Category: Organ Transplant

Organ donation is a new issue for Islamic jurisprudence. There are no clear provisions regarding this topic in the Quran or hadiths. However, the religion of Islam, which is universal and offers solutions to all problems that exist until the doomsday, will certainly have a solution in this regard. Therefore, Islamic scholars have made great efforts to clarify the issue, especially by using the analogy method[footnoteRef:1]. Although there are differences of opinion among scholars, this essay will focus more on the view accepting organ donation and some of their evidence. [1: Analogy (qıyas) is the assignment of the ruling (hukm) of an existing case found in the texts of the Qur’ān, Sunnah or ijmaʿ to a new case whose ruling (hukm) is not found in these sources on the basis of a common underlying attribute called the ʿillah (effective cause).]

Organ donation is a subject that brings along the organ transplant debate. Organ transplantation takes place either by an alive person gives an organ that will not endanger his own life, such as the kidney, the eye, to someone else who needs that organ; or by the declaration of deceased before his death or the consent of his heirs after his death. İn both cases, the goal is to save the lives of people who are sick and desperately await death. This is the main issue that scholars who accept organ transplants emphasize; saving a person’s life. There is a verse related to this goal; “whoever kills a soul unless for a soul or for corruption [done] in the land – it is as if he had slain mankind entirely. And whoever saves one – it is as if he had saved mankind entirely.” [5,32] Besides, the saving of life is one of the essentials (daruriyyat) accepted by all scholars and it even comes before protection of religion. Therefore, the scholars have prioritized human life and put this at the center point while making a decision regarding organ donation.

Since organ donation and organ transplantation is a new issue in many respects, there is no explicit judgment regarding the Qur’an and sunnah of the Prophet Muhammad (pbuh), which was descended fourteen centuries ago. It is not possible to find a clear statement on the subject in classical fiqh books. Because there was no such treatment method at that time, this was not an issue. Scholars, as with many issues, used the method of analogy in organ donation, while seeking solutions and new judgments for subjects in which there was no clear provision in the Qur’an and the hadith.

The first proof of scholars who accepted organ donation is “It is stated with the following verses that prohibited foods and beverages will be enjoyed in cases of necessity such as hunger and thirst that threaten human life.” The verse is “He has only forbidden to you dead animals, blood, the flesh of swine, and that which has been dedicated to other than Allah. But whoever is forced [by necessity], neither desiring [it] nor transgressing [its limit], there is no sin upon him. Indeed, Allah is Forgiving and Merciful” [2,173]. In this verse, Allah has forbidden some things first, but later, as a manifestation of His own mercy and forgiveness, He allowed those things that were forbidden in the necessary situations to be overcome. As a creator and legislator, Allah prioritizes the protection of human life and introduces an exceptional provision here. Although, in some verses and hadiths, it is said that man is created honorable, he does not possess his own body, and his body is entrusted to him; organ donation can be acceptable according to the above verse. Because, according to this verse, necessities can make forbidden things, halal. Here, even if the human body is dignified and untouchable, it is imperative to save someone else’s life by donating organs.

As it is known, in order to apply the analogical provisions on an issue, the effective cause (‘illah) of both issues must be same. Namely, there should be a union of causes between the subject that is clear judgment in the Quran or sunnah and the subject to be compared with it. In the first case, it is the effective cause to rescue from death by eating something that is forbidden. In the second case, it is the effective cause to donate the organ of a dead person to someone who is most likely to die due to organ failure, and to save his life. In both cases, there is certainly an effective cause for saving lives.

The second proof of scholars who accepted organ donation is a fatwa (new judgment) of Kasani in the book of al-Fatawa al Hindiyyah. [Kâsâni, a.g.e., I, 61-62; Fetâvâ el- Hindiyye, Beyrut, tsz, V, 355.] The fatwa is “It is considered permissible to use alcoholic and narcotic drugs, which are forbidden and filthy, if there is certain information or that is highly probable that patients who cannot be treated otherwise can be cured.” İf something that is forbidden can be used for treatment in necessary situations, human organs that are dignified and untouchable can also be used to save a person from death. There is an example in the life of Prophet (pbuh); He had forbidden men to wear silk clothes. However, He allowed some companions to wear silk because it is good for some skin diseases. [Bukhari, book of wear 29]

The third point is we can say that an evidence of organ donation is to avoid wastefulness. Waste is prohibited in the Qur’an and hadiths. Allah Almighty says in the Quran; “eat and drink, but be not excessive.”[7,31]. Allah Almighty says that in the Qur’an, He is also practicing this in the universe He created. When we look at the earth, we see that nothing is wasted. All beings help each other and prevent waste. For example, the corpses of each dead animal are consumed by other animals and reintroduced into the ecosystem. If we look at organ donation with this view, we will see how much waste will be prevented by organ transplantation. Some people die without donating their organs, all organs will fall into the ground when they die and they will miss the opportunity to find solutions to sick people in need. Otherwise, if people donate their organs, when they die, they will give life to other sick people with their organs. We know that waste is not limited to eating and drinking. Even in the simplest things like eating and drinking, Allah Almighty prohibits waste. It is unthinkable that He allows waste when it comes to human life. Therefore, scholars have said that when a person dies, Allah will not allow the organs to be wasted.

Finally we can add that Islam is a religion of convenience. Both people who are sick due to organ failure and their families have difficulties. Many people die while waiting in line for transplantation. This situation also causes an organization called “organ mafia” that darken the lives of many people. It is possible to overcome those difficulties by allowing organ donation. The Prophet (pbuh) had said “’Make things easy and do not make them difficult”.[ Bukhari 69, Book 3, Hadith 11] Therefore, it is the way that is suitable for the sunnah, not to bother people with the hard one while there is an easy one. When people donate their organs, people waiting for organs will recover with new organs and malicious people will not be given the opportunity. Furthermore, there is a principle in the civil law that prepared in the time of the Ottomans called “majallah” ; “the essential thing in the objects is exemption”. Namely, permissibility to benefit from the things or continuity of permissibility to act in a way where there is no evidence against them. Therefore, we can say that there is no explicit judgment for organ transplantation that prohibits it. Since the scholars could not find clear provisions in the Qur’an and sunnah, they concluded that organ transplantation is permissible with the method of analogy.

