The Origin of Life: What do we know?

[This is a transcript with references.]

The origin of life is without doubt one of the big open questions of science. We understand well how solar systems form and how planet Earth was created. We also understand how life evolved from the first microbes to bipedal mammals with opposing thumbs, though we’re still trying to figure out why the main use for those thumbs is hitting the poop emoji on a smartphone.

But somewhere in between the formation of our planet and the first microbes, inanimate matter assembled to self-replicating living creatures. How did this happen? How much do we know? And why are some scientists claiming that the emergence of life might be much more common in the universe than anyone thought? That’s what we’ll talk about today.

The Greek philosopher Aristotle thought life came about by “spontaneous generation” from inanimate matter. His belief was based on the observation that dead bodies and rotting fruit began to teem with maggots and flies.

This idea of “spontaneous generation” was widely accepted for more than a thousand years, though it always sat somewhat uneasily with the Catholic Church. But then, in the 17th century, the Italian scientist Francesco Redi showed that flies only emerged from rotten fruit if other flies laid eggs on them. The Catholic Church finally rejected the idea of spontaneous generation, and scientists began to have doubts.

Spontaneous generation was laid to rest in 1859 by the French chemist and microbiologist Louis Pasteur. He took broth that was full of nutrients and that would normally easily spoil. He put the broth into a flask whose neck had an “S” shape – a downward bend followed by an upward bend. It’s often called a swan neck flask. This flask allowed air to enter but kept out dust and microorganisms.

He boiled the broth and found that it didn’t spoil for months. No spontaneous generation of life! Based on this insight, Pasteur later invented a method to make food more durable. It’s now called “pasteurization” and is still used today, for example to preserve dairy products.

But throwing out the idea of spontaneous generation of life created a chicken and egg problem. If you needed life to create life, then where did the first life come from? When our planet was formed it was a big ball of hot molten rock, and that did one hell of a pasteurization. Nothing was alive then.

You may say that when our planet formed it wasn’t as well isolated as Pasteur’s flask. Meteorites and comets could, and did, reach it. A seed of life could have been planted on Earth in this way. This idea is known as “panspermia”. But it doesn’t solve the riddle, because if life came to us on a meteorite, it still must have originated somewhere, somehow. Nothing was alive during the Big Bang – atoms didn’t even exist back then.

Since Pasteur the world of science has been enriched with the discovery of the genetic code and electronic microscopes which make molecular structures visible. And scientists have returned to spontaneous generation.

The trouble begins with the question what we even mean by “life”. There’s no commonly accepted definition, but for the purposes of this video, we’ll stick with the definition that NASA uses, according to which life is a self-sustaining chemical system capable of Darwinian evolution. If it’s good enough for NASA, it’s good enough for us. So, if you want to explain the origin of life, you have to explain how a system arises on which Darwinian evolution can do its work.

And we do know a few things about the circumstances under which it must have happened. Planet Earth is about 4 point 54 billion years old. When it formed, it had no solid crust, and the surface temperature was several hundred degree Celsius. Over the next half billion years or so, lots of other chunks of matter impacted earth. A particularly large one is believed to have formed the moon. By around four billion years ago, the surface had cooled enough for a crust to develop.

Earth at this time was not exactly what you’d call a hospitable environment and I’m not talking about microaggressions. Back then, Earth still had a surface temperature above 100 degrees Celsius and loads of volcanic activity that frequently broke up the thin crust. The atmosphere was very different from what it is today, with high levels of carbon dioxide and nitrogen, water vapor, and toxic gases that were released during volcanic activity. Most scientists believe that life emerged after the surface temperature had dropped below the temperature where water boils, 100 degrees Celsius.

The oldest confirmed traces of life are biostructures called stromatolites, that’s layers of rock which contain remains of single-celled organisms. The organisms are believed to have been either algae or some kind of bacteria. Scientists have dated them back to about 3 point 5 billion years.

There are fossils that some researchers believe to be older, 3 point 8 or possibly even four point 3 billion years. But these have remained highly controversial. The issue is that old rocks don’t preserve records well, so you don’t really know what you’re looking at. Taking all this together puts the time window for the origin of life roughly between 3 point 9 and 3 point 7 billion years in the past. Though some scientists say life could have withstood the heavy meteorite bombardment and formed earlier.

And that pretty much sums up what we know. It admittedly isn’t much. How could you possibly go about finding out what happened so long ago? There are four major approaches that scientists have tried to make headway on the origin of life.

