Viv spent nearly an hour choosing her body.
She considered going as her eight year-old self. She would stand eye-to-eye with her father in his hospital bed, shedding tears and crying: please don't go, daddy. But that was too obvious. It would offend him.
He became data coursing through a network, able to embody any form, to outlive physical decay.
She considered her eighteen year-old self. She would lean over him, scrawny and tall, her lips trembling with anger: you're being selfish, dad. But that would lead to shouting.
She considered every form, even reviving people from the past: her mother, her grandfather, her little sister Mary. How would her father react to Mary walking in? He would think himself dead. She could whisper a message to him: Stay alive, dad. God commands it.
In the end, Viv chose the look of her last days as a biological person. Thirty-one years old, her auburn hair cut short, her black eyes full of longing. She watched the body print in silicon over robotic armature.
When it blinked to life, Viv stood in front of a mirror. Her face was appropriately somber, her mind in sync with her new muscles. Without thinking, she stretched her arms, arched her body, twirled on her tiptoes. She had forgotten the pleasure of sensation.
"I should do this…" The voice resonated through her. She could not help but smile. "I should do this more often… often… often." Every repetition thrilled her with sound. She began to sing an old favorite: "Times have changed… and we've often…"
But she stopped herself. This was not a day for singing.
Viv clothed her body in a blue dress, packed her tablet in a briefcase, stood in front of the mirror one last time. "I'll be there in five," she said aloud, though she did not need to.
A man's voice answered in her mind: I'm not coming.
There's no point, said the voice. We know what he'll say.
"We have to try."
I won't see him dying, Viv.
The clenching of her jaw felt like the old days. Her brother made a habit of last-minute decisions, without concern for how they affected other people, most often her.
She remembered the day he became an everperson. It was soon after their mother's death. They were supposed to visit their father in mourning, but Gabe disappeared without explanation. Viv took the full burden of solace on herself. She sat with her father in a small room, with an old Persian rug and stale furniture. His mustache was beginning to gray, his eyes beginning to wrinkle. "She's with your sister now," he said. "Your mom and Mary, I can…" He leaned in to whisper, "I can almost hear them, at night, laughing on the other side. They tell me to wait… they tell me to wait." Viv nodded for him, pretending to believe, wishing she could.
Gabe did not return her calls that evening. The next day, she began to worry. The day after, she began to look. He made no effort to hide, he simply neglected to tell her the new plan.
Gabe had taken the money from his inheritance, and booked himself an everence. It was something new back then. Viv did not understand the science, but she knew it was a destructive process. His physical brain was destroyed by lasers that scanned it neuron by neuron, creating a digital replica. He became data coursing through a network, able to embody any form, to outlive physical decay. He became an everperson.
It took three days to complete. Viv went to the facility, a converted warehouse by the Bay Bridge. She watched the new Gabe being printed over robotic armature, taking the form of his last biological self, to help with the transition. When he blinked to life, she did not know if he would be the same person, or an imperfect copy of an imperfect copy. But Gabe was totally oblivious to the pain he caused her by disappearing in that way. No robot, she thought, could be so callous.
When Viv made her own decision to everize, she deliberated for weeks, thinking through the consequences and conversations to come. Afterwards, she sat with her father in that same small room, with the Persian rug older, the furniture staler, a new cat purring at his feet.
"But it's suicide," he said.
"It's the opposite, dad. It's eternal life."
"You'd be a robot. You wouldn't be you."
"Gabe's the same as he ever was," she noted the resentment in her voice. "He's just not… physical, until he wants to be."
Her father exhaled an Arabic phrase he was using more often in his old age. La hawla wa la quwata illa billah. She had never learned his native tongue, but she looked up the phrase to understand him better. It meant something like: there is no power except in God. It was a sigh of resignation.
"Vivian," he said eventually, "Your soul is not your brain. Your soul lives on. If you kill yourself, you... it's unforgivable. Don't you want to see mom in heaven? Mary? Me?"
She wanted to believe. She wanted painfully. But when she spoke, it was barely a whisper. "I don't think that will happen, dad."
Fewer biological people meant little need for hospitals, or doctors. It would close soon.
