godfather of surgery

Chapter 1431 Handshake



Chapter 1431 Handshake

Chapter 1431 Handshake

The next morning, Weber arrived at the conference room on time, his tie perfectly tied—a dark gray one that looked mismatched with his dark blue windbreaker—but he seemed quite pleased with himself. Mainstein sat opposite him, spreading out the data he had compiled the night before. Weber put on his reading glasses and slowly examined each sheet, occasionally scribbling German words in the margin with a pencil.

“This,” he pointed to an immunofluorescence image, “is this a spinal cord section from M7?”

"Yes, eight weeks after the injury."

"The marker of the protocell?"

“Nestin and Sox2 are both positive, and this one too,” Mainstein handed over another one. “This is a 3D reconstruction. You see, they are concentrated in the transition zone from the lesion center to the caudal side, forming a gradient.”

Weber placed the two images side by side, looked at them against the light for a while, then put them down, took off his glasses, and rubbed the bridge of his nose.

“Mannstein, we’ve been doing stem cell research for fifty years, searching for the ‘seed.’ Transplanting the seed, culturing the seed, protecting the seed. And now you’re telling me the seed was already in the soil, just needing a rain.”

“It’s not rain,” Yang Ping walked in from the doorway, holding a cup of tea. “It’s awakening. The original cells have always been there, in the ependymal region of the adult spinal cord. After injury, they are activated, but the microenvironment is wrong, so they go astray and become astrocytes, becoming part of the scar. What we need to do is not to plant new seeds, but to make the original seeds germinate. In fact, seeds are everywhere; I’m just awakening them and making them become the cells we want.”

Weber was silent for a long time, then nodded: "So your job is to be gardeners, not sowers."

"You could say that."

“I like this analogy.” Weber put his glasses back on. “So, what can my team do? In stem cell research, we can be world-class.”

Yang Ping sat down and placed his teacup on the table: "Professor Weber, no one can match your experience in directed differentiation of stem cells. The problem we are facing now is: after the progenitor cells are activated, how do we guide them to differentiate into neurons, rather than glial cells? Your three-dimensional culture system and your induction protocol may be exactly what we need."

"You want me to combine exogenous stem cells with progenitor cell activation?"

"Yes! Exogenous stem cells provide immediate structural support and a nutritional microenvironment, while progenitor cell activation provides endogenous long-term repair. Let's take a two-pronged approach and see if it helps."

Weber's eyes lit up. He picked up a pencil and sketched a diagram in the blank space of the paper: a cross-section of a damaged spinal cord with a scar in the middle, surrounded by the labels "exogenous stem cell transplantation area" and "original cell activation area".

“Here,” he pointed with the tip of his pencil at the boundary between the two areas, “this is the key. How do the two systems communicate? Do exogenous cells inhibit endogenous activation? Or vice versa?”

“We don’t know,” Yang Ping said frankly, “so we need you to conduct research on this issue.”

Weber put down his pencil, looked at Yang Ping, and stared at him for a long time. Then he suddenly laughed, a laugh that brought all the wrinkles on his face together, like a crumpled and unfolded piece of paper.

“Professor Yang, do you know that before I came here, I had the idea of ​​working for you? My friends advised me not to come. They said that it wouldn’t sound good for a Nobel laureate to go to China to ‘work’ for a young man, even though that young man is also a Nobel laureate. I said, you don’t understand. Science has no age, no borders, and no face. There is only right and wrong.”

He reached out his hand, and Yang Ping grasped it.

"Pleasant to work with."

“Have a good job,” Mainstein corrected from the side, “Professor Weber insists on this statement.”

Filming ended on the third day. The producer showed Yang Ping a rough cut and asked if there was anything that needed to be cut. Yang Ping looked at it and found the footage to be very restrained, without any sentimentality or embellishment, only data, experiments, silhouettes, and a monkey's outstretched hand.

"can."

“Thank you for your trust,” the producer said. “This film is expected to air on ZDF (German television channel) next spring, and we will send you the final version in advance for your confirmation.”

Before leaving, Weber went to the rehabilitation room to see Chen Jianguo one last time. Chen Jianguo was doing gait training, using a walking aid to move step by step. Weber stood at the door and did not go in.

How far did he go?

“From the door to the window, it’s about fifteen meters,” Sister Li said from the side, “and it took twenty minutes.”

