Ethical Issues in Genetic Screening and Testing, Gene Therapy, and Scientific Conduct
Sunday, July 27, 2008

n Bioethics, as an interdisciplinary field involving clinicians, lawyers, philosophers, theologians, and other humanists, was born in the early 1970s amid technological advances in medicine and growing respect for persons in society.

n Respect for individuals' rights of self-determination came into conflict with some social values and with the medical profession's previously largely unchallenged paternalistic concern for patient welfare, as the medical profession and individual professionals—not patients—defined that well-being. In 1970, for example, Paul Ramsey published his patient-centered medical ethics treatise, The Patient as Person.

n The field of bioethics emerged in the wake of landmark legal cases, such as Karen Quinlan's parents' bid to remove her from her respirator (30) or the paralyzed Mr. Canterbury's suit claiming that he had not been fully informed of the risks of his surgery.

n Bioethics evolved to provide a legal and ethical framework within which to resolve conflicts between physician and patient and between social consensus and individual values.

n The individual patient's values came to trump the traditional values of medicine, and the privacy both of individuals and of the physician–patient relationship erected a boundary against the intrusion of society's interests.

n Developments in theoretical ethics, specifically feminist ethics, support bioethics' new focus.

n Feminist philosophers suggest that in order to provide just answers to ethical questions, ethics must pay increased attention to their social context and political dynamics, the balance of power, and the history of oppression

n Historically, the physician–patient relationship has been the primary focus of bioethics, but it is clear that the crisis of funding health care is emerging as the fundamental challenge of the 1990s.

n Social policies and institutional contexts are now considered in association with, or occasionally instead of, the physician or health-care provider and patient relationship.

n So it was in this intellectual and social climate that the Human Genome Project (HGP) was initiated in 1990 to support and coordinate efforts of the National Institutes of Health (NIH) and the Department of Energy (DOE) to produce a complete genetic map of all human genes.

n The Ethical, Legal, and Social Implications (ELSI) Program of the HGP was charged with anticipating the social consequences of the acquisition of this knowledge and developing policies to guide its use.

n With 5% of the genome budget supporting ELSI activities, the ELSI Program is both the first federally supported extramural research initiative in ethical issues and the largest source of public funds for bioethics

n However, the bioethical issues of the HGP are not unique. The topics of informed consent, justice, gender justice, privacy, confidentiality, discrimination, genetic discrimination, health-care needs, or private health insurance versus a national health service are familiar ones.

n Even those challenges to the premises of a private health insurance system presented by genetic screening are, for example, also presented by other predictive medical tests—for example, cholesterol screening for hypertension.

The code of conduct proposed by Harper (13) also points to some of the difficulties that will be faced as genetic technologies developed in the research context are applied in the clinical diagnostic or therapeutic context. The code states the following:

n 1. Family members "at risk" for a genetic disorder should not be sampled unless strictly necessary for the research, especially in late-onset or variable disorders. This statement applies particularly to children. Proposals should clearly justify the testing of unaffected subjects and should include a clear plan stating what will be done in the event that a genotypic abnormality is detected.

n 2. When consent is given for sampling by an unaffected person to assist a family member in determining his/her risk status, it should be made clear that the risk status of the unaffected person will not be disclosed and that the result of the test should not be expected nor will it be sent to his/her doctor nor placed in his/her medical record unless specifically requested.

n 3. If the sample is to be stored and used for future tests, new consent should be obtained if the implications for the person at risk resulting from the new research are likely to be considerably different; for example, if direct mutations analysis, rather than a general linkage analysis, is possible.

n 4. If the possibility of identifying defects in people at risk is foreseeable or inevitable, then such samples should be coded or made anonymous for the purpose of these tests unless the person concerned has specifically requested that relevant information should be disclosed and has received information that allows him/her to fully understand the implications of such disclosure.

n 5. If a person at risk who gave a research sample later requests presymptomatic testing or other genetic services, a new sample should be taken and the request handled in the same way as it would be for any other person electing presymptomatic testing.

n 6. When a test may show a specific genetic defect in people affected by a disorder not previously known to be genetic, the possible genetic implications (as well as psychosocial implications) should be made clear and new consent obtained if samples previously obtained are being restudied.

n 7. Ethics committees should pay at least as much attention to the consequences of a sample being taken as to the risks attached to the sampling procedure.

n Advances in genetics may, however, place ethical concerns on a grander scale because everyone is at an increased risk for developing some disease.

n New genetic technologies may cause ethical concerns to arise at a different stage of life or of decision-making (e.g., prior to conception or at a presymptomatic stage of a disease)

SCREENING FOR GENETIC DISEASES

Before population-based screening for genetic conditions occurs, programs should consider five points.

• First, screening programs should clearly state their purpose and goal.

