The Genesis Key

by James Barney

  The beam of light drew nearer and became brighter until, finally, it shone directly in his face, blinding him.

  “Daniel?” said a man’s voice.

  Daniel recognized that voice. Bewildered, he struggled to speak. At first, only labored gasps came from his throat. But, eventually, with great effort, he managed a weak whisper. “How . . . did . . . you . . . get . . . in here?”

  Part I

  And it came to pass, when men began to multiply on the face of the earth and daughters were born unto them, that the sons of God saw the daughters of men that they were fair; and they took them wives of all which they chose. And the Lord said, My spirit shall not always strive with man, for that he also is flesh: yet his days shall be an hundred and twenty years. There were giants in the earth in those days; and also after that, when the sons of God came in unto the daughters of men, and they bare children to them, the same became mighty men which were of old, men of renown.

  —GENESIS 6:1–4

  Chapter One

  Present Day. Rockville, Maryland.

  Dr. Kathleen Sainsbury peered into a twenty-four-ounce clear plastic container and frowned. She held it up to the light for a better view but still did not like what she saw. Inside, three black fruit flies were crawling over a brown, mushy slice of banana. It wasn’t the crawling fruit flies that bothered her, however. It was the two flies that weren’t crawling—the ones that appeared dead at the bottom of the container—that caused her great concern.

  She tapped the bottom with her pen, and the two listless flies suddenly took flight, buzzing in tight, frantic circles. At that, Dr. Sainsbury smiled and made a quick notation on her clipboard. Then, as she did every morning, she moved on to the next container, and the next, and the next . . .

  “Dr. Sainsbury?”

  Kathleen turned to see Carlos Guiterez, the office manager at Quantum Life Sciences, entering the laboratory. “Oh, good morning Carlos. How are you?”

  “I’m fine, Doctor. I just wanted to remind you about your interview at nine thirty.”

  “Got it, thanks.” But Kathleen hardly needed a reminder about the interview. She’d arrived at work a full hour early just to prepare.

  Tall and attractive, although in a bookish way, Kathleen looked much younger than her thirty-eight years. Her auburn hair was pulled back tightly in a no-nonsense ponytail. Her slender, athletic physique was more suggestive of a soccer player (which she’d been in high school and college) than a world-class biologist. Indeed, if not for the square half-rimmed glasses and lab coat that she habitually wore at work over her jeans and blouse, it would be easy to mistake Kathleen Sainsbury for anything but a serious scientist. And, for that reason, she’d become increasingly self-conscious over the years about her appearance. An interview is fine, she thought, but why do they have to take pictures?

  Checking her watch, she was surprised to find it was already 9:15. She quickly finished collecting data and hung her clipboard on the wall beside the door. Before exiting, she turned and surveyed the laboratory with a weary but satisfied look. She was proud of what she’d built at Quantum Life Sciences. In addition to various computers and peripheral equipment, her state-of-the-art lab boasted a mass spectroscopy machine, two centrifuges, a DNA synthesizer and sequencer, a digital osmometer, a thermocycler, and a sophisticated microinjection microscope that allowed biological material to be injected directly into individual cells through an ultra-thin needle. She’d purchased most of this equipment secondhand from contacts she had at the National Institutes of Health, or from one of several “scavenger” companies that specialized in buying used laboratory equipment from failed biomedical startups and reselling it to new startups. The ultimate recycling program, she often mused.

  Kathleen drew a deep breath and savored the faint smell of phenol that permeated the lab. It had a sweet aroma, which, at least to her, was oddly pleasant. She closed her eyes, exhaled, then turned and left the lab.

  At 9:30, Kathleen was pacing nervously outside the front entrance of Quantum Life Sciences, Inc., one of forty-eight business suites in the Gateway Office Park on the outskirts of Rockville. It was a cold, damp morning in late March, with a dark gray sky portending rain.

  As promised, a reporter and photographer from the Washington Post arrived exactly on time. Kathleen escorted them inside and led them to a small conference room, which doubled as QLS’s supply room.

