From Local Challenge to Global Breakthrough
Ho-Wang Lee and the Conquest of Epidemic Hemorrhagic Fever
The story of a Korean scientist's journey from wartime medicine to discovering hantavirus and developing the world's first vaccine
Introduction
In the tumultuous landscape of 20th-century Korea, a relentless killer stalked the population—a mysterious illness that began with fever and headache but could rapidly progress to fatal kidney failure and uncontrolled bleeding. For decades, the identity of this pathogen remained one of medicine's most stubborn mysteries, evading capture by top international research teams from the United States, Japan, and the Soviet Union.
Scientific Breakthrough
1976 discovery of the elusive pathogen that caused epidemic hemorrhagic fever
Vaccine Development
Creation of Hantavax, Korea's first home-developed new drug
That all changed in 1976, in a humble Seoul laboratory, when Korean scientist Ho-Wang Lee and his colleague Lee Pyeong-woo witnessed what no one had seen before—the ghostly glow of the culprit pathogen under their microscope. This article traces Lee's extraordinary journey from wartime medical student to world-renowned virologist, exploring how his groundbreaking work on what would become known as hantavirus emerged from Korean field conditions to achieve global impact.
The Disease Mystery: Epidemic Hemorrhagic Fever
Epidemic hemorrhagic fever—known today as hemorrhagic fever with renal syndrome (HFRS)—presented a formidable medical challenge throughout much of the 20th century.
Five-Stage Disease Progression
Febrile Stage
After a 2-3 week incubation period, patients experience sudden onset of high fever, chills, severe headache, and vomiting lasting 3-7 days2
Hypotensive Stage
Around the fifth day, blood pressure drops dangerously low, potentially leading to shock, delirium, or coma2
Oliguric Stage
By day seven, urine output dramatically decreases as kidney failure sets in, allowing waste products to accumulate in the blood2
Diuretic Stage
Around day ten, patients may produce 3-6 liters of urine daily, risking severe dehydration and electrolyte imbalances2
Convalescent Stage
A prolonged recovery lasting weeks to months as kidney function gradually normalizes2
Disease Impact Timeline
The disease gained particular notoriety during the Korean War, when it infected thousands of United Nations troops stationed near the ceasefire line, leading some to suspect it was a form of biological warfare1 . The U.S. Army established the Korean Hemorrhagic Fever Center and shipped specimens to research facilities in Japan and Washington, but despite systematic investigations by excellent researchers, the pathogen remained elusive1 .
The Scientist's Journey: From Wartime Medicine to Virology
Ho-Wang Lee's path to virology excellence began in 1928 in Shinheung, Hamgyongnam-do, in what is now North Korea3 . His medical studies at Hamheung Medical College were interrupted by the outbreak of the Korean War, forcing him to flee to Seoul where he continued his education at the Seoul National University College of Medicine through a wartime union university arrangement1 .
A pivotal opportunity emerged when Lee was selected for the "Minnesota Project," an educational exchange program that took him to the United States for advanced study1 . Despite initial language barriers—he once waited endlessly in an empty classroom, unaware that a cancelled lecture had been announced—Lee persevered, borrowing American classmates' notes to copy over weekends1 .
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1954Graduated from Seoul National University College of Medicine
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1959Earned Ph.D. from University of Minnesota
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1970Began hemorrhagic fever research with U.S. Army support
His doctoral research on Japanese encephalitis virus introduced him to cutting-edge tissue culture methods and established his foundation in virology1 . After earning his Ph.D. from the University of Minnesota in 1959 and returning to Korea, Lee continued Japanese encephalitis research until news of successful vaccine development in Japan prompted him to seek new directions1 .
The turning point came during a visit to the Walter Reed Army Institute of Research, where a former colleague suggested he study epidemic hemorrhagic fever1 . Lee recognized both the significance of the disease and his unique position as a researcher based in the outbreak area with modern virology training. He successfully obtained support from the U.S. Army Medical Research and Development Command beginning in 1970, launching his historic investigation into this medical mystery1 .
The Breakthrough Experiment: Discovering the Unseen Pathogen
By 1976, after years of frustrating failures using various approaches, Lee and his assistant Lee Pyeong-wou were working in a rudimentary laboratory in Seoul's Hyehwa district, where they coped with a hole-riddled ceiling and charcoal briquettes for heating1 . Their persistence was about to pay off in a historic moment of discovery.
