Acceptable Risk

by Robin Cook

  Next they prepared a ganglion preparation from Aplasia fasciata by inserting tiny electrodes into spontaneously firing nerve cells. Connecting the electrodes to an amplifier, they created an image of the cells’ activity on a cathode ray tube. Slowly they added their drug to the perfusing fluid. By watching the neuronal responses, they determined that the drug was indeed bioactive although it didn’t depress or increase the spontaneous activity. Instead the drug appeared to stabilize the rhythm.

  With mounting excitement, since everything they did yielded positive results, Eleanor began feeding the new drug to a new batch of stressed rats while Edward added the new drug to a fresh synaptosome preparation. Eleanor was the first to get results. She was quickly convinced the modified drug had even more calming effect on the rats than the unaltered alkaloid.

  It took Edward a little longer to get his results. He found that the new drug affected the levels of all three neurotransmitters, but not equally. Serotonin was affected more than norepinephrine, which was affected more than dopamine. What he didn’t expect was that the drug seemed to form a loose covalent bond with both glutamate and gamma-aminobutyric acid, two of the major inhibitory agents in the brain.

  “This is all fantastic!” Edward exclaimed. He picked up the papers from his desk that recorded all their findings and allowed them to rain down like massive sheets of confetti. “This data suggests that the potential of the drug is monumental. I’m willing to bet it’s both an antidepressant and an anxiolytic, and as such it could revolutionize the field of psychopharmacology. It might even eventually be compared with the discovery of penicillin.”

  “We still have the worry about it being hallucinogenic,” Eleanor said.

  “I sincerely doubt it,” Edward said. “Not after removing that LSD-like side chain. But I agree we have to be sure.”

  “Let’s check the tissue cultures,” Eleanor said. She knew Edward would want to take the drug. It was the only way to determine if it was hallucinogenic.

  They retrieved their tissue cultures from the incubator and examined them under a low-power microscope. One after another they appeared healthy. There was no sign of cellular damage from the new drug, even those subjected to high doses.

  “There doesn’t seem to be any toxicity at all,” Edward said with glee.

  “I wouldn’t have believed it if I hadn’t seen it,” Eleanor said.

  They went back to Edward’s bench area and made up several solutions of increasing strength. The starting point was a concentration that yielded a dose approximating the dosage of the unmodified alkaloid that Stanton had received. Edward was the first to try it, and when nothing happened, Eleanor took it. Again nothing happened.

  Encouraged by these negative results, Edward and Eleanor gradually increased their dosages up to a full milligram, knowing that LSD was psychedelic at 0.05 milligrams.

  “Well?” Edward questioned a half hour later.

  “No hallucinogenic effect as far as I can tell,” Eleanor said.

  “But there is an effect,” Edward said.

  “Most definitely,” Eleanor said. “I’d have to describe it as calm contentment. Whatever it is, I like it.”

  “I also feel as if my mind is particularly sharp,” Edward said. “It has to be drug-related because twenty minutes ago I was a basket case, thinking my ability to concentrate was nil. Now I’m energized as if I’d had a night’s rest.”

  “I have a sense my long-term memory has been awakened from a slumber,” Eleanor said. “Suddenly I remember my home phone number when I was a child of six. It was the year my family moved to the West Coast.”

  “What about your senses?” Edward asked. “Mine seem particularly acute, especially my sense of smell.”

  “I wouldn’t have thought of it until you mentioned it,” Eleanor said. She put her head back and sniffed the air. “I never realized the lab was such a cacophony of odors.”

  “There’s something else I’m feeling that I wouldn’t have even been sensitive to if I hadn’t taken a course of Prozac,” Edward said. “I feel socially assertive, like I could walk into a group of people and do whatever I wanted. The difference is that it took three months of Prozac before I felt that way.”

  “I can’t say I feel anything like that,” Eleanor said. “But I can say my mouth is a little dry. Is yours?”

  “Perhaps,” Edward admitted. Then he looked directly into Eleanor’s deep blue eyes. “Your pupils also might be a bit dilated. If they are, it must be the scopolamine side chain we couldn’t totally eliminate. Check your near vision.”

