“That's fine, Mr. Asherson,” Tom said, when he was through. “You can have your lunch now, and then a little nap, if you want. I'll tell your daughter that she can come in to see you, so that she can make sure that you're comfortable. I'll come back at five to do the second run—by which time, of course, you'll probably have forgotten all about the first run, so it will all seem fresh. We won't have to worry too much about the possibility of educative bias unless you actually begin to show some improvement. That's another advantage this trial has over the ones that only test the healthy, now I come to think about it. Things aren't as bad as we sometimes imagine, are they? Okay, Sarah—you're in charge."
“Officers are wankers,” Patient K opined. “Lions led by donkeys, we were. Sick sick sick."
According to Mr. Asherson's biography, which Tom had scrutinized more carefully since awarding the big tick, the teacher had served briefly in the Far East before completing his National Service, but he'd never been in anything the Army was prepared to define as a “conflict situation.” No matter what he'd told his children and his grandchildren thereafter, or what he was trying to tell Tom now, he'd never had the chance to be a real lion. He'd still been at school during World War II, and hadn't even suffered the indignity of being an evacuee.
“Lie down like a lamb, there's a good chap,” Tom said, in his best paternal manner. “We'll see what kind of hero you are tonight—when your brain might be a little clearer, with luck and the benefits of LAW-1917. If so, we should see some real improvement tomorrow—although I shouldn't tell you that, strictly speaking, in case the expectation actuates some kind of placebo effect."
By now, Tom was genuinely optimistic about the possibility of improvement. Patients A to J had all shown some improved brain function, although some had done far better than others—and none of it was likely to be the result of a placebo effect, given the condition of the subjects. Those who'd done best of all, in fact, were still showing clear benefits two to six weeks later, and there seemed to be every possibility that more than half of their number would hang on long enough to take further treatment, if and when the program was able to move into Phase Two. All in all, the trial was going well in spite of the time it was taking.
* * * *
Simon Phipps, the English rep from the company on whose behalf the trial was being carried out, was waiting in Tom's office when he got back.
“It's going well,” Tom said, turning his clipboard around so that Phipps could see the long columns of numbers, ticks, and crosses.
“Patient K,” Phipps read off the top of the sheet. “He's your only one this week? That still leaves L to P to find."
“Four more weeks,” Tom said. “Six tops. In the meantime, you can buy me lunch. Have to be the canteen, mind—the protocol requires me to stay on the premises during the period of administration, in case of an adverse reaction."
Phipps made no objection; bribing doctors with the occasional lunch was part of his job description. He even had the grace to wait until Tom had finished eating before he started whining about the time the trial was taking. “With the benefit of hindsight,” he said, “we'd have done better to split the trial between two hospitals, so as to cast the sampling net more widely."
“No you wouldn't,” Tom told him, wearily. “You've already got two for the price of one—the consultant at the Main is working with me, referring potential candidates for the trial here."
“A bigger city, then,” Phipps countered. “Birmingham or Manchester. There's no shortage of senile old fools in Manchester."
“No, but they mostly stay at home till they rot, because their offspring accept their decline as part of the normal pattern of life, and they all have complications—mostly lung cancer and chronic obesity. Down here, you have senile old fools whose loving offspring offload them on to the NHS at the first opportunity, some of whom are in pretty good physical nick, apart from their CAG-repeat neuronal intranuclear inclusions. The flow is slow, but it's good quality. Patient K is a pearl—a career teacher at a middle-of-the-road selective school, who started out in the days when you needed common sense and mental toughness and took his BEd in his spare time. Kept his mens sana in good shape teaching biology and his corpore sano in tip-top condition teaching PE. Never smoked, and stayed fit enough to con his grandchildren into believing that he was once in the SAS. You don't get many like him up in Manchester. We don't want our precious trial to turn up negative results because the subjects are all crap, do we?"
