sinovels Chapter 1427 Unified Theory
Chapter 1427 Unified Theory
Chapter 1427 Unified Theory
It was already dark when Mannstein left Yang Ping's office.
He stood in the corridor for a while, still clutching the notebook. Yang Ping's last few words were like nails driven into his mind: stem cell theory and three-dimensional guide gene theory should be unified at their core; the guidance that regulates cell differentiation and location is a single mechanism. This idea was too grand, so grand that he didn't know where to begin. At that moment, he also felt that he was far behind Professor Yang in terms of understanding.
He walked back to the lab and sat down in front of the microscope. The M21 slides were still on the stage, the red and green fluorescent cells glowing quietly in dark field. He stared at those cells for a long time, Yang Ping's words repeating in his mind. The desired cells appear in the desired locations. From the moment of fertilization, the human body repeats this process. Differentiation and migration, division and localization, becoming a certain type of cell and going where—these two things happen simultaneously in embryonic development, never separately. A neural progenitor cell is born in the subependymal region of the lateral ventricle, migrating along the fibers of radial glial cells to a specific layer of the cerebral cortex, where it differentiates into a specific type of neuron. Where it goes determines what it becomes, and what it becomes determines where it goes. Differentiation and migration are two sides of the same coin, not two independent processes.
This mechanism is shut down after adulthood; cells no longer migrate on a large scale, and tissues no longer remodel on a large scale. When damage occurs, the body's first reaction is not repair, but scarring. Evolution has chosen a conservative strategy: it's better to lose function than to grow uncontrollably. Tumors are the consequence of uncontrolled growth. Over millions of years of evolution, the body has learned one thing: the risks of repair are sometimes greater than the risks of not repairing. So the repair mechanism has been sealed away, like an instruction manual locked in a cabinet—you know it's there, but you can't access it.
Now, Yang Ping says that instruction manual can be unlocked. The way to unlock it is to reactivate the guidance signals from embryonic development, telling the body "this area needs repair," and telling the original cells "you should go there, you should become this." Precise gene editing, non-specific microenvironmental adjustments, and perhaps even some small chemical molecule. Different keys, same lock.
In his notebook, Mannstein wrote: "The unified regulatory mechanism of differentiation and migration—reactivation of embryonic development?"
He looked at the line of text, felt it wasn't accurate enough, crossed it out, and rewrote a new line below: "Repair is re-enactment of development."
He left that line; he didn't cross it out.
The next morning, Mainstein went to see Yang Ping. Yang Ping was already in his office, the manuscript of the review article spread out on the table, and a teacup beside him was steaming.
"Professor, you're not asleep?"
"How could that be? You need to rest before you can work." Yang Ping looked up. "You've come at the right time. I've figured some things out. Take a look."
Mannstein sat down, opened his notebook, and prepared to take notes.
“Let’s start with embryonic development.” Yang Ping stood up, walked to the whiteboard, and picked up a black whiteboard marker. “The fertilized egg divides, forming a cluster of cells. The cells begin to differentiate, migrate, and form tissues, organs, and systems. What rules does this process follow? There is only one rule—the cell appears in the right place at the right time, doing the right thing.”
He drew a circle on the whiteboard to represent a fertilized egg. Then he drew countless branches to represent the cell differentiation and migration pathways.
"What determines 'correctness'? It's position. When a cell reaches a certain position, it receives signals from that position and then knows what it should become. The sense of position precedes differentiation; it's not differentiation that determines position, but position that determines differentiation."
Mainstein nodded; this was the core of the three-dimensional guided gene theory, and he knew it.
“Let’s look at stem cell therapy.” Yang Ping drew another branch on the other side of the circle. “We extract stem cells, expand them in vitro, and then inject them into the damaged area, hoping they will differentiate into the cell types we want. The success rate is very low. Why? Because we only give them instructions on ‘what to become,’ not on ‘where to go.’ After the stem cells are injected, they don’t know where they are or what they should become. They differentiate randomly, most of them becoming useless cells, and a very small number becoming the right cells, but in the wrong place, with the wrong connections, and the wrong function.”
