22: Cell’s Kitchen

Episode 22: Cell’s Kitchen

For the past five episodes, we’ve assembled a team of organic molecules together in the Earth’s earliest oceans, more than four billion years ago. They don’t know it yet, but this ragtag group of misfits will work together to start the most impressive project in the universe- life.

In one corner is protein, the muscle of the group. When a cell needs a job done, needs something built, no questions asked, protein is your right-hand molecule. Next on the list are carbohydrates, aka carbs- the financial backer of the operation. There’s no money in the Hadean sea, but carbs have something better to sell- energy. The energy to build and grow a cell, the energy to stay alive. Last episode, we met the brains of the operation- the twins: RNA and DNA. The twins didn’t arrive with the goal to make life. In fact, their goals are far more selfish- to make copies of themselves, to live on forever. Turns out, the best way to do that is to build a backup team.

But we’re missing one last player. As we float around the ancient ocean, we see proteins, carbs, and RNA mingling together in a primordial soup. This soup is intricate and complex, but very fragile. One rogue wave, one small tweak in chemistry can change the recipe, can unravel everything RNA has worked for. What our team needs is a safehouse, a place isolated from the harsh, hellish Hadean world. In other words, to turn primordial soup into actual life, we need to shove it inside a cell. And that’s where the final team-mate comes in. It’s time to revisit our friends from Episode 17: fats.

Part 1: Oil and Water

When I talk about fats on this podcast, I’m really talking about a much larger family of molecules including oils and waxes. Together, these molecules are called lipids. For now, I’ll keep calling them fats, but keep the word “lipid” in your back pocket. This word will become more important in later seasons when we meet different forms of life.

No matter what you call them, there’s only one thing you need to know about fats: fats and water do not get along. You see this simple fact everyday in the kitchen. When you take bacon grease, olive oil, or melted butter and try to mix it with water, something weird happens. The fats will form small bubbles or discs in the water.

In contrast, when you take other organic molecules like protein powder or sugar, they usually dissolve and mix into a glass of water. So what gives? Why don’t fat and water get along?

Let’s start with water. A single water molecule is shaped like a boomerang: a broad, bent V. At the two tips of this boomerang sit hydrogen atoms, the two Hs in H2O. The O for oxygen sits in the bent crook in between.

Drops of oil surrounded by water- why do they always separate?

Here’s where things get interesting. The oxygen in the middle has a negative charge, while the two hydrogen tips are positive. This means that when two water molecules float next to each other, the positive tips of one boomerang will be attracted to the negative butt of another. It’s just like an early romance in your favorite fiction- two lovers are attracted to each other, but never find the courage to reach out and touch the other.

This tug-of-war, this will-they won’t-they between molecules gives water many interesting properties. It’s why water takes much longer to boil than other liquids, and it’s why ice floats instead of sinks. It’s also why so many materials dissolve in water, even though it’s not acidic. For example, sugar and salt are also split into negative and positive charges, just like water. When you drop a sugar cube in coffee, the gentle pull of positive and negative charges is enough to tear the cube apart, dissolving it into invisible pieces. For this reason, sugar and salt are called water-loving molecules- they’d rather hang out with water than with each other.

In contrast, there are other molecules that are simply above all of this drama. These molecules are well-adjusted, well-balanced- they have the same charge all over their tiny bodies. They don’t interact with water as much- they would rather stick with each other. In fact, you could even say these molecules hate water, but this still isn’t enough to form bubbles. Water-hating molecules will simply not interact with it as much.

Now let’s look at a fat molecule. They come in many shapes and sizes, but most look like tiny kites. The head of this fatty kite loves water, while the long stringy tail hates water. When you shove a bunch of fat molecules together, something very interesting happens. The water-hating tails all clump together in the center– they’d rather hang out with each other. In contrast, the water-loving heads of the same molecules all point outward, into the surrounding sea. The resulting shape is a bubble, with the water-hating tails on the inside and water-loving heads on the outside. It’s similar to a herd of cows protecting their calves from wolves- heads pointing outward in a circle, tails pointing inward.

This simple rule of opposites attract is why oil and grease form bubbles in water. The same idea can be seen in every single cell, every living thing from bacteria to Bruce Springsteen. Each cell is a self-enclosed bubble- the outer membrane of your cells is made from lipids, the distant cousins of olive oil and butter. Without these lipids, without these cellular enclosures, all your DNA and proteins would be floating naked in the universe, much easier to be destroyed by the elements.

