Graduate Spotlight: Arena Richardson

Expected Graduation: Fall 2009
Degree Objective: Ph.D. in Toxicology
Other Degrees: B.A. in Biology

Arena RichardsonWhile Arena N. Richardson labors in a University of Georgia lab, news reports surface of contaminated milk formulas produced in China. The formula is pulled from market shelves globally as accounts of thousands of children harmed by the tainted milk reverberate. Parents worldwide grow concerned about the reliability and safety of consumables.

The tainted milk scandal is yet another grave concern in a year of headline-making food contamination reports. Accounts of salmonella and E. coli in the food supply increasingly appear in news reports in the United States. Staples - lettuce, tomatoes, beef and milk - and even non-staples such as jalapeno peppers and candies - are called into question.

The scares evoke a fundamental worry about infants, for there are myriad sources and pathways for contamination of their food. And when the worst happens, can we find ways to intercede swiftly to save preemies - the most vulnerable of all?

Arena N. Richardson (PhD, '09) considers the red-stained slide of a rod-shaped bacillus named Enterobacter sakazakii, or E. sakazakii. For the past four years, she has studied the bacterium under the oversight of her professor, toxicologist Mary Alice Smith. What the scientists discover may hold critical significance for infants in neonatal intensive care (NIC) units.

E. sakazakii is associated with contaminated powdered infant formulas implicated in premature infant disease and mortality. Powdered formulas, once commonly used in NIC units to feed premature infants, can boost nutrition at a critical time. If the formula is contaminated, the outcome presents a medical crisis: when E. sakazakii reaches the brain, it can cause hydrocephaly, meningitis, mental retardation, or death.

It's rare, and knowledge of the pathogen is so limited that the incidence of infection is unknown. Infants who end up infected with E. sakazakii are usually born before 40 weeks of gestation. However, she mentions the case of a 35-day-old infant with meningitis. "It recovered and did not die, but did have hydrocephaly and developmental delays. The baby was born at 40 weeks, not premature, but most are born before 40 weeks."

Study of the bacteria is fairly new, says Richardson. "The first two cases of infection by E. sakazakii were reported in an article published in 1961, by authors Urmenyi and Franklin. Back then, E. sakazakii was classified as yellow-pigmented E. Cloacae.

In 1980, scientists classified E. sakazakii separately. "It's still emerging," reminds Richardson. "It hasn't been known for a long time."

The first goal of the research project was to identify an animal model that resembled infection in premature infants. "We selected a mouse strain (CD-1) based on Arena's first research project. The [research] project is now focused on how E. sakazakii, the pathogen isolated from powdered infant formula, gains access to the brain resulting in illness and, in some cases, death," explains Smith.

Low birth weight preemies are typically given supplemented milk. A powdered infant formula may be safe initially but becomes infected at a later point. "The formula is mixed with water, usually given to premature babies via a feeding tube," explains Smith.

"Pasteurization does kill off bacteria like E. sakazakii," says Richardson. "But the bacterium is found in soil, in the human intestine, all over the place. It's found in food production environments and factories. E. sakazakii can survive in those facilities. There's always the chance of it getting into a product and contaminating it." There are numerous ways formula becomes contaminated; no single solution could prevent it. However, it is commonly believed formula becomes contaminated after pasteurization.

The research underway by lead professor Smith and doctoral candidate Richardson will enable researchers to develop best methods for treating or preventing E. sakazakii infection in affected infants. When neonatal mice are infected with the bacterium, they hope that what happens mimics human outcomes.

"Somehow, it crosses the blood-brain barrier and gets into the brain to infect it," Richardson explains. "There is no known mechanism for how that happens. In mice, we were expecting that if E. sakazakii gets into the brain, it would eventually cause death in the mice. For those mice that survived, we were able to culture E. sakazakii out of the brain and there was no sign of illness in those mice. We don't know why some mice survive the infection and others do not. However, this presents an opportunity for us to look for possible mechanisms making some infants more susceptible or others less susceptible to infection."