“So I can tell the Germans that the results will be positive, then?” Phipps said, eagerly, as they left the canteen to walk back to Tom's office. “They might not mind the extra wait if I can promise them that it'll be worth it."
“It's too soon to sound the trumpet,” Tom said, scrupulously. “With K to P yet to be assessed, there's still time for the numbers to take a downturn, or for some perverse sod to have a bad reaction. On the whole, though, I'd say that all the signs are good. The stuff really does seem to gee up the T-cells almost immediately, and enables them to home in right away on the gunk that's doing the damage. If I were a betting man, I'd be prepared to have a judicious punt on the possibility that your bosses will one day be able to whisper the sacred syllable where it's never been whispered before. We'll have to be very careful about getting the dosage exactly right, though, so we'll have to be even more painstaking in Phase Two. It'll be worth it in the long run. Trust me."
Phipps knew that the “sacred syllable” was cure, but he'd been in the business too long to allow himself to get overly excited about Tom's carefully moderated optimism. “You'd better be very careful, then,” he said. “The one thing the Germans hate worse than things going wrong at the outset is having a trial drag on for years, spinning off promises and expectations all the while, and then have it go tits up at the last hurdle."
“It could happen,” Tom admitted, as he unlocked his office door and moved aside to let Phipps precede him. “Lap of the gods, mate—but we have to stay positive. One day at a time."
“I hate these monoclonal antibody deals,” Phipps confessed, as he leaned against the office wall, spurning the armchair that was set deliberately low so that Tom could look down on patients and visiting administrators alike. “Too nerve-racking."
“We'd better get used to it,” Tom said, as he took his own chair. “Monoclonal antibodies are here to stay, and there are thousands more in Big Pharma's pipeline. Anyway, it's me who'll take the worst of the shrapnel if anything does explode in our faces. I'm the guy at the sharp end—you're just a suit in a chain of command."
“Don't give me that, Tom,” the rep retorted. “If anything were to happen, you'd pass the buck to me without pausing to draw breath—and it wouldn't be nearly so easy for me to get rid...” He might have said more, but there was a knock on the office door just then, and Patricia Lockley, née Asherson, came in without waiting to be invited.
“He seems much better, doctor,” she gushed. “I can't thank you enough for getting him on to the trial. I'm really glad they referred us here from the Main. I think it's wonderful."
“Sit down, Mrs. Lockley, please,” Tom said, not bothering to glance sideways at Phipps to underline the significance of the remark about the referral. “There's no need to thank me—we're very grateful to you for allowing Bill to participate. This is Simon Phipps, by the way—he works for the company that developed LAW-1917."
“We're very optimistic about it,” Phipps said. “Dr. Wharton is doing a terrific job—your father is in good hands."
“You mustn't expect too much, though,” Tom put in. “Your father probably perked up a little because we've been giving him so much attention—and because he was pleased to see you, of course."
“That's exactly it,” she said. “He was pleased to see me, and he knew who I was—didn't call me Eileen once. I haven't seen him tuck into lunch like that for months. It's a miracle."
“No, Mrs. Lockley, it isn't,” Tom insisted. “It's too soon for the drug to have
taken effect—we won't see any authentic improvement until this evening at the earliest. If the human immune system weren't so reactive, we wouldn't be able to see results as soon as that—but because it is so reactive, we have to be very careful not to overdo the dosage. We want the new T-cells to clear out some of the accumulated proteins that are stopping your father's brain from working properly, but we have to make certain that they don't start attacking the component that's necessary for the brain to function at all. It's early days yet."
“I know,” Patricia Lockley said, blithely unaware of her own inconsistency, “but it's wonderful all the same."
* * * *
“Dr. Wharton, is it?” Asherson said, when Tom turned up to administer the second battery of tests. “All swings and roundabouts."
“Very good, Mr. Asherson,” Tom said. “I can see that you'll zoom through the tests without a hitch this time."
“I was in the SAS,” Asherson told him. “I've had survival training. Kill a man with my bare hands."
