Altered Genes: Genesis (7 page)

H
is own work long forgotten
, Tony Simmons gently rocked back and forth in his office chair, ignoring the sound of the squeaky springs as he studied the genome data Gore had sent him.

It had been a day and a half since their telephone conversation. After a couple of false starts, he had finally found time to look at the Brit’s data and once he did, he was drawn in immediately.

He blinked to relieve the soreness in his eyes and reached for the ceramic mug on the desk. Cup in hand, he took a long sip of the cold coffee and swirled the liquid around in his mouth as he thought back on what he had discovered.

The tcdA and tcdB genes from Gore's strain were all different from the RT 027 reference genome. The Brit was right, they had mutated. Simmons was amazed. The odds were astronomical that after generations of stability, the DNA of those key genes would change at the same time.

It’s a freak of nature,
he thought,
or genetically engineered—but that made no sense, who tweaks a stomach bug?

He swallowed the cold coffee and opened the protein sequence for the tcdC gene. As he looked at it more closely, he saw hints that mutations in the gene might have disabled its anti-sigma factor. That would limit its ability to repress toxin production.
The bacteria would produce toxins until it burned itself out.

He was about to dive back into his computer when the ring of his cell phone startled him. He watched as it vibrated across the top of the desk.
It was late, who would be calling at this time
? He picked up the phone and looked at the display—
a UK country code?

“Edward?” He answered, guessing at the caller.

“So sorry for calling at this time, Tony,” Gore said weakly.

He sounds tired,
Simmons thought as he looked at the clock on his desk—
just before 10 p.m. in Washington, nearly 3 a.m. in London.
“That’s quite an interesting strain. Thanks for sending me the data. I’m still looking at it but what can I do for you?”

Gore hesitated and then started, the words tumbled out of his mouth in a cathartic flood. “I’m sorry for not telling you earlier, but a hospital in Scotland sent the sample to the institute the day before yesterday. It was a rush, they needed the results immediately. I was asked—told really—to drop everything. It doesn’t look natural. That’s why I needed your assistance. I don’t under—we need to—”

“Whoa, slow down.” He interrupted Gore and leaned forward to rest his elbows on the desktop. “Take your time and start at the beginning.”

He heard Gore take a few breaths.

“The sequence data I sent you came from a patient at BurnsHouse General Hospital in Glasgow. I have more samples from other patients and a nurse. It looks as if they were all infected with the same strain of C. difficile.”

“An outbreak?” Simmons sat upright, slightly alarmed.

“Yes—but not just at BurnsHouse. Two other hospitals in Glasgow have also reported cases. The sequencing isn’t complete, but it appears to be the same strain.”

Simmons felt his pulse quicken. C. diff outbreaks in a single hospital were unfortunately common, but outbreaks across multiple facilities at the same time were rare.
“How did it spread?”

“The bacteria’s endospores are unique—very hardy,” the Brit answered. “They must have contaminated an infected patient’s clothing. They shuttle patients back and forth between the hospitals all the time.”

“How many cases now?”

“Thirty-seven at BurnsHouse and another twelve at the other two hospitals—all in the last three days,” Gore answered.

Simmons whistled in surprise.

“It’s infecting otherwise healthy patients, Tony. Nothing knocks it down…” Gore’s voice trailed off to a whisper.

Simmons heard the sound of knocking on a door through the phone. He waited while Gore asked who it was and listened as the Brit put the phone down and answered the door. A few seconds later, he heard the sound of voices arguing.

“Edward?”

"Edward, are you okay?”

“Hello?” a voice, not Gore’s, asked through the phone.

Startled, Simmons stammered. “Ah…I was just talking to Dr. Gore.”

“He’s busy,” the voice said and hung up.

What the hell?

Simmons stared at his phone. He decided to call the Brit back. The call went to voicemail after just a few rings. He hung-up and nervously drummed his fingers on the desktop. The encounter on the phone had left him with a sense of unease. He wondered what he should do.
Even if I knew who to call, what would I say? That someone hung up the phone?

Hoping that Gore would call again, he decided to keep working. But the Brit didn’t phone. After a couple of hours, he gave up and went home for some much-needed sleep.

His house, a rental property on the other side of the campus, was a short walk. Sleep didn’t come quickly and he lay in bed, tossing and turning for hours as he dwelled on the enigmatic strain of C. difficile and the mysterious voice on the phone.

