How scientists use pigs to save lives

Thursday, September 17, 2020

Better Pork explores some of the ways that pigs have contributed to biomedical research, and how scientists' use of these animals may support new medical advances.

by Jackie Clark

In the spring, a team of researchers – including University of Illinois at Urbana-Champaign scientists and industry partners – approached a professor in the university's animal sciences department to collaborate on a project intended to help address the COVID-19 crisis.

The team developed the Illinois RapidVent ventilator. The researchers designed the device so that manufacturers could rapidly produce it to address a potential ventilator shortage during the pandemic.

The scientists needed to test the device and wanted to use pigs as a model for human health. Dr. Matthew Wheeler, the professor in animal sciences, was a logical choice for the project. He has cross appointments in bioengineering and veterinary clinical medicine, and is experienced in the use of pigs in medical research.

"The pig is becoming more and more relied upon, not only to feed humans, but also to save human lives," Wheeler tells Better Pork. This ventilator testing serves as one recent example of that process.

This month, we connect with professors from Canada and the United States to learn why researchers use pigs to advance medical research. We explore how scientists manage pigs that researchers use in these studies. Finally, we review some medical advances made to date and consider what the future may hold.

Why use pigs?

Researchers began using pigs in medicine in the 1970s.

"I was director at the surgical lab at Johns Hopkins (School of Medicine) in the '80s and I taught surgery to medical students. At that time, they used dogs (to practice surgical methods). I decided to see if we could use pigs instead," Dr. Michael Swindle tells Better Pork.

He's an international leader in the use of swine as a human surgical model. He is a professor emeritus and he served as chair of the department of comparative medicine at the Medical University of South Carolina. He independently consults on the use of swine in biomedical research.

"Once they saw that it worked, the rest of the researchers involved in surgery labs (at Johns Hopkins) gradually made the switch from different species over to pigs," he says. However, some "companies and scientists were reluctant to change models because they had a lot of background working with dogs or primates."

Swindle and his colleagues published many articles and books about the use of pigs in medicine. In the early 1990s, the practice became more widespread in the North American scientific community.

In the late 1990s, the Food and Drug Administration (FDA) in the United States and the corresponding authority in the European Union announced they would accept data for new products from research conducted on pigs, Swindle says.

In Canada, Health Canada determines which animals are appropriate for pre-clinical studies. Pigs are included in the list of large animal models that scientists may use to help evaluate risks before conducting clinical trials on humans.

Once the FDA made its announcement, many scientists at pharmaceutical and medical companies transitioned to conducting research with pigs, Swindle adds.

"The pig is a great biomedical model. In a 200-pound (90-kilogram) pig, the heart, lungs and kidneys are pretty similar in size to a (155-lbs.) 70-kg human," Wheeler says.

Another benefit of using pigs in research is animal longevity, says Dr. Vilceu Bordignon. He's an associate professor in reproductive biology at McGill University in Montreal. Pigs "live longer than (traditional) laboratory animals," he says.

By using pigs instead of rodents, scientists can conduct "more translational research from fundamentals to clinical applications," he explains. Through translational research, scientists apply basic biology or medical science to developing devices and methods to address clinical needs.

"Pigs are a more representative animal model for testing new therapies," Bordignon says.

If a drug or device "works in a pig, there's a very high likelihood that the drug or device will work in humans," says Swindle.

Pigs' "DNA code is about 85 per cent analogous to humans," Wheeler says. Pigs and humans suffer from some of the same diseases, like the flu.

In contrast, the homology between a rodent and a human "tends to be less than 10 per cent," Swindle says. Homology refers to the similarity in chromosomal or internal structures between two species.

Breed selection

Dr. Dan Columbus has used a Yorkshire-Landrace cross-breed for his research because his studies mainly focus on early life. He's a nutrition research scientist at the Prairie Swine Centre in Saskatoon.

However, commercial breeds "are not acceptable for long-term projects because they grow so fast," Swindle says. "If you put a device into the blood vessels of a three-month-old farm pig and you go back and look three months later, the pig has quadrupled in size and, many times, the devices" have detached.

It's more expensive to work with and care for commercial pigs in biomedical research than mini pigs, Bordignon explains.

So, researchers conducting long-term studies will often use miniature pigs, Swindle says.

