The Cure: An addictive, page-turning pandemic thriller

By Glenn Cooper

'Cooper [...] is no ordinary thriller writer, but one who asks big questions' SUNDAY TELEGRAPH
If you catch it, you forget everything. Your only hope is the cure. . .
He wanted to cure Alzheimer's Disease. . .

Single parent and neurologist Dr. Jamie Abbott makes a key contribution to treating Alzheimer's Disease. But the principal investigator short-circuits the study safeguards, releasing a highly contagious virus that wipes the host's memories. His daughter is one of the first victims.

As the virus spreads and civil order breaks down, Jamie embarks on a perilous cross-country journey. He needs to reach Dr. Mandy Alexander. She has the other half of a potential cure.

If he fails, he'll leave most of mankind to the oblivion of total amnesia.
What everyone's saying about Glenn Cooper:
'Fast paced and original, Cooper delivers' SUN

'Outstanding style and tense, gripping storylines' EUROCRIME

'Dynamic, inspirational. . . you will not be disappointed' FRESH FICTION

'Incandescent and explosive' JAMES ROLLINS

'Trying to protect your loved ones while traveling and trying to save the world makes for some great reading!' Netgalley 5* Review

'I really enjoyed this book and will give it a huge thumbs up. With a great story line and excellent main characters – I would highly recommend this book' Netgalley 5* Review

'I thoroughly enjoyed reading The Cure [...] a page-turning read with thought-provoking conundrums and culturally relevant conflict' Netgalley 5* Review

'It's scary and makes you realise COVID-19 isn't as grim as it could be. But it also makes you think what's next?! I read this in one sitting' Netgalley 5* Review

'A thought-provoking and utterly relevant read that has you on the edge of your seat, rapidly turning the pages to read more. Fantastic and original plot, that will have you hooked' Netgalley 5* Review

• Language: English
• Publisher: Bloomsbury Publishing
• Release date: Aug 20, 2020
• ISBN: 9781800242210

Glenn Cooper

GLENN COOPER is the author of the internationally bestselling Will Piper trilogy: Library of the Dead, its sequel, Book of Souls, and The Keepers of the Library. His other books include The Tenth Chamber, The Resurrection Maker, The Devil Will Come, Near Death, and the Down Trilogy. He has sold over 6 million books worldwide. Glenn graduated from Harvard with a degree in archaeology and received his medical degree from Tufts University. After practicing medicine, he served as the chairman and CEO of a biotechnology company in Massachusetts. He is also a screenwriter, film producer, and chairman of Lascaux Media. Glenn lives in Sarasota, Florida. Visit him at glenncooperbooks.com.

Book preview

1

It sounded like something was rattling the bars of an animal cage. Her frail, purple-veined hands were tightly wrapped around the slats of the safety rails, and she was working them with the full force of her emaciated frame. The racket made it down the empty hall to the nurses’ station.

The young nurse said, She’s at it again.

The ward supervisor didn’t look up from her paperwork.

Are you sure we’re not allowed to restrain her? the young nurse asked.

She’s the only one on the ward. Who’s she going to bother?

Me?

The supervisor told her that if she was so irritated, she could call Dr. Steadman and ask for a restraint order.

I’m not calling him for that, the young nurse said, horrified. Can’t I page the fellow on call?

Steadman’s personally handling all her orders.

Well, I’m not calling him.

Fine.

Then the high-pitched shouting started.

Shrieks. Rattles. Shrieks. Rattles.

The young nurse buried her face in her palms. God, not that too. What’s she saying?

It’s Japanese. Do I look like I speak Japanese?

Can’t she speak English?

She did. She only remembers Japanese.

Another nurse, this one older, emerged from the medication room and said, I’m pretty sure she’s saying she’s hungry and wants rice.

How do you know? the young nurse asked.

Her daughter-in-law told me. It’s either that or she’s wet herself.

You don’t remember which? the supervisor asked.

A shrug. She cycles between them.

Would you check on her? the supervisor asked.

The young nurse complained about having to gown up again. When she returned a few minutes later she said, I guess she’s hungry.

Dry? the supervisor asked.

Bone dry. I just wasted twenty dollars of isolation garments to find out she wants rice half an hour after she had breakfast.

She forgets she’s eaten, the older nurse said. My father got that way.

What time is Steadman doing the deed? the young nurse asked.

Sometime this morning, the supervisor said.

Maybe by the time my shift starts tomorrow she’ll be using the call button and watching soaps.

Dream on.

