Talia wanted to start right away, but there was still plenty of ti left.
Actual dication administration was scheduled at 2 p.m.
Until then, there were preliminary tests, machine setup, and countless things to prepare.
So, I wondered what kind of commotion she might cause while waiting…
“I want to talk to Rachel for a mont.”
Talia quietly looked over , her mother, David, and Jessie in turn before speaking.
“Just the two of us.”
Since she insisted on sending us out, it must have been sothing she didn’t want to say in front of everyone.
Well, I could guess what it was about.
No matter how bold she acted, Talia was still a girl who hadn’t even reached adulthood yet.
When death stands right in front of you, anyone would be scared.
But Talia always tried to show only strength in front of , and in front of her mother, she was instead the one trying to comfort her.
So the only person she could truly open up to was Rachel.
Without saying anything, I led the others to the lounge.
But then.
When we returned to the room a while later, a middle-aged woman we didn’t know was standing there holding a docunt envelope.
“I’m a hospital social worker.”
“A social worker?”
“Miss Talia has requested to designate a dical proxy.”
A dical proxy.
That ans soone who can make dical decisions when the patient loses consciousness or becos unable to express their will.
Now that Talia was a legal adult, she had the right to make every dical decision for herself.
But if she lost consciousness during treatnt?
Soone else would need to take over that authority.
Normally, that person would be the closest family mber—her mother…
But if Talia designated soone else, that changed things entirely.
And.
The fact that she was deliberately appointing a different proxy ant one thing: she didn’t want her mother to take that role.
“This is an advance directive form. Once both sides sign and two witnesses verify, it takes imdiate effect. It can also be notarized.”
“Why… why would she give sothing like this… to soone else…”
On her mother’s face, betrayal and hurt were clearly visible.
Her daughter was entrusting a life-and-death decision to a stranger with no blood relation.
It was understandably hard to accept.
But Talia’s explanation was simple.
“I know you love , Mom.”
Her voice was gentle, but the resolve behind it was unwavering.
“That’s why you can’t do it. I want my last monts to be spent for the world. Not for myself. And we both know… you would never prioritize the world over .”
“But… why go this far…”
“You saw all that fuss—they even broadcasted that I’d beco a hero. I can’t bail out at the very end. I want to go out in style.”
The social worker carefully stepped in.
“This authority only applies if Miss Talia completely loses consciousness. Only in cases of severe coma or when she becos entirely unable to communicate. Until then, all decisions remain hers.”
Talia nodded and turned her gaze.
And surprisingly… she looked straight at .
“You’ll do it, right?”
“…?”
“Well, who else would it be?”
Honestly, I didn’t expect that.
I hadn’t even thought about a dical proxy, but even if she needed one… Rachel seed like the obvious choice.
She had spent the most ti with Talia and shared the deepest conversations with her.
Sure, Talia called herself my fan…
But this was on a completely different level.
Entrusting a life-or-death decision… based on fan loyalty?
“I discussed it with Rachel for a long ti before deciding.”
Talia answered as if she had read my thoughts.
Rachel quietly nodded beside her.
“You’ll do it, right?”
To be honest, I did not see this coming.
It didn’t feel comfortable either.
But I nodded.
“We do need this.”
This treatnt was essentially an expedition into unknown territory.
Unexpected ergencies were very likely, and imdiate—even unorthodox—dical decisions could be required.
In those monts, having hold the decision-making authority might be the most efficient option.
“This way, please.”
The social worker handed the docunts and a pen.
The paper felt like a bar of lead in my hand.
The pen hesitated above the signature line, but I slowly wrote my na.
Rachel, David, and Talia’s mother signed as witnesses.
Once everything was completed, Talia winked playfully.
“Sean! Now we’re legally connected! I bet none of your fans ever got this close! Pretty aweso, right?”
#
2 p.m., the dication finally began.
“Heart rate 134, temperature 39.1°C, oxygen saturation 93%…”
“IL-6 110pg/mL, sIL-2R 3400U/mL, CRP 170mg/L, ferritin 1800ng/mL, D-dir still rising.”
