Disease In Space

January 26, 2002

Heather Heilman
Phone: 865-5714

An astronaut's life is tougher than it looks in the movies. They spend days, weeks, maybe months enclosed in a small, self-contained space with several other people. They work 16 hours a day and find it very difficult to get a restful sleep at night, since their internal clocks are disrupted by several sunsets and sunrises in a 24-hour period. Their air and water is recycled over and over again. They're under constant stress.

"When you add in the fact that human immune systems don't function normally in space, it's not surprising to learn that they often get sick. It's not a secret that infectious disease events occur on essentially every mission," said Cheryl Nickerson, assistant professor of microbiology and immunology. "When you look at extended-duration space flight on the international space station or the proposed mission to Mars, there's potentially a very serious infectious-disease event waiting to happen."

Nickerson has been selected to receive NASA's Presidential Early Career Award for Scientists and Engineers for her work showing that at least one common biological pathogen, salmonella, actually becomes more potent in microgravity.

Several years ago, Nickerson was astonished to find that although the effect of microgravity on the human immune system had been studied, no one had looked at how it affected bacterial pathogens. Nickerson's lab was already working with salmonella typhimurium, a common cause of gastroenteritis that affects between two and four million Americans each year.

Usually it causes short-term nausea, vomiting and diarrhea, but it can be fatal in those with weakened immune systems. They put the bacteria in NASA-designed bioreactors that simulate weightlessness by keeping cells in a continuous state of free fall, a condition referred to as model microgravity.

"We used a fully virulent strain of salmonella that will normally cause a systemic infection in mice that's fatal in seven to 10 days. We cut three days off that time when we cultured the strain in modeled microgravity. Not only does it kill them faster, but it's fatal at lower doses."

They found that the bacteria cultured in the bioreactor better resisted the body's defenses and reached target tissues in the liver and spleen at higher numbers than the same strain grown under normal gravity. They also found significant differences in the genetic expression of salmonella grown in modeled microgravity.

In August, Nickerson will have the chance to send salmonella up on a space shuttle mission to see how space flight and true microgravity affect it. But that's only half the story. Nickerson's lab also has been using the bioreactor to develop a better model of the human intestine, the site of salmonella infection.

Right now, scientists have two main ways of modeling how a bug like salmonella infects the human intestine. They can use conventional tissue culture in a flask or work with animals. Animal testing has been considered the gold standard for infection studies, but there are many differences between a mouse or even a monkey and a person. And tissue culture lacks many of the features tissues have in the body. Neither of these models is a true replica of the conditions faced by salmonella in the human body. But when a similar cell is put in the bioreactor, it has many of the features of cells in the body.

"What's more, salmonella interacts with this new, three-dimensional model in different ways than it did with the old model. The differences are similar to what we see in a clinical setting when someone comes in with a nasty case of gastroenteritis," Nickerson said. "We have built a model of the small intestine that more effectively mimics what's in the body."

Models cultured in microgravity are being developed for other organs for use in the study of other pathogens. These new models will give more relevant results in the lab and may eventually eliminate the need for animal testing.

Nickerson is a Newcomb alumna who joined the Tulane faculty in 1998. After finishing her PhD at Louisiana State University, she did postdoctoral work with pioneering infectious-disease expert and vaccine developer Roy Curtiss III at Washington University. The news that she had won NASA's Presidential Early Career Award took her by surprise.

"I was thrilled because this means that NASA thinks the work we are doing is providing significant advancement and insight into infectious diseases in flight," she said. "It doesn't matter whose name is on the award; this is very much a team effort."

Tulane University, New Orleans, LA 70118 504-865-5000