Life’s Molecular Machines: By Chance or by Design?

Jed Macosko | Thursday, November 14, 2002
Copyright © 2002, Jed Macosko

Edited transcript from a lecture given at 194 Chemistry, University of California, Davis sponsored by Grace Valley Christian Center Thursday evening, November 14, 2002

Life’s molecular machines-are they by chance or by design? That’s the question I’m going to be addressing tonight. First I’d like to talk about the new paradigm in biology, and especially in molecular biology. Bruce Alberts, the president of the National Academy of Science, published a review where he said: “The entire cell can be viewed as a factory that contains an elaborate network of interlocking assembly lines, each of which is composed of a set of large protein machines.” People in molecular biology have already known about this for quite a while, that proteins work together to perform all the functions that happen inside of our cells. But molecular machines have sort of seized the day. It is no longer sufficient to look at a cell as a bag of chemicals. You have to see it as an assembly line of large protein machines.

This lecture will cover three questions: 1) What are molecular machines? 2) How can we know if something is designed? 3) Are these particular molecular machines by chance or by design?

Bacterial Flagella

I’ve got a couple of slides to show tonight. The first of them is from the “mascot” of Intelligent Design-the bacterial flagella. What we’re doing is we’re zooming underneath the membrane of the cell, and we’re watching as the bacterial cell puts together, out of protein building blocks, a ring, and then another ring, and then another ring. These rings work together to form an outboard motor, a motor that propels the bacterial cell through the liquid in which it lives. These are the stators that hold it fast, here’s the rod and the spindle, and there’s a universal joint that grows out of the membrane. It’s carefully regulated by this scaffolding protein. The scaffolding protein figures out when it makes a quarter of a turn in this U-joint, and then it leaves and it allows the rest of the flagella to be excreted through this hollow center, thus forming each of the building blocks of this outboard motor. You can see it as they slither up this channel and fit together.

These machines have been kind of the mascot of the Intelligent Design Movement because they really resemble the kinds of machines that we engineers put together. You can see that each of these little protein subunits is rotating around while the chain grows. Those tails grow to be several times the length of the bacteria itself, and they form a corkscrew. It’s this corkscrew that propels the bacteria through the liquid. The neat thing about it is if it reverses the direction, then these corkscrews unwind from one another, and the bacteria tumbles. That’s how a bacteria swims towards its food. Now, this is not what happens inside of one of your cells; this is what happens inside one of the cells that lives inside of your gut-E. coli, for example.

“A Voyage Inside the Cell”

This video shows what happens inside one of your own cells as it goes through the process of cell division. This movie is made by a French animation company; they’ve coordinated with molecular biologists to give us “A Voyage Inside the Cell.” This voyage is something that we would normally not be able to take because we can’t go this deep into the cell. Our microscopes are not able to get a picture of what happens.

These are computer animated cells. They have on their surface membranes that protect them from the outside world. They also have little finger-like extrusions calledmicrovilli, which are useful especially in the gut for making the surface area of the cell larger so that more nutrients can be taken up. There are lots of other uses for these microvilli, and I’ll be discussing a few of them in the second half of my talk.

Notice that the surface of this cell is actually made up of molecules. Each of these little egg-like structures is the head of a molecule. These molecules have one surface that likes water and one surface that doesn’t like water, just like oil and water don’t mix in a salad dressing. These tails don’t like to be in the water, and that’s why they organize themselves in these patterns.

This is a hormone molecule. It is partially soluble in water and partially soluble in lipids, so it can slither through the membrane; that’s how hormones get into your body. Other molecules never even get into your body, but they send a signal through the membrane using a protein machine called a receptor. Here is a receptor, and here is the ligand that binds to the receptor. That ligand matches the chemical structure of the receptor, which spans the membrane. As it binds it causes a conformational change in the body of this receptor molecule, and it sends a signal to the other side.

A lot of people, including myself, study these kinds of signal transduction pathways and the changes in the chemical nature of these messenger molecules, which are also protein machines that are phosphorylated. After their chemical composition is changed, they go to the endoplasmic reticulum, which is shown here as a kind of tube and sheet, and it can then release a calcium signal, for example. Many such signals are happening in your body right now as your body reacts to the environment and as each cell reacts to the local environment in which it lives. So this is an example of signal transduction, which is the passage of information across the membrane.

