NEWS OF THE WEEK
BLOOD-CLOTTING MODEL MICROFLUIDICS: Simple chemical system provides insights into complex biological phenomenon
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SIMPLE CHEMICAL SYSTEM could help re searchers understand the complex biological system governing blood clotting. Chemistry professor Rustem F. Ismagilov and gradu ate students Christian J. Kastrup, Matthew K. Runyon, and Feng Shen at the University of Chicago use a modu lar chemical system to mimic initiation of blood clot ting in the complex biological system of hemostasis, which comprises about 80 reactions (Proc. Natl. Acad. Sri. USA 2006,103,15747). "The clotting network is just too complex to model the reactions and transport and get some sort of intui tive understanding," Ismagilov says. "The problem with simplifying the network is that everything is im portant. You can't just study it one reaction at a time." To get around this problem, the Chicago research ers looked at the big picture and broke the network into three modules that describe the kinetics of the overall phenomenon. These modules demonstrate autocatalytic production of clotting activators, depletion of those activators by diffusion, and formation of a clot at high concentrations of activators. In their model system, catalytically generated acid initiates the gelling of alginic acid, much as tissue factor protein initiates clotting of blood. The researchers performed the experiments in microfluidic devices, one for the chemical system and one for blood plasma. "Microfluidics allows us to localize the components," Ismagilov says. Key to Ismagilov's chemical model are patches con taining clotting activators generated on the surface of
the microfluidic channels. The model predicts that clotting will not occur when the patches of activator are below a thresh old size. By using the chemical model, the team could predict the threshold size of patches required for clotting of blood plasma. The initiation of the clotting depends on the size of individual patches rather than the sum of all the patches. Sub threshold patches initiate clot ting only if they are clustered densely enough to behave as a single patch. "There is a lot of literature right now where people argue about whether certain concen trations of tissue factor can or cannot initiate clotting," Is magilov says. "The point we're making is that knowing the average concentration isn't enough. You actually have to T R I G G E R In both the chemical model know the localization of tissue (left) and human blood plasma (right), factor." clotting happens only when the activa tor patches reach a certain threshold In an accompanying com size, 4 0 0 Mm in the chemical system and mentary, Irving R. Epstein of 100 μιτι in plasma. Green = chemical ac Brandeis University writes: tivator, yellow = gelled alginic acid, red = "This tour de force signifi biological activator, purple = blood clot. cantly extends the scope of chemical reactions as a source of fruitful models for complex biological processes." Ismagilov wants to move to more medically relevant applications. "We need to push these results into mod el organisms and then into people," he says, ''because that's where these results will make the most impact" in understanding wound healing and clotting diseases such as deep vein thrombosis.—CELIA ARNAUD
GUILTY Crawford admits tofilingfalse financial documents Former FDA commissioner Lester M. Crawford pled guilty on Oct. 17 to federal charges that he failed to disclose owner ship of stocks in firms regulated by the agency. He was charged specifically with filing false documents and violating con flict-of-interest laws, both misdemeanors. In his financial documents, Crawford stated that his shares of Sysco and Kimberly-Clark had been sold when, in fact, he still owned them. He also failed to disclose ownership of PepsiCo stock and income from the exercise of Embrex stock options.
"One of the most important principles of our ethics laws is that public officials cannot have a financial interest in any decision they make," says U.S. Attorney Jeffrey A. Taylor. "Crawford blatantly vio lated these principles." Crawford was acting commissioner of FDA from March 2004 until July 2005, when he became commissioner. He resigned that position after only two months. While at the agency, he chaired the FDA Obesity Working Group. Deci sions of this group could have affected stock values of both PepsiCo and Sysco,
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leading manufacturers of food products. The Office of Inspector General at the Department of Health & Human Services initiated the investigation after several lawmakers said they were concerned about Crawford's sudden departure from FDA. Crawford is scheduled to be sentenced in January and could be sent to prison for up to one year for each charge. But his lawyer, Barbara Van Gelder, a partner at Wiley Rein & Fielding in Washington, D.C., says it is likely he will receive only fines and probation.-BETTE HILEMAN
