“Myelodysplastic syndrome is usually a problem because the quality and amount of the patient’s blood cells is very low,” said Professor Albert.
“The hematopoietic stem cells have dysplasia, so the white blood cells, red blood cells, and platelets from it can’t function properly. That’s why these patients have anemia and are susceptible to infections. If the white blood cells don’t work properly, their immune system will be a mess. And because they have low platelet counts, they bleed often, which doesn’t stop well either.”
“That’s why she bled so much from her arms and legs when she got shot,” Harris said.
“That’s right. Patients who have myelodysplastic syndrome can only have conservative, life-sustaining treatment by receiving normal blood, like how patients with renal failure receive dialysis,” Albert said. “Even that doesn’t work in the late stages. A significant portion of cases results in acute leukemia. The only solution is to be cured or anything like that is a bone marrow transplant.”
“Then, it’s fine, right? A-GenBio developed a bone marrow transplant method using hematopoietic stem cells made from induced pluripotent stem cells. All that’s left to do is for Doctor Ryu to treat her,” Harris said.
“But myelodysplastic syndrome usually occurs after the age of fifty. It’s rare for it to occur at such a young age. Isaiah seemed to be born with it; it was bad when she was a newborn, then developed in infancy,” Albert explained, though he seemed a little doubtful.
“To be honest, we chose myelodysplastic syndrome because it fits her symptoms the best, but we have to treat it as the first ever case to be reported since it’s due to genetic engineering. From a doctor’s perspective, no matter how great Doctor Ryu is, I don’t know what he can do about a disease he’s never seen in a week…”
“But he was able to revive brain-dead people.”
“That’s why I’m still inclined to trust him.”
Click.Young-Joon came out of Isaiah Franklin’s room.
“It must be uncomfortable to use one of the two rooms in this small hideout as a hospital room,” Young-Joon said.
“Have you talked to Isaiah?”
“Yes. I’m going to bring the clinical trial consent form tomorrow and explain it again.”
“Consent form…”
“I know time is of the essence, but we still have to do what’s necessary.”
*
Isaiah Franklin was a cloned human being—a human reconstructed from the nucleus of her mother, Elsie Franklin. As such, although Isaiah Franklin was born in 1986 and around the same age as Young-Joon, her cell biological age was similar to that of Elsie’s, which was in the late fifties.
—That’s where the problem arises.
Rosaline intervened from the side.
“It reminds me of Dolly, the cloned sheep,” Young-Joon
—The sheep that was cloned from a mammary gland cell?
“Yeah. That’s why the name…”
Young-Joon suddenly paused.
—Why?
“Nothing.”
—Why did you stop all of a sudden? How did she get the name?
Curious, Rosaline began nagging Young-Joon for a response.
“No, it’s nothing. Dolly, the name of the cloned sheep, came from a pop star named Dolly Parton.”
—Were the researchers fans of that pop star?
“...”
Dolly Parton was a pop star famous for her voluptuous breasts. They named the sheep Dolly to honor that she originated from the mammary glands.
Young-Joon glanced beside him. Rosaline, who looked exactly like Ryu Sae-Yi, was staring at him with innocent eyes.
“Well… Yeah, they were fans,” Young-Joon replied.
Why couldn’t this ridiculous and useless background knowledge get out of his head?
“Anyways, let’s think of a strategy to treat Isaiah’s bone marrow,” Young-Joon said, changing the subject.
—Yes. Ryu Young-Joon, do you know that cells can age, get old, and die?
“Are you talking about telomeres?” Young-Joon asked.
—Yes.
“The theory that Dolly died prematurely because of them once swept the scientific community.”
The lifespan of sheep was about eleven to twelve years. But Dolly, the cloned sheep, began aging at the age of three. By the time she was five, she was suffering from arthritis and other elderly diseases and eventually developed a serious lung disease. Eventually, Dolly, the first cloned organism and most famous lab animal in history was euthanized at six and a half years old.
Interestingly, the mother sheep that provided Dolly with her DNA was six years old when her mammary gland cells were harvested. In other words, the number of days lived by the mammary gland cell that Dolly originated from and the days Dolly lived was about twelve years combined, which was the normal lifespan for sheep.
This fact intrigued many scientists. A baby born to a couple in their twenties didn’t live longer than a baby born to a couple in their fifties. The conventional knowledge was that the biological clock started at zero. But Dolly, the cloned sheep, seemed to have been born with the age of the mammary gland cells from which she originated.
Then, wouldn’t scientists be able to find out one’s true biological age by exploring something within their cells? Furthermore, could it even be manipulated? Scientists have been exploring concepts like cellular lifespan and age for a while now, and this was a huge firestarter for the field.
A lot of researchers started digging into the field, hoping to write a scientific paper. One of the most prominent findings was telomeres.
—Dolly the sheep probably died because of telomeres.
Rosaline explained to Young-Joon.
