Genetics

The scientific understanding of genetics began with Mendel’s discovery of the basic laws of inheritance (1). The understanding of the genetic implications in human disease developed with the discovery of the laws of the inheritance of hemophilia (2). The ongoing Human genome Project will vastly increase our knowledge and understanding of the human genetic make-up (3). The application of medical genetic knowledge in individual human situations, or even the pursuit of this knowledge, can raise issues of the rightness or wrongness of these actions, and may therefore have ethical implications. Since genetics can include therapeutic gene manipulations, including germ (or inheritable) cell alterations, as well as genetic mapping and patient counseling, these bioethical issues can have profound ramifications. The Catholic ethical tradition, rooted in philosophy and religion, offers a traditional perspective regarding human medical genetics. This book is an application of these principles in this rapidly developing area of medicine.

Genetics is the study of heredity or the transmission of characteristics from one generation to the next (4). To oversimplify, it is the scientific; understanding of the biologic reason a living organism is constituted as it is (5). There are several aspects to genetics, 1) the biochemical aspects of the mechanism of the inheritance and expression of traits, 2) the active research into identifying these inheritance patterns and to presumably "improving" those deemed inferior, and 3) the ethics, or rightness or wrongness, of this genetic discovery and intervention. We will summarize, indeed oversimplify, each of these areas.

While efforts to understand and improve heredity, for instance in livestock, have existed from the beginning of recorded history, the scientific study of genetics began with Mendel, who in 1866 observed and recorded basic inheritance laws in the plant, the garden pea. While the chromosomes in each cell nucleus were known to be involved with heredity, it remained for Watson and Crick in 1953 to elucidate the role of the double strands of deoxyribonucleic acid (DNA) in the transmission of genetic information (6).

In summary, genes transmit discrete bits of hereditary information via messenger ribonucleic acid (RNA) resulting in specific proteins that mediate various aspects of an organism’s behavior. Each gene is a sequence of the double helix, or complimentary strands of DNA, which is a lengthy series of pairs of four chemical subunits. There are approximately 150,000 genes which constitute the inheritance code for the human person. Technologic advances such as in situ hybridization, reverse transcriptase and polymerase chain reaction allow the identification, localization, and replication of specific genes.

Gene function, whereby biologic activity proceeds, is usually an orderly process in somatic, or non-generative, cells comprising the vast majority of the human body mass. While gene abnormalities in somatic cells involve only the person with these changes, germ (or generative) cell genetic changes can be transmitted to future generations. Genetic defects, either as a direct (autosomal dominant disease) or indirect (polygenetic) gene change, or even as a later somatic cell mutation contribute to most human diseases. Genetic defects such as sickle cell anemia and Down’s syndrome are examples of the first, diabetes and hypertension of the second, and radiation induced cancer of the latter

Knowledge of the genome is increasing exponentially. The Human Genome Project (HGP), initiated in 1988 is an effort initially sponsored by the government but later by private enterprise as well, hoped to map the entire gene sequence of all 46 human chromosome several years into the 21" century. Remarkably, on June 26, 2000, Drs. Collins (HGP) and Venter (Celera Corp) announced that they had completely mapped human genetic DNA (7).

There are several imperatives driving the effort to unravel the human genome. The first is the quest for new knowledge in a area that promises to provide answers about the nature of human life itself. Second, knowledge of the normal human gene allows understanding of hereditary disease producing abnormalities and the potential to correct them. Finally, and perhaps most importantly, is the profit motive. Venture capitalists are fast patenting large segments of the human genome in the hope that their exclusive possession of this priceless knowledge will make them rich.

Defective genes can be identified and corrective genes inserted into the genome. These techniques have been developed in animal models. Clinical investigations in humans will be required to determine if gene therapy can be effective in humans as well. Human gene therapy trials will be required to conform to regulatory guidelines.

Human research guidelines began following the exposure of the Nazi medical atrocities at the Nuremberg Trials and are incorporated in the Nuremberg Code (8), and the Declaration of Helsinki (9). They acknowledge human dignity and autonomy and require informed consent for experimentation. The Belmont Report (1979) (10), citing problems with human experimentation in the United States, resulted in a requirement that clinical investigations begin with institutional review board (IRB) approval. For gene research additional National institutes of Health approval through the Recombinant DNA Advisory Committee (RAC) is also required. The implication in the formation of this additional regulatory agency is that gene research, because it deals with the human gene and its possible alteration, is more important than, say antibiotic research, because chromosomes determine heredity and altering them have implications for the human gene pool.

Gene therapy, because of its potential to cure incipient disease at the level of the chromosome, will, if it has not already, become the most important area in bioethics. Areas of concern include primarily germ line alterations but also issues regarding the diagnosis of, and counseling for, preexisting genetic abnormalities as well as harvesting of cells for genetic research. Any genetic alteration in germ cells can be passed to progeny and, while theoretically desirable, the full ramifications of these alterations cannot be known. Diagnosing genetic defects presents ethical problems because, in the case of prenatal detection, given our culture, many parents will elect abortion rather than risk defects, however correctable. Prenatal diagnosis could involve blastocyst intervention with an additional series of ethical issues. Identification of genes coding for intelligence or other desirable traits could result in efforts at enhancement genetics. Finally, genetic research includes the harvesting of cells for research which can come from human tissue including aborted fetuses or human blastocy sos obtained from in vitro fertilization. In 1994 the Human Embryo Research Panel of the NIH approved the use of human embryo for experimentation (11). All of these areas have profound medical ethical implications. A word or two on the status of medical ethics would be in order.

Medical ethics in the United States is made up of three predominant schools. These are: 1) the deontological, 2) the utilitarian, and 3) principlism. The deontologicial school speaks in terms of absolutes, such as the ten commandments. Kant’s categorical imperative is one example. The utilitarianism dominates ethics in the United States. Its guiding principle is "the gr