One of my favorite things that crosses the membrane does so in a process known asendocytosis. What you see up here at the top of the screen, kind of looking like a little blue disco ball, is actually a clathrin-coated vessicle. This clathrin molecule is another protein machine. It forms a geodesic dome, and that dome then forms a sphere that pinches off part of the membrane, so what you see inside of the dome is actually the same stuff that makes up the outside of the membrane. Inside there is probably some food and other molecules necessary for the cell.

Now here’s something that everybody likes to watch. This is mitochondria. It’s the powerhouse of the cell, so you’ll see that it’s just charged with energy. It produces the energy that the cell needs, in the form of ATP. Why does the cell need ATP? Because there are a lot of molecular motors in the cell, such as these little kinesin molecules which are walking down this microtubule. You may not realize it, but this is happening in your body right now. Things are being moved back and forth into different parts of the cell by little kinesin molecules that look a lot like those things. They have little heads that move forward on the microtubules, and it actually looks like a person walking.

The plot of this movie is cell division, and the main protagonist in our play is this little hormone. This hormone is going to cause all the changes that the cell undergoes when it divides. All of the biochemical transitions are started by that one molecule. What you see it flying past here is the centrosome. That’s where all the microtubules start. It’s kind of like the “command central” inside the cell; it tells where everything should go, and it pushes and pulls things around inside of the cell.

Here we have the brain of the cell, a sort of “library” of genetic information, called the nucleus. Only cells of our class, the eukaryotes, have this membrane around the nucleus. But everything that lives must have genetic information, and that’s what we’re seeing as we fly through this portal into the nucleus-genetic information. Here you can see strands of DNA wrapped up, like little beads and pearls, around histones.

Here you see the network of supporting membranes and proteins that hold up the inside of the nucleus, called the nuclear matrix. What you see here in pink is the receptor for this hormone. Every hormone has a receptor, and they go right together, just like coffee and cream. You can see that when that hormone binds to its receptor, the receptor takes good care of it, and it undergoes a conformational change that in this case allows this receptor to dimerize with one of its own buddies. That provides enough surface area to bind to a strand of DNA; not just any strand of DNA, but the specific strand of DNA that encodes the proteins necessary for cell division. So it bound to that region, and then it helped recruit the copying machine, the machine I studied in my postdoctoral work, called RNA polymerase.

Before we look at that machine, let’s do a little basic review of DNA. You’ve all seen the double-helix of DNA, and you all know that it has rungs. But you may wonder: What are those little ladder rungs that we always see in movies? Well that’s where the information is. It’s in the form of As, Ts, Gs, and Cs. Those are nicknames for the particular shape of chemical that binds across the gap. And A always binds with T, and G always binds with C in a molecule of DNA. That’s how a DNA strand is copied, because it will faithfully replicate itself by matching all the As with all the Ts. But the actual sequence of As, Ts, Gs and Cs is what gives it the rich information content that we’ll be talking about later in this lecture.

What you see lit up there now is the RNA. This DNA strand can be seen as a book on reserve in the library. You’re not allowed to check it out, but you certainly can make photocopies of it and take those home with you and study for the exam. And that’s what this RNA is. This is a little photocopy of the entire strand of DNA that’s relevant for this particular protein that the cell is going to synthesize. As soon as it hits the end of that relevant gene it releases the RNA. That folded strand of RNA then goes back out the nuclear pore, the one that we came in, and goes to the ribosome. The ribosome is responsible for turning that genetic information into useful protein information, and the useful protein information shows up a few hours later back inside of the nucleus as a factory for DNA replication.

Now we’re taking that book on reserve and we’re printing a new book. We’re making two copies where we only had one. This book was out of print, but we’re copying it, we’re binding it together, and then we’re going to make two separate libraries so we don’t have to walk across campus to get to the library. So here’s the book coming in, twisting its way through this factory, and out come two strands. These are the daughter strands and this is the mother strand. Those strands then need to be bound up, just like a book.

The first step is getting them to wrap twice around these little proteins calledhistones. The next is to form a fiber of compiled histones that can then be bound by the protein known as condensin. Condensin forms the loops, sort of puts the pages of the book together. Then you have the full book assembled into what you may recognize as a chromosome, X-chromosomes or Y-chromosomes. This is where all of the information is inside of the cell; it’s packed into those chromosomes, ready to be divided.

