Science meets tradition: Multinational teams of investigators put alternative medicine to the test

Scientists in the East and West are joining forces in an effort to create an evidence base for traditional medicine (TM) and complementary and alternative medicine (CAM). These investigators are using rigorous scientific methods to test ancient practices such as meditation, acupuncture, and herbal supplements, in the hopes of one day discovering which techniques work, and which do not, how they work (when they work), and how to best incorporate them into modern biomedicine.

These cross-cultural efforts carry different lessons about the delivery of health care in both the East and West. For practitioners in the East and in developing countries, continually enhancing the benefits of traditional medicine makes sense, as they represent the only affordable source of health care for some patients. And although traditional approaches are often embedded within a country’s wider belief system, international observers have often found that locally accepted treatments for a given disease do not provide the benefits that are promised, and in some cases do more harm than good. In developed countries, the need to study and validate TM/CAM has arisen in response to the growing interest of health care consumers who are dissatisfied with the care provided by the health care system, or who merely want to expand their options beyond the typical visit to the doctor.

Aside from the creation of new medicines and therapies, the collaboration between the modern West and traditional East could help to preserve ancient healing practices, and introduce them to future generations of doctors who may find in the past the key to uncovering more secrets of disease and treatment.

Dr. David Eisenberg: “There’s a shared desire on the part of non-Western medical practitioners as well as Western scientists to learn from each other and share what we can to improve health outcomes and to advance scientific knowledge.”

Like many a cross-cultural relationship, the marriage between East and West has its challenges, says Dr. David Eisenberg, Bernard Osher Associate Professor of Medicine at Harvard Medical School, and Director of the Division for Research and Education in Complementary and Integrative Medical Therapies. But with roughly one in three adults routinely using some form of TM/CAM, scientific testing is essential. “It’s not enough to just observe whether or not a traditional or complementary therapy works,” he says. “It’s increasingly clear that we need to understand how it works, if we’re going to adopt it as part of conventional medical care.”

Dr. Jack Killen, Jr., Director of the Office of International Health Research at the National Center for Complementary and Alternative Medicine (NCCAM), part of the National Institutes of Health (NIH), echoes these sentiments. It’s a matter of safety, he says. A recent NCCAM survey suggested that most people who use CAM do so without consulting a practitioner. “People make an assumption that CAM is safe because it’s natural,” says Killen. “That’s not necessarily a fair assumption.”

Some herbal dietary supplements, for instance, produce side effects, complications, and drug interactions that can be dangerous and even fatal. Research from NIH has shown that St. Johns wort affects how the body processes medications used to control HIV infection, anti-cancer drugs, and drugs that help prevent the body from rejecting transplanted organs. “Patients should talk to their doctors about any CAM they are using,” Killen stresses. “This is the only way we can document safety, where it exists, and problems where they exist.”

The quest to prove that TM/CAM works is nothing new. For millennia, practitioners in the East have observed the effects of their healing practices in a wide variety of patients. More recently, researchers in the West have conducted studies showing that certain herbs, acupuncture, and other CAM therapies have a clinical effect. But understanding their physiological effects and how to prescribe them safely is infinitely more complicated.

Big questions—and some answers
Increasingly, such questions are becoming the focus of CAM research worldwide. NCCAM has said that basic research aimed at elucidating the mechanisms of action underlying CAM practices is a high priority for the next five years. Now in its sixth year, NCCAM supports more than 300 research projects and has an estimated budget of over $120 million for 2005 (up from $50 million in 1999). Total spending on CAM by all NIH institutes and centers is expanding as well, and is expected to reach $315 million by 2005.

The World Health Organization (WHO), meanwhile, recognizes that TM/CAM use is widespread and growing. In response, the organization is collaborating with a wide range of United Nations agencies and international and non-governmental organizations to frame policy, and to ensure the safety, efficacy, quality, access, and rational use of traditional remedies.

Such lofty ambitions are becoming realizable, in part, through technological advances, particularly in the neurosciences, pscychoneuroimmunology, and behavioral medicine. Functional Magnetic Resonance Imaging (fMRI), for example, allows investigators to see which parts of the brain are affected by specific therapies. And high throughput screening facilities allow scientists to screen thousands of herbal extracts and other biological substances for their biological activity. Pilot studies in this area are ensuing at Harvard Medical School under the direction of Dr. Eisenberg at the Osher Institute in collaboration with the HMS Institute for Chemical and Cell Biology.