“I'm sure you can,” Tom agreed, taking his seat at the keyboard as Nurse Odiko moved the screen back into position, “but your experience as a teacher might stand you in better stead today. Can you spot the lemon?"
“Sandhurst wimp,” Asherson opined. “Never done a day's work in your life, have you? Bare hands. Met Eileen at the fair. Sick sick sick. Is she coming back?"
“Please try to concentrate, Mr. Asherson,” Tom said. “I really need to do these tests, to see whether the drug has begun to work yet."
“Law six six six” Asherson said—but he had already begun to tap the screen when the lemons appeared. “Stagger the trial. No meltdown. Swings and roundabouts. Arsehole."
“It's ell-ay-doubleyew-1917, Mr. Asherson,” Tom told him. “But you did well to notice that the letters spell law. That's the teacher in you, although you seem to have mislaid him temporarily and got stuck in your teens, way back in 1949. Now this one's a bit more complicated. Do you remember it?"
“Yes,” said Asherson, shortly—and it seemed that he did, because he passed with flying colors, without any need for an explanation of what he was supposed to do.
That was just the beginning. By the time the series of tests was complete, Tom's record sheet was a solid mass of ticks and tens. “That's very, very good, Mr. Asherson,” he said. “You've gone straight to the top of the class. If you can do that again tomorrow morning I'll have to move you on to the Level Two tests and open up a whole new category of potential improvement."
“Won't be here,” Asherson said. “Things to do, got to get out. Mission to take on. Agent K. Secret. Can I have more medicine now? I need more medicine before I go."
“That's Patient K, Mr. Asherson,” Tom told him. “Yes, you are on a mission—but your mission is to stay here. That's very important. We have a job to do, you and I. We need to prove that Alzheimer's will be curable one day, and that LAW-1917 is one of the magic bullets that can do the trick. You mustn't take any more medicine, because it would be dangerous. We can't even sedate you, I'm afraid—although you should try to get some sleep. Nurse Odiko's shift is over now, but Nurse Kasicka will stay with you all night. I'll be just down the corridor. I'll be here all night too."
Simon Phipps was waiting outside the door, having put off driving home until the latest results were in. “Good?” he said.
“Brilliant,” Tom said, dubiously. “Good enough to lift the average improvement between tests one and two by a point and a half—if he continues to improve he'll break the record easily."
“You don't sound unduly delighted about it,” Phipps remarked.
“It's never entirely good news when one set of results is so far out of line with the others,” Tom told him, “although I suppose it's expectable, given that he had a more intellectually demanding job than A to J. Even so, you don't want a drug's effects to be too variable, especially a dose-sensitive drug like this one. Patricia Lockley was right—he's made so much progress so fast that it's almost a miracle. The trouble is, if the effect continues to increase at this pace, he might already have overdosed. If the new T-cells start clearing healthy proteins as well as the NIIs, it could kill him."
“You mean he might go into the frenzy thing?"
“No. If something like that were going to happen his physiological indicators would already be going hyper, and they're not. His pulse and bp are sound as a bell. I mean that his brain might simply stop working—coma, PVS, then stone dead."
“You can't let that happen,” Phipps said.
“No, obviously not. At the first adverse sign, I'll start medication—but even if I can stop the process going all the way, your trial will be well and truly messed up."
“It's our trial, Tom—and that us isn't just you and me, but the expectant Germans as well. So far, it's just an improvement, right? So far, it's all good. I can tell them that."
“Sure you can,” Tom said. “If I were you, though, I'd let it simmer tonight and pop back first thing in the morning to see how things stand then. If the situation's stabilized ... well, if that's the case, you might just find the sacred syllable dancing on my lips."
“I'll do that,” Phipps promised.
* * * *
Phipps was as good as his word; he arrived at Asherson's room just as Sarah Odiko was changing places with Petra Kasicka again. The rep didn't wait outside this time; he came in to see what was going on.
