This week’s Science Corner will focus on xenotransplantation, a procedure that involves transplanting live cells, tissues or organs from a nonhuman animal source into a human recipient. Science has been looking into xenotransplantation as a solution to our shortage of organs available for donation for many years, as the demand for organs continues to exceed their supply. While animal advocates may already object to the animal suffering and loss of life associated with xenotransplantation, I would like to discuss the significant scientific challenges that surround xenotransplantation and a solution to our organ shortage problem that does not involve harming animals.
The trend in research has emphasized the pig as the preferred animal source for organ transplantation for a number of reasons, including the suitable size of its organs and the fact that genetic modification of this species has been done for years. However, there are also several problems with using the organs from a pig in xenotransplantation, one of the most important being the human immune system is designed to attack anything it deems as “foreign”- including pig organs. The immune system carefully distinguishes between its own cells, tissues, and organs and those that are “nonself,” and protects the body by eliciting immune responses against the entities it deems as foreign. Pig organs carry many biological signals that indicate that they are foreign to the human body and are an easy target for attack by the immune system. The immune system has several different types of immune responses it can elicit, and all of them are activated in the presence of xenotransplants. While many of the molecules known to activate an immune response in xenotransplantation have been identified and have served as targets for genetic modification in pigs, it is unclear to scientists how many genes and which combination of them would need to be altered to prevent immunological difficulties. The genetic modifications attempted in the pig thus far have been unsuccessful at overcoming this barrier. Researchers have found that when they “solve” a problem through genetic modification, that the immune system will use another mechanism of rejection to attack the foreign tissue, creating more problems for the researchers to solve, and harming more animals in the process.
Even with genetic manipulation, immunosuppressive drugs would still need to be administered to organ recipients to slow the immune reactions responsible for rejection. This procedure itself has complications, including making patients more susceptible to infections or malignant disease. This creates a problem, because another significant risk of xenotransplantation is the possibility of transmitting infectious agents to organ recipients, which may not only harm the organ recipient, but can potentially spread to the general population.
Another critical question to address is how well would a pig organ function in a human recipient? With regards to liver transplantation, it is known that the liver makes over 2000 different proteins, and it is very possible that the products of a pig liver will not function properly in another species. Can the difference in pig and human lifespan affect the organ used in donation? The natural lifespan of a pig is only about fifteen years, and the process of ageing in xenotransplanted organs remains elusive. How about the difference in body temperatures between pigs and humans? The body temperature of a pig is about 39 degrees Celsius, 2 degrees higher than the human body. Biochemistry indicates that temperature plays an important role in enzyme function, and the functional implications of this temperature change between pigs and humans is unclear.
Many scientific challenges stand in the way of xenotransplantation as a solution for the organ shortage problem. But what are other alternatives? I’m sure you’ve heard a lot about stem cells and their potential in tissue replacement. The use of stem cells is a double-edged sword though, because while stem cells have the potential to be manipulated to grow into specific tissue types, scientists will inevitably carry out many of these experiments in animal models. And the use of stem cells for the generation of whole organs is still a long way from the clinic. The best solution we have is to increase the number of organs available through cadaveric donation. One controversial approach, but an effective one, would be to use the “presumed consent” system, where an individual who doesn’t want to be an organ donor would have to “opt out” by entering their name on a national registry. Otherwise, their organs could be used for transplantation, dramatically increasing the number of organs available for donation. This approach would be safer and more effective than xenotransplantation and would spare human and animal suffering at the same time.
What are your thoughts on this issue? I’d love to hear from you! Email me at firstname.lastname@example.org
Genetic Alterations in Pig Tissue May Allow for Human Transplantation
For more information see: Science Daily
Pigs could grow human organs in stem cell breakthrough
For more information see: The Telegraph