Every indicator foretold an approaching cytokine storm.
Not critical yet, but if left unchecked, her immune system would soon go berserk and start attacking her organs indiscriminately.
A healthy person would rely on the WFOXO3A gene acting as a brake here, but Castleman patients don’t have that safeguard.
Now was the ti to uncover why.
“Administering now.”
The doctor approached with the prepared syringe.
A clear liquid flowed through the IV line, entering Talia’s bloodstream slowly.
Seconds passed.
“Hmm? I don’t feel any different.”
Talia laughed awkwardly, having expected sothing more dramatic—like in a movie.
“I an, it’s not like it’s poison… It’s a treatnt, right? Maybe I’ll even get cured from this?”
In theory, not impossible.
Just… extrely unlikely.
“Well, let’s start by checking the first step.”
We divided WFOXO3A analysis into five checkpoints:
Transcription, post-transcriptional regulation, translation, protein localization, and pathway-specific signaling.
Simply put:
WFOXO3A is the blueprint for the brake.
And transforming that blueprint into a real, working brake requires multiple production stages.
Copying the blueprint, transporting the copy inside the cell, decoding it into parts, shipping the parts to the correct location, and finally confirming that the parts actually function where they’re supposed to.
“Let’s check transcription first.”
Transcription is the process of making mRNA copies from DNA.
The epigenetic drug we just administered loosens histone proteins around the DNA, making the blueprint easier to read.
We needed to see if that alone improved things.
We confird it through precision tests:
qRT-PCR and RNA sequencing to asure mRNA production.
We would extract mRNA from her body, convert it to cDNA, and analyze its quantity.
To do that…
“A lymph node biopsy is required. We’ll make a small incision under local anesthesia to collect tissue. It’ll take about 30 minutes.”
“That’s surgery, right?”
Anxiousness filled Talia’s voice.
“Yes, a simple procedure. You’ve done it before, rember?”
Talia turned her eyes away.
She wasn’t asking because she didn’t know.
She was afraid because she did know.
Even with anesthesia, stepping into the OR was terrifying.
“Yeah… I know. Let’s go.”
She forced a small smile.
And a few days later, the results ca.
“qRT-PCR shows no significant difference in WFOXO3A transcription compared to the normal control group.”
“RNA-Seq results confirm expression within the normal range.”
That was good news.
Her mRNA production, which had been only 30% of normal before the drug, had now recovered.
“Maybe… maybe I am getting cured?”
Hope flickered in Talia’s voice.
“It’s been four days, and no attacks. My fever’s gone down, and my stomach doesn’t feel tight anymore!”
We initially expected an attack within 48 hours.
But four days passed with no signs.
Symptoms were clearly improving.
A definite indication the epigenetic drug was helping.
But I couldn’t ignore reality.
“The risk isn’t gone yet. Your cytokine levels are still above normal.”
The brake had started working, but only partially.
Like slowing down… but not being able to stop.
“Tch. You could at least pretend to be a little hopeful…”
Talia grumbled, but false hope wasn’t an option.
Partial braking still ant sothing was broken.
“Next is post-transcriptional regulation.”
Even if the mRNA was copied correctly, the copies themselves could be flawed.
Pages torn out, scrambled order—anything could go wrong.
mRNA degradation rates, splicing fidelity, and breakdown enzy activity all needed checking.
This ti, we needed a blood test.
“More blood? At this rate I’ll die from anemia before the disease gets …”
Talia complained but obediently held out her arm.
And soon, the results arrived.
“mRNA half-life is about 2 hours, identical to the control group.”
“No abnormal splice variants detected.”
“microRNA and degradation-related enzys all remain within the normal range.”
Second checkpoint: passed.
“Next is checking protein expression.”
We needed to confirm the blueprint copies were actually becoming functioning proteins.
And the results…
“Western blot shows normal WFOXO3A protein expression.”
“No abnormal phosphorylation or acetylation modifications detected.”
We cleared the third checkpoint without any problems.
We had verified more than half of the five stages, and every tric was normal.
