# Thread: One on One: Miller/Urey shows that life cannot form naturally

1. ## One on One: Miller/Urey shows that life cannot form naturally

The laws of thermodynamics also prohibit cells from arising spontaneously, and smaller DNA molecules from becoming bigger DNA molecules (that work).

Therefore, Miller/Urey proves (and by "prove" I mean "lends strong evidence to") that life cannot form naturally.

2. Can you go into more detail as to how the laws of thermodynamics prohibit cells from arising spontaneously, and small DNA molecules from becoming larger functional DNA molecules? I just want a starting point. To which laws do you refer?

Miller/Urey had little to do with thermodynamics other than they added energy to the system. Their intent was simply to show that under certain conditions, amino acids or amino acids precursors could form on their own.

3. "The entropy of an isolated system not in equilibrium will tend to increase over time, approaching a maximum value at equilibrium." (Rudolf Clausius)

First, we must define the world entropy. I will use the term entropy to describe the "disorder" of a system. The lower the entropy of the system, the more ordered it is. For example, ordered water molecules such as in an ice-cube have lower entropy than the surrounding water which has a random arrangement of water molecules (if you want to get picky liquid water also has a fair amount of organization, but relative to the rigid structure of ice, it can be described as "disordered".)

The laws of thermodynamics mandate that in any process the sum entropy of the entire system must never decrease. So what does this mean in a practical sense? Well, we've already discussed how an ice-cube has lower entropy than the surrounding water. In order to go from liquid water to frozen water, the entropy of the water molecules must decrease. So why isn't that a violation of thermodynamics? We must consider the entire system involved. Your freezer takes electrical energy (a low entropy system) and expends that energy to lower the air temperature, which then freezes the water. The energy that was used to lower the air temperature is now in a higher entropy state (heat exhaust from your freezer), while the ice-cubes molecules are now in a lower entropy state. Another way of stating this is that work must be done to lower the entropy of the water molecules.

Applying this concept to cells is quite straightforward. For every increase in organization of the cell, there must be a net expenditure of energy, just like in our freezer. Ultimately, the source of energy in most biological systems is the sun. Plants use the sun's energy to lower the entropy of carbon molecules and turn them into various carbohydrates. Animals eat plants and use their low-entropy carbon-chains to make high-energy (but low entropy) ATP. This ATP is then used as the "universal currency" for cellular energy. It's kind of like the electrical energy in our freezer example. Every process in the cell whic decreases entropy, be it synthesis of lipids, proteins, hormones, etc., uses ATP as the low-entropy energy source. The result is the net decrease in entropy of the organism and a net increase in entropy of the environment.

So let's look at a simple theoretical case about how a cell could potentially double it's genome content, increase it's information content, add complexity, and do this all according to the laws of thermodynamics!

Suppose we have a single replicating cell. In that cell's DNA content is a gene that codes for a single enzyme which pumps sodium (Na) back out into the space around the cell (extracellular space). We'll call this enzyme PUMP-A. PUMP-A works fantastic until the concentration of magnesium (Mg) inside the cell (intracellular) reaches a threshold value. When this happens, PUMP-A actually works in reverse, pumping Na back into the cell until the cell bursts. Here's our genetic code for the PUMP-A enzyme:

5' - AUG GAA GUA GAC CTA ACC TAA - 3'

Each time the cell replicates, it's internal copying mechanisms pass over this sequence and use ATP (our source of energy) to make a copy of this gene for one of the daughter cells. Now imagine that during one of the replications a mistake is made and the gene gets copied twice. We'll assume for the sake of argument that this gene duplication reduces entropy of the DNA content as a whole. We know from the laws of thermodynamics that in order to reduce local entropy, we have to expend some usable energy. So where could this energy come from? The same place the energy comes from during normal replication: cellular ATP stores. So while normal replication may have used 21 ATP (one for each base), the duplication error cost the cell 21 extra ATP for a total of 42 ATP. Notice that the total entropy of the system has been reduced, but at the cost of extra ATP energy. Now our gene looks something like this:

5' - AUG GAA GUA GAC CTA ACC TAA - AUG GAA GUA GAC CTA ACC TAA - 3'

Notice how the gene is doubled. We'll imagine this isn't a problem for the cell -- in fact, it actually helps the cell because it gives it 2 PUMP-A enzymes instead of just one! So this DNA sequence provides a slight advantage over other cells that have just a single copy of the gene. After a number of generations, let's assume this gene increases in frequency and is now found throughout 95% of the cells in the population.

