In the midst of the winter of 2020–2021, infections and deaths from the novel coronavirus are peaking. At any given time, outbreaks are amplified in some regions more than others, with peaks and troughs shifting as viral population dynamics interact with human metapopulations, prompting waves of transmission that propagate around the globe. With each evening’s news report, the scale of biology is compactly demonstrated: a single virion, measuring one billionth of a meter (~10^–9 m) in diameter, becomes a part of a pandemic that influences humans across the Earth, a little over ten million meters (10⁷ m) in diameter.

In introductory science textbooks, biology is conceptually organized within nested scales: molecules within organelles within cells, organs and tissues within organisms, populations and communities within ecosystems, and so on. But this traditional hierarchy of biological organization – where lower scales fit neatly within higher ones – is challenged in nature: for example, complex microbial ecosystems can be nested within individual organisms, or even tissues (think of the community of symbiotic microorganisms inside the gut of a caddisfly). Although such phenomena require reconciliation within the existing hierarchy, the trope persists: in every ecology and biology textbook on our bookshelves, the “scaling” figure occurs in the first chapter. While its place in concept lies somewhere between the landscape and the globe, the macrosystem scale is – so far – absent from the standard hierarchy, yet it may appear there over time, if the promise of the field is realized.

The challenge of macrosystems biology is to conduct quantitative, interdisciplinary, and systems‐oriented research that helps us understand interconnected patterns and processes from regional to continental scales. Indeed, macrosystems biology seeks not a single holy grail but rather a collection of grails, requiring effective collaboration across population and community ecology, biogeography, and biogeochemistry, and possibly other disciplines, all at once. It’s no real surprise that, since its emergence approximately 10 years ago and in light of its inherent complexity, the discipline has yet to reach its full potential.

The papers in this Special Issue describe many of the ongoing challenges in macrosystems biology, and the development of new tools to address them. For example, Patrick et al. provide evidence that preserving biodiversity locally and regionally promotes macrosystem stability, implying that the reduced diversity affiliated with environmental homogenization can be a destabilizing force. Likewise, Ballantyne et al. describe regional‐scale overestimates of terrestrial CO₂ uptake as measured by eddy covariance towers, possibly resulting from bias in tower site selection, and possibly because carbon taken up in the tower footprint is transported through groundwater and released from lakes and streams, a rebalancing the towers do not detect. These are just two of multiple non‐mutually exclusive possibilities, and application of tools like data assimilation may help discern whether such mismatches across biological scales are errors, insights, or, more likely, both.

Other tools address the difficulty of clearly attributing cause when drivers interact and change over time, as discussed in this issue by Rollinson et al. as nonstationarity. The need to integrate data across scales is as trumpeted a truism as occurs in ecology, an imperative where novel approaches in data assimilation (like those described by Zipkin et al.) hold both promise in assessing models and making inferences, as well as challenges in minimizing bias.

Tromboni et al. explore how metacoupling applies to the field of macrosystems biology, simultaneously evaluating nearby and distant connections with both ecological and socioeconomic dimensions, while LaRue et al. analyze the language of and themes in macrosystems biology to demonstrate that working across scales in self‐identified macrosystem studies is actually quite similar to doing so in other ecological disciplines. In addition, Farrell et al. discuss the importance of honing skills in collaboration to tackle macroscale problems and a mismatch in the training required for macrosystem scientists and practitioners to succeed.

The traditional scaling hierarchy depicts how biology is organized across space spanning at least ~16 orders of magnitude, from the cell to the planet, but fails to demonstrate how influence transmits between scales. Success in the field of macrosystems biology could help reimagine how we depict biological scaling. Global pandemics can be framed as macrosystems phenomena, where some of the controls across scales are reasonably well understood (viral population dynamics), some more speculative (the food–wildlife–disease interface), and some seemingly intractable (the intersection of human behavior, politics, and public health). The reports in this Special Issue capture the current state of macrosystems biology as dynamic and filled with potential as the discipline moves into its next phase.

