EPIDEMIOLOGY AND ETHICS

ETHICAL-LEGAL PROBLEMS OF TRANSPLANTATION

AND DONATION.

SURROGACY.

 

Bioethical problems are often discussed in legal as well as in moral contexts. Lawyers as well as ethicists are involved with such questions as abortion, euthanasia, and experimentation upon human beings. This is not surprising; the law is seriously concerned with protecting such basic rights as life, bodily integrity, and privacy—the rights involved in these ethical questions.

A lot of aspects of bioethics testify that modern scientific and technical revolution must not become a barrier between a doctor and patient, regress, when after the button of device a doctor does not see individuality of patient.

Bioethics takes into account the ethic problems and moral problems of transplantation, deaths and dyings and creates philosophy of medical activity which includes studies about principles of appeal of medical personnel at discharging professional duties the family. Bioethics is directed on creation of terms for the maximal increase of efficiency of treatment of patients and removing the harmful consequences of inferior medical activity.

Organs Transplantation in Human Beings

Organ donation is the donation of biological tissue or an organ of the human body, from a living or dead person to a living recipient in need of a transplantation. Transplantable organs and tissues are removed in a surgical procedure following a determination, based on the donor's medical and social history, of which are suitable for transplantation. Such procedures are termed allotransplantations, to distinguish them from xenotransplantation, the transfer of animal organs into human bodies.

Donation after death

As recently as the late 1960s and early 1980s, irreversible cardiopulmonary failure was the only standard for determining death for purposes of donation after cardiac death.[1] This was replaced by brain death, the irreversible loss of all function, including the brain stem, though donation after cardiac death is a resurgent source for transplantation.[1]

Legislation

The laws of different countries allow potential donors to permit or refuse donation, or give this choice to relatives. The frequency of donations varies among countries.

Opt-in vs. opt-out   (See also: Mandated choice)

There are two main methods for determining voluntary consent: "opt in" (only those who have given explicit consent are donors) and "opt out" (anyone who has not refused is a donor). Opt-out legislative systems dramatically increase effective rates of consent for donation.[2] For example, Germany, which uses an opt-in system, has an organ donation consent rate of 12% among its population, while Austria, a country with a very similar culture and economic development, but which uses an opt-out system, has a consent rate of 99.98%.[3]

 

However, because of public policies, cultural, infrastructural and other factors, this does not always translate directly into increased effective rates of donation. In terms of effective organ donations, in some systems like Australia (14.9 donors per million, 337 donors in 2011), family members are required to give consent or refusal, or may veto a potential recovery even if the donor has consented.[citation needed] Some countries with an opt-out system like Spain (34 effective donors per million inhabitants) or Austria (21 donors/million) have high donor rates and some countries with opt-in systems like Germany (16 donors/million) or Greece (six donors/million) have effective donation lower rates.[citation needed] However Sweden, which has an opt-out system, has a low rate as well (15 donors/million). Health authorities in Sweden have suggested that the government pay 30,000 - 40,000 Kronor for funeral costs if a person donates their organs.[4] The president of the Spanish National Transplant Organisation, has acknowledged Spain's legislative approach is likely not the primary reason for the country's success in increasing the donor rates, starting in the 1990s.[5]

United States

Under the law of the United States, the regulation of organ donation is left to states within the limitations of the Uniform Determination of Death Act, the National Organ Transplant Act of 1984, and the United Network for Organ Sharing (UNOS). Each state's Uniform Anatomical Gift Act seeks to streamline the process and standardize the rules among the various states. Many states have sought to encourage the donations to be made by allowing the consent to be noted on the driver's license. Donor registries allow for a central information center for an individual's wish to be a donor. It is a pure consent system rather than an extended consent system or a dissent opt-out system. The issue of consent is pressing, as the number of patients on the waiting list in the country has increased from approximately 20,000 in 1990 to over 100,000 in 2010. Alongside absolute organ donation increases from the late 1980s up until the mid-2000s, donation rates did not increase or decrease significantly from 2004-2010.[6]

Europe

Map showing the coverage of 3 international European organ donation associations: Balttransplant, Eurotransplant and Scandiatransplant

Within the European Union, organ donation is regulated by member states. As of 2010, 24 European countries have some form of presumed consent (opt-out) system, with the most prominent and limited opt-out systems in Spain, Austria, and Belgium yielding high donor rates.[7] In the United Kingdom organ donation is voluntary and no consent is presumed. Individuals who wish to donate their organs after death can use the Organ Donation Register, a national database.[8] The UK has recently discussed whether to switch to an opt-out system in light of the success in other countries and a severe British organ donor shortfall.[9] In 2008, the European Parliament overwhelmingly voted for an initiative to introduce an EU organ donor card in order to foster organ donation in Europe.[citation needed]

Landstuhl Regional Medical Center (LRMC) has become one of the most active organ donor hospitals in all of Germany, which otherwise has one of the lowest organ donation participation rates in the Eurotransplant organ network. LRMC, the largest U.S. military hospital outside the United States, is one of the top hospitals for organ donation in the Rhineland-Palatinate state of Germany, even though it has relatively few beds compared to many German hospitals. According to the German organ transplantation organization, Deutsche Stiftung Organtransplantation (DSO), 34 American military service members who died at LRMC (roughly half of the total number who died there) donated a total of 142 organs between 2005 and 2010. In 2010 alone, 10 of the 12 American service members who died at LRMC were donors, donating a total of 45 organs. Of the 205 hospitals in the DSO’s central region—which includes the large cities of Frankfurt and Mainz—only six had more organ donors than LRMC in 2010.[10]

Japan

See also: Organ transplantation in Japan

The rate of organ donation in Japan is significantly lower than in Western countries.[11] This is attributed to cultural reasons, some distrust of western medicine, and a controversial organ transplantation in 1968 that provoked a ban on cadaveric organ donation that would last thirty years.[11] Organ donation in Japan is regulated by a 1997 organ transplant law, which defines "brain death" and legalized organ procurement from brain dead donors.

India

Organ selling is legally banned in India. Numerous studies have documented that organ vendors have a poor quality of life (QOL) following kidney donation. Live related renal donors have a significant improvement in the QOL following renal donation using the WHO QOL BREF in a study done at the All India Institute of Medical Sciences from 2006 to 2008. The quality of life of the donor was poor when the graft was lost or the recipient died.[12]

Sri Lanka

Organ donation in Sri Lanka was ratified by the Human Tissue Transplantation Act No. 48 of 1987. Sri Lanka Eye Donation Society, a non-governmental organization established in 1961 has provided over 60,000 corneas for corneal transplantation, for patients in 57 countries. It is one of the major suppliers of human eyes to the world, with a supply of approximately 3,000 corneas per year.[13]

Donation rates and legislation

A lists of countries ordered by organ donation ranking created by the International Register of Organ Donation and Transplantation shows Spain, Belgium, France, and Italy — which all have "presumed consent" laws on organ donation, where everyone is considered a donor unless they specify otherwise — in the top in the top five. In contrast the USA — which practices an "opt in" consent law where their citizens provide express and informed agreement to donate organs and tissues in the event of their death — is also in the top five ahead of many other countries that are "opt in". This illustrates that there are many other factors beside legislation that affect donor rates internationally, including hospital processes, public awareness, religion and culture, and road death toll rates, and goes some way to help explain why rates are so low.[original research?][citation needed]

Bioethical issues

Deontological issues

Certain groups, like the Roma (gypsies), oppose organ donation on religious grounds, but most [14] of the world's religions support donation as a charitable act of great benefit to the community. Issues surrounding patient autonomy, living wills, and guardianship make it nearly impossible for involuntary organ donation to occur.

From the standpoint of deontological ethics, the primary issues surrounding the morality of organ donation are semantical in nature. The debate over the definitions of life, death, human, and body is ongoing. For example, whether or not a brain-dead patient ought to be kept artificially animate in order to preserve organs for procurement is an ongoing problem in clinical bioethics.

Further, the use of cloning to produce organs with an identical genotype to the recipient has issues all its own. Cloning is still a controversial topic, especially considering the possibility for an entire person to be brought into being with the express purpose of being destroyed for organ procurement.[citation needed] While the benefit of such a cloned organ would be a zero-percent chance[citation needed] of transplant rejection, the ethical issues involved with creating and killing a clone may outweigh these benefits. However, it may be possible in the future to use cloned stem-cells to grow a new organ without creating a new human being.

A relatively new field of transplantation has reinvigorated the debate. Xenotransplantation, or the transfer of animal (usually pig) organs into human bodies, promises to eliminate many of the ethical issues, while creating many of its own.[citation needed] While xenotransplantation promises to increase the supply of organs considerably, the threat of organ transplant rejection and the risk of xenozoonosis, coupled with general anathema to the idea, decreases the functionality of the technique. Some animal rights groups oppose the sacrifice of an animal for organ donation and have launched campaigns to ban them.

Ethics In Xenotransplantation

Transplantation represents a highly successful means of treating a variety of human illnesses. However, the number of transplants performed is limited by a shortage of human organs and tissues. Xenotransplantation, the transplantation of organs, tissues or cells from one species to another, if applied to man, would offer the possibility of a huge supply of organs, tissues and cells for transplantation thereby relieving the “chronic” shortage of human donor.

However, before xenotransplantation becomes a clinical reality, there are practical challenges that must be overcome. One is rejection, the process by which the body of the transplant recipient attempts to rid itself of the transplant. Another is to ensure the correct functioning, across species barriers, of the transplant in its new host. Also, there is the need to minimize the likelihood of the introduction of new infectious agents into the human population via the transplant.

 

 

In addition there are concerns about xenotransplantation that require theological, anthropological, psychological and ethical considerations, as well as an examination of legal issues and procedural matters.

 

Bioethical issues Organs Transplantation

Further investigation and clarification is needed for a wider bioethical analysis. The ethical evaluation of the practicability of xenotransplantation, in light of the current situation as summarized in the first part of this document, requires the consideration of a whole series of factors, some of which are derived from the general moral norms valid for all transplants, and others of which are more specifically related to xenotransplantation.

The Health Risk

As previously stated, one of the fundamental ethical questions that should be examined when judging the legitimacy of xenotransplantation is that of the health risk involved in such procedures. This risk is dependent on various factors which cannot always be predicted or assessed. Before going on, therefore, it may be useful to recall some general aspects of the ethics of risk.

Risk – understood as an unwanted or damaging future event, the actual occurrence of which is not certain but possible – is defined by means of two characteristics: the level of probability and the extent of damage. The probability of the occurrence of a certain damaging event in particular circumstances can be expressed as a risk percentage or as a statistical frequency. Furthermore, the presence or absence of certain chance factors of risk can sometimes alter the probability that a certain event will take place. The extent of the damage, in contrast, is measured by the effects that the event produces. Naturally, a very probable risk is easily tolerated if the extent of damage associated with it is very small; on the contrary, a risk that causes a high level of damage, however improbable, gives rise to much greater concern and require greater caution.

It is important to distinguish between a probable event (event with varying degrees of probability) and an event that is only hypothetical; this latter is an event which is not theoretically impossible but which is so improbable as to require no change in behaviour or choices

Together, these two criteria – probability and extent of damage – define the acceptability of the risk, as reflected by the risk/benefit ratio. Only when a risk can be concretely assessed it is possible to apply criteria for evaluating its acceptability.

Lastly, it is necessary to distinguish acceptability from what we can define as the acceptance of the risk, as defined by the reaction of the individual or of the general public to the existence of the risk. This is a response that has a significant subjective component, one which is not always completely thought out and which is influenced by culture, by the information available and how it is understood, by the way in which the information itself is communicated, and by common sensibilities.

In the absence of data that allow a reliable assessment of such a risk, greater caution should be used; this does not necessarily mean, however, that a total “block” should be put on all experimentation. Indeed, to move from ignorance to knowledge, from the unknown to the known requires the exploration of new approaches which in all likelihood, especially; during initial experimental stages, will not be without risks, at least potentially. In this situation, therefore, the imperative ethical requirements is to proceed by “small steps” in this acquisition of new knowledge, making use in experiments of the least possible number of subjects, with careful and constant monitoring and a readiness at every moment to revise the design of the experiment on the basis of new data emerging.

