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In Defense of Xenotransplantation, Part 1...

                                                                                                Alastair Gordon

The Islet Foundation

Toronto, ON

Canada

 

                                                                                                March 26, 2002

The Hon Annette King
Minister of Health

Parliament Buildings
Wellington, New Zealand


Tel:       (04) 470 6554
Fax:      (04) 389 4182 / (04) 387 2714 / (04) 495 8445
Email:   aking@ministers.govt.nz

 

Sent by regular mail, fax, and email

 

Dear Minister:

 

I would like to take this opportunity to speak with you regarding the current xenotransplantation debate underway in New Zealand. I hope you will take the time to read this letter and to consider the merits of each argument. I am sure that your ministry does not want to discriminate against a specific group of citizens in denying them a safe and potentially effective medical procedure, especially when there is no scientific or ethical basis for such a denial.

 

I believe you would agree that the decision on clinical trials of xenotransplantation in your country should be based on whether or not this procedure represents a public health risk. If the treatment can be shown to pose a new risk to the general population beyond what we now accept in everyday medical practice and other permitted activities, then a moratorium is defensible. If, on the other hand, an individual would prefer to accept a theoretical risk to his or her own self rather than face the known risks of diabetes, liver failure, or Parkinson’s disease, then that person should be free to do so.

 

Furthermore, I would hope you would not demand that one group of patients be denied medical treatment without some evidence of public risk, while another  group enjoys the benefits of medical procedures that present proven public health risks. I’m sure you agree that such legislation would be considered an arbitrary and discriminatory breach of human rights.

 

By way of introduction, The Islet Foundation (TIF) is a charitable body whose mission is the support of research that is likely to bring us closer to a cure for diabetes. This debate is very critical to TIF, as the xenotransplantation of pig islets is the only hope today for restoring the insulin-producing islet cells destroyed by the disease, and preventing the horrific complications of diabetes. So far, transplanted pig islets have shown considerable promise, while all other techniques, including stem cells and islet neogenesis, have demonstrated no efficacy in humans. Xenotransplantation is the best chance for curing diabetes, but only if small, well-regulated clinical trials are allowed to proceed.

 

What constitutes a public health risk?

 

The debate on whether or not to allow xenotransplantation seems to centre on the debate of whether Pig Endogenous Retrovirus (PERV) from transplanted pig tissue is capable of creating a public health risk. Before any virus could become a public health risk, there are five conditions that must be met:

 

1.      The virus must be capable of infecting living humans.

2.      The virus must be replication-competent.

3.      The virus must cause disease in its human host.

4.      The virus must be transmissible from the host to other human beings.

5.      Xenotransplantation must represent a significant new vector for infection, above and beyond normal vectors such as animal handling, veterinary care, pets, and food processing and consumption.

 

Toady, despite millions of opportunities, not even the first step has been demonstrated. If a moratorium were to be imposed, then a regulator would have to demonstrate a reasonable risk of meeting all five conditions.

 

Medical pig products have been used safely by millions…

 

For over eighty years, people with diabetes have injected pig insulin, many thousands of times in their lives. In the early decades following its discovery, animal insulin was not a very sterile product, and yet there has not been a single case of PERV infection in a diabetic, let alone any evidence of disease among their partners. Furthermore, many hemophiliacs have used Pig Clotting Factor VIII (PCF VIII) to prevent uncontrolled bleeding. In one test of PCF VIII, all batches were positive for PERV [J Infect Dis 2001 Feb 15;183(4):648-52], yet not a single user was found to be positive for PERV infection. In another study [Science 1999 Aug 20;285(5431):1236-41], people who received transplants of pig tissue over the previous 12 years were tested for PERV infection. Again, all were negative. Despite millions of opportunities for PERV to infect a human, it has never happened. The first step of a public health risk has not been reached.

