A boyhood fascination with the way things work leads to a multifaceted public health career.
From the time he was three years old, Rudy Richardson knew he wanted to be a scientist. That was the year his parents gave him a paint set, but instead of painting, he put the individual paints in a set of bud vases and then mixed the colors to see what happened. By the time he was six, he’d taken to studying the effect of insecticides on bugs. “I think I’ve always been fascinated by how things work, and by what happens when the workings go awry,” he says. “Can we figure that out and try to make it well again?”
Decades later, Richardson, the Dow Professor of Toxicology at the School of Public Health and an associate professor of neurology, is still trying to figure out how chemicals work. His chief interest today is neurotoxic chemicals, or neurotoxicants, and how they interact with target proteins. Neurotoxicants fascinate Richardson in part because they can be used for both nefarious and beneficial ends. As far back as the mid-19th century, he notes, the Parisian physiologist Claude Bernard recognized that poisons were “exquisitely powerful and specific in attacking particular mechanisms of the body. One agent would bring the nervous system to a halt, and another would stop the delivery of oxygen through the blood.” Bernard figured out how some poisons functioned, and Richardson says he and his fellow toxicologists are continuing that tradition.
“We still use poisons as tools to help us understand how living organisms do their thing,” Richardson says.
For example, he and his colleagues have been able to take organophosphorus compounds similar to those found in some pesticides and use them to create neurological diseases. The process lets the scientists uncover “all sorts of mechanisms about how neurons get sick and die,” Richardson says, and helps deepen their understanding of neurodegenerative diseases like Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis, or ALS.
Richardson views himself as a basic scientist who’s chiefly interested in phenomena, but who has lucked out by working in public health, where his work has applications that can benefit people.
Some of his current work on neurotoxicants, for example, is being used in the nation’s counterterrorism efforts. Richardson chairs an external advisory committee for a National Institutes of Health Center Grant that is developing catalytic “bioscavengers” for use in the treatment and prevention of the acute effects of nerve agents, which could be used to attack civilian populations. He also serves on several expert panels that are examining the impact of pesticide residues on human health—with a focus on the health of infants and children.
With former student Nichole Hein and colleagues in the University of Michigan Department of Neurology, Richardson is collaborating on a study of mutations in the target protein NTE (neuropathy target esterase), which is linked to motor-neuron disease in humans. He’s also working with former student Sanjeeva Wijeyesakere in the UM microbiology department to analyze a protein found in potatoes that mimics NTE. Wijeyesakere is developing computational modeling techniques to try to understand how neurotoxicants affect NTE, and thus the human brain.
Richardson says NTE appears to play a critical role in maintaining the correct balance of lipid metabolism in human nerve cells. “There are so many fascinating things about NTE that have eluded investigators for decades,” he says. “We’re just now bringing to bear the sophisticated tools of physics and molecular biology.”
If he could help decipher the three-dimensional structure of NTE and figure out how it functions in human cells, he says it would be the “holy grail.” And that quest is enough to keep Rudy Richardson going for years to come.
“We still use poisons as tools to help us understand how living organisms do their thing,” Rudy Richardson says.