There are some conditions for organ transplantation.[tdv islam Encyclopedia] 1- There should be a necessity for organ donation; The necessity of organ transplantation is related to its being a last resort. Firstly, all treatment methods should be applied, but if the patient has not recovered, an organ transplant can be applied. This will also encourage scientists to research and find new solutions for organ failure. If they find new treatments, there will be no need for organ transplants. 2- A strong opinion in the experts of the subject that the patient will recover with this treatment; There should be a definitive or close decision by the experts about the patient’s recovery. If the patient will not recover with organ donation, there is no need for an organ transplant. 3- The approval of donor before his death or approval of donor’s heirs after his death; The donor must be willing to donate his organs. If he does not have any explanation about this, heirs must be consent after his death. There are also different opinions here. For example, there is no need to obtain their permission, because heirs are not entitled to the organs of the deceased. 4- The definitive of medical and legal death; It is necessary for specialist doctors to decide at what stage someone dies completely. In cases such as brain death or vegetative life, the decisions of doctors should be taken into consideration. 5- The organs are not given for a fee and benefit; Allah Almighty says in the Quran “And We have certainly honored the children of Adam” [17,70]. Allah Almighty has given body of human as a trust. For this reason, people cannot sell their fleshes or any other organs for a fee. 6- The consent of person who will take organ; It says who takes organs should approve to take organ. But there must be an opposite view here. Because, if a person is life-threatening, there is no need to obtain permission from him to save his life. Scholars have said that organ transplantation can be done when these conditions are met. Although scholars determine these conditions, as we have seen, it is necessary to get the opinions of specialist doctors on many issues about organ donation. This makes the cooperation of fiqh scholars and specialist doctors inevitable.

On the other hand, some Islamic scholars say that organ donation is not permissible. They bring evidence the verse that is mentioned above; “And We have certainly honored the children of Adam” [17,70]. Therefore, human body is honored and untouchable even after they died. Likewise, there is a hadith that they use in this case; “It is like breaking the bone of the deceased while it is alive'[Abu Davud, Janaiz, 60]. Furthermore, according to their approachs, the right of the using on one’s organs ends with death, and the intervention in the body of the deceased for organ harvesting violates the right of Allah, not the right of human. Therefore, the testament of person is not valid in this regard. Additionally, these scholars said that the moment of death cannot be clearly determined. Brain death and subsequent removal of organs have affected the wiev of these scholars about organ transplantation. Because this will facilitate organ harvesting from a person not yet dead and maybe it will cause abuse organ transplantation.

After all these writings, we can say that; As Muslims, we believe that Islam offers a solution to all current and future problems. Thousands of people die every year due to organ failure. This is a serious problem worldwide and it is unthinkable that Islam does not offer a solution. However, when we look at the research, we see that the organ donation rate in Muslim countries is lower than that of non-Muslim countries. The fact that organ donation is permissible encourages Muslims to donate and it can be a solution to the problem. Right here, there is a great responsibility for Islamic scholars. They should enlighten and encourage Muslims and contribute to the solution of this problem.

İn conclusion, On the one hand, there are people who are desperately waiting for death because they are sick and unable to find suitable organs, and on the other, there are people who die and decay organs in the soil. Considering this, many scholars of Islamic jurisprudence have prioritized human life and said that organ transplantation is permissible. While making these judgment, they mostly used the method of analogy and consider the benefit of humanity. Although this topic is very new, they have worked hard and made positive provisions for the protection and survival of human life. According to verse whoever saves one – it is as if he had saved mankind entirely. Therefore they want to save lıves of people.

Artificial Organs

The scientific technology that I have chosen to research is artificial organs, the reason that I find this particular technology interesting is that I find it fascinating that scientific research and development has come so far that we are now able to replace our organs which are needed for the human body to survive, with artificial matter and it can still work perfectly.

Five important aspects of artificial organs are:

• They can be produced 2 ways – either grown in a lab or 3D bio-printed
• It helps with our health outcomes as it provides another possibility instead of having organ transplants
• Assists with organ donor shortages
• Real organs have the possibility of immunorejection, artificial organs eliminate this
• Economically efficient as it eliminates the cost of anti-rejection drugs which typically cost $17,000 each year at minimum

How they are produced

Artificial organs can be manufactured in two ways they can either be bio-artificially grown or 3D printed. To grow an organ bio-artificially there are four steps involved in this process – The architectural predesign, preparation of materials and construction tools, homogeneous or heterogeneous cell assembling and post multi tissue maturation. In the architectural pre design stage factors taken into consideration are the materials used to make the organ, so whether they are stem cells or other types of cells used to produce the organ. Stem cells are cells of a multicellular organism that are capable of establishing several more cells of the same type, because of their capability to refabricate cells of the exact same anatomical make up, stem cells are commonly used in the artificial organ manufacturing process. Cells from the patient receiving the organ are preferred for use so as to eliminate the high risk of immunorejection. Immunorejection is the body’s natural defence system to fight and defend against a foreign object. When a transplant occurs the recipients, immune system rejects the transplanted tissue and destroys it.

During the third cell assembling stage using stem cells is a promising approach to effectively grow an organ as they provide reproductive properties to efficiently grow the necessary organ. MSC’s have also become increasingly popular in the organ manufacturing field, particularly adipose derived stem cells, umbilical cord blood stem cells and bone marrow mesenchymal stem cells, as they are able to differentiate into many different cell types and therefore creating another way for scientists to develop artificial organs. MSC stands for mesenchymal stem cells they are multipotent which means they can produce more than one type of specialized cell in the human body, because of this they are valued and extremely necessary in the bio artificial organ manufacturing process. MSC cells can also develop into skeletal tissue, nerve cells, heart muscle cells, liver cells and endothelial cells which form the inner layer of blood vessels. Therefore the growth factors of the MSC cells are crucial for any convoluted organ construction that involves the incorporation of the vascular, neural or lymphatic network.