Exasperated and uneasy, he gave up on sleep a few hours before dawn and returned to Regent’s hall. He pulled the bacteria’s protein sequences up on his computer. As he studied them, he muttered to himself.
It’s like a game of scrabble. it's just a matter of fitting the pieces together to create something meaningful.
There were mysteries hidden within the genetic code. He would find them. But the hours went by and he found himself increasingly confused by the puzzle.
Nothing fits, maybe I’m just too tired
. He leaned back in his chair and began to rock.

The first few knocks on his office door were soft and went unheard, but the ones that followed couldn't be missed.

Thud…Thud…Thud
—It sounded like a battering ram. His heart raced as he remembered the conversation with Gore, the strange voice.
I’m being silly,
he thought.

“Professor Simmons?"

“Professor Simmons…are you there?”

The voice sounded familiar. He recognized it after a few seconds.

“It’s open,” he yelled.

THUD…THUD…THUD
—The knocking grew louder.

"Oh, for God's sakes.” He stomped to the door and pulled it open.

“What is it?"

Emma Rice stood in front of him with a sheepish look on her face, her fist raised in the air ready to knock again. She lowered it slowly and smiled.

“Hi, Professor Simmons, is now a good time?”

Flustered by her sudden appearance and odd question, he tilted his head and looked at her confused.

“Good time?”

“You said in class to stop by during office hours.”

Before he could answer, she edged her way past him and slid into the office. He sighed and closed the door.

“It’s as good a time as any. Have a seat.”

She moved quickly and sat down in front of his desk with her backpack on the floor. Seeing his computer, she leaned forward to sneak a peek.

“What are you working on?”

He snapped the lid of the laptop closed and sat. “Just reviewing a protein sequence, nothing too interesting. What can I do for you, Ms. Rice?”

She leaned back in her chair, not at all embarrassed at being caught snooping.

“I’d like to finish our conversation?”

“Conversation?”

“About antibiotic resistance,” she reminded him.

Seriously…now?
He thought about telling her he was too busy but decided to just get it over with.

He slumped forward in his chair and folded his hands together on the top of the desk. “What would you like to know?”

She shrugged. “You know—superbugs…that kind of stuff.”

Superbugs…are you kidding me? Maybe I can bore her into leaving.

With a sigh, he stood and walked to the whiteboard that hung on the wall. He took a marker from the tray below it and began to lecture.

“At the most basic level, superbugs are bacteria that are resistant to one or more types of antibiotics. They usually acquire this resistance in one of two ways, either through a mutation or through a gene transfer—like we talked about in class, remember?”

She nodded and he continued. “That, by itself is a problem but an equally large problem is the supply of new antibiotics is nearly depleted.”

“So you see, Miss Rice, it’s a perfect storm. On one hand, infectious bacteria are acquiring resistance to existing antibiotics and on the other hand, no new antibiotics are being discovered. There are a number of deadly superbugs. Methicillin-resistant Staphylococcus aureus is one. It causes skin infections and can be deadly if it gets into your bloodstream. There’s a form of tuberculosis called XDR that is resistant to treatment. STEC is a strain of E. coli that produces Shiga toxin. I could go on. The list gets longer every day.”

He put the marker down and walked back to his desk, hoping that was enough for her.

It wasn’t. She pointed to a framed magazine cover on the wall above his bookshelf. His picture was on the cover. The title above it read, ‘
Code Cracker’.

“What code did you crack? Are you famous?”

He followed her outstretched arm and cringed.

“No, I’m not famous. Magazines like catchy titles, the article is about a discovery I made on how certain types of bacteria develop antibiotic resistance.”

She rose from her chair and walked over to take a closer look at the framed picture.

“Wow…that’s exciting, just like what we were talking about. Do you have a copy I can read?”

He groaned inside and walked over to join her by the bookshelf.

Not sure what she’ll do with it but maybe if I give her one, she’ll leave.
He rummaged though a pile of magazines and pulled one out. “I have extra copies, you can keep this one.”

She took it and he stood with his hands on his hips, watching as she studied the cover and flipped the magazine open.

“I don’t know if you’ll find it interesting. The article is quite technical.”

“What’s fluoro…quino…lone?” she pointed to a word in the subtitle.

“Fluoroquinolone,” he corrected. “It’s an antibiotic like Colistin. It’s also widely used in animals.

