Setting the Standard

Not many middle school students read complicated books about cutting-edge science research and treatment, but Charles Xue did just that when he read about using viruses as a tool to deliver drugs. That book changed how the 12-year-old Xue viewed science and its impact on society.



“Here was something that is commonly associated with disease and death that was being used as a positive tool,” said Xue, a sophomore biomedical engineering undergraduate student at UC Irvine. “Objectively, a virus is merely a delivery mechanism. Since then, I have always marveled at the wonders that objective research can uncover.”



Xue, who comes from a family of individuals with science-related professions – chemistry professor, medical doctor, engineer, nurse – knew he wanted to study chemistry when he entered Monta Vista High School. However, back-to-back personal tragedies turned his attention to medical technology.



Two of Xue’s close high school friends unexpectedly died six months apart, one from an undiagnosed congenital heart condition, and the other in her sleep of unknown causes. These deaths dramatically changed the way Xue thought about life, school, and his future.



“Medical technology is far from where we want it to be,” said Xue, and he wanted to do something to stop things like the unexpected deaths of his friends from happening to others.



“A lot of my friends want to be doctors, but a doctor can only be in one place at a time,” he explained. “The solutions derived from research can affect millions of people simultaneously.”



He wasn’t interested in going to medical school, but the field of biomedical engineering, which incorporated many scientific and technological disciplines, provided him a path to advance medical technology on a large scale.



When Xue enrolled as a freshman biomedical engineering student in The Henry Samueli School of Engineering at the University of California, Irvine, he began conducting research in the lab of Young Jik Kwon, Ph.D., an assistant professor of chemical and biomedical engineering. Xue is searching for a more accurate measurement of the effectiveness of gene delivery mechanisms – or vectors – in gene and cell research, and presented a poster paper at the 2009 American Society of Gene and Cell Therapy (ASGCT) Annual Meeting in April. Xue was listed as the first author, which is quite a triumph for a college freshman.



“The ASGCT is the largest international scientific and clinical society in gene therapy, and having a paper accepted at an annual meeting or conference is highly competitive,” said Kwon. “Many presenters at the meeting were doctoral researchers and graduate students, but Charles’ paper received a lot of attention as a huge accomplishment for an undergraduate student.”



For his current experiments, Xue is growing millions of human epithelial and brain tumor cells to test different vectors. He works with both viral and non-viral vectors, which are DNA molecules that insert a desired gene into target cells to change the cell’s characteristics. Vector studies are a key component of drug delivery research for medical treatments and gene therapy research, which seeks to cure genetic disorders.



To test the vectors, Xue transfers genetic material to cells using vectors containing the green fluorescent protein (GFP) gene, and then places the cells in a solution in a petri dish. When using the non-viral vectors, he uses a polymer to bind the DNA together so it will incorporate into cells more easily. Viral vectors take advantage of a virus’ natural behavior to add DNA to the cells. The new cells are marked with the GFP, making it easier for Xue to determine how many new cells have been created.



Every day, Xue dons a lab coat and pulls a petri dish out of the incubator, carrying it to a counter and sliding it under a microscope to check on the cells and measure the amount of new cells marked with the GFP. He needs to grow cells for two weeks to have enough data to determine the efficiency of one vector for one cell type. He has already learned the hard way that it pays to continually check his cells’ progress – a temperature fluctuation killed the previous batch.



“I was in the beginning stages of my experiment when I neglected to check my cells for a day. I thought that because I didn’t need to change the solution in the petri dish that day, I wouldn’t need to come in to the lab,” Xue explained.



Unfortunately, when he returned to the lab, the cells were dead, and he had to unfreeze a new batch, delaying the experiment almost a week. “I shudder to think about that happening in the middle or near the end of the experiment,” he said.



Xue is analyzing the efficiency rates of vectors for application in drug delivery research. When using a vector to put genetic material in to a cell, the resulting number of changed cells can vary widely depending on several factors. When the vector is introduced in the life cycle of the cells, the stage of cell replication at which measurements are taken, how often measurements are taken, and the concentration of cells in the petri dish, all affect an experiment’s results. To top it off, scientists use many different types of vectors, or try to develop their own, making it more difficult for other researchers to duplicate study results.



“It’s important in the research community for study results to be duplicated and verified by multiple scientists, but the lack of a ‘standard’ vector or vectors, as well as the inability to simulate how a vector is expected to work, makes study verification difficult,” Xue explained. “Much research effort is focused on identifying the best vectors, but it is difficult to standardize the process due to small variations among experiments. Scientists can identify the optimal vector for one certain experiment, but that vector might not work as well for another scientist.”



The lack of an “industry standard” vector, or the ability to use computer simulation to hypothesize how well a vector will work, hinders research progress. Using his data analysis, Xue is writing a MATLAB program that he hopes will simulate how cells introduced to vectors will grow in certain conditions in order to quantify a vector’s true efficiency, and eventually predict how cells affected by vectors will behave, regardless of the experiment conditions.



This quantification will allow researchers to determine which vectors should be the standard for particular experiments, making the duplication and verification of experiment results easier and more efficient. Improving studies will help advance the progress of drug delivery and gene therapy research by reducing the amount of conflicting study results.



"By giving researchers a better measurement of vector efficiency, I hope to improve the rate of discovery in this field,” said Xue. “It’s not hard to imagine that if medical technology was more advanced, my friends may still be here. In fact, genetic therapy specifically may have saved one of them, if it was better understood.”



After completing his undergraduate degree, Xue would like to go on to graduate school, earn a Ph.D., and start his own company in the pharmaceutical industry.