Some time later, a single mutation happens in the second gene, changing the sequence to the following:

5' - AUG GAA GUA GAC CTA ACC TAA - AUG GAA GUA GAC CAA ACC TAA - 3'

Recall that during the copying of this gene, the cell expends 21 ATP. This changed gene represents an increase in complexity and organization, so we know by the laws of thermodynamics it came at the cost of "work" being performed of ATP. Now when this gene is transcribed it produces the normal PUMP-A, and a slightly different version of PUMP-A we'll call PUMP-B. PUMP-B has lost its ion selectivity (1), and now it pumps both magnesium AND sodium out of the cell. This means that the cell carrying this gene is much less susceptible to magnesium reversal because PUMP-B actively pumps magnesium out of the cell! Over a number of generations, this "version" of the gene becomes the predominant version in a population.

So let's take a look at what has happened here. The cellular genome has increased in both size AND content -- it now codes for two versions of the pump which give the cell a selective advantage over other cells which possess the older gene. Overall we can say that the cell has increased it's organization and thus reduced it's entropy. But this was not a free exchange -- it cost the cell ATP. In this scenario no laws of thermodynamics were violated. Each decrease in genome entropy was made possible by an equal or greater increase in entropy of ATP.

That should give us somewhere to start.

(1) I chose this wording intentionally to make a point. Creationists often claim that genes can only go downhill, and it's likely that this mutation would be called a "downhill" mutation because PUMP-B has "lost specificity". Carefully consider the ramifications of this. The exact opposite mutation (i.e. "A" back to "T") would give us the exact opposite response: PUMP-B would gain specificty and respond ONLY to sodium. Creationists might also call this reversal a "downhill mutation" and claim that it "lost" it's ability to respond to magnesium and now only responds to sodium! But we know that both mutations cannot be downhill mutations!

4. Originally Posted by Johnny
Can you go into more detail as to how the laws of thermodynamics prohibit cells from arising spontaneously, and small DNA molecules from becoming larger functional DNA molecules? I just want a starting point. To which laws do you refer?

Miller/Urey had little to do with thermodynamics other than they added energy to the system. Their intent was simply to show that under certain conditions, amino acids or amino acids precursors could form on their own.
They added energy to the system. That's pretty much where I'm concentrating on. Since I'm a layman, I'll have to move really slow. This is one of the reactions to create one of the amino acids in Miller, correct?
2 CH4 + NH3 + 2 H2O => H2N.CH2.COOH + 5 H2

I don't know the proper way to write where the energy is input in the system, but it should be there somewhere on the left side of the equation, correct?

5. Originally Posted by Johnny
"The entropy of an isolated system not in equilibrium will tend to increase over time, approaching a maximum value at equilibrium." (Rudolf Clausius)

First, we must define the world entropy. I will use the term entropy to describe the "disorder" of a system. The lower the entropy of the system, the more ordered it is. For example, ordered water molecules such as in an ice-cube have lower entropy than the surrounding water which has a random arrangement of water molecules (if you want to get picky liquid water also has a fair amount of organization, but relative to the rigid structure of ice, it can be described as "disordered".)

