New Drug Development (1)
Ohsung Medical Center, seventh floor.
Clinical Center Building B.
The corridor was quiet, steeped in the sharp, antiseptic smell that clung to every hospital.
“Im Hyeon-woo, please come in.”
“Yes.”
The patient answered the call of his own name and stepped inside. An IV line was taped into the thin white skin of his arm.
He was barely past twenty. Yet his face looked far older—wrinkled, sallow, freckled with age spots. Most of his hair had fallen out, and the scalp beneath was red and inflamed from chemotherapy side effects. Nothing about him suggested a young man of twenty. His body was wasted to bone, yet his abdomen and legs were irregularly swollen from the edema of the drugs.
The doctor quietly read the name on the chart.
“Im Hyeon-woo. Are you all right? Today we administer the new clinical drug.”
The patient answered with effort, his voice weak and raspy.
“Yes……”
The nurse supported his wrist and double-checked that the line was secure. Today’s injection was codenamed OS12-41, Ohsung Bio’s latest Phase I candidate aimed at a mutant form of pancreatic tumor. It had been given to human subjects only a handful of times.
The nurse prepared the syringe. The liquid inside was colorless and clear. Hyeon-woo swallowed dryly.
The doctor began the infusion through the small pump.
“Hyeon-woo, it’s going in now. Tell me if you feel nauseous.”
Since he was already on fluids, they injected into the port. The unknown drug began to trickle slowly into his veins.
A moment later the patient curled slightly in on himself. Whether from chemo after-effects or the new drug’s effect on body temperature, a subtle tremor ran between his chest and stomach. The nurse draped a blanket over him and whispered,
“It’s all right. Breathe slowly.”
Hyeon-woo clenched his teeth and gave a small nod. The trembling continued. His limp fingers clawed weakly at the air. The nurse took his hand.
The monitor numbers: oxygen saturation 89 percent. Pulse 108. Blood pressure 72/40. Hypoxemia, tachycardia, hypotension. Alarming figures for an ordinary patient; routine data in an oncology clinical ward.
The doctor checked the readings and said,
“Im Hyeon-woo, you did very well today. If this drug works… the pain may ease a little by next week.”
Behind the mask the young man managed a faint expression that might have been a smile.
Ohsung Medical. Upper-floor research lab.
Two PhDs who had forgotten quitting time were still reviewing data amid stacks of papers. Dr. Kang exhaled first. Dr. Choi across from him asked,
“What’s wrong? Not working?”
Dr. Kang swallowed a bitter smile.
“We ran the new concentration tests. Normal cells die before the cancer does.”
Dr. Na was silent for a moment. On the microscope feed the cancer cells still writhed stubbornly alive while the neighboring healthy cells had already shattered into debris. This clinical candidate was, for all practical purposes, a failure.
Dr. Kang spoke with hollow weariness.
“What we call treatment right now is just this—does the cancer die first, or does the patient?”
Dr. Na buried his face in both hands. After a while his lips moved.
“What choice do we have? We can’t selectively kill only the cancer, so we have to push with toxicity. That’s the reality.”
“The side effects this time are still too severe.”
“How bad?”
Dr. Kang continued in a tired voice.
“Hair falls out, weight drops, the immune system gets wrecked… anything that divides quickly gets hit. The gut is damaged, hematopoiesis tanks.”
The agent attacked rapidly dividing cells. Cancer cells divided fast, so that was the target. But they were not the only ones. Hair follicles divided quite rapidly as well; that was why patients lost their hair.
Dr. Na studied the data and slowly nodded.
“Should we design this one a little weaker to reduce the side effects?”
He shook his head at once.
“Then the cancer cells won’t die.”
He tapped the edge of the monitor with a fingertip.
“You know what moment stings me the most?”
“What?”
“When I explain the side effects to a patient. Honestly, the word ‘side effect’ feels… irresponsible.”
“Why?”
“The cancer has to die before the patient does. The chemo we give is poison, and we’re just packaging it nicely.”
A game of drinking poison and seeing which died first—normal cells or cancer cells. Both doctors let out long breaths. The sense of helplessness that had been buried under papers, charts, and experimental data slowly pooled on the table.
Then the door burst open.
“Doctors!”
The clinical professor strode in.
“We just got a call from JH.”
“What?”
“JH. The place that caused the uproar by solving protein structures.”
“Ah—that JH! What do they want?”
“They’re telling us to bring our samples.”
