Tissue Banking and Transplantation, Ethical Issues in
Tissue Banking and Transplantation, Ethical Issues in
TISSUE BANKING AND TRANSPLANTATION, ETHICAL ISSUES IN•••
Although the transplantation of solid organs such as kidneys and hearts is familiar to the general public, knowledge about transplants of tissues such as bone, skin, veins, and heart valves is only beginning to be disseminated broadly. In the first decade of the twenty-first century the tissue transplant industry grew rapidly as tissue transplantation became a standard treatment option for thousands of patients. Spurred by technological developments and new clinical applications, the transplantation of human tissue grew from a $20 million industry in the early 1990s to one that was approaching $1 billion. In 1994 an estimated 6,000 persons were tissue donors upon death; by 1999 that number had grown to 20,000, more than tripling.
The great majority of cadaveric organs come from brain-dead, heart-beating donors who are maintained on ventilators, of whom there are an estimated 10,000 to 20,000 each year. The pool of potential tissue donors is in the hundreds of thousands because tissue can be retrieved up to 24 hours after death, assuming that the donor is medically suitable and meets generally applied age criteria. With tissue from one donor going to as many as 50 to 100 recipients, the number of tissue transplants dwarfs that of organ transplants. It is estimated that there were more than 850,000 tissue transplants in 2002. The immunological properties of most tissue are reduced greatly or eliminated in the processing of tissue. Therefore, unlike recipients of solid organs, tissue recipients are not required to take antirejection drugs for the rest of their lives.
With this growth in transplantation have come changes in organization, financing, and regulation, and those changes have led to unique ethical concerns. Those concerns arise in great measure from the stark contrast between the selfless gift of human tissue by donor families and the commercial forces at play as tissue passes down a complex chain of distribution from donor to recipients.
This entry describes the history, organization, technological developments, clinical applications, and regulation of the tissue industry and then dicusses the ethical issues that have emerged. It is concerned solely with the transplantation of tissues that come as gifts from families whose members have died recently. Other human tissues also may be used for medical and research purposes, including gametes (sperm and eggs), tissue discarded during surgery, blood and blood products, and cell lines grown in laboratories. The collection, distribution, financial implications, regulation, and ethical issues raised by those tissues are different from those which apply to tissues transplanted from newly dead donors to recipients.
Although many human tissues can be transplanted, including corneas, heart valves, veins, and skin, the most common type of transplant by far involves musculoskeletal tissue. Legend has it that Saints Cosmos and Damian performed the first transplant (a leg) in 287 c.e., but the first documented successful transplantation of musculoskeletal tissue was performed by the Scottish surgeon William Macewan in 1881. In 1908 the U.S. surgeon Eric Lexer reported transplanting an entire knee joint. Although Inclan established a surgical bone bank (storing bone from living patients) in Cuba in 1942, the U.S. Navy Tissue Bank in Bethesda, Maryland, established in 1949, was the first modern tissue bank. The Navy Tissue Bank recovered and preserved tissues to treat injured servicemen and servicewomen and advanced the science of tissue banking through research programs.
Tissue banks have always attempted to provide tissues needed by surgeons in the form in which they can be used best. The organization and operation of tissue banks have changed in response to changes in practice and demand. In the 1960s and 1970s many hospitals maintained their own surgical discard bone banks, storing primarily femoral heads that were removed during hip replacement surgery. Advances in orthopedic surgery, especially the treatment of primary large bone (e.g., femur, humerus) cancers by replacing entire bones with those obtained from cadavers, increased the need for more sophisticated tissue banking. In the 1980s, local tissue banks began to proliferate and a few regional tissue banks were established. Over time banks began to distribute outside their traditional service areas. Currently, many U.S. tissue banks have allocation systems that return high-demand tissue to the area that provided the donation and distribute other tissue throughout the country. Some tissue banks distribute tissue to other countries.
Clinical and Organizational Developments
As the proportion of older patients in the United States has grown, there has been a dramatic increase in the types of tissues used for joint replacement surgery, which often requires transplanted bone in combination with a metallic prosthesis. There also has been a major increase in spinal fusion surgery. Some reports estimate that more than 200,000 patients in the United States have received cadaveric bone for spinal surgery. Enhanced techniques for limb salvage surgery in cancer patients have increased the demand for large tissue grafts. Sports medicine uses increasing amounts of soft tissues, primarily patellar and Achilles tendons, to repair damaged knee ligaments.