The laws of thermodynamics mandate that in any process the sum entropy of the entire system must never decrease. So what does this mean in a practical sense? Well, we've already discussed how an ice-cube has lower entropy than the surrounding water. In order to go from liquid water to frozen water, the entropy of the water molecules must decrease. So why isn't that a violation of thermodynamics? We must consider the entire system involved. Your freezer takes electrical energy (a low entropy system) and expends that energy to lower the air temperature, which then freezes the water. The energy that was used to lower the air temperature is now in a higher entropy state (heat exhaust from your freezer), while the ice-cubes molecules are now in a lower entropy state. Another way of stating this is that work must be done to lower the entropy of the water molecules.

Applying this concept to cells is quite straightforward. For every increase in organization of the cell, there must be a net expenditure of energy, just like in our freezer. Ultimately, the source of energy in most biological systems is the sun. Plants use the sun's energy to lower the entropy of carbon molecules and turn them into various carbohydrates. Animals eat plants and use their low-entropy carbon-chains to make high-energy (but low entropy) ATP. This ATP is then used as the "universal currency" for cellular energy. It's kind of like the electrical energy in our freezer example. Every process in the cell whic decreases entropy, be it synthesis of lipids, proteins, hormones, etc., uses ATP as the low-entropy energy source. The result is the net decrease in entropy of the organism and a net increase in entropy of the environment.

So let's look at a simple theoretical case about how a cell could potentially double it's genome content, increase it's information content, add complexity, and do this all according to the laws of thermodynamics!

Suppose we have a single replicating cell. In that cell's DNA content is a gene that codes for a single enzyme which pumps sodium (Na) back out into the space around the cell (extracellular space). We'll call this enzyme PUMP-A. PUMP-A works fantastic until the concentration of magnesium (Mg) inside the cell (intracellular) reaches a threshold value. When this happens, PUMP-A actually works in reverse, pumping Na back into the cell until the cell bursts. Here's our genetic code for the PUMP-A enzyme:

5' - AUG GAA GUA GAC CTA ACC TAA - 3'

Each time the cell replicates, it's internal copying mechanisms pass over this sequence and use ATP (our source of energy) to make a copy of this gene for one of the daughter cells. Now imagine that during one of the replications a mistake is made and the gene gets copied twice. We'll assume for the sake of argument that this gene duplication reduces entropy of the DNA content as a whole. We know from the laws of thermodynamics that in order to reduce local entropy, we have to expend some usable energy. So where could this energy come from? The same place the energy comes from during normal replication: cellular ATP stores. So while normal replication may have used 21 ATP (one for each base), the duplication error cost the cell 21 extra ATP for a total of 42 ATP. Notice that the total entropy of the system has been reduced, but at the cost of extra ATP energy. Now our gene looks something like this:

5' - AUG GAA GUA GAC CTA ACC TAA - AUG GAA GUA GAC CTA ACC TAA - 3'

Notice how the gene is doubled. We'll imagine this isn't a problem for the cell -- in fact, it actually helps the cell because it gives it 2 PUMP-A enzymes instead of just one! So this DNA sequence provides a slight advantage over other cells that have just a single copy of the gene. After a number of generations, let's assume this gene increases in frequency and is now found throughout 95% of the cells in the population.

Some time later, a single mutation happens in the second gene, changing the sequence to the following:

5' - AUG GAA GUA GAC CTA ACC TAA - AUG GAA GUA GAC CAA ACC TAA - 3'

Recall that during the copying of this gene, the cell expends 21 ATP. This changed gene represents an increase in complexity and organization, so we know by the laws of thermodynamics it came at the cost of "work" being performed of ATP. Now when this gene is transcribed it produces the normal PUMP-A, and a slightly different version of PUMP-A we'll call PUMP-B. PUMP-B has lost its ion selectivity (1), and now it pumps both magnesium AND sodium out of the cell. This means that the cell carrying this gene is much less susceptible to magnesium reversal because PUMP-B actively pumps magnesium out of the cell! Over a number of generations, this "version" of the gene becomes the predominant version in a population.

