UCSD Jacobs School of Engineering University of California San Diego
Pulse Subscribe | Archive | Survey
 

How We Die: A Bioengineering Explanation

Bioengineering professor Geert Schmid-Schönbein was recently elected to the National Academy of Engineering in recognition of research that used engineering principles to explain the behavior of white blood cells in both healthy and diseased conditions.

Geert Schmid-Schönbein and his colleagues are using the tools of bioengineering to examine inflammation, a central part of the body's repair and defense system. The redness, swelling, pain, and stiffness caused by inflammation, like a rejuvenating summer storm, can sometimes grow into a devastating internal hurricane. Schmid-Schönbein, a Jacobs School professor of bioengineering who was elected in February to the National Academy of Engineering, wants to defuse or block runaway inflammation before it causes death.

Schmid-Schönbein has focused his most recent research on the inflammatory tempest called shock, a critical condition caused by a sudden drop in blood flow through the body after a serious injury. He has demonstrated that during shock, oxygen-deprived cells lining the intestines loosen their attachments to each other and permit pancreatic digestive enzymes, the same enzymes that digest food, to flow into vulnerable tissue and cause massive tissue destruction. However, the next event is even more serious: inflammatory activators produced in the damaged tissue travel through the bloodstream and cause a lethal stimulation of distant blood cells, cardiovascular cells, and other cells as far away as the brain.

Schmid-Schönbein's group found that rinsing the intestine with mild salt water reduces intestinal tissue damage resulting from shock. They also demonstrated that temporary inhibition of digestive enzyme further reduced the injury.

INTESTINAL MUCOSAL DAMAGE
a) NON
ISCHEMIC
b) INTESTINAL
FLUID
c) SALINE
PERFUSION
d) ANGD
PERFUSION
Damage to intestines after shock can cause an inflammatory response so strong that it alone can kill. Normal intestinal microvilli (a) are severely damaged by digestive enzymes after shock (b), but a saline rinse (c) reduces the damage and the addition of a protease inhibitor (d) reduces the damage further.

His group, with Tony Hugi at the Torrey Pines Institute for Molecular Sciences, is isolating and identifying the enzymatic breakdown products, compounds which Schmid-Schönbein believes are responsible for prompting inflammation, coagulation events around the body, multi-organ failure, and death.

Using an engineering approach, he hopes to find a way to dampen the process and save lives. The Jacobs School 's von Liebig Center for Entrepreneurism and Technology Advancement has funded an effort by Schmid-Schönbein's group to commercialize a filtration technology to remove inflammatory mediators from blood plasma.

Schmid-Schönbein is unraveling another mystery. He wants to know why some individuals who suffer shock recover fully, while others die. The same question applies to other inflammatory crises, such as an infectious disease, that sometimes lead to debilitating setbacks or even death.

For example, in a clinic for stroke victims in Heidelberg , Germany , Schmid-Schönbein found a very unlikely group of patients: young women. They smoked and took birth control pills, two factors known to stimulate inflammation. "These women had a double risk when most of them contracted the flu, which amounted to a triple risk," says Schmid-Schönbein. He thinks the combination predisposed each woman to a massive microvascular cell activation and inflammation, which led to her stroke.

"Prevention of these serious cardiovascular complications all lead back to my original question: where does inflammation come from?" he says. "We are applying an engineering analysis to this important problem, to generate predictive models. With refinements of those models, we should be in a position to reliably predict which kind of interventions will be most effective for treating shock and for treating and preventing stroke and many other diseases in which inflammation leads to morbidity and mortality."

One of many inflammation-related molecules to draw widespread attention is C-reactive protein (CRP), which is synthesized in the liver and can activate the complement system. Elevated concentrations of CRP in the blood have been found in patients with rheumatoid arthritis, rheumatic fever, many cancers, tuberculosis, myocardial infarction, and macular degeneration. "In fact, show me one human disease that is not associated with inflammation," says Schmid- Schönbein. "This observation provides an entry point for systematic engineering analysis of human diseases at the molecular level."