It is important to consider the distinction between risk assessment and risk management.

To achieve an ethical assessment, both elements must be carefully examined.

This general discussion of the ethics of risk must now be applied to the specific case of xenotransplantation.

First of all, we note that there are issues connected with xenotransplantation, such as the probability of rejection and the increase in the probability of infection because of immunosuppressive therapies, about which some degree of knowledge already exists, although further study is necessary. The data which the scientific community already possesses, together with new data being gathered, can help to establish the threshold of risk that must not be crossed if a transplant operation to be considered morally acceptable.

More complex and uncertain is the assessment and evaluation of risks, connected to one specific aspect of xenotransplantation: the possible transmission to the recipient of infections arising from the xenotransplantation (zoonoses) by known or unknown pathogenic agents which are not harmful to the animal but which are possibly dangerous for man. Such infections could escape detection, with the consequent possibility of the spread of the infection to those having close contacts with the patient leading eventually to its being spread to the entire population.

Since clinical experience of xenotransplantation is quite limited and certainly insufficient to provide reliable statistics on the real probability of occurrences and spread of infections, any decision concerning clinical development of the new therapy can only be based on hypothesis.

There is, therefore, an ethical requirement to proceed with the greatest caution.

When the moment for clinical application of xenotransplantation arrives it will be necessary to select patients carefully, based on clear and well-established criteria, and to monitor the patient very closely and constantly. One must also contemplate the possibility of placing the patient in quarantine to prevent the epidemic spread of an infection. Arrangements for some kind of monitoring of those having close contacts with patient should also be made.

Moreover, during the experimental phase of clinical trials, patients should agree not to procreate because of the possible risk of genetic recombination that could affect the patient’s germ cells. Sexual abstinence would also be necessary to avoid the venereal transmission of possible viruses. In the clinical application of xenotransplantation, psychology should also play an important role. It should address the probable repercussions that the recipient could undergo in their psyche (e.g., because of the modification of one’s “bodily schema”) arising from the acceptance of a foreign organ, especially when it comes from an animal. In the post-transplant stage, psychology must also provide clinical support for the patient in the process of integration.

HUMAN GENE TRANSFER RESEARCH

Human gene transfer research (HGTR) involves the deliberate transfer of genetic material (naturally-occurring, genetically-modied, or synthetic DNA or RNA) into human subjects. Clinical success has come more slowly than was rst predicted, but HGTR remains a fundamentally novel approach to medical practice. It may one day enable clinicians to cure genetic disorders at their source, as well as provide oncologists with tools designed to disable or cure specic cancers. Nonetheless, HGTR differs from other clinical modalities in a number of ways. It involves creating genetically novel organisms that are potentially both transmissible and pathogenic, and there is a risk that this could modify the human genome. Human gene transfer techniques may also be extended beyond therapy into other, more controversial, areas (Verma). Consequently, while HGTR continues to capture the public’s imagination, it has received an unparalleled level of public oversight. However, only when HGTR nally achieves success will ethical concerns become real issues. Basic Terminology and Methods Two distinctions shape the analysis and practice of human gene transfer: between therapy and enhancement, and be tween somatic and germline cells. The rst refers to the transfer’s intended outcome. Researchers may seek to prevent or cure disease (therapy), or they may want to alter an individual’s characteristics or capabilities (enhancement). The second refers to whether research  reproductive (germline) cells. Somatic alteration would affect only the individual subject, while germline alteration would change genes passed on to an individual’s offspring.

As of 2003, federal regulatory bodies will only entertain somatic-cell gene transfer protocols conducted for preventing diseases or developing treatments (U.S. NIH). Genetic material can be transferred to human subjects in different ways, but most methods share certain similarities. Many protocols can be classied as either ex vivo or in vivo. Ex vivo protocols obtain tissue cells from the subject, genetically modify them in the lab, and return them to the subject’s body.  In vivo protocols employ different techniques to introduce genetic material into a subject’s body, hoping that it will reach the appropriate tissues. Most protocols to date have used disabled viruses as the vector for transferring genetic material, though other vectors are also under development. Information on how frequently different methods are used can be obtained from the “Human Gene Transfer Protocol List” compiled by the National Institutes of Health (NIH) Ofce of Biotechnology Activities (OBA).

Clinical Successes and Setbacks

Certain milestones and setbacks mark the progress of HGTR from 1989 through 2003. Within this period, over 545 human gene transfer protocols, involving over 4,000 patients, were registered with the OBA. The eld was launched on May 22, 1989, when Steven A. Rosenberg, Michael Blaese, and W. French Anderson injected genetically modied white blood cells into a male subject with advanced skin cancer. This protocol was not designed to intervene in his disease, but rather to track where the “marked” cells went in his body. The rst protocol that sought a therapeutic outcome began on September 14, 1990, when W. French Anderson and colleagues transferred genetically modied white blood cells to Ashanti DeSilva, a four-year-old girl with severe combined immune deciency (SCID). Ashanti’s immune system was strengthened, but her underlying condition was not cured. Throughout the 1990s no other protocol was able to report clinical efcacy. The rst unambiguous clinical successes were reported in the spring of 2000. In April 2000 the French researchers Marina Cavazzano-Calvo and Alain Fischer reported that two baby boys (a number later raised to nine) with a version of SCID had normal immune systems ten months after receiving cells that were genetically modied to replace a missing gene. In March 2000 Katherine A. High and Mark A. Kay reported that subjects with hemophilia B experienced an increase in factor IX protein activity for at least six months after the gene transfer.

Yet this long awaited clinical progress has been tempered by setbacks. In December 2002 a subject in the hemophilia-B study developed signs of liver injury, halting the trial. The same trial was briey halted in December 2001 when the gene-carrying virus was found in subjects’ semen, raising the specter of inadvertent germline gene transfer.And in January  2003 the second of the nine boys treated in France developed a leukemia-like illness.

More troubling for the eld was the death of Jesse Gelsinger. On September 17, 1999, Gelsinger, an 18-yearold subject, died from a gene transfer experiment being conducted at the University of Pennsylvania’s Institute for Human Gene Therapy. Gelsinger was affected by ornithine transcarbamylase (OTC) deciency. Patients with OTC deciency lack an enzyme needed for processing nitrogen with the result that toxic levels of ammonia accumulate in their bloodstreams, leading to severe mental impairment and even death. But Gelsinger’s symptoms were manageable so that, unlike subjects in other gene transfer trials, he approximated a healthy volunteer. The viral vector used in this protocol was an adenovirus—a virus that usually causes the common cold. Although used in many protocols prior to Gelsinger’s death, in his case the vector triggered a deadly immune response. An inquiry into his death resulted in severe sanctions against the University of Pennsylvania and the researchers involved, and it revealed major problems with HGTR oversight and conduct nationwide.

Public Oversight of Human Gene Transfer Research

HGTR is overseen in the United States by two agencies within the Department of Health and Human Services: the NIH and the Food and Drug Administration (FDA). While FDA review is “public” insofar as it involves federal oversight, NIH review through the Recombinant DNA Advisory Committee (RAC) is truly a forum open to the public.

This aspect is unique to HGTR and reects its historical  development.

EARLY CONCERNS ABOUT “GENETIC ENGINEERING.”

Serious debate about human gene transfer began in the 1960s, when scientists, theologians, and philosophers raised many concerns about genetic engineering, or genetic manipulation. Theoretical concerns evolved into real possibilities in 1972 when scientists discovered how to combine genetic material from different organisms. Recognizing that biologically novel organisms created through these techniques could, if inadvertently released, imperil the environment, individuals, or society, the scientic community called for a voluntary moratorium on this research—referred to as recombinant DNA research or  rDNA—until safety issues could be assessed (Berg et al., 1974). The 1974 moratorium was lifted after leading scientists met in Asilomar, California, and issued strict guidelines for the safe conduct of rDNA in 1975 (Berg et al., 1975). The self-imposed scientic moratorium on rDNA research unnerved the public, who were already disenchanted by a decade of research scandals. In response to these scientic and public concerns, the NIH established the RAC, on October 7, 1974. The RAC embodied a novel approach to federal oversight of a novel biotechnology. Because concerns about rDNA were societal as well as scientic, the RAC was staffed by both scientists and nonscientists, and its meetings were open to the public. In 1976 the RAC issued its rst set of guidelines. These guidelines focused on laboratory safety and containment, required federally funded institutions conducting rDNA research to establish an Institutional Biosafety Committee (IBC), and required all rDNA research to be reviewed rst by the local IBC and then by the RAC.

HGTR OVERSIGHT. The RAC’s early work focused on laboratory research that created recombinant organisms, and on work with animals and plants. As safety concerns raised by specic novel techniques were allayed, the RAC regularly shifted oversight responsibility to the IBCs. By 1983 the RAC’s attention had turned to HGTR. This shift was catalyzed by a number of events that captured public attention, including two unauthorized and scientically ill-founded human gene transfer experiments (the 1970 case of Dr. Staneld Rogers and the 1980 case of Dr. Martin Cline) as well as the controversial decision in Diamond v. Chakrabarty, allowing the patenting of genetically engineered organisms (for further information on these cases, see Walters and Palmer). One of the most important outcomes of these events was the 1982 publication of Splicing Life, a report on human gene transfer issued by the President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research. The commission argued that only transfer into somatic tissues to prevent or treat disease could be justied. The President’s Commission also recommended that the RAC broaden its responsibilities to include HGTR— and to attend to ethical and social implications as well as safety concerns. In 1983 the RAC created the Working Group on Human Gene Therapy (later renamed the Human Gene Therapy Subcommittee) to develop guidelines for human rDNA research and to review protocols (Walters, 1991). By 1985, this working group had produced “Points to Consider,” the rst version of the guidelines that would eventually govern HGTR.

CLINICAL TRIALS AND CHALLENGES TO PUBLIC OVER-

SIGHT. In April 1988 the RAC received its rst actual human gene transfer protocol, and federal oversight of HGTR began. The eld grew cautiously at rst, and thenexponentially, moving quickly from work with singlegene disorders to cancer research (Ross et al.). By 1995 the NIH was spending $200 million per year (2% of its budget) on HGTR. Harold Varmus, the director of NIH, commissioned two reports on the state of the eld. The rst, coauthored by Stuart H. Orkin and Arno G. Motulsky, criticized researchers for exaggerating prospects for therapeutic success. They argued that more basic research was needed before moving to and investing in clinical trials. The second assessed the work of the RAC and concluded that the committee continued to serve important functions (Verma).

From the outset, RAC oversight of HGTR was contested. As early as 1990, RAC review was assailed for delaying vital medical research (U.S. NIH-RAC; Culliton). Biotech companies objected to the public nature of RAC review, while researchers felt that RAC review unnecessarily duplicated FDA review, which holds statutory authority for such approval. Human gene transfer protocols, unlike other areas of research, must be reviewed both by the RAC and by the FDA, either simultaneously or sequentially. At the FDA, responsibility for human gene transfer lies with the Center for Biologics Evaluation and Research (CBER), and review focuses on the safety and efcacy of rDNA products, the safety of the manufacturing process, and the control of the nal product (Coutts). To protect proprietary interests, CBER review is closed, and it cannot, by charter, address the ethical or social implications of research. The FDA has developed its own “Points to Consider” document to advise investigators (U.S. FDA, 1998). In 1996, with the urging of biotech lobbyists, researchers, and politically powerful patient activists, Varmus proposed to abolish the RAC, and only overwhelming public support for the RAC averted its demise. Although not abolished, the RAC was downsized and could no longer recommend approval or disapproval of specic protocols. From 1996 through 2000, the RAC reviewed approximately 10 percent of the HGTR proposals submitted to the NIH (those proposing novel methodologies) and convened occasional Gene Therapy Policy Conferences.

