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Chapter 120: The Royal Swedish Academy of Sciences (7)

Young-Joon gathered a task force to test the side effects of the immune checkpoint inhibitor. The most talented people of the scientists at Lab One and A-Bio gathered after receiving the email. There were about thirty people from a variety of departments; they all had different nationalities, and there were also promising young scientists, professor-level scientists, and even experts like Carpentier. These people would be able to easily establish a start-up company just in terms of their combined research abilities.

‘Oh my...’

Hariot clicked his tongue as he watched them chatting in the seminar room. Hariot, who was a medical doctor, barely had the time to attend conferences because he was so busy with hospital work. It was the first time he saw them altogether. He already knew that they were at the conference as he heard that Young-Joon brought them, but it was quite shocking to actually see them in-person.

‘Some of these people could apply to Karolinska right now and become a professor...’

It was shocking that people like them were all working at one company, but it was also fascinating that they assembled with one word from Young-Joon when they had come all the way to a conference.

‘Scientists who are called experts in their field usually don’t like it when other people give them their research topic or direction because of their pride, but...’

Click.

The seminar room opened. Young-Joon came in and briefly greeted everyone.

“Are you all enjoying the seminar?”

“We were, before you assembled us here,” Carpentier said with a chuckle.

“I’m sorry.”

“I have traveled to other places as a visiting lecturer, but I have never been a visiting researcher.”

There was light laughter among the scientists.

“This conference was supposed to be a vacation-like benefit we were giving to you so that you would be able to take a break while listening to the lectures you wanted. I feel bad that I am making you work all of a sudden,” Young-Joon said. “However, I am so grateful and happy to see that so many of you have volunteered to work. Like me, you are all deep-rooted science nerds. I think I chose my colleagues well.”

“It’s difficult to do research for a living after studying this much if you don’t fanboy over academia,” Koh Soon-Yeol said as he fixed his glasses.

“Haha, thank you. Like I wrote in the email, we will provide plenty of compensation in the form of PTO and bonuses,” Young-Joon said.

“I would have still done it without the compensation because the research topic was so interesting. We couldn’t let you work alone sir, so we had to...” Choi Myung-Joon raised his hand and interrupted.

“Ah, Manager Kim, you’re going overboard.”

The other scientists lightly scolded.

“Anyways, thank you, everyone,” Young-Joon said. “Professor Hariot here will provide us with the lab mice. Since we are at war with the clock with this research, we will have to do a few experiments simultaneously.”

“Alright.”

“First, could Doctor Kim Myung-Shin and four members from the Protein Structure Analysis Team form a group with Doctor Cheon and the five members of the Life Creation Team and administer the inhibitor into the mice and control it?” Young-Joon asked. “We need to test the amount of drugs discharged and the toxicity, just like the pre-clinical data. And we must monitor the size of the tumor. From day four, the tumor will undergo hyperprogression and get huge rapidly.”

The scientists looked a little shocked. They knew that they were looking at the side effects of the immune checkpoint inhibitor, but it was the first they were hearing about hyperprogression.

“Hyperprogression?” Carpentier asked.

“That’s right. Doctor Carpentier and the Bone Marrow Differentiation Team, please work with the Diagnostic Device Department to analyze the pharmacological mechanism of hyperprogression in mice.”

“Alright.”

“Doctor Felicida’s team and Doctor Choi Myung-Joon’s Health Foods Department, please sacrifice the mice at the appropriate point and create data on the size of the tumor.”

* * *

In order to test an anticancer drug in a mouse model, the mouse obviously had to have a tumor as it would allow one to observe whether or not the tumor decreased when it was treated with anticancer drugs.

Then, how could one create a tumor in mice? They could treat them with drugs and naturally induce tumors, but usually, a cancer cell from a human was injected into a mouse and grown into a tumor. This method was called a tumor xenograft.

“These mice have tumors that were created using cancer cells from NSCLC(Non-small cell lung cancer) patients. These cells are known to have a mutation in their EGFR,” said Hariot as he gave Young-Joon twenty mice. “We were originally going to use them for an experiment, but we will let you use them first since it will be a waste of time for you to wait for a xenograft.”

“Thank you. What kind of cancer cell is it?”

“It originated from lung cancer, and the cell strain number is HCC1010.”

It was clearly a cell that was known to have a mutation in the EGFR. However, Young-Joon couldn’t just blindly trust existing data and begin the experiment; they had to check the condition of the EGFR mutation first.

“We do have a DNA analysis machine at Karolinska,” Hariot said.

“That’s perfect. Would we be able to use it once?” Young-Joon asked.

“But the technicians who do it are on vacation and not here...”

“It’s alright. Our people can do it.”

The scientists from the Diagnostic Device Department at A-Gen stepped forward.

“The technician you have didn’t maintain the machine well. We will take a look at the equipment itself as well,” they said.

“... Thank you...”

Hariot nodded in confusion.

In just half a day, the Diagnostic Device team got some data. They extracted the genome from the cancer cell that was used to create the tumor, amplified EGFR DNA, took it out, and read it with the DNA analysis machine.

“From the report I received, there’s a mutation in EGFR at L858R. Is that correct?” Young-Joon asked Hariot the next day.

“That’s correct.”

Leucine, the eight hundred eighty-fifth material that was made from the EGFR gene, had turned into arginine. It was the most famous type of EGFR mutation, and it was the most common mutation that induced cancer.

“Please give me the inhibitor now,” Young-Joon said.

“Of course.”