So let's take a look at what has happened here. The cellular genome has increased in both size AND content -- it now codes for two versions of the pump which give the cell a selective advantage over other cells which possess the older gene. Overall we can say that the cell has increased it's organization and thus reduced it's entropy. But this was not a free exchange -- it cost the cell ATP. In this scenario no laws of thermodynamics were violated. Each decrease in genome entropy was made possible by an equal or greater increase in entropy of ATP.

That should give us somewhere to start.

(1) I chose this wording intentionally to make a point. Creationists often claim that genes can only go downhill, and it's likely that this mutation would be called a "downhill" mutation because PUMP-B has "lost specificity". Carefully consider the ramifications of this. The exact opposite mutation (i.e. "A" back to "T") would give us the exact opposite response: PUMP-B would gain specificty and respond ONLY to sodium. Creationists might also call this reversal a "downhill mutation" and claim that it "lost" it's ability to respond to magnesium and now only responds to sodium! But we know that both mutations cannot be downhill mutations!
This is another decent path to go down, because as it turns out, energy problems lurk within this story in context of explaining how smaller DNA molecules get grow into bigger ones.

I'll go into this when the more straightforward example of Miller is more fully explained.

6. Originally Posted by Yorzhik
This is one of the reactions to create one of the amino acids in Miller, correct?
2 CH4 + NH3 + 2 H2O => H2N.CH2.COOH + 5 H2
I'm not sure what the proposed reaction was, I assume you got that from a source right?

I don't know the proper way to write where the energy is input in the system, but it should be there somewhere on the left side of the equation, correct?
You can just put it at the end of the equation and use (+) for energy being released and (-) for energy being required. Another notation commonly used is to write the equation, and then use dH = (+ / -) [quantitiy of energy] kJ/mol

So let's talk about the Miller experiment first, then. Did you have a starting point you wanted to work from?

7. Originally Posted by Johnny
I'm not sure what the proposed reaction was, I assume you got that from a source right?
Huh... you'd think it would be in Wikipedia. I can't seem to find that again.

Well, it shouldn't be that hard to figure out (from duke.edu):
The gases they used were methane (CH4), ammonia (NH3), hydrogen (H2), and water (H2O). Next, he ran a continuous electric current through the system, to simulate lightning storms believed to be common on the early earth.

and... here's more from Miller at duke.edu:
Formation of Glycine

1. CH20 + NH3 + HCN -> NH2CH2CN + H2O
Formaldehyde Ammonia Hydrogen Cyanide Ammonitrile Water

2. NH2CH2CN + 2H2O -> NH2CH2COOH + NH3
Ammonitrile Water Glycine Ammonia

We can work with the above reaction. In the above 2 reactions, there is energy input in both. In other words, when energy is added to the left side in reaction #1, you get the right side of the reaction. And when it is run through the system again and energy is added to reaction #2, you get the right side of the reaction, correct?

Originally Posted by Johnny
You can just put it at the end of the equation and use (+) for energy being released and (-) for energy being required. Another notation commonly used is to write the equation, and then use dH = (+ / -) [quantitiy of energy] kJ/mol
So if we added the energy notation to the above reactions, what would they look like?

Originally Posted by Johnny
So let's talk about the Miller experiment first, then. Did you have a starting point you wanted to work from?
The reactions.

8. My point isn't a secret. If we look at the actual reaction that took place in Miller we also know what the next step must be to get to a protein. Or, another way to put it; why didn't Miller get the next step in toward making a protein?

We can figure this out by looking at the energy involved in the reaction, and then looking at the energy required for the next step.

But the only way to see it is actually list he reactions and the energy involved. I don't think this is outside the scope of science.

9. I'm still here Yorzhik, I've got one more day of finals then a week off. I'll respond tomorrow or saturday!

10. Originally Posted by Yorzhik
My point isn't a secret. If we look at the actual reaction that took place in Miller we also know what the next step must be to get to a protein. Or, another way to put it; why didn't Miller get the next step in toward making a protein?
The right conditions weren't present.

We can figure this out by looking at the energy involved in the reaction, and then looking at the energy required for the next step.