Bordignon typically uses Yucatan mini pigs for his research involving cloned and genetically modified animals. For example, he produced cloned pigs with altered genomes using somatic cell nuclear transfer. In this technique, a scientist develops a viable embryo by implanting the nucleus of a body cell into an egg cell.

Mini pigs grow to be about 176 to 198 lbs. (80 to 90 kg) and have fewer piglets per litter than commercial sows.

Yucatan sows have about six piglets in a good litter, Dr. Lee-Anne Huber says.

Huber is an assistant professor in the department of animal biosciences at the University of Guelph in Ontario. She uses Yucatan pigs to ensure nutritional studies are more relatable to humans.

The way "pigs digest nutrients and how they use those nutrients within their bodies is very similar to how humans do it," she says. But "commercial pigs are selected to be so efficient at using those nutrients for growth and they grow so quickly." As a result, they aren't the best option for comparison to humans.

Pig management

Researchers must source healthy pigs for biomedical research and care for them judiciously.

A "research project can be destroyed if you spend thousands of dollars to build a product and then the animal dies of pneumonia," Swindle says.

At the University of Illinois, for example, "we have a facility where we can do surgical work. We also have a really nice biomedical swine housing facility, where we can house these animals under National Institutes of Health guidelines for biomedical models," Wheeler says.

The housing is like an agricultural setting in terms of ventilation, temperature and humidity, though those variables are maintained in a tighter range in a biomedical research facility than in a typical pig barn, he says.

"Feed and watering are essentially identical" to commercial barns, he adds. The big difference is stocking density.

"If we're going to use a surgical model, … we have to house the pigs individually for a period of time," Wheeler says.

North of the border, the Canadian Council on Animal Care sets standards for the housing and management of animals involved in biomedical research.

Scientists will also conduct behavioural training on some pigs.

"We need the pigs to not be afraid of people," Swindle says. So, he trained pigs to use a sling or hammock restraining device.

"We do behavioral training in pigs as part of our effort to have animals which are free from distress when put into a new environment," he adds. "Our personnel work to bond with the pigs in a positive manner. The pig slings/hammocks are devices which give us the opportunity to humanely restrain" the animals.

Scientists view animal welfare to be of the utmost importance in their biomedical work. "We don't take these studies lightly," Wheeler says.

Surgery, devices and regenerative medicine

Scientists use pigs in many types of research.

"I did medical and surgical device work," Swindle says. He tested "catheters used to treat heart disease in children" as well as stents. A stent is a type of mesh that dilates blood vessels or helps to hold other hollow structures in the human body open.

Surgeons sometimes use pig heart valves instead of artificial valves for cardiothoracic implants in human patients. Pig valves are "most commonly used in very elderly people" who require valve replacement surgery, Swindle says.

While these valves deteriorate faster, patients don't have to take anticoagulants (also known as blood thinners), like patients with artificial valves do. Typically, whenever possible, doctors prefer to simplify daily medication regimes for seniors.

Scientists have also advanced regenerative medicine through research using pigs.

"We've used stem cells from bone marrow and adipose (fatty tissue) from pigs for almost 20 years to look at things such as bone and cartilage regeneration," Wheeler says.

Some newer devices tested in pigs are well on their way to saving human lives.

"We used the 3D printing model to develop a stent for the trachea as a model for a disease called tracheomalacia. This cartilage-storage disease in the trachea is responsible for about 70 per cent of SIDS deaths in humans," Wheeler says. SIDS (sudden infant death syndrome) occurs in seemingly healthy babies under one year of age.

That stent research is now in human clinical trials. Tracheomalacia is usually fatal by the time patients reach 12 months of age, but children in the trial are now five years of age or older.

"The pig data was instrumental in allowing the FDA to give permission to save those babies," Wheeler says.

He's also tested "3D-printed stents in the small intestine as a model for bowel rupture in humans … (and) several other scaffolding types of materials for large bone defects in human's cranial facial skeleton."

The team testing the RapidVent ventilator "decided, because of the COVID-19 crisis, to provide (designs, plans and animal testing results) freely to anyone who wanted them. … All (interested parties) had to do was sign a non-exclusive, royalty-free licence," Wheeler says. Since then, representatives from a company called Belkin have said that, pending FDA approval, the company will manufacture a product based on the RapidVent design. Belkin is an international technology company headquartered in Playa Vista, California.

