Animal transplants

More on animal transplants

There are various types of transplants that are already being done, or are being researched:

Donated human organs such as kidneys are now regularly being transplanted into patients whose organs are failing. This process is called allotransplantation . However, because the rate of organ donation is low and not sufficient to meet the demand, research has been going on for some time to use animal organs and tissues. The intention is to produce transgenic animals containing human genes specifically chosen to minimise rejection of the tissue when it is transplanted into humans. The process of transplanting tissues from one species into another is called xenotransplantation .

There are several aspects to this topic:

  1. the ethics of exploiting animals;

  2. scientific problems of xenotranplantation;

  3. alternatives to xenotranplantation.

1. The ethics of exploiting animals

Even before any human transplants take place, many animals are being experimented on, especially primates and pigs. All these animals will die after organs have either been removed from them or transplanted into them, some with ill-health and pain. If full-scale xenotransplantation ever goes ahead, tens of thousands of animals will die in sterile laboratory conditions. They will cease to be regarded as living, feeling individuals, and will become nothing more than organ factories.

Xenotransplantation is another example of the attitude that denies non-human animals any right to live out their lives, free of suffering. They are seen only as commodities, to be exploited by humans in whatever way is convenient. As Alan Berger, Executive Director of the US Animal Protection Institute has observed (1):
" Behind xenotransplantation lies the age-old assumption that human beings are the masters of all creation and therefore entitled to use animals as they see fit. Animals have the right to live, to be free of pain and suffering, and to pursue their own natural and essential interests. All human and non-human animals have special and unique traits and deserve moral consideration in their treatment. "

Some people might ask why, if animals are killed for meat, they should not be killed for tissue transplants. On this point Peter Singer, formerly professor of philosophy at Monash University, has said (2):
" In a world that needlessly rears several billion animals in factory farms each year, and then kills them to satisfy a mere preference of taste, it is difficult to argue persuasively against the rearing and slaughter of a few thousand animals so that their organs can be used to save people's lives. That, however, is not a reason for using animals; it is, rather, a reason for changing our views about animals. "

Killing animals for meat when vegetarian diets are not only easily available, but also healthier (see section 3), is itself an ethical issue. Such unnecessary killing is morally dubious and therefore can't be used as a basis for justifying the killing of animals for transplants.

Exploiting animals and seeing the value of their lives only in terms of their usefulness to humans is based on an attitude known as "speciesism". It is basically a prejudice like racism or sexism that claims one's own group (eg humans) matters and has a right to consideration and respect that is denied to other groups (eg non-humans). This decision is not based on any particular characteristics of the individuals, purely which group they belong to.

People might argue that the exploitation of animals is justifiable because they are less intelligent and rational, can't speak or use tools, don't form societies, and so on. However, research continues to reveal amazing abilities in animals and, on the other hand, there are some humans who don't have these abilities, for example, those with severe brain damage. We don't eat or experiment on these people, but we do eat and experiment on animals, no matter how intelligent they are. The different treatment is based purely on which species the individuals belong to, not any particular characteristics they possess. This is the essence of speciesism.

For a more detailed discussion of ethics, go to Peter Singer's article Xenotransplantation and speciesism .

Apart from death and possible suffering, another stress factor is the sterile conditions in which the genetically engineered animals to be used for transplants will be kept. One description is as follows:

" To reduce the risk of exposure to disease, these genetically altered pigs are removed from the womb by caesarean section, never allowed to suckle or even come in contact with their dam, are hand-raised by humans wearing gloves, and maintained in a fairly sterile environment. " (1)

Another writer describes conditions as follows:

" Pigs and piglets will be raised in secure HEPA filtered units and fed only sterile food. All material used in these facilities will be sterile or sterilisable. Piglets will be derived by hysterectomy or medicated early weaning and reared on artificial foods containing no animal proteins. " (3)

In these conditions, animals can't express their natural behaviour and are likely to be frustrated and stressed. For all these reasons, animals should not be used for transplants.