THE AFTERMATH OF THE GELSINGER CASE. The Gelsinger case revealed major problems with the oversight of HGTR. A primary nding concerned the reporting of adverse events (bad reactions or deaths during a human gene transfer experiment). According to the NIH Guidelines, all adverse events must be reported in a timely fashion to the RAC, but Gelsinger’s investigators failed to report three adverse events to the FDA in a timely manner. Moreover, only 37 of 970 adverse events that occurred between 1993 and 1999 in trials using the adenovirus vector (approximately 25% of the HGT protocols underway at that time) were properly reported to the NIH (Walters, 2000)—these adverse events were reported to the FDA, but not relayed to the RAC. The inquiry also uncovered problems in the informedconsent process. The informed-consent document given to subjects in Gelsinger’s protocol differed from the one approved by the RAC and FDA, and it did not mention adverse events in animal studies. Public reporting about HGTR had led the Gelsingers to believe that patients had been cured by “gene therapy,” and they reported that the investigators had led them to believe subjects in their particular protocol had experienced clinical benet. Finally, adverse events experienced by other subjects in the protocol were not communicated to the Gelsingers, as required by federal guidelines (Stolberg). Ironically, the RAC’s attention to informed consent was one reason given by Varmus for abolishing it (Marshall).

The Gelsinger case led to Congressional inquiries, multiple hearings, and soul-searching at the NIH and FDA. The RAC provided a unique and crucial forum for gathering, analyzing, and publicizing information relevant to this crisis. This resulted in two notable outcomes: (1) the FDA formally agreed to inform the NIH of all adverse events reports it received, and (2) the Advisory Committee to the Director of the NIH recommended that the RAC receive novel protocols at an earlier stage in their development— namely, prior to submission to the IRB and FDA.

Ethical Issues in Human Gene Transfer Research

Early ethical and social concerns surrounding HGTR were outlined in 1985 in the NIH’s “Points to Consider.” Since then, broader public and commercial contexts of HGTR have raised additional concerns, especially involving subject recruitment and economic conicts of interest. These issues become increasingly important as HGTR moves toward new applications and methods.

 

TRANSGENESIS

The use of organs from engineered animals for xenotransplantation raises the need for certain reflections on transgenesis and its ethical implications.

The term “transgenic animal” is used to indicate an animal whose genetic make-up has been modified by the introduction of a new gene (or genes). In contrast, the term “knock out” is used to designate those animals in which a given endogenous gene (or genes) is no longer expressed. In either case, such animals will express particular characteristics which will be transmitted to the offspring.

As we have already observed, the possibility of working out such genetic modifications, using genes of human origin as well, is normally acceptable when done in respect for the animal and for biodiversity, and with a view to bringing significant benefits to man himself. Therefore, while recognizing the transgenesis does not compromise the overall genetic identity of the mutated animal or its species, and reaffirming man’s responsibility towards the created order and towards the pursuit of improving health by means of certain types of genetic manipulation, we will now enumerate some fundamental ethical conditions which must be respected:

1. Concern for the well-being of genetically-modified animals should be guaranteed so that the effect of the transgene’s expression, possible modification of the anatomical, physiological and/or behavioural aspects of the animal may be assessed, all the while limiting the levels of stress and pain, suffering and anxiety experienced by the animal;

2. The effects on the offspring and possible repercussions for the environment should be considered;

3. Such animals should be kept under tight control and should not be released into the general environment;

4. The number of animals used in experiments should be kept to a bare minimum;

5. The removal of organs and/or tissues must take place during a single surgical opera-tion;

6. Every experimental protocol on animals must be evaluated by a competent ethics committee.

INFORMED CONSENT FOR XENOTRANSPLANTATION

In the ethical discussion on xenotransplantation, the subject of informed consent also deserves special attention. Given the animal source of the organs which will be transplanted, this issues concerns only the recipient and, secondly, his relatives. At the outset the recipient should be given every information regarding his pathology and its prognosis, the xenotransplant operation and subsequent therapy, and the probability of success and the risks of rejection. Special attention should be paid to making sure that the patient is informed about the real and hypothetical risks of zoonoses, in light of current data, and about the precautions to be adopted in the case of infection (in particular the possible need for quarantine, which involves avoiding physical contact with others while the risk of contagion is present). The patient must also be informed about the need to remain under medical supervision for the rest of his life, so that the necessary constant monitoring following the transplant may be carried out. In addition, adequate information on possible alternative therapies to xenotransplant therapy should not be withheld.

This informed consent on the part of the patient should be understood as personal. For this reason, minors and those unable to give valid consent are to be excluded from the experimental phase.

However, if a patient incapable of giving valid consent should find himself in a previously unforeseen situation where there is danger of imminent death, recourse may be made to a legal representative (e.g., in the hypothetical case of a life-saving xenotransplant as a temporary solution for a patient in a coma), provided that the medical procedures to be used offers a reasonable hope of benefit for the patient.

The patient’s relatives should also be informed about what the transplant could entail regarding their contact with the patient and about the possible risks of contagion should an infection, as mentioned above, set in. In a strict sense, however, consent cannot be requested from them, since it is the patient who is ultimately responsible for the choices concerning his own health.

ALLOCATION OF HEALTH CARE RESOURCES

Xenotransplantation certainly represents a form of possible treatment requiring a great outlay of both health care resources and economic resources. For this reason, some people have expressed doubts about its ethical validity; given the large amounts of resources that it would take away from the other forms of therapeutic treatment and from other area of research, they consider both the uncertainty about its success and the risk entailed to be excessive.

Faced with these doubts, it is important to remember that, even taken into due consideration the costs-benefits balance, the huge amount of health care resources used in this case is justified by the urgent need to try to save the lives of so many patients who would otherwise have no chance of survival.

It should also be added that as long as xenotransplantation on man remains at an experimental stage it should not be subject to the criteria applied to treatment in strict sense; rather it should be evaluated according to the criteria used for trials. Therefore, the foreseeable collective benefits that it may accrue in the future should also be taken into account. We do well to recognize here that the research into xenotransplantation which has taken place so far has also brought about greater medical knowledge in the area of allotransplantation.

PATENTABILITY AND XENOTRANSPLANTATION

Research on xenotransplantation has hitherto in large measure been carried out largely by private pharmaceutical companies which have committed substantial economic resources to this endeavour; they have also been providing financing to public institutions for the purpose of obtaining better therapeutic results. It is therefore reasonable for them to expect an economic return on the investment made; one of the possible ways to do this is by acquiring patents.

From a formal point of view, there is no technical or legal obstacle standing in the way of the patenting genetically engineered animal organs intended for transplants. It should be emphasized however, that the norms drawn up by the European Community to regulate this matter could not, at the time they were being drafted, take into account the use of such organs for transplant from animal to man, since this therapeutic procedure had not yet been accomplished in clinical practice.

We therefore stress that, given the extraordinary financial commitment that has been made, now is the time to reconsider – or rather to be more precise about – the specific norms that apply.

We are aware of the broad debate underway on the basic question of whether the possibility itself of patenting living beings (even though genetically modified) or parts of them, especially when they contain genetic elements derived from humans (as is the case with animal organs genetically engineered for xenotransplantation into man), is ethically acceptable. We are also aware that there is a difference between a “discovery” (which cannot be patented) and an “invention” (which can be patented). Although it is our view that the transgenic animal as such – and all the more when they are used for transplantation into man – should be considered “nonpatentable”, we nonetheless believe that it is not the purpose of present document to address this complex question directly.

Here, we shall limit ourselves to emphasizing that, whatever answer may be given to this basic question, it is always necessary — as a bare minimum — to guarantee respect for the fundamental right of every person to equitable access to the health care they may be needed, without discrimination and without being impeded by excessive costs. This applies above all else to accessibility to treatment. This objective — in the phyothetical case of patents connected with xenotransplantation, a procedure which should be viewed from a therapeutic standpoint— can be reached by making appropriate legal requirements apply (for example, the introduction of compulsory licences), thus allowing “production” at accessible prices which would hopefully be controlled by a supranational body specifically set up for this purpose.

 ORGAN CULTURE

Not whole but pieces of organs can be cultured on artificial medium. For organ culture care should be taken to handle in such a way that tissue should not be damaged. Therefore, organ culture technique demands more tactful manipulation than tissue culture. The culture media on which organ is cultured are the same as described for cell and tissue culture. However, it is more easy to culture embryonic organs than the adult animals. Methods of culturing embryonic organ and adult organs differ. Besides, culture of whole or part of animal organ is difficult because these require high amount of O2 (about 95%). Special serum-free media (e.g., TS) and special apparatus (Towells type II culture chambered) are used for adult culture.

In addition, the embryonic organs can be cultured by applying any of the following three methods:

(i) Organ culture on plasma clots

A plasma clot is prepared by mixing five drops of embryo extract with 15 drops of plasma in a watch glass placed on a cotton wool pad. The cotton wool pad is put in a petridish. Time to time cotton is moistened so that excessive evaporation should not occur. Therefore, a small piece of organ tissue is placed on the top of plasma clot present in the watch glass. In the modified technique the organ tissue is placed into raft of tense paper or rayon. The raft makes easy to transfer the tissue, excess fluid can also be removed.

(ii) Organ culture on Agar

Solidified culture medium with agar is also used for organ culture. The nutrient agar media may or may not contain serum. When agar is used in medium, no extra mechanical support is required. Agar does not allow to liquefy the support. The tumours obtained from adults fail to survive on agar media, whereas embryonic organs grow well.

(iii) Organ culture in liquid media

The liquid media consist of all the ingredients except agar. When liquid media are used for organ culture, generally perforated metal gauze or cellulose acetate or a raft of lens paper is used. These possibility provides support.

ETHICAL ISSUES

Ethical issues concerning xenotransplantation include animal rights, allocation of resources, and distributive justice. In addition to obtaining consent for xenotransplants from individual patients, consent is also necessary from the populace, given the public health risks.

ANIMAL RIGHTS

The genetic make-up of larger primates is about 98 percent identical to humans. Opportunities exist to make medical breakthroughs by overcoming species’ immune barriers in ways that blur ethical boundaries. The British Medical Journal recently published a letter on xenotransplantation from Neville Goodman, a physician. He is outraged that expensive high technology treatments like this are going forward at a time when political will is lacking to make basic medical resources available in third world. With indignation, he quotes a researcher raising baboons for xenotransplant organs, who says her baboons “are treated better than some people in third world countries”, as if proper treatment of the monkeys ends any ethical questions about xenotransplantation. It seems that scientists are unclear and in profound disagreement among themselves as to where the lines should be drawn.

Although some researchers prefer to work with primates, such as baboons or chimpanzees, Jane Goodall makes a very compelling argument against using chimpanzees in any laboratory research. Her observations of their social behavior over a period of 29 years prove their capacity not only for emotional depth, but also for altruistic behavior. Goodall shows that capturing infant chimps by killing their mothers has contributed to their endangered status, because young monkeys separated from their mothers do not thrive or become prolific breeders.

Respect for the rights of all beings is a tenet of the world’s major religions, and it gives the animal rights movement the support of serious long-standing tradition. Daniel Rothman warns against taking the message of animal rights advocates lightly. He points out that what is most deplorable is unnecessary, frivolous use of animals that creates suffering. “The fear of being casual with life”, he says, “is a real one. Disrespect in one arena can breed disrespect elsewhere”.

He asks whether a “lifeboat” argument (the choice of lesser evils) can be used in defense of xenotransplantation.

Just as phylogenetic proximity is a measure of potential immune rejection, it also is a measure of how humans value other species. Is killing a primate more serious than killing a pig? Is it about how human-like the species is?

Do humans have the right to use other species for their own (medical) purposes? If so, what are the conditions or limits? Respect for living beings means not treating them as a means to an end, an object. Immanuel Kant said this applied to humans, but not to the rest of nature. Environmentalists point out that objectification and commodification of their life forms have caused us to create the ecological conditions that imperil our own species–A utilitarian ethic Judges an action by effects on humans, a utilitarian would argue that it is wrong to mistreat animals, because it can make them dangerous, not because mistretment is intrinsically wrong. By this kind of logic, raising pigs for transplant organs might be criticized for its effect of coarsening human sensibilities. This is essentially the old antivivisectionist argument, “Deep ecologists” would say humans are just one of many species, no more intrinsically worthy of respect than any other. Human behavior vis-à-vis other species might make them less worthy of respect. [pc] Another perspective, from Buddhism, is that of “dependent coarising”.

