Acceptable Risk (24 page)

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 removed 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.

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.