This paper focuses on the use of CRISPR, a genetic engineering technology to allow for xenotransplantation between humans and pigs. Currently, there are not enough human organs to go around. Approximately 21 people in the US die each day waiting for organs and only 0.3% of people can be organ donors. This paper discusses how xenotransplantation can provide a solution to this as scientists have identified that pig organs show potential for xenotransplantation as they are a similar size to humans organs and easy to breed. Xenotransplantation is currently impossible because pig organs provoke massive immune responses in humans and introduce DNA sequences containing diseases that can be harmful to humans such as porcine endogenous retroviruses: PERVS. The immunosuppressant drugs that help limit the immune responses of the recipient in human organ transplants make human immune systems more susceptible to these PERVS. However, Scientists have successfully used CRISPR, a gene editing molecule, to edit out PERVs in embryos which resulted in piglets that exhibited no signs of PERVs. Using CRISPR means that xenotransplantation is become a greater possibility in the near future, but what ethical considerations will need to be investigated before pigs are bred for the sole purpose of killing them for human benefit? Do human lives weigh above the lives of animals? After discussing the science behind these technologies, this paper dives into the ethical implications discussing values including safety and privacy and investigating questions such as ‘are we playing God?’ and ‘do non-human animals have a moral standing and if so is it lower than a human moral standing?’
Not too long ago, organ transplants between humans were impossible and appeared to be science fiction. However, they have grown to become everyday procedures. Similarly to how human transplants seemed to go against all reason just a few decades ago, the idea of organ transplants between two different species seems futuristic, however, the reality is that these transplants could be a part of our near future. The question now is how will non-human animal organs affect a human body? This paper will focus on the use of CRISPR, a genetic engineering technology to allow for xenotransplantation or the transplantation of living cells, tissues and organs from one species to another.
Doctors and scientists first began to experiment with xenotransplantation, in the early 1900s. After all their trials failed, scientists started searching for answers. They discovered that the recipient’s immune system identifies donor organs and tissues as foreign and attacks them. This attack causes organ rejection and failure (“History of Xenotransplantation.”). Immunosuppressant drugs work to weaken the immune response generated when the body identifies a foreign body and they have proven to be successful for organ transplants among humans. However, there are not enough human organs to go around. There are approximately 120,000 people on the national waiting list for organs, 21 people nationwide die each day waiting for organs, and only 0.3% of people can donate all of their organs (Hansman). Xenotransplantation could provide a solution to this organ shortages. Scientists have identified that pig organs have potential for xenotransplantation as they are a similar size to human organs and easy to breed. Xenotransplantation is currently impossible because pig organs provoke massive immune responses in humans. It would also introduce deoxyribonucleic acid (DNA) sequences that contain diseases, such as porcine endogenous retroviruses (PERVS), which can be harmful to humans. Additionally, immunosuppressant drugs make the human immune system more susceptible to these PERVS (Firger). To combat this, scientists have successfully used CRISPR, a gene-editing molecule, to edit out PERVs in pig embryos which resulted in piglets that exhibited no signs of PERVs. Using CRISPR means that xenotransplantation has become a greater possibility for our near future. However, before it becomes a common practice one must consider whether human lives outweigh the lives of non-human animals as well as the ethical implications of breeding and genetically modifying pigs just to kill them simply for human benefit.
Among these considerations, this paper will investigate the implications of CRISPR and xenotransplantation on the pig, patient, and society, keeping the value of safety in mind. It will also discuss the question of whether the practice of engineering pigs is ‘playing God,’ and it will discuss the different arguments of whether or not non-human animals are deemed to have moral standing.
History of Human Transplants
While organ transplants between human donors may seem like a practice that has been around for many years, the reality is that the first successful human transplant only occurred in 1954. It was performed by Joseph Murray, an American plastic surgeon. Unlike most of the human organ transplants that occur today, the transplant Joseph Murray carried out was a kidney transplant between identical twins (“History of Xenotransplantation.”). This means that both the patient and the recipient had the same DNA and the same genome. Therefore, there was no need to suppress the recipient’s immune system as the new organ matched the DNA of the old one and the DNA throughout the rest of the patient’s body and therefore it was not perceived as a foreign body. This means that there was little to no chance of rejection, which is a main reason why this procedure was successful.
While this was a huge leap forward in the introduction of this technology, it did not mean that human transplants between non-identical donors and recipients was possible yet. Researchers and scientists still struggled to conduct successful transplants between donors who did not share the same genome. In order to do this they needed to discover why organs were being rejected. Through research and experimentation, they discovered that when an organ is transplanted, the new organ generates a massive immune response in the recipient’s immune system. This is because the immune system works to protect the body from disease-causing pathogens (viruses and bacteria) and a transplanted organ is seen as a foreign body. Thus an immune response is generated when a new organ is introduced into the body and this causes the patient to fall into organ rejection and transplant failure in one of three types: hyperacute, acute, or chronic rejection. Hyperacute rejection occurs when pre-existing antibodies in the immune system react with the donor tissue and it typically happens fast, occurring prior to the completion of the procedure. Acute rejection occurs as the immune system develops a response and can occur over the course of the first few weeks or even months after surgery. Lastly there is chronic rejection which can occur gradually, over the course of many years post surgery. In order to conduct successful transplants, researchers needed to develop a way to lower or eliminate the risk of rejection between patients and recipients.
In the 1960s, immunosuppressant drugs were discovered. These are a class of drugs that work to prevent transplant failures. When a patient receives an organ they are put on immunosuppressant drugs, which greatly lowers the risk of rejection in the recipient. These drugs work by suppressing the immune response that this new organ generates. The discovery of these drugs helped to make human organ transplants grow to become a common practice in hospitals around the world (“History of Xenotransplantation.”).
