godfather of surgery

Chapter 1302 Identity Code
Wu Changde sat in the conference room with sunken eyes and a loose shirt collar. He held a report in his hand, his fingertips white from the pressure.

The platform launched seventeen major collaborative R&D projects from around the world, with more than eighty different module combinations. However, after entering the in vitro cell experiments and animal experiments, the success rate was zero. That's right, zero!
In other words, it is theoretically effective, but has no effect at all once it is put into practice.

"Where exactly is the problem?!" A representative from a pharmaceutical company in East China, which had participated in three projects, almost shouted. They had invested tens of millions of yuan and an entire elite team. "Our model showed an 85% kill rate in your simulation software, but in actual experiments it was less than 10%. And that's in vitro. Vector transfection efficiency, gene expression level, cytotoxicity... not a single parameter matched!"

Another university professor spoke in a slightly calmer but more pointed tone: "Professor Wu, we strictly followed the module sequences and operating procedures provided by the platform, but the constructed vector virus either completely perished in animals or triggered a fatal immune storm. We checked repeatedly, the module sequences were correct, and the preparation process was also standard. The only explanation is that there are many unknown influencing factors in the interaction between these modules, and your platform and theoretical model do not cover these at all!"

“And there’s off-target effect!” A young researcher stood up, his voice tinged with lingering fear. “The targeted vector we designed induced severe apoptosis in normal liver cell lines, while tumor cells were completely unaffected. We later discovered that this was because the targeting module accidentally formed a new spatial conformation when it folded inside the cell, and this conformation could bind to a widely expressed membrane protein… This is only in animal experiments, so it’s not a big deal. But if it were in clinical trials, do you think the consequences would be so severe?”

Accusations, doubts, confusion, and anger surged toward Wu Changde like a tide.

He tried to remain calm: "Everyone, calm down. It's normal to encounter setbacks in the innovation process, especially with such a complex systems biology problem. What we need is systematic analysis to find the root cause..."

"The root cause is that you underestimated the complexity!" Dr. Ward, a former senior scientist at BG Group who is now attending the meeting as an invited consultant, finally couldn't help but speak up. He had been sitting silently in the corner. "Professor Wu, and everyone here, you have made a fatal mistake. You only understand K therapy on the surface. I can tell you seriously that you have not even scratched the surface of this technology. You naively think that it is just a combination of modules such as adenovirus vectors, apoptosis initiators, and targets."

Everyone looked at him. Dr. Ward had a full head of silver hair and an expression of indifference that suggested he had seen it all before.

"You think that by breaking down K therapy into modules like 'carrier backbone,' 'promoter,' 'effect gene,' and 'target head,' and then assembling them like Lego bricks, you can create an effective treatment?" Dr. Ward shook his head, with a hint of pity. "Life systems are not Lego bricks. Their interfaces are not standard, their operating environment is not pure, and their feedback mechanisms are despair-inducingly complex. Professor Yang Ping's K therapy is far beyond your comprehension. I even think it's a product of a previous era. If he gave you detailed technical information, even if you assembled the best team, it would take five years to replicate it, let alone replicating a similar technology with limited, fragmented information."

Dr. Walker's words left Wu Changde sweating profusely. The facts were right there: he had suffered a complete failure. Even if he had succeeded in the slightest, he wouldn't be speechless.

Dr. Walker walked to a whiteboard, picked up a pen, and said, “To give you an analogy, the modules you designed are like exquisitely designed bullets. But what Yang Ping did was more than just design bullets. He spent countless hours understanding the characteristics of each ‘gun’ (carrier), mapping the terrain and weather of each ‘battlefield’ (tumor microenvironment), and studying the behavioral patterns and evolutionary strategies of the ‘enemy’ (tumor cells). Only then did he design the most effective bullet for this specific battlefield, with this specific gun, against this specific enemy. More importantly, he also monitored the changes in the battlefield in real time, adjusting the trajectory and even changing the bullet at any time.”

