by Glenn Cooper
“It’s going to spread like adenoviruses by the respiratory route,” she said, “and infect brains like the JE virus. It could be highly contagious.”
“The adenovirus is a DNA virus. JE is an RNA virus,” he said. “How the hell can they hybridize?”
“Hybrid DNA-RNA viruses have been reported,” she said. “It’s rare but it happens. The really scary thing is that the new virus seems to be able to do all the things we engineered the original virus not to do. It’s self-replicating and seems to be able to insert genetic material into nerve cells.”
He gave his scientific opinion. “Fuck.”
She told him that the memory centers of Mrs. Noguchi’s brain, particularly the medial temporal lobes, had lit up like a Christmas tree from her molecular probes. The new virus and Jamie’s NSF-4 payload were present in abundance, or rather a version of NSF-4 that was similar, though different.
“Your NSF-4 looks like it’s been mutated too.”
“Mutated how?”
“It’s not my area, so I ran the sequences through the NIH GenBank. The new sequence appears to be novel, but it’s similar to a known protein I’ve never heard of. It’s called CREB-1.”
He felt a spasm of nausea. “Oh, God.”
His reaction was contagious. She sounded scared too. “What is it?”
“It’s Cyclic-AMP Response Element Binding Protein-1. It’s a transcription activator responsible for the storage of memory in the brain. The biochemical pathways for laying down long-term memories are pretty well worked out. The pathways for retrieving stored memories are a lot less understood. Some people, me included, have been looking for new CREBs that might be responsible for memory retrieval within a family of factors related to NSF-4. The hypothesis is that these transcription factor activators open and shut memory retrieval gates. My patient in Boston and the patient in Baltimore—they’re both behaving as if a CREB-type factor is sitting on their retrieval gates blocking recall. It’s as if their memories have been wiped out.”
“Is it reversible?”
“By activating the suicide gene, I think so. I hope so. There’s no reason to think that the virus won’t respond to the suicide gene and self-destruct, right?”
“It should,” she said. “It was designed to work for any known virus or even a hybrid.”
“We can pat ourselves on the back for forcing Steadman to build it in.”
“You led that charge,” she said.
He wasn’t looking for a compliment. “Fortunately, we can blow this thing out of the water by activating the gene with doxycycline. If we destroy the virus then new CREB-like factors are going to stop being produced. The factors blocking the gates should naturally degrade and memory retrieval should return. I already dosed my patient and I told Colin to dose his too.”
“And?”
“We’re waiting to see.”
“Tell me you were wearing a mask when you examined him.”
“Afraid not.”
“Christ, Jamie. You need to take the doxy just in case. I’m worried about you.”
“I already took it. I’ve been passing it out like candy to everyone in quarantine.”
“That’s a relief.”
“First good news I’ve had tonight,” he said.
“What news?”
“That you’re worried about me.”
7
Jamie had been asleep in a house-staff on-call room for all of thirty minutes when he got a page that the CDC team had arrived from the airport in a caravan of screaming sirens and blue lights.
Through the window, he saw the first light of dawn painting the sky over Beacon Hill a blush pink. It was late September, always one of his favorite months, when the days were short-sleeves-warm, but the nights were cool and crisp. When Emma was younger, she counted September her favorite too. There was apple picking in the country and raking leaves into jumping piles in their backyard. She even used to like going back to school and writing her what-I-did-this-summer essay.
Where had that sweet little girl gone? His psychologist friends described her behavior as oppositional-defiant. He called it being a jerk.
He needed to call her before she left to catch the bus. He tried twice on the home line and twice on her mobile before she finally picked up on her mobile.
Her exasperation bled through the connection. “What?”
“I’ve been trying to get you.”
“I noticed.”
“I didn’t make it home last night.”
“You’re an adult. I’m not judgmental like some people I know.”
“Very funny.”
She was on her usual short fuse. “Look, I’m going to be late. What do you want?”
“I want you to skip school today.”
He could picture her doing a theatrical double take. “Say what?”
“You heard me. We’ve got a situation.”
“What kind of a situation?”
