By Joel Warner
By Michael Roberts
By Alan Prendergast
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By Patricia Calhoun
By William Breathes
Tom Keuer peers into the glass-doored storage cabinet like a television teen cruising the fridge, thirsting for a swig of Sunny D.
"Any of the good stuff around here?" he asks.
A blue-jeaned lab worker shrugs. "It's back in the freezer now."
Keuer pokes around among jugs of clear solutions and cylinders of brown muck--ongoing experiments in product development situated in a back room of the small-scale manufacturing plant owned by Somatogen, one of Boulder's premier biotech companies. After a moment he emerges with a small bottle of reddish-purple liquid in one hand.
"Here we go," says Keuer, Somatogen's vice president of manufacturing and process engineering. He shakes the bottle and watches the crimson fluid ooze down its glass sides: an elixir rich and strange, sacramental, like a blessed Bordeaux. "This is close to what the final product looks like."
What it looks like is blood. Or, to be more precise, hemoglobin. Whole blood, as any ER junkie knows, is a seething mess of red cells, white cells and platelets, all suspended in plasma. Hemoglobin is the protein complex in red cells that carries life-giving oxygen from the lungs to the tissues; its high iron content is what gives blood its distinctive shade of red.
The stuff in Keuer's hand isn't exactly human hemoglobin, but it is, he notes, "pretty close." Somatogen's hemoglobin, registered under the trademark Optro, doesn't come from any human source; it's a mutant strain, genetically altered and grown in a laboratory, through a process not unlike the fermenting of beer. Yet it looks like the real thing. Under the right circumstances, it acts like it, too. And that might be close enough to earn Somatogen a chunk of the worldwide red-cell transfusion market, which the company estimates at around $5 billion a year.
That market is up for grabs, thanks largely to fears about the safety of the blood supply. In the wake of the AIDS epidemic, the monitoring of blood banks has improved considerably, but that hasn't quelled public concern about AIDS, hepatitis or other viral infections that can be acquired through transfusion. Surging hemophobia (fear of blood) has also been blamed for a critical drop in the availability of banked blood, even though there is zero chance of a donor becoming infected while giving blood.
"The public is panicked about blood safety," says Dr. Joseph Fratantoni, director of the division of hematology at the Food and Drug Administration's Center for Biologics Evaluation and Research. "They're demanding 100-percent-safe transfusions, which, of course, can't be delivered. Transfusion of blood is much safer than it was ten or fifteen years ago. But there's still a finite risk."
The chance of contracting the HIV virus from a transfusion in the United States is more remote than most people realize--about 1 in 150,000, according to the National Institutes of Health. But in some parts of Asia and Africa, the risk is as high as one in four, and contamination isn't the only problem with donor blood. It must be typed and cross-matched for compatibility, a time-consuming process that can be particularly trying in cases of accident victims with rare blood types. It has a short shelf life, from 35 to 42 days. And even a well-matched transfusion can result in a temporary suppression of the immune system, which leaves the patient more susceptible to post-operative infections.
The safest way to avoid such risks is to put aside several units of your own blood for use during an operation. But not everyone has sufficient warning of upcoming surgery, and the procedure isn't an option for certain cancer patients and others whose blood has failed them.
Hence the market--in theory, at least--for a blood substitute. Something in a magenta, perhaps, with all the oxygen-carrying capacity of hemoglobin and none of the risks associated with red-cell transfusions. Disease-free. One type fits all. Shelf life of a year or more.
Since the late Eighties more than twenty companies have joined the race to develop a blood substitute, spending hundreds of millions of dollars in the quixotic effort. Some tinker with hemoglobin extracted from animal blood or outdated human blood; others test totally synthetic products, such as oxygen-carrying chemicals known as perfluorocarbons. None have yet reached the marketplace, although an elite few are now roughly halfway through the FDA's gauntlet of clinical trials. Somatogen, for example, has successfully administered up to a hundred grams (four units) of Optro to surgical patients, believed to be the largest dose of a genetically engineered protein ever given to a human.
All the companies still have technical problems to overcome. Analysts who once predicted that a blood substitute would be commercially available by 1995 are now talking about 1999 or beyond. "There's clearly still work to be done," says the FDA's Fratantoni. "When I read reports that this material is likely to be approved in 1997 or something--I don't know where that's coming from."
Certainly not from Somatogen. The company's Securities and Exchange Commission filings are full of caveats and disclaimers, as befits the grim attrition rate in the biotech industry. (For every long-awaited miracle drug that meets with FDA approval, dozens of other products fail.) Still, that an obscure Boulder startup, founded in 1985 on plenty of brains but not much cash, could not only survive but emerge as a serious player in what may be the highest-stakes game of them all, is fairly miraculous in itself.