Acceptable Risk

by Robin Cook

  “Eleanor,” Edward said over his shoulder.

  “She wasn’t terribly friendly,” Kim said, unsure if she should mention it.

  “Eleanor?” Edward questioned. “You must be mistaken. She gets along with everyone. Around here I’m the only bear. But both of us are worn a little thin. We’re on a roll. We’ve been working nonstop since late Saturday morning. In fact Eleanor has been working that way since Friday night. Both of us have hardly slept.”

  They arrived at Edward’s desk. He lifted a stack of periodicals off a straight-backed chair, tossed them in the corner, and motioned for Kim to sit. Edward sat in his desk chair.

  Kim studied Edward’s face. He seemed to be in overdrive, as if he’d drunk a dozen cups of coffee. His lower jaw was dancing nervously up and down while he chewed gum. There were circles under his cool blue eyes. A two-day stubble dotted his cheeks and chin.

  “Why all this frantic activity?” Kim asked.

  “It’s the new alkaloid,” Edward said. “We’re already beginning to learn something about it and it looks awfully good.”

  “I’m pleased for you,” Kim said. “But why all the rush? Are you under some sort of deadline?”

  “It’s purely an anticipatory excitement,” Edward said. “The alkaloid could prove to be a great drug. If you’ve never done research it’s hard to comprehend the thrill you get when you discover something like this. It’s a real high, and we’ve been reexperiencing that high on an hourly basis. Everything we learn seems positive. It’s incredible.”

  “Can you say what you’ve been learning?” Kim asked. “Or is it some kind of secret?”

  Edward moved forward in his chair and lowered his voice. Kim glanced around the lab but saw no one. She wasn’t even sure where Eleanor was.

  “We’ve stumbled onto an orally effective, psychoactive compound that penetrates the blood-brain barrier like the proverbial knife through butter. It’s so potent it is effective in the microgram range.”

  “Do you think this is the compound that affected the people in the Salem witchcraft affair?” Kim asked. Elizabeth was still in the forefront of her mind.

  “Without doubt,” Edward said. “It’s the Salem devil incarnate.”

  “But the people who ate the infected grain were poisoned,” Kim said. “They became the ‘afflicted’ with horrid fits. How can you be so excited about that kind of drug?”

  “It is hallucinogenic,” Edward said. “There’s no doubt about that. But we think it’s a lot more. We have reason to believe it calms, invigorates, and may even enhance memory.”

  “How have you learned so much so quickly?” Kim asked.

  Edward laughed self-consciously. “We don’t know anything for certain yet,” he admitted. “A lot of researchers would find our work so far less than scientific. What we’ve been doing is attempting to get a general idea of what the alkaloid can do. Mind you, these are not controlled experiments by any stretch of the imagination. Nevertheless, the results are terribly exciting, even mind-boggling. For instance we found that the drug seems to calm stressed rats better than imipramine, which is the benchmark for antidepressant efficacy.”

  “So you think it might be an hallucinogenic antidepressant?” Kim said.

  “Among other things,” Edward said.

  “Any side effects?” Kim asked. She still didn’t understand why Edward was as excited as he was.

  Edward laughed again. “We haven’t been worrying about hallucinations with the rats,” he said. “But seriously, apart from the hallucinations we’ve not seen any problems. We’ve loaded several mice with comparatively huge doses and they’re as happy as pigs in the poke. We’ve plopped even larger doses into neuronal cell cultures with no effect on the cells. There doesn’t seem to be any toxicity whatsoever. It’s unbelievable.”

  As Kim continued to listen to Edward, she became progressively disappointed that he did not ask her about her visit to Salem and about what happened to Elizabeth’s head. Finally Kim had to bring it up herself when there was a pause in Edward’s exuberant narrative.

  “Good,” Edward said simply when she told him the head had been replaced. “I’m glad that’s over.”