Forming a fat bubble isn’t too difficult- it happens all the time in nature and your kitchen. It’s the next few steps that are more puzzling. First, the bubble needs to trap just the right combination of RNA and proteins. If you only catch RNA, you can’t really build anything, and if you only catch protein, you don’t have a code to make new materials. And even if you do get all the right ingredients in one go- how do you keep the system going? How did the guts of the first cell interact with their new walls?

These are some of the biggest questions in the origin of life. We’re tantalizingly close to bridging this gap, but as of 2023, no one has successfully made a living cell from scratch.

There are two main ideas on how the first cells formed- one by sea, and one by land. Our next two segments will focus on each in turn. Now that we have a basic grasp of lipids and bubbles, it’s time to travel back four billion years ago and add some fat to the primordial soup.

Part 2: The Lost City

The year is 1977, the place- the Galapagos Islands, the same islands where Charles Darwin refined his ideas on evolution a century earlier. This new team of scientists is also looking for new life, but they’re not scouring beaches for finches or turtles, they’re patrolling the bottom of the sea. Three men are squeezed into a 7-ft wide sphere in a submarine more than 6000 feet deep, 2000 meters below the waves. The only light is from the sub’s headlamp- illuminating a bleak landscape of black rock, an underwater desert.

For hours, the water temperature has been hovering around freezing. At least it was nearly freezing, but now it’s starting to rise. If you hopped out of the sub, it would be like a pleasant bath, except the incredible water pressures would crush you instantly. This heat isn’t surprising- the crew knows they’re near some underwater volcanos- a rift where the crust is tearing itself apart. If you want to learn more about that, check out Episode 12- Scratching the Surface.

What is surprising is the appearance of new life. Until now, there had been a fish here, a squid there, but now they’ve stumbled across an oasis. Hundreds of pale crabs, translucent shrimp, clam-beds and huge white worms with red feather caps stretching up like demented trees in a ghost forest, all shoved together around the warm volcanic waters. Rising even higher above these creatures were pinnacles of hot volcanic rock. This was the first time humans had seen a world where life was powered by something other than sunlight. 

A black smoker on the Mid-Atlantic Ridge, 3300 m (~10,000 ft) deep

The team expanded their search, first in the Pacific, then around the world. Wherever they found underwater rifts, they found the same warm waters, and the same creatures over and over again. Technically, these features are called hydrothermal vents- they literally vent waters up to 450 C, 900 F, which quickly cools as it spreads in the frigid depths. But as more vents were uncovered, a new nickname stuck- “black smokers”. The vents often form chimneys several stories high, belching dark, sooty material like a smokestack. This black potion isn’t smoke, but water rich in minerals, metals, and sulfur. Black smokers are often given individual names that are even cooler, like the Rainbow, Loki’s Castle, and Godzilla.

Among the many researchers from San Diego, Woods Hole, and beyond, led primarily by Jack Corliss, one researcher in particular might ring a bell. His name is Robert Ballard, and he was on these voyages of discovery from the very beginning. Ballard would become far more famous years later for other deep-sea discoveries- the shipwrecks of the Bismarck, the Yorktown, and the Titanic. Yet even after a storied career in ship-hunting, Ballard still says that his most important work was on black smokers long before. 

Let’s pause. The discovery of black smokers is a highlight of recent science, and a great story, but what does it have to do with the origins of life? There weren’t worms or crabs in the ancient Hadean sea, were there?

No, but if you’re looking for a modern recipe for primordial soup, black smokers are a decent place to start. Remember Stanley Miller’s mad science experiment from Episode 20, where he made complex amino acids from carbon and lightning? In the last part of that episode, we discussed that Miller’s ideal recipe of methane and hydrogen probably didn’t resemble the Hadean ocean or air. However, black smokers provide concentrated sources of these ingredients, as well as a consistent source of energy through volcanic heat and chemicals like iron and sulfur. At black smokers, you don’t have to wait for the next lightning strike.

It's an interesting idea with many supporters. However, you can have too much of a good thing. A little heat is good to get some energy, but too much will ruin the recipe. Many of life’s essential molecules simply break down at the ridiculously high temperatures of black smokers, hundreds of degrees hot. Even worse, waters from black smokers are acidic, favoring the breakdown of certain molecules.

