Lethal Remedy (23 page)

Lillian Goodman settled into the chair in front of a computer terminal in the medical center library. She could have used her office for this, but this way she was away from any distractions. Her cell phone was silenced, her pager set to vibrate, and no one but her secretary knew where to find her. She was determined not to give up until she'd broken through some of the mystery that surrounded Jandramycin, the compound that began life as EpAm848.

She decided that her first order of business would be to figure out what Jack Ingersoll's original area of research was when he stumbled onto his wonder drug. For instance, if the components were substances that might cause lysis of a cell wall, it was reasonable that they could be combined in such a way as to cause bacteria to swell and pop like balloons blown up too much. If they were involved in cell reproduction, the combination might act to keep bacteria from proliferating so their population would eventually decrease to zero.

The only clue she had was the original name given the experimental preparation: EpAm848. She decided to start with the number. That was fairly clear-cut, and surely Google would help her run down its meaning. She had second thoughts when she saw that entering "848" yielded almost eighty million results. Then she tried "compound 848." Better—only three million. As she trolled through the answers, she discovered that Google put the most likely at the top of its list. Good.

After half an hour, Lillian was fairly certain that the number referred to R848, a compound associated with the immune response to harmful bacteria. Okay, immune response. That was a starting place. She jotted a note on the pad beside the computer monitor.

"Am" was more challenging. She dug deep, pounding the computer keys until her wrists were sore and her fingers stiff, but nothing seemed to click. Then she decided that maybe it wasn't "Am" at all. Maybe the designation had been "AM"— two words, each beginning with one of those letters. That led to a different search.

After an hour's digging into references, Lillian felt crosseyed. She stretched, moved around in her chair, and wondered if it was worth it. She dug into her purse, found a couple of Tylenols, and journeyed to the water fountain to combat the headache she was developing.

Finally, she found an obscure reference in the
Journal of Ethnopharmacology.
It dealt with Chinese herbs, and stated that
Astragalus membranaceus
was thought to have "immunomodulating and immunorestorative effects." In other words, it affected the immune system of the person receiving it, helping throw offinfections. That had to be it. Two-thirds of the compound name, and both referred to the immune response to bacterial infection. She felt the flush of victory, but determined to make sure.

Instead of searching for words that began with "Ep," Lillian tried the same tack that yielded her last positive result. She looked for two words that started with the letters E and P. This wasn't easy, and she was about to give up when she encountered
Echinacea purpurea.
She was aware that a number of homeopathic and herbal remedies contained
Echinacea
for its alleged ability to help cold sufferers throw offtheir infection. Lillian plowed through reference after reference until, in one paper, she encountered the phrase: "
Echinacea purpurea
is known for its ability to kick-start the immune system." She also found that many people were highly allergic to this natural remedy, experiencing reactions ranging from rash and swollen tongue to anaphylaxis and death. Could this be the "unpleasant result" Ingersoll sloughed offduring their discussion?

Lillian sat back and massaged her temples. This might be the clue she and her colleagues had sought. Jandramycin, in its final form, acted to kick-start the patient's immune system to make antibodies specific for the invader,
Staph luciferus.
Such a targeted response would undoubtedly assure that everyone capable of mounting a normal immune response would be rid of the bacteria within a few days. And the autoimmune responses? If these only occurred in patients with an allergic background, maybe the drug had an additional action on their immune system, generating antibodies to the patient's own tissue. Nervous system, bone marrow, thyroid, kidney, blood vessels—any of these could be the target of the process. That could explain the autoimmune complications seen in allergic patients who'd received Jandramycin.

It's all conjecture. And if it's true, what do we do to help those patients?
She scooped her notebook into her backpack, stuffed her purse in after it, and hurried from the library. She had to call John.

John opened the refrigerator and peered in, not really seeing the contents. He wasn't particularly hungry, but knew that he needed to eat. "Keep up your strength." He was startled when he realized the voice in his head that delivered the words wasn't Beth's. Instead, he heard Lillian Goodman. Did that mean Lillian was taking Beth's place? Oh, please God, no.

John loved Beth. He'd always love her. Was her memory fading already? He prayed that wasn't the case. He'd worked hard not to build what one popular book on the loss of a spouse called a "shrine to grief." He'd donated Beth's clothes to a shelter for battered women. Her books went to their church library. He'd cried while doing it, but John finally erased Beth's voice from her cell phone message, although now he wondered if that had been wise. But he knew he had to move on. He just wasn't ready for anyone to replace Beth in his life.

The ringing phone startled John from his reverie. He closed the refrigerator door and hurried into the living room to catch the phone before the answering machine kicked in. He didn't bother with the caller ID. When loneliness had him in its grip, he was even glad to talk with telephone solicitors.

"Dr. Ramsey."

"John, this is Lillian. Did I catch you at a bad time?"

He dropped into a chair and wondered if through some mind-reading magic Lillian knew he was wrestling at that moment with her role in his life. More than that, he felt guilty at the pleasure he felt when he recognized her voice. "No, I'm fine. Just browsing in the refrigerator."

