editorial We encourage our readers to consider whether principles of measurement science could have a role to play in their own disciplines. ost scientists receive little or no systematically and can vary between less consistent and predictable than that of formal training in metrology—the disciplines. chemical or physical ones. Mscience of measurement—and Defining the uncertainty of a Yet there is substantial value in biological indeed may not even be aware that this is measurement is a core activity of metrology. reference or calibration materials. They a discipline in itself. Though its tenets are For physical measurements there are can help tease out technical and biological not always directly applicable to the messy established practices for uncertainty variation in biological measurements multivariate world of biological research, analysis. Extending an uncertainty and can be used to compare results from metrology is due more attention from analysis to biological experiments is not orthogonal approaches. As attested in the biologists. straightforward, as there are often many pages of this journal, reference materials Metrology formalizes the practice of variables, several of them uncontrolled and can provide a benchmark for comparisons making a reliable measurement. Historically, probably even unknown, that can affect the of methods and tools, sometimes in an the discipline arose around the definition of outcome. Nevertheless, the principles of interlaboratory format. Simple known measurement units, and this remains a key uncertainty analysis could provide biologists mixtures of proteins or protein complexes, component. As a consequence, metrology with at least a heuristic for assessing how for instance, can help one gauge the shapes not only scientific activities but also confident one can be in a measurement, performance of mass spectrometric trade, air travel, satellite communication— as argued by researchers at the National pipelines. Fluorophore-labeled molecular anything that relies on agreed-upon Institute for Standards and Technology rulers built on DNA origami can be used to systems for measuring the physical world. (NIST), the US national metrological compare the resolving power of microscopes The importance of standard units has institute, in papers published in 2014 in and nanoscopes. indeed been recognized for a long time: in Nature Methods and more recently in PLoS These are relatively early days for the roughly 800 ad, Charlemagne attempted to Biology. Considering and testing sources of development of widespread, standardized standardize units of length, for instance, and uncertainty in a biological measurement also biological reference materials distributed much earlier examples can be found as well. gives scientists a better understanding of the by national metrological institutes. NIST, But it was not until the late 18th century, variables involved. via the Genome in a Bottle Consortium, in the wake of the French Revolution, that As has often been pointed out, if one does provides five well-characterized human states began to adopt standard units of an experiment twice and gets a different genomes that laboratories can use as length and weight. result each time, the likelihood is strong, reference materials to check the quality In the late 19th century, the Treaty of especially in complex biological systems, of DNA sequencing; these activities are the Meter, signed in Paris by 17 member that one has inadvertently done a different intended to extend to benchmarking states, established the Bureau International experiment (i.e., that some variable changed analytical approaches like variant calling. des Poids et Mesures (BIPM). This body from the first to the second attempt). The vanguard of applying metrological was at first set up to maintain standards for By paying closer attention to sources of principles to biology appears to be in quality the meter and the kilogram and to enable uncertainty, biologists may be able to better assurance of biologically based products, the implementation of these standards interpret and possibly even learn from such as in clinical genomics, diagnostics and internationally. Since then, its remit has situations where an experiment cannot be cell therapy, but such materials could been extended to additional units, the reproduced from one context to another. be productively applied in research contexts number of member states has grown to A different metrological concept, as well. 59, and the International System of Units traceability, can guide thinking about To determine which areas would benefit (SI) has been defined. These cover seven biological reference samples. Metrology most from a metrological approach and how so-called base units—the second, ampere, defines a traceable measurement as to implement this, and to design reference mole, kelvin and candela, in addition to the having an unbroken, documented chain of materials, the first step is communication meter and the kilogram—as well as many references back to an international standard. between biologists and measurement derived units. This ensures that measurements can be scientists. There is little to be lost, and much But metrology goes beyond the compared—that a third of a millimeter to be gained, through increased exchange definition of units; measurement scientists measured for a hypothetical Japanese aircraft between these groups. But perhaps more are concerned with how to make a good part will match the third of a millimeter of important, metrological principles can help measurement. The metrological mindset— its complementary surface on the chassis bring a biologist’s attention back to the an attention to minute detail and to the made in Canada. While it is quite easy to see fundamentals of experimental practice, even relationship between a measurement and the how the properties defined by the base SI as techniques get ever more sophisticated: true level of the measurand—is fundamental units can be calibrated to ensure traceability, how to measure and record accurately so to the ability to draw believable conclusions this is vastly more complicated for biological that one’s conclusions about a system are as in any domain of science, including measurements. Ground truth for even a close as possible to reality. ❐ biology. Although many biologists do relatively simple measurement, such as the consider the quality of their measurements, level of a surface marker on a particular Published online: 31 May 2018 including tests of technical variation and type of immune cell, is not trivial to define. https://doi.org/10.1038/s41592-018-0035-x method sensitivity, this is rarely tackled Also, the stability of biological materials is Nature Methods | VOL 15 | JUNE 2018 | 395 | www.nature.com/naturemethods © 2018 Nature America Inc., part of Springer Nature. All rights reserved.
Nature Methods – Springer Journals
Published: May 31, 2018
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