godfather of surgery

Chapter 1298 Changing the Carrier
Zurich, Switzerland, 8:00 AM.

Inside a secluded villa on the shores of Lake Geneva, the lights were on. Seven people sat around an oval conference table—representatives from the European Commission's Directorate-General for Health, the European Medicines Agency (EMA), the French National Institute of Health, and the German Federal Institute for Pharmaceuticals and Medical Devices, as well as three observers of special status: a medical advisor from a European royal family, a butler from an Italian industrial tycoon's family, and Lillian Windsor herself.

There were no official records or minutes of this meeting; even the participants' cell phones were left in a shielded box outside the door. But the content of the discussions could potentially influence the direction of healthcare policy across Europe for the next decade.

“The data is already very clear.” Sofia Bertrand, a senior reviewer at the EMA, pushed the tablet to the center of the table. “In the past three months, 87 limited clinical trials of K therapy have been completed globally, with an overall response rate of 80.46%, no serious adverse reactions, and no deaths. From a purely medical point of view, this is superior to any of our existing cancer treatment options.”

German representative Carl Schmidt frowned: "But all treatment data is transmitted back to China in real time. This is acceptable for limited clinical trials, but if it is still the case after the clinical trials are expanded and the product is launched, it means that the most sensitive health information of European citizens, such as genomic data, immune characteristics and disease progression trajectory, is stored on the servers of Chinese companies. This violates the basic principles of GDPR."

"So we need to amend the GDPR," the royal medical advisor said calmly, "or create exceptions for these special cases."

There was a moment of silence in the room. Amending the GDPR? This is almost one of the most sensitive and complex areas in the EU legal system.

“That’s impossible.” The French representative shook his head. “Data sovereignty is one of the core principles of the EU, and it’s impossible to give the green light to a particular treatment.”

“Similar to the limited clinical trial, we will establish a jointly overseen data pool,” Lillian began, her voice clear and firm in the conference room. “The data will be physically stored on servers within Europe, but the Chinese treatment team can access the portions needed for clinical decision-making in real time through an encrypted channel. Following the limited clinical trial model, we will maintain the EU-China joint oversight committee, and any data access will require dual authorization.”

"This requires enormous technological development and regulatory costs."

“The patient can’t afford to wait for a cost accounting.” The Italian butler spoke for the first time, his English thick with a Milanese accent. “My master’s pancreatic cancer has spread to his liver, and the standard treatment is ineffective. He’s only fifty-two years old and has three minor children. Every day we delay, his chances of seeing his children graduate decrease. When you discuss legal clauses, can you consider these specific lives?”

These words brought silence to the meeting room. Discussions on medical policy often get bogged down in abstract principles and numbers, but the specific lives and families are the ultimate goal of all policies.

Sofia presented a new set of data: "I have an analysis report here. If K therapy is fully approved in the EU, it is estimated that at least 5,000 patients with advanced solid tumors will have access to treatment in the first year. Based on current data, it is estimated that about 3,000 of them may achieve long-term survival or clinical cure. At the same time, because of the reduction in ineffective treatments and hospitalization time, the health insurance system may save more than one billion euros annually."

"But control of technology..."

“Technological control has never been in Europe,” Lillian pointed out. “For the past thirty years, American pharmaceutical companies have controlled the patents and production of the vast majority of innovative drugs, while Europe has paid high prices, ceded data, and relied on imports. Now it’s just that Chinese companies have taken over. What’s the essential difference? At least, the inclusive framework of Chinese companies promises accessibility and fair pricing.”

At noon, the meeting was adjourned. Lillian went out onto the terrace and looked at the mist rising from Lake Geneva. Carl Schmidt followed her out and handed her a cup of hot tea.

“Ms. Windsor, why are you so insistent?” Carl asked. “You’re cured.”

“Because I’ve witnessed the despair in hospital wards firsthand.” Lillian took the teacup. “And because I believe that medical progress isn’t real progress if it only benefits those who can afford it. K therapy and the universal healthcare framework may be our generation’s last chance to push for healthcare equity.”