It holds that there is no independent self or separate existence of species. Humans must treat other beings as they would treat themselves, because existence depends on and is inseparable from the rest of the web of living beings – if there ought to be some reciprocity in our relations with nature, then Xenotransplantation bestows no boon to animals.

Raising animal populations for research and drug production has become more sophisticated since the advent of recombinant DNA technology. Government regulations currently protect laboratory animals, but how will they protect genetically-modified farm cows, created to produce proteins in their milk for research experiments (onco-mouse, knockout mice) or animals to be “harvested” for their cells or organs ? Animals that are used as a source for tissue and cell transplant are regulated as biologicals, under FDA, Regulations on animals in a research setting also apply. The 1996 PHS Guideline suggests that existing regulations should be followed for transplant animals, and that transplant trails should be reviewed by animal care committees as well as institutional review boards (IRBs).

In what way do these uses of animals raise new ethical issues? Is a threshold crossed by raising larger mammals just to supply “spare pans” for humans ? The gift ethic is supported by regulation in the United States. Scandals surrounding human organ procurement argue for the preservation of this ethic — raising animals for their organs as a for-profit enterprise may raise temptations to stretch this ethic. It appears that the breeding and raising of animals for transplant purposes will require extensive monitoring to avoid transmissible diseases as well as genetic or pharmacological alterations to side-step various mechanisms of immune rejection. It is certain that the U.S. Patent and Trademark Office (PTO) will receive more applications in this area, and that the unacceptability of financial ability to pay as a selection criterion, the realistic odds that equal access to xenotransplantation can be achieved, given the potential expenditures that will be necessary, are slim.

Why is the federal government funding an expensive and risky new technology when it will benefit a few people and when one-third of the U.S. population, mostly women and children, are uninsured and, hence, without any health care? As Tristram Engelhardt puts it. The debates concerning the allocation of treatment resources such as transplantation recur and show no promise of abating. Some controversies have a staying power because they spring from unavoidable moral and conceptual puzzles. One cannot answer the question simply with scientific data, but only by balancing values. Background values of equity, decency, fairness, costbenefit tradeoffs, individual rights and the limits of state authority must be involved.

If an individual loses “nature’s lottery” by incurring a health condition that requires an organ transplant, and the “social lottery” by not having the economic resources to pay for a transplant, can or should a social insurance system redress this misfortune by spending common resources on transplants? Or should the system spend the resources on universal preventive health care? A sort of “global commons” argument exists; while big ticket technologies carry large opportunity costs out of the public funds available for basic services, administrators may choose to provide the higher ticket services in order to stay competitive with other institutions that provide them, and thus draw more prestige and patients – As in the global commons, each player contributes to the dissipation of the common resource by behavior that is rational to an individual, but not for the common good.

PUBLIC ASSENT

The ethics of human transplants takes a new twist with xenotransplants, in that the latter raises the serious possibility of diseases creating major public health risks:

“Xenotransplantation is a unique medical enterprise. It puts the public at risk ... [and] it has to be the public that says, they do not accept that risk, or they accept it”. The moral importance of this transaction should not be dismissed lightly just because the donor is an animal.

ALLOCATION OF ORGANS

Never enough organs to meet needs. Much of the raison d’etre for xenotransplantation is based on organ shortages. But even if we accept the xenotransplantation and the technology is successful, allocation issues still have to be worked out fairly, and not simply as an economic commodity.

A national structure of organ procurement and allocation, NOTA, establishes priority rules and procedures, A reliable supply of organs could increase U.S. annual expenditures for transplant surgeries, because more people would get them. If costs rise, as might be expected, how will this affect allocation, particularly to less-than-affluent patients? How will access to human organs be affected? What ethical problems arise in allocation?

Justice and fairness require that society’s burdens and benefits be borne equally. Democracy requires that the medical professionals, patients, and the body politic have a voice. Physicians should not be forced to choose between saving a life and distributing organs fairly.

DISTRIBUTION OF MEDICAL RESOURCES

Health insurers and health maintenance organizations must weigh the efficacy and costs of alternative treatments. In the case of kidney transplants, the cost of maintaining a patient with renal failure on dialysis for years is less than the cost of transplant surgery, but the net cost in public health care amount is huge in either case. In Oregon, where health care rationing has been developed to allocate public money as equitably as possible, organ transplants are not covered for reimbursement.

LIVING THINGS AS PROPERTY

One effort to raise public awareness of ethical issues in biotechnology was the recent patent application by researcher Stuart Newman and activist Jeremy Rifkin. Claimed are three methods of creating human-animal chimeras. Genetic material is moved from one species and placed into the embryo of another. Even though the inventors have stated that they have no intention of using the patent to produce such chimeras, they fist under possible applications of the techniques the production of organs for transplant into humans. On the surface, this patent does not differ from some patents already issued, such as the “geep” (sheep-goat chimera) or implantation of human “early passage” and embryonic stem cells into the embryos of another species. However, Newman and Rifkin seek to drive a nail into the heart of biotechnology by putting the morality of life patents at issue. As a way to challenge biotechnology patent issues, the tactic is clever. It gives these joint-inventors standing to have an “interfer ence proceeding” declared by PTO when any similar patents are filed. They hit their mark, because PTO released a statement within days, declaring that it would not allow patents on part-human inventions, PTO said that these inventions might violate public policy and the morality aspects of the utility requirement. PTO’s press release went on to cite an 1817 opinion by Justice Story on the utility requirement, which excludes inventions “injurious to the well being, good policy, or good morals of society”. Patent law authority Donald Chisum raised issue with the public policy doctrine, noting that, in fact, a patent approval can be withheld only if the invention has no honest and moral purpose. [ibs] Nonetheless, two days later, PTO Commissioner

Bruce Lehman asserted his authority to determine the morality of an invention. He said the press release was necessary to make it clear that “there will be no patents on monsters, at least while I am commissioner”.

What is interesting is that PTO policy was issued when it was. Is PTO really shocked by Newman and Rifkin’s patent’s subject matter? It is quite similar to many patents already issued or in process, Chimeric techniques have been around for several decades. In this case, researchers are attempting to use them to overcome immune barrier problems in xenotransplantation. Moving human cells into donor animals or animal cells into humans has not raised red flags at PTO before–Newman and Rifkin’s application is different only in that it calls a pig a pig, so to speak.

Rifkin and Newman’s goal is to prevent the commercial exploitation of the technology before it has had a fall public airing of its ethical implications. Rifkin has long been a critic of biotechnology; many industry representatives and academics concede that this move may force a high profile public debate on the issues. It may also buy time for researchers to clarify some of the risks of necessary limits in applying the technology, PTO rejected this patent in June 1999, but an appeal is being prepared.

Even biotechnology industry lawyers concede there is no legal consensus on drawing a line on which life forms can and cannot be patented. In the past, the Thirteenth Amendment to the U.S. Constitution, outlawing slavery, was understood to bar human cell patents. Commencing on issues raised by Newman and Rifkin’s application, David Mickei, of the Biotechnology Industry Organization, calls it a “grey area”, Researcher David Porteous, of the UK Medical Research.

Council’s Human Genetics unit, says, “Setting aside the biological arguments, this is very much a mix of a legal and philosophical discussion. It would certainly be a useful extension of the debate”. And Jonathan Marks, professor of biology and anthropology at the University of California/Berkeley says, “If this is what it takes to encourage geneticists to think more about humanitarian issues, I am all for it”.

The European Patent Office, on the other hand, is considerably more sensitive to ethical issues. The latest draft of its biotech patent policy specifically excludes as “unpatentable” any inventions whose exploitation or publication would be contrary to public policy or morality.

These include: (1) procedures for human cloning; (2) procedures for modifying the germ-line genetic identity of human beings (alterations to genetic materials that are inheritable);

(3) changes to the genetic identity of animals that are likely to cause suffering without substantial medical benefit to man or animal, and animals resulting from such processes; (4) methods in which embryos are used; and (5) methods for artificial production of human embryos containing the same genetic information as another human being, dead or alive.

BREAKING NEWS

In May 2000, a stack of internal documents was leaked to Uncaged Campaigns, a British animal rights group. It documented experiments financed by Imutran, a leading xenotransplant research company, and conducted by Huntigdon Life Sciences in Cambridgeshire, England.

The experiments involved transplanting genetically-modified pig organs into monkeys and baboons. These experiments are also being done in U.S. research and medical centers.

The documents covered the log of experiments over several years in the late 1990s. Over 420 monkeys and nearly 50 baboons died in the tests. The average survival time was 13 days, Uncaged published the documents on the Internet along with a summary report on them, “Diaries of Despair”, and called on the British government to halt xenotransplantation research and set up an independent Judicial inquiry. Not long after, Uncaged’s material was removed from the internet. Imutran, citing breach of confidentiality and copyright violation, got a British court order prohibiting uncaged from further publishing or discussing the documents, Britain’s Daily Express newspaper also received copies of the documents and wrote a scathing article in September 2000 reporting that the documents showed days or weeks of animal suffering, incompetence in the conduct of the experiments and for less success with the experiments than was claimed by Imutran. According to the Express, “Imutran has given a highly selective account of its achievements”. Responding to the furor, Imutran said the animals don’t suffer and the Daily Express report was misleading. The British court order also forbids any further publication or reporting on the documents by the newspapers.

An organ transplant is the transplantation of an organ (or part of one) from one body to another, for the purpose of replacing the recipient's damaged or failing organ with a working one from the donor. Organ donors can be living, or cadaveric (dead).

There are also extremely controversial issues regarding how organs are allocated between patients. For example, some believe that livers should not be given to alcoholics in danger of reversion, while some view alcoholism as a medical condition like diabetes.

Healthy humans have two kidneys, a redundancy that enables living donors (inter vivos) to give a kidney to someone who needs it. The most common transplants are to close relatives, but people have given kidneys to other friends; in one case, a teacher gave a kidney to one of her students.


The Spanish transplant system is one of the most successful in the world, but still can't meet the demand. Donations from corpses are anonymous, and a network for communication and transport allows fast extraction and transplant across the country. Under Spanish law, every corpse can provide organs unless the deceased person expressly rejected it. Nonetheless, doctors ask the family for permission. The enforcing of helmet wearing for bikers, though, reduced the number of young healthy donors.


Under United States law, the law of organ donation is left to the fifty U.S. states. A Uniform Anatomical Gift Act seeks to streamline the process and standardize the rules among the various states, but it still requires that the donor make an affirmative statement during his lifetime that he is willing to be an organ donor. Many states have sought to encourage the donations to be made by allowing the consent to be noted on the driver's license. Still, it remains an opt-in system rather than the Spanish style opt-out system.

Blood transfusion is not generally considered to be a form of organ transplant, though many of the same issues can apply. The purchase of blood for transfusion was common in the United States until the AIDS epidemic made people aware of the risks of transmitting disease through blood transfusion. (A substantial number of the people who sold blood also injected heroin, putting them at high risk for AIDS.) Some countries only allow altruistic blood donations to reduce the risk.

Safety issues

Donated organs, blood, and tissues have the potential to spread disease. While donated blood is screened for a wide variety of pathogens, donated organs are usually screened only for the most common and dangerous pathogens, typically HIV, hepatitis, and syphilis. Organ screening is complicated by two factors. First, organs spoil quickly and must be transplanted within hours of being obtained. This limits the amount of time available for pathogen screening. Second, an organ donor is often an accident victim who has succumbed to traumatic injuries -- such a patient has a much higher likelihood of having received blood transfusions in an effort to save his life.

Doctors have reported serious complications and death due to organ transplants from donors infected with herpes, West Nile Virus, cytomegalovirus, Epstein-Barr virus, and even (in one case) rabies. Infection from non-viral pathogens, including candida and the parasite Trypanosoma cruzi have also been reported.

Currently there is a lot of interest in how certain transplants (including bone marrow, stem cell, and bowel) can cause so-called "adoptive transfer" of diseases thought to have a genetic basis (such as Crohn's disease and other autoimmune disorders). While adoptive transfer of genetic disease is clearly not a desirable outcome, the cases so far reported may offer significant insight into how genetic susceptibility leads to a phenotypic manifestation of the disease.

Bioethical Issues in Organ Donation

Since the mid 1970s, a relatively new field in ethics, bioethics, has emerged at the forefront of modern clinical science. Many philosophical arguments against organ donation stem from this field.