The 1990s saw the development of proprietary processing technologies, patented tissue configurations, and advanced processing systems that result in tissue grafts with very specific dimensions and shapes designed by biomechanical engineers that are used primarily in spinal fusion surgery and sports medicine. These and other developments have resulted in the need to hire new and different kinds of personnel, the move by tissue banks to affiliate with traditional competitors to gain access to new technologies, the elimination of smaller tissue banks, and the consolidation of tissue banks. They also have facilitated the entry into the field of for-profit companies. In 1992 Grafton® demineralized bone matrix (DBM) was introduced by the for-profit company Osteotech. Grafton® and similar DBM products are made from demineralized cortical bone combined with various types of carriers that are designed to function as defect fillers or as adjuncts to traditional bone-grafting techniques to promote bone healing. This type of tissue originally was designed for use in dental and periodontic applications but now is being used broadly in orthopedics and neurosurgery. By 2000 at least five other DBM products were on the market, usually codeveloped and promoted by a nonprofit tissue bank and a for-profit device partner.
Another development that has spawned controversy has been the use of tissue for enhancement purposes. Deep layers of skin can be processed into an acellular form that can be used by plastic surgeons to reconstruct deep dermal defects and scars as well as to smooth out wrinkles and temporarily "puff up" lips. Despite the debate that this use of donated tissue has generated, the industry reports that this type of surgery accounts for only a minuscule proportion of tissue transplants.
By the 1990s larger tissue banks, most of which are nonprofit organizations, were moving toward a more traditional medical device–pharmaceutical sales and marketing system, using professionally trained sales representatives or agents to promote their tissue and services, developing advertisements and brochures, and implementing controversial market-driven practices such as consignment, discounting, and bundling. Nonprofit tissue banks also have entered into relationships with orthopedic and medical device companies, sometimes allowing a device company to process, package, market, and sell the tissue. These activities and relationships have blurred the line between an altruisitic gift and the distribution of a medical device and created ethical challenges relating to the handling of the gift. In 1996 the American Association of Tissue Banks (AATB) adopted a set of principles intended to provide guidance in the growing commercialization of tissue, Ethical Guidelines for Commercial Advertising and Activities.
Regulation and Safety
Although tissue safety is not the only medical and ethical issue in which regulation may come into play, it is a crucial one. The avoidance of potential infection has always been of paramount importance. This is not a simple task because transplant tissue is removed from a dead body that may have been exposed to bacteria, viruses, and other pathogens before death or during the decomposition process. Until the late 1980s processing techniques primarily entailed sterilization, which was felt by many to be mandatory despite concerns that sterilization techniques damage the biological and/or biomechanical properties of tissue.
In the late 1980s the construction of pharmaceutical-grade processing facilities allowed aseptic processing, which eliminated the need for sterilization of tissues while maintaining the biomechanical and biological properties of tissue. Clean room technology provides an environment with 10 to 100 microorganisms per cubic foot of air. In comparison, a standard operating room, normally the "cleanest" place any patient will enter, provides an environment with 1,000 to 10,000 microorganisms per cubic foot. As tissue transplantation becomes an increasingly integral part of modern medical treatment, processors must strike a balance between the goals of maximal tissue safety and viability.
Regulation of organ transplantation began in the mid-1980s with the passage of the National Organ Transplantation Act and other legislation that initiated federal influence on and regulation of organ procurement and transplantation policy and practice. A national Organ Procurement and Transplantation Network (OPTN) was created at government expense to set organ transplantation policy and gather data on organ transplantation events. The transplant community formed the United Network of Organ Sharing (UNOS), which obtained the OPTN contract. None of this authority, however, has been extended to tissue transplant practices. In addition, organ procurement organizations (OPOs) were given the authority to operate within a designated territory by the Health Care Financing Administration (HCFA, now the Centers for Medicare and Medicaid Services, or CMS), which also provided for financial reimbursement for the costs associated with kidney transplantation. Tissue banks, in contrast, were not and still are not compensated directly by the federal government for their operations, and there are no governmental regulations or guidelines that govern the organization of tissue banks.