Now, you may see this whole picture and think, “Wow! That is a lot of stuff going on.” The sheer beauty of it may be compelling enough for you to think that perhaps some or all of these machines are designed. But just the sheer wonder of it is not really enough to convince a scientist. A scientist needs to be convinced by numbers, by experiments, by data. And that’s what we’re going to be talking about in the rest of the talk. But I really wanted you to get a flavor for what these machines are actually doing inside of your body. Every time your cell has to do some function, machines are right there at the heart of it.

And we’re not done with these machines. For example, these microtubules that we saw being used as walkways for kinesin molecules are now being actively involved in a tug of war centered on these red disks, called the kinetochores. These red disks help to align the microtubules and make sure that each of the chromosomes has the same amount of pulling force on them; that will help line up the chromosomes along the middle axis of a dividing cell. It’s not until all of the chromosomes that exist inside of a particular cell (we have forty-six of them) are lined up in the middle that you get cell division, because the last thing a cell wants is for one chromosome to get stuck on one side and another chromosome to get stuck on the other side. If that happened, all that information would be lost to the two daughter cells.

After they’re all lined up it pulls them apart in a giant tug of war happening at the microscopic level. When that happens, chemical signals go throughout the cell and tell a contractile ring of molecular machines, little motors on the outside of the cell pulling towards one another, to squeeze the cell in the middle. That pinches off this membrane, and so instead of having one continuous membrane, it breaks right here in the middle, and the two daughter cells are now identical to the mother cell.

This is the beautiful pageant of life that is happening every time we regenerate our cells, and it goes on right now in your bodies. I find that to be completely fascinating, and I think we could end the talk right now. But like I said, we’ll go back and take apart these different machines.

Defining the Terms:

First we’ll talk about some important definitions that will help us as we try to decide whether these machines are by chance or by design. Our first important definition isevolution; the second one we’re going to define is creation, and our third one isscience. There have been many inaccurate definitions of these three words, and before we go on I think it’s important to precisely define what we mean by creation, evolution and science.

Evolution: When I say evolution I don’t mean small variations of bird’s beaks. I mean the process by which a simple one-celled organism became all of the different kinds of organisms that we see around us today-sharks, rabbits, turtles, you name it. That’s what I’m talking about when I say evolution.

Creation: When I talk about creation I’m not talking about a particular biblical account. I’m talking about the simple concept of going from not knowing something to knowing something, of having an idea. What we see around us, these animals and some of the systems that are working inside of their cells-some of that is the result of an idea; we don’t know whose idea, but it is an intelligent idea.

Science: Science, on the other hand, I would like to define as looking for evidence. Let’s say you are a scientist and you discover this never-before seen object (a lock). After you discover it’s existence you define it, you characterize it, and you make some hypotheses about it. Now, your colleagues don’t really know what you’re doing in your research lab, but you propose that the object is related to another object (a key) that was recently discovered in another laboratory. Your colleagues then will say, “Oh yes. I can see how these two objects are related.” You are following the evidence wherever it leads. Now, if your colleagues had a very strong distaste for these types of objects, say because they didn’t like things being locked up, you might have a hard time convincing them that they are indeed related. But the weight of the evidence will lead you to that conclusion.

So when I talk about science I’m not talking about playing by any set of rules that limit us to some philosophy of naturalism, or even a methodology that says only natural processes can be considered as explanations for the evidence. I’m saying science should be about following the evidence wherever it leads, even if the end result is something that falls outside of the boundaries of what is currently defined as science, because I think that current definition needs to be broadened a little bit.

Seven Molecular Machines - 1) Cilia

So now let’s return to our molecular machines. I’m going to pick out seven of them that I think are particularly interesting. Let’s start with the microvilli and cilia. A cilium is a protrusion from a cell, kind of like an active microvilli. Inside of a cilium you have a very interesting set of machines. These little guys you may recognize as microtubules, the green rods that you saw in the movie; they are similar to kinesin molecules. Here they are trying to move down the central microtubule. But they get stuck, because they are connected here by a stretchy protein, a diene molecule. This stretchy protein will basically allow this rod to slip along here so far, and then it will snap back.

The net result, as you slide these rods, is you get a power stroke and a recovery stroke. That’s just what you need in order to propel fluid across the membrane. So whether you’re a protozoa and you want to swim through a liquid using your cilia, or you’re a cell inside of an intestine and you want to move fluid along, or you’re a cell inside of somebody’s lungs and you want to move mucus up, these cilia are very important.

