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Advances in genomics research yield both promise, risk for medicine
For now, applications of genetic discoveries in some health care arenas have been limited.
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Advances in the studies of the human genome and in discoveries of the meaning of some of the genetic information within it have set in motion what some physicians are calling a revolution of medicine.
Discoveries about the human genome — in particular, the existence of multitudes of sequences of genetic information that correspond to certain diseases and conditions — have given researchers cause to begin searching for the roots of some common diseases at the genetic level.
“There was a significant milestone five years ago with the achievement of all the goals of the Human Genome Project, including the reading of up to 3 billion letters of the human DNA code,” Francis Collins, MD, PhD, former director of the Human Genome Project at the National Institutes of Health in Bethesda, Md., said in a presentation at the American Heart Association Scientific Sessions 2008 in New Orleans. “That has provided us with a foundation to begin investigating in all kinds of interesting ways how the genome functions.”
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According to Collins, the advent of new technologies that can assay millions of base pairs of the human genome in a short period have enabled researchers to move beyond candidate gene association studies and have enabled genome-wide association studies.
“The candidate gene approach ended up all too often like a guy who lost his key late at night on the street … We were forced to look under the lamppost, and often times the actual genetic variants responsible for risk were not under the lamppost at all,” Collins said. “It later became possible to take a thousand cases or more, and a thousand controls or more, and scan the whole genome to see where the variants are that are associated with disease — in effect, lighting up the whole street instead of being forced to look with such a narrow perspective under the lamppost.”
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Source: The Scripps Research Institute |
Ethical considerations
The rapid advances in genomic research have also given rise to ethical questions among many practitioners. One of the most common ethical issues has to do with the direct-to-consumer genetic testing, an industry which has grown in recent years. Private companies such as 23andMe and Navigenics now offer direct-to-consumer genetic tests, some for as little as $399. What patients and practitioners are to do with the information obtained from a genetic test is of concern, as many practitioners may not yet be certain what the clinical utility of such information is.
“The big ethical issues in this area are questions of information,” Hank Greely, JD, a professor of law at Stanford Law School, said in a presentation. “It is an ethical imperative that physicians get enough information in ways they can use, in ways that their schedules allow, to allow them to make better decisions on behalf of their patients. It is also imperative that we figure out better ways to inform patients of what these test results mean so that they do not do stupid things with the information.”
One of the concerns most commonly cited by clinicians is that the information obtained from a genetic test may not be clinically validated and could be unreliable. A March 2008 editorial published in the Journal of the American Medical Association noted that the FDA currently does not assess the clinical validity of most genetic tests, nor is there a requirement that test providers disclose information to support claims about the accuracy and validity of the tests. According to one report from the National Human Genome Research Institute, also published in the Journal of the American Medical Association, more investigation into the utility and safety of clinical genetic testing is needed.
“Despite remarkable progress, much remains unknown about the risks and benefits of genetic testing,” the report stated. “There are no effective interventions yet available to improve the outcome of most inherited disease; negative test results might not rule out the outcome of most inherited diseases and positive test results might not mean the disease will inevitably develop.”
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Although genetic counselors are equipped to help physicians assess the utility of some genetic information, a looming potential problem is the lack of genetic counselors needed to keep up with the amount of new information being generated.
“It does not look like the solution at this point is genetic counselors because there are only about 2,000 genetic counselors in the United States, and they are not going to be able to keep up with the flood of data in the public domain,” Eric J. Topol, MD, director of the Scripps Translational Science Institute and chairman of the department of CV medicine at the Scripps Research Institute in La Jolla, Calif., told Endocrine Today. “It is not that genetic counselors are not useful but rather that there simply will not be enough of them and that most of the findings will not be a pronounced risk. There are a lot of known unknowns and unknown unknowns.”
Potential effect
Advances in genomics have resulted in some changes in therapy in areas of medicine like cancer, diabetes and age-related macular degeneration. Genetic tests are required to assess the risks for some cancers, for example. There are fewer advances, however, in the field of cardiology.
“Genetic screening can be helpful in select individuals in certain cardiology tests, but at the moment, that cardiology information is far less valuable than with other diseases,” Topol said. “We do not have any genes for valvular heart disease, for example, or genes to tell which patients should get defibrillators and which should not. There are many holes and aspects of cardiology where there really has not been discovery.”
As with the discovery of genetic variants linked with other complex diseases, the next question health care professionals may ask once a questionable variant is discovered is: What can be done for the patient?
“The classic answer to that question is to rev up your preventive lifestyle program because most people do not take good care of themselves,” Topol said. “If you do not carry the variants, it does not mean that you do not have other sequence variants that have not been discovered.”
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Although the genetic discoveries in cardiology have been few, some progress has been made. Research into a variant known as 9p21 has revealed that the variant is not only common but is associated with the formation of coronary artery disease. Robert Roberts, MD, president and CEO of the Ottawa Heart Institute, and colleagues were the first to conduct a genome-wide association study on the 9p21 variant.
“We got the first 9p21 gene for coronary artery disease and myocardial infarction and it has since been confirmed across the world,” Roberts told Endocrine Today. “Carrying the variant increases your risk for developing CAD by 40% and it is very common — about 75% of all Caucasians have one or more copies of this gene.”
He thinks that the rapid pace of discovery and the multiple institutions researching the genome for CV information will assist in the development of specifically targeted drugs and therapies for various CV conditions.
“Things are falling fast now,” he said. “I would think that within three to five years, we could probably have multiple genes and drugs for MI and CAD.” – by Eric Raible
For more information:
- Collins F. #171.
- Greely H. #174. Both presented at: American Heart Association Scientific Sessions 2008; Nov. 8-12, 2008; New Orleans.
- JAMA. 2008;299:1335-1344.
- JAMA. 2008;299:1353-1355.
- For more information on the National Human Genome Research Institute, visit www.genome.gov.