• Second, peer-reviewed pilot studies are necessary to demonstrate that the stated goals of the program can be achieved at a reasonable cost and with few adverse effects. This proposed safeguard may come under pressure, because the potential of screening for literally hundreds of genetic traits or susceptibilities creates pressure to begin screening prior to either adequate review of pilot studies or public debate.

• Third, the target population must be educated about the disease or condition in question and receive counseling about the risks and benefits of screening.

• Fourth, the traditional standards of informed consent must be observed. Screening should remain voluntary. Individuals must be able to exercise their "right not to know."

• Fifth, confidentiality of the individual must be maintained. In addition, although some scientists do not specifically address this concern, universal access to testing must be ensured by public health agencies if genetic technologies are not to exacerbate existing social inequalities.

Genetic Screening

What genes are

The inheritance of all our characteristics, including susceptibility to

n genetic diseases, is dependent on genes and chromosomes.

n Genes are large molecules made up of a substance, DNA, whose double helical structure allows both copying and division. The particular sequence of individual chemical sub-units in a gene serves as a molecular code to specify the manufacture of a particular protein; an alteration (mutation) at even a single position of the DNA sequence may cause serious malfunction of the resulting protein.

n Modern advances in genetics are due to the ability to study DNA directly. It is estimated that about 75,000 different human genes exist. At present we have information on only one third of them at most.

n The genes are arranged in a fixed order on the chromosomes.

n The scientific basis of genetic screening

Medical genetics is the part of human genetics concerned with

n the role of genes in illness. Traditionally, the analysis of the genetic contribution to illness and human characteristics has been divided into :

n (i) disorders due to changes in single genes;

n (ii) disorders influenced by more than one gene (polygenic);

n (iii) chromosomal disorders.

Types of genetic tests

All forms of genetic test aim to identify particular genetic characteristics but approach this in different ways.

n Chromosomal tests (cytogenetics)

n Tests for disorders involving a single gene

n Indirect (biochemical) tests

n Ultrasound

n The importance of genetic variation

Most of the genetic differences that can be detected between individuals represent normal genetic variation and are not associated with disease. This variation has been essential for human evolution and is seen both within and between populations.

Genetic screening : current programs

n Genetic screening programs are not a new development. Since the 1960s pregnant women have been routinely tested for their rhesus blood group, so that damage to babies of rhesus negative women before and after birth can be prevented. Damage is prevented by ensuring that rhesus negative women are given an antibody within a few hours of delivery, miscarriage or abortion.

n Since 1973 it has been policy to screen all newborn babies in the UK for phenylketonuria (PKU). Severe mental retardation is characteristic of this disease, but can be prevented if dietary treatment is started in the first weeks of life. These two tests have now become an accepted part of primary health care, and are essentially genetic screening programs.

Genetic screening may be carried out in the following groups of people:-

n (i) the entire population, albeit a section defined by age or

n sex, where all within the group are at risk. This is appropriate for example in screening newborn babies for PKU;

n (ii) sub-groups within the population, where the risk is known to be concentrated. This is appropriate, for example, within the Ashkenazi Jewish population for Tay-Sachs disease, a fatal brain disease of children especially frequent in this group, where healthy carriers can be detected in order to provide information;

n (iii) broad groups in which genetic factors may be responsible for some but not all of certain disabilities. For example, individuals with learning difficulties could be screened in order to detect those with fragile X syndrome, and thus identify the families at further genetic risk.

n Existing screening programs

Screening programs are broadly divided into four groups, depending on the timing of the testing:-

n (i) neonatal (in the newly born)

n (ii) older children

n (iii) testing of couples or individuals before pregnancy (adults)

n (iv) antenatal (during pregnancy).

n The key ethical principles of genetic counselling should be:-

n (i) the voluntary nature of genetic screening, and the freedom and responsibility of the individual or couple to decide;

n (ii) the importance of ensuring that the individual or couple offered screening understand the purpose of the test and the significance of a positive result;

n (iii) an assurance of confidentiality in the handling of the results, coupled with an emphasis on the responsibility of individuals with a positive (abnormal) result to inform partners and family members; and

n (iv) an appropriate emphasis, at each stage in the screening process, on the fact that consent to screening, or to a subsequent confirmatory test, does not imply consent to any specific treatment, or to the termination of a pregnancy

n Persons requiring special safeguards

In some cases, it may not be possible to obtain properly informed consent. The testing of the following categories of persons should be subject to special safeguards:-

n (i) minors;

n (ii) the mentally ill and those with severe learning difficulties.

n Other vulnerable individuals

Special care is always needed when consent is being sought from vulnerable individuals, such as prisoners, student volunteers, and from individuals who do not speak English.

Posted byDoc Junhel at 7:07 PM  

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