*

Roger Steadman arrived mid-morning, trailed by an entourage. He sailed down the corridor, his unbuttoned, long white coat billowing like the spinnaker of the beautiful Beneteau he kept at Baltimore’s inner harbor. His ruddy tan and fluid mobility gave him the appearance of a younger man, but he was not young. He was one of the gray-beards at the Baltimore Medical Center, a legendary figure in American neuroscience, his curriculum vitae as thick as a small-town phone book.

Ruth? he called out to the nursing supervisor. Is my patient ready for her close-up?

All three nurses stood. He was old-school. He liked them on their feet. She is, Dr. Steadman.

Well, good. Get the syringe and come help me into my gear.

You’re going to dose her yourself?

I am. History’s being made today. Mark your calendars, boys and girls, he said to the students. Years from now, this day could be hailed as the day we began to effectively treat, maybe even cure Alzheimer’s disease. I couldn’t very well pass up the chance to administer the first dose to Patient One. Besides if it’s not me, then Dr. Pettigrew is the only other physician on my team who’s gone through virus screening. I need him to take the pictures. Tell me you brought the camera, Colin.

His research fellow, Colin Pettigrew, raised the Nikon and said in a doleful English accent, I’ve got it right here.

Remember, the left side’s my good side. The right side’s pretty awesome too. At the awkward silence he added, You students, it’s okay to laugh once in a while. Don’t go through life taking yourself too seriously.

Medical students and residents congregated in the hall outside the gowning anteroom while the nursing supervisor and two doctors donned gowns, masks, booties, and gloves. Via the intercom, Steadman put on a show, thinly disguised as a Q&A session.

Mrs. Noguchi is the first patient in this Phase One clinical trial of a novel gene therapy for Alzheimer’s, he said. This is for the students, not you residents: what is a Phase One study designed to detect? Anyone. Call it out.

An eager student raised her hand. Safety.

Correct. Safety. We treat a small number of people sequentially, in this case up to ten patients with severe disease, and we do extensive safety profiling along the way. If all goes well, and I’m quite sure it will, we’ll conduct a far larger Phase Two trial designed to look for efficacy. Of course, we may get an early Christmas or Hanukkah present in Phase One and see an efficacy signal. We’ll know because we’ll be doing daily mental status and memory tests. Now, as I’ve said, this is a gene therapy trial. What are the essential components of a gene therapy?

Another student piped up, A targeted therapeutic and a virus for delivering it.

Steadman let the nurse fasten his gown behind his back. Correct. A virus and a payload. In this case the payload is a novel transcription factor, NSF-4, the recently discovered neprilysin-stimulating factor that we found to have a profound boosting effect on the natural production of neprilysin. Does anyone know what neprilysin is?

A bearded student smoothly answered. It’s a protease that accelerates the degradation of beta-amyloid.

And what, pray tell, is beta-amyloid? Steadman asked.

Several students tried to answer but the bearded one jumped the queue. It’s the toxic substance that builds up in the brains of Alzheimer’s patients. The protein tangles that form are thought to produce the dementia.

Correct, Steadman said. And kudos for knowing about neprilysin. You’re the first student who’s been able to answer that.

The bearded one kept on going. I believe NSF-4 was discovered by Jamie Abbott at Harvard.

Steadman hid his irritation behind the surgical mask. How on earth did you know that?

I got a PhD in neuroscience before going to med school.

From where?

Harvard.

Well that explains Dr. Abbott. Jamie is a junior colleague of mine. My contribution to the discovery and elucidation of NSF-4 is well known, of course, and the construction of this gene therapy product was exclusively my work.

Steadman wiggled thick fingers into sterile gloves.

All right, almost ready, he said. The idea here is to get high concentrations of NSF-4 into the brain to chew up the beta-amyloid tangles and reverse the Alzheimer’s dementia. Before I do the procedure, who, other than our PhD friend knows why we just don’t administer neprilysin or NSF-4 directly instead of going through all the complexity of gene therapy?

Another student tentatively answered, Because they won’t cross the blood-brain barrier?

Correct. They are large peptides that won’t get absorbed into the bloodstream if given orally and won’t get into the brain if given intravenously. So, we piggyback our payload with a novel adenovirus that is not only perfectly harmless, but this new one, developed at Indianapolis, penetrates the central nervous system like a hot knife through butter. Once there, the virus delivers its payload inside the target neurons. Our virus has no ability to integrate with or alter the host genes. After doing its job the virus simply degrades. For that reason, we plan to re-dose our patients once a month.

Again, the bearded student: I don’t recall other gene therapy trials needing isolation procedures. Why this one?

