Super Genius DNA

“I told you to lay low, didn’t I?” said Xin Mao, the minister of the State Administration for Market Regulation.

He was visiting the Public Security Bureau to see He Jiankui, who had been detained.

“What’s going to happen to me now?” He Jiankui asked.

“It’s worse than you think. It’s all your fault, so who can you blame? Genetic modification alone is enough to get you in trouble, but you also blatantly disregarded clinical trial regulations, and you didn’t give the victims an explanation. Plus, the baby you created is about to die.”

Xin Mao clicked his tongue.

“The issue is genetically modified babies. You said it yourself at the GSC conference that it’s the dawn of a new era, didn’t you? What can you do when there’s a background like this behind a case that the entire world is watching?”

“I heard there was talk of the death penalty... Is it true?” He Jiankui asked in horror.

“It’s true. Nature is investigating and reviewing the case of organ transplants from executed prisoners. What do you think will happen if that blows up?” Xin Mao said. “Do you know what people are going to say? Their country sells the organs of executed prisoners and who knows what other unimaginably unethical things are going on? They are going to say that’s why a GSC scientist can violate clinical trial regulations and conduct a genetic modification study on their own citizens without any real preclinical data. ‘Look at our country; look at our dictator government that treats their people like lab rats. That’s why...’”

Xin Mao clenched his jaw out of frustration.

“...’that’s why they won’t even punish He Jiankui properly.’”

“...”

“That’s what people are going to say. I’m saying we will be internationally condemned. Now do you understand why your punishment has to be severe?”

“It still... won’t be the death penalty, is it?”

“I’m trying to prevent that, but the deputy minister has disliked you for a long time because you act like you’re above the law and do any research you want.”

“Science shouldn’t be so tangled up in the law! All I did was take a bold risk for the betterment of humanity!”

“Doctor Ryu developed a filter that captures micro-dust from the air. They created a technology to put filters on cars and recycle it as fertilizer.”

“What?”

“I guess you haven’t heard. Well, you won’t get newspapers in here, so... Anyway, apparently Doctor Ryu just gave that away to a small company called Cellijenner.”

“...”

“At least what’s a challenge to you is routine or child’s play to him.”

“That’s because...”

“We tried to recruit Doctor Ryu once, but it didn’t work. It was partly because his research base is all in Korea, but it was partly because of the closed-off research environment in China,” Xin Mao said.

“Maybe that restrictiveness was the real problem. And that’s where monsters like you are born.”

“...”

“All these years I’ve been cleaning up after you, thinking it was my patriotic duty, for the betterment of this country, but now I feel differently.”

“Mr. Minister!”

“I’ve approved your crazy research plans without asking, but that undisciplined system and the lack of transparency in the process is what ultimately prevented us from recruiting Doctor Ryu,” Xin Mao said. “And it’s also what allowed an arrogant genius like you to rise.”

“...”

“It’s probably going to be more than a life sentence, so be prepared. There’s nothing I can do anymore.”

* * *

“Sir,” Jacob said to Young-Joon. “Did you hear about the micro-dust thing? Korea is going crazy right now.”

“Attorney Park let me know yesterday,” Young-Joon replied bluntly.

“There’s talk about executing He Jiankui after the moratorium.”

“I heard.”

“And it looks like we won the first trial. The Wall Street Journal said that Atmox was already in a groggy state after the first round.”

“...”

“Everyone is also talking about how you gave away all of the micro-dust reduction devices to Cellijenner. Not people in science, but people in economics, political science, and sociology.”

“I see.”

“They’re saying that it’s the greatest move by the owner of a mega-company. They’re putting it on the headlines of every newspaper, and they are going to use it as a case study for a co-prosperity model between big and small businesses.”

“...”

“But why are you doing an experiment here...” Jacob asked, frustrated and not understanding. “Shouldn’t you be doing business up on stage where all these crazy spotlights are on you? You haven’t been sleeping because of the moratorium, so you should get some rest, too.”

“...”

“We can do a protocol like this ourselves, so don’t push yourself and go home.”

“Jacob, please be quiet for a moment,” Young-Joon said.

Young-Joon had amplified some DNA from the blood of a mouse with a genetically modified CCR5 gene and was doing an experiment called gel electrophoresis with it.

“A second-year student can do this as well... Just let us do it. You’re the CEO of the best pharmaceutical company in the world...”

“I trust you and the other scientists, but we’re working against the clock, and it’s a unique treatment,” Young-Joon said.

In drug development, in vivo[1] experiments were different from preclinical experiments. They both involved animals, but they had different purposes. The goal of in vivo experiments was to see if a drug candidate would work in an animal. This could be done relatively quickly with fewer samples and a smaller experimental group. All they had to do was prepare a disease model and normal mice, inject them with the drug or a placebo, and watch for changes in disease progression.

However, preclinical studies were a little different. At this point, it was also important whether the drug was produced in a GMP facility, as the production method could have negative repercussions in the clinical trial. Additionally, the researchers had to decide on the concentration of the drug and how many times to administer the drug at what intervals. This process was similar to in vivo experiments, but preclinical studies were more rigorous. whereas animal testing was relatively casual. It was because the goal of preclinical studies was not to prove the efficacy of the drug, but rather to determine a safe concentration for the patient.