The shift from human to human organ transplants to research on xenotransplantation is significant because this process would allow surgeons to have access to a whole new body of organs that could save hundreds of thousands of lives. Xenotransplantation occurs when living cells, tissues or organs from one species are transplanted into another. Research and many different types of experiments have taken place, ranging from attempts to xenotransplant full organs to simply the xenotransplantation of skin and heart valves. The first experiments with xenotransplantation took place in the early 1900s, which was even prior to the first successful human organ transplant. During this time, scientists attempted to utilize organs coming from pigs, goats, lambs, and monkeys to substitute failing human organs, however, these trials were unsuccessful. The first great successes with xenotransplantation came much later, in 1978, when doctors used porcine skin to treat burns on humans. The patients who received porcine skin experience faster recovery times, and less pain than patients felt undergoing the standard procedure. Other studies followed including one where mouse pancreases were grown inside of rats. Once grown, these pancreases were transplanted successfully into rats who had diabetes and the new pancreases reversed their disease (New Scientist). Additionally, the use of pig heart valves as a replacement for mechanical heart valves in humans has been practiced for approximately the past twenty years. These pig valves are very similar in structure and function to human heart valves which is what makes this procedure possible. The procedure has provided many advantageous factors including that the patient is not required to be on blood thinners and the pig valves do not make the same clicking noise that many of the mechanical ones produce. The downsides to this procedure include that the valves are temporary. Statistics have shown that 95% of people who receive mechanical valves will not need repairs after ten years and those statistics are similar after twenty years. This means that the vast majority of patients will not need to replace mechanical valves within twenty years. However, the average lifespan of a pig is only about ten to fifteen years. As a result, many younger patients question whether the pig valves are durable enough. However the success of this procedure among the others listed proves that humans can sustain tissues from pigs, which is encouraging for future advances with xenotransplantation (Pick).
To summarize, ever since 1954 organ transplants have been performed. However, after the discovery of immunosuppressant drugs, which are drugs that work to suppress the body’s immune system and immune response, organ transplants between humans became increasingly more common. These drugs help to limit the immune response that is generated by a recipient’s body when a foreign organ is transplanted into them and, in turn, these drugs lower the risk of rejection between human donors. Next, researchers began experimenting with xenotransplantation, or the transplantation of living cells and tissues from one species into another. Whole organs have yet to be successfully transplanted from a donor species into humans, however pig skin has been used to treat human burn victims, and pig heart valves have been transplanted successfully into humans.
Science Behind Xenotransplantation and CRISPR
The genetic engineering technology known as Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) is a technique that allows scientists to manipulate the function of a gene. It was first discovered in 1993 and it was first successfully used for genome editing in January of 2013.
This system is based off of a process that was discovered to exist in bacterium and simpler life forms. This process was initially identified in E.Coli. When a bacterium detects viral DNA, it produces two types of short ribonucleic acid (RNA) (one of which contains a sequence that matches the DNA of the invading virus). The two RNAs then form a complex with a protein called Cas9, which is a nuclease or a protein that cuts DNA. Essentially, Cas9 proteins are molecular scissors. When the matching sequence (guide RNA) finds its target in the viral genome, it cuts the target DNA and disables the virus (Kirkpatrick).
The CRISPR system is based off of this technique that is utilized by simpler life forms. This system works by relying on a guide molecule known as RNA, and an enzyme which in this case is Cas9. One end of the CRISPR molecule is the guide RNA and it binds to the target sequence. Then the Cas9 enzyme binds to the guide RNA and cuts both strands of the DNA double helix. By using a mutation, the cut is repaired and the original sequence can either be fully deleted or mutated (Harvard)
This diagram helps to illustrate how the CRISPR system works. As shown, the guide molecule first gets coded to replicate the target DNA sequence, or the DNA sequence that someone wants to delete or modify. Next the Cas9 nuclease forms a complex with the guide RNA and the complex is then transported to the DNA that the guide RNA identifies as the target. Once the guide RNA has brought the Cas9 to the target, Cas9 latches onto the DNA strand and cuts both strands of the double helix. This cut is followed by either a mutation or a DNA insertion that fixes the cuts by replacing the DNA with a new code.
This technology can make a multitude of incredible procedures possible. Some of these possibilities include that CRISPR can be used to remove malaria from mosquitoes. In a clinical study in 2015, scientists were able to use CRISPR to replace a segment of DNA within the mosquito’s genome in order to make them resistant to Plasmodium falciparum, the malaria causing parasite. There are two genes that code for this parasite and CRISPR was able to eliminate both of them. The altered mosquitoes passed their resistance onto their offspring 99% of the time (Kirkpatrick).
Additionally, CRISPR may be used to treat muscular dystrophy. This is a disease caused by a mutation in the genome that prevents someone’s body from producing the dystrophin protein that is essential to the development of muscle tissue. This disease is ultimately fatal and CRISPR has been used successfully by researchers testing on mice who were able to cut and repair the dystrophin gene.
Other possibilities for CRISPR include the use of the technology to cause non-human animals such as goats and dogs to grow more wool in order to promote a country’s wool and meat industries. To do so, scientists used CRISPR to remove genes that were identified to prevent muscle and hair growth (Bennett). CRISPR can also be used to treat diseases such as HIV which inserts DNA into the genome of a host. CRISPR can be used to remove the viral DNA from the host’s genome that causes these viral infections which are otherwise incurable (Bennett). Amazingly, CRISPR may even have the potential to treat or cure blindness. Researchers have successfully removed a genetic mutation in mice that causes a disease known as retinitis pigmentosa. This is a disease that leads to blindness. After one injection of CRISPR the mice experienced improved vision and there are plans to use a similar procedure on humans (Bennett). It is important to consider all the possibilities that come along with this technology as the use of CRISPR to make xenotransplantation possible could increase the familiarity and acceptability of the technology. In turn, this could lead society to be more comfortable using CRISPR for other procedures and practices including the ones listed above, as well as a multitude of others, which could impact society in either a harmful or beneficial way.