Despite their safety risks, tissue banks were subject to very little federal regulation until the 1990s. In 1976 the AATB was founded as scientific nonprofit peer group organization to address issues of donor criteria and recovery and processing systems with an eye toward maintaining quality and safety. In the mid-1980s it established standards for acceptable norms of technical and ethical performance, including a program of inspection and accreditation. However, the AATB is strictly voluntary. In 2002 it listed 73 accredited banks among the estimated 100-plus banks in the United States. Among the unaccredited banks are some of the largest tissue processors. Only a handful of states have any type of tissue bank regulation.
A seminal event occurred in 1991 with the report of the transmission of human immunodeficiency virus (HIV) from an organ and tissue donor who had tested negatively for the antibody to HIV. This focused the public's attention on the potential for disease transmission, especially the need for more rigorous donor screening. In 2001 safety issues resurfaced. The Federal Drug Administration (FDA) and the Centers for Disease Control (CDC) reported several cases of infection, possibly caused by donor tissue in recipients, including one that resulted in the death of the patient. In 2002 the CDC issued a report documenting fifty-four tissue infections that had occurred over several years, noting, however, that out of an estimated 650,000 annual tissue transplants, bacterial infection was a rare complication. Later in 2002 there were reports involving six organ and tissue recipients who contracted hepatitis C from an organ and tissue donor, and several organ recipients who were infected with West Nile virus, including a number who died. Creutzfeldt-Jakob disease, the human variant of mad cow disease, looms as a potential hazard, and new testing regimens to screen out potential donors with these diseases are awaited by the tissue banking and surgical communities.
FDA regulation of tissue banking began in earnest in 1993 with the Interim Rule for Banked Human Tissue, which was intended to require infectious disease testing, donor screening, and record keeping. Among the things required were extensive interviews about a potential donor's sexual history, use of illegal drugs, and other exposure to infectious diseases. This rule was finalized in 1997 and resulted in in-depth training of tissue bank and hospital staff and a lengthy interview (between thirty and sixty minutes) with a grieving family member. During that time the FDA also began routinely inspecting tissue banks, suggesting changes, and conducting mandatory recalls at large tissue banks that remained out of compliance. It is anticipated that additional FDA regulations for good tissue banking practices will be issued in 2004.
In 1997 the Centers for Medicare and Medicaid Services (CMS) established regulations that changed the system of organ and tissue donation dramatically. The Conditions of Participation (CoP) required that all hospital deaths be reported to the OPO that serves the hospital and that all those deaths be evaluated as potential donors. The results of the CoPs were most notable among tissue banks, which often experienced an increase of over 50 percent in their tissue donors.
As tissue transplantation has gained visibility, it has attracted the attention of critics. In April 2000 the Orange Country Register ran a series of articles titled "The Body Brokers." With provocative headlines such as "Assembly Line" and "Skin Merchants," the newspaper raised concern that the tissue industry was commodifying the human body, making outrageous profits, and irresponsibly allocating skin for "cosmetic" purposes. According to those and other allegations, the industry was violating the trust of grieving families that altruistically had donated tissue. The tissue industry replied that those allegations were inflammatory and inaccurate. However, press coverage brought the the industry to public attention. Several senators approached the secretary of the U.S. Department of Health and Human Services (DHHS), Donna Shalala, who asked the DHHS's inspector general to investigate. Out of that investigation came two thorough 2001 reports, Oversight of Tissue Banking and Informed Consent in Tissue Donation: Expectations and Realities.
As was mentioned above, the ethical issues of tissue banking arise largely from the apparent contrast between the way society views the source of human tissue and the industrial and commercial aspects of tissue processing and distribution. Like organs, tissue comes as an altruistic gift from grieving families. The notion of altruistic donation has been the bedrock of the ways in which organs and tissues are obtained. The National Organ Transplant Act specifically prohibited the sale of human organs and tissues, allowing only reasonable charges for the costs of retrieval, processing, and the like. Whereas some would argue that financial incentives and even outright payment should be allowed to increase the supply of organs, the law continues to recognize only altruistic donation.
