One Hand Clapping, page 6
All this engulfment and fusion of membranes—collectively known as vesicular transport—looks simple, natural, like the movement of oil droplets. Eukaryotic cells bustle with such movement, packed with semiliquid, undulating membrane compartments of all shapes and sizes. In fact, controlling such oil-like flexibility with seamless precision requires extraordinarily complex molecular technology. The flexible cell membrane must be suspended on a moveable cellular skeleton, or cytoskeleton. There must be proteins that control membrane curvature, membrane budding, and membrane fusion, proteins that drag vesicles and organelles around the cell, proteins that lay out the rails for those proteins to move, and proteins that take those rails apart.
It is this kind of machinery, in primitive form, that was found in Loki archaea, as if they were one step away from becoming eukaryotes but never quite got there. The shape of Prometheus, the live Asgardian that Japanese scientists were able to cultivate, also suggests a moving membrane: its cells resemble an amoeba or octopus—a loose ball with flexible arms protruding in all directions. These arms, in fact, were key to Prometheus’s survival: it refused to grow unless supplemented with another organism, a metabolic comrade, which it cuddled in its soft tentacles. Only in partnership with this additional creature, which aided it in digesting nutrients falling onto the seafloor, was Prometheus viable.
Suddenly, the pieces of the puzzle of eukaryotic origins started falling into place.
One day, about two billion years ago, as the world still reeled from the effects of the Oxygen Holocaust, two creatures met each other. The encounter must have happened at the border between the ocean’s water, which by now was saturated with oxygen, and some oxygen-free haven such as a methane seep—so perhaps on the seafloor. One of the creatures was a breathing bacterium. It didn’t fear oxygen because it mastered respiration and was looking for nutrients to burn. The other creature was an Asgard archaeon. It couldn’t breathe and so was restricted to living off seafloor detritus—and even for that, if Prometheus is any indication, this feeble creature needed help from some additional metabolic comrades. The breathing bacterium, in fact, would have been a perfect comrade—what better to help with digestion than an organism that can control fire? Using its flexible membrane, the Asgard archaeon drew the breathing bacterium into its orbit, pulled it close, wrapped its tentacles around it, tightened the grip, fusing the tentacles together, and then, suddenly, found the breathing bacterium inside of itself.
This was the moment that created our domain. A new compound organism consisting of an archaeon and a bacterium was born. This double origin meant it could do two things: engulf other cells, which was handled by the moving membrane of the archaeon, and burn them up into molecular shreds using oxygen, which was done using the bacterium’s respiratory abilities. As a result, this dual cell gained access to quantities of energy that individual bacteria and archaea could only dream—it could take energy away from others. Out of a friendly but feeble bottom feeder and a hardened survivor of the Oxygen Holocaust was born a new, magnificent, and terrifying creature capable of destroying other cells whole and thriving on their ashes: the Death Star of cellular life, a eukaryote.
The bacteria that gave eukaryotes the ability to breathe are still with us, inside each of our cells. Today we call them mitochondria. They still have their own genes and still divide semi-independently of the cells they inhabit, as if for them, our bodies are just a highly specialized environment as good as any. Think about it: there are ancient organisms inside all of your cells, and they are doing your breathing for you. There’s another Star Wars reference here: when George Lucas was creating the Jedi, mitochondria served as an inspiration for midichlorians, fictional microscopic creatures that give Jedi their powers.
Although human ancestors were not part of this particular journey, there actually has been a sequel to the birth of eukaryotes: another round of organisms fusing and merging their abilities. What I am talking about is the origin of the kingdom of plants. Just as the first eukaryote swallowed a breathing bacterium and turned it into a mitochondrion, the ancestor of plants, already a eukaryote with mitochondria, additionally swallowed a cyanobacterium—that oxygen-spewing photosynthetic organism—and turned it into part of itself, now called a chloroplast. These formerly free-living chloroplasts are what makes plants green. They perform photosynthesis for plant cells to this day.
So, technically, all breathing and all photosynthesizing in the world is still done by different kinds of bacteria, even if they live inside the cells of plants and animals.
