“So Simple A Beginning,” A Popular Science Book about Biophysics

Descriptions of my general-audience book on biophysics are scattered across multiple blog posts, in some cases with outdated information like old versions of the title. Since it’s useful to have one definitive post to point to, here it is!

So Simple a Beginning: How Four Physical Principles Shape Our Living World is a popular-science book (or “trade” book in publishing jargon) about how physics permeates the workings of living things. I describe how understanding the connections between physics and biology adds depth to our appreciation of life’s wonders and also helps generate increasingly powerful tools with which to study, and modify, organisms of all sorts.

The book is published by Princeton University Press, released in the US on February 8, 2022! The publisher’s site is here; there are blurbs, as well as the complete Introduction! Here’s Amazon, and Amazon UK (released April 2022). [Update Dec. 2, 2022: Here’s a recording of a virtual book talk/conversation w/ Harvard Book Store, which was a lot of fun.] [Update March 20, 2024: Now available in paperback!]

It’s a big book: about 80,000 words, not including references, and 119 illustrations I drew or painted myself. Seventy-five of these are in color, some simple schematics and some more elaborate, like this one of the motor protein kinesin:

Forty-four are gray, like this one of DNA melting:

I’m very happy with how the book turned out, and I hope others will be, too!

In this post I’ll recycle old material describing the book and comment briefly at the end about a few favorite topics. If you’d like updates on the book’s status, for example being notified when it’s available, please enter your email address in this form. (It’s the same form that I posted a long time ago.)

Motivations

[From March 10, 2020, with minor edits]

How does life work? I begin with this question, which seems overwhelming. Life, after all, manifests itself with awe-inspiring variety and daunting complexity. There are, however, commonalities in the materials from which living things are built and, more profoundly, commonalities in the principles that guide these materials into living forms. Understanding how these materials and principles shape life is the aim of biophysics. The insights of this field, especially in the past few decades, provide a deeply inspiring perspective into the natural world, as well as profound practical benefits. Biophysics, however, is conspicuously absent from the popular science literature. Even the recent proliferation of books on genetics and genetic manipulation are oddly cryptic in their explanations of what genes and proteins are, and what they actually do, making it difficult for the non-expert to make sense of subjects that are both beautiful and immensely important.

Hence, my book. I’ve been keen on conveying the wonders of biophysics to a broad audience for quite a while, and this has motivated things like public lectures, outreach activities, and my “Physics of Life” course for non-science-major undergraduates. A book, however, offers the possibility of being more permanent, deeper, and more comprehensive. Plus, I like books a lot! I’ve worked on this off and on for several years, but really got serious about it two or three years ago [edit: 4 years ago!]. I carefully studied How to write a book proposal, spent a lot of time crafting a query, sent it out to a few literary agents (nowhere near the requisite number), had those few queries rejected, met with an editor at Princeton University Press, and ended up with a book contract from them. In addition to textbooks and works for specialists, Princeton publishes “trade” books, i.e. books for the general public, including one of my favorite pop-science books of recent times, Oliver Morton’s “The Planet Remade: How Geoengineering Could Change the World.”

Who cares? This question doesn’t appear in the book but it’s ever-present in my mind, especially since going through the challenging exercise of writing a book proposal. One of the most difficult realizations that comes from teaching and outreach is that many of the things you find inherently interesting are not that interesting to most people. Looking through a microscope? Boring. Free energy landscapes? Boring. Math? Super-boring. I exaggerate, but the people excited by by these sorts of things are a small subset of the people I’d like to reach, in teaching and outreach but especially with this book.

I’ve therefore drawn lots of connections between science and technology, and especially between science and health. Issues of disease, treatment, or simply how we function are of intrinsic interest to a lot of people. It’s not hard to make such connections, from surface tension to the lungs of premature infants, or DNA packaging to birth defects. Most important, however, is the deeper understanding of genetics and its modifications through technology that, I believe, a biophysical perspective gives us. We live in an era in which stunning advances in genetic tools increasingly impact how we interact with plants, animals, and even future children. It’s hard to see how one can make sensible decisions about these tools without understanding not only what a “gene” is, but how genes assemble into circuits, how circuits assemble organisms, and how randomness and predictability coexist in all of us. There’s unfortunately a lot of contemporary popular writing on genetics that’s opaque or even misleading, typically leaning towards moral panic, and I hope to counteract that in ways that will hopefully be useful.

Structure

[Mostly from March 10, 2020. The book now has three parts, rather than four, and there’s a lot more about CRISPR and gene editing, briefly noted in the last paragraph below.]

