Systems Biology-Based Diagnostic Principles as Pillars of the Bridge between Chinese and Western Medicine

Abstract

Innovative systems approaches to develop medicine and health care are emerging from the integration of Chinese and Western medicine strategies, philosophies and practices. The two medical systems are highly complementary as the reductionist aspects of Western medicine are favourable in acute disease situations and the holistic aspects of Chinese medicine offer more opportunities in chronic conditions and for prevention. In this article we argue that diagnosis plays a key role in building the bridge between Chinese and Western medicine. Recent advances in the study of health, healing, placebo effects and patient-physician interactions will be discussed pointing out the development of a system-based diagnosis. Especially, a system biology-based diagnosis can be used to capture phenotype information, leading towards a scientific basis for a more refined patient characterization, new diagnostic tools and personalized heath strategies. Subtyping of rheumatoid arthritis patients based on Chinese diagnostic principles is discussed as an example. New insights from this process of integrating Western and Chinese medicine will pave the way for a patient-centred health care ecosystem.

Key words

personalized medicine - Chinese medicine - diagnosis - systems biology - rheumatoid arthritis - metabolomics - phenotyping - targeted care

References

• 1 Marshall E. Science and the stimulus. Medicine under the microscope.  Science. 2009;  326 1183-1185
• 2 Vries G D. De ontwikkeling van wetenschap: Een inleiding in de wetenschapsfilosofie. Groningen; Wolters-Noordhoff 1984
• 3 Pearcy L T. Diagnosis as narrative in ancient literature.  Am J Philol. 1992;  113 595-616
• 4 Pagel W. Prognosis and diagnosis: a comparison of ancient and modern medicine.  J Warburg Inst. 1939;  2 382-398
• 5 Hua-Ching N. The book of changes and the unchanging truth, 2nd edition. Los Angeles; SevenStar Communications 1999
• 6 Schroën J. Non-linear dynamics and Chinese medicine: an essay on research models, TCM and recent changes in modern scientific philosophy.  Clin Acupunct Orient Med. 2002;  3 92-98
• 7 Ni M. The Yellow Emperor's Classic of Medicine: A New Translation of the Neijing Suwen with Commentary, 1st edition. Boston; Shambhala 1995: 316
• 8 Wilber K. The marriage of sense and soul: integrating science and religion. Reprint. New York; Random House 1999
• 9 Hahn R A, Gaines A D. Physicians of Western medicine. Berlin; Springer 1985
• 10 Capra F. The hidden connections: integrating the biological, cognitive, and social dimensions of life into a science of sustainability. New York; Doubleday 2002
• 11 Antonovsky A. Unraveling the mystery of health. How people manage stress and stay well. San Francisco; Jossey-Bass 1987
• 12 Lindström B, Eriksson M. Salutogenesis.  J Epidemiol Community Health. 2005;  59 440-442
• 13 Wang M, Lamers R J A N, Korthout H A A J, van Nesselrooij J H J, Witkamp R F, van der Heijden R, Voshol P J, Havekes L M, Verpoorte R, van der Greef J. Metabolomics in the context of systems biology: bridging traditional Chinese medicine and molecular pharmacology.  Phytother Res. 2005;  19 173-182
• 14 Van der Greef J, Martin S, Juhasz P, Adourian A, Plasterer T, Verheij E R, McBurney R N. The art and practice of systems biology in medicine: mapping patterns of relationships.  J Proteome Res. 2007;  6 1540-1559
