OUTRAGE

author’s note

Outrageis a work of fiction . Nevertheless, the science behind the use of DNA is accurate. It is my hope that those who depend on DNA analysis will make every effort to prevent its misuse. 

Jasper Rine

Prologue

The DNA sequences that he needed were just copies of sequences of the human genome. But any order for these particular twenty-six sequences by anyone outside of law enforcement could be highly suspicious. If absolute secrecy were not essential to both his plan and his own survival, the work would have been so much easier. These days, synthesizing particular DNA sequences was done by commercial companies using highly automated robotics that miniaturized the phosphoramidite chemistry that had been a standard synthetic method for decades. To get an oligonucleotide primer for any DNA sequence you wanted to amplify in the Polymerase Chain Reaction, you simply went to the website of a DNA synthesis company and entered the sequences that you wanted along with a method of payment. Two days later, a Federal Express envelope would arrive containing small plastic tubes with the DNA sequences you had ordered inside¾and a record of the order remained with the company.  

Companies were obliged to maintain records of DNA orders to deter terrorists from using biological warfare. If law enforcement got a clue that someone might be genetically engineering a pathogen, they contacted the companies and had them search for any DNA sequence that would match the sequence of genes for toxin production, or viruses. The record of such an order could lead to rapid identification of suspects. The odds that anyone would get that far in an investigation were tiny, maybe one in a million. But he had no margin for error. He had no choice but to synthesize the twenty-six snippets of the genome with his own hands and leave no electronic record of his actions behind. 

The current pace of technical progress in biomedical research was rapid and expensive. The newest methods frequently involved instruments that cost many thousands of dollars but quickly became obsolete when they were replaced by even more expensive instruments that could do far more much faster. Nevertheless, because it was so hard to raise the funds for these instruments, older equipment tended to be kept around even after it was no longer used. Partly, the old stuff was kept as a backup for when the new gizmos failed, as they tended to do early in their life cycles. Keeping the old stuff also reflected a scientific nostalgia and appreciation that, like equipment, scientists aged too. Just because it was old didn’t mean it was useless. Every research building had a room in some out-of-the-way location that had become the cluttered garage of old instruments, often still serviceable but faded and dusty. 

That’s where he found his prizes. They weren’t much to look at, just beige boxes big enough to cover a small desk. One of the beige boxes had bottles of chemicals attached to it. That one was an Applied Biosystems oligonucleotide synthesizer from the late 1980s. When he looked more closely, he saw that the bottles contained the phosporamidite chemicals corresponding to the individual letters of DNA. The bottles were so old the chemicals had probably broken down already. Oddly, the labeling on the bottles indicated that the chemicals contained the deoxyribose sugar of the wrong kind. DNA in all creatures uses the d-form of deoxyribose, but these bottles contained A, T, G, and C nucleotides made of the l-form of deoxyribose. He smiled recognizing that this instrument must have belonged to Frank, an eccentric colleague, long retired, who thought he could find left-handed DNA and built his oligonucleotides out of ingredients of the opposite handedness in order to search for it. The old man had never succeeded and some folks thought the project was crazy. He had considered the search quixotic but brilliantly conceived. He would give this machine the chance to make the impact that Frank’s project never did.

In principle, for his project to work, all he needed was the ability to make the oligonucleotides needed for the thirteen PCRs, i.e. Polymerase Chain Reactions on each sample. But his plan would be successful only if the sequences that his primers amplified were absolutely the right ones. His old professor would never have let him get away without doing all of the controls for every experiment. The only way to be sure that the sequences were correct was to determine the sequence of the DNA that each primer pair amplified. Determining the sequence of a piece of DNA was simple enough. In modern labs like his, one just used the PCR to amplify the DNA of interest from a DNA sample and then sent that amplified DNA to a core facility for sequencing. By the end of the day, an email arrived from the facility with the string of letters¾all A, T, G or C¾that spelled out the sequence of the DNA. But he could never let any of his sequences be on any instrument connected to the Internet. He would need to go old-school.