2) Clathrin-coated Vessicles

The second molecular machine that we’ll be looking at is the clathrin-coated vessicle. You can watch this video on the web yourself. Basically, this molecular machine, this geodesic dome, is assembled by little three-fold pieces that work together, interlocking into a geodesic dome that does the activity of pinching off the membranes.

3) Kinesins

The third machine is everybody’s favorite-the kinesins, those little guys that make the inchworm walk. Let’s look a little closer at kinesin. Here is a closeup picture of the chemical shape of kinesin. It has a head region, a stalk region and a tail region. The head region is what binds to the microtubule surface. These are what I call the “feet” of the molecule, because as it walks down or takes steps, it burns up ATP energy, and it moves this little vessicle (or it can move a whole organelle, like the mitochondria) down the microtubule. Some kinesins move from the negative end of the microtubule to the positive end, then they fall off and come back and start over again. It’s kind of like a little conveyor belt. Other kinesins go back the other direction.

As you can imagine, this is very important for the nerve cells that stretch all the way from your spinal cord down to the tip of your toe. Imagine how long it would take for food from the center of the cell to reach the end of the cell, or for chemicals that are synthesized in the middle of the cell to go all the way down to the toe. If it were not for the activity of these little kinesin molecules, it would take forever. But these kinesin molecules are working day and night inside all of your nerve cells to bring materials down, and the ones that go in the opposite direction are bringing products up. So there’s a constant flow of traffic of these molecules.

4) ATP Synthase

Let’s look at another machine, the ATP synthase. ATP synthase is actually a part of mitochondria. It’s the mechanism by which mitochondria turn ADP, which is spent fuel, into ATP, fuel that’s ready to burn. It does that by using rotary torque. It turns out that if you give this molecule ATP and let it burn the ATP to ADP, it will drive the rotary torque motor the other direction. But the way it typically works is the energy comes from a proton motive force.

When you eat, the food is digested into molecules that have energy, but these molecules are not as useful as ATP. ATP is the currency of energy inside of the cell. Everything uses ATP. Not everything uses glucose or fructose or the other things that you may be eating. So fructose, glucose and all the other things you eat get converted into a proton motive force, basically a battery that spans the membranes inside of your cell. It’s a battery that has more positive on the outside than on the inside. This is the plus terminal and that’s the minus terminal. As the proton motive force goes across the membrane, it drives a rotary engine. This is showing a little two-stroke engine here, a rotary engine that moves around and around, driving the synthesis of ATP from ADP.

Now here’s the F1 rotary motor. This is the spindle, and it rotates around and around and around while the ATP and ADP bind here. That’s how this motor works-as it turns around it’s either creating more fuel or it’s burning fuel and sending force down through the membrane.

5) Nuclear Pore

Let’s look at another one here. This is the nuclear pore. It looks like just a hole in the membrane, but it’s much more than a hole. It’s actually a complex assembly of different parts. Many of you may have heard of a man named Michael Behe. He’s a professor at Lehigh University who coined the phrase irreducible complexity. What irreducible complexity says is that these machines are made up of many parts, and if you take away even one of these parts, say the nuclear ring or one of the cytoplasmic particles, the machine no longer functions in any way.

This machine functions as a gatekeeper. It keeps molecules that are not supposed to be inside the nucleus out, and prevents molecules that are supposed to remain in the nucleus from going into the cytoplasm. It also allows some things to go back and forth, and it may even actively transport them across the membrane. This machine would not do its job without all these parts. Biochemists and molecular biologists, whether they believe in Design or Darwinism or whatever, need to know which parts are essential and what each part does.

6) RNA Polymerase

Let’s look at the next machine. This is RNA polymerase; we call it RNA-p for short. Here we’re initiating RNA polymerase. If you just polymerized your entire genome, all of your DNA, into RNA you’d have a lot of useless photocopiers. And just like you don’t have a limitless supply of quarters when you’re in the library, the cell doesn’t have a limitless amount of energy to use or materials to spend on making photocopies of the DNA. So it’s very careful where it starts to make a copy. That process is called initiation.

