By Calvin J.
Despite how uncomfortable it may sound, the idea of growing human organs in pigs isn’t new. Scientists, ethicists and science fiction writers alike, have long been grappling with the concept of using animal hosts as a means of filling in a growing organ shortage. According to the US Department of Health and Human Services, the US alone is struggling to find appropriate organ donors for over 119,000 individuals currently on their national transplant waiting list. With the list growing annually, over a dozen individuals die each day waiting for a potential transplant.
Fortunately, science has long been working on potential solutions. Using stem cells, or cells that can develop into any other cell type in the body, researchers have been looking at new ways to grow human organs in the lab. In 2013, Japanese researchers took the world by storm, when they created a proto-liver from adult skin cells. A truly eerie moment in history when science fiction met reality. The scientists utilized chemical and electrical methods to shock adult skin cells back into a stem cell like state. They then tricked the naïve skin cells into thinking they were liver cells, before mixing them in a petri-dish with a combination of blood cells and other connective tissue. All in the hopes of encouraging them to develop into a 3-dimensional human organ. The team was blown away days later, when cells on the dish actually began to group together into miniature functioning liver buds. However, the groundbreaking work was still far from clinical use, as the livers were too small, and missing major component parts such as ducts needed for transporting waste. Growing complex 3-dimensional human organs in flat 2-dimensional petri-dishes have always been challenging, as they lack the proper biological environment needed for complete organ development. This has led other research groups such as the Belmont lab at the Salk Institute to take their work out of petri-dishes entirely. Instead, they’ve been moving their work into the womb, investigating the potential of growing human organs inside animal hosts.
In a recent paper published in the scientific journal, Cell, the Belmont research group took stem cell biology into an eerie new direction when they generated what scientists call, “interspecies chimeras”. Chimeras are essentially animal hybrids, organisms that contain cells from 2 different species. By injecting human stem cells into developing pig embryos prior to placing them back inside the pig’s womb, the researchers found that the human cells could divide and grow into human embryonic tissue within 4-5 weeks. The cells primarily clustered into simple muscle tissue, early organs, as well as in the spinal cord. The breakthrough in this field took over 4 years of work, requiring over 1,500 pig embryos, and stem cells from over 40 human individuals. Despite the costly investment, the lab is determined to forge ahead, looking to now guide the human stem cells into developing human organs inside the pigs.
While the research has indeed been a huge step forward in the field of stem cell research, their recent breakthrough has prompted numerous ethical questions. While this recent study sacrificed the developing embryos at 4-5 weeks, many researchers have wondered whether at full term, the fetus may begin to exhibit human like traits. Could the incorporation of human cells into an animal brain or other limbs, alter the consciousness and characteristics of the animals themselves? In the researcher’s initial study, they found no evidence of human cells in the brain. And with less than 1 human cell per every 100,000 pig cell (~0.001%), most human cells were rapidly outcompeted. Meaning that the likelihood of having a pig develop any sort of human-like features is essentially non-existent. Nonetheless, the researchers aim to develop new safeguards to prevent the migration of human cells into the brain and nervous system of their animal host.
One of the major ethical boundaries this type of research must tackle, are those regarding the treatment of the animals themselves. This includes both the animals producing these embryos, the animals carrying the embryos and, of course, the actual embryos. What boundaries must be put in place to protect their well-being, and can any of these chimeric experiments be done ethically at all? Just late last year the US National Institute of Health collected public comments on the use of human stem cells in research, specifically in the development of human-animal chimeras. (Comments have now closed). Depending on results, both policies and funding may change for many researchers working in this field. However, the facts remain, dozens of individuals die each day while waiting on the organ transplant list, and the numbers only continuing to rise. However uncomfortable it may seem, is continued research into this field the right choice for humanity?
Takebe, T. et al. Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature. 499, 481-484 (2013) http://www.nature.com/nature/journal/v499/n7459/full/nature12271.html
Wu, J. et al. Interspecies Chimerism with Mammalian Pluripotent Stem Cells. Cell. 168:3, 473–486 (2017)
Bouret, R. et al. Human–animal chimeras: ethical issues about farming chimeric animals bearing human organs. 7:87 (2016)