Lastly the fourth stage of organ manufacturing- the post multi tissue maturation stage, this is the final stage of artificial organ manufacturing and is the final step that binds everything together and makes it a fully functional organ. During this stage the fully assembled 3D constructs that consist of living cells need to be stable for implantation. During this stage, physical, chemical or biochemical cross linking of the supportive polymers takes place to immobilise the currently living cells, this process also improves the structural integrity of the organ. Within the 3D construct cell aggregation transpires to form homocellular and heterocellular tissues. Hence post multi tissue maturation is a self-sufficiently completing process in which homogenous and heterogenous cell populations are able to come into contact and amalgamate to create fully functional, coherent organ tissues. Only through this process with multi tissue formation and maturation can a bioartificial organ grow to the point where it has a full range of necessary physiological functions. For a major organ with more than three cell types such as the liver, heart or kidney considerable time and space factors need to be greatly considered.

During this stage stem cells can also be introduced to 3D printed organs into disparate cell and tissue types such as endothelial cells or tissues and adipose cells or tissues under the guidance of consecutive growth factors.

Providing another avenue instead of organ transplants

Artificial organs can eliminate the need for an organ transplant. Almost any organ you can think of is able to be bio artificially grown or 3D printed. In any instance where an organ transplant is not an available option an artificial organ can be the way to go. Although a negative to this is that if it is a life or death situation and an immediate organ transplant is necessary the time may not be in our favour for an artificial organ to be grown as it takes several months to grow an efficient organ.

As of currently there are no other alternatives to a real human organ transplant apart from bio-artificially manufactured organs or 3D printed organs, because of this, the development of bio-artificial or 3D printed organs has become a crucial technology in organ transplants, to assist in the lives of those who desperately need a transplant. Although there are dialysis machines that are available, they are not a permanent solution.

Assisting with organ donor shortages

There is a worldwide organ donor shortage. In Australia alone currently 1400 patients are waitlisted for an organ transplant and there is a further 11,000 that are currently on dialysis who could benefit from a kidney transplant. In the United States of America a remarkable 122,000 people are on a waitlist for patients awaiting a transplant, the majority of these patients will be waiting months or even years to find a donor and unfortunately some never will. At the end of this day 22 people would have died in the united states alone awaiting an organ donor. See figure 3 for organ donor statistics

The dilemma is that there simply are not enough people willing to donate organs to reach the high demand of life saving donor organs. Many initiatives have been implemented to rise the amount of available organ donors, such as offering for people to sign up to become an official organ donor when they go for their drivers’ licence. Despite these efforts, according to the U.S department of health and human services the amount of organ donors has remained stagnant over the last decade, proving that this is a growing crisis worldwide, but particularly in the United states of America.

There is a strong push for living donors to sign up on the organ donor registry as last year 450 patients on the organ donor wait list died simply because families were unsure of their deceased relatives wishes on whether they want to donate or not.

As mentioned previously, stem cells also have the capability to grow and produce a healthy fully functioning body tissue, this can majorly assist in the growing epidemic of tissue donor shortages. Similar to organ donor shortages, there is also a colossal tissue donor shortage as well. Tissue is in high demand of those with severe diseases or illnesses, but it is not only those with severe illness that are in need of tissue. According to associate professor Justin Roe who has a medical practice in Sydney and receives tissue from Victoria, he is seeing a further increasing rate in major tissue injuries that require tissue transplants as there is an ever increasing intensity in sport, not only contact sport, but sports such as netball which cause severe rupture of the anterior cruciate ligament can require a tissue transplant in severe cases, see figure 4 for representation of increasing sport injuries and reconstruction rates. Not only is it the increasing intensity in sport but there are much higher participation rates which can further the injury rates of tissue and ligaments.

Making organs bioartificially available can dramatically assist in our worldwide organ donor shortages as we can create organs as we need them, introducing the possibility of artificial organs also limits the patients time on the wait list for an organ to come naturally as scientists can get to work straight away on developing the required organ.

Eliminating the risk of immunorejection

A transplant is the act of relocating cells, tissue or organs for the purpose of reconstructing or replacing a damaged or diseased tissue or organ. Although this is a marvellous medical breakthrough the body’s immune system creates a significant and difficult barrier to endure a completely successful organ transplant

When an organ transplant occurs, the patient is highly susceptible to immunorejection, a process in which the human body recognises an object as foreign or “harmful”. During this process the human body recognises the transplanted organ or tissue as foreign, which results in the destroying of the transplanted tissue or organ.

Foreign invaders in the human body are presented to our immune system as an antigen, a substance that when inside the human body triggers an immune response, this immune response activates lymphocytes which are white blood cells, they are also one of the body’s main types of immune cells. Lymphocytes are made in bone marrow and are a part of the lymphatic system, hence why they are also made in lymph tissue. From this point some of these cells travel to the thymus where they become what is known as T cells, others remain in the bone marrow where they are made, these become known as B cells. In the case of organ transplants B cells play a major role in the immunorejection. B cells are responsible for making antibodies, antibodies are proteins produced by the immune system to fight and defend against antigens. In this case, the transplanted organ is recognised as an antigen and destroyed. T cells recognise and destroy virus infected cells, one of the most common infected cells that T cells destroy are cancerous cells.

When a surgical transplant occurs and the transplanted tissue or organ is identified as a non self antigen, it triggers an immune response which uses specific antibodies to mark the transplant for destruction and assists in amplifying the immune response. The human leukocyte antigen (HLA) is a complex gene group that contains proteins that have the responsibly of identifying foreign matter. These proteins are found on all cells and acts as self markers, indicating to the immune system not to destroy that particular tissue or organ as it is not harmful. The complication in this circumstance is that due to the fact that each person has a unique and different genetic makeup each person’s set of HLA is different and their immune system has learned not to react to their specific HLA gene, but when another organ or tissue enters the body with a different HLA gene it is immediately marked as non self and the immune system proceeds to destroy it.

The chances of immunorejection can be minimised but not fully eliminated by a few medical processes. First and foremost, the doctors check for a match in blood type between the recipient and the donor. If the blood group is not matched the transplant will be immediately rejected by the recipient’s immune system. Secondly a tissue match is searched for, another blood sample is taken from the person receiving the donor organ to identity the HLA agents present on their blood cells, the more alike the HLA agents are of the recipient and the donor the less likely the chances are of rejection. Although an identical match is not a possibility a similar match is. Family members are usually the best for finding a similar HLA match particularly siblings as they have genetic similarity. See figure 5 to view the development of HLA cells through the mother and father to the child and a visual representation of how they differ.