Initiation occurs only when the activators, bound to the enhancers, bind to the appropriate components in the initiation complex, which bind to the helper proteins and start RNA polymerase going. This is a typical cartoon that you might see in a biology textbook, keeping in mind that each one of these little blobs is actually a fine-tuned molecular system. Just like the hormone and the hormone receptor bound like a lock and a key, so also these proteins bind together in order to fit into a particular three dimensional shape.

Once you get initiation you also need to get transcription, the process of copying. This is the workhorse of the copying; this is the photocopy machine itself. What you see is that not only is a molecular system of machines very complex, but even one machine by itself is very complex. Within a machine you have a lobe, a flap, a tip, a channel, a clamp, switches, a bridging helix, the active site, and the jaws that clamp around it. This protein is full of complexity, even though it’s only one component of the cartoon we saw in the last slide. It’s very complex all the way down to the very smallest features of these complex systems.

7) Ribosomes

OK, let’s move on the ribosome. This is what I call the “Death Star” of molecular biology, because this makes all the other machines pale is comparison. I’m only showing half of a molecule. This is where the active site is. But as soon as a piece of RNA binds in this cleft, the other half snaps into place and covers it up. All the process of translation, which is taking the RNA copy and making it into a useful protein, happens deep inside of the Death Star. What you see in yellow are proteins. What you see in white is actually RNA, which is participating in this whole assembly line of molecular machines. That’s why I don’t like to call them protein machines, because RNA does a good job of catalyzing reactions and doing the work, so we usually refer to these things as molecular machines.

This is another movie that you can download from the web. It shows what happens when we take a slice from inside of the ribosome. Here you see the RNA. Here you see a transfer-RNA. This is the copy RNA. This is more of a working piece of RNA. At the tip of the RNA is one amino acid. That amino acid gets linked to another amino acid when another tRNA comes here through this channel, binds here, and makes a bridging bond between the two pieces of amino acid. Then everything ratchets forward. You see that this is color-coded. There are three green subunits, and this is the green tRNA. Each tRNA binds to one amino acid, one of the twenty that we have, and one of many possible codons (three-letter words in the RNA book) in the DNA book or the RNA copy. This is really the fundamentals of molecular biology. If you’re a molecular biologist, I apologize for going over it again; if you’re not, this is what you can learn first about molecular biology-that DNA gets copied into RNA, RNA gets put inside a ribosome and gets turned into proteins, and proteins in turn do all of the work inside of the cells.

Current Research Tools

We’ve talked about a lot of molecular machines, and I want to take a little step back and review where we’ve been. We’ve made three major points: We have molecular machines which are composed of interlocking parts; they perform essential cellular functions; and they need help from other machines. Now I want to talk a little bit more about the research that’s happening, and how we learned all about these machines.

First of all there’s the atomic force microscope. This works sort of like an old LP player: there’s a needle, there’s the vinyl, there’s a measuring device that measures the fluctuations in that needle, and instead of some kind of an electric signal we have a laser bouncing off the top of the needle. If you’ve ever used a laser pointer you know that if your hand jiggles a little bit, the laser pointer jiggles a lot. The same principle applies here-it amplifies any jiggling in the cantilever, in the needle. It can get down to subatomic differences in the surface. You can actually see orbitals of different atoms. It’s amazing.

But we don’t even need that kind of resolution to see DNA. We can just look at the strands of DNA. This is an actual image taken in our laboratory in Berkeley. We have this strand of DNA, and we have two promoter proteins binding to enhancer sites. When they bind together that really increases the amount of photocopies that are made from this downstream strand of DNA. So when you get these two proteins binding together like that, as opposed to like this, then this gene is hyperexpressed and you get a lot of that gene product.

We also have something called photon fields. Photon fields are kind of like the tractor beam in Star Wars or Star Trek. What you do is you capture a little tiny bead, usually made out of plastic, in a focused laser beam. That holds the little bead steady. You can then stretch pieces of DNA with that, and measure the forces exerted by little molecular machines. This is a pipette holding one bead while the other bead is caught in the laser. On the next slide is a fun little movie of fishing for beads with DNA. This movie shows how this bead, which is caught in the laser beam, can be fished out of the laser beam by a strand of DNA. You maneuver this pipette around with a little joy stick and fish for a bead. We do this all the time so that we can grab onto a single molecular machine and study it.

Finally, there’s a way of using centrifugal force to stretch DNA. Instead of using a laser beam to move it, now our focused laser is just used to track where our bead is. It’s the centrifugal force of spinning a platform, in this case a compact disk, that stretches the DNA and then allows us to detect the forces of these molecular machines, such as RNA polymerase. So these are just a few ways that we can study molecular machines on a case-by-case basis.

