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The Xenotransplantation Debate -
Science or Superstition?

Diabetes is a disease that costs the United States economy over $100 billion per year.  Diabetes costs its sufferers their eyes, kidneys, limbs, hearts, spontaneity, and eventually their lives.  Diabetes costs families their mothers, fathers, aunts, uncles, grandparents, and children.  Diabetes is a slow and cruel killer.

A primary cause of diabetes is the destruction of cells, known as islets, that produce insulin in our bodies.  Today there is promising research that offers the possibility of replacing these dead islets with living islets, thereby restoring normal insulin production to a person with diabetes.  Cured of the wildly fluctuating blood sugars that characterize every case of diabetes, the sufferer can look forward to a life that is not shadowed by the horrors of this disease.

For seventy-five years, people with diabetes have attempted crude control of their blood sugars through injections of pig insulin.  Today, we may be close to a time when the pig islets that produced that insulin are transplanted into the sufferer, providing perfect control of blood sugar at all times.  Many research centers are working on such a procedure, known as islet xenotransplantation.

Other than islet xenotransplantation, there is little demonstrated hope on the horizon for curing diabetes. Although other research activities are underway, none has achieved the level of demonstrated potential and safety of this procedure.

So why is such a promising technology not being funded almost as a latter-day Manhattan Project?  A major roadblock that can and should be lifted right away is the threatened moratorium on xenotransplantation by some governments.   In support of such a ban, certain scientists cite some theoretical risks, none of which has ever been proven or demonstrated, and use these risks as a reason to deprive people with diabetes of their best shot at a cure.  These scientists talk about the danger of infecting islet recipients with pig diseases and thereby creating a public health risk.

Today we have a situation in which some totally unproved and speculative risks are being used to prevent the elimination of the very real risks of diabetes.  It is an absurd situation in which the horrors of diabetes are allowed to continue in the face of opposition that is more superstition than science.

Why islet xenotransplantation trials should proceed immediately...

Xenotransplants have a clean track record…

In 1998, sensitive assays were performed on people who had received living pig cells. The objective was to see if there was any evidence of infection by pig viruses. The New Scientist (8 August 1998 Vol. 159 No. 2146) reported the results of this study. Below are excerpts from the article:

... fears that novel viruses might wreak havoc in transplant patients who receive pig organs may be groundless, according to findings due to be presented this week in London. The findings, based on screening samples from patients exposed to pig tissue, provide the first compelling evidence that dormant pig viruses do not spread to humans, causing new and incurable infectious diseases.

Even in patients where the cells survived for more than a year, the researchers found no pig virus DNA. Nor could they find any antibodies against pig viruses in their blood, suggesting the blood was free of infection. And there were no signs of viral reverse transcriptase enzymes, a telltale sign of any unidentified viruses.

Diacrin, a company in Charlestown, Massachusetts, was also due to present encouraging results this week. It has developed treatments for Parkinson's disease and  Huntington's disease using brain cells from pig fetuses. The company did not find pig viruses in any of its 24 patients, including one treated three years ago.

Other companies reported similar results last month in Montreal at the World Congress of the Transplantation Society, an international organisation. They included Circe Biomedical in Lexington, Massachusetts, a company that has used pig liver cells in a device that extracts toxins from the blood of patients with liver failure. Of the 25 traceable patients receiving the treatment, none has acquired pig viruses. Last week, following approval from the FDA, Circe resumed trials in the US and Europe.

These studies were looking specifically for any evidence of infection from living pig tissue in humans, and found none.

Transplants of pig islets into a number of humans in the United States, New Zealand, and Sweden have produced no adverse effects from pathogen crossover, despite the fact that many recipients were immunosuppressed, and hence much more susceptible to infection. Dr. Anthony Sun at the University of Toronto has successfully reversed diabetes in monkeys, our primate cousins, using microencapsulated pig islets.  Even though these islets were harvested from slaughterhouse pigs under non-optimum conditions, the monkeys experienced no adverse effects as a result of the transplants.

Similarly, pig skin has been used for graft purposes on serious burns in many thousands of cases, and there has been no evidence of pathogen transmissibility.