  “Sorry about the mess,” she said as she busily cleared stacks of paper from the chipped IKEA table that had once graced the dining room of her Bethesda apartment. “So how does this work?”

  The reporter—tall and handsome, in his early forties—introduced himself as Bryce Whittaker, a business and financial reporter for the Post. He explained that he was working on a story about biotech startup companies in the Washington area and that he wanted to include Quantum Life Sciences in the story. After confirming that Kathleen was, in fact, the president and CEO, he launched into a series of questions.

  “What’s the business of Quantum Life Sciences?”

  Kathleen responded quickly. “Our goal at QLS is to develop therapeutic products to fight Alzheimer’s, dementia, and other age-related diseases.” She’d given the same, well-rehearsed elevator pitch to hundreds of potential investors in the past two years. She could recite it in her sleep.

  “And how did you get involved in that field?”

  “I received a Ph.D. in microbiology from Johns Hopkins. Then, after my post-graduate work, I took a position as a research fellow at the National Institutes of Health, studying the biological processes of aging. When that fellowship was, uh . . . finished, I formed QLS, with the goal of continuing my research in that area.” Kathleen was relieved that she’d remembered to say “finished” instead of “terminated.”

  “When was that?”

  “About two years ago.”

  “And how many employees does QLS have now?”

  “Well, at this point, just four. There’s me and Carlos, whom you met, and two other biologists, Jeremy Fisher and Julie Haas.”

  “Does the company have any revenue?”

  Kathleen smiled at that. Everyone in the business world seemed intensely interested in revenue, whereas science often seemed to be just an afterthought. “Not yet,” she replied flatly. “We’re engaged solely in early-stage R&D at this point, so we’re not focused on generating revenue at this time. That’ll be several years off, I would guess.”

  “So how’s the company financed?”

  “Private equity. Some friends and family, a few angel investors, but mainly venture capital.”

  This line of questioning went on for some time, which made Kathleen uncomfortable. She disliked the business side of QLS, preferring instead to submerge herself in her research. She was happy to let Carlos run the books day to day, and she dreaded her “business” responsibilities as CEO, such as preparing quarterly progress reports for the investors. Truthfully, the only financial number she cared about was the company’s burn rate, the rate at which it was spending the 2.5 million dollars it had raised in its first round of financing. As far as Kathleen was concerned, her goal as CEO was to get as much research done as she could within that budget, so she could postpone the detestable process of begging for more money. To date, QLS had burned through more than three quarters of its first-round financing, and Kathleen was determined to make the remainder last as long as possible. For her, that meant long hours and weekends in the lab at little more than a subsistence salary.

  So much for the glamorous life of a CEO.

  “How close are you to developing a commercial product?” Whittaker asked.

  Kathleen hesitated. She’d heard that same question from investors since Day One of QLS’s founding. “I’m glad you asked,” she said, seizing the opportunity to change the subject. “Why don’t we go to the lab so I can explain what we’re working on.”

  At that, the photographer piped up. He was a thin, pale slacker in his mid-twenties. “Great, I can get s
ome pictures of you in front of your lab equipment. “

  Yeah, great.

  In the anteroom outside her lab, Kathleen pointed to a glossy poster titled “D. melanogaster Genetics.” It included a large illustration of a fruit fly, with various body parts and characteristics linked and color coded to hundreds of genes. “Curly wings,” for instance, was connected by a thin magenta line to “Cy0” on chromosome two. In the bottom left corner of the poster, a small circle of photographs was labeled “Life Cycle of D. melanogaster,” depicting the seven stages of fruit-fly development, from embryo to larva to pupa to the fully developed fruit fly.

  “Gross,” the photographer muttered, eyeing the poster.

  “Not at all,” Kathleen countered. “It’s actually quite beautiful. The genetic design of the fruit fly is both amazingly complex and beautifully simple.”

