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Tracking Bacteria in the Blood
By Emily Carlson
Posted November 26, 2008

A computer model of a small aggregate of bacteria growing in the bloodstream. Credit: John Younger, David Bortz
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May 6th was a monumental day for Scott Somers—his daughter turned 16 and he came down with sepsis, a leading cause of death in the United States.

"It wasn't bad, but it could have been a lot worse," he says. More than a third of the 750,000 Americans who get severe sepsis each year die from it.

What started out as a stomach bug turned into a bloodstream infection that sent his immune system into overdrive. Somers spiked a fever and could feel his heart racing.

"I knew exactly what was happening," says Somers, a scientific expert on sepsis at the National Institutes of Health. But, as he describes, a malaise had overtaken his body and mind and left him powerless to do anything until his family took him to the hospital. Four hours on an IV and a course of antibiotics helped him to recover.

Somers could have been any of the 300 patients John Younger's emergency department treats for bloodstream infections in a given year. An emergency medicine researcher and a doctor at the University of Michigan, Younger estimates that about one out of every eight patients who visits his emergency department is tested for bloodstream infections.

"Some cases are easy to treat while others aren't," says Younger, attributing the more difficult ones to antibiotic resistant bacteria and already compromised immune systems, typically from cancer therapies.

While bloodstream infections are an immunological problem, they are also a physical one, explains Younger. To better understand bloodstream infections caused by bacteria, he's teamed up with mathematicians and engineers to think about the problem in a whole new way.

Just as an engineer might use principles from physics and math to understand and predict the trajectory of a cannonball shooting through the air, Younger's group is developing similar rules to understand the fate of bacteria shuttling through blood vessels.

"The math doesn't need to be a foreign language—it's just a different way to think about what you see," says Younger, adding that working with experts in mathematical fields has really changed how he approaches biomedical research problems.

Emergency medicine researcher and doctor John Younger
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Because math has proven so critical to his work on bloodstream infections like sepsis, Younger took a year off from his research to study applied mathematics. Now, he keeps an introductory textbook on stochastic differential equations on his bedside table.

Younger and his interdisciplinary team developed a series of simple equations to model the movement of bacteria in the blood. Their model takes into account the physiology of a blood vessel, the fluid dynamics of blood, the rate of bacterial growth, and the passage of bacteria between blood and capillary-rich organs like the lung, spleen, and liver.

About the only way for a person's immune defenses to successfully attack invading bacteria, notes Younger, is to target them once they've been filtered from the blood into organs. That's because bacteria in the blood travel at the same speed as white blood cells and thus are nearly impossible for our healthy defenses to catch.

To figure out where bloodstream bacteria go and what happens to them, Younger also set up experimental studies in mice. He found that the bacteria spread to organs in a matter of minutes but that they are killed there at different rates—30 minutes in the lung versus 9 hours in the liver. Even though the liver is less effective at killing microorganisms, it is far superior at filtering them, making the organ a critical player in resolving bloodstream infections.

Younger used this information to validate his mathematical model and predict the likelihood that mice with bacterial bloodstream infections and comprised immune systems would survive. Most often, they didn't.

While he admits that the new model represents just a small step toward understanding bloodstream infections, Younger hopes that it will one day translate into better treatments for the patients he sees, helping him quickly assess their condition and optimize therapy.

In the meantime, Younger and his collaborators—applied mathematician David Bortz and chemical engineer Michael Solomon—have already seen other important results in their laboratories. Biology students are using serious mathematics for the first time, and math and engineering students are realizing the possibility of careers in solving important health problems.

"If we don't figure these problems out," Younger says, "I may have met the students who will."