Letters

Xenotransplantation

BMJ 2000; 320 doi: http://dx.doi.org/10.1136/bmj.320.7238.868 (Published 25 March 2000) Cite this as: BMJ 2000;320:868

This new form of treatment might benefit millions

  1. David K C Cooper, resident, International Xenotransplantation Society. (cooper{at}helix.mgh.harvard.edu),
  2. Carl G Groth, immediate past president, International Xenotransplantation Society.,
  3. Ian F C McKenzie, president elect, International Xenotransplantation Society.
  1. Massachusetts General Hospital, 13th Street, Boston, MA 02129, USA
  2. Huddinge Hospital, Huddinge S-14186, Sweden
  3. Austin Research Institute, Austin and Repatriation Hospital, Heidelberg, Victoria, Australia
  4. Department of Microbiology and Molecular Genetics, New Jersey Medical School - UMDNJ, 185 South Orange Avenue, Newark, NJ 07103, USA
  5. Campaign for Responsible Transplantation, PO Box 2751, New York, NY 10163, USA
  6. Institute for the Medical Humanities, University of Texas Medical Branch, Galveston, TX 77555, USA

    EDITOR—Fano has written a response in the eBMJ (and published here, the third letter) commenting on Vanderpool's article on xenotransplantation.1 2 He advocates a ban on xenotransplantation, largely on the grounds of the risk of the transfer of infection. Cells taken from carefully screened pigs have been used in the treatment of patients with diabetes, certain neurological diseases, and liver failure. There has been no definite evidence of the transfer of a porcine infection to human recipients.

    Nevertheless, as with almost every medical or scientific advance, it will be impossible to exclude all risk, even if this is related only to hitherto unknown pig bacteria or viruses. The ultimate decision whether to use any new therapeutic agent or procedure rests on an assessment of the risk to benefit ratio. As the potential benefits to individuals or society increase, the acceptance of slightly increased risk becomes warranted. We must not reduce our obligation to take all possible steps to minimise any perceived risk to society, but we have a moral obligation to accept a small risk to the community if the new treatment leads to great benefit to many individuals in that community.

    The potential benefits of xenotransplantation are immense. Many millions of people with such diverse conditions as diabetes and degenerative brain disease may have the quality of their lives vastly improved, and in those with advanced organ failure xenotransplantation will be lifesaving. In the United States over 60 000 people currently await a human donor organ but only 20 000 organs will become available this year. At least 10 people die every day while waiting. Similar figures could be quoted for other regions of the developed world.

    This new form of treatment may ultimately benefit millions of patients. Rather than calling for a ban on it we suggest that support should be given to the great efforts being made to ensure that it will be not only successful but also safe.

    References

    1. 1.
    2. 2.

    Public health risk must not be dismissed

    1. Emanuel Goldman, professor. (egoldman{at}umdnj.edu)
    1. Massachusetts General Hospital, 13th Street, Boston, MA 02129, USA
    2. Huddinge Hospital, Huddinge S-14186, Sweden
    3. Austin Research Institute, Austin and Repatriation Hospital, Heidelberg, Victoria, Australia
    4. Department of Microbiology and Molecular Genetics, New Jersey Medical School - UMDNJ, 185 South Orange Avenue, Newark, NJ 07103, USA
    5. Campaign for Responsible Transplantation, PO Box 2751, New York, NY 10163, USA
    6. Institute for the Medical Humanities, University of Texas Medical Branch, Galveston, TX 77555, USA

      EDITOR—Xenotransplantation of organs from animals is a seductive but inherently dangerous idea. The risk is not just to the patient, who will probably die shortly afterwards; the stakes are much higher, because the entire human population is put at risk.

      Viruses that inhabit animals, some of which are intrinsic to the animal's own genome, will gain a route of entry into the human population not ordinarily available. As Vanderpool notes, 1 pig DNA contains endogenous retroviruses (the same class that causes AIDS), and these infect human tissue culture cells.2 Vanderpool doesn't mention that postmortem analyses of two patients who died 70 and 27 days after receiving baboon livers showed two simian viruses that replicated after transplantation.3 Our state of knowledge is far too incomplete for us to breed totally virus-free animals, because we probably don't even know all the viruses that need to be eliminated.

      We do know that viruses jump species even without our help, and there are enough frightening precedents—as far back as the 1918 swine influenza pandemic that killed 20 million—to scare anyone contemplating xenotransplantation. More recently, millions of chickens had to be slaughtered in Hong Kong because of the unexpected jump to humans ofan avian influenza virus, and thousands of English cattle have been destroyed because of the jump to humans of bovine spongiform encephalopathy (“mad cow disease”).

      The spectacular advance of AIDS resulted from a virus given new routes of entry: widespread increases in certain lifestyle practices provided a conduit for efficient transmission. HIV-1 probably also resulted from a simian to human virus jump. Deadly Ebola virus is another virus transmitted to humans from primates, and there are at least another 10 primate viruses that infect humans, including a deadly form of herpes. Pigs aren't much safer: about a dozen pig viruses can be transmitted to humans, often with serious results.

      Not considered by Vanderpool is the fact that better alternatives exist. These includelifestyle changes (diet and exercise) that would considerably reduce the numbers of transplant candidates and presumed consent policies for human donors, which would greatly expand the pool of available organs. Research on unwanted human embryos is much more promising as a solution, but this is held hostage to abortion politics in the United States. Instead we are absurdly rushing down a path fraught with danger. Have we learnt nothing fromthe AIDS epidemic?

      References

      1. 1.
      2. 2.
      3. 3.