Mannstein wrote faster.
“Embryonic development isn’t like that.” Yang Ping connected the two branches on the whiteboard with a line. “In the embryo, differentiation and migration are regulated simultaneously. A cell constantly receives location signals during migration, and its differentiation program is updated every time it reaches a new location. By the time it finally reaches its destination, it has completed differentiation. It’s a perfect, integrated system.”
Mannstein stopped writing and looked up at Yang Ping.
"Professor, do you mean that the protocellular activation we observe in spinal cord injury repair is actually the reboot of this system?"
“It’s more than just a reboot!” Yang Ping wrote two large characters on the whiteboard—“Unification”. “What we observed was that the underlying logic of this system was at work. Whether it’s precise gene editing or non-specific microenvironmental adjustments, what we’re doing is essentially the same thing. We’re giving the body a signal, saying, ‘This is the embryonic stage; tissue needs to be built.’ The body receives this signal and activates that dormant mechanism. The progenitor cells know where they should migrate to, what type they should differentiate into, and what connections they should establish.”
Yang Ping put down his pen, turned around, and looked at Mainstein. "This instruction manual has always been there; it has never been lost. It was just locked away. What we did wasn't to create a new mechanism, but to find a way to unlock it."
As Mannstein stared at the dense text and diagrams on the whiteboard, his heart began to race. If Yang Ping was right, then the scope of this unified theory would extend far beyond spinal cord injury. All diseases involving tissue degeneration and damage—Parkinson's disease, Alzheimer's disease, myocardial infarction, cirrhosis, diabetes, and even aging itself—could be due to the sealed instruction manual not being opened, or being opened incorrectly.
"Professor, could the stem cell theory and the three-dimensional guide gene theory be parts of this unknown theory?"
"Yes!"
"Then how do we verify it?"
"Using Chen Jianguo's data, we have already observed functional recovery, cytokine activation, and dicortin-positive cells in his cerebrospinal fluid. Now we want to go a step further and prove that his recovery is not random or localized, but follows the temporal and spatial order of embryonic development. Sensory recovery proceeds from top to bottom, and motor recovery proceeds from proximal to distal, from the trunk to the limbs, and from large muscles to small muscles. This is the order of embryonic development, and it is also the order we have observed. If this order is consistent in all patients, then it is not a coincidence, but a pattern."
Mannstein quickly jotted it down in his notebook.
“Furthermore,” Yang Ping continued, “we need to conduct a crucial experiment on animal models. We'll block key guidance signals during embryonic development, such as netrin, slit, and ephrin… to see if protocellular cells can still be activated. If repair stops after the signals are blocked, then it proves that repair is indeed replaying development.” Mainstein stopped writing and looked at Yang Ping. “Professor, this experiment will take a considerable amount of time and requires a large number of animals. As for funding… I need to apply for some in Germany.”
"I'll take care of the funding; you just focus on your experiments."
"Professor, our team is a bit weak, you need to give me more manpower."
“I transferred a group of people from our lab over there.”
"Also, Professor, you are the one who leads this research project. I am just an executor now. Although spinal cord injury research is my topic, it is clear that the topic has been upgraded now."
Mannstein closed his notebook and stood up.
"Professor, stem cells and three-dimensional guide genes should be unified at the underlying level. Do you really think this is a verifiable scientific question?"
"It's a scientific question! It's verifiable, and I'm planning to propose a hypothesis now."
"Then let's write it in the review, put it in black and white. If it's right, people will follow this direction. If it's wrong, people will know that this path is blocked. Regardless of whether it's right or wrong, it has value."