This still leaves the problem of patients dying or organ failure. What should be done? Speaking of animal experiments in general, Peter Singer has said:
" If in our present situation we find ourselves faced with the dilemma of inflicting harm on an animal in an experiment, or allowing harm from a disease to go unchecked, the best possible solution is to find a way around such a dilemma. " (4)

In section 3, alternatives to animal tissue transplants are discussed. In the meantime, it is worth remembering that a strong push for xenotransplantation is coming from very powerful corporations who have a financial interest in the transgenic animals used for transplants. For example, the giant Swiss company Novartis is a major player and is prepared to invest up to US$1 billion in the near future. The market may be worth $6 billion in 2010, with Novartis taking more than half this fortune (5).

Companies like Novartis have a vested interest in promoting animal tissues as the solution to organ shortages. Obviously they will not make money from the largely non-profit options discussed in section 3,although these options are undoubtedly better for the animals and may better for the public as well (see next section).

2. Scientific problems with xenotransplantation

Between 1964 and 1993, a total of 29 people received a heart, kidney or liver from either a baboon or a chimpanzee. Some survived for as little as one day, with the longest survival time being 9 months (6).

Possible problems with transplantation of whole organs from animals to humans include:

  1. viral diseases transferred from animals;

  2. rejection of the organs by the patient's immune system;

  3. differences in structure and biochemistry between human and animal organs.

2a. Diseases transferred from animals

Baboons and chimpanzees were originally considered the animals of choice for transplants because the primates are most closely related to humans. However, they are now much less likely to be used because of the risk of transferring potentially fatal viruses. The following are examples of diseases transferred from primates to humans: (7)

This final point raises 2 very important issues.

Firstly, a virus that causes few clinical symptoms in its natural host can become much more dangerous when transferred into a new host. For example, Simian Haemorrhagic Fever Virus (SHFV), is widespread in African monkeys such as baboons and green monkeys, but it causes no clinical symptoms. When it was transferred to Asian monkeys, it caused thousands of deaths in macaques due to a rapidly fatal haemorrhagic fever (8). As virologist Jonathan Allen has stated: (7)
" A virus that seems ubiquitous in nature and induces little or no pathology in its natural host, may under the proper conditions wreak havoc in a foreign host. "

Secondly, because viruses can be present but cause no disease in their host, researchers don't know what to look for. There are probably many viruses that have never been identified for this reason. A new virus may become apparent only when it is transferred to a new species and begins to cause disease. As Jonathan Allen has said (7):
" Many animal viruses that pose a risk for initiating new diseases in humans generally cause no overt damage to their natural host reservoir so that identification of potential pathogens from those animals is not possible. "

Pigs are now the favoured animals for transplants, but they too carry viruses that can infect humans. As one researcher stated at a conference in 1999: (3)
" Some argue that, as pigs have lived alongside humans for so long, we would by now have picked up any of the microbes capable of infecting us. Yet pig calicivirus, closely related to human hepatitis E virus, was discovered within the last few years, and the Nipah virus, identified earlier this year, was only discovered during an outbreak of a fatal encephalitis in Malaysia. "

In 1997 a new virus, named Menangle virus, was found in piggeries in NSW. Two workers who had contact with the pigs developed a febrile illness (9). In 1997 another new virus, named swine hepatitis E virus, was identified in the US. It is widespread but causes only sub-clinical symptoms in young pigs. It is very similar to the human hepatitis E virus (10).

In addition pigs, like all mammals, contain endogenous retroviruses that are passed on to offspring in the DNA of normal chromosomes, and therefore can't be eliminated. As a virologist who works with these viruses has said: (11)
" These viral sequences in host DNA can be activated to produce infectious viruses that are closely related to leukaemia viruses of mice, cats and gibbons and second cousins to HIV. Last year we reported that two of three pig endogenous retroviruses can infect human cells in culture. "

Apart from the known viruses and endogenous retroviruses, there are undoubtedly others yet to be discovered. As virologist Jonathan Allen has warned:(7)

" One must also keep in mind that the greatest risk of xenotransplantation to humans comes from viruses that are waiting to be discovered. In general, viruses from newly emerging diseases are only identified once the target population has been significantly affected. "

There are several reasons why tranplant patients are particularly vulnerable to any viruses present (11):

  1. All physical barriers the body has evolved over millenia to block the entry of viruses are circumvented by one surgical procedure that places the foreign tissue inside that patient's body, in contact with his/her blood supply.

