Knockout Mouse Read online

  I responded with my own smile. I wanted to hear what Doug was about to say before McKinnon came in, but I had a feeling he was not going to unglue his eyes from that folder anytime soon. Not while McKinnon was here. I took my next best opportunity. “Dr. McKinnon, do you have a minute? I’d like to talk to you about Sheila Harros.”

  “Ah, now I remember. You visited us last week.” He shook his head. “I am so sorry about Sheila. What a loss. I’m—”

  The old beg-off was coming, I could tell. I didn’t give him the chance. “Her death was not an accident. People here at LifeScience were involved.”

  McKinnon straightened. His hands moved up, started to slide into his pockets, then stopped. “That’s a serious statement.”

  “It is. I’d like to speak to you.”

  He nodded toward the door. “We’ll go to my office.”

  We both turned at the sudden clatter of a chair. Doug was on his feet, coming around his desk. McKinnon gave me a small push out of the room, then positioned himself in the doorway. “Don’t stop your work, Doug. I can handle this.”

  25

  Frederick McKinnon’s office was a different story than Doug Englehart’s. It was in a tower attached to the annex, at the fulcrum of the company’s three departments. Windows looked east over the bay, now green under the shadows of clouds, and west over the mottled landscape of Palo Alto. The bookcases were built into the walls, their contents stacked neatly. A pair of couches faced each other over a glass coffee table, which was arrayed with scientific journals. The rear of the office was dominated by McKinnon’s walnut desk, nearly empty of clutter. A single folder was open next to a slim black laptop in front of his Herman Miller desk chair.

  I took a seat in one of the cushioned chairs facing the desk. McKinnon closed the folder and punched up a double-helix screensaver on the computer display. On our walk over, he’d asked for the background on my connection to Sheila. He asked intelligent questions and drew out various details about my film work. His voice was genial and refined, his gait loping, quite a contrast to Doug. Doug was a driven lab rat who didn’t have much of a life away from the bench. McKinnon, on the other hand, had the air of a man of the world. The wave in his hair, angled rakishly across his forehead, reminded me of a hero from a British movie, an RAF pilot perhaps. While Doug was perpetually distracted, McKinnon listened with what seemed his full attention. He gave the impression of being utterly concerned about you and your words—a technique, I knew, that certain executives cultivated. It worked nonetheless.

  Once we were seated, though, the casual chat was over. His sky-blue eyes lasered in on me. “Now tell me. What do you have to link LifeScience to Sheila’s death?”

  “She found a problem with MC124. The dead knockout mouse. Someone here was very upset about that. They wanted to make sure it didn’t get out.”

  McKinnon sat back and gazed out the window, wondering perhaps how I knew about the mouse. Whatever he decided, he didn’t let me in on it.

  “Yes, the mouse,” he said smoothly. “It concerned Sheila. I took it quite seriously myself. She had an intuitive feel for the work. I had such hopes—” He caught himself, then turned back to me. “We did a careful investigation. MC124 has no significant problems.”

  “I have some notes from her that say otherwise.” This was a stretch, but I wanted to gauge how close my theory was to being right. “These reactions are so complex—isn’t it possible something unexpected happened?”

  McKinnon leaned forward and folded his hands on the desk. “The unexpected is more than possible, it’s inevitable. This is what makes the field so challenging. I feel a personal responsibility to detect potential danger. We have only the beginning of a grasp on these processes. When you alter one pathway, you can alter many others down the line. We don’t always know what produces a reaction. You have to study the effects minutely, in vitro, in silico, in vivo.”

  He tapped his manicured fingers on the desk. “I’ve been working with monoclonal antibodies for fifteen years. The first time around, the subjects’ immune systems attacked the chimeric hybridomas as invaders. Monoclonals went out of favor, but I knew that with ingenuity they could succeed. Now, at last, we understand the role of the constant region more clearly, and we can be far more exact with the antigen-binding regions. MC124 is 90 percent humanized. It took some hard work to develop the framework and many versions of the antibody—124 to be exact—to get it right.”

