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Authors: Harry Stein

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BOOK: The Magic Bullet
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“No, sir. Based on what we see, the disease originated in the breast and metastasized to the bone.”

“Then what are we talking about”

he hesitated

“breast surgery? I don’t understand.”

The doctor shook his head sympathetically, secretly surprised that a man renowned for his wide-ranging knowledge could know so little about something that in his own circle was regarded as elementary. “I’m afraid, sir, that at this point surgery on the breast would only eliminate a small portion of the disease.”

“I see.” Briefly, he glanced out the window at the vast expanse of lawn. “I take it this is certain? No chance of a mistake?”

“No, sir. I’m afraid not.”

He placed a reassuring hand on her shoulder. “What is the next step? Can you give us any kind of realistic prognosis?”

“Look, we’ve come a long, long way. There are some very effective treatments. I recommend the first thing we do is call in Dr. Markell from the ACF.”

“How dare you?” she suddenly erupted
.

They both turned to her in surprise. She was in a rage, glaring at the doctor
.

“This is MY life! What in hell do you think gives you the right to supersede my wishes?”

“Mrs. Rivers, I’m sorry, it just seemed to me that your husband had the right


“Well, that’s not your call to make! How DARE you!”

“—that your husband had the right—”

“That’s crap, you were worried about your own ass!”

“Elizabeth, please, you’re upset.”

“Damn right I’m upset! I’ve got cancer! And his only thought is how he’s going to look in front of the President!”

“Mrs. Rivers, I assure you that’s not true. I’m sorry, perhaps
I did use poor judgment.” He looked to her husband, then back at her. “I can only tell you I’ve known many patients with metastatic breast cancer who have done very well. That’s what you must focus on now.”

But her fury was spent. Suddenly, there were tears in her eyes, and a moment later she was sobbing. “I don’t understand it, I’ve done everything I’m supposed to. Self-examinations. Mammograms.”

Her husband took her in his arms. “It’s not your fault, darling, it’s nobody’s fault. The doctor’s right—what we’ve got to think about now is fighting it.”

With his free hand, he snatched up a phone from the table and punched in three numbers. “Diane, cancel my appointments for the next couple of hours. I’ll be reachable upstairs in the private quarters.”

The doctor shifted uneasily. “I understand you want to be alone. You’ve got a lot to talk about.”

“Yes, well …” President Rivers rose to his feet and extended his hand to his wife. Slowly, wearily, she drew herself from the chair. “We should probably talk tomorrow.”

“I just want to say in the strongest possible terms that there is every reason for optimism.” He nodded out the window, in the general direction of the ACF, across the river in Virginia. “They’re doing remarkable things there, just remarkable.”

 

T
heir first year at the American Cancer Foundation came to an end the second week in June. That weekend, Shein held his annual party to welcome the new crop of raw rookies.

Logan elected to miss it. That was all he needed just now—to spend an entire afternoon making nice to Larsen and Stillman and their assorted underlings.

For, increasingly, he was aware that the Hannah Dietz case had left Compound J riper than ever for ridicule. True enough, in a strictly medical sense the protocol was not fundamentally compromised: Dietz’s toxicity having been minimal and eminently treatable.

But—especially coming as it did within weeks of Novick’s fall—there was also the
psychological
factor. Like it or not, the Compound J protocol was now regarded at the ACF as being in some trouble. Before, its opponents had merely been able to say it was a harebrained idea that amounted to nothing. Now they could say something else—and it made Logan almost physically ill to think of the pleasure they got saying it: It was a harebrained idea
that makes people even sicker
.

More than ever, Logan knew, time was working against them.

The great irony—at least if Shein could be believed—was that Stillman’s own protocol was already, demonstrably, a complete bust.

Then, again,
could
Shein be believed? Certainly Stillman gave no sign that his protocol was in trouble. His public posture was that it was proceeding exactly as planned; the drug’s lack of activity described as anticipated,
his sole aim at this early stage being to establish nontoxicity.