“It looks like we’re at the beginning of a viral epidemic.”
“Oh horror,” she said melodramatically. “Not bird flu in Boston! We’re so screwed.”
“This might be a lot worse than bird flu, kiddo.”
“Whatever. You don’t have to convince me. My shoes are already off. Who’s going to write the note?”
“I will.”
“Is everyone getting off?”
“Probably not. By tomorrow that could change. The news isn’t out yet.”
“Oh yay! Multiple days off? A whole week?”
“Too soon to tell.”
He couldn’t tell whether her yawn was real or manufactured. “Well, I’m going back to bed. Is Maria coming today?” She was the housekeeper and dog walker.
“I forgot about her. I’ll call to cancel. I don’t want you to be exposed to her or anyone else.”
“I’ll call her,” Emma said.
“Good. Thanks.”
“By-ee.”
“Wait a sec. I don’t want you leaving the house. And you can’t have any friends over. Okay?”
“Whatever.”
The second her father was off, Emma called her best friend, Kyra, and announced, “Guess what? I’m cutting.”
Kyra asked why.
“My dad is making me. Seems there’s an epidemic or some such shit.”
“I didn’t hear anything.”
“He said it’s not public yet. Come over and let’s hang out.”
“I don’t want to get detention.”
“You won’t. He’s going to write notes for us.”
“Seriously?”
“Yup. Where’s your mom?”
“She worked last night. She’s not home yet.”
Emma had one word for her. “Perfect.”
*
Jamie did the best he could to look presentable and hustled over to the small conference room in the Biocontainment Unit. The unit had six high-level isolation rooms. The last time one had been used was for a suspected case of Lassa fever a year earlier. He had turned the rest of the floor into a makeshift quarantine shelter for the medical workers and patients unlucky to be in the ER when Andy Soulandros came in. As a precaution, the emergency exits were alarmed, and the elevators programmed to skip the floor. Cots had been wheeled into the corridors and Jamie walked softly so as not to wake people.
The conference room had a video link to the O’Keefe Auditorium where medical grand rounds were held every week. Checking the video feed, he was surprised how many were present this early in the morning. The people he recognized were all from Mass General—the CEO and chief operating officers of the hospital, the physician-in-chief of the department of medicine, the chief of infectious diseases, the chief nurse, and the chief of the infection control unit.
Creighton Collins, the hospital CEO, was stooped over, talking to a much shorter man. He noticed Jamie when the projection screen came alive and transferred him from the large screen to a laptop on the podium.
“This is Dr. Abbott,” Collins said, calling
the shorter man over. “Jamie, this is Dr. Hansen from the Center for Disease Control.”
Hansen was mostly bald and a little fat. When he furrowed his brow, the folds extended up to his scalp.
“Mark Hansen,” the man said. “I’m the director of the Global Rapid Response Team. We’ve got a team of officers here from viral special pathogens, epidemiology, and emergency operations. I’m sure we’ll be making all the introductions. It looks like all the right people are here from the state and city. Good job mobilizing resources quickly.”
“We just called everyone we could think of,” Jamie said.
“Feeling okay?” Hansen asked, as a doctor would.
“I’m good. No symptoms. As far as I know, everyone in quarantine is well this morning.”
A burly fellow in a dark suit was standing nearby, talking to the Boston Police Commissioner. He joined the gaggle and was soon filling Jamie’s screen with his pugnacious face.
“So, you’re the asshole who got me out of bed at three this morning. I’m Dmitri Kovachek, the mayor’s chief of staff. You better not be the boy who cried wolf.”
Jamie wasn’t sure if this was tongue-in-cheek, but he didn’t think so. “You’d prefer a real crisis?” he said.
“To a highly embarrassing public relations disaster? The way I’m feeling right now, it’s a toss-up.”