Experimental Methodology
Lee's investigative approach was systematic and built upon careful analysis of previous research from the Soviet Union, Japan, and the United States1 . His strategy involved three parallel tracks:
Patient Serum Collection
Gathering blood samples from hemorrhagic fever patients to study immune responses and pathogen presence1
Wild Rodent Examination
Focusing particularly on mice from epidemic areas, as their population patterns correlated with disease outbreaks1
Ectoparasite Analysis
Collecting ticks, fleas, and lice from wild rodents, though these eventually proved less significant1
Key Rodent Species in Lee's Research
| Species | Common Name | Significance |
|---|---|---|
| Apodemus agrarius | Striped field mouse | Most frequently collected species |
| Microtus fortis | Reed vole | Ultimately linked to virus discovery |
The Discovery Moment
The historic night came in 1976, as Lee and his assistant peered through their fluorescence microscope at sample slides prepared from wild rodents1 . As Lee adjusted the microscope's focus, a spectacular sight appeared—a galaxy-like pattern of yellow light resembling the Milky Way against the dark background1 . This distinctive fluorescence signaled the presence of the long-sought pathogen.
The specific mice that yielded the discovery were reed voles (Microtus fortis) collected from areas near the Hantan River, north of Seoul1 . This geographical connection would later inspire the name "Hantaan virus" for the newly identified pathogen3 .
Key Innovation
The critical innovation came when Lee shifted to using lung tissue from wild rodents as his primary research material and employed the indirect immunofluorescence antibody technique, a sophisticated method for detecting pathogens by observing reactions with antibodies3 .
Beyond Discovery: Vaccine Development and Global Impact
Lee's identification of Hantaan virus was only the beginning of his contributions. In 1980, he discovered a second related virus from Seoul rats, which he named "Seoul virus"3 . These discoveries led the international scientific community in 1986 to officially recognize a new genus of viruses—Hantavirus—named in honor of Lee's original discovery3 .
From Pathogen to Prevention
Never one to rest on his accomplishments, Lee immediately turned his attention to developing preventive measures:
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Vaccine development: Beginning in 1987, Lee selected optimal vaccine strains from patient blood and adapted methods similar to Japanese encephalitis vaccine production3
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Large-scale production: He developed techniques for mass virus production, followed by purification and inactivation processes to ensure safety3
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Diagnostic innovation: Collaborating with Japanese researcher Tetsuo Komiyama from Tokyo University, Lee developed a new serum diagnostic method in 19893
By 1990, Lee's vaccine received manufacturing approval from the Korean Ministry of Health and Welfare, marking Korea's first home-developed new drug3 . Marketed as "Hantavax" two years later, it represented the culmination of over a decade of dedicated work3 .
Vaccine Development Timeline
Key Reagents and Materials in Hantavirus Research
| Research Reagent | Function | Role in Discovery |
|---|---|---|
| Fluorescence microscope | Visualize antibody-pathogen reactions | Enabled visualization of virus as yellow fluorescent patterns |
| Tissue culture cells | Support virus replication | Provided medium for attempting to grow pathogen |
| Wild rodent lung tissue | Source of suspected pathogen | Critical material that yielded successful virus isolation |
| Immunofluorescence antibodies | Identify specific pathogens | Key detection method for visualizing previously unknown virus |
Building a Global Research Hub
The international recognition of Lee's work transformed his laboratory at Korea University's Virus Disease Research Center into a World Health Organization (WHO) Collaborating Center for Hemorrhagic Fever Research3 . This designation established Korea as the global epicenter for hantavirus research.
Global Standardization
Standardization of testing methods across international laboratories
Epidemiological Surveillance
Global reporting of outbreak patterns and disease tracking
Researcher Training
Training scientists from around the world in diagnostic techniques
This transformation from a local research group tackling a regional health problem to an internationally recognized authority exemplifies how scientific excellence can elevate both an individual researcher and an entire nation's standing in the global scientific community.
International Recognition
Lee received numerous international honors including the U.S. Army's Highest Civilian Service Medal, Thailand's Prince Mahidol Award, and Japan's Nikkei Asia Prize3 .
Conclusion: A Legacy of Persistence and Global Collaboration
Ho-Wang Lee's journey from a war-disrupted student to a world-renowned virologist encapsulates several profound truths about scientific progress. His story demonstrates that transformative discoveries often emerge from challenging conditions—in his case, a humble laboratory with makeshift heating. It highlights the importance of persistence through years of failure before the breakthrough moment. Most significantly, it shows how addressing local health challenges with rigorous science can yield global benefits.
- Local problems can inspire global solutions when approached with scientific rigor
- Persistence through failure is essential for scientific breakthroughs
- International collaboration accelerates discovery and implementation
- Scientific excellence can elevate a nation's standing in global research
Lee's work fundamentally changed our understanding of hemorrhagic fevers worldwide, leading to the identification of related hantaviruses across multiple continents. His development of both preventive vaccines and diagnostic tools created a comprehensive approach to controlling a once-mysterious killer disease.