  Kim was about to describe how the episode had made her feel when Eleanor breezed into view and immediately monopolized Edward’s attention with a computer printout. Eleanor did not even acknowledge Kim’s presence nor did Edward introduce them. Kim watched as they had an animated discussion over the information. It was obvious Edward was pleased with the results. Finally Edward gave Eleanor some suggestions along with a pat on the back, and Eleanor vanished as quickly as she’d appeared.

  “Now where were we?” Edward said, turning to Kim.

  “More good news?” Kim asked, referring to Eleanor’s printout.

  “Most definitely,” Edward said. “We’ve started on determining the compound’s structure, and Eleanor has just confirmed our preliminary impression that it is a tetracyclic molecule with multiple side chains.”

  “How on earth can you figure that out?” Kim asked. In spite of herself she was impressed.

  “You really want to know?” Edward asked.

  “Provided you don’t go too far over my head,” Kim said.

  “The first step was to get an idea of molecular weight with standard chromatography,” Edward said. “That was easy. Then we broke the molecule apart with reagents that rupture specific types of bonds. Following that we try to identify at least some of the fragments with chromatography, electrophoresis, and mass spectrometry.”

  “You’re already beyond me,” Kim admitted. “I’ve heard those terms, but I don’t really know what the processes are.”

  “They’re not that complicated,” Edward said. He stood up. “The basic concepts are not difficult to comprehend. It’s the results that can be difficult to analyze. Come on, I’ll show you the machines.” He took Kim’s hand and pulled her to her feet.

  Edward enthusiastically dragged a reluctant Kim around his lab, showing her the mass spectrometer, the high-performance liquid chromatography unit, and the capillary electrophoresis equipment. The whole time he lectured about how they were used for fragment separation and identification. The only thing Kim understood completely was Edward’s obvious bent for teaching.

  Opening up a side door, Edward gestured inside. Kim glanced within. In the center of the room was a large cylinder about four feet high and two feet wide. Cables and wires emerged from it like snakes from Medusa’s head.

  “That’s our nuclear magnetic resonance machine,” Edward said proudly. “It’s a crucial tool with a project like this. It’s not enough to know how many carbon atoms, hydrogen atoms, oxygen atoms, and nitrogen atoms there are in a compound. We have to know the three-dimensional orientation. That’s what this machine can do.”

  “I’m impressed,” Kim said, not knowing what else to say.

  “Let me show you one other machine,” Edward said, oblivious to Kim’s state of mind. He led her to yet another door. Opening it, he again gestured inside.

  Kim looked in. It was a hopeless tangle of electronic equipment, wires, and cathode ray tubes. “Interesting,” she said.

  “You know what it is?” Edward asked.

  “I don’t think so,” Kim said. She was reluctant to let Edward know how little she knew about what he did.

  “It’s an X-ray defraction unit,” Edward said with the same degree of pride he’d evinced with the NMR unit. “It complements what we do with the NMR. We’ll be using it with the new alkaloid because the alkaloid readily crystallizes as a salt.”

  “Well, you do have your work cut out for you,” Kim said.

  “It’s work but it’s also extraordinarily stimulating,” Edward said. “Right now we’re using everything in our investigative arsenal, and the data is pouring in. We’ll have the structure in record time, especially with the new software that is available with all these instruments.”

  “Good luck,” Kim said. She’d derived only a sketchy idea o
f what Edward had explained, but she had certainly gotten a taste of his enthusiasm.

  “So what else happened up in Salem?” Edward asked suddenly. “How’s the renovation going?”

  Kim was momentarily nonplussed by Edward’s question. With his preoccupation involving his own work, she didn’t think he was currently interested in her puny project. She’d been just about to excuse herself.

  “The renovation is going well,” she said. “The house is going to be darling.”

  “You were gone quite a while,” Edward said. “Did you delve back into the Stewart family papers?”

  “I spent a couple of hours,” Kim admitted.

  “Find anything more about Elizabeth?” he asked. “I’m getting more and more interested in her myself. I feel as if I owe her an enormous debt. If it hadn’t been for her, I never would have come across this alkaloid.”