As mentioned, there are many uses for CRISPR, however this paper will focus solely on the use of CRISPR to allow for xenotransplantation in order to delve into the ethics related to this specific use of the technology. So how can CRISPR be used to make xenotransplantation possible? Before answering this question, it is important to understand a few of the conditions that make xenotransplantation currently impossible.
The non-human animal that has been identified as the best possible candidate for xenotransplantation with humans is the pig. This is because pigs have similar sized organs to humans and are relatively easy to breed. Additionally, the successful use of pig heart valves in humans has already drawn connections between pigs and humans and has proven that it’s possible for humans to sustain tissues from pigs (Hansman).
The xenotransplantation of full organs requires more aspects to be considered than the xenotransplantation of heart valves as it is a more complex procedure. One main reason that has made xenotransplantation impossible is the fact that pigs contain porcine endogenous retroviruses (PERVs) in their genome. Retroviruses are viruses that carry their genetic codes in RNA and transcribe them into DNA. This process is the reverse of the typical transcription process that takes place in humans which goes from DNA to RNA. This reversal means that it is possible for retrovirus genes to infect cells and become permanently incorporated into the cells’ genomes.
If organs containing these viruses are transplanted into humans, the retroviruses are capable of transmitting diseases including cancers into humans. Therefore, the presence of these PERVs mean, as of now, porcine organs cannot be safely transplanted into humans. Especially since the patient’s immune system would be suppressed due to immunosuppressive “anti-rejection” drugs that work to help prevent the patient from rejecting the organ but in turn, increase the susceptibility of the patient’s body to infections.
Scientists have identified CRISPR as a solution to this dilemma. Since the CRISPR technology allows a genome to be cut at any precise location, it has been proven to be able to deactivate the family of retroviruses (PERVs) within the pig’s genome. Researchers and scientists George Church and Luhan Yang suspected that CRISPR had this capability and in 2015 funded eGenesis, a company focused on engineering transplantable organs (Scutti).
Through their study, Church and Yang proved that CRISPR can be used to eliminate PERV genes at all 62 possible sites on the pig’s genome. To conduct this study, the scientists first took typical pig cells that came straight from a pig’s genome and were derived from the connective tissue, which is tissue that connects, binds, supports, or separates organs and other tissues of fetal, or unborn, pigs. They applied the CRISPR technology to these cells. Initially these cells proved to be fragile when subjected to the CRISPR technology: they failed to grow normally due to DNA, which may have been damaged during the editing process. The damaged DNA prompted the cells to stop dividing or to self-destruct. To combat this, scientists added a “chemical cocktail” which contained chemicals that encourage growth and suppressed growth-suppressing genes. As a result, the team’s success rate soared to 100% of cells being PERV-free in the dish.
The next step for the scientists was to turn these fetal cells into embryos and then into piglets. In order to do so, scientists used a cloning technique. First, the DNA-containing nuclei of the edited pig cells were planted into pig egg cells coming from a slaughterhouse. The scientists then allowed the individual eggs to develop and grow into an embryo. Once the cells became embryos, each was implanted in the uterus of a surrogate pig.
This technique was successful in producing living and seemingly healthy piglets. This process has the same success rate as the cloning method has without genetic modification: about 1 per 100 implanted embryos. Researchers tested tissues of the piglets that were created and found that of the 37 piglets born thus far, 100% of them appear to be PERV-free (Firger). This is significant as it proves that healthy pigs can be produced when CRISPR is used. For someone arguing that xenotransplantation is justifiable so long as the pigs are kept under good conditions and do not suffer, this would be a significant factor to their position. The fact that this produced pigs that are healthy and in good condition would mean that someone taking this stance may be inclined to deem this procedure justifiable.
A second study conducted by Tector (a transplant surgeon) used CRISPR to create a “triple-knockout pig.” These pigs are engineered without three genes, one of them being alha-gel, that are involved in creating molecules that provoke the human immune system to fall into hyperacute organ rejection. Tector believes that these engineered pig organs will have success in preventing hyperacute rejection in 30% of all people so long as they take the same immunosuppressant drugs that they would have if they were receiving a human organ transplant (Zhang).
To summarize, there is currently a need for organs that is greater than the amount of human organs available. Thus we must look to another source for organs. This is where xenotransplantation comes in. Pigs have been identified as good candidates for xenotransplantation because they have similarly sized organs to humans and they are easy to bread. However, before pigs can be used for xenotransplantation, the Porcine Endogenous Retroviruses in their genome must be eliminated because they can prove to be very harmful to humans as it is possible for them to incorporate themselves in the human genome. Using CRISPR, scientists were able to deactivate the PERVs at all 62 possible sites in the pig’s genome. Scientists used CRISPR in conjunction with growth-encouraging chemicals to create 100% PERV-free pig cells. Next, scientists used a cloning technique to turn these cells into piglets. Through this process, 32 PERV-free piglets were born. These piglets are healthy which proves that the PERVs in their genome were not essential to the health of the pig. Another researcher who has created the “triple-knockout pig” believes that he has eliminated the genes that enable the creation of molecules which provoke the human immune system to go into hyperacute rejection. He believes that these pigs will be successful in preventing hyperacute rejection in 30% of patients.
