Monday, June 7, North Stamford

Jake

Monday. The start of my first week alone. I try not to think about my family, rushing out of our home as if it’s a dorm room. For once, the sight of Greenbeck Dermatology, with its blond walnut reception desk staffed by permanently smiling young women, doesn’t annoy me. At least this part of my routine hasn’t changed.

Erin meets me at the nurses' station, previewing my morning as I inhale a second cup of coffee. “Nina squeezed a couple of study patients into your 8:30 slot,” she explains, raising her hand to cover a yawn. Apparently, I’m not the only one who had a restless night.

I set aside my coffee before greeting my first patients: a young, recently engaged couple who come in to see me every six months for their Botox fix, hers to treat imagined forehead wrinkles and his to soften the deep crease in his brow.  Both agreed to enroll in the Replacidin study when I saw them over the weekend.

“How’s the wedding planning coming along?” I ask as I wipe layers of make-up from Brooke Murray’s forehead. “Have you guys picked a date?”

She happily fills me in on the details as I draw her Replacidin into a syringe. Brooke does PR for UBS in Stamford, where her fiancé Dean works as a bonds trader, whatever that means. They’re both in their late twenties and make the kind of cute but superficial couple that should fit in perfectly with the pleasantly bland Fairfield County lifestyle.

Damn, I think as I position the needle above Brooke’s forehead. When did I become so jaded?

“Okay… Now make an angry face. Really angry.”

Brooke strains to wrinkle her forehead, barely managing to make it twitch.

“I can’t!” She giggles like a teenager. “Dean, cut it out! It’s not funny.”

Her fiancé is standing behind us, making goofy faces. “Come on, hon,” he jokes. “Just think of our folks arguing over the guest list.”

As she scowls, I inject her furrowed brow and then apply an ice pack. “Good. Now hold that there for a few seconds. You did great, as usual.”

We move on to Dean next, and a few minutes later, the young couple leaves the office hand in hand – the picture of pre-marital bliss.

I try not to hate them.

Although Brooke and Dean represent my forty-eighth and forty-ninth Replacidin test subjects, I have yet to see any significant complications from the experimental drug. In fact, not one of the twenty-five study centers worldwide has reported a significant Replacidin-related side effect – a truly remarkable fact given the lethal origins of the neurotoxin.

I wonder how many of my eager volunteers would still be lining up for their Replacidin shots if they knew the full story behind the drug’s development.

Amazingly, up until this point, no one has seemed to care what Replacidin actually is, but that all changes when I reach study volunteer number fifty.

“So,” Briana Caulder challenges as I draw up her syringe. “Tell me again. What exactly is it that you’re about to inject into my face?”

Once again, she’s the last patient to see me at the end of a hectic session. As she waits now for my answer, her forehead creases expectantly.

I tap the air bubbles out of her syringe of designer neurotoxin, setting it down on a metal tray as I consider the question. “Well… believe it or not, you’re the first study participant to ask me that question.”

“I can believe it,” she says knowingly. “Most people are very trusting, Jake. They just assume if you’re a doctor, you couldn’t possibly do anything to harm them. Right?”

“That is why we take an oath,” I say, wondering when we moved to a first-name basis.

“Sure,” she smirks, “but then again, so do politicians… and lawyers.”

“Point well taken. But in this case, I can reassure you that Replacidin’s perfectly safe. The drug’s already passed every safety test that’s been thrown its way. In order to reach the clinical trials stage, Pulsar Nanotechnologies basically had to prove it has the same safety profile as water. Besides, since this is a trial, there's a fifty percent chance you'll be getting the placebo.”

Briana frowns. "But you still haven’t told me what’s actually in the stuff.”

“All right.” I pull up a stool to sit next to her. “Then let me start with a question. Are you a sushi fan?”

That raises an eyebrow. “Um, is this your way of trying to ask me out on a date, doc?”

“Nope. Just trying to answer your question. Have you ever heard of fugu?”

Now her eyes twinkle with recognition. “Yeah, I think so. Isn’t that some kind of delicacy in Japan?”