After these processes are complete a blood sample is taken from the donor and the recipient, these two bloods are mixed. If it is evident that the recipient’s antibodies are attacking the donor cells they are considered positive and a transplant will not be possible as there is an increase risk of hyper acute rejection.

Due to all these risks organ or tissue transplantation is a difficult and time consuming process to ensure that the chances of immunorejection are as allow as possible.

With bio artificially grown organs, the stem cells and MSC’s can be taken from the recipient to ensure that immunorejection is as limited as possible. Due to the bio artificially grown organ having the same stem cells or MSC’s as the recipient, as it is their cells used to grow the organ the chances of immunorejection are dramatically lowered as it is an exact HLA match. It would also limit the patients time on the wait list to receive a natural donor organ.

Eliminating the cost of anti-rejection drugs

Once an organ transplant has been completed the patient is immediately put onto immunosuppressants, these are drugs that lower the body’s alibility to reject the transplanted organ. These drugs, although assisting in the anti-rejection of the donor organ, in this process cause the weakening of the immune system. Anti rejection or immunosuppressant drugs need to be given as soon as the transplant is completed in a large dose and from here they are then taken as long as the transplanted organ remains in the human body. Over time your doctor may lessen your dosage of anti rejection drugs, this is because the chance of rejection lessens over time.

The combination of drugs and the amount taken can greatly vary depending on the type of transplant. Due to a number of factors such as the patient experiencing an acute rejection episode the drug is subject to change and an increased dosage is highly likely. Side effects and reactions to the chosen drug can also result in a change of prescription.

These drugs come with major limitations such as a severe immunodeficiency, the drugs taken to reduce the chance of rejection are non-specific, this means that instead of targeting a particular subject it reduces the immune system overall, this leaves patients susceptible to opportunistic infections. Furthermore many of these drugs are associated with adverse side effects, these include: increased blood pressure, impaired renal function, diabetes mellitus and an increased risk of cancer, this is because the immune system is weakened and the T cells are no longer as active, T cells are the cells responsible for destroying virus infected cells such as cancerous cells.

Taking these immunosuppressants every day for the rest of their life can have a major impact on someone’s health and lifestyle, a careful balance needs to be put in place with sufficiently suppressing the immune function to avoid rejection, avoiding drug toxicity and maintaining enough immune function to fight of any diseases that enter the body.

On an annual basis anti-rejection drugs cost roughly $17,000 each year at a minimum. Introducing the increased use of artificial organs, grown from the patients own stem cells can eliminate the need for anti rejection drugs as the organ has the same HLA as that that is already present in the patients body. Not only would artificial organs become a much more economically efficient option for organ transplant patients, but the patient would no longer need to take anti rejection drugs which need to pass through the kidneys and over a prolonged period of time could lead to kidney damage. See figure 6 for organ transplant medical costs from 2 years prior to 3 years post surgery

Importance of artificial organs in the future of society

As discussed previously artificial organs could pose a huge improvement in the future of society as they contain many health and economic benefits.

Artificial organs can make a dramatic improvement in organ donor shortages. As of currently there are thousands of people on the wait list for a donor organ which could be a life saving organ but unfortunately there is a colossal difference between the amount of people who desperately need a life saving donor organ and the amount of people that are actually willing to donate their organs. Artificial organ technology could help close the gap and hopefully one day, everyone in need of an organ will receive one, with the assistance of this technology.

Organ transplants require a significant amount of planning and testing prior to the actual transplant to ensure that it will not be rejected and destroyed by the body’s immune system. Through the technology of artificial organs, organs can be grown using the recipients own mesenchymal stem cells this means that they can produce a multitude of different cells, which in turn can be used to make an organ that wont be rejected by the recipients body as it has come from the same cell and therefore has the same HLA cells which dramatically reduces the chances of the organ being rejected.

Additionally, as the bio artificially produced organs have anti-rejection properties, this adequately reduces the cost and need for anti rejection drugs. This becomes extremely cost efficient for the patient, as anti rejection medication can cost a minimum of $17,000 each year. Not only is it more cost efficient than receiving a natural organ but it also aids the kidneys. The kidneys have to process a lifetimes worth of anti rejection drugs which can be extremely damaging, given that the majority of anti rejection drugs are also steroids this could also cause severe kidney damage after processing the high initial dose and then a lifetimes supply of them afterwards. Anti rejection medication can also make it difficult in leading our day to day lives as they need to be taken constantly and therefore possibly disrupting work or school patterns. If a dose of anti rejection medication is missed it can also cause a problem as the immune system quickly builds itself back up, if more than one dose is missed this can cause a severe issue and the organ may need to be removed.

Finally it is firmly believed that with a more prominent use of artificial organs in the transplant industry, there could be an improved quality of life after a transplant as well as providing the patient with tens of thousands of dollars saved each year on anti rejection drugs, not taking these drugs also keeps their immune system healthy and doesn’t leave patients susceptible to illnesses due to a weakened immune system.

Artificial organs can also majorly assist in the international organ donor shortages and save thousands of lives in doing so, it would eliminate long wait lists and would end the death of a person simply waiting for an organ to save their lives and immediately provide them with their own specialized organ that doesn’t trigger an immune response.

Morality is rarely clear-cut without objections or questions. The morality of animal to human organ transplant is no exception. With innumerable factors created by beneficial techniques and harmful tactics, the dispute is far from irrelevant, especially with its crucial influence on life and death. Animal organs being transplanted into humans is lifesaving; however, it is also life taking and therefore can be argued to be either moral or not.

Xenotransplantation is the “process of grafting or transplanting organs or tissues between members of different species” (“Xenotransplantation”). This is primarily the transplant of animal organs into humans. This process was first witnessed in the seventeenth century by Jean Baptiste Denis when he “initiated the clinical practice of animal-to-human blood transfusion” but was unsuccessful in his venture which led to the basement of the practice in France, Denis’ home country (McNamee). In the nineteenth century, animals like sheep, rabbits, dogs, cats, rats, chickens, and pigeons were donated for their skin. In this xenotransplantation process, the living donor was strapped to the patient for several days. However, the frog, which was the most popular at the time, was skinned alive for immediate grafting onto its patient. Specifically, during the nineteenth century, a cornea from a pig was transplanted into a human in 1838 which proved successful. However, the first real successes took place in the twentieth century. In 1907, Alexis Carrel made organ transplantation feasible for the first time with consistency. More interestingly, Serge Voronoff attempted to return “the ‘zest of life’ of elderly men. He attempted to reverse this element of the aging process was to transplant slices of chimpanzee or baboon testicle into the testicles of his elderly patients” (McNamee). This was wildly popular in the United States and Europe during the 1920s with several hundred operations. In the 1960s, chimpanzees became animal donors for kidney patients. This trial, however, was extremely unsuccessful with 12 of the 13 transplants between chimpanzees and humans resulting in organ rejection or infectious issues within two months after the procedure (McNamee). The history of xenotransplantation is driven by the need for solutions to human medical issues. And while exceedingly unsuccessful, the few successes led to life-saving breakthroughs in the medical field.