  Eleanor picked up a reagent bottle and read the tiny print on the label. “No problem,” she said.

  “Anything else?” Edward said. “Any trouble with your circulation or breathing?”

  “Everything is fine,” Eleanor said.

  “Excuse me,” a voice called.

  Eleanor and Edward turned to see one of the second-year doctorate students had approached them. “I need some help,” she said. Her name was Nadine Foch. She was from Paris. “The NMR is not functioning.”

  “Perhaps it would be best to talk to Ralph,” Edward said. He smiled warmly. “I’d like to help, but I’m rather involved at the moment. Besides, Ralph knows the machine better than I, particularly from a technical point of view.”

  Nadine thanked them and went to find Ralph.

  “That was rather civil of you,” Eleanor said.

  “I feel rather civil,” Edward said. “Besides, she’s a nice person.”

  “Perhaps this is a good time for you to resume your normal activities,” Eleanor said. “We’ve made fantastic progress.”

  “It’s only a harbinger of what’s to come,” Edward said. “It’s good of you to worry about my teaching and supervisory responsibilities, but I assure you that they can slide for several weeks without causing anybody irreparable damage. I’m not about to forfeit any of this excitement with this new drug. Meanwhile I want you to start computerized molecular modeling to create a family of compounds from our new drug by substituting side chains.”

  While Eleanor went off to work at her computer terminal, Edward walked back to his desk and picked up the phone. He called Stanton Lewis.

  “Are you busy tonight?” Edward asked his old friend.

  “I’m busy every night,” Stanton said. “What’s on your mind? Did you read that prospectus?”

  “How about having dinner with me and Kim?” Edward said. “There’s something you should know.”

  “Ah ha, you old rogue,” Stanton said. “Is this going to be some sort of a major social announcement?”

  “I believe I’d rather discuss it in person,” Edward said smoothly. “What about dinner? It will be my treat!”

  “This is sounding serious,” Stanton said. “I have a dinner reservation at Anago Bistro on Main Street in Cambridge. The reservation is for two, but I’ll see that it gets changed to four. It’s for eight P.M. I’ll call back if there is a problem.”

  “That’s perfect,” Edward said. Then he hung up before Stanton could ask any more questions. Edward dialed Kim at work in the SICU.

  “Busy?” he asked when Kim came on the line.

  “Don’t ask,” Kim said.

  “I made dinner plans with Stanton and his wife,” Edward said excitedly. “It will be at eight unless I hear back from Stanton. I’m sorry it’s such short notice. I hope it’s OK for you.”

  “You’re not working tonight?” Kim asked with surprise.

  “I’m taking the evening off,” Edward said.

  “What about tomorrow?” Kim asked. “Are we still going up to Salem?”

  “We’ll talk about it,” Edward said noncommittally. “What about dinner?”

  “I’d rather eat just with you,” Kim said.

  “You’re sweet to say that,” Edward said. “And I’d rather eat just with you. But I have to talk with Stanton, and I thought we could make a little party out of it. I know I haven’t been so much fun this week.”

 
“You sound buoyant,” Kim said. “Did something good happen today?”

  “It’s all been good,” Edward said. “And that’s why this meeting is important. After the dinner just you and I can spend some time together. We’ll take a walk in the square like we did the evening we first met. How about it?”

  “You’ve got a date,” Kim said.

  Kim and Edward arrived at the restaurant first, and the hostess, who was also one of the owners, sat them at a cozy table wedged into a nook next to the window. The view was out over a portion of Main Street with its collection of pizza joints and Indian restaurants. A fire truck sped by with all its bells and sirens screaming.

  “I’d swear the Cambridge fire company uses their equipment to go for coffee,” Edward said. He laughed as he watched the truck recede. “They’re always out riding around. There can’t be that many fires.”

  Kim eyed Edward. He was in a rare mood. Kim had never seen him so talkative and jovial, and although he looked tired, he was acting as if he’d just had several espressos. He even ordered a bottle of wine.

