“I’m actually looking for both, Alice. Alzheimer’s affects the parietal lobes pretty early on, and that’s where we keep our internal representations of extrapersonal space. John, this is why I want you to go running with her.”

John nodded. They were ganging up on her.

“John, you know I can’t draw.”

“Alice, it’s a clock, not a horse.”

Stunned that he didn’t defend her, she glared at him and raised her eyebrows, giving him a second chance to verify her perfectly valid position. He just stared back at her and spun his ring.

“If you draw me a clock, I’ll show you three forty-five.”

Dr. Davis drew a clock face on a new sheet of paper, and Alice drew the hands pointing to the correct time.

“Okay, now I’d like you to tell me that name and address I asked you to remember earlier.”

“John Black, something West Street, Brighton.”

“Okay, was it forty-two, forty-four, forty-six, or forty-eight?”

“Forty-eight.”

Dr. Davis wrote something lengthy on the piece of paper with the clock.

“John, please stop shaking my chair.”

“Okay, now we can talk about clinical trial options. There are several ongoing studies here and at the Brigham. The one I like the most for you starts enrolling patients this month. It’s a phase three study, and it’s a drug called Amylix. It appears to bind soluble amyloid-beta and prevent its aggregation, so unlike the drugs you’re on now, there’s the hope that this could prevent the disease from progressing further. The phase two study was very encouraging. It was well tolerated, and after a year on the medication, the patients’ cognitive functioning seemed to have stopped declining or even improved.”

“I assume it’s placebo-controlled?” asked John.

“Yes, it’s double-blind and randomized to placebo or one of two doses.”

So I might get only sugar pills. She suspected that amyloid-beta didn’t give a shit about placebo effects or the power of wishful thinking.

“What do you think of the secretase inhibitors?” asked John.

John liked these best. Secretases were the naturally occurring enzymes that released normal, unharmful levels of amyloid-beta. The mutation in Alice’s presenilin-1 secretase rendered it insensitive to proper regulation, and it produced too much amyloid-beta. Too much was harmful. Like turning on a faucet that couldn’t be turned off, her sink was rapidly overflowing.

“Right now, the secretase inhibitors are either too toxic for clinical use or—”

“What about Flurizan?”

Flurizan was an anti-inflammatory drug like Advil. Myriad Pharmaceuticals claimed it decreased the production of amyloid-beta 42. Less water into the sink.

“Yes, there’s a lot of attention on that one. There’s an ongoing phase two study, but only in Canada and the UK.”

“How do you feel about Alice taking flurbiprofen?”

“We don’t have the data yet to say whether or not it’s effective for treating Alzheimer’s. If she decides not to enroll in a clinical trial, I would say that it probably couldn’t hurt. But if she wants to be in a study, flurbiprofen would be considered an investigational treatment for Alzheimer’s, and taking it would exclude her from the study.”

“All right, what about Elan’s monoclonal antibody?” asked John.

“I like it, but it’s only in phase one and enrollment is currently closed. Assuming it passes safety, they won’t likely initiate phase two until spring of next year at the earliest, and I’d like to get Alice in a trial sooner if we can.”

“Have you ever put anyone on IVIg therapy?” asked John.

John also liked the idea of this one. Derived from donated blood plasma, intravenous immunoglobulin was already approved safe and effective for treating primary immune deficiencies and a number of autoimmune neuromuscular disorders. It would be expensive and not reimbursable by their insurance company because of its off-label use but worth any price if it worked.

“I’ve never had a patient go on it. I’m not against it, but we don’t know the proper dosing, and it’s a very untargeted and crude method. I wouldn’t expect its effects to be anything more than modest.”

“We’ll take modest,” said John.

“Okay, but you need to understand what you’d be trading off. If you decide to go ahead with IVIg therapy, Alice wouldn’t be eligible for any of these clinical trials with treatments that are potentially more specific and disease modifying.”

“But she’d be guaranteed not to be in a placebo group.”

“That’s true. There are risks with either decision.”

“Would I have to go off the Aricept and Namenda to participate in the clinical trial?”

“No, you’d keep taking them.”

“Could I go on estrogen replacement therapy?”

“Yes. There’s enough anecdotal evidence to suggest that it’s at least to some degree protective, so I’d be willing to write you a prescription for CombiPatch. But again, it would be considered an investigational drug, and you wouldn’t be able to participate in the Amylix trial.”

“How long would I be in the trial for?”

“It’s a fifteen-month study.”

“What’s your wife’s name?” asked Alice.

“Lucy.”

“What would you want Lucy to do if she had this?”

“I’d want her to enroll in the Amylix trial.”

“So Amylix is the only option you can recommend?” asked John.

“Yes.”

“I think we should do the IVIg along with flurbiprofen and the CombiPatch,” said John.

The room became still and quiet. An enormous amount of information had just been passed back and forth. Alice pressed her fingers on her eyes and tried to think analytically about her treatment options. She did her best to set up columns and rows in her head to compare the drugs, but the imaginary chart didn’t help, and she tossed it into the imaginary trash. She thought conceptually instead and arrived at a single, crisp image that made sense. A shotgun or a single bullet.

“You don’t need to make a decision on this today. You can go home and think about it some more and get back to me.”

No, she didn’t need to think about it any further. She was a scientist. She knew how to risk everything with no guarantees in search of the unknown truth. As she’d done so many times over the years with her own research, she chose the bullet.

“I want to do the trial.”

“Ali, I think you should trust me here,” said John.

“I can still draw my own conclusions, John. I want to do the trial.”

“Okay, I’ll get you the forms to sign.”

(Interior of Doctor’s Office. The neurologist left the room. The husband spun his ring. The woman hoped for a cure.)

JULY 2004

John? John? Are you home?”

She was sure that he wasn’t, but being sure of anything these days was tattered with too many holes to contain the meaning that it used to. He had left to go somewhere, but she couldn’t remember when he left or where he was going. Did he run to the store for milk or coffee? Did he go out to rent a movie? If either were the case, he’d be back any minute. Or did he drive back up to Cambridge, in which case he’d be gone for at least several hours and possibly the night? Or did he decide, at last, that he couldn’t face what lay ahead for them, and he just plain left, never to return? No, he wouldn’t do that. She was sure of it.