platforms – Thinking with Nate

Universal Automata

A Cell’s Eye View of Evolution, Part 1

(This month’s image is a photo I took of the full-scale model of Babbage’s Difference Engine at the Mountain View Computer History Museum. This is one of the first examples of a programmable digital computer. It’s a completely mechanical device, operated by hand crank.)

This is part one of a three-part series. For an overview, check out the introduction.

In the traditional story of evolution, each organism lives a single lifestyle, and the forces of nature select which ones are fit enough to reproduce. From that perspective, evolution is something that happens to life. But this story fails to explain something very strange and important: cells are not single-purpose machines. Although they only live one lifestyle at a time, they have the capacity to live an infinite variety of lifestyles, depending on their DNA programming. That requires an enormous amount of complexity and effort that doesn’t directly contribute to a life well lived. In fact, being programmable doesn’t help at all in a single lifetime if the program never changes. So why does life work this way?

To make sense of this, let’s look at a parallel example in computer technology. Consider an ATM. It’s a highly specialized kind of machine, but these days if you look under the hood you’ll often find a Windows PC that’s programmed to be an ATM. That seems like an odd choice at first. ATMs do things most PCs don’t (like dispensing cash), and Windows supports things that you don’t want in an ATM (like running random programs off the internet). You could make a better, safer, more efficient ATM if you designed a custom machine for that purpose, but nobody does that, because it’s harder. Digital computers are so versatile and easy to reprogram that they show up everywhere. As they get used in new applications, their range of capabilities expands, enabling new use cases and further innovation.

Cells are very similar. Being programmable doesn’t help with any one lifestyle, but it makes it possible to explore new lifestyles relatively quickly and easily. Each individual operates in a complex, roundabout way that only uses a fraction of the cell’s potential. That seems like a bad thing, but the adaptability makes it worthwhile. The world is in constant flux, especially once organisms started actively changing things and competing with one another. Very few evolved lifestyles withstand the test of time. For this reason, nature doesn’t just select “the best lifestyles” for life. Life invested in a general purpose platform to make the search for new lifestyles more efficient.

Let’s take a closer look at how the platform works. A cell can be thought of as a kind of microscopic robot. The “programming” for that robot is stored in DNA, which is surrounded by a complex mechanism that reads that data and uses it to produce the form and behavior of the organism. Each cell has a very limited capacity for intelligence, but they’re very good at working together. Like a sort of “autonomous smart matter,” they collaborate by the trillions, which is how every form of intelligence on this planet is made. There’s no reason to think there’s an upper limit to what can be built in this way.

What makes this possible is the protein-synthesis engine at the core of every cell. The nucleus of a cell is a bit like the brain of a human, in that it’s a specialized sort of computer that’s “in control” of the cell. It’s surrounded by the cell’s body, which serves as the interface between the program in its nucleus and the outside world. This is where the similarity ends, though, because the nucleus and the brain are very different kinds of computing devices.

The nucleus works by continuously handling requests, looking up protein recipes, and sending those recipes back out to the cell for construction. A cell can make an astonishing variety of complex molecules this way. These proteins are what make up the cell, its inner workings, and outward behaviors. They serve as building material, messages, tools, or even nano-robots that move about within the cell, manipulating other molecules, and doing useful work all on their own. Sometimes a single protein can serve all of these roles, depending on context. They interact with each other in a vast complex network of activity that keeps the cell alive.

These cellular mechanisms continuously send messages back to the nucleus, reporting on the cell’s health, situation, and needs. The nucleus uses this information to figure out what proteins to make next, adapting the cell’s makeup and behavior to fit the circumstances. For instance, E. coli bacteria normally feed on glucose sugar, but they can eat lactose instead, if that’s what’s available. When that happens, the cell reports to the nucleus that it’s running low on energy and what molecules are around. The nucleus then decides to switch some genes on and off, which instructs the cell to make different enzymes, which results in different cascades of chemical reactions, in order to digest and use the lactose. By reading the DNA differently, the nucleus shifts the whole cell from one lifestyle to another, in response to a changing environment.

Another way to think of the nucleus is as the engine of the cell. The proteins it makes drive all the chemical reactions that keep the cell alive. Ultimately, everything the cell does is about collecting the energy and raw materials to feed that engine and keep it running. This is the cell’s metabolism. When the engine runs faster, the organism becomes more active, moving, “thinking,” and reacting with speed and vigor, but quickly burning through its energy stores. When it runs slowly, the cell becomes sluggish and conserves its energy. If it ever comes to a full stop, the cell dies, or, in special cases, enters suspended animation. In other words: cells live to make proteins, and making proteins is what makes cells alive.

DNA is where the cell keeps all these protein recipes, but the DNA molecule itself is completely inert. It just carries information, like a computer memory card. It can’t do anything by itself, and certainly can’t make a body from scratch. To build an organism, you need a cell to interpret the gene sequence and do the construction. This is why cells always reproduce by splitting in two. The daughter cell is basically just half of the parent cell, full of the same soup of proteins and organelles, in a fully operational state. The only part that’s really “new” are the DNA molecules in the nucleus, freshly copied from the parent(s). Any changes in that DNA program will only manifest when the daughter cell sends a message to the nucleus and gets a different response back than its parent would have seen.