“Just because we can, doesn’t mean we should,” Dr. Rezach. Like any new medical technology or procedure, these new techniques present ethical dilemmas that must be considered. The main ethical value that will be explored in this paper is safety. While considering this technology, there are many advantages reflected in the need for a technology like this as well as disadvantages or concerns. Consider this scenario: a patient has weeks, days, or even hours to live, and a porcine organ will save their life. Firstly, a discussion of the stakeholders in this situation will help unpack this dilemma. The stakeholders include at least the family of the patient, the patient or potential recipient of the organ, the doctor or surgeon performing the procedure, the pigs, and society/the human race. If the patient decides not to receive the organ, they will pass away which will cause emotional distress on the family, especially if they think that there was something they could have done to save the life of their loved one. On the contrary, if the patient decides to receive the organ, their family will not have to undergo the emotional trauma of losing their loved one; however, they may take on the responsibility of caring for their loved ones after undergoing this kind of a procedure. The patient is a stakeholder because whether they accept or deny the organ, it impacts their body and the way they feel. If they accept the organ, they must live with a porcine organ, and if they do not accept the new organ, they will pass away. The doctors are stakeholders; if the patient refuses the procedure and passes away they may feel guilty knowing that they didn’t try everything they could to save their patient and if they carry out the procedure, they are responsible for its success or failure. The pigs in relation to non-human animal cruelty are also stakeholders. They are giving up their organs in order to save humans and if they are treated cruelly throughout their lives and undergo a painful process of being put down, they will be undergoing unnecessary trauma and may have a lower quality of life than a pig who is not undergoing this procedure. The human race is a stakeholder because if this procedure becomes common practice, there is a potential for the recipient of the organ to introduce new diseases into the human race via an infection from the organ that can spread to other human beings. While all these stakeholders are incredibly important to this scenario, this paper will focus mainly on the impact to non-human animals. It seems that in order to justify this procedure the main hurdle philosophers, researchers, and scientists must overcome is to deem this justifiable to practice on a non-human animal. If this is not the case and this procedure is deemed unethical for the non-human animals involved, it should not come into practice. Additionally, there are a multitude of aspects to consider with the discussion of non-human animals as opposed to many of the other stakeholders as this procedure is directly manipulating their DNA and resulting in their deaths without their consent. Therefore, I believe that it is vital to allocate a lot of time to discuss the threats this procedure poses to non-human animals in more depth than the threats it poses to other stakeholders. However, this paper will also mention some of the prevalent concerns pertaining to the other stakeholders as they are still significant in this scenario.
Some of the advantages of the technology are rooted in the benefits they provide by solving the dilemma of a lack of organs. Currently, the demand for organs far exceeds the availability of organs. For example: across the world, approximately 2.8 million patients are undergoing dialysis, which is a substitute procedure for the functions of the kidney, however only 73,000 kidney transplants are performed annually. Other statistics include that in the United States alone, approximately 120,000 people are on the national organ transplant list but only 33,611 transplants were performed in 2016. This expresses that there is a much greater need for organs than what is being met. Approximately twenty people die each day waiting for organs, and every ten minutes another person is added to the national waiting list. One of the main reasons for the lack of organs is that only 3 in 1,000 people or 0.3% of people die of brain death which is the cause of death that makes them able to donate all their organs. A person who dies of brain death is able to donate eight life saving organs as well as other organs and tissues. Thus, they are able to save eight lives through donations of organs and improve the quality of life for over fifty people through donation of tissues. However, only 0.3% of people are able to donate all of their organs and of those people, 95% support organ donation but only 54% are signed up to be donors. If you multiply the percent of people who are able to donate all their organs by the percent of people who are signed up to and willing to (0.3% 54%) you get the percentage of people who are willing and able to donate all their organs: 0.16% or 1.6 people out of 1,000 (Hansman).
(Organ Donation Statistics)
This visual helps demonstrate the amount of donors vs. the number of transplants vs. the number of patients on the waiting list. This graphic portrays in a tangible way the lack of organ donors available to satisfy the people on the waiting list. As you can see, the number of organs donated has remained relatively steady throughout the past 25 years, however there was a huge increase in the number of patients on the waiting list. One reason for this could be that patients are increasingly comfortable with the idea of organ transplants now than they were in the early 1990s when organ transplants were still a relatively new practice. By using CRISPR to allow for xenotransplantation, these statistics would be drastically impacted. People would have access to either a human or porcine organ and this procedure would help save hundreds of thousands of lives.
One important value to consider in order to answer the posed questions ‘what ethical considerations will need to be investigated before pigs are bred for the sole purpose of killing them for human benefit? And do human lives weigh above the lives of non-human animals?’ is safety. Safety pertains mainly to the stakeholders of the patient, non-human animal, and society when considering this procedure.
Regarding humans and specifically the patient, a main concern with xenotransplantation is safety specifically in regards to the accuracy of the CRISPR technology. CRISPR is still a developing technology, and thus it is far from perfect. One prevalent issue is the off-target effects, or mistakes in the application of CRISPR. While many cases such as a study that used CRISPR to target the genes of three monkey simultaneously and a study that used CRISPR to target the dystrophin gene show no off target effects, some studies, such as a study that targeted human tripronuclear zygotes (zygotes that begin dividing as normal zygotes do but have an abnormal collection of genes that forces them to stop development when they are only a small clump of cells) showed an off-target effect. The off-target effects were minimal; thus it is probable that such off-target effects can be stopped with the creation of extremely selective guide RNA. However, this is a dangerous possibility because slight variations in allele or nucleotide combinations can have dramatic consequences on the patient’s health. For example, sickle cell anemia that causes an atypical breakdown of red blood cells, delayed development, inflamed fingers or toes, pallor, shortness of breath, yellow skin and eyes, dizziness, pain, and fatigue is caused from the mutation of only one nucleotide. Humans have 3.1 billion nucleotides in our bodies which are the code for genes, and severe diseases are caused when only one of those nucleotides is mixed up. This proves how important it is that the CRISPR technology is extremely precise. Safety related to accuracy also pertains to the non-human animal who is being engineered as it is their genome which is being manipulated and off-target effects could be detrimental to their health. However, this consideration of non-human animal health may only be prevalent to people who believe that non-human animals have moral status and believe that their safety matters.