It was the first she had ever confessed to him about God or Heaven. In as steady a voice as he could manage, her father said: "You're an adult, Viv. You do what you think is best."
She came to visit sometimes, as an everperson. He could not tell at first. But as the years went by, as his eyes wrinkled, and his hair grayed, he noticed that Viv never aged. One day he stopped talking to her. Another she stopped coming.
Now he was waiting out the last days of his life alone in a hospital bed. Viv did not want to say goodbye. It seemed such a waste.
You don't have to, Gabe spoke into her mind. Get him to sign, say anything, say it's for selling the house. Once we have full power of attorney, we can decide for him.
"It's not right." She noticed herself speaking aloud on the hoverbus. Nine nervous faces turned to her.
It's not right, she continued in her mind. Dad never forced us to pray, never forced us to —
That was mom.
But he loved her. He never changed her mind, he raised us to question, and he quietly believed. He has every right to live his way, just like we did.
To live. Not to die... When he's an everperson, he'll thank us.
That gave her pause. It might be true. She remembered her first moments as an everperson, suddenly linked to countless other minds, waking to the full expanse of human knowledge like sunlight through an open window, breathless and unexpected.
Still, she said, it's not right.
So you want him to die?
I want to convince him.
And what if you don't? There was panic in his voice. Gabe steadied himself. You brought your tablet, Viv. You know what it's for. Get him to sign.
And what if I don't?
I'll figure something out, with or without you. I won't let him die, Viv. Not this day and age.
Viv kept quiet the rest of her way there. She played memories in her mind, of every conversation she ever had with her father, every time he read her a verse or taught her a parable. She looked for a way to convince him, some doubt, some chink in his armor of belief. But she got distracted by the world outside.
It was strange to pass for a time through physical space. It took longer than she expected. Now watching the sunlight refract through the hoverbus window, she was mesmerized. Every sensation felt more real, more vivid than her memory. "I should do this more often," she said aloud.
The hospital smelled like death. It had fallen into disrepair since her mother's illness. Fewer biological people meant little need for hospitals, or doctors. It would close soon, she thought. Her footsteps echoed through the halls, along with the sounds of old televisions playing old films to keep the patients company.
The room she entered had no sound, except the whirring machines. No light, except an eerie glow filtering through the curtains. The figure on the bed was her father, his breathing strained, his skin cracked like the desert. She closed the door behind her.
When her father turned, she saw a flicker of joy in his eyes. It disappeared.
"La hawla wa la… I thought it was her."
"I am her."
He winced. "She died some twenty years ago."
Viv sat next to him. The machines whirred around them, keeping his body alive another day, or hour, or minute. "It doesn't look good, dad."
"You broke a promise."
He held her gaze. "I did?"
"You said we'd see the bats in Australia."
"You were scared of bats."
"And you said they were cute in Oz, the giant bats, like upside down puppies chewing bananas."
He smiled, but that was a long time ago. "Your mom was alive then… Gabe… You were alive…"
"I'm alive now, dad. Look at me. I'm Viv. Vivian Fatema. Your daughter. Half mom, half you. I'm the same person I was."
His eyes shifted. She sensed he wanted to believe. She held his hand and squeezed it. She felt him squeezing back. "I want you to stay, dad."
"There's nothing for me here."
"You don't love me, Viv. You're a robot."
His hand let go. "You're there… I don't know where. I have a lot to answer for, Viv. I pray. I pray every day, five times a day, sometimes more. I pray that God forgive you for what you did, forgive me for my part, forgive Gabriel... I wish I could stay, love, but… Everyone I love is on the other side."
It hurt her to say the next words: "It's not real, dad."
"Of course you'd say that." He turned his body away from her.
She listened to his breathing.
"I love you," she said.
"You don't love me, Viv. You're a robot."
She lowered her head against the bed. She kneeled for countless breaths. It took all her strength to stand up again.
Viv took her briefcase, pulled out her tablet. She stood tapping at the screen for some time. The clenching of her jaw felt like the old days.
"Before I go, I need you to sign something. It's a power of attorney for the house. We can't sell it without you."
"You're selling the house?"
She shrugged. "It's no use to a robot."
His bony finger signed the screen without reading it. She kissed his forehead goodbye.
"Viv?" She stopped. "Before you go, could you open the curtains?"