Steadman answered gruffly, In my opinion it’s overkill, but our overly cautious safety committee is requiring us to do so. His voice rolled into sarcasm. In their infinite wisdom, because this particular adenovirus has never been used before, they wanted to eliminate the highly remote possibility that a visitor might introduce a second virus. Hypothetically, and I stress, hypothetically, that virus might combine with our vector, creating a hybrid that could integrate into the patient’s genome, or become capable of making copies of itself. We’ve even been required to pre-screen the patient, all the medical workers, and the patient’s immediate family for active viral infections. Research is sometimes a pain in the rear, boys and girls. All right, it’s show time.

Steadman, Pettigrew, and the nurse entered the patient’s room. Mrs. Noguchi regarded them warily, scooted to the farthest side of her bed, and began spouting off in Japanese.

Kon’nichiwa, Mrs. Noguchi, Steadman said, approaching the bed. He played to his audience who were listening via intercom and watching behind two sets of windows. She has lost her ability to speak or understand English and has reverted to her native language. This has been a challenge in assessing her mental state, but we have a research nurse who speaks Japanese, so all is well. Mrs. Noguchi is seventy-eight. She has rapidly progressive disease. She has been on standard Alzheimer drugs with negligible impact. Without further experimental therapy I would expect her to be in a vegetative state within six months and dead within a year. Nurse, the syringe, please.

She handed him a pre-filled syringe attached to a thin catheter.

Hold her head, please, Steadman said. You can’t imagine the paperwork if the dose winds up on her cheek.

With her head clamped tightly, and Pettigrew pressing repeatedly on his shutter button, Steadman inserted the catheter all the way into one of her nostrils and pushed the plunger.

That’s it, Steadman said triumphantly. Patient One has been dosed. Did you get all the pictures I wanted, Colin?

*

The young Japanese man approached the nursing station. It was almost 9 p.m. The night nurse, with only one patient on the research ward, was absorbed in her book.

Excuse me, the man said.

The nurse was startled. How can I help you?

I know it’s past visiting hours, but I was hoping I could see my grandmother.

Mrs. Noguchi?

Yes. Is it possible?

Visiting hours were till eight.

I know. I’m sorry. I just got back from a trip. I heard she got treated today and I wanted to see her.

The nurse sighed. Are you on the list? I can’t let you see her if you’re not on the list.

I’m her grandson.

What’s your name?

Ken Noguchi.

She scanned the card taped to the desk. I’ve got Kenji Noguchi.

The young man smiled. Kenji was his father. That’s me.

Have you visited before?

I haven’t.

The nurse sighed again. All right. Let me show you how to put on the isolation clothes. They’re very strict around here. I’ll let you have ten minutes. You speak Japanese?

Another smile. I think so.

Good, ’cause I can’t get through to her. Be a dear and find out if she wants her pudding.

The nurse let him enter the anteroom. Via the intercom, she gave him instructions on gowning. As he dressed, he coughed and wiped a few beads of sweat from his forehead.

You’re not sick, are you? she asked. If you’re sick you can’t go in.

No, I’m not sick. It’s an allergy.

He took off his shoes.

You don’t have to do that. You put the booties over them.

It’s respectful to take off your shoes.

He finished with the booties and gloves.

All right, she said, you can go in. I’ll be back.

He slid the booties over the floor and stood by the bed, waiting for his grandmother to open her eyes. He would have stood there for the full ten minutes without disturbing her, but he began to cough into his mask.

She opened her eyes and seemed terrified.

Grandmother it’s me, he said in Japanese.

She gripped the bedrail and began tugging at it.

Don’t be scared, it’s your grandson.

She kept trying to get away from him. He looked over his shoulder to make sure the nurse wasn’t looking and pulled down his mask.

See, it’s me.

She stopped rattling the rail and tried to focus her watery eyes. Kenji, my son?

No, grandmother, it’s Kenneth, your grandson.

She smiled vacuously.

I was doing my work in Japan, grandmother. I have just returned. I came from the airport.

Do you know why I am here? she asked, searching the room. Who are these people? Why are they hiding behind masks?

You are here to get a new medicine. They are trying to help you.

Do you know why I am here? she asked again.

To receive medicine, he repeated.

You are my grandson, you say? Give me a kiss.

He leaned over to kiss her forehead and when he did, he coughed again.

Sorry, he said, taking a step back and pulling up the mask.

The aerosol from his mouth dispersed at a speed of fifty feet per second. It coated her blinking eyes with the finest of mists. The virus particles he carried from Japan settled on her shimmering, pink conjunctivae. Even before he left the room, they began to enter her bloodstream.

