08 July 2024

Protein Space and the Protein Universe: Introduction

Blue dots and smears in a circular graph, depicting structural links between protein clustersEvolution is easier than we think, and one great way to see why is to look at what we know about protein evolution.

Proteins have been evolving on our planet for about 4 billion years. Their appearance almost certainly precedes the beginning of life itself. We still don't know how the whole thing got off the ground, but once the stage was set (in living cells), evolution began exploring Protein Space. As it did so, it slowly created the Protein Universe. Since these two concepts — Protein Space and the Protein Universe — are so central to understanding and picturing protein evolution, we should carefully define what they mean.

28 April 2024

"I put the ways of childhood behind me" — my remembrance of Dan Dennett

For five years through 2018, our humanist community, the Humanist Hub*, met every Sunday afternoon at our suite in Harvard Square for fellowship, music, and a speaker. Our advisory board included luminaries of humanism such as Rebecca Goldstein, Steven Pinker, and Dan Dennett. These friends of the organization regularly spoke at Humanist Hub events. One of the most memorable, for me, was Dan Dennett's talk in November 2017, "The Science of the Soul (and where to go from here)."

I was lucky enough to be asked to introduce Dan, and shared thoughts about what his work had meant to me. I've included my lightly edited script below. The video on Facebook includes more jokes (and laughs) and shows a typical Sunday program at the Hub. The program starts at 13:30, with music at 20:30, my remarks starting at 27:30, and Dan's talk starting at 37:20.

16 August 2023

Science, intuition and the "strange inversion of reasoning"

A few days ago I wrote about scientific thinking as an antidote to intuition. Not just an alternative to it, but something like the opposite of intuition. The intentional, energy-consuming move to a systematic deliberative mode of thought is utterly different from the easy and instantaneous nature of intuition.

Some of our intuitions are clearly built-in. Many of the famous failings of our intuitive System 1, described by Daniel Kahneman in Thinking, Fast and Slow, seem to be hard-wired. Some are perhaps the unavoidable result of trade-offs that buy speed and decisiveness at the expense of accuracy and completeness. Others might be adaptive despite being occasionally delusional: I'm thinking here of optimism bias. Some days we just need some good old optimism bias!

But some of our most famous intuitions are more complex and a bit harder to attribute to brain wiring or adaptive tricks. These are intuitions that seem to affect how we see the whole world, all of existence, all day. I think it's intuition (and nothing else) that makes us feel that something complex, that shows design, must have come from a designer. That a universe has to have a beginning, and therefore a "beginner." That a mind like ours must somehow come from a bigger mind somewhere else. That seemingly uncaused events must have had a cause. Which are all probably related to a sense that the universe is haunted.

I'm not sure that these intuitions are all universally human—some are likely to be deeply cultural. But the point is that well beyond our intution that the sun moves through the sky or that the earth can't be a spinning ball, there are intuitions about the very fabric of existence.

12 August 2023

Scientific thinking as the antidote to intuition

As I work on a book that will claim that evolution is easy, I have a parallel task of exploring the reasons we sense that it is hard or even impossible. Some of those influences are the result of efforts by religions to maintain dependence on supernaturalism or to defend ancient sacred writings. Some are the result of antipathy to science itself, framed in terms of culture war. But others are less clearly related—at least directly—to religions or tribes. Our brains are wondrous indeed but are known to be prone to various kinds of error. To be brutally frank: there are things that can seem obvious to us but that are false.

Daniel Kahneman's 2011 book Thinking, Fast and Slow was a life-changer for me. As soon as I read it in 2013, I urged colleagues to read it, even convening a book club at work. (The job of a journal editor is fundamentally about making decisions and judgments, and that's what the book is about.) One of the key messages of the book is that our fast thinking system (Kahneman calls it System 1) is both speedy and utterly important for survival. It's not about reflexes—it's still a kind of thought. But it's quick and dirty, often making guesses or approximations, and is prone to error. "Intuition" is a function of System 1.

10 August 2023

What I learned about me when I started reading novels again

A few years ago, I somehow realized that I wanted to read more stories.