在2020-2021年冬季，新型冠状病毒的感染和死亡人数达到顶峰。在任何给定的时间，某些地区的暴发比其他地区的暴发要多，随着病毒种群动态与人类种群的相互作用，高峰和低谷也随之移动，从而促使传播波在全球传播。每天晚上的新闻报道中，生物学的规模都得到了紧凑的展示：直径为十亿分之一米（约^10–9 m）的单个病毒体成为影响整个地球人类的大流行的一部分，直径一千万米（10 ⁷ m）。

在入门级科学教科书中，生物学从概念上讲是在嵌套范围内组织的：细胞内细胞器内的分子，生物体内的器官和组织，生态系统内的种群和社区，等等。但是这种传统的生物组织层次结构-低尺度整洁地适合于高尺度-在自然界中受到挑战：例如，复杂的微生物生态系统可以嵌套在单个生物甚至组织中（例如肠道内的共生微生物群落）。球虫）。尽管这种现象需要在现有的层次结构中进行协调，但是这个问题仍然存在：在我们书架上的每本生态和生物学教科书中，“缩放”数字都出现在第一章中。虽然其概念上的位置位于景观和地球之间，

宏观系统生物学的挑战是进行定量的，跨学科的和面向系统的研究，以帮助我们了解从区域尺度到大陆尺度的相互联系的模式和过程。的确，宏观系统生物学寻求的不是一个单一的圣杯，而是一个grails的集合，需要一次跨人口与社区生态学，生物地理学，生物地球化学以及其他学科的有效合作。毫不奇怪，自大约十年前出现以来，鉴于其固有的复杂性，该学科尚未发挥其全部潜力。

本期特刊中的论文描述了宏观系统生物学中许多正在进行的挑战，以及开发了应对这些挑战的新工具。例如，Patrick等。提供的证据表明，在本地和区域范围内保护生物多样性可促进宏观系统的稳定性，这意味着与环境同质化相关的减少的多样性可能会破坏稳定。同样，Ballantyne等人。描述区域范围内对陆地CO _2的高估由涡度协方差塔测量的吸收，可能是由于塔位选择的偏见所致，也可能是因为塔足迹中吸收的碳通过地下水传输并从湖泊和溪流中释放出来，因此无法检测到塔的重新平衡。这些只是多种非互斥的可能性中的两种，而数据同化之类的工具的应用可能有助于辨别跨生物尺度的这种不匹配是错误，见识还是更可能是两者。

如Rollinson等人在本期杂志中所讨论的，其他工具可以解决在驾驶员互动和随时间变化时清楚地确定原因的困难。由于不稳定。跨尺度集成数据的需求像生态学一样被夸大了，这是当务之急，其中新的数据同化方法（如Zipkin等人描述的方法）在评估模型和做出推断方面都充满希望，同时也面临着挑战。减少偏见。

Tromboni等。探究元耦合如何应用于宏观系统生物学领域，同时评估具有生态和社会经济维度的近距离和远距离联系，而LaRue等人。分析宏观系统生物学的语言和主题，以证明在自我确定的宏观系统研究中跨尺度的工作实际上与在其他生态学科中的工作非常相似。另外，Farrell等人。讨论了珩磨技能在解决宏观问题方面的重要性，以及宏观系统科学家和实践者成功所需要的培训方面的不匹配。

传统的标度层次结构描述了从细胞到行星，生物学如何跨至少约16个数量级的空间组织，但未能证明影响力如何在标度之间传递。宏观系统生物学领域的成功可以帮助重新想象我们描述生物学尺度的方式。全球大流行可以被描述为宏观系统现象，其中一些跨规模的控制措施已被很好地理解（病毒种群动态），一些更具投机性（食物-野生生物-疾病的界面），有些似乎难以控制（人类行为的交叉点，政治和公共卫生）。本期特刊中的报告将宏观系统生物学的当前状态视为动态的，并随着该学科进入下一阶段而充满了潜力。