 

Thousands of laboratory pig xenografts and no infections…

 

For the past 25 years, countless pre-clinical tests of xenotransplantation have been performed in laboratories around the world. In thousands of cases, pig tissue has been transplanted into lab animals. Furthermore, those animals have bitten and scratched their human handlers on many occasions. Once again, there have been many opportunities for PERV infection to occur in animals and in people, and yet there is absolutely no evidence that it has ever happened. In other words, we have still not reached the first step of a public health risk.

 

The risk of pig prions is a red herring…

 

The issue of prions (the pathogens believed responsible for Mad Cow Disease) from pig tissue transplants has been raised as another risk of xenotransplantation. There is absolutely no merit to this argument. Since the inherent risk of prions is that they are not killed by high temperature, and hence they survive cooking, prion infection would have already occurred simply from eating pork. Further, prions would have survived the sterilization of pig insulin injected by millions of people. Even if there is any risk of prion disease from pigs, simply eating pork would be the dominant vector for infecting humans. I don’t believe there is any move to ban the eating of pork because of the risk of prion infection, so there is no justification for banning the medical use of that same tissue.

 

This is a scientific, not a cultural, debate…

 

The cultural or ethical discomfort of any group must not be part of this decision. In a letter sent to me on July 8, 1997, your then Minister of Health, the honourable Bill English, stated: In considering emergent technologies such as xenotransplantation, the Ministry of Health must consider both the cultural and scientific safety of a process or procedure. At the time, I had no idea what “cultural safety” meant, but it has since emerged that there are groups strongly opposed to xenotransplantation based on their own personal beliefs regarding animal rights and human identity. These groups certainly have the arguable right to deny the benefits of any medical procedure to themselves and to their children. However, they have no right to deny such benefits to others who do not share their beliefs. A significant percentage of your population is morally opposed to abortion, and yet your ministry does not ban that procedure. It would be both wrong and inconsistent to allow cultural factors to deny a medical benefit to one group, while affording a far more controversial benefit to another.

 

What if today’s process had been applied to the discovery of insulin?

 

We should look to 1921 when Banting and Best discovered that insulin from pigs and cows could be injected into children with diabetes, and save them from a horrible wasting death. At the time, there were voices decrying those who would “inject the filthy juices of pigs and dogs into our children.” Had those voices prevailed, tens of millions of children around the world would have died for no valid reason. In the future, history must not write of fearful and unscientific voices in the year 2002 that brought unwarranted suffering and death to millions.

 

Regulating xenotransplantation must not be arbitrary or discriminatory…

 

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 and the general public. These are not some purely speculative 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.

 

Beyond the field of health care, your government allows citizens to travel to ebola-infested countries and return to New Zealand. The public health consequences of an ebola outbreak are real and horrendous.

 

By way of example, you cannot tell a mother whose child is dying of diabetes that you are banning a promising research protocol because you think there might be some risk, even though you have absolutely no evidence. Can you then tell that same mother that people with AIDS are being treated in public hospitals when she knows the public health risk is so real? Is her child somehow more dispensable than people with AIDS?

 

The state permits and manages many practices with proven public health risks. It cannot therefore prohibit a practice for which no evidence of public risk exists. In summary, I hope you agree that your regulations must be ethically consistent – they cannot be arbitrary and discriminatory.

 

There is no animal rights issue…

 

Most groups opposing xenotransplantation are motivated by an animal rights agenda, even though they bolster their position through fear mongering about so-called risks that they hope will frighten the public. They ask if it is ethical that we should sacrifice animals for our own medical purposes. In a society that is willing to sacrifice millions of pigs for bacon, suede, and bristles, how could anyone question the ethics of sacrificing a pig to save a child from the horrors of diabetes?

 

For the state, there are no psychological or theological issues…

 

Some bioethicists have questioned the psychological effects of receiving tissue from a pig. They ask what that would do to the sense of “self”. While these are interesting philosophical speculations, they are issues for the individual, and have no place in legislation. If a person decides that being cured of a chronic disease is preferable to living with some compromised sense of “self”, then that is a decision for the individual, not the state.

 

It is interesting to note that no religion has opposed xenotransplantation for its own followers, despite prohibitions on eating pork. Jewish, Muslim and Christian clergy have all endorsed the use of transplanted pig tissue for medical purposes.