As much to the point, Shein had said not another word about it. In fact, the next time they saw each other, the conversation might as well never have happened.

“Hey,” the senior man greeted him, “you’re looking good. Good color. Looks like you’ve been getting some sun.”

“Thanks.”

“Don’t reach for compliments, Logan. Maybe if you worked a little harder you’d get some results.”

Shein’s return to humiliation mode could not have come at a worse time. With the rookies coming in to take over the hospital scut work, the second-year associates were now moving up to lab work—which, for both Logan and Sabrina, meant going to work directly under Seth Shein.

And, as if his opening put-down hadn’t been enough, ten minutes later, facing his entire flock of second-year associates, the senior man gave an introductory talk that registered as a personal message to the Compound J team.

“Well, boy and girls,” he began, “I know you and you know me, so we can save all kinds of time. The work we’re gonna do here won’t always be fun. And there won’t be a helluva lot of glory.” He glanced at Logan and Sabrina. “Sorry, it’s back to real life.”

That brought smirks from several others in the room. “But here’s the upside,” he continued. “As you all know—as some of you
especially
know—I do play favorites. So work hard to stay on my good side. And never, ever make me look bad.”

The worst part was that Logan was no longer sure he could blame him. If Compound J failed to pan out, he, Sabrina, and Reston would of course take the hardest hit. Pegged as arrogant kids whose ambition had proven greater than their judgment or skill, they’d be unceremoniously hustled off the fast track, and kept off it for the forseeable future. But as their most ardent supporter, Shein would be
in for his share of grief too. Surely it was his prerogative, now, to think about cutting his losses.

The pity, for Logan, was that there’d never been a time when favoritism would have been more welcome. While most other junior associates, including Sabrina, had little experience in organic chemistry beyond a few basic undergraduate courses, he not only held an advanced degree in the field but had trained under a renowned Nobelist; where the others found the routine lab work doled out by Shein instructive, he found it as mind numbing as anything they’d left behind at the hospital.

Not that the project to which Shein assigned them wasn’t ambitious: determining the base sequence of the gene that encodes a protein involved in transforming healthy prostate cells to malignant ones. It was just that he found himself the scientific equivalent of a laborer on the Great Wall of China; doing grunt work on a tiny section of a project so large that its importance to the big picture was almost beyond imagination.

The second-year associates’ role was simply to clone and sequence this gene so that other, more senior people would have material to work with. For Logan, day after day it was like following directions in a cookbook:
Add three lambdas of the restriction enzyme Xba to DNA; spin for fifteen minutes; cool at four degrees Celsius; add 300 microliters of chloroform and 150 microliters of phenol; spin for five minutes; remove phenol and chloroform; add 300 microliters of one molar sodium chloride and one milliliter ethanol; keep at minus twenty degrees overnight
.

Under the circumstances, he soon began regarding the routine sessions with the protocol patients as a relief; a chance, if only fleetingly, to exercise a little control. Now, even the hours perusing accumulated protocol data became less a chore than a pleasing change of pace. Studying the numbers, trying to discern the significance of modest fluctuations from week to week, was the only creative challenge he had left.

Thus it was that he and Sabrina happened to be in the
chart reading room—the librarylike chamber in the hospital basement—when Logan started going over the numbers of a patient named Marjorie Rhome. By the luck of the draw, he hadn’t seen Mrs. Rhome, a forty-eight-year-old dental assistant from Dover, Delaware, in over a month; on each of her last three visits, Reston had handled her.

Her file, like that of every other patient in the protocol, was now massive: over a hundred pages of printouts, nurses’ notes, and comments by the examining physician in the outpatient clinic. Every medicine she had ever taken was listed here, as well as the result of every test; for blood work alone, that meant thirty-three individual results for each semiweekly visit.

For fifteen minutes, sitting in a wooden carrel, he scanned the file. Then, on the fourth to last page, listing the results of her blood work from three weeks before, something caught his eye: the woman’s creatinine level, a measure of kidney function, was at 1.7. Immediately, he skipped ahead to the final page, listing the results of last week’s visit. The level had jumped to 1.8. Normal is 1.4.

