2021 Best Books

- 9 mins

In 2020, I learned the most from reading historical accounts of scientific progress and funding, particularly in my field of biotechnology. For 2021, I set a goal to cover a broader swath of the history of biomedical research paired with some longer-form non-fiction in business and economics. As always, I also kept up a steady intake of science fiction.

I’ve summarized a few favorites I can strongly recommend below. If these sound interesting to you, I’d be happy to hear any related recommendations by email!

Breath from Salt

Green Apple Books

As I’ve opined before, I think there are too few accessible accounts of how medicines are invented. To my delight, Breath from Salt is one more entry in the small canon of drug development stories that I can recommend widely.

Breath covers the first diagnosis of cystic fibrosis as a disease, the discovery of its molecular basis, and the various efforts to develop medicines that eventually resulted in Vertex’s remarkably effective drugs. Trivedi seamlessly integrates the stories of diverse CF families, highly-technical biomedical science, and drug R&D to take readers on a complete journey from patient to medicine and back again.

The drug development story in particular is quite striking. The Cystic Fibrosis Foundation proved pivotal as a source of differentiated funding for CF research and treatment development. In particular, they used a unique model where the Foundation provided early stage, high risk capital for research and development of new therapeutics in exchange for a portion of the ensuing royalties. They successfully deployed this model to first develop a series of symptomatic treatments, and later to fund a high risk small molecule screening campaign at Roger Tsien’s Aurora Biosciences.

This campaign was the first attempt to search for a “corrector” drug that rescued the ability of mutant protein to fold properly, rather than to inhibit protein activity like most small molecule therapies. Given the absurdity of the task, Vertex almost killed the program when they acquired Aurora, and only due to early positive results obtained with the CF Foundation funding was the program allowed to continue. Those efforts yielded the drugs that improved hundreds of thousands of lives, eventually helping the majority of CF patients and rescuing Vertex as a business when their HCV drug was disrupted by superior therapeutics.

It’s a remarkable story that highlights just how narrow the pathway to success can be even for some of the most successful medicines.

The Eighth Day of Creation

Review: The Eighth Day of Creation
Related Reflections: Learning representations of life

Eighth Day is perhaps the most complete historical account of molecular biology’s founding experiments and personalities. Despite working in the field for more than a decade, I found myself consistently surprised to learn of motivations, models, and ideas lost in the usual retelling of molecular biology’s triumphs. Horace Freeland Judson has a talent for communicating not just what we know about the molecules of life, not just how we came to know it, but the intellectual evolution or sequence of ideas that led to the key experiments at the basis of modern understanding. Highly recommended for any fans of the history of science, progress, or biotechnology.


Green Apple Books

In his second collection of stories, Ted Chiang cements his place as one of the twenty-first century’s most interesting science fiction writers. Chiang’s stories act as the seed for a crystal of an idea, such that the most interesting developments occur not on the page but within your own reflections, days later, beneath a eucalyptus tree. My favorites from this collection are the eponymous “Exhalation”, “Anxiety Is the Dizziness of Freedom”, and “Omphalos.”

Klara and the Sun

Review: Klara and the Sun

I love all of Ishiguro’s work, and Klara and the Sun is no exception. In his trademark empathetic science fiction style, Ishiguro imagines a near-future world where artificial general intelligence (AGI) has been achieved and serves at least in part to remedy the emotional ails of humans in that fractured world. The setting is somehow visceral and believable because of how little is revealed in direct exposition. We glimpse the world only in the shadows it casts upon the characters, one of whom may be the first AGI protagonist in popular literary fiction.

Seeing Like a State

Minimum-viable-summary: Seeing Like a State

An admission: I’ve had James C. Scott’s Seeing Like a State on my reading list for years based on the overwhelming number of times it’s been recommended to me. I finally got around to reading, and all of my friends were right!

Seeing Like a State dissects how the perceptions of large organizations (here, namely nation-states) are lossy representations of the real world and how these flawed perceptions can come to dictate the nature of reality. There’s an old adage that a truly accurate map of a kingdom would be the exact same size and scale as a kingdom itself, therefore rendering it unusable. Scott builds from this point and highlights in several distinct examples that large organizations require approximations, compressions of the real state of their circumstances to make useful operational decisions. In this frame, the legibility of different aspects of the real world – how easy it is for the larger organization to notice, accurately measure, and persistently record a given fact – becomes a central determinant of whether that quality is subject to optimization, taxation, exploitation, or investment. Many actions of large organizations can then be viewed as an attempt to render legible many of the tacit aspects of the world, and those very attempts to record and assess the state of reality have actually shaped our modern world quite profoundly, from our names to the shape of our domiciles.

Internally, I approximate the central lesson of Seeing Like a State as “Heisenberg’s principle for society” – by the very act of measuring a community, a culture, or an organization, you shape it in both subtle and dramatic ways.

Time, Love, Memory

Green Apple Books

Early molecular biology explained the mechanistic basis for macroscopic phenotypes like cell growth, metabolism, and gross morphological traits. Alas, the complexities of animal behavior – even in flies, to say nothing of humans! – remained out of reach for the earliest pioneers of the discipline. Late in his career, after building a successful program as a phage geneticist, Seymour Benzer pivoted his laboratory to focus on explaining the molecular basis of animal behavior.

This goal was audacious, but critically important! Behavior, personality, emotion – notions of time, love, and memory – remained perhaps the last bastions of vitalism, the last remnants of a belief that perhaps human life cannot be explained using the same principles of physics and chemistry that govern the rest of the known universe. Benzer’s lab began their investigations by leaning into their skill as engineers, building novel apparatuses to measure behavioral traits in genetically-tractable fruit flies. Through a series of ingenious screens, they proceeded to uncover the genetic-determinants that allows flies to tell night from day, to learn from experience, and to find mates. While flies are far from humans in a phylogenetic sense, these results were nonetheless powerful examples that the basic principles of molecular biology could explain even the most complex features of life.

Jonathan Weiner recounts the story of these discoveries in beautiful prose and helps imbue each with the personality of the investigator responsible.

Honorable Mentions

Crashed by Adam Tooze (Review) – Tooze provides a definitive account of the Great Financial Crisis at a level of technical sophistication that is rarely achieved even within the disipline of economics, to say nothing of financial history. Crashed is just shy of making it onto my “Best Books” list because the subject matter is challenging to ingest as a linear narrative. This is not a fault of Tooze, and I’m a huge fan of his other work. Rather, the GFC is such a technically complex subject that it cries out for hypertext, mouse-over reminders of key events, interactive tables, charts, and graphs, rather than a 700+ page continuous description. Tooze does a remarkable job at condensing this information given the presentation constraints of a traditional book, but nonetheless, I found myself grasping for understanding of events off-screen and cross comparisons between different time periods in the chronology, preventing an immersive reading experience.

Hard Landing by Thomas Petzinger (Link)Hard Landing is ostensibly the tale of America’s commercial aviation industry, but the description doesn’t quite do justice to the book. Rather, it’s a story that captures the rise and fall of corporate cultures under different external conditions during the transition from a heavily-regulated to free-market industry. Petzinger in particular has a talent for capturing the colorful characters of the industry’s early days. This makes for great fun as a reader and highlights the impact just a few operators can have on large organizations under the right circumstances. Recommended for fans of Business Adventures by John Brooks or Liar’s Poker by Michael Lewis.

Jacob C. Kimmel

Jacob C. Kimmel

Principal Investigator @ Calico. Interested in aging, genomics, imaging, & machine learning.

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