Guardians of the Immune Response
The Pioneers Honored by the European Histamine Research Society
Introduction: More Than Just an Allergy Molecule
Imagine a chemical so powerful that a tiny amount can trigger a body-wide allergic reaction, yet so essential that without it, we couldn't digest food, fight infections, or even maintain proper sleep-wake cycles.
This is histamine—one of the most fascinating and multifunctional molecules in our bodies. For over a century, scientists have been unraveling its mysteries, discovering that this simple compound plays astonishingly complex roles in our physiology.
At the forefront of this scientific exploration stands the European Histamine Research Society (EHRS), an organization dedicated to understanding histamine's full spectrum of effects. Within this community of researchers, the highest honor bestowed is honorary membership—an award reserved for those exceptional individuals whose contributions have fundamentally advanced our understanding of this crucial molecule 1 2 .
Histamine Facts
Discovered in 1910, histamine regulates over 20 different physiological functions
Allergic Response
Histamine is the primary mediator of allergic reactions, causing symptoms from mild itching to life-threatening anaphylaxis.
Neurotransmission
In the brain, histamine acts as a neurotransmitter, regulating sleep-wake cycles, appetite, and cognitive function.
Immune Defense
Histamine plays a crucial role in the immune system's response to pathogens and tissue injury.
The Honorary Members: Pioneers of Histamine Research
The European Histamine Research Society describes honorary membership as its "highest award," given only to "very special people who contributed significantly to the Society and histamine research." 1 These scientists represent the pinnacle of achievement in their field, having not only advanced theoretical knowledge but also developed practical treatments that have improved millions of lives.
The H2-Receptor Breakthrough: A Therapeutic Revolution
Among the most transformative contributions to medicine emerging from histamine research was the development of H2-receptor antagonists by Professor Charon Robin Ganellin and his colleagues. Prior to their work, peptic ulcers were typically treated with surgery or inadequate medications, often leading to prolonged suffering and complications.
The breakthrough came through brilliant application of physical organic chemistry, which enabled the design and sequencing of drugs from burimamide to metiamide and finally to cimetidine (Tagamet®) 1 . This drug revolutionized peptic ulcer treatment, providing the first effective medical therapy for this widespread condition.
Histamine receptor research has led to multiple therapeutic breakthroughs in medicine.
Anita Sydbom: Mast Cell Research
Sydbom's research at the Karolinska Institute, working with her mentor Professor Börje Uvnäs, focused on anaphylactic histamine release from mast cells 1 . Her work combined pharmacological innovation with methodological refinement, establishing fundamental principles of how and why mast cells release their histamine content.
Sydbom's commitment to histamine research extended beyond the laboratory. She has been a member of EHRS since 1979, participating in 34 meetings and holding numerous positions of responsibility within the society, including President from 2006-2012 1 .
Frederick Pearce: Mast Cell Heterogeneity
Frederick Lawrence Pearce's research on mast cell heterogeneity revealed that not all mast cells are identical—different populations in various tissues have distinct properties and responses 2 . This understanding has proven crucial for developing targeted therapies for allergic conditions.
Pearce's work took him to multiple international laboratories, including a research visit to Aachen in 1976 that sparked his lasting interest in mast cells, and sabbaticals at McMaster University that further developed his passion for understanding mast cell diversity 1 .
A Landmark Experiment: The Challenges of Measuring Histamine
To appreciate the contributions of EHRS honorary members, it's essential to understand a fundamental challenge in histamine research: accurately measuring this molecule in biological systems. A groundbreaking study published in 1980 exposed critical limitations in histamine quantification methods across laboratories—a finding that prompted major methodological improvements in the field 4 .
Methodology: A Cross-Laboratory Comparison
The study design was straightforward yet powerful: researchers prepared samples of plasma and buffered saline containing known concentrations of histamine. These samples were lyophilized (freeze-dried) in glass ampules and distributed to multiple laboratories for analysis 4 .
Each participating laboratory used their preferred method to measure the histamine content:
- Double-isotope dilution enzymatic assay - considered the most reliable method
- Single-isotope enzymatic method - a simpler variant
- Manual and automated fluorometry - earlier techniques based on fluorescence measurement
Histamine Measurement Method Performance
Results and Analysis: Surprising Variability
The findings revealed astonishing variability. When the same solutions were analyzed in the researchers' own laboratory over a six-month period using the double-isotope method, the values agreed with theoretical expectations within 12%, with a 26% coefficient of variation 4 . However, when multiple laboratories tested the identical samples, the results showed "marked variation"—especially for plasma samples, where the complex matrix presented additional challenges.
