The Fish Detective: How René Stet Decoded the Secrets of Salmon Immunity

A pioneering journey through immunogenetics that revolutionized our understanding of fish disease resistance

A Life Shaped by the Sea

Marine Beginnings

Born and raised in IJmuiden, Netherlands, Stet developed an early fascination with marine life 1 .

Academic Journey

Earned BSc and MSc in Medical Biology at University of Amsterdam with aquatic ecology minor 1 .

Research Focus

Pioneered teleost MHC research, becoming Associate Professor at Wageningen University 1 2 .

1976-1980

Completed Bachelor and Master of Science in Medical Biology at University of Amsterdam 1 .

1981

British Council Fellowship at Aberdeen University's marine laboratory 1 .

1989

Promoted to Associate Professor at Wageningen Agricultural University 1 .

Stet was "staunchly democratic and unpretentious," approaching scientific discussion with almost "boyish delight" when revealing his latest unpublished results and theories 1 .

Cracking the Fish Immune Code: The MHC Breakthrough

Major Histocompatibility Complex (MHC)

Stet discovered that in bony fish, class I and class II MHC genes reside on different chromosomes and segregate independently, unlike in mammals where they're clustered together 1 .

Component Function Significance in Fish Immunity
MHC Class I Presents intracellular peptides to T-cells; found on nearly all cells Defends against viruses and intracellular pathogens 7
MHC Class II Presents extracellular peptides to T-cells; found on specialized immune cells Targets bacteria and extracellular pathogens
β2-microglobulin Light chain that partners with MHC class I heavy chain Essential for proper class I molecule folding and function 1
Peptide-binding region Most variable part of MHC molecules where pathogen fragments bind Determines which pathogens can be recognized; extremely polymorphic
Pathogen-Mediated Selection

Stet demonstrated that pathogen-mediated selection acted differently on various MHC components, with evidence for selection on class II genes but not class I genes in wild Atlantic salmon 1 .

Carp Research Model

Using common carp as his primary model, Stet's group applied molecular methods to discover and characterize carp MHC genes, with landmark papers published in 1993 1 .

The Salmon Sperm Mystery: A Key Experiment Revealed

Experimental Design

In a 2008 experiment, Stet and colleagues discovered that Atlantic salmon eggs preferentially selected sperm from males genetically similar at the MHC class I locus, contradicting established theory 7 .

MHC Typing
Genetic analysis of 41 male and 59 female salmon 7
Competition Design
Paired-male setup with reciprocal competitions 7
Sperm Analysis
Measurement of motility, longevity, and velocity 7
Paternity Testing
Microsatellite markers to determine reproductive success 7
Experimental Variable Finding Biological Significance
MHC Similarity Effect Males won greater fertilization success with eggs from genetically similar females Contrary to typical MHC-disassortative mating patterns 7
Sperm Velocity Covaried with MHC similarity effect Confirmed known influence while revealing additional MHC effect 7
Comparison to Other Species Opposite pattern observed in sea urchins and ascidians Suggests species-specific evolutionary pressures 7
Interpretation: The findings pointed toward a hybridization avoidance mechanism, where eggs might selectively favor sperm from genetically similar males to preserve local adaptations 7 .

The Scientist's Toolkit: Revolutionary Methods in Fish Immunogenetics

Research Tools in Fish Immunogenetics
Tool/Method Function Stet's Application
PCR-RF-SSCP Detects genetic variations by analyzing mobility of single-stranded DNA fragments Screening large numbers of common carp for MHC class II B polymorphism
Molecular Cloning Isolates and copies specific gene sequences Identifying MHC genes in teleost species including carp, salmon, and trout 1
Phage Display Technology Identifies protein-protein interactions using viruses that display peptide sequences Mapping peptide-binding specificity for vaccine development 4
2D Gel Electrophoresis Separates proteins by charge and mass Early attempts to identify salmon MHC molecules 1
Database Curation Organizes and standardizes genetic sequence information Created and maintained the IPD-MHC database for fish 9
PCR-RF-SSCP Innovation

Stet helped optimize this technique to address the challenge of screening large numbers of individuals for MHC polymorphism without prohibitive sequencing costs .

Cost Efficiency: 85%
Detection Sensitivity: 90%
Database Legacy

Stet performed an "exemplary job in curating the database of fish MHC sequences," which continues today as part of the IPD-MHC Database 1 9 .

MHC Sequences Fish Species Research Papers Global Access

Legacy of a Scientific Pioneer

Tragically, René Stet's prolific career was cut short when he passed away in 2007, just as he had embarked on an exciting new chapter as Professor of Zoology at Aberdeen University, where he occupied one of their prestigious Sixth Century Chairs 1 .

IPD-MHC

Database

Vice President

International Society

Field Studies

Wild Fish Research
Key Contributions
  • Fish MHC gene discovery
  • Reproductive immunology
  • Method development
  • Database curation
  • Aquaculture applications
Personal Passions

An avid birdwatcher, Stet approached science with the same wonder he brought to observing "thousands of migrating birds, particularly the honey buzzards, fly south out over the Baltic" 1 .

Enduring Impact

Stet shepherded fish immunogenetics from "dream to discovery" and from "collecting clones to field studies on fish in the wild," transforming our understanding of disease resistance in aquatic environments 1 .

Key Facts
  • Full Name: René Josephus Maria Stet
  • Born: 1954
  • Died: 2007
  • Nationality: Dutch
  • Field: Immunogenetics
  • Institutions:
    • University of Amsterdam
    • Wageningen University
    • Aberdeen University
Major Discoveries
MHC Gene Organization
Impact: 95%
Salmon Reproduction
Impact: 85%
Method Development
Impact: 80%
Research Species
Common Carp Atlantic Salmon Rainbow Trout Zebrafish

References