“That’s right. It’s raw pufferfish.” I tap into my mental data base. “The most prized species is the torafuga, or Tiger Blowfish. The Japanese elite have been preparing and eating fugu sashimi for centuries, although it’s been banned at times. Today, only specially licensed chefs can prepare and sell the stuff, and it takes up to three years to complete a typical fugu apprenticeship. That’s the same amount of time as a standard medical residency.”

Briana’s eyes widen with disbelief. “You’re kidding, right? Three years of training just to learn how to make sushi?”

“Technically, it’s sashimi. The most popular dish – Fugu sashi – is sliced so thinly that you can see the pattern of the plate it’s served on through the meat. Most fugu chefs use a special knife to prepare the sashimi slices, which are often arranged in the form of a chrysanthemum flower. Here…” I root through a drawer to retrieve my binder of research notes. It takes me a minute, but I finally locate the color print I’m looking for and hand it to her.

“As you can see, the dish can be quite intricate.”

“Like a piece of artwork,” Briana notes. “It’s beautiful.”

“Yeah. Beautiful, but deadly. The Japanese call the chrysanthemum their ‘solar flower,’ symbolizing imperial power and longevity, but in European cultures, the flower represents something else entirely.” I pause for dramatic effect. “It’s also known as the ‘death flower.’”

Briana’s jaw drops. “Get out! Are you saying the stuff is poisonous?”

“Not when prepared correctly, but mistakes have been known to happen. The Japanese Ministry of Health puts out an annual list detailing which species and body parts can be eaten safely, but that doesn’t prevent a handful of people each year from dying of fugu poisoning. Most are fishermen who make the fatal mistake of eating the liver, which contains the highest concentration of a deadly neurotoxin called tetrodotoxin.”

“Tet-rodotoxin?”

“That’s right. The toxin works by blocking nerve conduction, which causes muscle paralysis. It’s actually made by a type of bacteria that lives in the pufferfish’s gut, and it’s also found in some crab species, newts, toads and the blue-ringed octopus. They use it for defense or to kill prey. There’s still no known antidote.”

“And that’s what you want to inject into my forehead?” She shakes her head emphatically. “Thanks, but I think I’ll pass.”

“But you’d be okay with me injecting botulinum toxin, right?”

She considers that for a moment. “Yeah… well sure.”

“Even though it’s one of the most potent neurotoxins known to man? What if I told you that less than 100 nanograms of botulinum toxin type A – that’s 100 billionths of a gram – could kill you? Tetrodotoxin is quite vanilla by comparison.”

“But people have been shooting up with Botox forever. The product is safe. It has a great track record.”

“When used the right way,” I counter. “Just like Replacidin. Like I said, the drug’s been studied for close to a decade now. That means there’ve been dozens of animal studies and three smaller human trials. We know it's safe."

“I don't know." She pouts, drawing my eyes to her lips. "You just said your drug causes irreversible paralysis. That there’s no antidote.  And that people die from it every year. No offense, but why would anyone be crazy enough to let you inject that into their body?”

 “I said those things about tetrodotoxin,” I correct. “Comparing Replacidin to tetrodotoxin is like comparing a cruise missile to a stick of dynamite. Here…” I hand her another sheet, this one a graphic illustrating the structure of a Replacidin nanosheath. “How technical do you want me to get?”

She smiles mischievously. “I took biochem in college, so knock yourself out.”

“Okay,” I answer, unable to hide my surprise. Could this really be the same superficial woman I met last week? “So do you know what carbon nanotubes are?”

“Sure,” she shrugs. “They’re just thin tubes of carbon molecules, right?”

“Basically… if by thin you mean that you could fit around 50,000 nanotubes into the width of a human hair.”

“Hmm. I guess the people who roll those must have pretty small hands, huh?”

“Cute. Actually, I don’t know how Pulsar makes their nanotubes. Rival companies would kill for that info. All I know is that they modified an older technique called chemical vapor deposition to create tubes that can contain long chains of drugs – in this case, cross-linked molecules of tetrodotoxin.”

