Alternative And Conventional Biomedical Research: A Creative Synergy

Editor's Note: This first part of a two-part series charts the shared ground between research into alternative medical therapies and basic biomedical research. Increasingly, researchers are using powerful cellular and molecular tools to uncover biochemical pathways that may, for example, explain increasingly evident mind-body connections in health and illness. The second part, to appear in the March 21 issue, will explore efforts to bring rigorous methodologies to alternative medicine and the roles being played by private foundations and medical schools in promoting new collaborations between alternative and establishment medicine. Despite tight budgeting in many sectors of biomedical research, the fledgling Office of Alternative Medicine (OAM) at the National Institutes of Health recently learned it is slated for a big financial uplift. In each of its first two years of existence, 1992 and 1993, the office received $2 million; for fiscal year 1994, however, President Bill Clinton requested and received $3.5 million. Although just a "drop in the bucket" of NIH's $11 billion overall budget, as OAM spokesman Jim Bryant notes, it is still a significant and symbolic increase for the young, high-profile office--likely to mean more money for grants. The jump in funding at OAM is indicative of the rising interest in and support for research in alternative medicine in many established biomedical settings, according to scientists and officials. Teaching programs also are in place or planned at several top medical schools. The establishment of such programs suggests that tomorrow's biomedical professionals may be open to new categories of inquiry that fall outside of what currently is considered mainstream biomedical investigation. For example, among the exploratory grants announced by OAM for 1994 were support for a Medical College of Ohio study of massage therapy to counter HIV; a Pennsylvania State University College of Medicine investigation of music therapy for psychosocial adjustment after brain surgery; research into dance/movement therapy for cystic fibrosis at Hahnemann University in Philadelphia; a Harvard Medical School exploration of hatha yoga for illicit drug use; a University of Miami School of Medicine study of massage therapy for HIV-exposed infants; a Southern Illinois University School of Medicine examination of ayurvedic herbals for Parkinson's disease; Northwestern University research into T'ai Chi to treat mild balance disorders; and a study of prayer intervention against drug abuse at the University of New Mexico. Several private foundations are also funding innovative work in these areas. And while most of the research is clinical or outcomes-oriented investigation, a synergy is developing with a number of basic science disciplines, some brand new, as questions arise about the underlying biochemical mechanisms of, for example, demonstrable mind-body interactions. The field is not easily defined. Many researchers say simply that alternative medicine comprises those medical practices that are not commonly taught or used in Western medicine. Many of the techniques now undergoing scientific scrutiny in OAM-sponsored studies come originally from ancient traditions practiced in China and India. One working definition of alternative medicine might be seen in six categories of grants currently offered by OAM: diet, nutrition, and lifestyle; mind/body control; traditional and ethnomedicine; structural manipulation and energetic therapies; bioelectric applications; and pharmacological and biological treatments. In 1993, 30 grants in these areas were awarded by OAM. The grants were small compared with other NIH awards; the top dollar amount was $30,000. Other agencies, including the National Heart, Lung, and Blood Institute (NHLBI), National Institute on Drug Abuse (NIDA), National Institute of Allergy and Infectious Diseases (NIAID), and National Cancer Institute (NCI), also have funded research into these nontraditional studies. A number of researchers in the field, however, say there is more to the concept of alternative medicine than its simply being unconventional; they claim that alternative medicine techniques share an integrative approach to human health that has been lost in much of Western medical practice. As such, they say, alternative medicine represents something of a corrective, whole- body view to the conventional, specialized approach of biomedical science. "It comes down to an old-fashioned word, which is physiology," says Candace Pert, a psychopharmacologist with Peptide Research, a Rockville, Md., consulting firm. Pert's research has detailed the ways in which messenger molecules, such as neuropeptides, and their receptors extensively interlink the brain, the immune system, and the endocrine system. The result is a seamless, communicating whole of the brain and body, she says, an information network with properties synonymous with the usual concept of mind. "The brain is not the mind," Pert says. "The molecules of the brain and the body are a manifestation of mind. But they're also just molecules and bands on gels." Pert, who is also a visiting professor with the Center for Molecular and Behavioral Neuroscience at Rutgers University in New Brunswick, N.J., prefers to speak of complementary--or interdisciplinary medicine--as opposed to alternative medicine. The integrative aspects of the new areas of study are crucial, in her view. "These separate disciplines make it difficult to make progress," Pert says. "I think we're moving toward a much more interdisciplinary way of looking at things." Other investigators agree that some of the new fields related to alternative medicine appear to be building bridges between fields. Researchers such as Pert say this aspect of their new disciplines mirrors the growing links they are discovering among major body systems, such as the nervous, immune, and endocrine systems. These disciplines include, for instance, psychopharmacology and psychoneuroimmunology. "The field of psychoneuroimmunology, as a scientific