Another comforting body of evidence lies in the thousands of animals that have been transplanted with pig tissue, and the total absence of retroviral transfection. Laboratories around the world have been implanting pig tissue into mice, rats, rabbits, dogs, monkeys and other animals for decades.  Many of these animals were severely immunosuppressed and some, such as SCID mice, had no immune system at all.  Yet even given these ideal opportunities, porcine retroviruses produced no infection. If retroviral infection were to be a real issue, then we would have seen infection not only in the animals themselves, but likely also in their human handlers who suffer periodic bites and other opportunities for transfection.

Thus, not only has retrovirus infection of humans never been demonstrated through centuries of intermingling, but actual xenografts have failed to infect any recipient.

Human infection by pigs has never been a public health issue…

The risk of infection of human beings by pig viruses such as Pig Endogenous Retrovirus (PERV) has been present for hundreds of years.  Humans have butchered pigs over the centuries, with literally millions of opportunities for viruses to enter human bodies through wounds and lesions.  Even in the massive industrial meat packing operations of this century, with each worker butchering hundreds of pigs every day, PERV infection of a human being has never been a public health issue.  In other words, there have been millions of inadvertent experiments seeking adverse clinical outcomes as a result of PERV infection on many millions of people.  If PERV could infect humans, it would have done so by now.

AIDS was not caused by xenotransplantation…

Those opposing islet xenotransplantation frequently talk about the scourge of AIDS.  It is important to remember that AIDS was not caused by the transplantation of animal tissue into people.  The Human Immunodeficiency Virus (HIV) found its way into humans through existing pathways. Islet xenotransplantation is not some new pathway where none existed before, and to use the specter of AIDS as a bogeyman against this procedure is irresponsible scare-mongering without any scientific integrity.

Mad Cow Disease…

Some opponents of xenotransplantation have cited Mad Cow Disease as an example of animal diseases infecting humans with disastrous consequences.  Once again, the pathway through which this disease was spread was not xenotransplants, but was the feeding of diseased animal protein to cows.  Such an infection pathway has absolutely no relevance to xenotransplants, since the cost of islets is insignificant compared to their benefit, and there will be no economic pressure to use diseased donors.

Medical science is all about risk and benefit…

Every medical advance and procedure carries both risk and benefit.  When the benefit outweighs the risk, we progress. To deny islet xenotransplantation to people with diabetes is to ignore the profound benefits while irresponsibly exaggerating the undemonstrated risks.

Consider medical practices that are performed every day.  Normal organ transplantation carries the risk of infecting the recipient with every pathogen present in the donor, including HIV.  Today, people with AIDS are routinely treated at hospitals, despite the risk of infection to medical staff.  These are not some abstract theoretical risks, but real dangers that have unfortunately been demonstrated many times.  Yet even this public health danger does not stop us from performing organ transplants or providing medical care to people with AIDS.  As a society, we have made the rational decision that the benefits outweigh the risks, however real those risks may be.

We should all be grateful that voices like the present xenotransplant opponents' were not heeded at the introduction of blood transfusions or organ transplants or any number of other medical advances.  If they had been, many of us would not be alive for this debate.

Pigs are cleaner than people…

As organ donors, pigs are a much safer source than human cadavers.  Pigs can be bred in a specific-pathogen-free environment to optimize the safety of their tissue for transplants.  We have no control over the lives led by human donors, or the safety of their organs after brain death. There are very few viruses which can cross from pigs to humans, and only pig tissue that is free of such viruses will be used.  Because pig tissue is so plentiful and cheap, it is possible to test extensively and to accept only the most pathogen-free sources.

Islet xenotransplant recipients retain a healthy immune system…

In most cases of organ transplant, the recipient is required to take life-long immunosuppressant drugs to prevent rejection of the transplanted tissue.  As a result of a weakened immune system, the recipient is much more prone to infections and to certain types of cancer.  Many of the concerns expressed about xenotransplantation are based on the expectation that the recipient will be immunosuppressed, whereas this is not the case.  Because islet xenotransplantation uses immunobarriers to protect the islets from rejection, the recipient retains a normal healthy immune system.  Therefore, any later infections are as controllable as in the general population and no additional public health risk is created.

An improbable chain of events...