  “I thought you told me you always let Stanton order the wine,” Kim said.

  Before Edward could answer, Stanton arrived, and true to character breezed into the restaurant as if he were an owner. He kissed the hostess’s hand, which the hostess endured with thinly disguised impatience.

  “OK, you guys,” Stanton said to Edward and Kim as he tried to help Candice into her chair. The table was narrow, and each couple had to sit side-by-side. “What’s the big news between you two? Do I have to pop for a bottle of Dom Pérignon?”

  Kim looked at Edward for some explanation.

  “I’ve already ordered some wine,” Edward said. “It will do nicely.”

  “You ordered wine?” Stanton questioned. “But they don’t serve Ripple here.” Stanton laughed heartily as he sat down.

  “I ordered an Italian white,” Edward said. “A cool dry wine goes nicely with hot summer weather.”

  Kim lifted her eyebrows. This was a side of Edward she’d not seen.

  “So what is it?” Stanton said. He eagerly leaned forward with his elbows on the table. “Are you two getting married?”

  Kim blushed. With some embarrassment she wondered if Edward had told Stanton about their plans to share the cottage. It wasn’t a secret as far as she was concerned, but she would have liked to tell her family herself.

  “I should be so lucky,” Edward said with a laugh of his own. “I’ve got some news—but it’s not that good.”

  Kim blinked and looked at Edward. She was impressed he dealt so adroitly with Stanton’s inappropriate comment.

  The waitress arrived with the wine. Stanton made a production of examining the label before allowing it to be opened. “I’m surprised, old boy,” he said to Edward. “Not a bad choice.”

  Once the wine was poured, Stanton started to make a toast, but Edward quieted him.

  “It’s my turn,” Edward said. He held out his glass toward Stanton. “To the world’s cleverest medical venture capitalist,” he said.

  “And I thought you never noticed,” Stanton said with a laugh. Then they all took a drink.

  “I have a question for you,” Edward said to Stanton. “Were you serious when you said recently that a new, effective psychotropic drug could potentially be a billion-dollar molecule?”

  “Absolutely,” Stanton said. His demeanor instantly became more serious. “Is this why we’re here? Do you have some new information about the drug that sent me on my psychedelic trip?”

  Both Candice and Kim questioned what psychedelic trip Stanton was referring to. When they heard what had happened they were appalled.

  “It wasn’t half bad,” Stanton said. “I rather enjoyed it.”

  “I’ve got a lot of information,” Edward said. “All of it is superlative. We eliminated the hallucinogenic effect by altering the molecule. Now I think we have created the next-generation drug to the likes of Prozac and Xanax. It seems to be perfect. It’s nontoxic, effective orally, has fewer side effects and probably a broader therapeutic capability. In fact, because of its unique side chain structure capable of alteration and substitution, it might have unlimited therapeutic capability in the psychotropic arena.”

  “Be more specific,” Stanton said. “What do you think this drug can do?”

  “We believe it will have a general, positive impact on mood,” Edward said. “It seems to be antidepressant and anxiolytic, meaning it lowers anxiety. It also seems to function as a general tonic to combat fatigue, increase contentment, sharpen the senses, and encourage clear thinking by enhancing long-term memory.”

  “My God!” Stanton exclaimed. “What doesn’t it do? It sounds like Soma from Brave New World.”

  “That analogy might have merit,” Edward said.

  “One question,” Stanton said. He lowered his voice and leaned forward. “Will it make sex better?”

  Edward shrugged. “It might,” he said. “Since it enhances the senses, sex could be more intense.”

  Stanton threw up his hands. “Hell,” he said. “We’re not talking about a billion-dollar molecule; we’re talking about a five-billion-dollar molecule.”

  “Are you serious?” Edward asked.

  “Let’s say a billion plus,” Stanton said.

  The waitress interrupted their conversation. They ordered their dinners. After she’d left, Edward was the first to speak. “We haven’t proven any of this,” he said. “There’s been no controlled experiments.”

  “But you’re pretty confident,” Stanton said.

