A gut enzyme could turn your Type A blood into precious Type O

A new breakthrough could dramatically improve the way we deliver blood transfusions to patients in need.

Donating blood is a laudable act, but it’s also limited by sheer biology. Different people have one of four different blood types—A, B, AB, and O—and this hampers the extent to which doctors can safely deliver blood to patients in need, especially when you consider how wildly blood type populations vary around the world. If someone’s transfusion doesn’t match their own blood type, the immune system turns up to 11 in an effort to cleanse out what it sees as foreign invaders, which can lead to severe complications and even death.

But Type O blood can mosey on into anyone’s veins, so finding a way to transform all donated blood into Type O would ostensibly solve problems caused by mismatched blood transfusions. Some scientists at the University of British Columbia believe they have such a solution, all because they trusted their guts—literally. In findings presented at the 256th National Meeting & Exposition of the American Chemical Society, research suggests that enzymes produced by gut bacteria can turn the restrictive three blood types into Type O blood, the universal donor brand.

“Probably the only realistic way to do this conversion is through use of enzymes,” says Stephen Withers, a biochemist at the University of British Columbia who led the study. As opposed to techniques like the artificial synthesis of Type O blood or the use of stem cells to propagate universal donor blood on an endless scale, which are plagued with high economic costs and safety issues and cannot always act as an entirely functional replacement of red blood cells, enzymatic blood conversion allows us to create more universal blood using the same influx of donations we already attain. Donated blood also degrades in as little as three weeks, so finding a way to turn any sort of donation into Type O could alleviate shortages during times of crisis.

Scientists actually first demonstrated we could convert Type B to Type O back in 1982, using enzymes from green coffee beans. But this required an enormous amount of enzyme, and since then there’s been slow progress to show that such a process could be practical at scale.

The new findings, while preliminary, show a potential promise of efficiency.

Blood type is determined by special sugars sitting on the surface of red blood cells. These sugars, called antigens, come in two varieties: A and B. People who are Type A have blood that presents the A antigen, Type B presents the B antigen, Type AB presents both antigens, and Type O presents neither. Antigens are used by the immune system as sort of cellular form of identification—if something in the body is presenting a foreign antigen, the immune system will assume it’s a threat and attack it.

But if you have an enzyme that cleaves off the antigens, you can turn any AB, A, or B blood into Type O. And the best place to look for these enzymes isn’t coffee beans, or leeches and mosquitoes that have demonstrated an ability to degrade blood. According to experts, we should turn our gaze inward.

“The most promising leads have come from microorganisms, mostly bacteria, that are commensal to us, and live in our bodies,” says David Kwan, a biologist an assistant professor at Concordia University in Montreal who has previously worked with Withers (but was not involved in the latest study). “They’re the ones most exposed to our cells and the [sugars] attached to our cells.” The structures that constitute the A, B, and O antigens are similar to sugars found on proteins that line intestinal walls, so it would make sense for gut bacteria to evolve enzymes that could precisely and efficiently cleave the sugars for their own sustenance.

Withers and his team used genomic analyses to isolate individual DNA chunks and insert them into E. coli, testing out nearly 20,000 different gene fragments to see which ones could produce enzymes active against A and B antigens. The team eventually identified one enzyme that was 30 times more effective at snipping out A antigens from human blood than anything previously found. (Withers and his team are still in the process of patenting the enzyme and chose not to identify what it is or how it works, but he does say it’s from a previously unrecognized family.)

The enzyme also managed to work very efficiently at small quantities, in a variety of different environmental conditions, which meant blood cells being converted wouldn’t have to be exposed to additional solutions. They are easily produced and purified, “so they could be made locally” in areas with more limited resources, says Withers. After combining the enzyme with others previously found to cleave to B antigens efficiently, the team finally found the breakthrough product they needed to convert any blood type into universal donor blood Type O.

There’s no question we’re still incredibly far from seeing this process used to transform blood donation. “We need to ascertain that no adverse changes to the red blood cell take place,” says Withers. He and his team are currently running tests to verify that. Another obstacle to overcome is to prove that the team can strip all traces of the enzyme before transfusion, in order to safeguard the recipient’s own blood as well as other cells that present similar sugar antigens. Clinical trials are unthinkable before these two steps are checked off.

It’s also worth emphasizing that blood type is influenced by more than just A, B, and O antigens. There’s Rh (a protein responsible for the positive or negative part of blood type), plus a whopping 31 other blood typing systems less commonly used. Withers’ process solves the enormous O obstacle, but other techniques will be necessary to strip Rh out of blood to create O negative, and manage other variables in blood type.

A perfect universal donor blood is probably impossible to achieve, but the new findings do create quite a bit of excitement that things are moving in the right direction. They also highlight the gut microbiome’s continued role as a strange, wondrous goldmine of health science. If there are bacteria in our intestines able to turn our blood into a different kind of blood, just imagine what other treasures they’re keeping safe and secret.

“I think this is really exciting,” says Kwan. “I might be biased, but I’ve been around this research for several years now, and I think the approach they are using in their lab with these enzymes is improving more and more. It’s showing real promise.”