Xenotransplantation in the New Millennium: Moratorium or Cautious Experimentation?

Introduction

Xenotransplantation is the transfer of organs, tissues, or cells from an animal of one species to an animal of another species or to a human being. This technology is being developed in response to the shortage of human donor organs for allotransplantation. Biological products harvested from human beings, other mammals, and genetically engineered bacteria are increasingly used in modern-day therapeutics. All such biological products can potentially transmit unusual or unknown infections, despite extensive screening of the donors and disinfecting processes. In the light of infections caused by various biological products, what are the ultimate dangers of xenotransplantation? Do the short-term benefits to individuals justify the potential long-term adverse events to the larger population? Are we sufficiently equipped with the knowledge to detect, treat, and prevent infections related to xenotransplantation and maintain effective surveillance afterwards? Can we learn from our many decades' experience with blood products and allotransplantation?

Risks of Blood Transfusion

Blood transfusion may not be the most accurate model to predict the risks of xenotransplantation, but the recent history and evolution of transfusion of blood and blood products provide valuable insights. In the early 1980s, prior to mandatory screening tests and heat treatment of clotting factor concentrates, several thousands of hemophiliacs who received anti-hemophilic factor concentrates fell victim to hepatitis and acquired immunodeficiency syndrome (AIDS). It has been estimated that as many as 80 percent of these multiply transfused hemophiliacs are human immunodeficiency virus (HIV) positive [1]. Many erstwhile health ministry officials and physicians were prosecuted in several countries, accused of laxity in enforcing strict guidelines to prevent contamination of blood and blood products [2]. This has happened over the past decade mainly because of our inability to anticipate a devastating unusual infection like AIDS, and because we lacked effective measures to curtail its spread in a timely manner.

Since mandatory screening of blood donors and donated blood was enforced, the risk of transmission of infections has decreased significantly. New viral inactivation methods, such as exposure to ultraviolet light, solvents and detergents, and heat pasteurization used in preparing blood components, contributed to this reduction. While each of these procedures is more effective than previous methods, none can guarantee total absence of infectious viruses [3].

New Viral Pathogens and Prions

The advent of sophisticated diagnostic methods has increased the list of infections transmitted through blood transfusion. Newly identified agents that can be transmitted through blood products include hepatitis G virus, human herpes virus 8 (HHV-8), porcine parvovirus, Borna virus [4], and a single-strand DNA virus known as TT virus (TTV). Though discovered in Japan only little more than a year ago, TTV is now believed to be distributed worldwide. Fifty-six percent of factor VIII and IX preparations studied in the United Kingdom were contaminated with TTV [5]. The pathogenicity of this new agent is still being elucidated. Most recently, human retrovirus 5 (HRV-5) was detected as an exogenous genome in association with arthritis and systemic lupus erythematosus [6].

Prions, or proteinaceous infectious particles, illustrate the difficulty in detecting novel infectious organisms. These tiny, infectious, naked proteins, which survive conventional techniques of sterilization, are the putative agents of the fatal neurodegenerative disorder, Creutzfeldt-Jakob disease (CJD). A long incubation period is another impediment to early detection of infections; though human pituitary growth hormone was introduced into clinical medicine in 1956, cases of CJD transmitted through infected samples were not recognized for the next 30 years [7].

Infective Potential of Allotransplantation

Allotransplantation has become the standard treatment option in several life-threatening illnesses. Even with improved techniques of detection and treatment, cytomegalovirus, Epstein-Barr virus, herpes simplex virus, hepatitis B and C viruses, and HIV are known to be transmitted to transplant recipients from donors. There are several well-documented cases of transmission of CJD associated with transplantation of dura mater and cornea [8, 9]. Latent or asymptomatic infection in an immunocompetent...