Questions about TM/CAM’s efficacy are more than academic. The use of these interventions remains widespread in all regions of the developing world, and is rapidly growing in industrialized countries, according to WHO. Countries in Africa, Asia, and Latin America use traditional medicine to help meet some of their primary health care needs. In China, traditional herbal preparations account for up to half of the total medicinal consumption. In Ghana, Mali, Nigeria, and Zambia, 60 percent of children with high fever resulting from malaria receive herbal medicines as the first line of treatment. Meanwhile, in Europe, North America, and other industrialized regions, over half of the population have used CAM at least once. The global market for herbal medicines stands at over $60 billion a year, and is growing steadily. A recent NCCAM survey of over 30,000 adults in the U.S. backs up these findings, showing that 36 percent use some form of CAM, and when prayer for health reasons is included in the definition of CAM, that number rises to 62 percent.

Dr. Jack Killen, Jr.: Health care consumers “are looking for more touch, more time with practitioners, and the health care system that we exist in today is often not able to provide that any more.”

Why are so many people turning to ancient practices in these modern technological times? In developing countries, traditional medicine is often more accessible and affordable than conventional (or “allopathic”) medicine, reports WHO. In Uganda, for example, there is one practitioner of traditional medicine for every 200 to 400 people, while the ratio of allopathic practitioners to population is 1 to 20,000 or worse. Moreover, allopathic practitioners tend to cluster around cities, making it hard for people in rural areas to get treatment.

In developed countries, many people turn to CAM to avoid the adverse effects of chemical drugs or because they are dissatisfied with the past_issues/Nov_Dec_2004 health care systems. Consumers are hungry for alternatives to the typical 15-minute office visit, explains Killen. “They are looking for more touch, more time with practitioners, and the health care system that we exist in today is often not able to provide that any more.” Further fueling the demand for CAM is an increase in debilitating chronic disease brought on by longer life expectancy. For some people, complementary therapies offer an expanded set of therapeutic options for managing heart disease, cancer, diabetes, and mental disorders. Many other patients seek relief from back pain, colds, neck pain, and joint pain or stiffness.

Mounting evidence
An increasing number of scientific studies now support—and reject—the use of certain TM/CAM therapies. For example, clinical trials have shown that the herb artemisinin is effective in treating malaria, while a recent study showed that St. John’s wort is no more effective than a placebo or the antidepressant medicine sertraline in treating major depression of moderate severity.

Nearly a dozen NIH-supported Phase III clinical trials of CAM therapies are underway, according to Killen. These include studies examining the use of shark cartilage for lung cancer, Ginkgo biloba for dementia, vitamin E for Down syndrome, and EDTA chelation therapy for coronary artery disease. What today is categorized as complementary and alternative medicine becomes, once it is converted into a capsule and validated by the proper regulatory authorities, just another medicine.

Scientific evaluation of complementary and alternative therapies is the mission of Harvard Medical School’s Osher Institute, at the Division for Research and Education in Complementary and Integrative Therapies. past_issues/Nov_Dec_2004ly, the Division and the Institute are designing and implementing a variety of research studies, continuing medical education programs, medical school courses, an NIH-sponsored research fellowship training program, and a plan for a model integrative care clinical facility. Rigorous scientific research forms the foundation for all activities within the Division. Early studies focused on survey research, back pain trials, and placebo research. Over the past year, research interests have been expanded to include basic and translational research in specific modalities, including acupuncture and herbal supplements.

The acupuncture research explores how acupuncture works, what physiological changes it induces, and what clinical conditions it might be used for, explains Eisenberg, who directs the Institute and Division. A closely associated line of research, he says, examines “placebo-related phenomena”—whether the placebo effect is reproducible, for example, and whether some people are more prone to it than others, and whether technology such as fMRI can reveal where in the brain and nervous system acupuncture alters pain sensation and other physiologic functions.

Other studies explore whether individual or complementary therapies, such as chiropractic, acupuncture, and massage, benefit patients with low back pain in predictable and measurable ways. These studies look at patients’ clinical outcomes (whether back pain improves) as well as the cost of these therapies compared with conventional treatment.

