Part 3
Other aspects of phytopharmacological research
Although extensive knowledge and cumulative experience of the clinical uses of KM have been acquired from CHM, Japanese workers have made great contributions to the scientific understanding of KM in the last two decades. Every year, hundreds of scientific papers are published. Most support the application of KM. Similarly, many hundreds of CHMs have potent therapeutic effects.
The literature on research into the mode of action of medicinal herbs has documented well the low molecular-weight fractions, but the larger molecules, such as polysaccharides have come under study only recently (Yamada 1994b; Matsumoto & Yamada 1995).
The Kitasato team is researching the action of JTT polysaccharides at the cellular and intracellular level. For example recent work on Bupleurum has given valuable new findings. Bupleurum is a very common CHM, mainly to treat liver disease. Recently, bupleuran 2IIb, a pectic polysaccharide isolated from Bupleurum falcatum, was shown to up-regulate the expression of Fc-receptors (FcRs) on macrophages; this action was mediated by enhancing the transcription of both Fc-gamma RI and Fc-gamma RII genes (Matsumoto et al 1993).
The regulation of intracellular signal transduction pathways can be determined by measuring second messengers in response to the presence of specific inhibitors. Macrophages from the peritoneal cavity of mice were used to study whether protein kinase C and A (PKC and PKA) were involved in FcR up-regulation by bupleuran 2IIb. Neither the PKC inhibitor, 1-(5-isoquinolinylsulphonyI)-2-methylpiperazine dihydrochloride, nor the PKA inhibitor, N-[2-(methylamino)ethyl]-5-isoquinoliny-sulphonamide dihydrochloride, inhibited bupleuran 2IIb-induced up-regulation of FcR. However, when macrophages were treated with Ca-antagonist, 8-(diethylamino)-octyl-3,4,5-trimethoxybenzate hydrochloride, bupleuran 2IIb-induced up-regulation of FcR was inhibited in a dose-dependent manner. The two calmodulin antagonists, trifluoperazine and N-(6-aminohexyl)-5-chloro-1-naphthalensulphonamide hydrochloride also blocked the action. Also, fluorescence image analysis, using the Ca-sensitive dye, Fura-2, showed that bupleuran 2IIb induced a rapid increase in intracellular levels of Ca. These results suggest that bupleuran 2IIb induced the up-regulation of FcR on macrophages by a mechanism dependent on an increase in intracellular Ca2+, followed by activation of the calmodulin, but not by a PKC or PKA pathway (Matsumoto & Yamada 1995).
HM: Controversial issues and possible solutions
HM, as with WM, has negative/unresolved as well as positive/resolved aspects and the status will change (a Law of TCM). It is possible to make the changes positive. To do this, leaders and workers in the fields of science, medicine and national government need to recognize the disadvantages of HM and work to solve them. Some disadvantages and possible solutions will be discussed now.
The supply of raw herbal ingredients
Some important raw materials used in HM are found only in a few areas of the world and, thus, are in limited supply. Some animal-derived ingredients used in the east (such as monkey tissues, tiger bone, rhino- or elephant- horn, antler velvet from deer etc) are banned in the west on grounds of unnecessary cruelty to animals, or conservation of endangered species.
Some countries have specific national legislation which bans the use of certain ingredients, such as ruminant brain tissue, due to public fear of bovine spongiform encephalopathy; tiger bone, due to conservation policy etc. Solutions could include guaranteed exclusion of banned ingredients from the marketplace, research into natural propagation of the rarer permitted ingredients and in-vitro production of active ingredients or suitable alternatives. This could include use of biotechnology and genetic engineering to clarify the active components, or synthesize similar alternatives (Chaudhury 1995).