discipline-- and I'm not talking about people who hang crystals from their rear-view mirrors, I'm talking about hard-core research--is showing that the nervous system and the immune system communicate with each other massively, extensively, and continuously," says David L. Felten, a professor of neurobiology and anatomy at the University of Rochester School of Medicine in New York. "There is as much a basis for biological signaling between these two systems as there is within each of the systems," Felten adds. "And, therefore, while it may have appeared that it was alternative medicine to begin with, I don't view it as alternative medicine. I view it as standard physiology, pharmacology, and neurotransmission." ALTERNATIVE MEDICINE: INFLUENTIAL PUBLICATIONS Two papers published in the past several years have served to stimulate widespread interest in alternative medicine. One was a study by Stanford University researcher David Spiegel and colleagues (Lancet, 2[8668]:888-91, Oct. 14, 1989). Spiegel divided 86 women with metastasized breast cancer into two groups. Both groups received standard medical care, but one also participated in group therapy. Originally, Spiegel expected the study to show little, if any, effect from the psychosocial support. To his surprise, he found that the women receiving group therapy lived an average of almost twice as long as those in the control group, 36.6 months vs. 18.9 months. In fact, after 10 years, only three women remained alive--all from the therapy group. The other study that captured broad interest was published by David Eisenberg of Harvard Medical School and Beth Israel Hospital in Boston (D. Eisenberg, et al., New England Journal of Medicine, 328[4]:246-52, Jan. 28, 1993). In a survey of about 1,500 people, Eisenberg found that one in three reported using alternative therapies in the previous year, a much higher rate of use than had previously been estimated. Most respondents said they also went to conventional physicians with their medical complaints, but did not tell their physicians about their use of alternative therapies. In addition, use of such therapies correlated with higher incomes and education levels, Eisenberg found. --F.H. Not everyone, however, sees significant connections emerging between alternative medicine and basic biomedical sciences--at least not yet. They say that the gap between the two is real and substantial, and that it will not soon be bridged. "The OAM is starting with clinical research of a very basic kind," says Barrie R. Cassileth, an adjunct professor of medicine at the University of North Carolina, Chapel Hill, and at Duke University, Durham, N.C. "Once some positive results emerge--if indeed there are any positive results--then people will start looking into mechanisms. But most of the regimens and therapies being investigated will be very difficult to examine in terms of underlying processes and principles." How strong the links between alternative medicine and conventional biomedicine appear to an individual depends very much on how each area is defined, and there is a distinct lack of consensus. Moreover, not all treatments in these categories are likely to interact productively with basic scientific disciplines, according to researchers, especially not in the near term. In some areas, developing a rigorous methodology to test efficacy alone will be difficult, without addressing possible explanations through better understanding of the body's biochemistry. In other areas--acupuncture, for example--alternative techniques are finding converts in conventional medicine and the underlying mechanisms are now being investigated. Cassileth, for instance, does not include such practices as biofeedback and acupuncture under the heading of alternative medicine. These, she says, are nearly mainstream, at this point. She also does not consider psychoneuroimmunology, which works to define the biochemical interactions between the nervous and immune systems, to be alternative medicine. "We now know that these various systems are interconnected," Cassileth says. "That's not really alternative medicine." "There is substantial demonstration that acupuncture is effective in certain situations, yet we don't know how acupuncture works," says Fredi Kronenberg, director of the Richard and Hinda Rosenthal Center for Alternative/Complementary Medicine at the Columbia University College of Physicians and Surgeons in New York. "People are beginning to explore this, looking into whether there are endorphins involved, looking into the biochemistry. But we don't have the physiology of acupuncture well defined." Mind-body medicine is, perhaps, the area in which biological discoveries are most likely to correlate with alternative medical techniques, scientists say. For example, Rochester's Felten has carefully mapped a number of important mind-body connections. "We've been able to show," Felten says, "that noradrenergic nerves, coming from the sympathetic nervous system and hard-wired back into the central nervous system, actually have terminal endings, not just on smooth muscles and blood vessels, but also deep in the parenchyma of lymphoid organs, ending among both developing and mature cells of the immune system." He adds: "So, there is an extensive communication network, going from the central nervous system to the immune system, with real functional consequences." Among the implications, he says, is that the mind may be able to directly control aspects of the immune system. "There is the possibility that, using behavioral interventions, we can influence the signaling, the transmitters, and the hormones every bit as much as if we gave pharmacological agents," Felten says. In discussing behavioral intervention, he refers to such treatments as stress- reduction therapies or peer support and counseling. Such inquiries may have far-reaching effects on conventional biomedicine, say some researchers. "You cannot ignore mind and have anything relevant to say about health and disease," says Peptide Research's Pert. "Health and disease have everything to do with emotions. They're not just