By the morning her grandson’s virus had overwhelmed her immune defenses and had sliced through her blood-brain barrier. Inside her brain, millions of virus particles infected millions of neurons and some of them came in contact with the gene therapy viruses that had already taken up residence. Where they met, the two viruses stuck like glue and fused membranes. Instantly, their genetic material began to combine.

The new virus that formed didn’t have a name.

*

Dr. Steadman fast-walked down the hall with Dr. Pettigrew loping at his heels. The nursing supervisor joined the procession.

How long has she been like this? Steadman asked.

Thirty minutes. I called as soon as we saw the change.

On her early morning vital-sign check, Mrs. Noguchi had registered a minor fever. By mid-morning her temperature had climbed, and she began to cough. When informed, Steadman ordered an infectious diseases consult.

The ID fellow isn’t on the pre-screened list, the nurse had told Steadman.

I don’t care, Steadman had said. This is an emergency.

An x-ray tech named Gonzalez had also gotten Steadman’s special dispensation to enter. While she was positioning the image detector under Mrs. Noguchi’s back, the patient coughed and showered her forehead and mask.

Please don’t do that again, Gonzalez had scolded. I can’t afford to catch your cold. I’m going on vacation.

Steadman, Pettigrew, and the nurse raced through the gowning, and once inside her room, Steadman took stock. Mrs. Noguchi was on her back, motionless, her eyes closed. He asked what the ID people thought.

They don’t know yet, the nurse said. They took cultures. We also did a portable chest x-ray. It was negative.

Did they do a lumbar puncture? Steadman asked.

They said neuro should do it, the nurse said.

Kon’nichiwa! Steadman said loudly. When there was no response, he stood directly over her and shouted it again, louder.

The nurse said, She’s completely unresponsive.

I can see that, Steadman muttered.

He ran through a rapid neurological exam and declared her motor and sensory pathways intact.

There’s nothing focal, he said, no sign of a stroke or a bleed. This is looking like a diffuse process. Get ID back up here. I want to talk to them in person. With fever and coma, we’ve got to rule out some kind of encephalitis.

Could it be from the gene therapy? the nurse asked.

Of course not, Steadman snapped angrily. Don’t be stupid. The vector is completely benign.

The nurse’s eyes widened over her mask and, stung by the insult, she retreated a step.

Steadman took no notice. Colin, I want you to do a lumbar puncture. Ruth, go and arrange an MRI. Tell them I want it done STAT. We’ll have to send her downstairs with a mask.

The nurse hurried off, leaving the doctors behind.

I’ll get an LP kit, Pettigrew said.

Send her CSF for a full serological screen.

Of course, the fellow said. By the way, he added, pointing to the camera under his gown, did you want me to take any pictures?

No, Colin, Steadman seethed, I don’t want you to take any pictures.

2

Jamie Abbott was sweating, and his heart was ticking along at about one-fifty.

Hey, is that Derek? he panted into the speaker.

Yeah, who’s this?

It’s Jamie Abbott. How’re you doing? I was looking for Mandy. I hope I’m not calling too late.

The reply was unfriendly. No, she’s available. I’ll get her.

Jamie pedaled and waited. As he leaned into the racing handlebars, sweat dripped from his forehead onto the bicycle. Ringlets of droopy dark hair fell over his eyes and he kept having to sweep them back. Growing up, his mother said he had poodle hair, and he supposed he still did. It defied styling and he always looked slightly unkempt. Adding to the impression was his heavy beard. By midday, he already sported a five-o’clock shadow.

Amanda Alexander came on the line. Derek said you sounded out of breath.

I’m on my bike.

It’s ten o’clock in Boston. You’re in Boston, right?

Yeah. It’s a stationary bike. I’m doing a thirty-mile sprint.

Why?

He kept up his furious pedaling. I turned forty. That’s when guys start to get fat.

That’ll be the day. What’s going on?

I tried your mobile.

I shut it off at night. I don’t see patients like you do, remember? What’s so urgent?

You didn’t see the email Steadman just sent out?

I told you, I power down. You pick up your emails on a bike?

Why wouldn’t I?

Oh, I don’t know, she said facetiously. What’s the email?

I think you should read it. I’ll hang on.

He did another half mile before she came back and said, Christ, Jamie.