Regarding the human race, safety presents the concern for cross-species infection and poses danger to people who are not even receiving porcine organs or involved in the transplants. The concern for this infection is rooted in the fact that humans do not have the same immunity that non-human animals do and thus they aren’t immune to the same diseases that non-human animals are immune to. Animals carry germs that infect people differently than non-human animals (ex: the AIDS virus has been said to originate from monkeys). A healthy-looking non-human animal, such as a pig, may carry a disease that doesn’t affect pigs or the non-human animal it originates from, but it could be dangerous to humans. For example, scientists at the Institute of Cancer Research in London revealed that a virus found in healthy pigs can be released from pig tissue and infect human cells. This study provided proof that there is potential for cross-species infection. Additionally, since patients receiving organ transplants have to be on immunosuppressant drugs, their immune systems are already weakened making them more susceptible to an infection like this. Thus, proving that one change can impact another, and validating fears that xenotransplantation could introduce new germs/viruses into the entire human population by first affecting the patient and then spreading to other healthy people (Hansman)
Safety regarding non-human animals is a concern mainly due to the issue of non-human animal cruelty. The safety of the pigs is a main concern for certain philosophers and ethicists. Some questions that arise when considering this dilemma include: What conditions will the non-human animals be kept in? What will their quality of life be like compared to non genetically engineered pigs? And will their deaths be painful or cruel? The answers to these questions and other questions like these can aid certain philosophers in forming their opinions and stances on this ethical dilemma.
A less pressing concern that this technology poses to society is the potential for overpopulation due to the increasing number of lives that would be prolonged or saved. Currently the national population of the US is 325.7 million and increasing. Each year this population increases by approximately 3.1 million people. In 2015, the population is projected to be 438 million people. Globally, the population increases by 80 million annually and is projected to be 10.1 billion in 2050, a huge increase from the current population of approximately 7.6 billion (Wooldridge). With the introduction of xenotransplantation, hundreds of thousands of lives could be saved annually in just the US. Globally, the impact of this technology would be even greater. This is worth considering because an increased population has implications on society which include but are not limited to fewer resources, houses, and jobs that are available to people.
To summarize, one of the main concerns that CRISPR poses is a threat to the safety of the patient, society, and pigs. The safety of the patient must be considered due to the slight potential for CRISPR to have off target effects that could be detrimental to the patient. The safety of society is a main concern as well because of the potential for xenotransplantation to introduce new new germs and viruses into the whole human population by first infecting the patient who then could spread the diseases to through the human population. Additionally there is a concern of non-human animal safety with regard to non-human animal cruelty. Some may claim that the pigs should be kept under very good conditions while they live their lives and that they must have painless deaths. One’s position on the question of the use of non-human animals in this sense can be formed based on their belief in either non-human animal rights or in non-human animal welfare.
Animal Welfare vs Rights and Religious Perspectives
Animal welfare and non-human animal rights are not the same thing and valuing one over the other can sway one’s perspective on topics such as xenotransplantation. When believing in ‘non-human animal rights,’ one believes that the rights of non-human animals are equal to the rights of humans. An non-human animal rights advocate would argue that xenotransplantation and the genetic engineering of non-human animals violate non-human animal rights due to the treatment of non-human animals as human property and the manipulation of these non-human animals for human benefit. Additionally an non-human animal rights believer would think that killing non-human animals to use their organs for human benefit lowers the status of the non-human animal and in turn violates their rights. Since non-human animals are unable to provide consent as humans are, they can undergo heavy trauma and their expression of pain and discomfort is not seen as a lack of consent. ‘Animal welfare’ refers to the state and treatment of non-human animals. According to non-human animal welfare, xenotransplantation/genetic engineering of non-human animals could be acceptable so long as the non-human animal’s physical and mental needs are provided for. This is the case because believing in non-human animal welfare means believing that humans have the right to alter/use non-human animals in order to meet the needs/wants of humans as long as the suffering of the non-human animals is outweighed by the benefits they provide for humans.
In sum, a person believing in non-human animal rights would oppose xenotransplantation due to the fact that the non-human animals aren’t given the same rights as humans and are essentially used as property for the humans. However, a person believing in non-human animal welfare may deem xenotransplantation and the use of CRISPR on non-human animals justifiable so long as the non-human animals don’t suffer much/at all and that the benefits provided to humans exceed the suffering that the non-human animal undergoes (Peta).
A very important ethical question posed by this scenario is do non-human animals have moral standings? Different philosophers such as Peter Singer and Kant have taken different perspectives on this question. However, at the most basic level this question can be answered from three different perspectives: yes, kind of, and no.