• 15 Clish C B, Davidov E, Oresic M, Plasterer T N, Lavine G, Londo T, Meys M, Snell P, Stochaj W, Adourian A, Zhang X, Morel N, Neumann E, Verheij E, Vogels J T W E, Havekes L M, Afeyan N, Regnier F, van der Greef J, Naylor S. Integrative biological analysis of the APOE*3-leiden transgenic mouse.  OMICS. 2004;  8 3-13
• 16 Wang J, van der Heijden R, Spruit S, Hankemeier T, Chan K, van der Greef J, Xu G, Wang M. Quality and safety of Chinese herbal medicines guided by a systems biology perspective.  J Ethnopharmacol. 2009;  126 31-41
• 17 Chang W T, Thissen U, Ehlert K A, Koek M M, Jellema R H, Hankemeier T, van der Greef J, Wang M. Effects of growth conditions and processing on Ehmannia glutinosa using fingerprint strategy.  Planta Med. 2006;  72 458-467
• 18 Callard R, George A J, Stark J. Cytokines, chaos, and complexity.  Immunity. 1999;  11 507-513
• 19 Higgins J P. Nonlinear systems in medicine.  Yale J Biol Med. 2002;  75 247-260
• 20 Van der Greef J, Stroobant P, van der Heijden R. The role of analytical sciences in medical systems biology.  Curr Opin Chem Biol. 2004;  8 559-565
• 21 Kwee S H, Tan H H, Marsman A, Wauters C. The effect of Chinese herbal medicines (CHM) on menopausal symptoms compared to hormone replacement therapy (HRT) and placebo.  Maturitas. 2007;  58 83-90
• 22 Van der Greef J. Systems biology, connectivity and the future of medicine.  Syst Biol. 2005;  152 174-178
• 23 Van der Greef J, Hankemeier T, McBurney R N. Metabolomics-based systems biology and personalized medicine: moving towards n = 1 clinical trials?.  Pharmacogenomics. 2006;  7 1087-1094
• 24 Tolle E. The power of now. Novato; New World Library 2004
• 25 Wilber K. Integral medicine: a noetic reader. Available at. http://wilber.shambhala.com/html/misc/intergal-med.pdf Accessed January 21, 2010
• 26 Lovelock J E, Margulis L. Atmospheric homeostasis by and for the biosphere – the Gaia hypothesis.  Tellus. 1974;  26 2-10
• 27 Kirsch I, Sapirstein G. Listening to Prozac but hearing placebo: A meta-analysis of antidepressant medication.  Prev Treat. 1998;  1 0002
• 28 Kirsch I, Deacon B J, Huedo-Medina T B, Scoboria A, Moore T J, Johnson B T. Initial severity and antidepressant benefits: a meta-analysis of data submitted to the food and drug administration.  PLoS Med. 2002;  5 260-268
• 29 Walach H, Sadaghiani C, Dehm C, Bierman D J. The therapeutic effect of clinical trials: understanding placebo response rates in clinical trials – a secondary analysis.  BMC Med Res Methodol. 2005;  5 26
• 30 Walach H, Falkenberg T, Fonnebo V, Lewith G, Jonas W B. Circular instead of hierarchical: methodological principles for the evaluation of complex interventions.  BMC Med Res Methodol. 2006;  6 29
• 31 Moerman D E, Jonas W B. Deconstructing the placebo effect and finding the meaning response.  Ann Intern Med. 2002;  136 471-476
• 32 Giordano J. Spirituality, suffering, and the self.  Mind and Matter. 2008;  6 179-191
• 33 Kohls N, Walach H, Lewith G. The impact of positive and negative spiritual experiences on distress and the moderating role of mindfulness.  Arch Psychol Relig. 2009;  31 357-374
• 34 Kohls N, Sauer S, Walach H. Facets of mindfulness – results of an online study investigating the Frieburg mindfulness inventory.  Pers Individ Dif. 2009;  46 224-230
