Perspective: All systems go

Various cultures have developed their own philosophies of science and, consequently, practices in medicine. The twentieth century has seemed to vindicate the Western approach, bringing huge advances in our understanding of physiology and biochemistry. This knowledge has fuelled the development of medicines and vaccines against countless diseases that had once wreaked havoc on humanity.

But in recent decades, the Western model has hit some turbulence. In particular, the concept of 'one disease — one target — one-size-fits-all' is shifting towards more personalized medicine tailored to individual patients, including the use of multiple therapeutic agents and the consideration of nutritional, psychological and lifestyle factors when deciding the best course of treatment. This shift in strategy has been most obvious in the prevention and management of chronic diseases such as diabetes and cardiovascular disease. The intellectual underpinnings for such a transition in medical practice are being laid in the discipline of systems science — and systems biology in the biomedical domain.

Systems science aims to understand both the connectivity and interdependency of individual components within a dynamic and non-linear system, as well as the properties that emerge at certain organizational levels. The relation to medicine is clear. Systems biology is particularly useful when it comes to describing homeostasis — the regulation of a system's internal environment to maintain a stable condition. In turn, the ability to cope with changing environments and stress is encompassed in the principle of allostasis — the physiological or behavioural changes required to stabilize the biological system.

JAN VAN DER GREEF

A flock of starlings relies on connectivity, dynamics and communication; these elements are embedded in TCM.

The concepts and practices of systems biology align very closely with those of traditional Asian medicine. Consider the very idea of 'health'. The current World Health Organization definition of the term is based on a 1948 consensus: “A state of complete physical, mental and social well-being and not merely the absence of disease or infirmity.” However, an emerging concept of health in the scientific literature describes an ability to adapt and self-manage in the face of social, physical and emotional challenges¹. This perspective has, of course, long been central to the concept of health in traditional Chinese medicine (TCM), which further includes spiritual fulfilment and a sense of individual well-being.

TCM is descriptive and phenomenological — it typically diagnoses patients using concepts based on the relationship between signs and symptoms, obtained through questioning, listening, palpation, visual inspection and smelling. In contrast, Western-style, modern medicine has mainly used single biomarkers to describe disease states, for example diagnosing type 2 diabetes by measuring glucose levels. But there is a growing realization in the West that single biomarkers are not enough. A better approach is to look at patterns of biomarker responses to a challenge. These data will provide insight into the resilience of allostatic mechanisms, and hence into a person's health, an approach not unlike the tenets of TCM.

In addition to giving Western medicine a basis for adopting some concepts of TCM, systems biology is also pushing the convergence from the other direction. Increasingly, TCM uses modern biochemical measurements and tools to refine or augment diagnostic descriptions. This is starting to facilitate the translation of TCM concepts into Western concepts based on biochemical, pathway or regulatory processes.

For instance, take diagnosis: the Sino-Dutch Centre for Preventive and Personalized Medicine in Zeist, the Netherlands, has conducted several studies that attempt to unify Eastern and Western diagnostic principles. In one such study of rheumatoid arthritis patients, selected according to Western (American College of Rheumatology) guidelines, TCM practitioners categorized patients into 'heat' or 'cold' pattern — based on the results of a questionnaire concerning joint issues, level and quality of pain, response to weather, and other symptoms such as fever and thirst, as well as the results of a tongue and pulse inspection. A systems biology investigation of the two groups found statistically significant differences between them in the expression of genes related to apoptosis and metabolite profiles².

Systems biology can also provide insight into the multi-target pharmacology of herbal formulae. A metabolomic study investigated changes in lipid levels in transgenic mice with mild hypercholesterolaemia given either a herbal concoction or a known drug (for example, rimonabant, atorvastatin or niacin). The study found that the herbal formula caused decreases in plasma cholesterol and triglycerides, and increases in high-density lipoprotein. How the herbal formula does this should help researchers pinpoint novel ways to treat metabolic disorders, especially those related to lifestyle³.

These early systems biology investigations suggest that the TCM method of qualitative subtyping could be of use in deciding the course of treatment for patients in modern medicine⁴, and provide momentum for the move towards personalized medicine. Furthermore the concept of health promotion alongside disease management will help to improve the current system of healthcare.