  2. Patients need powerful immunosuppressant drugs to stop rejection of new organs, even more so if they are of animal origin. Therefore the immune system is weakened and less able to fight off infection.

  3. One change introduced to reduce rejection involves genetically engineering pigs to express human complement regulating proteins. However, these proteins in the transplanted organs can also act as receptors for viruses.

Pig heart valves have been transplanted into humans for some time without any signs of pig viral infections. Some people argue that this proves how low the risk of disease transfer is. However, a New Scientist (8/8/98) editorial points out that such valves are soaked in gluteraldehyde and " are no more alive that a toenail ."

One study has examined the relatively small number of patients who so far have had contact with living pig tissue (12). The largest number had had their blood circulation perfused through a pig liver or spleen outside the body, with smaller numbers involved in pig pancreatic islet transplant or pig skin graft. Although 23 of 160 patients had pig DNA in their blood, none showed signs of viral infection.

However there have been problems of a different kind when foetal brain cells from pigs were injected into stroke victims in the US. In the first 3 patients there were no side effects, but a further patient developed seizures and another had brain swelling and muscular fatigue. The experiment has been suspended (13).

2b. Tissue rejection

The immune system attacks any foreign proteins, so transplant patients have to take powerful immunosuppressant drugs for the rest of their lives to stop their new organ being rejected in this way. The rejection occurs even when the new organ is human, but is an even greater problem when it is from another species.

There are 3 stages of rejection, the first 2 resulting from the action of antibodies, the third from the action of T cells (11).

  1. Hyperacute rejection , in which the blood vessels in the foreign tissue are destroyed within a matter of minutes. Pre-existing antibodies that recognise non-human cells, also called xenoreactive natural antibodies, bind to molecules on the surface of foreign blood vessels. This is turn leads other molecules, called Regulators of Complement Activation (RCAs) to activate complement (specific proteins in the blood) which rupture cells in the lining of foreign blood vessels, thereby destroying the tissue.

  2. Acute rejection , which begins within 24 hours and leads to the destruction of blood vessels in the following days. This reaction is also triggered by antibodies, and leads to swelling, inflammation and platelet coagulation.

  3. T-cell rejection , which occurs 1-2 weeks after transplantation and involves foreign cells being attacked by lymphocytes (white blood cells) called T-cells.

Researchers have tried to overcome Hyperacute rejection by creating transgenic pigs which express human Regulators of Complement Activation (RCAs). These proteins trick the patient's immune system into thinking that the organ isn't foreign and so stop the activation of complement that would normally rupture cells in the lining of the organ blood vessels.

Hearts from such pigs have been transplanted into monkeys. Without any immunosuppressive drugs they survived for a median of 5.1 days (only 1.6 days with non-transgenic pig hearts). With immunosuppressive drugs the monkeys survived for a median of 40 days (14).

While genetic engineering may overcome Hyperacute rejection, Acute rejection and T-cell rejection still have to be dealt with through powerful immunosuppressive drugs. It may be that even higher doses would be needed for xenotransplants than for allotransplants. Some researchers have commented as follows on the problems of immunosuppression: (15)
" ... although modern immunosuppressive regimens are successful in promoting short-term allograft survival, they have little impact on long-term survival, and are ineffective in preventing chronic rejection, which may be more prominent in xenografts than allografts. Secondly, the major complications of systemic immunosuppressive regimens, infection and neoplasia, may both be more serious in xenograft recipients needing high levels of maintenance immunosuppression. Finally, the risk of transmission of zoonoses (animal diseases) from xenografts may be exacerbated by generalised immunosuppression. "

