Use of Animals for Human Organ Transplant Hannah Johnson and Dr. Consuelo Alvarez Honors enhancement, Genetics, Biology 324-01 Abstract methods Results (graphical analysis) Literature Search Greenwood Library academic journal database Web of Science Survey IRB survey permission Surveyed students at the Greenwood Library and the Student Union Chimera Procedure The purpose of this project is to highlight the connections that exist between Genetics and animal research as a tool to gain more knowledge about using animals for future human organ transplant studies. The interactions between humans and animals are so diverse from social to therapeutically and to research. Since there is a great shortage of organs needed for human transplants, preliminary research shows that experiments are being done by using animal organs for human transplants as well as inserting human stem cells into animal embryos for them to then develop human organs. In order to determine how these trials work, a variety of literature databases were searched for evidence of these experiments and its results. Also a survey was developed to see if college students were aware of this animal experimentation and if they agreed with it. The survey results showed that majority of participants would accept an animal organ transplant and ethically agree with animal experiments for medical research. The future of animal organ transplants needs time and resources to increase the availability of human transplant organs. Figure 2. This figure explores the different options that the survey participants came up with pertaining to what animal would be their preferred donor choice. How gene editing could allow human organs to grow in pigs? Figure 3. This figure combines the survey questions three and four relating to the ethical questioning of using animals for medical research and experiments. 1. A day-old pig embryo is gene edited to delete the part of its DNA that would allow it to grow a pancreas. Introduction 2. Human stem cells are injected into the embryo. They should fill the gap and allow it to grow a human pancreas. A major world health issue, affecting individual’s ethical, religious, and social beliefs, is a lack of availability of transplant organs and tissues for those in need. There have been many ideas of alternate solutions to accommodate those patients in need of an organ transplant like the introduction of Xenotransplantation in 1997 by the World Health Organization (WHO). In the United States, twenty two people die every day who were on the waiting list to get an organ transplant. A very controversial question is then wondered: how far is one willing to go to save the life of someone in need of an organ transplant? The main concern with Xenotransplantation was regarding the spread of animal infectious diseases and the uncertainty of knowing how the agents that cause these infectious diseases (retroviruses) could affect the organs and the patients. However, there is an advancement in genetic engineering that looks at the process of removing the retroviruses by CRISPR gene editing from potential donor animals that could be used for transplantation (Walsh 2016). With this system of gene editing, there is research experimenting with editing the genes of animals to potentially be human organ donors. Large Animal Models There are two options of large animal models that have been considered as transplant donors. Non-human primates and pigs (Swine) have shown to possess the most similarities to humans. The non-human primates that are tested on include spider monkeys, owl monkeys, squirrel monkeys, macaques, baboons, marmosets, and chimpanzees. Phylogenetically, non-human primates seem to be the most ideal choice as donors because they have the most similar DNA sequences to humans (WHO 1997). However, using non-human primates is very discouraged as there is not a lot of knowledge about their diseases, possibly causing transmission risks. The cost of the care it would take to treat these animals, as well as the conservation issues, makes them unsuitable to be a donor transplantation option without further studies. 3. The embryo is implanted into the sow and allowed to develop to 28 days. Figure 4. This figure shows the survey participants who are registered organ donors and who are not. 4. It is hoped that the resulting pig fetus will have a human pancreas. The same technique could be used to grow other human organs. conclusions Figure 1. This figure shows the general process of how researchers plan to experiment implanting human stem cells in a pig embryo to produce human organs (Walsh 2016-BBC). The survey results showed that whether the participant was comfortable accepting an organ from an animal or not, the two top preferred choices were pigs and primates confirming the findings of the literature review. Students are aware of what could possibly be a realistic choice, but there are still the ethical issues behind it all. Once the iPS cells were created, there was no need to try to overcome the ethical issues of using human embryos; but, now comes the ethical issues of using human stem cells and putting them in animal embryos where they are not supposed to go just to help humans (Ravven 2107). Many trials need to be taken because although the animals being tested on are young and healthy, the conditions of the ill patients all vary with different diseases along with different medications used (Harding 2013). Time, money, and an ethical consensus is needed to further the stem cell treatments and research. Results (survey) Freshmen Sophomore Junior Senior Total 3 13 18 16 50 Non-Science majors Science major 23 27 On the contrary, pigs now seem to be the best option due to their similar organ size and structure compared to humans. There is also an abundant amount of knowledge about their diseases which allows scientists to be able to remove such diseases from the DNA prior to transplant (WHO 1997). Currently, pigs are already used as stem cell test models for spinal cord injuries, cystic fibrosis, and retinis pigmentosa (Harding et al. 2013). Furthermore, pigs will be investigated as the best option to develop an alternate source for the need of human organ transplantations. Q1. Would you feel comfortable accepting an organ transplant from an animal? Yes No 27 23 References Q2. What animal would be your preferred choice of donor? Harding, J., R.M. Roberts, and O. Mirochnitchenko. 2013. Large animal models for stem cell therapy. Stem Cell Research and Therapy 4:23. Ravven, Wallace. “The Stem-Cell Revolution Is Coming — Slowly”. The New York Timews, 16 January 2017, https://www.nytimes.com/2017/01/16/science/shinya-yamanaka-stem-cells.html?_r=0. Accessed 29 March 2017. Walsh, Fergus. “US bid to grow human organs for transplant inside pigs”. BBC, 6 June 2016, http://www.bbc.com/news/health-36437428. Accessed 29 March 2017. World Health Organization (WHO). 1997. Report of WHO Consultation on Xenotransplantation. Geneva, Switzerland, 28-30 October 1997. Retrieved from World Health Organization Website:http://apps.who.int/iris/bitstream/10665/65513/1/WHO_EMC_ZOO_98.2.pdf No answer Pig Primate Buffalo Cow Horse 12 16 17 1 3 Q3. Do you agree with animal experiments done for medical research? Yes No 34 16 Creating a Chimera An upcoming idea that many scientists are exploring is the process of inserting human stem cells in the embryo of an animal which then will start the development of human organs to then be used as organ transplants. This idea creates a chimera, which is the combination of these human-pig embryos, by using the CRISPR gene editing which removes the specific DNA sequences that enables the development of certain organs. Since these embryos are now missing a section of their DNA for a vital organ, scientists then place human induced Pluripotent Stem (iPS) cells in place of the missing DNA. This research is still being tested and modified to even be considered as a future organ donor option, but how do the ethical consequences of these techniques and the public knowledge of this research affect the outcome, is a question that still remains unanswered. Q4. Do you think it is ethical to insert stem cells into animals to develop human organs to later use them as donor organs? Yes No 29 21 Acknowledgements Q5. Are you a registered organ donor? Yes No 34 16 I would like to thank the Cormier Honors College. I would also like to thank Tammy Hines, Head of Collections & Information Services, at the Greenwood Library at Longwood University.