Currently, “pigs are a good choice of organ donor because of their short gestation period, rapid growth rate, and size of organs, which match those of humans” (Phillips). Pigs are the animal of choice because of their distinct match in many departments to humans, which many other animals, most surprisingly primates, lack. This makes pig organs “the most compatible with humans” which is leading to a higher success rate which is life-saving (“Genetics”).

The life-saving treatments created by xenotransplantation are easy solutions for thousands of individuals. If more people donated their organs, xenotransplantation would be non-essential. But with such a lack of people doing so, animal to human transplants have become almost necessary. In the United States, an “average of 79 people receive organ transplants every day, but that 18 people die each day because of a shortage of organs” (McNamee). While there is an exceeding number of people receiving organs, the number in need versus the number in supply are instrumentally different. “The search for transplantable animal organs is driven by a severe and chronic shortage of human organs” (Masci). In numerical terms, the shortage is drastic. For example, the United States in 2017 had 34,770 transplants. However, there were 115,759 patients on the waiting list (Phillips). There is a dire need for organs but a lack of them, xenotransplantation was born in this struggle. It was a response to the need and proves a valid reason as to why it was a moral decision. It is also known that “using animal organs would reduce the length of time many people wait for a suitable organ and would allow transplants to occur while the recipient is still somewhat healthy and better able to tolerate surgery” (Phillips). Philips here is arguing for the morality of xenotransplantation because it increases the chance of a successful surgery and lowers pain within the person. Animal organ transplantations into humans are immensely significant because of the lack of medical help for those in pain and it also proves to reduce the pain in a quicker and more effective manner because of its availability.

Animal to human transplant is a life-saving procedure in a time of need. However, there is a loss of animal life in the process to do so. It is, therefore, in many ways, extremely important. The animals, predominantly pigs at the moment, used for xenotransplantation are often raised for such procedures, which is an ethical concern for many. “Animal rights activists are appalled at the notion that pigs, baboons, and other creatures will be “harvested” for organs and other tissue” (Masci). The idea that animals are being used as involuntary donors is just one stance against xenotransplantation. Many “argue that receiving tissue from animals could expose the patient and possibly the entire human population to a dangerous virus” (Masci). Animal-borne diseases being introduced into the human population could have long-lasting effects and cause issues that could possibly be more detrimental than the ones the transplant of organs is solving. Pigs, specifically, are “carriers for a retrovirus called porcine endogenous retrovirus (PERV). The virus has been shown to infect human cells, but the consequences of infection have not yet been determined” (Phillips). So while there is a strong argument as to why xenotransplantation is beneficial, ethical concerns involving the loss of innocent life and the introduction of new diseases present a strong case against.

Over many centuries, philosophers have argued over the value of animal life. John Stuart Mill of the nineteenth century was at the forefront of utilitarianism. Utilitarianism is “judging an action by its utility meaning usefulness” which translates to an actions morality is determined by the consequences of such (Hirtzel). Utilitarianism focuses on what results in the most amount of happiness for the most amount of people. Utilitarianism would see xenotransplantation as moral because it focuses on the betterment of a significant number of people. It would also bring elation to the close ones of the patient, thereby spreading an immense amount of happiness. Hedonism, defined as “the belief that pleasure is the only good that exists,” is also one of one of utilitarianism’s primary principals (Hirtzel). In an article discussing the morality of animal to human organ transplant, writer justifies xenotransplantation through Hedonism saying, “the best consequences will be those that include the greatest possible balance of pleasure over pain. A good reason for permitting animal suffering, then, is that such suffering is a necessary price to pay in bringing about the best consequences, all considered” (Regan). Under Hedonism, the limiting of suffering would make animal organ transplant acceptable. Therefore, according to Mill and utilitarianism, xenotransplantation is moral because it amounts to the most amount of happiness for the most amount of people and equates to the intrinsic good.

Immanuel Kant, an eighteenth-century Prussian philosopher, believed in an “even moral playing field” that is guided by actions and not by consequences (Hirtzel). He does this through categorical imperatives. The first is the Formula of Universal Law. This categorical imperative first step is to determine if the reason for doing an action is a reason everyone could have. In simpler terms, it is asking if a special exception is being made. If so, it is not moral. In relation to xenotransplantation, a special exception would be made by the patients in order to end their suffering at the expense of another. The second step in this imperative is to decide that if everyone performed the action, would the world be substandard? If everyone killed animals for their organs, the world would suffer tremendously. Therefore, it is immortal. The second categorical imperative is the Formula of the End in Itself. This imperative focuses on people’s “intrinsic value because of their ability to reason” and how people are never a means to an end (Hirtzel). The question to ask is if another is being used as an object or their ability to reason is taken away. If yes, the decision is immoral. In the case of xenotransplantation, since animals are being used as a means to an end the need for organs, it is immoral. “The Kantian idea that animals are never to be treated merely as a means to human ends, however good these ends might be” (Regan). Kant makes clear that animals should not be treated cruelly by humans, especially for their benefit. Animal organ transplant cannot be justified as moral by Kant because every categorical imperative turns away from morality.