  “And you’re sure that it is right?”

  McKinnon’s eyes blazed into me. “No one has more depth in this field than myself. Myself and Doug. We’ve reviewed every result. Who could have more incentive to insure its safety than me? I’ve staked my career on it.”

  “You really can’t afford to have a mistake uncovered, then.”

  “True.” He indulged a smile. “Does that turn me into the prime suspect?”

  He was so smooth. He’d managed to disarm my thrust with a combination of honesty and style, even make it look a bit silly. My eyes strayed to the art on his walls. None of the usual suspects, meant to assure the executive of his taste, but mixed media tableaux that turned the letters and icons of genetics into children’s building blocks. His willingness to install such an ironic twist on biomedical symbols showed McKinnon had confidence in his choices. And in his style. Silicon Valley’s climate was Mediterranean, and his dress was calibrated to it—rather than to the power suit mode of the East Coast or the slick casualness of Hollywood. Accessible, jaunty, but still elegant and in charge.

  I dodged his question and said, “I appreciate your answering so fully.”

  He waved it off. “I’m not giving away any company secrets. We’re about to publish our paper on it.”

  “You sound very confident.”

  He inhaled deeply, arching his brows. “Frankly, yes. I have been injecting myself with the drug to test for safety.” He smiled and exhaled. “So you see, I have reason for confidence.”

  “And you’re going to have the rest of your team try it next? Doesn’t that violate some code of ethics?”

  I finally broke the surface of his cool. He blinked a couple of times. “Only if they withhold assent. But they haven’t. Now,” he added with a trace of impatience, “you mentioned notes of Sheila’s. You’ll need to give them to me immediately. We can make revisions to the paper if necessary.”

  “Neil Dugan must have given you the hard drive from her home computer already.”

  Now he was flustered. “Neil—? I don’t know a thing about this.”

  “He took the hard drive just after Sheila was found. He’s been trying his damnedest to get more documents from me. His private detectives have assaulted me twice.”

  “Dugan, dammit. He’s out of control. He—” McKinnon stopped and glared at me. “I can’t vouch for anything Neil Dugan does. Sometimes I wonder if we even work for the same company. If you think Dugan is somehow involved with Sheila’s death, come out with it. I want to know. I’ll examine those documents, and we’ll take any evidence you have to the police.”

  “Thank you for cooperating. I’ll be in touch with you.”

  The blue eyes hardened again. “Now look, you can’t come in here and lay down these accusations and then just walk away. I need to see those materials. We need to take action.”

  “I agree,” I said in my most polite voice. I wanted to remain on good terms with him, but I didn’t want him to take over. “I don’t have the materials here. Others have some of them. I’ll pull them all together.”

  McKinnon relinquished as gracefully as he could. “Quickly, please, unless you’d like a visit from the police. Time is of the essence.”

  “One other thing—why did you transfer Sheila out of the group?”

  McKinnon collapsed back into his chair. “She requested it herself. Terribly disappointing to me. I never fully understood her reasons. Something personal, perhaps. She was a bit troubled, I think—not by our work, but in her emotions.”

  “Did she te
st out MC124 on herself?”

  McKinnon stared out the window for a long moment. “I suppose she could have.”

  “Thanks for talking to me.” As I stood, the DAT recorder clicked off. I covered it with a cough. McKinnon gave me a long, hard look. I switched to a new subject. “Oh, I also meant to ask you about Carl Steiner.”

  McKinnon stood with me. “Steiner? The gardener?”

  “Yes. He was at the funeral. Had an attachment to Sheila.”

  “Ah… he tends to do that. I didn’t realize Sheila was his latest object. Well, he works in the agri department, you know. That part of the company was acquired by the new management. I can’t tell you much about it.”

  “All right. Thanks again. I can find my own way out.”

  “I’m sorry, I’ll need to accompany you.” He touched my arm and moved me toward the door.

  “Oh, you know what—I left my bag back in Doug’s office. He can show me out.”

