Fish for a Cure

Many people have fish tanks in their homes and some of them hold zebrafish, which are attractive and easy to care for. However, for Christian Lawrence, a 2002 Arizona State University graduate and freshwater fish enthusiast, tending the half-million zebrafish that reside at Children’s Hospital in Boston requires a much higher order of devotion.

Zebrafish are widely used as model organisms for biomedical research and their use has skyrocketed in the last 15 years. A nationally important center for zebrafish studies, Children’s Hospital chose Lawrence to oversee the care, breeding, and maintenance of many rare strains of zebrafish with unusual genetic properties. His continuing research helps improve both the welfare of the animals and their utility for scientific research.

Lawrence observes their behavior, identifies patterns, and develops research projects that improve our understanding of zebrafish biology. He credits the professors and graduate teaching assistants at ASU with helping him develop the technical and critical thinking skills to excel in this position. As he says, “ASU faculty, especially professors like David Brown, Bob Ohmart, and the late W.L. Minckley had a profound influence on me. Not only are they and were they giants in the fields of natural history and ecology of the Southwest desert, but they also taught their students the value of paying close and critical attention to the world around them.”

Lawrence didn’t come to ASU with zebrafish or biomedical research in mind, but his interests emerged from his studies in wildlife conservation biology. He says he was particularly influenced by Brown’s field-based ecology course. Lawrence remembers spending time with Brown and his teaching assistants as they traveled through Arizona to study populations of bats, pronghorn and fish. These experiences taught him how to observe animals carefully and find patterns in their behavior, and how to ask and answer questions based on these patterns to understand the behaviors of the animals.

When he graduated and left Arizona, Lawrence was hired to work in a zebrafish laboratory at Harvard. Near the beginning of the zebrafish revolution in biomedical research, many of his colleagues in molecular biology and neuroscience viewed the fish primarily as a model or a tool. Little was known about the optimal care of these animals in the laboratory environment. While zebrafish are hardy and can tolerate substandard treatment, Lawrence recognized early on that using fish in research required more critical, careful and standardized treatment, with attention to animal welfare as well as experimental reproducibility.

Through his careful study of zebrafish behavior in the laboratory and the wild, Lawrence has contributed to the understanding of many characteristics of these fish, including their optimal nutrition and reproductive biology. His work has helped to increase the wellbeing of the zebrafish in his care and raised the standard of care throughout the zebrafish community. Fish that are raised under consistent, speciesappropriate conditions will have more normalized genetic expression, better reproductive success and can be used in reproducible experiments. His efforts have made it possible to expand their use in biomedical study, and he has written numerous books and journal articles to share what he has learned.

One of Lawrence’s questions relates to zebrafish reproductive biology and behavior. Much of the biomedical work on zebrafish utilizes zebrafish embryos. Traditionally, generating 10,000 zebrafish embryos, a reasonable number for a study, would require extensive resources. Forty to 50 small tanks of fish would be used, requiring a significant amount of space and care. Collecting the embryos would also take a good deal of time as biologists must wait for the fish to spawn and collect embryos as they are produced. The embryos that result from this process would generally be generated over a period of several hours, meaning that their development would not necessarily be well-synchronized. This would add an additional variable, developmental stage, to any study utilizing the embryos.

From observations of wild zebrafish populations in India and Bangladesh, as well as in the laboratory, Lawrence noted that certain environmental conditions promoted spawning, for example, that the fish naturally spawn in shallow water. Lawrence and one of his colleagues in Boston designed an apparatus to simulate a flooded plain and replicate a key condition to achieve an ideal spawning environment in the lab. Now, using this apparatus, scientists can artificially trigger spawning to generate the needed 10,000 embryos with a high degree of developmental synchronization amongst the embryos – all within 10 minutes.

These kinds of discoveries and technical advancements highlight the importance of interdisciplinary collaboration within the life sciences. Molecular biologists and neurobiologists who utilize zebrafish as models for their research focus on different problems than Lawrence might, but his focus on aquaculture and ecology bridges the gap between the fish as organisms and the fish as models. Animal experimentation is a crucial aspect of biomedical research, but scientists need to continue to consider the welfare of their animals as organisms as well as the consistency and quality of the organisms supplied to researchers as experimental models. Lawrence’s work also shows how skills gained at ASU and in organismal biology can be applied to interesting and meaningful work – often in ways that are entirely unexpected.

“Back when I was a university student,” says Lawrence, “it was always my aspiration to become a professional fish biologist, but I never would have dreamed that I could do this in the setting of a pediatric research hospital. But here I am all these years later doing just that, thanks in large part to my experiences at ASU.”