Chapter 13
A/N: Hey guys! Here's the next chapter. Again, heavy science ahead. I hope that you all enjoy the chapter - let me know. Cheers!
Before Hood and Rachel headed for the NIH, Hood left Rachel for a few moments in order to consult with Dr. Wilkinson. The physician led him into a consultation room, dimly lit with a couple of desk lamps, and gestured him into one of two identical armchairs. He sat down in the opposite chair where he crossed his legs comfortably and proceeded to clean his glasses on his white coat. "Well," he said finally, "Dr. Loch brought me up to speed this morning. He told me that the cause of the trouble is a defective sodium channel gene." Hood nodded. Dr. Wilkinson appeared to have been granted a second wind - reenergized now that he knew what disease he was fighting, however, Hood was still troubled. He leaned forward slightly, elbows resting on his knees, "I understand how important it is to get these people treated as soon as possible, but at the same time..." Hood frowned fractionally, "at the same time I also recognize the need to track down the original source of this virus in order to prevent further releases." He paused for a moment, considering, " I think you will agree that this has all of the earmarks of an accidental release. The cases were sporadic with random victims all tracked back to a veterinary clinic with little potential as a terrorist target." Dr. Wilkinson nodded, conceding the point. "However," Hood continued, "there is every chance that even an accidental release could happen again." He sighed, tenting his fingers, "What I would suggest is beginning a two-pronged treatment of pyridostigmine with acetazolamide. These two drugs have proven efficacious in studies of this particular sodium channel mutation in the past. At best, they will help to control the myasthenic syndrome until we can devise a more permanent cure."
Dr. Wilkinson clicked his pen somewhat distractedly and then peered at Hood over the top of his glasses, "That sounds like a reasonable plan to me," he said. "You know, I understand how pyridostigmine functions but..." he shook his head, "I never understood how acetazolamide works in myotonia." Hood got up, grinning broadly. He clapped the other man on the shoulder, "Neither do the pharmacologists," he told him. Dr. Wilkinson startled himself with a laugh - the first genuine one for days.
Hood was sorry to break the mood, but he had to be going, "Rachel and I are heading over to the NIH," he told Dr. Wilkinson. "I think that we will find that the virus originated somewhere there. We will probably try the National Institute of General Medical Sciences first." He turned to go, but was stopped by an exclamation. "Oh," Dr. Wilkinson said, snapping his fingers, "Melissa told me to pass this along. She says that the fleas you gave her were full of the virus." Hood nodded in satisfaction, "That's fantastic," he told the other, "We have a man coordinating with the health department to deal with any fleas found on animals previously at Merriter Lane. I'm told that the health department has closed down the clinic for the time being. That should deal with the first wave of the virus." Both men smiled again, feeling that they were finally making meaningful progress.
Hood thanked Dr. Wilkinson again and went in search of Rachel. He found her just finishing up a phone conversation. Snapping the phone shut, she turned to Hood and bobbed her head in acknowledgement, "That was Felix. He tells me that he and the health department have been working with animal control to temporarily seize each and every potentially infested animal." She met Hood's questioning gaze, "He called to tell us that they just removed the last of the animals for treatment." Hood nodded in approval, "Good. Dr. Wilkinson just gave me a message from Melissa that the fleas all contained our virus." After her disastrous flirting yesterday, Rachel figured that Melissa must have been too embarrassed to deliver her message in person - but she chose not to comment. A few minutes later and they were on their way to the NIH.
The site of the NIGMS, the William H. Natcher building, was an impressive structure, all glass and white stone. As Hood and Rachel approached, the sunlight glinted with a fiery intensity off of the many windows and the single white tower, jutting like a finger toward the sky, took on a gilded tone. The glass and alabaster edifice made Rachel feel slightly small, displaced and irrelevant. Hood, however stepped forward with the easy familiarity of one who revisits an old friend. He paused at the door, turned slightly and smiled encouragingly at Rachel as he noted her hesitance, "Shall we?" he asked softly. Hood held the door for her and motioned her inside and Rachel rolled her eyes at this reassertion of his rather archaic manners. She looked pointedly in his direction and held the second door open for him, daring him to argue. He grinned at her and stepped through without comment.
