novelraw Chapter 333 : Talia (3)
Chapter 333 : Talia (3)
Back when we first met David and began discussing the development of a treatment for Castleman disease.
The method we agreed on was off-label prescription.
Like using Viagra for pediatric pulmonary hypertension—repurposing an existing FDA-approved drug for an entirely different indication.
That was why it was Russian roulette.
Because all we needed to do was find the right gun among ones that already existed and pull the trigger.
But after Milo, drug development became an entirely different game.
Because Milo’s genetic analysis revealed that the root cause of Castleman disease was a WFOXO3A mutation.
And paradoxically, even though we now knew more about Castleman, the solution became even further out of reach—because no drug targeting that gene existed anywhere on Earth.
It was like playing Russian roulette without a gun to begin with.
Now we had to build the gun ourselves before we could even spin the chamber.
But before we could finish preparing— a patient appeared.
“Are you sure?”
[Yes. At least based on the biomarkers we’ve measured so far.]
Milo left us another legacy.
He left behind a kind of fingerprint that lets us identify Russian-roulette patients early.
Before, we had to try the first drug, then the second when that failed, and if that failed too, a third, filtering patients along the way.
Which meant a patient had to pass through death’s door at least twice before earning the right to pull the trigger.
Now, if a patient matches the cytokine signature Milo exhibited, we know immediately—they are a Russian-roulette candidate.
And the result was clear.
[A new treatment is absolutely necessary.]
We had found a patient who would need the third treatment.
In reality, finding even one such patient was practically a miracle.
Because only around 2,000 people a year develop this disease.
Which means roughly 0.0006% of the U.S. population.
So simply identifying one was a massive breakthrough.
But…
The problem was the timing.
They appeared too early.
We didn’t even have the gun ready.
“Is there no way to delay the attacks? Even one year… No—just six months.”
One year.
If we could hold out until CRISPR was ready, we could attempt a legitimate cure.
If the patient was young with good physical resilience, they could probably endure one or two more episodes.
It was better to withstand the attacks and wait than to gamble blindly.
But David’s voice was grim.
[If only that were possible, but the patient’s cytokine levels are extremely unstable. There’s no telling when the storm will hit. And on top of that—this patient has severe renal failure complications.]
[Even a single inflammatory surge would be fatal. If we wait…]
They will die.
Without ever getting to pull the trigger.
[Waiting is ideal, but we don’t have that luxury. This patient is not a candidate for best-case options.]
“So… they’re a Plan B case.”
[Yes.]
Plan B.
The backup option we run when the best solution isn’t possible.
And I hadn’t exactly been idle while waiting for CRISPR.
I had built an emergency system anticipating this exact scenario.
“But with renal failure… are epigenetic drugs even an option?”
Epigenetic drugs.
That was our Plan B.
If CRISPR directly edits DNA, epigenetic drugs indirectly alter how DNA is read.
‘We still can’t definitively say this is a structural DNA defect.’
DNA is like tightly coiled thread. If it coils too tightly or too loosely, it becomes unreadable.
Epigenetic drugs work by manipulating histone proteins, loosening the coils so the genes can be read again.
In short: making unreadable genes readable again.
[We can try. Theoretically, there is a possibility. The problem is…]
“The side effects.”
[Exactly. Using this drug… may itself be lethal to a Castleman patient.]
Epigenetic drugs cannot target specific regions with precision.
Meaning they don’t only loosen the necessary genes—they act indiscriminately across the genome.
There is no way to predict which genes will be affected.
And the essence of Castleman disease is an immune system in overdrive.
What if this drug alters immune-related genes?
Instead of calming the storm, it could amplify it.
[There’s a chance it suppresses the immune system entirely… but we have no way of knowing which direction it will swing.]
Naturally.
A Castleman patient has never been given an epigenetic drug before.
We would be stepping into completely uncharted territory.
[My stance is that clinical use is far too dangerous. The likelihood that WFOXO3A dysfunction is purely expression-level regulation is extremely low. Not impossible—but exceedingly unlikely…]
Russian roulette is still a calculated gamble.
Up until now, we could weigh risk vs. predicted outcome to some degree.
With epigenetics, the expected benefit relative to risk is disproportionately small.
In other words—this was closer to blind betting than probability.