Generally, these arguments fall into two camps: teleological and deontological ethical considerations.

Deontological Issues

Pioneered by such giants as Paul Ramsey and Leon Kass, modern bioethicists disagree on the moral status of organ donation. Certain groups, like the Christian Scientists and traditional Jews, oppose organ donation on religious grounds. Issues surrounding patient autonomy, living wills, and guardianship make it nearly impossible for involuntary organ donation to occur. In issues relating to public health, it is possible that a compelling state interest overrules any patient right to autonomy.

From a philosophical standpoint, the primary issues surrounding the morality of organ donation are semantical in nature. The debate over the definition of life, death, human, and body is ongoing. For example, whether or not a brain-dead patient ought to be kept artificially animate in order to preserve organs for harvesting is an ongoing problem in clinical bioethics.

Further, the use of cloning to produce organs with an identical genotype to the recipient has issues all its own. Cloning is still a controversial topic, more so when the clone is created with the express purpose of being destroyed for harvesting. While the benefit of such a cloned organ is a zero-percent chance of transplant rejection, the ethical issues involved with creating and killing a clone may outweigh these benefits.

A relatively new field of transplantation has reinvigorated the debate. Xenotransplantation, or the transfer of animal (usually pig) organs into human bodies promises to eliminate many of the ethical issues while creating many of its own. While xenotransplantation promises to increase supply of organs considerably, the threat of organ transplant rejection coupled with the general anathema to the somewhat alien idea decreases the functionality of the technique.

Teleological Issues

Organ donation is fast becoming an important bioethical issue from a social perspective as well. While most first-world nations have a legal system of oversight for organ transplantation, the fact remains that demand far outstrips supply. Consequently, there has arisen a black market often referred to as the transplant trade.

On teleological or utilitarian grounds, the moral status of organ donation relies upon the ends, rather than the means. Insofar as those that donate organs are often impoverished and those that can afford afford black market organs are typically well-off, it would appear that there is an imbalance in the trade. In many cases, those in need of organs are put on waiting lists for legal organs for indeterminate lengths of time - many die while still on a waiting list.

The issues are weighty and controversial. On the one hand are those who contend that those who can afford to buy organs are "exploiting" those who are desperate enough to sell their organs. Many suggest this results in a growing inequality of status between the rich and the poor. On the other hand are those who contend that the desperate should be allowed to sell their organs, and that stopping them is merely contributing to their status as impoverished. Further, those in favor of the trade hold that "exploitation" is morally preferable to "death," and insofar as the choice lies between abstract notions of "justice" on the one hand and a dying person desperately in need of an organ on the other hand, the organ trade should be legalized.

Legalization of the organ trade carries with it its own sense of "justice" as well. Continuing black-market trade creates further disparity on the demand side: only the rich can afford such organs. Legalization of the international organ trade would lead to increased supply, lowering prices so that the poor might be able to afford such organs as well.

Exploitation arguments generally come from two main areas:

·                     Physical exploitation suggests that the operations in question are quite risky, and, taking place in third-world hospitals or "back-alleys," even more risky. Yet, if the operations in question can be made safe, there is little threat to the donor.

·                     Financial exploitation suggests that the donor (especially in the Indian subcontinent and Africa) are not paid "enough." This argument generally relies upon the assumption that there exists some financial amount that does indeed constitute "enough," but that the donors in question are not receiving this amount of money in return.

 

SURROGATE MOTHERHOOD

Surrogacy is an arrangement whereby a woman agrees to become pregnant for the purpose of gestating and giving birth to a child for others to raise. She may be the child's genetic mother (the more traditional form of surrogacy), or she may be implanted with someone else's fertilized egg.

Early History of Embryo Research

Until the 1990s most research involving human embryos was directed toward improving the chances for pregnancy in laboratory-assisted conception. These investigations, in turn, were based on many years of research with animal models, where virtually all research in the United States has been supported with federal funding. It was hoped that procedures developed in animal studies could later be applied to human reproduction and embryology, especially to the understanding and alleviation of human infertility. Attempts at laboratory fertilization of human oocytes (precursor eggs) showed some promise as early as 1944 in the work of American obstetrician-gynecologist John Rock and scientist Miriam Menkin. From that time until the birth of the first child conceived through IVF in 1978, various approaches were tried in order to achieve a pregnancy and live birth. The work of Robert Edwards, British reproductive endocrinologist, culminated in the birth of Louise Brown after he collaborated with Patrick Steptoe, an obstetrician who utilized laporoscopy for viewing and recovering a mature ovarian follicle containing an oocyte capable of fertilization.

According to embryologist Jonathan Van Blerkom, most current methods used in laboratory-based treatment of infertility have evolved from those used by Edwards and Steptoe and their predecessors. According to Van Blerkom, this work “established the basic science foundation of clinical IVF” (p. 9). Without these four decades of research on fertilizing oocytes, accompanied by study of the early cleavage and development of fertilized eggs or zygotes, the clinical practice of IVF, which is an almost universally accepted primary treatment for infertility, would not exist.

U.S. Funding and Regulation of Embryo Research

In 1975 the U.S. National Commission for the Protection of Human Subjects recommended guidelines for federal funding of research involving human fetuses, but stipulated that these guidelines did not cover research on IVF or on embryos resulting from IVF. It proposed that an Ethical Advisory Board be appointed to review such protocols, and this recommendation was incorporated into federal regulations. In 1978 an Ethics Advisory Board (EAB) was appointed to recommend a policy on federal funding for research involving IVF. In its 1979 report the EAB concluded that research on IVF was ethically acceptable for federal funding under these conditions: that all federally funded research is directed toward establishing the safety and efficacy of IVF; all gametes used to develop embryos in research protocols are provided by married couples; and no embryos are preserved in the laboratory beyond fourteen days of development. The EAB’s rationale was based on two main points. First, it would be irresponsible to offer clinical IVF without doing the studies necessary to insure its safety and efficacy. Second, given the high rate of embryo loss in natural procreation, a similar rate of loss could be tolerated for the goal of eventually achieving pregnancies and births. The EAB did not distinguish between embryos created for research purposes and embryos remaining from infertility treatment. In fact, the board implied that at times it might be necessary to create embryos with no intent to transfer them to a woman. For the sake of safety, the results of new types of procedures would have to be studied in the laboratory before the procedures were offered clinically. It would be unethical to transfer to a woman the embryos resulting from unvalidated novel procedures. The EAB report elicited an outpouring of letters opposing embryo research, and its recommendations were never implemented. When the EAB charter expired in 1980, a subsequent board was not appointed, thus leaving no body to review proposals for federal funding of IVF and embryo research. This situation effectively created a moratorium on federal funding in the United States, though it did not affect research that was privately funded.

Among the many applications of the new reproductive technologies (including artificial insemination by donor—AID, in vitro fertilization—IVF, embryo transfer, and embryo freezing) surrogate motherhood has such far-reaching consequences that it raises a multitude of ethical and legal questions. It has been hotly debated in courts and legislatures, and has merited consideration by Commissions, Inquiries, Working Parties and professional societies in Australia, Great Britain, France, Canada, and many other countries, as well as in the United States (see citations 1-14). What distinguishes surrogacy from other reproductive technologies is not the technology itself but the circumstances of its application—an arrangement whereby one woman bears a child for another, with the intent of relinquishing the infant at birth. The surrogate arrangement is most often made between a couple (where the wife is infertile) and a “surrogate”; in the contract signed by both parties, the surrogate agrees to be artificially inseminated with the husband’s sperm, to bear a child, and at birth to give up all parental rights and transfer physical custody of the child to the “commissioning couple.” Although contracts vary, they always include provisions concerning the rights and responsibilities of all parties, both before and during pregnancy and after the birth of the child. The heart of the arrangement is the promise by the surrogate to give up custody of the child and the promise of the other party to accept the child. Several authors (21)(28) distinguish between “full” and “partial” surrogacy, “full” surrogacy utilizing in vitro fertilization and embryo transfer and “partial” surrogacy using artificial insemination. Coverage in this Scope Note is restricted to “partial” surrogacy, the more common of the two.

What is the motivation for choosing to enter a surrogate arrangement? There are several reasons why a couple might choose to have a child through a surrogate. Infertility is a common reason. With approximately 15 to 20 per cent of all couples infertile and a decrease in adoptable babies, many argue that surrogate motherhood provides a unique opportunity for certain couples to have a child biologically related to the husband. Other reasons range from the desire to avoid passing on a genetic defect to convenience. Many ethical analyses draw a sharp distinction between these motivations. Some insist that surrogate motherhood is as old as the story of Abram, Sarai and Hagar in Genesis 16. Others underline the novelty of such arrangements. In fact, the first recorded surrogate arrangement involving artificial insemination was made in 1976 in Dearborn, Michigan, by Noel Keane, a lawyer, who founded Surrogate Family Services, Inc., an agency that matches infertile couples and women willing to act as surrogates. Three years later, Richard Levin, M.D., set up Surrogate Parenting Association, Inc., in Louisville, Kentucky. To date, there have been several hundred surrogate births, and there are more than 30 centers that match infertile couples and surrogate mothers.

Legal Actions to Date

What have the courts said about surrogate arrangements? Legal action in the state of Kentucky provides an example. In 1981, the Attorney General of Kentucky brought a civil suit against Surrogate Parenting Associates, Inc., declaring, in reference to state baby-selling statutes, that surrogate contracts are illegal when a fee is involved. In 1983, the Kentucky Circuit Court ruled that a fee paid to the natural mother is not equivalent to the sale of a child, but an Appeals Court upheld the Attorney General’s position. However, most recently, in a 1986 decision, the Kentucky Supreme Court ruled that state statutes prohibiting baby-selling do not apply to surrogate arrangements. Furthermore, two other recent court decisions, including the Baby M decision, strongly support commercial surrogate arrangements Curiously, legislation has been slow in coming. To date, the only national legislation specifically addressing the issue of surrogate motherhood has been enacted abroad: two acts prohibiting the commercialization of surrogacy, one in Victoria, Australia, and the other in Great Britain.

During the spring of 1986, a proposed amendment to the British Surrogacy Arrangement Act 1985 was introduced in the House of Lords as a Private Members’ Bill, but later “died.” In the United States, according to a 1987 American College of Obstetricians and Gynecologists’ compilation, there are 64 state bills that were introduced in the current legislatures from January to June 1987. Of those, according to an August 1987 compilation of the National Committee for Adoption, half would prohibit surrogacy arrangements while half would allow surrogacy arrangements. Twenty would set up a study of surrogacy. Two states have actually passed legislation on surrogacy—Louisiana has prohibited surrogate contracts and Nevada has allowed surrogate contracts. Several other states have passed legislation to set up study groups or task forces on surrogacy.

Ethical Issues

Perhaps legislation is slow in coming because society has not yet been able to resolve the myriad of ethical and legal questions surrounding surrogate motherhood. Ethical issues abound. Many argue that surrogate arrangements depersonalize reproduction and create a separation of genetic, gestational, and social parenthood. Others argue that there is a change in motives for creating children: children are not conceived for their own sakes, but for another’s benefit. Much is unknown. What is the degree of stress on the couple and especially on the surrogate mother? Can true informed consent ever be given by the surrogate, and can anyone predict the emotions associated with relinquishing a child? What are the possible adverse psychological effects on the child? What identity crisis might ensue, and will there be a desire on the part of the child to know his/her gestational mother? Will surrogate arrangements be used not only by infertile couples but also for the sake of convenience, or by single men or women? Should the surrogate be paid? Would this lead to commercialization of surrogacy and expose the surrogate mother to possible exploitation? What happens when no one wants a handicapped newborn? Should the couple and surrogate remain unknown to each other? Should the child be told? What kinds of records should be kept, and should the child have access to them? What kind of medical and psychological screening should be provided to all parties?

