Altered Genes: Genesis (4 page)

T
ao Jiali finished
her briefing and stood at attention. The three stars on the sleeve of her uniform signified a rank of importance. She was special, not only the youngest female colonel in the People’s Liberation Army but also the grand-daughter of the elderly man who sat at the end of the table.

“Questions?” she asked after a deferential pause.

The ten men who sat around the brightly polished table looked to the elderly man. He wore a plain green tunic and sat below a painting of Mao Zedong. Aside from two Chinese flags on a small pedestal in the middle of the table, the painting was the only decoration in the room.

“Proceed,” he said with a slight nod and pushed back his chair.

The generals jumped to their feet and stood at attention as he exited through a private door, flanked by two guards.

When he was gone and the door firmly closed, the room erupted as they debated the plan the President of the People's Republic of China had just approved.

Jiali watched them argue over her grandfather’s decision.
They were fools—old fools. What had been done was done. Now they all had to deal with the consequences.
She collected her papers and placed them neatly in a manila folder before giving the generals one final look and taking her leave.

“Come along, Captain, we have work to do,” she said as she stepped into the hallway.

Chen Gong jumped up from his chair and followed her down the corridor.
Always running,
he thought. It had been like that since her driver had picked him up at the airport. She was his boss now, had been from the moment he handed her the package from London. Even then he knew enough about Colonel Tao Jiali to not argue.

Some said she was callous, had ice in her veins. Perhaps,
he thought
, but it ran in her family. Rulers rule, and followers follow.

“Where are we going, Colonel,” he asked the back of her head.

“The research facility.”

He stopped mid-step, his feet rooted to the floor. A brave man in most matters, the thought of visiting the lab made him uneasy. He shook off his apprehension and ran after her.

A few hours later, they reached their destination, the Shahezhen Army base on the outskirts of Beijing. The car slowed to a crawl as they approached the gate.

From his position in the back seat, Gong surveyed their surroundings. Bright metal halide lamps on tall masts illuminated the grounds. Security was tight, much more so than the last time he had visited the base. He noted the razor-sharp concertina wire that ran along the top of the electric fence and the armed soldiers positioned every twenty feet.

There’s more that I don’t see,
he thought as two soldiers stepped forward and motioned the driver to halt. If they recognized Colonel Jiali’s car, it didn’t show with their abrupt manner.

“Identification,” one of them demanded while the other stood watch. Gong noted the soldier watching them had his weapon pointed directly at the car.

They handed over their identification cards and waited. A few minutes later, their cards were returned and they were waved on with a grunt.

They drove deeper into the base and stopped in front of a windowless gray concrete building. It looked like a bunker.

The only entrance Gong could see was a nondescript metal door that opened to a walkway. A pair of surveillance cameras mounted on the wall, panned back and forth.

“Remain in the car,” Jiali said.

As she approached the building, the door opened and two soldiers stepped out. One carried a small electronic device, the other, an assault rifle. She stepped towards the soldier with the device and inserted her finger into it. After a moment, she turned towards the car and motioned Gong to advance.

“Your turn,” she said when he reached her.

He studied the device, a gray box about the size of two packs of playing cards stacked on top of each other. The small LCD display was lit but showed nothing.

Fingerprint verification.
He inserted his index finger into the opening. The sharp prick came without warning and he yanked his hand from the device.

The soldier holding the machine scowled while the other stepped back and raised his rifle slightly. Gong held out his hands in a non-threatening manner. “Just surprised, that’s all,” he said with a tight smile.

“DNA sample,” Jiali explained curtly. “Once you're confirmed, we'll be allowed in.”

He re-inserted his finger and clenched his teeth as he waited for the inevitable prick. This time, he didn’t flinch. A few seconds later, his named showed on the display and the soldier nodded. He withdrew his finger, expecting to see a drop of blood. There was none.

The door to the building opened and they went inside. It was large and cavernous, empty except for a small room in the middle. A series of catwalks spanned the ceiling. He looked up to see armed soldiers watching them.
Are they there to keep people out or to keep them in
, he wondered.