(1) There are bottom-up approaches that aim at synthesizing the building blocks of life from molecules that were present on young Earth, often with laboratory experiments.

(2) There are top-down approaches which start from known organisms, deconstruct them into their parts, and try to figure out which way they might have come together.

(3) There are approaches that start in the middle with a particular ingredient of life and try to figure out how it could have been created and then evolved further. This leads to approaches starting for example, with just RNA, or just proteins, or just lipids and so on. The most popular one is currently RNA.

And (4), there are approaches which start not with specific molecules but with sustainable chemical reactions that allow for metabolic cycles that generate energy. We’ll look at those one by one.

The key question for bottom-up approaches is how you get organic molecules out of inorganic stuff? Organic molecules aren’t molecules you get at a farmers’ market. They’re molecules that contains carbon-hydrogen or carbon-carbon bonds. There are different ways that scientists think they could have come about. The first idea was that lightning strikes did it, going back to a now famous experiment by Stanley Miller and Harold Urey in 1952.

In their experiment, Miller and Urey created a closed system from two glass flasks and filled it with gasses that mimicked the atmosphere of early Earth: water vapor, methane, ammonia, and hydrogen. They then subjected this mixture to electric sparks to simulate lightning, which is believed to have been common on early Earth. After a week of this process, they analysed the contents of their system and found that it contained several amino acids, the building blocks of proteins.

In 1962, the biochemist Joan Oro did a follow-up experiment and showed that similar conditions could also produce adenine, one of the four bases of DNA. Other scientists were later able to demonstrate the presence of chemical reactions that could give rise the precursors of uracil and cytosine, two other bases of DNA.

This all sounds very nice, but these experiments have a problem. It’s that they all assumed the atmosphere on young Earth contained little to no oxygen. It was strongly “reducing” as chemist say. That the atmosphere was “reducing” means that the gases in it like to donate electrons to other atoms. Oxygen, in contrast, tends to take electrons. These two situations are chemically very different.

Trouble is, in 2011 a group pf American researchers published a paper in Nature, shed doubt on the idea that atmosphere back then was that low in oxygen. The did this by looking at the zircon crystals, that are the oldest materials we have, predating even rock. I mean actual rock, not the music genre, though that’s also a little dated I guess.They tried to recreate those crystals in the laboratory at different levels of oxygen, but it only worked out correctly in the presence of oxygen. They speculate that the gas was released by volcanic activity.

Then, however, in 2020 another group argued that there could have been a reducing atmosphere after all, but it was temporary. They say that the big impact that supposedly formed the moon left a lot of iron laid bare on the surface of earth, and that iron rapidly combined with all the oxygen. So it could be that during a period of time after that hypothesized monster impact there were reducing conditions on our planet, long enough to give rise to life.

Other scientists think that some of the earliest habitable environments may have been hydrothermal vents or underground pools. This is because in those places you have both metals and carbon dioxide dissolved in hot water, which then mixes with colder seawater. This creates conditions that allow the first organic molecules to form. The difference between the two cases is that the hydrothermal vents always contain water, whereas the ponds have wet-dry cycles.

The problem of bottom-up approaches is the large number of possibilities. Could have been a submarine vent, or a drying lagoon, or lightning, or whatever other scenario one can imagine. And if you think life was created on another planet and then brought here by a meteorite, all bets are off. It’s basically the many worlds interpretation of organic chemistry.

Let’s then talk about the top-down approaches. For those, one uses genome sequencing to trace species back in time. The biochemistry of today’s living creatures is extremely similar. This strongly suggests that that we all descended from a last universal common ancestor, LUCA, for short. Detailed analyses of protein sequences suggest that the LUCA had a complexity comparable to that of a simple modern bacterium and lived 3 point 2 to 3 point 8 billion years ago.

In the past years, the number of sequenced genomes has increased exponentially, and with that the intersection of genomes between all species has shrunk to a mere handful of genes. This basically allowed scientists to refine the recipe for life and to trace its origin further back in time. In a 2018 paper , scientists estimated the time it would have taken environmental factors to create the required number of mutations, and found that these first common genes were probably around already 3 point 9 billion years ago.  

The problem with this approach is that the gap between the first ancestor that we can infer from the surviving record and the earliest life might be too large. The way of self-replication could have changed multiple times, leaving no trace for us to follow to figure out what happened just going by what’s left today.

This brings us to the third approach, big molecules that can carry forward information and therefore lend themselves for natural selection to act on.

