quandary.”
She forced a snicker. “Boy, don’t I know it. Austin’s very concerned about data leaks. We’ve had some issues in the past.”
She was getting better at this.
“When we’re done here, we can go over to my office and I’ll give you access to the drive,” he said. “Okay, so we have two constructs for your chronic pain program.”
Funny, they didn’t have a chronic pain program. Despite her frequent reminder to Austin that initiating a pain program was the reason he hired her, Austin hadn’t taken an interest in chronic pain. It’d always frustrated her.
“They’re both delivered via the spinal fluid, but one targets nociceptors and the other targets neurons. I’ll start with the SCN9A mutant gene. This is just one of a handful of genes responsible for pain perception, and it’s the first one we’ve ever been able to target.”
Gilbert was watching her closely. Allison dropped her hands onto her lap, afraid her nervousness would be obvious.
“The SCN9A gene, when it’s functioning properly, opens ion channels that send pain signals to the brain. If you have a mutated 9A gene, those channels don’t work properly. One of two things can happen. They don’t open, resulting in no pain sensation, or they open too often, resulting in an oversensation of pain. You might have heard of Man on Fire Syndrome.”
She nodded. It seemed pretty self-explanatory.
“What Brad wanted us to do was see if we could deliver two edited fragments of the 9A gene to the cell—not replace the entire gene, just make a small modification to the gene in two locations to mutate it so that the ion channel gates wouldn’t open quite so frequently and the patient would feel less pain. It’s the effect you’d expect from a painkiller. Make sense so far?”
She nodded again.
Hwong displayed an image on the screen, which looked like a clamshell made of honeycomb. Sitting inside the clamshell were several spirals that looked like short DNA strands standing up. “So we designed a DNA scaffold that looks like this. This is literally just a 3-D nanoscale object built with short DNA strands that lock together like Legos. The idea is that we can enclose our nanorobots and cargo within this shell and send the whole package to the target cell.”
“I’m sorry, did you say nanorobots?”
“Y
eah, that’s right. This is very new technology. We can design and string together DNA strands with a specific set of instructions or purpose. We can make them walk, we can make them pick up items, sort them, or move them around the scaffold.”
Hwong clicked a button, and the clamshell came alive. The small DNA strands moved across the honeycomb grid. “See the blue one? That’s a nanobot whose task is to pick up the red cargo and move it to a different location. We can even make bots that are instructed to assemble DNA or RNA …”
She couldn’t hide her awe. It looked like science fiction, and Austin and Quandary were on the forefront of it. But her awe turned to resentment. Why hadn’t Austin told her about this? She’d begged him to consider starting a program in chronic pain. Pain was her area of expertise; she’d hoped to run a program like this someday. Why would he have given it to a consultant?
“ … whole package, the clamshell, gets locked with the nanobots, gene fragments, and viral vectors inside.” Hwong pointed his laser to a small floppy DNA strand outside the shell. “This strand here is looking for the target cells. In this case, it’s looking for nociceptors that run from the spinal cord all the way to the skin.” He clicked the Play arrow again. “The package gets injected into the spinal cord, seeks out the nociceptor, and attaches outside the cell membrane. Then the shell opens. The red cargo is the 9A fragment, encased in a gene editing platform—your CRISPR platform, actually. A nanobot attaches the cargo to a viral vector that will transport the whole package—we call it the payload—into the cell.” He pointed the laser at one of the DNA strands. “This bot here moves the payload to the cell surface. Then another bot transfers these gene fragments, one by one by means of this virus, into the nucleus of the cell and then builds the gene on the inside. Once the job is finished, the DNA scaffold self-destructs.”
Gilbert leaned forward to meet Allison’s eyes, sliding her slender hands along the gleaming cherrywood surface. “You can see why we’re so excited to move our work into animal models. This is cutting-edge technology. Spiragene is on the cusp of a breakthrough with gene delivery. No one in the world has been able to modify a gene so precisely. We could cure so many incurable diseases with these nanoscale DNA robots. In time, they’ll be able to do anything we can think of.”
“So this one, this SCN9A mutation robot—does it work?” Allison couldn’t wait to hear more.
“That’s the part that’s frustrating us,” Hwong answered. “By contract with Quandary, we’re not allowed to publish our work until the proof of concept. We haven’t yet actually seen if it works in cells or in an animal model, and we can’t even tell the world about this new platform.”
Allison frowned. “But I thought you’d built the construct already.”
“Oh, no. We’re not a wet lab. We don’t do any in vitro work. We’re an in-silico lab. We only design the constructs on the computer. It has to be synthesized in a gene synthesis lab, and then it can be cloned and screened for lab experiments.”
That explained the fancy high-rise office. It was just a computer lab. “Who’s doing the synthesis?”
Hwong exchanged a curious glance with Gilbert.
“Um, we thought you’re the one managing that. Brad said you were researching and had a short list of labs?”
Shit. Shit. Shit.
Gilbert frowned at her, leaning in a little closer.
She couldn’t come up with something to save herself. She stammered, “oh, yeah, right. I’m, uh, still working on that. Sorry. I’ve been really stressed lately. A lot of balls in the air.”
