Ethical and Legal Problems of Transplantation and

Transfusion. Surrogacy. Ethical problems of genetic engineering

technologies.

Organ donation

• 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.

Deontological issues• Certain groups oppose

organ donation on religious grounds, but most 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.

The use of cloning to produce organs

• 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.

• While the benefit of such a cloned organ would be a zero-percent chance of transplant rejection, the ethical issues involved with creating and killing a clone may outweigh these benefits.

Ethics In Xenotransplantation• Transplantation represents a highly successful means

of treating a variety of human illnesses. • 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.

• There is the need to minimize the likelihood of the introduction of new infectious agents into the human population via the transplant.

The Health 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.

Acceptability of the risk

• 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.

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.

Principle of heart transplantation

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.

Possibility of patenting living beings

• 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.

Donation after death

• 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.

• 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).

Donation rates and legislation

• 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".

Deontological issues

• 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.

The use of cloning to produce organs

• 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.

• While the benefit of such a cloned organ would be a zero-percent chance 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.

Ethical dilemmas in blood transfusion in Jehovah’s Witnesses

• It is common knowledge that JWs do not accept blood transfusion, even if life is threatened. This refutation is supported in the biblical texts Genesis and Leviticus, which recommend the faithful to abstain from meat for considering that it has a soul, and that the assimilation of blood in the organism by the mouth or the veins would violate Godís law.

• The JWs affirm that the human beingís soul lies in the blood and, as such, it cannot be passed on to another person. If that happened, the adept would disobey the commandment of loving God with all his or her soul.

Alternative hemotherapies

• The ethical dilemmas involving healthcare to JWs can be solved by means of alternative hemotherapies or by transferring such a person to a CLH (Commissions for Hospital Relations) in Brasil.

• If any of these procedures are impossible, there is an apparent collision between the fundamental right to life and the fundamental right to freedom of conscience and belief, which will force the professional to decide in favor of the prevalence of the personís dignity as the limit and base for other rights.

The ethics of blood management

• Blood transfusion practices have evolved empirically, with few or no research data supporting them. In the past several decades, fuelled by fears of infection and reports of mistakes, patients have increasingly demanded their rights to choice, both in the components given to them as well as to refuse to receive these therapies based on religious convictions.

• In parallel, episodic blood unavailability and growing awareness of the need to apply evidence-based methods have caused physicians to begin re-evaluating traditional practices and to focus on minimizing or eliminating unnecessary transfusions while learning and applying methods that permit reuse of the patient's autologous blood or rely on pharmacologic agents.

• Human gene transfer research (HGTR) involves the deliberate transfer of genetic material (naturally-occurring, genetically-modified, or synthetic DNA or RNA) into human subjects.

• Clinical success has come more slowly than was first 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 specific cancers.

Human gene transfer research

• 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.

Clinical Successes and Setbacks

• Gelsinger was affected by ornithine transcarbamylase (OTC) deficiency. Patients with OTC deficiency 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.

Ornithine transcarbamylase (OTC) deficiency

• 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.

Public Oversight of Human Gene Transfer Research

• 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.

• 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 justified.

Early concerns about “genetic engineering

• 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 conflicts of interest. These issues become increasingly important as HGTR moves toward new applications and methods.

Ethical issues in human gene transfer research

• 1. Concern for the well-being of genetically-modified animals should be guaranteed;

• 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.

Fundamental ethical conditions which must be respected

• Almost 20 years since the first gene-transfer trial was carried out in humans, the field has made significant advances towards clinical application.

• Nevertheless, it continues to face numerous unresolved ethical challenges — among them are the question of when to initiate human testing, the acceptability of germline modification and whether the technique should be applied to the enhancement of traits.

• .

History of gene-transfer

1) germ-line gene transfer offers a true cure, and not simply palliative or symptomatic treatment; 2) germ-line gene transfer may be the only effective way of addressing some genetic diseases;3) by preventing the transmission of disease genes, the expense and risk of somatic cell transfer for multiple generations is avoided; 4) medicine should respond to the reproductive health needs of prospective parents at risk for transmitting serious genetic diseases; 5) the scientific community has a right to free inquiry, within the bounds of acceptable human research.