"But there are risks..."

“Carl, you’ve been managing drug approvals for twenty years.” Lillian turned to look at him. “How many drugs have you approved, knowing they only extend a patient’s life by a few months, yet drain a family’s life savings? How many drugs have you rejected because, while effective, they were too expensive for health insurance to cover? Now there’s a treatment that’s far more effective, has far fewer side effects, and promises to price it based on affordability. If we delay or even block it because of concerns about data sovereignty, how will history judge us?”

Carl remained silent for a long time before finally saying, "I will push for expanded clinical trials, but the principle remains the same: a strict data oversight framework must be established. This is not about distrust, but about rules."

“Fair,” Lillian nodded. “Then let’s establish the rules.”

……

Southern Metropolis Daily, Sanbo Research Institute.

Yang Ping is still observing the pancreatic cancer cells, and the prototype of the newly designed vector has completed in vitro experiments. The results show that it can indeed effectively infect these pancreatic cancer cells that highly express a rare receptor; after K factor expression, the apoptosis rate reached 68%.

However, problems arose during the animal testing phase. Mouse models showed that while the new vector had an inhibitory effect on pancreatic tumors, it produced unexpected mild inflammatory responses in the liver and kidneys.

“Off-target toxicity.” Song Ziming looked at the pathology slides, his brows furrowed. “Although it’s not serious, it does exist. The vector may have recognized a similar receptor that is expressed at low levels in normal tissue.”

Tang Shun pulled up the receptor expression profile data: "This receptor is widely expressed during the fetal period, and only shows trace expression in a few tissues after adulthood. But our vector has such high affinity that it even captured the trace expression."

Yang Ping stood in front of the whiteboard, which was covered with signaling pathways and gene sequences. He had been working all day, but his mind was still clear.

“Once we can identify them and initiate the apoptosis process, that’s a victory. The rest is just a matter of continuing to improve. We need to add a verification lock.” He drew up a new gene circuit design. “If we don’t have a satisfactory single biomarker for the time being, we can use two, so that the vector only initiates K factor expression when it detects both biomarkers at the same time. Tumor cells usually have multiple abnormal biomarkers, while normal tissues rarely have two at the same time.”

"But this will reduce the efficiency of infection."

"Safety first." Yang Ping put down his pen. "Efficiency can be optimized, but safety cannot be compromised. Redesign, resynthesize, re-verify."

This means a delay of at least two weeks, and the pancreatic cancer patient may not be able to wait two weeks.

Just then, the laboratory door was pushed open, and Lu Xiaolu walked in, followed by a man in his sixties with a refined and scholarly demeanor.

“Professor Yang, I’m sorry to bother you so late,” Lu Xiaolu said. “This is Academician Chen Yongnian from Tsinghua University, an expert specializing in adenovirus vectors. We often discussed difficult problems together before. He looked at some of the data we published and came here specifically to share some thoughts with you.”

Yang Ping was somewhat surprised. Academician Chen is a leading figure in the field of viral vectors in China, but he has always focused on basic research and rarely gets involved in clinical translation.

"Professor Yang, I've heard so much about you." Academician Chen took the initiative to shake hands. "I see that you have made a very ingenious design in your targeting strategy, but I noticed a detail. The adenovirus serotype you used is type 5, which is the most common, but also the easiest to be cleared by the body's pre-existing immune system."

Yang Ping immediately understood what he meant: "You mean that some patients may develop antibodies because they have been previously infected with adenovirus type 5, which may cause the vector to be cleared prematurely and affect the treatment effect?"

“Yes! And this issue varies greatly among different ethnic groups.” Academician Chen pulled up data from his team that had not yet been made public. “We studied the adenovirus antibody profiles of East Asian, European, and African populations. The positive rate of neutralizing antibodies against adenovirus type 5 is about 40% in the Chinese population, up to 60% in the European population, and even more than 80% in some parts of Africa.”

