Algorithm

Part I

The Medallion

Dr. Adam Dove finished his curved chalk line, drawing an arrowhead which indicated the path a pair of electrons would take to complete a complex chemical reaction mechanism. And yet, he was still in his father's workshop twenty years ago, holding aloft the mystery medallion, his golden enigma. A cough from the audience shattered the flashback, and the gold in his upheld hand morphed into chalk. He turned to look at the classroom. The only sounds throughout the large auditorium were those of pens, pencils, and laptop keyboards belonging to students engaged in keeping up with second-year Organic Chemistry. A distant period bell signaled the end of class and completed Adam's return to the present day—a fall semester Monday in the year nineteen ninety-nine in the sprawling eastern Pennsylvania campus of the Schill University School of Medicine, just outside Scranton, where Adam taught and conducted research in Bio-organic Chemistry. His other hand had been unconsciously fiddling with the medallion hanging beneath his shirt, a habit born of many years and of which Adam had become barely aware.

A short walk along the adjacent hallway brought him to a second floor research lab and his inner sanctuary—a glass wall-enclosed, smallish office populated with piles of books, unfinished manuscripts, and uncorrected test papers stacked precariously in a random pattern of towers of various sizes, each threatening to topple onto his scrimshawed oak desk. He sunk into a cracked leather-lined swivel chair, balancing himself on the three working casters, and reached up to the top of the nearest and most threatening pile. He paused a moment.

Soon I'll be wandering around the hallways, lost in my thoughts, feeling my way along the walls while students point and snicker.

Adam had a good job, enjoyed the teaching and research. It was a scheduled life, one that seemed to be outlined in a course syllabus. At times, that structure was exactly what he needed, but there were moments that gave him pause, turning his mind inward, drifting him off to some far away imaginary world.

A gentle tap on his office door drew him back. He was still holding a sheaf of papers when he looked up to see a young woman's smiling face through the rectangular door window. Her long black hair was neatly tucked into a ponytail. Her eyes were big and brown, highlighted by dimpled rosy cheeks. The collars of a white lab coat finished the portrait. Adam knew her as the molecular biology prodigy from MIT, recently hired by the biochemistry department to coordinate and analyze incoming data from the Human Genome Project. Her name was Linda Garcia, and she was outstanding, both in intellect and looks.

He nodded and she let herself in.

"Professor Dove? I was wondering if you would like to be a part of the Human Genome Project analysis team?"

Her speech held the barest traces of a Hispanic lilt, made all the more exotic by her tanned complexion and beguiling smile. It was typical of Linda to speak directly, often without the usual schmooze associated with departmental politics. Most folks knew about the Genome Project, and most knew that Dr. Garcia was the hotshot coordinating efforts at Schill. To be a part of the team to help analyze the human genome was not only a great honor, but a great scientific opportunity.

"It's Linda, right?"

"Dr. Linda Garcia. I just started here last month."

"And you're heading up the university's contribution to the Human Genome Project, right?"

"Why, yes. The sequence data we are generating, coupled with incoming data from around the country is huge. It's the reason for my visit. I thought that you might be interested in joining my team."

Adam's heart opted for an extra beat. The Human Genome Project began in nineteen ninety as a massive effort coordinated by the US Department of Energy and the National Institutes of Health to identify all the genes in human DNA. Estimates suggested the characterization of the thousands of genes would take about fifteen years to complete. In actuality, nine years later the work was nearing a high point and was almost finished. Schill University had been granted the opportunity to analyze some of the latest data emerging from the project. Adam knew enough to realize that the scientists best suited to the task were molecular biologists, much like Linda. Although he was an organic chemist with some expertise in biochemistry and statistical analysis, Linda's request to join her team seemed out of place.

"Linda, don't you have enough scientists trained in DNA sequence analysis on your staff?"

Adam found himself hoping the answer was 'no.' Her large eyes widened as she answered. "Well, yes … however, Dr. Dove, there are aspects of the data analysis that I think someone with your background could really contribute to."

Her eyes entranced him. Adam was having difficulty paying attention to what Linda was actually saying. "Please call me Adam … what aspects?"

She stared at him for a beat, and her face grew solemn as she replied in a firmer voice. "Adam, why don't you join us tomorrow morning at our review meeting? After seeing the details of the analysis thus far, you'll be able to answer that question yourself." She turned, perhaps too abruptly, leaving the office door to slowly swing back. Before it closed, she added, "Gotta run. I hope to see you in the morning."

When she reached the outer laboratory door, he extended his arm to hold his office door ajar. "I'll be there. Where and when?" He noticed that his hands were sweaty, and his heart seemed to beat a bit harder.

Linda called back without turning. "Room 331B, nine sharp." And with a quick backward wave of her hand she was down the hall and out of sight.

Room 331B was Linda's laboratory office located on the third floor almost directly above Adam's. A note on the door led him to a small meeting room farther along the hallway. He approached its outer door and peered through the glass. About a dozen seated researchers surrounded an elongated conference table. All were dressed in white lab coats, while several fiddled with an overhead projector. A reflection in the glass revealed someone coming up behind him. It was Linda.

"Good morning, Adam. Glad to see you made it."