The ability to sequence DNA was figured out back in the 1970s by Walter Gilbert at Harvard University and Fred Sanger at the Medical Research Council (MRC) lab in Cambridge, England. By far, Sanger’s method became the dominant method for decades. This work had been done before the Internet was invented or before computers became commonplace in the lab. Sanger’s methods relied on the use of radioactive tracers to label DNA fragments prepared from a sample. The fragments were inserted into a gel and then separated according to their size when the gel was put into a strong electric field. The radioactive decay of the isotope of phosphorous used to label the DNA would leave a pattern of bands on photographic film exposed to the gel, and that pattern could then be directly read out as a DNA sequence. He had seen DNA being sequenced this way during his training and knew that he could make it work in his own government lab. But doing so would raise all kinds of questions, especially because his lab did not have a license for working with radioactive phosphorous. Sure, he could get one, but he would have to write up a justification and a protocol; those would be reviewed by a laboratory safety committee that met only once a month, and because he would be sequencing in such an old-fashioned way, there doubtless would be questions, more cycles of review, and more delays. 

This is where his other prize, a 1993 Applied Biosystems single-channel capillary sequencer fit in. Almost miraculously, the instruction manuals and CDs with the operating program were sitting in a box on top of the sequencer. Capillary sequencers were the instruments that had done the bulk of the work determining the first human genome DNA sequence. These instruments used Sanger’s method but replaced the radioactive tracers with fluorescent chemical tags that could be used to follow DNA fragments. These instruments also replaced big, ungainly gels with tiny capillary tubes that allowed the DNA fragments to be separated in the electric field much faster. His new-found instrument was the earliest version of these capillary machines, with a single capillary rather than the ninety-six-capillary capacity of later machines that could determine many thousands of DNA sequences per week. He figured that a couple hundred sequences would be enough to change the future. He wheeled the two instruments back to his lab early one morning before any of his team arrived and set them up in a remote corner of the lab where he could work undisturbed. 

Part I: War

1

Day 1 of the War

The Plantation

Deer hunting season had been over for several months and spring had been unusually wet and cold. He had been crouched in a drainage ditch for nearly an hour with cold water running through his sneakers. Numbness had removed all feeling in his toes and was headed upward, already at mid-calf. Only his head was visible above the concrete caisson that collected drain water from culverts on both sides of the road and sent the water on its way to Williams Creek. He had his quarry centered in the crosshairs of his variable 3-9X Leupold scope. When he shot his first deer, at age fourteen, he had been overwhelmed by sadness for the animal. The deer had been an innocent victim in that drama, and its death had fed him and his teacher for much of a winter. 

Today’s death would be different. The rifleman’s quarry was not an unwitting creature hunted for food. His mind replayed the unlikely string of events that had brought him to this precipice. He probed internally for the anticipatory guilt he thought would be there. If there, it was well hidden. Maybe guilt or regret would come afterword. There would be no undoing the deed, and if regret followed, well, as one of his high school teachers used to say, he would just have to burn that bridge when he got there.

His hiding place was directly across the road from the entrance to The Plantation, a housing development near Winston-Salem, home to the newly rich. The Plantation was outside the city limits just far enough to give the illusion of country living and to keep the property taxes lower. Not that it mattered aside from force of habit, but the rifleman checked the wind and was pleased that he was downwind of his target, Dexter Carter, who looked pretty much as expected: a well-dressed man in his late forties trying to look cool with a goatee favored by twenty-somethings. As the rifleman watched with his finger on the trigger guard, Carter patted his pockets as if checking for cigarettes, turned, and headed back inside. Of course. Carter would need a good fix before going through airport security, as there was no possibility of smoking on the flight he intended to catch. Once he passed security at the airport, it would be nearly impossible to light up until he got to his destination. The rifleman waited, unmoving, until Carter reemerged from his home at the end of Big Leaf Drive with his suit pocket and likely his briefcase loaded with fresh smokes retrieved from his pantry. 

The rifleman thought about dropping Carter right at his door, which he could have done from three hundred yards away with his .270 Remington 700. He had made more difficult shots on smaller targets before. But his mentor never would have approved of long-range show-off shots when a clean kill was the goal. Traffic on the county road that passed by The Plantation had been virtually nonexistent, but that would not last much past 6 am. The rifleman watched Carter lock his front door and climb into the gold Cadillac parked in his driveway. As Carter fastened his seatbelt, the rifleman chambered a round, took off the safety, and watched through the scope as Carter piloted the big car out of the driveway.