Philosophers who answer ‘yes’ and believe that non-human animals have moral standing argue that non-human animals have similar mental and physiological capacities of infants and some disabled human beings. They argue since infants and disabled people are human and have moral standing, non-human animals should also have moral standing. Another one of their arguments goes as follows: if a creature is able to perceive or feel things (if it is sentient), then it has direct moral status. Most non-human animals are sentient. Thus, most non-human animals have moral status. It is important to note, however, that some philosophers who believe that non-human animals have moral standing, still think that if the benefit of a medical procedure, technology, or process to the humans outweighs the harm that would be inflicted upon the non-human animals, then they deem the procedure, technology, or process morally acceptable to use. For example, Peter Singer, an Australian moral philosopher who takes an utilitarian perspective and focuses in applied ethics believes that non-human animals have moral standings. However, when applying his perspective to ethical dilemmas, such as xenotransplantation, it becomes more complicated. He believes that if there is a justifiable need or necessity for organs, which there is, and if this need surpasses the level of pain and suffering that would be inflicted upon the non-human animals, then a procedure like xenotransplantation should be justifiable (Wilson). Therefore, even some philosophers who believe in the moral status of non-human animals also believe that xenotransplantation can be justified.
Philosophers who believe that non-human animals have no moral standing believe that non-human animals lack consciousness, reason, and autonomy, and thus lack moral standing. However, these philosophers still do not advocate for random harm to non-human animals as they deem that harmful to a human’s morality. Their argument goes as follows: humans are the only beings with rights and they are the only rational, autonomous, and self-conscious beings. Morals are “the rules that govern which actions are right and which are wrong,” (Examples of Morals). Humans are the only beings able to use reason to make autonomous decisions while being fully aware of the consequences of their actions, thus they are capable of acting morally and have morals. A creature must have morals to be apart of the moral community, and since humans are the only beings with morals, they must be the only beings who are apart of the moral community. One philosopher who takes this side is Immanuel Kant. Kant believes that the only thing containing intrinsic value is goodwill. Additionally, he believes that humans are the only beings who are capable of surveying a situation and deciphering which actions they will take, which Kant claims is an action manifested by our wills. He argues that non-human animals lack this ability, and therefore they are not autonomous. He argues, non-human animals have no intrinsic value, and since they lack intrinsic value, they lack the essential value that would deem them to have moral status. Kantians, in turn, see no problems with technologies that are not deemed harmful to humans. Thus, Kantians would see no problem with the many genetic engineering techniques that are used and have the potential to be used on non-human animals. However, Kant does believe that humans should not harm non-human animals if they are deemed valuable to humans.
The last perspective that philosophers take is ‘kind of.’ One who believes in a direct but unequal theory believes that non-human animals have some moral standing, but due to their lack of ability to respect another being’s rights, they deny non-human animals a complete moral standing (Wilson).
Summary: Those who believe that non-human animals have moral standing base their argument on the fact that non-human animals are sentient and they claim that all sentient beings have moral standing. Those who believe that non-human animals have no moral standing state that non-human animals don’t have consciousness, reason, or autonomy, causing them to lack a moral standing. Lastly, those who believe that non-human animals have somewhat of a moral standing believe that non-human animals have moral standing but not a full moral standing due to their inability to respect the rights of another being. However, the position of philosophers on whether non-human animals should be used in xenotransplantation is not directly related to whether they deem that non-human animals have moral standing or not. For example, a philosopher believing that non-human animals have moral standing may agree that it is justifiable to use non-human animals for xenotransplantation under the right circumstances. Personally, I believe that humans have more of a moral standing than non-human animals because humans have the capacity to make well-informed decisions while fully aware of their consequences and I believe that this is an ability that non-human animals lack..
Additionally, the perspectives of different religious philosophers can be applied to topics like this. Some religious philosophers deny non-human animals moral standing due to their religious and philosophical theories about nature, specifically the nature of the world and designated places for the world’s creatures and inhabitants. One example of a philosopher deeming non-human animals to lack moral standing is Aristotle. Aristotle believes that there is a natural hierarchy that exists of living beings. The levels of the hierarchy are determined based upon the living creature’s abilities. For example: plants, humans, and non-human animals all are required to take in nutrition and therefore are able to grow, but plants are unable to have a conscious experience. Thus, Aristotle deems plants inferior to humans and non-human animals. Because plants are deemed inferior to non-human animals and humans, Aristotle justifies the use of plants to serve the needs of both non-human animals and humans. Additionally, non-human animals are deemed inferior to humans as non-human animals do not have the ability to use reason to justify or guide their actions and they are forced to rely on instinct. Aristotle concludes that non-human animals also exist to support the needs of humans as humans are able to use reason to guide them and thus are superior to non-human animals.
Christian Philosopher St. Thomas Aquinas took a similar perspective to Aristotle. St. Thomas Aquinas argued that because humans are the only beings with capacity to determine their actions, they are the only beings that should be considered with regard “for their own sakes.” St. Thomas believed that beings which are unable to guide their own actions should have others do so for them. He believes that those beings who cannot guide their actions are simply tools that exist to serve for the benefit of people, not for the sake of the being. St. Thomas bases his view on the fact that God is “the last end of the universe,” and only humans have the capacity to use their intellect to study and increase their knowledge of God. This perspective is also similar to the perspective of Immanuel Kant who argues that since non-human animals lack a goodwill to guide their actions, they are not autonomous.
Combining religious perspectives and moral standing the next question posed is “are we “playing God,” and if so is that a bad thing? Critics of genetic engineering believe that humans are trying to replace the decisions of God. Through genetic engineering, humans have the ability to create unnatural creatures, or beings that do not originate from nature. Thus, human beings are taking on the role of “creator” rather than being one who was created and in turn humans are “playing God.” Some critics also argue that it is going against what our bodies are accustomed to and to what is typical or normal for us when a non-human animal’s organ is placed into a human being’s body. These critics consider it wrong to obstruct nature which is essentially good.