Richardson describes her particular research role: "A newborn mouse is not as developed as a newborn human, particularly the brain, so we thought it might be a good model. We look at different mouse strains to see what strain might be best; then we can give it E. sakazakii and isolate it from their brain and intestinal tract." Once their model exists, researchers can develop methods for treating or preventing E. sakazakii infection in premature infants.

Richardson, a Sloan scholar, works with the animal model under Smith's auspices. She began graduate studies with Smith in August 2004, as a toxicology doctoral student in the Department of Environmental Health Science. Smith is a member of the Alfred P. Sloan Foundation faculty network.

Last August, the pair attended a meeting of the International Association for Food Protection in Ohio. Richardson won an award as a Developing Scientist for her research on E. sakazakii. "Over 100 people entered the competition," says Smith. "It was quite a nice thing to win third place."

Richardson grew up in Orangeburg, South Carolina, where scientists were not commonplace. She was surrounded by dream-nurturers. Her mother is an educator; her father is a social worker and a pastor. By the time she was in second grade, she knew she would be a scientist. "Yes, and many of my elementary school teachers knew. I would tell them science was my favorite subject," she says as she works. She is typically in the lab six hours daily in addition to studying for courses and writing research manuscripts.

She earned a bachelor's degree in biology and then shifted to toxicology. She interviewed with Smith, and entered an interdisciplinary graduate program. "It's really practical. Human health is really important, and toxicology will always be useful, as there are so many chemicals and biological agents being used. My being interested in the food safety aspect came about in grad school." Richardson also prefers research over teaching.

"There are educators on both sides of my family - plenty of teachers, counselors, professors. I've always known I preferred research. It's my passion." She anticipates completing her doctoral work in 2009. Then, Richardson says she will either begin a post-doctoral fellowship or a career in toxicology. "I think I would prefer to work for a federal agency, like the FDA or USDA."

At the Ohio conference, a man told Richardson about his grandchild developing an unidentified infection in a neonatal intensive care unit. "The doctors assumed it was E. sakazakii," Richardson says.

This was Richardson's first opportunity to speak firsthand with someone who had direct and personal experience with the pathogen she's spent years observing. "The chances of infection are increased when there is a contaminated powdered infant formula that has been reconstituted and it is left sitting at room temperature for several hours - allowing bacteria to grow to high concentrations and making it easier to infect an infant. Special care should be considered when preparing these formulas."

Richardson believes the work she does will have future significance. "Hopefully my work with E. sakazakii and its effects on mice will lead to a model. In understanding how it goes about causing infection in human infants, maybe better treatments can be developed to reduce the likelihood of morbidity and mortality."

In her research with mice there are sometimes no observable signs of infection, even though they're infected with E. sakazakii. By a post-mortem sectioning of the brain, liver, and intestines, she identifies the infection and how it has spread. "In the beginning, I didn't know what was going to happen. I didn't know if I could recover the bacterium from those tissues."

In other research with two different age groups of mice, Richardson has discovered another outcome. "We did begin a study on the susceptibility of mice of different ages to E. sakazakii. By looking at the data I have, it looks like the younger mice are much more susceptible than the older mice. That seems to mimic what we see in the reports on infection in human infants. Younger, less developed infants have a higher level of infection than older ones. Those who are immuncompromised are usually the ones to be infected."

Smith observes that "infants of full term birth might not have this problem."

Smith, though a faculty member in environmental health science, is also a member of the interdisciplinary program in toxicology. As a toxicologist she has investigated pathogens and chemicals that affect pregnancy. She has also worked with another pathogen found in food that causes stillbirth.

A colleague in Canada is also working with E. sakazakii using a different animal model - gerbils. Like Smith and Richardson, the Canadian discovered that the infection rate is higher than the mortality rate. Finding the way to block transmission to the brain is the desired "end-point," Smith says.

She praises her protégé Richardson. "I want to stress the importance of Arena to the success of this project," she says. "I am very excited about the potential she has. She'll be good at whatever she does, whether it's becoming an academician or working in industry."

By Cynthia Adams