The email was titled, Urgent Update to Study BMCH-44701, Phase 1 Trial of a Novel Gene Therapy Agent for Alzheimer’s Disease. It was from Steadman, addressed to Jamie, Mandy, and the other members of the study safety committee, with copies to various personnel at the FDA, National Institutes of Health, and Baltimore Medical. The email began, Patient 01 a 78 yo female who was enrolled three days ago has experienced a serious and unexpected adverse event. The message went on to describe her clinical status and lab values.

What do you think? Jamie asked. Is there any way this could be from the vector?

I put that strain through every imaginable model. It’s a hundred percent non-pathogenic and non-immunogenic. She sounded hurt. This was her baby he was talking about. I introduced it to dozens of severely immunocompromised mice. They didn’t turn a hair.

Cute. Immunocompromised mice were hairless.

There’s no way it could’ve caused encephalitis.

I’m not doubting you, but the patient clearly has an encephalitis of some type. We’ll know soon if anything shows up on serology.

Mandy said, Steadman says her MRI was unchanged from baseline. Are there portable MRI scanners?

Yeah, you noticed that too. No such thing. It means he broke isolation protocol and sent her to an MRI suite. Not smart.

He wants us to meet in person on Friday. Can you make it? she asked.

Jamie’s bike beeped at the thirty-mile mark. Can we talk?

We are talking.

You know what I mean.

She sounded tentative and weary. Yes, we can talk.

He stopped pedaling. I can’t believe I’m going to see you again so soon.

3

Theresa Gonzalez, the Baltimore Medical x-ray tech, was in a middle seat in coach silently cursing. She had been up since before dawn to catch an early flight from BWI to Miami. As the morning progressed, her throat was getting scratchy and she was starting to feel chesty.

She wound up saying, rather than thinking one of her damn-its and the elderly man in the window seat said, Excuse me, did you say something?

I apologize, she said, hacking into a tissue. I’m going on vacation and I think I’m catching a cold.

The man was pleasant enough. Don’t you hate it when that happens?

I think I know who coughed on me.

Well I hope you won’t do the same to me, he said cheerfully.

I’ll be careful.

Are you staying in Miami? he asked.

I’m boarding a cruise there.

That’s wonderful. Where to?

The Bahamas, British Virgin Islands, and St. Thomas. I can’t wait.

She coughed again but this time she was a little slow with her tissue. He must have felt some spray land on his forearm because he dabbed at it with a napkin.

I apologize, she repeated.

The man’s smile faded. He put the armrest down and pressed himself against the window.

The stewardess who handed Gonzalez a can of soda and a bag of chips would fly on to Dallas later in the day to attend a training seminar with flight attendants from twenty states.

That night, the window-seat passenger had dinner in Coral Gables with his three elementary-school grandkids, his daughter, a pharmaceutical sales rep with a busy schedule for the next day, and his son-in-law, an accountant who had an early tee-time in a foursome that included a Delta pilot who would fly to London Gatwick in the evening.

Terry Gonzalez, though a little feverish, had her first on-board meal with eleven randomly assigned passengers from five states, coughing her way through the appetizers and entrée before excusing herself. In the morning she was feeling too ill to leave her cabin, but the rest of her dinner companions disembarked at their first port-of-call in Nassau where some of them had lunch at a café next to a table of Japanese tourists on their next-to-last day of holiday. One couple stopped a Swede on the street on his final day of a business trip to see if he knew how to get to the pirate museum. Another couple asked an Italian schoolteacher to take their photo.

And so it began.

4

Mandy peered through the peephole then opened the door, shaking her head in disapproval. How’d you get my room number?

I asked, Jamie said. I’m told I have a trustworthy face. Can I come in?

I don’t think that’s a great idea. I’ll come down to the lobby bar in a few.

Just give me a minute, okay?

She didn’t look particularly happy. Come out of the hallway. We only know about twenty people staying here.

She sat on the bed, crossed her legs, and gestured at the chair. He wanted to sit beside her, to take her in his arms, to push her onto her back, but he managed to control himself.

Fourteen years with no contact then this. It was a year ago when they found themselves in Bethesda on the same safety committee. Meeting again after all those years was one of those happenstances in the world of science—not something either of them had expected, but not totally unexpected either. He’d been aware that Steadman had chosen her virus, and she’d been aware that Jamie had done the work on the NSF-4 payload. But until then, their research orbits had been separate.