"Well, be sure to eat something. You have to keep up your strength."

No doubt about it. The woman was a mind reader. "I will," John said. "But surely you didn't call to remind me to eat dinner. What's up?"

"This may sound strange, but I need to ask you if you're allergic."

"I don't understand what you mean. To medicines? To foods? What?"

"Do you have hay fever? Asthma? Eczema? That kind of allergy."

"Oh, I see. Well, I was allergy tested several years ago. He said I was allergic to grasses, trees, and weeds. But I never got around to taking shots. I just treat the symptoms when they get bothersome." He frowned. "But why do you ask?"

"I think we need to talk," Lillian said. "Would it be okay if I came over?"

"Sure. Why don't I order a pizza, and we can eat together? What do you like on yours?"

"Just order what you usually get," she said. "I'm sure it will be fine. Besides, after I tell you what I've learned, neither of us may have much of an appetite."

T
HE CALL CAME THROUGH ON HIS CELL PHONE, NOT HIS LANDLINE, WHICH
was the way he'd set things up with his informant. Either way, there would be a record of the call, but this way there was no possibility that anyone could be listening in. At least, not without some sophisticated electronics. As for his office, it was swept for bugs once a week by a man he paid in cash out of his own pocket. Absolute security was impossible, but this would do.

"So, who's still digging around looking for flaws in Jandramycin?" he asked.

"Still Sara Miles and Rip Pearson, but—" Traffic noise in the background intensified for a moment, and the caller waited for it to die down. "Sorry. I stepped outside to get some privacy. Anyway, Miles and Pearson are the main ones, but I'm pretty sure there are a couple of others involved."

"Give me the names, and we'll give them something to take their mind offthat witch hunt."

"I've got to tell you. I'm not really comfortable with what you've done already. Dr. Miles could have been hurt or killed by a gunshot."

"Not if the person behind the trigger had better aim." He struggled to keep his voice level. "I said to scare her, put a couple of bullets through the car window behind her. Instead, the shots almost hit her. That wasn't my fault."

"And ramming Pearson's car—"

"Pure incompetence. There are teenagers offthe street who'd be able to boost a car, follow someone, and sideswipe their vehicle just enough to run them offthe road. And they'd know not to choose a location that would involve hitting a concrete wall. Again, not my fault." Idiots. The whole world was populated with idiots, and the worst ones were the ones he had to work with. "Now get those other names. Call me back and we'll arrange something to distract them."

"I really don't like—"

"It doesn't matter what you like. You're ours, bought and paid for. Don't ever forget it."

The informant was saying something, but he hung up, cutting him offin mid-sentence.
Stay focused. Remember what's at stake. I can't stop now. Not when success was so close.

Morning rounds on the internal medicine floor of University Hospital found Sara frowning over Randall Moore's chart. Rip had started him on nafcillin yesterday, and he'd had four IV doses of two grams each since admission, but his fever remained high. True, it was early, but she'd be a lot happier if there was some evidence he was responding to treatment. If this were a run-of-the-mill
Staph
infection, even MRSA, she'd expect some improvement. Every hour that went by without that improvement made it more likely her patient was infected with The Killer,
Staph luciferus.

"How's our guy?" Rip slid into the chair beside her and peered over her shoulder. "Still febrile?"

She handed over the chart. "I'd be a lot happier if his temp were a bit lower. Think it might be . . . " She let the words trail off, hesitant to give voice to her fears.

"I'm afraid so. We might have a preliminary culture report today, although tomorrow seems more likely. And once we know for sure, the fun begins. Should I give him Jandramycin, knowing there's a chance he might get a severe late complication?"

"Can't you simply inform the patient and let him make that decision?"

Rip shook his head. "It's not as simple as that. Ingersoll categorically denies that Jandramycin therapy carries any risk. And, based on what you've told me, the people at Jandra say the same thing. So if we tell Moore about the possible complications, there's no foundation to back up our story. Besides that, if Ingersoll finds out, I can kiss my fellowship good-bye."

"But if we don't tell Moore, and he's one of the unlucky ones—"

"Then there's another lawsuit against the medical center and a bunch of doctors, us included," Rip said. "Yeah, this is a tough call."

"Excuse me, do you both have a moment?" Lillian Goodman stopped several paces away, apparently not wanting to invade the space of the two doctors who sat with their heads together.

Sara motioned her to the chair on the other side of her. "Have a seat. We were just talking about Randall Moore's case. You really dodged a bullet when you asked me to see him yesterday."

Lillian made a dismissive gesture. "I'm really sorry I got you involved. In retrospect, I should have called Donald Schaeffer over to see him."

"Don't worry about it," Rip said. "Besides, I think we can agonize over his treatment plan as well as the department chair could. Maybe even better."

Lillian leaned across to address her remarks to both Sara and Rip. "You guys do know that—"

Sara stopped her with an upraised palm. "Yes, we know he's suing you and half the staffof the medical center. But that doesn't make any difference to me, and I believe Rip feels the same way."

