A genius? I just love studying.

Chapter 318 Nirvana No. 1 (additional update)

Dana-Farber Cancer Institute, Latest Findings Release Conference

International mainstream media focused on the latest breakthrough at Dana-Farber Cancer Institute, where Professor Diana, the institute's director, attended a press conference in formal attire amidst flashing camera lights.

After answering questions about his team's groundbreaking paper published in Cell, "Pan-cancer analysis reveals the master switch of bypass drug resistance, targeting the PKA-mTOR signaling axis," a reporter asked about the achievements of Chinese scientists.

A BBC reporter stood up and asked, "Professor Diana, as far as we know, Professor Song Chaoming's team in China recently published research findings on cancer drug resistance pathways in *Chinese Journal of Mathematics*, which seems to be related to the research direction of your institute. What is your comment on this?"

When Diana heard this question, the corners of her mouth turned up slightly, revealing a barely perceptible smile that carried a sense of superiority.

She didn't answer immediately, but gracefully straightened her clothes and glanced at all the reporters present, as if to confirm that everyone should focus on her core findings.

“Oh, you mean the work published in *Chinese Mathematics*?” Her tone deliberately slowed, carrying a hint of the superior calm characteristic of academic authority. “Yes, we have noticed the relevant reports and the paper in *Chinese Mathematics*.” She deliberately emphasized the name of the mathematics journal.

Their research, focusing on a very specific non-classical EGFR pathway, represents a commendable initial attempt as a localized exploration.

She paused briefly, leaned forward slightly, and spoke with a clearer and more authoritative tone, “However, I want to clarify a very important conceptual distinction.”

She raised one hand, as if directing a grand painting, "Our research is fundamental, systematic and transcendent. We have revealed the PKA-mTOR signal axis, the master switch for drug resistance across multiple cancer types."

This is not only the key to drug resistance mechanisms, but also the core secret that our team has unlocked after years of dedicated effort and by integrating top global resources.

Diana's tone revealed undisguised confidence and pride: "Frankly speaking, their discovery was like sketching out the tip of this massive iceberg, while our work was to directly locate and dissect the foundation buried deep in the seabed that supports the entire iceberg structure, the main valve."

Their pathway is precisely one branch of the numerous downstream effector pathways coordinated by this master control hub that we discovered, a finding that perfectly corroborates the grand network of drug resistance we have described.

She casually ended her commentary and leaned back in her chair. "So, a more appropriate perspective on the achievements of our Chinese counterparts might be that their research provides an interesting and concrete case study to support our core findings."

That's how science works; pioneers always point the way, while successors provide the details. Of course, Dana Faber's leading role and pioneering spirit in this field, I think, are now beyond dispute after the publication of this work.

"Oh, by the way, I heard that 'Chinese Mathematics' is a mathematics journal. I still suggest that they submit such results to 'Cell' in the future. If it weren't for the extensive publicity from Chinese media, we might not have even noticed that paper."

"Professional matters should be left to professionals, and the same applies to journals!"

After she finished speaking, she flashed her signature victorious smile, signaling the end of the questioning session, and her gaze shifted to the next question.

……

In the editorial office of Cell, editor-in-chief Charlie was all smiles after reading Diana's interview. He couldn't suppress his grin. As expected of their best partner, she really gave them face. He decided that from now on, he would be lenient with any papers submitted by the Dana-Farber Institute.

As for Huaxia's thesis, he would naturally have to review it carefully.

Since they already have their own journals, why bother submitting to *Cell*? They should submit to *Huaxia Mathematics* instead.

……

"what happened?"

Song Chaoming looked at Tang Jian, who had returned, his eyes filled with doubt.

He also saw the message Tang Jian posted in the group. The other party canceled his vacation without his permission, so there must be some major discovery. Especially when he saw Chen Hui who came with Tang Jian, he couldn't help but narrow his eyes and a bold idea came to him.

"Could it be that there's been a breakthrough in the project?"

He asked in surprise.

"Let's talk about it all once everyone's here."

Chen Hui carried his laptop toward the main conference room, giving Song Chaoming a bright smile. Although he didn't answer, he had already given his answer.

Song Chaoming also laughed happily.

Soon, everyone in the lab was sitting in the large conference room. They didn't have any negative emotions because the holiday was suddenly canceled. Instead, they all looked at Chen Hui with anticipation.