“Sabrina!”

Sitting five feet away at the adjacent carrel, she was startled. “What is it, Logan?”

“Look at this.”

She, too, immediately grasped its significance. “My God,” she said softly.

An elevation of the blood creatinine level meant the kidneys were not clearing it properly. Which meant that in all probability they were not clearing far more dangerous substances; particularly potassium, which can make the human heart flutter chaotically or even come to a dead standstill.

“That idiot must’ve missed it,” said Logan bitterly. As far as Logan was concerned, the final straw on Reston—the definitive proof that he’d turned his back on the protocol—had been his erstwhile friend’s decision to do his lab work under Larsen’s associate, Kratsas. “He didn’t give a damn. For him it was just busywork.”

“No,” countered Sabrina who, now that Logan had adopted her own view of Reston, was prepared to be fair. “There were hundreds of lab values. It could have been any of us.”

They spent the next hour going over the files of all of the other patients on the protocol, looking for the same syndrome. They found it in one: Faith Byrne was also at 1.8.

“This is a problem, Dan,” said Sabrina intently. “A
real
one.”

“Yep,” he grimly agreed.

“If the level goes to two point zero or two point one …”

“They’ll have to leave the protocol. And if the creatinine level continues to rise, we may be talking a worst-case scenario of chronic renal failure, or even permanent hemodialysis.” He shook his head. “Kidney failure—not one of your better outcomes.”

“And this time there are no magic solutions.”

Looking at her, he was struck by how weary she looked; and, worse, how uncharacteristically discouraged.

“Come,” he said, “we have to go somewhere to talk.”

The fact was, Logan had been turning the idea over in his mind for a while—since Hannah Dietz’s toxicity. Only now, suddenly, it began to look less like just an intriguing possibility than like an imperative.

They retreated to a small restaurant in Alexandria. A classic Yuppie hangout down to the single flower vases on marble-topped tables, it was the sort of place that no one they knew at the ACF would ever go near.

“I really don’t think that we can be surprised by this,” he began deliberately. “There’ll always be unexpected toxicities with new therapeutic agents.”

A waitress came by and they ordered a couple of beers.

“Please, Logan,” she picked up, “I
know
that. Yes or no, do you have a way to treat this creatinine problem?”

“Uh-uh.” He hesitated; it sounded crazy even to him.
“What I’m thinking is we should take this drug back to the lab.”

“Try to
change
Compound J?”

“Not entirely. Take it apart, look at it in new ways. Try to find some way to cut down on its damn toxicity!”

She looked at him quizzically; he was talking high-level chemistry, far beyond anything in her experience. “How does one even start?”

“It’s not as tough as it sounds. I’m not talking anything drastic, just a slight adjustment in the molecule. I’ve got some ideas.”

“But what is the point?” she asked. “The drug we are using—
that
Compound J—by the terms of the protocol, it’s the one we must stay with. Even if we make something better, we cannot use it.”

They fell silent as the waitress placed their beers before them.

“You’re right,” he said when she was gone, “but I’m trying to think beyond that. Look, the fundamental idea is sound—we know that, right?”

She nodded.

“There’s just something about this molecule that makes it toxic. We’ve
got
to redesign the molecule.”

“Can you do this all by yourself?”

He gave her a look.

“Logan, you know I cannot help with this.”

“You?
Don’t you dare give me the helpless bit, it won’t wash. You got a pen?”

She handed him one.

“Now, then,” said Logan, sketching on a cocktail napkin, “this is the Compound J we’ve got, right?” He produced an awkward rendering of two spheres, with three spikes protruding from each, connected by a long, thick tube. “Basically, we’ve got three parts that more or less fit together: two naphthalene rings, each bound to three sulfonate groups—those are the spikes; and connected to one another by an organic polymer. Think of it as a modular couch thing, with the larger section in the middle.”

He looked up and she nodded. “To me it looks more like a lobster.”

BOOK: The Magic Bullet
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