He recalled the day he saw her at the breakfast buffet before the first general session. In his mind’s eye, the Mandy of fourteen years ago had long, wavy hair and always wore the same pair of faded, hip-hugger Levi’s in the lab. The older Mandy had a short, practical cut and a smart dress, but she hadn’t really changed all that much. Her delicate face had the same porcelain fragility, her body was still lean, the result of good genes she insisted, not exercise. She also smelled the same, like she had just rolled through a meadow of wildflowers. He never forgot her scent. It wasn’t from a bottle, it was her, and it was one of those sense memories that, to the present, triggered longings. He hadn’t known what to expect. She wasn’t someone who lived her life on social media—he had looked her up, but her online presence was light. All he could do was remember her as she had been when they were both so very young.

Sitting across from her now, he thought this might be the very same room she had during the first safety meeting. He had a perfect memory of how she looked the morning after the night they spent together. She had flitted between happiness to the point of giddiness and remorse. She acted the same way every time they saw each other at these quarterly meetings in Bethesda, the red-letter dates on his calendar.

How was your flight? he asked.

No problems. Yours?

It took me longer to drive to Logan than fly to Reagan National.

Why are we talking about travel? she asked.

He laughed and pushed away a lick of hair from his eye. Warming you up with small talk.

Warming me up for what?

He knew she knew the answer.

Derek didn’t seem too pleased to hear my voice.

Didn’t he?

He didn’t say anything?

She shook her head in thin-lipped discomfort.

He has no idea, right? he said.

Of course not! And he never will!

Look, I do feel guilty, in case you were wondering. I don’t know the guy, but I’m sure he’s in love with you. He sounded sincere because he was.

Her lower lip trembled.

He hit her with his blue eyes and let it fly before she could say anything. Look, I want to be with you. If you listened to your heart, I think you’d say the same thing.

She stood. I told you last time I couldn’t do this anymore. That’s why I wanted to talk in the lobby.

Come on, stay. I’ll be a perfect gentleman.

She sat again, working her jaw, dimpling her cheeks.

Nothing’s changed. It won’t hurt Derek. I have too much regard for him.

Regard, he said. It came out slathered in sarcasm and he regretted it.

Yes, regard. What’s happened between us is—was a mistake. I’m not going to let it happen again. And by the way, you wouldn’t have left Carolyn.

He looked out the window to the hotel parking lot. I don’t want to talk about her.

Mandy had learned about Carolyn’s death years after the fact. The two women had never met, although Mandy did know Jamie was married when they began their affair. He was doing a fellowship at Harvard on brain transcription factors. She was in a lab across the hall constructing viral vectors for gene therapy. They both worked late. These things happened. One day it slipped he had a baby. Mandy blew up and that was the beginning of the end. Within a year she had moved to Indianapolis to take a junior faculty position at the medical school. There she met Derek, a biophysicist. Mandy and Jamie’s lives diverged for what might have been forever.

You’re right, she said. Carolyn doesn’t have a voice, but Derek does. I’m just saying we made the right decision back when.

I would have left Carolyn if it weren’t for Emma.

How is she?

She’s more of a handful than ever. You and Derek were smart to keep things simple.

She didn’t tell him they had tried to conceive for years. Maybe we were, maybe we weren’t. Do you have enough help?

Some. Take tonight. This thing was short notice, but I was able to have her stay at her girlfriend Kyra’s house. Not my favorite of her friends, but it’s safer than leaving her home alone. Well, she wouldn’t have been alone, if you know what I mean.

Poor you. She sounded genuinely sympathetic. Let me buy you a drink at the bar. I think we’d both do well to have a touch of ethanol aboard before the meeting starts. It could be a rough one.

*

The safety committee chatted among themselves around a horseshoe table at a hotel conference room. The scheduled start time had passed, and twenty minutes later there was still no Roger Steadman. Jamie caught Mandy’s eye and pointed to his watch with an eye-roll. She reciprocated with a knowing look. Neither were great fans of the good doctor.

Steadman finally swept in with Colin Pettigrew and took his place at the head of the table.

Couldn’t be helped, Steadman said. We were delayed leaving Baltimore by certain events. Our patient died this afternoon.

When the room quieted, Steadman gave his report. Mrs. Noguchi had never regained consciousness. Her family insisted on withholding heroic measures and she had succumbed to respiratory arrest that afternoon.

An FDA official asked, You had indicated her clinical syndrome was compatible with an encephalitis. Has that been confirmed?

Pettigrew spoke up. We did a broad serological screen on samples of the patient’s blood, urine, and cerebrospinal fluid. The cause of death is Japanese encephalitis.

Could you repeat that? Mandy said, snapping to attention.

Japanese encephalitis. Yes, it is surprising, Pettigrew said, or at least it was.

What do you mean, was? Mandy asked.