The best candidate we know for this is currently RNA. RNA is not a double strand like DNA, but a single strand. In today’s organisms, the main function of the RNA is to read the DNA and create proteins from it. RNA executes the will of the DNA, so to speak.

RNA, like DNA, is a sequence of four molecules called nucleotides, but they’re slightly different. In DNA, the nucleotides contain the four familiar nucleobases A C G and T.

In RNA you have U instead of a T and it uses a different type of sugar. It’s been a long time since I had biology in high school, so let’s do this again the other way round. Nucleobases are part of the nucleotides, and nucleotides form both the DNA and RNA, though they each have different nucleobases.

However, RNA is by itself also able to encode information and it can self-replicate.  Better still, once you have RNA, fatty acid membranes form around it spontaneously. This gives rise to a rudimentary protocell. It’s even able to divide when more fatty acids get incorporated into the membrane, and the RNA could replicate inside.

Sounds good, but where does the RNA come from to begin with? RNA is a very long molecule. At present, scientists believe that it emerged from shorter strands, small RNA pieces that are called template molecules, and which then guide the formation of the long RNA.

Ok, but where do the template molecules come from? Scientists think that the wet-dry cycles of warm ponds create large chemical gradients that make it possible for such long molecule chains to form from nucleotides, the building blocks of RNA.

Ok, but where did the nucleotides come from? They come from the nucleobases plus other organic stuff. This too favours the hydrothermal vents. In 2017 paper a group of researchers from Canada and Germany build a numerical model for how nucleotides form from nucleobases in hydrothermal vents and found it takes only a few years. They said that this could have happened as early as 4 point 17 billion years ago.

Ok, but where did the nucleobases come from? They came from outer space! At least that’s what they assume in the paper. It’s plausible because these molecules have indeed been found on meteorites. They say the space dust wouldn’t work because the density is too low.

So, the idea is this. You get the nucleobases from outer space. They fall into a warm pond. There they undergo chemical reactions which create the nucleotides. The nucleotides combine to RNA template molecules. And the template molecules polymerize RNA. Then add a few billion years of evolution and you get YouTube. Simple enough!

And how did the nucleobases get onto the meteorite? Ah, yeah, good question.

Since the gap in complexity between molecules that easily pop into existence and the self-replicating molecules capable of carrying information is so large some scientists have proposed that maybe what came first was a type of metabolism, the ability of systems to extract energy from their environment to maintain themselves.

This idea was popularized by the American researcher Stuart Kauffman in his book “At Home in the Universe”. He suggested what he called “autocatalytic sets”, that are networks of chemicals that are both products and catalysts. This means they can keep on churning out new products while producing energy along the way. According to Kauffman, these autocatalytic sets are the missing link between inanimate and animate matter.

Indeed, in a 2020 paper a team including Kauffman looked into how these networks of reactions could have arisen from scratch. They looked at some single-celled organisms that still exist today. They found that the metabolic sets overlapped in an ancient core network of 172 reactions. It is self-sustaining, and can generate both amino acids and nucleobases.

In a follow-up paper from 2022 two of the same authors found an even larger set of more than 2700 elements. They spanned a surprising variety of sizes:  from as few as 3 to as many as 619 reactions. Most of these sets are smaller than those of creatures living today, which is interesting because it points to an intermediate state in the evolution of metabolisms.

The authors conclude that the ease at which these autocatalytic networks can emerge from basic chemical reactions indicates that molecular reproduction may be much more prevalent in the universe than predicted. If that is correct, life might not be rare in the universe, but the very opposite, it might be pretty much unavoidable. Because once you have sufficiently many molecules that can react with each other, the probability that you get a self-catalysing cycle approaches 100 percent.

And this really was the reason I made this entire video. Because it’s so stunning I don’t understand why this wasn’t front page news in all newspapers on the globe. Hey, the universe might be brimming with life. Yes, there’s still the problem of just exactly how those molecules assembled. You didn’t actually expect me to say the case has been settled, did you?

In summary, the prevailing scientific hypothesis for the origin of life is that it was not a single event, but a sequence of steps of increasing complexity. It required first the formation of organic molecules, then cyclic reactions of molecules that create energy and more of themselves, the formation of increasingly larger molecules that carry forward information in their sequence, the self-replication of this sequence, and the emergence of cell membranes.

The details on how it happened are unclear. And since the evidence may have been lost forever, we may never know for sure. Or maybe one day we will understand that life is an inevitable consequence of a universe that evolves towards increasing complexity, maybe just so that someone is there to admire its beauty.