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Exploring the Definition of Systems Biology

Review of "The Inner Workings of Life: Vignettes in Systems Biology"

By Richard Bertram

The Inner Workings of Life: Vignettes in Systems Biology. By Eberhard O. Voit. Courtesy of Cambridge University Press.
The Inner Workings of Life: Vignettes in Systems Biology. By Eberhard O. Voit, Cambridge University Press, Cambridge, United Kingdom, 2016, 218 pages, $29.99

If you’ve read anything about biology lately, you’ve probably come across the term “systems biology.” And if you’re like me, you’ve wondered, ‘what exactly does this mean?’ A little Google search will tell you that it’s the study of systems of biological components, such as molecules, cells, or organisms. Yet this explanation is somehow unsatisfactory, since it describes many different areas within biology, such as physiology and neuroscience. What distinguishes systems biology from these, or other, areas of biology? This is more than idle curiosity for me, since I serve on the editorial board of Biophysical Journal in the area of systems biophysics, which seems to be a combination of systems biology and physics. But what does systems biology really mean?

Fortunately, Cambridge University Press has just published a very nice book, The Inner Workings of Life: Vignettes in Systems Biology, by Eberhard O. Voit that addresses this question. Voit is a professor of biomedical engineering at the Georgia Institute of Technology, and has written many papers and a few textbooks on systems biology. Surely he should know the meaning of systems biology. The trick is to convey highly technical information to a broad audience without abandoning key elements of the many topics covered in the book. Not only is the field filled with biological technicalities, but modern systems biology is also wrought with mathematics. Yet there are no equations in this book! Amazingly, The Inner Workings of Life succeeds in describing the field so well while avoiding technical issues and equations. 

The book is organized as a sequence of short vignettes, which are informally written and focus on topics such as mathematical models, the various types of -omics research that have materialized over the past decade, gene microarrays, the scientific method, cell signaling, emergent systems, and chaos, among others. I found these vignettes to be informative, even on topics with which I am quite familiar. This is partly because each vignette contains some history of the topic, often dating back hundreds or even thousands of years, and partly because Voit is really good at explaining things.

One example is the vignette “What hath God wrought!” This starts with a brief history of the electrical telegraph and the impact of information transmission over long distances on human civilization. It soon moves to signaling in biology, both through extracellular signaling molecules like hormones and intracellular signaling molecules that form signaling cascades within cells. Ordinary differential equations can describe actions of all these molecules, and in the field of systems biology such descriptions are common. The vignette moves on to the physiological level of information transfer through our senses, using hunger as an example (the sensation of hunger is partially transmitted through the hormone ghrelin, and satiety through the hormone leptin). Along the way there is a discussion of G-proteins—key molecules that transduce extracellular signals to intracellular signals—and the discoverers of G-protein-coupled receptors, Alfred Gilman and Martin Rodbell, who share the 1994 Nobel Prize in Physiology and Medicine.     

Another example is the vignette “I’d rather be fishin’,” which describes how the development of the scientific method has driven scientific research for centuries. The bedrock of this is that experiments are designed to test hypotheses. The alternative, where experiments are done with the hope of finding something that looks interesting but without a specific hypothesis, is often derided as a fishing expedition. However, engineering advances over the past couple of decades have made it possible to do things like sequence genes or measure protein levels at a much faster rate than was previously possible. These high-throughput techniques have reshaped biology, and made scientific fishing expeditions useful and even fashionable. They have also provided great opportunities for those in the informatics community, since we are now almost drowning in biological data; new developments are necessary to analyze it all. On the down side, the data created by these techniques has led to the development of bewildering terms such as genomics, proteomics, lipodomics, metabolomics, metagenomics, connectomics, transcriptomics, microbiomics, and even foodomics (really, I’m not kidding here).  

The twenty vignettes in The Inner Workings of Life are both informative and fun to read. They also provide an overview of the field for anyone with a mathematics background who is considering stepping into systems biology. Although much of systems biology involves experiments, it also relies heavily on mathematical models for the experiment design and the interpretation of experimental results. This should not be surprising since, after all, a Google search defines systems biology as the study of systems of biological components, like molecules, cells, or organisms. What better way to understand such systems than with mathematical models?

Richard Bertram is director of the biomathematics program at Florida State University and the current chair of the SIAM Activity Group on the Life Sciences.

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