However.
There was a reason it existed as Plan B at all.
“Because we’ll learn more about the disease than ever before. And CRISPR’s odds of success will improve dramatically.”
[That much is true, but…]
WFOXO3A acts as the immune system’s final emergency brake.
CRISPR is like a pair of scissors that can snip, reroute, and rewire that brake.
Except—right now, we don’t know where to cut or how.
Epigenetic drugs could reveal the answer.
This drug works like removing rust that has built up across the entire brake system.
Meaning, it reveals exactly where the problem lies.
[But the chances of epigenetics solving the root cause are almost zero. The patient gains very little, while the cost is enormous. You’re basically asking them to sacrifice themselves for others. To go on a suicide scouting mission…]
In military terms, it’s a recon mission.
A scout gathers intel deep in enemy territory, but rarely lives to fight the actual battle.
Most are discovered, ambushed, and never make it back.
But the information secured through their sacrifice allows the main force to fight—and win.
From the perspective of a war effort, it’s a necessary loss.
From the perspective of the scout, it’s a death sentence.
We had no right to make that decision for anyone.
Only one person could choose it.
“What did the patient say?”
No matter how grim the odds, there is always someone brave enough to volunteer.
Maybe this patient was one of them.
So, we had built protocols for that exact scenario.
We disclose every risk, every unknown, every worst-case outcome without sugarcoating anything.
And if—after hearing it all—the patient still chooses to proceed…
Then, and only then, we pull the trigger on Plan B.
Because the final decision always belongs to the patient.
But then—
[The patient… wants to do it.]
“Even fully understanding the risks?”
[Yes. We’ve only completed the first-round explanation, but her position is firm. Rachel offered to spend a week giving her additional details to be sure, but…]
I tilted my head.
“If the patient understands the risks and consents, isn’t that exactly what the protocol allows? We can proceed as designed.”
The system we built was airtight.
But on the other end of the line came a long, heavy sigh.
[About that system… I don’t think it will work this time.]
“Why not?”
[Legal issues.]
“Are you telling me the hospital is rejecting it as off-label?”
[No, it’s not that…]
David hesitated, choosing his words carefully.
And when the answer finally came, I had to swallow a curse.
[The patient is a minor. Seventeen years old.]
Her name was Talia.
A seventeen-year-old girl raised by a single mother.
David laid out the situation.
[Talia herself understands the risks and wants to proceed, but… her mother strongly refuses. She insists on waiting for a real cure.]
Of course she would.
Even standard Russian roulette is avoided due to lack of data.
And this? This wasn’t even that. This was worse—an uncharted recon mission.
The chance of success was microscopic, and the danger was catastrophic.
It was practically a sacrifice by design.
[I can’t tell if I should respect Talia’s will, or protect her from herself. I’m at a loss. Maybe you should speak to them in person, Sean.]
That’s how I ended up on a flight to Philadelphia.
Watching clouds drift past the window, the same question looped in my mind.
'What outcome do I actually want?'
If this were purely about my own survival, the answer was simple.
Convince the mother to let Talia proceed.
If she takes the treatment, we get data, and my odds improve.
But I didn’t like that answer.
'This is too much.'
Plan B is built on sacrifice.
But the sacrifices I had imagined when designing it were different.
People who had lived full lives.
Those nearing the end, searching for a final purpose.
Not a seventeen-year-old kid.
Using a minor as a bullet sponge… even if she volunteered… didn’t sit right with me.
'First… figure out the motive.'
Why would a teenager willingly choose a recon mission that could kill her?
I needed to hear that first.
[We will begin our descent shortly. Please fasten your seatbelt…]
By the time the announcement ended, we were touching down in Philadelphia.
It was early morning when I arrived at the University of Pennsylvania Hospital.
The ward hallway was quiet. I made my way to the room I had been directed to.
Rachel and David were already standing outside.
“Sean, you made it. This is—”
Rachel recognized me first.
Then she gestured toward the middle-aged Hispanic woman beside her, nervously rolling a rosary between her fingers.
Clearly Talia’s mother.
“But why is everyone out here?”
I asked, eyes moving to the closed door.
“That… was Talia’s request.”
“Request?”
“Yes. She said she wants to speak to you alone when you arrive.”