This data stunned everyone in the lab. If true, it means that more than half of European patients may have pre-existing immunity to the K therapy vector, which would significantly reduce the effectiveness of the treatment.

"Before that... the treatment data for European patients..." Xu Zhiliang hesitated.

"We may have inadvertently filtered out patients with high antibody titers," Academician Chen said. "If multiple treatments are needed in the future, this problem will become more prominent."

Yang Ping quickly retrieved the patient data from the European Center and indeed discovered a pattern: all patients who responded to treatment had low levels of adenovirus neutralizing antibody titers detected before treatment.

“We overlooked this issue,” Yang Ping objectively admitted. “We focused on targeting but neglected the basic immunological characteristics of the delivery vector itself.”

“This isn’t your problem, because you don’t invest much effort in researching vector viruses; you can only use mature vector viruses. Vector viruses are our area of ​​expertise. Before our data became available, the adenovirus you chose was undoubtedly the best, but now it’s different. So I’m here to provide a solution.” Academician Chen opened his laptop. “Our lab has developed an ‘adenovirus serotype hybrid vector library’ technology. Simply put, it involves constructing multiple vector versions of different serotypes targeting the same therapeutic gene. Before treatment, the patient’s antibody profile is tested, and the serotype vector in which the patient does not have antibodies is selected for personalized delivery.”

The screen displays gene modification schemes for twelve different serotypes of adenovirus, each adapted to a K factor expression cassette.

"This requires a massive production system and complex testing procedures," Song Ziming said.

“But it solves the fundamental problem.” Yang Ping had already picked up his pen and started calculating. “Moreover, if combined with the dual-marker verification lock we just designed, both security and effectiveness can be greatly improved.”

Yang Ping began to analyze Professor Chen's new technology, and everyone started to discuss the carrier again.

Before we knew it, it was already midnight. The preliminary cooperation plan was finalized: Academician Chen's team would provide serotype modification technology and hybrid vector library, while Sanbo's team would be responsible for integrating the targeted system and clinical translation. Both parties would share intellectual property rights and work together to advance the project.

"This could be our biggest chance to overcome our technological bottleneck," Song Ziming said.

“But it’s also the biggest challenge.” Yang Ping rubbed his temples. “It means all production lines need to be modified, all training content needs to be updated, and all clinical protocols need to be revised. It’s like starting all over again.”

"Are you worried?" Song Ziming asked.

Yang Ping was silent for a while: "I'm worried, but I'm even more worried that if we know the problem exists but don't solve it, we won't be able to face the patients who fail to receive treatment because of it in the future."

Everyone nodded. This is Professor Yang, who always puts patient safety and technological perfection first, even at great cost. He is a technology fanatic.

“General Manager Huang said he would handle the production upgrades,” Song Ziming said. “We need to take the lead in training and updates, and as for the revision of clinical protocols…” He paused, “it may be necessary to temporarily slow down the rate of new patient admissions.”

“That pancreatic cancer patient can’t wait.” “We’ll arrange an emergency channel to perform one treatment using the existing protocol, while simultaneously accelerating the development of a new delivery system. This is the best balance we can achieve right now.”

Yang Ping looked at Lu Xiaolu and suddenly asked, "Why did you think of inviting Academician Chen?"

Lu Xiaolu frankly said, "Although I span multiple fields such as oncology and immunology, Professor Chen is currently at the forefront of the world in the field of vector viruses. I often discuss academic issues with him. When he shared his new findings with me, it suddenly enlightened me, so I quickly invited him over. Thank you for your hard work, Professor Chen."

Academician Chen waved his hand: "Not at all. I've spent half my life researching vector viruses, and now I've finally made it work."

“There is a Chinese scientist named Wu Changde. You should pay attention to him. He contacted me, hoping that I could join his team to indirectly replicate your technology.”

Yang Ping smiled and said, "Don't worry, it's futile. He's too naive. He thinks he can replicate it by using publicly available literature, K preparation samples, and stealing some technology. He doesn't understand K therapy at all. Even if I give him all the information, he still can't replicate it."