Hood consulted the directory on the wall, following one particular line with a finger. He tilted his head toward the bank of elevators and he and Rachel proceeded to the third floor. Outside of the elevator, a number of hallways branched off from the central axis, hallways which led to various labs and equipment. Various personnel, some carrying tubes nestled carefully in ice, others reading papers as they walked, bustled busily through the halls, occasionally nodding in acknowledgement. Hood began walking into the south wing of the building.
The walls here were decorated with the occasional poster displaying all manner of graphs, tables, and figures. One particular poster, tacked to the wall on the far side of a freezer, captured Hood's attention. The central figure of the poster was a set of brightly colored lines, arrayed so as to resemble the propeller of a box fan. To Rachel, the picture looked like silly string, however, the poster indicated that it was a model of the sodium channel. It was not in any case the figure which had attracted Hood's attention. He stood gazing at the sodium channel sequence presented in the next section. Abruptly he finished his perusal of the text and raised a finger to tap sharply a mutation highlighted in red, causing the poster to rattle slightly against the wall. Rachel glanced questioningly at Hood. He placed his hands in his pockets, slouching slightly, "Well," he said, "I think we're in the right place." Rachel studied the mutation he had indicated more closely. "V1442E," he told her, nodding in confirmation, "the mutation found in our patients." With that, he checked the position of his visitor's pass and stepped into the lab next to the poster, Rachel trailing behind.
Dr. Riley Wakefield sat in his office typing up an article response, occasionally bending down to check some fact or figure in the paper. Hood and Rachel stood just inside the door and Hood, mindful of the proper etiquette, stood quietly until he detected a brief lull in the other scientist's thought process, then he stepped forward slightly and began speaking softly so as not to startle him. "Hello Dr. Wakefield, I am Jacob Hood and this is Special Agent Rachel Young. I believe that the visitor's center phoned ahead to say that we were coming." Dr. Wakefield pivoted in his chair, his eyes falling briefly to Hood's visitor's pass before he stood and offered first Hood and then Rachel a hand in greeting.
Dr. Wakefield was a tall man of medium build, a perpetual stoop to his shoulders. His dark brown hair, shot through with gray, was carefully combed to one side in an effort to obscure a widening bald patch. A high brow, deeply furrowed, sloped gradually into a sharply angled nose, framed by two alert brown eyes. Dr. Wakefield studied each of them in turn and then turned to address Hood. "I'm afraid that I don't have time to show you around at the moment," he told them, speaking in a voice flavored with a slight British accent. "I have arranged for one of my graduate students to take you around the lab. By the time you get back, I should be able to answer any questions you might have." This said, Dr. Wakefield strode to the door and poked his head outside, "Kianga!" he called, one hand cupped around his mouth.
This exclamation was shortly followed by a young black woman of somewhat short stature with smooth, rounded features and golden amber eyes that peered at them from over the tops of her glasses. Her intricately braided hair was gathered into a neat ponytail that trailed down her back and she stood at ease next to her professor's shoulder awaiting introductions. Dr. Wakefield addressed Hood, "This is Kianga," he told him "my senior graduate student and currently involved in our work with the sodium channel gene." He turned to address her, "Kianga, this is Dr. Hood and this is Agent Young from the FBI." Kianga smiled at both of them and politely inclined her head, "Dr. Hood, Agent Young, if you would please follow me." Her speech pattern had a certain fluidity about it, the cadence and tonality rippling and flowing as a brook over smooth stones.
She led them through a number of halls and through a door into a conference room where she gestured to them to take a seat, "Dr. Wakefield told me that you asked to see our animals and that you were specifically interested in my project for some reason," Kianga said, pulling up a chair. Hood nodded in agreement, "Yes we are."
