ST. LOUIS — When red blood cells are poured into the test tubes here in Dr. Allan Doctor’s lab, tiny tools measure the reaction of the rabbit aortas strung up inside, computing if and how strongly the aortas constrict. Doctor and his team are trying to make sure that when they dump in the artificial blood they’re developing, the aortas react the same way.

The experiments being conducted on a recent day were not only just a few of the many the team will need to run before testing their blood substitute in people, but were also early steps to show that their design, with any luck, can steer them beyond the decades of failure in the field.

There has been “about 50, 60 years of research in trying to make a blood substitute that has not worked,” said Doctor, a pediatric critical care physician and researcher at Washington University in St. Louis.

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The need for such a product is clear. Blood loss from traumatic injuries is responsible for thousands of deaths annually, and even when people survive, oxygen depletion can leave tissue permanently injured. Fresh blood can only be stored for 42 days, and only lasts for a few hours unrefrigerated. A substitute could be vital in settings like battlefields or rural areas without easy access to blood, used as a stopgap measure to keep the injured alive until they get to a hospital.

But the quest to develop substitute blood has bedeviled researchers in academia, the military, and the biopharma industry, with several companies — including Baxter, Northfield Laboratories, and Biopure — abandoning their attempts.

The artificial blood researchers have been trying to cook up is not a true substitute, in that it wouldn’t perform all of blood’s functions, but rather provide a means to deliver oxygen throughout the body.

One key problem: Hemoglobin, the protein in red blood cells that carries oxygen from the lungs to needy tissues, can damage tissue and cause blood vessels to constrict. That’s one reason why hemoglobin is contained in cells — to isolate it and its toxic iron.

Any successful blood substitute will need to transport and deliver oxygen, while staving off the threat hemoglobin poses.

In past attempts, scientists have tried to tweak hemoglobin to make it safer, but so far, no blood substitute has been approved for use in the United States or Europe. (One substitute, Hemopure from HbO2 Therapeutics, is used in South Africa, and a clinical trial of a stem cell-based substitute is expected to begin this fall in the United Kingdom.)

But instead of trying to engineer hemoglobin, Doctor and his colleagues have encased it in a synthetic polymer designed by one of Doctor’s collaborators, Dipanjan Pan of the University of Illinois, Urbana-Champaign.

Dr. Allan Doctor
Doctor, in his office at Washington University in St. Louis, is trying to develop an artificial blood that could be used in places where blood from donors is not available. Dom Smith/STAT

They hope the case will ensure that their substitute blood, called ErythroMer, won’t cause a tightening in the blood vessels, which increases the risk of heart attack and stroke.

At the same time, ErythroMer detects where oxygen should be delivered based on the pH level of the blood, moving oxygen from the lungs to where it’s most needed like a junkyard magnet picking up a car in one spot and dropping it elsewhere.

If it’s successful, ErythroMer could be freeze-dried into a powder and stored safely for years, so that when it’s needed, it can be mixed with sterile water and administered. It’s designed to be “immune silent” so that the immune system doesn’t attack it and it could be given to people of any blood type.

Scientists not working on ErythroMer said it appears to be an improvement in some respects over earlier candidates, but note that it is not the first to attempt enclosing hemoglobin in various materials. So far, no one has cracked the code of creating an artificial blood, and it’s not clear this group will either.

“It’s not as easy as it sounds,” said Dr. Ernest Moore, the vice chair of trauma and critical care research at the University of Colorado, Denver, who has helped run clinical trials of other substitutes.

One concern for Mark Scott, a senior scientist at Canadian Blood Services, is the tininess of ErythroMer. Each particle is about one-fiftieth the size of a normal red blood cell, and Scott said that increased the risk that it could leak from the bloodstream into surrounding tissue. And when someone loses a lot of blood and goes into shock, their blood vessels only become more “leaky,” Scott said.

“These are all things that you really have to be concerned about,” said Scott, who also works at the Center for Blood Research at the University of British Columbia. “Is the size going to lead to a lot of vascular leakage? Is the hemoglobin that’s inside the shell stabilized so it won’t cause acute or chronic toxicity?”

