“The little bastards are sleeping?”
Eric Hagstrom, the director of research for Upright Pharmaceuticals, Inc., walked slowly back and forth in front of the steel-meshed cages which lined the room. Scores of rats filled the cages, all the subjects of various drug studies. More than twenty different drugs were being tested at the present time although Smythe’s primary focus had been on the new drug for the past six months. This was the first time in four months, Ken Smythe thought, that his boss had bothered to come into Smythe’s laboratory and the timing couldn’t be worse. Smythe was still reeling from the disclosure made to him by his lab assistant, Lisa Bernsdorf, a few moments before the big man had unexpectedly appeared. Hagstrom looked at him through hooded eyes and Smythe felt himself cringe. He needed to maintain his composure. Hagstrom’s size and demeanor were always intimidating and the guy scared the crap out of him, particularly in light of this new information.
“Yes. They are. They were dosed six hours ago.” Smythe gestured to a row of cages. “The effect should last another four hours. Four different doses to twenty four animals each for three weeks, six days left.”.
“Anything else?” Hagstrom had stopped pacing and looked directly at Smythe.
A slight hesitation. Smythe struggled to maintain eye contact with the big man.
“Not really. The high dose animals are sleeping quite a bit longer than the others. That is to be expected.” He knew that he should mention the problem. To mention the effect of the high dose without telling Hagstrom about the problem would come back and haunt him, he knew, but he just couldn’t force himself to say anything until he had the opportunity to check it our more thoroughly.
Hagstrom broke eye contact, looked around.
“What about the other studies?”
Smythe nodded toward his research assistant, Lisa Bernsdorf, who was weighing an animal at the instrument table in the middle of the room. She acted as though she wasn’t paying attention, but Smythe knew she was listening to every word.
“We’re right on schedule.”
“Keep it that way.” Hagstrom stared directly at him again and Smythe felt the air on his arms stand up. He watched the large man walk out of the lab, then turned to Bernsdorf.
“You missed your chance.”
“I know.” Smythe looked over at his diminutive assistant whose short dark hair framed her face in sharp contrast to the rest of the room. Everything else was white; cages, floor, walls, ceiling, lab costs, scrubs, shores, everything except for the color of her hair, he thought.“You’re pale as a ghost,” Bernsdorf said. She smiled demurely. “I’m glad I don’t have to tell him. He scares me.”
Smythe looked at her. He scares me too, he thought. He was afraid. It wasn’t just Hagstrom, but Hagstrom’s boss, Cyrus Messner. What if this information killed the drug? The company needed this drug. He didn’t want to be the bad guy whose research ended the promise of a blockbuster drug. Messner had made the point loud and clear. Upright needed this drug badly.
The problem was that the drug did have problems. If what Bernsdorf had discovered was correct, the drug was dead. It could never be given to humans. The problem was how to break the news.
“Any further thoughts?”
“My guess is that it’s dose-related. It only happens at the highest dose and I can’t think of any other reason.”
“Let’s go take a look.”
They walked to the back of the lab and entered a small room where more cages were stored. Smythe turned on the light.
“That one is running his ass off. Look at him go.” Smythe gestured toward one of the cages where a large rat scurried rapidly on the wheel inside the cage.
“At lower doses we don’t see this.”
“How long has this one been doing this?”
“Four hours now. Last dose was yesterday at noon. It slept for sixteen hours. When it woke up, it started running.” She paused to chew on a cuticle. “Hasn’t stopped since. It’ll run until it dies. If I put another animal into its cage, it’ll fight it to death.”
Smythe shivered. “Tell me again how you came up with this.”
She grimaced. “I made a mistake. I missed sacrificing one of the animals in an earlier group. Found it running just like this one the next day.” She nodded toward the animal in the cage.
“It’s peculiar that it happens only after the drug is stopped.”
Lisa looked miserable. She stared down at her feet.
“The research protocol didn’t call for observation after dosing was stopped. As you know, I sacrificed the rest of the animals on the day dosing ended. There was no way we could have known this if I hadn’t made the mistake.”
“What’s done is done.” Smythe forced himself to smile at her. Hagstrom was going to be angry. There was going to be hell to pay for this.
“Better to know now before the drug is given to humans.”
“Maybe it’s unrelated to the drug.”
“That’s what I thought at first. Four animals, including this one, have done the same thing and only on the highest dose.”
“We’ll have to finish this up and report our findings. We want to be able to explain what happened and understand it better before we write the report.”
Smythe shivered again. Why did this have to happen now? The high dose was scheduled to be given to prisoners at Jackson Prison. He couldn’t tell Bernsdorf about that because the project was shrouded in secrecy. He needed to tell Hagstrom or Messner right away, but first he needed to think.
“Have you kept accurate records?”
“Of course. I keep records on everything I do. You know that.” She looked offended.
“Let me see your notebook.”