That means that every cell has the crucial responsibility of reading and writing those DNA programs. They contain every useful protein recipe life has discovered, and must be actively maintained over generations or those recipes will be lost. But what does life actually record in the DNA? Geneticists say DNA is made of four amino acid base pairs (A, G, T, C), which are grouped into triplets called “codons” that serve as instructions for protein synthesis. That makes it seem “natural,” as if that were the only way to do it. The truth is, the code is totally arbitrary. Life made it up. By trial and error, life invented a coding scheme. It gave meaning to those molecules and all the ways they can be combined. The programming language of life was invented by life. It wasn’t the beginning, but a tool that cells made to manage their behaviors, learn new ones, and pass knowledge to future generations.

Let’s put that all together. A cell is a programmable micro-robot (in technical jargon, a “universal automaton”), capable of making virtually any protein and living virtually any lifestyle. In a sense, a cell is not just one organism, but potentially an infinite variety of organisms, depending on the programming in its nucleus. But how does the program get written? Life had to do all the work itself, without a programmer in the traditional sense. A cell has no mind with which to analyze its DNA and understand what it means. It cannot imagine the consequences of any changes to its programming, or test them out to make sure they are safe. And yet, somehow life invented a programming language and used it to write countless programs and build the full diversity of organisms we see on Earth.

We’ll delve into the details of how this happened in the next two blog posts. At a high level, though, there are two main parts of the story:

Life is self-made. Each cell is relatively simple and mindless, but working together in huge populations over long stretches of time, they develop their own programming. How they do it is quite different from how a human programmer would, but from a collective perspective, there are also some surprising similarities.
Life influences future generations. Organisms don’t just worry about their own survival, they put an enormous amount of time and energy into influencing the next generation for the better. Science is only beginning to understand this, but it offers the tantalizing possibility that, in some limited sense, life might steer its own evolution.

A Cell’s Eye View of Evolution

I’m trying something a little different. Over the next few months, I will publish a three-part series about evolution from some (hopefully) new perspectives. This represents how I, personally, have come to think about evolution. I’ll go beyond the scientific consensus to talk about some ideas that are uncommon and controversial. I believe I have a compelling story that’s consistent with established science, but this isn’t authoritative yet. In fact, I’m being a little bold and spicy in the hope of attracting criticism and feedback. I hope these ideas will frame my PhD research, so I’m excited to learn what people find interesting, useful, confusing, or problematic.

I’m doing this because I believe the way we usually talk about evolution obscures what’s really going on. In the “survival of the fittest” story, an individual organism lives its life, making choices that either help it thrive and reproduce, or not. If it’s successful, it will attract mates and have many children who are like them, but a little different, perhaps better. To follow the path of evolution, we then pick a new individual, maybe one of that organism’s children with a beneficial mutation, and see where life goes from there.

That’s an oversimplification of Darwin’s theory of Evolution by Natural Selection. It lacks nuance, but it’s basically correct and useful. The problem is, it’s just one way of looking at the situation, shaped by human bias. Each person is a multicellular individual that lives a long time and reproduces sexually, so it’s natural that we look at evolution from that perspective. But when it comes to life on Earth, we are the exception. The vast majority of life comes in colonies of single-celled organisms, living short lives and reproducing asexually. From that perspective, the process of evolution looks very different.

The next three blog posts will explore that perspective. Part one describes the cell as a tiny robot that uses DNA to program its own behavior. This will illustrate what it means to evolve such a program, and what purpose the program serves. Part two shifts perspective from a single cell to a population of cells over time. This illustrates how when individual cells work together in large numbers, they program themselves, using an evolutionary algorithm much more powerful than mere random variation and selection. Finally, part three discusses the complex ways that life influences the design of its own programming, and effectively “steers” its evolution, in a blind sort of way.

The first post goes out today, and you can read it here. I’ll release the other two installments in September and November. Each post is written to stand on its own, but together they tell a more powerful story, so I hope you’ll come back for more!

The Age of Microbes

(Image used under Creative Commons license, source)

There’s something very romantic about “the Age of Dinosaurs.” Before the familiar ecosystems of today, there was a completely different world order. Bizarre and fantastic species, strange environments and ways of living, another planet buried in the past of our familiar home. Yet, that was just one stage in our planet’s evolution—one that’s relatively recent, and similar to our own. It’s easy to forget that amniotes (reptiles, dinosaurs, birds, mammals, and the like) have only been around for 10% of Earth’s history, or about 300 million years. By comparison, single cells were the only life on Earth for 2.8 billion years. We sometimes hand wave over that period and say “not much happened,” but in that time life somehow went from accidentally self-perpetuating chemical reactions to swarms of intelligent microrobots that coordinate by the trillions to dominate every corner of the globe. This was the time of some of life’s most important and profound innovations, including essential concepts that made large-scale life possible.