One advantage of the small size of the substitute blood, both Scott and Doctor said, is that it could be used for people with sickle cell disease. During sickle cell crises, the misshapen red blood cells gum up blood vessels, and it’s possible that ErythroMer could get around the logjams and deliver oxygen past those points. Doctor also raised the idea that it could be used to oxygenate organs during transplant operations.

In addition to overcoming the biological hurdles, the ErythroMer team will eventually have to convince regulators that its product is safe enough to test in people (depending on its success in animals, that is). Several scientists said the Food and Drug Administration seems hesitant to green-light new trials of blood substitutes — and some said rightfully so — because of safety concerns from past products. Plus, clinical trials of trauma-related treatments often run into ethical quandaries about informed consent.

In an email, an FDA spokeswoman said that studies on these types of products have found they are not safe or effective, but that the agency recognizes they “potentially could be lifesaving in situations where blood transfusion is necessary, but blood is not available … or can’t be used.” She said future clinical studies “remain possible.”

Still, human studies are a long ways away, the researchers acknowledge. So far, Doctor and his team, whose work has been supported by the Department of Defense, have presented results from rodent studies at a scientific conference. And they have their own questions about how ErythroMer will perform as they test it in larger animals, first in rabbits: Does it damage other cells in the bloodstream? Does it interfere with the clotting process?

The team has formed a company called KaloCyte (Greek for “good cell”) to make the substitute for further studies. Doctor likened it to moving the production from a craft brewery scale — so far, Doctor said, it’s been “lovingly made by graduate students, batch by batch” — to the scale and standards of another St. Louis blend, Budweiser.

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  • id like to run a idea by you medical professionals. i read that certain protiens absorb iron. iron and b12 make new blood. b12 cannot be stored in the body.(unless u figure out a storage method) but the point off this is the fact that if we genetically modifie the protien that stores iron we can create large deposits of iron that just needs b12 to make new blood. if we get soldiers to be injected with these new protiens that stores more iron or we gmo our protiens then we have a stockpile of new blood just needs b12 like a vitamen pill extended release b12 you take before going into combat. or at the start of the day everyday for the military who spend all day on missions and patrols. so the idea is this large reserves of iron that become active when the body needs more blood converting that b12 pill and the iron from stockpile into vital new blood. but can we enhance the rate at which our body makes new blood. like makes blood faster then you normally do to keep up with bleed out levels.
    also try liquid oxygen injection. liquid oxygen has time release coating like a pill on the surface of oxygen molecules. im assuming nano spackleing of polymer or compound that forms a barrier for oxygen to not be absorbed right away but lets it linger in the muscles until coating weakens from water in our muscles or something. somehow it needs to be only used specifically when your say working out or when bleeding out your body should still maaintain about a five or ten minute window where it still has oxygen even though therees not enough blood to pump oxygen. but with liquid oxygen its already found itsway to where it will be needed. lets say your running and you start burning more oxgen then your intaking. with a injection of time released or as needed( either method. time release will just supply oxygen to sites during release where as the other method probly involving nano bot delivery would deploy oxygen only if your not getting enough to sustain the physical motion. hence powering threw combat or your daily workout with less effort or bodily stress.
    https://phys.org/news/2014-09-material-oxygen-air.html
    this article above states it crystal absorbs 160 times it volume in oxygen and can be 5 times more absorbtion of oxygen then hemoglobin. says in the article. but what im getting at is that the metal they made the crystal from is used to supply oxygen in idk something or soemthing but if we use the same processes on iron makeing it a crystal that absorbs tons more oxygen requireing less work from cardiovascular system to provide highier levels of oxygen. so blood carries more oxygen and we carry more crystallene iron in protiens making more blood or carry ing more oxygen double side effect.
    thank you for your time ladies and gentlemen. my question is any of that possible?

  • There is many researches going on to make an artificial blood. Thanks for sharing this because I don’t know about the substitute blood, called ErythroMer

  • I,m glad to read such a detailed description of your work. I,m sure you will make a great contribution to medical science. I liked your picture, too.

  • The authors’ presented results abstract speaks of future testing in large animal models of hemorrhagic shock. This is incorrect. Hemorrhage, yes, but proceeding to the shock state presents a myriad of unforeseen complications whereby their product will have no influence on survival.

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