Because they know that the only reason to cancel the vacation is that there is new progress in the project!

Chen Hui looked at everyone in the conference room and smiled brightly, first reassuring them before beginning to explain his thoughts: "Was our war against cancer wrong from the very beginning?"

Why must we see it as an enemy and try to kill it? Why can't we... guide it? Or even... educate it?

"Just like Yu the Great's flood control, it's better to dredge than to block!"

Time seemed to freeze in the conference room, with only the faint hum of the projector and the almost stagnant shock that filled the air.

Song Chaoming and his team members had just finished listening to Chen Hui's explanation.

Chen Hui's tone remained calm as always, without boasting or excitement, as if he were simply stating an obvious fact.

But the dazzlingly complex gene circuit designs, the precise structural simulations of nanocarriers, and the AI-based predictive efficacy curves that flow across the screen together weave a concept that is so subversive, so bold, that it sounds almost like science fiction.

The silence lasted for a full minute.

Finally, Song Chaoming broke the silence first. His voice was hoarse and trembling with disbelief, "Chen Hui... do you... do you know what this thing you proposed means?"

“It means we may have taken the wrong path,” Chen Hui answered succinctly, “It means we need to look at cancer in a different way.”

“But…this is too…” A PhD student in charge of animal models opened his mouth, wanting to say “too crazy,” but looking at the logically rigorous design drawings, he swallowed the word back and said, “…it’s too challenging to the existing paradigm, how is this possible?”

"That's why we need to verify it!" Chen Hui's gaze swept over everyone, finally landing on Song Chaoming.

The result was as expected. Song Chaoming's entire team sprang into action, and the verification process was launched immediately. The entire project team entered an unprecedented state of excitement and high pressure. But this was no longer a blind experiment; it was a precise exploration guided by a completely new theory.

The team's first action was not to rush into the lab, but to gather around the whiteboard and conduct the most rigorous logical review and computer simulation of every aspect of Chen Hui's theory.

"What makes your precise navigation system so certain that it only identifies cancer cells? Normal lung cells also have similar surface proteins!"

Tang Jian raised his questions to Chen Hui, which was also the point of confusion for everyone in the conference room.

Chen Hui accessed a database to showcase the membrane protein combinations he had screened that were common to various lung cancer cells and associated with key pathways crucial to their function, exhibiting extremely high combination specificity. Simulation results showed that the probability of mistakenly damaging normal cells was less than one in a million.

Seeing this simulation result, everyone temporarily put aside their doubts, but still remained skeptical. However, none of this is important; these questions will need to be answered in subsequent experiments.

Of course, if these issues can be understood before experimental verification, the experiment will be much more efficient. It is always better to discover problems early than late.

How is the expression of gene circuits controlled within cells? Will overexpression trigger an immune response or cause cancer?

Another junior brother stood up and looked intently at Chen Hui.

Chen Hui demonstrated the ingeniously designed self-destruct switch and feedback regulation module in the circuit. Its dynamic model shows that it will automatically degrade only after a specific therapeutic effect has been achieved.

Clearly, he had considered all of these issues.

After several days of heated debate and cluster computing by supercomputers, the theoretical loopholes were patched one by one. Although it still seemed incredible, the team had to admit that, at least in terms of logic and simulation, the solution was flawless.

The theory is sound; the next step is the brutal experimental verification.

Based on Chen Hui's design, the synthetic biology team began to try to synthesize the complex gene circuit and load it into a specially made nanocarrier. However, the gene circuit was too complex, had poor stability, and was difficult to package efficiently.

Finally, Chen Hui adjusted the structure of some non-critical sequences and optimized the packaging signal, ultimately successfully preparing the first batch of viral vectors.

They added fluorescently labeled gene loop vectors to culture dishes containing a mixture of various lung cancer cells, including drug-resistant, different mutation types, and normal human cells.

Twenty-four hours later, the sight seen under a confocal microscope made all the researchers watching gasp in astonishment.

The fluorescent signal was precisely concentrated within the nucleus of the cancer cell, while the surrounding normal cells showed almost no signal. The precise navigation was successful!

72 hours later, an even more shocking scene appeared: under time-lapse microscopy, the infected cancer cells began to show two completely different fates.

Some cells stopped proliferating and began to express surface markers of mature lung cells; they had differentiated!
The other group of cells rapidly shrinks, forming classic apoptotic bodies; they commit suicide!
In the petri dish, the territory of rampant cancer cells shrank at a visible rate, replaced by areas that either differentiated and became dormant or were eliminated.