Design Filter: Probability and Specificity

LAW : High probability (dominoes falling)

CHANCE: Low specificity (pair of dice)

DESIGN: Low probability, high specificity (three darts in bullseye)

Now let’s talk about the big questions, the questions that you’ve all been wondering. First of all, since some molecular machines are well studied and our knowledge of their details grows daily, we therefore ought to know more about their possible causes of origin. One would think if we spent all this money researching molecular machines that we should be able to tell how they got here. So we can ask the question: Is their origin best explained by chance, which is random mutation and selection, or design, the product of intelligence? Which one of these best explains the origin of the molecular machine? Is it a combination of chance and law, or is it design, what we just called “intelligence”?

I’m going to borrow from Bill Dembski, a mathematician who has studied the probabilities of different things and how a person would go about making an inference for design. For example, say you come home and there are potato chips all over the couch, the TV is warm and the kids are scampering up to their bedrooms. You may guess that they’ve stayed up late watching a scary movie. Now, you would infer that using a very simple design filter. First you would ask: Is there a law that explains the potato chips on the couch? Not that I’m aware of. Not unless you store your potato chips right over the couch and there has been an earthquake. Then the law of gravity plus the earthquake would explain the potato chips. But, short of that, a law would not explain those potato chips being on the couch.

You see these dominoes? They are falling by the law of gravity. If I push this domino, I should not be concerned that the fourth domino has also fallen. I should not think that maybe the angel of death dropped this last one. I would know that it’s the simple Newtonian laws of motion and the law of gravity that determines that this one knocks this one knocks this one knocks that one. Case closed. There is no design to this other than that I pushed it over in the first place. This is caused by natural processes that are law-like.

Now, we have another natural process, and that’s the natural process of chance. Chance is usually indicated by a low specificity. If I look at my couch and I see potato chips that spell “Hi, Dad,” that would not be low specificity. I would probably conclude that not only were my kids staying up late, but they were probably bored by the movie they were watching and they decided to be funny. But if the potato chips are strewn in some random pattern, I would assume that when my kids heard the door opening they threw the bowl into the air, the potato chips fell willy-nilly in a random pattern with a low specificity, and the exact order of those potato chips on the couch was by chance.

So that’s the second level of this filter. Here you see some dice. When you roll them, you expect one of six numbers to come up. If you roll a bunch of dice, you expect a bunch of different combinations to come up on any given time you throw the dice. Now, if you’re in Vegas and you keep throwing sevens again and again and again all night long and you’re making tons and tons of money, somebody might pick up your dice and say, “Hmm, I think these might be loaded.” That would be a law. If you’re always getting sevens every single time, there might be some law-the law of weighted dice and gravity-that would explain how you get sevens every time. That would be using the design filter. Or if I always get blackjack I might then assume that there’s a design, that the dealer is working for me and he’s stacked the deck in a design. Design is indicated by low probability plus high specificity.

Now instead of dominoes or dice we have darts. To win at darts we must hit a target. That’s our specificity. It doesn’t really make any sense to just say, “It was low probability.” For example, those potato chips on the couch were in a very improbable organization, yet I know the kids didn’t take the time to place each one of them. I would infer from this design filter that it was just by chance how they actually landed there. But if it spelled out “Hello, Dad” then I would know that it has a specificity.

So this is the essence of the design filter. This is the process we would go through for any situation. It is rigorously mathematically described with a lot of different symbols and variables and things like that. And it can be applied to parents coming home late at night, to cryptologists trying to break a code, to SETI people looking for extra-terrestrial intelligence, or insurance scam investigators trying to find out if you burned your house down. This is the same exact filter that everyone uses. It’s looking for low probability plus high specificity.

Conclusion

I’m going to make my conclusions right now. Molecular machines are complex. I think everybody can agree they’re complex. And they perform specific functions. The bacterial flagella performs the function of swimming through a liquid. The ribosome performs the function of turning RNA into protein. So, these complex molecular machines perform specified functions. But functional machines are unlikely. This is where we get our low probability. So we have high specificity and low probability. Only design explains low probability and high specificity.

Life requires molecular machines; life always has had molecular machines; therefore, I believe that life’s molecular machines originated by design.