Take a good, hard mental image of a long line of people stretched for blocks. If you expand the line to roughly 100,000, this is the number of people waiting for an organ transplant. The imbalanced patient-to-organ ratio leaves many to die while waiting their turn. In response, some researchers try to tap into animal organs to save human lives, but those organs do not always work.
Research in the University of Missouri’s Division of Animal Sciences may help solve this medical debacle by using genetic modification. When an organ goes from one animal to another (like to a human), preexisting antibodies in the human bind to the organ’s sugar molecules and kill the organ, making it useless. “When you take a pig cell and transfer it to a human, the molecule is immediately recognized as foreign,” explains MU’s Animal Science Professor, Randall Prather. “Within minutes you’ll get hyperacute rejection, and the cells will be destroyed.”
Prather has contributed to research associated with modifying genes to produce healthy bacon. In a study involving the University of Pittsburgh’s School of Medicine, researchers transferred a gene known as fat-1 to fetal pig cells. The fat-1 gene creates an enzyme that converts omega-6 fatty acids to omega-3 fatty acids, the type of fatty acid known to reduce heart disease and cancer. As a collaborator in the research, Prather cloned the pig fetal cells containing the gene that makes omega-3 fatty acids and creates pigs with their their own omega-3 fatty acids.
When asked, each individual reveals ideas about their post-graduation plans. When he graduates, for example, William Donald Thomas plans to continue the same type of research in molecular biology, in search of better treatments for breast cancer. Brian Bostick is a MD/Ph.D. student, earning a medical degree alongside a Ph.D. He explains: “My hope is to combine both clinical work as an MD, working with patients, but also to keep a research career going.” As such, Bostick intends to keep developing treatments for heart disease and “try to transfer those breakthroughs we are having in the laboratory to the bedside and help human patients.” Regarding his own ideal plans following graduation, Severin Stevenson says he would like to work in private industry for a while, but hopes that after some years of this he will return to teaching.
“There’s actually a lot you can do with a Ph.D.,” says Erica Racen. “Traditionally, people think that you go into academia and have your own lab. But I have a passion for teaching. Having come from a small liberal arts college, I would like to go back to that environment and teach.” Amy Replogle similarly reports a passion for teaching, saying, “I would love to become a professor at a small institution.”
While Andrew Cox is not certain what direction to take after graduation, he knows that he loves doing research. “I am less thrilled with the grant writing, the constant rejection, and the cut-throat nature of academia,” he responds. If he had to guess, Cox suspects that he will eventually teach: “I love interacting with students. There is really not much more thrilling than getting someone interested, involved, and engaged in research.”
As a graduate student in the Department of Molecular Microbiology and Immunology in MU’s School of Medicine, Brian Bostick works with professor Dongsheng Duan in the area of gene therapy. Bostick’s research seeks to develop a treatment for the most common form of muscular dystrophy, Duchenne muscular dystrophy, in which patients are missing a gene called dystrophin. Gene therapy involves the replacement or addition of a missing gene. Bostick’s research involves inserting this gene into a virus and then injecting it into an animal body. “Just by using the normal properties of how a virus works,” Bostick explains, “we can actually replace genes that are missing.”
Bostick’s research focuses specifically on the heart disease associated with Duchenne muscular dystrophy, where a gradual weakening of the muscles occurs—starting with the larger muscles—so that patients have trouble breathing by the time they are teenagers. For a long time, such respiratory problems had been the major cause of death among DMD patients, but doctors are now better able to treat the respiratory disease. Because the heart muscle also needs dystrophin to function properly, heart disease worsens as these patients live longer. Heart disease, in fact, is now a major cause of death among DMD patients, a problem that Bostick and his mentor Duan seek to address by developing a heart disease model in mice.
Bostick offers a quick tour of Duan’s laboratory, illustrating the processes involved in several research projects—from the mouse treadmill to the surgical area and where the mice are kept under observation. Delicately selecting several mice, Bostick shows examples of a normal mouse, one with MD, and another with MD undergoing gene replacement therapy. The difference, in both size and activity, between the untreated mouse and the one given gene therapy is remarkable and promising for future applications of this research.