  “I did learn some things,” Kim said. She told Edward about going to the statehouse prior to driving to Salem and that there was no follow-up petition concerning the mysterious evidence. She then told him about the Northfields deed with Elizabeth’s signature, and how it had angered Thomas Putnam.

  “That might be the most significant piece of information you’ve learned so far,” Edward said. “From the little reading I’ve done, I don’t think Thomas Putnam was the right person to irritate.”

  “I had the same thought,” Kim said. “His daughter, Ann, was one of the first of the girls to be afflicted, and she accused many people of witchcraft. The problem is, I can’t relate a feud with Thomas Putnam with the conclusive evidence.”

  “Maybe these Putnam people were malicious enough to plant something,” Edward suggested.

  “That’s a thought,” Kim said. “But it doesn’t answer what it could have been. Also, if something were planted, does it make sense that it was conclusive? I still think it had to be something Elizabeth made herself.”

  “Maybe so,” Edward said. “But the only hint you have is Ronald’s petition stating it was seized from his property. I don’t think it could have been anything indubitably associated with witchcraft.”

  “Speaking of Ronald,” Kim said. “I learned something about him that’s reawakened my suspicions. He remarried only ten weeks after Elizabeth’s death. That’s an awfully short grieving period, to say the least. It makes me think he and Rebecca might have been having an affair.”

  “Perhaps,” Edward said without enthusiasm. “I still think that we have no idea how difficult life was back then. Ronald had four children to raise and a burgeoning business to run. He probably didn’t have a lot of choice. I’d bet a long grieving period was a luxury he could not afford.”

  Kim nodded, but she wasn’t sure she agreed. At the same time she wondered how much her suspicious attitude toward Ronald was influenced by her father’s behavior.

  Eleanor appeared just as abruptly as she had earlier and again enlisted Edward in a private yet animated discussion. When she left, Kim excused herself.

  “I’d better be on my way,” she said.

  “I’ll walk you out to your car,” Edward offered.

  While descending the stairs and walking across the quadrangle, Kim detected a gradual change in Edward’s demeanor. As he’d done in the past, he became noticeably more nervous. From previous experience Kim guessed he was about to say something. She didn’t try to encourage him. She’d learned it didn’t help.

  Finally when they reached her car he spoke: “I’ve been thinking a lot about your offer to come to live with you in the cottage,” he said while toying with a pebble with his toe. He paused. Kim waited impatiently, unsure what he would say. Then he blurted: “If you’re still thinking positively about it, I’d like to come.”

  “Of course I’m thinking positively,” Kim said with relief. She reached up and gave him a hug. He returned the gesture.

  “We can go up on the weekend and talk about furniture,” Edward said. “I don’t know if there is anything from my apartment you’d want to use.”

  “It’ll be fun,” Kim said.

  With some awkwardness they separated, and Kim climbed into her car. She opened the passenger-side window and Edward leaned in.

  “I’m sorry I’m so preoccupied about this alkaloid,” he said.

  “I understand,” Kim said. “I can see how excited you are. I’m impressed with your dedication.”

  After they said their goodbyes, Kim drove toward Beacon Hill feeling a lot happier than she had just a half hour earlier.

  7

  * * *

  Friday,

  July 29, 1994

  EDWARD’S excitement escalated as the week progressed. The database on the new alkaloid grew at an exponential rate. Neither he nor Eleanor slept more than four or five hours each night. Both were living in the lab for all practical purposes and working harder than they had in their lives.

  Edward insisted on doing everything himself, which meant he even reproduced Eleanor’s work in order to be one hundred percent certain of no mistakes. In like manner he had Eleanor check his results.

  As busy as Edward was with the alkaloid, he had no time for anything else. Despite Eleanor’s advice to the contrary and despite mounting rumblings from the undergraduate students, he’d given no lectures. Nor had he devoted any time to his bevy of graduate students, many of whose research projects were now stalled without his continual leadership and advice.