Life in First Person
The birth of eukaryotes is so significant not just because it created the largest, most complex, most energetically expensive organisms that existed to that point. What is even more significant is that it broke the mold of the bacterial way of life. Bacteria operate not as individuals, but as populations, or strains. Eukaryotes, for the first time, begin operating not only as strains, but also as individuals.
In class, I show students a cartoon in which a grumpy kid microbe sits at a dinner table and the mom microbe beside him says, “But Timmy, you have to eat your antibiotics, or you’ll never become a big and strong bacteria.”14 The cartoon is funny, but it’s wrong. Timmy is not bacteria. Timmy is a bacterium. Bacteria is plural. Timmy himself will not actually become bigger or stronger by eating antibiotics. He will most likely die. But as long as Timmy has billions of siblings, there’s bound to be one that can withstand the antibiotic. That lucky sibling will be the one to survive and multiply. As a result, Timmy’s entire kin becomes stronger—resistant to the antibiotic through the brute force of selection. It’s basic Darwinism.
Although bacteria were first discovered in the seventeenth century, no one knew what to make of them until the advent of the germ theory of infectious disease in the late 1800s. Then, suddenly, scientists announced that not only was the world overrun with hordes of tiny, unseen creatures, but apparently it was them who had been making people sick all along. Understandably, the public’s gut response was panic: at the turn of the twentieth century bacteria were blamed for every possible human ailment including aging itself, and newspapers were full of snake oil remedies and disinfectant solutions claiming to facilitate their total eradication. When penicillin was first discovered, it was seen as a miracle cure, a triumph of the human mind over the microbial forces of disease—finally, we found a way to kill them all, for good. And indeed, no major epidemic since the discovery of antibiotics has been caused by bacteria (such as plague), while life expectancy in developed countries continued to grow seemingly without limits.15
But we misunderstood—and underestimated—bacteria. Bacteria are not like tiny humans or even tiny bugs. They are much more formidable—an amorphous, flowing mass of genes packaged into cells, capable of solving any problem they face. They are more like the liquid cyborg T-1000 from Terminator 2, the one who can turn into quicksilver and move through narrow spaces. Shortly after penicillin went into mass production—it started during World War II—doctors began reporting patients who were insensitive to the drug: they were apparently infected with bacteria that had evolved resistance to the antibiotic. Today, penicillin is rarely used for any serious infection because penicillin resistance among bacteria has become commonplace. Worldwide we are, in fact, running dangerously low on antibiotics that still work reliably and might soon find ourselves in a post-antibiotic era when a simple scratch could be life-threatening.16 Bacteria are catching up.
Antibiotic resistance is just one example, but this is how bacteria operate in general. They evolve their way around any problem, no matter what you throw at them. Their organisms are so simple and they reproduce so fast that they can bounce back from catastrophic devastation in a matter of hours. It is extremely difficult to kill them.
It is hard for us to understand bacteria because we humans associate ourselves with our organisms. When we say, “I,” we mean a material object with a voice, a hair color, and some genes contained inside. Bacteria don’t invest in their organisms nearly as much. Bacteria think in groups, strains, branches of the evolutionary tree. If they could say “I,” they would refer not to the organisms containing genes but to the genes traveling through time in replaceable organisms.
If you look at bacteria (and archaea) this way, it starts to make sense why they all look the same. From a bacterial perspective, organisms must remain as cheap and dispensable as possible. Bacteria are not interested in complexity. They must think of all our eukaryotic peacocking as rather daft. They keep their strains alive through constant, rapid, flexible evolution of their simple organisms.
On the other hand, eukaryotic organisms, from the very beginning, were precious. Thanks to their ability to swallow and consume other cells, eukaryotes were more complex than bacteria or archaea could ever be. But their mega-cells depended on an unprecedented supply of energy to sustain themselves, to swallow and not be swallowed. And once eukaryotes started investing in these complex organisms, the entire course of their evolution went into territory uncharted by any prokaryote.