Commerce is not absent from organ transplantation, however. Surgeons, hospitals, OPOs, and pharmaceutical companies, among others, make money from their participation in the transplantation process. However, with tissue transplantation, commodification and commercialization are much more evident. Unlike organs, which remain identifiable as organs in their relatively brief journey from donor to recipient, many tissue forms are highly processed and machined into forms that no longer resemble the bones or skin from which they were derived. Tissue forms are packaged much like pharmaceutical products and medical devices and can be stored for distribution years later. As they pass down the chain of distribution from donor to recipients, for-profit companies enter into the process. Many of those companies have invested capital to develop new processes for which they hold patents.
Unlike organs, tissue is rarely lifesaving, with skin for severe burn victims being the major exception. Instead, tissues are used to treat medical and surgical illnesses that are debilitating but not necessarily life-threatening. Sometimes tissue products are employed for cosmetic or enhancement purposes.
In summary, the chain of distribution of tissue from donor to recipient involves multiple players, including organ procurement organizations, nonprofit and for-profit tissue banks, and publicly held companies that process and distribute tissue. Tissue often is changed from its original form into packaged grafts that may sit on shelves to be distributed months or years later. Value is thus added to tissue as it passes along the chain of distribution. Sometimes donated tissue can be used for enhancement rather than saving lives or the treatment of serious medical and surgical conditions.
These characteristics make the commodification and commercialization of tissue much more evident than those of solid organs and, most important, present a stark contrast to the altruistic gifts of grieving families that make the entire enterprise possible. This contrast forms the basis for much of the criticism of the tissue industry. For example, if the families that selflessly donate do not make money, why should others? Another criticism is that families would not want their gifts used for cosmetic purposes.
Two potential solutions to these problems are not acceptable in the current legal and cultural context. On the one hand, society could abandon altruism and allow families to sell tissue at its fair market value. On the other hand, financial incentives could be eliminated from the processing and distribution of tissue. The first solution would eliminate the traditional basis of organ and tissue procurement: the gift. The second would bring an increasingly successful and desired clinical intervention to a halt.
As a more realistic alternative many have suggested a rigorous informed consent process. If families were informed about the commodification and commercial aspects of their gifts, they would have the freedom not to give them. This would avoid the abandonment of both altruism and the market forces that have allowed the tissue industry to flourish. Although this suggestion has great merit, it also has several limitations.
First, the informed consent model does not fit the situation perfectly. People think of informed consent as the principle governing the decision of patients to consent to treatment or that of research subjects to consent to research. With tissue donation, the patient is dead and no treatment or research is involved. The decision to donate generally is made by a family member. Second, the request is made under less than ideal conditions: The family is in the middle of a crisis, and the request most often is made by a stranger, frequently over the telephone. In these circumstances the ability and willingness of the family to receive and process large amounts of information are limited. Third, issues involving the financial aspects of donation are complicated and to some extent dependent on the political views of the requestor and the family member. Is it possible, for example, to give a robust description of the structure and function of the tissue transplant industry in the context in which the request is made? Even if one attempted to do that, what words and tone should be used? Should the difference between for-profit and not-for-profit organizations be explained? Should the realities of the market economy be presented? Should those realities be praised or criticized, and in what balance? Words such as for profit and making money used out of context can be provocative and even manipulative. However, avoiding a discussion of these issues might allow people to naïvely imagine that their gifts of tissue make their way to grateful recipients without money changing hands or acting as an incentive.
Some things are known about what families want to be told. In 2000 the University of Florida Tissue Bank released the results of two telephone surveys of 507 persons who had been offered the option of tissue donation at the death of a family member. Among those who donated, 86 percent said they had enough time to make a decision, whereas 73 percent of nondonors said they did not. Twenty-eight percent of donors and 36 percent of nondonors said they did not receive enough information. Thirty-five percent of donors and 43 percent of nondonors said it would have been helpful to know that recovered tissue is "sent to companies" and in that group 10 percent of donors said that knowing would have made a difference in their decisions. Forty-one percent of donors and 49 percent of nondonors said they would have wanted to know costs are associated with recovery, preparation, distribution, and surgery, including salaries, materials, shipping, and administration. Nineteen percent of donors said that knowing those facts would have made a difference in their decisions. Forty-eight percent of donors and 24 percent of nondonors said that profits should be permitted.