She did. Her last image of him was a frail old body gazing at the moving clouds.
On the hoverbus home, Viv turned against the window outside. She pressed the briefcase to her like a hug, her mechanical heart thumping against it. Every heartbeat brought a memory back of her biological life. "I should do this more…" She whispered to herself, not caring who might hear. The sunset turned violet.
You made him sign. Gabe sounded like triumph.
You did the right thing.
Let me see.
She pulled out her tablet and, with a touch, uploaded the file.
Where's my name? Gabe asked. I only see your name.
"I changed it."
What do you mean you "changed it"?
"I changed my mind last minute, Gabe. I didn't think to tell you."
That's funny, sis. Very funny.
"It's not funny at all, Gabe. It's dead serious. I have power of attorney. I'm going to bury him next to mom and Mary."
No… There's no way.
"It's my choice now."
I can't watch him go, Viv. I can't. Don't be selfish.
"I'll miss him." She felt a pain in her chest. "I'll miss him too." Her voice was different now. "But it's what he wanted."
Gabe left her. She heard nothing but her thoughts. Unbearable thoughts.
Viv turned to the darkening world outside. She found her reflection instead, her reflection in tears. She saw her father's eyes.
In late March, just as the COVID-19 pandemic was ramping up in the United States, David Fajgenbaum, a physician-scientist at the University of Pennsylvania, devised a 10-day challenge for his lab: they would sift through 1,000 recently published scientific papers documenting cases of the deadly virus from around the world, pluck out the names of any drugs used in an attempt to cure patients, and track the treatments and their outcomes in a database.
Before late 2019, no one had ever had to treat this exact disease before, which meant all treatments would be trial and error. Fajgenbaum, a pioneering researcher in the field of drug repurposing—which prioritizes finding novel uses for existing drugs, rather than arduously and expensively developing new ones for each new disease—knew that physicians around the world would be embarking on an experimental journey, the scale of which would be unprecedented. His intention was to briefly document the early days of this potentially illuminating free-for-all, as a sidebar to his primary field of research on a group of lymph node disorders called Castleman disease. But now, 11 months and 29,000 scientific papers later, he and his team of 22 are still going strong.
On a Personal Mission<p>In the science and medical world, Fajgenbaum lives a dual existence: he is both researcher and subject, physician and patient. In July 2010, when he was a healthy and physically fit 25-year-old finishing medical school, he began living through what would become a recurring, unprovoked, and overzealous immune response that repeatedly almost killed him.</p><p>His lymph nodes were inflamed; his liver, kidneys, and bone marrow were faltering; and he was dead tired all the time. At first his doctors mistook his mysterious illness for lymphoma, but his inflamed lymph nodes were merely a red herring. A month after his initial hospitalization, pathologists at Mayo Clinic finally diagnosed him with idiopathic multicentric Castleman disease—a particularly ruthless form of a class of lymph node disorders that doesn't just attack one part of the body, but many, and has no known cause. It's a rare diagnosis within an already rare set of disorders. Only about 1,500 Americans a year receive the same diagnosis. </p><p>Without many options for treatment, Fajgenbaum underwent recurring rounds of chemotherapy. Each time, the treatment would offer temporary respite from Castleman symptoms, but bring the full spate of chemotherapy side effects. And it wasn't a sustainable treatment for the long haul. Regularly dousing a person's cells in unmitigated toxicity was about as elegant a solution to Fajgenbaum's disease as bulldozing a house in response to a toaster fire. The fire might go out (though not necessarily), but the house would be destroyed.</p><p>A swirl of exasperation and doggedness finally propelled Fajgenbaum to take on a crucial question himself: Among all of the already FDA-approved drugs on the market, was there something out there, labeled for another use, that could beat back Castleman disease and that he could tolerate long-term? After months of research, he discovered the answer: sirolimus, a drug normally prescribed to patients receiving a kidney transplant, could be used to suppress his overactive immune system with few known side effects to boot.