A man emerged from the inner room and approached them. “Welcome Colonel, Captain. I'm Dr. Zhào. This way please.”

Their footsteps echoed in the empty space as they followed him across the concrete floor. He swiped an access card through a card reader. The door to the inner room opened with a hiss and a gentle breeze blew across the top of Gong’s head. He rubbed the nape of his neck reflexively.

“Negative pressure,” Zhào explained, “to keep the lab isolated.”

Isolated.
That one word brought the anxiety he had worked hard to suppress to the surface. He rubbed his sweaty hands on his pants and followed Jiali and Zhào through the door.

The inner vestibule was brightly lit and constructed of sterile plastic and stainless steel. Lockers lined one wall. Two change-rooms, separated by a floor-to-ceiling barrier, lined the other. Each room had an opaque plastic curtain for privacy.

Jiali retrieved some articles of clothing from one of the lockers and stepped into a change room. She closed the curtain behind her and Gong looked away as she began to disrobe, but not before catching a brief glimpse of the outline of her body.

“Get changed, Captain,” she said through the curtain.

Embarrassed, he quickly stepped away and accepted the white t-shirt and cotton underwear Dr. Zhào handed him. “These should fit you.”

He raised an eyebrow and looked at the two pieces of clothing. "Where are the rest?"

“Downstairs,” Zhào said with a smile.

Downstairs?

The doctor answered his unasked question by pointing to an elevator at the end of the vestibule. “The lab is six stories below us.”

Their ride was brief. When the elevator stopped, they stepped out into another room. It was similar to the one above but slightly smaller.

Bright orange containment suits lined one of the walls and a door, large enough for a single person, was positioned on the other.

“The lab is on the other side of the airlock,” Zhào explained to him, “but you will need to wear a containment suit.”

He reached up, carefully pulled one down and handed it to Gong.

Gong touched the arm of the suit. The material was soft and rubber-like.

Zhào spoke. “This is a BSL4 clean room. When you put on your containment suit and lock the helmet, you will have a small amount of air available from an internal tank. Once we're inside, you need to connect to the air supply in each room. It is straightforward—take one of the hoses hanging from the ceiling and plug it into the socket on the side of your suit. When it's connected, you'll feel a puff of air and the suit will expand slightly.

“In the extremely unlikely situation where a tear or breach in your suit occurs, you must immediately enter the nearest decontamination shower. Every room in the facility has one. The showers are airlocks that seal as you enter. They won't unlock until decontamination is complete. They also contain a temporary containment suit that you can put on.

“Lastly, the suits aren't soundproof but it’s difficult to hear when you’re wearing one. Each suit has a microphone and headset built into the helmet. Above the entrance to each room in the lab, you will see a number. That number is the channel used by the communication system in that room. In the corridor, we use channel zero. To switch from one frequency to another, turn the dial on the suit sleeve. Any questions?”

Plenty
, Gong thought as he watched Jiali take a suit from the rack and step into it with a practiced ease.

He shook his head.

“Good, suit up.”

Twenty minutes later they were all inside the lab. The main corridor was lined with windows that looked into rooms filled with workbenches and scientific equipment. He paused in front of one and watched a scientist removed a rabbit from a wire cage.

“Virulent Hemorrhagic flu,” Zhào said. He took Gong by the arm and guided him toward an increasingly impatient Colonel Jiali. She waited further down the corridor in front of another door.

She moved aside when they reached her and Zhào entered a code on the digital keypad. The door opened with a hiss and they stepped into the room. The door closed behind them.

Jiali and Zhào immediately connected their suits to the hoses that hung from the ceiling. Gong fumbled as he mimicked their steps. When the connector finally sealed, a relieving puff of cool air blew into his suit

What if it comes loose?

He decided to not move.

Zhào and Jiali approached one of the scientists and began to talk. He turned the audio selector dial on his sleeve until he could hear them.

“—the status?” Jiali asked.

“The strain has a high mortality rate,” the scientist answered.

Gong couldn’t see the scientist’s face but he heard the quiver in her voice. He moved closer.

“How high?”

“One hundred percent.”

