Chapter 59: A Hospital of the Next Generation (6)
Young-Joon established a hospital with funds raised through the A-Bio Foundation. He bought a large, old building in Mapo-gu in Seoul, applied for repurposing the building, and began to renovate it, and turn it into a hospital.
As Phase Three of the glaucoma clinical trial was going smoothly, they would be able to provide glaucoma treatment after the construction ended and it became a general hospital. If they could make just one small intestine organoid until then, they could perform precise diagnoses and treatment, although it would be limited to the small intestine.
These were the first services provided by the next-generation hospital. They would be able to broaden their range of treatments as the results from stem cell research came out one by one. As such, they had to get more research results as soon as possible.
And he was lucky enough to get a chance to accelerate his research even more.
“Long time no see.”
Carpentier and Young-Joon lightly hugged.
Carpentier, a professor from Caltech, was a Nobel Prize recipient. He had studied the regeneration of spinal nerves using stem cells for a long time. So, had he succeeded in recovering the nerves using stem cells? No, he hadn’t. If he had, Young-Joon wouldn’t have been doing this in the first place.
Sometimes, Nobel Prize-winning achievements sounded like magic to people, and this was the case for Carpentier as well. He had wirelessly connected the nerves of a patient with a broken spinal cord with an electrical chip. Stem cells were the main goal of his research, while this was only one of many plan-B theories, but he had actually succeeded with this instead.
The spinal cord was a long collection of nerves that was connected to the brain and ran all the way down to the waist. One of the clinical trial patients had damage in the upper region, in particular the thoracic nerves, and could not deliver messages from the brain to some regions below his chest.
Carpentier inserted extremely small electrical chips directly above and below the damaged area. As a result, when the patient wanted to walk, the excited electrical signals from the nerves would travel through the chip, skipping over the damaged area, and be sent to the living cells below it. The patient was able to take a few steps alone in just four weeks, and Carpentier received the Nobel Prize.
He worked on this project for about twenty years. It also took four years for this treatment to reach the patient after it succeeded on monkeys. This was how careful the study was done. It was amazing how the U.S. government and Caltech both steadily funded his research for twenty years, but Carpentier’s own persistence, which ultimately led to his success, was also astonishing.
Unfortunately, this technology still had limitations. Patients recovered enough to be able to walk, but they couldn’t run or bend their waist. They also had to always be careful to not hit their back, which had the electrical chip. Most of all, there was no way to treat spinal nerve damage if it was higher than the thoracic nerves, as there was no technology to implant a chip in the brain yet.
Thus, Carpentier was hoping to reach the next step at Young-Joon’s company.
“But Professor, aren’t you busy at work? You said that you were going to join us later in the year.” Young-Joon said.
“That’s correct.” Carpentier nodded. “But it’s my sabbatical year and I happen to not be supervising any students right now. I came a bit early because I had two months to spare after taking care of a couple of things.”
“Are you leaving in two months?”
“Yes, but I’ll be back during the second half of the year.”
“Great. Please lead our team for the two months you’re here. I am so glad you joined us, Professor.”
“I will try my best.”
“Thank you. But because you are still working at the university, you have to sign a short-term contract as an outside technical advisor.”
“Alright.”
“Is this okay with Caltech?”
“Yes. There are a lot of professors who work as technical advisors for companies.”
“Good.”
Young-Joon had Park Joo-Hyuk put together the contract and got Carpentier’s signature.
“You would be more comfortable with the spine if you were to join the stem cell differentiation teams, right?” Young-Joon asked as they scheduled a meeting.
“I’m fine with the bone marrow as well.”
“The nervous system and the bone marrow are two completely different fields.”
“I studied that a lot as well because I studied stem cells for a long time,” Carpentier replied with a chuckle.
* * *
Jacob was in the spinal regeneration team. He went into the meeting on spinal regeneration with stem cells with six other team members.
“Professor Carpentier?”
Jacob’s eyes widened.
“Hello, Jacob. Nice to see you again.”
“What about the university?”
“It’s my sabbatical year.”
“Then, should we discuss the current progress?” Young-Joon asked.
As it hadn’t been long since the project started, most of the presentation was about establishing detailed conditions for the experiment.
“... As such, we have currently created iPSCs, and we are planning to differentiate them after injecting them into the spinal paralysis model mice.”
Jacob finished his presentation. He stared at Carpentier and Young-Joon a little nervously.
Carpentier was the first to speak.
“The biggest problem with planting stem cells directly is the development of tumors. Do you have any ideas to solve this problem?”
“So, in our project, we have selected the mechanism whereby the iPSCs will be planted in the affected area, and then the cells that have not differentiated for a certain period of time will trigger apoptosis[1],” Jacob said.
“That is quite a good idea. But will the undifferentiated cells proceed to apoptosis well?”
“When the differentiation into spinal nerves occurs, the expression of the KRAK gene is inhibited. We have cloned TP54, a cell suicide gene, on the end of this gene and expressed it.”
“Then, the cells that haven’t differentiated into nerves would keep expressing KRAK and die as TP54 is expressed as well.”
It was quite complicated, but Carpentier understood the key details of the study right away. No wonder he was a Nobel Prize recipient.
“But won’t the stem cells die before they differentiate?” Carpentier asked.
“That’s why the number of cells that succeed in differentiating is low,” Young-Joon replied for Jacob. “But we can just put in a lot of stem cells in the first place. If ten nerves have to be recovered, we would put in about a thousand stem cells. The nine hundred ninety cells would be eliminated via apoptosis and the ten that remain would become nerves.”
Carpentier nodded his head. It seemed like a harsh method, but it was the most straightforward, safe, and effective way.