My work as a journal editor involved hours of intense scientific reading every day, and my insatiable interest in biology meant that my recreational reading was almost exclusively about science. But I could remember how much I loved stories as a kid: Tom Sawyer, The Black Stallion, all the Roald Dahl things. I read almost no fiction at all as a high schooler, then as a young Christian adult I read The Lord of the Rings trilogy and (urp) the Chronicles of Narnia. As a dad, I read (aloud with the family) all of the Harry Potter books, and that was great memorable fun. Somehow about 15 years ago I decided to read The Poisonwood Bible. (Unforgettable.) But my extensive reading habits were largely focused on science and Shakespeare.

To be sure, I derive both enjoyment and inspiration from science and from Shakespeare, but in retrospect it seems I needed to feed a part of me that finds inspiration in stories. In novels. And so I started collecting novels, specifically from female authors. I put a few on my Christmas list, and my loved ones obliged, and there they were on my shelves. Unread.

Then for some reason, not even two years ago, I decided to do it. I had a trip coming up: my annual journey to New York to co-lead the Scientific Writing Retreat at Cold Spring Harbor Laboratory. We had moved to Arizona, so the journey had evolved from a 4-hour ride on Amtrak to an all-day trip across the continent. I don't remember why, but I picked The Ten Thousand Doors of January by Alix Harrow, and started reading on the plane.

09 August 2023

The known unknowns of biology: welcome to the unknome

'Genome' is now a pretty standard word in our social vocabulary. We have to put up with overloaded metaphors like "blueprint" and reverent talk like "language of god" but it does seem to me that the word is reasonably well understood by laypeople—not as jargony as "gene expression" or as inscrutable as "chromatin." The word was born in 1920 when someone blended 'gene' with 'chromosome'. (The -some in 'chromosome' is from a root that means 'body' as in 'somatic' or 'psychosomatic'.)

So, a genome is a "body" of genetic material, and specifically the whole body of genetic material in an organism (or a cell or a species). For decades now, science has been regularly adding more -omes. The proteome is the full body of proteins. The transcriptome the full body of transcripts. It gets a bit weirder: the phenome is the full body of phenotypes. There's even the spliceome, the full body of splice variants. Many of those are pretty jargony; the point is that -ome is a suffix that's being used a lot like -gate is used in political news (to indicate a kind of scandal, as in Watergate or Gamergate). Among the -omes (let's call it the omeome, ha ha!), the best by far is the unknome: the set of all genes of unknown function.

How big is the unknome? In other words, how many of the 20,000 or so genes in the human genome are unknown (in function)? Is there a gradient of unknown-ness? A new paper in PLOS Biology by Rocha and colleagues introduces us to the unknome and then adds some good stuff, which is the least the authors can do after telling us how little we know about human gene function.

08 August 2023

Rebel scum

This week in the Blaugust 2023 blogging festival, the broad theme is "Introduce yourself." Yesterday I alluded to my bardolatry and its place in the cornerstone of Quintessence of Dust, but that's not really an introduction. So here is a bit more about me: I love the Star Wars universe and I'm into evolution, and both of those things are deeply connected to my main tendency—I'm a rebel.

That might sound romantic and all, but I'm actually being somewhat precise and referring to some useful counsel I got in the past few years as I considered Gretchen Rubin's Four Tendencies. The Rebel tendency describes me all too well. I hate being told what to do. I hate being controlled. I hate even suspecting that I'm being controlled. Here's how Rubin captures much of my life: "Telling a Rebel what to do makes them less likely to do it, even if it’s something they want to do."

There are advantages to being a Rebel but big weaknesses as well. Another tagline of the Rebel tendency is this LOLsob-inducing truism: "You can’t make me, and neither can I." So, the perhaps obvious disadvantage is that it can be extra difficult to get tasks done whenever there is a sense that someone or something is ordering it to be done. I'm not lazy; in fact, I work too much. But whenever I sense that someone is telling me what to do, I have to work around my natural instinct to resist their brazen attempt to control me. (Heh.) Otherwise, I'll find ways to not do the task (or meet the obligation, or whatever).

What are the advantages of that tendency? Are there any?

07 August 2023

Thoughts on quintessence, mutation, and evolution

This blog's name captures my longstanding interest in human nature: humans are apes, and animals, and yet somehow able to create music and gods, and sometimes plays like Hamlet. But what's that strange word at the beginning, 'quintessence'? Here's the context from Hamlet:

What a piece of work is a man, how noble in reason, how infinite in faculties, in form and moving how express and admirable, in action how like an angel, in apprehension how like a god: the beauty of the world, the paragon of animals — and yet, to me, what is this quintessence of dust?