“Treatment?” Jiali asked after a long pause.

Gong watched as she fixed her eyes on the scientist who had spoken.

“It’s a…It’s a chimera. There are genetic markers from different strains—genes we’ve never seen before…We don’t understand it.”

“Is there a treatment?” Jiali asked again, more impatient this time. The cold tone in her voice scared him and Gong stared at the scientist, willing her to say yes.

“We don’t know. Nothing appears to work.”

“Would the American be of assistance?”

Zhào and the scientist looked at each other. The scientist gave Jiali a barely perceptible nod.

She dismissed them with a short wave. “Get back to work. Let me know if anything changes.”

“Come along, Captain,” she said to Gong as she turned to leave. “You have work to do. I’ll brief you on the way to the airport.”

He followed her out of the lab, wondering who the American was and what he had to do with the deadly package from London.

P
rofessor Tony Simmons
stood at the podium and counted the handful of students in the lecture hall.  Eighteen, if he included the two guys in the top row, but he wasn't even sure if they were in his class, or asleep and left over from the previous one. He had his answer a few seconds later when they woke and left the hall. Depressed, he looked down at the class list.
Sixteen out of thirty-nine. That might just be a new record. Am I that boring?

Simmons, the youngest Assistant Professor of Biochemistry in Georgetown University’s history, was a world-renowned expert on bacterial genetics but not particularly knowledgeable when it came to sports. He had forgotten that the Hoya’s—Georgetown’s NCAA basketball team—had a pep rally that morning and the entire campus was virtually empty.

He reached down and pulled a laptop out of his briefcase. “Let’s get started,” he said as he plugged the projector’s cable into the back of his computer. “You won’t have to listen to me drone on today—I have a video for you.”

A smattering of applause greeted his announcement and he smiled. “I knew you’d like that.”

He dimmed the lights and fiddled with the computer. A video began to play on the large screen behind him.

Merlin Pryce followed Alexander Fleming into the room. The two men made their way to a workbench crowded with petri dishes and glassware. A light coating of dust covered those in the furthest corner while a handful lay submerged in a tray of Lysol.

It was September 3rd, 1928.

In the years to come, Fleming would be elected fellow of the Royal Society and knighted by the Queen of England, but right now, he was just another researcher at St Mary’s Hospital.

“Was your holiday enjoyable?” Pryce asked Fleming, who had spent the month of August in the countryside.

“It was, but I’m happy to be back.” He ran a finger across the dust-covered workbench and frowned. “Look at this mess, it will take the entire day to clean up. I’ll tidy the desk, you start with the glassware.”

Pryce frowned and looked at his pocket watch.

“Very well…I have two hours before I’m needed in the main wing,” he said and began in the furthest corner of the workbench, scraping the agar and bacterial culture off each petri dish before placing it in the disinfectant.

The two men worked without talking. Pryce cleaned while Fleming sat at his desk, reading his journals and refreshing his memory on the research he had done prior to summer vacation.

After an hour, only a handful of petri dishes remained. Pryce grabbed one from the pile, ready to scrub it, but stopped when he noticed the spots of bluish-green mold with no bacterial growth around them. He turned towards Fleming with the petri dish in his hand.

“Alexander, there's something odd.”

Fleming looked up. “Bring it here.”

Pryce placed the dish on the desk next to Fleming’s lab journal. He pointed at the mold.

“I see it. What's the label?” Fleming asked impatiently.

“127-A”

Fleming flipped through his journal until he found the entry. “127-A, Staphylococcus aureus.”

He slid the petri dish under the microscope that sat on his desk and adjusted the lens while he squinted into the eyepiece. With each turn of the knob, he became more excited.

“Hmm…there's a halo…as if the bacterial growth was inhibited by the mold.”

He looked up at Pryce and smiled broadly.

The video ended and Simmons turned the lights on. He leaned lazily against the podium, a mischievous grin on his face. “Sorry, that didn’t take as long as I thought it would. We have ten minutes left, you’ll have to listen to me lecture.”

A chorus of groans greeted his announcement and his grin widened. “I’m paid by the word—get ready.”