• 35 Benedetti F. Mechanisms of placebo and placebo-related effects across diseases and treatments.  Annu Rev Pharmacol Toxicol. 2008;  48 33-60
• 36 Benedetti F, Lanotte M, Colloca L, Drucati A, Zibetti M, Lopiano L. Electrophysiological properties of thalamic, subthalamic and nigral neurons during the anti-parkinsonian placebo response.  J Physiol. 2009;  587 3869-3883
• 37 Enck P, Benedetti F, Schedlowski M. New insights into the placebo and nocebo responses.  Neuron Rev. 2008;  59 195-206
• 38 Walach H, Jonas W B. Placebo research: the evidence base for harnessing self-healing capacities.  J Altern Complement Med. 2004;  10 (S1) s103-s112
• 39 Scharmer C O. Theory U: leading from the future as it emerges. Cambridge, MA; The Society for Organizational Learning 2007
• 40 Van der Greef J, McBurney R N. Innovation: Rescuing drug discovery: in vivo systems pathology and systems pharmacology.  Nat Rev Drug Discov. 2005;  4 961-967
• 41 Symmons D P M. Epidemiology of rheumatoid arthritis: determinants of onset, persistence and outcome.  Best Pract Res Clin Rheumatol. 2002;  16 707-722
• 42 Hochberg M C, Silman A J, Smolen J S, Weinblatt M E, Weisman M H. Rheumatology. Mosby; Elsevier Limited 2008
• 43 Welsing P M J, Fransen J, van Riel P L C M. Is the disease course of rheumatoid arthritis becoming milder? Time trends since 1985 in an inception cohort of early rheumatoid arthritis.  Arthritis Rheum. 2005;  52 2616-2624
• 44 Bridges S L. Personalized medicine in rheumatoid arthritis: hopes and challenges.  Bull NYU Hosp Jt Dis. 2007;  65 174-177
• 45 Anderson J J, Wells G, Verhoeven A C, Felson D T. Factors predicting response to treatment in rheumatoid arthritis: the importance of disease duration.  Arthritis Rheum. 2000;  43 22-29
• 46 Smolen J S, Aletaha D. Challenges of predicting treatment response in patients with rheumatoid arthritis.  Nat Clin Pract Rheumatol. 2005;  1 62-63
• 47 Gaston J S H. Cytokines in arthritis – the 'big numbers' move centre stage.  Rheumatology (Oxford). 2008;  47 8-12
• 48 Lundy S K, Sarkar S, Tesmer L A, Fox D A. Cells of the synovium in rheumatoid arthritis. T lymphocytes.  Arthritis Res Ther. 2007;  9 202
• 49 Van der Helm-van Mil A H M, Huizinga T W J, de Vries R R P, Toes R E M. Emerging patterns of risk factor make-up enable subclassification of rheumatoid arthritis.  Arthritis Rheum. 2007;  56 1728-1735
• 50 Van der Helm-van Mil A H M, Verpoort K N, Breedveld F C, Toes R E M, Huizinga T W J. Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis.  Arthritis Res Ther. 2005;  7 R949-R958
• 51 Van der Pouw Kraan T C T M, Wijbrandts C A, van Baarsen L G M, Voskuyl A E, Rustenburg F, Baggen J M, Ibrahim S M, Fero M, Dijkmans B A C, Tak P P, Verweij C L. Rheumatoid arthritis subtypes identified by genomic profiling of peripheral blood cells: assignment of a type I interferon signature in a subpopulation of patients.  Ann Rheum Dis. 2007;  66 1008-1014
• 52 Glocker M O, Guthke R, Kekow J, Thiesen H J. Rheumatoid arthritis, a complex multifactorial disease: on the way toward individualized medicine.  Med Res Rev. 2006;  26 63-87
• 53 Arnett F C, Edworthy S M, Bloch D A, McShane D J, Fries J F, Cooper N S, Healey L A, Kaplan S R, Liang M H, Luthra H S, Medsger T A, Mitchell D M, Neustadt D H, Pinals R S, Schaller J G, Sharp J T, Wilder R L, Hunder G G. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis.  Arthritis Rheum. 1988;  31 315-324