It would be useful also to study substitutes for some rare or special ingredients. It is warranted now to find good substitutes for certain human tissues (for example, human placenta is used in some HMs). Certain animal tissues (bone, horn, penis, testis, ovary etc) from domestic animals (buffalo, cattle, deer, pigs) might be used instead of similar tissues from rare or preserved species (tigers, primates, rhinos, elephants etc). Common tissues might be used instead of rare material (for example bovine bile instead of bovine gallstones.
It would also be useful to cultivate medicinal herbs which might have actions similar to much rarer or more expensive herbs, for example, Danhseng (Codonopsis pilosula) instead of ginseng.
Quality control
Used properly HM is very safe but, if overused, the ingredients used in HM also are toxic. Thus, great care is needed in their combinations and dosage. Quality control needs to be improved and increased (Chaudhury 1995; Dharmananda 1991).
The levels of active ingredients in the raw materials in HMs vary with time/place of collection, the parts of the plants used, methods of processing and other factors. For example, although the root is used, ginseng leaves contain more active compounds than the root (Dharmananda 1991; Sun et al 1992). At present, there is little or no quality control on the levels of active ingredients in the final prescriptions of many formulas. This is unacceptable to many professionals in WM.
A solution would be to develop guaranteed methods and standards of quality control. Product labelling and datasheets could be made mandatory. These should state clearly the dosage, the clinical indications, contraindications, side-effects, emergency procedures and/or antidotes (if known) in case of severe adverse reaction etc, as is the case with WMs.
Research is needed on the processing and purification of HMs. Decoctions usually are prepared by the patient from the dried crude formulas. Patient-errors may occur in the preparation and dosage of decoctions. They are bulky, hard to preserve and transport; they are tedious to decoct properly and may be unpalatable (Yamada 1994a). Unit-doses of pills or powders, made from the dried extracts, have many advantages over decoctions. Their preparation, purification and packaging as pillules and unit-doses would be beneficial. Sometimes, however, decoctions must be used. As a guide to doctors on their relative palatabilities, decocted KMs were submitted to a taste panel, who assigned a taste-rank score to each for the strength or weakness of the taste. A table of mean taste-ranks, with dosage guidelines is available (Kim et al 1995). Quality control should build on this work and see if flavouring agents, or other methods of preparation, could offset the more unpalatable tastes.
Registered versus unregistered medicines
Many countries, such as the United States and the European Union, make it difficult and expensive to register therapeutic drugs for use in humans or animals. A dossier on each formulation must list details of the type of animal, indications, dosage, contraindications, safety, toxicity studies, antidotes, labelling, levels of active ingredients, quality control procedures, shelf-life, residue levels, withholding time (in meat- and milk- animals) etc. These statements must be supported by research findings, especially by independent agencies.
HMs usually are unregistered as therapeutic products in most western countries. In the United Kingdom, at least 40 HMs are freely available without prescription (Chaudhury 1995). Use of unregistered products (or adverse interactions between registered and unregistered products) could present professionals with legal problems in the event of untoward (or adverse) effects in their patients. Most HMs used in animals are based on human prescriptions. Research is needed on their use in animals. Application of stringent rules to the main remedies or formulas used in HM would probably make it impossible to register them. Until then, most Veterinary Associations would not recognize HM as a valid therapy.
It would be unrealistic to expect western authorities and insurance companies to give a carte blanche to professionals to use anything they please as a medical therapy. There are at least possible solutions.
The State could adopt the Japanese medical model: to endorse the use of specific HMs in specific conditions by authorised professionals. It could authorise a list of HMs, mainly complex Formulas, validated as to their safety and efficacy by centuries of documentation and usage (Chaudhury 1995). The approved list could be drawn up in association with recognized experts in HM. Each State also could decide on what constitutes minimal competence before licensing the professionals. Use by registered professionals of Expert TCM Databases (see below) could qualify in that respect.
The State could licence the use and dosage of specific approved HMs in combination with accepted (conventional) therapies. Contraindications and adverse interactions between WMs and the approved HMs would need to be listed formally (Chaudhury 1995).