"As you may know," she continued musically, "we are currently collaborating both with an ion channel lab over at NINDS and with AstraZeneca. We are working together to test the efficacy of a new cholinesterase inhibitor, MC0349, against the myasthenic syndrome caused by V1442E." She smiled at them briefly, "The lab at NINDS works with the drug's activity at a molecular level while we introduce the gene of interest into our animal population and study the effects of the drug on our animals." She handed Hood a picture, "These chimpanzees are our test subjects. Those in the cages on the right are our control group and are being treated with an older cholinesterase inhibitor, while those on the left are the experimental group being treated with MC0349." Kianga grinned at them, "So far, the new drug is looking promising," she told them.
Hood was chewing his lip thoughtfully, "Am I right in thinking," he asked finally, "that your lab is working to develop a new technique for obtaining transgenic animals?" Kianga smiled again, nodding firmly, "Absolutely right," she told him. "We take our gene of interest and put it into a lentiviral vector behind a specific promoter - in this case a promoter specific to skeletal muscle." Hood leaned briefly in Rachel's direction and explained softly that a promoter was a sequence in DNA that enabled a gene to be turned on and off. In this case, an active promoter led to the manufacturing of the defective sodium channels.
Kianga continued with her explanation, "As you doubtless know," she said to Hood, "lentiviruses have the capability of inserting themselves into the DNA of the host - in this case, one of our chimps." Hood nodded distractedly, eager to hear the rest of the explanation. "Our lentiviruses are designed to find specific and well-defined sequences in the host DNA and to insert there," Kianga went on. "This results in the insertion of the mutant gene into the center of the native gene." Hood mused quietly for a moment and then looked directly at Kianga, "I see," he told her, "so the insertion of the mutant gene disrupts the sequence of the native gene and renders it non-functional." Kianga smiled at him, pleased that he understood, "That's right, and the genetic sequence of the chimpanzee is at least 96 percent identical to that in humans. So we can use the human sodium channel and get a very good indication of how well this drug works on the organismal level."
Hood gazed steadily at her and added seriously, "And if this virus should somehow get loose in the general population, then it would work with humans too." Kianga shook her head without hesitation, "No, no," she said, "that's not possible. Our lentiviruses are replication deficient." Hood turned to Rachel again, "Rachel," he said, "the viruses used in gene therapy have been altered so that they can't reproduce themselves." He paused, running a hand through his hair thoughtfully, "The typical virus has three genes called gag, pol,and env, that code for the viral protein coat - the package that wraps up the viral genetic material. The viruses used in gene therapy have had those three packaging genes removed. Scientists add the genetic material to specialized cell lines that express the packaging genes and those cells manufacture the viral protein coat and package the viral genetic material inside. This creates a complete virus that will not be able to manufacture a protein coat of its own." He paused for a beat, allowing Rachel to process that information, "If a virus can't make its own protein coat, then it can't spread."
He turned to face Kianga, "Somehow your lentivirus regained its capacity to replicate and escaped to infect the general population," he told her. Kianga was shaking her head. "Kianga," he said with difficulty, "the patients with the unexplained paralysis were found to be infected with a lentivirus carrying a gene with the exact same sequence reported on your poster." Kianga sat frozen in shock and as Hood and Rachel watched, her face acquired a grayish cast and she looked positively ill. "But how?" she muttered, half to herself, "How could the virus regain its capacity to replicate! And how," she added, "could it escape?" Hood shook his head negatively, "I don't know yet," he told her. His lips firmed into a thin line and his eyes narrowed in determination, "But I intend to find out."
"Kianga, will you take us to see your chimps?" he asked. Kianga nodded somewhat distractedly, still processing all that he had told her. Presently she stood and led them from the room. They passed through a large office area, the center partitioned into cubicles with four or five nicer offices lining the perimeter. Passing through a door on the other end of the office area, Kianga turned off to the right and tapped a key card against an access panel, unlocking the door with an electronic beep. She paused by a supply cart outside the next door and began to pull on a lab coat, gloves, and an eye shield, gesturing that Hood and Rachel should do the same. When she was sure that all of them had on the correct protective gear, she turned and keyed a pin code into the access pad next to the door. Pushing the door open, Kianga invited them inside.