I take a deep breath, checking Briana to see if she’s still following me. She doesn’t seem to be missing a beat. “The tubes are then bundled into sheaths,” I continue, “with one end open and the other end capped and attached to an antibody designed to bind to a specific target. For Replacidin, that target is a muscle protein called actin.”

“You weren’t exaggerating,” Briana notes, sounding impressed. “It really is like a cruise missile.”

“In some ways… yes. Once the drug reaches its target, the chain slowly breaks apart to release individual molecules of toxin. In the drug delivery world, they call it spatial and temporal selectivity: the precise control over where and when a drug is delivered to its target.”

“But how can you be so sure it actually works out that way?”

“It’s… well, it could take all day to answer that question, but I’ll put it to you this way: even if the molecules of toxin all released at the same time, we could still reverse the effects. Almost instantly.”

Briana eyes me suspiciously. “I thought you said there was no antidote.”

“There isn’t – to tetrodotoxin in its natural form. But for Replacidin…” I slide open a drawer labeled with the REST study logo. “We have a fail-safe option, kept in every treatment room.”

I reach in to retrieve a pre-drawn, auto-injecting syringe. “If we want to reverse the effects of Replacidin, we just have to inject this reversal agent.”

I offer her the syringe and she fingers it cautiously, as if the contents were radioactive. “What’s in there?”

“It’s a cocktail of neutralizing antibodies combined with drugs to boost the blood pressure and stimulate muscle contraction.”

“Sounds delightful.”

“It would be pretty scary if we ever had to use it,” I agree. “But that’s just about impossible. In fact, based on the safety data that’s already out there, the study protocol doesn’t even require us to carry the reversal agent any more. We just keep it around to reassure our more uptight patients.”

She purses her lips into a smile, handing me back the syringe. “Sounds like you’re pretty confident your drug is safe.”

“It’s not my drug,” I correct. “I’m only helping with the research. But yes, I’m one hundred percent convinced it’s safe. Otherwise, I wouldn’t be participating in this study.”

She drags the tip of her ballet flat over the floor, tracing a slow circle as she considers my answer. “So then let me ask you something. Would you trust the stuff enough to inject it into your own mother’s face?”

“Yes,” I say without hesitation. “If she were alive today and wanted Replacidin, I wouldn’t hesitate to sign her up.”

I look up to see the expected response – a cringe of embarrassment. Over the years, I’ve gotten used to watching people react this way whenever the subject of my parents comes up.

“I’m… sorry,” she says sheepishly. “I didn’t mean to –”

“No worries. You’re not a mind-reader. There’s no way that you’d know. Anyway, listen…” I glance at my wristwatch, suddenly aware that Erin must be wondering what’s taking so long. “I totally understand if you’d like to withdraw from the study. This is a voluntary program, so if you’re having any doubts, then you’re right to reconsider. Besides, between you and me, you’re not exactly the best candidate. Your skin’s pretty flawless.”

“Yeah, right. And how many times a day do you use that line?”

“A few times,” I admit. “But in this case, I really mean it.”

Briana looks down with a grin that’s almost bashful. “Okay. Let’s do this, before I change my mind.”

“You shouldn’t feel obligated –”

 “Hey Jake!” She cuts me off with a laugh. “Relax.”

“But –”

“Listen to me. I trust you.”

Before I can object further, Briana reaches over me to sign the consent form – curved, looping letters, ‘B’ puckered out like a full pair of lips, heart-shaped circle dotting the “i.” Then she sets down the pen with a determined nod, crossing her arms as she settles back into the exam chair.

“Now take that syringe of toxic sushi or whatever you’ve got in there and make me beautiful.”

Taking my cue, I pick up the Replacidin syringe, noticing the tremor in my usually rock-steady hand.

“No pressure,” Roy Caulder’s Trophy Wife teases before closing her eyes, and as she strains to crease her forehead, all I can think is that this must be how a rare art conservator must feel when they’re about to take a brush and caustic chemicals to a Botticelli masterpiece.

No pressure, right?

***

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