How do you ensure that your precious organism survives under the constant pressure to swallow and not be swallowed? There are many ways—defense, offense, tolerance, specialization. Each branch of eukaryotes picks its own way. Some eukaryotes grow big teeth; others grow thick shells. Some learn to survive without food for a long time; others learn to find food in places where no one else can.
But one strategy that always seems to be an option is to double down on complexity. To ensure that your investment—the mega-organism—is protected, you could choose to invest even more and make the organism even more mega. Even bigger. Even stronger. Even smarter. From the bacterial standpoint, it’s like gambling away your fortune on roulette. And indeed, all their expensive innovations make eukaryotes quite fragile as strains—dinosaurs die out a lot easier than, say, staphylococci. But eukaryotes always find among themselves someone who simply refuses to step away from the roulette table, someone who does double down on the complexity bet and keeps going further, who adds yet another element to its organism and by doing so finds a new way to interact with the environment, to exploit it for more energy—despite the risks of extinction. As time goes on, more and more complexity evolves to tap into more and more energy, even as stakes continue to grow.
Do you see where I am going with this? The birth of eukaryotes set in motion a chain of events that finally—almost predictably—led to the birth of the human species. Eventually, something like us humans—complex enough to extract energy from fossil fuels and even atoms but still hungry for more, even as we teeter on the edge of self-annihilation—was bound to happen.
I think complexity is a much better term for what the medieval scholars called “perfection”—whatever it is that makes humans second only to gods. It is not about physical power (alligators are stronger than humans) nor about resilience (worms can survive in acid), nor even about the overall impact on the world (cyanobacteria were unmeasurably more consequential). It’s about how complicated our interaction with the world is—how many different things our bodies and brains can do within it. If we use complexity as a measure of perfection, then eukaryotes are certainly more perfect than bacteria, and humans are indeed the most perfect creatures of all. But there is no objective reason why perfection should be defined in this way—being complex is not the only way to be. Complexity is just one essence among many. But it is an essence at which we uniquely excel, as a domain and as a species.
Complexity in exchange for copious energy use—this is the story of eukaryotes as a whole and of humans more than anyone. Nowhere in nature does this story reach quite such a climax as it does inside the human brain. Our enormous, warm-blooded bodies are already cranked up in terms of their fuel consumption to almost the biochemical maximum, but the brain uses ten times more energy per unit of weight than the body on average. This level of energy use is only possible thanks to oxygen that constantly burns through totally unreasonable quantities of fuel. Most of the energy thus released is used for maintaining the electrical charge on the membranes of a hundred billion neurons.17 If we stop breathing, within a few minutes the neurons in our brains run critically low on energy, even though they can still break down fuel—just not as efficiently. The charge on those membranes soon begins to drop, which ultimately triggers an uncontrollable release of neurotransmitters, leading to convulsions and death.
Humans have no greater addiction than to this toxic gas of complexity that at one point almost destroyed life on Earth: a few minutes without oxygen, and our brains fry themselves. Isn’t that ironic?
*He also popularized scientific racism, based on presumed patterns of human migration from the Garden of Eden. It was an era full of intellectual contradictions.
*Collectively they are referred to as “prokaryotes”—basically, “not quite the real deal.”
*Eukaryotes do have a greater biomass than bacteria and archaea overall, but this is largely due to trees—just think of all the wood in all the jungles and taigas weighed together.
*To be precise, what’s released as a byproduct of photosynthesis and consumed during combustion is molecular oxygen, O2, two atoms of oxygen that join hands on their way to attacking other molecules.
*As always, there are exceptions, and “swallowing whole” has recently been discovered in one bacterial species.13
Chapter 4.
When All Else Fails
It requires a great man to resist the common sense.
FYODOR DOSTOYEVSKY Demons
It is tempting to assume that we humans have stopped evolving.
Evolution, it seems, is a brutal enterprise. To get to where we are now, untold numbers of our potential ancestors had to be rejected and discarded. For every single thing our bodies do for our survival—from the sense of hunger to the shivering reflex; from breathing to blinking—there had to be someone who died, leaving no offspring, because their body couldn’t do that thing well. For there to be winners, there had to be losers.