Hope filled Talia’s face.
“My fever’s down now!”
“Maybe this really is the answer. In life, the hardest option isn’t always the right one.”
Talia’s face was brimming with energy.
She even started a livestream.
“Guys! They said the real problem starts after you clear all five checkpoints, but I’m already past halfway and I’m still totally fine!”
She flashed a V sign at the cara and laughed.
Then she even cracked a joke like this.
“I made this huge fuss about dying and even did a big bucket-list project… so if I end up surviving, don’t co after asking for a refund!”
In the anti.
The test results for the fourth stage ca back.
“Nuclear/cytoplasmic fractionation analysis shows WFOXO3A is correctly localized in the nucleus.”
“Confocal microscopy and live-cell imaging also confirm WFOXO3A’s nuclear translocation.”
The fourth checkpoint was cleared as well.
We had confird that all the brake components were in their proper places.
Now we were truly at the final stage.
Once we made it through this part, we’d finally be able to move on to the stage where we could say for sure whether the brake actually worked or not.
But right then.
“Cough, cough!”
Talia started coughing.
“Oh, right… they said… we were supposed to wait… a few more days…”
Her speech grew sluggish.
Her temperature began to rise, and her eyes grew unfocused.
“Why… am I suddenly like this?”
Talia was scared.
In a low voice, I barely managed to answer.
“It’s probably a side effect.”
“A side effect?”
“Epigenetic drugs don’t just regulate WFOXO3A. They affect other genes too, and so of those might… trigger unexpected reactions.”
“What kind of reactions…?”
I shook my head.
I couldn’t predict what would happen.
That was the essence of an “exploratory” mission.
“It’s not going to be worse than the seizures, right…?”
Talia asked, but I couldn’t answer.
Because that was unknown territory.
“Do you regret it?”
At my question, Talia stared into empty space for a while, then shook her head.
“No. I’m scared, sure… but roller coasters are scariest at the highest point too, right? Once we get past this stretch, it’ll be okay.”
And in the early hours of that sa night.
The seizure began.
“BP is 72 over 38!”
It started with acute hypotension.
“MAP 49, shock index worsening!”
“Increase norepinephrine to 12!”
“Starting NS 500 mL bolus infusion!”
“Central venous line placent and CVP monitoring in progress!”
Fluids were pushed in rapidly, and inotropes were administered at the sa ti.
A few minutes later, her BP climbed to 86 over 48.
But the crisis was far from over.
“Seizure! Generalized tonic-clonic seizure!”
Talia’s body began to jerk.
First her fingers.
Then her arms.
The tremors quickly spread through her entire body.
Her body arched like a bow and her jaw locked tight.
“Attach electrodes, oxygen at 15 L/min via high-flow mask!”
“Midazolam 2 mg IV, additional doses every minute as needed! Secure lorazepam and levetiracetam!”
While the dical staff struggled to control the seizure, a new crisis hit.
“Oxygen saturation has dropped to 68%!”
This ti it was hypoxia.
Talia’s lips turned blue.
Oxygen kept being delivered, but her lungs wouldn’t accept it.
An endotracheal suction catheter was inserted, pulling out phlegm and clots of blood.
“Switch to chanical ventilation now. Raise PEEP to 10 cmH2O, set FiO2 to 100%. ARDS pattern, suspect alveolar atelectasis!”
“Start recruitnt maneuver, check ABG!”
Beep, beep, beep—
The monitor alarms went off in rapid succession.
“ECG rhythm change! Ventricular tachycardia detected, possible pulseless VT!”
“Peripheral pulse is gone!”
The side effects flared up suddenly and vanished just as fast.
The staff could only rush after whatever symptom appeared in front of them.
It was like an endless ga of whack-a-mole.
One new ergency after another kept erupting.
And then the crisis reached Talia’s heart.
“Prepare defibrillation, 200 J, sync off!”
“Amiodarone 150 mg IV bolus ready, epinephrine 1 mg standing by.”
“Everyone back! Clear!”
As the current flashed through her, Talia’s body jerked.
There was a brief silence.