“Why?”
“Looks like JH is gathering the pharmaceutical companies.”
“Meaning they intend to develop new drugs for real?”
“Probably.”
JH Research.
Conference room.
Researchers in white coats stood on the dais preparing to present. The subject: new drug development.
Our company had released three hundred million protein structures. Collaboration proposals had poured in from every direction. But we were fundamentally a semiconductor, data-center, and AI firm. We did not really know pharmaceuticals. We had almost no staff in that field either.
Thanks to Illys we had trained the AI on protein data and mass-resolved the structures, yet turning that into actual drug development was another matter entirely.
I asked Manager Jang,
“Where is that person from?”
“Ohsung Bio.”
Ohsung Bio. Like most Ohsung affiliates it was a sizable pharmaceutical company.
“Ohsung does new-drug R&D too?”
“They do a lot of generics, but they haven’t completely abandoned original development.”
While we whispered, the presenter brought up the first slide.
Methods for New Drug Development Utilizing Protein 3D Structures
“Good afternoon. I am the head of new-drug development at Ohsung Bio. Thank you to JH for giving us this opportunity. I will begin the presentation.”
He pointed at the screen. A 3D protein structure floated there.
“As you can see, JH has completed the protein structures.”
Everyone in the room nodded.
“A truly astonishing achievement. Humanity now knows the shapes of all normal proteins. However—”
He looked out at the audience.
“This is only the first step.”
He indicated a specific pocket on the protein.
“With the structures public, we know the normals. What we still do not know well is how proteins change in disease states—which ones tangle, collapse, or bind incorrectly.”
He zoomed the image. A red distorted structure overlaid the normal one.
“Cancer, autoimmune disease, dementia… every one of them produces abnormal protein structures.”
He faced the room squarely.
“Yes. The structures are already solved. What matters now is directly confirming the interaction patterns of how those proteins malfunction in disease.”
Heads nodded again.
“Therefore Ohsung proposes the following to JH. We will supply protein structures from cancer patients. JH will complete the 3D structures of the cancer-cell proteins. After that we compare the normal proteins against the patients’ deformation patterns and establish the foundation for new-drug development.”
The proposal was simple: compare normal proteins with those that make up cancer cells.
I raised my hand.
“Once we compare the normal and abnormal proteins, what comes next?”
“An excellent question.”
The slide changed.
“This is an example protein. When this region twists, it can no longer bind its original partner. First we identify the cause. Second we search for candidate compounds that fit the abnormal site.”
First, diagnose the cause. Second, find candidate molecules for a fix. Protein comparison I could grasp; hunting candidates felt opaque.
“How do you find the candidates?”
“We have to try many approaches.”
“Excuse me?”
“Once we have both structures, the only way is to attempt every method that might restore the abnormal structure to normal.”
Hmm. Even with the structures solved, new-drug development still sounded like it would take forever.
“So we’ll need collaboration with pharmaceutical companies now?”
“Yes. Please look at the next slide. I’ve summarized the research status of the major firms.”
“Ohsung Bio, Cheongsipja, Doonggeundang, Idong Pharma… quite a few.”
Each company’s scale and rough research focus was laid out.
“Let’s see… Ohsung Bio’s pipeline is mostly oncology.”
“Correct.”
“Any success stories yet?”
“Unfortunately, none so far.”
The presenter looked a little embarrassed, then spoke calmly.
“Cancer has an extremely high failure rate. We kept stalling in Phase II and Phase III.”
“A hard road.”
“Yes. But our company has not completely pivoted to generics.”
Plenty of firms had given up original development and survived on price wars with copies. The presenter still showed the will to keep chasing a cancer therapy somehow.
“Manager Jang.”
“Yes.”
“Most of the companies here are oncology-focused.”
“It’s currently humanity’s great challenge, after all.”
“What about brain indications?”
“Some interest, but the brain is so difficult that domestic firms treat it as lower priority.”
“I see.”
“Why not start with cancer, build experience, then expand into the brain?”
“Do the easier one first?”
“Relative to brain therapies, yes.”
“All right. Let’s do that. Please shortlist the pharma partners for us—about ten should be enough.”
“Understood.”
I turned. Intern Oh stood in a corner.
“Intern Oh?”
“Yes.”
“You take Ohsung Bio.”
“Understood.”
Intern Oh was the son of the Ohsung Group chairman. Here he changed the water cooler bottles; over there he would be treated like a crown prince.