A senior female student covered her mouth, almost screaming. The doctoral student in charge of the cell experiments repeatedly checked the experimental group and the control group, his fingers trembling slightly with excitement.

Although it was only an initial success, it at least proves that Chen Hui's idea is feasible!

But having learned from their previous experience, they dared not be too happy, as no one knew how this gene circuit would perform in long-term animal experiments.

Successfully creating cell lines in vitro is only the first step; the more complex task is testing them in an environment closer to the human body.

Without stopping, Tang Jian immediately organized the development of organoid models. They used tumor-like organs derived from tumor cells of patients with advanced lung cancer, including those resistant to multiple drugs. This is an excellent model for predicting clinical outcomes.

Then, the gene circuit vector was injected into these organoids that mimic the structure of real tumors.

The same thing happened again!
The complex 3D tumor structure began to disintegrate and shrink within days.

Immunofluorescence staining and single-cell RNA sequencing analysis showed that the surviving cells were either successfully educated cells expressing differentiation markers or uninfected cancer cells, and no drug resistance was observed!

The nightmare of evolutionary catalysts did not repeat itself.

The experiment proceeded step by step in the expected direction, but the previous failures were like a Damocles' sword hanging over everyone's heads, making everyone dare not relax in the slightest. After the organoid model was successfully verified.

They immediately conducted animal experiments, transplanting lung cancer cells expressing luciferase into mice. After tumors formed, they injected gene loop vectors.

Using luciferase and an in vivo imaging system, they were able to observe tumor changes in mice in real time.

As everyone knows, the real test has just begun. The team is gathered in front of the screen, and even Chen Hui is waiting anxiously in the lab. Song Chaoming has also been staying in the lab this time, working with the team through every step of the experiment.

On the first day, the tumor continued to glow; on the second day, there seemed to be no change; and after the third day, some people began to feel anxious.

On the fifth day, one of the junior students in charge of observation suddenly shouted, "Look! The signal is weakening! Not just a little, but the whole signal is weakening!"

The glowing area on the screen really looked like a sandcastle being washed by the tide, gradually dimming and shrinking from the edges. There was no inflammation or severe adverse reactions, and the tumor disappeared so calmly yet so quickly!
"The first group of samples was dissected and analyzed, while the other sample groups will continue to be validated over a long period of time."

Song Chaoming made a judgment immediately, and everyone sprang into action.

Histological analysis following the autopsy provided the final evidence: the tumor area was infiltrated and cleared by a large number of immune macrophages, and what remained were some morphologically normal cell clusters, with no evidence of any invasive cancer cells found.

The junior female student in charge of the dissection looked up at Tang Jian, who then looked at Chen Hui. At that moment, everyone had a premonition that they might be about to succeed.

But no one dared to cheer; they feared it was all just a dream.

As a result, the following period became even more difficult, with everyone anxiously awaiting the results of the animal experiments.

Half a month has passed, and the experimental results and data have proven the correctness of the plan, but Chen Hui decided to wait a little longer.

A month later, the mice in the experiment were still in good condition, and no tumor cells could be detected in their bodies.

Three months later, the evolutionary catalyst effect that everyone had been worried about did not reappear, but they still decided to observe it for a while longer.

Six months later, when all the data, from computer simulations to cell experiments, from organoids to live mice, were compiled into the final report in front of Chen Hui, the laboratory fell silent once again.

Song Chaoming looked at Chen Hui, stared at him for a moment, then his lips slowly curled into a bright smile. "I think you should probably give it a proper name!"

"Let's call it Nirvana!"

These words were like a spell broken; instantly, the laboratory was engulfed in a huge, uncontrollable cheer and applause.

A female senior student excitedly hugged her colleague, while the male senior student who had initially questioned the idea rushed over and patted Chen Hui hard on the shoulder, rambling incoherently. Everyone understood that they were not just participating in an experiment, but in a medical revolution that was about to change the world.

Chen Hui stood in the center of the cheers, a faint, relieved smile finally appearing on his face. His gaze seemed to have already passed over the revelers and turned to the window.

He knew this was only the beginning of the verification process.

The next step is to open the door to a new life for his uncle, and for many more like him!
Hopefully, nothing unexpected will happen this time.

(End of this chapter)