“And you,” Dr. Ward paused heavily on his pen, “think that by obtaining the blueprints for bullets, you have mastered war. You have ignored countless possibilities such as changes in gun chamber pressure, the muddiness of the battlefield, and the thickness of enemy body armor. Each module on your platform, taken individually, may work in a simple system. But once combined and integrated into a real living system, all those ignored interplay ghosts will emerge, rendering all predictions invalid.”

The meeting room was completely silent. Dr. Ward's words stripped away all the technical details and pointed directly to the root of cognition.

Wu Changde was pale. He knew Ward was right, but he couldn't admit it, because admitting it would mean the collapse of the entire project's foundation.

“Dr. Ward, your insights are profound, but any new technology needs time to mature…” he argued with difficulty.

"The process?" Ward interrupted him, pulling out a thin photocopy of a document with a "confidential" watermark from his folder. "This is a summary of the latest research progress of Yang Ping's team that I saw through special channels. They have just made a breakthrough in pancreatic cancer research. Do you know what it is?"

He looked around at everyone and said, word by word, "They discovered that every type of tumor may have an identity code, a specific K factor, and a stable target that is permanently bound to it and cannot be changed during evolution. This target is embedded in the tumor cell's identity genes. Once it is changed or lost, the tumor cell loses its tumor properties of unlimited division and stops proliferating. In other words, what Yang Ping found is not an ordinary target, but the tumor's Achilles' heel and its identity card! I believe that his K therapy for osteosarcoma was already putting this theory into practice. Currently, we haven't found such a target and corresponding weapon for treating pancreatic cancer, so we have to take a different approach to treating pancreatic cancer."

“This…how is this possible?” a scholar exclaimed. “Tumors are known for their genetic instability and evolutionary escape; how could there be an unchangeable target?”

“This is the gap in understanding,” Dr. Ward sighed. “We have been chasing after the ever-changing disguises of tumors, while Yang Ping has directly found the underlying logic that makes it a tumor. This stable target is not a surface protein, but is likely related to fundamental mechanisms such as maintaining telomerase activity, the formation of oncogene transcription complexes, or unique epigenetic modification states. It is stable because it is one of the defining characteristics of a tumor state; changing it is tantamount to suicide.”

"Why didn't his pancreatic cancer achieve the same effect as osteosarcoma? Because pancreatic cancer uses ordinary promoters and ordinary targets, while you can't combine ordinary promoters and ordinary targets now, yet you're trying to challenge the true K therapy."

He looked at Wu Changde with piercing eyes: "Professor Wu, your platform is still based on known, variable surface markers to design modules. But Yang Ping has entered a deeper, defining dimension. It's like others are studying how to shoot a moving target, while he has found the trajectory that the bullet will inevitably hit, because the target must pass through there to be called a target. You are trying to use nineteenth-century physics knowledge to solve twenty-century quantum mechanics problems."

“Dr. Walker, you’re exaggerating. Things aren’t as bad as you think!” Wu Changde tried his best to maintain the situation. Dr. Walker didn’t mince words: “You lack basic objectivity. Let it end now that it’s just begun. You’re lucky you failed in the animal experiments. If you had succeeded in the animal experiments, that would have been the worst thing, because you would have caused a disaster in the subsequent clinical trials. You should have at least some respect for technologies you don’t understand. That’s basic courtesy, especially in the medical field.”

These words became the last straw that broke the camel's back, and the meeting ended hastily in a state of depression and despair.

That evening, news that "the open platform encountered a major technical bottleneck, and multiple projects were stalled" began to circulate through unknown channels. The next day, a highly influential financial and technological media outlet published an in-depth investigative article with a sharp title: "Open Source Myth Shattered? Wu Changde's Platform Stuck in a Quagmire, Huge Investments May Go to Waste."

The article details several project failures, interviews with anonymous researchers describing various bizarre setbacks, and quotes the views of "senior industry experts," pointing out that the platform's core design philosophy has fundamental flaws and underestimates the extreme complexity of living systems.

