In early December 2016, Dr Allan Doctor's research made the headlines; Medscape reported "For Trauma Use - Dried Blood Powder, Just Add Water"; CBS News reported "Another step closer to artificial blood".

Back in Doctor's lab, red blood cells are poured into test tubes as other tiny tools measure the reaction of rabbit aortas that are strung up inside, recording if and how strongly they constrict. Doctor, a paediatric critical care physician and researcher at Washington University in St. Louis, and his team are ensuring that the aortas react the same way when the artificial blood they are developing passes through.

These are just early steps to show that their design could possibly overcome the decades of challenges and 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.

The quest for a blood substitution

However the hunt for blood substitutions began during the times of ancient Incas in the 1400s according to medical folklore, but no real progress was made until 1616, when William Harvey described how blood circulated throughout the body.

The following years saw medical practitioners trying numerous substances such as beer, urine, milk, plant resins and sheep blood as a substitute for human blood. It was not until 1667 when the first successful human blood transfusions were done, but they were halted after patients who received subsequent transfusions died.

Red blood cell membrane protein found in normal red cells is labelled green in the cells that have been grown in the laboratory. Photo credit: Dr Tim Satchwell / University of Bristol
Red blood cell membrane protein found in normal red cells is labelled green in the cells that have been grown in the laboratory. Photo credit: Dr Tim Satchwell / University of Bristol


Three centuries later, Karl Landsteiner won the 1930 Nobel Prize in physiology or medicine for categorising blood into the four groups. But blood substitution and transfusion research was paused until World War II when soldiers had to be saved from haemorrhagic shock - leading to the establishment of blood banks in 1947.

Research was then propelled when blood banks were bled dry during the Vietnam conflict, and was further fuelled in 1986 when it was found that HIV and hepatitis could be transmitted through blood transfusions.

The challenges of developing artificial blood

Today, the need for artificial blood results from blood loss in traumatic injuries that is responsible for millions of deaths annually across the world. For those that survive, oxygen depletion could result in leaving tissue permanently injured.

Fresh blood could only be stored for 42 days and only lasts for a few hours if unrefrigerated. In settings such as battlefields or rural areas that do not have easy access to blood, artificial or substitute blood could aid as a stopgap measure to keep patients alive until they arrive at a hospital.

However, the quest to develop artificial blood by researchers in academia, the military and the biopharma industry has been abandoned due to multiple challenges. The design for artificial blood depends on it being safe and compatible, its ability to transport oxygen and the possibility of being shelf-stable. So far, no researcher has been able to meet all three criteria together.

The artificial blood that researchers have developed so far is not a true substitute as it would not be able to perform all of blood's functions such as combat diseases and clot - it would only deliver oxygen.

A novel approach to address previous challenges

Two substances have been extensively studied as blood substitutes - haemoglobin and PFC. For PFC, it is inexpensive and non-biological, however it is not soluble and delivers less oxygen as compared to haemoglobin.

Haemoglobin on the other hand, in its raw form, is toxic and unstable. Many attempts have been made on modifying haemoglobin such as cross-linking molecules or using recombinant-DNA technology to produce modified proteins, but no blood substitute has been approved in the United States or Europe.

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. Photo credit: DOM SMITH/STAT
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. Photo credit: DOM SMITH/STAT


Now, Doctor and his colleagues have tried a different approach. They have encased haemoglobin in a synthetic polymer designed by Dipanjan Pan of the University of Illnois, Urbana-Champaign, one of Doctor's collaborators.

The synthetic case is hoped to ensure that their substitute blood, called ErythroMer, will not cause a tightening in the blood vessels, which increases the risk of heart attack and stroke. At the same time, ErythroMer will detect where oxygen should be delivered based on the pH level of the blood.

If successful, ErythroMer could be freeze-dried into a powder and stored safely for years and when it is needed, be mixed with sterile water and administered. It is also designed to be "immune silent" to prevent an immune reaction from the recipient.

But other scientists are skeptical.

A distant possibility that could be lifesaving

"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 blood substitutes.

The size of ErythroMer was also a concern as each particle is approximately one-fiftieth the size of a normal red blood cell, increasing the risk of leakage from the bloodstream into surrounding tissue. But it could be used for people with sickle cell disease and oxygenating organs during transplant operations, Doctor said.

The team acknowledges that human studies are a long ways away, especially when the FDA have staved off studies such as this due to previous experiences. However, it also recognises they "potentially could be lifesaving in situations where blood transfusion is necessary, but blood is not available… or can't be used." MIMS

Read more:
The boardwalk sideshow that saved the lives of premature babies

Sources:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2738310/
http://thelantern.com/2017/02/ohio-state-researchers-pursue-artificial-substitutes-for-blood-transfusions/
http://stlouis.cbslocal.com/2016/12/06/wash-u-researchers-creating-powdered-artificial-blood-cells/
https://guardian.ng/features/advances-in-artificial-blood-drug-for-sickle-cell-pains/
https://www.statnews.com/2017/02/27/artificial-blood-substitute/
http://www.nbcnews.com/mach/science/long-quest-create-artificial-blood-may-soon-be-over-n708576