Tools That Are Transforming Discovery in CAM
The National Institutes of Health (NIH) is the nation's medical research agency-making important medical discoveries that improve health and save lives. NIH-supported scientists study ways to prevent disease, as well as the causes, treatments, and cures for common and rare diseases. The National Center for Complementary and Alternative Medicine (NCCAM), as a part of NIH, shares in these goals.
The NIH's Roadmap for Medical Research is a strategy intended to speed the process of discovery in biomedical research and bring innovations more quickly from the laboratory to patient care. An important piece of the Roadmap is to provide researchers with access to advanced technologies, databases, and other scientific resources. This article reviews some of these resources and NCCAM-supported studies that are using them. They are addressing questions like:
- What changes occur in the brain and elsewhere in the body (even down to the level of cells, molecules, and genes) when a CAM therapy is used?
- What is the chemical makeup of a natural product, such as an herb?
- How can a CAM therapy be used most effectively and safely?
A (Very) Close Look
Imaging techniques produce pictures of what is happening inside the body. Two examples of imaging techniques that are well known and date back decades are x-rays and ultrasound. However, there are also some newer players on the imaging stage.
Mapping brain differences, using imaging and other advanced tools.Photo Credit: Courtesy of Arthur Toga, University of California, Los Angeles, Center for Computational Biology
MRI, short for magnetic resonance imaging, uses a computer, powerful magnets, and radio waves to create three-dimensional images (scans) of the body's tissues and organs. As one example, investigators at the Consortial Center for Chiropractic Research (an NCCAM research center made up of a group of chiropractic colleges and institutions and headquartered at Palmer College of Chiropractic) are using MRI to study what happens in the spine when people with acute low-back pain receive chiropractic care. They hope to increase knowledge about chiropractic treatment and ultimately help the symptoms and functioning of people who have back pain.
With fMRI, short for functional magnetic resonance imaging, researchers can look at functioning in the brain or other organs by detecting changes in the chemical composition and/or blood flow in these areas. Some studies are using fMRI to better understand the brain's responses to mind-body therapies such as meditation. 1
1 See also Meditation for Health Purposes.
At the University of Wisconsin-Madison, researchers are studying the impact of a meditation practice on study participants' attention and emotions, and on the brain structures and systems that are involved.
One question is whether attention and emotion, as processes, are flexible enough that people can train themselves to have positive emotional states more often. Meditation can be one source of these states, which research has indicated may have health benefits. Part of the Wisconsin work includes the study of Buddhist monks who are longtime practitioners of meditation.
When someone has a PET (positron emission tomography) scan, the technician injects a small amount of a radioactive substance into a vein. The substance travels through the bloodstream to the target tissue, where it gathers in the cells and gives off extremely tiny radioactive particles. The PET device uses them to make three-dimensional images, not just of the body's structures, but also its metabolism.
One way PET is being used in CAM research is to study the placebo effect (the physical or psychological benefits that can occur with the use of a placebo-an inactive or sham treatment such as a sugar pill).
Recent research has shown that placebos may have value beyond simply being "controls" in clinical trials; they may have powerful therapeutic effects themselves. Researchers want to understand the underlying pathways in the body that lead to placebo effects, an endeavor that ultimately could benefit both CAM and conventional medical treatment. Johns Hopkins School of Medicine researchers are using PET to study how placebos affect brain neurons, 2 some of which have receptors for opiate-like substances that the body produces naturally and that function to reduce pain. In another project, a team at the University of Michigan at Ann Arbor is using both fMRI and PET to examine the metabolism of regions of the brain that are involved in placebo treatment of pain.
2 A neuron is a type of cell that receives and sends messages from the body to the brain and back to the body, through a weak electrical current. It is also called a nerve cell.
Down to the Genetic Level
New high-technology tools being used to analyze genetic material have helped create entirely new scientific disciplines, such as:
- Genomics, a "scaled-up" version of genetics research in which scientists can look at all the genes in a living creature at the same time. A research study at Chongqing University of Medical Sciences, China (with earlier work at the University of Chicago Medical Center), is using genomics to study human cancer cells treated with berberine (the main component of Coptis chinensis, a medicinal herb). The team hopes to identify genes that have a role in anticancer action in berberine, which might lead to new therapeutic approaches in cancer.
- Proteomics, the study of the structure and function of proteins (for example, the ways they interact with each other inside cells). Using proteomics, researchers at the University of Alabama at Birmingham have found that grape seed extract increases or decreases the levels of certain proteins in the brain in ways that might have a protective effect on brain function. Grape seed extract is rich in proanthocyanidins—molecules that help create intense colors in fruits and vegetables and are thought to have antioxidant properties.
This three-dimensional image, created by computers, illustrates how certain enzymes work together in a cell's metabolism (the focus of a new field called metabolomics).Photo Credit: Courtesy of Dr. James Stoops, University of Texas-Houston
- Metabolomics, the study, on a large scale, of metabolism (and the substances involved) in cells, tissues, and organ systems. In the Endocrinology Section of NCCAM's Division of Intramural Research, scientists are using metabolomics to study L-carnitine (a dietary supplement) for its potential in helping to prevent loss of muscle mass in certain chronic diseases and in the aging process.