But humans, it seems, are no longer as brutal as Darwinian evolution requires. The progress of humanity—both technological progress and moral progress—taught us both the ways and the reasons to support the weak, cure the ill, and even bring children to those who can’t have them. By doing that, we surely have dampened the force of selection that would otherwise keep pushing us to become stronger and healthier as a species. It is logical to conclude that our evolution has stalled.
And yet that conclusion is short-sighted. There’s a tongue-in-cheek principle in biology known as Orgel’s Second Rule: “Evolution is cleverer than you are.” As a biologist, you gradually understand that the rule is not a joke. For all intents and purposes, it is safe to assume that any logical conclusion about evolution’s constraints—that it can’t do this or it can’t do that—reflects a failure of imagination. And so it is here: we haven’t stopped evolving, we just fail to perceive how our evolution might proceed.*
So where, then, are we going? At least in principle, what could our future look like? Will we grow wings? Lose all hair? Develop distinct arms, one for fine tasks, one for hard labor? Will we learn to shut our ears like we close our eyes? (These were all features of a “man of the future” from a Russian children’s book I used to have—the ear shutters especially would be a boon in noisy Brooklyn.)
We can’t predict the future, but we can look into the past and search for what is possible. As a matter of fact, there has been a time in the history of our ancestors—the young domain of eukaryotes—when their evolution would have appeared to them similarly stalled as it does to us now.
It is almost unbelievable how similar all eukaryotes are at the level of cells and molecules, even if they look nothing alike from a distance. Look beyond surface appearances and into a eukaryotic cell, its molecular architecture, its busy protein machines hustling and bustling, its internal dance of vesicles and vacuoles moving in all directions. It is an entire world existing at the nanoscale. And almost every element of this world exists, in recognizable form, in humans, turtles, amoebas, trypanosomes, lichens, eucalyptuses, and all other eukaryotes alike. For example, there are two proteins called mTOR and AMPK that sense the cell’s energy and nutrient levels. They act like two opposing forces: AMPK is turned on when energy is depleted, blocking cell growth, and mTOR is turned on when nutrients are abundant, promoting cell growth.1 These two proteins do the exact same things in humans, plants, and even ciliates—bizarre microscopic eukaryotes that look like tiny fuzzy aliens. Another example: there’s a protein that I study inside neurons called MAPK that is part of the process of memory formation—when a neuron is repeatedly stimulated, MAPK is activated using two separate chemical switches situated side by side, whereupon it proceeds to restructure the neuron, thereby helping store the memory.2 Almost the same protein with the exact same two chemical switches exists in yeast, where it helps adapt the cells to a salty environment if the yeast accidentally end up in one.3 (It also exists in every other eukaryotic cell.) So the specifics can be distinct—we use this protein for memory, yeast for adapting to salt stress—but the core gears on which everything turns are preserved across all eukaryotes even if they look completely different. From an outsider’s perspective, all eukaryotic cells are basically the same—bacteria and archaea would certainly say so.
What this means is that eukaryotic cells were nearly done evolving before all these various branches of eukaryotes came apart—so pretty early into our domain’s tenure on the planet. At this stage, there was no such thing as an animal or plant—there were only single-celled microorganisms swimming in water. To be sure, eukaryotes were the largest and most complex creatures among them, compared to all the bacteria and archaea. In hindsight, we understand that these ancestral eukaryotes stood at the precipice of exploding complexity. They were soon to give rise to all the glorious and now-familiar branches of our domain, from ferns to mollusks to portobello mushrooms. These early single-celled eukaryotes had already developed molecules that later would be used by human neurons to store information, by fungi to break down starch, by plants to absorb water. But they had no way of knowing that yet. Even if they could think as well as we do, they would not have imagined the possibilities that evolution held for them. There wasn’t anything more complex than single cells, and once the cells stopped getting more complex, what else was there to do? Had we interviewed those early eukaryotes around that time, they would no doubt argue that evolution is something that happened to them in the past and was largely over due to technological progress.