  Whittaker interrupted. “I thought you were trying to cure Alzheimer’s. What do fruit flies have to do with Alzheimer’s?”

  “Ah . . .” Kathleen smiled and arched her eyebrows. “First of all, I said we’re looking for a potential cure for a number of age-related diseases, including Alzheimer’s. We believe many of these diseases are manifestations of the same genetic defect. And fruit flies have everything to do with our research.” She paused to allow Whittaker to finish scribbling in his notepad.

  “Biologists have been studying the genetics of Drosophila melanogaster for almost a century. Like a lot of things in science, this field actually started by accident. About a hundred years ago, researchers at the Carnegie Institution began noticing that some of the fruit flies they were studying had offspring with strange vein patterns on their wings and other mutations such as dwarfism or white eyes. They quickly realized that they could control these mutations through selective breeding. Since then, generations of biologists have studied D. melanogaster and have identified thousands of repeatable mutations. There are mutants with every conceivable eye color—white, pink, purple, maroon, bright red. There are mutants with truncated wings, extra wings, missing wings, and miniature wings. Some mutants are extra hairy; some are nearly bald. More recently, biologists have bred mutant flies with legs growing where their mouths should be, or fully functional eyes on their wings, legs, or antennae.”

  “Whoa, awesome!” exclaimed the photographer, suddenly interested in their conversation. “Can we see some of those?”

  “Sorry, we don’t have any of those.”

  “Aw, man.”

  Kathleen continued. “Some mutants are uncoordinated and can’t fly straight. Other mutants lack memory. Still others have no tolerance for alcohol. The list goes on and on. You get the picture.”

  Whittaker nodded.

  “The important thing is that each mutation has been carefully traced to the specific location in D. melanogaster’s DNA where the corresponding gene occurs. So, for instance,” she pointed to the poster behind her, “we know that TM3 on the right branch of chromosome three controls whether a fruit fly will have long or short bristles.

  “And Cy0 on chromosome two controls curly wings, right?” said Whittaker, pointing to the magenta line on the poster.

  “Exactly.” Kathleen was impressed and gave Whittaker a quick smile that said so. “So we now have a nearly complete, functional map of the fruit-fly genome.”

  “Wait a second,” said Whittaker, holding up his pen. “Hasn’t the entire human genome already been mapped? I remember covering that story several years ago. So what’s the big deal about mapping the fruit-fly genome?”

  “There’s a big difference.” Kathleen checked her voice, which had betrayed just a hint of defensiveness. She’d taken her fair share of ribbing from other biologists over the years for being a drosophilist—a “fly person”—which many biologists considered an antiquated field of study. “Although most of the human genome has been sequenced,” she explained, “that only tells us what the human genome is, not what it does. It’s like having billions of lines of computer code without knowing what any of it does. For instance, if you ask a human-genome researcher to locate the specific gene that, say, controls whether you will have long or short eyelashes, they can’t tell you. Because the only way to figure that out is by doing what biologists have painstakingly done for the past hundred years with D. melanogaster.”

  “You mean creating mutants?”

  Kathleen nodded, once again impressed with Whittaker’s intuition. “The only way to figure out what a particular gene does in an organism is to switch it on or off—mutate it—and see what the consequences are. Easy to do with fruit flies. Not so easy with humans.”

  “Okay, I get that,” said Whittaker. “But I still don’t understand what the fruit-fly genome has to do with human diseases like Alzheimer’s.”

  “One thing biologists have discovered over the years is that genetic mechanisms are surprisingly consistent from one living organism to another. Once evolution stumbles upon a genetic mechanism that works, it tends to use that same genetic code over and over again in many different organisms. These pieces of code are called ‘conserved regions.’ As a result, humans and fruit flies share much of the same genetic code.”

  The photographer’s eyes widened. “So we’re, like . . . related to flies?”

  “Well, in a way, yes. That is to say, we’re related to all living organisms through various portions of DNA that have weaved their way into virtually every living creature through the process of evolution.”