Hansen leaned into the laptop microphone, lowering his voice. “I’m afraid this is the real deal. We put out a network alert six hours ago, describing what we knew about Dr. Abbott’s index case and the related case from Baltimore. We’ve been getting pinged all night about possible cases from multiple states, the District of Columbia, and Puerto Rico. You’re not even alone in Massachusetts. The last data I got on board the plane indicated four other possible cases in Boston, one in Fall River and one in Worcester. Dr. LaMotta, the director of the Viral Special Pathogens Branch—the woman over there on her tablet—is getting real-time data. She’ll update us.”
“Jesus,” Kovachek said. “Do I need to be wearing a mask?”
Collins told Jamie that after the preliminaries, the CDC wanted him to present what he knew about the gene therapy trial and the clinical status of the first patient. Then the CEO stepped to the podium to call the meeting to order and pushed a key on the laptop to transfer Jamie’s feed to the big screen. To get everyone oriented, he had people stand and introduce themselves. It took several minutes to make it around the auditorium because, in addition to the hospital personnel, there were representatives from the Massachusetts and Boston departments of health, state and local preparedness and emergency services, law enforcement, and a sizable contingent from the CDC.
“All right,” Collins said, when the last person spoke. “It isn’t every day when a neurologist closes down the largest hospital in Boston, but Dr. Abbott sounded the alarm on a troubling case and our disaster protocols kicked in. Dr. Abbott is speaking to us from our Biocontainment Unit where he, and other personnel who were in the Emergency Department when the patient was brought in, are in quarantine. Dr. Abbott, you have the floor and given the video link, let’s everyone try to hold questions until he’s finished.”
Jamie started with a summary of the Baltimore clinical study and the events leading to Mrs. Noguchi’s death. He followed with Andy Soulandros’s presentation to the ER the night before. Then he segued into Mandy’s initial analysis of the hybrid virus and its altered NSF-4 payload.
Despite the CEO’s plea, Jamie saw a hand go up from the audience. It was the mayor’s chief of staff.
“Look, I’m not a brilliant doctor like a lot of you ladies and gentlemen,” Kovachek said, “but how the hell do you get off unleashing dangerous viruses into the world?”
Jamie chose his words carefully. “Over the past twenty years there have been thousands of gene therapy clinical trials approved and conducted worldwide. The vast majority have utilized adenovirus vectors similar to the one that Dr. Alexander developed in Indiana. Every aspect of the Baltimore trial was done under the auspices of an FDA-mandated safety committee. Multiple levels of checks and safeguards were built into the protocol.”
“And yet, here we are this fine morning,” Kovachek said.
Jamie said, “It’s undeniable that certain protocol violations occurred in Baltimore. They shouldn’t have happened, but they did.”
Jamie saw another hand go up. “I don’t know who that is but the woman in blue, your question?”
“Hi, I’m Heidi Moscowitz, one of the CDC epidemic intelligence officers. When are we going to have more data on the sensitivity of the suicide gene?”
“Soon, I hope,” Jamie said. “We’ve been trying all night to reach the principal investigator of the trial, Dr. Steadman. The assembly of the viral payload and the fail-safe gene took place in his lab. Hopefully, we’ll know more this morning.”
The commissioner of the Massachusetts Department of Public Health wanted to know who had received doxycycline.
“About thirty people, most of them staff. Everyone who was in the Emergency Department when the patient was admitted.”
CDC’s Dr. LaMotta asked, “Has the patient responded to doxycycline?”
“As of an hour ago, no, but I thought I’d suit up and examine him in front of you. I think you need to see what we’re up against.”
When Jamie finished, he excused himself to get into a biohazard suit.
Dr. LaMotta came to the front of the auditorium, laid her tablet onto the podium, and cabled it to the laptop.
“Good morning. I’m Cynthia LaMotta, director of Viral Special Pathogens at CDC. We reached out to Dr. Abbott soon after the city of Boston notified us about the index case of Mr. S who presented to this hospital last evening. Shortly afterwards, we contacted Dr. Colin Pettigrew at the Baltimore Medical Center regarding a patient in their ER, Ms. G, who is contextually related to Mr. S. Based on the data we had, namely a possible novel central nervous system virus and a novel clinical syndrome characterized by fever and amnesia, we opened an urgent epidemiological investigation. For the moment, we are descriptively calling the new agent, the Febrile Amnesia Virus, or FAV and the new disease, Febrile Amnesia Syndrome, or FAS. Last night we put out a be-on-the-lookout-alert for FAS to emergency departments throughout the US and its territories and here is where we are as of ten minutes ago.”