What was going on was that Tom was checking the log of the computer, whose keyboard was on William Asherson's lap. Asherson's eyes were glued to the screen, which displayed a chessboard.
“He's been playing for two hours,” Tom whispered to Phipps. “Petra says that he didn't sleep a wink all night. When he got bored he insisted on running though the test-program I'd set up, and she had to let him do it in order to keep him quiet. After that, he started searching for something better, first on the hospital intranet and then on the web. He played a few chase-and-shoot games before he found the lightning chess program. He played nine games on level one, losing all but the last, then moved on to level two. He lost the first game on that level but won the second, and he seems to be winning the third.
“I can hear you, you know,” Asherson said, without moving his eyes from the screen. “It took me a while to learn the game, but I think I've got the hang of it now."
Tom turned away from Simon Phipps to look at the patient. “You must have played chess before, Mr. Asherson. You haven't really learned it from scratch this morning. Don't you remember the school where you used to teach?"
“I tried it in the army,” Asherson said, “but I couldn't get the hang of it. I don't know why not—it seems easy enough now. It's just a matter of persisting until it clicks, I suppose. Can I have more medicine now? I really need to get out of here, but I need my medicine first."
“I'm sorry, Mr. Asherson,” Tom said, “but you're part of a clinical trial, and we have to stick very rigidly to the protocol. One dose is all you get—at least until you qualify for Phase Two, which we might be able to begin in a couple of months, if the rest of Phase One works out."
“To hell with protocol,” said Asherson, finally looking away from the screen, having checkmated the computer. “We're talking about my brain here. I'm better, and I intend to stay that way. You're right, of course—I could play chess. I do remember the school—but that's not important. I've got things to do. You'd better not mess me about, Dr. Wharton. I used to be in the SAS."
“No, you didn't, Mr. Asherson,” Tom replied, almost without thinking. “That's just a story you made up to tell your grandson."
Asherson's eyes narrowed momentarily, then widened again. “Is it?” he said, with sudden uncertainty. “I thought...” He fell silent.
“I suppose I'd better search out some new tests, Mr. Asherson,” Tom said. “Something tells me that you've moved beyond level two of Elementary Cognition. If the biology teacher's beginning to resurface, we'll need tests considerably more challenging."
“LAW-1
917,” Asherson said. “Monoclonal antibody originated in Germany, name of company withheld in accordance with client confidentiality policy. Original compound derived from mice, humanized to make it acceptable to the human immune system, tested in that form on rats. Stimulates the production of white blood corpuscles capable of the elective ingestion and metabolic breakdown of a CAG-repeat derivative of an enkephalin allegedly responsible for the renewal of neurons. Am I right?"
“That's the gist of it,” Tom agreed. “You haven't just been busy playing games, I see. If you understand that much, though, you must understand why it would be dangerous to risk an overdose."
“Wrong assumption,” Asherson said, in a blithely patronizing manner that he must have honed to perfection in the classroom. “You think it would be a bad thing to clear out all the CAG-repeat protein, because some of it must be performing some function that determined the selective value of the gene, albeit less efficiently than the normal version. That's not a danger. I need a second dose, Dr. Wharton. You have to give it to me. Admittedly, it'll remove one of the subjects from your trial—but efficient treatment takes ethical priority. I need the second dose, and you have no ethical grounds for withholding it."
There you go, Tom thought. Bring them back from Alzheimer's hell and they just turn into exactly the same kind of self-important prick that blights all the other trials. He'll be suing for compensation next because we refused to top up his medication.
“That's not true, Mr. Asherson,” Simon Phipps said, in the meantime. “If you were in mortal danger, Tom could abort this run of the trial to give you life-saving treatment, but you're obviously doing very well. We're not taking you out of the trial, Mr. Asherson. We need you in it. You're the best ad we've got!"
“Shut up, Simon,” Tom said, sharply. “What makes you think the assumption is wrong, Mr. Asherson?"
Asimov's SF, July 2007 Page 3