He clicked through the files on his laptop, opened a powerpoint slide deck and began to lecture.

“Think about it…the discovery of Penicillin, arguably one of the most important medical discoveries of all time, was a happy accident. Happy for Fleming, of course, he won a Nobel prize, but even happier for the rest of us. Millions of lives have been saved by antibiotics—but it isn’t all good news.”

He clicked to the next page of the presentation. A quote in block letters appeared on the lecture hall’s large screen.

He stepped around to the front of the podium, a few feet away from the students in the first row, and pointed to the screen. “Does anyone know who said that?”

Blank stares all around. He answered for them. “Alexander Fleming—during his Nobel prize acceptance speech on December 11th, 1945, a few months after the end of the second world war.”

A couple of knowing nods but mostly blank looks. That might have been a little hard.
Let’s try something more obvious.

“Any idea what he was talking about?”

A young woman, her brown hair tied up in a ponytail caught his eye. She wore horn-rimmed glasses and looked studious but the hand that waved furiously in the air was anything but.

“Professor Simmons…Professor Simmons!”

“Yes…Miss?” She looked vaguely familiar.

“Emma...Emma Rice,” she said, sounding disappointed he had forgotten her name. “I applied for one of your student lab assistant positions this year.”

He smiled as if he remembered. He didn’t.

“Okay, Emma, what was it that Fleming was talking about?”

She squinted through her glasses. “Resistance to antibiotics?”

“Very good, but what was it that specifically concerned him?” He addressed the question to her and then looked at the other students when she didn’t answer.

“Anyone?” Silence and blank stares.
Come on you guys, the answer is right there on the screen.

He waited a few more seconds and then answered his own question. “Fleming was concerned that over an extended period of time, bacteria would acquire resistance to antibiotic treatment if the dosage used wasn’t high enough to kill them. Was his concern justified?”

The young woman tentatively raised her hand again. “It was, right?” she asked, her forehead wrinkled in uncertainty.

“Yes,” he answered and clicked on the powerpoint slide deck.

“Antibiotic-resistant bacteria are arguably one of the greatest medical risks facing mankind—you should be worried, I am.” He pointed at the screen. “That number will increase twenty-fold in a post-antibiotic world. More people will die from infections than cancer.”

He walked over and stood in front of her. “Imagine a world where an under-cooked hamburger with E. coli bacteria doesn’t just make you feel lousy,
it kills you
”

Her eyes widened and she asked, “What causes it?”

He began to count on his fingers. “Prophylactic antibiotic premedication, use of antibiotics as growth enhancers in food animals, horizontal gene transfer.” He stopped at three as her eyes glazed over.

“Sorry, I’ll explain. Prophylactic use of antibiotics is when you give small doses of them to food animals as a preventative measure. The animals don’t get sick and the farmer is happy. It sounds good in principle—right?”

She nodded tentatively and he looked around the room. A few more heads nodded.
Good—they’re listening.

He shook his head. “Wrong! What actually happens is the bacteria the farmer is supposedly protecting his animals from slowly develops resistance to the antibiotic. After a while—a few years, a decade perhaps—the antibiotic stops being effective.”

He walked back to the podium and fiddled with his computer until he found the news article he was looking for. An unreadable magazine article appeared on the screen.

“Sorry about the print size. I’ll paraphrase.”

“Bacteria are incredible organisms, the ultimate survivor.” He became more excited as he spoke. “Part of their adaptive survival mechanism is the ability to transfer genes from one strain to another. That’s called horizontal gene transfer.

This article is about Colistin, a very old antibiotic. It’s been around for a long time but isn’t widely used in humans because it’s toxic at the effective dosage rates.

But it’s cheap, and not toxic in small quantities, so it’s been used as a prophylactic in animal feed for years. Guess what happened over time?”

The room was silent. He had their attention.

“E. coli bacteria in pigs developed resistance to Colistin and that resistance trait is now showing up in other bacteria—bacteria that affect humans. The resistance occurs as the result of a gene called MCR-1. It’s very easily swapped amongst different strains of bacteria using something called Plasmid-mediated resistance transfer.”

