Ghosts of Eternity

Inside Research Lab 2 at Aether Bio, the pressure valve on a liquid nitrogen tank released a brief hiss.

A researcher pulled a vial of frozen phage library from the rack.

The team incubated a billion-member scFv phage library with IL-11-coated magnetic beads. Phages that survived the wash conditions and remained bound to the beads were recovered and amplified.

By the end of the third round of panning, most of the initial library had been washed away. Only a few dozen sequences remained. Sequence analysis revealed that three of them repeatedly ranked at the top.

The team converted the top clone, A-17, into an IgG format, expressed it, and tested the purified antibody in a cell-based assay.

A few weeks later, concentration-dependent inhibition curves appeared on the monitor:

[IC50: 84 pM]

[Maximal inhibition of IL-11-induced STAT3 phosphorylation: 91.3%]

Once the results were confirmed, Seohan assigned the development code 'AX-11' to clone A-17. Over the following months, the team repeatedly validated its binding affinity, function, and production yield, with the final purified batch reaching 99.2% purity.

Next came animal trials using seventy-five-week-old mice with diet-induced obesity. The AX-11 antibody was administered subcutaneously at regular intervals.

Team Leader Kwon narrowed his eyes as he glanced back and forth between the figures on the monitor and the raw data sheets.

From the second week, the weight curve of the treated group began to diverge gradually from that of the control group. The issue was how the weight was being lost.

"Did you re-check the scale's zero point?"

At Kwon's question, a junior researcher nodded.

"Recalibrated it this morning, sir. We measured each animal three times, and the results were identical."

"What about food intake?"

"No lower than the control group. In fact, during certain weeks, the treated group ate slightly more."

Kwon’s hand froze. The weight loss wasn't caused by a lack of eating.

"Activity levels?"

"No significant difference. Both daytime and nighttime activity remained within the control range."

They weren't eating less, nor were they moving more. Yet, they had lost weight.

Kwon scrolled through the screen.

"Re-check for signs of diarrhea and dehydration, and bring me the fecal bomb calorimetry results."

"All normal, sir. No signals indicating malabsorption."

Just then, Seohan passed by the corridor and pushed open the lab door. His gaze went straight to the DEXA body-composition data on the monitor.

"Bring up the DEXA data."

As Kwon stepped aside, the screen displayed the distribution of fat mass, lean mass, and bone density. What had decreased in the treated group was almost entirely fat. Abdominal fat mass, in particular, had dropped by over 30%, while lean mass was preserved. The weight loss was not due to toxicity or muscle wasting.

"How much total weight was lost?"

"An average of fourteen percent over eight weeks."

Seohan slowly scrolled through the screen.

"What about liver fat?"

"Hepatic triglycerides are significantly lower than in the control group. Serum triglycerides and non-HDL cholesterol dropped alongside it."

"Glucose tolerance?"

Kwon brought up the next graph.

"Both GTT and ITT showed improvement. Fasting insulin levels are also lower."

Seohan checked the raw data for individual animals before looking at the graphs. This wasn't the result of a few outliers skewing the average; the same trend appeared across nearly every animal in the treatment group.

"Activity levels remain unchanged, food intake hasn't dropped, yet only fat mass has decreased," Kwon muttered under his breath. "It seems the way fat is stored or utilized has fundamentally shifted."

Seohan nodded. "Do we have RER data?"

"We are re-analyzing under fasting and refeeding conditions."

"Compare the rate of fuel switching after refeeding against the controls. We need to verify if metabolic flexibility—switching between fat and carbohydrates—has altered."

Kwon immediately jotted down a note. Seohan opened the next set of data. In the control group, inflammatory signaling and fibrosis markers were elevated in both liver and visceral adipose tissue. In contrast, those markers were broadly suppressed in the AX-11-treated group.

"Have we verified collagen content in the liver and visceral fat?"