Donor families that have written on the subject point out that not all donor families think alike and acknowledge their ambivalence about their right to information versus their ability to process information in the middle of a tragedy.
After interviewing 30 organizations involved in tissue recovery and receiving more than 50 responses to a questionnaire from donor families, the inspector general of the DHHS concluded that the expectations of altruistic motives among donor families are the foundation of tissue banking. The report, Informed Consent in Tissue Banking: Expectations and Realities, said that, among other things:
- Large-scale financial operations may overshadow the underlying altruistic nature of tissue donation.
- After processing, tissue and products containing tissue often are marketed and sold as a medical supply rather than as a donation.
- Some tissues, particularly skin, may be processed into products that are used for cosmetic puposes.
The inspector general concluded that the special nature of tissue and the way in which it is made available call for steps beyond those which apply to most other businesses and philanthropic enterprises. He called for the HHS Division of Transplantation to identify principles and guidelines that should underpin consent requests; make suggestions about the type, format, and content of written information that should be shared with families; make recommendations about training tissue bank staff and external requestors; and make recommendations about ways to evaluate the effectiveness of requestors. He also called on the tissue industry to give written materials to families at the time of a request or in the days immediately afterward, including a copy of the consent form, a full description of the uses to which donated tissue may be put, and a list of other companies and entities with which the bank has relationships, and to indicate clearly on all tissue packaging and marketing materials that the contents are derived from donated human tissue. Finally, the report called for the tissue banking industry to explore a process for public disclosure of tissue banks' financing and research into what types and how much financial information would be useful for families and to consider the impact of that disclosure on the rate of donation.
The report also asked the tissue banking industry to work with groups representing the interests of donor families. The most prominent of those groups is the National Donor Family Council of the National Kidney Foundation. The council is an organization of over 8,000 donor families whose mission is to nurture and protect the interests of donor families as well as to promote donation. In 2000 the Donor Family Council issued a report titled Informed Consent Policy for Tissue Donation that called for full disclosure of the facts, including the ways in which tissue is recovered, processed, stored, and distributed. The report also said that families should have the right to restrict use of the tissue they donate. It did not mention financial issues.
In response to those suggestions the transplant community has begun to strengthen the process of informed consent. Many tissue banks now offer informational brochures to donor families that more clearly outline the specifics of donation, including the fact that tissue may be processed into many forms and sizes and may be stored for extended periods and the fact that for-profit companies may be involved in the processing. Education for tissue requestors also has been expanded. Tissue banks routinely offer donor families follow-up information, including copies of the consent form. The AATB, the Association of Organ Procurement Organizations (AOPO), and the Eye Bank Association of America (EBAA) established guidelines for obtaining informed consent on tissue donation that formed the basis of many recovery agencies' consent policies. In addition, the AOPO established suggested guidelines for its members to use in selecting a tissue processor or tissue banking partner.
Many commentators think that the inherent limitations of those recommendations call for other mechanisms to protect potential donors and the integrity of the industry. One of those mechanisms is public education. If the general public better understood the way tissue is altered and the financial realities of tissue processing and distribution, there would be less need to place the burden for sharing that information only at the moment of the actual request. The inspector general, for example, recommended that the tissue banking industry work with groups representing donor families to explore a process for disclosure of tissue banks' financing, including knowledge about the sources of tissue banks' funding and other entities with which tissue banks have financial arrangements. Proposed legislation in California would mandate that families be given information about the involvement of for-profit companies and the possibility of cosmetic uses of tissue and be given the option to "opt out" of those scenarios.
Many states have passed laws that may further change the landscape as it relates to obtaining consent. Known as designated donation or first person consent, those laws give individuals an opportunity to declare their intention (or consent) to donate upon death and do not allow the next of kin to override that declaration. These laws present an entirely new set of challenges for OPOs, tissue banks, and eye banks: If an individual has declared his or her desire to "be an organ donor," does that necessarily refer to any body part that can be transplanted? Did that person receive full information about tissue donation so that the decision to donate was fully informed? What if the family objects strongly? Should the recovery agency move forward without regard for their feelings?
