Does the phrase ‘gene sequencing’ mean organizing your jeans according to shades of blue denim in your drawer? Is the Human Genome Project a discussion topic at your dinner table? Or does it seem so complicated and overwhelming that it’s hard to comprehend? Well, if this describes you, you are not alone. Many individuals know very little about the recent advances that have been accomplished with the human gene. I hope this article will help explain, in an easy-to understand way, the subject of genetics, the Human Genome Project, and genomics in today’s society.
I had the privilege of attending a meeting at the National Institutes of Health (NIH) where Alan E. Guttmacher, MD, gave an informative presentation about genetics and the Human Genome Project. Dr. Guttmacher is the Senior Clinical Advisor to the Director at the National Human Genome Research Institute (NHGRI) at the NIH. So I was learning from the best.
Our genes are the basic building blocks of the human body. They determine who we are as individuals. Genetics is the study of the genes and how they function. Traditionally, the term genetic condition refers to conditions wholly caused by an extra or missing complete chromosome or part of a chromosome (e.g., Down Syndrome), or a mutation in a single gene (e.g., cystic fibrosis, tuberous sclerosis).
These conditions are of great importance to the people they affect. But even when they are added together, they are still relatively rare. Since the majority of people are not affected, genetics plays a small role in the health care industry and society. But, did you know that nine out of ten leading causes of mortality have genetic components? Conditions such as heart disease, cancer and diabetes are all affected by genetics.
So what is the Human Genome Project? Begun formally in 1990, the Human Genome Project is a thirteen-year effort, coordinated by the U.S. Department of Energy and the National Institutes of Health. Project goals are to: • Identify all the approximately 30,000 genes in the human DNA. • Determine the sequences of the 3 billion chemical base pairs that make up the human DNA. • Store this information databases. • Improve tools for data analysis. • Transfer related technologies to the private sector, and • Address the ethical, legal and social issues that may arise from the project.
The human genome consists of three billion base pairs of the amino acids, Adenine, Cytosine, Guanine and Thymine. If you would print out the first letter of these amino acids in their order of four, A,C,G,T, the combinations would fill over 150,000 telephone book pages. Disease is often caused by a single variation in these three billion bases. It can be compared to one incorrect letter out of all those 150,000 telephone book pages. Genomics is the study of the human genome sequence.
Genomic Medicine refers to conditions partly caused by mutation(s) in gene(s) (e.g., breast cancer, Alzheimer disease) and prevented by mutation(s) in gene(s) (e.g., HIV). These conditions are of great importance to individuals and families who are affected by them because they are quite common and affect virtually everyone. This will create a large role for genetics in the health care industry and society.
Genomic medicine will change the health care industry by creating a fundamental understanding of the biology of many diseases, even the “non-genetic” ones. This understanding will lead to defining disorders by the mechanism that causes them, rather than by symptoms. Genomic medicine will change health care by providing knowledge of individual genetic predispositions and other technologies. Having the knowledge of genetic predispositions will allow individualized screening (e.g., mammography, colonoscopy), individualized behavior changes and presymptomatic medical therapies (diet, exercise and antihypertensive agents before hypertension develops). Genomic Medicine will change health care by creating pharmcogenomics. Pharmacogenomics will allow newapproaches to drug design, individualized medication based on genetically determined variation in effects and side effects, and new medications for specific genotypic disease subtypes.
Genomic Medicine will change health care by providing a better understanding of non-genetic (environmental) factors in health and disease, allowing genetic engineering, and emphasizing health maintenance rather than disease treatment.
All of these incredible advances are bringing us into the “New Genetics” era. New genetics will include knowledge about traits that most of us see as human characteristics, rather than diseases (e.g., height, intelligence, athletic ability, etc.). New genetics will change our lives by knowing our own (and others) diseases dispositions, knowing our (and others) characteristic dispositions, and showing us that we are all mutants!
New genetics may also change society by genetic stratification (e.g., in employment and marriage), genetic engineering against diseases and characteristics, cloning and an increased opportunity for ‘private eugenics.” All of these issues raise new concerns for all Americans such as discrimination against individuals and groups, nature vs. nurture (genetic determinism),genes running in families, and confidentiality/privacy issues. More concerns regarding fairness in access, the right not to know and not to act, what is an appropriate informed consent process, and patenting and licensing will also become areas of concern.
The National Human Genome Research Institute funds and conducts very little disease-specific research, knowing that other institutes and centers at the NIH are ably utilizing a genomics approach. The NHGRI attempts to fund and conduct research that provides crosscutting scientific and technologic tools that further such disease- and tissue-specific research. The NHGRI also funds and conducts some scientific research that promises to establish new ways of ooking at research and clinical care.
As completion of the sequencing of the human genome draws near, the NHGRI is enthusiastically planning for the era of genomic research and genomic medicine. Dr. Guttmacher explained that the entire human genome sequence will be mapped by April 2003. Ironically, that date will mark the 50th year anniversary of the discovery of DNA by Drs. Watson and Crick. The NHGRI is in the midst of developing a new plan which will look at the future of genomics and what role the NHGRI will play in helping to develop that future. Clearly translational research will be a primary focus that emerges from this planning process.
Translational research means translating the discoveries made into a medicine or therapy that someone can use to treat, prevent or cure a disease or condition. If you are interested in learning more about the planning process, log on to www.nhgri.nih.gov/ planning.
Why is the Human Genome Project and the resultant genomic medicine important for clinical research in the new millennium? As President Bush stated at the White House on April 10, “Our age may be known to history as the age of genetic medicine, a time when many of the most feared illnesses were overcome.” And former President Clinton stated on June 26, 2000 after the announcement of the completion of the human genome draft sequence, “It is now conceivable that our children’s children will know the term cancer only as a constellation of stars.”