The State also could encourage the use of specific HMs as experimental unregistered health products or supplements. In that case, their use would require that the professional obtain from the client a written consent for their experimental use and an indemnity against claims for negligence or malpractice in the event of untoward reactions (Schwartz 1994).
How to develop HM further
WM is highly developed today. The prevalence of acute infectious diseases of humans and animals has fallen significantly since the discovery, development and use of antibiotics and vaccines, and the use of improved auxiliary techniques (intensive care, fluid therapy, dialysis, blood filtration etc). Also essential to this success are improved diagnostic screening techniques and overall improvement of personal- and food- hygiene, improved overall nutrition, housing and control of the environment etc.
However, drug-resistant "superbugs", especially Staphylococcus aureus, are becoming prevalent. These and some chronic infectious diseases, such as AIDS, viral hepatitis and bovine tuberculosis, are especially difficult to eradicate. Also, the prevalence of other chronic diseases, especially those related to stress, environmental pollution, immunosuppression etc. seems to be increasing.
TCM is underdeveloped, mainly through lack of adequate funding for basic and clinical research and also due to lack of good information for education and training of practitioners. Even so, complementary therapies, using HMs, are used widely in the United States and Europe and their use is growing (Otsuka 1988; Yamada 1994a; Micozzi 1995). Although some regard the scientific nature of TCM as inferior to WM, each system has its validity, its strengths and weaknesses. HM will continue to grow in popularity and use, as an adjunct to WM. TCM has great potential to prevent and cure many chronic diseases (Dharmananda 1991) but one can not expect TCM to make great impact in WM without a pro-active approach from both sides and greatly increased international inputs in funding for research, education and training in TCM.
Personal effort, group effort, the activities of interested organisations, teaching and training at university level and financial support from governments and industries are the main factors in the development of all sciences. Recent development in biotechnology has shown that. Although modern veterinary medicine in China is underdeveloped, all these factors are present. However, most other countries lack these factors. Fortunately, the developed countries may use their modern facilities in veterinary science and their educational systems to study and develop HM. Some suggestions to help such developments are presented elsewhere (Lin & Panzer 1994).
Easy access to expert information on HM is essential
Why do practitioners prescribe the drugs which they use daily? Apart from the constraints of the availability of the product(s) and the ability of the client to pay for them, most practitioners prescribe the best drug(s), or other therapies, that they know for the diagnosed problem(s). In other words, the key factors in prescribing the "best drug(s)" are knowledge (especially of diagnostics and therapeutics) and belief (that the prescription will give satisfactory results). In any medical system (WM or TCM) the knowledge and belief of the practitioner are conditioned by his/her culture and limited by his/her education and by ongoing access to credible information.
With some exceptions, expert use of HM requires fast, easy access to Oriental medical theory and the ways to select the most appropriate ingredients or formulas (Otsuka 1988). Busy WM professionals who wish to learn HM must face this problem. Most are unable or unwilling to take 1-3 years or more out of their practice or research to study the huge volume of novel data that must be learned and assimilated. Unless professionals in WM can access the data rapidly and reliably, they are unlikely to use HM, even on an experimental basis.
If they can be developed, expert Windows-based TCM software could offer solutions to the knowledge problem. User-friendly, expert, interactive PC-based databases could incorporate all the key aspects of TCM, HM, the relevant HM remedies and formulas, TCM Syndromes and Diagnosis. All of these could be cross-referenced to the equivalent WM syndromes and medications. Novice (but professional) users could key-in the clinical findings. The software could prompt the user to add other relevant data. A preliminary cross-matching of the input data with the database could activate prompts for further relevant input. The database could then display the TCM diagnosis and the indicated (and contraindicated) HMs etc. Such databases would enable professionals to key in the clinical signs, receive prompts on other signs and make a TCM diagnosis. On the basis of the diagnosis, the software would suggest appropriate treatments. In this way, naive professionals could use HM quickly and effectively, and alter the HMs with changes in the Syndrome or Sho. Further refinements could allow users to browse the various files for study purposes, to enter hypothetical clinical data for self-testing purposes etc.