In the essay "The Gift and the Market" Courtney Campbell argues against the industrial perception of tissue banking, emphasizing instead that the tissue industry should "act in accordance with a model of 'stewardship of the gift'" (Campbell, p. 207). The acceptance of the gift of tissue, he writes, involves harmony between donor and recipient in regard to the meaning of the gift, the intention for its use, and the relationship of giver and recipient. Others also have emphasized this point. For example, Helen Leslie and Scott Bottenfield from LifeNet, one of the United States' leading tissue banks, in the essay "Donation, Banking and Transplantation of Allograft Tissues" note that "it is only through the humanitarian actions of donors and donor families— people helping people, the noblest of principles—that tissue transplantation is made possible" (Leslie and Bottomfield, p.281). Stewardship mediates the relationship of the donor to the recipient. It provides a moral connection between the gift and the use of the gift and establishes a framework for enhancing the value of the gift as long as the intent of the donor is respected and the benefits of the gift are directed toward the larger community, not claimed solely as proprietary interests by tissue bankers, processors, and distributors.
Good stewardship in the context of human tissue for transplantation means that the industry should take collective responsibility by doing the following:
- Minimizing commodification by insisting that all packaged tissue prominently reveal its origin as an altruistic gift;
- Adopting nationwide rules for the just allocation and distribution of tissues, for example, making sure that purely cosmetic uses of tissue occur only after more worthy needs are met;
- Working to make tissue as safe as possible;
- Making sure that all tissue recovery is done by nonprofit organizations whose finances are publicly known;
- Maintaining a publicly accessible national database against which potential problems can be assessed rationally; and
- Providing a public forum for discussion and debate of controversial issues.
Although the industry has begun to adopt some of these aspects of good stewardship, there is much room for improvement and it remains to be seen how active a role the federal government will assume in pushing for these important moral and social goals.
stuart j. youngner
American Association of Tissue Banks, Eye Bank Association of America, and Association of Organ Procurement Organizations. 2000. Model Elements of Informed Consent for Organ and Tissue Donation: Joint Statement.
Campbell, Courtney. 2003. "The Gift and the Market: Cultural Symbolic Perspectives." In Tissue Transplantation, Ethical Issues, ed. Stuart Youngner, Martha Anderson, and Renie Schapiro. Oxford: Oxford University Press.
Leslie, Helen W., and Bottenfield, Scott. 1989. "Donation, Banking and Transplantation of Allograft Tissues." Nursing Clinics of North America 24: 891–905.
National Donor Family Council, Executive Committee. 2000a. Position Statement on Tissue Donation. New York: National Kidney Foundation.
National Donor Family Council, Executive Committee. 2000b. Informed Consent Policy for Tissue Donation. New York: National Kidney Foundation.
National Organ Transplantation Act of 1984 (PL 98–507).
Scott, M.; Oppenheim, A.; and Rodrigue, J. 2000. Adequacy of Informed Consent for Tissue Donation: A Survey of Donor Families. Gainesville: University of Florida Tissue Bank, Inc.
Tomford, W. W. 1993. "A History of Musculoskeletal Tissue Banking in the United States." In Musculoskeletal Tissue Banking, ed. W. W. Tomford. New York: Raven Press.
U.S. Congress. 1984. National Organ Transplantation Act (PL 98–507).
U.S. Department of Health and Human Services, Office of the Inspector General. 2001. Informed Consent in Tissue Donation: Expectations and Realities. Washington, D.C.: Author.
U.S. Department of Health and Human Services, Office of the Inspector General. 2001. Oversight of Tissue Banking. Washington, D.C.: Author.
Youngner, Stuart; Anderson, Martha; and Schapiro, Renie. 2003. Tissue Transplantation: Ethical Issues. Oxford: Oxford University Press.
American Association of Tissue Banks, Eye Bank Association of America, and Association of Organ Procurement Organizations. 2000. Model Elements of Informed Consent for Organ and Tissue Donation: Joint Statement. Available from <http://www.aatb.org>.
Office of the Inspector General, Department of Health and Human Services. 2001a. Informed Consent in Tissue Donation: Expectations and Realities. Available from <http://www.fda.gov/cber/tissue/infrmcnsnt.pdf>.
Office of the Inspector General. 2001b. Oversight of Tissue Banking. Available from <http://www.fda.gov/cber/tissue/ovrst0101.pdf>.