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During his time in the trenches of World War I, Dr. Lawrence Bruce Robertson, a Canadian surgeon who pioneered methods for blood transfusion, watched three men die of ruptured blood cells, multi-organ damage, and eventual organ failure—symptoms of a condition called paroxysmal nocturnal hemoglobinuria (PNH).
It was a time before scientists had identified the four major blood types in humans: A, B, AB, and O. The men Robertson had seen die had passed away due to a violent reaction to the blood they were given, which was incompatible with their own blood type.
We now know that type O blood, which is a recessive trait, is the “universal donor.” If a blood transfusion is necessary, those with type O blood must receive type O blood; on the contrary, type O can be safely administered to all blood types. Now, in a new study, researchers report that they used newly discovered gut bacteria enzymes to convert type A blood to type O at a rate faster than ever before. Omnipresent blood shortages could soon be no more.
“What we’d be able to do, if this passes all the safety regulations, is to expand that reserve of available blood,” said Dr. Steve Withers, a professor of biochemistry at the University of British Columbia and the senior author of the new study, which he presented at the American Chemical Society National Meeting in Boston on Tuesday.
First developed by the late Jack Goldstein of the New York Blood Center, the idea of converting type A, B, or AB blood to O has been around for a while, explains Chief Scientist of the Canadian Blood Services Dr. Dana Devine, who was not involved in the new study. The challenge, she adds, has been how to commercialize it.
“He’s got an enzyme that’s way more active and you can use less of it,” Devine said of Withers. “He may have the breakthrough to get over the cost hurdle,” she adds, referring to older methods with price tags that prevented them from becoming marketable.
Some enzymes from bacteria that can be cultured in a lab––of which there are about 10,000, Withers points out––can be used to cut off the antigens, or small sugar or protein molecules, from type A or type B blood, effectively turning it to type O. (If an enzyme that feeds on type A antigens is paired with one that feeds on type B antigens, type AB blood can be converted to O.) In a 2015 study, published in the Journal of the American Chemical Society, Withers and his team found an enzyme that was capable of very slowly munching on type A antigens. Manipulating evolution, the researchers tweaked the enzyme, improving its ability to remove the sugar molecules by 170-fold.
But Withers, an enzymologist with 35 years of experience, suspected that nature––specifically the human gut––had an even greater solution.
“The human gut contains the A and B antigens,” he said. “It would make sense that bacteria would evolve to clip them off.”
To see if this was the case, Withers and his team partnered with Dr. Jayachandran Kizhakkedathu, a pathologist at the Centre of Blood Research, and Withers’ University of British Columbia colleague Dr. Steven Hallam, a microbiologist and immunologist whose lab specializes in metagenomics, the study of genetic materials recovered directly from nature as opposed to those produced in a lab.
Microbes are shaping the Earth’s environment and its other organisms, Hallam said, and there are far more of them than neurons and stars in the universe. “People are becoming more interested in tapping into that massive diversity of life, which creates an opportunity to discover enzymes and catalysts to solve worldwide problems,” he explains.
With the support of Hallam’s lab, Withers’ team sifted through human feces to extract their bacterial DNA, then chopped the DNA into very large chunks, which on average contain 20 to 30 genes. They inserted those genes into an infamous host that’s easily cultivated in the lab—E. coli. “And then,” Withers said with a small chuckle, “we basically crossed our fingers and hoped these genes could be encoded.”
It worked. The gut enzymes were even more efficient than those the team developed three years ago.
The potential significance for society is profound, Devine said. “It would allow blood systems to do a much better job of managing their industry. They’re always struggling to get enough O blood––O donors––in the door,” she said of blood drives.
In the event of an emergency transfusion, doctors automatically administer type O blood to a patient; taking time to conduct a screening could be life-threatening. Appeals for type O donors are therefore high, particularly in the summer months. “People start going on vacation and the general blood supply starts to drop,” Devine says. “Sometimes, you get increases in demand with people traveling. More traffic causes more accidents. It all lines up in the wrong way.”
The new research is still in its preliminary stages. Through collaborating with the CDC and Canadian Blood Services, the team will have to perform further in vitro testing to determine whether blood converted from type A to O using gut microbe enzymes––which researchers would remove from the blood before administering it–– could cause abnormal reactions in patients. But if it passes safety studies, including a Phase 3 clinical trial in, the societal significance would be tremendous.
“As scientists, we don’t often get the opportunity to make discoveries that make such a large human impact in the world. It’s rare. It’s a glorious thing. The idea of being able to take any kind of blood and transform it into any form would have a major health impact. It would literally save lives. And turning to the human body to find that solution is very elegant,” Hallam says. “It’s just beginning.”