In other words, if a concentration of one hundred worked the best in killing tumors in animal studies, that was it. They could get good data with that concentration, show efficacy, and publish a paper with that.

However, in preclinical studies, toxicity was more of an issue than the efficacy at a concentration of one hundred. If a concentration of one hundred did some damage to the liver, it couldn’t be used even if it killed all the tumors. If they did the experiment again and found that a concentration of fifty was less effective but significantly less toxic, the concentration would be set at fifty.

Furthermore, they also had to determine how long the drug stayed in the animal’s system and how long it took to be eliminated. The biggest difference between in vivo and preclinical studies in this aspect was the size of the animal. In vivo studies usually only used rats because they were the cheapest, had the most developed disease models, and could provide quick results.

In preclinical studies, however, it wasn’t uncommon to see larger animals, such as rabbits or beagles, in addition to mice. In general, the optimal dose of a drug was proportional to the subject’s bodyweight, so results from larger animals were naturally more accurate in determining the physiology of a drug in humans.

“But we’re only doing rat experiments. This shouldn’t really be called a preclinical study,” Young-Joon said. “The preparation of the drug was also done here, not the GMP facility at A-GenBio. We actually shouldn’t be able to use this.”

“That’s what I’m saying,” Jacob said in a dejected voice. “The public doesn’t know anything about this, sir. They won’t be understanding of the fact that there’s nothing we can do even if it fails. The public won’t understand why we used rats, or the fact that it would be impossible to do the experiment with beagles or rabbits because it takes so long for them to be born with genetic modifications.”

“...”

“I want you to be a scientist who doesn’t fail, sir. So give the experiment to us...”

“I won’t fail,” Young-Joon said. “The results from the gel electrophoresis are out. I tried cutting the CCR5 target location with an enzyme. The enzyme cut the gene in the control group, but not the experimental.”

Young-Joon pointed at the picture on the monitor.

“...”

Jacob’s eyes widened.

“Jacob, the CCR5 gene in the experimental group wasn’t cut because we repaired all the broken parts of the gene in cells of the mouse’s lymph nodes and bone marrow, leading to a change in the DNA structure. The experiment was a success, at least in vivo.”

“This is... definitely promising,” Jacob said. “But it’s not a preclinical...”

“It will work.”

“How are you going to determine the number, duration, and the concentration of doses, let alone validate the efficacy of the drug itself?

—Three times a week.

Rosaline intervened.

—The amount of Cas9 and the RNA complex is equal to 3.2 times the baby’s weight. The units are milligrams, and it should be dissolved in five hundred microliters of distilled water for injection. The following solutions should be dissolved in order to match the conditions in the blood and to prevent structural modification of Cas9.

—Procaine hydrochloride 10 mg

—Sodium citrate 2 mg

—-Sodium hydroxide 3 mg

...

As he read the messages in front of him, Young-Joon said, “In a situation where we can’t do a proper preclinical study, we have to go with our gut feeling and rely on in silico data and calculations.”

In silico referred to virtual experiments that combined biology and computer simulations.

“How is the baby doing?” Jacob asked.

“The hospital said she has a week at most. We really don’t have much more time now. Let’s check the purity for all the drugs we made today, and we’ll administer them tomorrow. I communicated this to the medical staff as well,” Young-Joon said.

“Who’s doing the administration?”

“Professor Dong Weimin is doing it.”

“Dong Weimin?”

“This treatment is done via injection. It’s a very difficult procedure that involves piercing the lymph nodes and bone marrow.”

“Hm...”

“It was very difficult to recruit him.”

* * *

Young-Joon was also a little uneasy about the lack of preclinical data. He was a scientist as well, and he naturally felt more confident in the experimental data in front of him than what Rosaline had taught him.

Mimi’s treatment was administered while her mother, Zhi Xuan, Young-Joon, Jacob, and other scientists watched from outside the sterile operating room. Zhang Haoyu, Mimi’s doctor, assisted Dong Weimin, one of China’s most respected doctors, in administering the treatment.

He was one of the leading experts on lymph node injection treatments. It was a technology called a sentinel node biopsy, which was usually used to treat breast cancer that had metastasized. But it was also Dong Weimin’s first time piercing a needle into such a tiny lymph node on a newborn baby.

‘I might fail.’

At first, he had declined because of the pressure, but he had eventually agreed after the persistent arguments of Young-Joon and the minister of the State Administration for Market Regulations.

Dong Weimin was determined. The patient was so small, there were more lymph nodes than normal, and they were in different positions. Although he was extremely concentrated on this, he was still nervous. The nape of his neck was damp with cold sweat. His fingertips trembled slightly. At that moment...

—Sir, it’s a little bit above where your needle is right now.

Dong Weimin heard Young-Joon’s voice from the speaker attached to his surgical gown.

“... I see.”

He had almost made a mistake.

Dong Weimin gulped. As he adjusted the position of the needle, he was confused about how Young-Joon could know something like that.

However, they had no idea that there was a shiny young girl in the operating room, besides the medical staff, guiding the needle of the old professor. Young-Joon was in Synchronization Mode, trying to match Rosaline’s position with Dong Weimin’s procedure.

1. In vivo is a term for procedures performed on whole living organisms ☜

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