Cutting-Edge Chemistry
Mass spectrometry (MS) uses a sophisticated instrument to identify chemicals in a substance by their mass and electrical charge. It has been around for almost a century, but is being used in new ways—for example, at the University of Illinois at Chicago College of Pharmacy, to study botanical dietary supplements in women's health. The goal is to analyze the supplements' chemical components and prepare standard formulations for use in clinical studies.
Inserting samples to be analyzed by accelerator mass spectrometry (AMS)Photo Credit:Lawrence Livermore National Laboratory
Accelerator mass spectrometry (AMS) uses an ultrasensitive technique that takes MS analysis to an even higher level through a very advanced device called a particle accelerator. Researchers at Purdue University (whose particle accelerator is as big as a football field) and the University of Alabama at Birmingham are using AMS to study isoflavones, a group of compounds found in some plants and especially in soy, for their effects on calcium absorption and bone loss in postmenopausal women.
Computing New Answers
Some research tools bring computer technology and expertise from other fields (for example, in biology, other life sciences, physics, and mathematics) to bear on CAM research questions.
Computer-assisted devices in medicine are becoming smaller and more powerful. One way to use them is to study changes in the body that are hard to measure. In studies of treatments for menopausal symptoms, for example, participants have often reported the frequency and severity of their hot flashes through diaries or in interviews. However, these methods can have drawbacks that affect studies' validity and reliability. For objective measuring, instruments called sternal skin conductance monitors can be used, but so far, many have had limitations—for example, where and how long users can wear them. NCCAM has been supporting the development of improved monitors for hot flashes. These should provide more effective measuring tools in clinical studies of CAM therapies for menopausal symptoms.
In bioinformatics, the researcher uses a computer to obtain, organize, analyze, and otherwise work with data from the life sciences. An NCCAM-funded study at the University of Southern California is using bioinformatics to analyze data on SAMe (S-adenosyl-L-methionine, a dietary supplement) as a potential treatment for liver disease.
Computational biology consists of developing and applying various methods, such as computer-derived mathematical models and simulation techniques, to study systems in the life sciences. In the chiropractic study discussed earlier, investigators are using computational biology to interpret their data from spinal manipulation in animal models, as it applies to people.
Looking to the Future
Margaret A. Chesney, Ph.D., Deputy Director of NCCAM, says, "NCCAM encourages innovation in the research enterprise. New tools, and innovative ways of using older tools, are ways that we learn more about not only CAM therapies, but the health problems for which people use CAM."
References
Benedetti F, Mayberg HS, Wager TD, et al. Neurobiological mechanisms of the placebo effect. Journal of Neuroscience. 2005;25(45):10390-10402.
Bren L. Metabolomics: working toward personalized medicine. FDA Consumer. 2005;39(6):6.Accessed at fda.gov/fdac/605_toc.html on November 7, 2006.
Clinical proteomic technologies for cancer: mass spectrometry.National Cancer Institute Web site. Accessed on November 7, 2006.
Formanek R Jr. Proteomics: moving beyond the human genome. FDA Consumer. 2005;39(6):3. Accessed at fda.gov/fdac/605_toc.html on November 7, 2006.
Kim H, Deshane J, Barnes S, et al. Proteomics analysis of the actions of grape seed extract in rat brain: technological and biological implications for the study of the actions of psychoactive compounds. Life Sciences. 2006;78(18):2060-2065.
National Human Genome Research Institute. A Brief Guide to Genomics. National Human Genome Research Institute Web site. Accessed at genome.gov/18016863 on November 7, 2006.
Warren Grant Magnuson Clinical Center. Positron Emission Tomography (PET) Scan—Diagnostic. Warren Grant Magnuson Clinical Center Web site.Accessed at cc.nih.gov/ccc/patient_education/procdiag/petdiag.pdf on November 7, 2006.
For More Information
NCCAM Clearinghouse
The NCCAM Clearinghouse provides information on CAM and NCCAM, including publications and searches of Federal databases of scientific and medical literature. The Clearinghouse does not provide medical advice, treatment recommendations, or referrals to practitioners.
Toll-free in the U.S.: 1-888-644-6226
TTY (for deaf and hard-of-hearing callers): 1-866-464-3615
Web site: nccam.nih.gov
E-mail: info@nccam.nih.gov
CRISP (Computer Retrieval of Information on Scientific Projects)
CRISP is a database of information on federally funded scientific and medical research projects being conducted at research institutions.
Web site: crisp.cit.nih.gov
National Institute of General Medical Sciences
Web site: nigms.nih.gov
National Institute of Biomedical Imaging and Bioengineering
Web site: nibib.nih.gov
These two institutes at NIH have glossaries (or links to them) on their Web sites, defining many technologies and tools being used in biomedical research.