  Whittaker rubbed his chin thoughtfully. “So you’re hoping to find a gene that cures Alzheimer’s in fruit flies?”

  “Well, not quite. Here, follow me.” She unlatched the airtight door to her lab and led the newspapermen in, closing it behind them. “Temperature control is very important when you’re working with fruit flies,” she explained. “Their breeding cycle and life span are heavily influenced by temperature, so we keep this room at a constant temperature of twenty-five degrees Celsius, which is about seventy-seven Fahrenheit.” She pointed to the digital temperature readout above the door. “In fact, we can refrigerate the eggs almost indefinitely until we’re ready for them to hatch.” She gestured toward a refrigerator in the far corner of the lab.

  “The average life span of D. melanogaster at twenty-five degrees Celsius is forty-seven days. At sixty days, ninety-nine percent of a typical generation of D. melanogaster will be dead. At seventy days, the mortality rate is essentially one hundred percent.”

  Whittaker and the photographer glanced at each other and shrugged.

  “Gentlemen, the fruit flies in this container are one hundred and forty-four days old.”

  Whittaker scrunched his eyebrows together, doing a quick mental calculation. “So that’s . . . three times their normal life span?”

  “Correct,” said Kathleen, nodding.

  “And how’d you do that?”

  “These fruit flies have a genetic mutation. A dormant gene on one of their chromosomes has been turned on.”

  “What do you mean, ‘turned on’?”

  “Activated. Made functional. It’s basically like turning on a light switch. You inject a vector into the fruit-fly embryo with a snippet of DNA that is designed to activate the gene. When it finds its target, it effectively turns that gene on.”

  “And by turning this gene on, you’re able to make the flies live longer?”

  “Exactly. The life span of these mutated flies is up to four times that of normal flies.”

  Whittaker was now scribbling furiously in his notebook. “So which gene did you turn on?”

  Kathleen suppressed a smile. “It’s called the INDY gene.”

  “Indy? Like Indianapolis?”

  “No. I–N–D–Y. It stands for ‘I’m Not Dead Yet.’ ”

  Suddenly, the photographer’s eyes lit up. “Like in Monty Python?”

  Kathleen nodded.

  “Oh man, that’s classic! Bring out your dead!” he cried in a mock cockney accent. “Bring out your dead!”

  Whittaker interrupted. �
��So are you saying you can also do this for humans?”

  “Not exactly,” said Kathleen hesitantly. “At least not yet. The INDY gene was discovered in fruit flies several years ago by a group at the University of Connecticut. Since then, researchers have been poring over the human genome looking for an INDY-like gene in humans. Unfortunately, no one’s been able to find one. Which, frankly, doesn’t surprise me given that the mechanisms of aging in humans are much more complex than in fruit flies. It may well be that the INDY mechanism doesn’t exist in humans. Or, if it does, it may be spread over multiple locations in the genome, rather than conveniently packaged in a single gene, as it is in D. melanogaster. That would make it exceedingly difficult to find . . . at least without some sort of a road map.”

  Whittaker scratched his head. “Okay, now I’m confused again. What’s the point of studying the INDY gene in fruit flies when you don’t even know if it exists in humans?”

  Kathleen nodded, acknowledging what she knew to be a very reasonable question. “One of the amazing things about these INDY flies is that their quality of life seems better than that of other flies. Not only do they live longer, but they’re more energetic throughout their entire lives. The female flies can reproduce well into old age, and the males are, how should I say . . . friskier. They mate more often than their non-INDY counterparts, and well into old age.”

  “Way to go, little dudes!” whispered the photographer, giving a goofy thumbs-up to the plastic container.

  “Anyway,” Kathleen continued, “we’re trying to understand—on a cellular and biochemical level—exactly what gives these INDY flies such vigor and longevity. Our goal is to eventually create a drug therapy that can stimulate those same biological processes in humans. If we can do that, then maybe we can give people a better quality of life as they grow old.”

  “How close are you to developing such a treatment?”