Suddenly, Gore’s final words came back to him. “
Nothing knocks it down,”
the Brit had said.

Damn! I’ve been looking in the wrong place,
he thought and ran to his desk. He flipped opened his laptop, his eyes darted across the screen. He began to talk to himself. “I should have been looking at gene regions that enable antibiotic resistance.”

His fingers flickered across the computer’s keyboard as he rearranged the alphabet soup of letters and numbers in the genomic analysis software. He worked at a feverous pace, stopping and then re-starting whenever he reached a dead-end and had to retrace his steps. As he worked, his excitement grew. He looked up at her and pointed to the screen.

“This gene region enables resistance to fluoroquinolone. It’s absolutely identical to the RT 027 strain—it’s as if the gene was copied and inserted. There may be more. I need to look.”

After studying the region for a few seconds longer, he jumped to his feet and grabbed her by the arm. “You have to go now,” he said as he ushered her towards the door. He pushed her into the hallway and slammed the door shut.

S
aanvi looked
up from her miserable breakfast when Dr. Brar walked into the room. He pulled up a chair and sat backward on it.

“Good morning,” he said brightly. “It looks like you've regained your appetite. Is it any good?”

She shook her head in disgust and poked at the doughy roti that filled half her plate. Covered with some kind of green puree, it tasted like rotten peas.

“This is possibly the worst food I’ve ever had.”

“I’d heard it was pretty bad,” he said sympathetically. “Sorry about that.”

She pushed the plate away and he turned serious. “The lab results are back, your toxin levels are down. We had to run the tests twice to be sure.”

He sounds surprised.
She cocked her head to the side and studied him. “Isn’t that good?”

“Oh yes, very good, you’re recovering nicely but—” He paused, seemingly at a loss for words.

“But what?”

“I have seven other patients with C. diff infections. They aren’t responding as well. I don’t know why.”

“I guess I’m special,” she said, relieved his concern wasn’t with her.

He looked at her as if she was a puzzle to be taken apart and then put back together. “You are,” he said in a voice that made her uncomfortable

“Why?”

“I don’t know,” he said with a shrug. “It might have something to do with how your body reacted to the treatment or perhaps we just didn’t get to the other patients soon enough.”

“What was my treatment?”

They hadn’t given her any medicine, at least not while she was awake and the nurse had removed the IV tube before breakfast.

He leaned over the back of the chair and began to explain in an earnest voice.

“I don’t know if you are aware of this, but India has the highest rate of antibiotic-resistant bacteria in the world. It’s become a crisis and our government has only taken token steps to address the problem.

“The medical community—my colleagues and I—are the ones who have to act. We need to be more judicious in prescribing antibiotics. As it is, we prescribe more than any other country. That has to stop.”

She half-listened as he continued to talk about things she didn’t know anything about.

“Shortly after you arrived, I called your parents and explained all of this. I asked their permission to try a procedure called fecal microbiota transplantation. It was first discovered and used by the Chinese more than a thousand years ago. It is very slowly coming back into favor as an alternative treatment.”

“What was it?” she asked, intrigued and a little wary.

“We transplanted bacteria from a donor’s fecal matter into your colon through a colonoscopy. This helped repopulate your gut with healthy bacteria.”

Fecal matter?

She opened and closed her mouth before the words “Fecal matter” finally squeaked out.

“Yes, from a screened donor,” he said with a nod, seemingly perplexed by her reaction. “It was perfectly safe.”

Horrified, she glared at him. “And my parent’s agreed?”

“Saanvi, it may sound odd,” he said, scolding her, “but the science is solid. It’s reactions like yours which have limited its acceptance.”

“It’s disgusting,” she spat.

“It probably saved your life,” he said defiantly.

Upset by his chastising tone and serious words, she looked away as her eyes began to water.
She wasn’t going to cry…not in front of him.

“I’d like to run some tests this afternoon, see if we can figure out why you’re special—figure out why it didn’t work on the other patients.”

She twisted her head further to avoid his eyes.

“Would you be willing to help?” he asked after a moment.

It’s gross but I’m being stupid.
Embarrassed, she wiped the dampness from her eyes and turned her head back towards him.”Do you really think it would help?”

He scraped his chair forward and leaned in towards her. “I don’t know…I hope so,” he said and then spoke more confidently, “I’m sure it will. It has to.”