Weber nodded, turned, and walked away. At the end of the corridor, he glanced back. Chen Jianguo was still moving, one step, two steps, three steps, his back resolute.

Soon, Weber sent Yang Ping an email with a draft memorandum of understanding attached, in both Chinese and English. Yang Ping printed it out, placed it on the table, and studied it for a long time.

The title of the memorandum is simple: "Collaborative Research Plan on the Synergistic Repair of Spinal Cord Injury by Progenitor Cell Activation and Exogenous Stem Cells".

He handed the memo to Mainstein: "Take a look and see if there are any problems."

Mannstein took it, read it from beginning to end, then turned to the last page and looked at Weber's signature.

“No problem,” he said. “That’s very Weber.”

"What do you mean?"

"Very rigorous and very pragmatic."

Yang Ping picked up a pen and signed his name next to Weber's.

The research institute entered an unprecedentedly busy period for the next month.

Weber's German team consisted of three people: a postdoctoral researcher named Hans, who works on stem cell culture; an associate professor named Eva, who works on electrophysiology; and a doctoral student named Lina, who works on bioinformatics. They brought two boxes of reagents, a portable electrophysiological recording device, and a complete three-dimensional culture protocol established in Weber's laboratory.

Hans was a blond, bespectacled young man in his early thirties who spoke quickly with a heavy Bavarian accent. On his first day at the lab, he locked himself in the cell culture room for six hours. When he came out, he told Mainstein, "The temperature of your CO2 incubator fluctuated a bit. I adjusted it, and it's now stable at 37.2 degrees Celsius."

Mainstein paused for a moment: "You changed our incubator?"

"Yes, I checked the records. The temperature has been fluctuating between 36.8 and 37.5 degrees Celsius over the past two weeks, which is not good for stem cells. I replaced the temperature control module. The old one is on the table; you can keep it as a backup."

Mainstein looked at the old temperature control module that had been removed from the table, feeling both amused and exasperated.

Eva, on the other hand, was completely different. She was a woman in her fifties, with short hair, a serious demeanor, and spoke slowly and deliberately. She was in charge of electrophysiological recordings and would appear in the animal room every afternoon to perform motor evoked potential tests on M7. She never spoke to M7, but would bring it a grape, place it next to its cage, and leave after the test. M7 seemed to like her very much; every time she came, it would extend its paw, but she never shook it.

“I don’t form emotional bonds with laboratory animals,” she explained. “That’s a principle.” But Mainstein noticed that after each test, she would tidy up the M7’s cage, smoothing out the bedding and straightening the food bowl. These were subtle actions, but she did them very carefully.

Lena, the youngest at twenty-six, wears round-framed glasses and always carries a laptop. She is responsible for integrating data from both China and Germany to create a unified database. She spent two weeks digitizing all of Yang Ping's team's experimental data from the past three years, labeling it with time, batch, operator, and quality control standards.

“Your raw data is well preserved,” she told August, “but the metadata is incomplete. For example, with this Western blot, I know the date it was done, but I don’t know the gel concentration, electrophoresis conditions, and development time. These are important for reproducibility.”

August scratched his head: "We hadn't paid attention to these things before."

“It’s okay. From now on, record every experiment according to this template.” She handed over an Excel spreadsheet with more than 30 fields, from “experiment date” to “room temperature and humidity”, everything was there.

August looked at the form and thought, "Not bad, very serious."

“Data is the foundation of science,” Lina pushed up her glasses. “If the foundation is not solid, nothing you put on top of it will help.”

The first month of cooperation was fraught with friction.

The biggest disagreement lay in the experimental design. Weber's team preferred to conduct numerous preliminary experiments to explore the conditions before formally launching the project; the Chinese team in charge of the project, on the other hand, preferred to proceed quickly, making adjustments as they went. These two styles clashed, often leading to heated arguments in the meeting room.

“Your plan has insufficient preliminary experiments, and the risk of failure in the formal experiment is too high,” Hans said, pointing to the flowchart on the projector.

“We don’t have time to do three months of preliminary trials,” the Chinese team leader retorted. “Patients can’t wait.”

"But failed formal experiments waste even more time and resources."

“We’ve been doing this for the past three years, and the success rate isn’t low.”

That was luck, not method.

Yang Ping sat beside them without saying a word. Only after they finished arguing did he speak: "Hans, what's the shortest time your preliminary experiment will take?"

"Two months, if everything goes well."