Yang Ping thought for a moment, then walked to the table and opened the manuscript of the review article. He turned to the last page: the "Future Outlook" section was still blank. He picked up a pen and wrote:
"We hypothesize that the differentiation regulation of stem cells and the three-dimensional spatial guidance of cells share the same molecular mechanism at the underlying level. This mechanism is responsible for coordinating what cells 'become' and 'go' during embryonic development, or what they 'become' in a certain place. It is sealed in adulthood, but can be reactivated under appropriate signal stimulation to mediate tissue repair after damage. Verifying this hypothesis will be the next important scientific question in this field."
He handed the manuscript to Mainstein. "Take a look."
Mainstein took it, read it once, and added a sentence below: "If this conjecture is true, then by reactivating the embryonic development program, we may be able to repair not only the spinal cord, but also almost all tissues and organs in the human body."
Yang Ping read the line of text and remained silent for a moment. "Are you sure you want to write such a bold prediction?"
"Absolutely! Science needs bold predictions, as long as those predictions can be falsified."
The next day, Yang Ping sent the first draft of the review to Tang Shun, Lu Xiaolu, and others for their feedback. He didn't ask "Is this theory correct?", but only asked one question... "If this theory can be proven, what kind of evidence do we need?"
Such a grand theory is difficult for a single team to study, so Yang Ping decided to propose a hypothesis to pique the interest of the world in studying it.
Soon, he published his preliminary hypothesis in the medical journal.
Responses arrived gradually over the next few days. Some were skeptical, some excited, some cautious, and some bluntly said, "You're thinking too far ahead; publish the data first." Yang Ping carefully read every email, extracting valuable comments and posting them on the whiteboard. The majority of the comments were skeptical, which actually reassured him somewhat. A theory that no one questions is either the truth or nonsense.
A week later, Yang Ping received an unexpected email. The sender was the president of the International Society for Stem Cell Research, a senior scientist who had worked in the field of stem cells for thirty years. The email subject was short, containing only one word: "Theory." The body of the email was also short, consisting of only three sentences:
“Professor Yang, I have read your paper. The hypothesis you wrote on the last page, if true, will completely change the direction of stem cell therapy. I have decided to devote all the resources of my laboratory for the next five years to verifying this hypothesis. If you have time, I would like to come to China to discuss it with you in person.”
Yang Ping forwarded the email to Mainstein, adding the comment: "The response to our hypothesis has been very positive."
Mainstein replied quickly: "It's not 'we,' it's 'you,' it's your conjecture. I'm just the executor."
Yang Ping looked at the message but didn't reply. He knew Mainstein was telling the truth. This German never claimed credit. When M7 was discovered, he said it was Yang Ping's theory; when the M21 slice came out, he said it was Yang Ping's conjecture; now that someone was willing to invest five years of resources to verify it, he still attributed it to Yang Ping. Sometimes Yang Ping felt that Mainstein wasn't like a typical German. Germans are usually very sensitive about attribution—whose paper was cited, who proposed the concept, who should be listed as an author—everything had to be clearly distinguished. Mainstein genuinely believed that Yang Ping was the true driving force, and that he couldn't have brought up such a theory on his own.
That night, Fritz was on night shift in the animal room. He sat next to M7's cage, a book in his hand, the light from the lamp falling on the pages and on M7's sleeping face. M7 had taken thirty-two steps that day, setting a new record. In its sleep, it kicked its hind legs again, and Fritz reached out and gently stroked its head through the cage.
“M7,” he said in German, “do you know you are witnessing history? You don’t know, you only know how to walk.”
Fritz turned a page in his book, the lamplight flickered, and M7, in his dream, kicked its hind legs again, more powerfully than before. Fritz smiled, a small smile, the corners of his mouth just slightly upturned.
Chen Jianguo was still standing in the rehabilitation room. There was no therapist, no Sister Li, just him. Holding onto the parallel bars, he had gone from standing for three minutes to five. He stood a little longer each day, making a little progress each day. He didn't know what embryonic development was, or what the unified regulation of cell differentiation and migration was. He only knew one thing: his legs were a little stronger today than yesterday—that was the ultimate test of all theories.