St. Louis Post-Dispatch
3-27-06
Scientists fish for health ideas with pigs
Pork — the other white fish?
Some day, pig farmers could have a new marketing campaign thanks to a group
of genetically engineered pigs at the University of Missouri at Columbia. The pigs
make a type of fat normally found in fish and plants. The fats, called Omega-3
fatty acids, help lower levels of heart-damaging cholesterol and may have other
health benefits.
But you won’t be able to bring home heart-healthy bacon any time soon. Randall
S. Prather, a reproductive biologist at the university, and his collaborators have
designed the pigs to help scientists learn how Omega-3 fats affect the body.
The pigs are some of the newest laboratory animals shedding light on human
diseases. Rats and mice have long been the experimental animal of choice, but
now a few researchers in the Midwest are turning to pigs to learn more about
human health.
“People are beginning to appreciate the pig more now,” said Kola Ajuwon, an
animal scientist at Southern Illinois University Carbondale. Ajuwon specializes in
the study of fat cells and is using pigs to model a pre-diabetes condition often
called metabolic syndrome.
There are good reasons to choose pigs over rodents for some of the diseases
that plague humans, biomedical researchers say.
Perhaps the most obvious reason is size. Pigs are big — certainly more similar in
size to humans than are either rats or mice, said Harold Laughlin, chairman of
the Department of Biomedical Sciences at the University of Missouri. The size
difference means that some porcine parts are constructed more similarly to
human organs than are those of rats and mice, Laughlin said.
Laughlin puts Yucatan miniature pigs on treadmills to study the effect of exercise
on the cardiovascular system. The pigs weigh about 150 pounds. They are more
docile than most domestic farm pigs and gladly trot on a treadmill, Laughlin said.
“Yucatan pigs would make good pets, if you can stand how they smell and some
of their pig habits,” Laughlin said.
Pig blood vessels are the same size as human blood vessels and contain
multiple layers of smooth muscle cells the way human blood vessels do, he said.
Blood vessels in mice are much thinner, containing only three layers of the
muscle cells. That difference in structure could affect the way the blood vessels
respond to diet and exercise.
Pigs mimic humans in other ways too. The swine tend toward laziness, lounging
in their cages unless the researchers train them to exercise. Rodents, on the
other hand, aren’t such great models for human couch potatoes.
“Rats and mice tend to be active. They run around the cage, so they don’t really
emulate people who lay around on the couch,” Laughlin said.
Try as they might, researchers have a hard time giving rodents the disease that
kills most humans.
Rats and mice “don’t die of heart attacks. They die of tumors and other things,
but certainly not full-blown atherosclerosis,” said Marc Hamilton, a University of
Missouri researcher who studies fat metabolism. “Our friend the rodent just
doesn’t develop disease for the cardiovascular system.”
Pigs get heart disease when fed a high-fat diet and allowed to live a sedentary
life, even when they don’t become obese. Hamilton, Laughlin and others are
working to find out how exercise influences the progression of heart disease in
pigs. The process is likely to be very similar to what happens in people, Hamilton
said.
Most pigs get fat in a different way from humans. People tend to pack fat on their
bellies. That type of fat deposition, called visceral fat, is associated with high
cholesterol, resistance to insulin, high blood pressure and other risky health
conditions.
Pigs generally store their excess fat under the skin on their backs, said Ajuwon.
But certain pigs resemble humans in the way they distribute their weight. One
type of pig, the Ossabaw breed, does gain abdominal fat and can get diabetes,
he said.
Ajuwon and others hope that studying the differences between hormones and
inflammation signals given off by different types of fat will help them understand
why obesity leads to diabetes. The information also may allow the researchers to
make pigs with less fat and more lean meat.
Rats and mice are still essential to study some diseases, such as cancer. Pigs
don’t get cancer, said Kattesh V. Katti, co-director of the International Institute for
Nano and Molecular Medicine at the University of Missouri at Columbia.
However, pigs are useful in some cancer studies. Katti and his colleagues have a
grant from the National Cancer Institute to develop nanotechnology for detecting
and treating cancer. Because pigs are human-scale, the researchers can give
them doses of gold nanoparticles similar to what a person would receive. The
researchers then can use various methods, including a nuclear reactor, to track
the movement of the tiny gold particles through the body.
Katti and his colleague Stan Casteel, a professor of Veterinary Medicine also at
the university, began working with pigs about five years ago as a model for
Wilson’s disease. Casteel was able to give pigs a version of the disease, which
causes copper to build up in the liver, leading to the formation of free radicals
that damage tissues and DNA. He and Katti tested a compound Katti invented
that mopped up copper in the liver and shuttled the metal into urine.
Many clinical trials that work well in lab rats fail in human studies. But testing on
larger animals, such as pigs, increases the probability that a therapy will work in
people too, Katti said.
“The chances of success (of clinical trial) going from pigs to humans are
astronomically high,” he said.
One limitation of working with pigs in the lab has been the lack of genetic
information, Ajuwon said. The pig genome is not yet sequenced, though a
consortium of researchers, including scientists at the University of Illinois and
Iowa State University, are working to decipher the pig’s genetic makeup.
And Prather and others are perfecting techniques for manipulating genes in pigs
the way scientists have done for years in mice.
Prather’s collaborator Yifan Dai of the University of Pittsburgh School of Medicine
used some of the new genetic techniques to transfer a gene called fat-1 into pig
fibroblast cells. Prather created the new Omega-3 producing pigs from the
altered cells using a process called nuclear transfer cloning.
These first-generation piglets won’t be used for medical studies, Prather said.
The Omega-3 piglet clones are now about four months old. Pigs reach puberty at
about eight or nine months old. Once the pigs are old enough, the researchers
will breed the engineered pigs and study the offspring.
Prather said he had no plans to develop the Omega-3 engineered pigs as a food
source, although he’d serve as a cheerleader for anyone willing to invest years
and millions of dollars to gain Food and Drug Administration approval to bring the
meat to the table, he said.