Nutrition studies

Researchers also use pigs for nutritional intervention studies for early human life, as piglets and infants can face some of the same nutritional challenges.

Ethically, it is difficult to conduct research on infants because you can't obtain consent from them, says Columbus.

"The low-birthweight pig always grows slowly and it's the same with the human infant," he says. He tested nutritional interventions to better understand the growth and development of low-birthweight piglets, and implications for human infants.

Huber has also studied early-life nutrition. Her research, however, focused on premature infants who must be fed intravenously.

"We found infants who are born premature are more likely to develop metabolic disease when they are adults such as Type 2 diabetes, obesity and high blood pressure," she says. "The same thing would happen with pigs."

In her postdoctoral research at Memorial University of Newfoundland, she tested "different interventions to see if we could stop these pigs from developing the metabolic syndrome when they reach adulthood.

"The cool thing about using pigs as models is that they reach adulthood within a year," Huber says. "So, you get your answer within a year or so," as opposed to waiting 50 years for human clinical trials.

Though she focuses her research at the University of Guelph on commercial swine nutrition, she is also collaborating with doctors at the Hospital for Sick Children (SickKids) in Toronto.

"Sometimes human infants are born too early because of heart defects, which cause respiratory issues and the infants can't breathe on their own," Huber says. "In these scenarios, those infants need life-saving surgeries to fix the heart defects, but their hearts and the lungs aren't developed enough for the infants to survive surgery in the first place."

Doctors at SickKids are "developing an artificial placenta," she says. "It's a fluid-filled incubator," so these infants can get oxygen and nutrients through the umbilical cord, but not have to breathe. This incubator decreases stress on hearts and lungs until infants have matured enough to undergo surgery.

Doctors are testing this method using pigs.

"The fetal mini pigs that (doctors) use are the same size as these extremely premature infants. These animals give fetal surgeons the opportunity to ensure their techniques are 100 per cent perfect and that the system will work well before the surgeons would attempt to try something like that with a human," Huber explains.

Future directions

At the Prairie Swine Centre, experts in swine research collaborate with medical doctors and dentists to study things like sutures, dentistry, and wound healing, Columbus says. Innovation is ongoing.

"The last great frontier in pig research involves brain research," Swindle says. "The anatomy and physiology of the brain have many similarities to humans," so the animals could be useful in studying traumatic brain injuries and other neurological studies.

Pigs may continue to play an important role in treating or even preventing coronavirus in humans, because pork producers deal with different types of the virus all the time, Wheeler says.

"As we move forward with (studying) infectious diseases, I think the pig will be a great model. (The pig) will continue to be a model in regenerative medicine," he adds.

Researchers are conducting groundbreaking work on transplants and genetic editing, Wheeler says.

"When I started, we didn't have those tools," he added.

Researchers can use genetic engineering technologies, called genome editing, to edit specific genes in pigs. This technology allows scientists to "create a unique model for a disease that would not exist in nature," Bordignon explains.

This approach is useful "if you need to study a genetic condition that is important for humans," but doesn't exist in the animal you want to use to study the condition, he adds. Scientists can create cells and then animals with the condition, which allows researchers to study it and test interventions.

Scientists can only use genetic manipulation of pigs for research purposes in Canada; these animals cannot enter the food system, Bordignon says.

Genetic research in pigs allows scientists to "test new therapies and understand the pathogenesis of disease as well as xenotransplantation. Researchers aim to develop cells and tissues that would potentially be used in humans," he says. Xenotransplantation involves transplanting tissues or organs from one species to another, in this case from pigs to humans.

Human medicine and pork production

Although the connections between pigs used in biomedical research and the animals we raise in barns for pork may seem to be minimal, livestock management is critically important in both scenarios.

"I was born and raised on a pig farm," Huber says. "There are not too many pigs in Newfoundland, and there are not too many people who know how to raise pigs. We worked at the hospital and most people there had no idea how to handle pigs. So, that's what I brought to the table."

The ability to raise and handle pigs may be a skill set that becomes more in demand as biomedical research using a swine model increases.

"I think pork producers need to stay tuned," says Wheeler. "In the future, there may even be specialized facilities that produce pigs for organs, cells and tissues. … Those farms will have to be managed differently than the standard production farm, but the pork producer knows how to raise pigs better than anybody else.

"Hopefully some forward-thinking (farmers) will get engaged," he adds. BP