A genius is indeed a genius; Professor Chen couldn't help but admire Yang Ping.

……

Nine o'clock in the morning, Sanbo International Medical Education College.

Yang Ping stood on the podium, facing thirty-seven international students, his expression serious. Behind him, a large screen displayed the adenovirus pre-existing immunity data that had just been confirmed the previous night.

"Everyone, today's course content needs an urgent adjustment," Yang Ping said bluntly. "We have discovered a major problem that we had previously overlooked: pre-existing adenovirus serotype immunity may seriously affect the efficacy of K therapy. This means that before we upgrade the K formulation, every case you implement after returning to your home country must first undergo antibody screening, which will help improve the treatment rate."

There was a commotion in the classroom as the trainees looked at each other in bewilderment; this was completely beyond what they had been taught in their previous training sessions.

“Professor, what about patients who test positive in the screening?” Griffin asked.

"This is precisely the new approach we're discussing today." Yang Ping pulled up the hybrid vector library design from Academician Chen's team. "If a patient has a high titer of antibodies against a certain type of adenovirus, we will switch to vectors of other serotypes. But this requires the production and stockpiling of multiple versions of vectors, as well as a more complex treatment regimen development process."

German trainee Hans raised his hand: "This would be very difficult in practice. The European center currently only has one formulation. If we want to stock multiple versions, the costs of supply chain, storage, and management will increase significantly."

“Yes,” Yang Ping admitted. “So this is a dilemma: either maintain the status quo, but some patients may not receive effective treatment; or upgrade the K preparation and related systems, but face huge implementation challenges. I would like to hear your thoughts.”

This question was posed to the future implementers, and the trainees engaged in a heated discussion.

Indian student Rajiv said, "In India, medical resources are already strained, and having multiple versions of the vaccine in stock is almost impossible. Perhaps we could screen patients and treat only those who are antibody negative."

“But what about those patients who test positive for antibodies?” Brazilian student Carlos objected. “They also have the right to live.”

“Perhaps we could develop a pretreatment program to clear antibodies,” suggested an American trainee. “We could use plasma exchange or immunoadsorption to reduce antibody titers before treatment.”

"That would increase the complexity and risks of treatment, and the results would be uncertain."

The discussion lasted for an hour. Yang Ping simply listened without making judgments, guiding the participants to think, debate, and find their own solutions.

Finally, Griffin stood up: "Professor, I have an idea. Perhaps we can establish a regionally shared carrier library. For example, the United States and Canada could share a multi-version reserve center, which could be used according to the patient's condition. Although the logistics are complicated, it is more realistic than each country having its own reserves."

"What about regulatory approvals in different countries?" Hans asked.

“This is an issue that requires coordination among health departments in various countries,” Carlos said. “But if our medical community unites and emphasizes that this is for the benefit of patients, it may be possible to push for a policy breakthrough.”

This suggestion was endorsed by most participants. Ultimately, addressing healthcare issues requires healthcare professionals to proactively drive systemic change.

After class, Yang Ping stopped Griffin: "Your idea is bold, but it's certainly feasible. After you return to China, would you be willing to take the lead in promoting North American regional cooperation?"

Griffin paused for a moment, then nodded solemnly: "I'm willing to try, even if it's fraught with difficulties, it's worth it for the patients."

In the afternoon, Huang Jiacai arrived at the training camp. He listened to the recording of the discussion from the morning and seemed to be deep in thought.

“These trainees have a higher level of thinking than we expected,” he told Yang Ping. “They not only want to learn technology, but are also thinking about system optimization and regional collaboration.”

“Because they come from the front lines, they know the real difficulties best,” Yang Ping said. “Perhaps we should adjust the training model, not only to teach them how to do it, but also to inspire them to think about how to do it better. The establishment of the K-therapy model is itself an experiment, and we should involve them, let them become the main body, and constantly change it.”