Such databases could be efficient learning aids for inexperienced professionals, as has been demonstrated some years ago by an expert Database in WM, developed in Harvard Medical School. Such technology is available to professionals interested in homeopathy and certain aspects of AP, both complementary therapies which MSM professionals find very difficult to master.
"Chinese Herbal Medicine (Green Medicine, Version 1.1)" is a database for Apple MacIntosh and Windows PCs (Weber 1992). This seems to be the first attempt to put TCM at the fingertips of PC users. It contains a wealth of data on clinical signs and symptoms, TCM Syndromes, herbal actions, indications, CHM formulas and dosages. However, it needs major revision to make it faster, more user-friendly and more "intuitive".
Computers can store and recall information faster and more accurately than many humans. But, for best results, skilled humans must interpret the data; one should not rely on computers for basic medical knowledge any more than one should rely blindly on fixed herbal formulations as a cure for all ills. However, computers and formulations have one thing in common; both can help the doctor to help the patient to cure him/her self. Also, computers can help doctors to better manage and reinforce their medical knowledge and can stimulate them to master that knowledge. However, no matter how good they are, computers can not replace adequate medical knowledge and skill, nor can they replace compassion for and desire to heal the patient. Compassion, love, and service is at the core of healing.
Additional research
Further pharmacological experiments are needed to evaluate plant compounds as clinically useful medicines. Plant cell culture, chemical synthesis, or biotechnological production methods of the compounds, may be needed to obtain sufficient amounts for sampling purposes. In the chemical synthesis of medicinal compounds, structure-activity relationships should be considered in order to prepare compounds that are more active and safe, and which exhibit bioavailability. The search for new drugs from HMs is justified because of the long term clinical evidence of their clinical value in humans and animals. Such research proves the experimental applications of HMs to be true and helps to explain their clinical effects (Dharmananda 1991). As with WMs, some HMs are toxic. It may be necessary to check for undesirable residues or metabolites in food products from HM-treated animals, for example the level of plant alkaloids in milk, cheese, meat etc.
Future prospects
The main aim of all good medicine is to improve the quality of human or animal life. TCM and WM have this aim. Advantages of TCM are the lower costs and the absence of side-effects relative to those of WMs. Also, most HMs come from natural biologically renewable sources. Cultivation and processing of HMs could be a valuable source of income for developing countries.
Development of TCM on the Internet
Information Technology in Acupuncture and Traditional Chinese Medicine is discussed in detail elsewhere (Rogers 1998).
Western professionals who wish to learn or use complementary therapies often feel isolated. They may have few colleagues nearby with whom to exchange information. Internet Bulletin Boards on TCM could be developed on all aspects, including HM. The Internet, also called the electronic information superhighway, is an electronic, computer-based worldwide communication web. Via the Internet, those with sufficient money and computer-based technology can communicate, almost instantly, with colleagues anywhere in the world with similar interests.
HM Abstracts: Occidental researchers have great difficulty accessing information written in oriental languages and vice-versa. Advances in optical scanning devices allow printed data to be scanned in ASCII text into computer files. Advances in computer software now allow articles digitised in one language to be translated into another. Scanners, translation- and communications- technology could convert documents in any of the main languages into many other languages for uploading onto the Internet or CD ROM. Access to the these media could radically enhance the exchange of research and clinical data on HM. Development of specialist areas on the Internet for HM Research Abstracts and HM Clinical Abstracts would accelerate its development.