</p><p>Fajgenbaum became hellbent on devoting his practice and research to making similar breakthroughs for others. He founded the Castleman Disease Collaborative Network, to coordinate the research of others studying this bewildering disease, and directs a laboratory consumed with studying cytokine storms—out-of-control immune responses characterized by the body's release of cytokines, proteins that the immune system secretes and uses to communicate with and direct other cells. </p><p>In the spring of 2020, when cytokine storms emerged as a hallmark of the most severe and deadly cases of COVID-19, Fajgenbaum's ears perked up. Although SARS-CoV-2 itself was novel, Fajgenbaum already had almost a decade of experience battling the most severe biological forces it brought. Only this time, he thought, it might actually be easier to pinpoint a treatment—unlike Castleman disease, which has no known cause, at least here a virus was clearly the instigator. </p>
Thinking Beyond COVID<p>The week of March 13, when the World Health Organization declared COVID-19 a pandemic, Fajgenbaum found himself hoping that someone would make the same connection and apply the research to COVID. "Then like a minute later I was like, 'Why am I hoping that someone, somewhere, either follows our footsteps, or has a similar background to us? Maybe we just need to do it," he says. And the CORONA Project was born—first as a 10-day exercise, and later as the robust, interactive tool it now is. </p><p>All of the 400 treatments in the CORONA database are examples of repurposed drugs, or off-label uses: physicians are prescribing drugs to treat COVID that have been approved for a different disease. There are no bonafide COVID treatments, only inferences. The goal for people like Fajgenbaum and Stone is to identify potential treatments for further study and eventual official approval, so that physicians can treat the disease with a playbook in hand. When it works, drug repurposing opens up a way to move quickly: A range of treatments could be available to patients within just a few years of a totally new virus entering our reality compared with the 12 - 19 years new drug development takes.</p><p>"Companies for many decades have explored the use of their products for not just a single indication but often for many indications," says Stone. "'Supplemental approvals' are all essentially examples of drug repurposing, we just didn't call it that. The challenge, I think, is to explore those opportunities more comprehensively and systematically to really try to understand the full breadth of potential activity of any drug or molecule."</p>
The left column shows the path of a repurposed drug, and on the right is the path of a newly discovered and developed drug.
Cures Within Reach
A Confounding Virus<p>The FDA declined to comment on what drugs it was fast-tracking for trials, but Fajgenbaum says that based on the CORONA Project's data, which includes data from smaller trials that have already taken place, he feels there are three drugs that seem the most clearly and broadly promising for large-scale studies. Among them are <a href="https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30503-8/fulltext" target="_blank" rel="noopener noreferrer"><u>dexamethasone</u></a>, which is a steroid with anti-inflammatory effects, and <a href="https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-drug-combination-treatment-covid-19" target="_blank" rel="noopener noreferrer"><u>baricitinib</u></a>, a rheumatoid arthritis drug, both of which have enabled the sickest COVID-19 patients to bounce back by suppressing their immune systems. The third most clearly promising drug is <a href="https://www.nih.gov/news-events/news-releases/full-dose-blood-thinners-decreased-need-life-support-improved-outcome-hospitalized-covid-19-patients" target="_blank" rel="noopener noreferrer"><u>heparin</u></a>, a blood thinner, which a recent trial showed to be most helpful when administered at a full dose, more so than at a small, preventative dose. (On the flipside, Fajgenbaum says "it's a little sad" that in the database you can see hydroxychloroquine is still the most-prescribed drug being tried as a COVID treatment around the world, despite over the summer being <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2021801" target="_blank" rel="noopener noreferrer"><u>debunked</u></a> widely as an effective treatment, and continuously since then.)