END OF THE (BLOOD) LINE? For decades scientists have labored to develop an artificial substance that could mimic blood's ability to ferry oxygen and carbon dioxide. Several projects looked promising up until a few years ago, when studies indicated they caused more harm than good. A handful of biotechs are still optimistic they can produce a safe, effective hemoglobin-based blood substitute, if they don't run out of money first. Image: © ISTOCKPHOTO/BOJAN FATUR
Efforts to develop blood substitutes that could be used to treat soldiers or trauma victims in remote settings have held great promise as a way to infuse oxygen-carrying liquids into patients, thereby saving their lives when real or safe blood is in short supply.
Biotech companies have even come up with long shelf life replacements that would work for all blood types without the need for refrigeration.
The companies developing these hemoglobin-based blood substitutes, however, are now fighting for their own lives—enduring failures and financial hardships in order to stay in business long enough to see their creations come to market. And making matters more complicated, some observers, including the U.S. Food and Drug Administration (FDA), question whether these surrogates do more harm than good—or are even necessary anymore.
On paper, blood substitutes look good. But when hemoglobin (an iron-enriched protein in red blood cells that transports oxygen from the lungs to the rest of the body) is introduced directly into the bloodstream without the protection of red blood cells, the body tends to break down and remove the protein, a process that can be toxic to the kidneys, constrict blood vessels (resulting in hypertension), and cause inflammation. If the blood substitutes are not designed to prevent this hemoglobin purging, they can increase a patient's risk of death or at least some serious complications, including inflammation of the pancreas (which helps the body digest food and produces insulin), elevated liver activity, and heart attack, according to studies assessing the safety of blood substitutes.
In an effort get the development of a safe and effective hemoglobin-based blood substitute back on track, the FDA in April 2008 met with several companies developing these products to deliver a new plan. (pdf) "One of the main messages from that meeting was that the first generation of products was too toxic and should be discontinued, which is what happened," says Arthur Bollon, chief executive of Dallas-based HemoBioTech, Inc., which is working to develop just such a product. "One of the FDA's recommendations was that these substitutes use adenosine-modified hemoglobin, which is the core of what HemoBioTech does." This process of modifying hemoglobin is what makes the company's HemoTech blood substitute nontoxic and anti-inflammatory, he adds.
The FDA put these substitutes for blood's oxygen-carrying capability on hold after determining that the "death rate was significantly higher in the patients who got these solutions, compared with those who got regular blood or nothing at all," says Paul Holland, a clinical professor of medicine and pathology in the Division of Hematology and Oncology at the University of California, Davis's medical center. "The FDA told all companies to go back to the drawing board and come up with better clinical trial designs."
Congressman steps in
HemoBioTech, one of the few companies that is still in business since the 2008 FDA meeting, may have an ally in Rep. Edolphus Towns (D–N.Y.), who earlier this month wrote an open letter to fellow House of Representatives members encouraging them to support funding for a "promising, cost-effective" blood substitute using hemoglobin modified with adenosine. "Fully 10 percent of [HIV and AIDS] infections and deaths can be prevented with a viable blood substitute that can deliver oxygen throughout the body with minimum or no toxicity," he wrote. He asserts that it would take an investment of less than $35 million to get these projects through human trials.