About four billion years ago, the molten Earth finally cooled enough to form a solid crust of rock that could hold liquid water. Just 200 million years later, we see evidence of cells in the fossil record. In other words, it took just 200 million years for chance chemical reactions to become “self aware.” These early cells had no minds, of course, but they had membranes separating their insides from their outsides. They actively monitored and maintained the delicate balance of metabolic processes keeping them alive. Yet that was just the beginning of the journey, the basic foundation that made all the rest possible. From there, it took cells another billion years to cover the planet’s surface, and they’ve been ubiquitous ever since.

In that time, not much happened… from the human perspective. If you visited Earth at the time, it would look pretty boring. You might notice some slimes or biofilms, but you’d need a microscope to really appreciate that as “life.” Yet, gradually, microbes terraformed the planet. They found and exploited every available source of energy, and developed a molecular toolkit for extracting resources from a dead world. They mined useful molecules from the air, water, and rock, transforming and concentrating them for future generations. They remade the atmosphere, filling it with volatile oxygen, providing an energy-dense fuel for organisms to come. They created a protective layer of ozone that blocked DNA-frying radiation and made land habitable for the first time. This would all be invisible to a human observer because it happened so slowly, but the scale and significance of this transformation is incredible, especially coming from such tiny, mindless lifeforms. How could this happen?

Perhaps the biggest misconception about evolution is that simpler forms of life are “less evolved” than we are. The reality is that everything alive today has a common ancestor, and has had just as much time to evolve from there. Even bacteria are highly sophisticated organisms. They sense light, heat, motion, and chemicals. They sniff out food and resources, and navigate their environment. They hunt and evade predators. They learn and remember. They coordinate their behaviors with pheromone signaling. They sustain themselves, repair themselves, and make copies of themselves. In many ways, a single bacterium is vastly more impressive than anything made by humans. Like all life, they’re very good at what they do, but appreciating that intelligence means taking their perspective, which is rather difficult for humans.

For example, microbes experience evolution quite differently than we do. For humans, it’s a very abstract concept. It only matters on the scale of many generations, which may take thousands or millions of years. In contrast, a colony of E. coli bacteria can double in number every 20 minutes. They evolve over the course of hours, so for them it’s a real-time problem solving tool. There’s a fascinating experiment where bacteria took just eleven days to incrementally evolve resistance to antibiotics at a concentration 1,000 times what was originally a lethal dose. You can actually watch as the population discovers innovations that allow them to resist the poison and expand into new territory. When they do, they get a brief moment of total freedom, spreading unhindered until they start to get competition from their fellow mutants for the limited space remaining.

This is what cells are really good at. Not just living one lifestyle, but finding new lifestyles. In a crowded, competitive world, the best way for an organism to set itself apart is novelty: gaining access to an empty niche, or finding some innovative way to out-compete its neighbors. Doing this over, and over, and over again is how life managed to colonize every corner of this planet, from underwater volcanic vents, to Antarctic ice, to your gut. Exploration and creativity is also critical for long-term survival. On a geologic time scale, niches and lifestyles are transient, coming and going as changes in environmental conditions and competition from other species reshape the landscape. Staying alive means constantly adapting and trying new strategies. On a fundamental level, this is what life does.

This perspective helps explain one of the strange things about cells. Every living thing we know—every single cell, even the most ancient and primitive Archaea—has a general-purpose design. At their core, there’s a 3D printer for proteins, capable of mass producing molecules in a mind-boggling variety of shapes. Those proteins form the structure and machinery of the cell, help digest various food stuffs, neutralize toxins, and perform computations. Importantly, this 3D printer doesn’t just produce every protein a cell needs to live. It can make any protein, from any species, even proteins that haven’t been discovered yet. This would be massively overkill for living in any single niche, but it’s the ideal tool for conquering every niche. This complex, general-purpose cell design was so powerful that it out-competed and replaced everything simpler.

DNA mostly consists of programs for that 3D printer. It’s a collection of recipes for proteins, and cues for when to make them. Life hoards those recipes. They represent tools and behaviors that were once useful in the past. Right now, they might not be useful. They may even be harmful, disabled, and packed away where they can do no damage, but they aren’t forgotten. They lie dormant, waiting to be re-enabled on demand or by accident, just in case they might one day prove useful again. After all, who knows when the next global catastrophe will completely rewrite the rules of survival on this planet?

In other words, cells specialize in exploring the space of possible forms and lifestyles. They build up massive libraries of tools and strategies in their DNA. They continuously reprogram themselves, adapting to any conditions in order to find new niches. Macroscopic life, from butterflies to avocados to whales, is only possible because of this polymorphic quality of cells. They are the secret ingredient. They are like “smart matter” that can act autonomously, respond in real time, take on any shape, produce any chemical, and implement any behavior. Once you have that, it’s relatively easy to program those cells to construct just the right mix of forms, organized in just the right way, to make something much greater than the sum of its parts.

I hope this conveys some of why I find cellular intelligence so exciting. Humans are most interested in human things, so it’s very easy to ignore the incredibly alien lives happening right under our noses. Yet, there’s so much to explore, and so much of what we are is that “alien” cellular intelligence. What do you think? Did this help you see single cells or life in general in a different light? Did this spark any questions or ideas? Anything you’d like to see me explore more in a future post? I’d love to hear from you in the comments.