—Hamlet, Act II, Scene II (Arden Shakespeare)

The word's history suggests that Shakespeare was (as usual) playing games with words and his audience (all quotes from the OED):

a quintessence can be a pure or perfect example of something and/or "The most essential part or feature of some non-material thing" as in "This seems to us the very quintessence of penny wisdom and pound folly in management"

and quintessence used to refer to a "In classical and medieval philosophy: a fifth essence existing in addition to the four elements, supposed to be the substance of which the celestial bodies were composed and to be latent in all things."

So, it seems Hamlet is saying that a human is a pure example of a blob of dust, but perhaps stardust. Either way (or both), he is commenting on what a human is at their core. Not just essence, but quintessence.

I don't know if this is a Western thing (I suspect it is), but essentialism like Hamlet's, in which we assume that a thing (a person, a gender, a gene, a protein, a species) has a definable essence, is a big hindrance to thinking about evolution.

06 August 2023

Sky Islands: one of Earth's great evolution laboratories

Let's think of places on Earth where scientists have done great big natural "experiments" on evolution.
Looking east from near the top
of Mount Lemmon, January 2021
Here are some that ought to come to mind (in no particular order other than the first):

1. The Galapagos Islands, with their famous finches and their less-famous tomatoes and all their otherworldly animals, probably belong at the top of the list. Mr. Darwin found inspiration there, but the greatest experiments began more than a century later. I can think of few more inspiring stories of great science done by great people than the lifetime-long work of Rosemary and Peter Grant. If you haven't yet read The Beak of the Finch, get thee to a library or a bookstore.

2. The Caribbean islands, and especially the Bahamas, are a fruitful laboratory for the study of the (rapid) evolution of lizards called anoles. Jonathan Losos was a major figure in launching and leading that subfield, and his 2017 book Improbable Destinies is a great lay-level exploration of evolution and a resounding rebuttal to the random/luck/contingency views associated with Stephen Jay Gould.

3. The Hawaiian Islands are home to hundreds of species of fruit fly (many of them are biology's adored Drosophila) and zero species of ant. These hundreds of species have all evolved in the last 25 million years! Check out the laboratory of Cassandra Extavour at Harvard for a glimpse into the latest research on the evolution of Hawaiian fruit flies.

4. The Great Lakes of East Africa (including Victoria and Tanganyika) hosted one of the most rapid and spectacular adaptive radiations known to humans. Hundreds (likely thousands) of species of cichlid fish live in these lakes, and all of them were "born" in a blink of evolutionary time.

5. The streams of Trinidad are home to guppies, an unremarkable fact until you learn about one of the best-known experiments in the history of evolutionary biology. Over many years, research teams led by John Endler and David Reznick used this natural laboratory to study natural selection (and other topics) in the wild.

There are surely more. But I'm here to tell you about the one that literally surrounds us here in Tucson.

05 August 2023

Contemplating libraries in biology. Not that kind. Not that one either.

What is a library? If you ask a biologist (especially a molecular biologist) this question, they are likely to ask for clarification. In their work, they are likely to make regular use of two very different kinds of libraries.

The first is the kind that we've had for millenia: a collection of books, journals, and media that is ordered and curated by people. These are the OG libraries, with 'book' at the very root of the word. They're rapidly evolving in our digital world, but I think they are still essentially what they've always been. Your friend the molecular biologist may not regularly go to a separate room or building to find materials, but they will use the library often.

The second is an extension of the OG concept of a library, but is still called a 'library' by your friend. It contains information, perhaps in vast amounts, but is not ordered or curated. Crucially, it is a specific collection of a particular type of information: genetic information. And while it's neither ordered nor curated, it is physical, and is designed to be searched. The contents of the library might be DNA sequences (genes or even just chunks of some interesting genome) or protein sequences. Unlike your favorite public library, this one doesn't come with a search feature: you have to do that yourself. The process of searching a library is called screening. Your molecular biologist friend can go to the institutional library to read about these kinds of libraries, and find techniques on how to screen one, then perhaps go to a colleague or a vendor to obtain a library. Or she will obtain tools to make one herself.

In my previous post, I talked of an even more radical extension of the concept of a library: a collection of all the versions of any kind of text (a book, a genome, a set of proteins).