“No, I don’t mean that early in the process. Say you’ve already developed a drug, or something you think might be a drug. What’s the next step?”
Goodkind thought a moment. “Well, you do stability testing. See what delivery vehicle it likes best: tablet, capsule, solution. Then you expose the drug molecule to a variety of conditions — relative humidity, UV light, oxygen, heat — make sure it doesn’t degrade, break down into harmful byproducts.” He grinned. “People always keep drugs in their bathroom cabinets, you know, which is probably the worst thing you can do. Heat and moisture can cause all sorts of nasty chemical reactions.”
“Go on.”
“You perform tox studies, qualify the degradation products. Determine what’s acceptable, what’s not acceptable. Then you do a Trap.”
“A what?”
“A Trap. Toxicological risk analysis procedure. That’s what we call it here at the center, anyway. You run the functional groups — the different parts of the drug molecule — against a knowledge base of existing chemicals and pharmaceuticals. You’re essentially looking for adverse reactions that might cause different, and more dangerous, functional groups. Toxicity potential. Carcinogenicity, neurotoxicity, so forth.”
“And if you find such toxic potential?”
“That’s known as a structure alert. Each alert is flagged and studied for severity.”
“I see. And if the drug passes?”
“Then it goes on to clinical trials, first in animals usually, then humans.”
“These structure alerts. Can a drug cause a structure alert and still go on to be developed?”
“Of course. That’s one reason you have warning labels on medicine bottles. ‘Don’t take with alcohol’ and the rest.”
“Are these alerts listed somewhere, in a book? The Physician’s Desk Reference, maybe?”
Goodkind shook his head. “Structure alerts are too low-level, too chemical, for the PDR.”
“So they’re proprietary? Kept secret by individual researchers or pharmaceutical companies?”
“Oh, no. They’re all stored in a central database. Government regulations.”
Lash sat forward slowly. “Who has access to this database?”
“The FDA. Pharmaceutical manufacturers.”
“Biochemistry labs?”
Goodkind inhaled sharply as he realized where Lash was headed. Then he nodded. “With the proper accreditation.”
“The Weisenbaum Center?”
Goodkind nodded again. “In the research library. Two flights up.”
“Mind leading the way?”
Goodkind licked his lips. “Chris, I don’t know. Access to that database is government-sanctioned. You sure this is official?”
“It’s of the greatest importance.”
Still, Goodkind hesitated.
Lash stood up. “Remember what you said when I called? That you couldn’t predict suicide, that it was just a roll of the dice? That it made no sense, for example, why Poland had a drastically higher suicide rate than normal in 2000?”
“I remember.”
“Perhaps you forgot something, a fact I just dug up on my way here. Poland is the country where, because of the low cost to run studies, most drugs were tested in 2000.”
Goodkind thought for a moment. “You mean—?”
“I mean you should show me that toxicology database. Right now.”
Goodkind hesitated just a second longer. And then he, too, stood up.
THIRTY-NINE
The center’s research library did not look like a library at all. It was a low-ceilinged space, uncomfortably warm, its walls lined with carrels of blond wood. Each contained a seat, a desk, and a computer terminal. The room’s only occupant was the librarian, who looked up from her typing to stare suspiciously at Lash.
Goodkind chose a carrel in the far corner. “Where are all the books?” Lash asked in a low voice as he pulled over the chair from the adjoining carrel.
“In the basement stacks.” Goodkind drew the keyboard toward him. “You need to requisition titles from Ms. Gustus, there. But almost everything we need is online, anyway.”
Lash watched as the man typed in his name. A menu appeared, and Goodkind made a selection. The screen refreshed:
FDA — DIVISION R
PBTK
PHARMACEUTICAL AND BIOMEDICAL
TOXICITY KNOWLEDGE BASE
REV. 120.11
LAST UPDATED: 10.01.04
PROPRIETARY AND CONFIDENTIAL. OFFICIALLY SANCTIONED USE ONLY.
UNAUTHORIZED ACCESS CONSTITUTES A FEDERAL CRIME.
ID: ____________
PASSWORD: ____________
Goodkind looked at Lash, who nodded encouragingly. With a shrug, Goodkind completed the fields. A new screen appeared:
FDA — R/PBTK 120.11/00012 10/04/04
ENTER QUERY BY:
1. CHEMICAL COMPOUND
2. TRADEMARK
3. GENERIC
PRESS F1 FOR INDEX:
Goodkind looked over again. “What’s the name of the medication you’re interested in?”
“Scolipane.”
“Never heard of it.” Goodkind tapped a series of keys, and the screen filled with text. “Here it is.”
Lash peered more closely:
FDA — R / PBTK 120.11 / 09817 10/04/04
SCOLIPANE
Hydoxene, 2 — ((6 — (p-methylparapine) phenylchloride) alkaloid) — , sodium salt
MR: PhG
MF: C23H5O5N3Na
USE: (primary) S. M. R. (secondary) see p. 20
MUTATION DATA: N/R
REPRODUCTIVE REFERENCES: p. 15
SYNONYMS: p. 28
DOSAGE DATA: p. 10
PAGE 1 OF 30
“Biochem was my worst subject at U. Penn. Remember?” Lash looked away from the screen. “Why don’t you hold my hand a little here.”
Goodkind scanned the text. “Scolipane’s primary use is as a skeletal muscle relaxant.”
“A muscle relaxant?”
“It’s a relatively new formulation, about five years old.”
“Dosage?”
“One milligram. A little feller.”
Lash slumped. The theory that had begun to seem so promising started to slip away again.
He glanced back morosely at the top of the screen. Between the chemical description and the formula was a line he didn’t recognize. “What’s ‘MR’ stand for?”
“Manufacturer. They all have codes. You know, sort of like airports. Take this one: PhG. That’s short for PharmGen.”
Lash straightened again.
PharmGen.
He began looking more closely at the data. The acute toxicity chart was a typical feature of such reports; it usually recorded the LD50, or dosage at which half the sample population would die. He ran down the columns.
“Canine mania,” he said quietly. “What the hell?”
“We have to scroll to page twenty for more information.”
“And look — it says to see page twenty for data on human overdosage, as well.” Lash glanced at Goodkind. “Primary use is as a muscle relaxant, you said.”
“Right.”
“But look here. There’s another use. A secondary use.” He pointed at the screen.
“Page twenty again,” Goodkind murmured. “Seems that page has a lot to tell us.”
“Then let’s go.”
Goodkind moused quickly forward, the screen blurring, until he reached page 20. Both men leaned in to read the dense text.