  “Very confident,” Edward said.

  “Who knows about this?” Stanton asked.

  “Only me, my closest assistant, and the people at this table,” Edward said.

  “Do you have any idea how the drug works?” Stanton asked.

  “Only a vague hypothesis,” Edward said. “The drug seems to stabilize the concentrations of the brain’s major neurotransmitters and in that way works on a multilevel basis. It affects individual neurons but also whole networks of cells as if it were an autocoid or brain hormone.”

  “Where did it come from?” Candice asked.

  Edward summarized the story by explaining the association between Kim’s forebear, the Salem witch trials, and the theory the accusers in Salem had been poisoned by a mold.

  “It was Kim’s question whether the poison theory could be proved which got me to take some samples of dirt,” Edward said.

  “I don’t deserve any credit,” Kim said.

  “But you do,” Edward said. “You and Elizabeth.”

  “Such irony,” Candice said. “Finding a useful drug in a dirt sample.”

  “Not really,” Edward said. “Many important drugs have been found in dirt like cephalosporins or cyclosporine. In this case the irony is the drug is coming from the devil.”

  “Don’t say that,” Kim said. “It gives me the creeps.”

  Edward laughed teasingly. He hooked his thumb at Kim and told the others that she was wont to have occasional attacks of superstition.

  “I don’t think I like the association either,” Stanton said. “I’d rather consider it a drug from heaven.”

  “The association with the witch frenzy doesn’t bother me at all,” Edward said. “In fact I like it. Although finding this drug can’t justify the death of twenty people, at least it might give their sacrifice some meaning.”

  “Twenty-one deaths,” Kim corrected. She explained to the others that Elizabeth’s execution had been overlooked by the historians.

  “I wouldn’t care if the drug were related to the biblical flood,” Stanton said. “It sounds like an extraordinary discovery.” Then, looking at Edward, he asked, “What are you going to do?”

  “That’s why I wanted to see you,” Edward said. “What do you think I should do?”

  “Exactly what I already told you,” Stanton said. “We should form a company and patent the drug and as many clones as possible.”

  “Y
ou really think this could be a billion-dollar situation?” Edward asked.

  “I know what I’m talking about,” Stanton said. “This is my area of expertise.”

  “Then let’s do it,” Edward said. “Let’s form a company and go for it.”

  Stanton stared into Edward’s face for a beat. “I think you are serious,” he said.

  “You bet I’m serious,” Edward said.

  “All right, first we need some names,” Stanton said. He took out a small notebook and pen from his jacket pocket. “We need a name for the drug and a name for the company itself. Maybe we should call the drug Soma for the literary set.”

  “There’s already a drug called Soma,” Edward said. “How about Omni, in keeping with its potentially wide range of clinical applications?”

  “Omni just doesn’t sound like a drug,” Stanton said. “In fact it sounds more like a company. We could call it Omni Pharmaceuticals.”

  “I like it,” Edward said.

  “How about ‘Ultra’ for the drug,” Stanton said. “I can see that working well for advertising.”

  “Sounds good,” Edward said.

  The men looked at the women for their reaction. Candice hadn’t been listening, so Stanton had to repeat the names. After he did she said they were fine. Kim had been listening, but she didn’t have an opinion; she was a bit taken aback by the discussion. Edward had shown no awkwardness in this sudden and unexpected interest in business.

  “How much money can you raise?” Edward asked.

  “How long would you estimate it would take before you were ready to market this new drug?” Stanton asked.

  “I don’t think I can answer that question,” Edward said. “Obviously I can’t even be one hundred percent sure it will ever be marketable.”

  “I know that,” Stanton said. “I’m just looking for a best-guess estimate. I know that the average duration from discovery of a potential drug to its FDA approval and marketing is about twelve years, and the average cost is somewhere around two hundred million dollars.”

  “I wouldn’t need twelve years,” Edward said. “And I wouldn’t need anywhere near two hundred million dollars to do it.”

  “Obviously the shorter the development time and the less money needed means more equity we can keep for ourselves.”