 

Xenotransplantation is a small step…

 

I would like to look at one specific example of xenotransplantation, the transplanting of pig islets into people with diabetes to cure the disease. As we know, injecting insulin keeps diabetics alive, but it is not a cure. By transplanting pig islets into a person, we are moving a small step upstream from using the hormone secreted by pig islets, to transplanting the actual islets themselves. Thus, there would be no need for injections and for the first time the diabetic would enjoy normal blood glucose control. The horrible consequences of imperfect blood glucose control – blindness, amputation, kidney failure, coma, and others – would be prevented.

 

I hope you see that transplanting pig islets is not a big step into the unknown. It is the next logical step after using pig insulin safely for the past eighty years.

 

What about whole organ xenografts?

 

There are two distinct branches to xenotransplantation research, cellular xenografts and whole organ xenografts.  Cellular xenografts involve the transplanting a tiny mass of pig cells, such as neurons, liver cells, or islets, into a person. In most cases, individual cells can be transplanted without the need to suppress the recipient’s immune system to prevent rejection. Immunobarriers can be used to protect the new cells while leaving the person with an uncompromised immune system. Many clinical trials have already been performed, with no adverse effects. In the case of an islet xenograft, failure would simply mean that the person returns to injecting insulin. Success would mean the end of one of the most devastating diseases of our time. Small, carefully-controlled clinical trials of cellular xenografts should be allowed to proceed.

 

Whole organ xenografts are a very different undertaking. Today, I believe that no one would propose any clinical trial of a vascularized pig organ, such as a heart or kidney, into a human. The reluctance would not, I believe, be based on a risk of infection, but simply on the lack of likely benefit to the patient. Absent suitable immunotolerance technologies, a whole organ xenograft is a risky experiment that today offers little benefit to the patient. Whole organ xenografts should not be allowed to proceed until pre-clinical results demonstrate a real possibility of preventing rejection and benefiting the patient.

 

From a regulatory perspective, it would seem defensible to demand more evidence of efficacy and patient safety before allowing clinical trials of whole-organ xenografts, but to permit small, well-regulated trials of cellular xenografts.

 

Xenotransplantation applies to both type 1 and type 2 diabetes…

 

Some people opposing xenotransplantation say that we could eliminate diabetes through changes in lifestyle and diet, and therefore this medical procedure is not necessary. That would be a difficult argument to make to the parents of a 6-month-old child who has just been diagnosed with type 1 diabetes, and faces a tragically diminished life. Type 1 diabetes is an autoimmune disease that has nothing to do with lifestyle. The person’s islet cells have been destroyed by his or her own immune system, and the only cure is to replace the dead islets with living islets.

 

Type 2 diabetes can in many cases be aggravated by obesity, lifestyle and poor diet. However, there are thousands of type 2 diabetics who suffer from profound insulin resistance despite a healthy diet and lifestyle. Because these people have functioning islets, it is often said that islet xenografts will offer no benefit. In the early stages of type 2 diabetes, this assertion is true. However, as the disease progresses, the person’s overworked islets die, and the production of insulin ceases, exactly as in type 1 diabetes. At this later stage, an islet xenograft could restore insulin production and hopefully prevent the horrible and costly complications of type 2 diabetes.



So what are we asking for? Simply that:

·        This decision will be made on a scientific and ethical basis;

·        Controls will be consistent with other regulations now in place;

·        Disease and suffering will not be prolonged through government delays, equivocation, and appeasement of  special interests; and

·        No group will face discriminatory and unscientific hurdles in seeking new treatment opportunities for devastating diseases.

 

I really should apologize for such a lengthy letter, but I felt it was essential that you be presented with all the facts before making a decision that means so much to so many people. If there is anything that you do not agree with in this letter, I would urge you to let me know specifically what you think is wrong. If there are factors that I have overlooked, I would ask that you enlighten me.

 

Many thanks for your time and consideration.

 

Yours very truly,

 

 

Alastair Gordon

President, The Islet Foundation