Then, slowly, the waveform returned.
Her heart found its rhythm again.
“Rhythm restored! Blood pressure 88 over 50.”
“ROSC confird—return of spontaneous circulation!”
However, Talia did not open her eyes.
The staff approached with a penlight.
“Pupillary light reflex… absent. Pupils fixed… corneal reflex gone.”
“Spontaneous breathing… has also stopped.”
“EEG as well…”
While we were busy hitting all those moles.
The most lethal side effect had been eating away at Talia where no one could see.
The doctor took off his gloves and lowered his head.
“I’m sorry. Based on the current test results… she ets the criteria for brain death.”
Talia’s consciousness was gone.
And then.
“Her vital signs continue to worsen. At this rate, cardiac arrest is imminent. We’re also seeing signs of multiple organ failure.”
Her body didn’t have much ti left to follow.
I looked at the bed.
Talia no longer showed any response.
Her head had slumped to the side, and her pupils barely reacted to light.
“What would you like us to do?”
A nurse asked .
Talia is no longer conscious.
And most likely… she will never co back.
So from this point on, every decision fell to as her dical proxy.
This was the mont I’d always known would co.
Ever since the mont I signed those papers.
But when it finally arrived, I suddenly couldn’t rember what I was supposed to do.
Only after flipping through my notes did it co back to .
'We have to keep checking.'
The reason her brake had failed.
We had to check the last checkpoint: pathway specificity.
“Let’s run RT-qPCR.”
The doctor tilted his head.
“In her current condition?”
“Yes. We need to look at the downstream target genes in the CREB, STAT3, and mTOR pathways—BCL2L11, CDKN1B, CAT, SOD2…”
I chanically listed the tests we needed.
What Talia had wanted.
Was to leave behind data for other patients, all the way to the end.
That was why she had chosen as her proxy.
“We’ll proceed with blood collection.”
The staff began to move.
Blood drawn from an unconscious patient felt heavy and silent.
The results ca back a few days later.
IL-10, borderline response.
GADD45A, moderate expression.
BIM (BCL2L11), no expression.
p27 (CDKN1B), no expression.
“Three of them are silent.”
As a result of using the epigenetic drug.
Every system involved in copying and transporting the WFOXO3A gene was functioning normally.
The problem was that the blueprint itself was flawed.
And we had just pinpointed that flaw.
'With this… it’s possible.'
The technology I’d wanted to use from the very beginning was CRISPR, the gene-editing “scissors.”
But no matter how precise your gene scissors are, they’re useless if you don’t know where to cut.
Now we finally knew the “where.”
The objective had been achieved.
But there was still one thing left.
“If we have to keep using epigenetic drugs…”
The sa side effects will happen again.
The ones Talia had just gone through.
In that case, we needed data on those side effects too.
“Let’s get an MRI.”
“But with contrast… her kidneys won’t hold out! They’re already at their limit!”
“She’s unlikely to last more than three days anyway.”
Talia is already unconscious.
We needed more data than three unconscious days could give us.
It was a rational decision, but even as I said it, I felt sickened by myself.
The MRI and CT results were devastating.
“These imaging findings can’t be explained by a typical cytokine storm. We’re seeing diffuse microhemorrhages throughout the brain, increased vascular perability, and lymphoid tissue formation within the central nervous system. In the liver, kidneys, and spleen, there are also atypical lymphoproliferative nodules and microthrombi…”
The radiologist paused, took a breath, and gave his conclusion.
“It appears the epigenetic drug broadly disrupted the gene-regulation networks of multiple organs. Genes that would never be expressed in a normal adult seem to have activated at random, creating an unprecedented pattern of complex lesions.”
If we had known about these side effects in advance, we might have taken preventive asures.
But we didn’t, so there was nothing we could do.
That, again, was the nature of an exploratory mission.
The price you pay for stepping into the unknown first.
But.
The information we gained through Talia’s sacrifice would beco a compass for the patients who ca after her.
After leaving behind those clues about the side effects…
“Ti of death, 20:30.”
Talia was gone.
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