To counter this argument, nature has no one, clear definition. It is mainly considered to be is the direct opposite of something that is deemed “artificial” or “man made.” Therefore, there is no reason to claim every natural thing is good and every unnatural thing is bad. Philosophers like Bernard Rollin claim that by agreeing that all things natural are good and all things unnatural are bad would be a full stop to life. This is because throughout all human and non human lives, beings do what they can to stay alive. Inventions have been made to help prevent natural disasters, fight diseases, etc, so claiming that all man made things are bad and inappropriate would be similar to deeming a dam which is preventing thousands of homes from flooding is a bad thing (Wilson).
To summarize, religious perspectives play a role in this dilemma as well. Certain religious philosophers have laid out opinions and groundwork for their perspectives on issues such as these. Aristotle believed that there is a natural hierarchy that exists between living beings and that humans are on top. St.Thomas Aquinas believes that beings which lack the ability to guide their own actions should have others guide them from them. This is a similar perspective to Kant who argued that since non-human animals do not have an intrinsic goodwill, they are are not autonomous. The issue of “playing God,” is also prevalent in this dilemma. Critics claim that genetic engineering allows humans to create beings which are unnatural and thus, they are playing God. They claim that all things natural are good and all things unnatural are bad. However to counter this, people argue that nature has no one definition and claim that the argument that all things natural are good and all things unnatural are bad is a full stop to life.
One question that can be posed to justify this procedure is: we already breed non-human animals to kill and eat them, how different would breeding non-human animals for xenotransplantation be? To argue for justification, one can claim that it isn’t that different in practice and it is saving human lives as opposed to just providing food sources for them which is nonessential because we can get food elsewhere. One could argue that breeding pigs for their organs which can save human lives is more just than breeding non-human animals for a human food source. Humans can find food sources elsewhere (ex by following a vegetarian/vegan diet), however if no human organs are available, humans can not find organs elsewhere. Therefore this technology would be saving human lives, not just acting as one of many sources that have the potential to sustain human lives.
To counter this, one may argue that altering their genetics makes this different and potentially more painful torturesome to the non-human animal. One could argue that altering the genetics of an non-human animal adds another potentially harmful layer to the comparison of using non-human animals for a food source and using them for their organs.
A counter to this counter argument is that non-human animals have already been genetically modified by humans to acquire certain traits related to providing food sources for humans. For example some pigs have been genetically engineered to contain the same level of omega-3 fatty acids that certain fish contain. Additionally, genetically modified organisms (or GMOs) are food sources for many human and non-human animals. Therefore, one could argue that humans are already consuming genetically modified organisms and they are already inside of our bodies. Additionally, you can argue that the genetic modification of non-human animals for human benefit is already a reality today, therefore genetically modifying non-human animals for the use of their organs ethically isn’t much different.
Finally, a counter to this counter-counter argument is to consider is the slippery slope that this could lead us down. If we justify all our actions based on the claim that we already do what is considered questionable in other forms that are deemed justifiable, this could lead us to justifying increasingly more controversial and harsh practices in the same way. In other words justifying killing non-human animals for organs because we already kill them for food could result in a slippery slope of justifying further harm to non-human animals by claiming that we have already deemed it okay to harm non-human animals when in reality, is it really okay? On the other hand, if the non-human animals are kept under good conditions while the are alive and don’t undergo suffering during their deaths, then it could be deemed just to use them in order to provide a great service that would benefit humans immensely. Additionally, I think that the fact that these non-human animals would provide organs to humans as opposed to simply acting as a food source would make them appear more valuable to humans. When non-human animals donate their organs they are donating something that is essential to the lives of humans, something that humans do not have a surplus of, and something humans cannot get enough of elsewhere. The organs must be in impeccable condition in order to provide a life saving function to humans which means that the non-human animals or pigs carrying the organs must also be in good condition. While human health is still a concern when receiving meat and other products from non-human animals, the consequences are typically much lower when consuming contaminated meat as opposed to receiving an infected organ. If something is faulty with the received organ, the patient will die whereas if a human consumes meat or other products from non-human animals that are contaminated they will most likely contract food poisoning or an infection, but the odds of them dying are not as high as they would be with a faulty organ. It is a comparison of death vs. illness. Therefore, humans would have more of a motive to keep the pigs under better conditions. This practice could potentially result in lowering the amount of non-human animal cruelty that exists today and possibly raise the moral status that some philosophers deem non-human animals to have.
A parallel situation to this could involve plants. Plants provide humans with a variety of medicines. Plants are used as materials in approximately forty percent of pharmaceuticals in the United States today meaning forty percent of pharmaceutical drugs either contain plant-based materials or have been synthesized from materials originally coming from plants. Certain medicines such as Taxol which is used to treat cancer and quinine which is used to treat malaria, are derived from plants (Medicine Hunter), but do we look at plants differently knowing that they help treat diseases contracted by humans? Do we treat them with more respect?
To summarize, we currently breed non-human animals to use them as food sources and we have already genetically modified non-human animals to provide us with more foods sources quicker, faster, and easier. Xenotransplantation and CRISPR could be deemed similar to these practices that currently exist, thus they could be justified in that way. However, it is dangerous to justify controversial practices in this way because it could lead to increasingly harsh and controversial practices being deemed based on the precedent of other controversial practices. Additionally it raises many questions including where would the line be drawn? Which non-human animals would it be deemed justifiably to genetically modify for human purposes? Would the species of the non-human animal matter? However, this practice does have the potential to allow for better treatment of non-human animals because they are carrying organs for humans, not just simply providing us with food. Thus, breeders may consider the non-human animals with more respect and care in order to protect those organs.