Lawrence Kohlberg, a twentieth-century psychologist, believed that morality is developed through a series of six stages. The higher the stage, the stronger the morality. Xenotransplantation can be argued under the first, second, fifth, and sixth stage. The first stage is about self-interest and the anticipation of pleasure or pain.“The immediate physical consequences of an action determine if it is good or bad” and therefore, a person in need of an organ transplant and undergoes animal-organ donation is working to achieve the best physical consequence of their action (Hirtzel). But there is a lack of a sense of others since the patient is taking their life above the lives of others. Although the second stage primary focuses on an exchange of favors, it also highlights how the best action is one that satisfies one’s own desires with a constant question of what is in it for the recipient (Hirtzel). As a dying patient on the waiting list for a donor, the most desirable outcome is life and the means by which it is achieved is animal organ transplant. The fifth stage centers on moral action and principles endorsed by the inalienable rights and liberties that individual is given by nature to ensure the most amount of good to the largest number of people. Things like life fall under this category. Therefore, when a patient or their family decides to use xenotransplantation, it is moral because it allows the patient to experience their inalienable rights despite the ethical concern for the loss of another life. And since multiple people could potentially benefit from the donation of one animal, it can be considered right because it is more life-giving than taking. Stage six focus on the worth of all living beings and how no being is to be used as a means to an end. This stage has important figures like Gandhi, Jesus, Buddha, and Martin Luther King Jr. Figures like this encouraged equality among all (Hirtzel). Therefore, through the perspective of stage six, animals are to be solely treated as equals and are not to be harmed. If on lower developmental stages such as one and two, is it easy to perceive xenotransplantation as a moral decision. However, if a step is taken back onto stages like five and six, it is tremendously immoral and is against important principles.

Buddhism, a major world religion, is a faith focused on inner peace and wisdom. The goal of Buddhists is to achieve enlightenment by “utilizing morality, meditation and wisdom” (History.com Editors). Buddhism encourages the avoidance of self-indulgences. All Buddhists live by five precepts which refrain from “killing living things, taking what is not given, sexual misconduct, lying, [and] using drugs or alcohol” (History.com Editors). Buddhism also has five aggregates which are a way to analyze “personal experiences” (“The Five Aggregates”). They are form, sensation, perception, mental formation, and consciousness. Aggregates are shared by humans and animals and therefore animals are not separate and are not to be harmed (Peto). Animals in the Buddhist faith are often symbols for teachings and are highly regarded. They are also seen as equal. Xenotransplantation, through the eyes of Buddhism, is not moral because it goes against two of the five precepts by killing another and taking what is not willingly given. And since animal organ transplants goes against another who shares the five aggregates, it is still immoral. “One who, while himself seeking happiness oppresses with violence other beings who also desire happiness, will not attain happiness hereafter” (Dhammapada 132). Therefore, if a patient in need of an organ hurts another, which includes animals under the five aggregates, happiness and nirvana cannot be reached. This also warns against how the animals are bred for xenotransplantations since they are being oppressed. “All living things fear being beaten with clubs. All living things fear being put to death. Putting oneself in the place of the other, let no one kill nor cause another to kill” (Dhammapada 129). This quote again speaks to how animals are equal. if the patient was willing to trade places with the animal they would be taking the life of, it would be moral. However, here it also states that harming and killing another is deplorable, making xenotransplantation still immoral. “He who lives only for pleasures, and whose soul is not in harmony, who considers not the food he eats, is idle, and has not the power of virtue — such a man is moved by Mara, is moved by selfish temptations, even as a weak tree is shaken by the wind” (Dhammapada 7). In this quote, Mara, a demon who tempts with self-indulgence, takes those who live only for themselves with ease. Animal organ transplant would be immoral because the patients would be acting under the influence of Mara because they are being selfish and not considering others. Because Buddhism considers all living things equal in soul, the killing of an animal for personal needs is not life saving and is extremely injudicious. It is unacceptable due to it being against key principles and its high level of selfishness.

Xenotransplantation is moral in terms of the saving of human life but immorality can be found in the harming of animals. Therefore, both sides are able to be seen. To Mill, many physicians, and people, animal to organ transplant is moral but to Kant, Buddhism, Kohlberg, and many members of the public, it is immoral. Personally, I can see how it is a quick and easy solution to an ever growing problem. However, I believe the animal organ transplant into humans is immoral. I also see it as a careless decision because of the potential ramifications that could become a future medical issue due to an obscene number of unknowns. Personally, my moral conscience screams out against xenotransplantation. However, a part of me understands the need for such procedures. I also do not know the pain many of the patients are experiencing and can understand how this would be a viable solution. I do not personally think I could do it, but I see how others could. With the evidence presented, I believe that the morality can truly be argued based on what the value of human life versus animal is and whether selfishness is in play. It is not the benefits or detriments in argument, for they have verifiable quality. The discussion is surrounding morality, which has no definite and explicit solution.

1. Abstract

1.1 Situation of organ transplant

According to World Health Organization, there are as high as 100,800 solid organ transplants performed around the world annually, in which the highest percentage was found as kidney transplantations. However, it was observed in the past three decades that patients who have had a kidney transplant suffer dramatically from nephrotoxicity created by the immunosuppressive drugs that are essential for their treatment. Traditional immunosuppressive drugs have been studied under the microscope and scientists are continuously exploring new possibilities for immunosuppressants that are non-nephrotoxic with minimum side effects.

1.2 What is Alemtuzumab and its impact on kidney transplant

Alemtuzumab as an FDA approved drug, is current used to treat autoimmune diseases such as multiple sclerosis (MS) and lymphocytic leukemia (U.S. Food and Drug Administration, 2019). Over the past few years, alemtuzumab has drew attention from many scientists for the consideration of its application in organ transplants as a solution for the observed kidney transplant problems and as a possible replacement and optimization for the current CNI drugs used in organ transplant surgeries.

1.3 The goal of this article is to take a closer look into the current status of Alemtuzumab and evaluate how far this drug is to become a treatment for organ transplant patients.

Introduction

Solid organ transplantation has been considered as a lifesaving surgery for many patients with a terminal stage organ failure for more than 30 years now since the discovery of cyclosporine in 1983(Grinyó 2013). According to World Health Organization, “around 100, 800 solid organ transplants are performed every year worldwide”, in which 69% constitute as kidney transplants (WHO 2008). However, the struggle of balancing the sufficient amount of immunosuppression to protect the graft organ and lowering the dosage enough to avoid related toxicity, especially nephrotoxicity has always been the center topic of organ transplantations and the final solution is still in search (Andrade-Sierra et al. 2018). These situations demonstrate the need of new immunosuppression drugs in the wide application of organ transplantation, which brought the attention to alemtuzumab.

