United Therapeutics and its subsidiary are operating a genetically modified pig facility to provide a source of transplantable organs to save many lives in the future.
The first genetically modified pig organs transplanted into humans come from animals born at a special research farm in the Blue Ridge Mountains. Behind locked doors, individuals entering must wash their vehicles, change clothing, and step into a disinfecting basin to clean their shoes between each climate-controlled pig pen. “These are precious animals,” said David Ayares of Revivicor Inc., who has spent decades attempting to clone pigs with genetic modifications suitable for the boldest experiments, according to Yahoo.
Biosecurity is even stricter just a few kilometers away in Christiansburg, Virginia, where a new herd of pigs is being raised. These pigs will supply organs for formal animal-to-human transplant research as early as next year. The unique and massive building resembles a pharmaceutical factory more than a farm. Carefully selected staff spend time showering, wearing company-provided clothing and footwear, before entering the pig nursery.
Piglets raised at United Therapeutics’ organ production facility. (Photo: United Therapeutics).
Behind the protective fence are some of the cleanest pigs in the world. They breathe air and drink purified water that has been filtered to a level exceeding what is required for humans. Even the pigs’ food is sterilized to prevent any pathogens that could harm the transplant recipients. “We designed this facility to protect the pigs from environmental and human contamination,” said Matthew VonEsch at United Therapeutics, the parent company of Revivicor. “Every person entering the building poses a potential disease risk.” The $75 million facility was constructed by Revivicor to meet the safety standards for xenotransplantation set by the U.S. Food and Drug Administration.
Thousands of Americans die each year while waiting for organ transplants. Many experts predict that there will never be enough organ donors to meet the demand. Animals have become a promising solution for a readily available organ supply. After decades of failures, several companies, including Revivicor, eGenesis, and Makana Therapeutics, are genetically modifying pigs to make them more human-like. To date, there have been four xenotransplantation trials in the U.S. involving critically ill patients, including two heart transplants and two kidney transplants. Revivicor provided both hearts and one kidney in these cases. Although all four patients died within months, the results provided valuable lessons for researchers testing on patients who are not yet critically ill.
Currently, the FDA is reviewing promising results from organ donation trials in humans and is awaiting results from other studies on pig organs in baboons before deciding on the next steps. These organs will be semi-customized. Ayares noted that they raise pigs to the size of the recipients. This organ source shows no signs of age or chronic disease, unlike most organs from human donors. Transplant surgeons have praised the organs from Revivicor’s farm as the most beautiful kidneys they have ever seen. “The same goes for when they received a healthy pink heart from a young animal,” Ayares recounted. The major challenge they face is finding ways to avoid rejection and whether the animal carries any unknown infection risks.
The process begins with gene editing in pig skin cells in the lab. Initially, Revivicor deletes a gene that produces the alpha-gal sugar, which triggers an immediate attack from the human immune system. Next, they deactivate three genes to eliminate other immune-triggering signals. Currently, the company is focusing on editing 10 genes, removing pig genes, and adding human genes to reduce the risk of rejection and blood clots while also limiting organ size. They clone pigs with these modifications, similar to how the famous sheep Dolly was created.
Twice a week, a slaughterhouse delivers hundreds of eggs harvested from the uterus of sows to Revivicor. Working in dim light with the sensitive eggs, scientists observe through microscopes while extracting DNA from the mother pig. They then introduce the genetic modifications. According to researcher Lori Sorrells, they must find the right spot without breaking the egg. A gentle electrical shock helps connect the new DNA and activates the embryo to develop.
Ayares, the molecular geneticist leading Revivicor and a contributor to the creation of the world’s first cloned pig in 2000, states that this technique requires one hand to hold the fixed egg while controlling it with the other. The company’s first genetically modified pig is now being bred rather than cloned. If xenotransplantation proves effective, other pigs with the desired gene combinations will be bred in the same manner. Hours later, the embryos are transferred to a research farm in hand-held incubators and implanted into waiting sows.
At the research farm, piglets are played music, including “Free Fallin'” by Tom Petty, to help them become accustomed to human voices. In temperature-controlled chambers, around 300 pigs of various ages are raised (the exact location of the farm is not disclosed for security reasons). Tags attached to their ears help identify their genetic profiles. A small group of pigs used for the most critical experiments is raised in a cleaner pen with more restricted access.
In the nearby town of Christiansburg, the most apparent sign that xenotransplantation is entering a new phase is the massive scale of United Therapeutics’ new pathogen-free facility. Within the 7,154 square meter building, the company hopes to produce around 125 pig organs annually, sufficient to supply clinical trials. In the company’s video, piglets can be seen frolicking behind protective fences, chewing on toys and rolling balls. They are born at a breeding center connected to the facility, weaned after 1-2 days, and transferred to ultra-clean pens for raising. In addition to on-site bathing facilities, staff must wear protective gear and masks before entering each pen to prevent pathogens.
The pig-rearing area is surrounded by a security system and machinery on all sides to protect the herd. Outside air passes through multiple filtration systems. Huge tanks hold backup supplies of drinking water. Above the pig pens, pipes and ventilation holes are installed to allow maintenance and repairs without coming into contact with the animals.
The clinical trial process will take years to demonstrate whether xenotransplantation truly works. However, if successful, United Therapeutics plans to build larger facilities capable of producing up to 2,000 organs annually in several locations across the country.