But the only way to see it is actually list he reactions and the energy involved. I don't think this is outside the scope of science.
We don't have to list the actual energies involved so long as we both agree that energy must be added to the system. Right?

My problem with your statement is that Miller/Urey in no way lends any evidence to the idea that life "can't" form naturally. Typically in science experiments aren't designed to lend evidence towards a negative, the outcome or lack of outcome lends evidence towards a positive.

11. Originally Posted by Johnny
The right conditions weren't present.
Yes, obviously. However the question in context included the statement "If we look at the actual reaction that took place in Miller we also know what the next step must be to get to a protein." So we can speculate, theorize if you will, what could be done to get to the next step even though we know Miller was not set up for that. What reaction must take place to get to the next step of creating a protein from an amino acid? We can also answer the question of why the next step didn't occur in Miller.

EDIT: I should say, "the next step to a nucleotide". Or, even, to the next small step of a building block of a nucleotide beyond an amino acid. I apoligize for the error.

Originally Posted by Johnny
We don't have to list the actual energies involved so long as we both agree that energy must be added to the system. Right?
No. In this case the amount of energy matters.

Originally Posted by Johnny
My problem with your statement is that Miller/Urey in no way lends any evidence to the idea that life "can't" form naturally. Typically in science experiments aren't designed to lend evidence towards a negative, the outcome or lack of outcome lends evidence towards a positive.
Actually the lack of outcome lends evidence towards a negative.

Perhaps this story can illustrate. We wanted to route certain data through a certain server without compromising certain security. The administrator tried it the normal way but it didn't work and no one was surprised about that. Thus we went to one of the IT engineers and after he checked some things he thought he could make a work-around. First, he did a proof of concept that tested only the function that failed when the administrator had tried to make it work. The proof of concept failed!

So did that mean that we proved the data could not go through that server? Of course not. But that didn't matter - we did learn the time/money that would go into making it work was more expensive than the way we were currently moving the data. So it was what we called "economically unfeasible". As soon as the IT engineer got done with the test, he quipped "it can't be done". Was he wrong? No, he wasn't, even though with enough work/time/money it could be done; he knew the comment was in the context of economic viability.

In the same manner, Miller is a proof of concept. And just like money, energy is currency. So just like figuring out whether data can be moved in a certain way we have to count the cost, we have to do the same thing with the energy in the reactions to know whether it is feasible or not.

And we don't have unlimited options. There are only so many amino acids to work with and only so many ways to make them. With Miller we have a starting point, we have some of the amino acids. Now what is the next step we need to take, if we could, to create a DNA or RNA? What reaction does it take, and what kind of energy is used?

12. Originally Posted by Yorzhik
EDIT: I should say, "the next step to a nucleotide". Or, even, to the next small step of a building block of a nucleotide beyond an amino acid. I apoligize for the error.
Your first question was correct -- amino acids are the building blocks of proteins. Nucleic acids are the building blocks of DNA.

Originally Posted by Yorzhik
What reaction must take place to get to the next step of creating a protein from an amino acid?
Well, the amino acids must be linked to each other via a peptide bond. This reaction is called a dehydration reaction because a water molecule is released when a carboxyl group and an amino group bond. The smallest protein that has been characterized is 20 amino acids, I believe -- although a google search turned up a synthetic 10 amino acid protein.

So as to speculating why this linkage didn't occur, the only possible answer is that the conditions weren't correct for the dehydration reaction. What specific parameters weren't correct I can't tell you, and I suspect it would take a professional organic chemist to even make a guess.

Originally Posted by Yorzhik
No. In this case the amount of energy matters.
The actual number is inconsequential because it changes depending what units you're using. It is only important that relative changes in energy be accurately represented by our units. In this case, let's define the amount of energy for an amino acid to form 10 energy units (10 EUs). This should provide workable numbers to tinker with.

