A Wall Street Genius's Final Investment Playbook-Chapter 290: Symptoms (4)

“Why?”

The answer came two days later. After I read the email from Quantum Genome.

Quantum Genome. This was the startup where I had requested an analysis of Milo’s genes. I had asked them to send me all newly discovered data in real time.

At last, a new report arrived from them.

<Across the entire follicular region within the lymph nodes, a ‘non-expression’ pattern has been observed............>

But this time, what was discovered wasn’t gene overexpression—it was the opposite, ‘non-expression.’ Genes that should absolutely be active in a healthy person were completely silent in Milo.

The name of that gene was...............

<WFOXO3A expression was not detected in any single region...............>

WFOXO3A.

It was a familiar name. That’s because it was often referred to as the so-called “longevity gene,” mentioned repeatedly in numerous studies.

“This shows up here?”

WFOXO3A performs a variety of roles. It protects cells from oxidative stress, repairs DNA damage, and slows down the aging process of cells. But that wasn’t the most important part right now. In the matter at hand, its role related to Castleman’s was................

<WFOXO3A suppresses abnormal cell proliferation and activates cell death pathways.>

That was it. When cells proliferate excessively, it detects the abnormal signals and induces those cells to self-destruct.

“In other words, the final brake.”

Whether cancer cells, abnormal cells, or immune cells running out of control—The moment WFOXO3A catches the signal of “this isn’t normal,” it coldly pulls the breaker and halts the spread.

But......... In Milo, this brake wasn’t working. Not merely weakly activated, but “completely” silent. In other words, the gene’s function was fully switched off in Milo.

“If this is the real cause of Castleman’s?”

This was the moment a long-standing mystery around Castleman’s was finally unraveled. It wasn’t that a “madness switch” had been flipped on. It was that the “brake” had broken.

If so, then the solution was simple. That “brake”—WFOXO3A—just needed to be turned back on. As long as there was a treatment that could activate this gene, everything would be resolved.

But then. As soon as I reached that thought, I found myself frowning. This wasn’t simply good news.

“If I recall correctly................”

I searched through related papers to confirm one detail.

<Exogenous activation of WFOXO3A is currently deemed unfeasible for clinical application with existing drug design and delivery technology...............>

Yes. As of now, there was no treatment capable of directly activating WFOXO3A. Quite literally, “nowhere in the world.”

But this completely shifted the essence of the problem. Up until now, the fight had been against “uncertainty.” Blindly administering various treatments without knowing what or how to treat. In short, a gamble against fate.

But now? The fog of “uncertainty” was gone, and the precise target to aim at was clear. The problem was, there wasn’t a bullet to hit that target. Or rather—There was a bullet, and there was a target. But the gun itself had no trigger. There was simply no treatment to fire.

“So that’s why.”

I had thought we had gained enough time, but still “Symptoms” warned me against spending recklessly. I suspected this was why.

“I can’t just repurpose existing drugs anymore.”

I had to create a new treatment with my own hands. This was a task that required enormous time and resources compared to using a drug already on the market.

Of course, I had braced myself for that from the start..................

<Given current technology, activating this gene remains difficult............>

But this was different from what I had prepared for. Because developing this treatment was considered outright “impossible” in academia.

I narrowed my brow and scanned the list of authors on the paper.

―

Clarence Pendleton (University of Pennsylvania, School of Medicine)

Conveniently, one of the authors was a professor at the hospital I sponsored.

“Should I meet him in person?”

Out of habit, I reached for my smartphone to call a driver............ then paused.

“Oh, right. No driver................”

Because of financial strain, I hadn’t rented a sedan this time. I turned my gaze toward the living room. There sat Rachel, quietly focused on the laptop screen.

***

Meanwhile.

Seated on the living room sofa, Rachel was staring intently at her laptop.

<The Dream Project>

A project she had been preparing for a long time was finally about to bear fruit. Just getting through this week, she had an important meeting lined up. So this was the time to throw herself into final checks................

“Rachel?”

Hearing Ha Si-heon’s sudden voice from behind, Rachel flinched and reflexively slammed her laptop shut. Ha Si-heon awkwardly scratched the back of his head.

“Sorry. I didn’t mean to startle you.”

“Oh, no. I wasn’t startled.............”

Her hesitant excuse sounded strangely awkward. As she faltered, unsure how to finish her words, Ha Si-heon asked first.

“Would you happen to have some time right now? Something’s come up, and I need to visit the hospital.”

“......Yes, of course!”

Rachel quickly grabbed the keys on the coffee table. They were the car keys David had left behind, telling her to use them freely.

“I’m sorry. I wish I could drive myself.”

“It’s fine. I actually enjoy driving!”

Recently, David had switched cars, and it was a classic model—with a manual transmission. But since Ha Si-heon, unexpectedly, couldn’t drive stick at all, Rachel had been the one behind the wheel for the past few days whenever they went anywhere.

‘Who would’ve thought.’

She couldn’t help but smile when she saw the man, who seemed like he could do anything, completely flustered in front of a manual gearbox. That unexpected side of him amused her.

“Perfect timing, I needed to do some shopping anyway. Let’s stop on the way!”

“I’m sorry. I keep causing you trouble.”

This time, Ha Si-heon’s apology wasn’t just about the driving. Ever since he had lost his wallet a few days ago, he had been relying on Rachel for all living expenses.

“So he does have surprisingly sloppy sides.”

During the days they had spent together, she had been discovering new, unfamiliar facets of him one by one. And strangely… every time she did, it stirred something in her.

Anyway, on the way to the hospital, Ha Si-heon gave a brief explanation.

“They found a decisive clue in Milo’s bio samples. A gene that suppresses cell proliferation was completely silent. That might be one of the main causes of Castleman’s.”