  McKinnon simply smiled and waited for me to walk with him down a floor to Doug’s office and the lab. Just outside the office, Doug and two white-coated researchers were engaged in a heated conversation over a series of printouts. McKinnon got drawn into the discussion. I sauntered over to Doug’s office, paused by the door, and waited for Doug to glance my way. When he did, I very deliberately closed the door.

  It burst open a few moments later. “What the—?” Doug demanded.

  “Close the door,” I said in a low voice. “Don’t you want to hear what Dr. McKinnon said to me?”

  His shoulders relaxed. It was clear he did. My hypothesis was correct. Some kind of fissure had opened up between mentor and protégé, and I intended to exploit it. If Doug believed I was on his side, he might cough up some new information.

  “Just a minute,” Doug said. He went back to the group, leaving the door ajar. I sat on the couch, out of sight of the scientists. I couldn’t follow their discussion, so I poked into a stack of papers next to me on the couch. On top was a book about golf, but underneath were reprints of technical papers. The words that appeared most often in the titles were phage display and Escherichia coli.

  The sound of my name brought my attention back. It was McKinnon, asking Doug where I was and telling him I needed to be escorted from the building.

  “I’ll do it, Frederick,” Doug said. “I want to speak to him again. The biocomputation matter.”

  “That’s not our priority, Doug. The Curaris Pharmaceutical people arrive at ten on Monday morning. This is it for us. Once they sign the licensing deal, Dugan has no choice. But everything must—”

  “I’m on it, Frederick.” Doug’s voice was curt. “Please, just leave me to do my work.”

  Even from my position on the couch, I could feel the tension. All conversation had ceased. I pictured the two men glaring at each other, McKinnon towering erect and imperious, Doug bristling below.

  Doug came into the office a moment later. He closed the door, then paced the small area in front of his desk.

  “You need a bigger office,” I said.

  He froze and stared me. “I’m getting one.”

  “Once MC124 is a success?”

  “Very soon.”

  “I imagine that will put you on more equal footing with Dr. McKinnon. You two have been very close, haven’t you?”

  He turned away and began to straighten papers. “I was his grad student. It’s long past time for me to have a program of my own.”

  “Will you still be working with monoclonal antibodies?”

  He spun on me. “What do you care? Just tell me what Frederick said to you!”

  “He said he’s tested MC124 on himself to prove its safety. I thought that was noble of him.”

  Doug stretched his neck and scratched. He had some kind of rash under his jowl. “I’ve tested it, too, but I don’t go around bragging about it.”

  “Did Sheila?”

  “Maybe Frederick tricked her into it,” he said after a pause. “Did Neil Dugan know about this?”

  Doug shook his head slowly. “No one did. You shouldn’t either. What do you want, anyway?”

  “I just want to know what killed Sheila.”

  His forehead bunched again. “All right. I’ll see what I can find out. I’ll check up on Dugan. But not until after Monday.”

  “Anything helps. I have some notes from Sheila—”

  His eyes widened and the phone buzzed at the same instant. Doug picked it up. “Yeah, I talked to him. No, he’s not here. Yeah, I know what he looks like.”

  He put down the phone. “Dugan. He’s looking for you.”

  I stood up. Doug appraised me for a minute, then said, “Go back down the corridor to the center of the building. Past the elevators, into the wing opposite this one. Turn right. Look for a stairway. It’ll take you down to the atrium. Turn left and go out the door in the back. A guard will be watching for you at the front.”

  “Thanks. Do you have a cell phone?”

  He scribbled the number on the back of his card. I took it and took off. The stairway was where he said it would be. I went down the stairs and opened the door into the atrium very slowly. The guard, near the reception desk, was looking the other way. I slid out and walked quickly toward the back exit. The guard called to me as I got to the door. I picked up my pace.

