A genetically modified version of the hemoglobin molecule is inserted into common bacteria, such as E-coli. The bacteria are then fermented to produce large quantities of the new hemoglobin, and the final product is purified to leave behind only the hemoglobin molecules. While the process sounds a little like science fiction, it is used routinely in the production of recombinant insulin.
The only recombinant product to pass into phase two research was Optro, produced by the Somatogen Corporation out of Boulder, CO. When Baxter Healthcare Corporation acquired Somatogen, production of Optro was halted in favor of other technologies. No other large firms are exploring recombinant techniques at this time.
Most everyone has seen pictures or video clips of mice swimming around in "liquid oxygen." The liquid is an oxygen-saturated perfluorocarbon (PFC) solution. PFC molecules are 1/100 the size of a red blood cell and can saturate 50 times more oxygen than hemoglobin. Oxygent is an example of a perfluorocarbon solution.
While the numbers make PFCs a tantalizing prospect, critics point out that PFCs don't mix well with blood and need to be mixed with oils or lipids to remain stable in the intravascular environment. Patients are also required to breathe 100% oxygen to maintain the effectiveness of the solution, creating another host of problems. Most researchers remain skeptical about PFC's practical applications in the trauma setting.
Better Than Blood?
Biochemists and researchers may be shy about using terms like "artificial blood," but they have no qualms about suggesting that these products may, in many ways, be better than blood. The clinicians who transfuse whole blood products are quick to remind us that allogeneic whole blood is not a volume replacement panacea.
Receiving six or more units of whole blood in the first 12 hours post-injury is an independent risk factor for multiple organ failure. Add to that the increases in nosocomial infection rates, the potential for viral transmission and the king of whole blood product errors, incorrect blood typing, and blood's limitations become clear. Oxygen therapeutics boast several characteristics that make them not only safer and more convenient for in-hospital use, but possible to carry into the prehospital setting.
Jeff Long, RRT, a critical care respiratory therapist at Denver Health Medical Center, has been involved in oxygen therapeutics research for several years. While he often speaks in the controlled and understated language of medical research, his excitement regarding the future potential of oxygen therapeutics occasionally breaks through. When I pressed him for details on what makes oxygen therapeutics like Polyheme superior to whole blood products, he says, "First, I would certainly say that it is superior to blood in its ease of administration. That's a strong statement, but because it is universally compatible, this product does not need to be typed and cross-matched, and that is probably its greatest advantage. There is no preparation. You walk over to where it is stored, walk it to the patient and put it through an IV. There is no risk of cross-reaction, as there is if someone gets the wrong blood type. There is no special equipment needed, no filters—it is really very simple to use."
I asked if the risk of viral transmission is still a concern.
"Any product that uses blood as its primary raw material carries at least a theoretical risk of viral transmission," he concedes. "We believe that the manufacturing and filtration process, coupled with the polymerization process, essentially sterilizes the product. It cannot be said that there is no risk of viral transmission, but the risk is greatly reduced. I personally believe the risk to be zero."
Pressing further, I asked the question that had been weighing on my mind. Is this stuff more effective than blood? Could it replace blood altogether?
Long is quick to answer. "These types of products are not going to ever take the place of blood. The half-life of these products is 24 hours. In 48-72 hours, they are out of the system. For that reason alone, they will never replace blood products. They serve as a bridge between the time a patient is first contacted to the time when whole blood is available. That is the key to this study. Polyheme will be given to patients where blood is not available. Ultimately, that is where it will have the most benefit. Whether it is in rural areas or long transport times, anywhere blood is not available and someone is bleeding to death, that is where this product will be most beneficial."