Alemtuzumab is an immunosuppressant drug which is currently in use to treat multiple sclerosis (MS), and lymphocytic leukemia (U.S. Food and Drug Administration, 2019). This medicine is manufactured by Sanofi Pasteur in North America and has common trade names of Campath and Lemtrada. In recent studies, the non-nephrotoxicity feature of this drug draw attentions of scientists to develop and improve this drug for its application in solid organ transplantation and specifically for kidney graft (Almendingen 2019).

What is alemtuzumab

Alemtuzumab is a monoclonal antibody which initially discovered by Herman Waldmann, a British immunologist in 1983. He randomly injected a rat with some human white blood cell residue, and he observed that the rat immune system raised a specific antibody against human lymphocytes. This antibody was named ‘Campath’ by the university of Cambridge at that time (Hale, Geoffrey et al. 1983)

Mechanism

Like a typical antibody, the Y shape molecule structure of alemtuzumab is made up of four polypeptide chains. The two binding sites of this monoclonal antibody are specific to the antigen CD52, which is located on the surface of T and B lymphocytes. The binding of alemtuzumab with CD52 will result in the deactivation and depletion of these cells. (Almendingen 2019)

In vivo bioassay of alemtuzumab

Many bioassays have been done for alemtuzumab. One of the preclinical bioassays that has been done on this drug to study the mechanism of action and estimate minimum efficient dose was “In vivo Cynomolgus Monkeys bioassay”. According to the studies, Non-human species cannot be selected for preclinical bioassays because the CD52 molecule expressed on their erythrocytes, causes massive hemolysis by administering alemtuzumab and the animal will eventually die. Therefore, an animal with a body type close to humans is needed to perform the bioassay. Based on the data collected from screening different types of monkeys, an Indonesian monkey, Cynomolgus Monkeys, demonstrate no CD52 on the erythrocytes and 85% homology with human CD52. (Van Der Windt et al. 2010).

The “In vivo Cynomolgus Monkeys” bioassay was performed on six Cynomolgus Monkeys. In two monkeys, mycophenolate mofetil (MMF) was added as maintenance therapy. Based on the result obtained from this bioassay, complete depletion of T and B lymphocytes (>99.5%) was achieved with 20 mg/kg of body weight (Van Der Windt et al. 2010).

Manufacture and purification of alemtuzumab

Alemtuzumab was previously marketed under the name Campath, but have been removed by Sanofi Pasteur for a higher-priced relaunch with the new name Lemtrada, targeting multiple sclerosis specifically (Mckee 2012).

There have been two main production lines being used for the manufacture of alemtuzumab: rat hybridoma cell line and Chinese hamster ovary (CHO) cell line, in which the CHO cell production line is the one currently being used for the manufacture by Sanofi Pasteur (FDA 2019).

A paper from the University of Cambridge described a detailed procedure for the manufacture of alemtuzumab. “The cells were cultured in hollow-fiber fermentors” and “a single bioreactor designed for adherent cells” was installed specifically for the CHO cell line production. After 7 days of establishment, the product was harvested using 25% fetal bovine serum, then continuously run through a 0.2 μm for 14 days and stored at -40°C until being further processed (Phillips et al. 2001).

The purification process of alemtuzumab consists 2 cycle of precipitations with ammonium sulphate first, and then a series of different chromatography purifications was carried on using Biopilot chromatography system (Pharmacia). Additional steps will be further proceeded to ensure the removal of DNA and viruses. At the end, quality control tests like radioactive labeled biological activity testing and antigen-binding activity testing by ELISA using microtitre plates will be performed on the product. Samples were saved and stored at -70°C for long-term stability testing and monitoring(Phillips et al. 2001).

Advantages of alemtuzumab

The most important advantage of Alemtuzumab is that there is no nephrotoxicity for patients with kidney transplantation, therefore, it could be considered as a replacement for drugs that has high nephrotoxicity, such as CNI drugs(calcineurin inhibitors). Moreover, the same effect can be achieved by administration of less amount of the drug. Alemtuzumab has the advantage of intravenous injection which reduces the annual relapse rate by 55% in and has a lower impact on patients’ daily life. Patients are able to get injections only a few times during a year instead of receiving daily dosage (given as two annual courses on five consecutive days at baseline and on three consecutive days 12 months later) (Ziemssen and Thomas).

Disadvantages of alemtuzumab

One of the most serious and life threatening problems with this drug is cytokine release syndrome caused by infusion reactions. based on clinical studies, 92% of LEMTRADA-treated patients experienced infusion reactions (U.S. Food and Drug Administration). Patients treated with alemtuzumab have also been seen to be vulnerable against norovirus-related (virus family Caliciviridae), a chronic diarrhea infection, due to partially inactive immune system (Ronchetti et al.), and have a high risk of serious autoimmune mediated conditions. Moreover, based on in controlled clinical studies, 0.3% LEMTRADA-treated patients developed thyroid cancer, MalIgnancies (U.S. Food and Drug Administration).

Conclusion

Despite the disadvantages alemtuzumab demonstrated, it is still considered as a very valuable molecule by many, especially for its non-nephrotoxic feature. It has already been considered by scientists for the application in organ transplants with a combination of other drugs to reach the final goal of having a balanced immunosuppression without toxicity and side effects (Andrade-Sierra et al. 2018). We believe that it also can be a great inspiration for future immunosuppressant development, especially for methods like rational drug design and side chain modifications. As our research goes on, other interesting immunosuppressive molecules was encountered, belatacept and efalizumab as two outstanding examples, drew our attention and are considered as very prospective options for the usage as a combination for immunosuppression in the near future (Almendingen 2019).