      Research in xenotransplantation will line drug industry's pockets

      1. Alix Fano, director. (alixfano{at}mindspring.com)
      1. Massachusetts General Hospital, 13th Street, Boston, MA 02129, USA
      2. Huddinge Hospital, Huddinge S-14186, Sweden
      3. Austin Research Institute, Austin and Repatriation Hospital, Heidelberg, Victoria, Australia
      4. Department of Microbiology and Molecular Genetics, New Jersey Medical School - UMDNJ, 185 South Orange Avenue, Newark, NJ 07103, USA
      5. Campaign for Responsible Transplantation, PO Box 2751, New York, NY 10163, USA
      6. Institute for the Medical Humanities, University of Texas Medical Branch, Galveston, TX 77555, USA

        EDITOR—It is naive to believe that research in xenotransplantation “is being propelled” by drug companies' desire to alleviate human suffering rather than the promise of billions of dollars in profits from the sale of “humanised” pig parts and expensive antirejection drugs.1 There would be safer and more cost effective ways of dealing with the perceived shortage of human organs and tissue. Aggressive investment in programmes to prevent disease; the passage of “presumed consent” laws, which have increased organ donation rates in several countries2; and growing human tissue to provide a safer source than animals would all help.

        Given the multitude of viruses lurking in animals, it will be impossible to breed germ free “donors.” Public health authorities admit that xenotransplantation could transmit deadly animal viruses to humans. Known pig viruses include the porcine endogenous retroviruses that have infected human cells. In 1998–9 the Malaysian Nipah virus causing viral encephalitis jumped from pigs to humans, infected 269 people, killed over 100, left dozens brain damaged, and led to the mass slaughter of one million pigs. Pig viruses have not been extensively studied: there may be dozens, many with long latency periods, waiting to be discovered.

        A retrospective study of 160 patients exposed to living pig tissue raised concerns3: 30 patients who underwent splenic perfusions gave positive results when tested for porcine endogenous retrovirus DNA; 23 had pig cells circulating in their bodies 8.5 years after treatment; and four injected with pig cells produced antibodies to porcine endogenous retroviruses, suggesting a potential active infection. The study's sponsor, Novartis, insists that patients are free of infection. But virologist Stoye and coauthors have said “the absence of infectious virus in, say, the first two hundred patients does not mean it will not occur in the two hundredand first.”4

        I am baffled as to why our public health authorities, mandated to protect public health and prevent disease, are encouraging the development of xenotransplantation while simultaneously acknowledging its epidemic potential. This could become a liability for them.

        In 1998 a group of physicians pointed out that global poverty (and lack of access to basic health care and sanitation) is the world's number one health problem.5 Today, some 50 million Americans lack access to basic health care. If we invest in xenotransplantation while ignoring the fundamental needs of a majority of the world's citizens we are simply lining the drug industry's pockets.

        References

        1. 1.
        2. 2.
        3. 3.
        4. 4.
        5. 5.

        Author's reply

        1. Harold Y Vanderpool, professor in the history and philosophy of medicine. (hvanderp{at}utmb.edu)
        1. Massachusetts General Hospital, 13th Street, Boston, MA 02129, USA
        2. Huddinge Hospital, Huddinge S-14186, Sweden
        3. Austin Research Institute, Austin and Repatriation Hospital, Heidelberg, Victoria, Australia
        4. Department of Microbiology and Molecular Genetics, New Jersey Medical School - UMDNJ, 185 South Orange Avenue, Newark, NJ 07103, USA
        5. Campaign for Responsible Transplantation, PO Box 2751, New York, NY 10163, USA
        6. Institute for the Medical Humanities, University of Texas Medical Branch, Galveston, TX 77555, USA

          EDITOR—Cooper et al's letter is commendable. Research on porcine cells, tissues, and organs in xenotransplantation should continue if certain conditions are met. There should be ongoing studies of risks and increased recognition that xenotransplantation offers enormous potential for alleviating human sickness, suffering, and untimely death. To assume that xenotransplantation must be free of risk before its benefits are pursued is out of keeping with the nature of human existence and represents a preoccupation with self protection that undermines beneficence.

          Goldman warns that the public health risk of xenotransplantation “must not be dismissed,” which no one seems to be doing. Goldman's points about the known infectivity of simian viruses have, as my article says, already been taken to heart by the United States Food and Drug Administration, which suspended clinical research involving primate-to-human xenografts.

          Goldman ends with a list of better alternatives to xenotransplants. Better for whom and how soon? Lifestyle changes would reduce the demand for transplanted organs, but they will neither end this demand nor be voluntarily and universally adopted. Presumed consent would expand the organ donor pool, but it is a form of coercion that would also not meet the great demand.

          Fano expresses the party line of the Campaign for Responsible Transplantation, which he directs and which claims to represent 2.5 million members. The campaign's publications advocate an immediate ban on xenotransplantation and charge the Food and Drug Administration with “playing Russian roulette with the public's health.”1

          Fano holds that xenotransplantation is being advanced to line “the drug industry's pockets,” not to alleviate human suffering. While few will quarrel with the influence, if not the necessity, of the profit motive, numerous researchers, surgeons, scientists, and regulators are additionally, and sometimes primarily, motivated by altruism, inquisitiveness, discovery, and the classic three factors in the Hippocratic oath: honour, fame, and enjoyment of life.

          Fano is baffled that public health authorities are encouraging the development of xenotransplantation in the light of its epidemic potential. His evidence for this potential with respect to clinical trials of xenotransplantation is attributed to a study that does not support his fears.2

          This study further validates other findings that persistent porcine endogenous retrovirus infection has not been detected in recipients of xenotransplants. The 30 (of a total of 160) patients that Fano refers to as testing positive for persistent porcine endogenous retrovirus evidenced microchimerism (the remaining presence of pig cells in their bodies), not persistent porcine endogenous retrovirus infection.

          References

          1. 1.
          2. 2.