She threw a slide from her tablet onto the projection screen. There was a collective gasp.
The map of the United States showed states reporting cases in red and non-reporting states in blue.
The map was a sea of red.
8
Dr. LaMotta waited for the audience to settle then continued, “We currently have reports of two hundred forty-seven cases of FAS in thirty-eight states, Puerto Rico, the US Virgin Islands, and Guam. Here in Massachusetts, there are currently nine cases, including a total of five within the city of Boston. Please note that we haven’t yet reached out to the international community, so we don’t know if the outbreak is confined to the United States and its territories.”
Someone interrupted and asked whether any of this had been made public.
“Not yet,” LaMotta answered, “but in all likelihood, the CDC and Department of Homeland Security will, in conjunction with the White House, be drafting a press statement for release sometime today. Dr. Fogarty, the CDC Director, is waiting for an update from this meeting before he takes it up the line. The medical community and the general public will be clamoring for information and guidance and I suspect that initially, we will have incomplete answers for them.”
Kovachek gesticulated toward the front of the hospital and said, “Any idea how many reporters are camped outside? This is going to get out faster than any of you think.”
The director of the Boston Public Health Commission asked about incubation periods.
LaMotta told her that she could only make an assessment based on Mr. S and Ms. G’s cases and said, “We can reasonably make the hypothesis that Ms. G, the MRI technician, was infected by th
e gene therapy patient, Ms. N, at the time the patient received her brain scan. One day later, Mr. S traveled to Baltimore where he stayed at Ms. G’s apartment. They spent about a day and a half together before Mr. S returned to Boston the day before yesterday. Based on this, the minimum incubation period appears to be approximately one to three days.”
“Mode of transmission?” someone asked.
LaMotta asked if anyone had Mr. S’s chest x-ray.
The chief of infectious diseases at MGH projected the x-ray onto the screen and said, “It’s likely respiratory, based on these findings of a diffuse bilateral pneumonitis. I talked to the clinicians in Baltimore who told me that the patient down there has similar pulmonary infiltrates and a similar presentation of cough and fever progressing to the central nervous system events. We’re awaiting cultures of sputum, blood, urine, and cerebrospinal fluid and extensive serologies. We’ll be sharing all our samples with the CDC, of course.”
LaMotta thanked him and said, “As you know, the mode of transmission of adenovirus infection is via respiratory droplets. The Japanese Encephalitis virus is a blood-borne virus that spreads via mosquito bites. The FAV may or may not have elements of both, but certainly there seems to be a respiratory component at play.”
Collins announced that Dr. Abbott was ready, and he switched the video feed to Isolation Room One where Jamie appeared in a full-helmeted Ebola suit with an autonomous oxygen supply. There was a microphone inside the helmet that allowed him to be heard over a Bluetooth speaker. He introduced his neurology fellow, Dr. Bowman, who was beside him in an identical biohazard rig.
In the background, the audience could see Andy Soulandros, moored to his hospital bed in four-point restraints.
Jamie approached the bed and said, “It’s Dr. Abbott. How are you feeling this morning?”
Soulandros stared at Jamie, wide-eyed, and tugged at his wrist restraints. “I-I-na-na-na.”
Jamie said, “Dr. Bowman’s been at his bedside all night and has the best handle on the clinical situation. Go ahead, Carrie.”
“I’ve been with the patient continuously since his arrival in the ER last night,” she said, her amplified voice gently reverberating. “As Dr. Abbott has told you, most of his neurological functions are intact. He has voluntary and involuntary control of his muscles including full bowel and bladder control. His gait is normal, his balance is normal, he perceives painful, cold, and hot stimuli, his vision and hearing are grossly normal. His neurological exam and brain MRI show no evidence of trauma, stroke, or hemorrhage. His clinical deficits relate solely to problems with memory and language.