• 54 Vangermeersch L. Bi-syndromes. Brussels; Satas 1994
• 55 Maciocia G. The foundations of Chinese medicine: a comprehensive text for acupuncturists and herbalists, 2nd edition. Kidlington; Churchill Livingstone 2005
• 56 Tao X, Younger J, Fan F Z, Wang B, Lipsky P E. Benefit of an extract of Tripterygium wilfordii Hook F in patients with rheumatoid arthritis: a double-blind, placebo-controlled study.  Arthritis Rheum. 2002;  46 1735-1743
• 57 Gu W Z, Brandwein S R, Banerjee S. Inhibition of type II collagen induced arthritis in mice by an immunosuppressive extract of Tripterygium wilfordii Hook f.  J Rheumatol. 1992;  19 682-688
• 58 Li E K, Tam L, Wong C K, Li W C, Lam C W K, Wachtel-Galor S, Benzie I F F, Bao Y X, Leung P C, Tomlinson B. Safety and efficacy of Ganoderma lucidum (lingzhi) and San Miao San supplementation in patients with rheumatoid arthritis: a double-blind, randomized, placebo-controlled pilot trial.  Arthritis Rheum. 2007;  57 1143-1150
• 59 Tong L, Moudgil K. Celastrus aculeatus Merr. suppresses the induction and progression of autoimmune arthritis by modulating immune response to heat-shock protein 65.  Arthritis Res Ther. 2007;  9 R70
• 60 Chen X, Oppenheim J J, Howard O M Z. Chemokines and chemokine receptors as novel therapeutic targets in rheumatoid arthritis (RA): inhibitory effects of traditional Chinese medicinal components.  Cell Mol Immunol. 2004;  1 336-342
• 61 He Y, Lu A, Zha Y, Yan X, Song Y, Zeng S, Liu W, Zhu W, Su L, Feng X, Qian X, Lu C. Correlations between symptoms as assessed in traditional Chinese medicine (TCM) and ACR20 efficacy response: a comparison study in 396 patients with rheumatoid arthritis treated with TCM or Western medicine.  J Clin Rheumatol. 2007;  13 317-321
• 62 Kamada T, Kawai S. An algorithm for drawing general undirected graphs.  Inf Process Lett. 1989;  31 7-15
• 63 Viswanathan G A, Seto J, Patil S, Nudelman G, Sealfon S C. Getting started in biological pathway construction and analysis.  PLoS Comput Biol. 2008;  4 e16
• 64 Beers M H. The Merck manual, 18th edition. Whitehouse Station; Merck 2006
• 65 Van Wietmarschen H A, Yuan K, Lu C, Gao P, Wang J, Xiao C, Yan X, Wang M, Schroen J, Lu A, Xu G, van der Greef J. Systems biology guided by Chinese medicine reveals new markers for subtyping rheumatoid arthritis patients.  J Clin Rheumatol. 2009;  15 330-337
• 66 Zhang G G, Lee W, Bausell B, Lao L, Handwerger B, Berman B. Variability in the traditional Chinese medicine (TCM) diagnoses and herbal prescriptions provided by three TCM practitioners for 40 patients with rheumatoid arthritis.  J Altern Complement Med. 2005;  11 415-421
• 67 Jiang W. Therapeutic wisdom in traditional Chinese medicine: a perspective from modern science.  Trends Pharmacol Sci. 2005;  26 558-563
• 68 Li S, Zhang Z Q, Wu L J, Wang Y Y. Understanding ZHENG in traditional Chinese medicine in the context of neuro-endocrine-immune network.  IET Syst Biol. 2007;  1 51-60
• 69 Capellino S, Straub R H. Neuroendocrine immune pathways in chronic arthritis.  Best Pract Res Clin Rheumatol. 2008;  22 285-297
• 70 Czura J, Tracey K J. Autonomic neural regulation of immunity.  J Intern Med. 2005;  257 156-166
• 71 Jackson D B. Clinical and economic impact of the nonresponder phenomenon – implications for systems based discovery.  Drug Discov Today. 2009;  14 380-385

1 Each of these authors has equally contributed to this paper.