Inside the room, numerous chimpanzees watched them curiously from inside the cages, occasionally calling out. Rachel was amazed at the intelligence reflected in their eyes. They appeared to know Kianga on sight, vocalizing happily as she stepped into the room. Even as troubled as she was, Kianga managed a smile behind her mask, "Hello my friends," she said quietly. Hood caught Kianga's attention with a raised hand, "Kianga, would it be all right if I approached the cages more closely?" Kianga considered for a moment, "Yes," she said finally, "but I would rather you didn't touch the chimps or the cages. We don't want any bites." Hood nodded once in understanding and moved slowly toward the cages on the left hand side of the room, "Hello," he said cheerfully. The chimps eventually decided that he was not a threat and began to chatter. The bravest of them even reached through the bars of his cage. Hood visually inspected each of the animals, occasionally speaking softly to them.
After a few minutes, he stepped back over to Rachel and Kianga. "Kianga," he said, his breath catching as if he were troubled, "have all of these animals been exposed to the virus?" Kianga nodded in affirmation, "Yes," she said, "they have to be kept separately from all of our other animals - including the other labs' animals." "Good," Hood muttered, half to himself. He raised his voice again, "Kianga, these animals seem to have fleas. Many of them are scratching and there are dead fleas on the bottoms of the cages." Kianga rushed over to the cages quickly enough to startle the chimps into screeching and hooting. She soothed them with a few softly spoken words and peered into several of the cages. In a moment, she turned back to Hood, desperation in every line of her face and in the tense way that she held her shoulders, "You're right," she said finally. "But all of the animals are quarantined for a month when they arrive here and they are examined for any health problems during that period of time." She shook her head in disbelief, "I am sure that the veterinary staff would have picked up on any fleas. All animal care is on site and no outside animals are allowed inside the building."
At last, Kianga led them from the room and they all disposed of their protective gear. She led them back to the office area and told them to sit in a cubicle whose occupant was currently elsewhere. "This desk belongs to our technician. He's taking a lunch break and he shouldn't be back for a while yet." She frowned worriedly, "I need to tell Dr. Wakefield what you found. I'll bring him back to talk with you in a few minutes." With that, she walked rapidly off, tension radiating from every motion she made. Rachel made herself at home at the desk while Hood paced around the cubicle. A couple of minutes later, Rachel looked up from her reverie to find Hood staring at a fixed point somewhere in the vicinity of the trash can at his feet. Presently, he seemed to return to himself and moved back to stand next to Rachel.
Shortly thereafter, Kianga returned with Dr. Wakefield, who was looking concerned and upset. He wrung his hands unconsciously and his comb-over was slipping. Hood didn't waste time, but stepped directly over to him and, folding his hands behind his back, said without preamble, "You have an unauthorized cat in the building." Dr. Wakefield's head jerked back sharply in shock, his comb-over becoming more disheveled, "That just can't be," he said finally. Hood reached over and removed a pencil from the desk which he then used to fish a small can out of the trash. He turned back to Dr. Wakefield, "Well," he told him, "either your technician really likes 'tuna surprise' or he is hiding a cat."
Dr. Wakefield stared disbelievingly at the can for a moment and then his brows drew down dangerously and his jaw tightened, "I, " he huffed severely, "am going to go have a little chat with Mr. Baker in the lunchroom. If you'll excuse me." He hurried off in the other direction and shortly thereafter, the somewhat muffled sounds of a one-sided shouting match echoed down the hall. The bellowing abruptly increased in volume and Hood and Rachel exchanged a glance, finding themselves rather impressed; Kianga shuffled uncomfortably from her post against the wall.
The door to the lunchroom sprung open and a young man, thin and with unruly black hair, rushed from the room as if all the hounds of hell were on his tail. Dr. Wakefield stalked after him, several curious pairs of eyes watching the scene play out from the door of the lunchroom. The technician charged into the cubicle and yanked open a drawer on the filing cabinet. He fished around for a moment while Dr. Wakefield tapped his foot impatiently and then turned and led them hurriedly to a large storage room, which he unlocked. Inside, a cat could be heard meowing to be let out. He opened the door and scooped up the gray tabby cat that came into the hall.