Originally Posted by Yorzhik
In the same manner, Miller is a proof of concept. And just like money, energy is currency. So just like figuring out whether data can be moved in a certain way we have to count the cost, we have to do the same thing with the energy in the reactions to know whether it is feasible or not.
Now I see why you're looking for actual values. I'll do some digging around and get back to you on those.

It's too simplistic to characterize a chemical reaction as a "proof of concept" because there are far too many variables. Indeed even if the energy requirements were extremely favorable, something as simple as a missing substrate could be preventing the reaction from occurring. For example, we can have two reactants interacting with each other just dying to bond -- but without the addition of free protons, they will never react. So then is it fair to use these two reactants alone as a "proof of concept" that the reaction will not occur naturally? Of course it isn't. If some protons happen to float along, the reaction will occur naturally.

13. Sorry for the long delay. I'll reply soon.

14. I had a much longer reply in the process of creation, but it would have moved the conversation too many steps ahead. Despite the current pace, slow and steady is better.

Originally Posted by Johnny
Your first question was correct -- amino acids are the building blocks of proteins. Nucleic acids are the building blocks of DNA.
Thanks for straightening me out on that. It was Juan Oro that came up with the nucleotide base Adenine. It isn't hard to mix them up from a layman's point of view because the same problem is endemic to both processes. But proteins are better to work with as opposed to DNA because the supporting structure isn't as complicated.

Originally Posted by Yorzhik
What reaction must take place to get to the next step of creating a protein from an amino acid?
Originally Posted by Johnny
Well, the amino acids must be linked to each other via a peptide bond. This reaction is called a dehydration reaction because a water molecule is released when a carboxyl group and an amino group bond. The smallest protein that has been characterized is 20 amino acids, I believe -- although a google search turned up a synthetic 10 amino acid protein.

So as to speculating why this linkage didn't occur, the only possible answer is that the conditions weren't correct for the dehydration reaction. What specific parameters weren't correct I can't tell you, and I suspect it would take a professional organic chemist to even make a guess.
No, we don't need to get anywhere near that complicated. The reaction, using the amino acids that Miller came up with, is enough for now. Do we know what that reaction is? Can we actually write it out?

Originally Posted by Yorzhik
No. In this case the amount of energy matters.
Originally Posted by Johnny
The actual number is inconsequential because it changes depending what units you're using. It is only important that relative changes in energy be accurately represented by our units. In this case, let's define the amount of energy for an amino acid to form 10 energy units (10 EUs). This should provide workable numbers to tinker with.
Okay. So it takes 10 EUs to form an amino acid. In the same context, how may EUs would it take to link 2 amino acids together?

Originally Posted by Johnny
Now I see why you're looking for actual values. I'll do some digging around and get back to you on those.
Okay.

Johnny continues:
It's too simplistic to characterize a chemical reaction as a "proof of concept" because there are far too many variables. Indeed even if the energy requirements were extremely favorable, something as simple as a missing substrate could be preventing the reaction from occurring. For example, we can have two reactants interacting with each other just dying to bond -- but without the addition of free protons, they will never react. So then is it fair to use these two reactants alone as a "proof of concept" that the reaction will not occur naturally? Of course it isn't. If some protons happen to float along, the reaction will occur naturally.
No. That's what "proof of concepts" are. It's why they exist, to use a reduced set of variables to answer a question. If there are variables we cannot know, then we either have to change what we are testing or wait until we can know the variables. And it doesn't matter if it's a computer program, a water works project or a chemical reaction.

That being said, the reason we are working with Miller is because we have a reduced set of variables. We know that we can get x amino acids. And we can get x amino acid chains. The proof of concept to consider is if we can get those chains long enough to do something with. How long, according to the reactions available, can the chains get? If we find them getting so long and no longer, then what is going on in the reaction that causes that particular phenomenon? If we look at the reaction, can we tell what is going on? I don't think these questions are outside the scope of science, and if we can list the reactions, and the energy involved, it won't be too complicated for laymen to follow.

15. This debate will be closed Friday May 18th at 1:15PM (MDT)

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