White smokers at the “Lost City”, also on the Mid-Atlantic Ridge

Recently, a modified version of this idea has become more popular. Black smokers have a milder cousin- the white smoker. Since white smokers form slightly farther away from volcanic sources, they’re much cooler and less acidic, forming a nice Goldilocks zone that’s even more favorable to early life than their intense neighbors. One white smoker in the north Atlantic has been the site of intense chemistry and biology studies, and has become one of the top candidates for a modern window onto the Hadean world. As always, scientists do not disappoint with their names- this hidden world of pale crystal towers is called the Lost City. Back on the surface, lab experiments replicating white smokers have made abundant fatty bubbles, indicating that the first cells might very well have formed in these environments.

Whether you side with black or white smokers, the idea that life arose in warm, dark oceans has been around in some form for many decades. But another contender has arisen in the past few years, one that brings us out of the surf and onto the Hadean turf. 

Part 3: Wet and Dry

You don’t need a submarine to see hot water bubble up from below Earth’s surface. Hot springs are found on every continent, wherever volcanic activity heats up local groundwater. These springs often form striking vistas of steaming blue waters, pale crystals, and rainbows of bacterial colonies. Imaging bison roaming around Yellowstone National Park, Turkish tourists in the white terraces of Pamukkale, or the monkey-filled pools of Japan. Just like the crabs in black smokers, these creatures weren’t around in the Hadean- just volcanos and hot water.

Several researchers argue that these hot springs are a better candidate for the first cells than seawater. Their main argument is that these pools dry up over time, losing their precious water.

At first glance, that might sound crazy. Life needs water to live, and all the experiments and reactions we’ve talked about need water to work. Yet, as we said before, you can have too much of a good thing. The ocean is a large place, and it can be hard to force molecules together to react and build larger shapes. Here’s another way to think about it. You’ve probably heard that your body is 70% water. While that’s true, the water inside your body is not pure at all- it’s stuffed with billions of proteins, carbs, fats, and other molecules. We’ve described the Hadean ocean as a “primordial soup”, but that soup was probably very thin and watery.

An Icelandic geyser. Pay attention to the wet surrounding plain- this is one possible habitat where the first cells assembled in the Hadean.

Let’s return back to our hot springs on land, specifically Old Faithful in Yellowstone National Park. Old Faithful is a famous geyser that erupts boiling water every few hours. The water settles into a pool and eventually dries up in certain spots. As the water evaporates, all the salts and chemicals within become concentrated together. In these shrinking pools, molecules like proteins, amino acids, and RNA were far more likely to run into each other than in the open ocean. When Old Faithful erupts again, more water is supplied before the whole system dries out, providing more materials for new cells to grow.

Modern experiments show that wetting and drying organic molecules over and over will eventually form fatty bubbles surrounding RNA. These bubbles aren’t real cells, but they’re a great first step.

Before we finish, there’s another way to concentrate life’s ingredients and shove them into cells. This process could have happened in the ocean or in hot springs- all you really need is clay. Clays are a large family of tiny minerals. They’re not flashy as quartz or diamond- they’re literally mud. But clay has many interesting properties- anyone who’s taken a pottery class can tell you this. Wet clay is soft and easily deforms in your hands, but dry it out, and it becomes hard and brittle.

Under the microscope, a single clay crystal looks like a club sandwich, with many layers of different materials. One difference is that these layers are floating apart from each other, like you had thrown the sandwich in the air. These gaps in the clay sandwich are perfect sanctuaries for organic molecules to meet and grow. Lab experiments with clay have grown long chains of RNA up to 50 bases long, without any need for life. Clays also trigger the bubble formation when placed in certain fats. In short, clays are secluded natural laboratories that can build life’s building blocks and store them away for safekeeping. Perhaps life didn’t start in a soup, but in a sandwich.

So, what’s the right answer? Did life start at the bottom of the ocean, or in a geyser field on land, or tucked away within clay or rocks? The jury is still out at the moment, but the fact that we have multiple potential answers instead of none is promising, and I feel that this stage of life’s origins could be resolved within the next few decades. Maybe the answer is something even stranger than we can imagine right now- only time will tell.

Summary: Every living thing on Earth is made of cells, which are lined by fatty molecules that both hate and love water. These molecules first circled together in the early Hadean world, encompassing RNA and proteins to make the first cells. This process is still murky, but we’ve narrowed the story to two spots: undersea towers belching hot water into a dark ocean, or hot springs boiling and drying on Earth’s earliest islands. In any case, we’ve assembled the whole gang together- RNA, protein, carbs, and fats together into one cell. There are still many steps in the process that we don’t know about, but for the sake of this podcast, we’ve finally made the first life on planet Earth. Next episode, we’ll take a closer look at our earliest ancestor, and finish Season 1.