Steadman took over. Patient One was born in Japan but she had not been there for several decades or, for that matter, anywhere else where the virus is endemic. Shortly after we received the serology results a twenty-nine-year-old man was admitted to the Baltimore Medical emergency ward with fever, vomiting, and altered consciousness. That patient is the grandson of Patient One. Presently he is in an isolation bed in our Neuro-ICU where his condition is critical. We learned from his family that two days ago he returned to Baltimore from Japan. Apparently, he is an ornithologist who had been studying wild bird populations in a remote area of Honshu Island. The JE virus is endemic there and there is some question whether he was ever immunized.

Jamie interrupted. Dr. Steadman, I don’t understand how this relates to our study patient. Surely this young man couldn’t have come in contact with her. Unless my memory fails me, a grandson wasn’t on the pre-screened list of permitted visitors you filed with the committee.

Steadman certainly would have known this moment was coming but he still looked as if he had taken a swig of something extremely bitter. He wasn’t on the list. It seems there was a breakdown at the level of a ward nurse. He showed up to see his grandmother. His name is similar to his father’s who is on the list.

Jamie glowered at Steadman and said angrily, This was exactly the kind of protocol violation I and others warned against every time we’ve met. As recently as last month!

Well, Steadman said, looking down at his papers, we shall endeavor to reinforce this safety aspect of the protocol for subsequent patients.

Jamie was incandescent, and it showed. I don’t think there should be further enrollment, not until we’ve had a chance to perform an exhaustive investigation of this incident.

The director of the FDA Office of Cellular Tissue and Gene Therapies, the division responsible for the trial, said, Dr. Abbott, tell us what investigations you’d want to see.

First and foremost, I think we need to do molecular probes on autopsy samples of the patient’s brain. There’s an autopsy, right?

Pettigrew indicated it was ongoing.

Are the pathologists using full biohazard protocols? Jamie asked.

They have been so advised, Pettigrew said.

Jamie addressed Mandy. Dr. Alexander, can you handle this kind of material at Indianapolis?

Absolutely, we have a P4 facility.

Then I think Dr. Alexander ought to do the probes for the presence of her adenovirus in the patient’s tissue and see if it’s been altered in any way.

Steadman was manifestly tired of being a whipping boy, especially at the hands of a researcher down the totem pole. Why are we going there, Jamie? This woman died from Japanese encephalitis. I know you’ve been beating this viral recombination drum incessantly, but this is not the time.

You’re right, Jamie said, and I hope like hell it’s not the time. We don’t need a new virus on our hands, do we? Mandy—sorry, Dr. Alexander—did you ever test for the recombination potential of your virus and the Japanese encephalitis virus?

"That one specifically? No. We couldn’t test for every virus known to man. We had to prioritize. JE is a member of the Flaviviridae, a family that includes West Nile and St. Louis’s encephalitis. I tested both of those, but JE is not identical. I certainly will test it now."

Steadman was not going to fade into the wallpaper just yet. While all of you are wringing your hands over extremely remote hypothetical concerns, I’ll be working on identifying the next patient so we can keep this critically important research moving forward. Millions of patients with Alzheimer’s and their families are waiting for us.

Jamie nodded curtly. Those of us around this table are every bit as committed to Alzheimer’s research as you are, but I for one am relieved that this committee required you to insert a suicide gene into the vector. In the worst-case scenario, and I’ll freely admit it’s remote, we’ll be able to destroy any new recombinant virus.

Jamie sat back and waited for him to respond, but Steadman remained largely quiet and sullen for the rest of the meeting.

5

She was resembling her mother more and more and Jamie worried it was affecting the way he reacted to her. She wore her red hair long, with fat spiraling curls the way Carolyn had worn hers, her lips seemed to be in a semi-permanent pout like her mother’s, and as the baby fat melted, her figure was starting to resemble Carolyn’s too. Sometimes, when he was especially tired, he had to catch himself from using the wrong name. Carolyn had been a master at pushing his buttons, and Emma was becoming an all-star herself. It had to be more nature than nurture; she was only two when Carolyn died.

Tonight, Emma marched in two hours later than promised, reeking of cigarettes, wearing too much makeup for his liking, her skirt ridiculously short. The positives: he was pretty sure she wasn’t stoned, and she didn’t have alcohol on her breath.

Where’ve you been?

The mall. She paused to rub the belly of their dog, Romulus, before making for the stairs.

You didn’t say you were going to the mall.

You didn’t ask.

He raised his voice. Do I have to? You said you were coming home.

Oh, please.