The Cadillac slowly climbed the slope on Big Leaf Drive toward the intersection with the county road, pausing at the stop sign with its wheels pointing to the right. The rifleman had expected only a moment for this shot, but Carter surprised him with a full stop and sat staring blankly at the roadway, perhaps reviewing the details of his departure. Had he remembered to lock the back door? Had he left the text of the next advertising campaign on his office desk, or had he secured it in his safe according to company policy? There were just too many things to worry about. This job paid well, but the pressure got to him sometimes. He needed a smoke.

With his cheek pressed against the walnut stock of the rifle, the rifleman again had Carter right in the crosshairs. At this distance, the cigarette now dangling from Carter’s lips looked enormous. Time seemed to slow. The rifleman had reached his Rubicon. If the muscles of his right index finger were not to contract, everything would continue in the highly successful trajectory of his life. Whereas one contraction of the muscles in that one finger would forever change the trajectory of two lives. One would end, and one would forever be a wanted man, at best, or in prison. The rifleman had expected this moment to be difficult, a point of no return that he consciously would have to negotiate. 

There was no going back. The rifleman began to squeeze the trigger just when he saw an orange glow of the lighter, as Carter lit his last cigarette. Halfway through his first draw, time stopped for Mr. Dexter Carter as a 150-grain bullet slammed through the driver’s-side window at nearly 3,000 feet per second and shattered into dozens of bullet fragments that entered his skull a few milliseconds before bits of his brains exploded out the other side, decorating the camel leather interior of his prized Cadillac in blood red and neuronal gray. The rifleman had planned the angle of the shot so that the rifle’s report would be directed upward rather than toward any nearby house. Nevertheless, he didn’t have much time, and he needed to act fast. Here, Carter performed one last favor. The bullet’s impact slammed Carter to the right, and as his body slumped, the steering wheel turned to the right, his foot left the brake, and the car turned slowly, but directly, into the culvert on the other side of the road from the rifleman’s position. As the front-right quarter of the car dropped into the trough, its gas tank conveniently cracked on top of the drainage pipe running under Big Leaf Drive, and gasoline started spreading beneath the car. The rifleman could not believe his good fortune. He had brought a geologist’s pick with him to punch a hole in the tank, but as Louis Pasteur had said: “Chance favors the prepared mind.” 

He quickly grabbed the soda can into which he had stuffed a rag and soaked the rag with lighter fluid. He guessed that half the cars in Winston-Salem carried a half pint of Zippo lighter fluid in the glove compartment, making its presence easy to explain should any cop stop and question him. He lit the soaked rag and pitched the can across the road toward the underside of the Cadillac of the late Dexter Carter. As the rifleman’s undergraduate chemistry professor would have said, the results were extremely exothermic. The blast of heat warmed his face in the predawn cold as he turned away from the fireball. He carefully ejected the spent cartridge into his rubber gloved hand, and then dipped the cartridge into the buffer solution spiked with DNA in the 30 ml Falcon tube. He then placed the cartridge in a depression where it could have landed if someone standing in the ditch had hastily ejected it from the gun. Ducking back into the culvert, he snapped the grating cover back in place and, keeping low, waded through the mud and flowing water in the drainage pipe. He emerged from the other end and, remaining low in the muddy water, limped the fifty yards to the junction of that ditch with another, where he had parked the old Volkswagen Beetle with out-of-state plates. 

As he slid into the driver’s seat, his adrenalin faded and the cold and fatigue overwhelmed him. He regarded himself in the rearview mirror. He looked no different than he had the day before: short brown hair, hazel eyes. He needed a shave, but otherwise, it was the familiar face that had stared back since he was tall enough to look in a mirror. What had he expected to see, horns? The various identities he associated with himself paraded in his mind: orphan, college athlete, then scientist, a physician, and now a killer of men. In the mirror, he could see the orange glow of the Cadillac as flames enveloped it. His memory returned to that first deer and the look it had given him just before it died.