Gilbert’s eyes narrowed, then she forced a smile. “Of course.”
Chapter 15
Allison stepped into the lobby of Quandary and paused, listening. It was 7:10 p.m., thanks to New Jersey rush-hour traffic, and the office had to be empty. But she didn’t want to answer questions about her whereabouts over the last five hours, least of all from the auditors. The floor seemed quiet as she moved down the hall toward her office. She peeked into the conference room. Rooney and his team were gone. Thank god.
Her head was spinning from everything she’d seen and heard at Spiragene. The pain research project appeared promising, especially given Austin’s commitment to supporting diseases that currently had no treatments. So why had he kept her in the dark about this? Worse, he had to have lied to her all those times she’d brought up moving into chronic pain.
None of this explained why her signature was on this invoice without her knowledge, and she still owed an explanation to the auditors about the scope of the work.
As she waited for her computer to boot, she twisted the ring on her right ring finger. A gift from Austin, it was cubic zirconia, but it sparkled like diamonds. He’d told her he would buy her the real deal when he finally left Jackie. Allison sighed. She wasn’t dumb. It would be years before he left his wife. But she loved the ring and wore it every day, and Austin smiled every time he saw it on her finger. It was their special secret.
Of course, that was before all this weirdness started.
She felt a flush of anger creep up to her face. She reflexively pulled out her phone but only scowled at it. Trying to get answers from Austin was a waste of time. He hadn’t taken her calls in a week.
She checked her notebook from the Spiragene meeting and logged in to the shared drive. Eight file folders. She drew a deep breath and opened the first, LXR101008—the Elixir portfolio, Hwong had said, the name being Bradley Elliott’s big contribution to the program. The boss had apparently thought it was a clever naming convention. Brilliant, Brad. Well done, sir. She despised that guy, and she hadn’t even met him.
“Hey, Cruella, wanna grab a beer?”
She yelped. “Jesus, Ryan! You scared the shit out of me.”
Ryan leaned casually against her door as if he were modeling his three-piece suit. He fancied himself a ladies’ man, but he tried way too hard. He had the pretty-boy, clean-cut look of Neil Patrick Harris—and the Barney Stinson attitude to go with it.
“Thanks for the visual,” he said. “Pack up. Let’s go to the bar.”
She narrowed her eyes. He’d never asked her for drinks before. “Can’t. My day isn’t over yet. Still have some things to do.”
“Really? What’s so important that needs to be done at 7:00 p.m. on a Wednesday?” He moved into her office and peered over her shoulder. “Since when did you have that kind of work ethic?”
Shit. She slammed her laptop closed, the only thing she could think of to keep him from seeing the Spiragene shared drive. “You know what? You’re right, I do deserve a beer. We both do. It’s been an incredibly lousy week. Let’s go. You’re buying.” She swiftly closed her notebook and swept the stack of Spiragene business cards into the trash can.
She could keep secrets, too.
***
“Cheers.”
She’d planned to make this a very quick happy hour so she could get back to the Spiragene–Quandary drive, but Ryan wasn’t drinking his beer. He sat next to her, looking at her suspiciously.
“What?” she snapped. She was in no mood for a long night of slow sipping and stories of Ryan’s Tinder dates. She had stuff to do.
“I’m just a little surprised you’re not taking this harder.”
She tilted her head. “What do you mean?”
“Listen, Al, I know you and Austin were bangin’ boots. I’m not an idiot.” He laughed. “Though even an idiot wouldn’t have missed it. Subtlety is not your greatest attribute.”
She opened her mouth for an indignant denial but gave up. “That obvious?”
He took a long drink. “So how are you doing with the news?”
“What news?”
“You didn’t talk to Kiran?”
She broke out in a cold sweat. Dammit, another Kiran announcement, and she’d missed it. No wonder Ryan was Austin’s golden boy; he was the one actually showing up and answering his phone.
She dropped her gaze back to her beer. “I saw his call, but I was in a meetin
g. I couldn’t pick up.”
“You don’t know.”
“Know what? For the love of god, just spit it out. What happened?”
Quandary was being acquired. That had to be it.
He kept his eye on the bartender as if he were too nervous to look her in the eye. “Austin’s AWOL. He didn’t show up for a deposition yesterday, so the feds stopped by his house. Jackie said he told her he was going to California on business, which was illegal in the first place. But there was no record of him getting on a flight. His limo driver confessed that he disappeared at a truck stop somewhere on the way to the airport, but the chicken-shit didn’t call the police. Now he’s busted for aiding and abetting. Dumbass.”
She gaped at him as she struggled to piece his words together. AWOL. Austin was running away. He was leaving Quandary and everything they’d worked for.
“Ryan, are you messing with me? Because if you are, that’s a really shitty joke.”
He still didn’t look up. “Sorry. I thought you’d talked to Kiran. And then I thought you might need a beer. Even Cruella de Vil needs a friend every now and then.”
Austin was leaving her.
She took a pull from her beer to hide her expression. She didn’t want to appear fragile in front of Ryan. Sleeping with the boss somehow carried a slightly higher dignity score than admitting that she was in love with a coward.
She changed tacks, hoping she could hold it together. “So what does this mean for Quandary?” Her voice shook.
