Blood Work: Scientists Seek to Identify All the Proteins in Plasma
Travis, John, Science News
In his 1998 book Blood: An Epic History of Medicine and Commerce, author Douglas Starr traced the rise of blood as a commercially exploited tissue. In the preface, he compared blood to oil and suggested that the former is more valuable. At the time of the book, a barrel of crude off sold for about $13, whereas Starr estimated that the same quantity of whole blood would fetch $20,000--and more than $67,000 if it were processed. "Just like the oil industry, the blood trade involves collecting a liquid resource, breaking it into components and selling the product globally; he wrote.
Consider the intense demand for plasma, the clear liquid portion of blood that contains therapeutic molecules such as clotting factors and albumin, a protein regularly used to treat shock and other conditions. The companies selling these natural compounds process more than 22 million liters of plasma each year, according to the Plasma Protein Therapeutics Association in Annapolis, Md.
The annual worldwide revenue from plasma-derived therapeutic products is around $5 billion, according to one estimate cited in Starr's book.
Plasma proteins also provide a wealth of diagnostic tools. For instance, physicians look at high blood concentrations of a protein called prostate-specific antigen as an indication of prostate cancer. And people view their blood concentrations of HDL and LDL, two cholesterol-carrying proteins, as signs of the health of their heart.
Still, there may be a lot more value hidden within plasma. To date, scientists have identified only several hundred of the estimated thousands of proteins typically coursing through a person's bloodstream.
Between 1977 and 2001, scientists screening human plasma for new proteins added only about 20 proteins to the tally, says N. Leigh Anderson, who founded the Plasma Proteome Institute, a nonprofit research organization in Washington, D.C. "That's just astoundingly, amazingly bad," he says.
Indeed, Anderson and other scientists suggest that human plasma contains some of every protein produced by the human body, perhaps hundreds of thousands of different molecules. Identifying this repertoire of plasma proteins could offer new ways to detect--or even treat and prevent--many diseases.
"It's a very broad and bold opportunity," says Gilbert Omenn of the University of Michigan in Ann Arbor, who leads an international consortium of scientists seeking to characterize plasma proteins.
The search for plasma proteins is speeding up. Last December, a team at Pacific Northwest National Laboratory in Richland, Wash., reported that it had identified almost 500 proteins in a sample of human plasma. That nearly doubles the number previously known, says team leader Joel G. Pounds.
"We're right at the cusp of a huge revolution in the field," says Anderson.
TOO MUCH OF A GOOD THING Spin a vial of blood in a centrifuge, and the red and white blood cells, as well as the disklike platelets responsible for normal clotting, sink to the bottom. A clear liquid remains above them. That fluid, the plasma, consists of water with salts, hormones, enzymes, antibodies, and other proteins dissolved in it.
Over the past few decades, Anderson and other scientists have largely used a process called gel electrophoresis to identify plasma proteins. In this approach, investigators put plasma at one end of a slab of gel and run an electric current through it. Migrating with the current through the gel at speeds based on their molecular weight and electric charge, plasma proteins separate from each other. The researchers then extract purified proteins from the gel.
In a review of plasma-protein research published in the November 2002 Molecular and Cellular Proteomics, Anderson and his father, Norman G. Anderson, estimate that about 290 plasma proteins have been identified in this way. They argue that gel electrophoresis used by itself will find few additional blood proteins. …