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This is: Book Review: Design Principles of Biological Circuits, published by johnswentworth on the LessWrong.
I remember seeing a talk by a synthetic biologist, almost a decade ago. The biologist used a genetic algorithm to evolve an electronic circuit, something like this:
(source)
He then printed out the evolved circuit, brought it to his colleague in the electrical engineering department, and asked the engineer to analyze the circuit and figure out what it did.
“I refuse to analyze this circuit,” the colleague replied, “because it was not designed to be understandable by humans.” He has a point - that circuit is a big, opaque mess.
This, the biologist argued, is the root problem of biology: evolution builds things from random mutation, connecting things up without rhyme or reason, into one giant spaghetti tower. We can take it apart and look at all the pieces, we can simulate the whole thing and see what happens, but there’s no reason to expect any deeper understanding. Organisms did not evolve to be understandable by humans.
I used to agree with this position. I used to argue that there was no reason to expect human-intelligible structure inside biological organisms, or deep neural networks, or other systems not designed to be understandable. But over the next few years after that biologist’s talk, I changed my mind, and one major reason for the change is Uri Alon’s book An Introduction to Systems Biology: Design Principles of Biological Circuits.
Alon’s book is the ideal counterargument to the idea that organisms are inherently human-opaque: it directly demonstrates the human-understandable structures which comprise real biological systems. Right from the first page of the introduction:
. one can, in fact, formulate general laws that apply to biological networks. Because it has evolved to perform functions, biological circuitry is far from random or haphazard. ... Although evolution works by random tinkering, it converges again and again onto a defined set of circuit elements that obey general design principles.
The goal of this book is to highlight some of the design principles of biological systems... The main message is that biological systems contain an inherent simplicity. Although cells evolved to function and did not evolve to be comprehensible, simplifying principles make biological design understandable to us.
It’s hard to update one’s gut-level instinct that biology is a giant mess of spaghetti without seeing the structure first hand, so the goal of this post is to present just enough of the book to provide some intuition that, just maybe, biology really is human-understandable.
This review is prompted by the release of the book’s second edition, just this past August, and that’s the edition I’ll follow through. I will focus specifically on the parts I find most relevant to the central message: biological systems are not opaque. I will omit the last three chapters entirely, since they have less of a gears-level focus and more of an evolutionary focus, although I will likely make an entire separate post on the last chapter (evolution of modularity).
Chapters 1-4: Bacterial Transcription Networks and Motifs
E-coli has about 4500 proteins, but most of those are chunked together into chemical pathways which work together to perform specific functions. Different pathways need to be expressed depending on the environment - for instance, e-coli won’t express their lactose-metabolizing machinery unless the environment contains lots of lactose and not much glucose (which they like better).
In order to activate/deactivate certain genes depending on environmental conditions, bacteria use transcription factors: proteins sensitive to specific conditions, which activate or repress transcription of genes. We can think of the transcription factor activity as the cell’s interna...
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