Smythe pored over her results. Everything was right there. Totally unexpected. There must be some explanation. He spent the rest of the afternoon surfing the internet for related research. Nothing. This was always a problem with research conducted in-house by the drug industry. No one, he thought, ever published their failures. No one ever published the results of research that might show a problem. Only the good results got published. There was no way of knowing whether anyone else had seen these results in this class of drugs.
He stood and stretched, walked over the window and stared out for a long time. The last thing he wanted was about to happen; he would be the jerk in research who pulled the plug on a promising new drug that was destined to bring a pharmaceutical giant back from the brink of bankruptcy. How could a drug that was supposed to cause sleep drive these animals into a sleepless frenzy? It didn’t make sense. More importantly, he thought, what would have happened if this drug had been marketed and used by thousands of human beings?
He thought back to the meeting when he’d first heard about this new drug and remembered how excited and proud he’d been about being taken into the inner circle of drug development. He walked back to his desk and looked at the results again, rubbed his chin with the back of his hand. He thought about the dying animals. They were certainly not what was expected, he thought. There must be an explanation. He needed to check the calculations again. He pulled out a notepad and wrote the basic information down for the third time. Thirty minutes later, he scratched his head. The results were the same. There was no getting around the fact that something was wrong. It was bite the bullet time, he thought. No sense in putting it off any longer. The project was already four weeks behind schedule. He picked up the phone and dialed.
“Hagstrom.” The rough voice on the other end of the line startled Smythe.
“Can you come back down to the lab for a minute? We need to talk.”
“Why don’t you come to my office?”
“I think its better if we speak down here. There are some things you might want to see.”
He stood and stretched. He needed to think about this while he waited for the Whale. He closed his eyes, tried to put the results of Bernsdorf’s findings into perspective. He located the cages of the most recent animals and watched them for a minute. They looked haggard and had neglected their grooming. He grimaced to himself. Their agitation was palpable.
“What happened to those animals?”
The Whale had approached so quietly that Smythe hadn’t heard him. He jumped at the sound of the other man’s voice.
“That’s what we need to talk about.”
Fifteen minutes later, Smythe completed the entire story. He felt cold and clammy. Hagstrom had looked at him throughout the presentation through those hooded eyes without comment.
“Maybe it’s a paradoxical effect. Like cats receiving morphine. Makes them agitated. Just the opposite effect as on humans."
The Whale looked at him. Smythe felt like the man was staring right through him.
“We certainly don’t want to do anything that would hurt this project.”
One thing about Hagstrom. You sure as hell couldn’t tell what he was thinking, whether he was joking or not, just by looking at him. Better keep his mouth shut. If the company was hell bent on putting this drug on the market, they were going to do it whether he complained about it or not. Besides, Smythe thought, the paradoxical reaction was a possible explanation. There were many examples of animals reacting differently to the same drug than effects which were seen in the human being.
“My suggestion,” Hagstrom said, “is to just forget about these studies. No conclusions. No summaries. Just put the raw data in the new drug submission to the FDA and see if they’re smart enough to figure it out.” He looked at Smythe again and continued. “If we make too much of this paradoxical effect, some mid-level bureaucrat at the FDA who’s never spent one day in the real world will kill this drug. Can’t let that happen, can we?”
Smythe nodded. He knew that there was only one answer to the pending question.
Hagstrom watched him. “Got any problem with this? Let me know right now and we’ll deal with it. If not, let’s move on to something important.”
Smythe swallowed. He felt like a deer caught in the headlamps of an onrushing car. He blinked. “The remaining studies should be finished next week.”
* * *
The Whale met with Messner that evening after work. Their favorite meeting place was a tavern, the Blue Goose, across town from Upright’s facilities. The out-of-the-way location afforded more privacy and lessened the chance of being spotted by other Upright personnel. The Whale relayed the conversation with Smythe to Messner who sat quietly until the big man finished.
“Paradoxical effect. That’s good. You’re a con man. You should be working in a carnival selling ring tosses three for a dollar, beating kids out of their allowances.”
The Whale’s facial expression never changed
“A man does what he has to do.”
The Whale looked down at his empty glass. Messner nodded toward it.
“Ready for another?”
“Sure. When the company’s paying, I’m drinking.”
Messner waved the waitress over and placed the order. In less than thirty minutes, the Whale had inhaled three double scotches. Messner sipped his glass of white wine.
“So what are we going to do about Smythe and his study? Paradoxical effect or not, it could mean trouble if Smythe talks about it.”
“We need to deal with him This is how we do it.”
The Whale laid out his plan and Messner sat and listened. It sounded good. They would put Smythe in charge of the submission of the new drug application to the Food and Drug Administration. To do so, Smythe wold have to put the very best spin on all of the studies, including his own. Making him the point man for the drug would neutralize him and his concerns about danger.
“You think it’ll work?”
“I’ll make it work.”“It’s risky. What are you going to do if Smythe doesn’t go along with it?”
“Do you think that you should know?”