Hood stepped over to Baker and investigated the cat in his arms carefully. He reached out to touch with one finger the flea collar around the little animal's neck. He looked up, for the moment utterly confused, "I don't understand," he said, "this cat doesn't have fleas." The technician was still somewhat shaken, but he looked up at that and protested, "Of course not! Sampson is a good cat and he always wears his flea collar. He..." He would have continued, but he was silenced by a look from Dr. Wakefield. "Get that miserable cat out of here," he said, enunciating carefully. "If you make one more mistake like that Mr. Baker..." he left the comment hanging, his meaning abundantly clear. The technician turned to go, but at that moment, Hood and Rachel shared another look, a horrible suspicion growing in both of their minds. "Wait!" Rachel called, her tone severe, "Where's the other cat?" "Yeah," Hood pitched in, folding his arms, "where's Delilah?"
The technician's shoulders jerked guiltily and he turned around to face them again. He stared at them for quite a while and then, seeing that he wasn't going to escape this one, volunteered the necessary information. "Delilah hasn't been at the NIH for about two weeks," he told them. Hood prompted him to continue, moving one hand in a circular pattern and staring fixedly at him. Finally Baker spoke up again, "She's at the vet's. She's been sick lately." Hood cocked his head like a raptor, "What veterinary clinic is she at and what did they say was wrong with her?" he asked. Baker shrugged, "She's at the Merriter Lane Animal Hospital and they said that she has FIV." Hood closed his eyes - of course! he thought. At last, the final pieces of the puzzle were slotting into place.
Hood nodded emphatically, "I understand now," he told the others. He turned to address Rachel, "Lentiviruses such as the ones used in gene therapy insert their genetic material into the DNA of the host cell. Once there, on occasion, they can pick up pieces of the host DNA and they can lose pieces of their own genes. This occasionally results in a virus that can no longer replicate itself." He glanced at Rachel, assessing her level of confusion, "This phenomenon," he continued, "is referred to as the defective virus. A defective virus needs to have the help of another virus in the same cell to manufacture new protein coats." He paused, jiggling his hand in midair as he prepared to move to the sticky part of his argument, "Delilah has Feline Immunodeficiency Virus - the cat equivalent of the AIDS virus. FIV is also a lentivirus. I think," he went on, "that what happened here is that the lentivirus carrying the defective sodium channel gene infected cells in Delilah that were already infected by FIV."
Hood took a deep breath, "Once there, they both inserted themselves into that cell's DNA. Because Delilah's DNA is different enough from a human DNA sequence, the lentivirus inserted randomly into her DNA and encountered the FIV genes." He glanced around at all of them in turn, "What I think might have happened is that the gene therapy virus picked up the three genes encoding the viral protein coat from FIV and thus, the virus regained its ability to replicate." He lifted a hand to forestall any arguments for the moment, "Now I know that the odds are astronomically against such an occurrence," he admitted, "but, I think that Delilah was exposed to a high quantity of both viruses. Given the number of cells that were probably infected by both viruses, the odds are much more favorable to such an unlikely event."
Dr. Wakefield was nodding, evidently finding such an argument plausible, "Yes," he said finally, "that is theoretically possible." Hood bobbed his head affirmatively, "And given that the sequence of the virus in the affected individuals is identical to your virus," he added, "I should think that this is the most likely explanation." Hood extended a hand, palm downward in the direction of Dr. Wakefield and Kianga, "Well," he said, "I think that we have all of the information that we need." He smiled apologetically at Kianga and Dr. Wakefield, "I'm afraid that Rachel and I need to leave now." He moved forward to shake both of their hands. He squeezed Kianga's shoulder encouragingly, "It wasn't your fault," he told her gently. He turned to go and Rachel quickly said her goodbyes to Dr. Wakefield and Kianga, studiously avoiding the shamefaced Baker.