After half a century of scientific investigation, researchers have finally unraveled one of hematology’s most persistent mysteries with the MAL blood group discovery. This breakthrough, identified through groundbreaking collaborative research between British and Israeli scientists, represents a significant advancement in transfusion medicine. The MAL blood group system provides critical answers for patients with rare blood types, solving a puzzle that began with an anomalous 1972 case.
- The MAL blood group system has been officially recognized, solving a 50-year mystery that began with a pregnant woman’s unusual blood test in 1972
- Researchers from NHS Blood and Transplant, the International Blood Group Reference Laboratory, and universities in the UK and Israel collaborated on the breakthrough
- The discovery enables better identification and treatment of patients with this rare blood type
- The MAL protein plays crucial roles in cell membrane stability and transport functions
- This advance joins other recent blood group discoveries, including the Er system identified in 2022
The story begins in 1972 when routine blood testing for a pregnant woman revealed something extraordinary: her red blood cells lacked a surface molecule that was considered universal at the time. This missing component, later designated as the AnWj antigen, presented a medical anomaly that would take five decades to fully understand.
“This discovery represents a huge achievement and the culmination of a long-term effort to finally establish this new blood group system and be able to offer the best care to patients with rare blood types,” said Dr. Louis Tilley, a hematologist with the UK National Health Service who was involved in the research. The team’s findings were published in early 2024 in the prestigious journal Blood Advances.
While most people are familiar with the ABO blood group system and the Rh factor (the “positive” or “negative” designation), human blood cell surfaces contain numerous proteins and carbohydrates that form over 40 different blood group systems.
Dr. Nicole Thornton, Head of Red Cell Reference at the International Blood Group Reference Laboratory, explains: “Blood group antigens function as identification markers that help our immune system distinguish between ‘self’ and ‘non-self.’ When blood transfusions aren’t properly matched for these markers, potentially fatal immune reactions can occur.”
The discovery of new blood group systems is relatively rare in modern medicine. Most major blood groups were identified in the early to mid-20th century. The Er blood system, discovered in 2022, was the most recent addition before MAL, affecting only a small subset of the global population.
The investigation into the MAL blood group system presented unique challenges. Researchers had previously established that more than 99.9% of people possess the AnWj antigen, making individuals who lack it exceptionally rare.
“This was particularly arduous work because these genetic cases are so uncommon,” noted Dr. Tilley. “Identifying the molecular basis of this blood group required sophisticated genetic analysis and protein characterization techniques that weren’t available when the anomaly was first discovered.”
Through extensive investigation, researchers determined that the AnWj antigen resides on a myelin and lymphocyte protein, leading to the designation of the new MAL blood group system. People who inherit mutated versions of both copies of their MAL genes have the extremely rare AnWj-negative blood type, like the pregnant patient from 1972.
To confirm their findings, the research team conducted a critical experiment. They inserted normal MAL genes into AnWj-negative blood cells, which successfully delivered the AnWj antigen to those cells. This definitive result validated their discovery of the genetic basis for this blood group.
Dr. Tim Satchwell from the University of the West of England, who participated in the research, explained some of the technical challenges: “MAL is a very small protein with unusual properties that made it difficult to identify. Our team had to pursue multiple investigative approaches simultaneously to characterize this blood group system properly.”
The discovery has immediate practical applications for transfusion medicine. Researchers identified three patients with this rare blood type who didn’t have the expected genetic mutation, suggesting that certain blood disorders can cause suppression of the antigen.
The team also made another intriguing discovery: the AnWj antigen is absent in newborns but appears shortly after birth. This developmental pattern provides valuable insights into how blood group antigens emerge during human development.
Surprisingly, patients with the AnWj-negative blood type did not show any other cellular abnormalities or associated diseases despite the mutation affecting a protein involved in fundamental cellular processes.
“Now that we’ve identified the genetic markers behind the MAL mutation, we can determine whether a negative MAL blood type is inherited or due to suppression related to another underlying medical condition,” said Professor Ashley Toye, Director of the NIHR Blood and Transplant Research Unit at the University of Bristol. “This distinction is crucial for proper patient management.”
The identification of the MAL blood group system joins a growing list of advances in transfusion medicine over the past decade. These discoveries are transforming how medical professionals approach blood compatibility testing and expanding options for patients with rare blood types.
Dr. Emanuele Di Angelantonio, Associate Medical Director at NHS Blood and Transplant, commented: “Every new blood group system we identify enhances our ability to provide compatible blood for all patients. Rare blood attributes can have devastating consequences if not properly matched during transfusion, making discoveries like the MAL system vital for comprehensive patient care.”
The research also demonstrates the value of long-term scientific persistence. The 50-year journey from initial observation to molecular characterization underscores how modern genomic technologies can finally solve longstanding medical mysteries.
The identification of the MAL blood group opens several promising research avenues:
- Prevalence studies: Determining the global distribution and frequency of AnWj-negative individuals across different ethnic populations
- Functional analysis: Further investigating the biological role of the MAL protein in membrane stability and cellular transport
- Clinical correlations: Exploring whether subtle variations in the MAL gene might contribute to other health conditions
- Diagnostic advances: Developing more accessible testing methods to identify patients with this rare blood type
- Transfusion protocols: Establishing specific guidelines for managing transfusions in AnWj-negative patients
The discovery highlights the importance of international scientific collaboration. Researchers from the UK’s NHS Blood and Transplant in Bristol, the International Blood Group Reference Laboratory, the University of Bristol, and partners in Israel pooled their expertise and resources to solve this longstanding mystery.
“This achievement demonstrates how persistence and collaboration across institutions and borders can unlock significant scientific advances,” said Dr. Nicole Thornton. “Many researchers have contributed to this work over decades, building gradually toward this conclusive finding.”
The identification of the MAL blood group system is unlikely to be the final chapter in blood group research. As genetic sequencing and protein analysis technologies continue to advance, scientists anticipate that additional rare blood group systems may be discovered.
“There are still several uncharacterized blood group antigens in our databases,” explained Professor Toye. “Each of these represents a potential new system waiting to be defined. The scientific methods we developed for identifying MAL will accelerate these future discoveries.”
The research team is now focused on developing practical applications of their discovery, including creating specialized testing reagents and establishing international registries of donors with rare blood types.
The discovery of the MAL blood group system represents more than just an academic achievement. For patients with rare blood types, proper identification can be literally lifesaving.
“These rare blood attributes can have devastating impacts on patients if transfusions aren’t properly matched,” emphasized Dr. Tilley. “Every advancement in our understanding of blood groups translates directly to better patient care and potentially saved lives.”
The 50-year journey to discover the MAL blood group system exemplifies how medical mysteries can eventually yield to persistent scientific inquiry. For the medical community, it provides vital tools for managing patients with rare blood types. And for the original patient from 1972, whose unusual blood test launched this five-decade investigation, it finally provides answers to a lifelong medical mystery.
As researchers continue to explore the complexities of human blood, discoveries like the MAL system remind us that even in areas of medicine that seem well-established, important revelations still await, potentially transforming patient care for generations to come.
Sources: This article is based on published research in Blood Advances (2024), statements from NHS Blood and Transplant, and interviews with the research team. All quotes and information have been updated to reflect the current state of knowledge as of April 2025.