The first part of the book, “The Ingredients of Life,” introduces the building blocks of living things — DNA, proteins, lipid membranes, etc. — focusing especially on how their physical characteristics govern their function. We see why the stiffness of DNA influences its packaging in cells, how proteins and genes interact to form decision-making circuits, and more. We encounter a variety of diseases, learning for example that cannibalism is best avoided if one wants protein folding to proceed normally, and technologies, learning for example that the sharp melting transition of DNA makes possible its routine processing and analysis.

The second part, “Living Large,” explores communities of cells. We see developing embryos, artificial assemblies such as lab-grown organs, and our internal microbiome, again laying out principles such as pattern formation that guide their construction. We then look at even bigger things, especially at scaling relationships that dictate that large animals need disproportionately thick bones and that small animals can walk on water. This part ends with a chapter on metabolic scaling — why large animals need fewer calories per kilogram than smaller ones — a messy and contentious topic that, unlike everything else in the book, I don’t want to revisit.

The third part, “Organisms by Design,” gets into the reading and writing of DNA. There’s a lot here about technology, especially the stunning ways in which contemporary DNA sequencing tools make use of the physical character of biological molecules to read the information they carry. I spend a whole chapter on “writing” DNA — early successes like coaxing bacteria to make human insulin as well as the more recent magic of CRISPR/Cas-9, modifying genes at will inside living creatures. We explore the physical machineries of modern genetic techniques and also some of the ethical issues involved in actions like embryo selection and ecosystem engineering which, I claim, can’t be properly considered without an understanding of how the techniques work. I end with thoughts on what it means to “understand” life, and what a biophysical perspective gives us.

Themes

[Mostly from March 10, 2020. ]

Four themes permeate all of this, elevated to the status of “principles” in the book’s subtitle:

• Self-assembly: The instructions for building with biological components — whether molecules, cells, or tissues — are encoded in the components themselves.
• Regulatory circuits: Within every cell, the wet, squishy building blocks of life assemble into machines that can sense their environment, perform calculations, and make logical decisions
• Predictable Randomness. The physical processes underlying the machinery of life are fundamentally random but, paradoxically, their average outcomes are robust and predictable
• Scaling: Physical forces depend on size and shape in ways that determine the forms accessible to living, growing, and evolving organisms.

Favorites [new]

I’m currently reviewing the copyedited manuscript, and so I’m re-reading everything I’ve written. There are a few parts that in retrospect I think could have been streamlined, but overall I like how it turned out.

A few parts I am especially fond of: Chapter 7, Assembling Embryos, on how each of us put ourselves together, reading the spatial information in clouds of diffusing chemicals and the temporal information in genetically-encoded clocks. Early in the chapter I note the case of pioneering embryologist Hans Driesch, who

“… was so struck by the apparent contradiction between the workings of an embryo and the physics at his disposal that he abandoned the study of development altogether to become a philosophy professor.”

So Simple A Beginning, Chapter 7

We, however, fare better.

Chapter 13, How We Read DNA, gets into how DNA sequencing works, a triumph of taking seriously the character of DNA as a physical object. Microfabrication, detecting little pulses of light, and even transistors appear in the chapter; all involve impressive applications of physics that most physics students are completely unaware of. It’s followed by a chapter, Genetic Combinations, that was challenging to write but that I think turned out well, on polygenic traits, how we can assess them, and the statistics that makes embryo selection possible in some cases and impossible in others. This chapter and the following ones also address the ethical issues that emerge from modern biotechnological capabilities, a topic that was challenging, though fascinating, to write about. I learned quite a bit while writing, for example about public response to the “unnatural” technology of in vitro fertilization. For example, a 1969 Life magazine poll of Americans reported that:

“…only about 60% of respondents (55% of men, 61% of women) believed that a child born through in vitro fertilization ‘would feel love’ for his or her family.”

So Simple A Beginning, Chapter 14; [L. Harris, The Life Poll. Life. 66 (23), 52–55 (June 13, 1969).]

Such views changed rapidly, and one wonders if this will be the case for currently cutting-edge technologies as well.

For a very incomplete list of topics that didn’t make the cut to include in the book, see the July 2020 post.

Considering what I’ve omitted, and how rapidly biophysics advances, there’s plenty of room for more books on the subject!

Interested?

If you’d like to get an email when the book is published, or be notified if anything significant changes, you can enter your email address in this form. This is the same link as posted earlier. I think I’ve emailed only twice so far — you needn’t worry about spam! [Update: I’m not regularly looking at the form, since the book has been published. Feel free to email me.]

Today’s illustration…

Part of an illustration of fractal shapes that will appear on the cover. This “tree” is one of six, growing as one moves up the page. I made this fairly recently (April), working with the publisher on the cover design, which I didn’t think until recently would have any of my illustrations on it. This painting is intentionally very minimal. I like how the colors turned out.

— Raghuveer Parthasarathy, June 20, 2021, with later updates