</p><p>One of the confounding attributes of SARS-CoV-2 is its ability to cause such a huge spectrum of outcomes. It's unlikely a silver bullet treatment will emerge under that reality, so the database also helps surface drugs that seem most promising for a specific population. <a href="https://jamanetwork.com/journals/jama/fullarticle/2773108" target="_blank" rel="noopener noreferrer"><u>Fluvoxamine</u></a>, a selective serotonin reuptake inhibitor used to treat obsessive compulsive disorder, showed promise in the recovery of outpatients—those who were sick, but not severely enough to be hospitalized. <a href="https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2772185" target="_blank" rel="noopener noreferrer"><u>Tocilizumab</u></a>, which was actually developed for Castleman disease, the disease Fajgenbaum is managing, was initially written off as a COVID treatment because it failed to benefit large portions of hospitalized patients, but now seems to be effective if used on intensive care unit patients within 24 hours of admission—these are some of the sickest patients with the highest risk of dying. </p><p>Other than fluvoxamine, most of the drugs labeled as promising do skew toward targeting hospitalized patients, more than outpatients. One reason, Fajgenbaum says, is that "if you're in a hospital it's very easy to give you a drug and to track you, and there are very objective measurements as to whether you die, you progress to a ventilator, etc." Tracking outpatients is far more difficult, especially when folks have been routinely asked to stay home, quarantine, and free up hospital resources if they're experiencing only mild symptoms. </p><p>But the other reason for the skew is because COVID is very unlike most other diseases in terms of the human immune response the virus triggers. For example, if oncology treatments show some benefit to people with the highest risk of dying, then they usually work extremely well if administered in the earlier stages of a cancer diagnosis. Across many diseases, this dialing backward is a standard approach to identifying promising treatments. With COVID, all of that reasoning has proven moot. </p><p>As we've seen over the last year, COVID cases often start as asymptomatic, and remain that way for days, indicating the body is mounting an incredibly weak immune response initially. Then, between days five and 14, as if trying to make up for lost time, the immune system overcompensates by launching a major inflammatory response, which in the sickest patient can lead to the type of cytokine storms that helped Fajgenbaum realize his years of Castleman research might be useful during this public health crisis. Because of this phased response, you can't apply the same treatment logic to all cases.</p><p>"In COVID, drugs that work late tend to not work if given early, and drugs that work early tend to not work if given late," says Fajgenbaum. "Generally this … is not a commonplace thing for a virus." </p>
Thursday, March 11th, 2021 at 12:30pm - 1:45pm EST
On the one-year anniversary of the global declaration of the pandemic, this virtual event will convene leading scientific and medical experts to discuss the most pressing questions around the COVID-19 vaccines. Planned topics include the effect of the new circulating variants on the vaccines, what we know so far about transmission dynamics post-vaccination, how individuals can behave post-vaccination, the myths of "good" and "bad" vaccines as more alternatives come on board, and more. A public Q&A will follow the expert discussion.
SPEAKERS:<img lazy-loadable="true" data-runner-src="https://leaps.org/media-library/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNTY3Mzc4NS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY0NjYwNjU4NX0.Tdrh5pze5P4XxgiJK3J4JFrsrijfabIzNJz-AATghDE/image.jpg?width=534&coordinates=365%2C3%2C299%2C559&height=462" id="87554" class="rm-shortcode" data-rm-shortcode-id="b6c7311be7aec25807f9af19b683bf1d" data-rm-shortcode-name="rebelmouse-image" data-width="534" data-height="462" />
Dr. Paul Offit speaking at Communicating Vaccine Science.commons.wikimedia.org<p><strong><a href="https://www.research.chop.edu/people/paul-a-offit" target="_blank" rel="noopener noreferrer">Dr. Paul Offit, M.D.</a>, is the director of the Vaccine Education Center and an attending physician in infectious diseases at the Children's Hospital of Philadelphia. He is a co-inventor of the rotavirus vaccine for infants, and he has lent his expertise to the advisory committees that review data on new vaccines for the CDC and FDA.</strong></p>
Dr. Onyema Ogbuagu, MBBCh, FACP, FIDSA
Yale Medicine<p><strong><a href="https://medicine.yale.edu/profile/onyema_ogbuagu/" target="_blank" rel="noopener noreferrer">Dr. Onyema Ogbuagu, MBBCh</a>, is an infectious disease physician at Yale Medicine who treats COVID-19 patients and leads Yale's clinical studies around COVID-19. He ran Yale's trial of the Pfizer/BioNTech vaccine.</strong></p>
Dr. Eric Topol
Dr. Topol's Twitter<p><strong><a href="https://www.scripps.edu/faculty/topol/" target="_blank" rel="noopener noreferrer">Dr. Eric Topol, M.D.</a>, is a cardiologist, scientist, professor of molecular medicine, and the director and founder of Scripps Research Translational Institute. He has led clinical trials in over 40 countries with over 200,000 patients and pioneered the development of many routinely used medications.</strong></p>