Doctors administered a large amount of insulin at once when treating type-2 diabetes. This allowed them to see the effects of insulin even if it was less effective due to insulin resistance. This was the same thing.
The reason they had been unable to use this method in the past was that it was impossible to grow that many stem cells. But with the iPSC technology, this was no longer an issue.
When one powerful technology was invented, it was bound to be able to solve a lot of problems.
* * *
After the spinal regeneration team meeting came to an end, Carpentier also attended the bone marrow regeneration meeting.
“By bone marrow regeneration, you are specifically talking about making hematopoietic cells, right?” Carpentier pointed out.
“Yes,” Young-Joon responded.
Bone marrow was the fluid tissue located in the center of bones, and it was an essential structure that produced blood cells, such as red and white cells. Then, how were blood cells made in the bone marrow?
There were things called hematopoietic cells that existed in small ratios, about one in every ten thousand cells, in the bone marrow tissue. They were a type of stem cell, but they could not differentiate into other types of cell, like how embryonic or induced pluripotent stem cells could. Their self-replicating ability was only limited to blood cells, meaning that all the blood cells in the human body were made by the division of hematopoietic cells. As such, bone marrow transplants that were used to treat leukemia patients were actually hematopoietic stem cell transplants.
“We will create hematopoietic cells from stem cells,” Young-Joon said.
“Leukemia will be our main target,” Carpentier said.
“That’s right. We will treat a lot of blood diseases with bone marrow regeneration, including leukemia.”
“Then let’s try something else since we’re doing it anyway.” Carpentier pitched an idea.
“What?”
“Treating AIDS.”
There was a moment of silence around the table.
“You can treat AIDS with this?” asked Doctor Lee Jung-Hyuk, the head of the bone marrow regeneration team.
“Yes. There is only one case of AIDS being cured,” Carpentier said.
“Has AIDS been cured before?”
This was the first time Young-Joon had heard of this as well.
“Yes.”
Carpentier nodded.
Young-Joon was amazed. Rosaline knew everything there was to know about molecular biology in the universe, but it was limited to scientific facts. She couldn’t have knowledge from experience or know about things that had actually happened in the history of science. In addition, Young-Joon used to work in anticancer; since AIDS was a viral infection, it was a little far from his specialty.
On the other hand, as Carpentier was a top scientist who had been in the industry for a long time, there were a lot of cases he knew from a lot of different fields.
“The patient’s name was Timothy Ray Brown. He was once one of the most unfortunate people in the world. The reason is... He had both AIDS and leukemia at the same time,” Carpentier said.
“My God!” Doctor Lee Jung-Hyuk and the other team members exclaimed at the same time.
Carpentier went on.
“They are both famous and fatal incurable diseases. Timothy first got a bone marrow transplant to treat leukemia.”
Among the sixty donors, they managed to find someone who met the conditions and he was able to receive a transplant. Fortunately, it worked well and his leukemia was considered cured. But weirdly, the AIDS virus, HIV, was no longer found in his body.
“HIV multiplies by infecting and destroying white blood cells. The white blood cell number continues to decrease because of that, eventually reducing immunity, and ultimately killing the patient from complications,” Carpentier said. “The hematopoietic cells in the bone marrow of the donor had resistance to HIV, and the white blood cells their cells created did not get infected by HIV.”
“...”
“After time, all the white blood cells that had no resistance to HIV died, establishing the resistant ones in the body. HIV continuously decreased as it had nothing to infect and eventually disappeared.
“There was a mutation in CCR5,” Young-Joon interrupted.
“That’s right.” Carpentier nodded.
The gene CCR5 was the infection route of HIV. The white blood cells that this gene was active in could be infected by HIV. But the hematopoietic cells of the person who donated bone marrow to Timothy Ray Brown had a mutation in CCR5, and the white blood cells that came from it had mutations as well.
“It’s an interesting case,” Young-Joon said.
Carpentier smiled.
“The bone marrow that Timothy Ray Brown was donated just happened to have a natural mutation. But if we could artificially make the bone marrow, or the hematopoietic cells, with stem cells...” Carpentier said. “Then, we could alter CCR5 and make it into bone marrow that has resistance to HIV, could we not?”
“That is a good idea,” Young-Joon said.
“But sir, how would we manipulate CCR5?” Doctor Lee Jung-Hyuk asked.
Young-Joon had manipulated a lot of genes before, but he had only introduced foreign DNA into cells using viruses. Creating a specific mutation in a gene that already existed in the cell was completely different.
“That’s the problem,” Carpentier said, frowning. “I think that we should treat the stem cells with a very low concentration of chemicals that damage the DNA and select the ones that have mutations in the CCR5 gene.”
“Won’t that take a long time?” Lee Jung-Hyuk responded.
“Mr. Technical Advisor, that seems like the only option, but I think we will also have to check if other mutations have occurred in other locations as well. Then, there will be a lot of tedious work to do.”
“It will be tedious, but if we can cure AIDS patients with that, we should do it.”
“The price of that treatment will skyrocket if you consider the labor and the price of DNA sequencing. It will take a long time to treat one patient as well. Wouldn’t it be hard to commercialize it?”
“Hm...”
Carpentier was lost in thought.
It wouldn’t be easy even if they used DNA scissors that could cut part of the DNA. As they would be experimenting with the entire genome, tens of thousands of places would be cut randomly at once. They needed scissors that precisely cut CCR5 and only that.
“We have no other way. Maybe this is an impossible project,” Carpentier said with a bitter smile.
“There is a way,” Young-Joon interrupted.
There was a message in front of his eyes.
[Synchronization Mode: Check how to induce mutations in the CCR5-Δ32 gene. Fitness consumption rate: 1.7/second.]
“I will research it and tell you at the next meeting.”
1. Self-destruction mechanism for cells ?
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