2c. Organ structure and biochemistry

Even if whole pig organs are not rejected, there is still a large question mark as to whether they can adequately carry out the function of human organs. One group of researchers has questioned:(15)
" ... almost nothing is known about how whole xenogeneic organs will perform over the medium and long term. For example, will a human microenvironment be suitable for efficient performance of a porcine organ? Also, what will be the natural lifespan of a xenogeneic organ in a human recipient? "

Anatomists have found some significant differences between human and pig hearts, related to the fact that blood has to be pumped through a body standing upright in humans, but not in pigs. These researchers have said: (16)
" We observed several important and notable anatomical differences between the hearts of pigs and man, and were indeed surprised at the accepted convention the the pig heart is virtually identical, anatomically, to the human heart. "

The situation is even more complex with other organs. For example, the kidneys do not only filter the blood, but also produce biological products different to those in pigs (11):
" Kidneys, as well as producing urine, synthesise erythropoietin, a hormone essential for regulating the production and maturation of red blood ells. Porcine erythropoietin does not function in humans because human erythropoietin receptors on red cell precursors in the bone marrow do not recognise the pig version of the hormone. Thus, human recipients of pig kidneys would need to be treated with recombinant human erythropoietin. There may be other discordant physiological signals between pigs and humans, including the factors that control the health and function of the bone marrow and liver. We do no yet know which tissues will function properly in the cross-species setting."

The liver carries out around 500 intricate metabolic functions, and a pig liver is highly unlikely to carry out these functions in the same way as a human liver. As a group of researchers pointed out (15):
" It is ... difficult to predict how effectively a porcine liver would perform, given the complexity of hepatic function and the number of vital proteins synthesised by the liver (which, in a pig xenograft recipient, would all be porcine)."

There are many major problems associated with the use of animal organs for transplantation.

Alternatives to xenotransplantation

3. Strategies to avoid the use of animal tissues include the following:

  1. Increase the supply of donor organs

  2. Decrease the need for new organs

  3. Use human tissues

3a. Increase the supply of donor organs

Referring to the situation in the US, the American Medical Association (AMA) has said: (17)
" Since organs are retrieved from only about 15% to 20% of the 15,000 to 20,000 eligible cadaveric donors available each year, increased efforts to encourage organ donation could save many more lives. "

To this end, the Council of the Ethical and Judicial Affairs of the AMA favours a system of Mandated Choice , where all adults would be forced to make a choice about organ donation (17). Official forms such as tax returns and driver's license renewals would contain a compulsory question: After your death would you be willing to donate your organs for transplantation? Yes/No.

Many countries in Europe in particular have adopted a different system, that of Presumed Consent , where it is assumed that everyone is a donor unless they register an objection. This system is also referred to as an opting-out system because only have to take any action if they want to opt out of the scheme. In Belgium an objection can be registered at any town hall, and is recorded on a central registry that can be accessed from any hospital. However, only 1.75% of the Belgian population has opted out (18).

Countries vary with regard to the role played by relatives of the potential organ donor. In Belgium relatives are informed that the organs will be retrieved, and at that point they have a legal right to register an objection. Less than 10% do so in Belgium (19), although in other countries such as Spain the family refusal rate is 25%-30% (20). However, in Austria if a person has not registered an objection to organ donation during their lifetime, the relatives have no right to object after the person is dead (21).

There is no doubt that presumed consent increases the number of organs retrieved. For example, Singapore changed to this system in 1988. From the first transplant in 1970 to 1987 an average of 4.7 kidneys a year were transplanted, but this rose to 31.3 in 1988-1990 after presumed consent was introduced (22).