Adam feigned mild surprise and turned to see Linda's infectious smile. While she opened the door, he replied, "Me too." He followed her inside, and wedged himself into an empty chair in a far corner of the room.

Linda began. "As you know, we are in the midst of collating and analyzing the remaining DNA sequence data for human chromosomes four and five, which would complete our portion of the preliminary sequencing of the human genome. The meeting this morning was called to brain-storm the current data, and to map out a plan of action." Looking directly at Adam, Linda continued, "Dr. Adam Dove will be joining us in a consulting capacity."

The announcement went largely without reaction, with several heads turning to look at Adam. He returned the curious glances with an innocent but studious façade as he pondered the confidence with which Linda assumed he would join the team. The meeting proceeded to detail various quirks and challenges surrounding chromatographic separation and identification procedures, sequencing options, purification issues, and other such technical bits typical of the project in general. As the presentations proceeded, Adam began reviewing what he actually knew about DNA.

The acronym was short for deoxyribonucleic acid—a polymer made up of four types of bases. The sequence of these four bases in a DNA strand represents all the instructions needed to build and maintain any biologic organism. A set of three bases, a triplet, generally encodes for a single amino acid, a building block for a protein that can be hundreds of amino acids long. The sequence of these triplets along the DNA constitutes the genetic code. Each chromosome held one DNA chain and that a chunk of DNA which codes for a specific protein is called a gene.

That's definitely all I know.

He guessed that the total amount of DNA which describes an organism is called a genome.

"Adam, now that you have an appreciation of the challenges we face, I would like your opinion on something."

Adam blinked, mentally filing away his DNA musings, and saw that the meeting room was empty.

It must have been a short meeting.

Linda was standing in front of him and with a smirk, turned and waved for Adam to follow. They entered her laboratory together, where she stopped just inside, letting the door close behind them.

"As you may know, the human genome project was designed to identify each and every gene, and in so doing, it would provide the world with a complete description, basically a roadmap of a human being. The idea was to determine the sequences of approximately three billion bases that make up our DNA, and then to figure out how many genes were present and what proteins they encoded for. Information obtained from this project would be invaluable to us, especially in tackling genetic disorders and developing new ways to design medicines tailored for the individual's biochemistry."

Pausing for a moment to gather her thoughts, Linda furrowed her brow as she caught Adam closing his eyes. She cleared her throat and raised her hands to emphasize a point. "However, we have run into a few surprises. Originally we assumed that hundreds of thousands of genes made up the human genome. Earlier observations indicated that simpler organisms had a smaller number of genes. For example, bacteria and fungi range from about two to eight thousand genes. Fruit flies get up to about fourteen thousand, and mice are at twenty-five thousand. Although the human genome project is not quite complete yet, our data indicate the gene count for humans to be less than thirty thousand."

"Not much more than in mice. Sounds a bit disappointing. What gives?"

"No one knows for sure, but it would appear that we may be using the same basic machinery present in lower species, but in a more complex way."

"Is that the issue that you'd like me to look at?"

Linda shook her head. "Not exactly. There's something else that has emerged which may be much more of a puzzle. It turns out that our genome is largely unused. That is, not only are we limited to thirty thousand genes, but recently we have discovered that a fairly large portion of our genome appears to be nonsense."

Linda took a step closer to Adam.

When he spoke, his voice cracked. "Exactly how much of the genome are we talking about?"

"Our analysis suggests that about two percent of all the sequences in our DNA codes for protein. This leaves the rest of our genome with no identifiable purpose. Some scientists have called these sequences 'junk DNA.' I prefer the term, 'non-coding DNA.' And, that's where you come in."

Adam's eyebrows involuntarily arched as he asked, "And why would that be?"

"Well, experimentalists have been working on the possible function of non-coding DNA, and the most likely theories suggest that it may be responsible for the regulation of all the processes which go into creating and maintaining us, basically acting to make sure each step in the process of our growth and development takes place at the right time and in the right way. Personally, I think that's a neat explanation, however, there's no concrete proof … and, besides, the non-coding sequences are a bit strange."

"Strange? In what way exactly?"

"There are many instances where apparently random sequences repeat themselves in many locations. Actually, they seem to be both random and organized. One other thing … as I mentioned, lower, simpler organisms have fewer genes. However, lower organisms also have less non-coding DNA. The trend that we are seeing is that as an organism becomes more complex, that organism has an increased amount of non-coding DNA."

"Whew. So, how do I fit into the picture?"

"You've done a great deal of work in the area of structure-activity correlations, mathematical procedures designed to detect relationships between molecular structure and biological activity."

Adam nodded as Linda continued. "I have a feeling that there may be more to the non-coding DNA issue than just a random set of sequences coupled to vague theories of cellular regulation."

"You want me to look for patterns within these sequences? Patterns that may correlate with some type of function?"

"You got it."

"Just how much non-coding sequence data do you have?"

"We are just now completing the sequencing for two chromosomes. The non-coding sections consist of about two hundred fifty million bases. We can get the sequence data from other labs which cover the rest of the human genome. Altogether the mystery sequences contain close to three billion bases."

The cylinder turned and its engines fired in a programmed series of short bursts to begin a controlled process of deceleration. The G-forces needed to be carefully regulated. Excessive forces would not damage the cocooned occupants, but could pose issues to the few awake and on duty.