Arguments in Favor of Gene Transfer Research

1) germ-line gene transfer research would involve too much scientific uncertainty and clinical risks, and the long term effects of such research are unknown; 2) such gene transfer research would open the door to attempts at altering human traits not associated with disease, which could exacerbate problems of social discrimination; 3) as germ-line gene transfer involves research on early embryos and effects their offspring, such research essentially creates generations of unconsenting research subjects; 4) gene transfer is very expensive, and would never be costeffective enough to merit high social priority; and 5) germ-line gene transfer would violate the rights of subsequent generations to inherit a genetic endowment that has not been intentionally modified

Arguments Against Gene Transfer Research

• Other commentators have pointed to the difficulty of following up with patients in long-term clinical research (III. Ledley 1993).

• Some are troubled that many gene transfer candidates are children too young to understand the ramifications of gene transfer research.

The difficulty of following up with patients in long-term clinical research

• Others have pointed to potential conflict of interest problems—pitting an individual's reproductive liberties and privacy interests, on the one hand.

• Against the interests of insurance companies, or society on the other—not to bear the financial burden of caring for a child with serious genetic defect. Issues of justice and resource allocation have also been raised: in a time of strain on our health care system, can we afford such expensive research?

Potential conflict of interest problems

• Progress in molecular biology has enabled us to better understand human genetic disease, and has helped enhance the quality of life. This has been possible with technical developments to detect genetic disease presymptomatically.

• Presymptomatic testing would not yield information about the carrier status of an individual but also about other family members. Such information may lead to unreasonable beliefs and could alter social relationships.

Human genome project

• The sequencing of the entire genome has already had a profound impact on the wider spectrum of clinical research, as it opens a new horizons for not only treatment of diseases but looking at the most fundamental causes of diseases. Already the genes for many diseases including for example, various cancers, Alzheimer’s disease, and polycystic kidney disease, have been identified.

• Genomic sequencing allows rapid and accurate diagnosis for individuals. Initially the sequencing of human genome has led to a shift towards preventive medicine rather than curative, because further research is needed to develop therapies.

Medical Prospects

• One of the ideals of science is freedom for self-understanding. The influence of Human Genome Project on human self-understanding has been heralded as revolutionary. The sequencing of the genome will provide new clues on how we evolved.

• It would help us to understand what it means to be a human from different historical perspectives of bioarchealogy, anthropology, evolution, and human migration.

Scientific Prospects

• Genetically-Modified Organisms (GMOs) are already a hot topic in agriculture and livestock breeding. GMOs are organisms with genes modified for one or the other trait. We now have plants that are insect resistant, disease resistant, drought and cold resistant.

• We have farm animals that are healthier, more productive and disease resistant. Other plants and animals that are genetically modified include ones that incorporate vaccines in an edible form, or deliver hormones.

Agricultural Prospects

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.

The Moral Status of the Early Embryo

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.

Fertilization of egg

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

Six- to eight-cell stage

• 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.

Moral status

Among the many applications of the new reproductive technologies (including artificial insemination by donor—AID, in vitro fertilization—IVF, embryo transfer, and embryofreezing) surrogate motherhood has such far-reaching consequences that it raises a multitude of ethical and legal questions.

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.

Surrogate motherhood

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.

Motivation

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?

The degree of stress

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.

Ethical considerations of the new reproductive technologies

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.

Catholic statements

• 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.

Assisted reproductive technologies in Ukraine

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.

The Family code of Ukraine

• 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.

Basis of legislation of Ukraine about health care

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/о-95(z0266-95) form.”

Rules of civil registration in Ukraine

• 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.

Civil Code of Ukraine

• 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.

Approval of order manual of appliance of assisted reproductive technologies

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.

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

Approval of order manual of appliance of assisted reproductive technologies

• 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.

Oocyte donors

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.

Requirements for oocyte donors

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.

List of necessary documents for oocyte donation

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.

A child born by a Surrogate are foreign citizens