www.latimes.com/health/la-he-in-the-works-blood-20101025,0,5769449.story
Scientists are working on synthetic replacements for blood. But many attempts have failed to meet safety standards.
October 25, 2010
In the "True Blood" television series, sexy vampires quaff bottles of artificial blood that allow them to live alongside humans in polite society.
In real life, people in distress need artificial blood, and scientists are working on several synthetic concoctions that could stand in for the crucial body fluid.
Every year, 4.5 million Americans receive lifesaving transfusions, according to the New York Blood Center, and 1 in 3 people will need blood at some point in their lifetime.
But real blood has many inconveniences. It requires refrigeration, which means ambulances can't stock it and medics can't administer it on the battlefield. It goes bad after 42 days. Donor blood must be compatible with the patient's blood type. And some people refuse transfusions — Jehovah's Witnesses, for instance, believe the Bible forbids them.
Although the U.S. blood supply is fairly safe and steady, that's not the case everywhere. In sub-Saharan Africa, the World Health Organization estimates that 44% of women who die in childbirth succumb to blood loss. The WHO also reports that in 41 countries, some blood isn't screened for HIV, hepatitis and syphilis, putting recipients at risk of developing serious infections.
"We definitely need a blood substitute out there," says Dr. Ernest Moore, a trauma surgeon at the University of Colorado's Denver Health Medical Center.
Blood is, as they say, thicker than water. Nearly half of the liquid is made up of red blood cells, which pick up oxygen in the lungs and deliver it to the rest of the body. The fluid also contains white blood cells, which patrol the body to fight infection, and platelets, which form clots to make wounds stop bleeding. In addition, there are numerous proteins and chemicals that regulate blood pressure, transport nutrients and perform many other vital functions.
Scientists agree that creating a fluid capable of performing all of these tasks is nearly as fantastical as discovering vampires living among us. But several researchers believe they can mimic one key function — the shuttling of oxygen — in a liquid that could help accident victims, injured soldiers and anyone else who requires a transfusion.
Synthetic oxygen carriers come in two main flavors. One is based on natural red blood cells, while another is entirely artificial.
Red blood cells are basically little dimpled bags full of hemoglobin, the molecule that collects and releases oxygen. So researchers have attempted to build oxygen carriers out of hemoglobin itself.
"It's a natural means for delivering oxygen," says Arthur Bollon, a molecular geneticist who serves on the board of HemoBioTech Inc., a biotech firm in Dallas.
But outside its little bag, pure hemoglobin is toxic. It tightens blood vessels, leading to high blood pressure and heart attacks. It also causes inflammation, including swelling and fevers.
Those problems have forced scientists to alter it for medical use. But many of their attempts have failed to meet rigid safety standards.
Moore led a clinical trial of a hemoglobin substitute called PolyHeme that was given to 349 accident victims en route to the hospital and during the first 12 hours of treatment. Compared with a control group of 364 patients who received saline solution followed by donated blood, those treated with PolyHeme were slightly more likely to suffer multiple organ failure and other adverse effects, such as high blood pressure and inflammation. However, they were just as likely to be alive 30 days later, according to results published last year in the Journal of the American College of Surgeons.
"Those of us who used PolyHeme in critically injured patients saw patients survive with this product," Moore says. "It works."
But 3% of the people treated with PolyHeme had heart attacks — three times as many as in the control group — and the Food and Drug Administration concluded that all hemoglobin-based carriers are dangerous. Northfield Laboratories, the Evanston, Ill., company that made the product, shut down last year, as have many artificial oxygen carrier companies.
Still, HemoBioTech has not given up. The firm is attempting to improve on the formula with a product called HemoTech that uses hemoglobin from cows hooked to a molecule called adenosine. Adenosine happens to be anti-inflammatory and causes blood vessels to widen, so it counters the side effects of pure hemoglobin. Moreover, HemoTech signals the body to produce more of its own red blood cells, Bollon says.
Sangart Inc. in San Diego is using a similar approach. Its MP4OX is a combination of hemoglobin from expired human blood — hemoglobin lasts longer than other components — plus additional chemicals to reduce side effects. It's intended to work as a supplement to help a patient's blood carry oxygen, says Sangart President Brian O'Callaghan.
More than 500 people have been treated with MP4OX in clinical trials. In one recent study, which has not yet been published, doctors examined 51 trauma patients who received standard treatment with or without MP4OX. The hemoglobin substitute appeared to do a better job of delivering oxygen, and there were no worrisome side effects, O'Callaghan says. An earlier study, published in the journal Haematologica in 2005, found that eight volunteers who received MP4OX had no more side effects than a control group that received saline.
The 100% man-made blood substitutes are based on chemicals called perfluorocarbons, or PFCs. They can stand in for red blood cells because they dissolve oxygen, just as water dissolves sugar. Then they can carry oxygen as they flow throughout the body.
The chemicals travel through the blood as tiny droplets that absorb oxygen in the lungs and drop it off in the tissues. The more oxygen available the better, so recipients often breathe oxygen-rich air from a tank as part of their treatment.
Sanguine Corp. in Pasadena is attempting to use PFCs as artificial oxygen carriers. PFCs don't naturally intermingle with water, so scientists at Sanguine mix up an emulsion — rather like making an oil-and-vinegar salad dressing — called PHER-O2.
"It looks like skim milk," says pharmaceutical scientist Thomas Dress, Sanguine's chief executive.
The PFC system isn't perfect; breathing in too much oxygen can prompt the release of dangerous free radicals, which can damage cells throughout the body.
And PFCs, due to their milky appearance, can interfere with blood tests that are meant to work with the red stuff, says Dr. Ross Herron, chief medical officer of the Western Division of the American Red Cross in Pomona.
Even if scientists ultimately succeed in creating workable and safe blood substitutes, they are unlikely to stand in for the real thing except in special circumstances, such as accidents. None of the products currently in development survives in the body for longer than a few days; a real blood transfusion, on the other hand, lasts for months.
Still, some scientists remain optimistic that someday every ambulance and field medic will pack a supply of artificial oxygen carriers.
"This is going to be the single biggest drug in the history of medicine," Drees says. "It's going to save a lot of lives."
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