Immune-deficient Pigs Offer Insight To Human Disease

A standard feed efficiency study on pigs at Iowa State University recently led to a startling discovery with implications for human health research. Scientists identified the first pigs with naturally occurring Severe Combined Immunodeficiency, known as SCID. The inherited disorder was known only to naturally affect humans, horses and dogs until this discovery.

Those born with SCID have no adaptive immune system, making them susceptible to infections. David Vetter, who had SCID was known as the “Bubble Boy,” in the 1970s for having to live in a sterile room to avoid germs.

Jack Dekkers, an animal science professor leading the SCID pig study, says the discovery came out of a feed efficiency study on pigs, a priority project for the pork industry because of the high cost of feed.

In the late 1990s, lines of pigs were selected for high and low feed efficiency leading to the current 10th generation of the lines. The more efficient pigs require about 12 percent less feed.

To test how the animals would respond to a “disease challenge,” pigs from each line were sent to a collaborator on a related project at Kansas State University. There they were to be inoculated with the PRRS virus, the costliest disease in pigs, and evaluated for an immune response.

“Four pigs from the efficient line died fairly early on, and when they did a necropsy they couldn’t find any of the major immune organs and they recognized it as SCID, which nobody had ever identified in pigs,” Dekkers says.

“Once we realized what it was, it was very exciting because it opened up a lot of opportunities,” he says.

Iowa State University researchers conduct many projects investigating human health concerns. Many of them use animals as models to research diseases including AIDS, muscular dystrophy, glaucoma and retinitis pigmentosa.

“Support of the Experiment Station allowed us to develop these lines of pigs, which in their own right are very important to be able to look at the genetics and physiology of feed efficiency,” he says. “But also, having access to those populations and studying them in such detail led to unexpected discoveries that could be even more valuable. It’s very costly maintaining these lines, but there can also be huge benefits.”

Already there has been some interest in the SCID pigs from cancer scientists, he says, and cardiovascular disease researchers are interested because human stem cells won’t be rejected since the animals don’t have an immune system to reject them.

SCID animals don’t have an adaptive immune system, making them a potential model for biomedical research. Transgenic SCID mice are used to grow cancer tumors.

Dekkers says the pig is a much better model than the mouse for many reasons. “One is just size, but also physiologically in terms of the function of the immune system. The pig is much more similar to humans. The results will be much more relevant to humans.”

Work with the SCID pigs has included injecting human tumor cells in the SCID pig’s ears. The fact that these cells were not rejected proved that the SCID pigs make a good cancer model for humans.

It’s challenging research in many ways. Although antibodies pass to the piglets from the sow as they nurse, the SCID pigs are susceptible to infections after weaning.

Animal scientist Chris Tuggle is working on giving a SCID pig a human immune system.

“If we could put a human immune system into these pigs then we could use the pig to more directly test pathogens that are important for humans and may not affect pigs,” he says. “That’s still at its very early stages.”

The future research opportunities offered by SCID pigs depends a lot on the work being done now. Dekkers said plans are to develop more data and apply for funding from the National Institutes of Health early next year.

Fighting Fatal Brain Diseases In Children

When Dr. Matthew Ellinwood began working on the Mucopolysaccharidoses (MPS) and related diseases in 1998 there were very limited therapies for these rare genetic diseases that afflict children.

Now there are drug and enzyme therapies, approved or under evaluation, for five of them. And states are beginning to require neonatal tests for some of these disorders. The animal science professor and veterinarian is part of a five-year grant from the National Institutes of Health that includes researchers at Harbor UCLA Medical Center, the University of Minnesota, Duke University and the University of Pennsylvania. The disease being studied is known as MPS I, and is caused by the lack of a key enzyme that breaks down substance the body needs to build nerves, bone, cartilage, tendons, corneas, skin and connective tissue.

The Iowa State role in the project involves using dogs with MPS I as a model to identify improved clinical measures of responses to therapy, which will help advance therapy for children.

“Discovering treatment and measurement of it in the dogs is important to get the enzyme to a point where it can be used to treat the neuro-degenerative disease in kids,” Dr. Ellinwood says.