Register of drug reactions: Though most states have a formal reporting system to record adverse effects of medication (or their suspicions of them), professionals may have difficulty accessing the data. Also, they may not be able to check if data submitted by them were actually recorded. Requests to commercial companies for data on adverse reactions may be futile: because of vested interest, companies may deny or play down reported iatrogenic disease. The Internet could help to solve this problem: a password-protected Register of Drug Toxicity/Iatrogenic Disease would allow validated professionals to record (against their name) adverse reactions to specified drugs (WMs and/or HMs). Other professionals anywhere in the world, who have authorised access to the Internet register, could read those data anytime.
Discussion and Conclusions
Ancient and modern medicine each contain a blend of art and science, as do most successful systems of animal production, managemant and husbandry. In this paper, we had no time to discuss the many positive aspects of western science and technology in animal production and welfare. It has much to offer in areas of animal breeding and genetics (sire selection, sperm sexing, AI/embryo transfer, synchronisation etc), housing design, mechanisation, automation etc. Modern concepts of epidemiology, record-keeping, routine monitoring of weight gains and production indices, animal nutrition, mineral and vitamin supplementation, optimum management of pastures, conservation of high quality animal feedstuffs etc are most valuable. Microelectronic sensors, telemetry and recording equipment are cheaper than ever before. Remote sensing technology offers the possibility of cost-effective routine automated monitoring of physiological states, and early detection of pathological states.
However, on its own, western-style intensive farming, depends heavily on high inputs of expensive and dangerous chemicals. Consumer perceptions are that it can not produce the high quality of human food for which demand is increasing rapidly.
We suggest that more humane and considerate handling and management of animals will reduce their stress levels. We argue for a greater input of love, respect, compassion, and common sense into animal management. In most cases, this is an economic investment; animals that are cared for well are more contented; they produce more than animals roughly or poorly treated. This may involve a move towards less intensive production systems [a policy of the EU now], a reduced input of potent synthetic chemicals into the systems, and their replacement with natural and less toxic forms of prophylaxis and therapy. In this area, there is a huge potential for the incorporation of CHM into an integrated system which takes the best from the East and combines it with the best from the west.
Widespread research, development and use of HM, could save billions of dollars annually on the international cost of conventional drugs, hospitalisation and lost time at work. This would force major changes in the modern (western-oriented) pharmaceutical industry and in agricultural production. Initially at least, this could have serious effects on investment and employment. If the major pharmaceutical industries can be persuaded to diversify slowly into HM, they could save many old jobs and create new jobs. New areas of work would include biological research, breeding, refining, tending, processing and replenishing the herbs, researching the active principles, upgrading quality control, refining the combinations of medicines to eliminate any risk of toxicity or adverse side-effects, etc. Also, governments could reinvest their savings on drug-bills into improved systems of health care for all.
TCM and HM have been used empirically over thousands of years in billions of human and animal patients, and their use is increasing. Those facts, are strong evidence of their overall safety and efficacy. As discussed above, recent research, both clinical and basic, has confirmed these claims.
In contrast to WMs, properly used CHMs can be given for long periods with minimal or no adverse effects (Hsu 1982; Hosoya & Yamamura 1988; Dharmananda 1991; Chan et al 1993; Schwartz 1994; Yamada 1994a). Thus, OM/TCM/HM shows great promise, especially for sustainable use of medicinal resources (Lin et al 1995a).
The problems of TCM are due mainly to lack of easily accessible information and lack of funding. Their solution needs greatly increased inputs from researchers, clinicians, relevant industries and governments. These problems must be resolved if the advantages of both medical systems (TCM and WM) are to be put to better use internationally. Resolution of the problems would lead to the dawn of a new age of medicine and animal welfare. The integration of the best aspects of WM and TCM, would be safer, less expensive and more sustainable than is the case today.
Acknowledgements
We thank the National Science Council, Republic of China for financial support to Professor JH Lin (32056F), without which this article could not have been finished. We thank all the cited authors, especially Drs. A Ackerson, D Bensky, RR Chaudhury, S Dharmananda, PK Tsung, whose material was reproduced in summary form. Finally, we thank Ms. A Yamasaki for excellent clerical assistance.