Legal Questions

Closely linked to such ethical questions are a multitude of legal questions concerning surrogacy, because laws were written for other circumstances, not specifically for surrogacy. Are surrogacy contracts enforceable? Are they illegal? Is payment of a fee in violation of baby-selling statutes, i.e., is it payment for services rendered or for the child? Is the contract counter to public policy? What happens if the surrogate decides to keep the child? What would be appropriate damages for breaches of the contract? Would they be monetary, or would they require specific performance? How could disputes over visitation rights be resolved? Who is the legal mother? How can the husband of the infertile woman establish his paternity rights? Who should participate in decisions affecting the welfare of the fetus and the newborn? Would prohibition of surrogate arrangements violate constitutional rights to privacy or rights to procreate? These are complex questions and issues. They have been studied in Great Britain (Warnock Committee), in Canada (Ontario Law Reform Commission), in France (Comité Consultatif National d’Éthique), in Victoria and New South Wales, Australia (Waller Committee and New South Wales Law Reform Commission), in other states of Australia (Queensland, Tasmania, South Australia, Western Australia), in Spain (Congress of Deputies’ Special Commission), in West Germany (Benda Commission), in the Netherlands (Dutch Health Council), as well as in the United States (American Fertility Society and Office of Technology Assessment).

Reports and Policy Statements

The American College of Obstetricians and Gynecologists, in a succinct statement of policy, identifies ethical issues unique to surrogate motherhood arrangements as well as those shared with artificial insemination by donor (AID). Other concerns raised by the presence of a fee are addressed. It concludes that while the decision of whether or not to participate in a surrogate arrangement is an individual one for each physician to make, the ACOG has “significant reservations” about this approach and makes several recommendations to physicians confronted with such a situation.

American Fertility Society. Ethics Committee.

Ethical considerations of the new reproductive technologies. Fertility and Sterility

The American Fertility Society issued a report, Ethical Considerations of the New Reproductive Technologies, setting forth the then-held ethical position of the Society on the various new reproductive technologies. In 1987, the Congregation for the Doctrine of the Faith issued the Instruction on the Respect for Human Life and Its Origin and on the Dignity of Procreation. While both documents state that very similar moral criteria were used to derive ethical positions with respect to various reproductive procedures, the conclusions as to the ethical acceptability of the various procedures differ sharply in the two documents. The question can be raised about the procedure used by the Congregation of the Faith to derive its conclusions from the stated premises. Thus, while stating that "the individual integrally and adequately considered" is to be the basis of the moral judgment, the fact is that most conclusions are based on and referenced to past Catholic statements. While the difference in conclusion from similar premises may be troubling to society, it can be especially paralyzing to four groups: (1) those who face problems that might be solved by one or another of the new reproductive technologies; (2) those who are involved in applying them; (3) those who are responsible for institutional policies where such techniques may be applied; and (4) those who are in a position to influence public policy in a legislative or regulatory way. Because of the conflicting conclusions of the two documents, the present Ethics Committee (1986-87) of The American Fertility Society was convened and considered these guidelines in the light of the Instruction.(ABSTRACT TRUNCATED AT 250 WORDS) Legislation of Ukraine

Ukraine is one of a few countries in the world where appliance of majority of assisted reproductive technologies, especially surrogacy, is absolutely legal. In this sphere Ukrainian legislators have proven to be more progressive than the main part of their European colleagues.

Legal aspects of surrogacy in Ukraine are regulated by:

Article 123 of The Family code of Ukraine (as amended from December 22, 2006 No. 524-V) regulates affiliation of the child, born in case of assisted reproductive technologies (ART):

Item 1. If the wife is fertilized by artificial procreation techniques upon written consent of her husband, the latter is registered as the father of the child born by his wife.

Item 2. If an ovum conceived by the spouses (man and woman) is implanted to another woman, the spouses shall be the parents of the child.

Item 3. Whenever an ovum conceived by the husband with another woman is implanted to his wife, the child is considered to be affiliated to the spouses.

Article 48 of the Law of Ukraine “Basis of legislation of Ukraine about health care” (as amended from February 12, 2008) indicates conditions of artificial fertilization:

Artificial fertilization and embryo implantation are performed according to conditions and order, prescribed by the Ministry of Health Care of Ukraine, for medical grounds of women of age, which undergoes this procedure upon written consent of spouses, anonymity of donor and medical secrecy.

Order of child registration is regulated by the Decree of the Ministry of Justice of Ukraine No. 140/5 from November 18, 2003 “About amendments and additions to Rules of civil registration in Ukraine:

Item 2.2. In case of child birth by the woman who was implanted by fetus, conceived by the spouses, the child is registered upon the declaration of spouses, who gave their consent for implantation. In this case together with the document, confirming the fact of child birth, the woman has to provide notarized written consent for registration spouse as legal parents of the child. Thereby, there is a certain note in column “For notes”: “The citizen (surname, name, patronymic) is the mother of the child according to medical birth certificate of 103/î-95(z0266-95) form.”

Civil Code of Ukraine (as amended from January 21, 2010 No. 1822-VI) regulates who has the right to participate in assisted reproductive programme:

Article 281. Women or men of full age are entitled to have been cured with assisted reproductive technologies in accordance with their medical indications in order, prescribed by the law.

Order of the Ministry of Healthcare of Ukraine from December 23, 2008 No 771 “Approval of order manual of appliance of assisted reproductive technologies” establishes order of ART appliance.

Subparagraph 3 of item1. Certified medical institutions are entitled to perform artificial fertilization.

Subparagraph.4 of item 1. Patients are entitled to freely choose a medical institution for ART treatment.

Subparagraph 6 of item 1. ART are applied according to medical indications upon written free consent of patients and Statement of a patient/patients of ART appliance.

Subraragraph 7 of item. 1. Woman and/or man of full age upon their medical indications are entitled to apply to ART treatment according to article 281 of Civil Code of Ukraine.

Subparagraph 5.1. Donation of gametes is a procedure, during which, according to written voluntary consent, donors grant their germinal cells – gametes (sperm, oocytes), or embryos for use in infertility treatment by other persons.

Implantation of an embryo is conducted according to medical indications of a full-aged woman, who undergoes such procedure, provided written consent of the patients, ensuring of a donor’s anonymity and maintenance of medical secrecy.

Subparagraph 5.2. Donors of gametes can not undertake parental rights towards a future child.

Subparagraph 5.5. Oocyte donors can be:

·                     female acquaintances and relatives;

·                     anonymous voluntary donors;

·                     patients of ART programmes, who according to written voluntary consent give part of their oocytes to recipient.

Subparagraph 5.6. Requirements for oocyte donors:

·                     woman in age from 20 to 32;

·                     presence of a born healthy child;

·                     absence of negative phenotypic manifestations;

·                     satisfactory somatic health;

·                     absence of medical contra-indications for oocyte donation;

·                     absence of hereditary diseases;

·                     absence of harmful habits: drug addiction, alcoholism, toxic substances abuse.

Subparagraph 5.10. List of necessary documents for oocyte donation:

·                     agreement with the oocyte donor, voluntary written informed consent for participation in donation, controlled stimulation of ovulation and oocyte retrieval;

·                     statement of a written consent of husband.

Subparagraph 7.4. A healthy woman of full age, who gave birth to a healthy child upon her written free consent and absence of medical contra-indications, is entitled to perform surrogacy.

Subparagraph 7.10. If parents of a child born by a Surrogate are foreign citizens they shall inform the address of their residence before processing of documents and departure from country for patronage by specialists-pediatrics and for supervision.

Subparagraph 7.11. Registration of a child born through ART by means of surrogacy is conducted according to the order set by the current legislation of Ukraine at the presence of a certificate of genetic relationship of parents (mother or father) with a child.

It is often a devastating and life changing experience for a woman to discover that for one reason or another she cannot become pregnant and have children of her own. In some cases, such as those involving repeated unsuccessful attempts involving assisted reproductive technology (ART) or having a non-functional uterus, the remaining option (besides that of adoption) for these women and their partners is surrogacy. However, a major concern with surrogacy is the potential harm that may be inflicted upon the surrogate mother and the child. There are a number of ethical issues relevant to this topic. The ideals and values we hold concerning liberty and autonomy, have to be weighed against other values such as informed consent, welfare and exploitation. Surrogacy, when occuring in the context of ART, is also an issue that forces us to reassess many concepts such as parenthood, family structure and best interests, which until the recent surge in the popularity of surrogacy, we took for granted.

Public Policy in Other Countries

It is not possible to review all legislation and policy recommendations throughout the world, but two early initiatives are of particular interest. They come from countries that share a common law tradition with the United States, Australia (Victoria), and the United Kingdom.

AUSTRALIA (VICTORIA). The earliest comprehensive legislation on reproductive technologies was enacted in the State of Victoria, Australia in 1984. The Infertility (Medical Procedures) Act addressed embryo research by prohibiting research that might damage the embryo or make it unfit for implantation. This prohibition appeared to outlaw any IVF or embryo research that was not directed toward benefiting each individual embryo. In 1986 the review committee established by the act received a proposal for research on the microinjection of a single sperm into an egg. In their application the investigators suggested a novel approach for circumventing the prohibition on embryo research. They proposed to examine the egg after the sperm had penetrated it, but before the genetic contributions of the sperm and egg had fused at the stage known as syngamy. Arguing that fertilization was not completed until syngamy had occurred, researchers claimed that the law did not apply until the time of syngamy, thus giving them approximately twenty-two hours after sperm penetration for conducting their studies.

Since the review committee was uncertain as to whether the 1984 act allowed this interpretation, it recommended that the act be amended to clarify that research was permissible if it ended by the time of syngamy, even if the research destroyed the embryo’s potential for implantation. The act was amended according to this recommendation in 1987.

UNITED KINGDOM. The issue of the regulation of reproductive technologies and embryo research was particularly pressing in the United Kingdom because of the publicity given to the birth of Louise Brown in England in 1978. The Warnock Committee was appointed to study the matter, and its 1984 report recommended national regulation of assisted reproduction. It also recommended that research on embryos resulting from IVF be permitted up to the fourteenth day after fertilization, under the jurisdiction of a licensing body. Based on the Warnock Report, the Human Fertilisation and Embryology Act (HFE Act) of 1990 commissioned a standing body, the Human Fertilisation and Embryology Authority (HFEA), to develop standards for licensing clinical facilities and research protocols, and mechanisms for auditing and oversight. Initially research protocols were restricted to the study of infertility, the causes of congenital diseases, and the detection of gene or chromosome abnormalities in embryos. Since its establishment in 1991 the HFEA has addressed new types of procedures and research through public consultation processes as well as the advice of experts. If a matter was beyond the scope of authority of the HFEA, it was referred to Parliament. In January 2001 Parliament extended the HFE Act to permit embryo research directed at increasing knowledge about treatments for serious diseases. This provision would allow the HFEA to issue licenses for research on embryonic stem cells, including stem cells derived from blastocysts resulting from somatic cell nuclear replacement (SCNR). However, the Pro-Life Alliance brought a challenge to this provision, arguing that the HFE Act applied only to embryos resulting from the fertilization of eggs by sperm. Despite a Court of Appeal ruling against the Pro-Life Alliance, in June 2002 the House of Lords agreed to hear a final appeal of the case. In March 2003 the House of Lords ruled that the HFE Act applied to all types of embryos, and hence the HFEA had authority over research with embryos created by nuclear transfer as well as embryos resulting from fertilization by sperm.

The U.S. Human Embryo Research Panel

After nearly twenty years of moratorium on federal funding of research involving IVF, the U.S. Congress in 1993 revoked the requirement of EAB review. Through the National Institutes of Health (NIH) Revitalization Act of 1993, Congress explicitly permitted the NIH to fund research on assisted reproductive technologies with the goal of improving the understanding and treatment of infertility. Since research on IVF includes the study of IVFfertilized embryos, the research authorized by Congress

included research involving human embryos. Recognizing the controversial issues raised by this research, NIH decided to conduct an examination of ethical issues before funding any research proposals. Consequently, the Director of NIH appointed the Human Embryo Research Panel (HERP) to provide advice and recommendations.