Before PERV infection from islet xenotransplantation ever becomes a public health issue, a series of conditions must be met.  To endanger the public, all the following questions must be answered with a yes.  Has PERV actually ever infected a human being?  If PERV infection is possible, is PERV replication-competent?  If it is replication-competent, can PERV actually cause disease? If it can cause disease, can the disease spread to other humans?  Considering that science cannot even answer yes to the first question, it is irresponsible to conclude that a prohibitive risk exists in the face of such overwhelming benefit to society.

Immunobarriers also block retroviruses...

In islet xenotransplants, immunobarriers are used to protect the islets from the recipient's immune system.  These barriers encapsulate the islets and have pore sizes thousands of times smaller than any retroviruses that may be trapped inside, thereby providing an additional, though unnecessary, level of protection against retrovirus infection.

Pigs are not primates…

Much of the fear of xenotransplantation derives from the proposed use of baboons and other primates as organ donors.  Because humans are also primates, the number of viruses than can cross from a primate donor to a human recipient is similar to a human-to-human transplant.  Pigs, on the other hand, are not primates and the species barrier is yet further protection against infection.

There is no animal rights issue…

Some have questioned the ethics of sacrificing pigs to cure human disease.  Surely it is more ethical to sacrifice a pig to spare a child the horrors of diabetes, than it is to slaughter pigs for bacon, suede, and paint brushes.

We can’t just rush ahead putting pig islets into young children…

Many critics of xenotransplantation raise the prospect of suddenly transplanting pig islets into thousands of young children with diabetes.  It is important to realize that no proponent of islet xenotransplantation is making any such proposal.  What is needed is immediate clinical trials of islet xenotransplants in adult diabetics who understand informed consent, and who are not taking immunosuppressive drugs.  As the procedure is shown to be safe and effective in adults, the age threshold can gradually be reduced until the medical community has the confidence to provide this treatment to children.

Let's stick to science...

Many of the arguments against xenotransplantation fail the test of reason or common sense.  The Ministry of Health in New Zealand last year banned further xenotransplant trials after Dr. Robert Elliott had demonstrated some encouraging early results.  As you can see in a letter from the Honourable Bill English, Minister of Health for New Zealand, he twice cites "cultural safety" as a major factor in his ban of xenotransplantation.  Furthermore, he has failed to deliver on every promised deadline.  Clearly, diabetes is of no interest to this man beyond its immediate political ramifications.  We must not allow some politician to delay or ban today's only hope for ending diabetes for reasons as indefensible as "cultural safety".   It would be laughable if it were not so tragic.

In conclusion…

All progress entails some risk, and to avoid all risk is to kill progress.  We know the risks of diabetes – blindness, kidney failure, heart disease, amputation, birth defects – as well as the staggering healthcare costs (over $100 billion per year in the US) and productivity losses.  Clinical trials of islet xenotransplantation are such a small and manageable risk compared to the horrible and near certain outcomes of this disease.

As people with a vested interest in curing diabetes, we must assure that our voices are heard.  In this debate over the benefits and safety of islet xenotransplantation, I have heard from several researchers and government policy makers who make statements such as, "We cannot just rush into this without proper investigation" and "While we understand your sense of urgency, we are not prepared to unleash a new epidemic on the general population."  Such dismissive pronouncements have been effective in the past in silencing debate and allowing our civil servants to avoid making a decision.  But we have science on our side, and we must demand that these people either back up such statements with science, or immediately stop their destructive rhetoric.  We are not the hysterical mob demanding what science cannot deliver.  We  are the ones who can defend, using the best science, our reasonable demand for immediate approval of limited clinical trials.  If there is any hysteria in this debate, it is from the opponents of xenotransplantation.

The last significant advance in the treatment of diabetes was the discovery of insulin over 75 years ago by Banting and Best.  Their practice of "injecting the filthy juices of dogs and pigs into children" was ridiculed and opposed back in 1921.  Fortunately, science prevailed as it must today for all our sakes, and for the sakes of our children.

Alastair T. Gordon, The Islet FoundationJanuary 14, 1998 (Updated August 14, 1998)

Go Back to Top of Page
Xenotransplantation: time to leave the laboratory - Lancet - November 13 1999
Ontario to pump millions into pig-to-people transplants - London Free Press - November 15 1999
Bioartificial organs and acceptable risk - Nature Biotechnology - November 1999
The Xenotransplantation Debate Continues...
New Scientist -- Xenotransplantation - So Far, So Good
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