“Is that how superbugs are created?” the young woman asked. “I read about them appearing in a hospital in California. I think they had to close it because a bunch of people got sick.”

He hated that term, but the media loved it.
“The scientific community doesn’t usually call them superbugs but yes, that’s one of the ways they develop.”

The sound of a throat being cleared reminded him he was holding up the next class. He nodded to the other professor and turned back to his students.

“Time’s up folks. This material won’t be on the exam but I strongly encourage you to read up on it. If you’re interested in discussing it further, stop by my office during the hours posted on my website.” Anxious to leave, most of the class ignored his offer and hurried out of the lecture hall.

He followed them out and strolled across campus towards Regents Hall, the location of his office and lab. By the time he reached the building, the lecture was forgotten but his morning cup of coffee and bagel with cream cheese wasn’t.

He darted into the bagel shop and was standing at the cash register when the muffled trill of his cell phone sounded from deep inside his briefcase.
Damn it…never fails.

The cashier offered him change. He shook his head with a nod towards the tip jar and grabbed his food. He looked for an empty table
.
They were all full. He spotted his
department head, John Thompson, a crusty old man in his late sixties sitting alone.

It would have to do.

When he placed his food on the table, he spilled his coffee on the paper the old man was reading. He mimed an apology.
I’ll never get tenure now
, he thought as he fished through his briefcase and pulled out his phone.

“Hello?”

“Dr. Simmons?” the voice asked with a British accent.

“Yes, speaking.”

“Dr. Simmons, my name is Edward Gore, Dr. Edward Gore. I'm a researcher at the Cambridge Institute for Medical Research. We met two years ago at the infectious disease symposium in Budapest.”

Simmons paused and searched his memory. The symposium was a busy event. He didn’t recall Edward Gore, but he had met a number of people from the Cambridge institute.

“What can I do for you?”

“I apologize for imposing,” Gore said, “but I have a favor to ask. I've been looking at what I believe are mutations in ribotype 027 and would appreciate a second set of eyes. I've read your work and can't think of anyone more suited.”

RT 027 was a virulent strain of Clostridium difficile bacteria. It was responsible for a worldwide epidemic in hospitals around the world. First seen in the 1980’s, it disappeared only to reappear twenty years later in an even more virulent form. Simmons wasn’t just familiar with it, he was an expert on it and had done groundbreaking research studying its genetic structure.

“The mutations are in the tcdR and tcdC genes,” the Brit added.

If the C. diff bacteria was likened to a car, the tcdR gene was the accelerator and the tcdC gene, the brake. One increased toxin production while the other slowed it down. Both genes were relatively stable

“A significant mutation in those genes isn’t likely,” he replied skeptically. “How do you know it's mutated? Have you compared it to the reference genome?” He tried not to sound critical. If the other man took offense, he didn’t show it.

“I’ve compared it and it does appear to have mutated, but a second look by a more experienced pair of eyes would confirm it. You're the first person I thought of with your expertise, .”

Still dubious, Simmons paid no attention to the compliment. “Where did the sample come from?”

“I'd rather not say,” Gore said apologetically. “I hope you understand.”

He wasn’t surprised by the man’s reluctance to share.
Publish or perish wasn’t a myth, it was a reality. No one wanted to risk giving away too much, too soon, in case the competition got a jump on them.

“I'm quite busy right now, but if you send me the DNA sequence data, I'll take a quick look.”

“Thank you. There may also be mutations in the tcdA and tcdB genes, but I haven’t had time to look more closely.”

The probability of all four genes mutating at the same time was low, but the Brit didn’t sound incompetent. It might be worth a quick look.

“Do you have my email address?” he asked.

“I do—thank you so much.”

By the time Gore had hung up, Simmons was already thinking about the bacteria’s genetic structure. He slid the phone into his pant’s pocket and hurried away from the table, not realizing until he reached the door of the cafe that he had forgotten his coffee and bagel. When he returned, Thompson shook his head in disbelief. Simmons grinned and grabbed the food. A few seconds later, he was back again. “Forgot my briefcase.”