Did you at least eat?

What does one do at the mall? I wonder? Oh, I know, eat.

Would you cut the crap, Emma? I had a messed-up day.

Well, boohoo. Join the club. And with that, she was gone. Heavy steps and, seconds later, a door slamming.

He kicked off his shoes and reached for the remote. Romulus, a black, wire-haired mutt, just turned eleven, jumped on board and rested his head on Jamie’s legs.

The Bethesda meeting had dragged on, and after a group dinner, knots of scientists talked in the bar until late. Steadman hadn’t stuck around. He begged off to return to Baltimore to check on the autopsy results. Jamie watched Mandy peel off and head to the elevators. He didn’t try to stop her.

In the morning he caught the first shuttle to Boston without seeing her again. When he landed, he went directly to the hospital to do clinical rounds with his neurology fellows. The afternoon was consumed by his outpatient clinic. Now he wanted nothing more than to watch something unchallenging for an hour before packing it in for the night, but his ringing mobile got in the way. He grunted at the number. It was the ER at Mass General.

Jamie, sorry to bother you but I’ve got a case that’s not making sense.

Carrie Bowman was his strongest neuro fellow. She was rarely stumped and rarely called for help.

He put the TV on mute. Okay, shoot.

She summarized the case. This is a twenty-six-year-old white male, a personal trainer, who presented a few hours ago with global amnesia after a day of low-grade fever and cough. There’s no history of head trauma or headache. The amnesia isn’t a type I’ve seen before. He’s fully conscious and alert, but over a period of several hours he seems to have progressively lost his memory, this according to his brother who brought him in. Now he’s largely non-communicative, but he responds to auditory stimuli with startle reactions. He can’t write or point to letters. He’s also got an intermittent, dry cough.

Jamie switched off the TV. He already knew he’d be heading into town. What’s his affect? he asked.

He looks like a scared animal. He’s making guttural and whimpering sounds mostly, with a few simple words scattered in—kind of a word salad.

You said he had a fever.

It was 38.1 a few minutes ago.

Chest x-ray? Scans? LP?

Give me a chance.

Sorry.

Other than his altered mental status and his temperature, his physical and neuro exams were normal. On chest x-ray he’s got a diffuse, ground-glass infiltrate the radiologist says is compatible with a viral pneumonia. His brain MRI was unremarkable. For labs, his white count was mildly elevated with a moderate lymphocytosis. His CSF was under normal pressure with slightly elevated protein and gamma globulin, a normal glucose, and eight mononuclear cells.

All compatible with a viral syndrome, Jamie said. Any exotic travel?

None. The house staff did send off cultures and serologies.

All right, he said, getting up. I’m coming in.

He got his jacket and car keys and bounded up the stairs. He had to knock loudly to be heard over the music.

Emma, I’ve got to go into the ER. Emma?

Through the door he heard, Knock yourself out.

Homework and bed. And walk Rommy. I’ll call you.

*

The patient’s name was Andy Soulandros. Jamie reviewed his chart and parted the curtain around his bed. He was a tall, well-muscled fellow who immediately alerted to the sight and sound of the moving curtain. Carrie’s scared-animal analogy was apt. He looked like a rabbit at night stunned by a flashlight. His eyes were fixed on Jamie’s every motion and he was shaking.

Hello, Andy, I’m Dr. Abbott. Do you remember Dr. Bowman? She examined you earlier. Nod your head if you remember her.

There was no sign of comprehension.

Jamie approached the bed.

The young man said, I-I-I— and then made a high-pitched sort of a moan and pulled at his wrist and ankle tethers.

They had to restrain him to keep him from bolting, Carrie said.

Look at the hairs on his forearms, Jamie said. They were bristling. He’s got a vigorous piloerection reflex, a primitive reaction to fright or cold and it’s not cold in here.

I didn’t notice that, Carrie said.

It’s okay, Andy, Jamie said. I know you’re frightened. We’re going to try to help you. Are you having any pain?

There was more pulling at his restraints.

Do you know where you are? Do you know your name?

When he didn’t respond, Jamie said, I’m going to examine you, if that’s okay.

Jamie took out a penlight and shone it into his eyes.

Oh-oh-oh-oh!

Does the light hurt?

I-I-I-I—

During the exam, the patient was rigid, grunting and spouting a few nonsense monosyllables and out-of-context words. When Jamie was done, they regrouped at the nurses’ station.

"I agree with your exam, Carrie. There’s not much that’s remarkable about it, certainly nothing helpful except for his pulmonary signs. I wonder if he