| Method | Number of Labs | Reported Accuracy | Limitations |
|---|---|---|---|
| Double-isotope dilution enzymatic assay | 12 | Marked variation among labs | Complex procedure; Requires specialized expertise |
| Single-isotope enzymatic method | 3 | Mixed results (one lab close to standard) | Less reliable than double-isotope method |
| Automated fluorometry | 5 | Marked variation among labs | Interference from other compounds |
| Manual fluorometry | 3 | Marked variation among labs | Labor-intensive; Susceptible to operator error |
The implications were clear: measurements of histamine by different laboratories vary greatly, meaning that "absolute values for histamine in biologic specimens in the literature must be regarded with caution." 4 This study drove the field toward standardized methodologies and quality control measures—advances that were essential for subsequent breakthroughs in understanding histamine's roles in health and disease.
The Scientist's Toolkit: Key Research Reagents and Solutions
Histamine research relies on specialized tools and reagents that enable scientists to detect, measure, and manipulate this molecule in experimental systems. These tools have evolved significantly over time, from basic chemical assays to sophisticated immunological tests.
| Reagent/Test | Function | Application Examples |
|---|---|---|
| ELISA Test Kits | Quantitative detection of histamine in various matrices | Food safety testing (fish, cheese, wine); Research samples 5 |
| Enzyme-linked Immunosorbent Assay | Highly sensitive detection using antibody-antigen binding | Measuring histamine in fresh fish, fish meal, cheese, sausage, milk, wine 5 |
| Histamine Receptor Antagonists | Block specific histamine receptor subtypes | H1 antagonists for allergies; H2 antagonists for gastric ulcers 1 2 |
| Histidine Decarboxylase Inhibitors | Block histamine synthesis from histidine | Research on histamine production pathways 2 |
| Leukotriene Synthesis Inhibitors | Block production of cysteinyl leukotrienes | Experimental asthma and food allergy research 3 8 |
Modern ELISA Technology
Modern enzyme-linked immunosorbent assays (ELISA) represent particularly important tools, allowing rapid and sensitive quantification of histamine in diverse samples. Tests like the AgraQuant® Histamine kits provide accurate results for concentrations ranging from approximately 0.1 to 6.0 ppm, crucial for both food safety monitoring and research applications 5 .
These commercial kits typically include histamine-coated plates, specific antibodies, substrates, and stop solutions in ready-to-use formats that minimize handling errors.
Receptor-Specific Antagonists
Similarly critical are the various receptor-specific antagonists that have been developed through medicinal chemistry. The creation of selective H2-receptor antagonists by researchers like Ganellin required not only brilliant chemistry but also sophisticated biological testing systems to verify their specificity and efficacy 1 2 .
These tools continue to evolve, with the most recent additions including H4-receptor antagonists that show promise for modulating immune responses in inflammatory conditions 2 .
Histamine Research Tools Evolution Timeline
Conclusion: The Future of Histamine Research
The journey through the world of histamine research reveals a dynamic field where fundamental discoveries have consistently translated into medical breakthroughs. From the early recognition of histamine's dual receptors to the latest findings about leukotriene-driven food allergies, each advance has built upon the work of dedicated scientists—many honored by the EHRS for their contributions.
Recent discoveries continue to highlight the complexity of histamine biology. A 2025 study revealed that specialized immune cells in the intestine respond to food allergens by producing leukotrienes rather than histamine—overturning long-standing assumptions and suggesting new therapeutic approaches for food-triggered anaphylaxis 3 8 . This finding exemplifies how histamine research continues to evolve, with each answered question revealing new mysteries to explore.
The honorary members of the European Histamine Research Society represent the best of this scientific tradition—collaborators who have shared their findings at annual meetings, mentors who have trained the next generation of researchers, and visionaries whose insights have transformed medical practice.
Their legacy lives on not only in the medications used worldwide but in the ongoing work of scientists who continue to unravel the complexities of this deceptively simple molecule.
As we look to the future, histamine research promises further innovations: more targeted receptor modulators, personalized approaches for histamine intolerance, and perhaps entirely new therapeutic applications for histamine pathway drugs. The foundation laid by honorary members ensures that the EHRS will remain at the forefront of these exciting developments, fostering the collaborative spirit that has characterized the field for decades.
Future Research Directions
- Personalized approaches for histamine intolerance
- H4-receptor modulators for inflammatory conditions
- Histamine's role in neuroimmunology
- Novel antihistamines with fewer side effects
- Histamine biomarkers for disease diagnosis
EHRS Legacy
Honorary members have shaped our understanding of histamine for over five decades, with impacts reaching millions of patients worldwide.