Academic journal article The Hastings Center Report

New Tools, New Dilemmas: Genetic Frontiers

Academic journal article The Hastings Center Report

New Tools, New Dilemmas: Genetic Frontiers

Article excerpt

New Tools, New Dilemmas: Genetic Frontiers

Under the aegis of "the new genetics" direct exploration of the human genome has exploded the boundaries of an earlier genetics. Already the new DNA technologies have brought us screening tests for Huntington disease and cystic fibrosis, as well as claims to the first complete (although admittedly low resolution) map of the human genome. The use of restriction enzymes and probes for mapping and sequencing human genes evokes visions of a genetics no longer limited to making statistical predictions for groups or populations, but instead able to detect with great accuracy the presence of disease in a given individual.

The powerful new methods, expansive scope, and accelerated pace of human molecular genetics combine to catapult us into ethically unfamiliar territory. The molecular method generates not simply diagnoses but presymptomatic and contingent diagnoses. Its scope potentially includes not only serious genetic disease but also mild conditions and bothersome or unusual traits and characteristics. And its pace threatens to outstrip our capacity to react sensibly to its implications.

To use these new genetic screening capabilities wisely thus requires anticipating novel stresses and preparing strategies responsive to both the opportunities and dangers afforded by enhanced diagnostic powers. It also requires understanding our tools and individual and societal options for shaping them to our purposes.

New Tools, New Powers?

The term "molecular" reveals the basic methodologic novelty of human molecular genetics. Traditional genetic inquiry proceeds from recognition of diseased states or abnormal gene products to inferences about genetic inheritance based on analysis of patterns of transmission. Its central diagnostic tools are assessments of symptoms and signs (at individual or social levels), pathology (at organ, tissue, and cellular levels), and assays of gene products, such as structural proteins or enzymes (at subcellular levels). [1] In human molecular genetics, however, the structure of a gene at the molecular level is often discovered before anything is known about the gene product it encodes.

The most basic molecular tools for studying genes are enzymes that generate strips of genetic material called restriction fragment length polymorphisms (RFLPs). Restriction enzymes generate DNA fragments of differing lengths that form patterns of lines in a special gel; skilled geneticists read these patterns in the same way that a scanning device at a supermarket checkout counter reads a "bar" or price code on the bottom of a box of cereal.

A marker becomes useful diagnostically if the RFLP pattern it generates is statistically associated with the occurrence of a particular condition. In most cases, interpreting a given individual's pattern requires comparing it with those of his or her affected and unaffected family members, a process called linkage analysis. Probes that generate these types of patterns are called "linkage markers," while markers that can establish a diagnosis without reference to family members are called "direct" markers. Linkage analysis generally requires the skills of a trained geneticist and is very costly and time-consuming, while direct tests theoretically can be conducted more cheaply and rapidly, and made more easily available. Currently, most molecular diagnosis is conducted via linkage analysis.

Whether direct testing becomes common depends partly on biologic realities, and partly on priorities and support for new research. Linkage analysis may be required because the gene for a given condition has not yet been isolated, or because the condition is marked by considerable genetic heterogeneity (that is, it has a large variety of genetic causes, making diagnosis on the basis of a small number of patterns difficult or impossible). Developing an assortment of new markers (as part of a coordinated national project to map the human genome, for example) increases the chances not only of identifying markers for specific genes but also of having multiple markers to compensate for problems of heterogeneity. …

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