Later that afternoon, he returned with a nurse to complete a battery of tests that ended with a request for a stool sample. She eyed the small plastic bottle with its tiny scoop.

“Seriously?”

“Just one, I promise,” he said as the nurse handed it to her. “We’ll be back in ten minutes to collect it.”

She accepted it reluctantly.

When they returned, she held the bottle gingerly between her thumb and forefinger. “Here,” she said, her lip curled up in disgust. The nurse left with the bottle.

A girl, around her age, stepped through the half-open door. Her eyes sparkled above the surgical mask that covered her mouth and nose. Her jet black hair, perfectly brushed and glossy, flowed down over her shoulder.

Saanvi gawked at her. Even with the ugly plastic gown that hid the rest of her body, Saanvi could tell she was beautiful.

Dr. Brar’s eyes lit up when he saw her. “Hi, Princess, come in.” He motioned her into the room.

She walked over and gave him a hug and then turned with a flourish to face the bed. She waved a gloved hand.

"Hi, I'm Dishita,” she said in a voice that bubbled with effervescence. The girl waved her hands excitedly as she talked. “My brother told me all about you. You must be terribly bored.”

Her brother?
Saanvi was surprised her doctor had a family.
Of course he does. Everyone does.

“I know your aunt and uncle visit every day,” he said, “but I thought you might enjoy talking to someone your own age for a change. Dishita was at the hospital today for a dedication ceremony. I asked her to drop by and say hello.”

He walked to the door and turned back. “I’m sorry, I have to go now. I’ll see you later, Saanvi—you too, Princess.”

“Why does he keep calling you Princess?” Saanvi asked after he had left.

“Because he's an ass,” Dishita answered flippantly and marched to the side of the bed.

“Do you mind if I sit?” She pulled up her plastic gown and sat without waiting for an answer.

Saanvi studied the girl from up close.
Her eyes look like emeralds, they almost glow.

Dishita blinked. “Is something wrong?”

“No, sorry. Your eyes—they’re amazing.”

“Thanks, they’re special contacts. My eyes are brown, but I think green looks better.”

“Did they cost a lot?” The words tumbled out of her mouth. “I'm so sorry that was rude of me.”

Dishita laughed at her discomfort. “That’s okay. They weren’t too expensive—I think. I don’t actually know, my Grandmother bought them for me. She pays for everything. She can afford it. She's the Rajmata of Gujarat.”

“What’s that?”

“It’s kind of like a member of the Indian royal family."

“Is that why your brother called you princess?”

“Yeah. He thinks it's a big joke.”

“I like him. I’m glad he's my doctor.”

Dishita gave her a wicked look. “He's much too old for you,” she said in a scandalous voice.

Saanvi felt the blood rush to her face. Her cheeks burned. “Don't be silly, I mean he's a good doctor,” she said stiffly.

Dishita bit her lip and tried not to laugh. “I know, I was just joking—besides, he’s married.”

“How come you have an American accent?” Saanvi asked, changing the subject.

“I don't, do I?”

“Yeah, a little.”

“I go to school in the states, at Madeira. It’s a boarding school in Washington. I’m flying back next week.”

“Sounds exciting…You're so lucky.”

A couple of hours passed quickly as they talked about music and movies. Dishita described living at the boarding school and Saanvi gave her an update on her boring life in London.

“I’ve never been to London,” Dishita said. “I think that would be wonderful.”

Dr. Brar opened the hospital room door and poked his head in. “It looks like you two are getting on well. I have a surprise for you, Saanvi.”

She looked at him expectantly. He disappeared and then re-entered the room, pushing a wheelchair. The wheelchair wasn’t what she noticed first, it was the smile on his face.
He wasn’t wearing his surgical mask!

Her eyes lit up. “Does that mean—“

“Yes, the infection is gone. You'll have to stay in the hospital for a few more days, but we'll need to move you to another room to free this one up for another case.”

“Did you learn anything from my tests?”

His shoulders sagged and he suddenly looked tired. “No, it’s still a mystery, but we’ll keep looking.”

Dishita looked at her watch and ran to the door. “I didn't realize it was so late, Nanni is expecting me for dinner.” She turned to Saanvi. “I’m sorry, I have to go, but I can come back and visit tomorrow if you want.”

Saanvi beamed at her. “That would be great, see you then.”