"Tissue staining shows a clear downward trend. Visceral fat pad weight decreased in the same direction, and quantitative results will be out within this week."

"What about muscle?"

"Muscle mass is preserved, and even after adjusting for body weight differences, grip strength is higher."

Seohan stared at the screen for a moment. Fat loss alone was not enough to qualify as an anti-aging intervention. However, fat accumulation, insulin resistance, tissue inflammation, fibrosis, and muscle decline were all moving in the same favorable direction.

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The changes were too broad to dismiss as a simple anti-obesity effect.

"Run ERK–mTORC1 activity alongside p16 and p21. We need to confirm whether tissue-level senescence markers are moving in the same direction, independent of weight change."

Kwon nodded. "I’ll initiate additional tissue analysis right away."

Seohan took a final look at the body weight and fat mass graphs for individual animals.

"It holds value even strictly as an obesity indication," he said, closing the screen. "But right now, the key isn't how much weight was lost. What matters more is whether aging-related signals across different organs are stepping down in unison."

Setting the data sheets down, Seohan walked toward his office. Behind him in the lab, researchers spoke in hushed voices.

"You said they didn't eat less or move more, right?"

"That's why everyone suspected the equipment first."

Team Leader Kwon turned his head. "If you have time to talk, move the tissue analysis up."

The researchers turned their eyes back to their respective monitors, though none could easily scroll past the fat mass curve displayed on their screens.

In the small treatment room beside Seohan’s office, a cool space illuminated by a single desk lamp, Seohan went through the checklist organized on his tablet PC, item by item.

The data Seohan reviewed wasn't limited to what they had obtained that day. Preclinical efficacy studies completed earlier, quality analysis of the final production batch, and toxicity assessment data were all compiled onto a single screen.

Efficacy in mice and efficacy in humans did not belong in the same sentence. At the very least, in mice, fat accumulation, insulin resistance, tissue inflammation, and fibrosis were improving in the same direction.

Fortunately, AX-11 bound both mouse and human IL-11, but there was no guarantee that the physiological response following binding would be identical inside the human body. Before self-administration, manageable risk factors had to be clearly filtered out.

First, manufacturing quality indicators:

• [ ] Endotoxin: Below the dose-adjusted allowable limit — PASS

• [ ] Aggregate content: 0.2% by SEC-HPLC — PASS

• [ ] Purity: 99.2% (Final purified batch) — PASS

• [ ] Sterility test: No microbial growth after 14-day culture — PASS

Trace impurities and protein aggregates could increase the risk of immunogenicity and acute administration reactions. No such manufacturing quality issues were found within the current testing scope.

Next, mechanism characteristics and uncertainty indicators:

• [ ] Non-specific binding: No significant signal within test panel — PASS

• [ ] Cytokine release assay: No significant increase in inflammatory cytokines in human whole-blood assay — PASS

• [ ] Binding to both mouse and human IL-11:PASS

• [ ] Human IL-11 affinity: Kd 12 pM — PASS

• [ △ Estimated half-life: ~18 days ]

• [ △ Long-term impact of IL-11 inhibition: Unknown ]

Acute tolerability and long-term safety were entirely separate questions. There was ample evidence that IL-11 was involved in pathological fibrosis. However, the consequences of blocking it long-term in normal tissues remained unmapped. Stopping excessive signaling was a different story from blocking it completely over an extended period.

Moreover, the estimated half-life was eighteen days. This was not a drug with an off-switch. Once administered, it could not be cleared from the body on demand.

Finally, setting the initial human dose.

Seohan laid out the Human Equivalent Dose (HED) calculated from animal toxicity data side by side with the estimated Minimum Anticipated Biological Effect Level (MABEL) based on target binding. He chose a starting dose one full step below the lower of the two estimates.

The purpose of this administration was not to confirm efficacy. Above all, he needed to identify any unexpected acute reaction and observe the initial response pattern.