"Can we reduce it to one month? We'll provide double the manpower and equipment."

Hans thought for a moment and said, "Okay, but on the condition that I have complete control over the experimental design, and you are only responsible for execution."

“No,” Yang Ping shook his head. “The experimental design must be decided jointly by both parties. But you can take full responsibility for the execution, and we will cooperate.”

Hans looked at Weber, and Weber nodded.

"Okay, one month."

Similar negotiations occur daily. Eva insists that all electrophysiological tests must be conducted at fixed times because the animals' circadian rhythms can affect the results; however, the animal facility's schedule is fixed and cannot be adjusted individually for her. In the end, both sides compromised: Eva changed the testing time to 10:00 AM, and the animal facility moved M7's feeding time forward to 8:30 AM to ensure that M7 was active during the testing.

A month later, the data from the first batch of joint experiments came out.

The results were better than anyone expected.

In the combined treatment group, after activating the original cells and then transplanting exogenous neural stem cells, the mice's motor function recovery scores were 40% higher than the activation group alone and 60% higher than the transplantation group alone. More importantly, histological analysis showed a significant increase in the number of regenerated neurons in the damaged area and a significant reduction in the area of ​​glial scars.

Weber stared at the bar chart, his fingers tightening on the table again.

“This is a synergistic effect,” he said. “One plus one is greater than two.”

“It’s not just greater than two,” Mainstein added, “it’s greater than three. Look at this, the axonal regeneration distance in the combined group is twice as far as that in the transplantation-only group, which shows that the activation of the progenitor cells changes the microenvironment, making it easier for exogenous stem cells to survive and differentiate.”

“The reverse is also true,” Eva said, pointing to the electrophysiological data. “Exogenous stem cells provide immediate neurotrophic support, preventing the original cells from undergoing apoptosis during the critical window period after activation. The two systems support each other.”

The meeting room was silent for a long time. Then Weber suddenly stood up, walked to the whiteboard, and drew a diagram: two circles, some of which overlapped, with the word "Collaboration" written on the overlapping area.

"For the past fifty years, we have been debating whether endogenous repair or exogenous transplantation is more important. Stem cell proponents say transplantation is the way to go, neurotrophic proponents say protection is the core, and gene therapy proponents say regulation is the key. We have been arguing for decades, each saying their own thing, and no one is willing to concede to the other."

He turned around and looked at everyone in the conference room.

"Now I know. The answer isn't 'which is more important,' but 'how to make them work together.' Like a band, it's not about which instrument sounds the best, but how all the instruments work together. The secret lies in the unified theory that Professor Yang hypothesized."

Yang Ping nodded: "Professor Weber is right. But we are far from understanding the mechanism of this 'cooperation'. Why is the combined treatment so effective? What signals are being exchanged between the original cells and the exogenous stem cells? Is it cytokines? Exosomes? Or direct cell contact?"

“This is the next step,” Weber said. “Hans, you’re in charge of isolating the conditioned medium from the combined treatment group and doing proteomics. Eva, you continue with electrophysiology and see what the characteristics of neural circuit remodeling are in the combined group. Lina, you integrate all the omics data and find pathways.”

He paused, then looked at Yang Ping: "Professor Yang, where is your team?"

“We continue to optimize the protocell activation protocol,” Yang Ping said. “At the same time, I would like to launch a prospective observational study to verify the safety and efficacy of this combined protocol in primates.”

"M7?"

"Yes, the M7. It's been waiting long enough."

Immediately afterwards, the institute held a plenary meeting, attended by everyone from both China and Germany. Yang Ping projected the results of the joint experiment onto the wall and explained them one by one. When he got to the exciting parts, his voice trembled slightly.

"Comrades, what does this result mean? It means that we may have found a completely new path. It's not replacement, it's awakening; it's not transplantation, it's synergy, it's some kind of higher mechanism. All our previous theories only saw small parts of the problem. Whether this path will work, we don't know yet. But at least, we have proven that two seemingly contradictory directions can come together."

Weber stood up and said something in German, which Mainstein translated: "Professor Weber said that he had done fifty years of research and won the Nobel Prize, but he had never been as excited as he was today. Because today, he saw the future of science, not the future of one person, one team, or one country, but the future of all those who are willing to put aside their prejudices and cooperate sincerely."

Applause broke out in the conference room, starting sparsely and then growing louder and louder.


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