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A Bacon of Hope

A visit with Randall Prather, Professor, Division of Animal Sciences

By Sean Powers
Published: - Topics: genes genetic modification cloning pigs organs

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 it, making the organ 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 worked in collaboration with scientists at Immerge Biotherapeutics to create a pig whose organs would not be rejected. With due diligence, he and his team genetically modified a pig’s genes by removing a sugar molecule known as Alpha 1,3-galactosyltransferase (GGTA1). Knocking out the GGTA1 sugar linkage eliminates the hyperacute response from the antibodies. This may make it possible to transfer organs between different species, for instance from a primate to a human.

Standing in the center of his office, Prather points proudly one at a time to different pictures—of pigs—that encircle the walls. Some of the swine have green florescent snouts, which serve as protein markers for genetic modification. Prather identifies one pig named Goldie. After her embryo was modified, she was born without the GGTA1 sugar linkage. Goldie made the ultimate sacrifice to science; her organs were transferred into a baboon, after which there was no sign of the hyperacute rejection.

Had Goldie survived to breed, her offspring would have carried the modified genes, passing them down to future generations: “For the enhanced green florescent protein pigs, some of them have great-great-grand-pigs that carry the gene. And they still fluoresce.”

Beyond organ transplants, gene modifications might also be used to make heart-healthy pork. Collaborating with researchers out of the University of Pittsburgh’s School of Medicine, Prather cloned pig fetal cells that made their own omega-3 fatty acids, which are known to reduce heart disease and cancer. Pigs cannot make omega-3s on their own; they must eat them, just like humans. The researchers at Pittsburgh gave normal pig cells fat-1 genes to convert omega-6 fatty acids into the healthier omega-3s. Prather then cloned the pigs from the cells.

The main purpose of this modification is for studying cardiovascular disease, cancer, and other widespread human ailments. Beyond these goals, Prather says that “should the FDA permit something like this,” eventually grocery stores could start selling pork from these clones, and “you may be able to eat pork in the morning and get your omega-3s,” an appeasing complement to sugary donuts and buttery toast.

Gene modification doesn't just end with organ transplants and healthier breakfasts. It can also be used to advance medicine in other ways. For example, Prather has studied these techniques in order to develop treatments for Cystic Fibrosis, a condition that leaves mucus build-up in the lungs. People get long-term respiratory problems because they inherit a pair of mutated genes (CFTR) that are responsible. Animals do not have this mutation and thus are not susceptible to the same long-term illness. This lack creates a problem for researchers who want to test drugs on animals, but “we now have pigs where we have disrupted the CFTR gene to simulate what happens in people.” With the addition of this mutation into their genetic makeup, these pigs now have symptoms similar to humans with cystic fibrosis. Hopefully it will be possible to test medicines on pigs with this deadly disease to stop the long-term respiratory problems in people.

Animal science has come a long way. Back when Prather was in college, genetic modification and cloning amounted to science fiction. “At the time I didn’t envision it,” he admits. But now such advances may make it possible to prolong human life.