In developing its position and recommendations, the panel focused on two distinct sources of guidance: viewpoints on the moral status of the early human embryo, and ethical standards governing research involving human subjects. It considered a wide range of possible views on the moral status of the embryo, from the position that full human personhood is attained at fertilization, to the argument that personhood requires self-consciousness and is not attained until after birth. In the end, all nineteen members of the panel agreed to the following statement: Although the preimplantation embryo warrants serious moral consideration as a developing form of human life, it does not have the same moral status as an infant or child. (Human Embryo Research Panel, p. x)

This conclusion implied that the preimplantation embryo is not a full human subject and thus is not a fully protectable human being. As a result, some research that might be destructive to the embryo could be acceptable for federal funding. But the panel also asserted that the human embryo “warrants serious moral consideration,” requiring that it be treated differently from mere human cells or animal embryos. The panel proposed restrictions on embryo research that would express such moral consideration, for example, that human embryos be used in research only as a last resort, that the number of embryos used be carefully limited, and that embryos not be allowed to develop longer than required by a specific research protocol, and in no case longer than fourteen days of development. In applying the ethical standards governing researchinvolving human subjects, panel members invoked the criteria used by Institutional Review Boards (IRBs) in approving research protocols. Donors of eggs, sperm, or embryos were to be informed of the specific goals, procedures, and risks of research projects. Risks to donors, particularly egg donors, were to be minimized. Eggs for research could be donated only by women who were undergoing diagnostic or therapeutic procedures where egg retrieval would present little additional risk. The most controversial issue facing the panel was the question of whether human oocytes could be fertilized solely for research purposes. The panel decided to allow such fertilization only under very special circumstances, most particularly, if certain research by its very nature could not otherwise be conducted. For example, research on the laboratory maturation of human oocytes, which could eliminate the need for egg donors as well as infertile women to be subjected to high levels of hormonal stimulation, requires study as to whether such oocytes can be successfully fertilized.

The Aftermath in the United States and Beyond

Despite President Clinton’s directive that NIH not fund research involving the creation of embryos, most types of research on IVF and human embryos were still eligible for federal funding. However, in its next appropriations bill Congress reversed its previous stance and prohibited NIH from funding any research that might involve damaging or destroying human embryos. In 2003 this prohibition was still in effect. During the 1990s scientific advances raised new questions regarding research with human embryos. In 1998 the first embryonic stem cell lines were developed from the inner cell mass of human blastocysts, and at the same time, similar stem cell lines were produced from the germ cell tissue of aborted fetuses. Deriving stem cells from blastocysts was clearly prohibited for federal funding. However, the derivation of stem cells from the tissue of aborted fetuses was eligible for federal funding under previous legislation (U.S. Public Law 103–43, Manier). Another discovery was the successful cloning of a variety of nonhuman animals from adult cells, beginning with the cloning of the sheep Dolly in 1997. Research on human cloning arguably involves research on human embryos. These embryos are produced by transfer of somatic cell nuclei into enucleated oocytes, rather than through fertilization of eggs by sperm, yet their development and potential appear to be similar to those of fertilized eggs. Thus cloning research raises similar ethical questions.

The day after the announcement of the cloning of Dolly, President Clinton instructed the National Bioethics Advisory Commission (NBAC) to undertake a thorough review of the technology and to report within ninety days. Given this short deadline, it is understandable that NBAC had to focus on issues specific to the cloning process. In particular, NBAC decided to “not revisit … the issues surrounding embryo research,” since the topic had “recently received careful attention by a National Institutes of Health panel, the Administration, and Congress” (Shapiro). In contrast, when the President’s Council on Bioethics appointed by President George W. Bush issued its report on cloning in 2002, it called for a broader debate on the entire topic of human embryo research. The ten-member majority of the council wanted cloning discussed “in the proper context of embryo research in general and not just that of cloning” (p. 133). Both the majority and minority reports call attention to the fact that human embryo research of all types remains essentially unregulated in the private sector, with the minority noting that “it seems inappropriate to halt promising embryo research in one arena (cloned embryos) while it proceeds essentially unregulated in others” (p. 143). In the United States, public policy at the national level is focused on what types of research are eligible for public funding. There is essentially no regulation of research in the private sector. This situation contrasts sharply with that of most other countries, where laws apply to all research, regardless of the funding source. As of April 2003, Germany, Austria, and Ireland prohibit embryo research unless intended to benefit the individual embryo subject. Germany does allow some importation of established stem cell lines for research. France prohibits any embryo research that would harm the embryo. However, in January 2002 the French assembly passed a bill that, if enacted, would permit research using surplus embryos originally created for reproductive purposes. Sweden allows research on surplus embryos up to day fourteen, including research on deriving stem cell lines. Creating IVF embryos solely for research is prohibited, but creating embryos through nuclear transfer is not mentioned in Swedish law and thus has an uncertain legal status. The United Kingdom arguably has the most permissive policies on embryo research within the European Union. It explicitly sanctions the granting of licenses to create embryos, including cloned embryos, for specific research projects. Because of the diverse views and policies of its member states, the European Union has taken an intermediate position, providing support for research on surplus embryos in countries where that is permitted, but discouraging the creation of embryos for research. In April 2003 the European parliament voted for a ban on cloning or otherwise creating embryos for stem cell research. However, this decision becomes law only if approved by all fifteen member states of the European Union.

In May 2002 the Assisted Human Reproduction Act was introduced into the Canadian Parliament. The act prohibits the creation of a human clone for any purpose. It also prohibits the creation of an IVF embryo for research purposes with the exception of “improving or providing instruction in assisted reproduction procedures.” In April 2003 the bill was in its third reading in the House of Commons.

In some non-Western countries, embryo research is proceeding with few restrictions. Chinese laboratories are forging ahead with cloning research to develop stem cells.

Though Chinese scientists have been slow to publish their work, they may well be ahead of their Western counterparts (Leggett and Regalado). India has developed a number of internationally recognized stem cell lines, and scientists are developing additional lines. Dr. Firuza Parikh, Director of Reliance Life Sciences in Bombay, links their success to the absence of cultural and political opposition to embryo research (Lakshmi).

The Moral Status of the Early Embryo

In contrast to China and India, most Western countries are deeply divided over ethical issues related to embryo research. Does the embryo merit full protectability from the moment of fertilization, or does it gradually attain full protectability as it moves through a series of developmental stages? If fertilization is not the point of greatest moral significance, is there some later developmental marker beyond which embryo research ought not be conducted?

FERTILIZATION. Fertilization of egg by sperm marks the initiation of a new and unique genotype, that of a human being distinct from either of its progenitors. The zygote or fertilized egg not only contains the plan or blueprint for a new human being, but it has the potential within itself to develop into that human being. Based on these facts, many would argue that the zygote is a full human being from the moment it comes into existence. This view would preclude any research that might be harmful or destructive to an embryo, unless intended to be therapeutic for that embryo or to improve its chances for implantation. This position has received able defense in contemporary terms by opponents of embryo research (McCarthy and Moraczewski).

It is possible to hold this position while acknowledging that fertilization is a process rather than an instantaneous event, and hence that the new human life begins only when the process of fertilization is completed. At least two possible candidates marking the completion of fertilization have been suggested. The first is the time of syngamy, when the chromosomes from the male and female gametes unite to form the genotype of the embryo. Since syngamy is not completed until about twenty-four hours after the sperm penetrates the egg, this view would allow some study of the early development of the embryo.

A second proposal maintains that the embryo does not begin its life as a new human being until the regulation of its development switches from oocyte genes to embryonic genes. In 1988 Peter Braude and colleagues showed that this occurs at the six- to eight-cell stage, approximately two days after penetration of egg by sperm. Arguably the embryo begins its own life distinct from that of the oocyte at the time that its own internal regulatory mechanism begins to function. This interpretation would allow investigation of questions such as why a large proportion of embryos are arrested in their development during the earliest cell divisions (Van Blerkom).

Such variant views of the process of fertilization do not counter the claim that the human being begins its life at fertilization. Rather, they provide differing interpretations as to what constitutes fertilization, under the assumption that the formation or activation of the unique genotype of the new organism is the crucial event.

IMPLANTATION. Implantation is the process by which the embryo imbeds itself in the uterine wall and begins to take nourishment from the woman, thus marking the beginning of pregnancy. It is at this time that the U.S. federal regulations define the product of conception as a fetus, and the research regulations begin to apply (45 CFR 46.201–207). From a moral point of view, some have argued that the IVF embryo lacks the potential to develop into a human being as long as it is simply maintained in culture in the laboratory. Only those embryos that are transferred to women and that implant successfully acquire the potential for development. This type of argument has been utilized by politicians like U.S. Senator Orrin Hatch, who support some forms of embryo research while they take pro-life positions in relation to abortion. In his testimony to a Congressional subcommittee in July 2001, Hatch stated, “I believe that a human’s life begins in the womb, not in a petri dish or refrigerator.” This view can be linked to a philosophic distinction between possible persons, entities that could possibly develop into persons if certain actions were taken with respect to them, and potential persons, entities that will develop into persons in the normal course of events unless something happens or is done to interrupt that development. The embryo in the laboratory or freezer is a possible person that might develop into a person if action were taken to transfer it to a uterus. The already-implanted embryo or fetus is a potential person that, under normal circumstances, will continue to develop into a person. Proponents of this distinction argue that while we may have a moral obligation not to interfere with the development of a potential person, we do not have a similar obligation to bring every possible person into existence (Singer and Dawson; Tauer 1997a).

PRIMITIVE STREAK. In the late twentieth century, scholars were faced with biological data about early embryonic development that led to new perspectives on the ontological and moral status of the early embryo. Particularly within the Catholic tradition, writers such as Norman Ford, John Mahoney, Richard McCormick, and Karl Rahner developed arguments questioning whether the zygote or early embryo is a full human being or human person. Their arguments appealed to the following points:

1. Twinning of the embryo is possible until implantation, and at least through the morula stage, several embryos may aggregate (recombine) to form one embryo. Thus the embryo lacks developmental individuation at this early stage. Philosophic arguments that rely on the continuity of personal identity and religious arguments based on ensoulment must deal with the phenomena of twinning and recombination, which occur naturally and can also be induced scientifically.

2. Until the blastocyst stage at approximately five days after fertilization, the cells of the embryo are totipotent or completely undifferentiated. Each cell has the capacity to differentiate into any of the cell or tissue types of the fetus, or more likely, not to become part of the fetus at all but rather to form placental and other extra-embryonic tissues. The early embryo is a collection of undifferentiated cells rather than an organized individual.

3. At approximately fourteen days after fertilization, the primitive streak appears, the groove along the midline of the embryonic disk that establishes in the embryo its cranio-caudal (head-to-tail) and left-right axes. The primitive streak marks the beginning of the differentiation of cells into the various tissues and organs of the human body, and thus initiates the development of the embryo proper (the cells that will become the fetus) as an organized, unified entity. The primitive streak is also the precursor of the neural system.

4. In normal procreation, during the period between fertilization and the completion of implantation a large proportion of embryos (generally estimated at over 50%) are discarded naturally. Karl Rahner argues that it is implausible that such a large number of human beings could come into existence and disappear without anyone’s knowing about it. Others have argued that given nature’s prodigality with human embryos, it ought to be morally acceptable to allow similar types of embryonic losses in research as part of the effort to achieve healthy pregnancies.

These sorts of arguments have been utilized in public policy debates since 1978, and the appearance of the primitive streak has come to be accepted internationally as a marker carrying moral significance. The prohibition of embryo research after fourteen days of development is almost universally accepted. Opponents of embryo research have responded to claims that the early embryo is not yet a full human being. These commentators find arguments based on twinning and recombination, totipotency of cells, and embryo loss to be unpersuasive (Ashley; Ashley and Moraczewski; Mirkes). In its 2002 report on cloning, the majority members of the U.S. President’s Council on Bioethics questioned the significance of the primitive streak as a moral marker, stating: Because the embryo’s human and individual genetic identity is present from the start, nothing that happens later … —at fourteen days or any other time—is responsible for suddenly conferring a novel human individuality or identity. (p. 97)

GASTRULATION AND NEURULATION. Some persons regard the initiation of the neural system or the presence of brain activity to be the most significant marker for the beginning of the life of a human being. This view is based on the belief that the brain is the essential organ underlying our specifically human capacities. It also represents an effort to identify a criterion at the beginning of human life that is analogous to the criterion of whole-brain death marking the end of life. For those who regard the presence of sentience as a necessary condition for personhood, the neural system is significant since sentience is impossible in the absence of any neural structures.