  The door led onto a patio bordered by a line of raised flower beds. I stepped around them and broke into a run. I had to turn right to get around the annex, the agri division, which stood between me and my car. As I came around the blind corner, I nearly ran straight into a high wire fence around a garden tall with corn. I cut left into the parking lot and got in the Scout. As I was backing up, I saw the guard huffing his way around the building. By the time he yelled at me to stop, I was already pulling away.

  26

  Karen answered the door in shorts and a red T-shirt. She was hiding out at her friend’s condo in Redwood City, about five miles north of Palo Alto. Yesterday, she and a posse of friends had managed to rescue her car from Gregory’s lot and to retrieve Sheila’s leather bag from Karen’s apartment. I thought it was a good idea for her to stay put for a while. I was more concerned than ever that Dugan and Pratt were hunting for her, and I’d watched to make sure no one was following me as I drove over. Scrutinizing my rearview mirror had become second nature lately.

  The condo’s owner had gone out for the day. On a table in a nook of the kitchen, Karen had spread what Sheila had given her: notebooks, disks, and printouts. I’d brought the diary and the zip disks from their hiding place in the Scout. We sat next to the humming refrigerator. Karen plunked some leftover Chinese food and a Coke in front of me and said, “So what did you get?”

  I told her about my visit to LifeScience. “McKinnon had a strong case for MC124 being safe. Both he and Doug Englehart tested it on themselves. The autopsy said Sheila had needle puncture marks in her arm. Doug as much as admitted she’d been dosed too.”

  Karen shook her head in disapproval. “She should’ve told me about it. Then again, she knew what I’d say. I would have chewed her out. She might have felt like she had no choice but to test it.”

  “To keep her job?”

  “To keep McKinnon’s respect. To show her loyalty to the team. There’s an intense togetherness on a project like that. Sheila cared so much about being part of it. She cared what McKinnon thought of her.”

  “Well, her injecting it cuts both ways,” I said. “On the one hand, I want to look even harder at MC124. On the other, the fact that her two superiors have tried it and are fine so far means it’s a less likely cause of her death.”

  Karen stopped with a string of noodles in front of her mouth. “Wait a minute. What does this remind you of?”

  “Someone about to make a big slurping sound?”

  Karen went ahead and slurped. “It reminds you of the knockout mouse. One died. The others that we know of are fine.”

  “Right. The question is, what is it that got that one?”

  We sat
for a minute, pondering the mouse. The only insight that came to me was that it was time for lunch. I shoveled some food onto a plate, then managed to spray soy from a little packet onto a printout.

  “Try to control yourself,” Karen said in a dry voice.

  “It’s a boy thing,” I said. Then a small pang hit me as I recalled my dinner conversation with Sheila.

  “Are you all right?”

  I shook it off. “Tell me what you’ve learned about this mouse.”

  “I’ve combed through Sheila’s research. MC124 was being tested on three populations. One was mice with tumors. Another was mice without tumors, a control group. A third was a population with and without tumors that was receiving high doses of MC124. The focus in that group was toxicity. Our knockout mouse was in the third group. Sheila named her Smidge because she had just a smidgen of white on her back foot. The necropsy showed the mouse was strangled by her own immune system. Doug declared that she’d simply been overdosed or had a reaction to some other antigen. It didn’t matter which, because it was an anomaly: no other mice died. Sheila wondered if the problem had more to do with the bit of white on the foot.”

  “What does the foot have to do with it?”

  “Very little, of course, except that the white was a marker. It designated a mouse population that was humanized. Smidge had a number of mouse immune genes knocked out and human ones knocked in. Sheila conjectured that a technician put Smidge in the wrong cage because the white mark on her foot was so small. You could easily miss it.”

  “How sure are you that Smidge didn’t belong in the test population? If the marking was so clear on the others but not on her, maybe she was in the right place after all.”

  “You’re right. That’s the biggest flaw in Sheila’s hypothesis, and the biggest question we have to answer. Anyway, McKinnon backed Doug’s interpretation. He said fine, at worst it means we need to be careful about the dose regimen. The lower dose seemed to do the job on tumors, so there was nothing to worry about. Sheila thought that conclusion was a little too convenient.”