Telomeres were highly specialized bits of DNA at the end of chromosomes. As a cell aged, its telomeres became shorter and shorter. When it reached a certain point, the cell lost its ability to reproduce and was no longer able to divide, meaning telomeres were structures associated with cellular lifespan. However, cellular lifespan led to macroscopic aging and the lifespan of an organism.
Further research revealed more surprising findings: organisms that lived longer had longer telomeres in their cells than organisms with short lifespans. The mammary gland cells that gave rise to Dolly the sheep had shortened telomeres, and Dolly started life with those short telomeres.
Then in 2013, an even more shocking paper was published. It suggested that telomere length could increase lifespan and inhibit aging.
Mice that had lengthened telomeres through genetic manipulation of the egg were compared to a control group. The mice with longer telomeres showed fewer signs of aging and lived twenty percent more on average.
This sensational news quickly made its way over the walls of the scientific community. The public was turned upside down before the paper was even thoroughly reviewed by the scientific community.
The media was buzzing, talking about how humans had reached the realm of immortality, and telomeres quickly became a keyword in the cosmetic and healthcare industries.
“But it’s kind of faded away nowadays. The follow-up research is too difficult, and we can’t manipulate human telomeres in the same radical way as you can in mice. It’s also hard to apply it in the clinic,” Young-Joon said. “But since we’re talking about telomeres, does this mean that Isaiah Franklin’s body has telomere problems?”
—Yes, especially in the bone marrow.
Rosaline began explaining.
—The blood cells produced by hematopoietic stem cells in the bone marrow that have shortened telomeres have a much shorter lifespan than normal. And because the other genes are also messed up, the blood cells quickly become nonfunctional.
“Then when we make the stem cells to be transplanted into the bone marrow, we have to also fix the telomeres on top of fixing the genes?” Young-Joon asked.
—That’s right. Then the myelodysplastic syndrome will be cured.
Young-Joon thought for a moment, then asked, “Will that cure her?”
—Are you going to include aging as your target for treatment?
“...”
—The patients with genetic conditions we saw at Kukra Hill weren’t born like Isaiah Franklin. They didn’t have their mother’s nucleus, so their cell biological age was normal.
Rosaline went on.
—But Isaiah Franklin was congenitally born with about thirty years’ worth of aging. Isaiah’s holding up okay right now as Elsie wasn’t a senior or anything, but all of her organs will start to age rapidly in about ten years.
“Then what happens?”
—She will have geriatric disease when she’s in her forties, and she will look like a grandma. However, humans haven’t categorized aging as a pathological condition yet; they think it’s natural. What do you think?
“Progeria syndrome is already a disease. It’s already been classified as a disease, no matter what I think of it.”
—If you want to cure it, there’s a way.
“How?”
—When you do the bone marrow transplant, put a slightly modified version of the telomerase gene into the hematopoietic stem cells.
“Telomerase?”
Telomerase was a biomolecule that lengthened telomeres. It was discovered during the height of the telomere boom, and many scientists tried to use it to extend human life. However, despite the enormous amount of money and labor invested by many scientists to uncover clinical applications of telomerase, there was ultimately no progress. This was because while telomerase could extend telomeres, it could also cause cancer. It was like opposites attracting.
Cells with extended telomeres could divide again and again beyond the limit of division. If controlled properly, they could become immortal by replacing damaged cells, but they became tumors if they spiraled out of control.
Eventually, scientists gave up because the technology was too difficult and dangerous to apply to humans, and the craze died down.
—We’ll use blood cells as carriers of telomerase through bone marrow transplantation. We need to send telomerase throughout Isaiah Franklin’s body to extend the telomeres of approximately ten trillion cells, each for a specific duration, and then stop.
“Is that possible?”
—I can. We just need to administer trace amounts of the inhibitor at specific times, either intravenously or through injections, while I look at it in Synchronization Mode. The problem is that you have no way of explaining how you figured out those timings and injection locations.
“...”
—Or you could just give up thirty years of aging that Isaiah Franklin was born with. It wouldn’t cure her though.
*
Ryu Ji-Won came out of the library at seven in the evening.
“You guys go ahead. I have to eat at home today.”
Ryu Ji-Won said goodbye to her friends and walked down the main street outside the campus. Today was a day of much pain for Ryu Ji-Won’s family: it’s the remembrance day of Ryu Sae-Yi, their youngest sister.
‘What is Young-Joon doing…’
Young-Joon always came home on this day, but at some point, he started traveling around the world with a superhuman schedule. He ended up calling today to say he wouldn’t be able to come home.
Ryu Ji-Won considered calling him out of concern, but she didn’t.
‘I’m sure he’s busy…’
Ryu Ji-Won arrived at the entrance of their apartment complex. As she was about to go inside…
“Ms. Ryu Ji-Won?”
A man suddenly came up to her.
“Who are you?” she asked.
“Do you know this person by any chance?”
The man, with his hat pulled low over his face, held out a photo. It was a picture of Young-Joon and Rosaline taken at an amusement park.
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