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
-
The Best Science Writing Online 2012
Showcasing more than fifty of the most provocative, original, and significant online essays from 2011, The Best Science Writing Online 2012 will change the way...
Read More »
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.
FDA advice
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.
See what we're tweeting about
9 Comments
Add CommentJust keep the lid closed on Darwin's black box. It's easier not to know&
Reply | Report Abuse | Link to thisUmm... what?
Reply | Report Abuse | Link to thisI would think that it's shortsighted to let those substitute development firms go bust. I think that HIV is not the only pathogen that can be transmitted by donated blood. I'm not telling that donated blood is not a great product, but why shut down the search for substitutes that can one day be better solution at least in some situations.
Reply | Report Abuse | Link to thisIt would seem that safe blood substitutes might also be useful given the chronic shortages of sufficient donated blood products in many parts of the country.
Reply | Report Abuse | Link to thisThere is something very wrong at the FDA. No matter what these companies submit for clinical trials the FDA always finds resons to deny their applications.
Reply | Report Abuse | Link to thisOne must remember that a patient will most likely only get a blood substitute once in a lifetime. These are not drugs intended for longterm treatment.
The FDA should be investigated.
There is something very wrong at the FDA. No matter what these companies submit for clinical trials the FDA always finds resons to deny their applications.
Reply | Report Abuse | Link to thisOne must remember that a patient will most likely only get a blood substitute once in a lifetime. These are not drugs intended for longterm treatment.
The FDA should be investigated.
It would be a huge mistake for Congress to fund a company like this through legislation. If the company actually has good ideas and a good product, it should apply for grants from the NIH which is competent to review their material. If the ideas are really good, the NIH will fund the needed research to prove the point. The clinical trials and commercializtion will cost way way more than $35,000,000 and no one should be fooled about the cost of this project. This story is not balanced because it does not say that most of these products do more harm than good. The FDA is not doing anything wrong. It is protecting patients from products which are not ready for use yet. If this company has not done studies to document its safety yet, it is hardly reasonable to conclude that this is better than any of the other products or that it should be funded directly by Congress. Finally, the risk of AIDS is so small that if there is really an increase in safety when it comes to AIDS, it will be very hard to measure. THAT IS NOT A REASON TO BE INTERESTED IN BLOOD SUBSTITUTES ANY MORE. Scientific American should be more rigorous before publishing.
Reply | Report Abuse | Link to thisI personally prefer the idea using umbilical cord blood cells to cultivate the so-called universal blood cells. This seems more promising and long-term focused, though the surrogates which are under difficulty in development have certain merits before other options are accomplished in practice.
Reply | Report Abuse | Link to thisIf you advocates for using the drugs which are still shown to be unsafe, should learn about Thalidomide.
Reply | Report Abuse | Link to thisThalidomide was used as an anti-depressant/sedative for pregnant women and as a sleeping pill in the 1950s and found in 1961 to have caused severe deformities in children born to mothers taking it.
This caused Governments to legislate much more stringent controls on new drugs.
Although Thalidomide is effective in the treatment of Leprosy and Multiple Myeloma , it is under strict control.
The drug manufacturers now do a lot of testing and it is surprising that in this present drug for blood replacement is being pushed when it has known bad side effects.
Any lawmaker with any knowledge of the Thalidomide tragedy will not seek to fast track drug.