1. Almendingen, Tora Elisabeth. 2019. “Immunosuppression and Tolerance in Adult Liver Transplantation.” UiT The Artic University of Norway.
2. Andrade-Sierra, Jorge et al. 2018. “Immunosuppressive Minimization Strategies in Kidney Transplantation.” In Organ Donation and Transplantation – Current Status and Future Challenges, InTech. http://www.intechopen.com/books/organ-donation-and-transplantation-current-status-and-future-challenges/immunosuppressive-minimization-strategies-in-kidney-transplantation.
3. Grinyó, Josep M. 2013. “Why Is Organ Transplantation Clinically Important?” Cold Spring Harbor Perspectives in Medicine 3(6): 1–10.
4. Hale, G., Bright, S., Chumbley, G., Hoang, T., Metcalf, D., Munro, A. J., & Waldmann, H. (1983). Removal of T Cells From Bone Marrow for Transplantation:A Monoclonal Antilymphocyte Antibody That Fixes Human Complement. October, 62(4), 873–882.
5. Mckee, Selina. 2012. “Sanofi Withdraws Campath in US and EU.” Pharmatimes: 1–3. http://www.pharmatimes.com/news/sanofi_withdraws_campath_in_us_and_eu_976762.
6. Phillips, J. et al. 2001. “Manufacture and Quality Control of CAMPATH-1 Antibodies for Clinical Trials.” Cytotherapy 3(3): 233–42.
7. Van Der Windt, D. J., Smetanka, C., MacEdo, C., He, J., Lakomy, R., Bottino, R., … Lakkis, F. G. (2010). Investigation of lymphocyte depletion and repopulation using alemtuzumab (Campath-1H) in cynomolgus monkeys. American Journal of Transplantation, 10(4), 773–783. https://doi.org/10.1111/j.1600-6143.2010.03050.x
8. Ziemssen, Tjalf, and Katja Thomas. “Alemtuzumab in the Long-Term Treatment of Relapsing-Remitting Multiple Sclerosis: An Update on the Clinical Trial Evidence and Data from the Real World.” Therapeutic Advances in Vaccines, vol. 10, 2017, doi:10.1177.
9. Ronchetti, Anne Marie, et al. “Norovirus-Related Chronic Diarrhea in a Patient Treated with Alemtuzumab for Chronic Lymphocytic Leukemia.” BMC Infectious Diseases, vol. 14, no. 1, 2014, pp. 2–5, doi:10.1186/1471-2334-14-239.

Organ transplantation is a significant technique that can prolong a person’s life, enhance the quality of life, and considerably minimize the overall healthcare costs in patients who have end-stage liver, renal, and heart disease. Distribution of limited resources has ethical, moral, and social implications. Given that some causes of end-stage diseases are preventable; the questions arise as to whether the finite resources should be awarded to individuals who could have prevented their disease. While appealing to personal responsibility to prioritize patients has the potential to produce beneficial outcomes, lifestyle choices should not be used as a criterion to influence lifestyle choices.

Personal behavior is influenced by an individual’s lifestyle choice. Lifestyle refers to a person’s way of living; the activities that an individual or a particular group engage in (Mayes 3). In this context, lifestyle choices can be defined as the decisions which people make concerning how they live. These decisions shape almost every aspect of contemporary medicine, and at the same time, are particularly pertinent to clinical decisions regarding organ transplantation or surgery.

However, deciding whether personal choices, as well as the extent to which these choices should shape surgical decisions, are complex. For example, should a 57-year-old smoker and drug dealer undergo a costly and potentially futile organ transplant? What about Sansa, a 23-year-old social worker, who has sustained bone fracture for the second time while playing hockey? Presented with such questions, there is no definitive answer as to who the most deserving candidate for an organ transplant is, although the scenarios present how personal prejudices might adversely and undeservedly bias the organ transplantation decision-making process.

When determining how an individual’s personal behavior should influence who gets to receive an organ transplant, patients should not be categorized by the traditional vices: a sedentary lifestyle, drinking, and smoking. Instead, lifestyle choices or personal behavior should be defined using a systemic and more structured set of the framework. Intrinsic individual behaviors are those which encompass any level of personal patient choices. Consequently, besides the negative examples listed above (poor dieting, alcohol consumption, and smoking), intrinsic lifestyle choices can also include positive lifestyle choices. Hence, in the same manner, smoking might increase the lifetime risk of needing organ transplant for lung cancer, is the same way engaging in exercise may increase the chance of needing an organ transplant due to sporting injury (as illustrated in the Sansa case). Therefore, both positive and negative lifestyle choices have the potential of increasing a person’s likelihood of needing organ transplantation.

Compared to intrinsic lifestyle choices, determining extrinsic lifestyle decisions is increasingly challenging. Fundamentally, extrinsic lifestyle choices are those that people do not exercise individual autonomy. On this note, Marmot and Bell (4-10) emphasize that environmental, economic, cultural, and social behaviors are antecedent to personal behaviors associated with diseases. He argues that structural factors (geographic location, household income, education level) and not lifestyle choices should be the main target of interventions to prevent certain health-related issues. Accordingly, these socio-economic factors are inherently related to several negative health behaviors including alcohol and substance abuse, sedentary lifestyle, and socio-economic status is, consequently, correlated with that of a person’s parents. A presumption that intrinsic lifestyle choices imply a person’s true choices might be a fallacy. Therefore, personal behaviors have a part to play in health status but focusing on the individual without considering the social determinants of the health issue fails to address the complexity of who is deserving of medical surgery.

One of the ethical principles that are usually applied to the issue of organ transplantation is that of beneficence, that is, “the moral obligation to act for the benefit of others” (Bedford and Jones 17). This argument is based on the theory of utility which calls for the greatest good for the largest number. Based on the utility principle, presented with a choice between two or more possible causes of action, the morally justifiable act is to that which leads to the greater good. It can then be argued that transplanting an organ into an individual who has caused the damage leading to the requirement for a transplant is less likely to produce the greatest good for the greatest number. In this situation, the lifestyle choice is considered because objective evidence exists indicating that lifestyle choices will indicate the possible outcome of organ transplant. Moreover, the issue of cost presents a compelling line of reasoning. In a healthcare system with scarce resources, Bedford and Jones (17) note, economics plays an important role in informing the allocation of those resources to optimize benefits.

However, if the patients who make unhealthy lifestyle decisions are denied access to the organ transplants they need to survive, it becomes complex to determine where the line should be drawn. Organ transplantation is a costly business and the government seeks to get value for its investment. The policy makers together with the healthcare practitioners could as well say that organs are only allocated to, for example, parents of young children or individuals in valued professions, instead of the childless, unemployed, or the older people.

This paper has argued that a patient’s personal behavior should not influence clinical decisions regarding whether or not he or she should receive an organ transplant. Also, the due difficulty of defining what actually constitutes an autonomous choice, Priority must, therefore, be given to patients subject to their clinical needs and not personal beliefs that the patient’s behavior or lifestyle has led to their condition.