He decided to start far below the estimated effective exposure level. Even if no acute reaction occurred, the next dose could only be reviewed after a sufficient observation period. Once injected, a drug could not be taken back. A low dose, however, limited the potential consequences if something went wrong.

The passed items on the checklist turned gray and disappeared. Yet, a single item at the very bottom remained unchecked, highlighted in red:

[ ! ] Human AX-11 Administration Data: NONE

No in vitro experiment or animal study could substitute for that single missing line.

Following formal development procedures, it would take years before it could be administered to humans in an official clinical trial, and far longer for approval. While waiting out that time, his own body would continue to age.

He had no intention of passing the initial uncertainty onto anyone else.

On one side of the treatment table, an emergency kit, an automated blood pressure monitor, and a pulse oximeter stood ready. He had configured the system so that if vital signs in the treatment room drifted past critical thresholds, an automated alert would be sent to the night-duty officer’s terminal.

Seohan took out the vial containing the candidate antibody AX-11 from the refrigerated unit.

Before picking up the syringe, Seohan quietly checked his phone screen. The display linked to the internal emergency terminal was on. He picked up the syringe without turning off the screen.

The needle pierced the rubber cap. As he pulled back the plunger, clear liquid filled the syringe barrel.

Rolling up his shirt sleeve, he lightly pinched the skin of his upper arm. A brief chill spread across his skin as the alcohol evaporated from the swab.

Seohan inserted the needle and pushed the plunger all the way in. After withdrawing the syringe, he pressed a sterile gauze over the red dot and applied a bandage.

3 minutes post-administration.

Heart rate, blood pressure, and oxygen saturation all remained within baseline ranges. No wheal or localized erythema appeared at the injection site. Seohan recorded the figures and reset the timer.

11 minutes post-administration.

His smart ring showed a heart rate six beats per minute above his usual baseline.

Seohan did not immediately classify this as a drug reaction. Simply focusing on his own heartbeat could easily produce a transient increase of that magnitude.

[Slight heart rate elevation / Causality undetermined]

24 minutes post-administration.

Seohan felt a faint warmth at the injection site. Rolling up his sleeve, he photographed the skin condition with his camera, but found no visible erythema or swelling.

[Perceived localized heat / No objective skin changes observed]

Outside the treatment room, only the steady rhythm of the night HVAC system vibrated through the hallway. The door remained half-open, and the latch on the emergency kit was unfastened.

38 minutes post-administration.

Systolic and diastolic blood pressure remained stable. Oxygen saturation and body temperature showed no fluctuation. The likelihood of an immediate hypersensitivity reaction was diminishing with every passing minute.

Yet it was too early to relax. Systemic changes driven by target blockade or immune response could manifest hours, or even days, down the line. Seohan pre-scheduled the primary blood draw time for the following day in the system.

52 minutes post-administration.

His heart rate returned to baseline. The heat at the injection site faded.

Seohan closed the lid of the emergency kit and powered down the monitoring display.

Continuous monitoring remained active through the smart ring and patch sensors, with manual checks scheduled for blood pressure and oxygen saturation. If any vital signs breached critical thresholds, an alert would simultaneously transmit to both Seohan’s phone and the night-duty officer’s terminal.

Seohan unlocked his tablet and entered the next development orders beneath the self-administration log:

• [Initiate repeat-dose primate toxicity study immediately]

• [Initiate transition to GMP-grade clinical manufacturing process]

• [Expand tissue cross-reactivity panel]

• [Draft Phase 1 clinical protocol]

Self-administration and formal development were entirely separate matters. No step would be bypassed. However, every possible process would be run in parallel.

[AX-11 First Self-Administration Log]

[Time of Administration: 22:14]

[Administered Dose: One-tenth of the estimated effective exposure]

[52 Min Post-Administration: No specific acute reaction]

Seohan saved the log and walked out of the treatment room.

The first line of AX-11 human data had been written.