Eisenberg is also working with co-investigators from the Chinese University of Hong Kong, the Academy of Traditional Chinese Medicine in Beijing, and Keio University in Japan to create a U.S.-China-Japan Research Consortium on Herbal Medicine. Funded by a NCCAM planning grant, the researchers hope to identify candidate herbs for treating conditions such as cancer, reproducibly obtain the herbs, and authenticate and fractionate them to create a novel natural products library. Once they have authentic, reproducible components, they will be able to explore their biologic activity, or lack thereof, and to eventually conduct animal studies and human clinical trials with those herbal fractions found to be biologically active.

The project is one of nearly a dozen planning grants awarded by NCCAM to encourage partnerships between the U.S. and international research teams. Others include collaborations with institutions in India, China, Japan, Hong Kong, Korea, and the Republic of South Africa. The goal is to create international centers of excellence for studying traditional medical approaches as they are practiced in their countries of origin.

The boundaries of science
CAM research is not for the faint of heart. Efforts to scientifically validate traditional remedies push science to its limits. Even NCCAM recognizes that the double-blind, placebo-controlled clinical trial—the gold standard for testing drugs and conventional therapies—may not be the most appropriate or feasible for all CAM therapies.

The challenges are numerous. For example, some approaches—such as yoga, Ayurveda, and traditional Chinese medicine—are tailored to individual patients and, explains Eisenberg, “can’t always be given in a formulaic or cookbook fashion.” Moreover, some approaches rely on single therapies, whereas others require multiple therapies given simultaneously. Further confounding matters, some non-Western therapies are based on distinct diagnostic considerations, so that 10 patients with the same condition in the West (migraine or pneumonia, for instance) may have 10 different underlying diagnoses in the East. As a result, says Eisenberg, “you wouldn’t expect them to respond to the same single acupuncture point or herb.”

Add to this the lack of standardization, particularly among botanicals, and one may wonder how anyone has the stomach for such endeavors. Because botanicals are regulated as dietary supplements in the U.S., they are not subject to the same strict standards of purity, efficacy, and safety as drugs, and they may be contaminated with unwanted ingredients. Further, the concentration of active ingredients varies widely. So while it’s possible to isolate an herb, test it in a group of patients with a certain condition, and observe the results, such testing doesn’t fully answer the question of whether a given herb works for a given condition. “Embedded in that question is making sure you have the herb you think you have and demonstrating that if you get that herb again and reproducibly extract it, you can begin to understand the mechanism through which it is leading to some beneficial clinical outcome,” says Eisenberg. In addition, there are past_issues/Nov_Dec_2004ly no standards when it comes to dosing.

NCCAM has confronted many such problems. In the draft of its next five-year plan, it describes a litany of lessons learned the hard way and plans to avoid these pitfalls in the future. But while these obstacles loom large, Eisenberg believes they are not insurmountable. He and his colleagues in China and Japan are using high-tech platforms to identify fractions of herbs and combinations that are worth testing in animal models. Over time, if they succeed, their work will lead to a new means for conducting human clinical trials of herbal remedies.

Such multinational and interdisciplinary teams represent an important component of CAM research. To succeed, investigations should include well-trained methodologists, clinicians, and basic science researchers, as well as experts who practice the modality being tested.

Eisenberg reports that such teams are coming together with increasing frequency. “There’s a shared desire on the part of non-Western medical practitioners as well as Western scientists to learn from each other and share what we can to improve health outcomes and to advance scientific knowledge.”

Ironically, he believes it may be modern science that saves ancient practices from extinction. Traditional Chinese medicine no longer attracts the best and brightest of China’s youth. “My guess is that this observation may also apply to other non-Western cultures and their medical systems, which may unfortunately die out in a generation or two if there isn’t a give and take and sharing of research between East and West, modern and ancient healing traditions,” says Eisenberg. “And because the globe is increasingly a smaller and smaller village of sorts, our ability to understand each other’s medical approaches, learn from one another, and jointly validate those approaches which work and dismiss those that don’t will, over time, improve delivery of health care world wide. I’m also quite confident that along the way we will make discoveries that we could not anticipate. And this will also be a valued achievement.”