It is evident that there are many aspects of this dilemma and many things to consider throughout this discussion. With each of the considerations brought up throughout this section, there is no single side that one may take on one of these questions that will guide someone to form their opinion on this concept of xenotransplantation as a whole. It is rather a combination, and taking all of these questions into account will guide someone to form an opinion on the specific practice in question: using CRISPR to allow for xenotransplantation.
Personally, I side with a mix of Kant and Singer. I believe that as long as the pigs are kept under good condition and have painless deaths, it should be ethical to use them as a source of organs because one pig could save up to eight human lives. Therefore, following a utilitarian perspective, like Peter Singer, I believe that there is a justifiable need for more organs and the benefit this technology would provide to humans outweighs the harm it would inflict upon the non-human animals. For me it also comes down to the safety and well being of the non-human animal versus the lives of humans. With regards to values, it also comes down to life versus life. I think that humans have a higher moral standing than non-human animals, due to our ability to justify our actions and use our reason to guide us. Therefore I place humans above non-human animals, however, I do have a high value for non-human animals and I think that so long as the non-human animals’ well being is taken into account while they are alive and that they are killed towards the end of their lives in a painless manner, then humans who are suffering should be able to benefit from the use of their organs. Additionally, I believe that this practice has the potential to increase the treatment of non-human animals and raise the standard of living for non-human animals in slaughterhouses. While some may argue it could worsen it due to the potential for humans to justify crueler practices based on the precedent set by the justification of this practice, I believe that since these non-human animals would be giving organs to humans they are providing humans with life which is invaluable. Therefore, the treatment of these non-human animals would be better than the treatment of non-human animals who are simply used as a food sources as they are more valuable. I based this off of the fact that non-human animals providing food sources won’t need to be preserved and cared for in the same way due to their purpose, despite that they deserve to be. If pigs are able to provide us with organs, something that we cannot get by simply looking at another non-human animal or plant, something that is specific to that non-human animal, they treatment of those non-human animals could be improved. This aligns with Kant’s perspective that humans should not harm non-human animals that are deemed valuable to humans. The better treatment of these non-human animals could set off a chain reaction leading to the better treatment of non-human animals who are used as food sources.
I recognise that the parallel situation provided earlier in this paper of using plants as medicine did not have the same result that I predict. Plants as a whole are not thought of with more respect because they provide us with medicine, however, individual plants may be more protected and valued than other plants. For example the Taxus brevifolia, that provides humans with the taxus medicine which is used as a cancer treatment may be valued above a plant such as a dandelion. A similar situation could result with non-human animals where the non-human animals providing organs to humans are valued higher than the non-human animals providing food sources to humans. Additionally, I think there is a clear difference in how plants and non-human animals are perceived. While they are both used by humans to provide similar functions such as a food source, it is easier for humans to relate to non-human animals than it is for them to relate to plants due to an non-human animal’s ability to move, make noise, express pain, etc. Therefore, to begin with I would consider an non-human animal with more respect and of a higher moral standing than a plant and this difference could set the scenarios apart, therefore my prediction could still be a possibly outcome with regards to non-human animals.
Personally, I believe that xenotransplantation will be apart of our future due to the functions that it can provide for the human race. The technology has recently become closer and closer to becoming successful, and could solve the huge problem that the human race currently faces: a lack of organs. This technology thus has the potential to save hundreds of thousands, and eventually even millions of lives in the United States alone. It is for these reasons that I believe our society will deem it justifiable and it will be part of our future.
However, there is a slippery slope that this technology could lead us down. If xenotransplantation becomes the norm, it could potentially lead to extreme abuse of non-human animals and the use of non-human animals to enhance the lives of humans in non essential ways. Additionally, xenotransplantation could impact survival of the fittest and natural selection by impacting the gene pool. People who have received porcine organs and potentially the offspring of people who have received porcine organs will be genetically different in slight ways to people who have not received porcine organs. This could mean that conditions including environmental threats or changes, and new diseases or strands of diseases could impact people containing porcine organs differently than people who do not contain porcine organs. Depending on the number of organs transplanted, a question that must be considered is: eventually could this could lead to a possible cross-species or new species?
Additionally, along with all the good that the CRISPR technology could be used for, there are also malicious techniques that CRISPR has the capability of fulfilling if the technology were to get into the wrong hands. The regular use of CRISPR for xenotransplantation could increase the likelihood of this technology being used for harmful purposes. One of these actions includes the possibility of using CRISPR to produce bioweapons. For example, mosquitoes could be engineered to be deadly or poisonous and viruses that snip people’s DNA could be produced. The dangerous effects of a virus such as a DNA snipping virus are impossible to fathom. The possibilities of CRISPR are endless, therefore the potential slippery slopes that increased familiarity and use of this technology would bring are unforeseen. There are so many ‘what ifs’ regarding this technology that no one can be sure of the advantageous and hazardous possibilities CRISPR entails.
Something else to consider is the lifespan of the pigs and, in turn, the lifespan of their organs. Pigs are expected to live anywhere from ten to fifteen years. Does this mean that their organs will only last and be viable in a human body for a maximum of fifteen years? Will humans need to replace these organs after a certain amount of time?
Lastly, more work would need to be done after removing the PERVs from the genome of pigs before these organs would be safe to transplant into humans. There are other factors within the genome of pigs that could cause organ rejection. For example in the study conducted by Tector, mentioned early on in this paper, he removed three genes from a pig’s genome that he thought contributed to hyperacute rejection (Zhang). This proves that there is still more work to be done before porcine organs are transplanted into humans, however, the removal of PERVs is a substantial step towards seeing xenotransplantation as a common practice in our future.