Belgium introduced presumed consent in 1986, and the table below shows that increase in organs available for transplant (23). The numbers in brackets refer to organs per million of population (pmp):



1982-5

1987

1988

1989

Kidneys

187 (18.9)

371 (37.5)

377 (38.8)

409 (41.3)

Hearts

9 (0.9)

77 (7.8)

89 (9.0)

118 (11.9)

Livers

7 (0.7)

42 (4.2)

66 (6.7)

106 (10.7)



There was a 119% increase in the number of kidneys within 3 years of the introduction of presumed consent and, at least in the context of Europe, the researchers concluded (23):
" The problem of organ shortage can adequately be solved in the setting of an opting-out legislation.>"

In Austria presumed consent legislation came into effect in 1982. In 1986 special doctors were appointed as transplant coordinators in hospitals and, as the table below shows, this further increased available organs (21):

1965-1981

4.6 pmp

1982-1985

10.1 pmp

1986-1990

27.2 pmp



In 1990 the rate of organ retrieval was 31.9 per million of population (pmp), leading researchers to conclude (21):
" There are enough donors for all patients on the waiting lists, at least for kidneys."

Countries such as Belgium and Austria with presumed consent legislation have higher rates of organ retrieval that countries such as Germany and the Netherlands with informed consent, where individuals have to register their willingness to donate organs. The following table shows organ retrievals from 1993-1995 per million of population in these 4 countries (24). The row marked "Increase" indicates how much higher the rate of organ retrieval was in the 2 countries with presumed consent than in the 2 countries with informed consent.

Kidneys

Livers

Pancreas

Hearts

Lungs

Belgium

39.9

13.0

1.6

12.1

5.7

Austria

46.0

14.7

2.0

12.6

6.3

Germany

24.2

5.9

0.6

5.8

1.5

Netherlands

27.9

7.3

1.2

4.3

2.0

Increase

+65%

+110%

+100%

+145%

+71%



Clearly presumed consent legislation dramatically increases the supply of donor organs, which is why the British Medical Association has called for this system to be introduced in England (25). It is based on the fact that a majority of people support organ donation, but don't get around to filling out a donor card. For example, in a Swedish survey 65% of people agreed with organ donation but less than 10% had filled out donor cards (26). In Australia over 60% supported organ donation, yet in NSW hospitals only 26% of potentially suitable organs were retrieved (27). In Belgium 80% of people supported organ donation (28).

Presumed consent has the added advantage that doctors don't have to ask relatives for permission to use organs at a time of great stress, as one writer comments (19):
" It would seem from the Belgium experience that relatives may be reluctant to take a personal decision about the removal of organs but they find it easier to agree if they are simply confirming the intention of the dead person. If this is so, a contracting out system has the moral benefit of relieving grieving relatives of the burden of deciding about donation at a time of great psychological stress. "

However, presumed consent legislation on its own will not achieve maximum results. Transplant co-ordinators in hospitals also play a role, as shown by the high rate of organ retrieval in Spain, and the increase in Austria after this system was introduced. In South Australia, the rate of organ retrieval increased to almost 23 pmp after such co-ordinators were appointed, double the national average (29). The rate of donation is still below that of Austria or Spain, however, countries where there is presumed consent legislation in addition to hospital co-ordinators.

In addition, public education is essential so that the public fully supports the concept of organ donation both for themselves and their next of kin. As one advocate has said: (30)
" To avoid misinterpretation, massive amounts of public education would be needed before any shift to presumed consent. Debates and education campaigns could be used to raise awareness of the need for organs, the success of transplants, medical criteria for death and the compatibility of organ donation and religious belief. In Singapore, where presumed consent has been the rule since 1987, all residents receive a letter upon attaining the age of majority. It states that they are presumed to consent to organ donation if they do not explicitly object to it "

Recognising the importance of education, a Presidential decree in Argentina in 1998 created the National Education Program on Organ Donation. Curriculum materials are being developed for all levels of education (31).

Educational presentations in high school increase knowledge about organ donation and transplantation. In a German study, the presentation decreased transplantation-related fears and increased willingness to donate in some groups (32). In a US study, the presentation increased willingness to donate. In this case the presentation included testimonials from transplant recipients of the same age as the students. Being able to see the positive outcomes of organ donation may make it a more appealing option (33).