Hariot had given Young-Joon a portion of the immunity checkpoint inhibitor that was kept at the Karolinska Institute. Cheon Ji-Myung and the Life Creation Team administered the immune checkpoint inhibitor intravenously as they grew the mice in appropriate conditions. The daily dosage varied from a very small amount of ten micrograms to a high dose of ten milligrams; they had created a variety of conditions.

The Diagnostic Device Department used imaging equipment and measured the size of the tumor that was in the mice’s lungs. They tracked the tumor size of all twenty mice every day and gathered data.

On the third day, there was still no sign of hyperprogression in the mice. The tumors had gotten smaller than before, and the mice seemed healthy.

* * *

“This is nonsense. This drug has already been commercialized,” Jamie Anderson said.

“We administered the drug to thirty-two patients as we progressed through Phase Three of the clinical trial, but nothing like hyperprogression was observed,” said Oliver.

“Ryu Young-Joon is testing NSCLC. Were there patients with that type of cancer?”

“... I don’t think so.”

“Apparently, there are a lot of EGFR mutations in that type of lung cancer.”

“How would we have data about whether clinical trial patients had EGFR mutations or not? We had a lot of samples, like blood, but we didn’t analyze their DNA or anything.”

“Because the only bastards who do that kind of stuff is the A-Bio Next-Generation Hospital. But you can’t let them do this. The Nobel Committee is a conservative organization,” Jamie Anderson said. “Oliver, even if side effects don’t happen in this experiment, people like Professor Hariot may be uncomfortable with it and withhold the Nobel Prize since they’re all possessed by Ryu Young-Joon.”

“Then what should we do?”

“The Karolinska Institute is not only a research institute, but a university hospital. There are NSCLC patients here, too.’

“Are you saying that we should use the immune checkpoint inhibitor on NSCLC patients?”

“I heard that the patient is already past the third stage of lung cancer and they have no other options left. They were going to be given the immune checkpoint inhibitor anyways. The primary doctor seemed to be hesitant because Ryu Young-Joon brought up side effects, but you should go see him.”

“Um...”

“If you cure them, Ryu Young-Joon will no longer be able to stubbornly argue that there are side effects.”

“...”

Oliver hesitated.

“You are the one who made this drug. Are you not confident in it?” Jamie Anderson asked.

“No, of course not. But...” Oliver trailed off.

Oliver had researched for more than ten years to create this drug. This technology was like his child. Of course, he believed in it; he was confident in the efficacy of the immune checkpoint inhibitor. He had checked all the pharmacological mechanisms, and he saw that it did not have toxicity.

However, his opponent was Young-Joon. The person who was criticizing the side effects of this drug, which had gotten the FDA’s approval, was not just some third-rate rando, but Young-Joon. That weighed on Oliver’s mind. What if this technology, which was like his child, ended up killing someone? What if hyperprogression really occurred, like Young-Joon said?

‘Will I be able to handle the consequences?’

To Oliver, who was lost in thought, Jamie Anderson said, “Oliver, it has already been commercialized. Have confidence. The fact that the FDA approved it means that its safety was proven in the medical community. This is not a clinical trial; it’s normal treatment. The drug deserves to be administered to the patient.”

* * *

Doctor Song Yu-Ra from the Diagnostic Device Department was given twenty mice from Cheon Ji-Myung’s team in the morning. She used a PET/CT scan and took a picture of the mice’s lungs. The size of the tumor was about half the size of her pinky fingernail until the third day. It was barely distinguishable on the screen, and it was continually getting smaller.

However, on the fourth day, Song Yu-Ra doubted her eyes.

“What...?”

The tumor became larger. The tumor size in the mouse that received one hundred micrograms of the immune checkpoint inhibitor had visibly changed. The tumor had become as big as the space between her knuckles in mice that had received one milligram and ten milligrams.

“...”

How could it get this big all of a sudden? Song Yu-Ra took a photo to save the data, then observed the other mice. The mice that only received trace amounts of the immune checkpoint inhibitor and those who hadn’t received the drug as the control group had no problems.

It was clear: the immune checkpoint inhibitor had impacted it negatively. Although, the tumor hadn’t become too big yet.

‘Is it really hyperprogression?’

Her hands trembled. It was approved by the FDA, and it was the most promising drug from several years ago. It was the most famous anticancer drug in the world before Young-Joon appeared and created the pancreatic cancer cure or Cellicure. It was an anticancer immunotherapy that was expected to change the landscape of the anticancer market along with chimeric immunotherapy.

‘But it has a side effect.’

Song Yu-Ra sent this data to all the scientists who were participating in the research.

Soon, Young-Joon and Carpentier came running.

“Sacrifice a set of mice we are using for the experiment and experimentally analyze the pharmacological mechanism. The EGFR signal should have increased. Please confirm that with western blotting,” Young-Joon said.

Reporting the side effects alone would have a strong impact, but it was the responsibility of scientists to figure out the mechanism.

“And please tell the Life Creation Team to keep administering the drug to the rest of the mice and continue with the research. We will be able to see the hyperprogression clearly from tomorrow.”

“Okay,” Song Yu-Ra replied.

Young-Joon was correct. The next morning, the tumor nearly doubled in size in the mice that had received the ten milligrams of the inhibitor, the largest dose. The tumor, which was about half the length of a finger, was too much for the mice’s small body

“You can see angiogenesis, too...”

The scientists who gathered behind Song Yu-Ra watched the monitor in shock.

The cancer had metastasized.

“It’s hyperprogression,” Carpentier said. “This mouse will not survive until tomorrow.”

The scientists glanced at Young-Joon.

“Thank you for working so hard to create important data. Since there’s still more than a week left until the allotted time, please obtain data from the remaining mice as well. And...” Young-Joon said. “Write the paper. I will contact Science.”