On July 4, I finished a draft of the fourth and final part of Building Life, my popular-science book on biophysics. There’s still a lot to revise, based in part on comments from my editor and others on Parts 1-3 and, I’m sure, comments to come on Part 4, but nonetheless I’m delighted to say that the draft is complete! If I disappeared tomorrow the text as-is could stand on its own — not ideal, but decent enough to show people. In total, it’s about 79,000 words, spread over sixteen chapters plus an introduction, with about 80 color illustrations I drew or painted.
I’ve described the aims and structure of the book before (blog post here). Briefly, the overarching theme is that physical principles help us make sense of how life works, both in its natural state and in the context of increasingly powerful biotechnologies. In the first part of the book I describe the pieces from which all the variety of life is made, tangible things like DNA, proteins, and membranes, and intangibles like self-assembly and random motion, with examples touching on phenomena like viral infection and cells making clocks. In the second part, I cover communities of cells, such as embryos and organs, asking, for example, how a tiny embryo calculates the patterns in space and time necessary to make a backbone. The third part deals with size — asking for instance why and how to have lungs, and seeing how understanding the physics of surface tension saves the lives of premature infants. The fourth part covers our newfound ability to read and write genomes, perhaps the ultimate expression of the physical nature of biological information.
The point of this post, however, is to note a few of the topics that didn’t make the cut, that I initially thought of including but then decided against. There’s a near-infinite number of fascinating things to write about, and for each a near-infinite depth of detail. Constantly pruning, asking myself, “Does this really need to be here?” occupied a lot of my time when writing. To be kept, a topic had to be interesting, had to illustrate some broader biophysical theme that wasn’t otherwise sufficiently fleshed out, and couldn’t require too much explanation relative to the benefit of including it. Here are one example each of a biophysical entity, a concept, and a tool that fell by the wayside:
On the cutting room floor
The cytoskeleton. I briefly describe the internal scaffolding of cells, especially its self-assembly from individual protein molecules, but I had originally intended an entire chapter on the cytoskeleton. Its dynamism is fascinating. Actin filaments and microtubules look, in a static snapshot, like the rigid girders of a building, but a movie would show them constantly in flux, growing at one end and falling apart at the other, even if the overall length remains the same. Manipulating this activity can be useful — some anticancer drugs, for example, stop microtubules from disassembling, thereby freezing them in place. The strings of cellular scaffolds are linked together into meshworks, physically similar in some ways and different in others to the meshworks of non-living materials like rubber and plastic. All this would have been interesting to explore, but the key themes of self-assembly and molecular motion are illustrated in many other examples, and it would take considerable space to explain cytoskeletal dynamics well, describing the directionality of filaments, how they use energy, and so on.
Entropy and Free Energy. One of the most powerful concepts in all of physics is that systems organize themselves to minimize something called free energy, and in doing so balance two often conflicting tendencies driving them towards having as little energy as possible and as much entropy as possible. Phenomena from phase transitions to the cytoskeletal self-assembly noted above can be understood as manifestations of free energy minimization, but despite its depth and utility, few non-physicists have heard of it. They’re not going to learn it from my book, though! It is too abstract, and moreover involves layers of abstraction, first introducing entropy, and energy, and then something that combines the two. Moreover, appreciating the generality I claim requires seeing a lot of examples of free energy minimization in action, which would be a large distraction.
Microscopy. I wrote, and will delete, an entire half chapter on microscopy. Specifically, it dealt with the challenge of visualizing what goes on in an embryo, in one of Part II’s chapters on collections of cells. We explored why fluorescence is useful, how to make fluorescent proteins report on whether genes are being read or not, and methods for three-dimensional microscopy. Three-dimensional microscopy, of course, led to illustrations of light sheet imaging, which my lab does a lot and which I’m very fond of. (Blog post, which includes a link to a review paper.) But, as others noted and as I agreed in retrospect, all this is a digression. There is a lot to be said about methods — how we know what we know — but this isn’t the place for it.
Other concluding thoughts
I expected that writing this book would be difficult, but I underestimated how difficult it would be! Though it’s perhaps 100 times longer than a blog post, it’s far more than 100x harder to write. Maintaining a sense that the story one is telling is going somewhere, and that each individual piece contributes to the overall whole, is challenging over the span of a chapter, and even more so over the span of many chapters. Quite often I found myself wondering: what’s the point of this paragraph relative to the others? Does the reader really need this? Hopefully, I’ve done a decent job of answering these questions well, and making the whole thing coherent and compelling!
It has definitely been the case, though, that writing Building Life has been very enjoyable, stimulating, and satisfying. The final draft is due to the publisher at the end of August, at which point they’ll send it to others to read, and then to the presses!
Mosquitos, from a gene drive illustration for the last chapter that I ended up not using.
— Raghuveer Parthasarathy, July 8, 2020