“I agree,” Huang Jiacai said. “I suggest adding innovative practical projects in the last month of the training camp. The trainees will be divided into groups to design and optimize solutions for practical problems in their own countries or regions. We can provide start-up funding to support the implementation of the best solution.”

This suggestion caught Yang Ping's eye. Cultivating executors is important, but cultivating change agents is even more important.

How much funding is needed?

"We've prepared ten million US dollars for the first phase. If it works well, we can continue," Huang Jiacai said. "This money won't come from Ruixing's operating funds, but from my personal funds and those of several investors. It's an investment for the future."

Yang Ping looked at him and suddenly laughed: "Your current style of doing things doesn't seem like that of a businessman?"

“Businessmen also need to have ideals, otherwise no matter how much money they make, they will feel empty when they wake up in the middle of the night.” Huang Jiacai also laughed. “Moreover, investing in these young people is investing in the real establishment of K therapy in the world, which is more worthwhile than any advertising. Investing in people is the most long-term investment.”

In the hall, trainees were having group discussions. Doctors from different countries and cultural backgrounds had gathered here because of a technology, and now they were starting to think about how to make this technology better serve their respective countries and people.

“Sometimes I think,” Yang Ping said, “that perhaps the greatest value of K therapy is not how many diseases it can cure, but that it is like a seed that inspires healthcare workers around the world to think about and pursue a more equitable and effective healthcare system.”

……

Three days later, in a conference room at a hospital in Shanghai.

Wu Dechang's plan has made substantial progress. After Academician Chen Yongnian "defected" to support Sanbo, Wu Dechang quickly adjusted his strategy and instead joined forces with a group of mid-career scientists to launch the "Open Tumor Targeted Therapy Platform" project.

Today's meeting is the project launch meeting. In addition to scientists, there are representatives from three domestic pharmaceutical companies, and most importantly, two experts from the National Science and Technology Major Project Review Committee.

"Ladies and gentlemen, we are not here today to replicate K therapy, but to build an open and iterative tumor targeted therapy technology platform." Wu Dechang's opening remarks were very strategic. "The core principles of this platform are: modularity, open source, and collaboration."

In fact, he just wanted to replicate K therapy and use these people to replicate K therapy.

The screen displays a platform architecture diagram: the bottom layer is a public knowledge base, which contains a validated tumor marker database, vector safety data, and preclinical research guidelines; the middle layer consists of tool modules, including different types of viral/non-viral vector construction schemes, various pro-apoptotic/immune activation gene elements, and targeted system design tools; the top layer is the application layer, where researchers can combine different modules like building blocks to construct their own treatment plans.

"The design schemes, security data, and construction methods of all modules will be open source and shared," Wu Dechang emphasized. "Any certified research institution can use these modules for research and clinical translation free of charge. The only condition is that the data from the translation results must be fed back into the public knowledge base to form a positive cycle."

A pharmaceutical company representative asked, "How are intellectual property rights and commercial profits distributed?"

“The intellectual property rights of the application layer results belong to the R&D team and can be commercialized. But the basic modules will always be open source,” Wu Dechang said. “This is similar to the Android system. Google provides the open source system, and mobile phone manufacturers develop their own products on this basis and profit from it. We provide an open source treatment technology platform, and pharmaceutical companies develop specific therapies on this basis.”

This analogy helps everyone understand that openness does not mean there is no profit to be made, but rather that the distribution of benefits has changed.

The experts on the review committee asked, "Is this platform and Ruixing's technological approach competitive or complementary?"

“It should be complementary,” Wu Dechang replied shrewdly. “Ruixing has already proven the feasibility of this technical route. They are pioneers who have paved the way. What we need to do is broaden this path so that more people can take it. Moreover, the open-source nature of the platform means that Ruixing can also use the platform’s modules to optimize its own technology, if they wish.”

This positioning is very clever: not a challenger, but a complement; not a competitor, but an ecosystem builder.

Wu Changde planned to feign an attack while secretly advancing, and by then everything would be out of their control.