some optional thing. And that really breaks the paradigm of Western medicine." Because of its affiliation with the prestigious NIH, OAM has received a great deal of attention since its inception. Some scientists, however, say that OAM was thrust upon NIH by Congress and was not the result of scientific interest within the institutes. "OAM came about not because of anyone in the scientific community believing that these things had merit or that they were appropriate for NIH to involve itself in," says William Jarvis, a professor of health promotion and education at Loma Linda University School of Public Health and president of the National Council Against Health Fraud, both based in Loma Linda, Calif. "Certainly no one at NIH thought that. "Rather, it was because of political influence." Sen. Tom Harkin (D-Iowa), chairman of the subcommittee on labor, health, and human services and education of the House Appropriations Committee, which oversees the NIH budget, pressed strongly for the office's creation. Former Iowa congressman Berkeley Bedell, who claimed he had had success with an alternative medical intervention for his prostate cancer, lobbied Harkin on the issue, according to OAM spokesman Bryant. Harkin himself took bee pollen therapy for allergies with some success, as well, Bryant says. A number of other institutes at NIH, however, are also providing substantial funding for research that might otherwise be considered alternative medicine, according to Joseph J. Jacobs, director of OAM. This has been the case for a decade or more. NHLBI, for example, funded the work of Dean Ornish, director of the Preventive Medicine Research Institute in Sausalito, Calif., Jacobs says. Ornish developed and clinically tested a successful heart disease reversal program based on a vegetarian diet, meditation, exercise, and support groups. As a sign, perhaps, of the growing acceptance of such therapies as a part of established medicine, Ornish's program was recently approved for reimbursement by a major insurer. NHLBI is also funding a project at the Maharishi International University in Fairfield, Iowa, to study the effects of transcendental meditation on hypertension, he says. NIDA has funded projects looking at the use of acupuncture in treating substance abuse, Jacobs says, and NIAID is interested in the use of acupuncture to help people with AIDS who have peripheral neuropathy. The relationship between nutrition and cancer prevention is being studied at NCI, as well. Overall, Jacobs says, this increasing activity represents important shifts in perspective on the parts of both patients and clinicians. "There's a general awareness among clinicians that there are significant limitations in conventional medicine," Jacobs says, "especially if you're a primary-care practitioner, on the front line, dealing with chronic and debilitating diseases and the management of them." At the same time, he says, patients often have access to research findings as they are published. This results in their participating, to a degree, in the ongoing controversies in medicine. "Physicians are no longer the high priests of this mystery," Jacobs says. "Everybody has access to information now." Another factor in bringing alternative medicine to the fore at this time is doctors' inability to counter such highly publicized, intractable diseases as AIDS, according to Sue Estroff, a medical anthropologist and an associate professor of social medicine at the University of North Carolina School of Medicine in Chapel Hill. "People with AIDS, since there seems to be little hope for them [with conventional medicine], have very consistently used all kinds of other therapies," Estroff says, "and I think it's forcing neurologists and infectious disease researchers into closer contact with these alternative therapies than they've ever been in their clinical and research lives. Some of them have had conversion experiences, where they've seen a patient's T cells do better than they should have. These are the most basic of the basic science types, those who would be the most skeptical." Estroff met recently with Jacobs to discuss ways that medical anthropologists, many of whom have experience assessing non- Western healing systems and views of illness, might contribute to OAM's efforts. "There are complicated analyses of, for example, the physiological and biochemical effects of three days of dancing and drum beats," she says. As interest in the area continues to grow, collaborations and interactions between the researchers and practitioners of alternative medicine are expected to increase, too. The two groups may be able to mutually influence each other, giving greater scientific rigor to studies of alternative therapies and illness models, while simultaneously serving as a source of fresh insights for at least some segments of the conventional research community. "One of the real benefits to come from this field [of psychoneuroimmunology] is not only the reductionist delving into mechanisms, but then the synthesis that's required, also," says Rochester's Felten. "It's no longer acceptable just to look at, for example, neurotransmitter effects on a cloned cell line. That's nice, and it will give you some clues. But then the next step is to take that back in vivo and ask what it means to the well-being of a mouse--or of a human. "We're actually able to span from a level of cellular and molecular biology on the one hand, all the way to the more holistic, in vivo, physiologic approach on the other," Felten adds. "In fact, in this field, neither of those approaches by itself is suitable and satisfactory alone." The combination of new and old medical perspectives holds great promise, Felten says: "It's an exciting new aspect of medicine that we've had our heads in the sand over for many, many years. Now, all of a sudden, we've reinvented the wheel; but we've reinvented it at a time when the cellular and molecular technology is such that we can really go places with it."

Alternative And Conventional Biomedical Research: A Creative Synergy

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