While there is debate as to the stage at which brain activity first occurs, it is certain that there is no brain activity before fourteen days of gestational age. The emergence of the primitive streak marks the very beginning of the development of the nervous system. If the presence of neural structures is the significant criterion for the beginning of a human life, then it might be permissible to extend embryo research slightly beyond fourteen days of development. Several possible cut-off points have been suggested. By the completion of gastrulation at about seventeen days, the three germ layers of the embryo are in place, with cells of each layer committed to forming tissues and organs of one of three types. Subsequent neural development leads to the  beginning of closure of the neural tube around twenty-one days, with the primitive nervous system in place by the completion of neurulation around twenty-eight days.

However, given the widespread consensus that fourteen days of gestational age is a morally defensible boundary for embryo research, there has been limited discussion of extending research to a later embryonic stage.

Ethical Implications for the Life Sciences: A Cautionary Tale

What are the bioethical implications of these various conceptions of human nature? First, a cautionary note. Practical ethics reflects on a host of considerations in practical contexts and cannot simply deduce specific moral conclusions from general ethical principles, let alone from some general conception of human nature. Thus, the relation between the various conceptions of human nature and any specific bioethical position is unlikely to be one of logical entailment. This does not mean, however, that concepts of human nature have no relevance to bioethical issues. They may serve as starting points for bioethical analysis, raise suspicions about certain bioethical claims, or even rule out certain bioethical positions. In general, certain conceptions of human nature may be said to cohere, or provide a better fit, with certain bioethical stances than with others. The dominant pre-Darwinian conceptions of human nature view physical nature, including the human body, as the realm of the material, the immanent, and the profane, and identify God with the spiritual, the transcendent, and the sacred. It is only because human beings are endowed with a soul that they are regarded as capable of partaking in the sacred, and their mission is to transcend their bodies and realize their spiritual nature. Insofar as they are part of God’s creation, nonhuman animals are sometimes assigned a degree of moral worth, but the view that they lack souls typically rationalizes the claim that nonhuman animals are merely resources to serve human purposes. Saint Francis of Assisi notwithstanding, the dominant view of the Judeo- Christian tradition is that God created nonhuman animals and, indeed, all of nonhuman nature, primarily for the use of human beings. This sharp bifurcation between human and nonhuman nature not only permits but even legitimates the human subjugation and exploitation of all nonhuman nature, and may therefore contribute to the contemporary ecological crisis.

Within this ontology, the human body occupies a unique and somewhat ambiguous moral status. Although material, and therefore a source of temptation, the body is nevertheless sacrosanct because it is indispensable to human life. God is thought to have a divine plan for humanity, and any attempt to subvert this plan by tinkering with the human body is regarded as at least prima facie wrong.

When applied to humans as opposed to nonhuman animals, therefore, reproductive technology, genetic engineering, and euthanasia are viewed with suspicion, if not censure; and brain death may not be considered sufficient reason to switch off a life-support system, depending on when the soul is believed to leave the body. If, for example, the soul is thought to remain in the body until the last breath of life, then euthanasia can never be justified: Even the suffering and dying body must be revered as the house of the soul. Finally, because humans are morally distinguished by the possession of a soul, abortion is condemned at whatever point the fetus is believed to acquire a soul. It is interesting to note that the Catholic Church has not always held that fetal ensoulment occurs at the moment of conception: Saint Thomas Aquinas, for instance, argued as an Aristotelian that the fetus did not have a soul until it assumed human form, which he thought occurred after three months’ gestation for the male fetus and six months’ for the female. In contrast with the pre-Darwinian dichotomies between human and nature, spiritual and material, sacred and profane, post-Darwinian conceptions of human nature posit an evolutionary continuity between human and nonhuman animals. This continuity is sometimes used as a basis for moral challenges to the human exploitation and domination of animals, especially animals that are close to human beings in evolutionary terms. It is precisely those nonhuman animals most like humans, however, that are most useful for many purposes, such as medical experiments and organ transplants; in consequence, some philosophers have sought to undercut moral challenges to the human exploitation of nonhuman animals by arguing that beings lower on the evolutionary scale may be sacrificed for the good of higher species. Opposing this position is a growing minority in the bioethics community that argues that such a position is an example of unwarranted human chauvinism or speciesism, a term invoked to suggest parallels with racism and sexism. Although post-Darwinian assumptions of an evolutionary continuity between humans and nonanimals may be used to challenge the view that animals are simply a resource for human use, they have also been used to justify radical interventions in human life processes. If it is legitimate to experiment on nonhuman animals, for instance, it may be equally legitimate to experiment on human beings. If Homo sapiens is the accidental outcome of natural selection, if there is no inherent purpose for which we are created, then there is no a priori reason to assume that further modifications in human biological processes should not be made via reproductive technologies or even genetic engineering. Since the human nervous system is a defining component of human life, the fetus at an early stage of brain development is likely to have a different moral status than it does once the brain has developed. Certainly, the post-Darwinian conception of human nature would generally assume that brain dead means dead.

These conclusions reflect the absence of the concept of a soul in post-Darwinian views of human nature, since it was the soul that, in earlier conceptions, provided the philosophical grounding for human dignity. Unless an adequate substitute for the concept of the soul can be found, post-Darwinian conceptions of human nature may permit the drastic manipulation of human beings. Behavior regarded as undesirable may be treated either as a biological abnormality or as a failure of social conditioning. Biological determinists may regard alcoholism, addictive gambling, violent criminal behavior, schizophrenia, depression, and even homosexuality as candidates for treatment with a variety of biological techniques: psychosurgery, shock therapy, hormonal therapy, psychopharmacological interventions, and perhaps, in the future, even genetic manipulation. Behaviorists, of course, emphasize the use of various conditioning techniques to modify human behavior, raising the prospect of a Clockwork Orange world. Skinner, in fact, wrote a utopian novel, Walden Two (1948), in which behavioral managers conditioned people from birth to make choices in accord with the goals and institutions of that society. Both biological and behavioral interventions often work toward the same goal— direct control of human behavior. But who will control the controllers, and how far will such control be allowed to extend? There are already biological determinists who advocate the use of genetic manipulation to raise IQ or to alter certain undesirable tendencies in the human species, perhaps to create a Superman. Others would clone the embryo and store it for future use, perhaps in case of some failure of the original stock. Brave New World may be just around the corner unless we can reclaim the concept of human dignity. Social and historical conceptions of human nature offer a secular basis for doing so. Although people who accept a social and historical conception of human nature may still utilize some concept of naturalness in describing various human activities, such as conceiving or giving birth, they recognize that what is taken to be natural or unnatural changes historically and culturally, so that ethical decisions cannot be grounded in home unchangeable concept of human nature. However, this does not prevent us from ethically evaluating various attempts to manipulate and control human nature. Indeed, those who accept social and historical conceptions of human nature are likely to urge caution in the use of biological interventions and conditioning techniques for the purposes of altering human behavior. They will be suspicious of all treatment and research modalities that fail to respect human agency, reflective intelligence, and decision-making capabilities, since it is precisely these transhistorical capacities that make possible the continuous transformation of our historical natures. In short, social and historical conceptions of human nature will tend to reaffirm the concept of human dignity. In the sphere of medicine, for instance, they are likely to insist on the dignity of medical subjects and emphasize informed consent and coparticipation in physician-patient relationships. The recognition that human beings individuate themselves within and through social processes may also have implications for the abortion controversy; at the very least, it suggests that women and fetuses cannot have the same moral status. Moreover, social and historical conceptions of human nature emphasize that consideration of bioethical problems must be sensitive to concrete social and political contexts; in a society with an expressed commitment to human equality, for example, questions like procreative technology or contract parenting must be evaluated with special reference to their implications for people of different classes, genders, abilities, races, and ethnicities. Finally, social and historical conceptions regard human beings as transhistorically creative, productive, social, and capable of reforming their habits through reflective intelligence; and people who accept these conceptions are likely to valorize those capacities and seek to develop social institutions— including healthcare, psychiatric, and research institutions— through which they would be enhanced. The open-ended nature of these last implications serves as a reminder that ethical conclusions are not strictly entailed by any general conception of human nature, especially by social and historical conceptions. In addressing particular bioethical problems, therefore, the values implicit in these conceptions must be supplemented by explicitly ethical criteria, such as historically specific understandings of justice, freedom, and human well-being.

Research on Aborted, Life Embryos and Fetuses

There are major conceptual difculties involved in describing a previously implanted entity that is expelled or removed alive from a pregnant woman’s body (or removed alive from attachment to an articial placenta). One candidate term is abortus; another is fetus ex utero or embryo or fetus outside the uterus. Adjectives applied to such entities include previable or nonviable and viable. A viable fetus outside the uterus is in fact a newborn infant, albeit one that may be seriously premature. In addition the notion of viability is elastic, sometimes seeming to mean the gestational age, weight, or length at which the smallest known infant has survived, at other times seeming to mean the stage at which a stipulated percentage of infants survive, given the assistance of technological means of life support.

Three circumstances can be envisioned in which the question of research on formerly implanted, living embryos or fetuses could arise. First, the surgical removal of an ectopic pregnancy could provide a still-living embryo or fetus. Second, a spontaneous miscarriage could result in the delivery of a live embryo or fetus. Third, an already implanted embryo or fetus could be aborted by means that make it either possible or likely that an intact, living embryo or fetus will result from the abortion procedure. There is no clear consensus on the ethical justiability of research on living human embryos or fetuses outside the uterus. In the United Kingdom, two ofcial reports reect a clear trend in a more conservative direction. In 1972 the Peel Committee afrmed the scientic value of research on clearly previable fetuses outside the uterus and permitted many kinds of research on such fetuses (United Kingdom, 1972). However the Polkinghorne Committee report of 1989 expressly rejected the position of the Peel Committee, arguing that the only morally relevant distinction was between living and dead fetuses, not the distinction between previable and viable fetuses (Polkinghorne). In the United States the U.S. Commission for the Protection of Human Subjects allowed no signicant procedural changes in the abortion procedure solely for research purposes and restricted what could be done with the live, delivered embryo or fetus to intrusions that would not alter the duration of its life. Recommendation 1100 by the Parliamentary Assembly of the Council of Europe (1989) also discussed “the use of human embryos and fetuses in scientic research.” Its recommendation clearly reflected the ambivalence of ethical opinion on research involving live embryos or fetuses outside the uterus. After stating that “Experiments on living embryos or foetuses, whether viable or not, shall be prohibited,” the recommendation continued as follows: “None the less, where a state authorises certain experiments on nonviable foetuses or embryos only, these experiments may be undertaken in accordance with the terms of this recommendation and subject to prior authorisation from the health or scientific authorities or, where applicable, the national multidisciplinary body” (Council of Europe, p. 6).

Reproductive technology encompasses a range of techniques used to overcome infertility, increase fertility, influence or choose the genetic characteristics of offspring, or alter the characteristics of a population. Each type of reproductive technology brings with it a range of ethical issues. With the accelerated pace of progress in modern medical technology, these issues have been brought squarely into the public arena, where they continue to provoke controversies involving the boundaries of government control, private choice, religious belief, and parental wishes.

References:
A. Main:

1.     The Cambridge Textbook of Bioethics / Edited by Peter A. Singer and A. M. Viens. - Cambridge University Press, The Edinburgh Building, Cambridge CB2 8RU, UK, 2008. – 526p.

2.     Encyclopedia of Bioethics, Third Edition in 5 vols / Stephen G. Post, Editor in Chief. - Macmillan Reference USA, 2004. – 3300p.

B - Additional:

1.     Bioethics and Biosafety/ M K Sateesh. - I K International Pvt Ltd, 2008. - 820 p

2.     Bioethics and public health law / David Orentlicher, Mary Anne Bobinski, Mark A. Hall. -Aspen Publishers, 15 ôåâð. 2008 – 687p.

3.     Professionalism in Health Care: A Primer for Career Success / Sherry Makely, Vanessa J. Austin, Quay Kester. - Pearson, 2012 – 238p.

4.     Stevens, M. L. Bioethics in America: Origins and Cultural Politics. Baltimore, Md.: Johns Hopkins University Press, 2000.