  Edward was unconcerned. Like an artist in a fit of creation, he was mesmerized by the new drug and oblivious to his surroundings. To his continued delight the structure of the drug was emerging atom by atom from the mists of time in which it had been secreted.

  By early Wednesday morning, in a superb feat of qualitative organic chemistry, Edward completely characterized the four-ringed structural core of the compound. By Wednesday afternoon all of the side chains were defined both in terms of their makeup and point of attachment to the core. Edward jokingly described the molecule as an apple with protruding worms.

  It was the side chains that particularly fascinated Edward. There were five of them. One was tetracyclic like the core and resembled LSD. Another had two rings and resembled a drug called scopolamine. The last three resembled the brain’s major neurotransmitters: norepinephrine, dopamine, and serotonin.

  By the wee hours of Thursday morning, Edward and Eleanor were rewarded by the image of the entire molecular structure appearing on a computer screen in virtual three-dimensional space. The achievement had been the product of new structural software, supercomputer capability, and hours of heated argument between Edward and Eleanor as each played devil’s advocate with the other.

  Hypnotized by the image, Edward and Eleanor silently watched as the supercomputer slowly rotated the molecule. It was in dazzling color, with the electron clouds represented by varying shades of cobalt blue. The carbon atoms were red, the oxygen green, and the nitrogen yellow.

  After flexing his fingers as if he were a virtuoso about to play a Beethoven sonata on a Steinway grand piano, Edward sat down at his terminal, which was on-line with the supercomputer. Calling upon all his knowledge, experience, and intuitive chemical sense, he began to work the keyboard. On the screen the image trembled and jerked while maintaining its slow rotation. Edward was operating on the molecule, chipping away at the two side chains he instinctively knew were responsible for the hallucinogenic effect: the LSD side chain and the scopolamine side chain.

  To his delight, he was able to remove all but a tiny two-carbon stump of the LSD side chain without significantly affecting either the three-dimensional structure of the compound or its distribution of electrical charges. He knew altering either of these properties would dramatically affect the drug’s bioactivity.

  With the scopolamine side chain it was a different story. Edward was able to amputate the side chain partially, leaving a sizable portion intact. When he tried to remove more, the molecule folded on itself and drastically changed its three-dimensional shape.

  After Edward had r
emoved as much of the scopolamine side chain as he dared, he downloaded the molecular data to his own lab computer. The image now wasn’t as spectacular, but was in some respects more interesting. What Edward and Eleanor were looking at now was a hypothetical new designer drug that had been formed by computer manipulation of a natural compound.

  Edward’s goal with the computer manipulations was to eliminate the drug’s hallucinogenic and antiparasympathetic side effects. The latter referred to the dry mouth, the pupillary dilation, and partial amnesia both he and Stanton had experienced.

  At that point Edward’s true forte, synthetic organic chemistry, came to bear. In a marathon effort from early Thursday to late Thursday night, Edward ingeniously figured out a process to formulate the hypothetical drug from standard, available reagents. By early Friday morning he produced a vialful of the new drug.

  “What do you think?” Edward asked Eleanor as the two of them gazed at the vial. They were both exhausted, but neither had any intention of sleeping.

  “I think you’ve accomplished an amazing feat of chemical virtuosity,” Eleanor said sincerely.

  “I wasn’t looking for a compliment,” Edward said. He yawned. “I’m interested to know what you think we should do first.”

  “I’m the conservative member of this team,” Eleanor said. “I’d say let’s get an idea of toxicity.”

  “Let’s do it,” Edward said. He heaved himself to his feet and lent Eleanor a hand. Together they went back to work.

  Empowered by their accomplishments and impatient for immediate results, they forgot scientific protocol. As they had done with the natural alkaloid, they dispensed with controlled, careful studies to get a rapid, general data to give them an idea of the drug’s potential.

  The first thing they did was add varying concentrations of the drug to various types of tissue cultures, including kidney and nerve cells. With even relatively large doses they were happy to see no effect. They put the cultures in an incubator so that they could periodically access them.