前景介绍：一应俱全——人体的所有系统都考虑

    不同的文化都发展出自身独有的科学哲学并随之应用到医学上。二十世纪我们在理解生理学和生物化学上的巨大进步似乎证明了西方方法的正确。这些知识刺激了针对曾肆虐人类的数不清的疾病的药物和疫苗的研发。

    但近几十年以来，西方模式遭遇了好些湍流。尤其是“一种疾病—一个目标—一个治疗方式应付所有人”的观念正转变为对个别病人更个体化的医疗，其中包括多种疗法的使用，营养、心理和生活方式方面的考虑，这些都决定着治疗是否起到最佳的效果。这种策略上的改变在预防和管理诸如糖尿病和心血管疾病等慢性病方面尤其明显。医疗实践上的这种转变需要以系统科学和生物医学领域中的系统生物学的积累为智力基础。

    系统科学的目标是理解在一个动态和非线形系统中的个体组成之间的联系和相关性，和在某些组织层面显现的性质。它和医学的关联是显而易见的。系统生物学在描述内稳态——一个系统内部环境保持稳定状态的规律运作——上尤其有用。其次是它在处理变化的环境和压力上的能力包含在“应变稳态allostasis”的原理上——生理上和行为上的改变是为了维持生物系统的平衡。

    系统生物学的思想和实践与那些亚洲传统医学非常匹配。细想“健康”这个特别的概念，世界卫生组织基于1948年的共识提出的最新定义是：“在身体上、精神上和社交幸福感上全面完好的状态，而不仅仅是没有疾病和虚弱”。然而在科学文献上的新兴观点则描述为“面对社会、身体和情绪上的挑战（challenge）能够适应和自我管理的能力”。这个观念其实很早就被中医当做健康的核心了，而中医对健康的理念还包括精神的满足和个人的幸福感。

    中医是描述性和唯象的——它使用望闻问切来获取体征和症状的信息，使用基于体征和症状相互关系的基本观念来诊断病人。相反，西方现代医学的模式主要是使用单个的生物指标去描述疾病的状态，例如通过测量尿糖含量来诊断2型糖尿病。然而在西方已经有越来越多人意识到单一的生物指标是不够的。更好的做法是去关注生物指标对挑战的应变模式。这些数据将有助于人们深刻理解应变稳态机制的恢复力，从而找出不同于中医理论的洞察人体健康的方法。

    为了提供西方医学一个采纳中医某些概念的基础，系统生物学也从另一个方向来推动这种结合。中医越来越多地使用现代的生化工具和测量指标去改善或扩大诊断的描述。通过生物化学的途径或者有规则的步骤来促使中医概念向西医概念的转换正在兴起。

    例如，位于荷兰Zeist的中-荷预防和个性化医疗中心已经着手开始了几项研究，尝试去统一东方和西方的诊断原则。其中一项关于类风湿性关节炎病人的研究，根据西医的标准（美国风湿病学学院制订）来筛选出的病人被中医师划分为”寒“或”热“——依据一份涉及关节问题、痛感和疼痛度、对天气的反应以及其它的症状例如发热和口渴、舌头和脉象等的调查问卷。对这两类人群的系统生物学研究表明他们在涉及细胞凋亡和代谢谱的基因表达上存在统计上的显著差异。

    系统生物学同样能使研究者深入了解多靶标中药方剂的药理学。一项代谢物组学的研究对患有轻度的高胆固醇血症的转基因老鼠给予中药方剂或一种已知的降脂药物（如利莫那班、阿托伐他汀或尼克酸）后进行了脂质水平的分析发现，中药方剂降低了血液中胆固醇和甘油三酯的水平，并且提高了高密度脂蛋白的含量。理解中药方剂是如何做到这一点的将有助于研究者查明新的途径来治疗代谢紊乱，特别是涉及生活方式上的。

    这些初期的系统生物学研究表明中医的定性分类方法能够应用到现代医学中，决定病人的治疗过程并提供向个体化医疗转变的动力。而伴随着疾病管理的养生观念也有助于现代医疗保健系统的改善。