“Really? Then if we can just reactivate that gene… doesn’t that mean it can be cured?”

“Yes, there’s a high chance.”

“That’s… that’s incredible news!”

It was nothing short of a miracle. And the one who had brought about this miracle was—

“Amazing, Milo is…”

In Rachel’s mind flashed the image of the little boy clutching his dinosaur plushie with a determined look on his face. That small, fragile child… might be the key to saving thousands, maybe tens of thousands of lives around the world.

Her eyes grew hot with emotion. But Ha Si-heon calmly grounded her back in reality.

“Of course, it would be wonderful if that’s the case… but there’s still a lot we need to figure out.”

“Ah… so that’s why you’re going to see a specialist?”

“Yes. Pharmacology isn’t my main field. I need to seek advice.”

“If it’s just advice, then…!”

Rachel’s eyes shone with cautious hope. As someone who had lived closest to Castleman’s patients, she knew better than anyone the despair and pain they endured every day. But now. Maybe, just maybe—Those long days of hopelessness might finally come to an end. A quiet but clear hope stirred within her.

***

“It’s impossible.”

But. That hope crumbled all too quickly, shattered in an instant. The professor’s voice, when they finally met him, was resolute.

“Of course, I know it’s difficult. But there must be some way—”

“With current technology, it’s impossible.”

Rachel’s face hardened. She had braced herself for a tough road, but she hadn’t expected an answer that shut down every possibility outright. The professor’s cold words felt like a death sentence, sealing off all hope.

“Then may I ask… the specific reason why it’s impossible?”

Unlike the shaken Rachel, Ha Si-heon didn’t waver at all. He seemed almost as if he had anticipated such an answer, his demeanor calm and steady.

“Because WFOXO3A is a transcription factor.”

“A transcription factor…?”

Seeing Rachel’s confusion, Ha Si-heon explained gently.

“Transcription factors are proteins that bind directly to DNA and switch certain genes on and off. They’re extremely difficult to manipulate with drugs.”

The professor shook his head at Ha Si-heon’s addition.

“No. This isn’t just ‘difficult.’ Structurally, it’s impossible.”

Without hesitation, the professor laid out his reasoning point by point.

“For a drug to work, it must first reach and bind accurately to the target protein. The problem is that WFOXO3A is located inside the cell nucleus. That means the drug has to be carried across the nuclear membrane. And that’s not as easy as it sounds. To pass through, it needs to bind with a transport protein carrying a highly specialized NLS signal—”

The explanation was complicated. But Ha Si-heon simplified it for Rachel’s understanding.

“Most drugs only need to cross the cell membrane to reach their target. But WFOXO3A is behind another barrier: the nuclear membrane. Think of it as having to pass through a double set of doors.”

To cross the nuclear membrane, the drug had to pass through a narrow channel called the nuclear pore complex (NPC), and that required, in a sense, a “special entry ticket.” And that wasn’t the only problem.

“Designing a drug that can bind to WFOXO3A is extremely difficult as well. Structurally, the protein is thin and flat, leaving almost no active sites for a drug to latch onto.”

Ha Si-heon added more clarification.

“Typically, target proteins have grooves or pockets on their surfaces—like a lock and key mechanism—so a drug can fit in. But WFOXO3A is too smooth, too seamless, making it nearly impossible for drugs to bind.”

Yet again, the professor cut him off with a grim look.

“It’s not just ‘difficult.’ It’s impossible. As I said, leaving binding aside, molecules larger than 40 kDa simply cannot cross the nuclear membrane at all. But for any drug to be effective, the molecule inevitably becomes too large. If you make it small enough to enter, it won’t function. If you make it functional, it becomes too large to pass through. Finding a compound that is both small enough and effective enough—it’s practically impossible.”

Still, despite the professor’s definitive statement, Ha Si-heon’s expression never faltered. He quietly nodded and spoke again.

“I understand. Could you please continue your explanation?”

The professor frowned deeply. Even after being told repeatedly “it’s impossible,” Ha Si-heon looked utterly unfazed, as though the word didn’t exist in his vocabulary. Annoyed by that attitude, the professor paused—but then remembered that Ha Si-heon was the hospital’s largest benefactor.

With effort, he resumed.

“The most important point is that you can’t just recklessly activate this protein. WFOXO3A induces apoptosis—cell suicide. For cancer or aged cells, that’s beneficial. But if normal cells were indiscriminately affected—”

WFOXO3A triggers cells to self-destruct. If that function spread uncontrollably into healthy cells? It wouldn’t be medicine at all—it would be pure poison.

The professor pressed his words firmly.

“That’s why we can’t forcibly and indefinitely activate WFOXO3A. Doing so would be like flooding the body with toxins. Its activity has to be turned on and off with precision depending on the situation. But the more finely tuned you try to make a drug, the more complex the molecular structure becomes. And then, once again, nuclear penetration becomes virtually impossible.”

Finally, the professor summed it all up.

“Do you understand now? Even if you designed a drug meeting all these conditions, it still couldn’t be delivered. That’s why I’m telling you—it’s impossible.”

Once more, he cut down every sprout of hope. His tone was cold, unshakable, as though he were merely stating facts. Rachel’s eyes sank with sorrow. There was undeniable logic in everything he had just said.

“This is science, after all.”

Just when she thought she had found a breakthrough, an insurmountable wall loomed before her. A wall that no human effort could climb. Scientifically, physically, chemically—“impossible.”

Rachel lowered her head, unable to shake off her gloom. Then she lifted her gaze toward Ha Si-heon. How would he take this news?

And then—

“…?”

His expression surprised her. There wasn’t even the faintest trace of despair or disappointment. His face was calm as always. No—calmer still. In fact, the corners of his lips were curling upward.

Ha Si-heon slowly opened his mouth.

“Is that all that’s standing in the way?”