There is a shortage of Type O-negative blood in medical facilities around the United States.
Researchers are testing the use of gut microbe enzymes to convert Type A and B blood to Type O blood.
This enzymatic conversation also has the potential to apply to donor organs.
In the United States, there’s a blood transfusion every 2 seconds. According to the American Red Cross, about 12% of those blood transfusions occur in emergency rooms. All emergency transfusions need to be done with Type O blood. Type O blood is often broadly referred to as the universal donor blood, but only Type O-negative blood is safe for any recipient. However, most people are Rh-positive, leading to a high demand for both O-positive and O-negative blood.
“A single car accident victim might need up to 100 units of donated blood, but blood still needs to be available for all the other patients who desperately need it. Otherwise, transfusions can be reduced or delayed,” says emergency medicine physician Frank McGeorge, MD. “Type O negative is particularly essential because it can be given to anyone regardless of their blood type. In an emergency, Type O blood is incredibly important. It’s the blood type we need an abundance of.”
O-negative blood is the rarest blood type. It’s estimated that between 7% and 8% of the United States population has Type O-negative blood. Another 39% are estimated to have Type O-positive blood. Exact percentages can vary by gender, ethnicity, and region, but Type O-negative is the rarest in all groups and locations. This adds to the demand and shortage of this universal donor type.
Some researchers believe that lab-created universal donor blood could address the demand. At the Centre for Blood Research at the University of British Columbia, researchers are conducting tests using enzymes to convert Type A or B blood to Type O blood. Currently, testing is in pre-clinical stages working with donated human blood.
All red blood cells have about 1 million sugar molecules coating their surfaces. Type A and B red blood cells have additional sugar molecules not found on Type O red blood cells. An enzyme capable of selectively removing the sugar molecules only found on Type A and B red blood cells could potentially turn those cells into Type O red blood cells.
This possibility has been discussed for over 4o years. In 1982, a group of researchers at the New York Blood Center, led by Jack Goldstein, PhD, were able to strip the Type B group sugars from red blood cells using an enzyme derived from coffee beans. Small amounts of the converted blood were transfused successfully to three volunteers.
Successful early-phase trials of this coffee bean enzyme were conducted in the 1990s. However, some of the converted blood had crossmatch reactions with samples of Type A and O serum, and anti-B titers increased in five trial volunteers who had Type A or O blood. Additionally, the coffee bean enzyme technique itself had drawbacks. Creating the enzymes was inefficient, costly, and had to be performed at a high pH that could damage the blood cells. 
Researchers began to look toward other methods of converting A and B red blood cells. Throughout the 2000s and 2010s, other enzymatic conversion methods were developed, but crossmatch reactions continued to occur during trials. In 2019, Stephen Withers, PhD, and his team at the Centre for Blood Research at the University of British Columbia identified gut microbe enzymes that were able to quickly and efficiently convert Type A blood. These enzymes are the subject of testing today.
In addition to testing on human donor blood, researchers are looking into the possibility of using these enzymes on donor organs. If successful, this could create universal donor organs, increasing the chances of matches for individuals on transplant waiting lists. Transplanted organs produce new sugars, but researchers believe it’s possible that could be addressed by existing immunomodulation regimens.
Another avenue for creating universal blood
Researchers at the University of Bristol use stem cells to grow red blood cells. These lab-grown blood cells would be universal and safe for all recipients. Researchers believe they could be a good option for people who receive frequent blood transfusions, reducing both the risk to these individuals and the larger demand for donor blood. However, this research is still in its early stages. Currently, the volume of blood that can be produced in the lab is limited. Large amounts of lab-grown blood cells cannot be produced, and the process is costly.
What’s next for universal blood research
These new strides toward addressing the demand for universal blood are promising, but more research and testing are needed. It’s still unknown if these converted blood cells can safely transfer to humans. Tests to ensure that conversion doesn’t make cells too fragile for use, as well as tests to make sure reactions don’t occur, will be vital as research continues.
Additionally, some recent data has raised questions about the safety of all transfusions of Type O blood to people with other blood types. It’s been suggested that these transfusions might trigger inflammation and could lead to worse patient outcomes. However, most of the current data prompting these questions about Type O blood donations is observational. Trials are needed before any conclusions are drawn. The results of these trials might have an impact on how the research and testing for enzyme conversation and universal donor blood proceeds.