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Examples have been identified where common variants in genes involved in drug metabolism or drug action are associated with the likelihood of a good or bad response. The expectation is that such correlations will be found for many drugs over the next 10 years, including agents that are already on the market.
This field of pharmacogenomics promises to individualize prescribing practices. The field of gene therapy, having sustained a series of disappointments over the past few years, especially with the death of a volunteer in a gene therapy trial in the fall of , has gone back to wrestling with the basic science questions of finding optimal methods for gene delivery.
There already have been promising reports of the application of gene therapy for hemophilia B 23 and severe combined immunodeficiency. The power of the molecular genetic approach for answering questions in the research laboratory will catalyze a similar transformation of clinical medicine, although this will come gradually over the course of the next 25 years Figure 1. By the year , it is expected that predictive genetic tests will be available for as many as a dozen common conditions, allowing individuals who wish to know this information to learn their individual susceptibilities and to take steps to reduce those risks for which interventions are or will be available.
Such interventions could take the form of medical surveillance, lifestyle modifications, diet, or drug therapy. Identification of persons at highest risk for colon cancer, for example, could lead to targeted efforts to provide colonoscopic screening to those individuals, with the likelihood of preventing many premature deaths. Predictive genetic tests will become applicable first in situations where individuals have a strong family history of a particular condition; indeed, such testing is already available for several conditions, such as breast and colon cancers.
But with increasing genetic information about common illnesses, this kind of risk assessment will become more generally available, and many primary care clinicians will become practitioners of genomic medicine, having to explain complex statistical risk information to healthy individuals who are seeking to enhance their chances of staying well. This will require substantial advances in the understanding of genetics by a wide range of clinicians.
Another crucial step is the passage of effective federal legislation to outlaw the use of predictive genetic information in the workplace and in obtaining health insurance.
Although more than 2 dozen states have taken some action in this regard, a patchwork of different levels of protection across the United States is not satisfactory and this vexing problem must be dealt with effectively at the federal level. By , the impact of genetics on medicine will be even more widespread. The pharmacogenomics approach for predicting drug responsiveness will be standard practice for quite a number of disorders and drugs. New gene-based "designer drugs" will be introduced to the market for diabetes mellitus, hypertension, mental illness, and many other conditions.
Improved diagnosis and treatment of cancer will likely be the most advanced of the clinical consequences of genetics, since a vast amount of molecular information already has been collected about the genetic basis of malignancy. By , it is likely that every tumor will have a precise molecular fingerprint determined, cataloging the genes that have gone awry, and therapy will be individually targeted to that fingerprint. Despite these exciting projections, certain tensions also will exist.
Access to health care, already a major problem in the United States, will complicate these new advances, unless our medical care systems change in significant ways. Antitechnology movements, already active in the United States and elsewhere, are likely to gather momentum as the focus of genetics turns even more intensely on ourselves. Though the benefits of genetic medicine will be profound, there will be those who consider this advancement unnatural and dangerous.
Efforts at public education need to start now to explain the potential benefits and to be honest about the risks. In conclusion, this is a time of dramatic change in medicine. As we cross the threshold of the new millennium, we simultaneously cross a threshold into an era where the human genome sequence is largely known.
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We must commit ourselves to exploring the application of these powerful tools to the alleviation of human suffering, a mandate that undergirds all of medicine. At the same time, we must be mindful of the great potential for misunderstanding in this quickly developing field and make sure that the advancement of the social agenda of genetics is equally as vigorous as the medical agenda.
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All Rights Reserved. The rate of progress for applying a genetic approach to the diagnosis and treatment of each disease will be different depending on the research investment and the degree of biological complexity underlying the disease. Diagnostic opportunities may then come along rather quickly, but will be of greatest clinical usefulness once prevention measures are developed that have proven benefit to those at high risk.
Some gene variants will also show clinically useful associations with drug responsiveness pharmacogenomics. In general, full-blown therapeutic benefits from identification of gene variants will take longer to reach mainstream medicine. In some instances, the gene itself will be the drug gene therapy , while in others, a sophisticated knowledge of the underlying disease mechanism, built upon genetics, may allow the design of targeted and highly effective drug therapy. National Center for Biotechnology Information. Online Mendelian Inheritance in Man.
Accessed November 30, Shattuck Lecture: medical and societal consequences of the Human Genome Project. N Engl J Med.
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Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am J Hum Genet. A polymorphic DNA marker genetically linked to Huntington's disease.
Mapping and Sequencing the Human Genome. Understanding Our Genetic Inheritance. The U. A new five-year plan for the U. Human Genome Project.
New goals for the U. Human Genome Project: Positional cloning moves from perditional to traditional. Nat Genet. The DNA sequence of human chromosome Variations on a theme: cataloging human DNA sequence variation. Genomics, gene expression and DNA arrays. Molecular classification of cutaneous malignant melanoma by gene expression profiling. Proteomics to study genes and genomes. Lessons learned from the development of an abl tyrosine kinase inhibitor for chronic myelogenous leukemia. J Clin Invest. Pharmacogenetics and the practice of medicine.
This Issue. Citations View Metrics. Opportunities for Medical Research. Francis S. McKusick, MD. Genetics in the 20th Century. The Human Genome Project. Current Research Focus. Genetics in the Medical Mainstream. Sign in to access your subscriptions Sign in to your personal account. Create a free personal account to download free article PDFs, sign up for alerts, and more.
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Get free access to newly published articles. These individuals are generating genomics discoveries and innovations as well as using genomic tools and products. Explore G-SIN. Finally, there are number of technology platforms scattered throughout the province of Ontario, providing world class support and infrastructure for innovative research and services in genomics and proteomics.
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