“Good. Then each pharmaceutical company, please send us samples. We will return the 3D structures of the abnormal proteins.”
“CEO, when we introduce candidate drugs in stages, can you also show us how the proteins change at each step?”
“Ah—so you want the progressive changes in the proteins as the drug is administered little by little?”
“Exactly.”
“No problem at all. Just send them; we’ll give you everything down to the molecular level.”
“Thank you!”
One way or another, once we received the samples we only had to ship them into the Nano World and ask for some drawings. Nothing particularly difficult.
A few days later.
JH Research, basement level B2.
We had newly built a biospecimen storage zone. White boxes stood in neat layers on stainless-steel shelves. Each box was a sample shipment from a different pharmaceutical company. The labels were crowded with carefully written terms.
I pulled on gloves and opened the first box.
“So… this is melanoma.”
A tumor tissue slide with abnormally clumped black pigment was carefully wrapped in plastic. I checked the next box.
“Gastric cancer sample.”
Beside it a small tube was labeled “BT-Cell line – BD-45.”
What was this?
“Ah, it says here. State after 1 ml of new drug BD-45.”
They wanted to see the post-treatment condition. I read the labels one by one.
“Melanoma, breast cancer, gastric cancer, colorectal cancer, pancreatic cancer, ovarian cancer, lung cancer… almost every cancer cell is here. Even states after various drugs have been applied.”
I held one small tube up to the light. A faintly turbid liquid. This work I had to do alone. The method: send it into the Nano World. I needed the sponsorship function.
Sponsoring cancer cells felt a little strange, but they had to go into the Nano World so drawings could be made. If we were going to create cancer therapies, a few dozen sponsorships were nothing.
…
Sending whole tubes would not work. Only an invisible micro-amount was suitable for analysis in the Nano World. Of course I was used to this kind of sponsorship as well.
Ziiing.
As soon as the sponsorship went through, Illys called.
“Constellation, are these the cancer cells you mentioned?”
“Yes. Please draw each of them for me.”
“Understood. I’ll draw them right away.”
“Thank you.”
“When you give us work, Constellation, that is our happiness.”
“Why?”
“It means we are useful. Sometimes I feel uneasy only receiving. When you assign us tasks like this, I cannot tell you how glad I am.”
Illys, speaking with those bright, earnest eyes, was a 6-Circle Mage. When she put on a fire show in the magic training grounds she looked like a walking bomber, yet when she spoke like this she reminded me of a child who lights up at being sent on an errand.
“Constellation, what role do cancer cells play?”
Curious eyes.
“They form inside the human body, and over here they’re a disease that’s hard to treat.”
“So these cause illness?”
“Well… strictly speaking, cancer cells are the person’s own cells. Originally theirs, but cells that proliferate without limit.”
“Unlimited proliferation?”
“Yes. Cancer cells keep multiplying and monopolize every nutrient. Because they’re originally the body’s own cells, the body doesn’t even try to remove them. And because they’re the body’s own, it’s hard to wipe out only the cancer cells with drugs.”
“Ah… I see. Cells that have lost their order.”
Order. That was one way to look at it. Cells divide, grow, perform their roles, and die when their time comes. That was the order of cells. Cancer cells simply refused to die when they should. Unlimited proliferation. By breaking order they multiplied, yet in the end the person who was their host died.
Through the smartphone I watched Illys summon one cancer cell. At a glance it was a little larger than she was. It pulsed and quivered.
“My, it looks just like a slime. It’s cute.”
Cute? A cancer cell?
“Constellation, shall we try raising it here?”
“Raise what?”
“The cancer cell.”
“Why would you raise that?”
“You asked us to observe the ones that had been put into drugs step by step, didn’t you? Then why not simply grow the cancer here, sprinkle various medicines on it, and observe?”
“Is that even possible?”
Seen like this the wriggling cancer cell really did look like a slime—one larger than a person. I worried whether it might be dangerous for Illys. She beamed and spread both hands.
“I am a 6-Circle Mage, you know.”
Right. At 6-Circle she was practically a human weapon. If a 5-Circle was a fully equipped special-forces operator, a 6-Circle looked about like a tank battalion. Nothing that looked like a slime cancer cell was going to frighten her.
“You’ll be all right?”
“Of course. It would be my joy.”
“Then I’ll leave it to you.”
And with that I now possessed a nano-scale new-drug clinical trial facility. Its director was a 6-Circle Mage.