This is my first post of 2014, and it’s a story about chance and luck in biomedical research. Also, it’s a story about pigs. Not little piggies that went to market or little piggies that made roast beef, but piggies that once saved the life of shipwrecked sailors and today could help the lives of people with type I diabetes.
The story starts a long time ago, back in the 1800s, in a remote part of the world, somewhere in the Pacific Ocean between New Zealand and Antartica, in a place called Auckland Island. It’s a part of the world, which in those days was excellent territory for whaling and sealing, and which was quite close to the major sailing route from Europe to Australasia. However, with all that traffic, shipwrecks were also not uncommon. Therefore, to provide a relief food source for victims who might become stranded on Auckland Island a bunch of pigs were released on the island. The pigs thrived, establishing a large population of mixed origin. Later, as whaling and sealing became less common and the shipping routes changed, Auckland Island became increasingly isolated and the pigs almost forgotten.
Then, by the late 20th century priorities changed, and the Auckland Islands became recognized as a UNESCO World Heritage site, for it’s “biodiversity, wildlife population densities and […] the large number and diversity of pelagic seabirds and penguins that nest there”. However, the pigs were eating the native vegetation and endangering the endemic ground-nesting birds, so the New Zealand Department of Conservation decided to remove them from the island. Luckily, during their extended period of isolation, the pigs had developed a range of traits that set them apart from other New Zealand pigs. Therefore the New Zealand Rare Breeds Society arranged for a rescue plan before they were eradicated, and in 1999 17 pigs, including several pregnant sows, were captured and taken back back to the mainland, where they were taken in by the city of Invercargill.
Meanwhile, biomedical researchers had become interested in pigs for a completely different reason. Years of research had revealed that type I diabetes was an autoimmune disorder, caused by the destruction of insulin-producing beta-cells in pancreatic islets, which results in a lack of insulin in the blood. By and large the disease can be controlled by regularly supplementing insulin with injections, but for some severe cases this is complicated. As an alternative, researchers started looking into the option of implanting healthy beta-cells from piglets (since it would be difficult to obtain sufficient transplantable material of human origin) into sick people, to produce the necessary insulin in situ. However, as research progressed, they discovered that using pig islet cells is not straightforward, because there’s potential danger of transmitting porcine viruses (such as swine Hepatitis E virus or porcine cytomegalovirus, for example summarised here and here) from the transplanted cells to humans. The risk of transmission is further increased, because transplant recipients are generally on immunosuppressant drugs to avoid rejection of the foreign cells by the human immune system. And since practically all pig herds world-wide are infected with these viruses, things looked rather bleak for the transplantation efforts.
But then, in an unexpected turn of events, it was discovered that the Auckland Island pigs that had been so valiantly rescued by the Rare Breeds Society, are free of almost all pathogens that modern herds carry, because they had been living in isolation for so long. Thus, Living Cell Technologies (LCT), a company involved in such transplantation development*, was able to start clinical trials using islet cells from Auckland Island piglets. The trials, conducted with patients from Russia, Argentina and New Zealand, assess(ed) safety, dosage and efficacy of the treatment. So far, the results look promising, according to information from the company and from a single patient.
I cannot assess how successful this approach will be in the long run. However, it is fascinating how random events have come together so fortuitously. Actions more than 200 years ago, when noone even knew what caused diabetes, or how it could be cured, have contributed to medical advances today**. Sometimes, luck can be on your side. Let this be an inspiration for the new year!
This post was inspired by this video by David White and Paul Wedel of White Balance Pictures, which not only tells the recent story of these pigs, but also shows some wonderful pictures of them.
* While LCT has clearly been a forerunner in the field, they are by no means the only company working on the transplantation of porcine cells. However, their use of the Auckland Island pigs is unique, and they have invested a lot into maintaining a pathogen-free herd. They have built animal care facilities, where the herds are now housed under strict biosecurity measures: no pigs are allowed within 10km of the facility, animal caretakers are not allowed contact with pigs or rodents, and the facility itself is also kept competely clean. The air that goes in is filtered, water, food and other goods are sterilised before they can enter, and all staff has to shower in and change clothes when they go in. In addition, LCT has developed a method of encapsulating the pig cells in alginate, a substance from algae. This substance can let nutrients in and insulin out of the islet cells, but it blocks the human immune system from “seeing” the pig cells. This means that less immunosuppressants are needed.
** Again, this is not to say that xenotransplantation from pigs would not have proceeded without the Auckland Island pigs. There are other ways of generating pathogen-free herds, as pursued by the Spring Point Project in the US, for example. It’s just that the availability of the Auckland Island pigs has largely facilitated developments.