The article concludes: "This open-source experiment, which began with a grand ideal, is now facing a severe test of reality: In the field of cutting-edge life sciences, especially gene therapy which is directly related to human life, can the open-source collaborative model really replace rigorously validated, highly integrated heavy-modal research and development? When the ghost effects of modular combinations are unpredictable, who will be responsible for the potential risks to patients? Professor Wu Changde's dream may need to be re-examined in light of the huge gap between itself and the complexity of life."

More media outlets followed up, and the questions spread from the technical aspects to project management, fund usage, and underlying motives. The stock prices of pharmaceutical companies participating in the platform plummeted, and institutions that had previously announced high-profile collaborations fell silent or became vague. Public opinion began to shift, from initial cheers for "open source" and "inclusive benefits" to criticism of "recklessness" and "risk," and a renewed appreciation and admiration for the truly capable Yang Ping team.

"It seems that the eyes of the masses are ultimately discerning." Huang Jiacai calmly read the public opinion briefing at an internal meeting of Ruixing. "The iron law of the technology world still applies: shortcuts are often the longest way, especially in medicine, where respect for complexity is the most basic rule."

……

Southern Metropolis Daily, Sanbo Research Institute.

Yang Ping paid no attention to the media storm outside. His entire focus was on the astonishing discovery that had just surfaced.

The discovery began with continuous deep sequencing of the latent tumor cells in Shen Guohua's body. When the team tried to track them using various known targets, they found that these cell surface markers continued to undergo dazzling drifts and recombinations, seemingly without any pattern. Just when everyone was once again struggling with this challenge, Yang Ping proposed a reverse approach:

"Since they are changing, is there anything they absolutely cannot change? If they change, then they are no longer tumor cells?"

The team retrieved and integrated unprecedented whole-genome, transcriptome, and epigenome data of Shen Guohua's tumor cells at various time points before, during, and after treatment. Instead of searching for highly expressed or specifically expressed genes, they looked for gene regulatory regions or protein complex structures that maintained a specific active state in all tumor cells and at all time points.

This is a computationally intensive analysis, and the supercomputing cluster at Nandu University of Technology has begun operating at full speed.

Ultimately, a set of core features hidden behind the complex data emerged: In Shen Guohua's pancreatic cancer cells, regardless of surface changes, a specific non-coding RNA located on chromosome 7 was always in a high transcriptional state, named PANC-ID1; at the same time, a complex formed by three specific proteins was always stably bound to the enhancer regions of several key oncogenes, maintaining the continuous activity of these genes.

More importantly, when they used gene editing technology in the lab to artificially suppress the expression of PANC-ID1 or disrupt the formation of the three-protein complex, something amazing happened: pancreatic cancer cells rapidly stopped proliferating, and some cells began to express and stop dividing. To restore their proliferation, they must simultaneously restore both high PANC-ID1 expression and stable binding of the three-protein complex; neither is dispensable.

"This is the identity lock!" Song Ziming's voice trembled with excitement. "This non-coding RNA and protein complex together constitute the core switch that allows pancreatic cancer cells to maintain their cancerous identity. The surface protein can be replaced, but it cannot be lost. If it is lost, the tumor cell will lose its essence!"

Yang Ping gazed at the exquisite and robust molecular interaction network model on the screen and slowly nodded: "It's not just a target, it's the cornerstone of a tumor's existence. The targets we were looking for before were external features, but the targets we've found now are its essential characteristics."

The subsequent research followed this line of thought, and the team began conducting similar analyses on other types of tumors in the database. Although the specific molecules varied and the search was difficult, the excitement of the new discovery kept everyone working day and night. If all tumors behaved this way, what a significant discovery it would be!

Unfortunately, they haven't found the target in other tumor cells yet. This discovery in pancreatic cancer is just the beginning. If the discovered PANC-ID1 and the three-protein complex are indeed the identity code, they will need to find the corresponding factor K, which is the most difficult part.