3b. Decrease the need for new organs

Demand for transplants is increasing. However, some of the diseases that lead to organ failure are preventable, for example, type II or mature-onset diabetes. This disease is linked to poor diet, obesity and lack of exercise, and can lead to kidney and heart failure.

A 21-year study of Seventh Day Adventists, who are advised by their church to be vegetarian, found that diabetes as a cause of death was only 45% that of the general population, in other words, less than half. Among the Adventists, those who ate meat were more likely to develop diabetes that those who did not (34).

When patients with diabetes were put on a low-fat vegan diet, they reduced their fasting glucose levels, weight and the amount of medication they were taking, to a much greater extent that another group on a standard diabetes diet (35).

Heart disease is much lower in vegetarians. A British study found that the incidence of heart disease was 24% lower in lifelong vegetarians and 57% lower in lifelong vegans (36). Among middle aged Seventh Day Adventists, those who ate meat daily were 3 times more likely to have a fatal heart attack than those who did not eat meat (37).

A low-fat vegetarian diet can not only prevent but also reverse heart disease once it is established. After 1 year of dietary change and exercise, patients reduced their weight and cholesterol, and arteries were less blocked by atherosclerotic plaques. In contrast, in a group that did not make dietary changes the arteries became more blocked over the course of the year (38). The reduction in arterial plaques was even more pronounced after 5 years of intervention (39).

Aggressive advertising campaigns against smoking have had an effect, at least in older age groups. Fewer people are now smoking. However, obesity, high blood pressure and high cholesterol continue to increase, and with them lifestyle diseases such as diabetes and heart disease. Advertising campaigns similar to those against smoking should be mounted against lifestyle diseases, promoting exercise and vegetarian foods.

It is even more important to decrease the need for organ transplants than it is to increase the supply of organs, because reduction in disease not only has personal benefits but saves the community large sums of money in hospital costs.

3c. Use human tissues

In cases where tissues or cells rather than whole organs are transplanted, it would be possible to use human material. For example, an artificial skin called Apligraf based on cultured human cells has recently been marketed (40).

In some diseases, such as type I diabetes and Parkinsons disease, only a few cell types are malfunctioning, and if these cells could be replaced the disease would be cured. One approach is to use stem cells from pre-implantation embryos, for example, embryos left over after IVF treatment and donated for research instead of being destroyed (41). Stem cells are the first kinds of cells in an embryo, with the capacity to turn into any kind of cell, such as muscle or nerve. Such cells can now be grown in test tubes for 4-5 months, and then still have the capacity to differentiate into any kind of cell type, including pancreatic cells to produce insulin for diabetics and nerve cells to produce dopamine for Parkinsons sufferers. These differentiated stem cells could then be transplanted into patients. In some studies neurones from terminated embryos up to 9 weeks old have been transplanted into the brains of patients with Parkinsons disease. This tissue containing dopamine cells was not rejected and improved the condition of most patients (42, 43).

Another approach is to use the patient's own cells. The nucleus of a healthy cell could be transferred into a donor egg to produce an early stage cloned embryo, from which stem cells could be isolated and differentiated into the appropriate type. Because the cells are genetically identical to the patient, there would be no problem with rejection when they are transplanted into position. In relation to the ethics of such therapeutic cloning, one researcher has commented (44):
" This approach, involving human cloning, is bound to raise controversy but may be ethically acceptable as it generates only a very early embryo (with around 100 cells) which current ethical opinion does not consider a human being, principally because at this stage it has not yet begun to develop a nervous system. "

As knowledge of cell culture and stem cell development increases, more and more of such therapeutic human tissues could be generated, without the risk of introducing new diseases or causing distress and death to fully-formed, sentient nonhuman individuals.

Another option is mechanical organs. For example, a new mechanical heart has recently been trialled to keep a patient alive until a human heart is available for transplant. Such devices are also likely to become more efficient in future.

Further documents on animal organ transplants, you could see:
Xenotransplantation: the Ethics, the Science, the Risks
Xenografts and Animal Rights

Click here to see References for this document on transplantation.