"Suit? Has another lawsuit been filed?" John Ramsey slid into the chair beside Rip. "I'm seeing more of those since coming here than I ever saw in forty years of private practice."

"No, this is the same one you and I know about," Lillian said. "Sara, do you want to tell John what's going on?"

John sat quietly while Sara explained the situation. When she finished, he said, "Wow. I guess the best thing would be that the culture comes back as something other than
Staph luciferus.
Even MRSA would be better, I suppose."

"It would, but I'm not betting on it," Rip said.

Lillian held out her hand in silent request, and Rip passed her the chart. "What are you looking for?" he asked.

She thumbed through until she found the history sheet Moore had filled out when he first entered the clinic. "I'm looking for something in his history." Lillian frowned, flipped a page, frowned again. "Here it is. He has a history of hay fever and asthma, and both parents are allergic."

"What does that mean?" Rip asked.

"I'll give you my theory. Realize, this is all supposition," Lillian said, "but it makes sense to me, and it's all we have to work with right now. I began with your finding that about 15 percent of the people receiving Jandramycin ended up with late autoimmune complications. That's about the percentage of people in the U.S. with allergy."

"Yes," Rip said. "But so what?"

"I decided to look for a connection, and I think I found it. I took the original name of the experimental compound that became Jandramycin and searched for the components Ingersoll could have been working with to develop it. I started with 848 . . . "

John listened quietly as Lillian laid out what she'd found and knit together her hypothesis. Jandramycin stimulated a patient's immune system to form antibodies against
Staph luciferus.
Natural antibodies attacked the bacteria, destroying them and preventing them from multiplying. The action of this drug was different from that of other antibiotics, drugs that attacked bacterial cell walls or stopped their metabolism, but the end result was the same. The patient recovered.

Unfortunately, in patients with an underlying predisposition to allergy, the drug also did something to the immune system that turned it upon itself, making antibodies to the patient's own organs. For some reason, this was only seen in allergic patients. And he was allergic and had been treated with Jandramycin. The only question in his mind was which autoimmune disease he'd be stricken with, and how severe it would be.

"Assuming your hypothesis is correct," Rip said, "this still doesn't tell us how we can modify the process in vulnerable patients so they don't develop autoantibodies."

"Let's approach this logically," John said. "What do we use to treat autoimmune disorders?"

"Corticosteroids" came the reply from three mouths almost in unison.

"But that's a temporary measure at best. The patient with temporal arteritis may have to receive multiple courses of ste roids as the symptoms recur. Steroid therapy doesn't cure rheumatoid arthritis. It only alleviates the symptoms," John said. "What else?"

"Antimetabolites," Sara suggested. "Methotrexate, for instance."

"Again, a temporary measure," John said. "What if there were something that, instead of cleaning up the symptoms they produce, could block those antibodies from attacking the person's own tissues in the first place?"

Rip shook his head. "That would be perfect, but unfortunately we don't have such a drug."

Lillian and John exchanged glances. Maybe being older did translate into being wiser and able to think outside the box. In response to a faint nod from Lillian, John spoke up again. "I have a suggestion. Omalizumab."

He told them what he had in mind. Perhaps this compound, developed specifically to block the antibodies responsible for hay fever and asthma, would neutralize the abnormal antibodies made by the patients who'd received Jandramycin.

John watched expressions in the group change as disbelief gradually gave way to the realization that it might actually work.

"It's an off-label usage for a preparation that might—I emphasize might—do what we want it to do. It's expensive, and we don't know how many doses it might take. Most important, there's risk in using it on patients whose immune system has probably already been modified by Jandramycin."

Rip frowned. "Wouldn't we have to get the approval of the IRB?"

"It would take weeks to get a proposal before the Investigational Review Board," Sara said, "and if we did, they might not approve it." She looked down at her clasped hands. "And I have a little girl who, despite large doses of steroids, is losing a fight with ascending paralysis with each day that passes."

"That's why I'm making this suggestion. And it can't go beyond the four of us in this room." He waited until he'd received nods of assent from the others. "I want to volunteer to test it on me."

"But you haven't developed any complications," Rip said.

"No, but I have a history of allergy, so I'm in line to do just that. I'll take it. If there are no adverse effects, if it doesn't appear that the Jandramycin has set me up to react adversely to the drug, that's a big step. Then if I don't develop an autoimmune complication, that tells us even more." He spread his hands. "Sure, it's not a double-blind, placebo-controlled study, but it's all we've got."

"How soon do you think we'd know something?" Sara asked.

"It generally takes effect within a few days. But if there are going to be complications from it, they'll show up within an hour or two," John said.

"And if it works, maybe I could give it to Chelsea?" Sara asked.

"Do you have something better?" John asked.

The silence in the room effectively answered the question. Finally, Rip spoke. "Since I'm what passes for the secondin-command on this investigation, and none of us trust the principal investigator, I'll speak up. Go for it."

"I'm going to talk with Chelsea Ferguson's mother about giving it to her," Sara said. "I'm pretty sure she'll jump at the chance."

"Don't you want to wait—" Rip said.